Biomarkers of Inflammation Kussmann

MARKERS AND LAB TESTS OF INFLAMMATION EVIDENCE IN FAVOUR OF TOLLE CAUSAM USE OF NATUROPATHIC MEDICINE TO REDUCE THE

INCIDENCE OF CHRONIC DISEASE

Heidi Kussmann ND FABNO

THE VALUE OF LAB MEDICINE TO HEALTH CARE

bull Objective data that enables

bull Screening for risk factors

bull Accurate and early diagnosis

bull Determination of disease severity

bull Recoverysurvivalprognostic value

bull Treatment selection

bull Evaluation of adverse eventsoutcomes

bull Chronic diseasemedication management

Subjective frustration translation to whole systems


bull Services provided

bull Matching blood to patient

bull Public health infectious disease identification and control

bull Rapid testing for triage and emergency care

bull Assessment of quality of care in chronic diseases

bull A basis for evidence-based medicine for cost-effective testing therapeutic treatment and interventions screening and design of therapies based in pharmacogenomics or nutrigenomics

2httpswwwfuturelabmedicineorgpdfs200720status20report20laboratory_medicine_-_a_national_status_report_from_the_lewin_grouppdfaccessed Dec 15 2012

HISTORY OF LAB SCIENCES AND INFLAMMATIONIt all started whenhellip

BRIEF HISTORY OF MEDICAL DIAGNOSIS

bull Middle ages-18th century bedside medicine

bull 1794-1848 hospital medicine

bull 1848-present laboratory medicine

bull Laboratory medicine is appreciated as the seat of modern medicine

bull Early lab techniques of diagnosis

bull Observation (palpation taste vision smell hearing)

bull Late 19th century tools Microscope thermometer stethoscope

FOUNDER OF EXPERIMENTAL PHYSIOLOGY ndash GALEN (AD

131-201)bull Combined hippocrates humoral and pythagorean

theories to correspond to various combinations of drycoldhotmoist with earthairfirewater

bull Hot + moist = blood

bull Hot + dry = yellow bile

bull Cold + moist = phlegm

bull Cold + dry = black bile

bull Ancient diagnostic methods3 Berger D A brief history of medical diagnosis and the birth of the clinical laboratory Part 1 July 1999 wwwmlo-onlinecom

The 5 cardinal signs of inflammation originally described by Celsus 2000 years ago

Source httpwwwnaturecomnrijournalv2n10fig_tabnri915_F1html accessed March 8 2013

INFLAMMATORY MARKERS AND TESTS USED IN THE

MIDDLE AGES

bullUrineStool inspection

bull Temperature

bullPulse

bullPalpitation

bullPercussion

bullDreams3 Berger D A brief history of medical diagnosis and the birth of the clinical laboratory Part 1 July 1999 wwwmlo-onlinecom

17TH CENTURY ndash A CENTURY OF URINE

bull William Harvey ndash blood circulation

bull 32-power microscope

led to the study of cellshistology

bull Urine tasting to differentially diagnose diabetes insipidus and diabetes mellitus

bull Urinalysis became more qualitative

bull Blood transfusions IV drug injections

bull Pulse and temperature as indicators of health3 Berger D A brief history of medical diagnosis and the birth of the clinical laboratory Part 1 July 1999 wwwmlo-onlinecom

18TH CENTURY ndash THEORETICAL ADVANCEMENT OF MEDICINE

bull Digitalis and opium discovered for medical use

bull Septicemia was highest cause of mortality in hospitals

bull Prothrombin time and plasma prothrombin time fibrinogen (ldquocoagulable lymphrdquo) was discovered as the cause of coagulation by William Hewson (1739-1774)

bull Pulse measurement refined but rejected due to skepticism for the Galenic doctrine of there being a special pulse for every disease

bull Arterial blood pressure measurement quantified by Stephen Hales (1677-1761)

bull Discovery of sediment in the urine of febrile patientsBerger D A brief history of medical diagnosis and the birth of the clinical laboratory Part 1 July 1999 wwwmlo-onlinecom

19TH CENTURY DATA

The microscope the X-raybull Enabled several doctors to view and discuss resultsbull Team approach to diagnosis strengthened the medical

communityrsquos claim to objective judgment

Set standards for physiology deviations and classifications

Quantitative diagnosis in the hospital laboratory allowed diagnosis of TB cholera typhoid diphtheria and syphilis

Standardized testing became the norm

Hematological testing discoveries calcium salts in the coagulation of blood mast cells white blood cell classifications

3 Berger D A brief history of medical diagnosis and the birth of the clinical laboratory Part 1 July 1999 wwwmlo-onlinecom

INFLAMMATION GOOD BAD UGLY

bull Good necessary to promote an immune response in otherwise healthy individuals

bull Bad in allergenic and auto-immunogenic unhealthy individuals

bull Ugly chronic disease and cancer are the result of long-standing chronic inflammation

Inflammation is an incendiary process that if properly detected and treated could save lives

THE START OF INFLAMMATION

bull The start of inflammation depends on the genetics of the host and that individualrsquos response

bull Oxidized pholpholipids are potent stimuli that trigger macrophage recruitment and contribute to both the initiation and progression of chronic inflammation

4 Orozco L et al Unraveling Inflammatory Responses using Systems Genetics and Gene-Environment Interactions in Macrophages Cell 151 658ndash670 October 26 2012

5 Berliner JA Leitinger N and Tsimikas S (2009) The role of oxidized phospholipids in atherosclerosis J Lipid Res Suppl 50 S207ndashS212

THE IMPORTANCE OF INFLAMMATION

bull Defined Complex non-linear set of interactions among soluble factors and cells which arise in any tissue in response to traumatic infectious post-ischemic toxic or auto-immune injury

bull Normal inflammatory process leads to recovery but if the targeted destruction and assisted repair are not controlled then inflammation can lead to persistent tissue damage by leukocytes lymphocytes or collagen

6 Carl Nathan Review article points of control in inflammation Nature 420 846-852 (19 December 2002) | doi101038nature01320

7Brown KL et al Complexities of targeting innate immunity to treat infection Trends Immunol 2007 Jun28(6)260-6 Epub 2007 Apr 30 in 1 Yoram Vodovotz Translational Systems Approaches to the Biology of Inflammation and Healing Immunopharmacol Immunotoxicol 2010 June 32(2) 181ndash195 doi 10310908923970903369867 PMCID PMC313415 NIHMSID NIHMS230084

WHY MEASURE INFLAMMATION

bull Inflammation and angiogenesis occur during infections auto-reactive diseases chronic inflammation as well as being hallmarks of cancer

bull Proteins are involved in the systemic response of inflammation

bull Inflammation causes cell and genome damage stimulating cellular turnover by cytokines and growth factor release and create a tissue microenvironment that can enhance invasion migration and angiogenesis 8 Karin M Lawrence T and Nizet V Innate Immunity Gone Awry Linking Microbial Infections to

Chronic Inflammation and Cancer 2006 Cell 124(4) pp823-835 Available from httpdxdoiorg101016jcell200602016 accessed Dec 8 2012

FIGURE 1 A GENERALIZED SCHEME TO EXPLAINTHE ORIGIN OF CHRONIC INFLAMMATION

THE COST OF INFLAMMATION

bull Non Communicable Diseases (NCDs) including cardiovascular diseases chronic respiratory diseases cancer and diabetes are the major global health problem of the century 9 Rosenbaum L Lamas D (2011) Facing a lsquolsquoSlow-Motion Disasterrsquorsquo - The UN Meeting on

Noncommunicable Diseases New England Journal of Medicine in PLoS One 2012 7(5) e37483 in Alvar Agustiacute Persistent Systemic Inflammation is Associated with Poor Clinical Outcomes in COPD A Novel Phenotype Published online 2012 May 18 doi 101371journalpone0037483 PMCID PMC3356313

bull They are the world leading cause of disease burden and mortality are increasing in prevalence even in low-and middle-income countries the costs incurred by uncontrolled NCDs are substantial and they are an under-appreciated cause of poverty and hinder economic development 10 Bousquet J Anto J Sterk P Adcock I Chung K et al (2011) Systems

medicine and integrated care to combat chronic noncommunicable diseases Genome Medicine 3 43 in 11 Alvar Agustiacute Persistent Systemic Inflammation is Associated with Poor Clinical Outcomes in COPD A Novel Phenotype Published online 2012 May 18 doi 101371journalpone0037483 PMCID PMC3356313

ENVIRONMENTAL CAUSES OF INFLAMMATION

bull Environmental hypothesis for allergic and autoimmune diseasesbull Northern Geographical location high social economical

educational or occupational status stress intestinal permeability 12 Danese S Sans M Fiocchi C Inflammatory Bowel disease the role of environmental factors

Autoimmunity Reveiws 3(5) 2004 pp 394-400

bull Air Pollution plasma markers of inflammation oxidative stress and insulin resistance in children 13 Kelishadi R Mirghaffari N Poursafa P and Gidding S

Lifestyle and environmental factors associated with inflammation oxidative stress and insulin resistance in children Atherosclerosis 203 (1) 2009 311-319

bull Metabolic syndrome diabetes and atherosclerosis influence of gene-environment interaction 14 Andreassi MG Mutat Res 2009 Jul 10667(1-2)35-43 doi 101016jmrfmmm200810018 Epub 2008 Nov

5

bull Detrimental Effects of Environmental Tobacco Smoke in Relation to Asthma Severity 15 Comhair SAA Gaston BM Ricci KS Hammel J Dweik RA et al

(2011) Detrimental Effects of Environmental Tobacco Smoke in Relation to Asthma Severity PLoS ONE 6(5) e18574 doi101371journalpone0018574

bull Inflammatory Bowel disease appendectomy oral contraceptives infectionsvaccinations antibiotics childhood hygeine 16 Molodecky N and Kaplan G Environmental Risk Factors for Inflammatory Bowel Disease Gastroenterology an dHepatology

6(5) May 2010 pp 339-346

GENE X ENVIRONMENT

bull GxE interactions can be observed in the lab when cells of different genetic background respond differently when exposed to the same inflammatory environmental stimulus 4 Orozco L et al Unraveling Inflammatory Responses using Systems Genetics and

