Macgregorterp3801

High-throughput metabolite profiling provides the opportunity to reveal metabolic mechanisms and identify biomarkers. Psoriasis is an immune-mediated chronic inflammatory disease. However, the role of metabolism in psoriasis pathogenesis remains unclear. Methods Plasma samples of individuals (45 psoriasis and 45 sex-, age-, and BMI-matched healthy controls) were collected. Non-targeted metabolomics and amino acid- or carnitine-targeted metabolomics were conducted, then, plasma samples of mice induced by imiquimod (IMQ) were subjected to the amino acid- and carnitine-targeted metabolomic profiling. Flow cytometry was used to study the effect of L-carnitine (LC(C0)) on IMQ-induced psoriatic inflammation. Results Through the non-targeted metabolomics approach, we detected significantly altered amino acids and carnitines in psoriasis patients. Amino acid-targeted metabolomic profiling identified 37 amino acids altered in psoriasis, of these 23 were markedly upregulated, including essential amino acids (EAAs), and branched-chain amino acids (BCAAs), whereas glutamine, cysteine, and asparagine were significantly down-regulated. Carnitine-targeted metabolomic profiling identified 40 significantly altered carnitines, 14 of which included palmitoylcarnitine (C16) and were markedly downregulated in psoriasis, whereas hexanoylcarnitine (C6) and 3-OH-octadecenoylcarnitine (C181-OH) were significantly upregulated. Interestingly, glutamine, asparagine, and C16 levels were negatively correlated with the PASI score. Moreover, a higher abundance of LC(C0) was associated with markedly reduced IMQ-induced epidermal thickening and infiltration of Th17 cells in skin lesions, indicating LC(C0) supplementation as a potential therapy for psoriasis treatment. Conclusion Our results suggested the metabolism of amino acids and carnitines are significantly altered in psoriasis, especially the metabolism of EAAs, BCAAs, and LC(C0), which may play key roles in the pathogenesis of psoriasis.The coronavirus disease 2019 (COVID-19) is a viral disease caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that affects the respiratory system of infected individuals. COVID-19 spreads between humans through respiratory droplets produced when an infected person coughs or sneezes. The COVID-19 outbreak originated in Wuhan, China at the end of 2019. As of 29 Sept 2020, over 235 countries, areas or territories across the globe reported a total of 33,441,919 confirmed cases, and 1,003,497 confirmed deaths due to COVID-19. Individuals of all ages are at risk for infection, but in most cases disease severity is associated with age and pre-existing diseases that compromise immunity, like cancer. Numerous reports suggest that people with cancer can be at higher risk of severe illness and related deaths from COVID-19. Therefore, managing cancer care under this pandemic is challenging and requires a collaborative multidisciplinary approach for optimal care of cancer patients in hospital settings. In this comprehensive review, we discuss the impact of the COVID-19 pandemic on cancer patients, their care, and treatment. Further, this review covers the SARS-CoV-2 pandemic, genome characterization, COVID-19 pathophysiology, and associated signaling pathways in cancer, and the choice of anticancer agents as repurposed drugs for treating COVID-19.Rationale Brain-derived neurotrophic factor precursor (proBDNF) is expressed in the central nervous system (CNS) and the immune system. However, the role of proBDNF in the pathogenesis of multiple sclerosis (MS) is unknown. Methods Peripheral blood and post-mortem brain and spinal cord specimens were obtained from multiple sclerosis patients to analyze proBDNF expression in peripheral lymphocytes and infiltrating immune cells in the lesion site. The proBDNF expression profile was also examined in the experimental autoimmune encephalomyelitis (EAE) mouse model, and polyclonal and monoclonal anti-proBDNF antibodies were used to explore their therapeutic effect in EAE. Finally, the role of proBDNF in the inflammatory immune activity of peripheral blood mononuclear cells (PBMCs) was verified in vitro experiments. Results High proBDNF expression was detected in the circulating lymphocytes and infiltrated inflammatory cells at the lesion sites of the brain and spinal cord in MS patients. In the EAE mouse model, proBDNF was upregulated in CNS and in circulating and splenic lymphocytes. Systemic but not intracranial administration of anti-proBDNF blocking antibodies attenuated clinical scores, limited demyelination, and inhibited proinflammatory cytokines in EAE mice. Immuno-stimulants treatment increased the proBDNF release and upregulated the expression of p75 neurotrophic receptors (p75NTR) in lymphocytes. The monoclonal antibody against proBDNF inhibited the inflammatory response of PBMCs upon stimulations. Conclusion The findings suggest that proBDNF from immune cells promotes the immunopathogenesis of MS. Monoclonal Ab-proB may be a promising therapeutic agent for treating MS.Rationale PLAGL2 (pleomorphic adenoma gene like-2), a zinc finger PLAG transcription factor, is aberrantly expressed in several malignant tumors. However, the biological roles of PLAGL2 and its underlying mechanism in gastric cancer (GC) remain unclear. Methods A series of experiments in vitro and in vivo were conducted to reveal the role of PLAGL2 in GC progression. Results The data revealed that PLAGL2 promotes GC cell proliferation, migration, invasion, and EMT in vitro and in vivo. Mechanistically, we demonstrated the critical role of PLAGL2 in the stabilization of snail family transcriptional repressor 1 (Snail1) and promoting Snail1-mediated proliferation and migration of GC cells. PLAGL2 activated the transcription of deubiquitinase USP37, which then interacted with and deubiquitinated Snail1 protein directly. In addition, GSK-3β-dependent phosphorylation of Snail1 protein is essential for USP37-mediated Snail1 deubiquitination regulation. selleck chemical Conclusions In general, PLAGL2 promotes the proliferation and migration of GC cells through USP37-mediated deubiquitination of Snail1 protein. This work provided potential therapeutic targets for GC treatment.