Diverse Biomarkers Research Articles

Development and validation of a tumor marker-based model for the prediction of lung cancer: an analysis of a multicenter retrospective study in Shanghai, China.

The incidence and mortality rates of cancer are the highest globally. Developing novel methodologies that precisely, safely, and economically differentiate between benign and malignant lung conditions holds immense clinical importance. This research seeks to construct a predictive model utilizing a combination of diverse biomarkers to effectively discriminate between benign and malignant lung diseases. This retrospective study included patients admitted to the two general hospitals in Shanghai from 2014 to 2015. This study was developed using five tumor markers: carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), cytokeratin fragment 21-1 (CA211), squamous cell carcinoma antigen (SCC), and neuron specific enolase (NSE). The entire sample was divided into two groups according to the hospital: 1033 cases were included in the development cohort and 300 cases in the validation cohort. Logistic regression analysis was used for univariate analysis to explore individual correlations between each selected clinical variable and lung cancer diagnostic outcome. Diagnostic prediction models were constructed and validated based on independent prognostic factors identified using multifactorial analysis. A nomogram was created using these tumor markers (age and sex were additionally included) and validated using the concordance index and calibration curves. Clinical prediction models were evaluated using decision curve analysis. Fully adjusted multivariate analysis showed that the risk of lung cancer was 2.38 times higher in men than in women. CEA positivity was associated with an 13.41-fold increased risk in lung cancer. The area under the curve (AUC) values for the development cohort and validation cohort models were 0.907 and 0.954, respectively. In the established nomogram, the AUC for the receiver operating characteristic curve was 0.907 (95% CI, 0.889-0.925). The validation model confirmed the strong discriminative power of the nomogram (AUC = 0.954). The described calibration curves demonstrated good fit predictions and observation probabilities. In addition, decision curve analysis concluded that the newly established nomogram has important implications for clinical decision making. Combined prediction models based on CEA, CA199, CA211, SCC, and NSE biomarkers could significantly the differentiation between benign and malignant lung diseases, thus facilitating better clinical decision making.

Amplified Sensitivity in SERS Detection of L1CAM With Silver Plasmonic Mesoporous Silica Capsules on an Imprinted Films

AbstractThis study presents a novel approach for dual detection, leveraging a combination of a Raman reporter‐bearing nanomaterial and molecular imprinting polymers (MIP). A core‐shell Au‐Ag nanoparticles (Au‐Ag NPs) encapsulated in mesoporous silica nanocapsules (Au‐Ag NCs) and a new MIP‐based material targeting L1CAM are used. The MIP prepared via surface imprinting on a carbon screen‐printed electrode (C‐SPE) used thionine (TH) as a monomer. The plasmonic Au‐AgNCs are further functionalized with the Raman reporter 4‐mercaptobenzoic acid (MBA) and anti‐L1CAM for selective detection by surface‐enhanced Raman scattering (SERS) spectroscopy. The biosensor's analytical performance is evaluated using both SERS and electrochemical impedance spectroscopy (EIS). EIS analysis reveals a linear response within the concentration range of 0.1 to 100 ng mL−1 in buffer and serum samples. SERS demonstrates a sensitivity ten times higher than EIS. Selectivity study demonstrates the biosensor's excellent specificity toward L1CAM, with minimal interference from other compounds such as creatinine, glucose, and carbohydrate antigen 19‐9 (CA 19‐9). The Raman signal from the reporter molecule correlates with increasing L1CAM concentrations, reinforcing the analytical findings obtained through electrochemical analysis. Thus, the combination of dual detection and recognition capabilities presents promising potential for detecting diverse biomarkers, especially in critical scenarios where reducing false‐positive or false‐negative errors is crucial.

Investigation of endoplasmic reticulum stress-regulated chaperones as biomarkers in idiopathic nonobstructive azoospermia.

