Biomarkers For Monitoring Research Articles

BTK and YKL-40 Levels and Their Association with Acute AQP4-IgG-Positive Neuromyelitis Optica Spectrum Disorder.

This study investigated the potential correlation between BTK/YKL-40 levels and the severity of AQP4-IgG + NMOSD, aiming to identify biomarkers for disease monitoring and treatment assessment. Plasma YKL-40 expression was measured in 135 AQP4-IgG + NMOSD patients using ELISA. Patients were categorized into pre- and post-IVMP treatment acute phases, as well as during remission, with a healthy control group included. BTK and NF-κB mRNA levels in PBMCs were detected via q-PCR, and BTK/P-BTK protein expression was assessed using Western blotting. Disability was evaluated using the EDSS score, and clinical characteristics were evaluated alongside laboratory tests. Acute-phase NMOSD patients receiving pre-IVMP therapy presented significantly elevated plasma YKL-40 concentrations compared with those of post-treatment patients, patients in remission, and healthy controls. Additionally, these patients presented significantly higher levels of PBMC BTK mRNA, NF-κB mRNA, BTK, and P-BTK protein expression than remission patients and healthy controls. Plasma YKL-40 levels and PBMC BTK/P-BTK protein levels were positively correlated with EDSS scores. The plasma YKL-40 concentration significantly contributes to disease severity and serves as an independent risk factor for acute NMOSD. Elevated BTK, P-BTK, NF-κB, and YKL-40 levels were observed in acute-phase AQP4-IgG + NMOSD patients. These biomarkers are related to disease activity and may predict treatment efficacy. There is a connection among YKL-40, BTK, and P-BTK levels and disease severity, suggesting their potential involvement in the pathogenic mechanism of AQP4-IgG + NMOSD.

Differential gene expression of immune response in COVID-19 and its relationship with progression of COVID-19

Human immune response evolved in virus clearance and gene expression levels of immune response may be associated with progression of Coronavirus disease 2019 (COVID-19). Our current study aims to investigate the relationship between differential gene expression of immune response and progression of COVID-19. A total of 50 participants of COVID-19 group were studied, compared with 39 participants of healthy control group. There were different gene expression profiles in pathways of activation of neutrophil, defense response and adaptive immune response for COVID-19 group before treatment compared to the healthy control group. Distinct gene expression profiles showed that pathways of chemotaxis, immune response and antibacterial humoral response involved in rehabilitation of severe COVID-19 group while pathways of immune system process, defense response to virus and negative regulation of viral genome replication involved in rehabilitation of moderate COVID-19 group. Both protein expression of ATP-binding cassette transporter A1 levels and protein expression of low affinity Fc-receptor FcγRIIIb levels were significantly and positively correlated with COVID-19-IgM levels and might be suitable as biomarkers for monitoring of COVID-19. This study showed that differential gene expression of immune response predicted onset and rehabilitation of COVID-19.

Severe Uncontrolled Asthma: A Longitudinal Retrospective Study Illustrating the Experience of the Pulmonology Clinic of Târgu-Mureș, Romania

Introduction: Severe uncontrolled asthma (SUA) affects approximately 5% of asthma patients, leading to frequent exacerbations, reduced lung function, and lower quality of life. Recent biologic therapies target specific inflammatory pathways, offering new options for SUA. Objective: This study aimed to evaluate clinical characteristics, treatment outcomes, and biomarkers in patients with SUA treated with biologics (Omalizumab, Benralizumab, and Dupilumab) at our clinic. Material and Methods: A six-month retrospective longitudinal study was conducted on 28 patients aged 36–83 years with SUA. Patients were divided into three groups: Omalizumab (n = 4), Benralizumab (n = 18), and Dupilumab (n = 6). Lung function tests and biomarkers such as eosinophil and IgE levels were measured over 3-month periods (T0, T1, and T2). Asthma control was assessed using asthma control tests (ACT), and non-parametric statistical methods were applied. Results: The median patient age was 64 years, with 75% showing elevated eosinophil counts (>300 cells/µL). Benralizumab significantly improved lung function (p < 0.05) and ACT scores (p < 0.001), reducing eosinophil counts to zero (p < 0.001). Patients on Dupilumab and Omalizumab showed improved asthma control (p < 0.05) and reduced exacerbations, albeit to a lesser extent (p > 0.05). Conclusions: Biologics, particularly Benralizumab and Dupilumab, improved asthma control, lung function, and quality of life in SUA patients, with improved ACT scores and spirometry values. Some patients remained poorly controlled, emphasizing the need for personalized treatment and regular biomarker monitoring. Multidisciplinary management and lifestyle changes are critical for better outcomes in SUA.

