Cerebral small vessel disease is a condition caused by chronic cerebral hypope rfusion due to microvascular damage and is a major contributor to stro ke and dementia.Traditionally,its diagnosis has relied primarily on...Cerebral small vessel disease is a condition caused by chronic cerebral hypope rfusion due to microvascular damage and is a major contributor to stro ke and dementia.Traditionally,its diagnosis has relied primarily on neuroimaging findings.However,recent advances in the understanding of cerebral small vessel disease pathophysiology have opened new avenues for early detection and targeted therapeutic interventions.Notably,the identification and investigation of cerebral small vessel disease-related biomarkers have emerged as a promising strategy for early diagnosis.This review provides an ove rview of recent research on cerebral small vessel disease biomarkers,including plasma biomarke rs,cerebrospinal fluid biomarke rs,and genetic markers.Finally,we discuss future directions and trends in the clinical validation of these biomarke rs.展开更多
The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral bloo...The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral blood biomarkers in neurological and psychiatric disorders based on the assertion that disease pathology is limited to the brain.The discovery that all tissues,including the brain,release extracellular vesicles(Raposo and Stoorvogel,2013)and cell free DNAs(Chan et al.,2013)into various body fluids has provided a potential way to measure activity from inaccessible tissues like the central nervous system(CNS)and has given rise to the term“liquid biopsy.”The development of liquid biopsies that can diagnose and predict the course of psychiatric and neurological disorders would be transformative.The ability to predict episodic events such as mania,depression,and risk for suicide would be particularly useful for psychiatric care as it would enable the development of interventions that prevent mortality and improve outcomes.Additionally,biomarkers that are informative about drug response and aid in treatment decisions would be a significant advance in psychiatric care as it would prevent patients from having to endure multiple courses of ineffective treatments and side effects.展开更多
Background:Locally advanced laryngeal squamous cell carcinoma(LA-LSCC)presents clinical challenges due to the lack of reliable non-invasive biomarkers.This study aimed to evaluate miR-449a as a diagnostic and prognost...Background:Locally advanced laryngeal squamous cell carcinoma(LA-LSCC)presents clinical challenges due to the lack of reliable non-invasive biomarkers.This study aimed to evaluate miR-449a as a diagnostic and prognostic biomarker in LA-LSCC.Methods:miR-449a expression was analyzed in tumor tissues,adjacent normal tissues,and serum from 81 LA-LSCC patients and 50 controls using quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR).We assessed the diagnostic accuracy by Receiver Operating Characteristic curve(ROC curves),clinicopathological associations,survival outcomes(Kaplan-Meier),and treatment response dynamics.Results:miR-449a was significantly downregulated in LA-LSCC tissues(p<0.0001)and serum(p<0.0001),with a strong tissue-serum correlation(R^(2)=0.988).Tissue miR-449a demonstrated a diagnostic accuracy(Area Under the Curve,AUC=0.857),while serum showed moderate accuracy(AUC=0.734).High miR-449a expression correlated with favorable clinicopathological features and improved survival(median overall survival:67.82 vs.23.74 months;p=0.0012).Multivariate analysis confirmed miR-449a as an independent prognostic factor(p<0.001).miR-449a levels increased post-treatment,particularly in responders to chemotherapy/radiation(p<0.0001).Conclusion:miR-449a serves as a non-invasive biomarker for LA-LSCC diagnosis,prognosis,and treatment monitoring.Its dynamic expression highlights potential for risk stratification and therapy response prediction,warranting further validation in larger cohorts.展开更多
Methamphetamine(METH)addiction is a severe and increasingly prevalent neuropsychiatric disorder for which current diagnostic and therapeutic approaches remain limited and predominantly symptom-oriented.Exercise,as a s...Methamphetamine(METH)addiction is a severe and increasingly prevalent neuropsychiatric disorder for which current diagnostic and therapeutic approaches remain limited and predominantly symptom-oriented.Exercise,as a safe,accessible and cost-effective non-pharmacological intervention,has emerged as a promising strategy to ameliorate METH-induced neurotoxicity and addiction-related behaviors.Growing evidence indicates that these benefits are closely linked to the regulation of exercise-induced biomarkers,defined as molecular indicators whose expression or activity is dynamically altered during or after physical activity.This review focuses on the core regulatory role of exercise-induced biomarkers in METH addiction and systematically summarizes their involvement in key neurobiological pathways,outlining molecular pathological mechanisms such as dysregulation of dopamine,glutamate and GABA neurotransmitter systems,neuroinflammation and oxidative stress,and epigenetic remodeling,and emphasizing how these processes converge on changes in candidate biomarkers in the brain and periphery.On this basis,the review describes how exercise modulates neural plasticity,neurotransmitter systems,inflammation and oxidative stress through biomarkers such as brain-derived neurotrophic factor(BDNF),exerkines,inflammatory cytokines,metabolites and noncoding RNAs,with particular attention to neurotrophic and immune-related markers,microRNAs and other epigenetic regulators that can reverse METH-induced synaptic and structural abnormalities and promote recovery of cognitive and emotional functions.Advances in high-throughput omics technologies,including transcriptomics,metabolomics and multi-omics integration,are summarized to illustrate the screening and identification of key exercise-responsive biomarkers.Studies in METH-addicted animal models have revealed differentially expressed genes,signaling pathways(e.g.,PI3K-Akt,mTOR,Wnt)and core nodes such as NFKBIA and CXCL12 that may mediate the protective effects of exercise.The review further discusses the potential of exercisemediated biomarkers as objective indicators for diagnosis,dynamic monitoring of therapeutic efficacy and patient stratification.Multi-gene diagnostic models based on peripheral samples(e.g.,hair follicles,blood)demonstrate how biomarker panels can distinguish non-recovered,almost-recovered and healthy individuals,providing a molecular basis for staging METH use disorder and evaluating the impact of exercise interventions.The temporal dynamics of biomarker changes before and after exercise are highlighted,underscoring the value of longitudinal monitoring of factors such as BDNF,immune-related genes and circulating microRNAs to capture treatment-relevant windows of plasticity.In addition,the underlying molecular basis of exercise as an adjunct therapy and gene-targeted exercise strategies that leverage individual biomarker and gene expression profiles to optimize exercise prescriptions are summarized.Current conceptual and technical challenges are outlined,including heterogeneity of biomarker responses,individual variability,assay sensitivity and specificity,and gaps between preclinical findings and clinical application,together with future directions for integrating exercise with multi-omics,artificial intelligence-assisted biomarker discovery and,prospectively,gene-editing-based interventions.Particular emphasis is placed on the need to standardize exercise protocols,incorporate stage-specific and sex-sensitive designs,and combine exercise with pharmacotherapy and psychosocial rehabilitation in real-world clinical settings across diverse healthcare systems.Overall,this review aims to provide a comprehensive and integrated mechanistic framework and updated theoretical support for the application of exercise-mediated biomarkers in the diagnosis,therapeutic effect monitoring and personalized intervention of METH addiction,and to offer new and clinically relevant insights into the development of precision medicine strategies for substance use disorders.展开更多
