Viruses can alter the expression of host microRNAs(miRNA s) and modulate the immune response during a persistent infection. The dysregulation of host miRNA s by hepatitis B virus(HBV) contributes to the proinflammator...Viruses can alter the expression of host microRNAs(miRNA s) and modulate the immune response during a persistent infection. The dysregulation of host miRNA s by hepatitis B virus(HBV) contributes to the proinflammatory and profibrotic changes within the liver. Multiple studies have documented the differential regulation of intracellular and circulating miRNA s during different stages of HBV infection. Circulating miRNA s found in plasma and/or extracellular vesicles can integrate data on viral-host interactions and on the associated liver injury. Hence, the detection of circulating miRNA s in chronic HBV hepatitis could offer a promising alternative to liver biopsy, as their expression is associated with HBV replication, the progression of liver fibrosis,and the outcome of antiviral treatment. The current review explores the available data on miRNA involvement in HBV pathogenesis with an emphasis on their potential use as biomarkers for liver fibrosis.展开更多
The clinical course ofchronic liver diseases is significantly dependent on the progression rate and the extent offibrosis, i.e. the non-structured replacement of necrotic parenchyma by extracellular matrix. Fibrogenes...The clinical course ofchronic liver diseases is significantly dependent on the progression rate and the extent offibrosis, i.e. the non-structured replacement of necrotic parenchyma by extracellular matrix. Fibrogenesis, i.e. the development offibrosis can be regarded as an unlimited wound healing process, which is based on matrix (connective tissue) synthesis in activated hepatic stellate cells, fibroblasts (fibrocytes), hepatocytes and biliary epithelial cells, which are converted to matrix-producing (myo-)fibroblasts by a process defined as epithelial-mesenchymal transition. Blood (noninvasive) biomarkers offibrogenesis and fibrosis can be divided into class and class analytes. Class biomarkers are those single tests, which are based on the pathophysiology offibrosis, whereas class biomarkers aremostly multiparametric algorithms, which have been statistically evaluated with regard to the detection and activity ofongoing fibrosis. Currently available markers fulfil the criteria ofideal clinical-chemical tests only partially, but increased understanding ofthe complex pathogenesis offibrosis offers additional ways for pathophysiologically well based serum (plasma) biomarkers. They include TGF-β-driven marker proteins, bone marrow-derived cells (fibrocytes), and cytokines, which govern proand anti-fibrotic activities. Proteomic and glycomic approaches ofserum are under investigation to set up specific protein or carbohydrate profiles in patients with liver fibrosis. These and other novel parameters will supplement or eventually replaceliver biopsy/histology, high resolution imaging analysis, and elastography for the detection and monitoring of patients at risk ofdeveloping liver fibrosis.展开更多
BACKGROUND Hepatitis C virus(HCV)infection and its consequent complications are undeniably a public health burden worldwide,particularly in Egypt.Emerging evidence suggests that many lncRNAs have relevant roles in vir...BACKGROUND Hepatitis C virus(HCV)infection and its consequent complications are undeniably a public health burden worldwide,particularly in Egypt.Emerging evidence suggests that many lncRNAs have relevant roles in viral infections and antiviral responses.AIM To investigate the expression profiles of circulating lncRNAGAS5,lncRNAHEIH,lncRNABISPR and mRNABST2 in naïve,treated and relapsed HCV Egyptian patients,to elucidate relation to HCV infection and their efficacy as innovative biomarkers for the diagnosis and prognosis of HCV GT4.METHODS One hundred and thirty HCV-infected Egyptian patients and 20 healthy controls were included in this study.Serum lncRNAs and mRNABST2 were measured using quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS Our results indicated that serum lncRNAGAS5 and LncRNABISPR were upregulated,whereas mRNA BST2 and LncRNA HEIH were downregulated in naïve patients.In contrast,HCV patients treated with sofosbuvir and simeprevir;with sofosbuvir and daclatasvir;or with sofosbuvir,daclatasvir and ribavirin exhibited lower levels of lncRNAGAS5 and lncRNABISPR with higher mRNABST2 compared to naïve patients.Notably,patients relapsed from sofosbuvir and simeprevir showed higher levels of these lncRNAs with lower mRNABST2 compared to treated patients.LncRNAGAS5 and lncRNABISPR were positively correlated with viral load and ALT at P<0.001,whereas mRNABST2 was negatively correlated with viral load at P<0.001 and ALT at P<0.05.Interestingly,a significant positive correlation between lncRNA HEIH and AFP was observed at P<0.001.CONCLUSION Differential expression of these RNAs suggests their involvement in HCV pathogenesis or antiviral response and highlights their promising roles in diagnosis and prognosis of HCV.展开更多
AIM: To explore the value of serum M2-pyruvate kinase (M2-PK) in colorectal cancer (CRC) mass screening. METHODS: We conducted a molecular epidemiology study in Hangzhou, China, from year 2006 to year 2008. Serum samp...AIM: To explore the value of serum M2-pyruvate kinase (M2-PK) in colorectal cancer (CRC) mass screening. METHODS: We conducted a molecular epidemiology study in Hangzhou, China, from year 2006 to year 2008. Serum samples were collected from 93 CRC, 41 advanced adenomas, 137 adenomas, 47 non-adenomatous polyps, and 158 normal participants in a community setting. Serum M2-PK and carcinoembryonic antigen (CEA) were measured using Enzyme-linked immunosorbent assay. SPSS 16.0 software was used to perform data analysis. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificities were estimated for serum M2-PK in diagnosis of colorectal lesions and compared with CEA. RESULTS: Average serum M2-PK value among 158 normal people was 2.96 U/mL and not affected by gender (P = 0.47) or age (P = 0.59). Average serum M2-PK (U/mL) was 14.75 among stage III and 13.10 among stage?I?and II CRC patients, about 4 times higher than that among normal people. Average serum M2-PK was 8.58, 6.70, 5.13 and 2.51 U/mL among advanced adenoma, adenomas, non-adenomatous polyps, and inflammatory bowel disease patients, respectively. AUC for serum M2-PK was greater than that for CEA among all colorectal lesions. AUC for serum M2-PK was 0.89 (0.84, 0.94) (95% confidence interval), higher than that for CEA [0.70 (0.62-0.79)] in CRC stage?I?and II, 0.89 (0.84-0.94) vs 0.73 (0.63-0.83) in CRC stage III, 0.81 (0.74-0.86) vs 0.63 (0.53 - 0.73) in advanced adenomas, 0.69 (0.64-0.76) vs 0.54 (0.47-0.60) in adenomas, and 0.69 (0.62-0.78) vs 0.58 (0.48-0.68) in non-adenomatous polyps. The diagnostic sensitivity for all colorectal lesions increased with decrease in the cut-off value of serum M2-PK. The diagnostic sensitivity (%) of serum M2-PK was 100.00 for CRC, 95.12 advanced adenoma, 82.48 adenoma, and 82.98 non-adenomatous polyp. There were no CRC cases missed and 40.51% of unnecessary colonoscopies were avoided when the cut-off value was 2.00 U/mL. CONCLUSION: Serum M2-PK can be used as a primary screening test in CRC mass screening. It may be a promising non-invasive biomarker for CRC early detection.展开更多
Inflammatory bowel diseases(IBD)comprise two major forms:Crohn’s disease and ulcerative colitis.The diagnosis of IBD is based on clinical symptoms combined with results found in endoscopic and radiological examinatio...Inflammatory bowel diseases(IBD)comprise two major forms:Crohn’s disease and ulcerative colitis.The diagnosis of IBD is based on clinical symptoms combined with results found in endoscopic and radiological examinations.In addition,the discovery of biomarkers has significantly improved the diagnosis and management of IBD.Several potential genetic,serological,fecal,microbial,histological and immunological biomarkers have been proposed for IBD,and they have been evaluated for clinical routine and clinical trials.Ileocolonoscopy,especially with biopsy collection,has been considered the standard method to diagnose IBD and to assess clinical activity of the disease,but it is limited to the colon and terminal ileum and is considered invasive.For this reason,non-invasive biomarkers are necessary for this type of chronic inflammatory disease,which affects mostly young individuals,as they are expected to have a long follow-up.展开更多
AIM To evaluate the efficacy of peripheral blood concentrations of angiopoietins(Ang) as cirrhosis biomarkers of chronic hepatitis C(CHC).METHODS Ang1 and Ang2 serum levels were measured by enzyme-linked immunosorbent...AIM To evaluate the efficacy of peripheral blood concentrations of angiopoietins(Ang) as cirrhosis biomarkers of chronic hepatitis C(CHC).METHODS Ang1 and Ang2 serum levels were measured by enzyme-linked immunosorbent assays(ELISA) in samples from 179 cirrhotic and non-cirrhotic CHC patients, classified according to the METAVIR system.Groups were compared by non-parametric MannWhitney U test. Subsequently, the association of peripheral concentrations of angiopoietins with the stage of fibrosis was analyzed using Spearman correlation test. Finally, the accuracy, sensitivity and specificity of circulating angiopoietins for cirrhosis diagnosis were determined by the study of the respective area under the curve of receiver operator characteristics(AUC-ROC).RESULTS Peripheral blood concentrations of Ang1 and Ang2 in CHC patients were significantly related to fibrosis. While Ang1 was decreased in cirrhotic subjects compared to non-cirrhotic(P < 0.0001), Ang2 was significantly increased as CHC progressed to the end stage of liver disease(P < 0.0001). Consequently, Ang2/Ang1 ratio was notably amplified and significantly correlated with fibrosis(P < 0.0001). Interestingly, the individual performance of each angiopoietin for the diagnosis of cirrhosis reached notable AUC-ROC values(above 0.7, both), but the Ang2/Ang1 ratio was much better(AUC-ROC = 0.810) and displayed outstanding values of sensitivity(71%), specificity(84%) and accuracy(82.1%) at the optimal cut-off(10.33). Furthermore, Ang2/Ang1 ratio improved the performance of many other previously described biomarkers or scores of liver cirrhosis in CHC.CONCLUSION Ang2/Ang1 ratio might constitute a useful tool for monitoring the progression of chronic liver disease towards cirrhosis and play an important role as therapeutic target.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)represents a growing public health concern,with patients having higher risk of morbidity and mortality.It has a considerably high prevalence in the general population...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)represents a growing public health concern,with patients having higher risk of morbidity and mortality.It has a considerably high prevalence in the general population,estimated 20%-40%in Europe,and is asymptomatic until late in the disease course.It is therefore important to identify and validate tools that predict hard outcomes such as mortality for use in clinical practice in risk-stratifying NAFLD patients.AIM To evaluate available evidence on the use of non-invasive test(s)as prognostic factors for mortality in NAFLD.METHODS We performed electronic searches of Medline and EMBASE(Ovid)until 7^(th)January 2021 of studies in NAFLD populations.Prognostic markers included serum biomarkers,non-invasive scoring systems,and non-invasive imaging.The population included all spectrums of disease severity,including NAFLD and non-alcoholic steatohepatitis(NASH).Outcomes included all-cause,and cardiovascular mortality.All non-invasive tests were synthesised in a narrative systematic review.Finally,we conducted a meta-analysis of non-invasive scoring systems for predicting all-cause and cardiovascular mortality,calculating pooled hazard ratios and 95%confidence(STATA 16.1).RESULTS Database searches identified 2850 studies-24 were included.16 studies reported non-invasive scoring systems,10 studies reported individual biomarkers,and 1 study reported imaging modalities.4 studies on non-invasive scoring systems(6324 participants)had data available for inclusion in the meta-analysis.The non-invasive scoring system that performed best at predicting all-cause mortality was NAFLD fibrosis score(NFS)[pHR 3.07(1.62-5.83)],followed by fibrosis-4 index[pHR 3.06(1.54-6.07)],BARD[pHR 2.87(1.27-6.46)],and AST to platelet ratio index[pHR 1.90(1.32-2.73)].NFS was also prognostic of cardiovascular-related mortality[pHR 3.09(1.78-5.34)].CONCLUSION This study reaffirms that non-invasive scoring systems,especially NFS,are reliable prognostic markers of all-cause mortality and cardiovascular mortality in NAFLD patients.These findings can inform clinical practice in risk stratifying NAFLD patients.展开更多
