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: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
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
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
The advent of precision medicine has underscored the importance of biomarkers in predicting therapy response for bladder cancer,a malignancy marked by considerable heterogeneity.This review critically examines the cur...The advent of precision medicine has underscored the importance of biomarkers in predicting therapy response for bladder cancer,a malignancy marked by considerable heterogeneity.This review critically examines the current landscape of biomarkers to forecast treatment outcomes in bladder cancer patients.We explore a range of biomarkers,including genetic,epigenetic,proteomic,and transcriptomic indicators,from multiple sample sources,including urine,tumor tissue and blood,assessing their efficacy in predicting responses to chemotherapy,immunotherapy,and targeted therapies.Despite promising developments,the translation of these biomarkers into clinical practice faces significant challenges,such as variability in biomarker performance,the necessity for large-scale validation studies,and the integration of biomarker testing into routine clinical workflows.We also highlight the need for standardized methodologies and robust assays to ensure consistency and reliability.Future directions point towards longitudinal studies and the development of combination biomarker panels to enhance predictive accuracy.This review emphasizes the transformative potential of predictive biomarkers in improving patient outcomes and advocates for continued collaborative efforts to overcome existing barriers in this rapidly evolving field.展开更多
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective d...Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.展开更多
Pancreatic cancer is usually associated with a poor prognosis.Surgery is the main curative treatment but pancreatic operations are aggressive and new tools that help clinicians to predict surgical and prognostic outco...Pancreatic cancer is usually associated with a poor prognosis.Surgery is the main curative treatment but pancreatic operations are aggressive and new tools that help clinicians to predict surgical and prognostic outcomes are necessary.Lu et al recently published a retrospective,single centre cohort study evaluating the impact of seven nutritional and inflammatory markers in pancreatic cancer surgical patients:The albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune-inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),nutritional risk index,and the geriatric nutritional risk index.A significant correlation was found between the PNI,SII,NLR,and PLR and a hospital discharge of less than 15 days.In a univariable analysis,PNI,SII,NLR and PLR were significantly related to recurrence-free survival and,in a multivariable analysis PNI was associated with overall survival.Various meta-analyses corroborate the results in terms of prognosis but individual studies are discordant on their usefulness.Besides,the cut-off values for these markers vary significantly between studies and there are no clinical trials comparing them to identify the most relevant ones.These are limitations when implementing nutritional and inflammatory biomarkers into clinical practice and further studies are needed in order to answer these questions.展开更多
Cancer is a major threat to human health worldwide.Colorectal cancer(CRC),a highly prevalent malignant tumor,poses a significant public health challenge.Therefore,the identification of effective biomarkers is of great...Cancer is a major threat to human health worldwide.Colorectal cancer(CRC),a highly prevalent malignant tumor,poses a significant public health challenge.Therefore,the identification of effective biomarkers is of great significance[1].The NFKBIE gene encodes an inhibitor of nuclear factorκBε(IkBε).IκBε,a key regulator of the NF-κB signaling pathway,is closely associated with tumorigenesis.However,their roles in CRC remain unclear[2].Pan-cancer research is crucial for accelerating the identification of biomarkers and translational medical research,as it can reveal molecular commonalities and differences among different tumor types[3].展开更多
The active ingredient(a.i.)glyphosate is frequently detected in waterways at relatively high concentrations,posing a risk to aquatic organisms including freshwater mussels,North America’s most endangered animal group...The active ingredient(a.i.)glyphosate is frequently detected in waterways at relatively high concentrations,posing a risk to aquatic organisms including freshwater mussels,North America’s most endangered animal group.This research aims to evaluate for the first time the effect of a glyphosate-based herbicide on a freshwater mussel(Unionid)using a battery of biomarkers.Themussel Elliptio complanata was exposed for 21 days to CreditR Xtreme(at 0,50,100,and 150μg/L a.i.of glyphosate).An integrated biomarker response(IBRv2)was used to visualize the overall impact of each glyphosate-based herbicide concentration on mussels’health conditions.The biomarker results showed that glyphosate(used at 100μg/L and 150μg/L)induced lipid peroxidation in the gills and digestive gland and inhibited acetylcholinesterase in the foot and gills,indicating oxidative damage and neurotoxicity.Other