Optimized rAAV8 targeting acinar KLF4 ameliorates fibrosis in chronic pancreatitis via exosomes-enriched let-7s suppressing pancreatic stellate cells activation.

Chronic pancreatitis (CP) is marked by progressive fibrosis and the activation of pancreatic stellate cells (PSCs), accompanied by the destruction of pancreatic parenchyma, leading to the loss of acinar cells (ACs). Few research studies have explored the mechanism by which damaged ACs (DACs) contribute to PSCs activation and pancreatic fibrosis. Currently, there are no effective drugs for curing CP or limiting the progression of pancreatic fibrosis. In this research, co-culture with intact acinar cells (IACs) suppressed PSC activation, while co-culture with DACs did the opposite. Krüppel-like factor 4 (KLF4) was significantly upregulated in DACs and was established as the key molecule that switches ACs from PSCs-suppressor to PSCs-activator. We revealed the exosomes of IACs contributed to the anti-activated function of IACs-CS on PSCs. MiRNome profiling showed that let-7 family is significantly enriched in IAC-derived exosomes (>30% miRNome), which partially mediates IACs' suppressive impacts on PSCs. Furthermore, it has been observed that the enrichment of let-7 in exosomes was influenced by the expression level of KLF4. Mechanistic studies demonstrated that KLF4 in ACs upregulated Lin28A, thereby decreasing let-7 levels in AC-derived exosomes, and thus promoting PSCs activation. We utilized an adeno-associated virus specifically targeting KLF4 in ACs (shKLF4-pAAV) to suppress PSCs activation in CP, resulting in reduced pancreatic fibrosis. IAC-derived exosomes hold potential as potent weapons against PSCs activation via let-7s, while activated KLF4/Lin28A signaling in DACs diminished such functions. ShKLF4-pAAV holds promise as a novel therapeutic approach for CP.

A Novel Serum Exosomal miRNA Signature in the Early Prediction of Persistent Organ Failure in Patients with Acute Pancreatitis.

OBJECTIVE: Current study aims to investigate whether serum exosomal microRNAs (miRNAs) could be potential biomarkers in predicting APs with POF at early phase. BACKGROUND: Novel biomarkers are sorely needed for early prediction of persistent organ failure (POF) in acute pancreatitis (AP) patients. METHODS: In the discovery stage, exosomal miRNAs were profiled in sera from APs with or without POF (5 vs. 5) using microarrays. POF-associated miRNA signatures then were assessed in training cohort (n=227) and further validated in three independent cohorts (n=516), including one nested case-control cohort. RESULTS: A total of 743 APs were recruited in this large-scale biomarker identification study with a nested case-control study. Data from the discovery cohort demonstrated that 90 exosomal miRNAs were significantly dysregulated in APs with POF compared with controls. One miRNA classifier (Cmi) comprising 3 miRNAs (miR-4265, 1208, 3127-5p) was identified in the training cohort, and was further evaluated in two validation cohorts for their predictive value for POF. AUCs for Cmi ranged from 0.88 to 0.90, which was statistically superior to AUCs of APACHE-II and BISAP, and outperformed BUN and creatinine in POF prediction across all cohorts (P<.05). Higher levels of Cmi indicated increased need for ICU admission, prolonged hospitalization, and elevated mortality rate, thus poor prognosis. In the nested case-control study, Cmi could help identify prediagnostic POF in post-ERCP pancreatitis cases within "golden hours" after ERCP with high efficacy. CONCLUSIONS: Serum exosomal Cmi may be an early predictor for POF in AP, even within "golden hours" after AP onset. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02602808).

MKLN1-AS promotes pancreatic cancer progression as a crucial downstream mediator of HIF-1α through miR-185-5p/TEAD1 pathway.

In pancreatic ductal adenocarcinomas (PDAC), profound hypoxia plays key roles in regulating cancer cell behavior, including proliferation, migration, and resistance to therapies. The initial part of this research highlights the important role played by long noncoding RNA (lncRNA) MKLN1-AS, which is controlled by hypoxia-inducible factor-1 alpha (HIF-1α), in the progression of PDAC. Human samples of PDAC showed a notable increase in MKLN1-AS expression, which was linked to a worse outcome. Forced expression of MKLN1-AS greatly reduced the inhibitory impact on the growth and spread of PDAC cells caused by HIF-1α depletion. Experiments on mechanisms showed that HIF-1α influences the expression of MKLN1-AS by directly attaching to a hypoxia response element in the promoter region of MKLN1-AS.MKLN1-AS acts as a competitive endogenous RNA (ceRNA) by binding to miR-185-5p, resulting in the regulation of TEAD1 expression and promoting cell proliferation, migration, and tumor growth. TEAD1 subsequently enhances the development of PDAC. Our study results suggest that MKLN1-AS could serve as a promising target for treatment and a valuable indicator for predicting outcomes in PDAC. PDAC is associated with low oxygen levels, and the long non-coding RNA MKLN1-AS interacts with TEAD1 in this context.