AI-Enabled Ultra-large Virtual Screening Identifies Potential Inhibitors of Choline Acetyltransferase for Theranostic Purposes.

Alzheimer's disease (AD) and related dementias are among the primary neurological disorders and call for the urgent need for early-stage diagnosis to gain an upper edge in therapeutic intervention and increase the overall success rate. Choline acetyltransferase (ChAT) is the key acetylcholine (ACh) biosynthesizing enzyme and a legitimate target for the development of biomarkers for early-stage diagnosis and monitoring of therapeutic responses. It is also a theranostic target for tackling colon and lung cancers, where overexpression of non-neuronal ChAT leads to the production of acetylcholine, which acts as an autocrine growth factor for cancer cells. Theranostics is a hybrid of diagnostics and therapeutics that can be used to locate cancer cells using radiotracers and kill them without affecting other healthy tissues. Traditional virtual screening protocols have a lot of limitations; given the current rate of chemical database expansion exceeding billions, much faster screening protocols are required. Deep docking (DD) is one such platform that leverages the power of deep neural network (DNN)-based virtual screening, empowering researchers to dock billions of molecules in a speedy, yet explicit manner. Here, we have screened 1.3 billion compounds library from the ZINC20 database, identifying the best-performing hits. With each iteration run where the first iteration gave ∼116 million hits, the second iteration gave ∼3.7 million hits, and the final third iteration gave 168,447 hits from which further refinement gave us the top 5 compounds as potential ChAT inhibitors. The discovery of novel ChAT inhibitors will enable researchers to develop new probes that can be used as novel theranostic agents against cancer and as early-stage diagnostics for the onset of AD, for timely therapeutic intervention to halt the further progression of AD.

Serum Levels of Protein Z, Laminin Subunit Alpha 2, Mixed Lineage Leukemia 4, and Plexin Domain Containing 2 in Newly Diagnosed and Metformin-Treated Type 2 Diabetes Patients

Diabetes mellitus is a globally prevalent disease with several parameters that may be involved in diagnosis or altered throughout disease progression. In this study, 120 patients with type 2 diabetes and healthy controls were recruited, with ages ranging from 30-65 years old. The research focused on determining levels of Protein Z (PROZ), Laminin Subunit Alpha 2 (LAMA2), Mixed Lineage Leukemia 4 (MLL4), and Plexin Domain Containing 2 (PLXDC2). Participants were divided into four groups: group I (n=30) with long-term metformin treatment, group II (n=30) with short-term metformin treatment, group III (n=30) newly diagnosed without medication, and group IV (n=30) healthy controls. Protein markers were measured by ELISA, while fasting blood glucose, lipid profiles, and HbA1c were determined by spectrophotometry and HPLC. ROC curve analysis revealed PLXDC2 had high sensitivity and specificity as a potential biomarker for diabetes diagnosis. LAMA2, MLL4, and PROZ also distinguished between diabetes patients and controls. Overall, these results identify promising biomarkers for diabetes detection and monitoring.