biomarkerswere influenced at the lowest concentration of glyphosate tested(50μg/L):lipids(decrease),triglycerides(increase)and,to a lesser extent,vitellogenin(decrease).For the latter biomarkers,the sexeswere not affected similarly,and theywere only sensitive at 50μg/L,only females showed a trend toward a decrease for vitellogenin and a decrease for lipids.Using IBRv2,we found a clear discrimination between concentrations,and the index values increased with glyphosate concentration,attesting to the deterioration in biomarker-defined mussel health when exposed to Credit® Xtreme at realistic glyphosate concentrations in agricultural rivers.This study shows that glyphosate-based herbicides can alter neurological function,induce oxidative damage,and selectively modify the E.complanata metabolism at relatively low concentrations.展开更多
Urinary tract infections(UTIs)are the most common bacterial infections.Escherichia coli is the most common cause of UTIs,accounting for 50%of hospital-reported and 90%of community-reported cases.Also,this includes spe...Urinary tract infections(UTIs)are the most common bacterial infections.Escherichia coli is the most common cause of UTIs,accounting for 50%of hospital-reported and 90%of community-reported cases.Also,this includes species of Klebsiella,Proteus,Acinetobacter,Pseudomonas,Staphylococcus,Streptococcus,and Enterococcus.Patients experience cystitis,polyuria,and dysuria.If untreated,this affects the kidneys,further leading to septicemia.UTIs majorly affect adult females(40%-60%).Microbiological culture has been proven to be the standard method.However,it takes 48-72 hours for the tests to be reported.In cases of recurrent UTI,it is mandatory to have a quick,sensitive,and specific diagnostic procedure.Dipstick tests are considered early methods for diagnosing UTIs;however,they have limitations.Recently,biomarkers are being used to assess the severity of the disease.To achieve the United Nations Sustainable Development Goals 3 and 8,the expertise from General Medicine,Biotechnology,and Microbiology come together in achieving the set targets by 2030.In addition to diagnosis of UTI,resistance to antibiotics should not be neglected.This review aimed to examine the clinical relevance of biomarkers such as neutrophil gelatinase-associated lipocalin,kidney injury molecule-1,interleukin(IL)6,IL-8,heparin-binding protein,procalcitonin,lipopolysaccharide-binding protein,xanthine oxidase,cell-free DNA,and transrenal DNA.展开更多
Background Biomarkers-based prediction of long-term risk of acute coronary syndrome(ACS)is scarce.We aim to develop a risk score integrating clinical routine information(C)and plasma biomarkers(B)for predicting long-t...Background Biomarkers-based prediction of long-term risk of acute coronary syndrome(ACS)is scarce.We aim to develop a risk score integrating clinical routine information(C)and plasma biomarkers(B)for predicting long-term risk of ACS patients.Methods We included 2729 ACS patients from the OCEA(Observation of cardiovascular events in ACS patients).The earlier admitted 1910 patients were enrolled as development cohort;and the subsequently admitted 819 subjects were treated as valida-tion cohort.We investigated 10-year risk of cardiovascular(CV)death,myocardial infarction(MI)and all cause death in these pa-tients.Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was de-rived using main part of these variables.Results During 16,110 person-years of follow-up,there were 238 CV death/MI in the development cohort.The 7 most import-ant predictors including in the final model were NT-proBNP,D-dimer,GDF-15,peripheral artery disease(PAD),Fibrinogen,ST-segment elevated MI(STEMI),left ventricular ejection fraction(LVEF),termed as CB-ACS score.C-index of the score for predica-tion of cardiovascular events was 0.79(95%CI:0.76-0.82)in development cohort and 0.77(95%CI:0.76-0.78)in the validation co-hort(5832 person-years of follow-up),which outperformed GRACE 2.0 and ABC-ACS risk score.The CB-ACS score was also well calibrated in development and validation cohort(Greenwood-Nam-D’Agostino:P=0.70 and P=0.07,respectively).Conclusions CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS.This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.展开更多
Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarke...Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed in manic patients compared to controls, and dysregulation of miR-134,-152,-607,-633,-652,-155 occurred in euthymic patients compared to controls. Finally, microRNAs such as miR-34a,-34b,-34c,-137, and-140-3p,-21-3p,-30d-5p,-330-5p,-378a-5p,-134,-19b-3p were shown to have diagnostic potential in distinguishing bipolar disorder patients from schizophrenia or major depressive disorder patients, respectively. Further studies are warranted with adolescents and young adults having bipolar disorder and consideration should be given to using animal models of the disorder to investigate the effects of suppressing or overexpressing specific microRNAs.展开更多
Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomar...Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.展开更多