Osteoarthritis(OA) and rheumatoid arthritis(RA) have long been framed as degenerative and autoimmune entities, respectively;mounting evidence instead supports a unified mechano-immune paradigm in which joint loading a...Osteoarthritis(OA) and rheumatoid arthritis(RA) have long been framed as degenerative and autoimmune entities, respectively;mounting evidence instead supports a unified mechano-immune paradigm in which joint loading and inflammatory signaling are reciprocally reinforcing. In this review, we synthesize advances across mechanotransduction(Piezo1;YAP/TAZ), focaladhesion/cytoskeletal regulation(vinculin, filamin-A;upstream talin-1/Kindlin-2/paxillin), and niche inflammatory mediators(HE4, IL-36/IL-38) to explain how mechanical stress and cytokines co-produce persistent catabolism, synovial invasion, and fibrotic remodeling. We articulate a dual-hit model in which OA is predominantly mechanical-overload-driven, with secondary inflammation, whereas RA is immune-driven but imposes abnormal mechanical stress that further distorts joint biomechanics;both converge on canonical hubs(NF-κB/MAPK/JAK-STAT) to accelerate matrix degradation and apoptosis. Building on this framework, we propose integrated multi-marker panels that combine mechanosensors and adhesion proteins with conventional assays(CRP, ESR, anti-CCP) to enhance differential diagnosis and prognostication, particularly in postmenopausal women, where estrogen decline heightens mechano-immune susceptibility, thereby offering a means to quantify the impact of mechano-immune dysregulation. Integrating mechanotransductive and cytoskeletal biomarkers with conventional serological indices has been reported to improve differential diagnosis between osteoarthritis and rheumatoid arthritis in exploratory studies. While the magnitude of diagnostic gain varies across cohorts, combined biomarker strategies generally show enhanced discriminatory performance compared with single-marker approaches. These findings highlight translational potential but require validation in large, standardized clinical populations before routine implementation. Finally, we map translational opportunities spanning Piezo1 inhibition(GsMTx4), YAP/TAZ blockade(verteporfin), IL-36 axis antagonism(IL-36Ra, IL-38), anti-HE4 strategies for RA-ILD, and adhesion-stabilizing approaches, alongside mechanoresponsive biomaterials for regenerative applications and precision medicine guided by biomarker profiles. Collectively, this review reframes OA and RA as mechano-immune syndromes and delineates a clinically actionable roadmap from biophysics to bedside.展开更多
Sport-related concussion(SRC)and its potential neurological sequela represent an emerging global health concern,requiring improved recovery management and strategies for return-to-play(RTP)to enhance brain health in a...Sport-related concussion(SRC)and its potential neurological sequela represent an emerging global health concern,requiring improved recovery management and strategies for return-to-play(RTP)to enhance brain health in athletes.Given the dynamic and multifaceted nature of SRC recovery,the purpose of this review is to synthesize existing literature on post-SRC outcomes in adult athletes,and to outline the temporal trajectories of key recovery indicators(symptoms,cognitive function,blood biomarkers)across distinct recovery phases until resolution.In the acute phase of SRC(first 48 h),symptom scores and brain damage markers peaked immediately,while cognitive impairments and neuroinflammation emerged with a slight delay.Following the initial rise,brain damage marker concentrations rapidly dropped below baseline levels at approximately 48 h following SRC injury.During the early recovery phase,neuroinflammation and most cognitive alterations resolved after 3–5 days,though symptom burden and attention deficits persisted for up to 7 days.Despite prolonged alterations reported in some individuals,recovery markers typically returned to pre-injury levels in the transition phase(≤2 weeks),though mild attention deficits were detected up to 3 weeks,and TNF-α concentrations remained elevated throughout late recovery(>2 weeks).These results reveal distinct temporal discrepancies across recovery markers and emphasize that physiological disturbances can outlast symptom resolution,underscoring the need for both multimodal assessments and appropriately timed evaluations to accurately track recovery progression.Incorporating structured follow-ups at key time points,particularly beyond symptom resolution,may improve RTP decision-making and reduce the risk of premature return and long-term neurological consequences.展开更多
AIM:To identify early biomarkers associated with glaucomatous visual field(VF)progression in patients with normal-tension glaucoma(NTG).METHODS:This study included patients were divided into two groups based on diseas...AIM:To identify early biomarkers associated with glaucomatous visual field(VF)progression in patients with normal-tension glaucoma(NTG).METHODS:This study included patients were divided into two groups based on disease progression status.Tear samples were collected for proteomic analysis.Dataindependent acquisition(DIA)mass spectrometry combined with bioinformatic analyses was performed to identify and validate potential protein biomarkers for NTG progression.Additionally,differentially expressed proteins(DEPs)were evaluated using mediating effect models and receiver operating characteristic(ROC)curve analysis.RESULTS:A total of 19 patients(20 eyes)with NTG participated in this study,including 10 patients(4 males and 6 females;10 eyes)in the progression group with mean age of 67.70±9.03y and 10 patients(4 males and 6 females;10 eyes)in the non-progression group with mean age of 68.60±7.58y.A total of 158 significantly differentially expressed proteins were detected.UniProt database annotation identified 3 upregulated proteins and 12 downregulated proteins.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that these DEPs were mainly enriched in pathways such as oocyte meiosis.Gene Ontology(GO)enrichment analysis revealed functional clusters related to cellular processes.Weighted gene coexpression network analysis(WGCNA)indicated that the core proteins were primarily involved in the neurodegenerationmultiple diseases pathway and cellular processes.Mediating effect analysis identified PRDX4(L)as a potential protein biomarker.ROC curve analysis showed that GNAI1 had the largest area under the curve(AUC=0.889).CONCLUSION:This study identifies 15 differentially expressed proteins in the tear fluid of NTG patients,including PRDX4(L).PRDX4(L)plays a key role in oxidative stress.展开更多
Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-through...Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.展开更多
Ischemic stroke,a neurological impairment caused by cerebral vascular occlusion,accounts for 87%of the cases of stroke.Recent studies have shown that changes in the abundance of metabolites can directly reveal the cel...Ischemic stroke,a neurological impairment caused by cerebral vascular occlusion,accounts for 87%of the cases of stroke.Recent studies have shown that changes in the abundance of metabolites can directly reveal the cellular phenotypes and identify the clinical implications of stroke diagnosis and therapy.However,systematic research to clarify the relationship between biomarkers and the mechanisms of ischemic stroke remains limited.In this study,we reviewed articles on ischemic stroke metabolites from 2005 to 2024,identified metabolites showing significant changes,and constructed a metabolite database based on the findings from 128 studies.The database included 125 differential metabolites detected in a middle cerebral artery occlusion mouse model,246 detected in an middle cerebral artery occlusion rat model,and 764 identified in ischemic stroke patient samples.Differential metabolites from various samples were then screened and classified into positive and negative categories based on their correlation with stroke prognoses.Based on this analysis,three positive metabolites and two negative metabolites were identified.Glutamic acid,glycerol,and 1-octadecanoyl-sn-glycero-3-phosphocholine(LysoPC(18:0))were further recognized as potential biomarkers.Imbalances in metabolic pathways such as alanine,aspartate,and glutamate metabolism as well as the citrate cycle(tricarboxylic acid cycle)were analyzed.These imbalances may influence the pathogenesis of ischemic stroke by altering biological processes such as excitotoxicity,oxidative stress,inflammation,and energy metabolism.The identification and analysis of these potential biomarkers may provide valuable targets and strategies for prediction,diagnosis,and prognostic assessment of ischemic stroke.展开更多