Comprehensive expression analysis reveals several miRNAs against acute pancreatitis via modulating autophagy.

Acute pancreatitis (AP) had been one of the main reasons for hospitalization worldwide. However, the mechanisms related to AP remained to be unclear. This study identified 37 miRNAs and 189 mRNAs were differentially expressed in pancreatitis and normal samples. Bioinformatics analysis showed DEGs were significantly related to PI3K-Akt signaling, FoxO signaling, Oocyte meiosis, Focal adhesion, and Protein digestion and absorption. By constructing a signaling-DEGs regulation network, we found COL12A1, DPP4, COL5A1, COL5A2, and SLC1A5 were related to regulating Protein digestion and absorption, THBS2, BCL2, NGPT1, EREG, COL1A1 were related to regulating PI3K signaling, CCNB1, CDKN2B, IRS2, PLK2 were related to modulating FOXO signaling. Next, we constructed 1 miRNA-mRNA regulation network in AP, consisting of 34 miRNAs and 96 mRNAs. The protein-protein interaction networks and the miRNA-targets networks analysis show that hsa-miR-199a-5p, hsa-miR-150, hsa-miR-194, COL6A3 and CNN1 acted as hub regulators in AOf note, through comprehensive expression analysis, we found several miRNAs and mRNAs were significantly related to modulating autophagy signaling in AP, including hsa-miR-181c, hsa-miR-181d, hsa-miR-181b, hsa-miR-379 and hsa-miR-199a-5Overall, this study screening differently expressed miRNAs in AP and revealed miRNA- autophagy regulation may serve as a potential prognosis and Therapeutic marker for AP.

Independent risk factors for esophageal refractory stricture after extensive endoscopic submucosal dissection.

BACKGROUND: Endoscopic submucosal dissection (ESD) is accepted as a standard therapeutic technique for superficial esophageal neoplasms (SENs). However, esophageal refractory stricture is a serious adverse event secondary to extensive ESD (≥ 3/4 of the luminal circumference). This retrospective study aimed to investigate the risk factors for refractory postoperative stricture after extensive ESD. METHODS: The data of patients who underwent esophageal ESD at the Endoscopy Center of Changhai Hospital were reviewed between January 2011 and September 2019. Risk factors for postoperative refractory stricture [≥ 6 sessions of endoscopic balloon dilation (EBD)] after extensive ESD were then identified using univariate analysis and multivariate logistic regression analysis. RESULTS: A total of 69 SENs in 67 patients treated by extensive ESD were enrolled in this study. The refractory stricture incidence was 62% (43/69). Significant differences between non-refractory stricture group and refractory stricture group were observed in depth of infiltration (m1or m2/m3 or sm1:20/6 vs. 17/26, P = 0.003), longitudinal resection length (< 50 mm/ ≥ 50 mm:19/7 vs. 10/33, P < 0.001), circumferential range (3/4~ < 1/1:20/6 vs. 19/24, P = 0.008), muscular injury (NO/YES:18/8 vs. 19/24, P = 0.043), and clip number (≤ 5/ > 5:15/11 vs. 12/31, P = 0.014). Multivariate analysis revealed that longitudinal resection length ≥ 50 mm (odds ratio [OR] 11.099, 95% confidence interval [CI] 2.620-47.019), depth of infiltration above m2 (OR 5.716, 95%CI 1.324-24.672) and muscular injury happened (OR 4.431, 95%CI 1.052-18.659) were independent risk factors for refractory stricture. In addition, the EBD sessions for treatment of refractory stricture was related to longitudinal resection length (relation coefficient γ = 0.528; P <0.05). CONCLUSIONS: The longitudinal resection length, depth of tumor infiltration and muscular injury are the reliable risk factors for esophageal refractory stricture after extensive ESD.

