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Induction of ovarian cancer cell apoptosis by 1,25-dihydroxyvitamin D3 through the down-regulation of telomerase. Jiang F, Bao J, Li P, Nicosia SV, Bai W. J Biol Chem. 2004 Dec 17;279(51):53213-21. Epub 2004 Oct 12. PMID: 15485861 doi: 10.1074/jbc.M410395200 Overall, the study suggests that the down-regulation of telomerase activity by 1,25(OH)2VD3 and the resulting cell death are important components of the response of OCa cells to 1,25(OH)2VD3-induced growth suppression. Progressive shortening of telomere associated with cell divisions limits the life span of normal cells and eventually leads to senescence. To become immortal, human cancers including OCa are invariably associated with activation of mechanism that maintains telomere length. Approximately 85-90% of cancers show reactivation of telomerase. The present study shows that telomerase in OCa cells is down-regulated by 1,25(OH)2VD3. Down-regulation of telomerase is due to decreased stability of hTERT mRNA rather than VDRE-mediated transcriptional repression through the putative VDRE present in the regulatory region of the hTERT gene. It is known that the inhibition of telomerase may lead to a phenotypic lag during which cells would continue to divide until the point at which the telomeres became critically short. This phenomenon may explain why the apoptotic induction by 1,25(OH)2VD3 needs the treatment for more than 6 days. As mentioned in the results, no detectable shortening of telomeric repeats was observed in parental OVCAR3 cells after 9 days of treatment with 1,25(OH)2VD3 (Fig. 4D). This is likely due to the fact that the short telomere (about 3 kb) in OVCAR3 cells is very close to the minimal length required for survival and that cells with detectably shorter telomere may have been selected against apoptosis. It has been shown that transformed human cells enter crisis once the terminal restriction fragment of the telomere reaches a length of about 4 kb. This is insufficient to protect chro

The vitamin D-antimicrobial peptide pathway and its role in protection against infection. Gombart AF. Future Microbiol. 2009 Nov;4:1151-65. PMID: 19895218 Vitamin D deficiency has been correlated with increased rates of infection. Since the early 19th century, both environmental (i.e., sunlight) and dietary sources (cod liver) of vitamin D have been identified as treatments for TB. The recent discovery that vitamin D induces antimicrobial peptide gene expression explains, in part, the 'antibiotic' effect of vitamin D and has greatly renewed interest in the ability of vitamin D to improve immune function. Subsequent work indicates that this regulation is biologically important for the response of the innate immune system to wounds and infection and that deficiency may lead to suboptimal responses toward bacterial and viral infections. The regulation of the cathelicidin antimicrobial peptide gene is a human/primate-specific adaptation and is not conserved in other mammals. The capacity of the vitamin D receptor to act as a high-affinity receptor for vitamin D and a low-affinity receptor for secondary bile acids and potentially other novel nutritional compounds suggests that the evolutionary selection to place the cathelicidin gene under control of the vitamin D receptor allows for its regulation under both endocrine and xenobiotic response systems. Future studies in both humans and humanized mouse models will elucidate the importance of this regulation and lead to the development of potential therapeutic applications

Mangoes may very well be the king of all fruits. They Prevents Cancer, alkalize the body, aid in weight loss, regulate diabetes, help digestion, clean your skin, and make the perfect snack. and many reasons why you should be Drinking a mango juice every day. They are Many reasons of mango juice 1. Prevents Cancer Antioxidants like quercetin, isoquercitrin, astragalin, fisetin, gallic acid and methylgallat present in mango protect the body against colon, breast, leukemia and prostate cancers. 2. Helps in Lowering Cholesterol Mango has high level of vitamin C, pectin and fibres that help to lower serum cholesterol levels. Fresh mango is a rich source of potassium, which is an important component of cell and body fluids that helps to control heart rate and blood pressure. 3. Mangoes Nourishes Skin Mango is beneficial for skin health. It is a source of antioxidants which delays the onset of skin aging and pigmentation. Vitamin-C in mango helps in curing pimples and acne. It can be directly applied on the skin as it smoothens it and acts as a natural moisturizer. Antioxidants are responsible to protect against harmful free radicals which can cause skin cancer. Vitamin-A and beta carotene helps in rejuvenating the skin and brings glow to the skin. 4. Alkalizes the body According to natural health, mango juice is rich in tartaric acid, malic acid and traces of citric acid that primarily help in maintaining the alkali reserve of the body. 5. Weight loss Mango has a lot of vitamins and nutrients that help the body feel fuller. Also, the fibrous fruit boosts the digestive function of the body by burning additional calories, helping in weight loss. 6. Regulates diabetes Mango Juice Not only the fruit Juice but the leaves of mangoes are healthy too. For people suffering from diabetes, just boil 5-6 mango leaves in a vessel, soak it through night and drink the filtered decoction in the morning. This is helps in regulating your insulin levels. 7. Ap

Your cells use vitamin D to directly regulate your genes, making it one of the most powerful compounds in human health.

Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Kidd P. Altern Med Rev. 2003 Aug;8(3):223-46. Review. PMID: 12946237 Th1 pathways typically produce activation of cytotoxic T lymphocytes (Tc), NK cells, macrophages, and monocytes, all of which can attack cancer cells and generally defend against tumors. 55 IFN-gamma and other Th1 cytokines are typically lower in advanced cancer patients, while the Th2 marker IL-4 can be higher or unchanged.56 Nodules of non-small cell lung cancer freshly removed from patients expressed a marked imbalance toward Th2, as did biopsy samples from basal cell carcinoma.57 In prostate cancer patients IL-2 was low (Th1) and IL-10 high.58 IL-10 is a confirmed Th1-suppressive cytokine, and heightened IL-10 is a common factor in cancer.55 IL-10 has a variety of suppressive effects that include inhibiting Th1 cytokine production, down-regulating APC and NK cell function, and lowering overall T-cell proliferation.57 Especially under the influence of IL-4 (Th2), tumor cells apparently up-regulate IL-10 that suppresses nearby killer cells. Tumor-derived IL-10 has been documented in lymphoma, ovarian carcinoma, melanoma, neuroblastoma, and renal cell and colon carcinoma.57 IL-12 is another cytokine that can be up-regulated by Th1 activity and inhibited by Th2.59 A low IL-12/IL-10 ratio was found in cervical cancer patients.55 Recent clinical studies suggest elevated IL-10 is predictive of a poor prognosis. 57 With both IL-4 and IL-10 being proven inhibitors of Th1 and promoters of Th2 activity, the recognized capability of cancerous tissue to suppress immunity is readily rationalized.

The present study, thus, raises the possibility that DHA may exert pro-apoptotic and antitumoral effects through proteasomal regulation of beta-catenin levels and alterations in the expression of TCF-beta-catenin target genes. Docosahexaenoic acid induces proteasome-dependent degradation of beta-catenin, down-regulation of survivin and apoptosis in human colorectal cancer cells not expressing COX-2. Calviello G, Resci F, Serini S, Piccioni E, Toesca A, Boninsegna A, Monego G, Ranelletti FO, Palozza P. Carcinogenesis. 2007 Jun;28(6):1202-9. Epub 2006 Dec 20. PMID: 17183061 doi:10.1093/carcin/bgl254

Vitamin D may suppress infections which lead to development of Multiple Sclerosis Steven R Brenner, None (16 August 2007) J Neurol Neurosurg Psychiatry 2008 I read the article with reference to the inverse relationship between multiple sclerosis clinical activity and deficiency of vitamin D by Soilu-Hannienen (1) with interest, and was considering what mechanism could be in play to cause such a relationship. 25-hydroxylated metabolites of vitamin D act as intracellular regulators of the synthesis and action of defensin (2) molecules against bacterial antigens, defensin being an endogenously synthesized antimicrobial substance (2). Human cathelicidin antimicrobial peptide gene is a target of vitamin D receptor and is strongly up-regulated by 1,25-dihydroxyvitamin D3, indicating vitamin D receptor and the 1,25-dihydroxyvitaminD3 regulate primate innate immunity (3)

Holick, M. F., MacLaughlin, J. A. & Doppelt, S. H. (1981) Factors that influence the cutaneous photosynthesis of previtamin D3. Science 211:590-593 When human skin was exposed to simulated solar ultraviolet radiation, epidermal 7-dehydrocholesterol was converted to previtamin D3. During prolonged exposure to simulated solar ultraviolet radiation, the synthesis of previtamin D3 reached a plateau at about 10 to 15 percent of the original 7-dehydrocholesterol content, and previtamin D3 was photoisomerized to two biologically inert isomers, lumisterol3 and tachysterol3. Increases either in skin melanin concentration or in latitude necessitated increases in the exposure time to simulated solar ultraviolet radiation required to maximize the formation, but not the total content, of previtamin D3. In order of importance, the significant determinants limiting the cutaneous production of previtamin D3 are (i) photochemical regulation, (ii) pigmentation, and (iii) latitude.

