BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated ...BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated and multifactorial;Therefore,sensitive and specific biomarkers are needed.Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney.The microRNAs(miRNAs)in urinary exosome are remark-ably stable and highly tissue-specific for the kidney.METHODS Type 2 diabetic mellitus(T2DM)patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups:DM,diabetic pa-tients without albuminuria[urinary albumin to creatinine ratio(UACR)<30 mg/g]and DKD,diabetic patients with albuminuria(UACR≥30 mg/g).Healthy subjects were the normal control(NC)group.Urinary exosomal miR-145-5p,miR-27a-3p,and miR-29c-3p,were detected using real-time quantitative polymerase chain reaction.The correlation between exosomal miRNAs and the clinical in-dexes was evaluated.The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic(ROC)analysis.Biological functions of miR-145-5p were investigated by performing RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group(miR-145-5p:4.54±1.45 vs 1.95±0.93,P<0.001;miR-27a-3p:2.33±0.79 vs 1.71±0.76,P<0.05)and the NC group(miR-145-5p:4.54±1.45 vs 1.55±0.83,P<0.001;miR-27a-3p:2.33±0.79 vs 1.10±0.51,P<0.001).The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate.miR-27a-3p was also closely related to blood glucose,gly-cosylated hemoglobin A1c,and low-density lipoprotein cholesterol.ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88[95%confidence interval(CI):0.784-0.985,P<0.0001]in diagnosing DKD than miR-27a-3p with 0.71(95%CI:0.547-0.871,P=0.0239).Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament,cytoskeleton,and extracellular exosome and were involved in the pathological processes of DKD,including apoptosis,inflammation,and fibrosis.CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.展开更多
Prostate cancer (PCa) has become to have the highest incidence and the second mortality rate in western countries, affecting men's health to a large extent. Although prostate-specific antigen (PSA) was discovered...Prostate cancer (PCa) has become to have the highest incidence and the second mortality rate in western countries, affecting men's health to a large extent. Although prostate-specific antigen (PSA) was discovered to help diagnose the cancer in an early stage for decades, its specificity is relative low, resulting in unnecessary biopsy for healthy people and over-treatment for patients. Thus, it is imperative to identify more and more effective biomarkers for early diagnosis of PCa in order to distinguish patients from healthy populations, which helps guide an early treatment to lower disease-related mortality by noninvasive or minimal invasive approaches. This review generally describes the current early diagnostic biomarkers of PCa in addition to PSA and summarizes the advantages and disadvantages of these biomarkers.展开更多
In this editorial,we commented on the article by Akers et al published in the recent issue of the World Journal of Clinical Cases.We focused specifically on the role of the transcription factor paired box protein 8(PA...In this editorial,we commented on the article by Akers et al published in the recent issue of the World Journal of Clinical Cases.We focused specifically on the role of the transcription factor paired box protein 8(PAX8)belonging to the family PAX in the carcinogenesis of a gynecologic tumor,endocervical adenocarcinoma,arising from the tissue of mesonephric origin,and the potential diagnostic value for the same type of neoplasms.The global vaccination program of human papillomavirus(HPV)has dramatically reduced the incidence of cervical cancer,including cases of adenocarcinoma.The type of adenoid epithelial origin has a lower frequency of HPV detection but tends to be more aggressive and fatal.Cases of endocervical adenocarcinoma occurring in females of menopause age have been described in the 2023 volume of the World Journal of Clinical Cases and in our study recently published in Oncol Lett.The histopathological findings and immunohistochemical assays showed that the lesions had glandular morphology,and the specimens in these two reports were immunohistochemically positive for the transcription factor PAX8,albeit that they had opposing expression profiles of tumor suppressor p16 and estrogen receptor and the presence of the HPV genome.The presence of a mucin protein,MUC 5AC,as revealed in both studies suggested target molecules for the diagnosis of mucinous adenoid type of uterine tumor and other histological origins.The clinical outcome was unfavorable due to metastasis and recurrence.This prompted the improvement of the antitumor modality,with the introduction of precise targeting therapy.Mucin has now been reported to be the therapeutic target for adenocarcinomas.展开更多
BACKGROUND Breast cancer is regarded as a highly malignant neoplasm in the female population,posing a significant risk to women’s overall well-being.The prevalence of breast cancer has been observed to rise in China,...BACKGROUND Breast cancer is regarded as a highly malignant neoplasm in the female population,posing a significant risk to women’s overall well-being.The prevalence of breast cancer has been observed to rise in China,accompanied by an earlier age of onset when compared to Western countries.Breast cancer continues to be a prominent contributor to cancer-related mortality and morbidity among women,primarily due to its limited responsiveness to conventional treatment modalities.The diagnostic process is challenging due to the presence of non-specific clinical manifestations and the suboptimal precision of conventional diagnostic tests.There is a prevailing uncertainty regarding the most effective screening method and target populations,as well as the specificities and execution of screening programs.AIM To identify diagnostic and prognostic biomarkers for breast cancer.METHODS Overlapping differentially expressed genes were screened based on Gene Expression Omnibus(GSE36765,GSE10810,and GSE20086)and The Cancer Genome Atlas datasets.A protein-protein interaction network was applied to excavate the hub genes among these differentially expressed genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses,as well as gene set enrichment analyses,were conducted to examine the functions of these genes and their potential mechanisms in the development of breast cancer.For clarification of the diagnostic and prognostic roles of these genes,Kaplan–Mei-er and Cox proportional hazards analyses were conducted.RESULTS This study demonstrated that calreticulin,heat shock protein family B member 1,insulin-like growth Factor 1,interleukin-1 receptor 1,Krüppel-like factor 4,suppressor of cytokine signaling 3,and triosephosphate isomerase 1 are potential diagnostic biomarkers of breast cancer as well as potential treatment targets with clinical implications.CONCLUSION The screening of biomarkers is of guiding significance for the diagnosis and prognosis of the diseases.展开更多
Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic mi RNAs and downregulated tu...Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic mi RNAs and downregulated tumour-suppressor mi RNAs in this type of cancer. In this review, we provide an overview of the role of mi RNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer. Moreover, we discuss the influence of polymorphisms and epigenetic modifications on mi RNA activity.展开更多
Gastric cancer(GC)remains a leading cause of cancer-related death worldwide.Less than half of GC cases are diagnosed at an advanced stage due to its lack of early symptoms.GC is a heterogeneous disease associated with...Gastric cancer(GC)remains a leading cause of cancer-related death worldwide.Less than half of GC cases are diagnosed at an advanced stage due to its lack of early symptoms.GC is a heterogeneous disease associated with a number of genetic and somatic mutations.Early detection and effective monitoring of tumor progression are essential for reducing GC disease burden and mortality.The current widespread use of semi-invasive endoscopic methods and radiologic approaches has increased the number of treatable cancers:However,these approaches are invasive,costly,and time-consuming.Thus,novel molecular noninvasive tests that detect GC alterations seem to be more sensitive and specific compared to the current methods.Recent technological advances have enabled the detection of blood-based biomarkers that could be used as diagnostic indicators and for monitoring postsurgical minimal residual disease.These biomarkers include circulating DNA,RNA,extracellular vesicles,and proteins,and their clinical applications are currently being investigated.The identification of ideal diagnostic markers for GC that have high sensitivity and specificity would improve survival rates and contribute to the advancement of precision medicine.This review provides an overview of current topics regarding the novel,recently developed diagnostic markers for GC.展开更多
Background:Recent studies have demonstrated that microRNAs(miRNAs)in the blood circulation can serve as promising diagnostic markers for cancers.This four-stage study aimed at finding serum miRNAs as potential biomark...Background:Recent studies have demonstrated that microRNAs(miRNAs)in the blood circulation can serve as promising diagnostic markers for cancers.This four-stage study aimed at finding serum miRNAs as potential biomarkers for lung adenocarcinoma(LA)diagnosis.Methods:The study was carried out between 2016 and 2017.The Exiqon miRNA qPCR panel(3 LA vs.1 normal control[NC]pooled serum samples)was used for initial screening to acquire miRNA profiles.Thirty-five dysregulated miRNAs were further evaluated in the training(24 LA vs.24 NCs)and testing stages(110 LA vs.110 NCs)using quantitative real-time polymerase chain reaction assays.Results:Four serum miRNAs(miR-133a-3p,miR-584-5p,miR-10b-5p,and miR-221-3p)were significantly overexpressed in LA patients compared with NCs.The diagnostic value of the four-miRNA panel was validated by an external cohort(36 LA vs.36 NCs).The areas under the receiver operating characteristic curve of the four-miRNA panel in the training,testing,and external validation stages were 0.734,0.803,and 0.894 respectively.Meanwhile,the expression level of miR-221-3p was much higher in LA tumor samples than that in the adjacent normal tissues(19 LA vs.19 NCs).The expression level of miR-10b-5p was also elevated in the serum-derived exosomes samples(18 LA vs.18 NCs).The expression of miR-133a-3p,miR-584-5p,and miR-10b-5p was significantly elevated in LA patients with epidermal growth factor receptor mutation compared with NCs.Conclusion:The study established a four-miRNA signature in serum that could improve the diagnostic capability of LA.展开更多
Background: Acute Kidney Injury (AKI) stands as a prominent postoperative complication in on-pump cardiac surgery, with repercussions on morbidity, mortality, and hospitalization duration. Current diagnostic criteria ...Background: Acute Kidney Injury (AKI) stands as a prominent postoperative complication in on-pump cardiac surgery, with repercussions on morbidity, mortality, and hospitalization duration. Current diagnostic criteria relying on serum creatinine levels exhibit a delayed identification of AKI, prompting an exploration of alternative biomarkers. Aims and Objectives: This study is designed to overcome diagnostic constraints and explore the viability of serum Cystatin C as an early predictor of Acute Kidney Injury (AKI) in individuals undergoing on-pump cardiac surgery. The investigation aims to establish the relationship between serum Cystatin C levels and the onset of AKI in patients subjected to on-pump cardiac surgery. Primary objectives involve the assessment of the diagnostic effectiveness of serum Cystatin C, its comparison with serum creatinine, and the exploration of its potential for the early identification and treatment of AKI. Methodology: Conducted as a single-center study at the cardiac surgery department of BSMMU in Bangladesh from September 2020 to August 2022, a comparative cross-sectional analysis involved 31 participants categorized into No AKI and AKI groups based on Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Data collection encompassed preoperative, post-CBP (cardiopulmonary bypass) conclusion at 2 hours, postoperative day 1, and postoperative day 2 intervals. Statistical analyses included Chi-squared tests, independent Student’s t-tests, and one-sample t-tests. Significance was set at P Results: The study revealed no significant differences in baseline characteristics between the No AKI and AKI groups, except for CPB time and cross-clamp time. Serum Cystatin C levels in the AKI group exhibited statistical significance at various time points, highlighting its potential as an early detector. Conversely, Serum Creatinine levels in the AKI group showed no statistical significance. The Receiver Operating Characteristic (ROC) curve analysis further supported the efficacy of serum Cystatin C, with an Area under the ROC Curve of 0.864 and a cut-off value of 0.55 (p Conclusion: This study supports the superior utility of serum Cystatin C as an early detector of AKI in on-pump cardiac surgery patients compared to serum creatinine. Its ability to identify AKI several hours earlier may contribute to reduced morbidity, mortality, and healthcare costs. The findings underscore the significance of exploring novel biomarkers for improved post-cardiac surgery renal function assessment.展开更多
