Vitamin D deficiency might contribute to the pathogenesis of metabolic syndrome and could cause immune disturbance. The aim of this study is to analyze the associations between Vitamin D receptor (VDR) gene polymorphism, serum 25-hydroxy vitamin D, metabolic and inflammatory biomarkers in Egyptian obese women. The study included 201 obese women with vitamin D deficiency and 249 obese matched age healthy controls with sufficient vitamin D levels. Their age ranged between 25 and 35 years. Inflammatory biomarkers (interleukin-6 and C-reactive protein) and serum 25(OH) D were measured by enzyme-linked immunosorbent assay. Insulin resistance (IR) was determined by the homeostasis model assessment of insulin resistance (HOMA-IR).Vitamin D receptor (VDR) gene polymorphisms of FokI, ApaI, and TaqI were studied by PCR using the restriction fragment length polymorphism (RFLP) technique. Obese women with vitamin D deficiency had significant higher values of inflammatory and metabolic parameters compared to controls. Multivariable-logistic regression showed associations between 25(OH) D deficiency and metabolic components when comparing cases with controls. Moreover, cases carrying polymorphic alleles showed significant lower levels of serum 25(OH) D and higher HOMA-IR, blood pressure levels and lipid parameters compared to those with the wild type homozygote in obese cases with vitamin D deficiency. Vitamin D deficiency in Egyptian obese women with vitamin D deficiency is associated with abnormal metabolic components and abnormal inflammatory biomarkers. Moreover, VDR polymorphisms play important role in immune and inflammation status.

The MafB transcription factor is expressed in pancreatic α and β cells during development but becomes exclusive to α cells in adult rodents. -null ( ) mice were reported to have reduced α- and β-cell numbers throughout embryonic development. To further analyze the postnatal function of MafB in the pancreas, we generated endocrine cell-specific ( ) and tamoxifen-dependent ( ) knockout mice. mice exhibited reduced populations of insulin-positive (insulin) and glucagon cells at postnatal day 0, but the insulin cell population recovered by 8 weeks of age. In contrast, the Arx glucagon cell fraction and glucagon expression remained decreased even in adulthood. mice, with deleted after pancreas maturation, also demonstrated diminished glucagon cells and glucagon content without affecting β cells. A decreased Arx glucagon cell population in mice was compensated for by an increased Arx pancreatic polypeptide cell population. Furthermore, gene expression analyses from both and islets revealed that MafB is a key regulator of glucagon expression in α cells. Finally, both mutants failed to respond to arginine, likely due to impaired arginine transporter gene expression and glucagon production ability. Taken together, our findings reveal that MafB is critical for the functional maintenance of mouse α cells , including glucagon production and secretion, as well as in development.

Nerium oleander ( N. oleander ) is a well-known poisonous shrub that is frequently grown in gardens and public areas and contains numerous toxic compounds. The major toxic components are the cardiac glycosides oleandrin and neriin. The aim of our study was to evaluate the toxic effects of an ethanolic N. oleander leaf extract on haematological, cardiac, inflammatory, and serum biochemical parameters, as well as histopathological changes in the heart. N. oleander extract was orally administered for 14 and 30 consecutive days at doses of 100 and 200 mg of dried extract/kg of body weight in 0.5 mL of saline. The results showed significant increases in mean corpuscular volume, white blood cell counts, platelet counts, interleukins (IL-1 and IL-6), tumour necrosis factor alpha, C reactive protein, alanine aminotransferase, lactate dehydrogenase, creatine kinase and creatine kinase MB, especially at high doses. Marked pathological changes were perceived in the heart tissue. Thus, it can be concluded that exposure to N. oleander leaf extract adversely affects the heart and liver.

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Metabolic syndrome (MS) is a cluster of metabolic abnormalities. Obesity and MS are always accompanied by elevated oxidative stress which might affect cellular bio-molecules such as DNA. The aim of the present study is to investigate DNA damage profile in obese premenopausal women and its relation to the risk of MS, polycystic ovary syndrome (PCOS) and history of recurrent pre-eclampsia. The study included 90 obese women included cases with MS (n = 30), PCOS (n = 30) and previous history of recurrent preeclampsia (n = 30) and, age-matched healthy non-obese control women (n = 50). The assessment of leukocyte DNA damage was done by comet assay for all cases and controls. Anthropometry and biochemical parameters have been measured. Results showed that mean percent of DNA damage was significantly higher in MS, PCOS as well as in women with the recurrent preeclampsia as compared to healthy controls. The high level of mean DNA damage frequency in obese women was significantly associated with the increased number of metabolic syndrome components. Cases with 2, 3 and 3–5 components showed significantly higher levels of DNA damage than controls. Moreover, cases with 3–5 MS components showed significant higher DNA compared to those with the two components. Regarding PCOS, significant positive association between the mean frequency of DNA damage and waist circumference was observed. The study suggests that metabolic abnormalities, PCOS and recurrent pre-eclampsia might be contributed in development of DNA damage in obese women. DNA damage can serve as an early marker for obesity complications in premenopausal women.