Epigenetic changes of DNA, including methylation, have long been recognized as key indicators of various diseases, including aging, cancer, and neurological disorders. Biomarker discoveries based on distinct methylati...Epigenetic changes of DNA, including methylation, have long been recognized as key indicators of various diseases, including aging, cancer, and neurological disorders. Biomarker discoveries based on distinct methylation patterns for both hypermethylation and hypomethylation lead the way in discovery of novel diagnosis and treatment targets. Many different approaches are present to detect the level of methylation in whole genome (whole genome bisulfite sequencing, microarray) as well as at specific loci (methylation specific PCR). Cell-free DNA (cf-DNA) found in body fluids like blood provides information about DNA methylation and serves as a less invasive approach for genetic screening. Cell-free DNA and methylation screening technologies, when combined, have the potential to transform the way we approach genetic screening and personalized therapy. These technologies can help enhance disease diagnostic accuracy and inform the development of targeted therapeutics by providing a non-invasive way for acquiring genomic information and identifying disease-associated methylation patterns. We highlight the clinical benefits of using cell-free DNA (cf-DNA) liquid biopsy analysis and available methylation screening technologies that have been crucial in identifying biomarkers for disease from patients using a non-invasive way. Powering such biomarker discoveries are various methods of cf-DNA methylation analysis such as Bisulfite Sequencing and most recently, Methylation-Specific Restriction Enzyme (MSRE-seq) Analysis, paving the way for novel epigenetic biomarker discoveries for more robust diagnosis such as early disease detection, prognosis, monitoring of disease progression and treatment response as well as discovery of novel drug targets.展开更多
Chronic kidney disease(CKD)is a degenerative disorder that affects millions of people throughout the world,causing considerable morbidity and healthcare burden.Frequent blood sampling is the current gold standard for ...Chronic kidney disease(CKD)is a degenerative disorder that affects millions of people throughout the world,causing considerable morbidity and healthcare burden.Frequent blood sampling is the current gold standard for monitoring CKD to evaluate biochemical and mineral indicators.However,there are draw-backs to frequent blood draws,such as pain for patients,the possibility of infe-ction,and higher medical expenses.Saliva-based diagnostics offer advantages such as ease of collection,reduced invasiveness,and improved patient compli-ance.A comprehensive literature review was conducted to analyze studies eva-luating the diagnostic utility of salivary creatinine,urea,calcium,and parathyroid hormone(PTH)in patients with CKD.Various saliva collection methods,inc-luding stimulated and unstimulated approaches,were investigated for efficiency and reliability,and a correlation was shown between serum and salivary crea-tinine,urea,PTH,and calcium levels,indicating their potential as CKD biomar-kers.Despite these promising findings,challenges such as standardization of collection methods,variability in salivary flow rates,and predictive value in association with blood parameters are addressed to ensure clinical applicability.This review explores the potential and challenges of saliva as a non-invasive alternative for CKD diagnostics.展开更多
Novel brominated flame retardants(NBFRs)are a group of chemicals applied mainly as alternatives to the phased-out polybrominated diphenyl ethers(PBDEs).However,toxicological studies show that NBFRs may pose health ris...Novel brominated flame retardants(NBFRs)are a group of chemicals applied mainly as alternatives to the phased-out polybrominated diphenyl ethers(PBDEs).However,toxicological studies show that NBFRs may pose health risks similar to PBDEs.The present study reviews available information on the biomonitoring of NBFRs and their metabolites in humans through invasive and non-invasive biomarkers,as well as the toxicological effects of these chemicals both in vivo and in vitro.In general,higher concentrations of NBFRs were reported in tissues of occupationally exposed adults from NBFR production facilities,e-waste recycling facilities and inhabitants living close to these areas,compared to the general population.It is worth noting that NBFR human biomonitoring data are limited to few countries located in North America,Europe and Asia,while data from developing countries are scarce.Evidence from in vivo and in vitro toxicity studies show that several NBFRs can cause adverse health effects through various modes of action,mainly:hormone disruption,genotoxicity,endocrine disruption,and behavioural changes.Although few studies have investigated the biotransformation of NBFRs in humans,evidence suggests that the toxicity of some NBFRs may be augmented through their metabolites,as in the case of 2,3,4,5-tetrabromobenzoic acid(TBBA),which may exhibit higher toxicity than its parent compound 2-ethylhexyl-2,3,4,5-tetrabromobenzoate(EH-TBB).More research is required to assess toxicity thresholds,toxic endpoints,and tolerable intakes for various NBFRs,and their metabolites in human.Comprehensive epidemiological studies are highly recommended to further understand the risk arising from human exposure to different NBFRs,particularly in occupational settings.