Biomarkers in medicine最新文献

Background: Low-grade inflammation remains a clinical concern in virally suppressed people living with HIV-1 (PWH). Identifying reliable biomarkers is essential for monitoring inflammation-related risk.

Methods: This exploratory cross-sectional study evaluated NF-κB p65 as a biomarker in 60 virally suppressed HIV-1 infected individuals and 60 controls. NF-κB p65 and high-sensitive C-reactive protein (HS-CRP) levels were quantified. Statistical analyses were performed in R (v4.3.2) using multivariable logistic regression model, adjusting for age, gender, HS-CRP, and socio-economic status. Predictive performance was assessed using AUC, calibration, and decision curve analysis. Additional analysis includes principal component analysis (PCA), k-means clustering, and linear regression was performed.

Results: NF-κB p65 levels were significantly elevated in PWH than controls (p < 0.001), while HS-CRP was not independently associated. NF-κB p65 remained the strongest predictor of low-grade inflammation (OR = 2.3, AUC = 0.816) than HS-CRP. The model demonstrated good calibration and clinical utility. PCA and k-means clustering revealed heterogenous inflammatory profiles, and NF-κB p65 showed a borderline inverse association with CD4+ T cell counts. Low SES was also linked to increased inflammation (p < 0.001).

Conclusion: NF-κB p65 is a promising biomarker for monitoring subclinical inflammation in virally suppressed HIV-1 infection.

Introduction: Polycystic ovary syndrome (PCOS) is a complicated endocrine condition marked by reproductive, metabolic and chronobiological perturbations. Despite a number of biomarkers that can be used in its diagnosis, they only show the existence of the syndrome and not much information about prognosis. This prognostic blindness complicates disease management and contributes to increased healthcare and economic burden.

Areas covered: The review summarizes the literature on prognostic biomarkers in PCOS, including hormone biomarkers, metabolic biomarkers, circadian regulatory biomarkers, and non-coding RNAs. Clinical, observational, and preclinical findings indicate that these markers reflect early molecular and cellular perturbations, disease progression, and vulnerability to reproductive and metabolic issues.This review primarily focuses ondiagnostic and prognostic biomarkers associated with PCOS, highlighting their relevance in early detection, disease stratification, and risk assessment. Therapeutic biomarkers are discussed only where they offer mechanistic or clinical insight into disease progression.

Expert opinion: The combination of endocrine, metabolic, circadian, and RNA-based biomarkers offers a dynamic approach to PCOS prognostication. These biomarkers can improve the early diagnosis of high-risk patients, individual interventions, and reproductive and metabolic management. Future research should focus on validating these markers in large cohorts and developing predictive models to support clinical decision-making beyond static diagnostic criteria.

Objective: To investigate the relationship between Group B Streptococcus (GBS) infection in pregnant women and adverse pregnancy events (APEs), as well as serum inflammatory factors (IFs) and coagulation parameters.

Methods: A retrospective analysis was conducted on 2,200 late-pregnancy women who delivered at Maternal and Child Health Hospital from March 2020 to January 2023. Data on GBS infection, serotyping, immunofluorescence, coagulation parameters, and APEs were collected. APE incidence was compared between groups, and logistic regression was performed to analyze inflammatory factors and coagulation parameters in GBS-positive women with and without APEs.

Results: Among the participants, 593 (26.95%) were GBS-positive, and 1,607 (73.05%) were GBS-negative. The GBS-positive group had significantly higher rates of preterm birth, intrauterine infection, premature rupture of membranes, placental abruption, postpartum hemorrhage, and meconium-stained amniotic fluid compared to the GBS-negative group (p < 0.05). Logistic regression identified white blood cell count, high-sensitivity C-reactive protein, tumor necrosis factor-α, interleukin-6 (IL-6), interleukin-1β, procalcitonin, and fibrinogen as independent risk factors for APEs (p < 0.05).

Conclusion: GBS infection increases the risk of adverse pregnancy events and is closely associated with alterations in inflammatory and coagulation markers.

