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Epigenetic modifications play a fundamental role in the regulation of gene expression and cell fate. During the development of cancer, epigenetic modifications appear that favor cell proliferation and migration, but at the same time prevent differentiation and apoptosis, among other processes. KDM6B is a histone demethylase that specifically removes methyl groups from H3K27me3, thus allowing re-expression of its target genes. It is currently known that KDM6B can act as both a tumor suppressor and an oncogene depending on the cellular context. Therefore, in this work we summarize the current knowledge of the role that KDM6B plays in different oncological contexts, and we try to orient it towards its clinical application.Diabetes mellitus (DM) is a global health burden, affecting about 463 million of the adult population worldwide. Approximately 94% of diabetic male individuals develop varying degrees of testicular disorders (TDs), which usually result in hypogonadism, hypotestosteronemia and defective spermatogenesis and steroidogenesis. Short chain fatty acids (SCFAs) have shown potential benefits in metabolic health. However, its effect on TD associated with DM is not clear. Howbeit, the present study investigated the hypothesis that SCFAs, acetate would ameliorate TD accompanying DM, possibly by suppressing proprotein convertase subtilisin/kexin type 9 (PCSK9). Male Wistar rats (210-240 g) were allotted into groups (n = 6/group) control (vehicle; po), DM with/without 200 mg/kg (po) of sodium acetate (SAc). Diabetes was induced by streptozotocin 65 mg/kg (iv) after a dose of nicotinamide (110 mg/kg). Semen/biochemical and histological analyses were performed with appropriate methods. In addition to hyperglycemia, hyperinsulinemia and reduced insulin sensitivity, DM led to increased serum and testicular triglyceride or total cholesterol/high-density lipoprotein cholesterol ratio, low-density lipoprotein cholesterol, malondialdehyde, TNF-α, IL-6 and PCSK9 as well as reduced high-density lipoprotein cholesterol and glutathione. Moreover, DM caused TD which is characterized by altered sperm parameters, disrupted tissue architecture, atrophied seminiferous tubules, deleterious spermatogonia, disappearance of lumen and cellular degeneration as well as decreased luteinizing hormone and testosterone. However, the administration of SAc attenuated these alterations. The study demonstrates that DM-induced TD is accompanied by elevated PCSK9. The results however suggest that SAc rescues testicular disorder/dysfunction associated with DM by suppression of PCSK9 and improvement of insulin sensitivity.Valvular heart diseases have long been considered to be similar in men and women and across races/ethnicities. Recently, studies have demonstrated major differences between sexes. Unfortunately, studies on valvular heart diseases, as on other cardiovascular diseases, are mostly performed in Caucasian men or in cohorts with a vast majority of Caucasian men. Therefore, our knowledge on valvular diseases in women and non-Caucasians remains limited. Nevertheless, aortic stenosis has been shown to be almost as prevalent in women as in men, and less prevalent in African Americans. Men appear to have a more calcified aortic valve lesion, and women tend to have a more fibrosed one. Mitral regurgitation is more frequent in women who have more rheumatic and Barlow etiologies, whereas men have more fibroelastic deficiency and posterior leaflet prolapse/flail. Left ventricular remodelling due to valvular heart diseases is sex related in terms of geometry and probably also in composition of the tissue. Outcomes seem to be worse in women after surgical interventions and better than or equivalent to men after transcatheter ones. Regarding other valvular heart diseases, very few studies are available Aortic regurgitation is more frequent in men, isolated tricuspid regurgitation more frequent in women. Rheumatic valve diseases are more frequent in women and are mostly represented by mitral and aortic stenoses. Many other sex/gender- and race/ethnic-specific studies are still needed in epidemiology, pathophysiology, presentation, management, and outcomes. This review aims to report the available data on sex differences and race specificities in valvular heart diseases, with a primary focus on aortic stenosis and mitral regurgitation.The concept that origins of cardiovascular disease (CVD) begin in childhood is supported by substantial evidence. Prospective studies beginning in childhood report associations of childhood obesity, abnormal blood pressure (BP), dyslipidemia, diabetes, and tobacco use with intermediate CVD markers, including left ventricular hypertrophy and vascular stiffness in young adulthood. Trajectory analyses from longitudinal studies describe discrete BP pathways from childhood to young adult status of hypertension and prehypertension. Among individuals with familial hypercholesterolemia, abnormal low-density lipoprotein cholesterol levels are present in childhood. Some children are at risk for future CVD owing to hereditary factors, psychosocial stress, race, low birth weight, or other nonmodifiable exposures. Behavioural factors, including suboptimal diet, sedentary activity, and tobacco use, in childhood augment risk and can be modified to reduce risk. Pharmacologic treatments are reserved for those at high levels of the BP and cholesterol distributions and for those with diabetes and additional risk factors.The intestinal mucosa plays an important role as an immune barrier due to its continual exposure to invading pathogens, including viruses. It is thus highly important to evaluate virus infection profiles in the intestinal mucosa for prevention of virus infection and development of antivirus medicines; however, only a few enterocyte lines are available as in vitro intestinal models for the evaluation of virus infection. In this study, we evaluated profiles of infection and innate immune responses following infection with a mammalian orthoreovirus (hereafter reovirus), which has often been used as a tractable model for studies of viral pathogenesis, in human iPS cell-derived small intestinal epithelial-like cell (hiPS-SIEC) monolayers and cells of a human colon adenocarcinoma cell line, Caco-2. The levels of reovirus infection were similar between hiPS-SIEC and Caco-2 cell monolayers, which are often used as an intestinal model, after apical and basolateral infection. https://www.selleckchem.com/products/tabersonine.html In hiPS-SIEC monolayers, more efficient replication of the virus genome was observed following basolateral infection than apical infection, while apical infection resulted in higher levels of virus protein expression and progeny virus production than basolateral infection.
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