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally.Current diagnostic methods,such as liver biopsies,are invasive and have limitations,highli...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally.Current diagnostic methods,such as liver biopsies,are invasive and have limitations,highlighting the need for non-invasive alternatives.AIM To investigate extracellular vesicles(EVs)as potential biomarkers for diagnosing and staging steatosis in patients with MASLD using machine learning(ML)and explainable artificial intelligence(XAI).METHODS In this single-center observational study,798 patients with metabolic dysfunction were enrolled.Of these,194 met the eligibility criteria,and 76 successfully completed all study procedures.Transient elastography was used for steatosis and fibrosis staging,and circulating plasma EV characteristics were analyzed through nanoparticle tracking.Twenty ML models were developed:Six to differentiate non-steatosis(S0)from steatosis(S1-S3);and fourteen to identify severe steatosis(S3).Models utilized EV features(size and concentration),clinical(advanced fibrosis and presence of type 2 diabetes mellitus),and anthropomorphic(sex,age,height,weight,body mass index)data.Their performance was assessed using receiver operating characteristic(ROC)-area under the curve(AUC),specificity,and sensitivity,while correlation and XAI analysis were also conducted.RESULTS The CatBoost C1a model achieved an ROC-AUC of 0.71/0.86(train/test)on average across ten random five-fold cross-validations,using EV features alone to distinguish S0 from S1-S3.The CatBoost C2h-21 model achieved an ROC-AUC of 0.81/1.00(train/test)on average across ten random three-fold cross-validations,using engineered features including EVs,clinical features like diabetes and advanced fibrosis,and anthropomorphic data like body mass index and weight for identifying severe steatosis(S3).Key predictors included EV mean size and concentration.Correlation,XAI,and SHapley Additive exPlanations analysis revealed non-linear feature relationships with steatosis stages.CONCLUSION The EV-based ML models demonstrated that the mean size and concentration of circulating plasma EVs constituted key predictors for distinguishing the absence of significant steatosis(S0)in patients with metabolic dysfunction,while the combination of EV,clinical,and anthropomorphic features improved the diagnostic accuracy for the identification of severe steatosis.The algorithmic approach using ML and XAI captured non-linear patterns between disease features and provided interpretable MASLD staging insights.However,further large multicenter studies,comparisons,and validation with histopathology and advanced imaging methods are needed.展开更多
BACKGROUND Hepatitis C virus(HCV)infection process of progression encompasses multiple stages,commencing with inflammation and culminating in hepatocellular cancer.Numerous invasive and non-invasive procedures exist f...BACKGROUND Hepatitis C virus(HCV)infection process of progression encompasses multiple stages,commencing with inflammation and culminating in hepatocellular cancer.Numerous invasive and non-invasive procedures exist for diagnosing chronic HCV infection.Though beneficial,invasive procedures can cause morbidity and inadequate representation of the overall degree of fibrosis.Due to these reasons,non-invasive liver fibrosis biomarkers are becoming more prevalent to diagnose and track liver fibrosis without a liver biopsy.These biomarkers can detect liver fibrosis early,improving treatment and preventing cirrhosis and liver failure.Micro ribonucleic acid(MiRNA)dysregulation causes and worsens several diseases including liver disease.MiRNAs can facilitate the diagnosis of liver fibrosis and serve as a predictive tool to enhance patient care by minimizing invasive procedures and enabling more efficient and prompt therapy.AIM To investigate the diagnostic effectiveness of several miRNAs(miRNA-122,miRNA-21,miRNA-199a,miRNA-155)in assessing the liver fibrosis severity in untreated HCV patients from the Indian Punjab population.We seek to identify the intricate diagnostic relationship of miRNAs with the extent of fibrosis among individuals with HCV.METHODS We considered 100 persons determined as HCV infected by a quantitative Real-Time Polymerase Chain Reaction examination.We employed statistical as well as probabilistic tools to ascertain the diagnostic validity of miRNAs for determining the liver fibrosis stages.We employed Bayesian Networks,to introduce a unique diagnostic paradigm for miRNAs that can be adopted as benchmark to evaluate the liver fibrosis severity in HCV cases.RESULTS We found that miRNAs(miR-122,miR-155 and miR-21)showed significant upregulation when compared with control and according to severity of fibrosis(P≤0.05).The area under the curve for miR-122,miR-155,miR-21 and miR-199a in HCV group in relation to Liver Stiffness Measurement was calculated as 0.889,0.933,0.912 and 0.035 respectively.MiR-199a was downregulated according to degree of fibrosis.CONCLUSION Depending on the diagnostic accuracy,we have concluded that miR-122,miR-155 and miR-21 are reliable markers to detect fibrosis in Hepatitis C patients.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
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
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
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
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