Exploring Salivary Alpha-Amylase as a Biomarker in Periodontitis: A Comparative Analysis of Disease Stages and Clinical Correlations

Periodontal disease, characterized by bacterial plaque accumulation and subsequent immune response, can lead to gingivitis and periodontitis if untreated. Salivary alpha-amylase (sAA) has emerged as a potential biomarker with implications in periodontal disease progression. Objectives: This study aimed to assess and compare salivary alpha-amylase levels in individuals with periodontitis and healthy controls and to investigate its relationship with clinical parameters of periodontal disease. Forty-five participants were categorized into periodontally healthy (n = 13), Stage I and II Periodontitis (n = 17), and Stage III and IV periodontitis (n = 15) groups. Saliva samples were collected and analyzed using ELISA kits. Statistical analyses included tests for normality, group comparisons, post hoc analysis, and correlation analysis. Significant differences in salivary alpha-amylase levels were observed among severity groups (p < 0.05), with higher levels in periodontitis patients than healthy controls. Spearman correlation revealed moderate positive associations between alpha-amylase levels and probing depth (PD) and clinical attachment loss (CAL). Elevated salivary alpha-amylase levels were found to be associated with more severe periodontal disease, suggesting its potential as a biomarker for periodontitis severity. These findings support the utility of salivary biomarkers in periodontal disease diagnosis and monitoring, although further validation and standardization are warranted for clinical application.

Evaluating off-target drug effects seen in RCTs using proteomics and mendelian randomisation

Abstract Introduction Serious adverse drug effects are often not detected until late in drug development after thousands of patients have been exposed to an investigational drug in long and costly clinical trials. More efficient approaches are desirable. Proteomics-informed Mendelian randomisation (MR) can identify potential molecular mechanisms underlying off-target effects of pharmaceuticals and drug repurposing opportunities. Purpose As a demonstration of this approach, we used findings from a previous plasma proteomics study nested within a clinical trial of torcetrapib, which was terminated early because of an increased risk of cardiac events and mortality, in which 200 plasma proteins significantly increased (n=68) or decreased (n=132) after three months of torcetrapib use. We surveyed potential plasma protein-mediated causal effecs of torcetrapib on a wide array of relevant phenotypes in three broad domains: cardiovascular(n=10), immunological(n=9) and cancer(n=4), representing major categories of adverse outcomes that were more common in the treatment arm. Methods We performed three-sample MR on torcetrapib-associated proteins. First, we identified independent cis-pQTL instruments for these proteins in the Atherosclerosis Risk in Communities (ARIC) Study. Then, we used pQTL effect estimates from the deCODE study, to reduce the potential for bias due to winner’s curse and to increase precision. Lastly, we conducted MR analyses on disease-relevant phenotypes using a debiased-IVW estimator and summary results from the largest available GWAS on these phenotypes: coronary artery disease, ischaemic stroke, blood pressure, lipids, heart rate, QT interval, eGFR, serious infections, blood cell counts, immune cell fractions, and several cancers. The significance level for causal protein-phenotype associations was p=1.85E-5 (0.05/(104*26)), correcting for the 104 proteins with valid instruments and the 26 tested outcomes. Results Thirty-three proteins had evidence of a causal association with at least one phenotype. Seventeen proteins were associated with cardiovascular outcomes, including 8 for blood pressure and 9 for lipid levels. We identified more proteins, 25, associated with immune-related phenotypes. One protein was associated with cancer. Of note, 9 proteins had pleiotropic effects across several domains. Conclusions Our approach of using Mendelian randomisation to investigate the causal effects of plasma proteins impacted by medication with known off-target adverse effects revealed several novel causal relationships, highlighting the role of immune function in the development of cardiovascular disease. These results support the use of intermediate omics evaluation to identify potential biomarkers for safety monitoring for drug development and reveal avenues of investigation for drug repurposing.

Long‐Term Monitoring of ApoE4 within Aqueous Humor Using Intraocular Lenses Containing Target‐Responsive Inverse Opal Hydrogel