Gene-Environment Interactions in Macrophages Cell 151 658ndash670 October 26 2012

bull Play a role in the extent of inflammatory responses

bull Chronic inflammatory conditions atherosclerosis

bull The gene-environment interactions are potentially implicated in the pathogenesis of metabolic syndrome diabetes and cardiovascular disease

GXE

bull These genes (peroxisome proliferator activated receptor gamma alcohol dehydrogenase type 1C apo E glutathione S transferases T1 and M1)are all known to be modified by diet and lifestyle (fat diet alcohol and smoking habits)

bull There is limited understanding of the role of genetic variants of xenobiotic metabolizing enzymes and their interactions with environmental toxicants

bull There inter-individual differences in detoxification of environmental toxicants which are essential in the role of developing CVD and contribute thus to environmental cardiology as an emerging profession and the subsequent development of a personalized intervention program based upon the genomic profiling of detoxification pathways for xenobiotics 14 Andreassi MG Metabolic syndrome diabetes and atherosclerosis influence of gene-environment interaction Mutat Res 2009 Jul 10667(1-2)35-43 doi 101016jmrfmmm200810018 Epub 2008 Nov 5

NUTRITIONAL CAUSES OF INFLAMMATION TOO MUCH

bull Over-nutrition during gestation or lactation17 Morris MJ 2009 Early life influences on obesity risk maternal overnutrition and programming of obesity Expert Rev Endocronol Metab 4 625ndash

637 doi101586eem0945

18 Bruce KD Cagampang FR 2011 Epigenetic priming of the metabolic syndrome Toxicol Mech Methods 21 353ndash361

Both in 19 Neil A Youngson and Margaret J Morris 2013 What obesity research tells us about epigenetic mechanisms Phil Trans R Soc B 2013 368 20110337

bull Fructose and vascular inflammation independent of NF-kB fructose decreased intracellular ATP Increased NO levels and decreased both serum ICAM-1 and endothelial ICAM-1 expression (in rat kidney)

20 Glushakova O et al Fructose Induces the Inflammatory Molecule ICAM-1 in Endothelial Cells J Am Soc Nephrol 2008 September 19(9) 1712ndash1720 doi 101681ASN2007121304 PMCID PMC2518440

bull Greater than 2x Increased risk of Crohnrsquos disease following consumption of sugarssweeteners sweets fats and oils and total fat 21 Sakamoto N Kono S Wakai K et al Dietary risk factors for inflammatory bowel disease a

multicenter case-control study in Japan Inflamm Bowel Dis 200511154ndash163 in 16 Molodecky N and Kaplan G Environmental Risk Factors for Inflammatory Bowel Disease Gastroenterology an dHepatology 6(5) May 2010 pp 339-346

Figure A

Immunohistochemistry for ICAM-1

in 20 fructose-fed rat kidney

(a and b) Tubulointerstitium

(c and d) Glomerulus

(e and f) Arcuate artery

Figure B

Compared with rats on a control

diet (a c e) ICAM-1 expression is

significantly increased

20 Glushakova O et al Fructose Induces the Inflammatory Molecule ICAM-1 in Endothelial Cells J Am Soc Nephrol 2008 September 19(9) 1712ndash1720

NUTRITIONAL CAUSES OF INFLAMMATION TOO LITTLE

bull Famine in the first 10 weeks of conception causes less DNA methylation of the imprinted IGF-2 gene resulted in persistent (6 decades) epigenetic changes

bull Vitamin D status and all cause mortality22 Skaaby T Husemoen LLN Pisinger C

Joslashrgensen T Thuesen BH et al (2012) Vitamin D Status and Cause-Specific Mortality A General Population Study PLoS ONE 7(12) e52423 doi101371journalpone0052423

bull 23 Ginde AA Scragg R Schwartz RS Camargo CA (2009) Prospective study of serum 25-hydroxyvitamin D level cardiovascular disease mortality and all-cause mortality in older US adults J Am Geriatr Soc 57 1595ndash603

bull 24 Hutchinson MS Grimnes G Joakimsen RM Figenschau Y Jorde R (2010) Low serum 25-hydroxyvitamin D levels are associated with increased all-cause mortality risk in a general population the Tromso study Eur J Endocrinol 162 935ndash42

bull 25 Autier P Gandini S (2007) Vitamin D supplementation and total mortality a meta-analysis of randomized controlled trials Arch Intern Med 167 1730ndash7

bull Innate immunity via the antimicrobial peptide cathelicidin a class of antimicrobial peptides called defensinsbull Can induce expression of cathelicidin in myeloid cell

lines bronchial epithelial cells and keratinocytes 26 Adams JS Hewison M

(2008) Unexpected actions of vitamin D new perspectives on the regulation of innate and adaptive immunity Nat Clin Pract Endocrinol Metab 4 80ndash90

Table 2 Main causes of death during follow-up in the Monica10 and Inter99 studies and vitamin D status

22 Skaaby T Husemoen LLN Pisinger C Joslashrgensen T et al (2012) Vitamin D Status and Cause-Specific Mortality A General Population Study PLoS ONE 7(12) e52423 doi101371journalpone0052423`

VITAMIN D STATUS AND LIVER DISEASE

bull Low levels associated with Liver disease could be a result of the disease process ndash fat malabsorption bile salt deficiency loss of absorptive surface increased intestinal permeability impaired hepatic hydroxylation reduced hepatic production of Vit D binding protein

bull Vit D supplementation in this case may not prove effective at correcting deficiency

LIFESTYLE CAUSES

bull InactivitySedentary Lifestyle

Various forms of physical activity decrease both acute and chronic inflammation as measured by reductions in CRP and cytokines such as TNF and IL-6

Regular physical activity is important in reducing risk for obesity and chronic diseases associated with inflammation

27 Woods JA Vieira VJ Keylock KT Exercise inflammation and innate immunity Neurol Clin 2006 Aug24(3)585-99 Review PubMed PMID 16877125

28 Bruunsgaard H Physical activity and modulation of systemic low-level inflammation J Leukoc Biol 2005 Oct78(4)819-35 Epub 2005 Jul 20 Review PubMed PMID 16033812

LIFESTYLE

bull Early life exposure to stress 29 Pervanidou P Chrousos GP 2011 Metabolic consequences of stress during childhood and adolescence Metabolism 61 611ndash619

bull Calorie Restriction and prolonged life ndash decreases inflammatory cytokines growth factors anabolic hormones and oxidative markers which are all involved in aging and cancer

30 Pallavi R Giorgio M Pelicci PG (2012) Insights into the beneficial effect of caloricdietary restriction for a healthy and prolonged life Front Physiol3 318 in

31 Gomes MVM Toffoli LV Arruda DW Soldera LM Pelosi GG et al (2012) Age-Related Changes in the Global DNA Methylation Profile of Leukocytes Are Linked to Nutrition but Are Not Associated with the MTHFR C677T Genotype or to Functional Capacities PLoS ONE 7(12) e52570

ADIPOCYTOKINES AND INFLAMMATION

bull Fat tissue exerts endocrine and immune functions through the release of adipocytokines released by adipocytes leptin resistin adiponectin or visafatin as well as cytokines released by inflammatory cells infiltrating fat such as TNF- IL-6 MCP-1 (CCL-2) and IL-1

bull Effects act on immune cells to cause inflammation modulate vascular NO and SOD release mediating vascular disorders hypertension diabetes atherosclerosis and insulin resistance cancer and NASH

Adipocytokine Immune system effects Vascular Effects

Leptin bullPro-inflammatory

bullIncrease in T cell activation

and cytokine release

proliferation

bullPromotes Th1 response

bullIncreases NK cell activation

bullIncreases macrophage

activation and cytokine

release (TNF-aIL-6 etc)

bullActivates neutrophils and

increases their chemotaxis

and oxidative burst

Prevents inflammatory

damage in conditions of

overt

immune system stimulation

bullInduces endothelial

dysfunction

bullIncreases blood pressure

bullAtherosclerosis

bullIncreases ICAM VCAM

bullPlasma levels related to

hard clinical endpoints

bullAcutely releases NO

from

endothelium

32 Guzik TJ Mangalat D and Korbut R Adipocytokines Novel Link Between Inflammation

And Vascular Function Review Article Journal of Physiology and Pharmacology 2006 57(4)

505-528

Adipocytokine Immune System

Effects

Vascular Effects

Resistin bullAnti-inflammatory

bullDecreases T cell

activation and

proliferation

bullInhibits NFkB

dependent cytokine

release and adhesion

molecule expression

(including TNF-aIL-6)

bullIncreases IL-10

bullInhibits phagocytosis

and oxidative burst ()

bullVasculo-protective

bullPrevents atherosclerosis

bullIs decreased in

hypertension

bullCorrelated with HDL and

bullinversely with LDL

bullPlasma levels not related

to

bullhard endpoints

32 Guzik TJ Mangalat D and Korbut R Adipocytokines Novel Link Between Inflammation And

Vascular Function Review Article Journal of Physiology and Pharmacology 2006 57(4) 505-528

Adipocytokine Immune System Effects Vascular Effects

Adiponectin bullPro-inflammatory

bullActivates NFkB dependent

cytokine release and

adhesion

molecule expression


bullPathogenic

bullImpairs bradykinin-

dependent

vasorelaxations (NO and

EDHF)

bullNo effect on

acetylcholine

dependent

vasorelaxations

(NO)

bullVEGF and MMP up-

regulation

32 Guzik TJ Mangalat D and Korbut R Adipocytokines Novel Link Between

Inflammation And Vascular Function Review Article Journal of Physiology and

Pharmacology 2006 57(4) 505-528

NUTRITION TO REVERSE INFLAMMATION

bull Vitamin D for insulin sensitivity for glucose regulation

bull An enriched diet containing antioxidants such as vitamin E vitamin C β-carotene and phenolic substances has been suggested to improve symptoms by reducing disease-related oxidative stress 33 DOrazio N Gammone MA Gemello E De Girolamo M

Cusenza S Riccioni G Marine bioactives pharmacological properties and potential applications against inflammatory diseases Mar Drugs 2012 Apr10(4)812-33

bull In obesity how can epigenetic modifications started or set by a high-fat diet be reversed through a reduced calorie diet or exercise

REVERSING THE IRREVERSIBLE

bull Hookworm protein therapy condition the immune system to prevent allergic asthma and inflammatory bowel diseases 34 Navarro S Ferreira I Loukas A The hookworm pharmacopoeia for inflammatory diseases Int J Parasitol

