Targeting therapy for hepatocellular carcinoma by delivering microRNAs as exosomal cargo

Exosomes,the smallest extracellular vesicles,have gained significant attention as key mediators in intercellular communication,influencing both physiological and pathological processes,particularly in cancer progression.A recent review article by Wang et al was published in a timely manner to stimulate future research and facilitate practical developments for targeted treatment of hepatocellular carcinoma using exosomes,with a focus on the origin from which exosomes derive.If information about the mechanisms for delivering exosomes to specific cells is incorporated,the concept of targeted therapy for hepatocellular carcinoma using exosomes could be more comprehensively understood.

ExosomalmicroRNA let-7c-5p enhances cell malignant characteristics by inhibiting TAGLN in oral cancer

Background:Oral cancer,a malignancy that is prevalent worldwide,is often diagnosed at an advanced stage.MicroRNAs(miRNAs)in circulating exosomes have emerged as promising cancer biomarkers.The role of miRNA let-7c-5p in oral cancer remains underexplored,and its potential involvement in tumorigenesis warrants comprehensive investigation.Methods:Serum samples from 30 patients with oral cancer and 20 healthy controls were used to isolate exosomes and quantify their RNA content.Isolation of the exosomes was confirmed through transmission electron microscopy.Quantitative PCR was used to assess the miRNA profiles.The effects of let-7c-5p and TAGLN overexpression on oral cancer cell viability,migration,and invasion were analyzed via CCK-8 and Transwell assays.Moreover,we conducted mRNA sequencing of exosomal RNA from exosomes overexpressing let-7c-5p to delineate the gene expression profile and identify potential let-7c-5p target genes.Results:let-7c-5p was upregulated in serumderived exosomes of patients with oral cancer.Overexpression of let-7c-5p in the TCA8113 and CAL-27 cell lines enhanced their proliferative,migratory,and invasive capacities,and overexpression of let-7c-5p cell-derived exosomes promoted oral cancer cell invasiveness.Exosomal mRNA sequencing revealed 2,551 differentially expressed genes between control cell-derived exosomes and overexpressed let-7c-5p cell-derived exosomes.We further identified TAGLN as a direct target of let-7c-5p,which has been implicated in modulating the oncogenic potential of oral cancer cells.Overexpression of TAGLN reverses the promoting role of let-7c-5p on oral cancer cells.Conclusion:Our findings highlight the role of exosomal let-7c-5p in enhancing oral cancer cell aggressiveness by downregulating TAGLN expression,highlighting its potential as a diagnostic and therapeutic strategy.

Exosomal microRNAs in hepatocellular carcinoma,expanding research field

In this editorial we comment on the review by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.Small extracellular vesicles(exosomes)play important roles in the tumor microenvironment.In this review,the authors introduce the following points:(1)The composition and function of exosomal microRNAs(miRNAs)of different cell origins in hepatocellular carcinoma(HCC);(2)the crosstalk between exosomal miRNAs from stromal cells and immune cells in the tumor microenvironment and the progression of HCC;and(3)the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC.In addition,the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC was introduced.In this review,the authors give us an overview of the exosomal RNA and summarize the function of exosomal RNA in HCC,which provides a deeper understanding of exosomal miRNAs to the readers.

Urinary exosomal microRNA-145-5p and microRNA-27a-3p act as noninvasive diagnostic biomarkers for diabetic kidney disease

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.

Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend.A more sensitive in-house assay suggested possible inflammasome activation during the disease course.A trend for clinical stabilization was observed during the infusion period.Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles.Initial findings suggest that this approach is safe.

Application of exosomal miRNA mediated macrophage polarization in colorectal cancer:Current progress and challenges

Colorectal cancer(CRC)is a major global health problem with high morbidity and mortality rates.Surgical resection is the main treatment for early-stage CRC,but detecting it early is challenging.Therefore,effective therapeutic targets for advanced patients are still lacking.Exosomes,tiny vesicles in body fluids,play a crucial role in tumor metastasis,immune regulation,and drug resistance.Interestingly,they can even serve as a biomarker for cancer diagnosis and prognosis.Studies have shown that exosomes can carry miRNA,mediate the polarization of M1/M2 macrophages,promote the proliferation and metastasis of cancer cells,and affect the prognosis of CRC.Since the gastrointestinal tract has many macrophages,understanding the mechanism behind exosomal miRNA-mediated macrophage polarization in CRC treatment is crucial.This article summarizes recent advancements in the study of exosomal miRNAs in CRC and their potential as diagnostic and prognostic markers.

