Resveratrol activates the histone H2B ubiquitin ligase,RNF20, in MDA-MB-231 breast cancer cells

Resveratrol, a polyphenolic compound found in grapes, has been shown to partially exert its anti-cancer function through the modulation of epigenetic events. However, the epigenetic targets of resveratrol in breast cancer are not yet fully understood. Here, we identified that the gene encoding the histone H2B ubiquitin ligase RNF20 (ring finger protein 20), a chromatin modifying enzyme and putative tumour suppressor, is up-regulated by resveratrol in MDA-MB-231 breast cancer cells. Up-regulation of RNF20 is achieved through an increase of active histone marks around its promoter. The increase in RNF20 in MDA-MB-231 likely contributes to p21 regulation and the anti-growth effects of resveratrol, as RNF20 knockdown diminished these effects. Our findings suggest that RNF20 is a novel epigenetic target of resveratrol, and increase our understanding of how it contributes to the chemopreventive effect of resveratrol in a more aggressive breast cancer cell line, MDA-MB-231.     

A Review on Dietary Flavonoids as Modulators of the Tumor Microenvironment

The tumor microenvironment (TME) is the local environment where malignant cells strive and survive, composed of cancer cells and their surroundings, regulating essential tumor survival, and promotion functions. Dietary flavonoids are abundantly present in common vegetables and fruits and exhibit good anti-cancer activities, which significantly inhibit tumorigenesis by targeting TME constituents and their interaction with cancer cells. This review aims to synthesize information concerning the modulation of TME by dietary flavonoids, as well as to provide insights into the molecular basis of its potential anti-tumor activities, with an emphasis on its ability to control intracellular signaling cascades that regulate the TME processes, involving cell proliferation, invasion and migration, continuous angiogenesis, and immune inflammation. This study will provide a theoretical basis for the development of the leading compound targeting TME for anti-cancer therapies from these dietary flavonoids.     

Epigenetic effects of natural polyphenols: A focus on SIRT1‐mediated mechanisms

Polyphenols are a class of natural compounds widely distributed in fruits, vegetables, and plants. They have been reported to possess a wide range of activities in prevention and alleviation of various diseases like cancer, neuroinflammation, diabetes, and aging. Polyphenols are effective against chronic diseases and recent reports indicated strong epigenetic effects of polyphenols. Most of the studies investigating epigenetic effects of natural polyphenols have focused on their beneficial effects in cancer treatment. However, epigenetic defects have been demonstrated in many other diseases as well, and application of polyphenols to modulate the epigenome is becoming an interesting field of research. This review summarizes the effects of natural polyphenols in modulating epigenetic‐related enzymes as well as their effect in prevention and treatment of chronic diseases with a focus on SIRT1 modulation. We have also discussed the relation between the structure and function of epigenetic‐modifying polyphenols.     

An optimized FAIRE procedure for low cell numbers in yeast

We report an optimized low‐input FAIRE‐seq (Formaldehyde‐Assisted Isolation of Regulatory Elements‐sequencing) procedure to assay chromatin accessibility from limited amounts of yeast cells. We demonstrate that the method performs well on as little as 4 mg of cells scraped directly from a few colonies. Sensitivity, specificity and reproducibility of the scaled‐down method are comparable with those of regular, higher input amounts, and allow the use of 100‐fold fewer cells than existing procedures. The method enables epigenetic analysis of chromatin structure without the need for cell multiplication of exponentially growing cells in liquid culture, thus opening the possibility of studying colony cell subpopulations, or those that can be isolated directly from environmental samples.     

The relevance of selenium to immunity, cancer, and infectious/inflammatory diseases.

Selenium is an essential trace element involved in several key metabolic activities via selenoproteins, enzymes that are essential to protect against oxidative damage and to regulate immune function. Selenium also may have other health benefits unrelated to its enzymatic functions. It may provide important health benefits to people whose oxidative stress loads are high, such as those with inflammatory or infectious diseases like rheumatoid arthritis or human immunodeficiency virus/acquired immunodeficiency syndrome, or who are at high risk for cancers, particularly prostate cancer. Some studies have generated compelling evidence that selenium is beneficial, either alone or in conjunction with other micronutrients. Additional data from large clinical trials that provide the highest level of evidence will be key to determining the benefits accrued at various selenium intake levels. When the strength of the evidence becomes sufficient, clinical health professionals will need to use dietary and clinical assessment methods to ensure that people at increased risk for cancer or inflammatory and infectious diseases can be appropriately advised about selenium intake.     