Liver cancer,particularly hepatocellular carcinoma(HCC),remains a significant global health challenge due to its high mortality rate and late-stage diagnosis.The discovery of reliable biomarkers is crucial for improvi...Liver cancer,particularly hepatocellular carcinoma(HCC),remains a significant global health challenge due to its high mortality rate and late-stage diagnosis.The discovery of reliable biomarkers is crucial for improving early detection and patient outcomes.This review provides a comprehensive overview of current and emerging biomarkers for HCC,including alpha-fetoprotein,des-gamma-carboxy prothrombin,glypican-3,Golgi protein 73,osteopontin,and microRNAs.Despite advancements,the diagnostic limitations of existing biomarkers underscore the urgent need for novel markers that can detect HCC in its early stages.The review emphasizes the importance of integrating multi-omics approaches,combining genomics,proteomics,and metabolomics,to develop more robust biomarker panels.Such integrative methods have the potential to capture the complex molecular landscape of HCC,offering insights into disease mechanisms and identifying targets for personalized therapies.The significance of large-scale validation studies,collaboration between research institutions and clinical settings,and consideration of regulatory pathways for clinical implementation is also discussed.In conclusion,while substantial progress has been made in biomarker discovery,continued research and innovation are essential to address the remaining challenges.The successful translation of these discoveries into clinical practice will require rigorous validation,standardization of protocols,and crossdisciplinary collaboration.By advancing the development and application of novel biomarkers,we can improve the early detection and management of HCC,ultimately enhancing patient survival and quality of life.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
基金Ministerul Cercetarii si Inovarii,Programul 1,subprogramul 1.2.Performanta institutionala,No.PFE_23/2018。
文摘Viruses can alter the expression of host microRNAs(miRNA s) and modulate the immune response during a persistent infection. The dysregulation of host miRNA s by hepatitis B virus(HBV) contributes to the proinflammatory and profibrotic changes within the liver. Multiple studies have documented the differential regulation of intracellular and circulating miRNA s during different stages of HBV infection. Circulating miRNA s found in plasma and/or extracellular vesicles can integrate data on viral-host interactions and on the associated liver injury. Hence, the detection of circulating miRNA s in chronic HBV hepatitis could offer a promising alternative to liver biopsy, as their expression is associated with HBV replication, the progression of liver fibrosis,and the outcome of antiviral treatment. The current review explores the available data on miRNA involvement in HBV pathogenesis with an emphasis on their potential use as biomarkers for liver fibrosis.
文摘The clinical course ofchronic liver diseases is significantly dependent on the progression rate and the extent offibrosis, i.e. the non-structured replacement of necrotic parenchyma by extracellular matrix. Fibrogenesis, i.e. the development offibrosis can be regarded as an unlimited wound healing process, which is based on matrix (connective tissue) synthesis in activated hepatic stellate cells, fibroblasts (fibrocytes), hepatocytes and biliary epithelial cells, which are converted to matrix-producing (myo-)fibroblasts by a process defined as epithelial-mesenchymal transition. Blood (noninvasive) biomarkers offibrogenesis and fibrosis can be divided into class and class analytes. Class biomarkers are those single tests, which are based on the pathophysiology offibrosis, whereas class biomarkers aremostly multiparametric algorithms, which have been statistically evaluated with regard to the detection and activity ofongoing fibrosis. Currently available markers fulfil the criteria ofideal clinical-chemical tests only partially, but increased understanding ofthe complex pathogenesis offibrosis offers additional ways for pathophysiologically well based serum (plasma) biomarkers. They include TGF-β-driven marker proteins, bone marrow-derived cells (fibrocytes), and cytokines, which govern proand anti-fibrotic activities. Proteomic and glycomic approaches ofserum are under investigation to set up specific protein or carbohydrate profiles in patients with liver fibrosis. These and other novel parameters will supplement or eventually replaceliver biopsy/histology, high resolution imaging analysis, and elastography for the detection and monitoring of patients at risk ofdeveloping liver fibrosis.
文摘BACKGROUND Hepatitis C virus(HCV)infection and its consequent complications are undeniably a public health burden worldwide,particularly in Egypt.Emerging evidence suggests that many lncRNAs have relevant roles in viral infections and antiviral responses.AIM To investigate the expression profiles of circulating lncRNAGAS5,lncRNAHEIH,lncRNABISPR and mRNABST2 in naïve,treated and relapsed HCV Egyptian patients,to elucidate relation to HCV infection and their efficacy as innovative biomarkers for the diagnosis and prognosis of HCV GT4.METHODS One hundred and thirty HCV-infected Egyptian patients and 20 healthy controls were included in this study.Serum lncRNAs and mRNABST2 were measured using quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS Our results indicated that serum lncRNAGAS5 and LncRNABISPR were upregulated,whereas mRNA BST2 and LncRNA HEIH were downregulated in naïve patients.In contrast,HCV patients treated with sofosbuvir and simeprevir;with sofosbuvir and daclatasvir;or with sofosbuvir,daclatasvir and ribavirin exhibited lower levels of lncRNAGAS5 and lncRNABISPR with higher mRNABST2 compared to naïve patients.Notably,patients relapsed from sofosbuvir and simeprevir showed higher levels of these lncRNAs with lower mRNABST2 compared to treated patients.LncRNAGAS5 and lncRNABISPR were positively correlated with viral load and ALT at P<0.001,whereas mRNABST2 was negatively correlated with viral load at P<0.001 and ALT at P<0.05.Interestingly,a significant positive correlation between lncRNA HEIH and AFP was observed at P<0.001.CONCLUSION Differential expression of these RNAs suggests their involvement in HCV pathogenesis or antiviral response and highlights their promising roles in diagnosis and prognosis of HCV.
