Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

The outbreak of novel coronavirus (SARS-CoV-2) infection has brought great harm to people's life and social development. Although SARS-CoV-2 infection is more common in mild patients at present, considering the characteristics of crtical disease, rapid progress and high mortality, the treatment of critical patients are the focus of clinical attention. Immune imbalance which is characterized by cytokine storm plays a vital role in SARS-CoV-2 induced acute respiratory distress syndrome (ARDS), extrapulmonary multiple organ failure and even death. Therefore, the application of immunosuppressive agent in crtical coronavirus disease patients has a promising prospect. In this paper, different immunosuppressive agents and their application in crtical SARS-CoV-2 infection are reviewed, so as to provide reference for crtical coronavirus disease therapy.

Objective:To explore the risk factors for postoperative delirium in colorectal cancer patients based on Meta-analysis.Methods:A computer search was conducted on PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, VIP and China Biology Medicine disc, and literatures on influencing factors of postoperative delirium of colorectal cancer published by each database until April 6, 2022 were selected. Two researchers independently screened the literature, extracted the data, and evaluated the quality of the literature using Newcastle-Ottawa Scale (NOS) . Stata 15.0 statistical software was used to conduct a Meta-analysis of the included literatures.Results:A total of 19 articles were included, including 5 295 patients. The Meta-analysis results showed that the combined odds ratio ( OR) values and 95% confidence interval (95% CI) of various factors for postoperative delirium in colorectal cancer patients were advanced age [1.10 (1.06-1.14) ] , male [2.29 (1.81-4.44) ] , alcohol abuse [3.14 (1.63-6.06) ] , preoperative physical condition grading (≥level 3) [1.47 (1.13-1.91) ] , comorbidities [1.59 (1.16-2.17) ] , history of mental illness [7.86 (4.57-13.54) ] , history of cerebrovascular disease [5.74 (3.78-8.72) ] , cognitive impairment [3.31 (1.20-9.08) ] , albumin [0.81 (0.66-0.99) ] , perioperative blood transfusion [2.29 (1.41-3.69) ] and C-reactive protein [2.24 (1.11-4.53) ] , all P<0.05. Conclusions:The risk factors for delirium in colorectal cancer patients after operation are old age, male, alcoholism, preoperative physical condition grading≥level 3, combined diabetes and other basic diseases, history of mental disease, history of cerebrovascular disease, cognitive dysfunction, low albumin, perioperative blood transfusion and elevated C-reactive protein.

How follicular T-helper (Tfh) cells develop is incompletely understood. We find that, upon antigen exposure in vivo, both naïve and antigen-experienced T cells sequentially upregulate CXCR5 and Bcl6 within the first 24 h, relocate to the T-B border, and give rise to phenotypic Bcl6(+)CXCR5(+) Tfh cells before the first cell division. CXCR5 upregulation is more dependent on ICOS costimulation than that of Bcl6, and early Bcl6 induction requires T-cell expression of CXCR5 and, presumably, relocation toward the follicle. This early and rapid upregulation of CXCR5 and Bcl6 depends on IL-6 produced by radiation-resistant cells. These results suggest that a Bcl6(hi)CXCR5(hi) phenotype does not automatically define a Tfh lineage but might reflect a state of antigen exposure and non-commitment to terminal effector fates and that niches in the T-B border and/or the follicle are important for optimal Bcl6 induction and maintenance.
Animals ; CD40 Ligand ; metabolism ; Cell Differentiation ; physiology ; DNA-Binding Proteins ; metabolism ; Inducible T-Cell Co-Stimulator Protein ; metabolism ; Interleukin-6 ; metabolism ; Mice ; Proto-Oncogene Proteins c-bcl-6 ; Receptors, CXCR5 ; metabolism ; T-Lymphocytes, Helper-Inducer ; metabolism