Search Results (1,814)

Histone post-translational modifications (PTMs) have emerged as promising epigenetic biomarkers with increasing forensic relevance. Unlike conventional genetic markers such as short tandem repeats (STRs), histone modifications can offer additional layers of biological information, capturing individual-specific regulatory states and remaining detectable even in degraded forensic samples. This review highlights recent advances in understanding histone PTMs in forensic contexts, focusing on three key domains: analysis of degraded biological evidence, differentiation of monozygotic (MZ) twins, and postmortem interval (PMI) estimation. We summarize experimental findings from human cadavers, animal models, and typical forensic samples including bone, blood, and muscle, illustrating the stability and diagnostic potential of marks such as H3K4me3, H3K27me3, and γ-H2AX. Emerging technologies including CUT&Tag, MALDI imaging, and nanopore-based sequencing offer novel opportunities to profile histone modifications at high resolution and low input. Despite technical challenges, these findings support the feasibility of histone-based biomarkers as complementary tools for forensic identification and temporal analysis. Future work should prioritize methodological standardization, inter-laboratory validation, and integration into forensic workflows. However, the forensic applicability of these modifications remains largely unvalidated, and further studies are required to assess their reliability in casework contexts. Full article

Recent studies have demonstrated that the development and progression of hypertensive kidney injury comprise not only elevated systemic blood pressure but also a complex interplay of cellular, molecular, and genetic mechanisms. In this report, we outline the key emerging pathways—ranging from dysregulated renin–angiotensin system signaling, oxidative stress, immune-mediated inflammation, and metabolic abnormalities to epigenetic alterations and genetic susceptibilities—that contribute to kidney damage in hypertensive conditions. In addition, we also discuss precision medicine approaches like biomarker-directed therapies, pharmacologically targeted therapies, and device-based innovations for modulating these pathways. This integrative review emphasizes the application of omics technologies and genetically guided interventions to better stratify patients and offer personalized care for hypertensive kidney disease. Full article

Blood-based biomarkers allow monitoring of an individual’s health status and provide insights into metabolic and inflammatory processes in conditions like obesity, cardiovascular, and liver diseases. However, selecting suitable biomarkers and optimizing analytical assays presents challenges, is time-consuming and laborious. Moreover, knowledge of potential sex differences remains incomplete as research is often carried out in men. This study aims at enabling researchers to make informed choices on the type of biomarkers, analytical assays, and dilutions being used. More specifically, we analyzed plasma concentrations of >90 biomarkers using commonly available ELISA or electrochemiluminescence-based multiplex methods, comparing normal weight (BMI < 25; n = 40) with obese (BMI > 30; n = 40) adult blood donors of comparable age. To help choose optimal biomarker sets, we grouped frequently employed biomarkers into biological categories (e.g., adipokines, acute-phase proteins, complement factors, cytokines, myokines, iron metabolism, vascular inflammation), first comparing normal-weight with obese persons, and thereafter exploratively comparing women and men within each BMI group. Many biomarkers linked to chronic inflammation and dysmetabolism were elevated in persons with obesity, including several adipokines, interleukins, chemokines, acute-phase proteins, complement factors, and oxidized LDL. Further exploration suggests sex disparities in biomarker levels within both normal-weight and obese groups. This comprehensive dataset of biomarkers across diverse biological domains constitutes a reference resource that may provide valuable guidance for researchers in selecting appropriate biomarkers and analytical assays for own studies. Moreover, the dataset highlights the importance of taking possible sex differences into account. Full article

