Biomarkers最新文献

Background: The heterogeneous nature of c-MET overexpression in gastric cancer (GC) leads to a lack of consensus on its prognostic significance.

Objective: To evaluate the predictive value of c-MET protein expression in gastric cancer patients.

Methods: A systematic review of studies from PubMed, Web of Science, Embase, and Cochrane Library up to April 2025. Heterogeneity and robustness were assessed using the Cochrane Q test, I² statistic, and sensitivity analysis. Publication bias was evaluated with Egger's and Begg's tests. The Newcastle-Ottawa Scale (NOS) assessed methodological quality.

Results: From 2,322 articles, 22 studies were included. High c-MET expression was significantly associated with reduced overall survival (OS) (Hazard Ratio [HR] = 1.22; 95% Confidence Interval [CI]: 1.13, 1.31; I² = 6.8%; P = 0.371) and disease-free survival (DFS) (pooled HR = 1.39; 95% CI: 1.11, 1.68; I² = 42.4%; P = 0.139). Definitions of c-MET positivity varied across studies regarding thresholds, staining intensity, and detection methods. Subgroup analysis of OS revealed conflicting conclusions based on study design, cutoff values, and c-MET assays.

Conclusion: High c-MET expression may independently predict poor GC prognosis. Future efforts should focus on standardized detection methods and high-quality prospective studies to validate its prognostic value.

Background: Identifying patients benefiting from implantable cardioverter defibrillators (ICD) especially when replacing one that has never served may be challenging.

Objectives: We assessed the association between plasma levels of mid-regional-pro-A-type-natriuretic peptide (ANP), Mid-regional-pro-adrenomedullin (ADM) and aldosterone and, appropriate Implantable Cardioverter Defibrillator (ICD)-therapy in patients with an ICD but no prior therapy.

Methods: A cohort of 331 consecutive patients with an ICD but no prior ICD-therapy was prospectively included in 2 centers and followed-up for a median of 7.9 years. Plasma aldosterone, ANP and ADM levels were measured at inclusion. The primary outcome was the occurrence of appropriate ICD-therapy.

Results: Appropriate ICD-therapy and death occurred in 106(32%) and 114(34%) patients respectively. Rates of ICD generator replacement were 62% regardless of ICD-therapy. The multivariable model showed significant relationships between ANP > median (adjusted HR 1.73[95% CI 1.04-2.86]) and ADM > median (HR 0.53 [95% CI 0.32-0.89]) but not aldosterone, and ICD-therapy. The Fine and Gray analysis accounting mortality as a competing risk showed similar results.

Conclusions: The combination of ANP and ADM are independently associated with the risk of ICD-therapy in patients with an ICD that has never served, and may participate in stratifying patients who may benefit most from ICD generator replacement.

Background: Acute carbon monoxide poisoning triggers complex metabolic derangements including acidosis and alkalosis, but their correlation with neurological injury severity remains insufficiently characterized clinically.

Methods: Consecutive poisoning patients (age ≥14) admitted between January 2019 and February 2025 were classified by neurological impairment severity. Acid-base parameters were analysed using Kruskal-Wallis tests, Spearman's correlation, and principal component analysis with varimax rotation.

Results: Among 940 patients (37.2% male), participants were categorized into three groups by neurological impairment severity: Mild (n = 597), moderate (n = 225), and severe (n = 118). Severe cases showed lower pH (7.39 vs. 7.41), reduced PaCO₂ (34.5 vs. 38.2 mmHg), greater base excess deficit -3.3 vs. 0.4), and higher lactate (3.7 vs. 1.6 mmol/L) (all p < 0.001). Neurological severity positively correlated with lactate (rho = 0.338) and inversely with base excess (rho = -0.268). Principal component analysis identified two components: Factor Component 1 (FAC1) (metabolic compensation, 47-65% variance) and FAC2 (respiratory regulation, 26-41% variance), with FAC1 inversely correlating with severity (rho = -0.319, p < 0.001).

