Review Article

Target Elimination-Denatured and Unstable Proteins, Environmental Toxins, Metabolic Wastes, Immunosuppressive Factors and Chronic Inflammatory Factors of Medical System for Chronic Diseases Prevention and Health Promotion: A Narrative Review


Background: The incidence of chronic diseases, such as cardiovascular disease, diabetes, overweight, obesity, cancer and other diseases has been increasing. It is a huge challenge to public health industry about how to provide risk intervention and preventive medical services and explore advanced technology platform for effective prevention and control of chronic diseases.

Methods: We collaborated domestic and international experts on preventive medicine, and analyzed pathogenesis and risk factors for the major chronic diseases.

Results: We established Target Elimination--denatured and unstable proteins, environmental toxins, metabolic wastes, immunosuppressive factors and chronic inflammatory factor (TE-PEMIC) system that offer us the standard and methods to eliminate and intervene pathogenic factors of the chronic diseases.

Conclusion: It provides new researches and exploring new ideas to prevent and intervene chronic diseases by applying the TE-PEMIC chronic diseases prevention medical technology system.


1. Ghazy HA, Abdel-Razek MAS, El Nahas AF, Mahmoud S (2017). Assessment of complex water pollution with heavy met-als and Pyrethroid pesticides on tran-script levels of metallothionein and im-mune related genes. Fish Shellfish Immunol, 68: 318-26.
2. Rajeshkumar S, Liu Y, Ma J, Duan HY, Li X (2017). Effects of exposure to multiple heavy metals on biochemical and histo-pathological alterations in common carp, Cyprinus carpio L. Fish Shellfish Immunol, 70:461-72.
3. Korashy HM, Attafi IM, Famulski KS, Bak-heet SA, Hafez MM, Alsaad AMS, Al-Ghadeer ARM (2017). Gene expression profiling to identify the toxicities and po-tentially relevant human disease outcomes associated with environmental heavy metal exposure. Environ Pollution, 221: 64-74.
4. Yuan W, Yang N, Li X (2016). Advances in Understanding How Heavy Metal Pollu-tion Triggers Gastric Cancer. Biomed Res Int, 2016: 7825432.
5. Aliomrani M, Sahraian MA, Shirkhanloo H, Sharifzadeh M, Khoshayand MR, Ghahremani MH (2017). Correlation be-tween heavy metal exposure and GSTM1 polymorphism in Iranian multiple sclero-sis patients. Neurol Sci, 38(7):1271-1278.
6. Ledda C, Iavicoli I, Bracci M, Avola R, Senia P, Santarelli L, Pomara C, Rapisarda V (2017). Serum lipid, lipoprotein and apolipoprotein profiles in workers ex-posed to low arsenic levels: Lipid profiles and occupational arsenic exposure. Toxicol Lett, 282: 49-56.
7. Rudd JH, Hyafil F, Fayad ZA (2009). In-flammation imaging in atherosclerosis. Arterioscler Thromb Vasc Biol, 29 (7): 1009-16.
8. Meyer JN, Leung MCK, Rooney JP, Sendoel A, Hengartner MO, Kisby GE, Bess AS (2013). Mitochondria as a Target of Envi-ronmental Toxicants. Toxicol Sci, 134 (1): 1-17.
9. Alissa EM, Ferns GA (2011). Heavy metal poisoning and cardiovascular disease. J Toxicol, 2011:870125.
10. Wu D, Cederbaum AI. (2003). Alcohol, oxi-dative stress and free radical damage. Al-cohol Res Health,27(4):277-84.
11. McElroy JA, Shafer MM, Trentham-Dietz A, Hampton JM, Newcomb PA (2006). Cadmium exposure and breast cancer risk. J Natl Cancer Inst, 98 (12): 869-73.
12. Antwi SO, Eckert EC, Sabaque CV, et al (2015). Exposure to environmental chemicals and heavy metals, and risk of pancreatic cancer. Cancer Causes Control, 26 (11): 1583-91.