Evaluation of the Prognostic Role of the Wall Motion Score Index and the SYNTAX Score II in Patients with Acute Coronary Syndrome Following Percutaneous Coronary Intervention by Evaluation of Major Adverse Cardiovascular Events at 12-Month Follow-Up.

BACKGROUND This study aimed to evaluate the wall motion score (WMS) index and the SYNTAX score II (SSII) in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI) by evaluation of major adverse cardiovascular events (MACEs) at the 12-month follow-up at a single center. MATERIAL AND METHODS An observational study of 430 patients with ACS undergoing PCI at the Second Affiliated Hospital of Soochow University over a 1-year period was performed. Baseline data including WMS and SSII were recorded and compared with the rates of MACEs in the study group. WMS and SSII were stratified by the tercile from low to high. RESULTS Both WMS and SSII were associated with the rates of MACEs (P<0.001 and P=0.003, respectively). The incidence of MACEs was positively correlated with terciles of the WMS and SSII groups (3.7% vs 1.6% vs 7.0% [P<0.001] and 2.6% vs 5.8% vs 11.6% [P<0.001], lowest to highest, respectively). Logistic regression analyses identified combined predictors for 12-month outcome, including WMS and SSII. The use of a model combining both scores yielded a higher predictive value (area under the curve [AUC]=0.78; 95% confidence interval [CI], 0.733-0.835; P<0.001) than the use of either score alone. Using WMSs alone, the AUC was 0.73 (95% CI, 0.660-0.793; P<0.001). Using SSII alone, the AUC was 0.71 (95% CI, 0.649-0.769; P<0.001). CONCLUSIONS This study showed that the combined methods of the WMS index and the SSII were predictive factors of MACEs in patients with ACS following PCI at the 12-month follow-up.

Long noncoding RNA CCAL transferred from fibroblasts by exosomes promotes chemoresistance of colorectal cancer cells.

Long noncoding RNAs (lncRNAs) are involved in the pathology of colorectal cancer (CRC). Current efforts to eradicate CRC predominantly focused on targeting the proliferation of rapidly growing cancer epithelial cells. This is largely ineffective with resistance arising in most tumors after exposure to chemotherapy. Despite the long-standing recognition of the crosstalk between carcinoma-associated fibroblasts (CAFs) and cancer cells in the tumor microenvironment, how CAFs may contribute to drug resistance in neighboring cancer cells is not well characterized. Here, we show that lncRNA CCAL (colorectal cancer-associated lncRNA) promotes oxaliplatin (Oxa) resistance of CRC cells. RNA-ISH shows higher CCAL expressed in the tumor stroma compared to cancer nests of CRC tissues. Functional studies reveal that CCAL is transferred from CAFs to the cancer cells via exosomes, where it suppresses CRC cell apoptosis, confers chemoresistance and activates ß-catenin pathway in vitro and in vivo. Mechanistically, CCAL interacts directly with mRNA stabilizing protein HuR (human antigen R) to increase ß-catenin mRNA and protein levels. Our findings indicate that CCAL expressed by CAFs of the colorectal tumor stroma contributes to tumor chemoresistance and CCAL may serve as a potential therapeutic target for Oxa resistance.

[Pathogenesis, prevention and management of edema after prepuce surgery].

Prepuce diseases are very common conditions in urology and andrology, and quite a few cases need to be treated by surgery. Preputial edema is a common complication after prepuce surgery, with a higher incidence rate in children than in adults. Although preputial edema is just moderate symptom and does not affect urination, it worries or even distresses the patient both physically and psychologically. In recent years, rapid achievements have been made in prepuce surgery, as in prepuce circumcision, preputial neoplasm excision, and penile degloving repair, which can now be accomplished with shorter time and higher efficiency. Despite constant improvement in the methods and techniques for prepuce surgery, postoperative edema remains difficult to be totally prevented. Pathogenic factors for postoperative preputial edema vary from disturbance of blood circulation to inflammatory factor-induced change in capillary permeability, lymphatic circulation disorders, and neurogenic edema. Elimination of the pathogenic factors and precautionary measures after surgery count significantly to the prevention and management of postoperative preputial edema. This review focuses on the pathogenesis, prevention and treatment of edema after prepuce surgery.

A new descriptor for computer-aided diagnosis of EUS imaging to distinguish autoimmune pancreatitis from chronic pancreatitis.