2012 Dec 5

bull Evidence in support of epigenetic alterations through nutritional supplementation

NOVEL TARGETS OF NATUROPATHIC TREATMENT AND INTERVENTION

The tissue is the issue

Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism

References in 35 Choi SW and Friso S

Epigenetics A new bridge between nutrition and health Advances in Nutrition 2010 11-16

Embryonic

Developme

nt

Folate DNA

Methylation

imprinting

36 Steegers-Theunissen RP et al Periconceptional maternal folic acid use of 400 microg per day is related to increased methylation of the IGF2 gene in the very young child PLoS ONE 20094e7845

37 Sinclair KD et al DNA methylation insulin resistance and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status Proc Natl Acad Sci USA 200710419351ndash6

Choline DNA

Methylation

38 Uekawa A et al Change of epigenetic control of cystathionine beta-synthase gene expression through dietary vitamin B12 is not recovered by methionine supplementation J Nutrigenet Nutrigenomics 2009229ndash36

Protein

Restriction

DNA

Methylation

histone

modifications

39 Lillycrop KA et al Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the hepatic PPAR alpha promoter of the offspring Br J Nutr 2008100278ndash82

40 Lillycrop KA et al Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyl-transferase-1 expression is involved in impaired DNA methylation and changes in histone modifications Br J Nutr 2007971064ndash73

Stem Cell Butyrate Histone

acetylation

DNA

methylation

41 Mali P et al Butyrate greatly enhances derivation of human induced pluripotent stem cells by promoting epigenetic remodeling and the expression of pluripotency-associated genes Stem Cells 201028 713ndash20

Retinoic

Acid

Polycomb

Repressive

Complex 2

42 Lee ER Murdoch FE Fritsch MK High histone acetylation and decreased polycomb repressive complex 2 member levels regulate gene specific transcriptional changes during early embryonic stem cell differentiation induced by retinoic acid Stem Cells 2007252191ndash9

Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism

References in 35Choi SW and Friso S


Aging Folate DNA

methylation

43 Keyes MK et al Older age and dietary folate are determinants of genomic and p16- specific DNA methylation in mouse colon J Nutr 20071371713ndash7

44 Li Y Liu Y Strickland FM Richardson B Age-dependent decreases in DNA methyltransferase levels and low transmethylation micronutrient levels synergize to promote overexpression of genes implicated in autoimmunityand acute coronary syndromes Exp Gerontol 201045312ndash22

Calorie

Restriction

Histone

acetylation

45 Qiu X et al Sirtuin regulation in calorie restrictionBiochim Biophys Acta 201018041576ndash83

46 Vaquero A Sternglanz R Reinberg D NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs Oncogene 2007265505ndash20

Immune

function

Folate DNA

Methylation

44 Li Y Liu Y Strickland FM Richardson B Age-dependent decreases in DNA methyltransferase levels and low transmethylation micronutrient levels synergize to promote overexpression of genes implicated in autoimmunity and acute coronary syndromes Exp Gerontol 201045312ndash22

Inflammation Resveratrol Histone

acetylation

47 Sanchez-Fidalgo S et al Dietary supplementation of resveratrol attenuates chronic colonic inflammation in mice Eur J Pharmacol 201063378ndash84

48 Donnelly LE et al Anti-inflammatory effects of resveratrol inlung epithelial cells molecular mechanisms Am J Physiol Lung Cell Mol Physiol 2004287L774ndash83

AdoMet Histone

acetylation

49 Ara AI et al S-adenosylmethionine inhibits lipopolysaccharide-induced gene expression via modulation of histone methylation Hepatology 2008471655ndash66

Methyl-

deficient

diet

mRNA50 Pogribny IP et al Difference in expression of hepatic microRNAs miR-29c miR-34a miR-155 and miR-200b is associated with strainspecific susceptibility to dietary nonalcoholic steatohepatitis in mice Lab Invest Epub 2010 Jun 14

Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism

References in 37 Choi SW and Friso S Epigenetics

A new bridge between nutrition and health Advances in Nutrition 2010 11-16

Cancer Methyl-

deficient

diet

Histone

modification

mRNA

51 Pogribny IP et al Histone H3 lysine 9 and H4 lysine 20 trimethylation and the expression of Suv4ndash20h2 and Suv-39h1 histone methyltransferases in hepatocarcinogenesis induced by methyl deficiency in rats Carcinogenesis 2006271180ndash6

52 Tryndyak VP et al Down-regulation of the microRNAs miR-34a miR-127 and miR-200b in rat liver during Hepato-carcinogenesis induced by a methyl-deficient diet Mol Carcinog 200948479ndash87

Genistein DNA

Methylation

mRNA

53 Qin W et al Soy isoflavones have an antiestrogenic effect and alter mammary promoter hypermethylation in healthy premenopausal women Nutr Cancer 200961238ndash44

54 Tang WY et al Persistent hypomethylation in the promoter of nucleosomal binding protein 1 (Nsbp1) correlates with over-expression of Nsbp1 in mouse uteri neonatally exposed to diethylstilbestrol or genistein Endocrinology 20081495922ndash31

55 Salerno E et al Correcting miR-15a16 genetic defect in New Zealand Black mouse model of CLL enhances drug sensitivity Mol Cancer Ther 200982684ndash92

Inhibiting

EGC-3G

DNA

methylation

PRC

56 Fang M Chen D Yang CS Dietary polyphenols may affect DNA methylation J Nutr 2007137S223ndash8

57 Balasubramanian S Adhikary G Eckert RL The Bmi-1 polycomb protein antagonizes the (2)-epigallocatechin-3-gallate-dependent suppression of skin cancer cell survival Carcinogenesis 201031496ndash503

Curcumin mRNA58 Sun M Estrov Z et al Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells Mol Cancer Ther 20087464ndash73

59 Yang J Cao Y Sun J Zhang Y Curcumin reduces the expression of Bcl- 2 by upregulating miR-15a and miR-16 in MCF-7 cells Med OncolEpub 2009 Nov 12

Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism

References in 37 Choi SW and Friso S Epigenetics A

new bridge between nutrition and health Advances in Nutrition 2010 11-16

Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA

60 Widiker S Karst S Wagener A Brockmann GA High-fat diet leads to a decreased methylation of the Mc4r gene in the obese BFMI and the lean B6 mouse lines J Appl Genet 201051193ndash7

61 Cirera S Birck M Busk PK Fredholm M Expression profiles ofmiRNA-122 and its target CAT1 in minipigs (Sus scrofa) fed a high cholesterol diet Comp Med 201060136ndash41

Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation

63 Chiu J Khan ZA Farhangkhoee H Chakrabarti S Curcumin prevents diabetes-associated abnormalities in the kidneys by inhibiting p300 and nuclear factor-kappaB Nutrition 200925964ndash72

NATUROPATHIC APPROACHES TO QUELLING

INFLAMMATIONbull Ginger

bull Diabetes Hypertension 64 Al-Amin ZM Thomson M Al-Qattan KK Peltonen-Shalaby

R Ali M Anti-diabetic and hypolipidaemic properties of ginger (Zingiber officinale) in streptozotocin-induced diabetic rats Br J Nutr 2006 Oct96(4)660-6 PubMed PMID 17010224

bull Osteoarthritis 65 Shen CL Hong KJ Kim SW Effects of ginger (Zingiber officinale Rosc) on decreasing the

production of inflammatory mediators in sow osteoarthrotic cartilage explants J Med Food 2003 Winter6(4)323-8 PubMed PMID 14977440

bull Anti-thrombotic and anti-inflammatory 66 Thomson M Al-Qattan KK Al-Sawan SM Alnaqeeb MA Khan I Ali M The use of ginger (Zingiber officinale Rosc) as a potential anti-inflammatory and antithrombotic agent Prostaglandins Leukot Essent Fatty Acids 2002 Dec67(6)475-8 PubMed PMID 12468270

67 Nicoll R Henein MY Ginger (Zingiber officinale Roscoe) a hot remedy for cardiovascular disease Int J Cardiol 2009 Jan 24131(3)408-9 Epub 2007 Nov 26 Review PubMed PMID 18037515

68 Grzanna R Lindmark L Frondoza CG Ginger--an herbal medicinal product with broad anti-inflammatory actions J Med Food 2005 Summer8(2)125-32 Review PubMed PMID 16117603

QUELLING INFLAMMATION

bull Marine omega-3 polyunsaturated fatty acids bioactive peptides isolated from fish protein hydrolysates as well as algal fucans galactans and alginates have been shown to possess anticoagulant anticancer and hypocholesterolemic activities Crustaceans and seaweeds contain powerful antioxidants such as carotenoids and phenolic compounds

69 Lordan S Ross RP Stanton C Marine bioactives as functional food ingredients potential to reduce the incidence of chronic diseases Mar Drugs 20119(6)1056-100 doi 103390md9061056

bull Indications

bull Diabetes heart disease IBS Alzheimerrsquos disease Parkinsonrsquos disease allergies asthma cancer 33 DOrazio N Gammone

MA Gemello E De Girolamo M Cusenza S Riccioni G Marine bioactives pharmacological properties and potential applications against inflammatory diseases Mar Drugs 2012 Apr10(4)812-33

bull Rheumatoid Arthritis 70 Miles EA Calder PC Influence of marine n-3 polyunsaturated fatty acids on immune

function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis Br J Nutr 2012 Jun107 Suppl 2S171-84


bull Curcumin and human cell line studies

bull Anti-cancer

bull Inh cyclin D1 (colon cancer)

bull Inh MMP aminopeptidase N (melanoma fibrosarcoma breast cancer intestinal epithelial)

bull Inh HIF-1 (hepatocellular carcinoma)71 Epstein J Sanderson I and MacDonald T (2010) Curcumin as a therapeutic agent the evidence from in vitro animal and human studies British Journal Of Nutrition 103 (11) 1545-1557


bull Curcumin

bull Anti-inflammatory

bull Inh NF-kB (myeloid leukemia B non-Hodgkinrsquos Lymphoma embryonic kidney)

bull Inh COX-2 (intestinal microvascular endothelial colonic epithelial microglial)

bull IL-1 IL-6 IL-8 TNF- (Esophageal epithelial head and neck cancer)

bull Down-regulates MMP2 and MMP9 invasion migration and production in human fibrosarcoma cells

