Expression of Concern.

被引量：- 发表：1970

Retraction Statement.

被引量：- 发表：1970

Tranilast Treatment Prevents Chronic Radiation-Induced Colitis in Rats by Inhibiting Mast Cell Infiltration.

Mast cells are the principal cells involved in acute and chronic colitis due to radiation, known as radiation-induced colitis (RIC). In this study, we investigated whether pretreatment with tranilast, a mast cell inhibitor, could alleviate chronic RIC. A total of 23 Sprague-Dawley rats were randomly divided into three groups: control group (n = 5), radiation group (RG, n = 9), and tranilast-pretreated radiation group (TG, n = 9). The rats in the RG and the TG were irradiated in the pelvic area (1.5 cm from the anus) with a single dose of 20 Gy under general anesthesia. Tranilast (100 mg/kg) was administered intraperitoneally to the rats of the TG for 10 days, starting from the day of pelvic radiation. Ten weeks after radiation, the rats were euthanized. Rectal tissue samples were histologically evaluated for the total inflammation score (TIS) and mast cell count. The expression of MUC2, MUC5AC, and matrix metalloproteinase-9 (MMP-9) was also assessed immunohistochemically. Both the TIS and specific components of TIS such as epithelial atypia, vascular sclerosis, and colitis cystica profunda (CCP) were significantly higher in the RG than in the TG (p = 0.02, 0.038, 0.025, and 0.01, respectively). Thein number of infiltrating mast cells was significantly higher in the RG than in the TG (median [range]: 20 [3-54] versus 6 [3-25], respectively; p = 0.034). Quantitatively, the number of MMP-9-positive cells was significantly higher in the RG (23.67 ± 19.00) than in the TG (10.25 ± 8.45) (mean ± standard deviation; p < 0.05). TIS and MMP-9 exhibited a strong association (correlation coefficient r = 0.56, p < 0.05). Immunohistochemically, the mucin-lake of CCP showed no staining for MUC5AC but was stained positive for MUC2. Tranilast pretreatment of chronic RIC showed an anti-inflammatory effect associated with the reduction of mast cell infiltration and MMP-9 expression.

被引量：- 发表：1970

Semaglutide Ameliorates Hepatocyte Steatosis in a Cell Co-Culture System by Downregulating the IRE1α-XBP1-C/EBPα Signaling Pathway in Macrophages.

Non-alcoholic fatty liver disease (NAFLD) is currently the most common type of chronic liver disease. Semaglutide is a glucose-lowering drug administered for the treatment of type 2 diabetes mellitus (T2DM) and is clinically effective in the treatment of NAFLD. X-box binding protein 1 (XBP1) is related to the pathogenesis of both NAFLD and T2DM. The aim of the present study was to demonstrate whether the underlying mechanism of semaglutide treatment for NAFLD is via downregulation of the inositol-requiring transmembrane kinase/endonuclease-1α (IRE1α)-XBP1-CCAAT/enhancer binding protein α (C/EBPα) signaling pathway in macrophages. In the present study, NAFLD cell modeling was induced by oleic acid (0.4 m<sc>m</sc>) and palmitic acid (0.2 m<sc>m</sc>). Hepatocytes (AML12) and macrophages (RAW264.7) were co-cultured in 6-well Transwell plates. Semaglutide (60 or 140 n<sc>m</sc>) was administrated for 24 h, while pioglitazone (2 μ<sc>m</sc>) and toyocamycin (200 n<sc>m</sc>) were used as a positive control drug and a XBP1 inhibitor, respectively. Autophagy and apoptosis of AML12 cells were detected by transmission electron microscopy and Western blotting (WB). Hepatocyte steatosis was evaluated by adopting total intracellular triglyceride determination, analysis of the relative expression of proteins and genes associated with lipid metabolism and hepatocyte Oil red O staining. Detection of inflammation factors was conducted by ELISA and WB. To explore the underlying mechanism of NAFLD treatment with semaglutide, the relative expression of related proteins and genes were tested. Our study demonstrated that semaglutide treatment improved autophagy and inhibited apoptosis of hepatocytes, while notably ameliorating steatosis of hepatocytes. In addition, inflammation was attenuated in the NAFLD cell co-culture model after semaglutide administration. Semaglutide also significantly reduced the protein and gene expression levels of the IRE1α-XBP1-C/EBPα signaling pathway in macrophages. Semaglutide partially ameliorated NAFLD by downregulating the IRE1α-XBP1-C/EBPα signaling pathway in macrophages. These findings may provide a potential theoretical basis for semaglutide therapy for NAFLD.

被引量：- 发表：1970

Negative Prognostic Associations of Selective Serotonin Reuptake Inhibitors Use in Hospitalized COVID-19 Patients and Potential Contribution of Cardiovascular Comorbidities.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative agent of coronavirus disease 2019 (COVID-19), a very contagious systemic disease dominantly affecting the respiratory tract. Recent findings oppose earlier suggestions that selective serotonin reuptake inhibitors (SSRIs) might be protective during acute SARS-CoV-2 infection, prompting the current study. The institutional registry of a tertiary referral center was retrospectively evaluated for SSRI use and associated clinical outcomes among hospitalized COVID-19 patients with mostly severe and critical disease. Among 1,558 patients, there were 78 (5%) exposed to SSRI during hospitalization. SSRI users in comparison to non-users did not significantly differ in their demographic characteristics, comorbidity profile or the severity of COVID-19 symptoms and associated inflammatory response at admission. In multivariate analyses adjusted for clinically meaningful variables, SSRI use was significantly associated with higher risks of death, mechanical ventilation, intensive care unit treatment, and bacteremia, whereas no significant relationship with risks of venous, arterial thrombosis, and major bleeding was present. Patients with less severe initial COVID-19 presentation, lower inflammatory burden, higher platelet count, lower cumulative comorbidity burden, presence of hyperlipidemia, atrial fibrillation, chronic heart failure and nonexposed to acetylsalicylic-acid had higher mortality associated with SSRI use. Findings of the current study validate findings of higher mortality but also report higher tendency for respiratory deterioration, intensive care unit treatment, and bacteremia associated with SSRI use among hospitalized COVID-19 patients. These findings also suggest the potential contribution of cardiovascular comorbidities to detrimental clinical course of SSRI exposed patients.

被引量：- 发表：1970