Background/Objectives: Acute kidney injury (AKI) is a common and severe complication in patients with acute myocardial infarction (AMI). Very elderly patients are at a heightened risk of developing AKI. Fibrinogen and albumin are well-known biomarkers of inflammation and nutrition, which are highly related to AKI. We aim to explore the predictive value of the fibrinogen-to-albumin ratio (FAR) for AKI in very elderly patients with AMI. Methods: A retrospective cohort of AMI patients ≥ 75 years old hospitalized at the First Affiliated Hospital of Xi’an Jiaotong University between January 2018 and December 2022 was established. Clinical data and medication information were collected through the biospecimen information resource center at the hospital. Univariate and multivariable logistic regression models were used to analyze the association between FAR and the risk of AKI in patients with AMI. FAR was calculated as the ratio of fibrinogen (FIB) to serum albumin (ALB) level (FAR = FIB/ALB). The primary outcome is acute kidney injury, which was diagnosed based on KDIGO 2012 criteria. Results: Among 1236 patients enrolled, 66.8% of them were male, the median age was 80.00 years (77.00–83.00), and acute kidney injury occurred in 18.8% (n = 232) of the cohort. Comparative analysis revealed significant disparities in clinical characteristics between patients with or without AKI. Patients with AKI exhibited a markedly higher prevalence of arrhythmia (51.9% vs. 28.1%, p < 0.001) and lower average systolic blood pressure (115.77 ± 25.96 vs. 122.64 ± 22.65 mmHg, p = 0.013). In addition, after adjusting for age, sex, history of hypertension, left ventricular ejection fraction (LVEF), and other factors, FAR remained an independent risk factor for acute kidney injury (OR = 1.47, 95%CI: 1.36–1.58). ROC analysis shows that FAR predicted stage 2–3 AKI with superior accuracy (AUC 0.94, NPV 98.6%) versus any AKI (AUC 0.79, NPV 93.0%), enabling risk-stratified management. Conclusions: FAR serves as both a high-sensitivity screening tool for any AKI and a high-specificity sentinel for severe AKI, with NPV-driven thresholds guiding resource allocation in the fragile elderly. Full article

Background: Pleural mesothelioma (PM) is a type of cancer that is difficult to diagnose and treat. Patients may have vastly varying prognoses, and prognostic factors may help guide the clinical approach. As a recently identified biomarker, the pan-Immune-Inflammation-Value (PIV) is a simple, comprehensive, and peripheral blood cell-based biomarker. Methods: The present study represents a retrospective observational analysis carried out within a single-center setting. Ninety-five patients with PM stages I–IV were enrolled in the study. We analyzed the correlation between patients’ demographic characteristics, clinicopathological factors such as histological subtypes, surgery status, tumor thickness, blood-based parameters, and treatment options with their prognoses. PIV was calculated by the following formula: (neutrophil count × monocyte count × platelet count)/lymphocyte count. Additionally, blood-based parameters were used to calculate the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII). Results: We categorized the patients into two groups, low PIV group (PIV ≤ 732.3) and high PIV group (PIV > 732.3) according to the determined cut-off value, which was defined as the median. It was revealed that high PIV was associated with poor survival outcomes. The median follow-up period was 15.8 months (interquartile range, IQR, 7.1 to 29.8 months). The median overall survival (OS) was significantly longer in patients in the low PIV group (median 29.8 months, 95% confidence interval (CI), 15.6 to 44) than the high PIV group (median 14.7 months, 95% CI, 10.8 to 18.6 p < 0.001). Furthermore, the study revealed that patients with low PIV, NLR, and SII values were more likely to be eligible for surgery and were diagnosed at earlier stages. Additionally, these markers were identified as potential predictors of disease-free survival (DFS) in the surgical cohort and of treatment response across the entire patient population. Conclusions: In addition to well-established clinical factors such as stage, histologic subtype, resectability, and Eastern Cooperative Oncology Group (ECOG) performance status (PS), PIV emerged as an independent and significant prognostic factor of overall survival (OS) in patients with PM. Moreover, PIV also demonstrated a remarkable independent prognostic value for disease-free survival (DFS) in this patient population. Additionally, some clues are provided for conditions such as treatment responses, staging, and suitability for surgery. As such, in this cohort, it has outperformed the other blood-based markers based on our findings. Given its ease of calculation and cost-effectiveness, PIV represents a promising and practical prognostic tool in the clinical management of pleural mesothelioma. It can be easily calculated using routinely available laboratory parameters for every cancer patient, requiring no additional cost or complex procedures, thus facilitating its integration into everyday clinical practice. Full article