Neurodegenerative diseases, including Alzheimer's disease (AD), pose significant challenges to global healthcare because of their irreversible postsymptomatic progression. Conventional radiographic techniques have limitations in early detection, owing to the time lapse between symptom recognition by individuals and precise inspection using medical instruments. Current research explores ophthalmic approaches to address this gap, investigating the physiological link between ocular health and brain diseases. Intraocular lenses (IOLs), widely used in cataract and refractive surgeries, provide a safe and minimally invasive platform for the continuous monitoring of neurodegenerative disease biomarkers, including those associated with AD. By integrating biomolecule‐responsive sensors with IOLs, it becomes feasible to achieve early diagnosis and long‐term, noninvasive monitoring postimplantation. Herein, a fluorescently labeled inverse opal hydrogel (FIOH) is merged with IOLs for ApoE4 detection, a key risk factor for AD. The permeability and inherent photonic properties of FIOH facilitate the cumulative enhancement of the fluorescence signal. In a simulation of the aqueous humor circulation, the detection limit for ApoE4 is determined to be 0.1 nM. Therefore, FIOH‐integrated IOLs hold promise not only for early detection but also for providing a reliable platform for the continuous, noninvasive monitoring of neurodegenerative diseases after the initial, minimally invasive implantation.

Continuous monitoring of heart failure biomarker using a sensitive graphene-based electrical sensor

Abstract Heart Failure (HF) is a complex condition that imposes significant burdens on both patients and healthcare systems. The economic impact of HF therapy and management is substantial, underscoring the urgency for proactive measures to mitigate its development. Regular assessments play a pivotal role in identifying individuals at risk and initiating timely interventions to prevent or delay HF progression [1, 2]. NT-proBNP, an amine-terminated form of brain natriuretic peptide, emerges as a promising biomarker in the realm of chronic HF diagnosis, prognosis, and risk assessment [3]. Its utility lies in providing valuable insights into disease progression and prognosis. In recent years, biosensors based on Field Effect Transistors with Graphene (Gr) gate (GFET) have garnered attention for their rapid response, sensitivity, and on-chip integration [4]. Here, we present a sensitive miniaturized GFET sensor for continuous NT-proBNP measurement. The sensor is an array of GFET devices with sensing gates of a monolayer Gr decorated with aptamers as catch probes. Averaging over similar devices in an array approach ensures measurement consistency throughout the experiment. Moreover, the significant challenge posed by the Debye length in FET biosensors is effectively addressed through the functionalization with short folding aptamers [4]. The sensor is built based on a chip comprising an array of 28 individual micro GFETs (Fig. 1a). For the functionalization of Gr gates, we utilized 1-pyrene butyric acid N-hydroxysuccinimide ester as a linker between the aptamer probes and the Gr surface. Subsequently, the Gr surface was incubated with an amine-terminated aptamer solution (Fig. 1c). A schematic diagram of the sensory chip having a droplet of the sample is shown in Fig. 1b. To quantify NT-proBNP levels an 8µL droplet of the buffer solution containing a specific NT-proBNP concentration was deposited onto the sensor. The drain current (IDS) served as the sensor signal for each target concentration (Figs. 2a and 2b). The sensor signal decreased with increasing target concentration, while negligible response was observed when injecting blank buffers. This phenomenon can be attributed to the folding of aptamers upon binding to their target. Also, continuous measurement was conducted at a fixed gate voltage of 0.9V, recording the drain current while the target concentration gradually increased in the sample droplet. This process revealed a decrease in sensor current as we expected (Fig. 2c). The sensor exhibits remarkably low detection limits of 50 pg/mL and a linear range from 100 pg/mL to 10 ng/mL, which are highly conducive for early HF diagnosis and aligning well with reported NT-proBNP levels in patient biofluid [5]. The proposed sensor holds promise as a wearable device for continuous monitoring of high-risk patients. Additionally, this technology shows potential as a detection tool for acute heart failure in hospitalized patients.Sensor viewSensor responses

Low-cost fabrication of digital light processing 3D printed conical microneedles for biomedical applications