Exosomal miR-23b from bone marrow mesenchymal stem cells alleviates oxidative stress and pyroptosis after intracerebral hemorrhage

Our previous studies showed that miR-23b was downregulated in patients with intracerebral hemorrhage(ICH). This indicates that miR-23b may be closely related to the patho-physiological mechanism of ICH, but this hypothesis lacks direct evidence. In this study, we established rat models of ICH by injecting collagenase Ⅶ into the right basal ganglia and treating them with an injection of bone marrow mesenchymal stem cell(BMSC)-derived exosomal miR-23b via the tail vein. We found that edema in the rat brain was markedly reduced and rat behaviors were improved after BMSC exosomal miR-23b injection compared with those in the ICH groups. Additionally, exosomal miR-23b was transported to the microglia/macrophages, thereby reducing oxidative stress and pyroptosis after ICH. We also used hemin to mimic ICH conditions in vitro. We found that phosphatase and tensin homolog deleted on chromosome 10(PTEN) was the downstream target gene of miR-23b, and exosomal miR-23b exhibited antioxidant effects by regulating the PTEN/Nrf2 pathway. Moreover, miR-23b reduced PTEN binding to NOD-like receptor family pyrin domain containing 3(NLRP3) and NLRP3 inflammasome activation, thereby decreasing the NLRP3-dependent pyroptosis level. These findings suggest that BMSC-derived exosomal miR-23b exhibits antioxidant effects through inhibiting PTEN and alleviating NLRP3 inflammasome-mediated pyroptosis, thereby promoting neurologic function recovery in rats with ICH.

Bioengineered exosomal-membrane-camouflaged abiotic nanocarriers: neurodegenerative diseases, tissue engineering and regenerative medicine

A bio-inspired strategy has recently been developed for camouflaging nanocarriers with biomembranes,such as natural cell membranes or subcellular structure-derived membranes.This strategy endows cloaked nanomaterials with improved interfacial properties,superior cell targeting,immune evasion potential,and prolonged duration of systemic circulation.Here,we summarize recent advances in the production and application of exosomal membrane-coated nanomaterials.The structure,properties,and manner in which exosomes communicate with cells are first reviewed.This is followed by a discussion of the types of exosomes and their fabrication methods.We then discuss the applications of biomimetic exosomes and membrane-cloaked nanocarriers in tissue engineering,regenerative medicine,imaging,and the treatment of neurodegenerative diseases.Finally,we appraise the current challenges associated with the clinical translation of biomimetic exosomal membrane-surface-engineered nanovehicles and evaluate the future of this technology.

Exosomal miRNA in early-stage hepatocellular carcinoma

The incidence and mortality of hepatic carcinoma(HCC)remain high,and early diagnosis of HCC is seen as a key approach in improving clinical outcomes.However,the sensitivity and specificity of current early screening methods for HCC are not satisfactory.In recent years,research around exosomal miRNA has gradually increased,and these molecules have emerged as attractive candidates for early diagnosis and treatment of HCC.This review summarizes the feasibility of using miRNAs in peripheral blood exosomes as early diagnostic tools for HCC.

Exosomal miR-30a-5p targets NLRP3 to suppress podocyte pyroptosis in diabetic nephropathy