Conclusions: Neurological impairment severity shows dose-dependent correlation with metabolic dysfunction (lactate accumulation, mixed metabolic acidosis-respiratory alkalosis). FAC1 (metabolic compensation) is a strong prognostic biomarker in acute carbon monoxide poisoning.

Objective: C-reactive protein (CRP) levels are generally not correlated with systemic lupus erythematosus (SLE) disease activity. We aimed to develop an algorithm to evaluate juvenile SLE (JSLE) patients with elevated CRP.

Methods: JSLE patients diagnosed at <18 years were included. Each episode of CRP elevation was evaluated separately.

Results: Of 190 JSLE patients (F/M:4/1), 88 (46.3%) never had an elevated CRP, while 102 (53.7%) had 174 episodes of CRP elevation. Causes were infection (n = 139), arthritis (n = 15), macrophage activation syndrome (MAS) (n = 9), MAS and infection (n = 3), serositis (n = 6), and vasculitis (n = 2). MAS was more common in the SLE disease activity index (SLEDAI)>4 group, while infections were more frequent in the SLEDAI ≤ 4 group. MAS episodes were more prevalent among patients with CRP >2x the upper limit of normal. We developed an algorithm to prioritize etiology in JSLE patients with elevated CRP. It led to the correct etiology in 164 of 165 episodes (99.4%) in the primary cohort. In an external JSLE cohort including 37 patients with 68 elevated CRP episodes, the algorithm led to the correct etiology in 67 (98.5%).

Conclusion: Our algorithm could assist physicians evaluating elevated CRP episodes in JSLE patients. Validation in larger cohorts may improve its performance.

Heavy metals have been reported to induce neurotoxicity associated with neurodegenerative disorders. However, there is a dearth of information on Al, Pb and Mn mixture exposure on cerebral cortex functions. This study is aimed at evaluating the effects of Al, Pb and Mn mixture on the cerebral cortex functions. Rats were exposed to Pb 20 mg/kg, Al 35 mg/kg and Mn 0.564 mg/kg body weight singly or in combination for 90 d. Our results showed that Al, Pb and Mn singly or in combination exposure significantly (p ≤ 0.05) decreased antioxidant enzymes activities, glutathione level and increased oxidative stress and neuroinflammation biomarkers in the cerebral cortex of the exposed rats. Moreover, induction of inflammation maker, i.e. COX-2 was associated with increases in apoptotic induction. Furthermore, Al, Pb and Mn singling or in combination exposure significantly (p ≤ 0.05) increased Nrf-2 and decreased BDNF and HO-1 induction as well as increased amyloid precursor proteins and decreased occludin level. Taken together, our result indicates that Al, Pb and Mn mixture exacerbates oxidative stress, neuroinflammation, and apoptosis via downregulation of Nrf2/HO-1/BDNF signalling pathway.

Introduction: The mechanism of cell death during pulsed-field ablation (PFA) appears distinct from thermal energy sources like radiofrequency ablation (RFA), with apoptosis often cited as the primary cause in PFA. This study aimed to clarify the mechanism by comparing markers of necrosis and apoptosis after PFA and RFA.

Methods and results: Patients undergoing pulmonary vein isolation (PVI) for atrial fibrillation were randomized to receive either PFA (Farapulse, Boston Scientific) or RFA (CARTO Smart Touch, Biosense Webster). Myocardial necrosis was assessed via troponin I, and apoptosis via soluble cleaved caspase-3 and Fas ligand, measured pre- and one day post-ablation.

Results: Sixty-five patients were enrolled (PFA: n = 33; RFA: n = 32), with comparable baseline characteristics. One day post-procedure, troponin I levels were significantly higher in the PFA group (median 10,102 ng/L; IQR 8,272-14,207) versus the RFA group (1,006 ng/L; IQR 603-1,433). No post-procedure increase in caspase-3 or Fas ligand was observed in the PFA group, and no differences in apoptotic markers were found between groups.

Conclusion: In vivo, apoptosis does not appear to be the predominant mechanism of cardiomyocyte death following PFA for atrial fibrillation.

