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HepG2.2.15-derived exosomes facilitate the activation and fibrosis of hepatic stellate cells

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World Journal of Gastroenterology 2024年第19期30卷 2553-2563页

作者： Yang Gao li li sheng-ning zhang Yuan-Yi Mang Xi-Bing zhang shi-Ming Feng department of hepatobiliary pancreatic and Vascular surgery The Affiliated Calmette Hospital of Kunming Medical University and The First Hospital of KunmingKunming 650011Yunnan ProvinceChina

BACKGROUND The role of exosomes derived from HepG2.2.15 cells,which express hepatitis B virus(HBV)-related proteins,in triggering the activation of LX2 liver stellate cells and promoting liver fibrosis and cell proliferation remains *** focus was on comprehending the relationship and influence of differentially expressed microRNAs(DE-miRNAs)within these *** To elucidate the effect of exosomes derived from HepG2.2.15 cells on the activation of hepatic stellate cell(HsC)LX2 and the progression of liver *** Exosomes from HepG2.2.15 cells,which express HBV-related proteins,were isolated from parental HepG2 and WRL68 *** blotting was used to confirm the presence of the exosomal marker protein *** activation of HsCs was assessed using oil red staining,whereas DiI staining facilitated the observation of exosomal uptake by LX2 ***,we evaluated LX2 cell proliferation and fibrosis marker expression using 5-ethynyl-2′-deoxyuracil staining and western blotting,***-miRNAs were analyzed using *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were used to annotate the target genes of *** Exosomes from HepG2.2.15 cells were found to induced activation and enhanced proliferation and fibrosis in LX2 cells.A total of 27 miRNAs were differentially expressed in exosomes from HepG2.2.15 *** analysis indicated that these DE-miRNA target genes were associated with cell differentiation,intracellular signal transduction,negative regulation of apoptosis,extracellular exosomes,and RNA *** pathway analysis highlighted ubiquitin-mediated proteolysis,the MAPK signaling pathway,viral carcinogenesis,and the toll-like receptor signaling pathway,among others,as enriched in these *** These findings suggest that exosomes from HepG2.2.15 cells play a substantial role in the activation,proliferation,and fibrosis of LX2 cells and that DE-miRNAs within these exos

关键词： Hepatic stellate cells liver fibrosis Exosomes small RNA sequencing HepG2.2.15

strategy for Detecting systemic Treatment sensitivity of Primary liver Cancer Based on a Novel Infrared-emissive Organic Nanoparticle

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Chemical Research in Chinese Universities 2024年第1期40卷 145-152页

作者： WU Jun li Yongzhi QIN Hanjiao GAO Ying YANG Bing sheng Jiyao zhang Xuewen department of hepatobiliary and pancreatic surgery the Second Hospital of Jilin UniversityChangchun130022P.R.China department of Radiation Oncology the Second Hospital of Jilin UniversityChangchun130022P.R.China state Key Laboratory of supramolecular structure and Materials Institute of Theoretical ChemistryCollege of ChemistryJilin UniversityChangchun130012P.R.China

In this study,we synthesized an organic material with near-infrared emission capabilities:4-(2-(4-(9-(4-(diphenylamino)phenyl)naphtho[2,3-c][1,2,5]thiadiazol-4-yl)phenyl)-1H-phenol-1-ylidene)malononitrile(TPA).Furthermore,TPA-PEG2000 fluorescent nanoparticles were prepared via coating the shells with ***-PEG2000 exhibited strong near-infrared emission near 700 nm,with a photoluminescence quantum yield of 15.09%,indicating a high emission *** biology experiments have confirmed its low toxicity and excellent *** cholesterol and phospholipid levels in liver cancer cell membranes with low sensitivity or high drug resistance lead to increased rigidity,reduced membrane fluidity,reduced endocytic efficiency,and reduced ***,the uptake of TPA-PEG2000 nanoparticles into cells and the near-infrared fluorescence intensity can be used to evaluate the sensitivity of systemic liver cancer treatment in a simple and efficient manner.

