Biomarkers最新文献

Background: Iron overload can promote the generation of reactive oxygen species (ROS), leading to oxidative stress and different human diseases. The trace element selenium has biological functions and can act as both an antioxidant and a prooxidant. This study aimed to evaluate the protective effects of selenium against iron overload-induced toxicity in rats. Adult Wistar rats were exposed to three increasing concentrations of iron (25, 50, and 100 mg/kg body weight [b.w.]), either alone or in combination with selenium (0.5 mg/kg b.w.).

Methods: The biological interactions between these two compounds were investigated at the biochemical level in the liver, spleen, kidney, and pancreas.

Results: Our results indicated that iron used alone induces oxidative stress. In all tissues studied and at all the administered doses, we observed changes in the levels of catalase (CAT), glutathione (GSH), glutathione-S-transferase (GST), malondialdehyde (MDA), and acetylcholinesterase (AChE). The responses were dose- and organ-dependent. Selenium administered at 0.5 mg/kg b.w. attenuate the adverse effects of the different iron dosages.

Conclusion: These findings highlight the potential application of selenium in mitigating oxidative stress and organ toxicity associated with iron overload. Our research carries significant implications for the development of nutritional and therapeutic strategies aimed at managing disorders related to iron metabolism.

Objective: Lenvatinib shows efficacy for tumor response and survival in patients with advanced hepatocellular carcinoma (HCC). We aim to assess the effect of lenvatinib on liver function.

Methods: This single-center retrospective cohort study included 40 patients with advanced HCC who received ≥ 2 months of lenvatinib treatment from January 2020 to January 2024 and had at least one efficacy and safety assessment.

Results: The ALBI score showed a slight but significant increase of 0.112 points, from -2.517 at baseline to -2.405 following 2-month of treatment (P < 0.05). With a median follow-up of 18.5 months, the median overall survival was 22.8 months (95% CI: 16.3-29.3), and the median progression-free survival was 12.7 months (95% CI: 9.1-16.3). Both COX regression and Kaplan-Meier analyses indicated that impaired baseline liver function was associated with adverse clinical outcomes. Additionally, treatment response emerged as an independent prognostic factor.

Conclusions: The baseline ALBI score serves as a key prognostic marker, highlighting the necessity for meticulous monitoring of hepatic function, particularly in patients with compromised baseline liver reserve.

Limitations: The limitations of this study include its retrospective design and the potential for selection bias arising from the requirement for at least 2 months of treatment.

BACKGROUND: Conflicting results on the association of the Val66Met polymorphism in the BDNF gene with anxiety-related disorders are observed from previous studies and meta-analyses. We performed an updated meta-analysis to obtain more precise estimates and add additional analyses not performed by previous reviews.METHODS: Using combinations of various key terms, articles in PubMed, Google Scholar, and Web of Science, written in English were collected until October 31, 2024. Data were extracted independently by two authors and analyzed using Review Manager 5.4.RESULTS: Fifteen studies that are compliant with the HWE, providing a total of 14,184 participants were included in this meta-analysis after applying predefined inclusion/exclusion criteria based on study design, DSM-based diagnosis, and availability of genotype counts. Most pooled models demonstrated low to moderate heterogeneity with significant associations in the recessive model only. In the subgroup analysis, a significant effect was observed in the PD-uncategorized cohort. The Met/Met genotype demonstrated a suggestive association with increased susceptibility to panic disorder.CONCLUSION: Our updated meta-analysis suggests that the Met/Met genotype of the BDNF Val66Met polymorphism may increase susceptibility to PD under a recessive genetic model; however, this evidence remains preliminary.

Aim: Our study aimed to preliminarily investigate the role of combined detection of serum CCL20 and Oncostatin M in the diagnosis of early-stage endometrial cancer (EC).

Methods: A retrospective study was conducted on 109 patients with early-stage EC. Serum CCL20 and Oncostatin M levels were determined, and their correlations with sex hormone indicators (TTE and DHEAS) in EC patients were analyzed. Influencing factors for EC and the early diagnostic value of each indicator were analyzed.