A global increase in the incidence of pancreatic cancer(PanCa)presents a major concern and health burden.The traditional tissue-based diagnostic techniques provided a major way forward for molecular diagnostics;howeve...A global increase in the incidence of pancreatic cancer(PanCa)presents a major concern and health burden.The traditional tissue-based diagnostic techniques provided a major way forward for molecular diagnostics;however,they face limitations based on diagnosis-associated difficulties and concerns surrounding tissue availability in the clinical setting.Late disease development with asymptomatic behavior is a drawback in the case of existing diagnostic procedures.The capability of cell free markers in discriminating PanCa from autoimmune pancreatitis and chronic pancreatitis along with other precancerous lesions can be a boon to clinicians.Early-stage diagnosis of PanCa can be achieved only if these biomarkers specifically discriminate the non-carcinogenic disease stage from malignancy with respect to tumor stages.In this review,we comprehensively described the non-invasive disease detection approaches and why these approaches are gaining popularity for their early-stage diagnostic capability and associated clinical feasibility.展开更多
BACKGROUND: This study aimed to explore the risk factors associated with intensive care unitacquired weakness(ICU-AW) in critically ill patients at risk of malnutrition and to evaluate the efficacy of early enteral nu...BACKGROUND: This study aimed to explore the risk factors associated with intensive care unitacquired weakness(ICU-AW) in critically ill patients at risk of malnutrition and to evaluate the efficacy of early enteral nutrition(EEN) and the role of biomarkers in managing ICU-AW.METHODS: This retrospective, observational cohort study included 180 patients at risk of malnutrition admitted to the emergency intensive care unit of the First Affiliated Hospital of Xiamen University Hospital from January 2022 to December 2023. Patients were divided into ICU-AW group and non-ICU-AW group according to whether they developed ICU-AW, or categorized into EEN and parenteral nutrition(PN) groups according to nutritional support. ICU-AW was diagnosed using the Medical Research Council score. The primary outcome was the occurrence of ICU-AW.RESULTS: The significant factors associated with ICU-AW included age, sex, type of nutritional therapy, mechanical ventilation(MV), body mass index(BMI), blood urea nitrogen(BUN), and creatinine(Cr) levels(P<0.05). The PN group developed ICU-AW earlier than did the EEN group, with a significant difference observed(log-rank P<0.001). Among biomarkers for ICU-AW, the mean prealbumin(PAB)/C-reactive protein(CRP) ratio had the highest diagnostic accuracy(area under the curve [AUC] 0.928, 95% confidence interval [95% CI] 0.892–0.946), surpassing the mean Cr/BUN ratio(AUC 0.740, 95% CI 0.663–0.819) and mean transferrin levels(AUC 0.653, 95% CI 0.574–0.733).CONCLUSION: Independent risk factors for ICU-AW include female sex, advanced age, PN, MV, lower BMI, and elevated BUN and Cr levels. EEN may potentially delay ICU-AW onset, and the PAB/CRP ratio may be an effective diagnostic marker for this condition.展开更多
Gastrointestinal(GI)cancers,which predominantly manifest in the stomach,colorectum,liver,esophagus,and pancreas,accounting for approximately 35%of global cancer-related mortality.The advent of liquid biopsy has introd...Gastrointestinal(GI)cancers,which predominantly manifest in the stomach,colorectum,liver,esophagus,and pancreas,accounting for approximately 35%of global cancer-related mortality.The advent of liquid biopsy has introduced a pivotal diagnostic modality for the early identification of premalignant GI lesions and incipient cancers.This non-invasive technique not only facilitates prompt therapeutic intervention,but also serves as a critical adjunct in prognosticating the likelihood of tumor recurrence.The wealth of circulating exosomes present in body fluids is often enriched with proteins,lipids,microRNAs,and other RNAs derived from tumor cells.These specific cargo components are reflective of processes involved in GI tumorigenesis,tumor progression,and response to treatment.As such,they represent a group of promising biomarkers for aiding in the diagnosis of GI cancer.In this review,we delivered an exhaustive overview of the composition of exosomes and the pathways for cargo sorting within these vesicles.We laid out some of the clinical evidence that supported the utilization of exosomes as diagnostic biomarkers for GI cancers and discussed their potential for clinical application.Furthermore,we addressed the challenges encountered when harnessing exosomes as diagnostic and predictive instruments in the realm of GI cancers.展开更多
Background:Heat shock protein B8(HSPB8)is implicated in autophagy,and its aberrant expression has been linked to both the ini-tiation and progression of tumors.However,the role and function of HSPB8 in colorectal canc...Background:Heat shock protein B8(HSPB8)is implicated in autophagy,and its aberrant expression has been linked to both the ini-tiation and progression of tumors.However,the role and function of HSPB8 in colorectal cancer(CRC)and across multiple cancer types remain unclear.This study aimed to map the transcriptome of autophagy-related genes in CRC and to conduct a pan-cancer analysis of HSPB8 as both a prognostic and immunological biomarker.Methods:We performed bioinformatics analyses on GSE113513 and GSE74602 to identify differentially expressed genes(DEGs)in CRC.These DEGs were then compared with autophagy-related genes to identify critical overlapping