Beta-sitosterol (BS) is a phytosterol, widely distributed throughout the plant kingdom and known to be involved in the stabilization of cell membranes. To compile the sources, physical and chemical properties, spectral and chromatographic analytical methods, synthesis, systemic effects, pharmacokinetics, therapeutic potentials, toxicity, drug delivery and finally, to suggest future research with BS, classical as well as on-line literature were studied. Classical literature includes classical books on ethnomedicine and phytochemistry, and the electronic search included Pubmed, SciFinder, Scopus, the Web of Science, Google Scholar, and others. BS could be obtained from different plants, but the total biosynthetic pathway, as well as its exact physiological and structural function in plants, have not been fully understood. Different pharmacological effects have been studied, but most of the mechanisms of action have not been studied in detail. Clinical trials with BS have shown beneficial effects in different diseases, but long-term study results are not available. These have contributed to its current status as an “orphan phytosterol”. Therefore, extensive research regarding its effect at cellular and molecular level in humans as well as addressing the claims made by commercial manufacturers such as the cholesterol lowering ability, immunological activity etc. are highly recommended.
SummaryActivation of the alpha7 receptor (a7nAChR) has been shown to be important in inflammation and immune regulation, and is also essential in the neural cholinergic anti-inflammatory pathway. The aim of this study was to investigate the role of a7nAChR in the development of experimental arthritis and immune activation. Mice lacking the a7nAChR were immunized with collagen II and the development of arthritis was assessed. Another group of a7nAChR-deficient mice was immunized with ovalbumin, spleen and lymph node cells were isolated and the proliferative responses to restimulation with ovalbumin or concanavalin A were investigated. We could demonstrate significantly milder arthritis and less cartilage destruction, together with a decrease of T cell content in lymph nodes in mice lacking the a7nAChR compared to wild-type controls. In addition, mice lacking the a7nAChR had a deficient proliferative response to concanavalin A, whereas antigen presentation-dependent proliferation was not affected. These results indicate important roles for a7nAChR in arthritis development as well as in regulation of T cell-dependent immunological mechanisms. In addition, the data implicate a7nAChR as a therapeutic target for modulation of adaptive immune responses.
Nipah virus (NiV) is highly pathogenic single-stranded negative sense RNA virus. It can cause severe encephalitis and respiratory disease in humans. In addition, NiV infects a large range of host including mammals. As a result of its higher zoonotic potential and pathogenicity for human, it has been rated as an alert in recent days. A therapeutic treatment or vaccines has become elusive to fight against this virus. In this study, the attachment (G) and fusion (F) glycoproteins of NiV, responsible for the viral attachment and entry to the host cell, were selected to develop epitope-based vaccine against Nipah virus. Epitopes were identified from the conserved region of G and F protein of NiV. Both B-cell and T-cell immunity were checked to affirm it that these epitopes will be able to induce humoral and cellular immunity. A total of 6 T-cell epitopes and 19 significant HLA-epitope interactions were identified. Eventually it has shown an acceptable percentage in population coverage (46.45 %) and efficient binding with HLA molecule by molecular docking study.
A major challenge in evaluating the success of HIV eradication approaches is the need for accurate measurement of persistent HIV during effective antiretroviral therapy (ART). Previous studies have reported that the anti-HIV antibody assay “luciferase immuno-precipitation systems (LIPS)” can distinguish HIV-infected individuals harboring different sizes of the viral reservoirs. We performed antibody profiling of HIV-1 proteomes using LIPS in viremic progressors (n = 38), elite controllers (ECs; n = 19) and patients with fully suppressive long-term antiretroviral therapy (ART) (n = 19) (mean 17 years). IgG was quantified against six HIV-1 fusion proteins: p24, gp41, RT, Tat, integrase and protease. Lower antibody levels to all six-fusion proteins were observed in long-term ART patients compared to viremics (p < 0.05). In contrast ECs had lower antibody levels only against Tat and Integrase (p < 0.05). Principal component analysis and cluster-network analysis identified that 68% (13/19) of the long-term ART patients clustered together with 26% (5/19) ECs. The remaining ECs clustered together with the viremics indicating non-homogeneity among the ECs. The low anti-HIV levels in the long-term treated patients may indicate a restricted remaining viral replication. In contrast, the higher levels in ECs suggest a continuous viral expression with a limited concomitant release of extracellular virus.