Liver is prone to viral infection.Viral hepatitis can be roughly divided into hepatitis A,B,C,D and E.Accurate diagnosis of viral hepatitis is crucial for accurate treatments.Different types of biomarkers,including no...Liver is prone to viral infection.Viral hepatitis can be roughly divided into hepatitis A,B,C,D and E.Accurate diagnosis of viral hepatitis is crucial for accurate treatments.Different types of biomarkers,including non-invasive biomarkers have been explored for the diagnosis of viral hepatitis.With the fast development of multi-omics technology,non-invasive biomarkers can be detected from blood,saliva,urine,stool,and other body fluids.The advantages of non-invasive biomarkers are:1)non-invasive;2)convenient to test and 3)repeatable.The application of non-invasive biomarkers significantly improves the diagnostic accuracy of viral hepatitis.The non-invasive biomarkers can be sugars,proteins,nucleic acids,and even microorganisms.In this review,we summarized recent advances in identifying non-invasive biomarkers using multi-omics technology and discussed their potential diagnostic values for viral hepatitis.展开更多
Background:High-mobility group box 1(HMGB1)is a critical damage-associated molecular pattern protein that participates in diverse physiological and pathological processes.However,its relevance to the prognosis of arti...Background:High-mobility group box 1(HMGB1)is a critical damage-associated molecular pattern protein that participates in diverse physiological and pathological processes.However,its relevance to the prognosis of artificial liver support therapy in patients with acute liver injury(ALF)remains unclear.Methods:Bioinformatics analyses were performed to identify HMGB1-interacting proteins and associated inflammatory signaling pathways.Peripheral blood samples were collected from ALF patients before and after artificial liver support therapy,and serum HMGB1 concentrations were quantified using ELISA.Primary mouse hepatocytes were stimulated with lipopolysaccharide(LPS)in vitro and HMGB1 expression was verified by western blot.Results:Single-cell transcriptomic profiling showed that HMGB1 is widely expressed across tissues and predominantly localized in the nucleus.In the liver,HMGB1 was primarily expressed in hepatocytes and hepatic stellate cells.STRING database analysis revealed that human HMGB1 interacts with multiple proteins,including TLR4,TP53,and BECN1.The constructed interaction network comprised 11 nodes with an average local clustering coefficient of 0.888,and the protein–protein interaction enrichment P-value was 1.42×10^(-5),indicating significant enrichment.Gene Ontology and KEGG pathway enrichment analyses demonstrated that HMGB1 is closely linked to inflammatory and injury-related signaling pathways,including the TLR and NLR pathways.Metabolomic profiling revealed significant metabolic alterations between patients with ALF and healthy controls under both positive and negative ion modes and functional analysis showed necroptosis was activated.The cell viability gradually decreased with time and dose under LPS treatment and extracellular HMGB1 was upregulated in LPS induced ALF model and patients(P<0.05).Serum HMGB1/RIPK3/MLKL levels were markedly elevated in ALF patients compared with controls(P<0.05)and progressively declined following artificial liver support therapy.Furthermore,elevated HMGB1 concentrations were positively correlated with unfavorable clinical outcomes.Conclusion:Peripheral blood HMGB1 levels are significantly increased in patients with acute liver failure,decrease following artificial liver support therapy,and are positively associated with poor clinical prognosis.展开更多
Objectives:Phosphodiesterase 1A(PDE1A)regulates intracellular cyclic nucleotide signaling and has been implicated in tumor progression,but its clinical relevance and functional role in epithelial ovarian cancer(EOC),p...Objectives:Phosphodiesterase 1A(PDE1A)regulates intracellular cyclic nucleotide signaling and has been implicated in tumor progression,but its clinical relevance and functional role in epithelial ovarian cancer(EOC),particularly in relation to the response to platinum remain unclear.This study aimed to evaluate the clinical significance of PDE1A in EOG and to clarify its functional role in tumor progression and response to platinum-based chemotherapy.Methods:PDE1A mRNA and protein levels were analyzed using public databases,RNA sequencing,and immunohistochemistry.Correlations between PDE1A expression,clinicopathological features,and prognosis were assessed.Functional roles were investigated in ovarian cancer cell lines.Results:PDE1A was significantly overexpressed in EOC tissues compared with that in normal ovarian epithelial tissues.Overexpression correlated with advanced International Federation of Gynecology and Obstetrics(FIGO)stage,poor tumor grade,and reduced response to platinum-based chemotherapy.High PDE1A levels were linked to worse disease-free survival and overall survival,and multivariate analysis confirmed PDE1A as an independent prognostic factor.To elucidate its functional role,we performed in vitro experiments showing that PDE1A knockdown suppressed cell proliferation and colony formation,induced G1 arrest,and downregulatedβ-catenin signaling with reduced cyclin D1 and c-Myc expression.Notably,these inhibitory effects were partially rescued by lithium chloride(LiCl),a Wingless-related integration site(Wnt)/β-catenin activator.Conclusions:In conclusion,our findings identify PDE1A as a Wnt/β-catenin-linked biomarker of tumor progression and platinum resistance in EOC and provide a biological rationale for further investigation of PDE1A-targeted strategies in preclinical models.展开更多
MicroRNAs(miRNAs),small non-coding RNAs ranging from 19 to 25 nucleotides in length,are key regulators of gene expression that function primarily by inhibiting the translation of target mRNAs.Recent studies have sugge...MicroRNAs(miRNAs),small non-coding RNAs ranging from 19 to 25 nucleotides in length,are key regulators of gene expression that function primarily by inhibiting the translation of target mRNAs.Recent studies have suggested that miRNAs play important roles in regulating key aspects in the pathology of Alzheimer's disease,including the modulation and accumulation of amyloid-beta and tau proteins.Moreover,miRNAs have been implicated in the regulation of neuroinflammation thro ugh various inflammatory pathways,notably the nuclear factor kappa B signaling cascade.Additional emerging evidence has shown that miRNAs regulate synaptic growth and maturation,and they perform promising roles in regulating neuronal death and development.miRNAs also offer a novel avenue for direct reprogramming of neurons,representing a promising strategy for Alzheimer's disease treatment.The regulation of miRNA biogenesis and the post-transcriptional modifications of miRNAs are critical factors in Alzheimer's disease pathology,influencing miRNA activity and disease progression.In this review,we comprehensively explore the role of different miRNAs in regulating various pathological processes associated with Alzheimer's disease,focusing primarily on four representative miRNAs:miR-9,miR-29,miR-126,and miR-146a for further exploration.We also discuss the influence of miRNA biogenesis on Alzheimer's disease,emphasizing how dysregulation of miRNA processing may contribute to the disease.Additionally,we highlight the potential of miRNAs as both diagnostic biomarke rs and therapeutic targets in Alzheimer's disease,along with promising vector delive ry strategies aimed at improving clinical outcomes.Finally,we discuss the challenges and limitations associated with the use of miRNAs in the diagnosis and treatment of Alzheimer's disease.By reviewing the current clinical applications of miRNAs as biomarkers and therapeutic agents,we aim to provide insights that will inform future research and development in this promising field.展开更多
This narrative review examines recent advances in salivary biomarkers for oral squamous cell carcinoma(OSCC),a major subtype of oral cancer with persistently low five-year survival rates due to delayed diagnosis.Saliv...This narrative review examines recent advances in salivary biomarkers for oral squamous cell carcinoma(OSCC),a major subtype of oral cancer with persistently low five-year survival rates due to delayed diagnosis.Saliva has emerged as a noninvasive diagnostic medium capable of reflecting both local tumor activity and systemic physiological changes.Various salivary biomarkers,including microRNAs,cytokines,proteins,metabolites,and exosomes,have been linked to oncogenic signaling pathways involved in tumor progression,immune modulation,and therapeutic resistance.Advances in quantitative polymerase chain reaction,mass spectrometry,and next-generation sequencing have enabled comprehensive biomarker profiling,while point-of-care detection systems and saliva-based omics platforms are accelerating clinical translation.Remaining challenges include variability in salivary composition,lack of standardized collection protocols,and insufficient validation across large patient cohorts.This review highlights the mechanistic relevance,diagnostic potential,and translational challenges of salivary biomarkers in OSCC.展开更多
Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder and the leading cause of dementia worldwide.It is characterized by the accumulation of extracellular amyloid-beta(Aβ)plaques and intracellul...Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder and the leading cause of dementia worldwide.It is characterized by the accumulation of extracellular amyloid-beta(Aβ)plaques and intracellular tau neurofibrillary tangles,leading to synaptic dysfunction,neuronal loss,and cognitive decline.These pathological changes can begin decades before clinical symptoms emerge,highlighting the critical need for early,accessible,and accurate diagnostic tools.展开更多
Glioblastoma(GBM),the most aggressive and lethal primary brain tumor in adults,continues to resist conventional therapeutic approaches,withmedian survival remaining dismally low.Immune checkpoint inhibitors(ICIs),whic...Glioblastoma(GBM),the most aggressive and lethal primary brain tumor in adults,continues to resist conventional therapeutic approaches,withmedian survival remaining dismally low.Immune checkpoint inhibitors(ICIs),which have revolutionized the treatment of several solid tumors,have shown limited efficacy inGBMowing to the highly immunosuppressive and heterogeneousmicroenvironment of the tumor.The unique immune landscape of the central nervous system(CNS),characterized by low immunogenicity,restricted T-cell infiltration,and an abundance of regulatory and myeloid-derived suppressor cells,poses considerable barriers to effective immune reactivation.This review provides a comprehensive synthesis of the mechanistic barriers undermining ICI efficacy in GBM,including the blood-brain barrier,low tumor mutational burden,adaptive immune resistance,and iatrogenic immunosuppression.It also explores emerging predictive and prognostic biomarkers,such as programmed death-ligand 1(PD-L1)expression,immune gene signatures,tumor-infiltrating lymphocyte profiles,and circulating markers in cerebrospinal fluid and plasma,which hold promise for guiding patient selection and therapeutic monitoring.Importantly,recent breakthroughs in combinatorial immunotherapy strategies are highlighted,including the integration of ICIs with radiotherapy,anti-angiogenic agents,oncolytic viruses,personalized neoantigen vaccines,and tumor microenvironment reprogramming approaches.Innovative delivery platforms,such as nanoparticles,focused ultrasound,and convection-enhanced delivery,are also discussed for their potential to improve drug bioavailability and local immune activation in the CNS.This review hypothesizes that the therapeutic efficacy of ICIs in GBM can be considerably enhanced by disrupting immune exclusion and reversing immunosuppression through integrated,multimodal strategies guided by dynamic biomarker profiling and spatially resolved immunemapping.This hypothesisdriven approach aims to bridge translational gaps and inform next-generation clinical trial designs that may unlock the potential of immunotherapy for GBM.展开更多
GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,i...GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,it spans a wide range of neurological clinical manifestations,that may include epileptic seizures,motor dysfunctions,developmental and intellectual delay,and other symptoms(Sáez González et al.,2023).展开更多
Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regula...Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.展开更多
The Neogene Shawan Formation in the Chepaizi Uplift of the Junggar Basin(NW China)has obtained high oil flow,demonstrating a good potential for oil and gas exploration.The multi-source hydrocarbon generation backgroun...The Neogene Shawan Formation in the Chepaizi Uplift of the Junggar Basin(NW China)has obtained high oil flow,demonstrating a good potential for oil and gas exploration.The multi-source hydrocarbon generation background and strong tectonic activity have led to the simultaneous production of heavy oil and light oil from multi-layer in the area,which makes it very difficult to identify oil origins,presently,the hot debate on the oil origins needs to be clarified.In this paper,due to the selective consumption of different types of compounds in crude oils by severe and intense biodegradation,the commonly used oilsource correlation tools are ineffective or may produce misleading results,this study adopted a biomarker recovery method based on the principle of mass conservation that uses the sum of the mass of the residual biomarkers and their corresponding biodegradation products to obtain the mass of the original biomarkers,improving the reliability of oil origins determination.Based on the nature and occurrence of crude oils,the investigated oils are subdivided into three types,Group A,Group B and Group C.Group A,light oils occurred mainly in lower structure Neogene Shawan Formation in the western Chepaizi Uplift,while Group B,heavy oils occurred mainly in higher structure Neogene Shawan Formation in the western Chepaizi Uplift.The two types of crude oils may come from the mixed source of Jurassic Badaowan Formation source rocks(J_(1)b)and Paleogene Anjihaihe Formation source rocks(E_(2-3)a)in the Sikeshu Sag,and Jurassic Badaowan Formation source rocks(J_(1)b)are the main source of crude oils.Group C,heavy oils occurred mainly in Neogene Shawan Formation in the eastern Chepaizi Uplift,showing good correlation with the Permian(P_(1)f and P_(2)w)source rocks in the Shawan Sag.At the same time,by combining stable carbon isotope and parameters related to triaromatic steroids,the accuracy of the oilsource correlation results by biomarker recovery method was further verified.展开更多
Aberrant RNA modification has been linked to the pathogenesis of various diseases;however,its specific molecular mechanisms in spinal cord injury remain poorly understood.The objective of this study was to explore RNA...Aberrant RNA modification has been linked to the pathogenesis of various diseases;however,its specific molecular mechanisms in spinal cord injury remain poorly understood.The objective of this study was to explore RNA modification-related biomarkers of spinal cord injury.The mRNA expression profiles of mice with spinal cord injury were retrieved from the Gene Expression Omnibus(GEO)database(GSE18179).We identified 185 differentially expressed genes using bioinformatics approaches.Functional enrichment analysis demonstrated aberrant activation or inhibition of common metabolism-related pathways,including sulfur metabolism and steroid biosynthesis,in mice with spinal cord injury.An integrated strategy comprising weighted gene co-expression network analysis,a random forest model,a support vector machine model,and a generalized linear model was employed to identify four genes whose aberrant RNA modification was linked to spinal cord injury:Elovl6,Idi1,Sqle,and Stbd1.We verified the expression levels and diagnostic performance of these four genes in the original training dataset and mouse samples via receiver operating characteristic curve analysis.Quantitative reverse transcription-polymerase chain reaction demonstrated variations in the mRNA levels of the four genes between the Sham and spinal cord injury groups at different time points following injury.We also constructed microRNA-mRNA and transcription factor-mRNA interaction networks using Cytoscape.Additionally,we evaluated the proportions of 22 types of immune cells in the spinal cords of mice using the CIBERSORT tool,revealing significant alterations in the numbers of memory B cells,resting dendritic cells,M0 macrophages,activated mast cells,resting mast cells,and CD8+T cells in spinal cord injury mice compared with Sham controls.Microglia and T cells were identified as key cell types by single-cell sequencing analysis.These findings provide new directions for the development of RNA modification-related therapeutic strategies for spinal cord injury and suggest that Elovl6,Idi1,Sqle,and Stbd1 are potential biomarkers of spinal cord injury.展开更多
基金Natural Science Foundation of Shandong Province,No.ZR2021MH043。
文摘Cerebral small vessel disease is a condition caused by chronic cerebral hypope rfusion due to microvascular damage and is a major contributor to stro ke and dementia.Traditionally,its diagnosis has relied primarily on neuroimaging findings.However,recent advances in the understanding of cerebral small vessel disease pathophysiology have opened new avenues for early detection and targeted therapeutic interventions.Notably,the identification and investigation of cerebral small vessel disease-related biomarkers have emerged as a promising strategy for early diagnosis.This review provides an ove rview of recent research on cerebral small vessel disease biomarkers,including plasma biomarke rs,cerebrospinal fluid biomarke rs,and genetic markers.Finally,we discuss future directions and trends in the clinical validation of these biomarke rs.