The 3D printing of microneedles has become an emerging area of research focus due to its ability to rapidly create microneedle arrays with parametrically variable geometry and composition. Through direct fabrication or via replica molding, 3D printed microneedles can facilitate iterative array assessment and act as a screening tool to quickly establish optimal parameters for tissue insertion and capacity for biomarker monitoring or drug release. However, the widespread adoption of 3D printing by microneedle array researcher group faces multiple barriers: (1) Investment in 3D printing systems that are traditionally associated with high-resolution pose a significant financial cost, (2) Current high-resolution printing methods are often slow and not conducive to rapid manufacturing, (3) Material selection can be limited in some ‘proprietary’ 3D printing systems (e.g. CLIP, SLA, or 2PP), (4) Given the multidisciplinary nature of the microneedle-field, researchers may not have the expertise to optimize printing parameters for a given material or printer. This work explores how ultra-low-cost digital light processing (DLP) printers can rapidly produce functional microneedle arrays for a variety of purposes, whether direct print, master mold production, or creation of coated microneedles, at a fraction of the cost of currently used systems. Further, this work highlights that high quality microneedle arrays can be created using DLP printing methods with reliability exceeding 98 %, tip radii on the order of 30 µm, and with appropriate parameter input optimization, high quality microneedle arrays can be fabricated that express desirable characteristics for multiple forms of solid microneedle array production.

The relation between dietary polysaccharide intake and urinary excretion of tetraglucoside.

The urinary metabolite tetraglucoside (Glc4) is a potential biomarker for hepatic glycogen storage diseases (GSDs). Glc4 is believed to reflect body glycogen content and/or turnover. However, dietary polysaccharide intake may influence Glc4 excretion, potentially limiting the utility of Glc4 as a monitoring biomarker in hepatic GSDs. We aimed to investigate the association of dietary polysaccharide intake with Glc4 excretion. Urinary Glc4 excretion (mmol/mmol creatinine and mmol/24 h) was analyzed using a validated LC-MS/MS method. Data was analyzed from 65 kidney transplant recipients and 58 healthy kidney donors in the TransplantLines cohort study. Spearman's correlation and multivariable linear regression analyses were performed. In the multivariable analysis, dry lean body mass (DLBM), dietary polysaccharide intake, transplantation status, age, sex, and glycated hemoglobin (HbA1c) served as independent variables. Daily variation was examined in 21 healthy individuals of urinary Glc4 excretion in 2-h collections over a 24-h period. Mixed generalized additive models were built to study the association of prior polysaccharide intake with Glc4 excretion. No (univariate) associations were found between polysaccharide intake and Glc4 excretion. However, a significant interaction between DLBM and polysaccharide on 24 h Glc4 excretion was observed in the multivariate analysis. Glc4 excretion throughout the day exhibited no relationship to prior polysaccharide intake. Our findings suggest an indirect effect of polysaccharide intake on Glc4 excretion, potentially due to changes in muscle glycogen content and/or turnover. We have found no evidence that dietary polysaccharides under normal intakes increase urinary Glc4 directly.

The Role of Biomarkers in Monitoring Chronic Fatigue Among Male Professional Team Athletes: A Systematic Review

This systematic review synthesizes evidence on biomarker responses to physiological loads in professional male team sport athletes, providing insights into induced fatigue states. Structured searches across major databases yielded 28 studies examining various biomarkers in elite team sport players. Studies evaluated muscle damage markers, anabolic/catabolic hormones reflecting metabolic strain, inflammatory markers indicating immune activity and tissue damage, immunological markers tied to infection risk, and oxidative stress markers showing redox imbalances from excessive physiological load. Responses were examined in official matches and training across competitive seasons. The evidence shows that professional team sports induce significant alterations in all studied biomarkers, reflecting measurable physiological strain, muscle damage, oxidative stress, inflammation, and immunosuppression during intensive exercise. These effects tend to be larger and more prolonged after official matches compared to training. Reported recovery time courses range from 24-h to several days post-exercise. Monitoring biomarkers enables quantifying cumulative fatigue and physiological adaptations to training/competition loads, helping to optimize performance while mitigating injury and overtraining. Key biomarkers include creatine kinase, testosterone, cortisol, testosterone/cortisol ratio, salivary immunoglobulin-A, and markers of inflammation and oxidative stress. Further research should extend biomarker monitoring to cover psychological stress and affective states alongside physiological metrics for deeper insight into athlete wellness and readiness.