genes.The Kaplan-Meier plotter was used to verify the ex-pression of autophagy-linked DEGs and evaluate its prognostic value.The protein expression of Hub gene in CRC was analyzed using the Human Protein Atlas database.The cBioPortal was used to analyze the type and frequency of Hub gene mutations.The TIMER(Tumor Immune Estimation Resource)database was used to study the correlation between HSPB8 and immune infiltration in CRC.Results:In total,825 DEGs were identified,including 8 autophagy-linked DEGs:ATIC,MYC,HSPB8,TNFSF10,BCL2,TP53INP2,ITPR1,and NKX2-3.Survival analysis showed that increased HSPB8 expression significantly correlates with poor prognosis in patients with CRC(p<0.05).HSPB8 was also found to be differentially expressed in various cancer types,correlating with both prognosis and immune infiltration.Further,changes in HSPB8 methylation and phosphorylation status were observed across several cancers,suggesting potential regulatory mechanisms.Therefore,HSPB8 may serve as a crucial prognostic and immunological biomarker in CRC and other cancers.Conclusions:This study provides new insights into the role of autophagy-related genes in cancer progression and highlights HSPB8 as a potential target for cancer diagnostics and therapy.展开更多
BACKGROUND Irritable bowel syndrome with predominant constipation(IBS-C)is a chronic gastrointestinal disorder that significantly impacts the quality of life of patients and currently lacks a definitive treatment.The ...BACKGROUND Irritable bowel syndrome with predominant constipation(IBS-C)is a chronic gastrointestinal disorder that significantly impacts the quality of life of patients and currently lacks a definitive treatment.The use of electroacupuncture(EA)has demonstrated clinical efficacy in treating IBS-C and the gut-brain axis modulation,though its mechanisms remain unclear.AIM To investigate gut-brain-microbiota axis alteration and EA-associated microbial changes in IBS-C patients and treatment responders.METHODS This study consisted of two phases.The first phase was a cross-sectional study recruiting sixteen IBS-C patients and 16 healthy controls.Baseline fecal samples were collected to assess gut microbiota profiles between the two groups.The second phase was an observational longitudinal study in which the 16 IBS-C patients underwent nine EA sessions over one month.Gut microbiota profiles and clinical outcomes were assessed post-treatment course and at a one-month follow-up.RESULTS IBS-C patients exhibited significant gut dysbiosis,as indicated by altered beta diversity compared to healthy controls.EA significantly improved clinical outcomes and gut dysbiosis,with sustained therapeutic effects and normalization of neurotransmitter-related metabolic pathways observed at one-month follow-up.Notably,the gut bacterium Senegalimassilia was positively associated with symptom improvement,suggesting its potential as a predictive biomarker of EA responsiveness.CONCLUSION These findings support the integration of EA into IBS-C management and highlight Senegalimassilia as a candidate microbial biomarker for treatment response.展开更多
Advances in the identification of molecular biomarkers and the development of targeted therapies have enhanced the prognosis of patients with advanced gastric cancer.Several established biomarkers have been widely int...Advances in the identification of molecular biomarkers and the development of targeted therapies have enhanced the prognosis of patients with advanced gastric cancer.Several established biomarkers have been widely integrated into routine clinical diagnostics of gastric cancer to guide personalized treatment.Human epidermal growth factor receptor 2(HER2)was the first molecular biomarker to be used in gastric cancer with trastuzumab being the first approved targeted therapy for HER2-positive gastric cancer.Programmed death-ligand 1 positivity and microsatellite instability can guide the use of immunotherapies,such as pembrolizumab and nivolumab.More recently,zolbetuximab has been approved for patients with claudin 18.2-positive diseases in some countries.More targeted therapies,including savolitinib for MET-positive patients,are currently under clinical investigation.However,the clinical application of these diagnostic approaches could be hampered by many existing challenges,including invasive and costly sampling methods,variability in immunohistochemistry interpretation,high costs and long turnaround times for next-generation sequencing,the absence of standardized and clinically validated diagnostic cut-off values for some biomarkers,and tumor heterogeneity.Novel testing and analysis techniques,such as artificial intelligence-assisted image analysis and multiplex immunohistochemistry,and emerging therapeutic strategies,including combination therapies that integrate immune checkpoint inhibitors with targeted therapies,offer potential solutions to some of these challenges.This article reviews recent progress in gastric cancer testing,outlines current challenges,and explores future directions for biomarker testing and targeted therapy for gastric cancer.展开更多
In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release f...In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.展开更多
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 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 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).
