Oral lesions and immune status of HIV infected adults from eastern Nepal

Objective: To document the prevalence, age and gender distribution of oral lesions in HIV infected adults and the influence of highly active antiretroviral therapy and correlate them to the immune status of the patients. Materials and Methods: Oral lesions were diagnosed by a detailed physical examination by trained and calibrated examiners according to the case definitions established by the Oral HIV/AIDS research alliance. Demographic details, risk behavior patterns and oral symptoms and habits were collected by a questionnaire. Results: 81 patients; 54 men and 27 women aged between 20 ' 55 years participated in the study. A total of 49 patients; 60.5% had some oral lesion when examined. Oral candidiasis (21 %) and oral melanosis (21%) were the most common lesions, followed by linear gingival erythema, oral hairy leukoplakia, necrotizing ulcerative periodontitis/ gingivitis, herpes labialis, parotid gland enlargement and reccurent apthous ulcers. Oral hairy leukoplakia was exclusively seen in men (p=0.018). All six cases of herpes simplex lesion were seen in non - anti retro viral group (p=0.073) while oral candidiasis was commonly noted in the anti retro viral group (p=0.073). Lowering CD4 counts had the strongest association with the prevalence of oral candidasis (p=0.012), pseudomembranous candidiasis (p=0.014) and oral hairy leukoplakia (p= 0.065). Conclusion: This study shows a high prevalence of oral candidiasis, melanosis, linear gingival erythema and oral hairy leukoplakia in the patients

BASP1 labels neural stem cells in the neurogenic niches of mammalian brain

The mechanisms responsible for determining neural stem cell fate are numerous and complex. To begin to identify the specific components involved in these processes, we generated several mouse neural stem cell (NSC) antibodies against cultured mouse embryonic neurospheres. Our immunohistochemical data showed that the NSC-6 antibody recognized NSCs in the developing and postnatal murine brains as well as in human brain organoids. Mass spectrometry revealed the identity of the NSC-6 epitope as brain abundant, membrane-attached signal protein 1 (BASP1), a signaling protein that plays a key role in neurite outgrowth and plasticity. Western blot analysis using the NSC-6 antibody demonstrated multiple BASP1 isoforms with varying degrees of expression and correlating with distinct developmental stages. Herein, we describe the expression of BASP1 in NSCs in the developing and postnatal mammalian brains and human brain organoids, and demonstrate that the NSC-6 antibody may be a useful marker of these cells.We are grateful to Grigori Enikolopov for critically reviewing the manuscript, Dwight Martin for expert technical assistance, and Huda Zoghbi for the use of flow cytometer. This work was supported by the NIGMS (5R01GM120033), U.S. Army Medical Research (DAMD170110754), Cynthia and Antony Petrello Endowment, and Mark A. Wallace Endowment (M.M.S.); the National Institute of Diabetes and Digestive and Kidney Diseases (T32DK07521-16) (L.N.M.); MINECO SAF-2015-70866R (J.M.E), FPI MICINN predoctoral Fellowship (I.D.); the Proteomics Center at Stony Brook University (NIH/NCRR 1S10 RR023680), and the BCM IDDRC Grant (P50HD10355) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development for use of the Microscopy Core facilities, the RNA In Situ Hybridization Core facility, and the Human Neuronal Differentiation Core facilit

Oleic acid is an endogenous ligand of TLX/NR2E1 that triggers hippocampal neurogenesis

Altres ajuts: Cancer Prevention and Research Institute of Texas (CPRIT), Core Facility Support Award (CPRIT-RP180672, R1313, 1R01GM138781-01); NIH (CA125123, RR024574); Eunice Kennedy Shriver National Institute of Child Health & Human Development of the NIH (P50HD103555); BCM start-up funds; Albert and Margaret Alkek Foundation; McNair Medical Institute; Robert and Janice McNair Foundation; BCM Seed Funding (1P20CA221731-01A1); National Institute of General Medical Sciences (R01 GM120033); Cynthia and Antony Petrello Endowment; Mark A. Wallace Endowment; McKnight Foundation; Dana Foundation; BCM Computational and Integrative Biomedical Research Center seed grant.Neural stem cells, the source of newborn neurons in the adult hippocampus, are intimately involved in learning and memory, mood, and stress response. Despite considerable progress in understanding the biology of neural stem cells and neurogenesis, regulating the neural stem cell population precisely has remained elusive because we have lacked the specific targets to stimulate their proliferation and neurogenesis. The orphan nuclear receptor TLX/NR2E1 governs neural stem and progenitor cell self-renewal and proliferation, but the precise mechanism by which it accomplishes this is not well understood because its endogenous ligand is not known. Here, we identify oleic acid (18:1ω9 monounsaturated fatty acid) as such a ligand. We first show that oleic acid is critical for neural stem cell survival. Next, we demonstrate that it binds to TLX to convert it from a transcriptional repressor to a transcriptional activator of cell-cycle and neurogenesis genes, which in turn increases neural stem cell mitotic activity and drives hippocampal neurogenesis in mice. Interestingly, oleic acid-activated TLX strongly up-regulates cell cycle genes while only modestly up-regulating neurogenic genes. We propose a model in which sufficient quantities of this endogenous ligand must bind to TLX to trigger the switch to proliferation and drive the progeny toward neuronal lineage. Oleic acid thus serves as a metabolic regulator of TLX activity that can be used to selectively target neural stem cells, paving the way for future therapeutic manipulations to counteract pathogenic impairments of neurogenesis

Trailing TRAIL Resistance: Novel Targets for TRAIL sensitization in Cancer cells

Resistance to chemotherapeutic drugs is the major hindrance in the successful cancer therapy. The tumor necrosis factor- related apoptosis- inducing ligand (TRAIL) is a member of the Tumor Necrosis Factor (TNF) family of ligands which initiates apoptosis in cancer cells through interaction with the death receptors DR4 and DR5. TRAIL is perceived as an attractive chemotherapeutic agent as it specifically targets cancer cells while sparing the normal cells. However TRAIL therapy has a major limitation as a large number of the cancer develop resistance towards TRAIL and escape from the destruction by the immune system. Therefore, elucidation of the molecular targets and signaling pathways responsible for TRAIL resistance is imperative for devising effective therapeutic strategies for TRAIL resistant cancers. Although, various molecular targets leading to TRAIL resistance are well studied, recent studies have implicated that the contribution of some key cellular processes towards TRAIL resistance need to be fully elucidated. These processes primarily include aberrant protein synthesis, protein misfolding, ubiquitin regulated death receptor expression, metabolic pathways, epigenetic deregulation and metastasis. Novel synthetic/natural compounds that could inhibit these defective cellular processes may restore the TRAIL sensitivity and combination therapies with such compounds may resensitize TRAIL resistant cancer cells towards TRAIL-induced apoptosis. In this review, we have summarized the key cellular processes associated with TRAIL resistance and their status as therapeutic targets for novel TRAIL-sensitizing agents