Gene sequence mutations may alter mRNA transcription, transcript stability, protein translation, protein stability and protein folding. Apolipoprotein L1 (APOL1) has two sets of sequence variants that are risk factors for kidney disease development, APOL1G1 (substitution mutation) and APOL1G2 (deletion mutation). Our present study focuses on the impact of these variants on APOL1 mRNA transcription and translation. APOL1 plasmids (EV, G0, G1 and G2) were transfected into human embryonic kidney (HEK) 293T cells. APOL1 variant expression was observed to be significantly lower than that of APOL1G0. Podocyte cell lines stably expressing APOL1 transgenes also showed lower levels of APOL1 expression of APOL1 variants (G1 and G2) compared with APOL1G0 by Western blotting and FACS analysis. The enhanced expression of GRP78 by podocytes expressing APOL1 variants would indicate endoplasmic reticulum (ER) stress. Bioinformatics evaluation using two different programs (MUPro and I-Mutant 2.0) predicted that APOL1 variants were less stable than APOL1G0. Concomitant with protein levels, APOL1 mRNA levels were also depressed following induction of APOL1 variant compared with APOL1G0 in both proliferating and differentiated podocytes. APOL1 mRNA transcript stability was tested after actinomycin D pulsing; APOL1G1 and APOL1G2 mRNAs transcript decayed 10–15% and 15–20% (within a period of 0.5–3 h) respectively. Our data suggest that down-regulated APOL1 protein expression in APOL1 variants is due to compromised transcription and decay of the APOL1 variant transcripts.

Background:Molecules stimulating regeneration and proliferation of cells are of significance in combating ailments caused due to tissue injury, inflammation, and degenerative disorders. Moringa oleifera is one of the most valued food plants having the profile of important nutrients and impressive range of medicinal uses.Objective:To evaluate the potential of M. oleifera aqueous leaf and flower extracts to promote the proliferation of cells and explore their effect on cancer cell lines for assessment of safety.Materials and Methods:Aqueous leaf and flower extracts of M. oleifera were investigated for effect on rat-derived primary fibroblast, mesenchymal stem cells (MSCs), and cancer cell lines using cell proliferation assay. They were also tested and compared for wound healing, angiogenesis, and hepatoprotective effect using in vitro assays.Results:Statistically significant increase in the proliferation of primary rat fibroblast, MSCs, and angiogenesis was observed after treatment with aqueous flower extract. The aqueous leaf extract determined a comparatively moderate increment in the proliferation of MSCs and angiogenesis. It however showed prominent cytotoxicity to cancer cell lines and a significant hepatoprotective effect.Conclusion:A very clear difference in response of the two extracts to different types of cells was detected in this study. The aqueous flower extract exhibited a higher potential to stimulate cell proliferation while not exerting the same effect on cancer cell lines. The leaf extract on the other hand, had a prominent antitumor and hepatoptotective effects.SUMMARY Moringa oleifera flower extract showed significant ability to promote proliferation of rat fibroblast and mesenchymal stem cells. The extract also had prominent angiogenic and hepatoprotective effects.The extract did not influence proliferation of cancer cell lines indicating its safety for human consumption and use in pharmaceuticals.The Moringa oleifera leaf extract showed relatively less potential to stimulate cells but had prominent cytotoxic effect on cancer cell lines. Abbreviations Used: ALT: Alanine transaminase, AST: Asparatate amino transferase, ATCC: American type culture collection, BMMSC: Bone marrow mesenchymal stem cells (used in this paper), CAM: Chick chorioallantoic membrane, CCl4: Carbon tetra chloride, DMEM: Dulbecco's modified Eagle medium, DMSO: Dimethyl sulfoxide, EDTA: Ethylene diamine tetraacetic acid, HBL 100: Human breast epithelial cell line, Mcf-7: Human breast adenocarcinoma cell line, aMEM: Minimum Essential Medium Eagle alpha modification, MOF: Moringa oleifera aqueous flower extract (used in this paper), MOL: Moringa oleifera aqueos leaf extract (Used in this paper), OD: Optical density, PBS: Phosphate buffered saline

Background: Multiple studies have shown that children with HIV are at risk for impaired cognition. However, there are limited data on longitudinal cognitive outcomes in children with HIV. Methods:We conducted a prospective cohort study of 208 perinatally infected children with HIV ages 8-17 years, all treated with antiretroviral therapy, and 208 HIV-exposed uninfected controls. Participants were followed for 2 years. Cognition was assessed with a custom NIH Toolbox Cognition Battery, and tests were combined to generate a Summary Cognition Score (SCS). The contribution of potential risk factors to outcomes was explored using regression models and group-based trajectory modeling.Results: HIV was strongly associated with lower SCS at baseline [b-14, 95% confidence interval (CI): 220 to 27, P , 0.001]. Change scores over time were similar between groups, but poorer average performance in children with HIV persisted at the 2-year follow-up visit (adjusted b = 211, 95% CI: 222 to 20.3, P = 0.04). Other than HIV, the strongest predictors of baseline SCS included socioeconomic status index (b =3, 95% CI: 1, 5, P = 0.004), history of growth stunting (b=214, 95% CI: 223 to 26, P = 0.001), history of CD4 count below 200 (b = 219, 95% CI: 235 to 22, P = 0.02), and history of World Health Organization stage 4 disease (b = 210, 95% CI: 219 to 20.2, P = 0.04). In the group-based trajectory model, HIV+ status predicted membership in the lowest performing trajectory group (odds ratio 2.5, 95% CI: 1.2 to 5.1, P = 0.01). Conclusions:Children with HIV are at risk of poor cognitive outcomes, despite chronic treatment with antiretroviral therapy.

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Background: Tobacco consumption is a major health problem worldwide. India the second largest consumer of tobacco products and the third largest producer of tobacco in the world that places India in the second rank after China in tobacco-related mortalities. Commonly, the habit of tobacco consumption begins at adolescence, carry forwarded into adult life. Hence, if awareness has been created in adolescence then will help to eradicate tobacco consumption habit from India. Hence, a comparative study to determine the awareness regarding hazardous effect of tobacco consumption habit among rural and urban children has been planned. Materials and Methods: A cross-sectional study was conducted among schoolgoing children from rural and urban areas. The study was conducted in schools present in the districts of central India on students from classes 3rd–10th standard (age 8–16 years). Total numbers of students enrolled were about 806, of which about 380 students were from rural schools and 426 students were from urban schools. A pretested, close-ended, self-administered questionnaire that was derived from the GYTS-based questionnaire has been distributed after consent, and then analysis was done. Results: The prevalence of tobacco use in urban and rural areas has been calculated which came more in rural areas with 5.5%, age of commencement of habit at rural areas was from 10 years of age while in urban it was in teen ages, i.e., from 12 years. Furthermore, the smokeless form of tobacco was preferred in rural areas while in urban it was smoke form of tobacco. In rural area parents, 3.9% knowing about habit of their children and themselves were also habitual while urban areas parents were unaware of habit. Conclusion: There is more prevalence of tobacco consumption in rural schoolgoing children than urban schoolgoing children. Urban and rural area children were aware of hazardous effect of tobacco but still consumption is more in children from rural area. Hence, the focus of tobacco cessation program should be in rural area as well as in urban areas. However, the programs should be specifically designed for the area where it should be implementing keeping the difference between socioeconomic status in mind to eradicate tobacco consuming habit from India.