Azoospermia is a condition in which sperm cells are completely absent in a male's ejaculate. Typically, sperm production occurs in the testes and is regulated by a complex series of cellular and molecular interactions. Endoplasmic reticulum (ER) stress arises when there is a deviation from or damage to the normal functions of the ER within cells. In response to this stress, a cascade of response mechanisms is activated to regulate ER stress within cells. This study aims to investigate the role of ERstress-regulated chaperones as potential biomarkers in male infertility. ER stress associated with azoospermia can manifest in cells such as spermatogonia in the testes and can impact sperm production. As a result of ER stress, the expression and activity of a variety of proteins within cells can be altered. Among these proteins are chaperone proteins that regulate the ER stress response. The sample size was calculated to be a minimum of 36 patients ineach group. In this preliminary study, we measured and compared serum levels of protein disulfide-isomerase A1, protein disulfide-isomerase A3 (PDIA3), mesencephalic astrocyte-derived neurotrophic factor (MANF), glucose regulatory protein 78 (GRP78), clusterin (CLU), calreticulin (CRT), and calnexin (CNX) between male subjects with idiopathic nonobstructive azoospermia and a control group of noninfertile males. Serum PDIA1 (P=0.0004), MANF (P=0.018), PDIA3 (P<0.0001), GRP78 (P=0.0027), andCRT (P=0.0009) levels were higher in the infertile group compared to the control. In summary, this study presents novel findings in a cohort of male infertile patients, emphasizing the significance of incorporating diverse biomarkers. It underscores the promising role of ER stress-regulated proteins as potential serum indicators for male infertility. By elucidating the impact of ER stress on spermatogenic cells, the research illuminates the maintenance or disruption of cellular health. A deeper understanding of these results could open the door to novel treatment approaches for reproductive conditions, including azoospermia.

Evolution of Liquid Biopsies for Detecting Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterised by late diagnosis and poor prognosis. Despite advancements, current diagnostic and prognostic strategies remain limited. Liquid biopsy techniques, including circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), circulating tumour exosomes, and proteomics, offer potential solutions to improve PDAC diagnosis, prognostication, and management. A systematic search of Ovid MEDLINE identified studies published between 2019 and 2024, focusing on liquid biopsy biomarkers for PDAC. A total of 49 articles were included. ctDNA research shows some promise in diagnosing and prognosticating PDAC, especially through detecting mutant KRAS in minimal residual disease assays. CTC analyses had low sensitivity for early-stage PDAC and inconsistent prognostic results across subpopulations. Exosomal studies revealed diverse biomarkers with some diagnostic and prognostic potential. Proteomics, although relatively novel, has demonstrated superior accuracy in PDAC diagnosis, including early detection, and notable prognostic capacity. Proteomics combined with CA19-9 analysis has shown the most promising results to date. An update on multi-cancer early detection testing, given its significance for population screening, is also briefly discussed. Liquid biopsy techniques offer promising avenues for improving PDAC diagnosis, prognostication, and management. In particular, proteomics shows considerable potential, yet further research is needed to validate existing findings and comprehensively explore the proteome using an unbiased approach.

Filter Membrane-Based Colorimetric Approach for Point-of-Care Detection of Biomarkers Using CRISPR-Cas12a.

CRISPR-Cas-based point-of-care testing (POCT) strategies have been widely explored for the detection of diverse biomarkers. However, these methods often require complicated operations, such as careful solution transfer steps, to achieve high sensitivity and accuracy. In this study, we combine a filter membrane-based POCT method with CRISPR-Cas12a for colorimetric detection of biomarkers. For the nucleic acid target, the trans-cleavage activity of CRISPR-Cas12a is directly triggered, cutting the single-stranded DNA linkers on glucose oxidase (GOx)-modified polymer nanoparticles. Due to the size difference between GOx and the polymer nanoparticles, GOx can be separated using a filter membrane. The filtrate containing GOx reacts with the substrate to generate a colorimetric signal. For the non-nucleic acid target, the non-nucleic acid signal is converted into a nucleic acid signal that activates CRISPR-Cas12a, resulting in a colorimetric signal. The entire operation is easy to perform, and the signal can be directly observed via the naked eye, which circumvents the use of costly instruments. The developed strategy holds great promise for accurate and accessible POCT detection of disease biomarkers in resource-limited settings.