Introduction: Early cancer detection significantly improves treatment outcomes; however, many cancers remain undiagnosed until advanced stages. This highlights the urgent need for rapid and precise diagnostic tools. Biosensors offer a transformative approach in cancer diagnostics by enabling early detection and continuous monitoring through the identification of molecular biomarkers.

Methods: Biosensors function by converting biological elements-such as proteins, RNA, or genetic material-into measurable electrical signals. These devices are tailored to detect specific biomarkers, including proteins, peptides, gene mutations, or abnormal gene expression levels associated with various cancers.

Results: Biosensors provide high sensitivity and specificity in identifying cancer cells. They enable real-time monitoring of tumour progression, angiogenesis, and treatment responses. These tools also facilitate accurate imaging of cancer cells and help evaluate the effectiveness of targeted therapies such as chemotherapy.

Conclusion: The integration of biosensors into clinical practice could revolutionize cancer diagnostics by offering early, accurate, and minimally invasive detection methods. This review explores recent advances in biosensor development, the evolving landscape of cancer biomarkers, and the application of different biosensor technologies in cancer detection. Additionally, it addresses current limitations and challenges in clinical implementation, emphasizing the potential of biosensors to enhance patient outcomes through early intervention.

Background: Mitochondria play a crucial role in cellular processes, such as energy metabolism, reactive oxygen species (ROS) generation and apoptosis. Mitochondrial dysfunction induced by stress has been implicated in various health conditions. Circulating cell-free mitochondrial DNA (CFC-MT-DNA) has emerged as a potential biomarker reflecting mitochondrial damage under stress.

Methods: To evaluate the association between CFC-MT-DNA levels and human stress through a systematic review and meta-analysis of case-control studies. A comprehensive literature search was conducted across PubMed, Web of Science and ScienceDirect databases up to September 2023. Eight eligible studies assessing CFC-MT-DNA levels in stressed vs. control individuals were included. Data were analysed using RevMan version 5.4 software.

Results: The meta-analysis revealed significantly elevated CFC-MT-DNA levels in individuals experiencing stress (p = 0.03), particularly in psychological stress-related conditions, such as bipolar disorder (BD) and major depressive disorder (MDD). However, no significant increase was observed in physiological stress conditions, including diabetes and sports training. High heterogeneity (I² = 96%) was observed across studies.

Conclusions: CFC-MT-DNA shows promise as a non-invasive biomarker for psychological stress. Further longitudinal and mechanistic studies are needed to clarify its role across different types of stress and its potential clinical utility.

Background: Breast cancer (BC) is the most common cancer in women. Taxanes are widely used, but their neurotoxicity affects patients' quality of life. Genetic polymorphisms in CYP450 enzymes influence taxane metabolism, leading to variability in toxicity risk.

Methods: A literature search was conducted to identify studies on the association between CYP450 polymorphisms and Taxane-Induced Peripheral Neuropathy (TIPN) in BC patients. Odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI) were estimated using a random-effects model in RStudio.

Results: Nine studies with 3034 patients were included. Overall CYP polymorphisms showed a significant association with TIPN (OR: 1.2877, 95% CI: 1.0262-1.6157). CYP1B1 polymorphism had an inconsistent link to TIPN by OR of 1.1524 (95% CI: 0.7441-1.7849). CYP2C8 polymorphism demonstrated the strongest association (OR: 1.5532, 95% CI: 1.2013-2.0082; HR: 1.5236, 95% CI: 1.1317-2.0512). CYP3A4 showed no significant association (OR: 1.0988, 95% CI: 0.5022-2.4404).

Conclusions: CYP2C8 polymorphisms were significantly linked to TIPN. While CYP1B1 showed inconsistent results, CYP3A4 had no significant association. These findings imply that CYP2C8 genetic variations may affect taxane metabolism and neurotoxicity risk, indicating that pharmacogenomic profiling could help personalize chemotherapy and reduce adverse effects.