关键词： Nanoparticle Near-infrared Fluorescence systemic treatment sensitivity Cell membrane fluidity

Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

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hepatobiliary & pancreatic Diseases International 2024年第4期23卷 393-398页

作者： Mei-Zi li Tao Guo Yun-Lu Feng sheng-Yu zhang Xiao-Yin Bai Xi Wu Kai Xu Ai-Ming Yang department of Gastroenterology State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China department of Radiology Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China

Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is ***,evidence on the circumstances under which corticosteroid therapy(CsT)for AIP improves or worsens DM is *** study aimed to demonstrate and identify predictors of DM control under the influence of ***:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CsT were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM *** incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM *** the 52 patients with DM,CsT was administered in 48 *** logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CsT(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control ***:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP *** exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CsT.

关键词： Type 1 autoimmune pancreatitis Diabetes mellitus Corticosteroid therapy Predictive factor pancreatic atrophy

Circulating RNA ZFR promotes hepatocellular carcinoma cell proliferation and epithelial-mesenchymal transition process through miR-624-3p/WEE1 axis

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hepatobiliary & pancreatic Diseases International 2024年第1期23卷 52-63页

作者： li zhang sai He Hao Guan Yao Zhao Di zhang department of General surgery the Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004China department of Breast Cancer Shaanxi Provincial Cancer HospitalXi’an 710000China

Background:Hepatocellular carcinoma(HCC),the most common type of primary liver cancer,is the fourth leading cause of cancer-related deaths *** evidence shows that the expression of circulating RNA ZFR(circZFR)is upregulated in HCC ***,the molecular mechanism of circZFR in HCC is ***:Quantitative reverse transcriptase polymerase chain reaction(qRT-PCR)was employed to detect the expression of circZFR,microRNA-624-3p(miR-624-3p)and WEE1 in HCC tissues and *** R assay and actinomycin D treatment assay were used to analyze the characteristics of *** functional analysis,the capacities of colony formation,cell proliferation,cell apoptosis,migration and invasion were assessed by colony formation assay,5-ethynyl-2-deoxyuridine(EdU)assay,flow cytometry assay and transwell *** blot was used to examine the protein levels of WEE1 and epithelial-mesenchymal transition(EMT)-related *** interactions between miR-624-3p and circZFR or WEE1 were validated by dual-luciferase reporter assay and RNA immunoprecipitation(RIP)*** models were established to determine the role of circZFR in ***:circZFR and WEE1 were upregulated,while miR-624-3p expression was reduced in HCC tissues and *** could sponge miR-624-3p,and WEE1 was a downstream gene of *** of circZFR significantly reduced the malignant behaviors of HCC and that co-transfection with miR624-3p inhibitor restored this *** of WEE1 abolished the inhibitory effect of miR624-3p mimic on HCC ***,circZFR acted as a competitive endogenous RNA(ceRNA)to regulate WEE1 expression by targeting ***,in vivo studies have illustrated that circZFR knockdown inhibited tumor ***:circZFR knockdown reduced HCC cell proliferation,migration and invasion and promoted apoptosis by regulating the miR-624-3p/WEE1 axis,suggesting that the circZFR/miR-624-3p/WEE1 axis might

关键词： Hepatocellular carcinoma circZFR miR-624-3p WEE1 liver cancer

Long Non-coding RNA PCED1B Antisense RNA 1 Promotes Cell Proliferation and Invasion in Hepatocellular Carcinoma by Regulating the MicroRNA-34a/CD44 Axis

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Current medical science 2024年第3期44卷 503-511页

作者： Jian-gang BI Qi li Yu-sheng GUO li-ping liU shi-yun BAO Ping XU department of hepatobiliary and pancreatic surgery Shenzhen People's HospitalThe Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China department of Endocrinology Shenzhen People's HospitalThe Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China

Objective This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1(PCED1B-As1)in the development of hepatocellular carcinoma(HCC).Methods A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC *** interactions of PCED1B-As1 and microRNA-34a(miR-34a)were detected by dual luciferase activity assay and RNA pull-down *** RNA expression levels of PCED1B-As1,miR-34a and CD44 were detected by RT-qPCR,and the protein expression level of CD44 was determined by Western *** cell proliferation was detected by cell proliferation assay,and the cell invasion and migration by transwell invasion *** HCC tumor growth after PCED1B-As1 was downregulated was determined by in vivo animal *** PCED1B-As1 was highly expressed in HCC tissues,which was associated with poor survival of HCC ***,PCED1B-As1 interacted with miR-34a in HCC cells,but they did not regulate the expression of each ***,PCED1B-As1 increased the expression level of CD44,which was targeted by *** cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro,while CD44 exhibited the opposite ***,PCED1B-As1 suppressed the role of ***,the knockdown of PCED1B-As1 repressed the HCC tumor growth in nude mice in *** PCED1B-As1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.