Identification of oxidative stress biomarkers in apical periodontitis: A scoping review with bibliometric analysis

AbstractOxidative stress (OS) is a ubiquitous process for protecting against microorganisms' challenges. This review maps the most used methods for obtaining samples and analysing reactive oxygen species levels in apical periodontitis, following the PRISMA Extension for Scoping Reviews and is registered in Open Science Framework ([https://doi.org/10.17605/OSF.IO/D5U76]). A systematic search was conducted in electronic databases MEDLINE (PubMed), Embase, Scopus, Web of Science, LILACS, SciElo, OATD and DANS up to 17 July 2023. A total of 18 studies were included, with periapical tissue being the most common sample. Twenty‐eight different oxidative stress markers were identified, with inducible nitric oxide synthase being the most prevalent. The use of diverse biomarkers for oxidative stress assessment lacks specificity in identifying particular OS species for evaluating apical periodontitis and potential systemic effects. Studies are necessary to compare results obtained from less invasive methods (such as saliva and crevicular fluid) with those from periapical lesion samples.

Assessing Aflatoxin Exposure: Exploring Types of Exposure and Diverse Biomarkers – A Minireview

Assessing Aflatoxin Exposure: Exploring Types of Exposure and Diverse Biomarkers – A Minireview

Malignant Peripheral Nerve Sheath Tumor, a Heterogeneous, Aggressive Cancer with Diverse Biomarkers and No Targeted Standard of Care: Review of the Literature and Ongoing Investigational Agents.

Malignant peripheral sheath tumor (MPNST) is a rare, aggressive form of soft-tissue sarcoma that presents a unique set of diagnostic and treatment challenges and is associated with major unmet treatment medical needs. The chief aim of this review is to consider the epidemiology, histology, anatomic distribution, pathologic signaling pathways, diagnosis, and management of MPNST, with a focus on potential targeted therapies. A subordinate objective was to establish benchmarks for the antitumor activity of such treatments. MPNST has an incidence of 1:100,000 in the general population and 1:3500 among patients with the inherited condition of neurofibromatosis-1. Spindle-cell sarcomas of neural-crest origin, MPNSTs are frequently situated in the extremities and pelvis/trunk, often at the confluence of large nerve roots and bundles. Highly copy-number aberrant and enriched in chromosome 8, MPNSTs have a complex molecular pathogenesis that likely involves the interplay of multiple signaling pathways, including Ras/AKT/mTOR/MAPK, EGFR, p53, PTEN, and PRC2, as well as factors in the tumor microenvironment. A combination of magnetic resonance imaging (MRI) and positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) enables comprehensive assessment of both morphology and metabolism, while MRI- and ultrasound-guided core needle biopsy can confirm histopathology. Although surgery with wide excisional margins is now the chief curative approach to localized disease, MPNST-specific survival has not improved in decades. For advanced and metastatic MPNST, radiation and chemotherapy (chiefly with anthracyclines plus ifosfamide) have somewhat promising but still largely uncertain treatment roles, chiefly in local control, downstaging, and palliation. No single druggable target has emerged, no objective responses have been observed with a number of targeted therapies (cumulative disease control rate in our review = 22.9-34.8%), and combinatorial approaches directed toward multiple signal transduction mechanisms are hallmarks of ongoing clinical trials. Despite advances in our understanding of the genetics and molecular biology of MPNST, further research is warranted to: (1) unravel the complex pathogenesis of this condition; (2) improve diagnostic yield; (3) delineate the appropriate roles of chemotherapy and radiation; and (4) develop a targeted therapy (or combination of such treatments) that is well tolerated and prolongs survival.

Deciphering AKI in Burn Patients: Correlations between Clinical Clusters and Biomarkers.

