It seems that gentamicin\'s toxicity to the liver is caused by reactive oxygen species production. The antioxidant and anti-inflammatory properties of Acacia nilotica extract (AN) have been demonstrated in recent studies. This research focused on how AN\'s extract affected gentamicin-induced liver damage in rats. Twenty-four Wister rats of male type were divided into four groups: first group received saline as a control, second group received AN (5%) for fifteen days, group three received daily intraperitoneal injections of gentamicin (100 mg/kg) for fifteen days, and group four, as mentioned in groups 2 and 3, also received gentamicin injections and AN extraction (5%) for fifteen days. In order to conduct biochemical analysis, serum was extracted. Histopathology, immunohistochemistry analyses for hepatic toxicity were all performed on the collected tissue samples. Serum levels of ALT, AST, total bilirubin, and GGT were all elevated after using gentamicin. The inflammatory cytokines)IL-1, TNF-α and IL-6(, all were increased in gentamycin-injected group. There were showing deformity of bile duct, hepatocellular necrosis and infiltration of inflammatory cells congestion of portal vein, and hepatic sinusoids besides fibrosis of portal area (white arrows), hypertrophy in gentamycin-injected group compared to AN plus gentamycin administered rats. There were upregulation in the immunoreactivity of COX-2, IFNkB and TGF-beta1 (TGF-β1) in gentamycin intoxicated rats. When gentamicin and AN were administered together, hepatic biomarkers, inflammatory cytokines, histological, and immunohistochemical markers were all ameliorated by AN administration.

The aim of this study was to assess L-carnitine\'s effects on adult male rats\' lung damage brought on by amiodarone, which is a potent antiarrhythmic with limited clinical efficacy due to potentially life-threatening amiodarone-induced lung damage. Because of the resemblance among the structural abnormalities in rats\' lungs that follows amiodarone medication and pulmonary toxicity in human beings, this animal model may be an appropriate example for this disease entity. Amiodarone produced pulmonary toxicity in twenty-four healthy male albino rats (150-180 g) over a period of 6 weeks. Four groups of six rats each were established: control, sham, amiodarone, and L-carnitine plus amiodarone. Histological, ultrastructural, oxidative stress, and inflammatory markers were determined during a 6-week exposure experiment. Amiodarone-induced lung damage in rats may be brought on due to oxidative stress producing significant pulmonary cytotoxicity, as evidenced by the disruption of the mitochondrial structure, severe fibrosis, and inflammatory response of the lung tissue. Lungs already exposed to such harmful effects may be partially protected by the antioxidant L-carnitine. Biochemical markers of lung damage brought on by amiodarone include lung tissue levels of the enzyme\'s catalase, superoxide dismutase, and reduced glutathione. The levels of lipid peroxides in lung tissue measured as malondialdehyde increased significantly upon exposure to amiodarone. In addition, the levels of tumor necrosis factor alpha were significantly elevated in response to amiodarone. The effect of L-carnitine on amiodarone-induced pulmonary toxicity was studied in rats. It is interesting to note that the intake of L-carnitine in rats treated with amiodarone partially restored the biochemical and histopathological alterations brought on by amiodarone to their original levels. Tumor necrosis factor alpha levels were significantly reduced upon L-carnitine exposure. These results suggest that L-carnitine can be used to treat amiodarone-induced pulmonary dysfunction.

Gastroesophageal reflux disease (GERD) is a prevalent chronic condition affecting the well-being of both adults and children in general medical practice. Research on the effects of fermented soybean (SB) supplementation in managing GERD is relatively new, with limited studies available. The existing research often lacks sufficient dosing regimens and study durations to differentiate between transient placebo effects and sustained benefits. In this study, the beneficial effects of FSB supplementation were investigated in 110 voluntary participants (NCT06524271). The participants were required to take 1 g of FSB supplement once daily for 12 weeks. GERD symptoms were evaluated using the Reflux Disease Questionnaire (RDQ), while inflammatory markers, including interleukin-4 (IL-4), interleukin-6 (IL-6), and interleukin-8 (IL-8), were measured to assess inflammation. The Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire was used to evaluate participants\' quality of life. The results indicated that FSB supplementation significantly (p < 0.05) alleviated heartburn and regurgitation symptoms and reduced levels of IL-4, IL-6, and IL-8, indicating a notable anti-inflammatory effect. Additionally, significant (p < 0.05) improvements were observed in QOLRAD scores, particularly in vitality, emotional distress, and physical/social functioning. Collectively, our findings support the use of FSB as an adjuvant approach in managing GERD, with notable improvements in patients\' quality of life.