MicroRNAs are a family of small, genome-encoded endogenous RNAs that are transcribed but are not translated into proteins. They serve essential roles in virtually every aspect of brain function, including neurogenesis...MicroRNAs are a family of small, genome-encoded endogenous RNAs that are transcribed but are not translated into proteins. They serve essential roles in virtually every aspect of brain function, including neurogenesis, neural development, and cellular responses leading to changes in synaptic plasticity. They are also implicated in neurodegeneration and neurological disorders, in responses to hypoxia and ischemia, and in ischemic tolerance induced by ischemic preconditioning. In recent developments, miRNA expres- sion profiling has been examined in stroke, and these studies indicate that miRNAs have emerged as key mediators in ischemic stroke biology. Both increased and decreased miRNA levels may be needed either as prevention or treatment of stroke. Novel approaches are being developed to get miRNA related therapeu- tics into the brain across an intact blood-brain barrier, including chemical modification, use of targeting molecules and methods to disrupt the blood-brain barrier.展开更多
Proper medical treatment of a stroke victim relies on accurate and rapid differentiation between ischemic and hemorrhagic stroke,which in current practice is performed by computerized tomography(CT) or magnetic reso...Proper medical treatment of a stroke victim relies on accurate and rapid differentiation between ischemic and hemorrhagic stroke,which in current practice is performed by computerized tomography(CT) or magnetic resonance imaging(MRI) scans.A panel of micro RNAs could be an extremely useful clinical tool for distinguishing between hemorrhagic and ischemic stroke.This review has shown that blood miRNA profile can distinguish hemorrhagic from ischemic stroke in patients and in experimental animal models.It also seems likely they can differentiate between intracerebral and subarachnoid hemorrhage stroke.The miRNA profile in cerebrospinal fluid could be a useful diagnostic tool for subarachnoid hemorrhagic stroke.Decreased or increased miRNA levels may be needed either as prevention or treatment of stroke.Administration in vivo of miR-130 a inhibitor or miRNA mimic(miR-367,miR-223) in an intracerebral hemorrhage animal model improved neurological outcomes.展开更多
Dear Editor,Alterations in the human microbiome are closely related to various hepatobiliary diseases.Gut microbial dysbiosis has been found in patients with cholangiocarcinoma(CCA)[1].However,the characteristics of o...Dear Editor,Alterations in the human microbiome are closely related to various hepatobiliary diseases.Gut microbial dysbiosis has been found in patients with cholangiocarcinoma(CCA)[1].However,the characteristics of oral microbiome in patients with CCA have not been studied.展开更多
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by progressive muscle wasting,breathing and swallowing difficulties resulting in patient’s death in two to five years after disease ons...Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by progressive muscle wasting,breathing and swallowing difficulties resulting in patient’s death in two to five years after disease onset.In amyotrophic lateral sclerosis,both upper and lower motor neurons of the corticospinal tracts are involved in the process of neurodegeneration,accounting for great clinical heterogeneity of the disease.Clinical phenotype has great impact on the pattern and rate of amyotrophic lateral sclerosis progression and overall survival prognosis.Creating more homogenous patient groups in order to study the effects of drug agents on specific manifestations of the disease is a challenging issue in amyotrophic lateral sclerosis clinical trials.Since amyotrophic lateral sclerosis has low incidence rates,conduction of multicenter trials requires certain standardized approaches to disease diagnosis and staging.This review focuses on the current approaches in amyotrophic lateral sclerosis classification and staging system based on clinical examination and additional instrumental methods,highlighting the role of upper and lower motor neuron involvement in different phenotypes of the disease.We demonstrate that both clinical and instrumental findings can be useful in evaluating severity of upper motor neuron and lower motor neuron involvement and predicting the following course of the disease.Addressing disease heterogeneity in amyotrophic lateral sclerosis clinical trials could lead to study designs that will assess drug efficacy in specific patient groups,based on the disease pathophysiology and spatiotemporal pattern.Although clinical evaluation can be a sufficient screening method for dividing amyotrophic lateral sclerosis patients into clinical subgroups,we provide proof that instrumental studies could provide valuable insights in the disease pathology.展开更多
Inflammatory bowel diseases(IBD)are a group of chronic relapsing gastrointestinal inflammatory diseases with significant global incidence.Although the pathomechanism of IBD has been extensively investigated,several as...Inflammatory bowel diseases(IBD)are a group of chronic relapsing gastrointestinal inflammatory diseases with significant global incidence.Although the pathomechanism of IBD has been extensively investigated,several aspects of its pathogenesis remain unclear.Long non-coding RNAs(lncRNAs)are transcripts with more than 200 nucleotides in length that have potential protein-coding functions.LncRNAs play important roles in biological processes such as epigenetic modification,transcriptional regulation and posttranscriptional regulation.In this review,we summarize recent advances in research on IBD-related lncRNAs from the perspective of the overall intestinal microenvironment,as well as their potential roles as immune regulators,diagnostic biomarkers and therapeutic targets or agents for IBD.展开更多
Background:Diagnosing latent tuberculosis(TB)infection(LTBI)and active TB(ATB)is crucial for preventing disease progression and transmission.However,current diagnostic tests have limitations in terms of accuracy and s...Background:Diagnosing latent tuberculosis(TB)infection(LTBI)and active TB(ATB)is crucial for preventing disease progression and transmission.However,current diagnostic tests have limitations in terms of accuracy and sensitivity,making it challenging to diagnose these different infection states.Therefore,this study intends to develop a promising biomarker for LTBI and ATB diagnosis to overcome the limitations of the current diagnostic tests.Methods:We developed a novelmultiepitope-based diagnostic biomarker(MEBDB)fromLTBI region of differentiation antigens using bioinformatics and immunoinformatics.Immune responses induced byMEBDM were detected using enzyme-linked immunosorbent spot and cytometric bead assays.This study was conducted from April 2022 to December 2022 in the SeniorDepartment of Tuberculosis at the 8thMedical Center of PLA General Hospital,China.Blood samples were collected from participants with ATB,individuals with LTBI,and healthy controls(HCs).The diagnostic efficacy of MEBDB was evaluated using receiver operating characteristic curves.Results:A novel MEBDB,designated as CP19128P,was generated.CP19128P comprises 19 helper T lymphocyte epitopes,12 cytotoxic T lymphocyte epitopes,and 8 B-cell epitopes.In silico simulations