13. Malandrino P, Scollo C, Marturano I, et al (2013). Descriptive epidemiology of hu-man thyroid cancer: experience from a regional registry and the "volcanic factor". Front Endocrinol (Lausanne), 4: 65.
14. Bolognesi C (2003). Genotoxicity of pesti-cides: a review of human biomonitoring studies. Mutat Res, 543 (3): 251-72.
15. Roy C, Tremblay PY, Ayotte P (2017). Is mercury exposure causing diabetes, met-abolic syndrome and insulin resistance? A systematic review of the literature. Envi-ron Res, 156: 747-60.
16. Sowers JR, Epstein M, Frohlich ED (2001). Diabetes, hypertension, and cardiovascu-lar disease: an update. Hypertension, 37 (4): 1053-9.
17. Verhagen SN, Wassink AM, van der Graaf Y, Gorter PM, Visseren FL (2011). Insu-lin resistance increases the occurrence of new cardiovascular events in patients with manifest arterial disease without known diabetes. The SMART study. Cardiovasc Diabetol, 10: 100.
18. Weinsier RL, Fuchs RJ, Kay TD, Triebwas-ser JH, Lancaster MC (1976). Body fat: its relationship to coronary heart disease, blood pressure, lipids and other risk fac-tors measured in a large male population. Am J Med, 61 (6): 815-24.
19. Whelton PK (2014). Sodium, potassium, blood pressure, and cardiovascular dis-ease in humans. Curr Hypertens Rep, 16 (8): 465.
20. Cibulka R, Racek J (2007). Metabolic disor-ders in patients with chronic kidney fail-ure. Physiol Res, 56 (6): 697-705.
21. Braun S, Bitton-Worms K, LeRoith D (2011). The link between the metabolic syndrome and cancer. Int J Biol Sci, 7 (7): 1003-15.
22. Matsuzawa Y (2008). The role of fat topolo-gy in the risk of disease. Int J Obesity, 32: S83-S92.
23. Greaves DR, Gordon S (2001). Immunity, atherosclerosis and cardiovascular dis-ease. Trends Immunol, 22 (4): 180-1.
24. Hansson GK (2001). Immune mechanisms in atherosclerosis. Arterioscler Thromb Vasc Biol, 21 (12): 1876-90.
25. Fagerberg B, Gnarpe J, Gnarpe H, Agewall S, Wikstrand J (1999). Chlamydia pneu-moniae but not cytomegalovirus antibod-ies are associated with future risk of stroke and cardiovascular disease: a pro-spective study in middle-aged to elderly men with treated hypertension. Stroke, 30 (2): 299-305.
26. Amaya-Amaya J, Montoya-Sanchez L, Ro-jas-Villarraga A (2014). Cardiovascular in-volvement in autoimmune diseases. Bio-med Res Int, 2014: 367359.
27. Liu Y, Cao X (2016). Immunosuppressive cells in tumor immune escape and metas-tasis. J Mol Med (Berl), 94 (5): 509-22.
28. Gorgun GT, Whitehill G, Anderson JL, et al (2013). Tumor-promoting immune-suppressive myeloid-derived suppressor cells in the multiple myeloma microenvi-ronment in humans. Blood, 121 (15): 2975-87.
29. Whiteside TL (2006). Immune suppression in cancer: Effects on immune cells, mechanisms and future therapeutic inter-vention. Semin Cancer Biol, 16 (1): 3-15.
30. Silva JM, Videira M, Gaspar R, Preat V, Florindo HF (2013). Immune system tar-geting by biodegradable nanoparticles for cancer vaccines. J Control Release, 168 (2): 179-99.
31. Grivennikov SI, Greten FR, Karin M (2010). Immunity, Inflammation, and Cancer. Cell, 140 (6): 883-99.
32. Landskron G, De la Fuente M, Thuwajit P, Thuwajit C, Hermoso MA (2014). Chronic Inflammation and Cytokines in the Tumor Microenvironment. J Immunol Res 2014:149185.
33. Cassell GH (1998). Infectious causes of chronic inflammatory diseases and can-cer. Emerg Infect Dis, 4 (3): 475-87.
34. He Y, Yue Y, Zheng X, Zhang K, Chen S, Du Z (2015). Curcumin, inflammation, and chronic diseases: how are they linked? Molecules, 20 (5): 9183-213.