A longitudinal study of serum 25-hydroxyvitamin D and intact parathyroid hormone levels indicate the importance of vitamin D and calcium homeostasis regulation in multiple sclerosis. Soilu-Hänninen M, Laaksonen M, Laitinen I, Erälinna JP, Lilius EM, Mononen I. J Neurol Neurosurg Psychiatry. 2008 Feb;79(2):152-7. Epub 2007 Jun 19. PMID: 17578859 doi:10.1136/jnnp.2006.105320 Conclusions: The endocrine circuitry regulating serum calcium may be altered in MS. There is an inverse relationship between serum vitamin D level and MS clinical activity. The role of vitamin D in MS must be explored further.

Vitamin D signaling, infectious diseases, and regulation of innate immunity. White JH. Infect Immun. 2008 Sep;76(9):3837-43. Epub 2008 May 27. Review. PMID: 18505808 doi:10.1128/IAI.00353-08

The vitamin K dependant protein osteocalcin may have a positive effect on reducing obesity and diabetes, suggests a new study with mice.\nResearchers writing in the journal Cells studied the effect bone cells have in energy regulation, and found that osteocalcin plays a key role in regulating insulin activity.

Vitamin D A Key Player In Overall Health Of Several Body Organs, Says Biochemist In a paper published in the August issue of the American Journal of Clinical Nutrition, Norman identifies vitamin D's potential for contributions to good health in the adaptive and innate immune systems, the secretion and regulation of insulin by the pancreas, the heart and blood pressure regulation, muscle strength and brain activity. In addition, access to adequate amounts of vitamin D is believed to be beneficial towards reducing the risk of cancer. Norman also lists 36 organ tissues in the body whose cells respond biologically to vitamin D. The list includes bone marrow, breast, colon, intestine, kidney, lung, prostate, retina, skin, stomach and the uterus.

Conclusion We demonstrated that the VDRE in the CAMP gene originated from the exaptation of an AluSx SINE in the lineage leading to humans, apes, OWMs and NWMs and remained under purifying selection for the last 55-60 million years. We present convincing evidence of an evolutionarily fixed, Alu-mediated divergence in steroid hormone nuclear receptor gene regulation between humans/primates and other mammals. Evolutionary selection to place the primate CAMP gene under regulation of the vitamin D pathway potentiates the innate immune response and may counter the anti-inflammatory properties of vitamin D. Exaptation of an ancient Alu short interspersed element provides a highly conserved vitamin D-mediated innate immune response in humans and primates. Gombart AF, Saito T, Koeffler HP. BMC Genomics. 2009 Jul 16;10:321. PMID: 19607716 doi:10.1186/1471-2164-10-321

Here we propose that the beneficial effect of (n-3) PUFA diet is related to down-regulation of the mutually positive interactions of platelet activation and coagulation. In addition, we consider the possibility that the dietary effect on hemostatic and lipid factors involves transcription regulation of multiple genes, perhaps in a subject-dependent manner. Fish oil consumption and reduction of arterial disease. Vanschoonbeek K, de Maat MP, Heemskerk JW. J Nutr. 2003 Mar;133(3):657-60. Review. PMID: 12612132

Research has uncovered the fact that vitamin K also plays a crucial role in maintaining bone health. It was found that the amount of vitamin K required to halt bone absorption leading to osteoporosis requires much greater intakes than that required for blood clot regulation. Further, it appears that bone and vascular tissue (like coronary arteries) maintain a preference for a different form of vitamin K than that required for blood clotting regulation. Rather than vitamin K1 needed for clotting, vitamin K2 is the form preferred by bones and arteries (Schurgers LJ et al 2001). It appears that much of the information generated over the years for vitamin K focused on the K1 form, ignoring the K2 form necessary for bone and vascular health. Normal deposition of calcium occurs only in bone and in teeth. Abnormal deposition of calcium in the body occurs in three places: the inner lining of the arteries of the body (the intima) that causes atherosclerotic plaque; the muscle layer of arteries ("medial calcification"); and heart valves. K2 appears to be the form of vitamin K responsible for controlling these phenomena.

Vitamin D-induced up-regulation of tumour necrosis factor alpha (TNF-alpha) in prostate cancer cells. Golovko O, Nazarova N, Tuohimaa P. Life Sci. 2005 Jun 17;77(5):562-77. Epub 2005 Feb 25. PMID: 15904673 doi:10.1016/j.lfs.2004.10.072 Combined addition of human recombinant TNF-alpha with calcitriol or CB1093 cause enhanced effect in induction of apoptosis. We conclude that under physiological conditions vitamin D activates only the transcription of TNF-alpha gene, for TNF-alpha protein synthesis additional cofactors are required. Therefore a cooperation of vitamin D and TNF-alpha may play an important role in the control of cell growth in prostate cancer.