Background/Objectives: Traumatic brain injury (TBI), especially mild TBI (mTBI), is frequently caused by traffic accidents, falls, or sports injuries. Although computed tomography (CT) is the gold standard for diagnosis, overuse can lead to unnecessary radiation exposure, increased healthcare costs, and emergency department saturation. Blood-based biomarkers have emerged as potential tools to optimize CT scan use. This systematic review aims to evaluate recent evidence on the role of specific blood biomarkers in guiding CT decisions in patients with mTBI. Methods: A systematic search was conducted in the PubMed, Cochrane, and CINAHL databases for studies published between 2020 and 2024. Inclusion criteria focused on adult patients with mTBI evaluated using both CT imaging and at least one of the following biomarkers: glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and S100 calcium-binding protein B (S100B). After screening, six studies were included in the final review. Results: All included studies reported high sensitivity and negative predictive value for the selected biomarkers in detecting clinically relevant intracranial lesions. GFAP and UCH-L1, particularly in combination, consistently identified low-risk patients who could potentially forgo CT scans. While S100B also showed high sensitivity, discrepancies in cutoff values across studies highlighted the need for harmonization. Conclusions: Blood biomarkers such as GFAP, UCH-L1, and S100B demonstrate strong potential to reduce unnecessary CT imaging in mTBI by identifying patients at low risk of significant brain injury. Future research should focus on standardizing biomarker thresholds and validating protocols to support their integration into clinical practice guidelines. Full article

Introduction: Cystic fibrosis (CF) is a genetic condition affecting several organs and systems, including the pancreas, colon, respiratory system, and reproductive system. The detection of a growing number of CFTR variants and genotypes has contributed to an increase in the CF population which, in turn, has had an impact on the overall statistics regarding the prognosis and outcome of the condition. Given the increase in life expectancy, it is critical to better predict outcomes and prognosticate in CF. Thus, each person’s choice to aggressively treat specific disease components can be more appropriate and tailored, further increasing survival. The objective of our narrative review is to summarize the most recent information concerning the value and significance of clinical parameters in predicting outcomes, such as gender, diabetes, liver and pancreatic status, lung function, radiography, bacteriology, and blood and sputum biomarkers of inflammation and disease, and how variations in these parameters affect prognosis from the prenatal stage to maturity. Materials and methods: A methodological search of the available data was performed with regard to prognostic factors in the evolution of CF in children and young adults. We evaluated articles from the PubMed academic search engine using the following search terms: prognostic factors AND children AND cystic fibrosis OR mucoviscidosis. Results: We found that it is crucial to customize CF patients’ care based on their unique clinical and biological parameters, genetics, and related comorbidities. Conclusions: The predictive significance of more dynamic clinical condition markers provides more realistic future objectives to center treatment and targets for each patient. Over the past ten years, improvements in care, diagnostics, and treatment have impacted the prognosis for CF. Although genotyping offers a way to categorize CF to direct research and treatment, it is crucial to understand that a variety of other factors, such as epigenetics, genetic modifiers, environmental factors, and socioeconomic status, can affect CF outcomes. The long-term management of this complicated multisystem condition has been made easier for patients, their families, and physicians by earlier and more accurate identification techniques, evidence-based research, and centralized expert multidisciplinary care. Full article

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, necessitating novel therapeutic approaches. Oncolytic treatments, particularly oncolytic viruses (OVs), have emerged as promising candidates by selectively infecting and lysing tumor cells while stimulating anti-tumor immunity. Various virus-based therapies are under investigation, including genetically engineered herpes simplex virus (HSV), adenovirus, poliovirus, reovirus, vaccinia virus, measles virus, and Newcastle disease virus, each exploiting unique tumor-selective mechanisms. While some, such as HSV-based therapies including G207 and Delytact^TM, have demonstrated clinical progress, significant challenges persist, including immune evasion, heterogeneity in patient response, and delivery barriers due to the blood–brain barrier. Moreover, combination strategies integrating OVs with immune checkpoint inhibitors, chemotherapy, and radiation are promising but require further clinical validation. Non-viral oncolytic approaches, such as tumor-targeting bacteria and synthetic peptides, remain underexplored. This review highlights current advancements while addressing critical gaps in the literature, including the need for optimized delivery methods, better biomarker-based patient stratification, and a deeper understanding of GBM’s immunosuppressive microenvironment. Future research should focus on enhancing OV specificity, engineering viruses to deliver therapeutic genes, and integrating OVs with precision medicine strategies. By identifying these gaps, this review provides a framework for advancing oncolytic therapies in GBM treatment. Full article