关键词： long non-coding RNA PCED1B antisense RNA 1(PCED1B-As1) hepatocellular carcinoma microRNA-34a(miR-34a) CD44 proliferation invasion

Profile, spectrum and significance of hepatitisB virus genotypes in chronic HBV-infected patients in Yunnan, china

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hepatobiliary & pancreatic Diseases International 2008年第3期7卷 271-279页

作者： Hutcha sriplung Virasakdi Chongsuvivatwong Alan Geater Epidemiology Unit Faculty of Medicine Prince of Songkla University Hat Yai Songkhla 90110 Thailand

BACKGROUND: There are significant variations in the geographical distribution of hepatitis B virus (HBV) genotypes throughout the world, and some genotypes are associated with different clinical outcomes. Eight genotypes of human HBV (designated A-H) have been reported. The present study was designed to examine the distribution of HBV genotypes among patients at various stages of chronic type B liver disease in Yunnan Province, china, and to explore its significance and the relationship of HBV genotype with gender and age, clinical spectrum of chronic HBV infection, and viral replicative activity. METHODs: serum samples from 126 patients with chronic HBV infection from Yunnan Province, including 26 chronic asymptomatic HBV carriers (AsC), 61 patients with chronic hepatitis B (CHB) (21 mild, 30 moderate and 10 severe), 20 patients with chronic fulminant hepatic failure (CFHF), 12 patients with HBV-related liver cirrhosis (LC) and 7 patients with HBV-related hepatocellular carcinoma (HCC) were analyzed using reverse dot blot (RDB) methodology, which is based on the reverse hybridization principle for HBV genotyping. The relations of HBV genotype with gender and age, clinical patterns, and serological data of the patients were analyzed. REsULTs: In this series, genotypes A, B, C, and D were found. 38.1% patients (48/126) belonged to B, 54.8% (69/126) to C, 0.8% (1/126) to D, 1.6% (2/126) to a mixture of B and C, and 1.6% (2/126) to a mixture of A and C. 3.2% patients (4/126) had unknown genotypes. No other genotypes (E, F, G, and H) were found. Genotypes B and C were predominant. There was a statistically significant difference in the distributions of genotypes C and B (chi(2)=7.04, P=0.008), and C was the dominant genotype in all patient categories. The rate of genotype B in the mild CHB group was significantly higher than that in the moderate and severe groups (chi(2)=12.16, P=0.0001; chi(2)=11.98, P=0.001, respectively), the AsC group (chi(2)=5.46, P=0.02), the CFHF

关键词： hepatitis B virus genotype reverse dot blot distribution clinical interrelation

Key role of interferon regulatory factor 1(IRF-1)in regulating liver disease:progress and outlook

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Journal of Zhejiang University-science B(Biomedicine & Biotechnology) 2024年第6期25卷 451-470页

作者： Tao CHEN shipeng li Dewen DENG Weiye zhang Jianjun zhang Zhongyang sHEN first Central Clinical school Tianjin Medical UniversityTianjin 300192China department of Organ Transplant Tianjin First Central HospitalTianjin 300192China Research Institute of Transplant Medicine Nankai UniversityTianjin 300192China department of hepatobiliary surgery Henan Provincial People’s HospitalZhengzhou 450000China Key Laboratory of Organ Transplant Tianjin First Central HospitalTianjin 300192China

Interferon regulatory factor 1(IRF-1)is a member of the IRF *** is the first transcription factor to be identified that could bind to the interferon-stimulated response element(IsRE)on the target gene and displays crucial roles in the interferoninduced signals and ***-1,as an important medium,has all of the advantages of full cell cycle regulation,cell death signaling transduction,and reinforcing immune surveillance,which are well *** studies indicate that IRF-1 is of vital importance to the occurrence and evolution of multifarious liver diseases,including but not limited to inhibiting the replication of the hepatitis virus(A/B/C/E),alleviating the progression of liver fibrosis,and aggravating hepatic ischemiareperfusion injury(HIRI).The tumor suppression of IRF-1 is related to the clinical characteristics of liver cancer patients,which makes it a potential indicator for predicting the prognosis and recurrence of liver cancer;additionally,the latest studies have revealed other effects of IRF-1 such as protection against alcoholic/non-alcoholic fatty liver disease(AFLD/NAFLD),cholangiocarcinoma suppression,and uncommon traits in other liver diseases that had previously received little ***,several compounds and drugs have featured a protective function in specific liver disease models in which there is significant involvement of the IRF-1 *** this paper,we hope to propose a prospective research basis upon which to help decipher translational medicine applications of IRF-1 in liver disease treatment.