BACKGROUND AND AIMS: Computer-aided diagnosis of EUS images was quite useful in differentiating pancreatic cancer from normal tissue and chronic pancreatitis. This study investigated the feasibility of using computer-aided diagnostic techniques to extract EUS image parameters to distinguish autoimmune pancreatitis from chronic pancreatitis. METHODS: A new descriptor, local ternary pattern variance, was introduced to improve the performance of the classification model. Patients with autoimmune pancreatitis (n = 81) or chronic pancreatitis (n = 100) were recruited for this study. Representative EUS images were selected, and 115 parameters from 10 categories were extracted from the region of interest. Distance-between-class and sequential forward selection algorithms were used for their ideal combination of features that allowed a support vector machine predictive model to be built, trained, and validated. The accuracy, sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) were used to evaluate the performance of experimental results. RESULTS: Fourteen parameters from 3 categories were selected as an ideal combination of features. The sample set was randomly divided into a training set and a testing set by using two different algorithms-the leave-one-out algorithm and the half-and-half method. The half-and-half method yielded an average (± standard deviation) accuracy of 89.3 ± 2.7%, sensitivity of 84.1 ± 6.4%, specificity of 92.5 ± 3.3%, PPV of 91.6 ± 3.7%, and NPV of autoimmune pancreatitis of 88.0 ± 4.1%. CONCLUSIONS: This study shows that, with the local ternary pattern variance textural feature, computer-aided diagnosis of EUS imaging may be valuable to differentiate autoimmune pancreatitis from chronic pancreatitis. Further refinement of such models could generate tools for the clinical diagnosis of autoimmune pancreatitis.

High serum carbohydrate antigen 125 concentration can predict serous effusion but not gastrointestinal malignancy in male patients.

This study aims to evaluate the diagnostic accuracy of carbohydrate antigen 125 (CA125) in male patients for predicting gastrointestinal malignant diseases. One hundred twenty consecutive male patients underwent CA125 test after admission to the Department of Gastroenterology in Changhai Hospital, the Second Military Medical University, from April to June 2013. Data of age, main symptoms, and final diagnosis were summarized. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of CA125 for malignancy were estimated, and the receiver operating characteristic (ROC) analysis and the area under the curve (AUC) were also performed to evaluate the diagnostic value of CA125 in male patients. The PPV, NPV, PLR, and NLR of CA125 in malignancy were 55 %, 69 %, 1.90, and 0.71, respectively. However, we found that an elevated serum CA125 level was more common in male patients with serous effusion than those with malignancy. The PPV, NPV, PLR, and NLR of CA125 in serous effusion were 85 %, 96 %, 12.70, and 0.09, respectively. In the ROC analysis, the AUC values for CA125 was 0.96 (95 % confidence interval, 0.93-0.99) for discriminating patients with serous cavity effusion from those without serous effusion. CA125 has a higher accuracy in detecting serous effusion than malignancy in male patients with gastrointestinal diseases. It is of little significance for male patients to perform CA125 test for malignancy.

Engineered bacterial outer membrane vesicles: a versatile bacteria-based weapon against gastrointestinal tumors.

Outer membrane vesicles (OMVs) are nanoscale lipid bilayer structures released by gram-negative bacteria. They share membrane composition and properties with their originating cells, making them adept at traversing cellular barriers. These OMVs have demonstrated exceptional membrane stability, immunogenicity, safety, penetration, and tumor-targeting properties, which have been leveraged in developing vaccines and drug delivery systems. Recent research efforts have focused on engineering OMVs to increase production yield, reduce cytotoxicity, and improve the safety and efficacy of treatment. Notably, gastrointestinal (GI) tumors have proven resistant to several traditional oncological treatment strategies, including chemotherapy, radiotherapy, and targeted therapy. Although immune checkpoint inhibitors have demonstrated efficacy in some patients, their usage as monotherapy remains limited by tumor heterogeneity and individual variability. The immunogenic and modifiable nature of OMVs makes them an ideal design platform for the individualized treatment of GI tumors. OMV-based therapy enables combination therapy and optimization of anti-tumor effects. This review comprehensively summarizes recent advances in OMV engineering for GI tumor therapy and discusses the challenges in the clinical translation of emerging OMV-based anti-tumor therapies.

Progress in Biomarkers Related to Biliary Atresia.