文摘The advent of precision medicine has underscored the importance of biomarkers in predicting therapy response for bladder cancer,a malignancy marked by considerable heterogeneity.This review critically examines the current landscape of biomarkers to forecast treatment outcomes in bladder cancer patients.We explore a range of biomarkers,including genetic,epigenetic,proteomic,and transcriptomic indicators,from multiple sample sources,including urine,tumor tissue and blood,assessing their efficacy in predicting responses to chemotherapy,immunotherapy,and targeted therapies.Despite promising developments,the translation of these biomarkers into clinical practice faces significant challenges,such as variability in biomarker performance,the necessity for large-scale validation studies,and the integration of biomarker testing into routine clinical workflows.We also highlight the need for standardized methodologies and robust assays to ensure consistency and reliability.Future directions point towards longitudinal studies and the development of combination biomarker panels to enhance predictive accuracy.This review emphasizes the transformative potential of predictive biomarkers in improving patient outcomes and advocates for continued collaborative efforts to overcome existing barriers in this rapidly evolving field.
文摘Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.
文摘Pancreatic cancer is usually associated with a poor prognosis.Surgery is the main curative treatment but pancreatic operations are aggressive and new tools that help clinicians to predict surgical and prognostic outcomes are necessary.Lu et al recently published a retrospective,single centre cohort study evaluating the impact of seven nutritional and inflammatory markers in pancreatic cancer surgical patients:The albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune-inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),nutritional risk index,and the geriatric nutritional risk index.A significant correlation was found between the PNI,SII,NLR,and PLR and a hospital discharge of less than 15 days.In a univariable analysis,PNI,SII,NLR and PLR were significantly related to recurrence-free survival and,in a multivariable analysis PNI was associated with overall survival.Various meta-analyses corroborate the results in terms of prognosis but individual studies are discordant on their usefulness.Besides,the cut-off values for these markers vary significantly between studies and there are no clinical trials comparing them to identify the most relevant ones.These are limitations when implementing nutritional and inflammatory biomarkers into clinical practice and further studies are needed in order to answer these questions.
基金supported by the Basic Research and Talent Cultivation Program of Zhangjiakou City(No.2511028A).
文摘Cancer is a major threat to human health worldwide.Colorectal cancer(CRC),a highly prevalent malignant tumor,poses a significant public health challenge.Therefore,the identification of effective biomarkers is of great significance[1].The NFKBIE gene encodes an inhibitor of nuclear factorκBε(IkBε).IκBε,a key regulator of the NF-κB signaling pathway,is closely associated with tumorigenesis.However,their roles in CRC remain unclear[2].Pan-cancer research is crucial for accelerating the identification of biomarkers and translational medical research,as it can reveal molecular commonalities and differences among different tumor types[3].
基金funded by Environment and Climate Change Canada(Fonds pour dommages a l’environnement)under a grant given to L.Vandelac and L.Parentthe Fondation UQAM(2020 to 2022)+2 种基金the Collectif de recherche Ecosante sur les pesticides,les politiques et les alternatives(CREPPA)the Natural Sciences and Engineering Research Council of Canada(NSERC)under a grant given to M.Boily(No.RGPIN-2016–05142)the Centre de recherche en ecotoxicologie du Quebec(EcotoQ) and the Centre interdisciplinaire de recherche en operationnalisation du developpement durable(CIRODD)for scholarships attributed to Y.Nombre.
文摘The active ingredient(a.i.)glyphosate is frequently detected in waterways at relatively high concentrations,posing a risk to aquatic organisms including freshwater mussels,North America’s most endangered animal group.This research aims to evaluate for the first time the effect of a glyphosate-based herbicide on a freshwater mussel(Unionid)using a battery of biomarkers.Themussel Elliptio complanata was exposed for 21 days to CreditR Xtreme(at 0,50,100,and 150μg/L a.i.of glyphosate).An integrated biomarker response(IBRv2)was used to visualize the overall impact of each glyphosate-based herbicide concentration on mussels’health conditions.The biomarker results showed that glyphosate(used at 100μg/L and 150μg/L)induced lipid peroxidation in the gills and digestive gland and inhibited acetylcholinesterase in the foot and gills,indicating oxidative damage and neurotoxicity.Other biomarkerswere influenced at the lowest concentration of glyphosate tested(50μg/L):lipids(decrease),triglycerides(increase)and,to a lesser extent,vitellogenin(decrease).For the latter biomarkers,the sexeswere not affected similarly,and theywere only sensitive at 50μg/L,only females showed a trend toward a decrease for vitellogenin and a decrease for lipids.Using IBRv2,we found a clear discrimination between concentrations,and the index values increased with glyphosate concentration,attesting to the deterioration in biomarker-defined mussel health when exposed to Credit® Xtreme at realistic glyphosate concentrations in agricultural rivers.This study shows that glyphosate-based herbicides can alter neurological function,induce oxidative damage,and selectively modify the E.complanata metabolism at relatively low concentrations.