35. Bloomgarden ZT (2005). Inflammation, ath-erosclerosis, and aspects of insulin action. Diabetes Care, 28 (9): 2312-9.
36. Chen L, Chen R, Wang H, Liang FX (2015). Mechanisms Linking Inflammation to Insulin Resistance. Int J Endocrinol 2015: 508409.
37. Zhang JY, Chen CY, Hu B, et al (2016). Ex-osomes Derived from Human Endothe-lial Progenitor Cells Accelerate Cutaneous Wound Healing by Promoting Angiogen-esis Through Erk1/2 Signaling. Int J Biol Sci, 12 (12): 1472-87.
38. Araki A, Hosoi T, Orimo H, Ito H (2005). Association of plasma homocysteine with serum interleukin-6 and C-peptide levels in patients with type 2 diabetes. Metabo-lism, 54 (6): 809-14.
39. Joshi MB, Baipadithaya G, Balakrishnan A, et al (2016). Elevated homocysteine levels in type 2 diabetes induce constitutive neu-trophil extracellular traps. Scientific Reports, 6: 36362.
40. Fukuma H, Morshed SA, Watanabe S, et al M (1996). Increased expression of cyto-kines in liver and serum in patients with extrahepatic diseases. J Gastroenterol, 31 (4): 538-45.
41. Yoshida N, Ikemoto S, Narita K, et al (2002). Interleukin-6, tumour necrosis factor alpha and interleukin-1beta in pa-tients with renal cell carcinoma. Br J Can-cer, 86 (9): 1396-400.
42. Zhang DQ, Guo Q, Zhu JH, Chen WC (2013). Increase of cyclooxygenase-2 in-hibition with celecoxib combined with 5-FU enhances tumor cell apoptosis and antitumor efficacy in a subcutaneous im-plantation tumor model of human colon cancer. World J Surg Oncol, 11: 16.
43. Hocaoglu C, Kural B, Aliyazicioglu R, Deger O, Cengiz S (2012). IL-1beta, IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha and its relationship with lipid parameters in pa-tients with major depression. Metab Brain Dis, 27 (4): 425-30.
44. Stemerman MB, Ross R (1972). Experi-mental arteriosclerosis. I. Fibrous plaque formation in primates, an electron micro-scope study. J Exp Med, 136 (4): 769-89.
45. Langheinrich AC, Bohle RM (2005). Ather-osclerosis: humoral and cellular factors of inflammation. Virchows Arch, 446 (2): 101-11.
46. Gu HF, Tang CK, Yang YZ (2012). Psycho-logical stress, immune response, and ath-erosclerosis. Atherosclerosis, 223 (1): 69-77.
47. Brahmbhatt A, Remuzzi A, Franzoni M, Misra S (2016). The molecular mecha-nisms of hemodialysis vascular access failure. Kidney Int, 89 (2): 303-16.
48. Morawe T, Hiebel C, Kern A, Behl C (2012). Protein Homeostasis, Aging and Alzhei-mer's Disease. Mol Neurobiol, 46 (1): 41-54.
49. Eakin CM, Miranker AD (2005). From chance to frequent encounters: Origins of beta 2-microglobulin fibrillogenesis. Bio-chim Biophys Acta, 1753 (1): 92-9.
50. Hoffner G, Djian P (2015). Polyglutamine Aggregation in Huntington Disease: Does Structure Determine Toxicity? Mol Neurobiol, 52 (3): 1297-314.
51. Anderson KA, Hirschey MD (2012). Mito-chondrial protein acetylation regulates metabolism. Essays Biochem, 52: 23-35.
52. Peleg S, Feller C, Ladurner AG, Imhof A (2016). The Metabolic Impact on Histone Acetylation and Transcription in Ageing. Trends Biochem Sci, 41 (8): 700-11.
53. Pan H, Luo XG, Guo S, Liu ZP (2010). [Histone methylation and its relationship with cancer]. Sheng Li Ke Xue Jin Zhan, 41 (1): 22-6 [Article in Chinese].
54. Lim S, Metzger E, Schule R, Kirfel J, Buett-ner R (2010). Epigenetic regulation of cancer growth by histone demethylases. Int J Cancer, 127 (9): 1991-8.
55. Abu-Ghazaleh R, Kabir J, Jia H, Lobo M, Zachary I (2001). Src mediates stimulation by vascular endothelial growth factor of the phosphorylation of focal adhesion kinase at tyrosine 861, and migration and anti-apoptosis in endothelial cells. Biochem J, 360 (Pt 1): 255-64.