72Yodkeeree S Garbisa S amp Limtrakul P (2008) Tetrahydrocurcumin inhibits HT1080 cell migration and invasion via downregulation of MMPs and uPA Acta Pharmacol Sin 29 853ndash860 in

71 Epstein J Sanderson I and MacDonald T (2010) Curcumin as a therapeutic agent the evidence from in vitro animal and human studies British Journal Of Nutrition 103 (11) 1545-1557

CLINICAL EFFECTS OF CURCUMIN HUMAN TRIALS

CURCUMIN

67

Type 2 Diabetes Atherosclerosis Raised serum Cholesterol

Alzheimerrsquos Disease

Familial Adenomatous

Polyposis Cancers

Irritable Bowel Syndrome

Functional Biliary Disorders

Tropical Pancreatitis

Gastric Ulcers

Rheumatoid Arthritis

Psoriasis

Inflammatory eye disease

Renal Graft function Post-

Operative inflammation

Inflammatory Bowel

Disease

Inflammation Pathway and

Resulting Condition

Naturopathic

Prevention or

Treatment Options

References in 72 Epstein J Sanderson I and MacDonald T (2010) Curcumin as a therapeutic agent the evidence from in vitro animal and human studies British Journal Of Nutrition 103 (11) 1545-1557

Stress response ndashgt heat

shock protein (HSP) to

protect cells from stress

Alzheimerrsquos

Vitamin E and Phenolic

substances which

promote anti-oxidation

and chemo-

prevention induce

HSP response1

73 Calabrese V Butterfield DA Stella AM Nutritional antioxidants and the heme oxygenase pathway of stress tolerance novel targets for neuroprotection in Alzheimers disease Ital J Biochem 2003 Dec52(4)177-81 Review PubMed PMID 15141484

Prostaglandin production

via COX-1 or COX-2 -

Arthritis

Modulate genetic

expression of NF-kB1

Ginger2

Thunder God Vine

Tryptergium wilfordii3

74 Terracciano S Aquino M Rodriquez M Monti MC Casapullo A Riccio R Gomez-Paloma L Chemistry and biology of anti-inflammatory marine natural products molecules interfering with cyclooxygenase NF-kappaB and other unidentified targets Curr Med Chem 200613(16)1947-69 Review


20 Progress in Autoimmune Diseases Research NIH Autoimmune Disease Coordinating Committee Report to Congress March 2005 p 75 httpwwwniaidnihgovtopicsautoimmuneDocumentsadccfinalpdf accessed Dec 16 2012

Inflammation Pathway

and Resulting Condition

Naturopathic Prevention

or Treatment Options

References in 72 Epstein J Sanderson I

and MacDonald T (2010) Curcumin as a therapeutic agent the evidence from in vitro animal and human studies British Journal Of Nutrition 103 (11) 1545-1557

Increased Plasma IL-6

and TNF-alpha

Aging

Increased morbidity in

elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75

Weight loss via exercise

related metabolic

changes - induce IL-6

and induce lipolysis and

hepatic glucose output76


74 Bruunsgaard H Andersen-Ranberg K Jeune B Pedersen AN Skinhoslashj P Pedersen BK A high plasma

concentration of TNF-alpha is associated with dementia in centenarians J Gerontol A Biol Sci Med Sci 1999 Jul54(7)M357-64 PubMed PMID 10462168

75 Okun ML Reynolds CF 3rd Buysse DJ Monk TH Mazumdar S Begley A Hall M Sleep variability health-related practices and inflammatory markers in a community dwelling sample of older adults Psychosom Med 2011 Feb-Mar73(2)142-50

76 Pedersen BK Steensberg A Schjerling P Exercise and interleukin-6 Curr OpinHematol 2001 May8(3)137-41 Review PubMed PMID11303145

NF-kappaB -gt TNF-Alpha

IL-6

Aging

Chronic inflammation

Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine

homeostasis ndash meat and

high zinc containing

foods1

77Vasto S Mocchegiani E Malavolta M Cuppari I Listigrave F Nuzzo D Ditta V Candore G Caruso C Zinc and inflammatoryimmune response in aging Ann N Y Acad Sci 2007 Apr1100111-22 Review

C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome

Weight loss increased

physical activity

Metformin1

Alteration in dietary

composition2

carbohydrate restricted

78 Levy J Cobas RA and Gomes MB Asessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus Diabetes 5451566 -1572

79 Beavers KM Nicklas BJ Effects of lifestyle interventions on inflammatory markers in the metabolic syndrome Front Biosci (Schol Ed) 2011 Jan 13168-77 Review

80 Al-Sarraj T Saadi H Calle MC Volek JS Fernandez ML Carbohydrate restriction as a first-line dietary intervention effectively reduces biomarkers of metabolic syndrome in Emirati adults J Nutr 2009 Sep139(9)1667-76

INFLAMMATORY DEBATES

Genomics vs Epigenetics vs Proteomics

WHY BIOMARKERS

bull Biomarkers have the potential to enable diagnosis before the onset of symptoms predict specific organ involvement and disease flares identify clinically meaningful disease subsets predict and monitor response to therapy and describe organ or tissue damage

bull Can be useful in identifying genetic predisposition to disease or environmental triggers

bull May provide early information about potential efficacy of experimental agents or mechanisms underlying drug activity

bull Can become validated surrogate endpoints for prevention trials


CURRENT MARKERS EPIGENETIC VS PROTEOMIC

VALUEbull Proteomics show functional disease state since proteins

(and not transcripts) represent current status 81 Stroncek DF Burns C

Martin BM Rossi L Marincola FM Panelli MC Review Advancing cancer biotherapy with proteomics J Immunother 2005 May-Jun 28(3)183-92

bull Epigenetics have causal status

The two can be combined for patient care depending on the goalpriority

DEFINITIONS PROTEOMICS

bull Molecular patterns via protein analysis functional analysis

bull Uses immunoassays ELISA MSIA SISCAPA to assess complex biologic processes such as immunotherapy for cancer

bull Acute phase reactant proteins

bull At present a comprehensive proteomics signature is not achievable due to the highly variable protein concentrations the biochemical diversity of proteins and the need for better profiles to measure the significant fraction of the proteome 82 Kikuchi T Carbone DP Proteomics analysis

in lung cancer challenges and opportunities Respirology 2007 Jan12(1)22-8 Review PubMed PMID 17207021

bull Difficulty with reproducibility across different labs

DEFINITIONS EPIGENETICS

bull Transcripts of DNA or mRNA levels do not reflect expression activity due to post-translational modifications ubiquitination protease cleavage glycosylation phosphorylation methylation and acetylation

Bottom line Protein concentration (and activity) may be different than gene expression due to post-translational modification

DEFINITIONS GENOMICS

bull Functional Genomics

bull Computational Genomics

bull Personal Genomics

bull Epigenomics

BIOMARKERS PROTEOMICS

bull Acute phase reactant proteins (APRP)

bull CRP and hsCRP

bull Ferritin hepcidin

bull Leukocyte Global DNA Methylation

bull F2-Isoprostanes Hp-beta Ccl-18

bull Fasting insulin

bull IL-6

bull MMP-2 and MMP-9

bull α1-microglobulin fibrinogen Apo lipoproteins A and E complement C3 and C4B and retinol binding protein

bull LRG1

bull IA-2 and IA-2 beta gene anti-bodies endogenous C-peptide

Biomarker Name Condition Notes

Acute phase reactant

proteins (APRP)

Cancer APRP expressions

distinct for type

subtype and stages

CRP and hsCRP bacterial infection rheumatic

fever active arthritis myocardial

infarction malignancies and in

the post-operative state

Ferritin hepcidin inflammation liver disease

chronic infection autoimmune

disease and some types of

cancer

Leukocyte Global DNA

Methylation

cancer cardiovascular disease

pediatric syndromes autoimmune

disease and genetic disorders

F2-Isoprostanes atherosclerosis (obesity and

cigarette smoking)

hypercholesterolemia diabetes

HIV asthma neurodegenerative

RA and certain cancer types

83 Pang WW Abdul-Rahman PS Wan-Ibrahim WI and Hashim OH Can the acute phase reactant proteins be used as cancer

biomarkers Int J Biol Markers 2010 25(1) 1-11

CRP AND HS CRP

bull Increased CRP levels are found in inflammatory conditions including bacterial infection rheumatic fever active arthritis myocardial infarction malignancies and in the post-operative state 84

httpwwwquestdiagnosticscomtestcenterTestDetailactionntc=4420 accessed Jan 6 2013

bull A high-sensitivity CRP (hs-CRP) test may be used by itself in combination with other cardiac risk markers or in combination with a lp-PLA2 test that evaluates vascular inflammation

bull 85 httplabtestsonlineorgunderstandinganalyteshscrptabtest accessed Jan 6 2013

FERRITIN AND HEPCIDIN

bull Ferritin is an acute phase reactant and can be increased in inflammation liver disease chronic infection autoimmune disease and some types of cancer Damage to the liver spleen and bone marrow can cause elevation of ferritin with normal iron results 86

httplabtestsonlineorgunderstandinganalytesferritintabtest accessed Jan 6 2013

bull Hepcidin is an iron-regulatory hormone Its receptor and iron channel ferroportin control absorption storage and distribution of iron

bull Hepcidin function is protectively altered during infections and inflammation to decrease iron availability to invading pathogens and may cause or contribute to the anemia associated with infectious and inflammatory disorders 87 Ganz T Hepcidin and iron regulation 10 years later Blood 2011 1174425-4433

EPIGENETICS LEUKOCYTE GLOBAL DNA METHYLATION

PROFILEbull DNA methylation of cytosine followed by guanine

(CpG nucleotides) is the most widely studied epigenetic markerbull Implications in the control of embryo development cell

differentiation X chromosome inactivation in females genomic imprinting suppression of endogenous retroviruses and chromosomal instability

bull Abnormalities in DNA methylation patterns associated with disease etiologies cancer cardiovascular disease pediatric syndromes autoimmune disease and genetic disorders

bull In the aging process via specific hypermethylation of the promoter regions of various genes

88 Portela A Esteller M (2010) Epigenetic modifications and human disease Nat Biotechnol 28(10) 1057ndash1068

EPIGENETICS DNA METHYLATION

Recent studies indicate the potential for using global DNA methylation profiles of peripheral blood leukocytes as a suitable biomarker for cancer 89 Woo HD Kim J (2012) Global DNA hypomethylation in

peripheral blood leukocytes as a biomarker for cancer risk a meta-analysis PLoS One 7(4) e34615