文摘Urinary tract infections(UTIs)are the most common bacterial infections.Escherichia coli is the most common cause of UTIs,accounting for 50%of hospital-reported and 90%of community-reported cases.Also,this includes species of Klebsiella,Proteus,Acinetobacter,Pseudomonas,Staphylococcus,Streptococcus,and Enterococcus.Patients experience cystitis,polyuria,and dysuria.If untreated,this affects the kidneys,further leading to septicemia.UTIs majorly affect adult females(40%-60%).Microbiological culture has been proven to be the standard method.However,it takes 48-72 hours for the tests to be reported.In cases of recurrent UTI,it is mandatory to have a quick,sensitive,and specific diagnostic procedure.Dipstick tests are considered early methods for diagnosing UTIs;however,they have limitations.Recently,biomarkers are being used to assess the severity of the disease.To achieve the United Nations Sustainable Development Goals 3 and 8,the expertise from General Medicine,Biotechnology,and Microbiology come together in achieving the set targets by 2030.In addition to diagnosis of UTI,resistance to antibiotics should not be neglected.This review aimed to examine the clinical relevance of biomarkers such as neutrophil gelatinase-associated lipocalin,kidney injury molecule-1,interleukin(IL)6,IL-8,heparin-binding protein,procalcitonin,lipopolysaccharide-binding protein,xanthine oxidase,cell-free DNA,and transrenal DNA.
基金funded,in part,by the National Natural Science Fund (NSFC,China) under award number 81900382supported,in part,by the Yang talents Program of Beijing (QML20200302)Beijing Municipal Natural Science Foundation (7222072).
文摘Background Biomarkers-based prediction of long-term risk of acute coronary syndrome(ACS)is scarce.We aim to develop a risk score integrating clinical routine information(C)and plasma biomarkers(B)for predicting long-term risk of ACS patients.Methods We included 2729 ACS patients from the OCEA(Observation of cardiovascular events in ACS patients).The earlier admitted 1910 patients were enrolled as development cohort;and the subsequently admitted 819 subjects were treated as valida-tion cohort.We investigated 10-year risk of cardiovascular(CV)death,myocardial infarction(MI)and all cause death in these pa-tients.Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was de-rived using main part of these variables.Results During 16,110 person-years of follow-up,there were 238 CV death/MI in the development cohort.The 7 most import-ant predictors including in the final model were NT-proBNP,D-dimer,GDF-15,peripheral artery disease(PAD),Fibrinogen,ST-segment elevated MI(STEMI),left ventricular ejection fraction(LVEF),termed as CB-ACS score.C-index of the score for predica-tion of cardiovascular events was 0.79(95%CI:0.76-0.82)in development cohort and 0.77(95%CI:0.76-0.78)in the validation co-hort(5832 person-years of follow-up),which outperformed GRACE 2.0 and ABC-ACS risk score.The CB-ACS score was also well calibrated in development and validation cohort(Greenwood-Nam-D’Agostino:P=0.70 and P=0.07,respectively).Conclusions CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS.This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.
文摘Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed in manic patients compared to controls, and dysregulation of miR-134,-152,-607,-633,-652,-155 occurred in euthymic patients compared to controls. Finally, microRNAs such as miR-34a,-34b,-34c,-137, and-140-3p,-21-3p,-30d-5p,-330-5p,-378a-5p,-134,-19b-3p were shown to have diagnostic potential in distinguishing bipolar disorder patients from schizophrenia or major depressive disorder patients, respectively. Further studies are warranted with adolescents and young adults having bipolar disorder and consideration should be given to using animal models of the disorder to investigate the effects of suppressing or overexpressing specific microRNAs.
基金supported by the Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education&Shanghai,No.CCTS-2022205the“Double World-Class Project”of Shanghai Jiaotong University School of Medicine(both to JZ)。
文摘Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.
