This study suggests an association between HLA-B*1502 and carbamazepine-induced SJS in Indian patients.
The novel Corona Virus Disease (COVID-19) pandemic has spread a blaze of increasing fatality rates across the world. The dearth of potential vaccines has left the survival of mankind with doubts. The development of multi-epitope vaccine in this current situation could be a possible COVID treatment. We have designed a novel multi-epitope, multi-protein vaccine with different proteins of Severe Acute Respiratory Syndrome - Corona Virus -2 (SARS-CoV-2) with immuno-informatics approaches, which has been validated in silico to be stable and potential. It has been prepared with Cytotoxic T-cell (TC) and Helper T-cell (TH) binding epitopes overlapping with B-cell binding epitopes predicted for 6 proteins conserved among 4 different viral strains isolated across the world. Both the humoral and cell-mediated immune responses are ensured due to the presence of T cell and B-cell inducing epitopes along with interferon-gamma inducing epitopes present in the vaccine. The final vaccine construct comprises of an adjuvant at the N terminal, Cytotoxic T Lymphocyte and Helper T Lymphocyte epitopes. The construct showed potential antigenicity and was non-allergic. The molecular docking of the refined, validated tertiary structure model of the vaccine was performed with immune-stimulatory Toll Like Receptors (TLR), TLR-2,3,4. The study of binding energetics of the docked complexes revealed binding interactions of receptor with vaccine. The immune simulation of the vaccine even confirmed the initiation of elevated host immune responses. The efficient translation of the vaccine in an expression vector was confirmed with in silico cloning approach. Certainly, the development of such vaccine candidate could possibly be an effective therapy for COVID-19.
Lynch syndrome (LS) is a cancer predisposition disorder wherein patients have a 70–80% lifetime risk of developing colorectal cancers (CRC). Finding germline mutations in predisposing genes allows for risk assessment of CRC development. Here we report a germline heterozygous frame-shift mutation in the mismatch repair MLH1 gene which was identified in members of two unrelated LS families. Since defects in DNA mismatch repair genes generate frame-shift mutations giving rise to highly immunogenic neoepitopes, we postulated that vaccination with these mutant peptide antigens could offer promising treatment options to LS patients. To this end we performed whole-exome and RNA seq analysis on the blood and tumour samples from an LS-CRC patient, and used our proprietary neoepitope prioritization pipeline OncoPeptVAC to select peptides, and confirm their immunogenicity in an ex vivo CD8+ T cell activation assay. Three neoepitopes derived from the tumour of this patient elicited a potent CD8+ T cell response. Furthermore, analysis of the tumour-associated immune infiltrate revealed CD8+ T cells expressing low levels of activation markers, suggesting mechanisms of immune suppression at play in this relapsed tumour. Taken together, our study paves the way towards development of a cancer vaccine to treat or delay the onset/relapse of LS-CRC.
Cancer remains to be an unresolved medical challenge despite of tremendous advancement in basic science research and clinical medicine. One of the major limitations is due to the side effects of chemotherapy which remains to be palliative without offering any permanent cure for cancer. Cancer stem cells (CSCs) are the subpopulation of cells in tumors that remain viable even after surgery, chemo- and radio-therapy that eventually responsible for tumor relapse. Hence, by eliminating non-stem cancer cells and cancer stem cells from the patient, permanent cure is expected. Phytochemicals have been under the intensive study to target these CSCs effectively and permanently as they do not cause any side effects. Resveratrol (RSV) is one such compound attaining lot of interest in recent days to target CSCs either alone or in combination. RSV has been used by several researchers to target cancer cells in a variety of disease models, however its CSC targeting abilities are under intensive study at present. This review is to summarize the effects of RSV under in vitro and in vivo conditions along with advantages and disadvantages of its uses against cancer cells and cancer stem cells. From the first reports on phytochemical applications against cancer and cancer stem cells in 1997 and 2002 respectively followed by later reports, up to date observations and developments are enlisted from PubMed in this comprehensive review. RSV is shown to be a potential compound having impact on altering the signal transduction pathways in cancer cells. However, the effects are variable under in vitro and in vivo conditions, and also with its use alone or in combination with other small molecules. Past research on RSV is emphasizing the importance of in vivo experimental models and clinical trials with different prospective combinations, is a hope for future promising treatment regimen.
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