Bladder 90 Cash HL Tao L Yuan JM Marsit CJ Houseman EA et al (2012) LINE-1 hypomethylation is associated with bladder cancer risk

among nonsmoking Chinese Int J Cancer 130(5) 1151ndash1159

Breast 91 Choi JY James SR Link PA McCann SE Hong CC et al (2009) Association between global DNA hypomethylation in leukocytes and

risk of breast cancer Carcinogenesis 30(11) 1889ndash1897

Renal cell 92 Liao LM Brennan P van Bemmel DM Zaridze D Matveev V et al (2011) LINE-1 methylation levels in leukocyte DNA and risk of

renal cell cancer PLoS One 6(11) e27361

In 31 Gomes MVM Toffoli LV Arruda DW Soldera LM Pelosi GG et al (2012) Age-Related Changes in the Global DNA Methylation Profile of Leukocytes Are Linked to Nutrition but Are Not Associated with the MTHFR C677T Genotype or to Functional Capacities PLoS ONE 7(12) e52570

CORRELATION WITH LAB PARAMETERS

bull DNA methylation profile of leukocytes showed a statistical correlation to the mean level of total protein (p = 00004) alpha 2 globulin (p = 00013) and albumin (p = 00015)

bull The mean global leukocyte DNA methylation of the elderly population showed a statistical association with daily ingestion of carbohydrates (p = 00494) lipids (p = 00494) vitamin B6 (p = 00421) and magnesium (p = 00302)

31 Gomes MVM Toffoli LV Arruda DW Soldera LM et al (2012) Age-Related Changes in the Global DNA Methylation Profile of Leukocytes Are Linked to Nutrition but Are Not Associated with the MTHFR C677T Genotype or to Functional Capacities PLoS ONE 7(12) e52570 doi101371journalpone0052570

Table 1 Correlation between global DNA methylation and clinical laboratorial values

31 Gomes MVM Toffoli LV Arruda DW Soldera LM et al (2012) Age-Related Changes in the Global DNA Methylation Profile of Leukocytes Are Linked to Nutrition but Are Not Associated with the MTHFR C677T Genotype or to Functional Capacities PLoS ONE 7(12) e52570 doi101371journalpone0052570 httpwwwplosoneorgarticleinfodoi101371journalpone0052570

BIOLOGICAL PROCESS MARKERS FOR INFLAMMATION AND CANCER

bull Inflammation F2-Isoprostane Hpβ Ccl8 and Fasn

bull Angiogenesis thrombospondin 1 and 4 renin 1 and 2 platelet factor 4 trefoil factor 1 and collagen binding protein 2

93 Kelly-Spratt KS Pitteri SJ Gurley KE Liggitt D Chin A et al (2011) Plasma Proteome Profiles Associated with Inflammation Angiogenesis and Cancer PLoS ONE 6(5) e19721 doi101371journalpone0019721

INFLAMMATION F2-ISOPROSTANES

bull Isoprostanes are the most important biomarker of oxidative stress in human disease

94 Lawson JA Rokach J Fitzgerald GA (1999) Isoprostanes formation analysis and use as indices of lipid peroxidation in vivo J Biol Chem 27424441ndash24444

95 Montuschi P Barnes P Roberts JL (2004) Isoprostanes markers and mediators of oxidative stress The FOSEB J 181792ndash1796

96 Milne GL Musiek ES Morrow JD (2005) F2-Isoprostanes a marker of oxidative stress in vivo Biomarkers 1S10ndashS23

97 Milne GL Yin H Brooks JD Sanchez S Jackson RL Morrow JD (2007) Quantification of F2-isoprostanes in biological fluids and tissues as a measure of oxidant stress Methods Enzymol 433113ndash126

98 Brys M et al 2013 Relationship of urinary isoprostanes to prostate cancer occurrence Mol Cell Biochem 372149-153

bull Isoprostanes are a prostaglandin-like molecule They are formed from peroxidation of arachidonic acid DHA EPA and adrenic acid They should not be measured by radio-immunoassay but by GCMS

bull Urinary F2-Isoprostanes validated biomarker of oxidative stress increased risk of prostate cancer independent of central adiposity or obesity PSA family history and smoking history

99 Barocas D et al 2011 Oxidative stress measured by Urine F2-Isoprostane level is associated with prostate cancer J Urol 185(6) 2102-2107

METABOLISM OF F2-ISOPROSTANES

bull Initially formed from arachidonic acid esterified in tissue phospholipids and then released as free fatty acids by phospholipase

bull Circulate in plasma metabolized in the liver filtered in the kidney and appear in urine

bull Diseases associated with increased F2-Isoprostanes

bull atherosclerosis (obesity and cigarette smoking)

bull hypercholesterolemia

bull diabetes

bull HIV

bull asthma

bull neurodegenerative

bull RA

bull and certain cancer types100 Milne GL Et al 2011 Isoprostane Generation and Function Chem Rev 111(10) 5073-5996


Haptoglobin beta Hgβ Lung cancer

Infiltrating ductal carcinoma

Epithelial ovarian cancer

Sepsis ndash need

addrsquol CRP

CCL-18 Bladder Ovarian and Cervical

cancer

Fasting Insulin Insulin Resistance

IL-6 Post op infection

MM survival time

Cardiovascular w CRP

Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml

HAPTOGLOBIN BETA CHAIN (HP)

Supportive biomarker for prognostic value and overall survival

bull human lung cancer101 Kang SM et al 2011 The Haptoglobin beta chain as a supportive biomarker for human lung cancers Mol Biosyst 7(4) 1167-75

bull prostate cancer 102 Fujimura T et al Glycosylation status of haptoglobin in sera of patients with prostate cancer vs benign prostate disease or normal

subjects Int J Cancer 2008 Jan 1122(1)39-49

bull epithelial ovarian cancer 103 Zhao C et al 2007 Circulating Haptoglobin is an Independent Prognostic Factor in the Sera of Patients with Epithelial Ovarian Cancer Neoplasia January 9(1) 1-7

During times of acute inflammation and requires other tests (CRP) to confirm sepsis infection etc because generally it is a test for hemolytic anemia and extravascular hemolysis

Can be increased with use of the following drugs androgens corticosteroids

Can be decreased with the following drugs isoniazid chlorpromazine quinidine streptomycin nitrofurantoin and birth control pills

104 httplabtestsonlineorgunderstandinganalyteshaptoglobintabtest accessed Jan 20 2013

INFLAMMATION CCL-18

bull CCL 18 C-C motif chemokine 18

bull Bladder cancer when used with nuclear matrix protein-22 and bladder tumor antigen Cystoscopy still gold standard

105 Urquidi V Kim J Chang M Dai Y Rosser CJ et al (2012) CCL18 in a Multiplex Urine-Based Assay for the Detection of Bladder Cancer PLoS ONE 7(5) e37797 doi101371journalpone0037797

bull Ovarian cancer 106 Zohny SF Fayed ST (2010) Clinical utility of circulating matrix metalloproteinase-7 (MMP-7) CC chemokine ligand 18 (CCL18) and CC chemokine ligand 11 (CCL11) as markers for diagnosis of epithelial ovarian cancer Med Oncol 27 1246ndash1253 doi 101007s12032-009-9366-x

107 Wang Q Li D Zhang W Tang B Li QQ et al (2011) Evaluation of proteomics-identified CCL18 and CXCL1 as circulating tumor markers for differential diagnosis between ovarian carcinomas and benign pelvic masses Int J Biol Markers

bull Cervical cancer108 Rajkumar T Sabitha K Vijayalakshmi N Shirley S Bose MV et al (2011) Identification and validation of genes involved in cervical tumourigenesis BMC Cancer 11 80 doi 1011861471-2407-11-80

BIOMARKER FASTING INSULIN

bull Obesity related Insulin resistance and diabetes ndash dietary leucine as an environmental modifier acting on multiple metabolites stimulated phosphorylation of p70S6 Kinase (indicates inc levels of mTOR normally associated with insulin resistance)

bull 8 week old male mouse model design mouse chow and high fat diets with or without supplemental leucine (15wv) in water x 8 weeks

bull Prevents hepatic steatosis reduces obesity induced adipose tissue inflammation rescues insulin signaling in muscle liver and fat

bull Mouse dose 130mgdaymouse

109 Macotela Y Emanuelli B Baringng AM Espinoza DO Boucher J et al (2011) Dietary Leucine - An Environmental Modifier of Insulin Resistance Acting on Multiple Levels of Metabolism PLoS ONE 6(6) e21187 doi101371journalpone0021187

BIOMARKER IL-6

bull Pleotropic Cytokine normal value lt0-5pgml 110 httpwwwaruplabcomguidesugtests0051537jsp accessed Jan 26 2013

bull Diagnostically most accurate for detecting intraoperative prosthetic joint infection in comparison to WBC ESR CRP and the time of revision arthroplasty

111 Berbari E Mabry T Tsaras G Spangehl M Erwin PJ Murad MH Steckelberg J Osmon D Inflammatory blood laboratory levels as markers of prosthetic joint infection a systematic review and meta-analysis J Bone Joint Surg Am 2010 Sep 192(11)2102-9

bull Prognostic significance for survival time in multiple myeloma patients if IL-6 was above 7pgml

bull 50 survival rate if below 7pgml was 537 months compared to 27 months if above 7pgml

112 Ludwig H Nachbaur DM Fritz E Krainer M and Huber H Interleukin-6 is a prognostic factor in multiple myeloma (letter) 1991 Blood 77 2794-2795

CRP AND IL-6 TRANS FATS

bull CRP and IL-6 are independent predictors of

cardiovascular disease in healthy women Nursesrsquo Health Study I cohort 730 healthy women followed between 1989-1990 CRP was 73 higher in those with the highest trans fat intake IL-6 was 17 higher

bull Trans fats adversely affect endothelial function as measured by CRP sTNFR E-selectin sICAM-1 and sVCAM-1 regardless of fiber cholesterol Vitamin E intake and glycemic load

113 Blake G J amp Ridker P M (2003) C-reactive protein and other inflammatory risk markers in acute coronary syndromes J Am Coll Cardiol 41 37Sndash42S In