Berberine inhibits adipogenesis in high-fat diet-induced obesity mice. Hu Y, Davies GE. Fitoterapia. 2009 Oct 25. [Epub ahead of print] PMID: 19861153 doi:10.1016/j.fitote.2009.10.010 Our previous studies illustrated that berberine inhibited adipogenesis in murine-derived 3T3-L1 preadipocytes and human white preadipocytes. In this study, the effects of berberine on the adipogenesis of high-fat diet-induced obesity (FD) or normal diet (ND) mice and possible transcriptional impact are investigated. The results demonstrated that in FD mice, berberine reduced mouse weight gain and food intake and serum glucose, triglyceride, and total cholesterol levels accompanied with a down-regulation of PPARgamma expression and an up-regulation of GATA-3 expression. Berberine had no adverse effects on ND mice. These encouraging findings suggest that berberine has excellent pharmacological potential to prevent obesity.

Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression. Li Y, Liu L, Tollefsbol TO. FASEB J. 2009 Dec 17. [Epub ahead of print] PMID: 20019239 doi: 10.1096/fj.09-149328 Cancer cells metabolize glucose at elevated rates and have a higher sensitivity to glucose reduction. However, the precise molecular mechanisms leading to different responses to glucose restriction between normal and cancer cells are not fully understood. We analyzed normal WI-38 and immortalized WI-38/S fetal lung fibroblasts and found that glucose restriction resulted in growth inhibition and apoptosis in WI-38/S cells, whereas it induced lifespan extension in WI-38 cells. Moreover, in WI-38/S cells glucose restriction decreased expression of hTERT (human telomerase reverse transcriptase) and increased expression of p16(INK4a). Opposite effects were found in the gene expression of hTERT and p16 in WI-38 cells in response to glucose restriction. The altered gene expression was partly due to glucose restriction-induced DNA methylation changes and chromatin remodeling of the hTERT and p16 promoters in normal and immortalized WI-38 cells. Furthermore, glucose restriction resulted in altered hTERT and p16 expression in response to epigenetic regulators in WI-38 rather than WI-38/S cells, suggesting that energy stress-induced differential epigenetic regulation may lead to different cellular fates in normal and precancerous cells. Collectively, these results provide new insights into the epigenetic mechanisms of a nutrient control strategy that may contribute to cancer therapy as well as antiaging approaches.

In the field of molecular biology, the peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes.[1] PPARs play essential roles in the regulation of cellular differentiation, development, and metabolism (carbohydrate, lipid, protein), and tumorigenesis[2] of higher organism.

They are Many reasons of mango juice 1. Prevents Cancer Antioxidants like quercetin, isoquercitrin, astragalin, fisetin, gallic acid and methylgallat present in mango protect the body against colon, breast, leukemia and prostate cancers. 2. Helps in Lowering Cholesterol Mango has high level of vitamin C, pectin and fibres that help to lower serum cholesterol levels. Fresh mango is a rich source of potassium, which is an important component of cell and body fluids that helps to control heart rate and blood pressure. 3. Mangoes Nourishes Skin Mango is beneficial for skin health. It is a source of antioxidants which delays the onset of skin aging and pigmentation. Vitamin-C in mango helps in curing pimples and acne. It can be directly applied on the skin as it smoothens it and acts as a natural moisturizer. Antioxidants are responsible to protect against harmful free radicals which can cause skin cancer. Vitamin-A and beta carotene helps in rejuvenating the skin and brings glow to the skin. 4. Alkalizes the body According to natural health, mango juice is rich in tartaric acid, malic acid and traces of citric acid that primarily help in maintaining the alkali reserve of the body. 5. Weight loss Mango has a lot of vitamins and nutrients that help the body feel fuller. Also, the fibrous fruit boosts the digestive function of the body by burning additional calories, helping in weight loss. 6. Regulates diabetes Mango Juice Not only the fruit Juice but the leaves of mangoes are healthy too. For people suffering from diabetes, just boil 5-6 mango leaves in a vessel, soak it through night and drink the filtered decoction in the morning. This is helps in regulating your insulin levels. 7. Eye care Did you know that mango is rich in vitamin A. One cup of sliced mangoes equals 25% intake of your daily need of vitamin A. Mangoes help in promoting good eye sight, fights dry eyes and also prevent night blindness. 8. Helps in digestion Mango Juice c