Alprazolam is used as an anxiolytic drug for generalized anxiety disorder and it has been reported to produce sedation and anterograde amnesia. In the current study, we randomly divided 26 healthy male volunteers into two groups: one group taking alprazolam 0.5 mg and the other taking placebo daily for two weeks. We utilized the Cambridge Neuropsychological Test Automated Battery (CANTAB) software to assess the chronic effect of alprazolam. We selected Paired Associates Learning (PAL) and Delayed Matching to Sample (DMS) tests for memory, Rapid Visual Information Processing (RVP) for attention, and Choice Reaction Time (CRT) for psychomotor performance twice: before starting the treatment and after the completion of the treatment. We found statistically significant impairment of visual memory in one parameter of PAL and three parameters of DMS in alprazolam group. The PAL mean trial to success and total correct matching in 0-second delay, 4-second delay, and all delay situation of DMS were impaired in alprazolam group. RVP total hits after two weeks of alprazolam treatment were improved in alprazolam group. But such differences were not observed in placebo group. In our study, we found that chronic administration of alprazolam affects memory but attentive and psychomotor performance remained unaffected.
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) belongs to the coronaviridae family. In spite of several outbreaks in the very recent years, no vaccine against this deadly virus is developed yet. In this study, the receptor binding domain (RBD) of Spike (S) glycoprotein of MERS-CoV was analyzed through Computational Immunology approach to identify the antigenic determinants (epitopes). In order to do so, the sequences of S glycoprotein that belong to different geographical regions were aligned to observe the conservancy of MERS-CoV RBD. The immune parameters of this region were determined using different in silico tools and Immune Epitope Database (IEDB). Molecular docking study was also employed to check the affinity of the potential epitope towards the binding cleft of the specific HLA allele. The N-terminus RBD (S367-S606) of S glycoprotein was found to be conserved among all the available strains of MERS-CoV. Based on the lower IC50 value, a total of eight potential T-cell epitopes and 19 major histocompatibility complex (MHC) class-I alleles were identified for this conserved region. A 9-mer epitope CYSSLILDY displayed interactions with the maximum number of MHC class-I molecules and projected the highest peak in the B-cell antigenicity plot which concludes that it could be a better choice for designing an epitope based peptide vaccine against MERSCoV considering that it must undergo further in vitro and in vivo experiments. Moreover, in molecular docking study, this epitope was found to have a significant binding affinity of -8.5 kcal/mol towards the binding cleft of the HLA-C*12:03 molecule.
The aim of the current study was to evaluate the antioxidant, antimicrobial and thrombolytic potentials of the exocarp of Spondias pinnata fruits. The crude ethanolic extract of the exocarp of S. pinnata fruit was partitioned successively by solvents of different polarity. All fractions were then investigated for qualitative preliminary phytochemical screening by specific standard procedure. The antioxidant potential of all fractions were then evaluated in terms of total phenolic content, total flavonoid content, DPPH free radical scavenging potential, reducing potential and total antioxidant capacity by specific standard procedure. The disc diffusion method was incorporated to evaluate the in vitro antimicrobial activity on nutrient agar medium. The highest total phenolic content was found in aqueous fraction (570.20±0.48 mg GAE/g of dried extract) while the lowest in the n-Hexane fraction (337.51±0.21 mg GAE/g of dried extract). However, ethyl acetate fraction exhibited the highest flavonoid content which amounted to 132.27±0.25 mg quercetin equivalents/g of dried extract. Likewise, ethyl acetate fraction showed the highest antioxidant capacity (21.61±0.11 g of L-ascorbic acid equivalents/g of dried extract) along with the lowest IC 50 (1.72±0.39 µg/ml) & EC 50 (2.25±0.75 µg/ml) value. However, DPPH free radical scavenging activity and reducing power of all fractions were found to be concentration dependent. Nonetheless, comparatively more polar fractions (ethyl acetate and aqueous fraction) were found to be ineffective against all the microbial strains except S. dysentery and P. aeruginosa while nonpolar fractions (n-hexane and dichloromethane fraction) showed variable antimicrobial activity. In addition, all fractions produced statistically significant (P<0.05 for ethyl acetate and aqueous fraction, P<0.001 for others) thrombolytic activity. To conclude, our present study suggested that exocarp of S. pinnata fruit exhibits antimicrobial activity against a wide variety of strains while it produces noteworthy
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