114 Lopez-Garcia E et al Nutiritonal Epidemiology Consumption of Trans Fatty Acids is Related to Plasma Biomarkers of Inflammation and Endothelial Dysfunction Journal of Nutrition March 2005 135(3) 562-566

CORONARY HEART DISEASE MARKERS

NURSES HEALTH STUDY AND HEALTH PROFESSIONALS FOLLOW UP STUDY

bull Plasma soluble TNF receptors 1 and 2

bull CRP

bull IL-6

Better predictors when combined not individually assessed

Increased risk of CHD with combined elevations in CRP and IL-6 for both sexes but elevated TNF levels were significant among women

115 Pai JK et al Inflammatory markers and the risk of coronary heart disease in men and womenN Engl J Med 2004 Dec 16351(25)2599-610

INHIBITION OF IL-6 CLINICAL VALUE

bull In RA

bull IL-6 is involved in the pathogenesis of RA development via TNF

118 Hennigan S and Kavanaugh A Interleukin-6 inhibitors in the treatment of rheumatoid arthritis Ther Clini Risk Manag 2008 4(4) 767-775

bull Inhibiting IL-6 signaling positively affected insulin sensitivity and lipoprotein A levels in diabetic patients with RA Long term elevated IL-6 can be causal in the pathogenesis of insulin resistance

119 Schultz O Oberhauser F Saech J Rubbert-Roth A Hahn M et al (2010) Effects of Inhibition of Interleukin-6 Signaling on Insulin Sensitivity and Lipoprotein (A) Levels in Human Subjects with Rheumatoid Diseases PLoS ONE 5(12) e14328 doi101371journalpone0014328


MMP-2 and MMP-9 Arthritis type 1 collagen

degradation in cartilage

α1-microglobulin fibrinogen

Apo lipoproteins A and E

complement C3 and C4B and

retinol binding protein

Systemic Auto-Immune

Disease

Leucine Rich α2 Glycoprotein

LRG1α

Multiple Sclerosis Twin studies

serum and

CSF fluid

elevations

Auto-antibodies to human IA-2

and IA-2 beta C- Peptide

Type 1 Diabetes

BIOMARKERS MMP-2 FOR ARTHRITIS

bull MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in type 1 collagen degradation in cartilage

bull In RA patients synovial fluids include increased levels of MMP-2 and MMP-9 but MMP-2 has a dual role and MMP-9 has a direct inflammatory role


BIOMARKERS SYSTEMIC AUTOIMMUNE DISEASE

bull SLE

bull Juvenile idiopathic arthritis

bull Juvenile dermatomysitis

All share common alterations of plasma protein expression and molecular pathways α1-microglobulin fibrinogen Apo lipoproteins A and E complement C3a and C4b and retinol binding protein

120 Terrance P OHanlon1 et al Plasma proteomic profiles from disease-discordant monozygotic twins suggest that molecular pathways are shared in multiple systemic autoimmune diseases Arthritis Research amp Therapy 2011 13R181 doi101186ar3506

Chronic Lyme disease and AIDS C4a levels highest

121 Stricker RB Savely VR Motanya NC and Giclas PC Complement split products C3a and C4a in chronic lyme disease (2009) Scand J Immunol 69(1) 64-69

MULTIPLE SCLEROSIS

bull Leucine-rich α2 glycoprotein marker (LRG1) - a molecule involved in signal transduction cell adhesion and granulocyte differentiation - was elevated in plasma from affected twins and was also found elevated in both the cerebrospinal fluid and serum proteomes from multiple sclerosis patients

121 OConnor KC et al Comprehensive phenotyping in multiple sclerosis discovery based proteomics and the current understanding of putative biomarkers Dis Markers 2006 22213-225 PMID 17124343 in 121 Terrance P OHanlon1 et al Plasma proteomic profiles from disease-discordant monozygotic twins suggest that molecular pathways are shared in multiple systemic autoimmune diseases Arthritis Research amp Therapy 2011 13R181 doi101186ar3506

TYPE 1 DIABETES

bull Auto-antibodies to the human genes IA-2 and IA-2 beta appear years before the development of clinically apparent type 1 diabetes and therefore can serve as predictive markers for this disease

20 Progress in Autoimmune Diseases Research NIH Autoimmune Disease Coordinating Committee Report to Congress March 2005 p 62

httpwwwniaidnihgovtopicsautoimmuneDocumentsadccfinalpdf accessed Dec 16 2012

bull Endogenously produced C-peptide secretion is the hallmark for monitoring beta cell function and preserving beta cell function equates to normal glycemic control



SUMMARY

bull Brief history of lab medicine

bull Causes of inflammation

bull GxE

bull Nutritional

bull Lifestyle

bull Body Compositional

Stopping inflammation with novel targeted therapies used in naturopathic medicine

Genomics vs Epigenetics vs Proteomics as biomarkers in evaluating diagnostic and treatment status of various inflammatory conditions

Process or

Condition

Naturopathic

Approaches

Proteomic Diagnostic

Marker

References

Lung cancer Vitamin D3

Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1

122 Indovina P Marcelli E Maranta P and Tarro G 2011 Lung Cancer Proteomics Recent Advances in Biomarker Discovery Int J Proteomics 2011 doi 1011552011726869

Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors

123 Hamrita B Chahed K Trimeche M et al Proteomics-based identification of α1-antitrypsin and haptoglobin precursors as novel serum markers in infiltrating ductal breast carcinomas Clinica Chimica Acta 2009404(2)111ndash118

Epithelial

Ovarian Cancer

Haptoglobin103 Zhao C Annamalai L Guo C Kothandaraman N Koh SC Zhang H Biswas A Choolani M Circulating haptoglobin is an independent prognostic factor in the sera of patients with epithelial ovarian cancer Neoplasia 2007 Jan9(1)1-7

Type 1 Diabetes Omega-3 fatty

acids

Vitamin D3

20 Progress in Autoimmune Diseases Research NIH Autoimmune Disease Coordinating Committee Report to Congress March 2005 p 73httpwwwniaidnihgovtopicsautoimmuneDocumentsadccfinalpdf accessed Dec 16 2012

Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol

IL-6124 Gonzales AM and Orlando RA Curcumin and Resveratrol inhibit NFK-B mediated cytokine expression in adipocytes 2008 Nutrition and Metabolism 517

Type 2 Diabetes Leucine Vitamin

D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in

125 Zamperion ER Kamhi EJ 2012 Natural Support for Autoimmune and Inflammatory Disease J Rest Med 138-47

Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid

126 Lukazer D Darland G Tripp M et al A pilot trial evaluation Meta050 a proprietary combination of reduced iso-alpha acids rosemary extract and oleanolic acid in patients with arthritis and fibromyalgia Phytotherapy research 2005 19(10)864-869

SLE RA

borelliosis and

co-infections

Artemesia127 Zhang YX Sun HX Immunosuppresive effect of ethanol extract of Artemesia annua on specific antibody and cellular responses of mice against ovalbumin Immunopharmacol Immunotoxicol 200931(4)625-30

Autoimmune

disease

Cancer

RA

Reishi Mushroom IL-18 TNFα 128 Vanderhem LG Vandervliet JA Bocken CFM et al Studies of a new immunemodulating agent Transplantation 1995 60(5) 438-443129 Bao YX Wong CK Li EKM et al Immunomodulatory effects of Lingzhi and San-Miao-San supplementation on patients with rheumatoid arthrtitis Immunopharmacol Immunotoxicol 2006 28(2)197-200

OA COX-2

AutoImmune

disease

Ashwagandha TNFα IL-1β 130 Aggarwah SD Maurya R et al Withania somnifera inhibits ND-kappa B and AP-1 transcription factors in human peripheral blood and synovial fluid mononuclear cells Phytotherapy research 2007 21(10) 905-913

Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α

131 Kim EH Shim B Kang S et al Anti-inflammatory effects of Scutellaria baicalensis extract via suppression of immune modulators and MAP kinase signaling molecules J Ethnopharmacol 2009 126(2)320-331

QUESTIONS

bull Heidi Kussmann ND FABNO

bull hk365kingmailcom


bull Objective data that enables

bull Screening for risk factors

bull Accurate and early diagnosis

bull Determination of disease severity

bull Recoverysurvivalprognostic value

bull Treatment selection

bull Evaluation of adverse eventsoutcomes

bull Chronic diseasemedication management

Subjective frustration translation to whole systems





























MIDDLE AGES


bull Temperature

bullPulse

bullPalpitation

bullPercussion

















19TH CENTURY DATA









































5




6(5) May 2010 pp 339-346

GENE X ENVIRONMENT






GXE






637 doi101586eem0945







Figure A






Figure B




















LIFESTYLE CAUSES






LIFESTYLE












proliferation








and oxidative burst



overt



dysfunction


bullAtherosclerosis





from

endothelium



505-528


Effects

Vascular Effects



activation and

proliferation

bullInhibits NFkB

dependent cytokine


molecule expression


bullIncreases IL-10





bullIs decreased in

hypertension




to

bullhard endpoints







adhesion

molecule expression


bullPathogenic


dependent


EDHF)

bullNo effect on

acetylcholine

dependent

vasorelaxations

(NO)


regulation



Pharmacology 2006 57(4) 505-528








2012 Dec 5




Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Embryonic

Developme

nt

Folate DNA

Methylation

imprinting



Choline DNA

Methylation


Protein

Restriction

DNA

Methylation

histone

modifications




acetylation

DNA

methylation


Retinoic

Acid

Polycomb

Repressive

Complex 2


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Aging Folate DNA

methylation



Calorie

Restriction

Histone

acetylation



Immune

function

Folate DNA

Methylation



acetylation



AdoMet Histone

acetylation


Methyl-

deficient

diet


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Cancer Methyl-

deficient

diet

Histone

modification

mRNA



Genistein DNA

Methylation

mRNA




Inhibiting

EGC-3G

DNA

methylation

PRC





Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA



Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation














bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS































MIDDLE AGES


bull Temperature

bullPulse

bullPalpitation

bullPercussion

















19TH CENTURY DATA









































5




6(5) May 2010 pp 339-346

GENE X ENVIRONMENT






GXE






637 doi101586eem0945







Figure A






Figure B




















LIFESTYLE CAUSES






LIFESTYLE












proliferation








and oxidative burst



overt



dysfunction


bullAtherosclerosis





from

endothelium



505-528


Effects

Vascular Effects



activation and

proliferation

bullInhibits NFkB

dependent cytokine


molecule expression


bullIncreases IL-10





bullIs decreased in

hypertension




to

bullhard endpoints







adhesion

molecule expression


bullPathogenic


dependent


EDHF)