The transcription factor MAFB is an important regulator of the development and differentiation of various organs and tissues. Previous studies have shown that MAFB is expressed in embryonic and adult mouse testes and is expected to act as the downstream target of retinoic acid (RA) to initiate spermatogenesis. However, its exact localization and function remain unclear. Here, we localized MAFB expression in embryonic and adult testes and analyzed its gene function using Mafb-deficient mice. We found that MAFB and c-MAF are the only large MAF transcription factors expressed in testes, while MAFA and NRL are not. MAFB was localized in Leydig and Sertoli cells at embryonic day (E) 18.5 but in Leydig cells, Sertoli cells, and pachytene spermatocytes in adults. Mafb-deficient testes at E18.5 showed fully formed seminiferous tubules with no abnormal structure or differences in testicular somatic cell numbers compared with those of control wild-type mice. Additionally, the expression levels of genes related to development and function of testicular cells were unchanged between genotypes. In adults, the expression of MAFB in Sertoli cells was shown to be stage specific and induced by RA. By generating Mafbfl/fl CAG-CreER™ (Mafb-cKO) mice, in which Cre recombinase was activated upon tamoxifen treatment, we found that the neonatal cKO mice died shortly upon Mafb deletion, but adult cKO mice were alive upon deletion. Adult cKO mice were fertile, and spermatogenesis maintenance was normal, as indicated by histological analysis, hormone levels, and germ cell stage-specific markers. Moreover, there were no differences in the proportion of seminiferous stages between cKO mice and controls. However, RNA-Seq analysis of cKO Sertoli cells revealed that the down-regulated genes were related to immune function and phagocytosis activity but not spermatogenesis. In conclusion, we found that MAFB is dispensable for fetal testis morphogenesis and spermatogenesis maintenance in adult mice, despite the significant gene expression in different cell types, but MAFB might be critical for phagocytosis activity of Sertoli cells.

Spermatogenesis is a complex and highly regulated process by which spermatogonial stem cells differentiate into spermatozoa. To better understand the molecular mechanisms of the process, the Cre/loxP system has been widely utilized for conditional gene knockout in mice. In this study, we generated a transgenic mouse line that expresses Cre recombinase under the control of the 2.5 kbp of the Prolactin family 3, subfamily b, member 1 (Prl3b1) gene promoter (Prl3b1-cre). Prl3b1 was initially reported to code for placental lactogen 2 (PL-2) protein in placenta along with increased expression toward the end of pregnancy. PL-2 was found to be expressed in germ cells in the testis, especially in spermatocytes. To analyze the specificity and efficiency of Cre recombinase activity in Prl3b1-cre mice, the mice were mated with reporter R26GRR mice, which express GFP ubiquitously before and tdsRed exclusively after Cre recombination. The systemic examination of Prl3b1-cre;R26GRR mice revealed that tdsRed-positive cells were detected only in the testis and epididymis. Fluorescence imaging of Prl3b1-cre;R26GRR testes suggested that Cre-mediated recombination took place in the germ cells with approximately 74% efficiency determined by in vitro fertilization. In conclusion, our results suggest that the Prl3b1-cre mice line provides a unique resource to understand testicular germ-cell development. genesis 54:389-397, 2016. © 2016 Wiley Periodicals, Inc.

BackgroundAdipose tissue hormones, Adipokines, play an important role in obesity-associated complications. Apelin has recently been added to the family of adipokines. The aim of this study was to evaluate the relationship between serum apelin levels and metabolic abnormal parameters in Egyptian obese women.Materials and methodsThe study included 400 unrelated women; they were 200 obese women and 200 non- obese matched healthy women. All participants underwent clinical, anthropometric and biochemical examinations. Insulin resistance (IR) was determined by the homeostasis model assessment of insulin resistance (HOMA-IR). Serum apelin levels and obesity biomarkers were measured using enzyme-linked immunoassay (ELISA) kits. Fat mass was measured by Tanita Body Composition Analyzer.ResultsObese women showed significant higher levels of serum apelin, leptin, triglycerides, LDL-C, total cholesterol, fasting insulin HOMA-IR and blood pressure levels than controls. Significant positive correlations between apelin and leptin levels with abnormal metabolic markers were noted in obese women.ConclusionThe present study suggests the significant role that might be mediated by apelin for developing abnormal metabolic parameters among Egyptian obese women.