基金Supported by The National 11th 5-Year Key Programs for Department of Science and Technology of China, No. 2006BAI02A08
文摘AIM: To explore the value of serum M2-pyruvate kinase (M2-PK) in colorectal cancer (CRC) mass screening. METHODS: We conducted a molecular epidemiology study in Hangzhou, China, from year 2006 to year 2008. Serum samples were collected from 93 CRC, 41 advanced adenomas, 137 adenomas, 47 non-adenomatous polyps, and 158 normal participants in a community setting. Serum M2-PK and carcinoembryonic antigen (CEA) were measured using Enzyme-linked immunosorbent assay. SPSS 16.0 software was used to perform data analysis. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificities were estimated for serum M2-PK in diagnosis of colorectal lesions and compared with CEA. RESULTS: Average serum M2-PK value among 158 normal people was 2.96 U/mL and not affected by gender (P = 0.47) or age (P = 0.59). Average serum M2-PK (U/mL) was 14.75 among stage III and 13.10 among stage?I?and II CRC patients, about 4 times higher than that among normal people. Average serum M2-PK was 8.58, 6.70, 5.13 and 2.51 U/mL among advanced adenoma, adenomas, non-adenomatous polyps, and inflammatory bowel disease patients, respectively. AUC for serum M2-PK was greater than that for CEA among all colorectal lesions. AUC for serum M2-PK was 0.89 (0.84, 0.94) (95% confidence interval), higher than that for CEA [0.70 (0.62-0.79)] in CRC stage?I?and II, 0.89 (0.84-0.94) vs 0.73 (0.63-0.83) in CRC stage III, 0.81 (0.74-0.86) vs 0.63 (0.53 - 0.73) in advanced adenomas, 0.69 (0.64-0.76) vs 0.54 (0.47-0.60) in adenomas, and 0.69 (0.62-0.78) vs 0.58 (0.48-0.68) in non-adenomatous polyps. The diagnostic sensitivity for all colorectal lesions increased with decrease in the cut-off value of serum M2-PK. The diagnostic sensitivity (%) of serum M2-PK was 100.00 for CRC, 95.12 advanced adenoma, 82.48 adenoma, and 82.98 non-adenomatous polyp. There were no CRC cases missed and 40.51% of unnecessary colonoscopies were avoided when the cut-off value was 2.00 U/mL. CONCLUSION: Serum M2-PK can be used as a primary screening test in CRC mass screening. It may be a promising non-invasive biomarker for CRC early detection.
基金Supported by National Council for Scientific and Technological Development(CNPq),No.301388/2018-0Funding for Education,Research and Extension Support(FAEPEX),University of Campinas.
文摘Inflammatory bowel diseases(IBD)comprise two major forms:Crohn’s disease and ulcerative colitis.The diagnosis of IBD is based on clinical symptoms combined with results found in endoscopic and radiological examinations.In addition,the discovery of biomarkers has significantly improved the diagnosis and management of IBD.Several potential genetic,serological,fecal,microbial,histological and immunological biomarkers have been proposed for IBD,and they have been evaluated for clinical routine and clinical trials.Ileocolonoscopy,especially with biopsy collection,has been considered the standard method to diagnose IBD and to assess clinical activity of the disease,but it is limited to the colon and terminal ileum and is considered invasive.For this reason,non-invasive biomarkers are necessary for this type of chronic inflammatory disease,which affects mostly young individuals,as they are expected to have a long follow-up.
基金Supported by the Ministerio de Ciencia e Innovación(SAF:2010/21805,partially)CIBERehd(Instituto de Salud CarlosⅢ,Madrid)+1 种基金Fundación Mutua Madrile■a(to Moreno-Otero R)a grant from Asociación Espa■ola Contra el Cáncer(AIO 2010,AECC,to Sanz-Cameno P)
文摘AIM To evaluate the efficacy of peripheral blood concentrations of angiopoietins(Ang) as cirrhosis biomarkers of chronic hepatitis C(CHC).METHODS Ang1 and Ang2 serum levels were measured by enzyme-linked immunosorbent assays(ELISA) in samples from 179 cirrhotic and non-cirrhotic CHC patients, classified according to the METAVIR system.Groups were compared by non-parametric MannWhitney U test. Subsequently, the association of peripheral concentrations of angiopoietins with the stage of fibrosis was analyzed using Spearman correlation test. Finally, the accuracy, sensitivity and specificity of circulating angiopoietins for cirrhosis diagnosis were determined by the study of the respective area under the curve of receiver operator characteristics(AUC-ROC).RESULTS Peripheral blood concentrations of Ang1 and Ang2 in CHC patients were significantly related to fibrosis. While Ang1 was decreased in cirrhotic subjects compared to non-cirrhotic(P < 0.0001), Ang2 was significantly increased as CHC progressed to the end stage of liver disease(P < 0.0001). Consequently, Ang2/Ang1 ratio was notably amplified and significantly correlated with fibrosis(P < 0.0001). Interestingly, the individual performance of each angiopoietin for the diagnosis of cirrhosis reached notable AUC-ROC values(above 0.7, both), but the Ang2/Ang1 ratio was much better(AUC-ROC = 0.810) and displayed outstanding values of sensitivity(71%), specificity(84%) and accuracy(82.1%) at the optimal cut-off(10.33). Furthermore, Ang2/Ang1 ratio improved the performance of many other previously described biomarkers or scores of liver cirrhosis in CHC.CONCLUSION Ang2/Ang1 ratio might constitute a useful tool for monitoring the progression of chronic liver disease towards cirrhosis and play an important role as therapeutic target.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)represents a growing public health concern,with patients having higher risk of morbidity and mortality.It has a considerably high prevalence in the general population,estimated 20%-40%in Europe,and is asymptomatic until late in the disease course.It is therefore important to identify and validate tools that predict hard outcomes such as mortality for use in clinical practice in risk-stratifying NAFLD patients.AIM To evaluate available evidence on the use of non-invasive test(s)as prognostic factors for mortality in NAFLD.METHODS We performed electronic searches of Medline and EMBASE(Ovid)until 7^(th)January 2021 of studies in NAFLD populations.Prognostic markers included serum biomarkers,non-invasive scoring systems,and non-invasive imaging.The population included all spectrums of disease severity,including NAFLD and non-alcoholic steatohepatitis(NASH).Outcomes included all-cause,and cardiovascular mortality.All non-invasive tests were synthesised in a narrative systematic review.Finally,we conducted a meta-analysis of non-invasive scoring systems for predicting all-cause and cardiovascular mortality,calculating pooled hazard ratios and 95%confidence(STATA 16.1).RESULTS Database searches identified 2850 studies-24 were included.16 studies reported non-invasive scoring systems,10 studies reported individual biomarkers,and 1 study reported imaging modalities.4 studies on non-invasive scoring systems(6324 participants)had data available for inclusion in the meta-analysis.The non-invasive scoring system that performed best at predicting all-cause mortality was NAFLD fibrosis score(NFS)[pHR 3.07(1.62-5.83)],followed by fibrosis-4 index[pHR 3.06(1.54-6.07)],BARD[pHR 2.87(1.27-6.46)],and AST to platelet ratio index[pHR 1.90(1.32-2.73)].NFS was also prognostic of cardiovascular-related mortality[pHR 3.09(1.78-5.34)].CONCLUSION This study reaffirms that non-invasive scoring systems,especially NFS,are reliable prognostic markers of all-cause mortality and cardiovascular mortality in NAFLD patients.These findings can inform clinical practice in risk stratifying NAFLD patients.