bullNo effect on

acetylcholine

dependent

vasorelaxations

(NO)


regulation



Pharmacology 2006 57(4) 505-528








2012 Dec 5




Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Embryonic

Developme

nt

Folate DNA

Methylation

imprinting



Choline DNA

Methylation


Protein

Restriction

DNA

Methylation

histone

modifications




acetylation

DNA

methylation


Retinoic

Acid

Polycomb

Repressive

Complex 2


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Aging Folate DNA

methylation



Calorie

Restriction

Histone

acetylation



Immune

function

Folate DNA

Methylation



acetylation



AdoMet Histone

acetylation


Methyl-

deficient

diet


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Cancer Methyl-

deficient

diet

Histone

modification

mRNA



Genistein DNA

Methylation

mRNA




Inhibiting

EGC-3G

DNA

methylation

PRC





Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA



Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation














bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS


















19TH CENTURY DATA









































5




6(5) May 2010 pp 339-346

GENE X ENVIRONMENT






GXE






637 doi101586eem0945







Figure A






Figure B




















LIFESTYLE CAUSES






LIFESTYLE












proliferation








and oxidative burst



overt



dysfunction


bullAtherosclerosis





from

endothelium



505-528


Effects

Vascular Effects



activation and

proliferation

bullInhibits NFkB

dependent cytokine


molecule expression


bullIncreases IL-10





bullIs decreased in

hypertension




to

bullhard endpoints







adhesion

molecule expression


bullPathogenic


dependent


EDHF)

bullNo effect on

acetylcholine

dependent

vasorelaxations

(NO)


regulation



Pharmacology 2006 57(4) 505-528








2012 Dec 5




Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Embryonic

Developme

nt

Folate DNA

Methylation

imprinting



Choline DNA

Methylation


Protein

Restriction

DNA

Methylation

histone

modifications




acetylation

DNA

methylation


Retinoic

Acid

Polycomb

Repressive

Complex 2


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Aging Folate DNA

methylation



Calorie

Restriction

Histone

acetylation



Immune

function

Folate DNA

Methylation



acetylation



AdoMet Histone

acetylation


Methyl-

deficient

diet


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Cancer Methyl-

deficient

diet

Histone

modification

mRNA



Genistein DNA

Methylation

mRNA




Inhibiting

EGC-3G

DNA

methylation

PRC





Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA



Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation














bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS




































5




6(5) May 2010 pp 339-346

GENE X ENVIRONMENT






GXE






637 doi101586eem0945







Figure A






Figure B




















LIFESTYLE CAUSES






LIFESTYLE












proliferation








and oxidative burst



overt



dysfunction


bullAtherosclerosis





from

endothelium



505-528


Effects

Vascular Effects



activation and

proliferation

bullInhibits NFkB

dependent cytokine


molecule expression


bullIncreases IL-10





bullIs decreased in

hypertension




to

bullhard endpoints







adhesion

molecule expression


bullPathogenic


dependent


EDHF)

bullNo effect on

acetylcholine

dependent

vasorelaxations

(NO)


regulation



Pharmacology 2006 57(4) 505-528








2012 Dec 5




Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Embryonic

Developme

nt

Folate DNA

Methylation

imprinting



Choline DNA

Methylation


Protein

Restriction

DNA

Methylation

histone

modifications




acetylation

DNA

methylation


Retinoic

Acid

Polycomb

Repressive

Complex 2


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Aging Folate DNA

methylation



Calorie

Restriction

Histone

acetylation



Immune

function

Folate DNA

Methylation



acetylation



AdoMet Histone

acetylation


Methyl-

deficient

diet


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Cancer Methyl-

deficient

diet

Histone

modification

mRNA



Genistein DNA

Methylation

mRNA




Inhibiting

EGC-3G

DNA

methylation

PRC





Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA



Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation














bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS



GENE X ENVIRONMENT






GXE






637 doi101586eem0945







Figure A






Figure B




















LIFESTYLE CAUSES






LIFESTYLE












proliferation








and oxidative burst



overt



dysfunction


bullAtherosclerosis





from

endothelium



505-528


Effects

Vascular Effects



activation and

proliferation

bullInhibits NFkB

dependent cytokine


molecule expression


bullIncreases IL-10





bullIs decreased in

hypertension




to

bullhard endpoints







adhesion

molecule expression


bullPathogenic


dependent


EDHF)

bullNo effect on

acetylcholine

dependent

vasorelaxations

(NO)


regulation



Pharmacology 2006 57(4) 505-528








2012 Dec 5




Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Embryonic

Developme

nt

Folate DNA

Methylation

imprinting



Choline DNA

Methylation


Protein

Restriction

DNA

Methylation

histone

modifications




acetylation

DNA

methylation


Retinoic

Acid

Polycomb

Repressive

Complex 2


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Aging Folate DNA

methylation



Calorie

Restriction

Histone

acetylation



Immune

function

Folate DNA

Methylation



acetylation



AdoMet Histone

acetylation


Methyl-

deficient

diet


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Cancer Methyl-

deficient

diet

Histone

modification

mRNA



Genistein DNA

Methylation

mRNA




Inhibiting

EGC-3G

DNA

methylation

PRC





Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA



Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation














bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS



GXE






637 doi101586eem0945







Figure A






Figure B




















LIFESTYLE CAUSES






LIFESTYLE












proliferation








and oxidative burst



overt



dysfunction


bullAtherosclerosis





from

endothelium



505-528


Effects

Vascular Effects



activation and

proliferation

bullInhibits NFkB

dependent cytokine


molecule expression


bullIncreases IL-10





bullIs decreased in

hypertension




to

bullhard endpoints







adhesion

molecule expression


bullPathogenic


dependent


EDHF)

bullNo effect on

acetylcholine

dependent

vasorelaxations

(NO)


regulation



Pharmacology 2006 57(4) 505-528








2012 Dec 5




Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Embryonic

Developme

nt

Folate DNA

Methylation

imprinting



Choline DNA

Methylation


Protein

Restriction

DNA

Methylation

histone

modifications




acetylation

DNA

methylation


Retinoic

Acid

Polycomb

Repressive

Complex 2


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Aging Folate DNA

methylation



Calorie

Restriction

Histone

acetylation



Immune

function

Folate DNA

Methylation



acetylation



AdoMet Histone

acetylation


Methyl-

deficient

diet


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Cancer Methyl-

deficient

diet

Histone

modification

mRNA



Genistein DNA

Methylation

mRNA




Inhibiting

EGC-3G

DNA

methylation

PRC





Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA



Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation














bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS





637 doi101586eem0945







Figure A






Figure B




















LIFESTYLE CAUSES






LIFESTYLE












proliferation








and oxidative burst



overt



dysfunction


bullAtherosclerosis





from

endothelium



505-528


Effects

Vascular Effects



activation and

proliferation

bullInhibits NFkB

dependent cytokine


molecule expression


bullIncreases IL-10





bullIs decreased in

hypertension




to

bullhard endpoints







adhesion

molecule expression


bullPathogenic


dependent


EDHF)

bullNo effect on

acetylcholine

dependent

vasorelaxations

(NO)


regulation



Pharmacology 2006 57(4) 505-528








2012 Dec 5




Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Embryonic

Developme

nt

Folate DNA

Methylation

imprinting



Choline DNA

Methylation


Protein

Restriction

DNA

Methylation

histone

modifications




acetylation

DNA

methylation


Retinoic

Acid

Polycomb

Repressive

Complex 2


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Aging Folate DNA

methylation



Calorie

Restriction

Histone

acetylation



Immune

function

Folate DNA

Methylation



acetylation



AdoMet Histone

acetylation


Methyl-

deficient

diet


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Cancer Methyl-

deficient

diet

Histone

modification

mRNA



Genistein DNA

Methylation

mRNA




Inhibiting

EGC-3G

DNA

methylation

PRC





Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA



Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation














bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS



Figure A






Figure B




















LIFESTYLE CAUSES






LIFESTYLE












proliferation








and oxidative burst



overt



dysfunction


bullAtherosclerosis





from

endothelium



505-528


Effects

Vascular Effects



activation and

proliferation

bullInhibits NFkB

dependent cytokine


molecule expression


bullIncreases IL-10





bullIs decreased in

hypertension




to

bullhard endpoints







adhesion

molecule expression


bullPathogenic


dependent


EDHF)

bullNo effect on

acetylcholine

dependent

vasorelaxations

(NO)


regulation



Pharmacology 2006 57(4) 505-528








2012 Dec 5




Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Embryonic

Developme

nt

Folate DNA

Methylation

imprinting



Choline DNA

Methylation


Protein

Restriction

DNA

Methylation

histone

modifications




acetylation

DNA

methylation


Retinoic

Acid

Polycomb

Repressive

Complex 2


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Aging Folate DNA

methylation



Calorie

Restriction

Histone

acetylation



Immune

function

Folate DNA

Methylation



acetylation



AdoMet Histone

acetylation


Methyl-

deficient

diet


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Cancer Methyl-

deficient

diet

Histone

modification

mRNA



Genistein DNA

Methylation

mRNA




Inhibiting

EGC-3G

DNA

methylation

PRC





Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA



Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation














bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS


















LIFESTYLE CAUSES






LIFESTYLE












proliferation








and oxidative burst



overt



dysfunction


bullAtherosclerosis





from

endothelium



505-528


Effects

Vascular Effects



activation and

proliferation

bullInhibits NFkB

dependent cytokine


molecule expression


bullIncreases IL-10





bullIs decreased in

hypertension




to

bullhard endpoints







adhesion

molecule expression


bullPathogenic


dependent


EDHF)

bullNo effect on

acetylcholine

dependent

vasorelaxations

(NO)