Background:Mesenchymal stem cell(MSC)-derived exosomes are closely related to pyroptosis in diabetic nephropathy(DN).This study aimed to explore the protective effect of exosomal miR-30a-5p on podocyte pyroptosis in DN.Methods:Streptozotocin was used to establish the mouse model of DN.Human bone marrow MSC-derived exosomes were extracted and identified via transmission electron microscopy,nanoparticle tracking analysis,and western blotting.MiR-30a-5p mimics and non-control(NC)mimics were transfected into MSCs and podocytes,and exosomes were isolated from the MSCs.High glucose(HG)-induced podocyte model was established to determine the effect of exosomal miR-30a-5p on pyroptosis and inflammation in vitro.Results:MiR-30a-5p was expressed at low levels in DN models,while NLR family pyrin domain containing 3(NLRP3),caspase-1,gasdermin-N(GSDMD-N),and pro-inflammatory factors(tumor necrosis factor-alpha,interleukin(IL)-1beta,and IL-18)were augmented.In vitro,miR-30a-5p expression in the HG-damaged podocytes was down-regulated,while NLRP3 was up-regulated.Interestingly,miR-30a-5p overexpression diminished HG-induced podocyte injury,as proven by increased activity and decreased pyroptosis of podocytes.Concurrently,the up-regulation of miR-30a-5p could inhibit the expression of pro-inflammatory factors,caspase-1,GSDMD-N,and NLRP3 in HG-induced podocytes.MSC-derived exosomal miR-30a-5p treatment of HG-damaged cells has similar effects to miR-30a-5p mimics treatment.Overexpression of NLRP3 reversed the effect of miR-30a-5p mimics on HG-induced podocytes.Conclusion:This research confirmed that exosomal miR-30a-5p regulates pyroptosis via mediating NLRP3 in DN.

Function and biomedical implications of exosomal microRNAs delivered by parenchymal and nonparenchymal cells in hepatocellular carcinoma

Small extracellular vesicles(exosomes)are important components of the tumor microenvironment.They are small membrane-bound vesicles derived from almost all cell types and play an important role in intercellular communication.Exosomes transmit biological molecules obtained from parent cells,such as proteins,lipids,and nucleic acids,and are involved in cancer development.MicroRNAs(miRNAs),the most abundant contents in exosomes,are selectively packaged into exosomes to carry out their biological functions.Recent studies have revealed that exosome-delivered miRNAs play crucial roles in the tumorigenesis,progression,and drug resistance of hepatocellular carcinoma(HCC).In addition,exosomes have great industrial prospects in the diagnosis,treatment,and prognosis of patients with HCC.This review summarized the composition and function of exosomal miRNAs of different cell origins in HCC and highlighted the association between exosomal miRNAs from stromal cells and immune cells in the tumor microenvironment and the progression of HCC.Finally,we described the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC.

Plasma exosomal hsa_circ_0079439 as a novel biomarker for early detection of gastric cancer

BACKGROUND Due to the poor prognosis of gastric cancer(GC),early detection methods are urgently needed.Plasma exosomal circular RNAs(circRNAs)have been suggested as novel biomarkers for GC.AIM To identify a novel biomarker for early detection of GC.METHODS Healthy donors(HDs)and GC patients diagnosed by pathology were recruited.Nine GC patients and three HDs were selected for exosomal whole-transcriptome RNA sequencing.The expression profiles of circRNAs were analyzed by bioinformatics methods and validated by droplet digital polymerase chain reaction.The expression levels and area under receiver operating characteristic curve values of plasma exosomal circRNAs and standard serum biomarkers were used to compare their diagnostic efficiency.RESULTS There were 303 participants,including 240 GC patients and 63 HDs,involved in the study.The expression levels of exosomal hsa_circ_0079439 were significantly higher in GC patients than in HDs(P<0.0001).However,the levels of standard serum biomarkers were similar between the two groups.The area under the curve value of exosomal hsa_circ_0079439 was higher than those of standard biomarkers,including carcinoembryonic antigen,carbohydrate antigen(CA)19-9,CA72-4,alpha-fetoprotein,and CA125(0.8595 vs 0.5862,0.5660,0.5360,0.5082,and 0.5018,respectively).The expression levels of exosomal hsa_circ_0079439 were significantly decreased after treatment(P<0.05).Moreover,the expression levels of exosomal hsa_circ_0079439 were obviously higher in early GC(EGC)patients than in HDs(P<0.0001).CONCLUSION Our results suggest that plasma exosomal hsa_circ_0079439 is upregulated in GC patients.Moreover,the levels of exosomal hsa_circ_0079439 could distinguish EGC and advanced GC patients from HDs.Therefore,plasma exosomal hsa_circ_0079439 might be a potential biomarker for the diagnosis of GC during both the early and late stages.

