Background and Objectives: Liver fibrosis, a chronic process caused by various pathogenic factors, including drug toxicity, metabolic disorders, and chronic inflammation, is associated with liver-related mortality rates worldwide. It has been established that methotrexate (MTX), a pharmaceutical agent utilised in the treatment of numerous diseases, induces hepatic fibrosis. Currently, there is still a paucity of clinically efficacious antifibrotic drugs for the management of hepatic fibrosis. Thus, the present research sought to evaluate the antifibrotic effects of baricitinib in a rat model of MTX-induced liver fibrosis through the yes-associated protein (YAP) pathway. Materials and Methods: A total of 36 Wistar rats were assigned to three groups (n = 12) randomly: a control group, an MTX-induced liver fibrosis group, and a baricitinib-treated group, which received 20 mg/kg/day of baricitinib following fibrosis induction. All treatments were administered for 10 days. Results: Biochemical analyses revealed significant increases in plasma alanine aminotransferase (ALT), cytokeratin-18 (CK-18), and malondialdehyde (MDA) levels, as well as liver transforming growth factor-beta (TGF-β), YAP1, and MDA levels, in the MTX-induced fibrosis group in comparison to the control group (p < 0.05). Notably, baricitinib addition significantly reduced these biomarkers (p < 0.05). A histopathological evaluation further confirmed a marked reduction in fibrosis, hepatic necrosis, and cellular infiltration in the baricitinib-treated group relative to the MTX-induced fibrosis group. Conclusions: Accordingly, our findings suggest that baricitinib mitigates MTX-induced liver fibrosis, potentially through its anti-inflammatory and antifibrotic effects mediated by the suppression of the YAP signalling pathway. These results highlight that baricitinib could be a potential treatment option for patients with liver fibrosis.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is a growing global health concern closely linked to metabolic disorders, including obesity, insulin resistance, and dyslipidemia. Emerging evidence suggests that the gut–liver axis plays a critical role in the pathogenesis of NAFLD, with recent research highlighting the influence of gut microbiota, including fungal species such as Saccharomyces boulardii (S. boulardii). This study aimed to evaluate the effects of S. boulardii on lipid metabolism and oxidative stress in a rat model of fructose-induced NAFLD. Materials and Methods: Thirty Wistar rats were divided into three groups: a control group, a fatty liver group induced by 35% fructose supplementation, and a treatment group receiving S. boulardii (100 mg/kg/day) after fructose induction. Results: Biochemical analyses revealed that the treatment group exhibited significantly lower plasma levels of malondialdehyde (MDA), alanine aminotransferase (ALT), total triglycerides, and cholesterol compared to the untreated fatty liver group (p < 0.05). Furthermore, liver tissue analysis showed a marked reduction in lipid accumulation and fatty infiltration in the treatment group, with no visible lipid vacuoles in hepatocytes. The expression of aquaporin-8 (AQP8) and sirtuin-1 (SIRT1), key markers associated with hepatocyte function and lipid metabolism, was significantly higher in the S. boulardii group compared to the fatty liver group (p < 0.001). Conclusions: These findings indicate that S. boulardii supplementation mitigates the metabolic and oxidative stress-related alterations associated with fructose-induced NAFLD. In conclusion, our study suggests that S. boulardii exerts protective effects on the liver by reducing lipid accumulation and oxidative stress, highlighting its potential as a therapeutic intervention for NAFLD.

Antibiotics have been fundamental in the treatment of bacterial infections in both human and veterinary medicine; however, their extensive and often inappropriate use has accelerated the emergence and global spread of antimicrobial resistance (AMR). Antimicrobial resistance has become a major public health concern, threatening both the effectiveness of current therapies and the achievements of modern medicine. Global projections suggest that, if appropriate control measures are not implemented, AMR could result in up to 10 million deaths annually by 2050. Resistance arises from targeted adaptive strategies developed by bacteria in response to antibiotic exposure, involving complex molecular and biochemical processes that enable bacterial survival. This review provides a comprehensive overview of antibiotic mechanisms of action and the resistance strategies employed by bacteria, highlighting the dynamic reciprocal relationship between these two processes. This interplay underscores the critical importance of an in-depth molecular understanding for informing effective therapeutic approaches and the development of future antimicrobial strategies.