demonstrated that CP19128P possesses strong affinity for Toll-like receptors and elicits robust innate and adaptive immune responses.CP19128P generated significantly higher levels of tumor necrosis factor(TNF-α),interleukin 4(IL-4),and IL-10 in ATB patients(n=7)and LTBI(n=8)individuals compared with HCs(n=62)(P<0.001).Moreover,CP19128P-induced specific cytokines could be used to discriminate LTBI and ATB from healthy subjects with high sensitivity and specificity.Combining IL-2 with IL-4 or TNF-α could differentiate LTBI from HCs(the area under the receiver operating characteristic curve[AUC],0.976[95% confidence interval[CI],0.934-1.000]or 0.986[0.956-1.000]),whereas combining IL-4 with IL-17A or TNF-α could differentiate ATB from HCs(AUC,0.887[0.782-0.993]or 0.984[0.958-1.000]).Conclusions:Our study revealed that CP19128P is a potential MEBDBfor the diagnosis of LTBI andATB.Our findings suggest a promising strategy for developing novel,accurate,and sensitive diagnostic biomarkers and identifying new targets for TB diagnosis and management.展开更多
Immune checkpoint inhibitors represent a major therapeutic advance in non-small-cell lung cancer with several approved anti-programmed death-1 and anti-programmed death-L1 immunotherapies.A majority of patients howeve...Immune checkpoint inhibitors represent a major therapeutic advance in non-small-cell lung cancer with several approved anti-programmed death-1 and anti-programmed death-L1 immunotherapies.A majority of patients however,will not respond to immune checkpoint inhibitors and display primary resistance while a subset of initially responsive patients will present secondary resistance.Thus,there is a crucial need for biomarkers to enable better prediction and diagnosis,and to overcome such resistance.Along with improvement in the understanding of immune escape,new biomarkers are being developed,including large scale proteomic,genomic and transcriptomic approaches in tumor and blood samples.We review the novel biomarkers that have been investigated in non-small-cell lung cancer and discuss how they can rationalize therapeutic strategies.展开更多
The human endometrium and embryo both produce microRNAs(miRNAs),which are involved in various physiological activities.Accumulating evident suggested that endometrial miRNAs are regulated by steroid hormones that modu...The human endometrium and embryo both produce microRNAs(miRNAs),which are involved in various physiological activities.Accumulating evident suggested that endometrial miRNAs are regulated by steroid hormones that modulate endometrial functions,whereas embryo-derived miRNAs play vital roles in maternal–embryo communication.The aberrant expression of endometriumor embryo-derived miRNAs can cause early pregnancy and gestational disorders,including repeated implantation failure,recurrent miscarriage,and pathological conditions such as endometriosis.miRNAs are,therefore,ideal candidates for conducting clinicopathological tests.Potential diagnostic and prognostic tests using miRNAs are under development;however,the therapeutic applications of miRNAs in regulating gestational disorders require further investigation.展开更多
Colorectal cancer(CRC)is one of the most frequently diagnosed cancers and the leading cause of cancer-associated deaths.Epidemiological studies have shown that both genetic and environmental risk factors contribute to...Colorectal cancer(CRC)is one of the most frequently diagnosed cancers and the leading cause of cancer-associated deaths.Epidemiological studies have shown that both genetic and environmental risk factors contribute to the development of CRC.Several metagenomic studies of CRC have identified gut dysbiosis as a fundamental risk factor in the evolution of colorectal malignancy.Although enormous efforts and substantial progresses have been made in understanding the relationship between human gut microbiome and CRC,the precise mechanisms involved remain elusive.Recent data have shown a direct causative role of the gut microbiome in DNA damage,inflammation,and drug resistance in CRC,suggesting that modulation of gut microbiome could act as a powerful tool in CRC prevention and therapy.Here,we provide an overview of the relationship between gut microbiome and CRC,and explore relevant mechanisms of colorectal tumorigenesis.We next highlight the potential of bacterial species as clinical biomarkers,as well as their roles in therapeutic response.Factors limiting the clinical translation of gut microbiome and strategies for resolving current challenges are further discussed.展开更多
Background:MicroRNAs(miRNAs)are small non-coding RNA molecules that function as posttranscriptional regulators of gene expression.Measurements of miRNAs in cerebrospinal fluid(CSF)and blood have just started gaining a...Background:MicroRNAs(miRNAs)are small non-coding RNA molecules that function as posttranscriptional regulators of gene expression.Measurements of miRNAs in cerebrospinal fluid(CSF)and blood have just started gaining attention as a novel diagnostic tool for various neurological conditions.The purpose of this exploratory investigation was to analyze the expression of miRNAs in CSF and blood of patients with Alzheimer’s disease(AD)and other neurodegenerative disorders in order to identify potential miRNA biomarker candidates able to separate AD from other types of dementia.Methods:CSF was collected by lumbar puncture performed on 10 patients diagnosed with AD and 10 patients diagnosed with either vascular dementia,frontotemporal dementia or dementia with Lewy bodies.Blood samples were taken immediately after.Total RNA was extracted from cell free fractions of CSF and plasma,and a screening for 372 known miRNA sequences was carried out by real time quantitative polymerase chain reactions(miRCURY LNA™Universal RT miRNA PCR,Polyadenylation and cDNA synthesis kit,Exiqon).Results:Fifty-two miRNAs were detected in CSF in at least nine out of ten patients in both groups.Among these,two miRNAs(let-7i-5p and miR-15a-5p)were found significantly up-regulated and one miRNA(miR-29c-3p)was found significantly down-regulated in patients with AD compared to controls.One hundred and sixty-eight miRNAs were frequently detected in the blood,among which miR-590-5p and miR-142-5p were significantly up-regulated and miR-194-5p was significantly down-regulated in AD patients compared to controls.Conclusions:Detection of miRNA expression profiles in blood and in particular CSF of patients diagnosed with different types of dementia is feasible and it seems that several expressional differences between AD and other dementia types do exist when measured in a clinically relevant setup.In this explorative pilot study,the deregulated miRNAs in CSF of AD patients may be associated with relevant target genes related to AD pathology,including APP and BACE1,which suggests that miRNAs are interesting candidates for AD biomarkers in the future.展开更多
基金Supported by the Nature Science Foundation of Hebei Province,No.H2023104011.