Background/Objectives: Although numerous prognostic biomarkers have been proposed for colorectal cancer (CRC), their longitudinal evaluation remains limited. The aim of this study was to investigate longitudinal changes in biomarkers calculated from routinely used laboratory markers and their relationships to common chronic diseases (comorbidities). Methods: A retrospective longitudinal observational study was completed with the inclusion of 817 CRC patients and a total of 4542 measurement points. Pan-immune inflammation value (PIV), prognostic nutritional index (PNI), and systemic immune-inflammation index (SII) were calculated based on complete blood count and albumin measurement data. Results: Longitudinal data analyses confirmed the different values and slopes of the parameters tested at the different endpoints. Survivors had the lowest and most constant PIVs and SII values, and the highest and most slowly decreasing PNI values. Those patients with non-cancerous death had similar values to the previous cohort, but an increase/decrease occurred towards the death event. Patients with CRC-related death had significantly higher PIVs and SII values and significantly lower PNI values (p < 0.0001), and a significant increase/decrease was observed at the early observational periods. The presence of lymph node and/or distant metastases, adjuvant chemotherapy, and hypertension significantly affected PIVs and SII and/or PNI values. The changes in PIVs and SII and PNI values toward pathological values are poor prognostic signs (p < 0.0001). Conclusions: Each of the three calculated markers demonstrates suitability for longitudinal patient follow-up, and their pathological alterations over time serve as valuable prognostic indicators. They may also be useful to detect certain clinicopathological parameters early. Full article

Childhood obesity increases chronic disease risk, but no comprehensive synthesis has evaluated the impact of school-based combined nutrition education and physical activity interventions on cardiometabolic biomarkers in children aged 3 to 12 years. This systematic review was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420251085194). Five databases were systematically searched through June 2025. Twelve randomized controlled trials involving 18,231 children were included and assessed using the PEDro scale. Ten trials demonstrated significant improvements in at least one cardiometabolic biomarker. Blood pressure (8 studies) outcomes showed systolic reductions of 1.41–6.0 mmHg in six studies. Glucose metabolism (5 studies) improved in two studies with reductions of 0.20–0.22 mmol/L. Lipid profiles (7 studies) improved in three studies, including total cholesterol (−0.32 mmol/L). Insulin levels (5 studies) decreased significantly in two investigations. Anthropometric improvements included BMI and body fat. Physical activity increased by >45 min/week and dietary habits improved significantly. Programs with daily implementation (90-min sessions 4x/week), longer duration (≥12 months), family involvement (parent education), and curriculum integration (classroom lessons) showed superior effectiveness. Interventions targeting children with overweight/obesity demonstrated higher changes compared to the general population. However, methodological limitations included a lack of assessor blinding, absence of subject/therapist blinding, and inadequate retention rates. School-based interventions combining nutrition and physical activity can produce significant improvements in cardiometabolic biomarkers, supporting comprehensive, sustained multicomponent programs for early chronic disease prevention. Full article

Background and Objectives: The long-term renal and cardiovascular effects of neonatal acute kidney injury (AKI) in preterm infants remain unclear. This study investigated whether neonatal AKI leads to persistent subclinical kidney injury and blood pressure changes in school-aged children born preterm. Methods: In this prospective cohort, preterm-born children (≤35 weeks’ gestation) with (n = 19) and without (n = 38) neonatal AKI were evaluated at 7–12 years. A term-born control group (n = 44) was included for biomarker comparison. Assessments included perinatal data, anthropometry, office and ambulatory blood pressure monitoring (ABPM), and renal ultrasonography. Kidney function was evaluated using serum creatinine (sCr), cystatin C, and estimated glomerular filtration rate (eGFR). Tubular injury was assessed using urinary kidney injury molecule-1/Cr (KIM-1/Cr), neutrophil gelatinase-associated lipocalin/Cr (NGAL/Cr), and trefoil factor 3/Cr (TFF3/Cr) ratios, as well as serum TFF3. Results: Conventional kidney function markers were similar among groups. However, the AKI group had higher serum cystatin C, lower cystatin C–based eGFR, and elevated urinary KIM-1/Cr and NGAL/Cr compared to no-AKI and term controls. Serum TFF3 was also higher in the AKI group. ABPM revealed higher nocturnal systolic blood pressure and blood pressure load in the AKI group. Kidney size did not differ between preterm subgroups. Conclusions: Neonatal AKI in preterm infants is associated with subtle alterations and potential renal stress or injury at school age, detectable only with sensitive biomarkers and ABPM. Further prospective studies are needed to validate these biomarkers and determine their role in predicting long-term outcomes in preterm infants with neonatal AKI. Full article