Results: Serum CCL20 and Oncostatin M were high in EC patients and positively correlated with TTE and DHEAS. Elevated CCL20 and Oncostatin M were independent risk factors for EC. The diagnostic efficacy of serum CCL20 + Oncostatin M in combination was better than that of serum CCL20, Oncostatin M, CA125, and HE4 alone. The diagnostic test combining serum CCL20 and Oncostatin M in endometrioid carcinoma demonstrated an AUC of 0.855, with a sensitivity of 68.00% and a specificity of 92.86%, comparable to that in the whole early-stage endometrial carcinoma group (AUC = 0.867).

Conclusion: Combined detection of serum CCL20 and Oncostatin M may offer a promising adjunctive approach for the diagnosis of early-stage EC, with their levels correlated to sex hormone and clinicopathological characteristics.

Background: This study investigates the pathogenesis of Pigmented Villonodular Synovitis (PVNS) using bioinformatics approaches shared with atherosclerosis (AS).

Methods: Common genes from GSE3698 and GSE28829 were identified. A PPI network was constructed using the STRING database and analyzed with Cytoscape, MCODE, and cytoHubba to determine hub genes. These underwent GO and KEGG enrichment analysis. Candidate genes were identified by integrating cytoHubba and machine learning, and validated via immunohistochemistry and the GSE100927 dataset. Immune infiltration in PVNS and its association with candidate genes were examined, followed by scRNA-seq analysis using GSE155527.

Results: Analysis of 43 shared genes implicated immune responses in both diseases. CSF2RB was identified as a key candidate gene through PPI, machine learning, and immunohistochemistry. Immune infiltration confirmed immune dysregulation and linked CSF2RB to multiple immune cells. scRNA-seq revealed increased macrophages, T cells, and endothelial cells in PVNS, with CSF2RB highly expressed in macrophages and mast cells.

Conclusion: CSF2RB may serve as a diagnostic and therapeutic target for PVNS. scRNA-seq indicates disrupted immune cell composition in PVNS, characterized by significant increases in macrophages and T cells.

Introduction: Volatile gas exposure and self-reported liver conditions share pathophysiologic risk factors, but their exact association remains unclear.

Methods: We used a weighted multivariable-adjusted logistic regression model, using data from the National Health and Nutrition Examination Survey (NHANES) 2009-2018. Integrative analyses of Non-alcoholic fatty liver disease (NAFLD), liver fibrosis, liver cirrhosis GWAS summaries and blood expression quantitative trait loci (eQTLs) were conducted via summary data-based MR (SMR) and colocalization analysis to prioritize putative blood smoking-related genes and their associations with each liver condition risk. Finally, we further verified these gene-disease causal links through MR and colocalization analysis.

Results: 12,099 NHANES participants were included. Male sex, 46-75 years, and smoke exposure correlated positively with LC; age and smoke exposure remained positively associated with LC incidence after adjustment, while non-Hispanic Black was a LC protective factor. SMR identified three blood-derived candidate genes: RGPD8 (Beta = -0.207), COX6B2 (Beta = -0.567), DNAJC27 (Beta = 0.859). MR and colocalization confirmed their associations with cirrhosis, fibrosis, and NAFLD, respectively.

Conclusion: This study confirms a causal link between smoke exposure and increased LC risk, identifies novel gene-disease associations, and provides cross-disciplinary insights for targeted LC prevention and personalized research.

Background: Diquat poisoning is associated with high mortality, and accurate prognostication remains challenging in resource-limited settings. This retrospective cohort study evaluated white blood cell count (WBC) as both a prognostic biomarker and mechanistic mediator in acute diquat poisoning.

Methods: This retrospective cohort included 134 patients with acute diquat poisoning (2016-2025). WBC was analysed continuously and categorically (median and ROC-derived cut-offs). Multivariable regression, subgroup, and mediation analyses were performed.