基金supported by Department of Defense grant HT9425-24-1-0030 a grant from the Stanley Medical Research Institute(to SS).
文摘The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral blood biomarkers in neurological and psychiatric disorders based on the assertion that disease pathology is limited to the brain.The discovery that all tissues,including the brain,release extracellular vesicles(Raposo and Stoorvogel,2013)and cell free DNAs(Chan et al.,2013)into various body fluids has provided a potential way to measure activity from inaccessible tissues like the central nervous system(CNS)and has given rise to the term“liquid biopsy.”The development of liquid biopsies that can diagnose and predict the course of psychiatric and neurological disorders would be transformative.The ability to predict episodic events such as mania,depression,and risk for suicide would be particularly useful for psychiatric care as it would enable the development of interventions that prevent mortality and improve outcomes.Additionally,biomarkers that are informative about drug response and aid in treatment decisions would be a significant advance in psychiatric care as it would prevent patients from having to endure multiple courses of ineffective treatments and side effects.
基金The authors extend their appreciation to Taif University,Saudi Arabia,for supporting this work through project No.(TU-DSPP-2024-54).
文摘Background:Locally advanced laryngeal squamous cell carcinoma(LA-LSCC)presents clinical challenges due to the lack of reliable non-invasive biomarkers.This study aimed to evaluate miR-449a as a diagnostic and prognostic biomarker in LA-LSCC.Methods:miR-449a expression was analyzed in tumor tissues,adjacent normal tissues,and serum from 81 LA-LSCC patients and 50 controls using quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR).We assessed the diagnostic accuracy by Receiver Operating Characteristic curve(ROC curves),clinicopathological associations,survival outcomes(Kaplan-Meier),and treatment response dynamics.Results:miR-449a was significantly downregulated in LA-LSCC tissues(p<0.0001)and serum(p<0.0001),with a strong tissue-serum correlation(R^(2)=0.988).Tissue miR-449a demonstrated a diagnostic accuracy(Area Under the Curve,AUC=0.857),while serum showed moderate accuracy(AUC=0.734).High miR-449a expression correlated with favorable clinicopathological features and improved survival(median overall survival:67.82 vs.23.74 months;p=0.0012).Multivariate analysis confirmed miR-449a as an independent prognostic factor(p<0.001).miR-449a levels increased post-treatment,particularly in responders to chemotherapy/radiation(p<0.0001).Conclusion:miR-449a serves as a non-invasive biomarker for LA-LSCC diagnosis,prognosis,and treatment monitoring.Its dynamic expression highlights potential for risk stratification and therapy response prediction,warranting further validation in larger cohorts.
基金supported by grants from The National Natural Science Foundation of China(82472611)The“14th Five Year Plan”Scientific Research and Innovation Team of Chengdu Sport University(23CXTD02)Sports Medicine Key Laboratory of Sichuan Province/Key Laboratory of Sports Medicine,General Administration of Sport of China(2025-A028)。
文摘Methamphetamine(METH)addiction is a severe and increasingly prevalent neuropsychiatric disorder for which current diagnostic and therapeutic approaches remain limited and predominantly symptom-oriented.Exercise,as a safe,accessible and cost-effective non-pharmacological intervention,has emerged as a promising strategy to ameliorate METH-induced neurotoxicity and addiction-related behaviors.Growing evidence indicates that these benefits are closely linked to the regulation of exercise-induced biomarkers,defined as molecular indicators whose expression or activity is dynamically altered during or after physical activity.This review focuses on the core regulatory role of exercise-induced biomarkers in METH addiction and systematically summarizes their involvement in key neurobiological pathways,outlining molecular pathological mechanisms such as dysregulation of dopamine,glutamate and GABA neurotransmitter systems,neuroinflammation and oxidative stress,and epigenetic remodeling,and emphasizing how these processes converge on changes in candidate biomarkers in the brain and periphery.On this basis,the review describes how exercise modulates neural plasticity,neurotransmitter systems,inflammation and oxidative stress through biomarkers such as brain-derived neurotrophic factor(BDNF),exerkines,inflammatory cytokines,metabolites and noncoding RNAs,with particular attention to neurotrophic and immune-related markers,microRNAs and other epigenetic regulators that can reverse METH-induced synaptic and structural abnormalities and promote recovery of cognitive and emotional functions.Advances in high-throughput omics technologies,including transcriptomics,metabolomics and multi-omics integration,are summarized to illustrate the screening and identification of key exercise-responsive biomarkers.Studies in METH-addicted animal models have revealed differentially expressed genes,signaling pathways(e.g.,PI3K-Akt,mTOR,Wnt)and core nodes such as NFKBIA and CXCL12 that may mediate the protective effects of exercise.The review further discusses the potential of exercisemediated biomarkers as objective indicators for diagnosis,dynamic monitoring of therapeutic efficacy and patient stratification.Multi-gene diagnostic models based on peripheral samples(e.g.,hair follicles,blood)demonstrate how biomarker panels can distinguish non-recovered,almost-recovered and healthy individuals,providing a molecular basis for staging METH use disorder and evaluating the impact of exercise interventions.The temporal dynamics of biomarker changes before and after exercise are highlighted,underscoring the value of longitudinal monitoring of factors such as BDNF,immune-related genes and circulating microRNAs to capture treatment-relevant windows of plasticity.In addition,the underlying molecular basis of exercise as an adjunct therapy and gene-targeted exercise strategies that leverage individual biomarker and gene expression profiles to optimize exercise prescriptions are summarized.Current conceptual and technical challenges are outlined,including heterogeneity of biomarker responses,individual variability,assay sensitivity and specificity,and gaps between preclinical findings and clinical application,together with future directions for integrating exercise with multi-omics,artificial intelligence-assisted biomarker discovery and,prospectively,gene-editing-based interventions.Particular emphasis is placed on the need to standardize exercise protocols,incorporate stage-specific and sex-sensitive designs,and combine exercise with pharmacotherapy and psychosocial rehabilitation in real-world clinical settings across diverse healthcare systems.Overall,this review aims to provide a comprehensive and integrated mechanistic framework and updated theoretical support for the application of exercise-mediated biomarkers in the diagnosis,therapeutic effect monitoring and personalized intervention of METH addiction,and to offer new and clinically relevant insights into the development of precision medicine strategies for substance use disorders.