Diabetic nephropathy affects approximately 30–40% of individuals with diabetes mellitus (DM) and is a major contributor to end-stage renal disease (ESRD). While angiotensin II receptor blockers (ARBs) have long served as a standard treatment, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have recently gained attention for their renal and cardiovascular benefits. However, comparative real-world data on their long-term renal effectiveness remain limited. We conducted a retrospective, longitudinal study over a 2-year period to compare the impact of ARB monotherapy versus SGLT2i and angiotensin-converting enzyme inhibitor (ACEi) combination therapy on the progression of chronic kidney disease (CKD) in patients with DM. A total of 126 patients were included and grouped based on treatment regimen. Renal biomarkers were analyzed using t-tests and ANOVA (p < 0.01). Albuminuria was qualitatively classified via urinalysis as negative, level 1 (+1), level 2 (+2), or level 3 (+3). The ARB group demonstrated higher estimated glomerular filtration rate (eGFR) and lower serum creatinine (sCr) levels than the combination therapy group, with glycated hemoglobin (HbA1c), potassium (K⁺), and blood pressure remaining within normal limits in both cohorts. Albuminuria remained stable over time, with 60.8% of ARB users and 73.1% of combination therapy users exhibiting persistently or on-average negative results. Despite the expected additive benefits of SGLT2i/ACEi therapy, ARB monotherapy was associated with slightly more favorable renal function markers and a lower incidence of severe albuminuria. These findings suggest a need for further controlled studies to clarify the comparative long-term renal effects of these treatment regimens. Full article

Lower respiratory tract infections remain a leading cause of morbidity and mortality among Intensive Care Unit patients, with severe cases often progressing to acute respiratory distress syndrome (ARDS). This life-threatening syndrome results from alveolar–capillary membrane injury, causing refractory hypoxemia and respiratory failure. Early detection and management are critical to treat the underlying cause, provide protective lung ventilation, and, eventually, improve patient outcomes. The 2012 Berlin definition standardized ARDS diagnosis but excluded patients on non-invasive ventilation (NIV) or high-flow nasal cannula (HFNC) modalities, which are increasingly used, especially after the COVID-19 pandemic. By excluding these patients, diagnostic delays can occur, risking the progression of lung injury despite ongoing support. Indeed, sustained, vigorous respiratory efforts under non-invasive modalities carry significant potential for patient self-inflicted lung injury (P-SILI), underscoring the need to broaden diagnostic criteria to encompass these increasingly common therapies. Recent proposals expand ARDS criteria to include NIV and HFNCs, lung ultrasound, and the SpO₂/FiO₂ ratio adaptations designed to improve diagnosis in resource-limited settings lacking arterial blood gases or advanced imaging. However, broader criteria risk overdiagnosis and create challenges in distinguishing ARDS from other causes of acute hypoxemic failure. Furthermore, inter-observer variability in imaging interpretation and inconsistencies in oxygenation assessment, particularly when relying on non-invasive measurements, may compromise diagnostic reliability. To overcome these limitations, a more nuanced diagnostic framework is needed—one that incorporates individualized therapeutic strategies, emphasizes lung-protective ventilation, and integrates advanced physiological or biomarker-based indicators like IL-6, IL-8, and IFN-γ, which are associated with worse outcomes. Such an approach has the potential to improve patient stratification, enable more targeted interventions, and ultimately support the design and conduct of more effective interventional studies. Full article