PCOS is a heterogeneous, multifactorial endocrine disorder with a complex pathophysiology. It is a globally rising infertility disorder that affects a large percentage of women of reproductive age, with a relatively high prevalence of 8-13%. Genome-wide association studies have revealed associations of genetic variations with many diseases, including PCOS. The cellular activity of IL8 is mediated by the receptor CXCR2, and transcription of IL8 is controlled by TNF-α. Therefore, this study aimed to investigate the association of TNF-α, CCR5-delta32, and CXCR2 gene variations with PCOS.
METHODS: In this case control study, we used amplification-refractory mutation system (ARMS)-PCR to detect and determine the presence of the polymorphic variants TNF-α, CCR5-delta32, and CXCR2 in the study subjects. These gene polymorphs may serve as critical candidate gene variants in PCOS pathogenesis and therapeutics.
RESULTS: The case-control study\'s findings revealed that the majority of the biochemical and endocrine serum biomarkers examined in the investigation-including lipids (LDL, HDL, and cholesterol), T2DM markers (fasting glucose, free insulin, and HOMA-IR), and hormones (FSH, LH, testosterone, and progesterone)-exhibited statistically significant changes in PCOS patients. The distributions of TNF-α (rs1800629), CCR5-delta32, and CXCR2 (rs2230054) genotypes analyzed within PCOS patients and healthy controls in the considered population were significant (p < 0.05). The heterozygosity of CXCR2-CA, TNF-α GA, and CCR5(WT+Δ32*) genotypes was significantly associated with PCOS susceptibility, with high OR and p < 0.05 in the codominant model. Similarly, the A allele of the TNF-α and CXCR2 genes, along with the CCR5Δ32*(mutant) allele, was significantly associated with PCOS susceptibility, with high OR and p < 0.05. Likewise, the CXCR2 (CA+AA) vs CC genotype was associated with increased susceptibility to PCOS, with OR 2.25, p < 0.032.
CONCLUSIONS: Our study concludes that TNF-α rs1800629G>A, CXCR2-rs2230054C>T, and CCR5-Delta32 rs333 are potential loci for developing PCOS in the Tabuk population. These findings might eventually be useful in identifying and classifying those who are at risk for PCOS. To validate these results, it is advised that further longitudinal studies be conducted in diverse ethnic populations and with larger sample sizes.

Being overweight and obesity are significant global public health challenges due to their association with adipose tissue dysfunction, pro-inflammatory marker production, and alterations in gut microbiota composition. To explore the relationship between gut microbiota, dietary factors, and inflammatory markers in overweight or obese women, we conducted a cross-sectional study involving a healthy group (n = 20) and an overweight or obese group (n = 75). We collected data, including clinical, anthropometric, and dietary assessments, and carried out a blood biochemical analysis, the measurement of inflammatory biomarkers (hs-CRP, IL-6, and TNF-α), and the 16S rRNA gene sequencing of fecal samples. The gut microbiota analysis revealed notable differences in alpha and beta diversity between the two groups. Moreover, the abundance of gut microbiota in the overweight or obese group correlated positively with adiposity markers, blood pressure, lipid profiles, and inflammatory markers. These findings highlight significant changes in gut microbiota associated with obesity, potentially implicating pathways such as lipopolysaccharide biosynthesis. Understanding the role of the gut microbiome in obesity could reveal specific avenues for intervention.

Inflammatory bowel diseases (IBD), including Crohn\'s disease (CD) and ulcerative colitis (UC), are chronic conditions marked by persistent inflammation, impacting patients\' quality of life. This study assessed differences in coffee consumption between CD and UC patients and its potential effects on the subjective perception and objective changes in inflammation markers in these two categories of patients. Using questionnaires, coffee consumption patterns, and perceived symptom effects were evaluated. Biological samples were collected to measure the following inflammatory markers: leukocytes, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and fecal calprotectin (FC). Among 148 patients, 60% reported regular coffee consumption, with no significant difference between CD and UC patients. While 45.93% perceived no impact on symptoms, 48% of those reporting exacerbation continued their regular coffee consumption. FC values were significantly lower in coffee consumers than in non-consumers (p < 0.05), particularly in those consuming natural coffee (p < 0.001), and the case was observed for UC patients (p < 0.05). No significant differences were observed in other inflammatory markers, regardless of coffee type, frequency, or milk addition. This study highlights the commonality of coffee consumption among IBD patients and the association of lower FC levels with coffee consumption, especially in UC patients, suggesting that coffee may influence intestinal inflammatory responses.