Biliary atresia (BA) is a congenital cholestatic disease that can seriously damage children's liver function. It is one of the main reasons for liver transplantation in children. Early diagnosis of BA is crucial to the prognosis of patients, but there is still a lack of reliable non-invasive diagnostic methods. Additionally, as some children are in urgent need of liver transplantation, evaluating the stage of liver fibrosis and postoperative native liver survival in children with BA using a straightforward, efficient, and less traumatic method is a major focus of doctors. In recent years, an increasing number of BA-related biomarkers have been identified and have shown great potential in the following three aspects of clinical practice: diagnosis, evaluation of the stage of liver fibrosis, and prediction of native liver survival. This review focuses on the pathophysiological function and clinical application of three novel BA-related biomarkers, namely MMP-7, FGF-19, and M2BPGi. Furthermore, progress in well-known biomarkers of BA such as gamma-glutamyltransferase, circulating cytokines, and other potential biomarkers is discussed, aiming to provide a reference for clinical practice.

Characterization of a cuproptosis-related signature to evaluate immune features and predict prognosis in colorectal cancer.

Purpose: Cuproptosis is a newly discovered type of cell death. Little is known about the roles that cuproptosis related genes (CRGs) play in colorectal cancer (CRC). The aim of this study is to evaluate the prognostic value of CRGs and their relationship with tumor immune microenvironment. Methods: TCGA-COAD dataset was used as the training cohort. Pearson correlation was employed to identify CRGs and paired tumor-normal samples were used to identify those CRGs with differential expression pattern. A risk score signature was constructed using LASSO regression and multivariate Cox stepwise regression methods. Two GEO datasets were used as validation cohorts for confirming predictive power and clinical significance of this model. Expression patterns of seven CRGs were evaluated in COAD tissues. In vitro experiments were conducted to validate the expression of the CRGs during cuproptosis. Results: A total of 771 differentially expressed CRGs were identified in the training cohort. A predictive model termed riskScore was constructed consisting of 7 CRGs and two clinical parameters (age and stage). Survival analysis suggested that patients with higher riskScore showed shorter OS than those with lower (P<0.0001). ROC analysis revealed that AUC values of cases in the training cohort for 1-, 2-, and 3-year survival were 0.82, 0.80, 0.86 respectively, indicating its good predictive efficacy. Correlations with clinical features showed that higher riskScore was significantly associated with advanced TNM stages, which were further confirmed in two validation cohorts. Single sample gene set enrichment analysis (ssGSEA) showed that high-risk group presented with an immune-cold phenotype. Consistently, ESTIMATE algorithm analysis showed lower immune scores in riskScore-high group. Expressions of key molecules in riskScore model are strongly associated with TME infiltrating cells and immune checkpoint molecules. Patients with a lower riskScore exhibited a higher complete remission rate in CRCs. Finally, seven CRGs involved in riskScore were significantly altered between cancerous and paracancerous normal tissues. Elesclomol, a potent copper ionophore, significantly altered expressions of seven CRGs in CRCs, indicating their relationship with cuproptosis. Conclusions: The cuproptosis-related gene signature could serve as a potential prognostic predictor for colorectal cancer patients and may offer novel insights into clinical cancer therapeutics.

Nuclear GRP78 Promotes Metabolic Reprogramming and Therapeutic Resistance in Pancreatic Ductal Adenocarcinoma.

PURPOSE: Stromal fibrosis limits nutritional supply and disarrays metabolism in pancreatic cancer (PDA, pancreatic ductal adenocarcinoma). Understanding of the molecular basis underlying metabolic cues would improve PDA management. The current study determined the interaction between glucose-regulated proteins 78 (GRP78) and hypoxia-inducible factor 1α (HIF-1α) and its mechanistic roles underlying PDA response to oxygen and glucose restrains. EXPERIMENTAL DESIGN: Gene expression and its association with clinicopathologic characteristics of patients with PDA and mouse models were analyzed using IHC. Protein expression and their regulation were measured by Western blot and immunoprecipitation analyses. Protein interactions were determined using gain- and loss-of-function assays and molecular methods, including chromatin immunoprecipitation, co-immunoprecipitation, and dual luciferase reporter. RESULTS: There was concomitant overexpression of both GRP78 and HIF-1α in human and mouse PDA tissues and cells. Glucose deprivation increased the expression of GRP78 and HIF-1α, particularly colocalization in nucleus. Induction of HIF-1α expression by glucose deprivation in PDA cells depended on the expression of and its own interaction with GRP78. Mechanistically, increased expression of both HIF-1α and LDHA under glucose deprivation was caused by the direct binding of GRP78 and HIF-1α protein complexes to the promoters of HIF-1α and LDHA genes and transactivation of their transcriptional activity. CONCLUSIONS: Protein complex of GRP78 and HIF-1α directly binds to HIF-1α own promoter and LDHA promoter, enhances the transcription of both HIF-1α and LDHA, whereas glucose deprivation increases GRP78 expression and further enhances HIF-1α and LDHA transcription. Therefore, crosstalk and integration of hypoxia- and hypoglycemia-responsive signaling critically impact PDA metabolic reprogramming and therapeutic resistance.