Technical note: Droplet digital PCR as a new molecular method for a simple and reliable diagnosis of freemartinism in cattle

Freemartinism is the most common type of disorder of sex development in cattle. It leads to sterility in the female co-twin in heterosexual twin pregnancy, and is thus a serious problem in cattle production. The incidence of freemartin syndrome is directly dependent on the prevalence of twinning, which has increased in dairy cattle populations in recent years. Thus, early and rapid identification of freemartins is needed to reduce economic loss. Of the various methods used to diagnose this condition, identifying the XX and XY cell lines in blood samples using cytogenetic techniques is the gold standard; however, this technique is time consuming. Faster and more reliable techniques are thus being sought. Droplet digital PCR (ddPCR) is a third-generation PCR method and it has not previously been used to detect XX/XY leukocyte chimerism in cattle. The aim of the present study was to verify the usefulness of ddPCR to detect and quantify leukocyte chimerism in this species. The X and Y copy numbers were estimated by identifying the copy numbers of 2 genes located on the sex chromosomes: amelogenin X-linked (AMELX) on the X chromosome and amelogenin Y-linked (AMELY) on the Y chromosome. In the first step, we performed ddPCR on samples prepared from female DNA mixed with male DNA in serially diluted proportions. We determined that the sensitivity of this method was sufficient to detect a low-frequency (<5%) cell line. In the next step, ddPCR was used to analyze 22 Holstein Friesian freemartins. Cytogenetic evaluation of these cases revealed leukocyte chimerism; the proportion of XX and XY metaphase spreads varied over a wide range, from XX (98%)/XY (2%) to XX (4%)/XY (96%). The use of ddPCR facilitated the precise estimation of the ratio of the copy number of X to Y sex chromosomes. In all cases, the XX/XY chimerism detected by cytogenetic analysis was confirmed using ddPCR. The method turned out to be very simple, accurate, and sensitive. In conclusion, we recommend the ddPCR method for fast and reliable detection of XX/XY leukocyte chimerism in cattle.     

The success and the challenge of all-trans retinoic acid in the treatment of cancer

Abstract

All-trans retinoic acid (ATRA), an active metabolite of vitamin A, plays important roles in cell proliferation, cell differentiation, apoptosis, and embryonic development. The effects of ATRA are mediated by nuclear retinoid receptors as well as non-genomic signal pathway, such as MAPK and PKA. The great success of differentiation therapy with ATRA in acute promyelocytic leukemia (APL) not only improved the prognosis of APL but also spurred the studies of ATRA in the treatment of other tumors. Since the genetic and physiopathological simplicity of APL is not common in human malignancies, the combination of ATRA with other agents (chemotherapy, epigenetic modifiers, and arsenic trioxide, etc) had been extensively investigated in a variety of tumors. In this review, we will discuss in details about ATRA and its role in cancer treatment.     

益生菌对高血压影响的研究进展

肠道菌群在代谢综合征、心血管疾病和结直肠癌等疾病中的研究已经成为焦点,但是肠道微生物与这些疾 病的因果关系以及相应的致病机制尚不清楚。通过分析肠道菌群结构、组成以及代谢活动的变化对高血压的影响, 能够揭示肠道以及肠道微生物的活动与高血压之间的相关性。益生菌是对机体健康产生有益作用的活的微生物,可 以调节肠道微生态的平衡以及肠道微生物的代谢活动,从而对高血压的调节产生影响,进而为以肠道微生物为靶点 干预治疗高血压疾病提供理论参考,同时也为疾病的干预治疗提供新的途径和方法。     

Molecular alterations in hepatocarcinogenesis induced by dietary methyl deficiency

A chronic deficiency of major dietary methyl group donors--methionine, choline, folic acid, and vitamin B12--can induce the development of liver cancer in rodents. Feeding methyl-deficient diets causes several molecular alterations, including altered lipid metabolism, oxidative stress, deregulated one-carbon metabolism, and a number of epigenetic abnormalities that result in progressive liver injury culminating in the development of primary liver tumors. Importantly, this methyl-deficient model of endogenous hepatocarcinogenesis is one of the most relevant models of human liver carcinogenesis that allows studying liver cancer pathogenesis by substantially complementing many shortcomings of humans-only studies. In this review, we describe molecular changes and their role in pathogenesis of liver carcinogenesis induced by methyl deficiency.