Biomarkers最新文献

Background: Osteoarthritis (OA) is a debilitating joint disorder characterized by the progressive degeneration of articular cartilage. Although the role of ion channels in OA pathogenesis is increasingly recognized, diagnostic markers and targeted therapies remain limited.

Methods: In this study, we analyzed the GSE48556 dataset to identify differentially expressed ion channel-related genes (DEGs) in OA and normal controls. We employed machine learning algorithms, least absolute shrinkage and selection operator(LASSO), and support vector machine recursive feature elimination(SVM-RFE) to select potential diagnostic markers. Then the gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed to explore the potential diagnostic markers' involvement in biological pathways. Finally, weighted gene co-expression network analysis (WGCNA) was used to identify key genes associated with OA.

Results: We identified a total of 47 DEGs, with the majority involved in transient receptor potential (TRP) pathways. Seven genes (CHRNA4, GABRE, HTR3B, KCNG2, KCNJ2, LRRC8C, and TRPM5) were identified as the best characteristic genes for distinguishing OA from healthy samples. We performed clustering analysis and identified two distinct subtypes of OA, C1, and C2, with differential gene expression and immune cell infiltration profiles. Then we identified three key genes (PPP1R3D, ZNF101, and LOC651309) associated with OA. We constructed a prediction model using these genes and validated it using the GSE46750 dataset, demonstrating reasonable accuracy and specificity.

Conclusions: Our findings provide novel insights into the role of ion channel-related genes in OA pathogenesis and offer potential diagnostic markers and therapeutic targets for the treatment of OA.

Background: Smoking cessation reduces the risk of developing smoking-related diseases. Although smoking prevalence has declined, many continue smoking cigarettes. Switching completely to smoke-free alternatives like the Tobacco Heating System (THS) 2.2-a heated tobacco product for which there is evidence demonstrating significantly reduced formation and exposure to harmful chemicals compared to cigarettes-has the potential to reduce the harm caused by continuing to smoke cigarettes.

Methods: We conducted a 6-month clinical study (NCT02396381) with a 6-month extension (NCT02649556), initially randomizing 984 adult smokers to continue smoking or switch to THS (non-mentholated), of which 672 continued into the extension study. Endpoints were evaluated at baseline and at 3, 6, and 12 months. We longitudinally assessed biomarkers of potential harm (BoPHs) known to be reversible upon smoking cessation as indicators of pathways involved in the pathogenesis of cardiovascular or respiratory diseases and carcinogenicity. The need to cough and safety profile were also assessed. Impact on eight key BoPHs was used as a proxy to evaluate harm reduction potential.

Results: At 12 months, comparison of BoPH levels between the predominant THS use and cigarette smoking groups showed a positive effect in favor of switching, partially or in full, to THS.

Conclusion: These results provide additional evidence of the harm reduction potential of THS for smokers who would otherwise continue smoking, but they need to be verified in long-term confirmatory studies.

Clinical trial registration: Clinicaltrials.gov Identifier: NCT0264955. Date of registration: January 7, 2016 https://clinicaltrials.gov/ct2/show/NCT02649556.

Background: Biomarkers play a role in identifying, managing, and predicting cancer outcomes. In lung cancer, they are used at various time points. Doubts remain regarding their accuracy for differential diagnosis and histological subtyping. A diagnostic test study was conducted. It included malignant lesions and controls with benign lesions. Before lung biopsy, all patients had the following biomarkers measured in serum (Pro-GRP,NSE,CYFRA21-1,SCC-Ag,CEA).

Methods: The predictive capacity of serum biomarkers was evaluated to discriminate between lung cancer and benign pathology. The accuracy was also assessed for distinguishing between SCLC and NSCLC and explored their ability to perform histological subtyping.

Results: 93 patients were included, 60 with lung cancer, 33 with benign pathology. Pro-GRP and NSE were elevated in SCLC compared with NSCLC or nonmalignant disease. The most accurate for differentiating between malignant and benign pathology were CEA and CYFRA21-1. Pro-GRP had a poor predictive capacity for distinguishing NSCLC from SCLC. However, combined with CEA and CYFRA21-1, performance improved. For SCLC, the diagnostic capacity of Pro-GRP increased by combining with biomarkers, such as NSE/CYFRA21-1.

Conclusions: Biomarkers lacked the sensitivity and specificity for independent differential diagnosis or histological subtyping. However, the observed patterns in biomarker levels associated with specific histological subtypes suggest potential utility in a multi-biomarker approach or in conjunction with other diagnostic tools. This insight could guide future research to improve diagnostic accuracy and personalized treatment strategies in lung cancer.

Materials and methods: The study assessed major adverse cardiac events (MACE) (myocardial infarction, coronary artery bypass graft, percutaneous intervention, stroke, and death. Cox proportional hazards models assessed apolipoprotein AI (ApoA1), apolipoprotein B (ApoB), ceramide score, cystatin C, galectin-3 (Gal3), LDL-C, Non-HDL-C, total cholesterol (TC), N-terminal B-type natriuretic peptide (NT proBNP), high-sensitivity cardiac troponin (HscTnI) and soluble interleukin 1 receptor-like 1. In adjusted models, Ceramide score was defined by from N-palmitoyl-sphingosine [Cer(16:0)], N-stearoyl-sphingosine [Cer(18:0)], N-nervonoyl-sphingosine [Cer(24:1)] and N-lignoceroyl-sphingosine [Cer(24:0)]. Multi-biomarker models were compared with C-statistics and Integrated Discrimination Index (IDI).