文摘BACKGROUND Diabetic kidney disease(DKD),characterized by increased urinary microalbumin levels and decreased renal function,is the primary cause of end-stage renal di-sease.Its pathological mechanisms are complicated and multifactorial;Therefore,sensitive and specific biomarkers are needed.Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney.The microRNAs(miRNAs)in urinary exosome are remark-ably stable and highly tissue-specific for the kidney.METHODS Type 2 diabetic mellitus(T2DM)patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups:DM,diabetic pa-tients without albuminuria[urinary albumin to creatinine ratio(UACR)<30 mg/g]and DKD,diabetic patients with albuminuria(UACR≥30 mg/g).Healthy subjects were the normal control(NC)group.Urinary exosomal miR-145-5p,miR-27a-3p,and miR-29c-3p,were detected using real-time quantitative polymerase chain reaction.The correlation between exosomal miRNAs and the clinical in-dexes was evaluated.The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic(ROC)analysis.Biological functions of miR-145-5p were investigated by performing RESULTS Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group(miR-145-5p:4.54±1.45 vs 1.95±0.93,P<0.001;miR-27a-3p:2.33±0.79 vs 1.71±0.76,P<0.05)and the NC group(miR-145-5p:4.54±1.45 vs 1.55±0.83,P<0.001;miR-27a-3p:2.33±0.79 vs 1.10±0.51,P<0.001).The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate.miR-27a-3p was also closely related to blood glucose,gly-cosylated hemoglobin A1c,and low-density lipoprotein cholesterol.ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88[95%confidence interval(CI):0.784-0.985,P<0.0001]in diagnosing DKD than miR-27a-3p with 0.71(95%CI:0.547-0.871,P=0.0239).Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament,cytoskeleton,and extracellular exosome and were involved in the pathological processes of DKD,including apoptosis,inflammation,and fibrosis.CONCLUSION Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.
基金This study was supported by the National Basic Research Program of China (No. 2012CB518306), the National Natural Science Foundation of China (No. 81101946), the Prostate Cancer Foundation Young Investigator Award, and the Shanghai Pujiang Program (No. 12PJD008).
文摘Prostate cancer (PCa) has become to have the highest incidence and the second mortality rate in western countries, affecting men's health to a large extent. Although prostate-specific antigen (PSA) was discovered to help diagnose the cancer in an early stage for decades, its specificity is relative low, resulting in unnecessary biopsy for healthy people and over-treatment for patients. Thus, it is imperative to identify more and more effective biomarkers for early diagnosis of PCa in order to distinguish patients from healthy populations, which helps guide an early treatment to lower disease-related mortality by noninvasive or minimal invasive approaches. This review generally describes the current early diagnostic biomarkers of PCa in addition to PSA and summarizes the advantages and disadvantages of these biomarkers.
文摘In this editorial,we commented on the article by Akers et al published in the recent issue of the World Journal of Clinical Cases.We focused specifically on the role of the transcription factor paired box protein 8(PAX8)belonging to the family PAX in the carcinogenesis of a gynecologic tumor,endocervical adenocarcinoma,arising from the tissue of mesonephric origin,and the potential diagnostic value for the same type of neoplasms.The global vaccination program of human papillomavirus(HPV)has dramatically reduced the incidence of cervical cancer,including cases of adenocarcinoma.The type of adenoid epithelial origin has a lower frequency of HPV detection but tends to be more aggressive and fatal.Cases of endocervical adenocarcinoma occurring in females of menopause age have been described in the 2023 volume of the World Journal of Clinical Cases and in our study recently published in Oncol Lett.The histopathological findings and immunohistochemical assays showed that the lesions had glandular morphology,and the specimens in these two reports were immunohistochemically positive for the transcription factor PAX8,albeit that they had opposing expression profiles of tumor suppressor p16 and estrogen receptor and the presence of the HPV genome.The presence of a mucin protein,MUC 5AC,as revealed in both studies suggested target molecules for the diagnosis of mucinous adenoid type of uterine tumor and other histological origins.The clinical outcome was unfavorable due to metastasis and recurrence.This prompted the improvement of the antitumor modality,with the introduction of precise targeting therapy.Mucin has now been reported to be the therapeutic target for adenocarcinomas.
基金Supported by the Natural Science Foundation of Inner Mongolia,No.2021GG0298.
文摘BACKGROUND Breast cancer is regarded as a highly malignant neoplasm in the female population,posing a significant risk to women’s overall well-being.The prevalence of breast cancer has been observed to rise in China,accompanied by an earlier age of onset when compared to Western countries.Breast cancer continues to be a prominent contributor to cancer-related mortality and morbidity among women,primarily due to its limited responsiveness to conventional treatment modalities.The diagnostic process is challenging due to the presence of non-specific clinical manifestations and the suboptimal precision of conventional diagnostic tests.There is a prevailing uncertainty regarding the most effective screening method and target populations,as well as the specificities and execution of screening programs.AIM To identify diagnostic and prognostic biomarkers for breast cancer.METHODS Overlapping differentially expressed genes were screened based on Gene Expression Omnibus(GSE36765,GSE10810,and GSE20086)and The Cancer Genome Atlas datasets.A protein-protein interaction network was applied to excavate the hub genes among these differentially expressed genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses,as well as gene set enrichment analyses,were conducted to examine the functions of these genes and their potential mechanisms in the development of breast cancer.For clarification of the diagnostic and prognostic roles of these genes,Kaplan–Mei-er and Cox proportional hazards analyses were conducted.RESULTS This study demonstrated that calreticulin,heat shock protein family B member 1,insulin-like growth Factor 1,interleukin-1 receptor 1,Krüppel-like factor 4,suppressor of cytokine signaling 3,and triosephosphate isomerase 1 are potential diagnostic biomarkers of breast cancer as well as potential treatment targets with clinical implications.CONCLUSION The screening of biomarkers is of guiding significance for the diagnosis and prognosis of the diseases.
