The purpose of this study is to investigate the molecular interactions and potential therapeutic uses of Eltrombopag (EPAG), a small molecule that activates the cMPL receptor. EPAG has been found to be effective in increasing platelet levels and alleviating thrombocytopenia. We utilized computational techniques to predict and confirm the complex formed by the ligand (EPAG) and the Thrombopoietin receptor (TPO-R) cMPL, elucidating the role of RAS, JAK-2, STAT-3, and other essential elements for downstream signaling.
View Article and Find Full Text PDFMurine neural stem cells (NSCs) were recently shown to release piRNA-containing exosomes/microvesicles (Ex/Mv) for exerting antiviral immunity, but it remains unknown if these Ex/Mv could target SARS-CoV-2 and whether the PIWI-piRNA system is important for these antiviral actions. Here, using in vitro infection models, we show that hypothalamic NSCs (htNSCs) Ex/Mv provided an innate immunity protection against SARS-CoV-2. Importantly, enhanced antiviral actions were achieved by using induced Ex/Mv that were derived from induced htNSCs through twice being exposed to several RNA fragments of SARS-CoV-2 genome, a process that was designed not to involve protein translation of these RNA fragments.
View Article and Find Full Text PDFBy testing pseudotyped SARS-CoV-2 and HIV-based lentivirus, this study reports that exosomes/microvesicles (Ex/Mv) isolated from murine hypothalamic neural stem/progenitor cells (htNSC) or subtype htNSC as well as hippocampal NSC have innate immunity-like actions against these RNA viruses. These extracellular vesicles also have a cell-free innate antiviral action by attacking and degrading viruses. We further generated the induced versions of Ex/Mv through prior viral exposure to NSCs and found that these induced Ex/Mv were stronger than basal Ex/Mv in reducing the infection of these viruses, suggesting the involvement of an adaptive immunity-like antiviral function.
View Article and Find Full Text PDFBisphenol-B (BPB), an analogue of bisphenol-A is used in the plastic industry. It has been found to leach from plastic containers leading to its contamination in canned food products. Moreover, it has also been detected in human samples such as sera and urine.
View Article and Find Full Text PDFAlthough Bisphenol-A (BPA) has been found to exhibit toxicological properties such as genotoxicity and oxidative stress, yet there is very little data available on its analogues. Since the replacement of BPA by its analogues, their presence has been found to increase in the environment leading to increased human exposure that makes it essential to investigate their toxic effects. Therefore, we explored the genotoxic and oxidative potential of two common BPA analogues, Bisphenol-B (BPB) and Bisphenol-F (BPF).
View Article and Find Full Text PDFRecent imposition of restriction on the use of Bisphenol-A (BPA) paved the way for entry of its analogues in the market. Bisphenol-B and Bisphenol-F are the major analogues of commercial value. Thus, their increasing production and application make them vulnerable to human exposure.
View Article and Find Full Text PDFInteraction studies of bisphenol analogues; biphenol-A (BPA), bisphenol-B (BPB), and bisphenol-F (BPF) with bovine serum albumin (BSA) were performed using multi-spectroscopic and molecular docking studies at the protein level. The mechanism of binding of bisphenols with BSA was dynamic in nature. SDS refolding experiments demonstrated no stabilization of BSA structure denatured by BPB, however, BSA denatured by BPA and BPF was found to get stabilized.
View Article and Find Full Text PDFSpectrochim Acta A Mol Biomol Spectrosc
February 2018
Guggulsterone, a sterol found in plants is used as an ayurvedic medicine for many diseases such as obesity, internal tumors, ulcers etc. E and Z are two isoforms of guggulsterone, wherein guggulsterone-E (GUGE) has also been shown to have anticancer potential. Most of the anticancer drugs target nucleic acids.
View Article and Find Full Text PDFMetformin has been known for its antidiabetic effects for decades and is used as a first line therapy in type 2 diabetes. But recently its anticancer potential has also been discovered. Metformin targets many pathways that play an important role in cancer cell proliferation and angiogenesis, mTORC1 signaling is a crucial pathway among them.
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