Background: TNF receptor 1 (TNF-R1) mediates the proinflammatory and proapoptotic effects of TNF-alpha, with its soluble form predicting incident heart failure (HF). While there is evidence linking TNF pathway activation to cardiac dysfunction, the mechanisms involved remain unclear. This study aimed to investigate the association between TNF-R1, exercise capacity, and cardiac function in asymptomatic patients with hypertensive heart disease (HHD). Methods: We enrolled 80 patients (mean age 55 ± 12 years) with HHD and no clinical symptoms of HF (stages A and B). Echocardiography, including tissue Doppler and left atrial and left ventricular (LV) strain assessment, was performed at rest. Peripheral venous blood samples were collected to measure serum TNF-R1 concentration. Results: The study population was divided into two subsets based on the median exercise capacity (peak VO₂) value. Patients with higher VO₂ had lower serum TNF-R1 concentration and higher early peak mitral annular velocity (e’) and peak atrial longitudinal strain (PALS). After adjusting for other covariates, multivariable regression analysis identified TNF-R1 as an independent determinant of peak VO₂. Mediation analysis revealed that the relationship between TNF-R1 and peak VO₂ was mediated by LV diastolic function (PALS or e’), with a decrease in the beta coefficient after including mediator variables from 0.37 (p < 0.001) to 0.30 (p < 0.006) and 0.31 (p = 0.004), respectively. Conclusions: In patients with HHD, higher TNF-R1 levels are associated with lower exercise capacity, which may be mediated by impaired LV diastolic function. These findings might suggest a role of TNF signalling in early HF development, justifying further studies to evaluate TNF-R1 as a biomarker for risk of HF progression. Full article

Pyridoxine-dependent epilepsy (PDE) represents a group of rare developmental and epileptic encephalopathies. The most common PDE is caused by biallelic pathogenic variants in ALDH7A1 (PDE-ALDH7A1; OMIM #266100), which encodes α-aminoadipate semialdehyde (α-AASA) dehydrogenase, a key enzyme in lysine catabolism. Affected individuals present with seizures unresponsive to conventional anticonvulsant medications but responsive to high-dose of pyridoxine (vitamin B6). Adjunctive lysine restriction and arginine supplementation have also shown potential in improving neurodevelopmental outcomes. Given the significant benefit of early intervention, PDE-ALDH7A1 is a strong candidate for newborn screening (NBS). However, traditional biomarkers are biochemically unstable at room temperature (α-AASA and piperideine-6-carboxylate) or lack sufficient specificity (pipecolate), limiting their utility for biomarker-based NBS. The recent identification of two novel and stable biomarkers, 2S,6S-/2S,6R-oxopropylpiperidine-2-carboxylate (2-OPP) and 6-oxo-pipecolate (oxo-PIP), offers renewed potential for biochemical NBS. We evaluated the feasibility of incorporating 2-OPP, oxo-PIP, and pipecolate into routine butylated FIA-MS/MS workflows used for biochemical NBS. A total of 9402 dried blood spots (DBS), including nine confirmed PDE-ALDH7A1 patients and 9393 anonymized controls were analyzed using a single multiplex assay. 2-OPP emerged as the most sensitive biomarker, identifying all PDE-ALDH7A1 patients with 100% sensitivity and a positive predictive value (PPV) of 18.4% using a threshold above the 99.5th percentile. Combining elevated 2-OPP (above the 99.5th percentile) with either pipecolate or oxo-PIP (above the 85.0th percentile) as secondary marker detected within the same multiplex FIA-MS/MS assay further improved the PPVs to 60% and 45%, respectively, while maintaining compatibility with butanol-derivatized method. Notably, increasing the 2-OPP threshold above the 99.89th percentile, in combination with either pipecolate or oxo-PIP above the 85.0th percentile resulted in both 100% sensitivity and 100% PPV. This study supports the strong potential of 2-OPP-based neonatal screening for PDE-ALDH7A1 within existing NBS infrastructures. The ability to multiplex 2-OPP, pipecolate and oxo-PIP within a single assay offers a robust, practical, high-throughput and cost-effective approach. These results support the inclusion of PDE-ALDH7A1 in existing biochemical NBS panels. Further prospective studies in larger cohorts are needed to refine cutoffs and confirm clinical performance. Full article