文摘Osteoarthritis(OA) and rheumatoid arthritis(RA) have long been framed as degenerative and autoimmune entities, respectively;mounting evidence instead supports a unified mechano-immune paradigm in which joint loading and inflammatory signaling are reciprocally reinforcing. In this review, we synthesize advances across mechanotransduction(Piezo1;YAP/TAZ), focaladhesion/cytoskeletal regulation(vinculin, filamin-A;upstream talin-1/Kindlin-2/paxillin), and niche inflammatory mediators(HE4, IL-36/IL-38) to explain how mechanical stress and cytokines co-produce persistent catabolism, synovial invasion, and fibrotic remodeling. We articulate a dual-hit model in which OA is predominantly mechanical-overload-driven, with secondary inflammation, whereas RA is immune-driven but imposes abnormal mechanical stress that further distorts joint biomechanics;both converge on canonical hubs(NF-κB/MAPK/JAK-STAT) to accelerate matrix degradation and apoptosis. Building on this framework, we propose integrated multi-marker panels that combine mechanosensors and adhesion proteins with conventional assays(CRP, ESR, anti-CCP) to enhance differential diagnosis and prognostication, particularly in postmenopausal women, where estrogen decline heightens mechano-immune susceptibility, thereby offering a means to quantify the impact of mechano-immune dysregulation. Integrating mechanotransductive and cytoskeletal biomarkers with conventional serological indices has been reported to improve differential diagnosis between osteoarthritis and rheumatoid arthritis in exploratory studies. While the magnitude of diagnostic gain varies across cohorts, combined biomarker strategies generally show enhanced discriminatory performance compared with single-marker approaches. These findings highlight translational potential but require validation in large, standardized clinical populations before routine implementation. Finally, we map translational opportunities spanning Piezo1 inhibition(GsMTx4), YAP/TAZ blockade(verteporfin), IL-36 axis antagonism(IL-36Ra, IL-38), anti-HE4 strategies for RA-ILD, and adhesion-stabilizing approaches, alongside mechanoresponsive biomaterials for regenerative applications and precision medicine guided by biomarker profiles. Collectively, this review reframes OA and RA as mechano-immune syndromes and delineates a clinically actionable roadmap from biophysics to bedside.
文摘Sport-related concussion(SRC)and its potential neurological sequela represent an emerging global health concern,requiring improved recovery management and strategies for return-to-play(RTP)to enhance brain health in athletes.Given the dynamic and multifaceted nature of SRC recovery,the purpose of this review is to synthesize existing literature on post-SRC outcomes in adult athletes,and to outline the temporal trajectories of key recovery indicators(symptoms,cognitive function,blood biomarkers)across distinct recovery phases until resolution.In the acute phase of SRC(first 48 h),symptom scores and brain damage markers peaked immediately,while cognitive impairments and neuroinflammation emerged with a slight delay.Following the initial rise,brain damage marker concentrations rapidly dropped below baseline levels at approximately 48 h following SRC injury.During the early recovery phase,neuroinflammation and most cognitive alterations resolved after 3–5 days,though symptom burden and attention deficits persisted for up to 7 days.Despite prolonged alterations reported in some individuals,recovery markers typically returned to pre-injury levels in the transition phase(≤2 weeks),though mild attention deficits were detected up to 3 weeks,and TNF-α concentrations remained elevated throughout late recovery(>2 weeks).These results reveal distinct temporal discrepancies across recovery markers and emphasize that physiological disturbances can outlast symptom resolution,underscoring the need for both multimodal assessments and appropriately timed evaluations to accurately track recovery progression.Incorporating structured follow-ups at key time points,particularly beyond symptom resolution,may improve RTP decision-making and reduce the risk of premature return and long-term neurological consequences.
基金Supported by The Eye Hospital of Wenzhou Medical University(No.KYQD20220304)The Fifth Batch of Provincial Ten Thousand Personnel Program Outstanding Talents Funding(No.474092204)+1 种基金Innovative Talents and Teams(2024)-The Fifth Batch of Funding Funds for Scientific and Technological Innovation Leading Talents Under the Provincial Ten Thousand Personnel Program(No.4240924003G)The Key R&D Program of Zhejiang(No.2022C03112).
文摘AIM:To identify early biomarkers associated with glaucomatous visual field(VF)progression in patients with normal-tension glaucoma(NTG).METHODS:This study included patients were divided into two groups based on disease progression status.Tear samples were collected for proteomic analysis.Dataindependent acquisition(DIA)mass spectrometry combined with bioinformatic analyses was performed to identify and validate potential protein biomarkers for NTG progression.Additionally,differentially expressed proteins(DEPs)were evaluated using mediating effect models and receiver operating characteristic(ROC)curve analysis.RESULTS:A total of 19 patients(20 eyes)with NTG participated in this study,including 10 patients(4 males and 6 females;10 eyes)in the progression group with mean age of 67.70±9.03y and 10 patients(4 males and 6 females;10 eyes)in the non-progression group with mean age of 68.60±7.58y.A total of 158 significantly differentially expressed proteins were detected.UniProt database annotation identified 3 upregulated proteins and 12 downregulated proteins.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that these DEPs were mainly enriched in pathways such as oocyte meiosis.Gene Ontology(GO)enrichment analysis revealed functional clusters related to cellular processes.Weighted gene coexpression network analysis(WGCNA)indicated that the core proteins were primarily involved in the neurodegenerationmultiple diseases pathway and cellular processes.Mediating effect analysis identified PRDX4(L)as a potential protein biomarker.ROC curve analysis showed that GNAI1 had the largest area under the curve(AUC=0.889).CONCLUSION:This study identifies 15 differentially expressed proteins in the tear fluid of NTG patients,including PRDX4(L).PRDX4(L)plays a key role in oxidative stress.
基金the Deanship of Research and Graduate Studies at King Khalid University,KSA,for funding this work through the Large Research Project under grant number RGP2/164/46.
文摘Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.
基金supported by the National Natural Science Foundation of China,No.82104144(to LZ)The Fifth Affiliated Hospital of Sun Yat-sen University of Outstanding Young Talents Cultivation Program,No.3320104100322(to WC)+1 种基金“Five Five”Young Talents Program,No.220904094231(to LZ)the Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine Foundation of Guangdong Province,No.2023LSYS001(to WC).
文摘Ischemic stroke,a neurological impairment caused by cerebral vascular occlusion,accounts for 87%of the cases of stroke.Recent studies have shown that changes in the abundance of metabolites can directly reveal the cellular phenotypes and identify the clinical implications of stroke diagnosis and therapy.However,systematic research to clarify the relationship between biomarkers and the mechanisms of ischemic stroke remains limited.In this study,we reviewed articles on ischemic stroke metabolites from 2005 to 2024,identified metabolites showing significant changes,and constructed a metabolite database based on the findings from 128 studies.The database included 125 differential metabolites detected in a middle cerebral artery occlusion mouse model,246 detected in an middle cerebral artery occlusion rat model,and 764 identified in ischemic stroke patient samples.Differential metabolites from various samples were then screened and classified into positive and negative categories based on their correlation with stroke prognoses.Based on this analysis,three positive metabolites and two negative metabolites were identified.Glutamic acid,glycerol,and 1-octadecanoyl-sn-glycero-3-phosphocholine(LysoPC(18:0))were further recognized as potential biomarkers.Imbalances in metabolic pathways such as alanine,aspartate,and glutamate metabolism as well as the citrate cycle(tricarboxylic acid cycle)were analyzed.These imbalances may influence the pathogenesis of ischemic stroke by altering biological processes such as excitotoxicity,oxidative stress,inflammation,and energy metabolism.The identification and analysis of these potential biomarkers may provide valuable targets and strategies for prediction,diagnosis,and prognostic assessment of ischemic stroke.