This study aimed to assess the diagnostic utility of routine laboratory biomarkers in adults with mTBI. We conducted a prospective study of patients who were admitted to the neurosurgical department with mTBI, had admission laboratory data available, and a brain CT scan was performed. The cohort included 101 patients (mean age: 59 ± 23.14 years). Falls were the most frequent mechanism of TBI (73.2%). Subdural hematoma (SDH) was the most frequent type of intracranial injury (31.7%), followed by contusions (28.7%), and subarachnoid hemorrhage (22.7%). Patients with intracranial trauma had higher neutrophil-to- lymphocyte (NLR) ratio (p = 0.042) and higher glucose levels (p = 0.021) than patients with concussion. Additionally, patients with SDH had significantly higher NLR and glucose levels than patients with other intracranial trauma concussion. ROC analysis showed that NLR and glucose discriminated SDH from contusion with AUCs of 0.74 (95% CI: 0.59 - 0.89) and 0.80 (95% CI: 0.7-0.9), respectively. These findings require validation in larger cohorts and suggest a meaningful role of routine biomarkers in the emergency management of mTBI. However, the single-center design and modest sample size, exclusion of patients suffering from multiple injuries, diabetes or hematologic diseases may affect measured associations.

Introduction: Circular RNAs (circRNAs) are emerging as potential biomarkers due to their role in gene regulation. We explored whether specific circRNAs could serve as biomarkers for cervical cancer screening by distinguishing between different stages of cervical disease.

Areas covered: We analyzed circRNA expression from archival formalin-fixed paraffin-embedded cervical tissues obtained from 272 women, of which 36% were benign, 33% were precancerous and 31% were cancerous. We performed differential expression analysis using DESeq2 to identify circRNAs that showed log2 fold change ≥2.

Expert opinion/commentary: We identified 5790 statistically significant circRNAs that were differentially expressed between benign and cancerous cervical tissues; circ_0123115 (log2FC = 5.10, p = 1.66 × 10^-55), associated with FGF12, was the most significant. Comparing benign to precancerous tissues, we found 1439 circRNAs with statistically significant differential expression, with circ_0100775 (log2FC = 2.13, p = 1.38 × 10^-18), associated with TDRD3, being the most significant. Between precancerous and cancerous tissues, 4915 circRNAs were differentially expressed with statistical significance; circ_0006038 (log2FC = 4.74, p = 1.22 × 10^-40), associated with STXBP6, was the most significant. In a three-way comparison, 57,749 circRNAs were differentially expressed, with circ_0106394 (p = 3.02 × 10^-21), associated with USP22, being the most significant. Our study identified circRNAs with significant differential expression across benign, precancerous, and cancerous cervical tissues, demonstrating their potential role in cervical cancer progression.

Background: Metformin-sulfonylurea combination is a widely prescribed as second-line therapy for type 2 diabetes mellitus (T2DM), yet patient responses vary due to individual genetic variation. These variations, particularly in AMP-activated protein kinase (AMPK) and its upstream regulator liver kinase B1 (LKB1), may contribute to differences in treatment response. This study investigated the association of PRKAA2(rs2746338) and LKB1(rs741765) polymorphisms with metformin-sulfonylurea response in T2DM patients.

Methods: We enrolled 193 T2DM patients on metformin-sulfonylurea therapy after obtaining written consent. Glycemic and lipid parameters were assessed at baseline and after 3 months. Genotyping was performed by PCR-RFLP and ARMS-PCR for PRKAA2(rs2746338) and LKB1(rs741765), respectively. Statistical analysis was conducted using SPSS v27.

Results: Genotype and allele distributions were not significantly different between responders and non-responders. Carriers of PRKAA2(rs2746338) AA and AG and LKB1(rs741765) CT genotypes showed greater FBG reduction (p = 0.028, p < 0.001, and p < 0.001 respectively). Additionally, PRKAA2(rs2746338) AG and LKB1(rs741765) CT genotypes showed significant improvements in PPG, HbA1c, triglycerides, and LDL (all p < 0.05).

