Ozkan Simsek

The aim of this study was to compare selected trace element levels in umbilical cord blood plasma of pregnant women residing in rural and urban areas and to investigate the relationship between trace elements and oxidative stress parameters. Umbilical cord blood samples were collected from 50 pregnant women living in rural and urban areas. Total antioxidant status (TAS) and total oxidant status (TOS) in plasma were determined by colorimetric method. Levels of nickel (Ni), manganese (Mn), aluminum (Al), iron (Fe), mercury (Hg), cadmium (Cd), vanadium (V), and selenium (Se) were measured by inductively coupled plasma optical emission spectrometry. Ni, Mn, Al, Fe, Hg, and Cd levels in cord blood plasma were significantly higher in pregnant women residing in rural areas compared to those in urban areas ( p < 0.001). In contrast, V and Se concentrations were significantly higher in the urban group ( p < 0.001). TAS and TOS levels in umbilical cord blood plasma were also significantly elevated in the rural group. The increased TAS levels observed in pregnant women residing in rural areas may reflect a compensatory and adaptive antioxidant response to elevated oxidative stress, as indicated by higher TOS levels, which may be associated with increased exposure to trace elements. This study provides preliminary data of significant differences in trace element levels, oxidative stress, and antioxidant status in umbilical cord blood plasma collected at delivery from women residing in rural and urban areas. These findings highlight environmental disparities between the two regions and provide a basis for future studies investigating prenatal exposure to trace elements and oxidative stress.

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.

Methotrexate (MTX) is a commonly used drug to treat various cancers and autoimmune disorders, but its clinical utility is often limited by hepatotoxicity.

Background and Objectives: Methotrexate (MTX) is a widely utilised pharmaceutical agent in the treatment of various malignancies and inflammatory diseases. However, its clinical utility is often constrained by its potential for hepatotoxicity. Although pyridostigmine is a well-established reversible acetylcholinesterase inhibitor, its potential therapeutic role in preventing hepatic injury remains incompletely defined. The present study aimed to investigate whether pyridostigmine provides protective effects against MTX-triggered liver damage in a rat model. Methods: Thirty-six female Wistar albino rats randomly assigned to three groups: control (n = 12), MTX + saline (n = 12), and MTX + pyridostigmine (n = 12). Hepatotoxicity was induced by a single-dose MTX injection (20 mg/kg), followed by daily oral administration of either pyridostigmine (5 mg/kg) or saline for ten consecutive days. Hepatic function markers, oxidative stress parameters, fibrosis-associated mediators, and histopathological changes were assessed. Results: Pyridostigmine significantly attenuated MTX-induced elevations in plasma alanine aminotransferase (p < 0.05) and cytokeratin-18 levels (p < 0.001), and reduced liver and plasma malondialdehyde (MDA) levels (p < 0.05). Additionally, pyridostigmine treatment resulted in reduced levels of transforming growth factor-beta (p < 0.05), bone morphogenetic protein-9 (p < 0.001), and endoglin levels (p < 0.05), as well as increased sirtuin 1 level (p < 0.05). Histopathological examination revealed that pyridostigmine treatment significantly reduced MTX-induced hepatocyte necrosis, fibrosis, and cellular infiltration. Conclusions: Pyridostigmine exerted hepatoprotective effects against MTX-induced liver injury by attenuating oxidative stress, restoring SIRT1 expression, and suppressing pro-fibrotic signaling. These findings indicate that pyridostigmine may hold therapeutic potential for the prevention of MTX-associated hepatotoxicity.

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.

The aim of this research was to examine the effects of forskolin and PGE2 on steroid synthesis in goat luteal cells cultured at early and late corpus luteum. Therefore, the luteal cells removed from both stage of corpus luteum were cultured with newborn calf serum for the first 18 h. Then, media was changed and different concentrations of forskolin (10, 100ng/ml) or PGE2 (10, 100ng/ml) were added to the fresh media for another 96 h. The culture media was replaced every 48 h and the retrieved media was kept frozen at -20 °C until hormone analysis. Luteal cells treated with forskolin produced a higher production of progesterone in a dose-dependent manner, compare to the control well at early and late stage of corpus luteum. Lower dose of PGE2 increased the progesterone secretion in luteal cells compare to the control groups at the late stage of corpus luteum but not at early stage. The cells treated with higher dose of PGE2 had no significant effect on progesterone synthesis at early and late phase of goat corpus luteum in comparison to control groups. As a result, this study in goat shows that forskolin promotes progesterone synthesis of the luteal cells at the early and late corpus luteum, but PGE2 is only effective in cells treated with low dose at the late stage.

The purpose of this study was to evaluate certain heavy metal levels in young and adult cattle in the Şiran district of Gümüşhane. For this, a total of 100 blood samples were taken from 50 young (aged 1 to 3 years old) and 50 adult (aged 4 to 6 years old) cattle slaughtered at an abattoir in the Şiran. Serum was then separated from the blood samples by centrifugation, and analysed for certain heavy metals by using the ICP-MS method. The levels of serum heavy metals in the serum of young and adult cattle breed in the Şiran were determined. When comparing young and adult cattle, the adult cattle had significantly higher concentrations of Al, V, Ni, and Sn. As a result, in this study, serum heavy metal concentrations and age-related bioaccumulation in cattle farmed in the Şiran district were determined for the first time. The periodic monitoring of the levels of these heavy metals may be helpful in improving animal health and production.