regulation



Pharmacology 2006 57(4) 505-528








2012 Dec 5




Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Embryonic

Developme

nt

Folate DNA

Methylation

imprinting



Choline DNA

Methylation


Protein

Restriction

DNA

Methylation

histone

modifications




acetylation

DNA

methylation


Retinoic

Acid

Polycomb

Repressive

Complex 2


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Aging Folate DNA

methylation



Calorie

Restriction

Histone

acetylation



Immune

function

Folate DNA

Methylation



acetylation



AdoMet Histone

acetylation


Methyl-

deficient

diet


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Cancer Methyl-

deficient

diet

Histone

modification

mRNA



Genistein DNA

Methylation

mRNA




Inhibiting

EGC-3G

DNA

methylation

PRC





Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA



Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation














bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS



LIFESTYLE












proliferation








and oxidative burst



overt



dysfunction


bullAtherosclerosis





from

endothelium



505-528


Effects

Vascular Effects



activation and

proliferation

bullInhibits NFkB

dependent cytokine


molecule expression


bullIncreases IL-10





bullIs decreased in

hypertension




to

bullhard endpoints







adhesion

molecule expression


bullPathogenic


dependent


EDHF)

bullNo effect on

acetylcholine

dependent

vasorelaxations

(NO)


regulation



Pharmacology 2006 57(4) 505-528








2012 Dec 5




Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Embryonic

Developme

nt

Folate DNA

Methylation

imprinting



Choline DNA

Methylation


Protein

Restriction

DNA

Methylation

histone

modifications




acetylation

DNA

methylation


Retinoic

Acid

Polycomb

Repressive

Complex 2


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Aging Folate DNA

methylation



Calorie

Restriction

Histone

acetylation



Immune

function

Folate DNA

Methylation



acetylation



AdoMet Histone

acetylation


Methyl-

deficient

diet


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Cancer Methyl-

deficient

diet

Histone

modification

mRNA



Genistein DNA

Methylation

mRNA




Inhibiting

EGC-3G

DNA

methylation

PRC





Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA



Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation














bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS










proliferation








and oxidative burst



overt



dysfunction


bullAtherosclerosis





from

endothelium



505-528


Effects

Vascular Effects



activation and

proliferation

bullInhibits NFkB

dependent cytokine


molecule expression


bullIncreases IL-10





bullIs decreased in

hypertension




to

bullhard endpoints







adhesion

molecule expression


bullPathogenic


dependent


EDHF)

bullNo effect on

acetylcholine

dependent

vasorelaxations

(NO)


regulation



Pharmacology 2006 57(4) 505-528








2012 Dec 5




Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Embryonic

Developme

nt

Folate DNA

Methylation

imprinting



Choline DNA

Methylation


Protein

Restriction

DNA

Methylation

histone

modifications




acetylation

DNA

methylation


Retinoic

Acid

Polycomb

Repressive

Complex 2


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Aging Folate DNA

methylation



Calorie

Restriction

Histone

acetylation



Immune

function

Folate DNA

Methylation



acetylation



AdoMet Histone

acetylation


Methyl-

deficient

diet


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Cancer Methyl-

deficient

diet

Histone

modification

mRNA



Genistein DNA

Methylation

mRNA




Inhibiting

EGC-3G

DNA

methylation

PRC





Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA



Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation














bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS




Effects

Vascular Effects



activation and

proliferation

bullInhibits NFkB

dependent cytokine


molecule expression


bullIncreases IL-10





bullIs decreased in

hypertension




to

bullhard endpoints







adhesion

molecule expression


bullPathogenic


dependent


EDHF)

bullNo effect on

acetylcholine

dependent

vasorelaxations

(NO)


regulation



Pharmacology 2006 57(4) 505-528








2012 Dec 5




Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Embryonic

Developme

nt

Folate DNA

Methylation

imprinting



Choline DNA

Methylation


Protein

Restriction

DNA

Methylation

histone

modifications




acetylation

DNA

methylation


Retinoic

Acid

Polycomb

Repressive

Complex 2


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Aging Folate DNA

methylation



Calorie

Restriction

Histone

acetylation



Immune

function

Folate DNA

Methylation



acetylation



AdoMet Histone

acetylation


Methyl-

deficient

diet


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Cancer Methyl-

deficient

diet

Histone

modification

mRNA



Genistein DNA

Methylation

mRNA




Inhibiting

EGC-3G

DNA

methylation

PRC





Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA



Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation














bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS







adhesion

molecule expression


bullPathogenic


dependent


EDHF)

bullNo effect on

acetylcholine

dependent

vasorelaxations

(NO)


regulation



Pharmacology 2006 57(4) 505-528








2012 Dec 5




Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Embryonic

Developme

nt

Folate DNA

Methylation

imprinting



Choline DNA

Methylation


Protein

Restriction

DNA

Methylation

histone

modifications




acetylation

DNA

methylation


Retinoic

Acid

Polycomb

Repressive

Complex 2


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Aging Folate DNA

methylation



Calorie

Restriction

Histone

acetylation



Immune

function

Folate DNA

Methylation



acetylation



AdoMet Histone

acetylation


Methyl-

deficient

diet


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Cancer Methyl-

deficient

diet

Histone

modification

mRNA



Genistein DNA

Methylation

mRNA




Inhibiting

EGC-3G

DNA

methylation

PRC





Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA



Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation














bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS










2012 Dec 5




Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Embryonic

Developme

nt

Folate DNA

Methylation

imprinting



Choline DNA

Methylation


Protein

Restriction

DNA

Methylation

histone

modifications




acetylation

DNA

methylation


Retinoic

Acid

Polycomb

Repressive

Complex 2


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Aging Folate DNA

methylation



Calorie

Restriction

Histone

acetylation



Immune

function

Folate DNA

Methylation



acetylation



AdoMet Histone

acetylation


Methyl-

deficient

diet


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Cancer Methyl-

deficient

diet

Histone

modification

mRNA



Genistein DNA

Methylation

mRNA




Inhibiting

EGC-3G

DNA

methylation

PRC





Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA



Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation














bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS





Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Embryonic

Developme

nt

Folate DNA

Methylation

imprinting



Choline DNA

Methylation


Protein

Restriction

DNA

Methylation

histone

modifications




acetylation

DNA

methylation


Retinoic

Acid

Polycomb

Repressive

Complex 2


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Aging Folate DNA

methylation



Calorie

Restriction

Histone

acetylation



Immune

function

Folate DNA

Methylation



acetylation



AdoMet Histone

acetylation


Methyl-

deficient

diet


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Cancer Methyl-

deficient

diet

Histone

modification

mRNA



Genistein DNA

Methylation

mRNA




Inhibiting

EGC-3G

DNA

methylation

PRC





Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA



Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation














bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS



Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Aging Folate DNA

methylation



Calorie

Restriction

Histone

acetylation



Immune

function

Folate DNA

Methylation



acetylation



AdoMet Histone

acetylation


Methyl-

deficient

diet


Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Cancer Methyl-

deficient

diet

Histone

modification

mRNA



Genistein DNA

Methylation

mRNA




Inhibiting

EGC-3G

DNA

methylation

PRC





Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA



Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation














bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS



Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Cancer Methyl-

deficient

diet

Histone

modification

mRNA



Genistein DNA

Methylation

mRNA




Inhibiting

EGC-3G

DNA

methylation

PRC





Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA



Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation














bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS



Process or

Condition

Nutrient or

Diet

Epigenetic

Mechanism



Obesity Insulin

Resistance

High-fat

diet

DNA

methylation

mRNA



Methyl-

deficient

diet

DNA

methylation


Curcumin Histone

acetylation














bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS















bull Indications







bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS





bull Anti-cancer





bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS




bull Curcumin









CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS




CURCUMIN

67




Polyposis Cancers




Gastric Ulcers


Psoriasis




Inflammatory Bowel

Disease


Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS




Resulting Condition

Naturopathic

Prevention or

Treatment Options





Alzheimerrsquos


substances which


and chemo-

prevention induce

HSP response1




Arthritis

Modulate genetic


Ginger2

Thunder God Vine












and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS










and TNF-alpha

Aging


elderly people

Type 2 diabetes

Atherosclerosis


Regular physical

activity26 74

Regular sleep75


related metabolic










IL-6

Aging


Atherosclerosis

Type 2 Diabetes

Zinc turnover via

Metallothionine



foods1


C-reactive Protein

Obesity

Insulin resistance

Metabolic syndrome


physical activity

Metformin1


composition2







WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS





WHY BIOMARKERS


























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS























bull Epigenomics



bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS





bull CRP and hsCRP





bull IL-6



bull LRG1




proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS





proteins (APRP)


distinct for type

subtype and stages








cancer


Methylation





cigarette smoking)






CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS



CRP AND HS CRP





















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS



















































bull diabetes

bull HIV

bull asthma


bull RA






Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS







Sepsis ndash need

addrsquol CRP


cancer



MM survival time


Osteosarcoma

Gastric Cancer

Multiple Myeloma

RA and Diabetes

Insulin Resistance

normal value

lt0-5pgml











INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS













INFLAMMATION CCL-18













BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS









BIOMARKER IL-6
















bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS












bull CRP

bull IL-6





bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS




bull In RA













Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS











Disease


LRG1α


serum and

CSF fluid

elevations



Type 1 Diabetes






bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS








bull SLE







MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS



MULTIPLE SCLEROSIS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS



TYPE 1 DIABETES







SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS



SUMMARY



bull GxE

bull Nutritional

bull Lifestyle




Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS



Process or

Condition

Naturopathic

Approaches


Marker

References


Melatonin EPA

Haptoglobin chain

serum amyloid A and

Apo lipoprotein A-1


Infiltrating ductal

breast

carcinoma

Melatonin EPA

EGCG Vitamin

D3

1-antitrypsin

haptoglobin

precursors


Epithelial

Ovarian Cancer



acids

Vitamin D3


Rheumatoid

Arthritis

Insulin

Resistance

Curcumin Green

Tea and

Resveratrol



D3

Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS



Process or

Condition

Naturopathic

Approaches

Proteomic

Diagnostic Marker

References in


Cox-2 inhibition

RA

Hops iso-alpha

acids with

oleanolic acid and

rosmarinic acid


SLE RA

borelliosis and

co-infections


Autoimmune

disease

Cancer

RA


OA COX-2

AutoImmune

disease


Anti-

inflammatory

Anti-cancer

Anti-viral

Anti-bacterial

Amphoteric

Scutellaria

baicalensis

Reducing NO

expression COX-

2 PGE2 NFk-B

and inflammatory

cytokines IL-1 2

6 12 and TNF-α


QUESTIONS



QUESTIONS



Biomarkers of Inflammation Kussmann

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Transcript of Biomarkers of Inflammation Kussmann