Circulating exosomal lncRNA contributes to the pathogenesis of spinal cord injury in rats

Exosome-derived long non-coding RNAs(lncRNAs)are extensively engaged in recovery and repair of the injured spinal cord,through different mechanisms.However,to date no study has systematically evaluated the differentially expressed lncRNAs involved in the development of spinal cord injury.Thus,the aim of this study was to identify key circulating exosome-derived lncRNAs in a rat model of spinal cord injury and investigate their potential actions.To this end,we established a rat model of spinal cord hemisection.Circulating exosomes were extracted from blood samples from spinal cord injury and control(sham)rats and further identified through Western blotting and electron microscopy.RNA was isolated from the exosomes and sequenced.The enrichment analysis demonstrated that there were distinctively different lncRNA and mRNA expression patterns between the two groups.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis and Gene Ontology(GO)functional analysis were performed to determine the possible involvements of upregulated and downregulated lncRNAs in various pathways and different biological processes,as well as their cellular locations and molecular functions.Furthermore,quantitative reverse transcription-polymerase chain reaction showed that the expression of five lncRNAs––ENSRN0T00000067908,XR_590093,XR_591455,XR_360081,and XR_346933––was increased,whereas the expression of XR_351404,XR_591426,XR_353833,XR_590076,and XR_590719 was decreased.Of note,these 10 lncRNAs were at the center of the lncRNA-miRNA-mRNA coexpression network,which also included 198 mRNAs and 41 miRNAs.Taken together,our findings show that several circulating exosomal lncRNAs are differentially expressed after spinal cord injury,suggesting that they may be involved in spinal cord injury pathology and pathogenesis.These lncRNAs could potentially serve as targets for the clinical diagnosis and treatment of spinal cord injury.

Bone marrow mesenchymal stem cell-derived exosomal microRNAs target PI3K/Akt signaling pathway to promote the activation of fibroblasts

BACKGROUND Fibroblast plays a major role in tendon-bone healing.Exosomes derived from bone marrow mesenchymal stem cells(BMSCs)can activate fibroblasts and promote tendon-bone healing via the contained microRNAs(miRNAs).However,the underlying mechanism is not comprehensively understood.Herein,this study aimed to identify overlapped BMSC-derived exosomal miRNAs in three GSE datasets,and to verify their effects as well as mechanisms on fibroblasts.AIM To identify overlapped BMSC-derived exosomal miRNAs in three GSE datasets and verify their effects as well as mechanisms on fibroblasts.METHODS BMSC-derived exosomal miRNAs data(GSE71241,GSE153752,and GSE85341)were downloaded from the Gene Expression Omnibus(GEO)database.The candidate miRNAs were obtained by the intersection of three data sets.TargetScan was used to predict potential target genes for the candidate miRNAs.Functional and pathway analyses were conducted using the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases,respectively,by processing data with the Metascape.Highly interconnected genes in the protein-protein interaction(PPI)network were analyzed using Cytoscape software.Bromodeoxyuridine,wound healing assay,collagen contraction assay and the expression of COL I andα-smooth muscle actin positive were applied to investigate the cell proliferation,migration and collagen synthesis.Quantitative real-time reverse transcription polymerase chain reaction was applied to determine the cell fibroblastic,tenogenic,and chondrogenic potential.RESULTS Bioinformatics analyses found two BMSC-derived exosomal miRNAs,has-miR-144-3p and hasmiR-23b-3p,were overlapped in three GSE datasets.PPI network analysis and functional enrichment analyses in the GO and KEGG databases indicated that both miRNAs regulated the PI3K/Akt signaling pathway by targeting phosphatase and tensin homolog(PTEN).In vitro experiments confirmed that miR-144-3p and miR-23b-3p stimulated proliferation,migration and collagen synthesis of NIH3T3 fibroblasts.Interfering with PTEN affected the phosphorylation of Akt and thus activated fibroblasts.Inhibition of PTEN also promoted the fibroblastic,tenogenic,and chondrogenic potential of NIH3T3 fibroblasts.CONCLUSION BMSC-derived exosomes promote fibroblast activation possibly through the PTEN and PI3K/Akt signaling pathways,which may serve as potential targets to further promote tendon-bone healing.