BACKGROUND: This study aimed to evaluate alterations in the concentrations of matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8) within gingival crevicular fluid (GCF) extracted from the intrabony periodontal defect site before and after minimally invasive regenerative surgery, with or without supplemental laser application. The surgical procedure was performed using the modified minimally invasive surgical technique (M-MIST).
METHODS: Thirty-eight patients, each presenting with a single vertical defect, were randomly assigned to either the test (M-MIST + Er:YAG + Nd:YAG) or the control group (M-MIST). IL-8 and MMP-9 levels (primary outcomes of the study) were assessed prior to therapy, after 2 and 4 weeks, and 6 months following the surgical procedure by means of dedicated ELISA kits.
RESULTS: Both procedures were clinically effective as evidenced by probing depth (PD) reduction and clinical attachment level (CAL) gain at the 6-month follow-up. No statistical differences were observed in the levels of MMP-9 and IL-8 between the groups at any time point assessed. The changes in the level of MMP-9 and IL-8 over time were not statistically significant in any group. IL-8 was positively correlated with MMP-9 in the control group throughout the study and in the test group 2 weeks and 6 months post-op.
CONCLUSIONS: Within the limitations of this study, the additional application of Er:YAG + Nd:YAG lasers alongside the M-MIST procedure did not enhance the clinical and biochemical treatment outcomes compared to M-MIST alone.

Aim: This meta-analysis investigates the association between testosterone replacement therapy [TRT] and carotid artery atherosclerosis. Methods: 3 databases were searched for studies up to June 2023 per the PRISMA guidelines. The eligibility criteria comprised RCTs and observational studies involving hypogonadal males receiving exogenous testosterone, in which CIMT was assessed. CAA was the primary outcome, whereas secondary outcomes included HDL, LDL, CRP, total cholesterol and total testosterone. The statistical analysis was performed using Review Manager. Results: Statistical analysis revealed no association between TRT and assessed outcomes. There was a significant increase in total testosterone levels, depicting indirect anti-atherosclerotic effects of TRT. Conclusion: Meta-analysis shows no relation between TRT and CIMT or other markers, allowing its safe usage for hypogonadal males.
[Box: see text].

BACKGROUND: Trigeminal neuralgia (TN), marked by chronic pain from neural damage, is closely associated with inflammation. The role of OTULIN, a key regulator in inflammation and autophagy, is not fully understood in TN. The regulatory mechanism of OTULIN, a key protein involved in modulating inflammatory responses and autophagy processes, remains incompletely elucidated, particularly in the context of TN and neuroinflammation.
METHODS: An infraorbital nerve ligation-induced rat model of TN was used. OTULIN\'s expression was modulated using adenovirus vectors and short hairpin RNA. The impact on pain and inflammatory responses was assessed via quantitative real-time polymerase chain reaction, western blot, immunofluorescence, and transcriptomic analysis.
RESULTS: Enhanced OTULIN expression significantly increased head withdrawal thresholds and reduced pain sensitivity and neuroinflammatory markers in the model. Conversely, silencing OTULIN exacerbated pain and inflammation. Transcriptomic data revealed OTULINs influence on both inflammatory and autophagy pathways, specifically in suppressing NLR family pyrin domain containing 3 (NLRP3) inflammasome and promoting autophagy. In vitro experiments demonstrated OTULIN\'s inhibition of inflammatory markers in microglia and neurons.
CONCLUSIONS: OTULIN is crucial in modulating TN, reducing neuropathic pain and neuroinflammation by activating the autophagy pathway and inhibiting the NLRP3 inflammasome.

OBJECTIVE: To explore the influence of circulating lymphocyte subsets, serum markers, clinical factors, and their impact on overall survival (OS) in locally advanced nasopharyngeal carcinoma (LA-NPC). Additionally, to construct a nomogram predicting OS for LA-NPC patients using independent prognostic factors.
METHODS: A total of 530 patients with LA-NPC were included in this study. In the training cohort, Cox regression analysis was utilized to identify independent prognostic factors, which were then integrated into the nomogram. The concordance index (C-index) was calculated for both training and validation cohorts. Schoenfeld residual analysis, calibration curves, and decision curve analysis (DCA) were employed to evaluate the nomogram. Kaplan-Meier methods was performed based on risk stratification using the nomogram.
RESULTS: A total of 530 LA-NPC patients were included. Multivariate Cox regression analysis revealed that the circulating CD8+T cell, platelet-to-lymphocyte ratio (PLR), lactate dehydrogenase (LDH), albumin (ALB), gender, and clinical stage were independent prognostic factors for LA-NPC (p < 0.05). Schoenfeld residual analysis indicated overall satisfaction of the proportional hazards assumption for the Cox regression model. The C-index of the nomogram was 0.724 (95% CI: 0.669-0.779) for the training cohort and 0.718 (95% CI: 0.636-0.800) for the validation cohort. Calibration curves demonstrated good correlation between the model and actual survival outcomes. DCA confirmed the clinical utility enhancement of the nomogram over the TNM staging system. Significant differences were observed in OS among different risk stratifications.
CONCLUSIONS: Circulating CD8+ T cell, PLR, LDH, ALB, gender and clinical stage are independent prognostic factors for LA-NPC. The nomogram and risk stratification constructed in this study effectively predict OS in LA-NPC.