关键词： Interferon regulatory factor(IRF-1) Hepatitis virus liver fibrosis Hepatic ischemia-reperfusion injury(HIRI) liver cancer

Prox1 suppresses Proliferation and Drug Resistance of Retinoblastoma Cells via Targeting Notch1

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Current medical science 2024年第1期44卷 223-231页

作者： Hong-li zhang Na li lin DONG Hong-xia MA Mo-chi YANG department of Ophthalmology General Hospital of Ningxia Medical UniversityYinchuan 750004China

Objective Retinoblastoma(RB)is a prevalent type of eye cancer in *** homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,hepatocyte,pancreatic,heart,lens,retinal,and cancer *** goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance,as well as to explore the underlying Notch1 *** Human RB cell lines(sO-RB50 and Y79)and a primary human retinal microvascular endothelial cell line(ACBRI-181)were used in this *** expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction(RT-qPCR)and Western *** proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTs ***-resistant cell lines(sO-RB50/vincristine)were generated and treated with Prox1 to investigate the role of Prox1 in drug *** employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of ***,a xenograft model was constructed to assess the effect of Prox1 on RB in *** Prox1 was significantly downregulated in RB *** of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to ***1 was involved in Prox1’s regulatory ***1 was identified as a target gene of Prox1,which was found to be upregulated in RB cells and repressed by increased Prox1 *** pcDNA-Notch1 was transfected,the effect of Prox1 overexpression on RB was ***,by downregulating Notch1,Prox1 overexpression slowed tumor development and increased vincristine sensitivity in *** These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1,implying that Prox1 could be a potential therapeutic target for RB.

关键词： Proxl Notch1 retinoblastoma cells proliferation drug resistance

Early systemic anticoagulation reduces hospital readmission in acute necrotizing pancreatitis patients:A retrospective cohort study

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hepatobiliary & pancreatic Diseases International 2024年第1期23卷 77-82页

作者： Wen-Jian Mao Jing Zhou Guo-Fu zhang Fa-Xi Chen Jing-Zhu zhang Bai-Qiang li Lu Ke Wei-Qin li department of Critical Care Medicine Jinling HospitalNanjing Medical UniversityNanjing 210002China department of Critical Care Medicine Jinling HospitalMedical School of Nanjing UniversityNanjing 210002China National Institute of Healthcare Data science Nanjing UniversityNanjing 210010China

Background:Early systemic anticoagulation(sAC)is a common practice in acute necrotizing pancreatitis(ANP),and its impact on in-hospital clinical outcomes had been ***,whether it affects long-term outcomes is *** study aimed to evaluate the effect of sAC on 90-day readmission and other long-term outcomes in ANP ***:During January 2013 and December 2018,ANP patients admitted within 7 days from the onset of abdominal pain were *** primary outcome was 90-day readmission after *** proportional-hazards regression model and mediation analysis were used to define the relationship between early sAC and 90-day ***:A total of 241 ANP patients were enrolled,of whom 143 received early sAC during their hospitalization and 98 did *** who received early sAC experienced a lower incidence of splanchnic venous thrombosis(sVT)[risk ratio(RR)=0.40,95%CI:0.26-0.60,Pssion with an RR of 0.61(95%CI:0.41-0.91,P=0.02)than those who did *** the quality of life,patients who received early sAC had a significantly higher score in the subscale of vitality(P=0.03)while the other subscales were all comparable between the two *** Cox regression model showed that early sAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57(95%CI:0.34-0.96,P=0.04).Mediation analysis showed that sVT mediated 37.0%of the early sAC-90-day readmission ***:The application of early sAC may reduce the risk of 90-day readmission in the survivors of ANP patients,and reduced sVT incidence might be the primary contributor.

关键词： Anticoagulation splanchnic venous thrombosis Acute necrotizing pancreatitis Readmission Long-term outcomes