Circulating Exosomal Lnc RNAs as Novel Diagnostic Predictors of Severity and Sites of White Matter Hyperintensities

Objective Exosomal long noncoding RNAs(lnc RNAs) are the key to diagnosing and treating various diseases. This study aimed to investigate the diagnostic value of plasma exosomal lnc RNAs in white matter hyperintensities(WMH).Methods We used high-throughput sequencing to determine the differential expression(DE) profiles of lnc RNAs in plasma exosomes from WMH patients and controls. The sequencing results were verified in a validation cohort using q RT-PCR. The diagnostic potential of candidate exosomal lnc RNAs was proven by binary logistic analysis and receiver operating characteristic(ROC) curves. The diagnostic value of DE exo-lnc RNAs was determined by the area under the curve(AUC). The WMH group was then divided into subgroups according to the Fazekas scale and white matter lesion site, and the correlation of DE exo-lnc RNAs in the subgroup was evaluated.Results In our results, four DE exo-lnc RNAs were identified, and ROC curve analysis revealed that exolnc_011797 and exo-lnc_004326 exhibited diagnostic efficacy for WMH. Furthermore, WMH subgroup analysis showed exo-lnc_011797 expression was significantly increased in Fazekas 3 patients and was significantly elevated in patients with paraventricular matter hyperintensities.Conclusion Plasma exosomal lnc RNAs have potential diagnostic value in WMH. Moreover, exolnc_011797 is considered to be a predictor of the severity and location of WMH.

Exosomal miR-320e through wnt2targeted inhibition of the Wnt/β-catenin pathway allevisate cerebral small vessel disease and cognitive impairment

BACKGROUND Exosomal miRNAs play crucial roles in many central nervous system diseases.Cerebral small vessel disease(CVSD)is a small vessel disease that is affected by various factors.This study aimed to investigate the role of exosomal miR-320e in the Wnt/β-catenin pathway stimulated by oxidative stress and assess its clinical correlation with psychiatric symptoms in patients with CVSD.AIM To explore whether exosomal miR-320e could suppress the Wnt/β-catenin pathway and play a protective role in CVSD progression,as well as examine its potential correlation with cognitive impairment and depression in patients with CVSD.METHODS Differentially expressed exosomal miRNAs were filtered by sequencing plasma exosomes from patients with CVSD and healthy controls.Bioinformatics and dual luciferase analyses were used to confirm the binding of miR-320e to Wnt2,and the mRNA and protein levels of downstream components in the Wnt/β-catenin pathway were evaluated when overexpressed or with knockdown of miR-320e under H2O2-induced oxidative stress.In addition,Wnt2-targeting siRNA was used to confirm the role of miR-320e in the Wnt2-mediated inhibition of the Wnt/β-catenin pathway.A retrospective analysis was conducted among patients with CVSD to confirm the correlation between miR-320e expression and the severity of cognitive impairment and depression,which were quantified using the Montreal Cognitive Assessment(MoCA)/Executive Function Assessment(EFA),and the Hamilton Depression Scale(HAMD)/Beck Depression Inventory(BDI),respectively.RESULTS High-throughput sequencing revealed that exosomal miR-320e was downregulated in patients with CVSD.Bioinformatics analysis and dual-luciferase reporter gene experiments showed that exosomal miR-320e inhibited the Wnt/β-catenin pathway in response to oxidative stress by targeting the 3'noncoding region of Wnt2.Uptake of exosomes carrying miR-320e into endothelial cells could also target Wnt2 and inhibit the Wnt2/β-catenin pathway.Elevated miR-320e expression may protect patients with CVSD from relatively severe cognitive impairment and depression,as it was found to have a positive correlation with the MoCA/EFA and HAMD/BDI scores.CONCLUSION Our results suggest that exosomal miR-320e suppresses the Wnt/β-catenin pathway and may play a protective role in CVSD progression.

