Biomarkers最新文献

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.

Background: Gastric cancer (GC) is the fifth leading cause of cancer-related death worldwide, with a median overall survival of approximately 12 months. The proto-oncogene c-MYC is among the most frequently activated oncogenes, implicated in roughly 20% of all malignancies.

Methods: PubMed, Embase, and Web of Science were systematically searched for studies evaluating the association between c-MYC expression and (1) disease-specific survival (DSS) and (2) overall survival (OS). Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using a fixed-effects model. A two-sided p ≤ 0.05 was considered statistically significant.

Results: Across 15 studies encompassing 2,372 gastric cancer patients (802 c-MYC-positive; 410 male), male gender was strongly associated with c-MYC positivity (OR 8.83; 95% CI 5.74-13.56; p < 0.00001), as were deeper invasion (T3-T4 vs T1-T2: OR 0.38; 95% CI 0.24-0.60; p < 0.00001) and advanced stage (III-IV vs I-II: OR 2.69; 95% CI 1.71-4.23; p < 0.00001). Patients with c-MYC-negative tumors exhibited a markedly higher DSS compared to those with c-MYC-positive tumors (HR 3.73; 95% CI, 2.22-6.26; p < 0.0001).

Conclusion: Our findings identify c-MYC as a significant prognostic biomarker for disease-specific survival in gastric cancer.

Introduction: Endometriosis is an estrogen-dependent condition characterized by ectopic implantation of endometrial tissue; molecular mechanisms underlying lesion persistence remain incompletely understood. Aquaporins (AQPs), transmembrane water channels involved in migration and proliferation, have been implicated in endometriosis pathophysiology, although data on AQP9 are limited.

Methods: This prospective case-control study evaluated AQP9 concentrations in serum, peritoneal fluid, and cervicovaginal secretions of women with endometriomas compared with healthy surgical controls. Twenty-seven women with unilateral endometrioma and 30 undergoing bilateral tubal ligation were included. AQP9 levels were measured using ELISA, and analyses included correlation, receiver operating characteristic (ROC) curve analysis, and logistic regression adjusted for age, body mass index (BMI), gravida and parity.

Results: Peritoneal fluid AQP9 concentrations were significantly higher in women with endometriomas than in controls (275 [58-669] vs. 171.5 [6.6-507] ng/mL, p = 0.023), whereas serum and cervicovaginal AQP9 levels showed no differences. ROC analysis demonstrated high sensitivity (92.6%) but limited specificity (43.3%). Logistic regression confirmed that peritoneal AQP9 > 128 ng/mL was independently associated with endometrioma (OR 4.40, 95%CI 1.66-29.28, p = 0.025). Serum AQP9 was inversely correlated with endometrioma size (p = 0.008).

Conclusion: Peritoneal AQP9 elevation reflects alterations in the local peritoneal microenvironment, supporting its potential role in the pathophysiology of endometriosis.

This study evaluates dielectric conductivity as a diagnostic tool for assessing lead (Pb) levels in albino rats. It also investigated the ameliorative potentials of nano-ZnO-capped sodium carboxymethyl cellulose (nZnO/CMC), synthesized using co-precipitation technique. The average crystallite size obtained from X-ray diffraction measurements is 33 nm. The effect of Pb induced toxicity were evaluated using four groups of six albino rats each, administered with Pb for 61 days. Haematological results show decreasing trends in packed cell volume, red blood and white blood cell counts, and haemoglobin concentration with Pb administration, indicating anaemia. Upon nZnO/CMC administration, both haematological and erythrocyte surface sialic acids parameters were restored, suggesting that nZnO/CMC has Pb chelating capabilities. Toxicity studies revealed nZnO/CMC to be non-toxic to tissues below 2000 mg/kg body weight per os. Dielectric conductivity of normal and exposed blood samples measured between 200 Hz and 4 MHz shows dominance of ionic conductivity; highest for Pb-exposed samples and lowest for the normal/control sample. It also showed a decreasing trend for samples treated with nZnO/CMC at 100 and 200 mg/kg. This work strongly correlates changes in dielectric ionic conductivity with haematological/Pb exposure concentration, suggesting that dielectric ionic conductivity of blood is a promising biomarker for Pb-exposed animals.

Background: The leukocyte-specific protein 1 (LSP1) has been implicated in cancer progression, and this paper aims to reveal the prognostic value and pathogenic role of LSP1 in acute myeloid leukemia (AML).

Methods: The TCGA and GTEx datasets were performed to assess the expression and prognostic significance of LSP1 in AML. qRT-PCR was utilized to detect LSP1 expression in AML patients. The impact of LSP1 knockdown on AML was assessed using CCK-8, 7-AAD/Annexin-V assays, and xenograft mouse models. Gene Set Enrichment Analysis (GSEA), qRT-PCR, and functional experiments were employed to explore and verify the potential signaling pathway of LSP1 in AML.

Results: Our findings revealed that a high expression level of LSP1 indicated poor prognosis for AML. Meanwhile, the knockdown of LSP1 could inhibit AML in vitro and in vivo. Next, we observed that the NF-κB signaling pathway, associated with anti-apoptotic effects, was significantly upregulated in the high LSP1 expression group, and knocking down LSP1 could inhibit it. In addition, we also found that the NF-κB pathway-related anti-AML effect of bortezomib partially relied on LSP1.

Conclusions: This study revealed that LSP1 plays a crucial role in the progression of AML, indicating its potential as a prognostic biomarker and therapeutic target.

Background: Among 6.7 million Americans with heart failure (HF), 40%-60% are estimated to have mild cognitive impairment (MCI) and are at-risk for vascular contributions to cognitive impairment and dementia (VCID). This pilot study examined whether neurodegenerative and inflammatory serum biomarkers are elevated in HF and whether a combination of these biomarkers predicts cognitive performance.

Methods: Thirty-four HF patients (mean age = 69 years, 62% male) were recruited from Banner-University cardiology clinics and underwent blood sampling and neuropsychological testing to derive an 'Actual Composite Cognitive Score.' Age-matched healthy controls included (i) 11 individuals (mean age = 63 years, 20% male) who completed identical procedures and (ii) 24 individuals used exclusively for biomarker analysis. Biomarkers-serum neurofilament light chain (NfL), plasma phosphorylated tau (pTau181, pTau217), placental growth factor (PlGF), cytokines, and NT-proBNP-were quantified using Quanterix Simoa, Milliplex, and Elecsys (Roche) assays.

Result: HF participants scored worse in cognitive assessments than controls (p = 0.0001). Serum NfL (p = 0.02), IL-6 (p < 0.0001), IL-12p40 (p < 0.0001), IL-15 (p = 0.005), MIP-1α (p = 0.007), TNFβ (p = 0.03), and TNFα (p = 0.0002) were increased in HF. NfL and pTau181 correlated with NT-proBNP; NfL, IL-6, and TNFα inversely correlated with cognitive scores. The Composite Biomarker Cognitive Score = NfL + NT-proBNP + IL-6 + TNFα negatively correlated with the Actual Composite Cognitive Score (r = -0.60, p = 0.0002).

Conclusion: These results establish a Composite Biomarker Cognitive Score, which is predictive of cognitive impairment in HF, and may aid in identifying HF patients suitable for cognitive-protective therapies.