基金Supported by the Department of Biotechnology,Government of India Grant Sanction,Ramalingaswami Re-entry Fellowship,No.RLS/BT/Re-entry/05/2012.
文摘A global increase in the incidence of pancreatic cancer(PanCa)presents a major concern and health burden.The traditional tissue-based diagnostic techniques provided a major way forward for molecular diagnostics;however,they face limitations based on diagnosis-associated difficulties and concerns surrounding tissue availability in the clinical setting.Late disease development with asymptomatic behavior is a drawback in the case of existing diagnostic procedures.The capability of cell free markers in discriminating PanCa from autoimmune pancreatitis and chronic pancreatitis along with other precancerous lesions can be a boon to clinicians.Early-stage diagnosis of PanCa can be achieved only if these biomarkers specifically discriminate the non-carcinogenic disease stage from malignancy with respect to tumor stages.In this review,we comprehensively described the non-invasive disease detection approaches and why these approaches are gaining popularity for their early-stage diagnostic capability and associated clinical feasibility.
文摘BACKGROUND: This study aimed to explore the risk factors associated with intensive care unitacquired weakness(ICU-AW) in critically ill patients at risk of malnutrition and to evaluate the efficacy of early enteral nutrition(EEN) and the role of biomarkers in managing ICU-AW.METHODS: This retrospective, observational cohort study included 180 patients at risk of malnutrition admitted to the emergency intensive care unit of the First Affiliated Hospital of Xiamen University Hospital from January 2022 to December 2023. Patients were divided into ICU-AW group and non-ICU-AW group according to whether they developed ICU-AW, or categorized into EEN and parenteral nutrition(PN) groups according to nutritional support. ICU-AW was diagnosed using the Medical Research Council score. The primary outcome was the occurrence of ICU-AW.RESULTS: The significant factors associated with ICU-AW included age, sex, type of nutritional therapy, mechanical ventilation(MV), body mass index(BMI), blood urea nitrogen(BUN), and creatinine(Cr) levels(P<0.05). The PN group developed ICU-AW earlier than did the EEN group, with a significant difference observed(log-rank P<0.001). Among biomarkers for ICU-AW, the mean prealbumin(PAB)/C-reactive protein(CRP) ratio had the highest diagnostic accuracy(area under the curve [AUC] 0.928, 95% confidence interval [95% CI] 0.892–0.946), surpassing the mean Cr/BUN ratio(AUC 0.740, 95% CI 0.663–0.819) and mean transferrin levels(AUC 0.653, 95% CI 0.574–0.733).CONCLUSION: Independent risk factors for ICU-AW include female sex, advanced age, PN, MV, lower BMI, and elevated BUN and Cr levels. EEN may potentially delay ICU-AW onset, and the PAB/CRP ratio may be an effective diagnostic marker for this condition.
文摘Gastrointestinal(GI)cancers,which predominantly manifest in the stomach,colorectum,liver,esophagus,and pancreas,accounting for approximately 35%of global cancer-related mortality.The advent of liquid biopsy has introduced a pivotal diagnostic modality for the early identification of premalignant GI lesions and incipient cancers.This non-invasive technique not only facilitates prompt therapeutic intervention,but also serves as a critical adjunct in prognosticating the likelihood of tumor recurrence.The wealth of circulating exosomes present in body fluids is often enriched with proteins,lipids,microRNAs,and other RNAs derived from tumor cells.These specific cargo components are reflective of processes involved in GI tumorigenesis,tumor progression,and response to treatment.As such,they represent a group of promising biomarkers for aiding in the diagnosis of GI cancer.In this review,we delivered an exhaustive overview of the composition of exosomes and the pathways for cargo sorting within these vesicles.We laid out some of the clinical evidence that supported the utilization of exosomes as diagnostic biomarkers for GI cancers and discussed their potential for clinical application.Furthermore,we addressed the challenges encountered when harnessing exosomes as diagnostic and predictive instruments in the realm of GI cancers.
基金supported by the NationalNatural Science Foundation of China(no.32360888)the Jiangxi Students’Platform for Innovation and Entrepreneurship Training Program(no.202411843023).
