Dukehove2291

Oxidative stress induced by long-term cyclosporine A (CsA) administration is a major cause of chronic nephrotoxicity, which is characterized by tubular atrophy, tubular cell apoptosis, and interstitial fibrosis in the progression of organ transplantation. Although hydrogen-rich water (HRW) has been used to prevent various oxidative stress-related diseases, its underlying mechanisms remain unclear. This study investigated the effects of HRW on CsA-induced nephrotoxicity and its potential mechanisms. After administration of CsA (25 mg/kg/day), rats were treated with or without HRW (12 mL/kg) for 4 weeks. Renal function and vascular activity were investigated. Histological changes in kidney tissues were analyzed using Masson's trichrome and terminal deoxynucleotidyl transferase dUTP nick-end labeling stains. Oxidative stress markers and the activation of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway were also measured. We found that CsA increased the levels of reactive oxygen species (ROS) and malonaldehyde (MDA), but it reduced glutathione (GSH) and superoxide dismutase (SOD) levels. Such alterations induced vascular dysfunction, tubular atrophy, interstitial fibrosis, and tubular apoptosis. This was evident secondary to an increase in urinary protein, serum creatinine, and blood urea nitrogen, ultimately leading to renal dysfunction. Conversely, HRW decreased levels of ROS and MDA while increasing the activity of GSH and SOD. This was accompanied by an improvement in vascular and renal function. Moreover, HRW significantly decreased the level of Keap1 and increased the expression of Nrf2, NADPH dehydrogenase quinone 1, and heme oxygenase 1. In conclusion, HRW restored the balance of redox status, suppressed oxidative stress damage, and improved kidney function induced by CsA via activation of the Keap1/Nrf2 signaling pathway. © 2020 Wiley Periodicals, Inc.Systemic TNF neutralization can be used as a therapy for several autoimmune diseases. To evaluate the effects of cell type-restricted TNF blockade, we previously generated bispecific antibodies that can limit TNF secretion by myeloid cells (myeloid cell-specific TNF inhibitors or MYSTIs). In this study several such variable domain (VH) of a camelid heavy-chain only antibody-based TNF inhibitors were compared in relevant experimental models, both in vitro and in vivo. Pretreatment with MYSTI-2, containing the anti-F4/80 module, can restrict the release of human TNF (hTNF) from LPS-activated bone marrow-derived macrophage (BMDM) cultures of humanized TNF knock-in (mice; hTNFKI) more effectively than MYSTI-3, containing the anti-CD11b module. MYSTI-2 was also superior to MYSTI-3 in providing in vivo protection in acute toxicity model. Finally, MYSTI-2 was at least as effective as Infliximab in preventing collagen antibody-induced arthritis. This study demonstrates that a 33 kDa bispecific mini-antibody that specifically restricts TNF secretion by macrophages is efficient for amelioration of experimental arthritis. ©2020 Society for Leukocyte Biology.Acetaminophen (APAP) overdose leads to liver injury. NLRP3 inflammasome is a key player in APAP-induced inflammation. Also, apoptosis and liver regeneration play an important role in liver injury. Therefore, we assessed allicin's protective effect on APAP-induced hepatotoxicity and studied its effect on NLRP3 inflammasome and apoptosis. Mice in the APAP group were injected by APAP (250 mg/kg, intraperitoneal). The allicin-treated group received allicin orally (10 mg/kg/d) during 7 days before APAP injection. Serum and hepatic tissues were separated 24 hours after APAP injection. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, alkaline phosphatase (ALP), and hepatic malondialdehyde (MDA) were assessed using the colorimetric method. Hepatic NLRP3 inflammasome, caspase-1, and interleukin-1β (IL-1β) were estimated using enzyme-linked immunosorbent assay. Hepatic Bcl-2 and Ki-67 were investigated by immunohistochemistry. APAP significantly increased AST, ALT, and ALP, whereas allicnc.OBJECTIVE Gastrointestinal (GI) symptoms appear frequently in patients with anorexia nervosa (AN), but the associations between psychopathological, GI, and eating disorder (ED) symptoms remain unclear. This study aimed to determine the relationships of GI complaints with psychopathological measures, ED symptoms, and body mass index (BMI) in patients with AN. METHOD Thirty outpatients with AN aged >16 years were included. Psychopathological measures (Symptom Checklist-90-Revised, Beck Depression Inventory-II, and Beck Anxiety Inventory), ED symptoms (Eating Disorder Examination Questionnaire), ED-associated impairment (Clinical Impairment Assessment Questionnaire), GI complaints (Irritable Bowel Syndrome Severity Scoring System [IBS-SSS]), and BMI were assessed prior to starting treatment, and correlation and multiple regression analyses were applied to data from 19 patients. selleck RESULTS IBS-symptoms were significantly correlated only with ED symptoms (r = 0.583, p = .009) and somatization (r = 0.666, p = .002). Multiple regression analysis revealed that somatization significantly predicted worse IBS symptoms (beta = 0.5, p = .04), while ED symptoms did not. DISCUSSION Higher IBS-SSS scores were associated with higher severities of other somatic complaints. GI complaints and somatization should be addressed in treatments for AN in order to prevent these factors impeding the establishment of healthy eating patterns. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT02745067. © 2020 The Authors. International Journal of Eating Disorders published by Wiley Periodicals, Inc.OBJECTIVE In the general population, body weight is-on average-higher in the winter than in the summer. In patients with anorexia nervosa (AN), however, the opposite pattern has been reported. Yet, only a handful of studies exist to date that suffer from small sample sizes and inconsistent results. Therefore, the current study examined seasonal effects on body weight in a large sample of patients with AN to dissolve previous inconsistencies. METHOD Clinical records of N = 606 inpatients (95.4% female) who received AN treatment at the Schoen Clinic Roseneck (Prien am Chiemsee, Germany) between 2014 and 2019 were analyzed. RESULTS Patients with restrictive type AN had lower body mass index at admission in the winter than in the summer. This difference was not found for patients with binge/purge type AN and patients with atypical AN. DISCUSSION Individuals with restrictive type AN show seasonal variations in body weight that are opposite to seasonal variations in body weight in individuals without AN. These seasonal effects are specific to the restrictive subtype and cannot be found for the binge/purge or atypical subtypes.