文摘Epigenetic changes of DNA, including methylation, have long been recognized as key indicators of various diseases, including aging, cancer, and neurological disorders. Biomarker discoveries based on distinct methylation patterns for both hypermethylation and hypomethylation lead the way in discovery of novel diagnosis and treatment targets. Many different approaches are present to detect the level of methylation in whole genome (whole genome bisulfite sequencing, microarray) as well as at specific loci (methylation specific PCR). Cell-free DNA (cf-DNA) found in body fluids like blood provides information about DNA methylation and serves as a less invasive approach for genetic screening. Cell-free DNA and methylation screening technologies, when combined, have the potential to transform the way we approach genetic screening and personalized therapy. These technologies can help enhance disease diagnostic accuracy and inform the development of targeted therapeutics by providing a non-invasive way for acquiring genomic information and identifying disease-associated methylation patterns. We highlight the clinical benefits of using cell-free DNA (cf-DNA) liquid biopsy analysis and available methylation screening technologies that have been crucial in identifying biomarkers for disease from patients using a non-invasive way. Powering such biomarker discoveries are various methods of cf-DNA methylation analysis such as Bisulfite Sequencing and most recently, Methylation-Specific Restriction Enzyme (MSRE-seq) Analysis, paving the way for novel epigenetic biomarker discoveries for more robust diagnosis such as early disease detection, prognosis, monitoring of disease progression and treatment response as well as discovery of novel drug targets.
文摘Chronic kidney disease(CKD)is a degenerative disorder that affects millions of people throughout the world,causing considerable morbidity and healthcare burden.Frequent blood sampling is the current gold standard for monitoring CKD to evaluate biochemical and mineral indicators.However,there are draw-backs to frequent blood draws,such as pain for patients,the possibility of infe-ction,and higher medical expenses.Saliva-based diagnostics offer advantages such as ease of collection,reduced invasiveness,and improved patient compli-ance.A comprehensive literature review was conducted to analyze studies eva-luating the diagnostic utility of salivary creatinine,urea,calcium,and parathyroid hormone(PTH)in patients with CKD.Various saliva collection methods,inc-luding stimulated and unstimulated approaches,were investigated for efficiency and reliability,and a correlation was shown between serum and salivary crea-tinine,urea,PTH,and calcium levels,indicating their potential as CKD biomar-kers.Despite these promising findings,challenges such as standardization of collection methods,variability in salivary flow rates,and predictive value in association with blood parameters are addressed to ensure clinical applicability.This review explores the potential and challenges of saliva as a non-invasive alternative for CKD diagnostics.
基金funded by the UK government via a Commonwealth Scholarship split-site scholarship(NGCN-2020-230)funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no.734522(INTERWASTE)project.