Acute kidney injury (AKI) is a significant complication in burn patients, impacting outcomes substantially. This study explores the heterogeneity of AKI in burn patients by analyzing creatinine time-series data to identify distinct AKI clusters and evaluating routine biomarkers' predictive values. A retrospective cohort analysis was performed on 2608 adult burn patients admitted to Hangang Sacred Heart Hospital's Burn Intensive Care Unit (BICU) from July 2010 to December 2022. Patients were divided into four clusters based on creatinine trajectories, ranging from high-risk, severe cases to lower-risk, short-term care cases. Cluster A, characterized by high-risk, severe cases, showed the highest mortality and severity, with significant predictors being PT and TB. Cluster B, representing intermediate recovery cases, highlighted PT and albumin as useful predictors. Cluster C, a low-risk, high-resilience group, demonstrated predictive values for cystatin C and eGFR cys. Cluster D, comprising lower-risk, short-term care patients, indicated the importance of PT and lactate. Key biomarkers, including albumin, prothrombin time (PT), cystatin C, eGFR cys, and total bilirubin (TB), were identified as significant predictors of AKI development, varying across clusters. Diagnostic accuracy was assessed using area under the curve (AUC) metrics, reclassification metrics (NRI and IDI), and decision curve analysis. Cystatin C and eGFR cys consistently provided significant predictive value over creatinine, with AUC values significantly higher (p < 0.05) in each cluster. This study highlights the need for a tailored, biomarker-driven approach to AKI management in burn patients, advocating for the integration of diverse biomarkers in clinical practice to facilitate personalized treatment strategies. Future research should validate these biomarkers prospectively to confirm their clinical utility.

Biomarkers of occupational benzene exposure: A Systematic Review to estimate the exposure levels and individual susceptibility at low doses.

Benzene is associated with diverse occupational and public health hazards. It exhibits an ability to rapidlypermeate the skin and contaminate water and food sources, leading to dermal and ingestion exposures. Despite numerous studies examining the associations between benzene and various indicators of harm, the findings have yielded inconsistent results. Furthermore, relying solely on air concentration as a measure of benzene exposure is limited, as it fails to account for internal exposure dose and individual susceptibility. This study aimed to conduct a comprehensive review in order to present current knowledge on benzene biomarkers and their significance in evaluating exposure levels and associated health hazards. The search methodology adhered to the PRISMA guidelines and involved the application of specific inclusion and exclusion criteria across multiple databases including PubMed, Embase, and Web of Science. Two researchers independently extracted and evaluated the relevant data based on predetermined criteria. Following the screening process, a total of 80 articles were considered eligible out of the initially retrieved 1053 articles after undergoing screening and assessment for inclusion. As the level of exposure decreased, specific biomarkers demonstrated a gradual increase in limitations, including heightened background concentrations and vulnerability to confounding factors. The advancement of sampling and analysis techniques will yield new biomarkers. Additionally, when conducting practical work, it is crucial to employ a comprehensive utilization of diverse biomarkers while excluding individual metabolic variations and combined exposure factors.

All-in-one platform: Versatile, Easy, and User-friendly System (VEUS) based on automated and expert-independent antibody immobilization and immunoassay by utilizing customized movement of magnetic particles.

The ELISA is the most worldwide method for immunoassay. However, the ELISA is losing ground due to low reproducibility of manual experimental processes in both R&D and IVD areas. An automated platform is a good solution, but there are still limitations owning to extremely high cost and requiring large space to set up especially for a small size laboratory. Here, we present a novel all-in-one platform called "VEUS" settable on the laboratory table that offers comprehensive automation of the entire multiplex immunoassay process by exploiting antibody conjugated magnetic particles, quality control and then immunoanalytical reaction, thereby enhancing detection sensitivity and high reproducibility. As a proof of concept, the system exhibits a sensitive LOD of 0.6 and 3.1 pg mL-1 within 1 h run, comparable precision that of molecular diagnostic systems based on PCR method, enabling rapid multiplex diagnosis of Influenza A, Influenza B, and COVID-19 viruses with similar symptoms. Through automation by the all-in-one system, it can be used by novice users, something innovative for immunoassays, relying heavily on user experience. Furthermore, it can contribute to streamline entire immunoassay processes of diverse biomarkers with high reproducibility and convenience in laboratories.

Electrochemical detection of extracellular vesicles for early diagnosis: a focus on disease biomarker analysis

This review article presents a detailed examination of the integral role that electrochemical detection of extracellular vesicles (EVs) plays, particularly focusing on the potential application for early disease diagnostics through EVs biomarker analysis. Through an exploration of the benefits and challenges presented by electrochemical detection vetted for protein, lipid, and nucleic acid biomarker analysis, we underscore the significance of these techniques. Evidence from recent studies renders this detection modality imperative in identifying diverse biomarkers from EVs, leading to early diagnosis of diseases such as cancer and neurodegenerative disorders. Recent advancements that have led to enhanced sensitivity, specificity and point-of-care testing (POCT) potential are elucidated, along with equipment deployed for electrochemical detection. The review concludes with a contemplation of future perspectives, recognizing the potential shifts in disease diagnostics and prognosis, necessary advances for broad adoption, and potential areas of ongoing research. The objective is to propel further investigation into this rapidly burgeoning field, thereby facilitating a potential paradigm shift in disease detection, monitoring, and treatment toward human health management.