基金Supported by Fundacao de Amparoà Pesquisa do Estado de Sao Paulothe Conselho Nacional de Desenvolvimento Científico e Tecnológicoand the Coordenacao de Aperfei?ooamento de Pessoal de Nível Superior
文摘Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic mi RNAs and downregulated tumour-suppressor mi RNAs in this type of cancer. In this review, we provide an overview of the role of mi RNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer. Moreover, we discuss the influence of polymorphisms and epigenetic modifications on mi RNA activity.
基金the National Cancer Center Research and Development Fund,No.23-A-9.
文摘Gastric cancer(GC)remains a leading cause of cancer-related death worldwide.Less than half of GC cases are diagnosed at an advanced stage due to its lack of early symptoms.GC is a heterogeneous disease associated with a number of genetic and somatic mutations.Early detection and effective monitoring of tumor progression are essential for reducing GC disease burden and mortality.The current widespread use of semi-invasive endoscopic methods and radiologic approaches has increased the number of treatable cancers:However,these approaches are invasive,costly,and time-consuming.Thus,novel molecular noninvasive tests that detect GC alterations seem to be more sensitive and specific compared to the current methods.Recent technological advances have enabled the detection of blood-based biomarkers that could be used as diagnostic indicators and for monitoring postsurgical minimal residual disease.These biomarkers include circulating DNA,RNA,extracellular vesicles,and proteins,and their clinical applications are currently being investigated.The identification of ideal diagnostic markers for GC that have high sensitivity and specificity would improve survival rates and contribute to the advancement of precision medicine.This review provides an overview of current topics regarding the novel,recently developed diagnostic markers for GC.
基金grants from the National Natural Science Foundation of China(No.81672400,and No.81672788)Natural Science Foundation of Jiangsu Provincial Department of Education(No.17KJB320007)CSCO-Hausoh Cancer Research Foundation(No.YHS2017-032)。
文摘Background:Recent studies have demonstrated that microRNAs(miRNAs)in the blood circulation can serve as promising diagnostic markers for cancers.This four-stage study aimed at finding serum miRNAs as potential biomarkers for lung adenocarcinoma(LA)diagnosis.Methods:The study was carried out between 2016 and 2017.The Exiqon miRNA qPCR panel(3 LA vs.1 normal control[NC]pooled serum samples)was used for initial screening to acquire miRNA profiles.Thirty-five dysregulated miRNAs were further evaluated in the training(24 LA vs.24 NCs)and testing stages(110 LA vs.110 NCs)using quantitative real-time polymerase chain reaction assays.Results:Four serum miRNAs(miR-133a-3p,miR-584-5p,miR-10b-5p,and miR-221-3p)were significantly overexpressed in LA patients compared with NCs.The diagnostic value of the four-miRNA panel was validated by an external cohort(36 LA vs.36 NCs).The areas under the receiver operating characteristic curve of the four-miRNA panel in the training,testing,and external validation stages were 0.734,0.803,and 0.894 respectively.Meanwhile,the expression level of miR-221-3p was much higher in LA tumor samples than that in the adjacent normal tissues(19 LA vs.19 NCs).The expression level of miR-10b-5p was also elevated in the serum-derived exosomes samples(18 LA vs.18 NCs).The expression of miR-133a-3p,miR-584-5p,and miR-10b-5p was significantly elevated in LA patients with epidermal growth factor receptor mutation compared with NCs.Conclusion:The study established a four-miRNA signature in serum that could improve the diagnostic capability of LA.
文摘Background: Acute Kidney Injury (AKI) stands as a prominent postoperative complication in on-pump cardiac surgery, with repercussions on morbidity, mortality, and hospitalization duration. Current diagnostic criteria relying on serum creatinine levels exhibit a delayed identification of AKI, prompting an exploration of alternative biomarkers. Aims and Objectives: This study is designed to overcome diagnostic constraints and explore the viability of serum Cystatin C as an early predictor of Acute Kidney Injury (AKI) in individuals undergoing on-pump cardiac surgery. The investigation aims to establish the relationship between serum Cystatin C levels and the onset of AKI in patients subjected to on-pump cardiac surgery. Primary objectives involve the assessment of the diagnostic effectiveness of serum Cystatin C, its comparison with serum creatinine, and the exploration of its potential for the early identification and treatment of AKI. Methodology: Conducted as a single-center study at the cardiac surgery department of BSMMU in Bangladesh from September 2020 to August 2022, a comparative cross-sectional analysis involved 31 participants categorized into No AKI and AKI groups based on Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Data collection encompassed preoperative, post-CBP (cardiopulmonary bypass) conclusion at 2 hours, postoperative day 1, and postoperative day 2 intervals. Statistical analyses included Chi-squared tests, independent Student’s t-tests, and one-sample t-tests. Significance was set at P Results: The study revealed no significant differences in baseline characteristics between the No AKI and AKI groups, except for CPB time and cross-clamp time. Serum Cystatin C levels in the AKI group exhibited statistical significance at various time points, highlighting its potential as an early detector. Conversely, Serum Creatinine levels in the AKI group showed no statistical significance. The Receiver Operating Characteristic (ROC) curve analysis further supported the efficacy of serum Cystatin C, with an Area under the ROC Curve of 0.864 and a cut-off value of 0.55 (p Conclusion: This study supports the superior utility of serum Cystatin C as an early detector of AKI in on-pump cardiac surgery patients compared to serum creatinine. Its ability to identify AKI several hours earlier may contribute to reduced morbidity, mortality, and healthcare costs. The findings underscore the significance of exploring novel biomarkers for improved post-cardiac surgery renal function assessment.
文摘MicroRNAs are a family of small, genome-encoded endogenous RNAs that are transcribed but are not translated into proteins. They serve essential roles in virtually every aspect of brain function, including neurogenesis, neural development, and cellular responses leading to changes in synaptic plasticity. They are also implicated in neurodegeneration and neurological disorders, in responses to hypoxia and ischemia, and in ischemic tolerance induced by ischemic preconditioning. In recent developments, miRNA expres- sion profiling has been examined in stroke, and these studies indicate that miRNAs have emerged as key mediators in ischemic stroke biology. Both increased and decreased miRNA levels may be needed either as prevention or treatment of stroke. Novel approaches are being developed to get miRNA related therapeu- tics into the brain across an intact blood-brain barrier, including chemical modification, use of targeting molecules and methods to disrupt the blood-brain barrier.