Intestinal fibrosis in aganglionic segment of Hirschsprung's disease revealed by single-cell RNA sequencing.

BACKGROUND: Hirschsprung's disease (HSCR) is a relatively common congenital disability. Accumulating extracellular matrix (ECM) prompts intestinal fibrosis remodelling in the aganglionic segments of HSCR. The contributions of various cellular subsets in the fibrogenesis of HSCR segments are poorly understood. METHODS: Single-cell transcriptomics from 8 aganglionic segments and 5 normal segments of 7 HSCR subjects and 26 healthy segments of seven healthy donors were analysed. Fibrotic phenotype and alterations were explored using differential expression analysis and single-cell trajectory analysis. Fibrosis-related transcription factors were inferred through single-cell regulatory network inference. Bulk transcriptomic data, proteomic data, immunohistochemistry (IHC) and real-time polymerase chain reaction were used to validate the alterations in the HSCR intestine. RESULTS: Various collagen, fibronectin and laminin protein-coding genes expression were up-regulated in the stromal and glial cells of the HSCR intestine. The number of fibroblasts and myofibroblasts in the aganglionic segments increased, and more myofibroblasts were activated at an earlier stage in HSCR segments, which infers that there is an intestinal fibrosis phenotype in HSCR segments. The fibrotic regulators POSTN, ANXA1 and HSP70 were highly expressed in the ECM-related cellular subsets in the transitional segments and aganglionic segments. The transcription factor regulatory network revealed that fibrosis-related and megacolon-related NR2F1 in the fibroblasts and glial subsets was up-regulated in the aganglionic segment. CONCLUSIONS: This work identifies intestinal fibrosis and related regulators in aganglionic segments of HSCR; hence, anti-fibrotic therapy may be considered to prevent HSCR-associated enterocolitis (HAEC), relieve intestinal stricture and improve cell therapy.

Identification of three lncRNA-related prognostic signatures in gastric cancer by integrated multi-omics analysis.

Aims: The systematic identification of molecular features correlated with the clinical status of gastric cancer (GC) in patients is significant, although such investigation remains insufficient. Methods: GC subtyping based on RNA sequencing, copy number variation and DNA methylation data were derived from The Cancer Genome Atlas program. Prognostics lncRNA biomarkers for GC were identified by univariate Cox, LASSO and SVM-RFE analysis. Results: Three molecular subtypes with significant survival discrepancies, and their specific DEmRNAs and DElncRNAs were identified. Three reliable prognostic-associated lncRNA, including LINC00670, LINC00452 and LINC00160, were selected for GC. Conclusion: Our findings expanded the understanding on the regulatory network of lncRNAs in GC, providing potential targets for prognosis and treatment of GC patients.

Bacteria derived extracellular vesicles in the pathogenesis and treatment of gastrointestinal tumours.

Extracellular vesicles are fundamentally significant in the communication between cells. Outer Membrane Vesicles(OMVs) are a special kind of EVs produced by Gram-negative bacteria, which are minute exosome-like particles budding from the outer membrane, which have been found to play essential roles in diverse bacterial life events, including regulation of microbial interactions, pathogenesis promotion, stress responses and biofilm formation. Recently, and more researches have explored the substantial potentials of EVs as natural functional nanoparticles in the bioengineering applications in infectious diseases, cardiovascular diseases, autoimmune diseases and neurological diseases, such as antibacterial therapy, cancer drugs and immunoadjuvants, with several candidates in clinical trials showing promising efficacy. However, due to the poor understanding of sources, membrane structures and biogenesis mechanisms of EVs, progress in clinical applications still remains timid. In this review, we summarize the latest findings of EVs, especially in gastrointestinal tract tumours, to provide a comprehensive introduction of EVs in tumorigenesis and therapeutics.