Evaluating smartphone-based optical readouts for immunoassays in human and veterinary healthcare: A comparative study

Recent advances have significantly enhanced the use of smartphone devices for medical diagnostics. This study uses high-resolution cameras in mobile devices to capture and process bioassay images, enabling the quantification of diverse biomarkers across a range of diagnostic tests conducted on 96-well microplates. The study evaluates the effectiveness of this technology through protein quantification techniques and immunoassays that generate colorimetric responses at specific wavelengths. It includes the assessment of bicinchoninic acid and Bradford protein quantification methods, alongside a conventional immunoassay for detecting mare antibodies in colostrum to monitor foal immunodeficiencies. Further application involves the readout of magneto-actuated immunoassays aimed at quantifying bacteria. The results obtained from benchtop spectrophotometry at 595, 562, and 450 nm are compared with those acquired using a smartphone, which identified color intensities in shades of blue, purple, and yellow. This comparison yields promising correlations for the samples tested, suggesting a high degree of accuracy in the smartphone capability to analyze bioassay outcomes. The analysis via smartphone is facilitated by a specific app, which processes the images captured by the phone camera to quantify color intensities corresponding to different biomarker concentrations. Detection limits of 12.3 and 22.8 μg mL−1 for the bicinchoninic acid assay and 36.7 and 45.4 μg mL−1 for the Bradford are obtained for protein quantification using the spectrophotometer and the smartphone app, respectively. For mare's antibodies in colostrum, the values are 1.14 and 1.72 ng mL−1, while the detection of E. coli is performed at 2.0 x 104 and 2.9 × 104 CFU mL−1, respectively. This approach offers further advantages, including wide availability, cost-effectiveness, portability, compared to traditional and expensive benchtop instruments.

Identification of Putative Causal Relationships between Blood-Based Biomarkers and Prediabetes-Induced Senescence: A Comprehensive Review

Prediabetes, a pivotal phase in glucose metabolism between normalcy and diabetes, exerts a profound influence on the aging process and the risk of age-related diseases. This comprehensive review delves into the intricate web of blood-based biomarkers that collectively expedite senescence, marking the transition from a state of health to age-related complications. Key findings underscore the significance of diverse biomarkers, such as telomere length, p16INK4a, senescence-associated secretory phenotype (SASP) factors, DNA methylation clocks, advanced glycation end products (AGEs), inflammatory and oxidative stress markers, circulating hormones, and additional factors such as folate, B12, and osteocalcin. Not only do these biomarkers serve as indicators of senescence but they also actively fuel chronic inflammation, oxidative stress, and metabolic dysregulation, all of which contribute to accelerated aging. The implications of this understanding are profound, as prediabetes emerges as a critical period in an individual’s life, influencing various physiological systems, including the vascular and neural systems, metabolic functions, hormonal regulation, and bone health. Recognizing the profound influence of prediabetes on senescence provides a foundation for personalized intervention strategies to mitigate age-related complications and promote healthy aging. Future research directions call for a more diverse array of biomarkers, the in-depth exploration of their roles, and the development of tailored precision medicine strategies to ensure a holistic understanding and effective management of prediabetes-induced senescence and its implications for aging. This knowledge has far-reaching implications for public health and clinical practice, emphasizing the need for early detection and intervention in prediabetic individuals to enhance the quality of life in an aging population with diverse needs.

Advances and Challenges of Sensing in Water Using CRISPR-Cas Technology.