文摘Liver is prone to viral infection.Viral hepatitis can be roughly divided into hepatitis A,B,C,D and E.Accurate diagnosis of viral hepatitis is crucial for accurate treatments.Different types of biomarkers,including non-invasive biomarkers have been explored for the diagnosis of viral hepatitis.With the fast development of multi-omics technology,non-invasive biomarkers can be detected from blood,saliva,urine,stool,and other body fluids.The advantages of non-invasive biomarkers are:1)non-invasive;2)convenient to test and 3)repeatable.The application of non-invasive biomarkers significantly improves the diagnostic accuracy of viral hepatitis.The non-invasive biomarkers can be sugars,proteins,nucleic acids,and even microorganisms.In this review,we summarized recent advances in identifying non-invasive biomarkers using multi-omics technology and discussed their potential diagnostic values for viral hepatitis.
基金supported by the National Natural Science Foundation of China(No.82360120)the Kunming Medical University Joint Special Project on Applied Basic Research(202401AY070001-134),and project iGandanF-1082022-RGG049+2 种基金the Open Project of Yunnan Provincial Clinical Medical Center for Digestive System Diseases(2022LCZXXF-XH07/17)the 14th Undergraduate Scientific Research Project of Mudanjiang Medical University(2024057)Yunnan Provincial Key Laboratory of Clinical Virology(No.2023A4010403-04).
文摘Background:High-mobility group box 1(HMGB1)is a critical damage-associated molecular pattern protein that participates in diverse physiological and pathological processes.However,its relevance to the prognosis of artificial liver support therapy in patients with acute liver injury(ALF)remains unclear.Methods:Bioinformatics analyses were performed to identify HMGB1-interacting proteins and associated inflammatory signaling pathways.Peripheral blood samples were collected from ALF patients before and after artificial liver support therapy,and serum HMGB1 concentrations were quantified using ELISA.Primary mouse hepatocytes were stimulated with lipopolysaccharide(LPS)in vitro and HMGB1 expression was verified by western blot.Results:Single-cell transcriptomic profiling showed that HMGB1 is widely expressed across tissues and predominantly localized in the nucleus.In the liver,HMGB1 was primarily expressed in hepatocytes and hepatic stellate cells.STRING database analysis revealed that human HMGB1 interacts with multiple proteins,including TLR4,TP53,and BECN1.The constructed interaction network comprised 11 nodes with an average local clustering coefficient of 0.888,and the protein–protein interaction enrichment P-value was 1.42×10^(-5),indicating significant enrichment.Gene Ontology and KEGG pathway enrichment analyses demonstrated that HMGB1 is closely linked to inflammatory and injury-related signaling pathways,including the TLR and NLR pathways.Metabolomic profiling revealed significant metabolic alterations between patients with ALF and healthy controls under both positive and negative ion modes and functional analysis showed necroptosis was activated.The cell viability gradually decreased with time and dose under LPS treatment and extracellular HMGB1 was upregulated in LPS induced ALF model and patients(P<0.05).Serum HMGB1/RIPK3/MLKL levels were markedly elevated in ALF patients compared with controls(P<0.05)and progressively declined following artificial liver support therapy.Furthermore,elevated HMGB1 concentrations were positively correlated with unfavorable clinical outcomes.Conclusion:Peripheral blood HMGB1 levels are significantly increased in patients with acute liver failure,decrease following artificial liver support therapy,and are positively associated with poor clinical prognosis.
基金supported by the National Research Foundation of Korea(NRF)grant,funded by the Korean government(MIST),Jae-Hoon Kim(NRF-2020R1A2C2004782)Hanbyoul Cho(NRF-RS-2025-00522191)of Funderssupported by the Bio&Medical Technology Development Program of the National Research Foundation(NRF),funded by the Korean Government(MSIT),Jae-Hoon Kim of Funder(NRF-2017M3A9B 8069610).
文摘Objectives:Phosphodiesterase 1A(PDE1A)regulates intracellular cyclic nucleotide signaling and has been implicated in tumor progression,but its clinical relevance and functional role in epithelial ovarian cancer(EOC),particularly in relation to the response to platinum remain unclear.This study aimed to evaluate the clinical significance of PDE1A in EOG and to clarify its functional role in tumor progression and response to platinum-based chemotherapy.Methods:PDE1A mRNA and protein levels were analyzed using public databases,RNA sequencing,and immunohistochemistry.Correlations between PDE1A expression,clinicopathological features,and prognosis were assessed.Functional roles were investigated in ovarian cancer cell lines.Results:PDE1A was significantly overexpressed in EOC tissues compared with that in normal ovarian epithelial tissues.Overexpression correlated with advanced International Federation of Gynecology and Obstetrics(FIGO)stage,poor tumor grade,and reduced response to platinum-based chemotherapy.High PDE1A levels were linked to worse disease-free survival and overall survival,and multivariate analysis confirmed PDE1A as an independent prognostic factor.To elucidate its functional role,we performed in vitro experiments showing that PDE1A knockdown suppressed cell proliferation and colony formation,induced G1 arrest,and downregulatedβ-catenin signaling with reduced cyclin D1 and c-Myc expression.Notably,these inhibitory effects were partially rescued by lithium chloride(LiCl),a Wingless-related integration site(Wnt)/β-catenin activator.Conclusions:In conclusion,our findings identify PDE1A as a Wnt/β-catenin-linked biomarker of tumor progression and platinum resistance in EOC and provide a biological rationale for further investigation of PDE1A-targeted strategies in preclinical models.
基金National Natural Science Foundation of China,No.82405067(to YW)。
文摘MicroRNAs(miRNAs),small non-coding RNAs ranging from 19 to 25 nucleotides in length,are key regulators of gene expression that function primarily by inhibiting the translation of target mRNAs.Recent studies have suggested that miRNAs play important roles in regulating key aspects in the pathology of Alzheimer's disease,including the modulation and accumulation of amyloid-beta and tau proteins.Moreover,miRNAs have been implicated in the regulation of neuroinflammation thro ugh various inflammatory pathways,notably the nuclear factor kappa B signaling cascade.Additional emerging evidence has shown that miRNAs regulate synaptic growth and maturation,and they perform promising roles in regulating neuronal death and development.miRNAs also offer a novel avenue for direct reprogramming of neurons,representing a promising strategy for Alzheimer's disease treatment.The regulation of miRNA biogenesis and the post-transcriptional modifications of miRNAs are critical factors in Alzheimer's disease pathology,influencing miRNA activity and disease progression.In this review,we comprehensively explore the role of different miRNAs in regulating various pathological processes associated with Alzheimer's disease,focusing primarily on four representative miRNAs:miR-9,miR-29,miR-126,and miR-146a for further exploration.We also discuss the influence of miRNA biogenesis on Alzheimer's disease,emphasizing how dysregulation of miRNA processing may contribute to the disease.Additionally,we highlight the potential of miRNAs as both diagnostic biomarke rs and therapeutic targets in Alzheimer's disease,along with promising vector delive ry strategies aimed at improving clinical outcomes.Finally,we discuss the challenges and limitations associated with the use of miRNAs in the diagnosis and treatment of Alzheimer's disease.By reviewing the current clinical applications of miRNAs as biomarkers and therapeutic agents,we aim to provide insights that will inform future research and development in this promising field.
基金supported by the College of Oral Medicine,Taipei Medical University,Taipei,Taiwan(Grant No.TMUCOM202502)supported by Taipei Medical University Hospital,Taipei,Taiwan(Grant No.114TMUH-NE-05).