文摘Background:Heat shock protein B8(HSPB8)is implicated in autophagy,and its aberrant expression has been linked to both the ini-tiation and progression of tumors.However,the role and function of HSPB8 in colorectal cancer(CRC)and across multiple cancer types remain unclear.This study aimed to map the transcriptome of autophagy-related genes in CRC and to conduct a pan-cancer analysis of HSPB8 as both a prognostic and immunological biomarker.Methods:We performed bioinformatics analyses on GSE113513 and GSE74602 to identify differentially expressed genes(DEGs)in CRC.These DEGs were then compared with autophagy-related genes to identify critical overlapping genes.The Kaplan-Meier plotter was used to verify the ex-pression of autophagy-linked DEGs and evaluate its prognostic value.The protein expression of Hub gene in CRC was analyzed using the Human Protein Atlas database.The cBioPortal was used to analyze the type and frequency of Hub gene mutations.The TIMER(Tumor Immune Estimation Resource)database was used to study the correlation between HSPB8 and immune infiltration in CRC.Results:In total,825 DEGs were identified,including 8 autophagy-linked DEGs:ATIC,MYC,HSPB8,TNFSF10,BCL2,TP53INP2,ITPR1,and NKX2-3.Survival analysis showed that increased HSPB8 expression significantly correlates with poor prognosis in patients with CRC(p<0.05).HSPB8 was also found to be differentially expressed in various cancer types,correlating with both prognosis and immune infiltration.Further,changes in HSPB8 methylation and phosphorylation status were observed across several cancers,suggesting potential regulatory mechanisms.Therefore,HSPB8 may serve as a crucial prognostic and immunological biomarker in CRC and other cancers.Conclusions:This study provides new insights into the role of autophagy-related genes in cancer progression and highlights HSPB8 as a potential target for cancer diagnostics and therapy.
文摘BACKGROUND Irritable bowel syndrome with predominant constipation(IBS-C)is a chronic gastrointestinal disorder that significantly impacts the quality of life of patients and currently lacks a definitive treatment.The use of electroacupuncture(EA)has demonstrated clinical efficacy in treating IBS-C and the gut-brain axis modulation,though its mechanisms remain unclear.AIM To investigate gut-brain-microbiota axis alteration and EA-associated microbial changes in IBS-C patients and treatment responders.METHODS This study consisted of two phases.The first phase was a cross-sectional study recruiting sixteen IBS-C patients and 16 healthy controls.Baseline fecal samples were collected to assess gut microbiota profiles between the two groups.The second phase was an observational longitudinal study in which the 16 IBS-C patients underwent nine EA sessions over one month.Gut microbiota profiles and clinical outcomes were assessed post-treatment course and at a one-month follow-up.RESULTS IBS-C patients exhibited significant gut dysbiosis,as indicated by altered beta diversity compared to healthy controls.EA significantly improved clinical outcomes and gut dysbiosis,with sustained therapeutic effects and normalization of neurotransmitter-related metabolic pathways observed at one-month follow-up.Notably,the gut bacterium Senegalimassilia was positively associated with symptom improvement,suggesting its potential as a predictive biomarker of EA responsiveness.CONCLUSION These findings support the integration of EA into IBS-C management and highlight Senegalimassilia as a candidate microbial biomarker for treatment response.
基金support by grants from Capital’s Funds for Health Improvement and Research(Grant No.2024-2-1024)Beijing Natural Science Foundation(Grant No.7232018).
文摘Advances in the identification of molecular biomarkers and the development of targeted therapies have enhanced the prognosis of patients with advanced gastric cancer.Several established biomarkers have been widely integrated into routine clinical diagnostics of gastric cancer to guide personalized treatment.Human epidermal growth factor receptor 2(HER2)was the first molecular biomarker to be used in gastric cancer with trastuzumab being the first approved targeted therapy for HER2-positive gastric cancer.Programmed death-ligand 1 positivity and microsatellite instability can guide the use of immunotherapies,such as pembrolizumab and nivolumab.More recently,zolbetuximab has been approved for patients with claudin 18.2-positive diseases in some countries.More targeted therapies,including savolitinib for MET-positive patients,are currently under clinical investigation.However,the clinical application of these diagnostic approaches could be hampered by many existing challenges,including invasive and costly sampling methods,variability in immunohistochemistry interpretation,high costs and long turnaround times for next-generation sequencing,the absence of standardized and clinically validated diagnostic cut-off values for some biomarkers,and tumor heterogeneity.Novel testing and analysis techniques,such as artificial intelligence-assisted image analysis and multiplex immunohistochemistry,and emerging therapeutic strategies,including combination therapies that integrate immune checkpoint inhibitors with targeted therapies,offer potential solutions to some of these challenges.This article reviews recent progress in gastric cancer testing,outlines current challenges,and explores future directions for biomarker testing and targeted therapy for gastric cancer.
基金supported by the National Natural Science Foundation of China,No.81971269 (to DP)the Science and Technology Commission of Shanghai,No.YDZX20213100001003 (to DP)。
文摘In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.