The groundbreaking gene-editing mechanism, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), paired with the protein Cas9, has significantly advanced the realms of biology, medicine, and agriculture. Through its precision in modifying genetic sequences, CRISPR holds the potential to alter the trajectory of genetic disorders and accelerate advancements in agriculture. While its therapeutic potential is profound, the technology also invites ethical debates centered on responsible use and equity in access. Parallelly, in the environmental monitoring sphere and sensing in water, especially biosensors have been instrumental in evaluating natural water sources' quality. These biosensors, integrating biological components with detection techniques, have the potential to revolutionize healthcare by providing rapid and minimally invasive diagnostic methods. However, the design and application of these sensors bring forth challenges, especially in ensuring sensitivity, selectivity, and ethical data handling. This article delves into the prospective use of CRISPR-Cas technology for sensing in water, exploring its capabilities in detecting diverse biomarkers, hazardous substances, and varied reactions in water and wastewater systems.

Application of enzyme-linked immunosorbent assay in cancer detection

The enzyme-linked immunosorbent assay (ELISA) has emerged as an indispensable method in the realm of cancer detection., serving as a significant factor in the timely identification, prediction, and surveillance of many forms of cancer. ELISA as a highly sensitive immunological assay, utilizes the binding affinity between antibodies and antigens to detect and quantify cancer-associated biomolecules, such as tumor markers, oncogenic proteins, and specific antibodies. The recently adopted methodology facilitates the identification of cancer-associated biomarkers in various types of samples, such as plasma, urine, and tissue extracts. In the context of cancer diagnosis, ELISA aids in the early detection of malignancies by detecting cancer-specific biomarkers at low concentrations, allowing for timely intervention and improved patient outcomes. This research provides a concise overview of the multifaceted applications of ELISA in the field of oncology, especially in electrochemical ELISA and gold nanoparticle–based ELISA. It discusses the diverse biomarkers employed, and elucidates its significance in cancer research and clinical practice.

A Fully Integrated Microfluidic Device with Immobilized Dyes for Simultaneous Detection of Cell-Free DNA and Histones from Plasma Using Dehydrated Agarose Gates.

Sepsis, a life-threatening condition resulting from a failing host response to infection, causes millions of deaths annually, necessitating rapid and simple prognostic assessments. A variety of genomic and proteomic biomarkers have been developed for sepsis. For example, it has been shown that the level of plasma cell-free DNA (cfDNA) and circulating histones increases considerably during sepsis, and they are linked with sepsis severity and mortality. Developing a diagnostic tool that is capable of assessing such diverse biomarkers is challenging as the detection methodology is quite different for each. Here, a fully integrated microfluidic device capable of detecting a genomic biomarker (cfDNA) and a proteomic biomarker (total circulating histones) using a common detection platform has been demonstrated. The microfluidic device utilizes dehydrated agarose gates loaded with pH-specific agarose to electrophoretically trap cfDNA and histones at their respective isoelectric points. It also incorporates fluorescent dyes within the device, eliminating the need for off-chip sample preparation and allowing the direct testing of plasma samples without the need for labeling DNA and histones with fluorescent dyes beforehand. Xurography, which is a low-cost and rapid method for fabrication of microfluidics, is used in all the fabrication steps. Experimental results demonstrate the effective accumulation and separation of cfDNA and histones in the agarose gates in a total processing time of 20 min, employing 10 and 30 Volts for cfDNA and histone accumulation and detection, respectively. The device can potentially be used to distinguish between the survivors and non-survivors of sepsis. The integration of the detection of both biomarkers into a single device and dye immobilization enhances its clinical utility for rapid point-of-care assessment of sepsis prognosis.

Heterogeneity of aging and mortality risk among individuals with hypertension: Insights from phenotypic age and phenotypic age acceleration