文摘This narrative review examines recent advances in salivary biomarkers for oral squamous cell carcinoma(OSCC),a major subtype of oral cancer with persistently low five-year survival rates due to delayed diagnosis.Saliva has emerged as a noninvasive diagnostic medium capable of reflecting both local tumor activity and systemic physiological changes.Various salivary biomarkers,including microRNAs,cytokines,proteins,metabolites,and exosomes,have been linked to oncogenic signaling pathways involved in tumor progression,immune modulation,and therapeutic resistance.Advances in quantitative polymerase chain reaction,mass spectrometry,and next-generation sequencing have enabled comprehensive biomarker profiling,while point-of-care detection systems and saliva-based omics platforms are accelerating clinical translation.Remaining challenges include variability in salivary composition,lack of standardized collection protocols,and insufficient validation across large patient cohorts.This review highlights the mechanistic relevance,diagnostic potential,and translational challenges of salivary biomarkers in OSCC.
文摘Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder and the leading cause of dementia worldwide.It is characterized by the accumulation of extracellular amyloid-beta(Aβ)plaques and intracellular tau neurofibrillary tangles,leading to synaptic dysfunction,neuronal loss,and cognitive decline.These pathological changes can begin decades before clinical symptoms emerge,highlighting the critical need for early,accessible,and accurate diagnostic tools.
文摘Glioblastoma(GBM),the most aggressive and lethal primary brain tumor in adults,continues to resist conventional therapeutic approaches,withmedian survival remaining dismally low.Immune checkpoint inhibitors(ICIs),which have revolutionized the treatment of several solid tumors,have shown limited efficacy inGBMowing to the highly immunosuppressive and heterogeneousmicroenvironment of the tumor.The unique immune landscape of the central nervous system(CNS),characterized by low immunogenicity,restricted T-cell infiltration,and an abundance of regulatory and myeloid-derived suppressor cells,poses considerable barriers to effective immune reactivation.This review provides a comprehensive synthesis of the mechanistic barriers undermining ICI efficacy in GBM,including the blood-brain barrier,low tumor mutational burden,adaptive immune resistance,and iatrogenic immunosuppression.It also explores emerging predictive and prognostic biomarkers,such as programmed death-ligand 1(PD-L1)expression,immune gene signatures,tumor-infiltrating lymphocyte profiles,and circulating markers in cerebrospinal fluid and plasma,which hold promise for guiding patient selection and therapeutic monitoring.Importantly,recent breakthroughs in combinatorial immunotherapy strategies are highlighted,including the integration of ICIs with radiotherapy,anti-angiogenic agents,oncolytic viruses,personalized neoantigen vaccines,and tumor microenvironment reprogramming approaches.Innovative delivery platforms,such as nanoparticles,focused ultrasound,and convection-enhanced delivery,are also discussed for their potential to improve drug bioavailability and local immune activation in the CNS.This review hypothesizes that the therapeutic efficacy of ICIs in GBM can be considerably enhanced by disrupting immune exclusion and reversing immunosuppression through integrated,multimodal strategies guided by dynamic biomarker profiling and spatially resolved immunemapping.This hypothesisdriven approach aims to bridge translational gaps and inform next-generation clinical trial designs that may unlock the potential of immunotherapy for GBM.
文摘GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,it spans a wide range of neurological clinical manifestations,that may include epileptic seizures,motor dysfunctions,developmental and intellectual delay,and other symptoms(Sáez González et al.,2023).
基金supported by Shenzhen Science and Technology Program, No. JCYJ20230807110259002 (to JL)The Seventh Affiliated Hospital of Sun Yat-sen University, No. ZSQYRSFPD0050 (to JL)The Postdoctoral Fellowship Program of CPSF, No. GZC20242074 (to KT)
文摘Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.
基金co-funded by the National Natural Science Foundation of China(42372160,42072172)。
文摘The Neogene Shawan Formation in the Chepaizi Uplift of the Junggar Basin(NW China)has obtained high oil flow,demonstrating a good potential for oil and gas exploration.The multi-source hydrocarbon generation background and strong tectonic activity have led to the simultaneous production of heavy oil and light oil from multi-layer in the area,which makes it very difficult to identify oil origins,presently,the hot debate on the oil origins needs to be clarified.In this paper,due to the selective consumption of different types of compounds in crude oils by severe and intense biodegradation,the commonly used oilsource correlation tools are ineffective or may produce misleading results,this study adopted a biomarker recovery method based on the principle of mass conservation that uses the sum of the mass of the residual biomarkers and their corresponding biodegradation products to obtain the mass of the original biomarkers,improving the reliability of oil origins determination.Based on the nature and occurrence of crude oils,the investigated oils are subdivided into three types,Group A,Group B and Group C.Group A,light oils occurred mainly in lower structure Neogene Shawan Formation in the western Chepaizi Uplift,while Group B,heavy oils occurred mainly in higher structure Neogene Shawan Formation in the western Chepaizi Uplift.The two types of crude oils may come from the mixed source of Jurassic Badaowan Formation source rocks(J_(1)b)and Paleogene Anjihaihe Formation source rocks(E_(2-3)a)in the Sikeshu Sag,and Jurassic Badaowan Formation source rocks(J_(1)b)are the main source of crude oils.Group C,heavy oils occurred mainly in Neogene Shawan Formation in the eastern Chepaizi Uplift,showing good correlation with the Permian(P_(1)f and P_(2)w)source rocks in the Shawan Sag.At the same time,by combining stable carbon isotope and parameters related to triaromatic steroids,the accuracy of the oilsource correlation results by biomarker recovery method was further verified.
文摘Aberrant RNA modification has been linked to the pathogenesis of various diseases;however,its specific molecular mechanisms in spinal cord injury remain poorly understood.The objective of this study was to explore RNA modification-related biomarkers of spinal cord injury.The mRNA expression profiles of mice with spinal cord injury were retrieved from the Gene Expression Omnibus(GEO)database(GSE18179).We identified 185 differentially expressed genes using bioinformatics approaches.Functional enrichment analysis demonstrated aberrant activation or inhibition of common metabolism-related pathways,including sulfur metabolism and steroid biosynthesis,in mice with spinal cord injury.An integrated strategy comprising weighted gene co-expression network analysis,a random forest model,a support vector machine model,and a generalized linear model was employed to identify four genes whose aberrant RNA modification was linked to spinal cord injury:Elovl6,Idi1,Sqle,and Stbd1.We verified the expression levels and diagnostic performance of these four genes in the original training dataset and mouse samples via receiver operating characteristic curve analysis.Quantitative reverse transcription-polymerase chain reaction demonstrated variations in the mRNA levels of the four genes between the Sham and spinal cord injury groups at different time points following injury.We also constructed microRNA-mRNA and transcription factor-mRNA interaction networks using Cytoscape.Additionally,we evaluated the proportions of 22 types of immune cells in the spinal cords of mice using the CIBERSORT tool,revealing significant alterations in the numbers of memory B cells,resting dendritic cells,M0 macrophages,activated mast cells,resting mast cells,and CD8+T cells in spinal cord injury mice compared with Sham controls.Microglia and T cells were identified as key cell types by single-cell sequencing analysis.These findings provide new directions for the development of RNA modification-related therapeutic strategies for spinal cord injury and suggest that Elovl6,Idi1,Sqle,and Stbd1 are potential biomarkers of spinal cord injury.