56. Okuyama Y, Umeda K, Negishi M, Katoh H (2016). Tyrosine Phosphorylation of SGEF Regulates RhoG Activity and Cell Migration. Plos One, 11 (7): e0159617.
57. Cloos PA, Christgau S (2002). Non-enzymatic covalent modifications of pro-teins: mechanisms, physiological conse-quences and clinical applications. Matrix Bio, 21 (1): 39-52.
58. Barbariga M, Curnis F, Spitaleri A, et al (2014). Oxidation-induced Structural Changes of Ceruloplasmin Foster NGR Motif Deamidation That Promotes Integ-rin Binding and Signaling. J Biol Chem, 289 (6): 3736-48.
59. Luibl V, Isas JM, Kayed R, Glabe CG, Langen R, Chen J (2006). Drusen depos-its associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers. J Clin Invest, 116 (2): 378-85.
60. Sommer F, Backhed F (2013). The gut mi-crobiota - masters of host development and physiology. Nat Rev Microbiol, 11 (4): 227-38.
61. Blottiere HM, de Vos WM, Ehrlich SD, Dore J (2013). Human intestinal meta-genomics: state of the art and future. Curr Opin Microbiol, 16 (3): 232-9.
62. Lin CS, Chang CJ, Lu CC, Martel J, Ojcius DM, Ko YF, Young JD, Lai HC (2014). Impact of the gut microbiota, prebiotics, and probiotics on human health and dis-ease. Biomed J, 37 (5): 259-68.
63. Koboziev I, Webb CR, Furr KL, Grisham MB (2014). Role of the enteric microbiota in intestinal homeostasis and inflamma-tion. Free Radical Bio Med, 68: 122-33.
64. Jin CC, Flavell RA (2013). Innate sensors of pathogen and stress: Linking inflamma-tion to obesity. J Allergy Clin Immun, 132 (2): 287-94.
65. Parracho HMRT, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autis-tic spectrum disorders and that of healthy children. J Med Microbiol 2005; 54(10): 987-91.
66. Benassi B, Leleu R, Bird T, Clifton P, Fenech M (2007). Cytokinesis-block mi-cronucleus cytome assays for the deter-mination of genotoxicity and cytotoxicity of cecal water in rats and fecal water in humans. Cancer Epidem Biomar, 16 (12): 2676-80.
67. Blachier F, Davila AM, Mimoun S, et al (2010). Luminal sulfide and large intestine mucosa: friend or foe? Amino Acids, 39 (2): 335-47.
68. Shen W, Gaskins HR, McIntosh MK (2014). Influence of dietary fat on intestinal mi-crobes, inflammation, barrier function and metabolic outcomes. J Nutr Biochem, 25 (3): 270-80.
69. Tang WHW, Wang ZE, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL (2013). Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascu-lar Risk. New Engl J Med, 368 (17): 1575-84.
70. Kim E, Coelho D, Blachier F (2013). Review of the association between meat con-sumption and risk of colorectal cancer. Nutr Res, 33 (12): 983-94.
71. Chan YK, Estaki M, Gibson DL (2013). Clinical Consequences of Diet-Induced Dysbiosis. Ann Nutr Metab, 63: 28-40.
72. Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R (2008). Changes in gut microbiota con-trol metabolic endotoxemia-induced in-flammation in high-fat diet-induced obe-sity and diabetes in mice. Diabetes, 57 (6): 1470-81.
IssueVol 48 No 6 (2019) QRcode
SectionReview Article(s)
TE-PEMIC Prevention Chronic diseases

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How to Cite
ZHANG J, JIANG Z, WEI W, LI X, SUN C, ZHANG Y, FU S, ZHENG J. Target Elimination-Denatured and Unstable Proteins, Environmental Toxins, Metabolic Wastes, Immunosuppressive Factors and Chronic Inflammatory Factors of Medical System for Chronic Diseases Prevention and Health Promotion: A Narrative Review. Iran J Public Health. 2019;48(6):994-1003.