Results: The high-WBC group (≥ 17.11 × 10⁹/L) had significantly higher mortality (64.3% vs. 7.8%, p < 0.001). After adjustment, patients with WBC ≥ 17.235 × 10⁹/L had a 3.43-fold higher mortality risk (95% CI: 1.37-8.60). Each 1 × 10⁹/L WBC increase predicted a 6% mortality risk rise (adjusted OR = 1.06, 95% CI: 1.01-1.12). WBC mediated 15.5% (p = 0.02) of plasma diquat's total lethal effect. ROC analysis showed WBC had an AUC of 0.724 (95% CI: 63.5%-81.2%) at the optimal cut-off of 17.235 × 10⁹/L, comparable to plasma diquat concentration's AUC of 0.817 (95% CI: 74.4%-88.9%).

Conclusions: WBC serves as both a continuous predictor and triage tool at 17.235 × 10⁹/L, providing a practical risk-stratification framework for settings lacking toxicological testing.

Background: Poisoned patients presenting with rhabdomyolysis are at a higher risk of Acute Kidney Injury (AKI), and consequently, an increased risk of Renal Replacement Therapy (RRT) and mortality. We aimed to compare the prognostic significance of creatine kinase (CK) with the McMahon score for AKI, RRT, and mortality in acutely poisoned patients with rhabdomyolysis.

Methods: This prospective study included 50 patients admitted to the Intensive Care Unit (ICU) with poisoning-induced rhabdomyolysis between the beginning of January 2023 and the end of September 2023.

Results: The incidence of rhabdomyolysis was 6.6% in a total of 949 acutely poisoned patients. AKI and mortality rates were 34% and 6% respectively. Antipsychotics were the leading cause of rhabdomyolysis (52%), while substance abuse was the most common cause in the AKI group (58.9% of the AKI group). The initial CK and McMahon scores could predict AKI at the optimum cut-off values of CK > 982 and McMahon score > 6, with an AUC of 0.712 and 0.807, respectively.

Conclusion: The variables independently associated with AKI development were age > 33 years, McMahon score ≥ 6, and WBC count > 18 (10³/µL). The McMahon score is superior to CK in predicting the need for hemodialysis and mortality.

Background: Ring finger 186 (RNF186) is implicated in cancer development, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear.

Methods: RNF186 expression was analyzed using TCGA, GEO, and clinical samples. Its diagnostic and prognostic significance, protein interactions, functional pathways, immune microenvironment associations, and drug sensitivity were evaluated. Single-cell analysis and molecular docking were also performed.

Results: RNF186 was significantly upregulated in ccRCC and negatively correlated with advanced tumor stage. High RNF186 expression indicated better prognosis and showed diagnostic value. It participated in key biological processes and immune modulation, with predominant enrichment in malignant cells. Elevated RNF186 expression was linked to enhanced sensitivity to targeted therapies like sunitinib, which exhibited a favorable predicted binding energy.

Conclusion: RNF186 serves as a potential biomarker for prognosis prediction, tumor microenvironment characterization, and personalized targeted therapy in ccRCC.

Background: PM2.5-induced COPD lacks effective therapies due to unclear pathogenesis. This study explores the role of miR-122 and PTEN in PM2.5-related COPD.

Methods: Using a combination of in vitro and in vivo assays, including cigarette smoke extract (CSE)-induced NR8383 cells and a rat smoke model, combined with MTT, qPCR, flow cytometry, WB, HE staining, Masson staining, HIC, and TUNEL assays, we investigated the role of microRNA-122 (miR-122) and phosphatase and tensin homolog (PTEN) in the molecular mechanisms underlying PM2.5-induced COPD.

Results: Our findings demonstrate that CSE-induced the down-regulated expression of miR-122 leads to the activation of PTEN, which in turn regulates the AKT signaling pathway in NR8383 cells. This modulation results in decreased expression of B-cell lymphoma 2 (BCL2), promoting cell apoptosis. Besides, the result from a rat model of COPD exposed to smoke also confirms this molecular axis which ultimately exacerbating COPD. Specifically, compared with the control, there is significant pulmonary structural damage in model rats exposed to PM2.5, including enlarged alveolar intervals, increased alveolar cavity size, pulmonary fibrosis, and evidence of alveolar destruction with concomitant parabronchial inflammation.

Conclusion: Our research reveals novel insights of PM2.5-induced COPD and proposes the miR-122/PTEN pathway as a potential therapeutic target.