ObjectivesHypertension, a key contributor to mortality, is impacted by biological aging. We investigated the relationship between novel biological aging metrics - Phenotypic Age (PA) and Phenotypic Age Acceleration (PAA) - and mortality in individuals with hypertension, exploring the mediating effects of arterial stiffness (estimated Pulse Wave Velocity, ePWV), and Heart/Vascular Age (HVA). MethodsUsing data from 62,160 National Health and Nutrition Examination Survey (NHANES) participants (1999–2010), we selected 4,228 individuals with hypertension and computed PA, PAA, HVA, and ePWV. Weighted, multivariable Cox regression analysis yielded Hazard Ratios (HRs) relating PA, PAA to mortality, and mediation roles of ePWV, PAA, HVA were evaluated. Mendelian randomization (MR) analysis was employed to investigate causality between genetically inferred PAA and hypertension. ResultsOver a 12-year median follow-up, PA and PAA were tied to increased mortality risks in individuals with hypertension. All-cause mortality hazard ratios per 10-year PA and PAA increments were 1.96 (95% CI, 1.81–2.11) and 1.67 (95% CI, 1.52–1.85), respectively. Cardiovascular mortality HRs were 2.32 (95% CI, 1.97–2.73) and 1.93 (95% CI, 1.65–2.26) for PA and PAA, respectively. ePWV, PAA, and HVA mediated 42%, 30.3%, and 6.9% of PA’s impact on mortality, respectively. Mendelian randomization highlighted a causal link between PAA genetics and hypertension (OR = 1.002; 95% CI, 1.000–1.003). ConclusionPA and PAA, enhancing cardiovascular risk scores by integrating diverse biomarkers, offer vital insights for aging and mortality evaluation in individuals with hypertension, suggesting avenues for intensified aging mitigation and cardiovascular issue prevention. Validations in varied populations and explorations of underlying mechanisms are warranted.

Pyruvate is modified by tea/coffee metabolites and reversely correlated with multiple system atrophy and Parkinson's disease

IntroductionMultiple system atrophy (MSA) is a rapidly progressing neurodegenerative disorder. Although diverse biomarkers have been established for Parkinson's disease (PD), no widely accepted markers have been identified in MSA. Pyruvate and lactate are the end-product of glycolysis and crucial for brain metabolism. However, their correlation with MSA remains unclear. Moreover, it is elusive how lifestyles modify these metabolites. MethodsTo investigate the correlation and diagnostic value of plasma pyruvate and lactate levels in MSA and PD. Moreover, we explored how lifestyle-related metabolites interact with these metabolites in determining the disease risk. We assayed the 3 metabolites in pyruvate/lactate and 6 in the tea/coffee metabolic pathways by targeted mass spectrometry and evaluate their interactions and performance in diagnosis and differentiation between MSA and PD. ResultsWe found that 7 metabolites were significantly different between MSA, PD and healthy controls (HCs). Particularly, pyruvate was increased in PD while significantly decreased in MSA patients. Moreover, the tea/coffee metabolites were negatively associated with the pyruvate level in HCs, but not in MSA and PD patients. Using machine-learning models, we showed that the combination of pyruvate and tea/coffee metabolites diagnosed MSA (AUC = 0.878) and PD (AUC = 0.833) with good performance. Additionally, pyruvate had good performance in distinguishing MSA from PD (AUC = 0.860), and the differentiation increased (AUC = 0.922) when combined with theanine and 1,3-dimethyluric acid. ConclusionsThis study demonstrates that pyruvate correlates reversely with MSA and PD, and may play distinct roles in their pathogenesis, which can be modified by lifestyle-related tea/coffee metabolites.

Aptamer/Peptide-Functionalized Nanoprobe for Detecting Multiple miRNAs in Circulating Malignant Cells to Study Tumor Heterogeneity.

Identification of diverse biomarkers in heterogenic circulating malignant cells (CMCs) such as circulating tumor cells (CTCs) and circulating tumor endothelial cells (CTECs) has crucial significance in tumor diagnosis. However, it remains a substantial challenge to achieve in situ detection of multiple miRNA markers in living cells in blood. Herein, we demonstrate that an aptamer/peptide-functionalized vector can deliver molecular beacons into targeted living CMCs in peripheral blood of patients for in situ detection of multiple cancer biomarkers, including miRNA-21 (miR-21) and miRNA-221 (miR-221). Based on miR-21 and miR-221 levels, heterogenic CMCs are identified for both nondistant metastatic and distant metastatic cancer patients. CMCs from nondistant metastatic and distant metastatic cancer patients exhibit similar miR-21 levels, while the miR-221 level in CMCs of the distant metastatic cancer patient is higher than that of the nondistant metastatic cancer patient. With the capability to realize precise probing of multiple intracellular biomarkers in living CMCs at the single-cell resolution, the nanoprobe can reveal the tumor heterogeneity and provide useful information for diagnosis and prognosis. The nanoprobe we developed would accelerate the progress toward noninvasive precise cancer diagnosis.