Glutathione S-transferase A3 (GSTA3) is known as an antioxidative protease, however, the crucial role of GSTA3 in liver fibrosis remains unclear. As a recently we developed water-soluble pyridone agent with antifibrotic features, fluorofenidone (AKF-PD) can attenuate liver fibrosis, present studies were designed to explore the role of GSTA3 in liver fibrosis and its modulation by AKF-PD in vivo and in vitro. Rats liver fibrosis models were induced by dimethylnitrosamine (DMN) or carbon tetrachloride (CCl4). The two activated hepatic stellate cells (HSCs) lines, rat CFSC-2G and human LX2 were treated with AKF-PD respectively. The lipid peroxidation byproduct malondialdehyde (MDA) in rat serum was determined by ELISA. The accumulation of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescein fluorescence analysis. The expression of α-smooth muscle actin (α-SMA), fibronectin (FN), and phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK) and glycogen synthase kinase 3 beta (GSK-3β) were detected by western blotting (WB). GSTA3 was substantially reduced in the experimental fibrotic livers and transdifferentiated HSCs. AKF-PD alleviated rat hepatic fibrosis and potently inhibited HSCs activation correlated with restoring GSTA3. Moreover, GSTA3 overexpression prevented HSCs activation and fibrogenesis, while GSTA3 knockdown enhanced HSCs activation and fibrogenesis resulted from increasing accumulation of ROS and subsequent amplified MAPK signaling and GSK-3β phosphorylation. We demonstrated firstly that GSTA3 inhibited HSCs activation and liver fibrosis through suppression of the MAPK and GSK-3β signaling pathways. GSTA3 may represent a promising target for potential therapeutic intervention in liver fibrotic diseases.

Background and Aims: Crohn’s disease (CD) is usually accompanied by malnutrition. CD-related malnutrition can increase morbidity, disability, mortality, and hospitalization costs. The purpose of this study was to find a reliable indicator for evaluating CD patients’ nutritional status. Methods: All data were retrospectively collected from Xiangya Hospital, Central South University between May 2021 and February 2022. All patients were evaluated for nutritional status using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Body composition, resistance, and reactance were recorded by a body analyser, and the phase angle (PhA) was calculated simultaneously. The Mann–Whitney U test, chi-square test, Fisher’s exact test, and univariate and multivariate logistic regression analyses were used. A receiver operating characteristic (ROC) curve was built to evaluate the predictive value of differential variables for diagnosing malnutrition based on the GLIM criteria. Results: A total of 169 CD patients were enrolled, of which 74 (58.3%) males and 32 (76.2%) females were diagnosed with malnutrition; 34 (45.9%) males and 22 (68.8%) females were severely malnourished. Univariate analysis identified that as nutritional status deteriorated, body mass index, PhA, and levels of haemoglobin and albumin decreased, while platelet count, erythrocyte sedimentation rate, and levels of C-reactive protein and fibrinogen increased (p < 0.05). Logistic regression analysis revealed that the PhA was significantly independently associated with malnutrition (p < 0.05). The ROC curve analysis indicated that the optimal PhA cut-off levels of 6.11° and 5.55° could be used to predict malnutrition according to the GLIM criteria in males and females, respectively, with a PhA < 5.53° and < 5.12° indicating severe malnutrition in males and females, respectively. Conclusion: The PhA is a sensitive, noninvasive, portable, inexpensive tool that can be used to monitor and manage the nutritional status of CD patients.

Tubular epithelial-mesenchymal transition (EMT) has been widely accepted as the underlying mechanisms of renal interstitial fibrosis (RIF). The production of reactive oxygen species (ROS) plays a vital role in tubular EMT process. The purpose of this study was to investigate the involved molecular mechanisms in TGF-beta-induced EMT and identify the potential role of glutathione S-transferase alpha 3 (GSTA3) in this process. The iTRAQ screening was performed to identify protein alterations of the rats underwent unilateral-ureteral obstruction (UUO). Protein expression of GSTA3 in patients with obstructive nephropathy and UUO rats was detected by immunohistochemistry. Protein and mRNA expression of GSTA3 in UUO rats and NRK-52E cells were determined by Western blot and RT-PCR. siRNA and overexpression plasmid were transfected specifically to assess the role of GSTA3 in RIF. The generation of ROS was measured by dichlorofluorescein fluorescence analysis. GSTA3 protein and mRNA expression was significantly reduced in UUO rats. Immunohistochemical analysis revealed that GSTA3 expression was reduced in renal cortex in UUO rats and patients with obstructive nephropathy. Treating with TGF-β1 down-regulated GSTA3 expression in NRK-52E cells, which have been found to be correlated with the decreased expression in E-cadherin and megalin and increased expression in α-smooth muscle actin. Furthermore, knocking down GSTA3 in NRK-52 cells led to increased production of ROS and tubular EMT, whereas overexpressing GSTA3 ameliorated ROS production and prevented the occurrence of tubular EMT. GSTA3 plays a protective role against tubular EMT in renal fibrosis, suggesting GSTA3 is a potential therapeutic target for RIF.

Infliximab (IFX) has revolutionised the treatment for Crohn’s disease (CD) recently, while a part of patients show no response to it at the end of the induction period. We developed a random forest...

Background: Dysbiosis of the gut microbiota is pivotal in Crohn’s disease (CD) and modulated by host physiological conditions. Hyperbaric oxygen therapy (HBOT) is a promising treatment for CD that can regulate gut microbiota. The relationship between HBOT and the gut microbiota in CD remains unknown. Methods: CD patients were divided into an HBOT group (n = 10) and a control group (n = 10) in this open-label prospective interventional study. The fecal samples before and after HBOT were used for 16 S rRNA gene sequencing and fecal microbiota transplantation (FMT). A colitis mouse model was constructed using dextran sulfate sodium, and intestinal and systematic inflammation was evaluated. The safety and long-term effect of HBOT were observed. Results: HBOT significantly reduced the level of C-reactive protein (CRP) (80.79 ± 42.05 mg/L vs. 33.32 ± 18.31 mg/L, P = 0.004) and the Crohn’s Disease Activity Index (CDAI) (274.87 ± 65.54 vs. 221.54 ± 41.89, P = 0.044). HBOT elevated the declined microbial diversity and ameliorated the altered composition of gut microbiota in patients with CD. The relative abundance of Escherichia decreased, and that of Bifidobacterium and Clostridium XIVa increased after HBOT. Mice receiving FMT from donors after HBOT had significantly less intestinal inflammation and serum CRP than the group before HBOT. HBOT was safe and well-tolerated by patients with CD. Combined with ustekinumab, more patients treated with HBOT achieved clinical response (30%vs.70%, P = 0.089) and remission (20%vs.50%, P = 0.160) at week 4. Conclusions: HBOT modulates the dysbiosis of gut microbiota in CD and ameliorates intestinal and systematic inflammation. HBOT is a safe option for CD and exhibits a promising auxiliary effect to ustekinumab. Trial registration: Chinese Clinical Trial Registry, ChiCTR2200061193. Registered 15 June 2022, https://www.chictr.org.cn/showproj.html?proj=171605.

Inflammatory bowel disease (IBD) is closely related to changes in the gut microbiota, with proton pump inhibitors (PPIs) possibly playing a role. PPIs use is associated with altering gut microbiota and potentially influencing IBD onset and progression. This review explores the mechanisms by which PPIs affect gut microbiota and IBD, suggests strategies to mitigate dysbiosis, outlook on the causal relationship validation between PPIs use and IBD risk, emphasizing the broader impact of acid suppressants on gut health.