文摘Proper medical treatment of a stroke victim relies on accurate and rapid differentiation between ischemic and hemorrhagic stroke,which in current practice is performed by computerized tomography(CT) or magnetic resonance imaging(MRI) scans.A panel of micro RNAs could be an extremely useful clinical tool for distinguishing between hemorrhagic and ischemic stroke.This review has shown that blood miRNA profile can distinguish hemorrhagic from ischemic stroke in patients and in experimental animal models.It also seems likely they can differentiate between intracerebral and subarachnoid hemorrhage stroke.The miRNA profile in cerebrospinal fluid could be a useful diagnostic tool for subarachnoid hemorrhagic stroke.Decreased or increased miRNA levels may be needed either as prevention or treatment of stroke.Administration in vivo of miR-130 a inhibitor or miRNA mimic(miR-367,miR-223) in an intracerebral hemorrhage animal model improved neurological outcomes.
基金supported by the National Natural Science Foundation of China (U2004121, 82070643, and U1904164)the Research Project of Jinan Microecological Biomedicine Shandong Laboratory (JNL-2022015B and JNL-2022001A)the National Key Research and Development Program of China (2018YFC2000500).
文摘Dear Editor,Alterations in the human microbiome are closely related to various hepatobiliary diseases.Gut microbial dysbiosis has been found in patients with cholangiocarcinoma(CCA)[1].However,the characteristics of oral microbiome in patients with CCA have not been studied.
文摘Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by progressive muscle wasting,breathing and swallowing difficulties resulting in patient’s death in two to five years after disease onset.In amyotrophic lateral sclerosis,both upper and lower motor neurons of the corticospinal tracts are involved in the process of neurodegeneration,accounting for great clinical heterogeneity of the disease.Clinical phenotype has great impact on the pattern and rate of amyotrophic lateral sclerosis progression and overall survival prognosis.Creating more homogenous patient groups in order to study the effects of drug agents on specific manifestations of the disease is a challenging issue in amyotrophic lateral sclerosis clinical trials.Since amyotrophic lateral sclerosis has low incidence rates,conduction of multicenter trials requires certain standardized approaches to disease diagnosis and staging.This review focuses on the current approaches in amyotrophic lateral sclerosis classification and staging system based on clinical examination and additional instrumental methods,highlighting the role of upper and lower motor neuron involvement in different phenotypes of the disease.We demonstrate that both clinical and instrumental findings can be useful in evaluating severity of upper motor neuron and lower motor neuron involvement and predicting the following course of the disease.Addressing disease heterogeneity in amyotrophic lateral sclerosis clinical trials could lead to study designs that will assess drug efficacy in specific patient groups,based on the disease pathophysiology and spatiotemporal pattern.Although clinical evaluation can be a sufficient screening method for dividing amyotrophic lateral sclerosis patients into clinical subgroups,we provide proof that instrumental studies could provide valuable insights in the disease pathology.
基金supported by the National Natural Science Foundation of China (Grants No.82270011 and 81960513)the Scientific Research Foundation of the Affiliated Hospital of Xuzhou Medical University (Grant No.2020KA010)+2 种基金the Priority Academic Program Development of jiangsu Higher Education Institutions (PAPD),and Postgraduate Research&Practice Innovation Program of Jiangsu Province (Grant No.KYCX22_2815)the Natural Science Foundation of Guizhou Provincial Scientific and Technology Department Grant (Grant No. (2022)626)Scientific Research Foundation of Wenzhou Institute,University of Chinese Academy of Sciences.
文摘Inflammatory bowel diseases(IBD)are a group of chronic relapsing gastrointestinal inflammatory diseases with significant global incidence.Although the pathomechanism of IBD has been extensively investigated,several aspects of its pathogenesis remain unclear.Long non-coding RNAs(lncRNAs)are transcripts with more than 200 nucleotides in length that have potential protein-coding functions.LncRNAs play important roles in biological processes such as epigenetic modification,transcriptional regulation and posttranscriptional regulation.In this review,we summarize recent advances in research on IBD-related lncRNAs from the perspective of the overall intestinal microenvironment,as well as their potential roles as immune regulators,diagnostic biomarkers and therapeutic targets or agents for IBD.
基金supported by the BeijingMunicipal Science&Technology Commission(7212103)the Eighth Medical Center of PLA General Hospital(MS202211002).
文摘Background:Diagnosing latent tuberculosis(TB)infection(LTBI)and active TB(ATB)is crucial for preventing disease progression and transmission.However,current diagnostic tests have limitations in terms of accuracy and sensitivity,making it challenging to diagnose these different infection states.Therefore,this study intends to develop a promising biomarker for LTBI and ATB diagnosis to overcome the limitations of the current diagnostic tests.Methods:We developed a novelmultiepitope-based diagnostic biomarker(MEBDB)fromLTBI region of differentiation antigens using bioinformatics and immunoinformatics.Immune responses induced byMEBDM were detected using enzyme-linked immunosorbent spot and cytometric bead assays.This study was conducted from April 2022 to December 2022 in the SeniorDepartment of Tuberculosis at the 8thMedical Center of PLA General Hospital,China.Blood samples were collected from participants with ATB,individuals with LTBI,and healthy controls(HCs).The diagnostic efficacy of MEBDB was evaluated using receiver operating characteristic curves.Results:A novel MEBDB,designated as CP19128P,was generated.CP19128P comprises 19 helper T lymphocyte epitopes,12 cytotoxic T lymphocyte epitopes,and 8 B-cell epitopes.In silico simulations demonstrated that CP19128P possesses strong affinity for Toll-like receptors and elicits robust innate and adaptive immune responses.CP19128P generated significantly higher levels of tumor necrosis factor(TNF-α),interleukin 4(IL-4),and IL-10 in ATB patients(n=7)and LTBI(n=8)individuals compared with HCs(n=62)(P<0.001).Moreover,CP19128P-induced specific cytokines could be used to discriminate LTBI and ATB from healthy subjects with high sensitivity and specificity.Combining IL-2 with IL-4 or TNF-α could differentiate LTBI from HCs(the area under the receiver operating characteristic curve[AUC],0.976[95% confidence interval[CI],0.934-1.000]or 0.986[0.956-1.000]),whereas combining IL-4 with IL-17A or TNF-α could differentiate ATB from HCs(AUC,0.887[0.782-0.993]or 0.984[0.958-1.000]).Conclusions:Our study revealed that CP19128P is a potential MEBDBfor the diagnosis of LTBI andATB.Our findings suggest a promising strategy for developing novel,accurate,and sensitive diagnostic biomarkers and identifying new targets for TB diagnosis and management.
