Treatment strategies for steatohepatitis are of special interest given the high prevalence of obesity and fatty liver disease worldwide. This study aimed to investigate the potential therapeutic mechanism of L-carnitine (LC) and Ginkgo biloba leaf extract (GB) supplementation in ameliorating the adverse effects of hyperlipidemia and hepatosteatosis induced by a high-cholesterol diet (HCD) in an animal model. The study involved 50 rats divided into five groups, including a control group, a group receiving only an HCD, and three groups receiving an HCD along with either LC (300 mg LC/kg bw), GB (100 mg GB/kg bw), or both. After eight weeks, various parameters related to lipid and glucose metabolism, antioxidant capacity, histopathology, immune reactivity, and liver ultrastructure were measured. LC + GB supplementation reduced serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, glucose, insulin, HOMA-IR, alanine transaminase, and aspartate transaminase levels and increased high-density lipoprotein cholesterol levels compared with those in the HCD group. Additionally, treatment with both supplements improved antioxidant ability and reduced lipid peroxidation. The histological examination confirmed that the combination therapy reduced liver steatosis and fibrosis while also improving the appearance of cell organelles in the ultrastructural hepatocytes. Finally, the immunohistochemical analysis indicated that cotreatment with LC + GB upregulated the immune expression of GLP-1 and β-Cat in liver sections that were similar to those of the control animals. Mono-treatment with LC or GB alone substantially but not completely protected the liver tissue, while the combined use of LC and GB may be more effective in treating liver damage caused by high cholesterol than either supplement alone by regulating hepatic oxidative stress and the protein expression of GLP-1 and β-Cat.

Background: Acetaminophen (APAP)-induced acute liver injury (ALI) is increasingly becoming a public health issue with high rate of morbidity and mortality. Therefore, there is a critical demand for finding protective modalities by understanding the underlying proposed mechanisms including, but not limited to, ferroptosis and inflammation. Objectives: This study seeks to investigate the possible hepatoprotective effect of empagliflozin (EMPA) against APAP-induced ALI through modulation of ferroptosis and inflammatory cascades. Methods: Mice were allocated into the following five groups: vehicle control, APAP, EMPA 10, EMPA 20 (10 and 20 mg/kg/day, respectively, P.O.), and N-acetylcysteine (NAC, hepatoprotective agent against APAP-induced ALI). The hepatic injury was detected by determining liver enzymes and by histopathological examination. Inflammation, oxidative stress, apoptosis, and ferroptosis were also evaluated. Results: The APAP group showed an elevated level of hepatic enzymes with disrupted hepatic architecture. This toxicity was promoted by inflammation, oxidative stress, apoptosis, and ferroptosis, as indicated by elevated cytokines, lipid peroxidation, reduced antioxidants, increased caspase-3, decreased Bcl-2, and activation of the NF-κB/STAT3/hepcidin pathway. Pretreatment with EMPA remarkably reversed these features, which was reflected by restoration of the histoarchitecture of hepatic tissue, but the higher dose of EMPA was more efficient. Conclusions: APAP can induce ALI through initiation of inflammatory and oxidative conditions, which favor ferroptosis. EMPA hindered these unfavorable consequences; an outcome which indicates its anti-inflammatory, antioxidant, anti-apoptotic, and anti-ferroptotic effects. This modulatory action advocated EMPA as a potential hepatoprotective agent.

: Staphylococcus aureus causes a wide range of illnesses, from skin infections and persistent bone infections to life-threatening septicemia and endocarditis. Methicillin-resistant S. aureus (MRSA) is one of the most common bacteria that cause nosocomial and community-acquired infections. Clindamycin is one of the most effective treatments for several bacterial infections. Despite this, these infections may develop inducible clindamycin resistance during treatment, leading to treatment failure. This study determined the incidence of inducible clindamycin resistance among S. aureus clinical isolates. A total of 800 S. aureus strains were identified from clinical samples collected from several university hospitals in Egypt. All isolates were examined for the presence of MRSA using cefoxitin (30 μg) and the Kirby Bauer disk diffusion technique. The induction phenotypes of all 800 S. aureus strains were evaluated using the disk approximation test (D test), as recommended by the Clinical and Laboratory Standard Institute. Of the 800 strains of S. aureus, 540 (67.5%) were identified as MRSA and 260 (32.5%) were classified as methicillin-sensitive S. aureus (MSSA). In MRSA infections, clindamycin constitutive and inducible resistance was more frequent than in MSSA infections (27.8% versus 11.5% and 38.9% versus 15.4%, respectively). Clindamycin-sensitive strains were more prevalent in MSSA (53.8%) than in MRSA (20.4%) infections. In conclusion, the frequency of constitutive and inducible clindamycin resistance in MRSA isolates emphasizes the need to use the D test in routine antimicrobial susceptibility testing to evaluate clindamycin susceptibility, as the inducible resistance phenotype can inhibit the action of clindamycin and thus affect treatment efficacy.

Background and Aim. Hepatitis B virus (HBV) infection causes a variety of clinical manifestations, including liver cirrhosis and hepatocellular carcinoma (HCC). Toll‐like receptors (TLRs) have crucial functions in immune and inflammatory control. Therefore, this study highlights the impact of TLR2 gene polymorphism on the progression of HBV‐linked liver diseases (liver cirrhosis and HCC). Methods. In total, 170 chronic HBV patients and 50 healthy controls of comparable age and gender were included in this case‐control study. Clinical, laboratory, and imaging evaluations were conducted. ELISA was used to determine serum IL‐6 levels, and TLR2 (rs3804099) genotyping allelic discrimination assay was performed using real‐time PCR. Results. IL‐6 values were significantly higher in the HCC group, followed by the cirrhotic group, than those in chronic hepatitis and control groups (p < 0.001), with a significant correlation with disease activity and progression parameters. TRL2 homozygous TT was the most frequent in the control group, but the CC genotype was significantly more prevalent in the HCC group than that in the other groups. Furthermore, the CC genetic variant was associated with higher levels of IL‐6 and viral load in all HBV patients, whereas the TT genotype was associated with larger tumor size. Multivariate regression analysis demonstrated that in chronic HBV patients, viral load and TRL2 polymorphism are independent risk factors associated with the progression from chronic hepatitis to liver cirrhosis and to HCC. Similarly, the HBV viral load (p = 0.03, OR = 2.45, and 95% CI: 1.69–3.65), IL‐6 levels (p = 0.04, OR = 3.45, and 95% CI: 2.01–6.9), and TRL2 variants (p = 0.01, OR = 4.25, and 95% CI: 2.14–13.5) are independent risk factors associated with disease progression from cirrhosis to HCC. Conclusion. In chronic HBV patients, TRL2 polymorphism and higher IL‐6 levels were positively correlated with a higher likelihood of HCC and chronic hepatitis B disease activity and progression.