Responsive Theranostic Nanoprobe for Ratiometric Photoacoustic Monitoring of Hypochlorous Acid‐Mediated Inflammation in Cancer Photothermal Therapy

AbstractCancer detection and inflammation monitoring during photothermal therapy (PTT) enable timely cancer intervention and precise inflammation control, advancing to address inflammation‐related tumor recurrence and metastasis associated with PTT. This can be achieved through real‐time monitoring biomarker for cancer and inflammation, like hypochlorous acid (HOCl), a highly reactive oxygen species (hROS) in body with elevated levels in inflammation. Here, a HOCl‐responsive theranostic nanoprobe is introduced, AuNRs@SiO2‐CAA for ratiometric photoacoustic (PA) cancer detection and inflammation monitoring during PTT. AuNRs@SiO2‐CAA emits PA signals at 680 and 820 nm, with only PA680 undergoing changes in the presence of HOCl, enabling precise HOCl imaging via recording changes of ratiometric PA signals (PA680/PA820). AuNRs@SiO2‐CAA exhibits high selectivity and sensitivity, with a detection limit of 0.34 µM for ratiometric PA imaging of HOCl. In vivo, it effectively detects tumor, drives PTT, and monitors inflammation during PTT by sensing HOCl. The successful development of AuNRs@SiO2‐CAA offers a novel theranostic nanoprobe system for cancer diagnosis, poised to enhance PTT through precise inflammation control.

Sweat‐powered, skin‐adhesive multimodal sensor for long‐term and real‐time sweat monitoring

AbstractThe importance of continuous healthcare management has significantly accelerated the development of wearable devices for monitoring health‐related physical and biochemical markers. Despite extensive research on wearable devices for physiological and biochemical monitoring, critical issues of power management and device/skin interfacial properties restrict the advancement of personalized healthcare and early disease detection. Here, we report a multimodal sweat monitoring device featuring a real‐time display and long‐term data analysis based on self‐powered format of sweat‐activated batteries (SABs). The polyvinyl alcohol‐sucrose (PVA‐Suc) hydrogel serves as the key component for the SAB, offering not only great long‐term adhesive properties for conformable wearability but also significant power generation capabilities. A maximum current density of 44.06 mA cm−2 and a maximum power density of 21.89 mW cm−2 can be realized for the hydrogel based SAB. The resulting device integrates an advanced colorimetric and electrochemical sensor array to measure pH levels, glucose concentrations, and chloride ion levels in human sweat, with data wirelessly transmitted by Near Field Communication. The self‐powering features and multiple mode sensing function offer sufficient power to support real‐time monitoring of metabolic biomarkers in sweat, with the ability to visually observe changes in the colorimetric sensors for long‐term data monitoring.

Short Term Treatment Monitoring of Renal and Inflammatory Biomarkers with Naturally Occurring Leishmaniosis: A Cohort Study of 30 Dogs

Various inflammatory and renal biomarkers have already been assessed for monitoring the response to anti-leishmanial therapy in canine leishmaniosis. This study assessed the parasite load, various inflammatory and renal biomarkers pre- and post-treatment, and any association between the studied variables and the degree of disease severity at diagnosis. This is a prospective cohort study of 30 client-owned dogs with leishmaniosis, classified according to LeishVet’s guidelines as stage I (n = 2), stage IIa (n = 7), stage IIb (n = 6), stage III (n = 8), and stage IV (n = 7). In addition to Leishmania real-time PCR in the bone marrow, blood and urine, previously studied biomarkers, and several inflammatory and renal markers never investigated in canine leishmaniosis, such as fibrinogen, antithrombin, urinary fractional excretion of sodium, and urinary amylase-to-creatinine ratio were measured pre- and post-treatment (meglumine antimoniate or miltefosine + allopurinol). A positive Leishmania real-time PCR in the blood at diagnosis predicted a positive Leishmania real-time PCR in the bone marrow post-treatment (p = 0.003). Following treatment, antithrombin and urinary amylase-to-creatinine ratio were significantly changed (p < 0.001, respectively). Urinary amylase-to-creatinine ratio, total iron-binding capacity, and antithrombin were the variables most strongly associated with disease severity (p < 0.005, respectively). Urinary amylase-to-creatinine ratio can be a useful marker to monitor treatment response and to classify the degree of disease severity.