文摘Immune checkpoint inhibitors represent a major therapeutic advance in non-small-cell lung cancer with several approved anti-programmed death-1 and anti-programmed death-L1 immunotherapies.A majority of patients however,will not respond to immune checkpoint inhibitors and display primary resistance while a subset of initially responsive patients will present secondary resistance.Thus,there is a crucial need for biomarkers to enable better prediction and diagnosis,and to overcome such resistance.Along with improvement in the understanding of immune escape,new biomarkers are being developed,including large scale proteomic,genomic and transcriptomic approaches in tumor and blood samples.We review the novel biomarkers that have been investigated in non-small-cell lung cancer and discuss how they can rationalize therapeutic strategies.
基金the RGC General Research Fund(17120720)Health and Medical Research Fund,Hong Kong(08192326)Conference and Research Committee grant from the University of Hong Kong to K.F.L.
文摘The human endometrium and embryo both produce microRNAs(miRNAs),which are involved in various physiological activities.Accumulating evident suggested that endometrial miRNAs are regulated by steroid hormones that modulate endometrial functions,whereas embryo-derived miRNAs play vital roles in maternal–embryo communication.The aberrant expression of endometriumor embryo-derived miRNAs can cause early pregnancy and gestational disorders,including repeated implantation failure,recurrent miscarriage,and pathological conditions such as endometriosis.miRNAs are,therefore,ideal candidates for conducting clinicopathological tests.Potential diagnostic and prognostic tests using miRNAs are under development;however,the therapeutic applications of miRNAs in regulating gestational disorders require further investigation.
基金This work was supported by the Research Grants Council(RGC)Theme-based Res Scheme Hong Kong(Grant No.T21-705/20-N)the RGC Collaborative Research Fund(Grant Nos.C4039-19GF and C7065-18GF)+1 种基金the RGC-General Research Fund(GRF)Hong Kong(Grant No.14163817)the Vice-Chancellor’s Discretionary Fund Chinese University of Hong Kong,China.
文摘Colorectal cancer(CRC)is one of the most frequently diagnosed cancers and the leading cause of cancer-associated deaths.Epidemiological studies have shown that both genetic and environmental risk factors contribute to the development of CRC.Several metagenomic studies of CRC have identified gut dysbiosis as a fundamental risk factor in the evolution of colorectal malignancy.Although enormous efforts and substantial progresses have been made in understanding the relationship between human gut microbiome and CRC,the precise mechanisms involved remain elusive.Recent data have shown a direct causative role of the gut microbiome in DNA damage,inflammation,and drug resistance in CRC,suggesting that modulation of gut microbiome could act as a powerful tool in CRC prevention and therapy.Here,we provide an overview of the relationship between gut microbiome and CRC,and explore relevant mechanisms of colorectal tumorigenesis.We next highlight the potential of bacterial species as clinical biomarkers,as well as their roles in therapeutic response.Factors limiting the clinical translation of gut microbiome and strategies for resolving current challenges are further discussed.
基金This project was supported by grants from the Research Foundation of Nordsijallands Hospital,the Research Foundation for Health Research of the Capital Region of Denmark,and Helen Rude's Foundation.
文摘Background:MicroRNAs(miRNAs)are small non-coding RNA molecules that function as posttranscriptional regulators of gene expression.Measurements of miRNAs in cerebrospinal fluid(CSF)and blood have just started gaining attention as a novel diagnostic tool for various neurological conditions.The purpose of this exploratory investigation was to analyze the expression of miRNAs in CSF and blood of patients with Alzheimer’s disease(AD)and other neurodegenerative disorders in order to identify potential miRNA biomarker candidates able to separate AD from other types of dementia.Methods:CSF was collected by lumbar puncture performed on 10 patients diagnosed with AD and 10 patients diagnosed with either vascular dementia,frontotemporal dementia or dementia with Lewy bodies.Blood samples were taken immediately after.Total RNA was extracted from cell free fractions of CSF and plasma,and a screening for 372 known miRNA sequences was carried out by real time quantitative polymerase chain reactions(miRCURY LNA™Universal RT miRNA PCR,Polyadenylation and cDNA synthesis kit,Exiqon).Results:Fifty-two miRNAs were detected in CSF in at least nine out of ten patients in both groups.Among these,two miRNAs(let-7i-5p and miR-15a-5p)were found significantly up-regulated and one miRNA(miR-29c-3p)was found significantly down-regulated in patients with AD compared to controls.One hundred and sixty-eight miRNAs were frequently detected in the blood,among which miR-590-5p and miR-142-5p were significantly up-regulated and miR-194-5p was significantly down-regulated in AD patients compared to controls.Conclusions:Detection of miRNA expression profiles in blood and in particular CSF of patients diagnosed with different types of dementia is feasible and it seems that several expressional differences between AD and other dementia types do exist when measured in a clinically relevant setup.In this explorative pilot study,the deregulated miRNAs in CSF of AD patients may be associated with relevant target genes related to AD pathology,including APP and BACE1,which suggests that miRNAs are interesting candidates for AD biomarkers in the future.