Exosomal miRNAs在肿瘤治疗中的研究进展

microRNAs(miRNAs)是一组由20~22个核苷酸组成的小的非编码RNA超家族,主要在转录后水平调节靶基因的表达。miRNAs在维持机体正常的发育、器官形成和内环境稳态等方面发挥着重要的调节作用,其异常的表达与许多疾病的发生具有密切的关联,例如肿瘤等。目前已有大量的研究表明,miRNAs在肿瘤的发生发展、耐药和转移等方面发挥着重要的作用。近几年的研究发现,miRNAs不仅存在于细胞内,也来源于多种细胞类型(包括树突状细胞、淋巴细胞和肿瘤细胞等)的外泌体(exosomes)中。exosomal miRNAs在细胞间遗传信息的传递中发挥着重要的功能,并被认为是重要的肿瘤诊断和预后的生物标志物。本文总结了miRNAs和exosomes的生物学特性和功能,exosomal miRNA在肿瘤发生发展中的作用,以及以exosomal miRNA为靶点的抗肿瘤治疗策略的研究进展,以期为肿瘤的治疗提供新的思路。

Blood exosomal micro ribonucleic acid profiling reveals the complexity of hepatocellular carcinoma and identifies potential biomarkers for differential diagnosis

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related deaths worldwide,but there is a shortage of effective biomarkers for its diagnosis.AIM To explore blood exosomal micro ribonucleic acids(miRNAs)as potential biomarkers for HCC diagnosis.RESULTS The principal component analysis suggested that daily alcohol consumption could alter the blood exosomal miRNA profiles of hepatitis B virus positive non-HCC patients through miR-3168 and miR-223-3p.The miRNA profiles also revealed the tumor stages of HCC patients.High expression of miR-455-5p and miR-30c-5p,which significantly correlated with better overall survival in tumor tissues,could also be detected in blood exosomes.Two pairs of miRNAs(miR-584-5p/miR-106-3p and miR-628-3p/miR-941)showed a 94.1%sensitivity and 68.4%specificity to differentiate HCC patients from non-HCC patients.The specificity of the combination was substantially influenced by alcohol consumption habits.CONCLUSION This study suggested that blood exosomal miRNAs can be used as new noninvasive diagnostic tools for HCC.However,their accuracy could be affected by tumor stage and alcohol consumption habits.

Exosomal microRNAs from mesenchymal stem/stromal cells: Biology and applications in neuroprotection

Mesenchymal stem/stromal cells(MSCs)are extensively studied as cell-therapy agents for neurological diseases.Recent studies consider exosomes secreted by MSCs as important mediators for MSCs’neuroprotective functions.Exosomes transfer functional molecules including proteins,lipids,metabolites,DNAs,and coding and non-coding RNAs from MSCs to their target cells.Emerging evidence shows that exosomal microRNAs(miRNAs)play a key role in the neuroprotective properties of these exosomes by targeting several genes and regulating various biological processes.Multiple exosomal miRNAs have been identified to have neuroprotective effects by promoting neurogenesis,neurite remodeling and survival,and neuroplasticity.Thus,exosomal miRNAs have significant therapeutic potential for neurological disorders such as stroke,traumatic brain injury,and neuroinflammatory or neurodegenerative diseases and disorders.This review discusses the neuroprotective effects of selected miRNAs(miR-21,miR-17-92,miR-133,miR-138,miR-124,miR-30,miR146a,and miR-29b)and explores their mechanisms of action and applications for the treatment of various neurological disease and disorders.It also provides an overview of state-of-the-art bioengineering approaches for isolating exosomes,optimizing their yield and manipulating the miRNA content of their cargo to improve their therapeutic potential.

Exosomal microRNA在儿童肾母细胞瘤诊断中的作用

目的探讨exosomal microRNA在儿童Wilms瘤(WT)诊断中的作用。方法选取30例儿童WT患儿为观察组,以30例同期健康体检儿童为对照组。采用差速离心法提取2组患儿尿液中外泌体(exosome);采用荧光定量PCR检测exosome中特异性表达的microRNA;以miRNA-21相对表达量绘制ROC曲线。结果观察组miRNA-21相对表达量为2.92高于对照组的0.65,差异有统计学意义(P<0.001)。观察组miRNA-21在儿童WT诊断效能中曲线下面积AUC值为0.95(95%CI=0.903~0.996);当miRNA-21相对表达量的截断值为0.75时,诊断灵敏度为82.1%,特异度为94.1%。结论exosomal microRNA作为分子标志物在儿童WT中表达异常,可获得较高的诊断灵敏度及特异度,以辅助临床诊断。