Absolute Quantitative Targeted Monitoring of Potential Plasma Protein Biomarkers: A Pilot Study on Healthy Individuals.

The development of blood tests for the early detection of individual predisposition to socially significant diseases remains a pressing issue. In this pilot study, multiple reaction monitoring mass spectrometry (MRM-MS) with a BAK-270 assay was applied for protein concentrations analysis in blood plasma from 21 healthy volunteers of the European cohort. The levels of 138 plasma proteins were reliably and precisely quantified in no less than 50% of samples. The quantified proteins included 66 FDA-approved markers of cardiovascular diseases (CVD), and other potential biomarkers of pathologies such as cancer, diabetes mellitus, and Alzheimer's disease. The analysis of individual variations of the plasma proteins revealed significant differences between the male (11) and female (10) groups. In total, fifteen proteins had a significantly different concentration in plasma; this included four proteins that exhibited changes greater than ±1.5-fold, three proteins (RBP4, APCS, and TTR) with higher levels in males, and one (SHBG) elevated in females. The obtained results demonstrated considerable agreement with the data collected from 20 samples of a North American cohort, which were analyzed with the similar MRM assay. The most significant differences between the cohorts of the two continents were observed in the level of 42 plasma proteins (including 24 FDA markers), of which 17 proteins showed a ≥1.5-fold change, and included proteins increased in North Americans (APOB, CRTAC1, C1QB, C1QC, C9, CRP, HP, IGHG1, IGKV4-1, SERPING1, RBP4, and AZGP1), as well as those elevated in Europeans (APOF, CD5L, HBG2, SELPLG, and TNA). The results suggest a different contribution of specific (patho)physiological pathways (e.g., immune system and blood coagulation) to the development of socially significant diseases in Europeans and North Americans, and they should be taken into account when refining diagnostic panels.

Aptamer-Based Electrochemical Biosensing Platform for Analysis of Cardiac Biomarkers.

Monitoring biomarkers secreted by cardiomyocytes is critical to evaluate anticancer drug-induced myocardial injury (MI). Cardiac troponin I (cTnI) is considered the gold standard biomarker for MI. Herein, an electrochemical aptasensor is engineered for cTnI detection based on lanthanide europium metal-organic frameworks (Eu-MOFs) and a hybridization chain reaction-directed DNAzyme strategy. Three types of Eu-MOF morphologies were easily synthesized by changing the solvent, and the Eu-MOF modulated by mixing the solvent of dimethylformamide and H2O (D-Eu-MOF) exhibited the best performance compared to other morphologies of the Eu-MOFs. Multifunctional nanoprobes were constructed from D-Eu-MOF@Pt loaded with natural horseradish peroxidase and combined with an aptamer-initiated nuclear acid hybridization chain reaction to form G-quadruplex/hemin DNAzymes for signal amplification. A novel capture probe is constructed on the basis of DNA nanotetrahedrons modified on screen-printed gold electrodes to enhance the capture of the target and multifunctional nanoprobes for signal amplification. It exhibits a detection limit of 0.17 pg mL-1 and a linear range from 0.5 pg mL-1 to 15 ng mL-1. The practicality of the platform is evaluated by measuring cTnI in real samples and secreted by cardiomyocytes after drug treatment, which provides great potential in drug-induced MI evaluation for clinical application.

Spectrum of delayed post-hypoxic leukoencephalopathy syndrome: A systematic review