文摘Novel brominated flame retardants(NBFRs)are a group of chemicals applied mainly as alternatives to the phased-out polybrominated diphenyl ethers(PBDEs).However,toxicological studies show that NBFRs may pose health risks similar to PBDEs.The present study reviews available information on the biomonitoring of NBFRs and their metabolites in humans through invasive and non-invasive biomarkers,as well as the toxicological effects of these chemicals both in vivo and in vitro.In general,higher concentrations of NBFRs were reported in tissues of occupationally exposed adults from NBFR production facilities,e-waste recycling facilities and inhabitants living close to these areas,compared to the general population.It is worth noting that NBFR human biomonitoring data are limited to few countries located in North America,Europe and Asia,while data from developing countries are scarce.Evidence from in vivo and in vitro toxicity studies show that several NBFRs can cause adverse health effects through various modes of action,mainly:hormone disruption,genotoxicity,endocrine disruption,and behavioural changes.Although few studies have investigated the biotransformation of NBFRs in humans,evidence suggests that the toxicity of some NBFRs may be augmented through their metabolites,as in the case of 2,3,4,5-tetrabromobenzoic acid(TBBA),which may exhibit higher toxicity than its parent compound 2-ethylhexyl-2,3,4,5-tetrabromobenzoate(EH-TBB).More research is required to assess toxicity thresholds,toxic endpoints,and tolerable intakes for various NBFRs,and their metabolites in human.Comprehensive epidemiological studies are highly recommended to further understand the risk arising from human exposure to different NBFRs,particularly in occupational settings.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally.Current diagnostic methods,such as liver biopsies,are invasive and have limitations,highlighting the need for non-invasive alternatives.AIM To investigate extracellular vesicles(EVs)as potential biomarkers for diagnosing and staging steatosis in patients with MASLD using machine learning(ML)and explainable artificial intelligence(XAI).METHODS In this single-center observational study,798 patients with metabolic dysfunction were enrolled.Of these,194 met the eligibility criteria,and 76 successfully completed all study procedures.Transient elastography was used for steatosis and fibrosis staging,and circulating plasma EV characteristics were analyzed through nanoparticle tracking.Twenty ML models were developed:Six to differentiate non-steatosis(S0)from steatosis(S1-S3);and fourteen to identify severe steatosis(S3).Models utilized EV features(size and concentration),clinical(advanced fibrosis and presence of type 2 diabetes mellitus),and anthropomorphic(sex,age,height,weight,body mass index)data.Their performance was assessed using receiver operating characteristic(ROC)-area under the curve(AUC),specificity,and sensitivity,while correlation and XAI analysis were also conducted.RESULTS The CatBoost C1a model achieved an ROC-AUC of 0.71/0.86(train/test)on average across ten random five-fold cross-validations,using EV features alone to distinguish S0 from S1-S3.The CatBoost C2h-21 model achieved an ROC-AUC of 0.81/1.00(train/test)on average across ten random three-fold cross-validations,using engineered features including EVs,clinical features like diabetes and advanced fibrosis,and anthropomorphic data like body mass index and weight for identifying severe steatosis(S3).Key predictors included EV mean size and concentration.Correlation,XAI,and SHapley Additive exPlanations analysis revealed non-linear feature relationships with steatosis stages.CONCLUSION The EV-based ML models demonstrated that the mean size and concentration of circulating plasma EVs constituted key predictors for distinguishing the absence of significant steatosis(S0)in patients with metabolic dysfunction,while the combination of EV,clinical,and anthropomorphic features improved the diagnostic accuracy for the identification of severe steatosis.The algorithmic approach using ML and XAI captured non-linear patterns between disease features and provided interpretable MASLD staging insights.However,further large multicenter studies,comparisons,and validation with histopathology and advanced imaging methods are needed.
文摘BACKGROUND Hepatitis C virus(HCV)infection process of progression encompasses multiple stages,commencing with inflammation and culminating in hepatocellular cancer.Numerous invasive and non-invasive procedures exist for diagnosing chronic HCV infection.Though beneficial,invasive procedures can cause morbidity and inadequate representation of the overall degree of fibrosis.Due to these reasons,non-invasive liver fibrosis biomarkers are becoming more prevalent to diagnose and track liver fibrosis without a liver biopsy.These biomarkers can detect liver fibrosis early,improving treatment and preventing cirrhosis and liver failure.Micro ribonucleic acid(MiRNA)dysregulation causes and worsens several diseases including liver disease.MiRNAs can facilitate the diagnosis of liver fibrosis and serve as a predictive tool to enhance patient care by minimizing invasive procedures and enabling more efficient and prompt therapy.AIM To investigate the diagnostic effectiveness of several miRNAs(miRNA-122,miRNA-21,miRNA-199a,miRNA-155)in assessing the liver fibrosis severity in untreated HCV patients from the Indian Punjab population.We seek to identify the intricate diagnostic relationship of miRNAs with the extent of fibrosis among individuals with HCV.METHODS We considered 100 persons determined as HCV infected by a quantitative Real-Time Polymerase Chain Reaction examination.We employed statistical as well as probabilistic tools to ascertain the diagnostic validity of miRNAs for determining the liver fibrosis stages.We employed Bayesian Networks,to introduce a unique diagnostic paradigm for miRNAs that can be adopted as benchmark to evaluate the liver fibrosis severity in HCV cases.RESULTS We found that miRNAs(miR-122,miR-155 and miR-21)showed significant upregulation when compared with control and according to severity of fibrosis(P≤0.05).The area under the curve for miR-122,miR-155,miR-21 and miR-199a in HCV group in relation to Liver Stiffness Measurement was calculated as 0.889,0.933,0.912 and 0.035 respectively.MiR-199a was downregulated according to degree of fibrosis.CONCLUSION Depending on the diagnostic accuracy,we have concluded that miR-122,miR-155 and miR-21 are reliable markers to detect fibrosis in Hepatitis C patients.
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.
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.
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.
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.
文摘Liver cancer,particularly hepatocellular carcinoma(HCC),remains a significant global health challenge due to its high mortality rate and late-stage diagnosis.The discovery of reliable biomarkers is crucial for improving early detection and patient outcomes.This review provides a comprehensive overview of current and emerging biomarkers for HCC,including alpha-fetoprotein,des-gamma-carboxy prothrombin,glypican-3,Golgi protein 73,osteopontin,and microRNAs.Despite advancements,the diagnostic limitations of existing biomarkers underscore the urgent need for novel markers that can detect HCC in its early stages.The review emphasizes the importance of integrating multi-omics approaches,combining genomics,proteomics,and metabolomics,to develop more robust biomarker panels.Such integrative methods have the potential to capture the complex molecular landscape of HCC,offering insights into disease mechanisms and identifying targets for personalized therapies.The significance of large-scale validation studies,collaboration between research institutions and clinical settings,and consideration of regulatory pathways for clinical implementation is also discussed.In conclusion,while substantial progress has been made in biomarker discovery,continued research and innovation are essential to address the remaining challenges.The successful translation of these discoveries into clinical practice will require rigorous validation,standardization of protocols,and crossdisciplinary collaboration.By advancing the development and application of novel biomarkers,we can improve the early detection and management of HCC,ultimately enhancing patient survival and quality of life.
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.