Conclusion: We conclude that PRKAA2(rs2746338) and LKB1(rs741765) variants were linked to favorable glycemic and lipid changes, suggesting reduced cardiovascular risk in T2DM. These variants may serve as pharmacogenetic markers for personalized therapy, warranting validation in larger studies.

Aims: This study aimed to evaluate urinary C-megalin in relation to disease staging and diagnostic accuracy in Indian patients with type 2 diabetes mellitus (T2DM).

Materials and methods: In this cross-sectional study, 325 participants were classified into No-DKD, early-DKD, and late-DKD based on kidney disease improving global outcomes (KDIGO) criteria. Urinary C-megalin was quantified by enzyme-linked immunosorbent assay (ELISA) as absolute and creatinine-normalized values. Group comparisons, correlation analyses, and multinomial logistic regression were performed to assess associations with disease stage.

Results: Creatinine-normalized C-megalin excretion was higher in early-DKD compared with No-DKD (median 125.0 vs. 92.0 ng/mg Cr; p = 0.02) and independently associated with early disease [odds ratio (OR) = 1.26, 95% confidence interval (CI): 1.03-1.55; p = 0.02). In late-DKD, absolute C-megalin levels were significantly associated with disease status (OR = 1.23, 95% CI: 1.02-1.48; p = 0.03), while normalized values lost significance. Diagnostic evaluation showed moderate accuracy for detecting early-DKD [area under curve (AUC): 0.69, 95% CI: 0.62-0.76, p = 0.001).

Conclusion: Urinary C-megalin demonstrates stage-dependent diagnostic behavior in DKD, suggesting potential as a complementary marker for early tubular injury and advanced disease in high-risk diabetic populations.

Objectives: This study aimed to investigate the predictive value of the C-reactive protein-albumin-lymphocyte (CALLY) index for mortality in patients diagnosed with Infective Endocarditis (IE).

Methods: We retrospectively analyzed 100 patients diagnosed with IE based on Duke criteria between 2016 and 2024. The CALLY index was calculated at admission using the formula: [(albumin × lymphocyte count)/CRP]. Demographic, clinical, laboratory, and echocardiographic data were collected.

Results: Mortality occurred in 55% of patients. The deceased group had significantly lower CALLY index values compared to survivors (median: 1.7 vs. 6.9, p < 0.001). Multivariate analysis identified male sex (OR 3.791, p = 0.043), diabetes mellitus (OR 4.126, p = 0.022), and a lower CALLY index (OR 0.824, p = 0.005) as independent predictors of mortality, with lower CALLY values being associated with a higher risk of death. The CALLY index demonstrated moderate discriminative power (AUC = 0.792) with a cutoff value of 3.3, which yielded 68.9% sensitivity and 69.1% specificity.

Conclusions: The CALLY index, an accessible and cost-effective biomarker, is independently associated with mortality and may serve as a hypothesis-generating tool for risk stratification in IE patients. Its incorporation into routine clinical assessment may enhance early risk stratification and guide management strategies.

The use of biomarkers in nonclinical species has gained significant attention for improving predictive accuracy in toxicological studies and early disease detection. This article focuses on glutamate dehydrogenase (GLDH), a mitochondrial enzyme currently under regulatory review for qualification as a clinical biomarker to detect hepatocellular injury in patients with elevated serum transaminases due to muscle injury. GLDH has shown effectiveness in evaluating liver injury, particularly in rodents and non-human primates. This opinion paper outlines the potential of GLDH as a biomarker for monitoring drug-induced liver injury (DILI), drawing on the expertise of authors from the IQ DILI Initiative. It highlights industry consensus on GLDH use in nonclinical studies and its relevance in toxicology and drug development. The advantages and challenges of GLDH are discussed, including its interpretation as a mechanistic biomarker with translational relevance. Recent advancements in GLDH research in nonclinical species with different disease backgrounds and therapeutic modalities are explored. The integration of GLDH with other biomarkers to enhance the overall assessment of nonclinical species is reviewed. Our collective consensus opinion on GLDH is that it may offer an additional benefit over traditional biomarkers for hepatotoxicity, particularly when test articles cause increased serum transaminases due to concurrent muscle injury.