BACKGROUND Delayed post hypoxic leukoencephalopathy syndrome (DPHLS), also known as Grinker’s myelinopathy, is a rare but significant neurological condition that manifests days to weeks after a hypoxic event. Characterized by delayed onset of neurological and cognitive deficits, DPHLS presents substantial diagnostic and therapeutic challenges. AIM To consolidate current knowledge on pathophysiology, clinical features, diagnostic approaches, and management strategies for DPHLS, providing a comprehensive overview and highlighting gaps for future research. METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes guidelines, we systematically searched PubMed, ScienceDirect and Hinari databases using terms related to delayed post-hypoxic leukoencephalopathy. Inclusion criteria were original research articles, case reports, and case series involving human subjects with detailed clinical, neuroimaging, or pathological data on DPHLS. Data were extracted on study characteristics, participant demographics, clinical features, neuroimaging findings, pathological findings, treatment, and outcomes. The quality assessment was performed using the Joanna Briggs Institute critical appraisal checklist. RESULTS A total of 73 cases were reviewed. Common comorbidities included schizoaffective disorder, bipolar disorder, hypertension, and substance use disorder. The primary causes of hypoxia were benzodiazepine overdose, opioid overdose, polysubstance overdose, and carbon monoxide (CO) poisoning. Symptoms frequently include decreased level of consciousness, psychomotor agitation, cognitive decline, parkinsonism, and encephalopathy. Neuroimaging commonly revealed diffuse T2 hyperintensities in cerebral white matter, sometimes involving the basal ganglia and the globus pallidus. Magnetic resonance spectroscopy often showed decreased N-acetylaspartate, elevated choline, choline-to-creatinine ratio, and normal or elevated lactate. Treatment is often supportive, including amantadine, an antioxidant cocktail, and steroids. Hyperbaric oxygen therapy may be beneficial in those with CO poisoning. Parkinsonism was often treated with levodopa. Most of the patients had substantial recovery over the course of months and many cases had some residual neurocognitive deficits. CONCLUSION DPHLS remains a complex and multifaceted condition with various etiologies and clinical manifestations. Early recognition and appropriate management are crucial to improving patient outcomes. Future research should focus on standardizing diagnostic criteria, using advanced imaging techniques, and exploring therapeutic interventions to improve understanding and treatment of DPHLS. Conducting prospective cohort studies and developing biomarkers for early diagnosis and monitoring will be essential to advance patient care.

Blood Extracellular Vesicles Beyond Circulating Tumour Cells: A Valuable Risk Stratification Biomarker in High-Risk Non-Muscle-Invasive Bladder Cancer Patients.

Non-muscle-invasive bladder cancer (NMIBC) prognosis varies significantly due to the biological and clinical heterogeneity. High-risk stage T1-G3, comprising 15-20% of NMIBCs, involves the lamina propria and is associated with higher rates of recurrence, progression, and cancer-specific mortality. In the present study, we have evaluated the enumeration of tumour-derived extracellular vesicles (tdEVs) and circulating tumour cells (CTCs) in high-risk NMIBC patients and their correlation with survival outcomes such as time to progression (TTP), and cancer-specific survival (CSS). Eighty-three high-risk T1-G3 NMIBC patients treated between September 2010 and January 2013 were included. Blood samples were collected before a transurethral resection of the bladder (TURB) and analysed using the CellSearch® system. The presence of at least one CTC was associated with a shorter TTP and CSS. Extending follow-up to 120 months and incorporating automated tdEV evaluation using ACCEPT software demonstrated that tdEV count may additionally stratify patient risk. Combining tdEVs and CTCs improves risk stratification for NMIBC progression, suggesting that tdEVs could be valuable biomarkers for prognosis and disease monitoring. Further research is needed to confirm these findings and establish the clinical significance of tdEVs in early-stage cancers.

Evaluating Circulating Biomarkers for Diagnosis, Prognosis, and Tumor Monitoring in Pediatric Sarcomas: Recent Advances and Future Directions.

Pediatric sarcomas present a significant challenge in oncology. There is an urgent need for improved therapeutic strategies for high-risk patients and better management of long-term side effects for those who survive the disease. Liquid biopsy is emerging as a promising tool to optimize treatment in these patients by offering non-invasive, repeatable assessments of disease status. Circulating biomarkers can provide valuable insights into tumor genetics and treatment response, potentially facilitating early diagnosis and dynamic disease monitoring. This review examines the potential of liquid biopsies, focusing on circulating biomarkers in the most common pediatric sarcomas, i.e., osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma. We also highlight the current research efforts and the necessary advancements required before these technologies can be widely adopted in clinical practice.