Results: A total of 1131 patients were included. Adjusted NT proBNP per 1 SD resulted in a 31% increased risk of MACE/death (HR = 1.31) and a 31% increased risk for stroke/MI (HR = 1.31). Adjusted Ceramide per 1 SD showed a 13% increased risk of MACE/death (HR = 1.13) and a 29% increased risk for stroke/MI (HR = 1.29). These markers added to clinical factors for both MACE/death (p = 0.003) and stroke/MI (p = 0.034). HscTnI was not a predictor of outcomes when added to the models.

Discussion: Ceramide score and NT proBNP improve the prediction of MACE and stroke/MI in a community primary prevention cohort.

Introduction: Colorectal cancer (CRC) is the second most common cause of cancer-related deaths. The hippo pathway works as a regulator of organ growth and is often a target for mutations in cancer. Ferm domain containing protein 6 (FRMD6) is an activator of the hippo pathway. This study aimed to explore the role of FRMD6 in CRC and to determine how well it works as a prognostic factor among CRC patients.

Methods: The tumor expression of FRMD6 was evaluated using immunohistochemistry in 538 colorectal patients operated on at Helsinki University Hospital. We assessed FRMD6 expression with clinicopathological parameters and the impact of FRMD6 expression on survival.

Results: Patients with a high FRMD6 expression exhibited a better prognosis (univariable hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.41-0.81), with a 5-year disease-specific survival (DSS) of 66.3%. By contrast, patients with a low FRMD6 expression had a 5-year DSS of 52.8%. A high FRMD6 expression level served as an independent predictor for better survival in the Cox multivariable survival analysis (HR 0.53, 95% CI 0.33-0.86).

Discussion: To our knowledge, this is the first study to show that a high FRMD6 expression is an independent marker for a better prognosis in CRC and could help determine the prognosis for CRC patients.

Background and objective: Several genetic variations are associated with acute myeloid leukemia (AML) susceptibility, including the GSTP1 Ile105Val polymorphism. Even with the existing meta-analysis conducted on the topic, no consensus has been reached since none of the studies available performed in-depth data analysis. Hence, we performed an updated systematic review and meta-analysis in this paper to obtain more precise estimates.

Materials and methods: We searched various databases and calculated the odds ratio (OR) and 95% confidence interval (CI) to examine whether the GSTP1 Ile105Val polymorphism is associated with AML susceptibility. Further statistical analysis was also done to obtain more accurate and reliable findings.

Results: A total of 15 studies are included in the systematic review, but only 9 were included in the meta-analysis due to the studies deviating from the Hardy-Weinberg equilibrium. The analysis showed significantly increased susceptibility to AML in the allelic, co-dominant, and recessive models. Furthermore, subgroup analysis noted increased AML susceptibility in the non-Asian population. Comparing the proportions of the genotypes and alleles showed a significantly higher proportion of the Val/Val genotype and Val allele in the non-Asian cohort.

Conclusion: The GSTP1 Ile105Val polymorphism is significantly associated with AML susceptibility, especially among non-Asians. Further investigation should be performed to strengthen the current results.

Introduction: The present study aimed at investigating the effect of dietary supplementation of Phoenix dactylifera, an important component of aphrodisiac supplements, on sexual performance, oxido-inflammatory mediators and purinergic signaling system in hypertensive rats.

Material and methods: Hypertension was induced via oral administration of 40 mg/kg L-NAME. Thereafter, the sexual performance of the experimental animals was determined and the hypertensive rats with impaired sexual activities were placed on P. dactylifera-supplemented diet for 21 days, and the effects of the treatment on the overall sexual behavior, antioxidant status, oxido-inflammatory biomarkers, and enzyme activity of the purinergic system were assessed.

Results: Hypertensive rats showed a significant (p < 0.05) decrease in sexual performance, elevated level of oxido-inflammatory mediators, and altered purinergic enzymes activity when compared with the control. However, sub-chronic feeding with P. dactylifera-supplemented diet improved sexual performance, significantly lowered oxido-inflammatory biomarkers, and enhanced the activity of purinergic enzymes in hypertensive rats.

Conclusion: Findings presented in this study suggest that dietary inclusion of P. dactylifera could be useful in managing erectile dysfunction (ED) commonly observed in subjects with hypertension. Findings highlighted in this study thus provide the scientific basis supporting the folkloric use of P. dactylifera as a key ingredient in aphrodisiac supplements.

Background: The study aimed to analyze cytokine levels, including interleukin (IL)-1β, IL-10, and IL-36γ, to investigate the link between pro- and anti-inflammatory responses in periodontal conditions and assess their potential as diagnostic biomarkers for distinguishing between different types of periodontal conditions.

Methods: 80 systemically healthy non-smokers (25 periodontally healthy, 25 with gingivitis, 30 with periodontitis) were included. Clinical periodontal parameters were recorded, and gingival crevicular fluid (GCF) samples were obtained. Receiver operating characteristic (ROC) curve analysis was applied to determine the diagnostic value of cytokines.

Results: IL-36γ had the highest sensitivity for diagnosing periodontitis, although its specificity for identifying those without periodontitis was relatively low. The combination of IL-1β and IL-36γ was the most effective in differentiating periodontitis from periodontal health. IL-10 was found to be an acceptable discriminator for distinguishing gingivitis from healthy conditions. However, its sensitivity and specificity for identifying gingivitis were lower. The combination of the three cytokines showed the highest ability to distinguish between periodontitis and gingivitis.

Conclusion: The levels of IL-1β, IL-10, and IL-36γ in GCF may provide insights into periodontal health and disease status. Further studies are needed to validate these results and explore the potential of these cytokines in periodontal disease management.