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Patient-derived pancreatic cancer-on-a-chip recapitulates the tumor microenvironment

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Microsystems & Nanoengineering 2022年第2期8卷 135-147页

作者： Muhammad R.Haque Caitlin R.Wessel Daniel D.Leary Chengyao Wang Abhinav Bhushan Faraz Bishehsari Division of digestive diseases Rush Center for Integrated Microbiome&Chronobiology ResearchRush University Medical CenterChicagoIL 60612USA University of Louisville School of Medicine LouisvilleKT 40202USA Department of Biomedical Engineering Illinois Institute of TechnologyChicagoIL 60616USA

The patient population suffering from pancreatic ductal adenocarcinoma(PDAC)presents,as a whole,with a high degree of molecular tumor *** heterogeneity of PDAC tumor composition has complicated treatment and stalled success in clinical *** in vitro techniques insufficiently replicate the intricate stromal components of PDAC tumor microenvironments(TMEs)and fail to model a given tumor's unique genetic *** development of patient-derived organoids(PDOs)has opened the door for improved personalized medicine since PDOs are derived directly from patient tumors,thus preserving the tumors'unique behaviors and genetic *** study developed a tumor-chip device engineered to mimic the PDAC TME by incorporating PDOs and stromal cells,specifically pancreatic stellate cells and *** PDOs in a multicellular microfluidic chip device prolongs cellular function and longevity and successfully establishes a complex organotypic tumor environment that incorporates desmoplastic stroma and immune *** primary cancer cells in monoculture were subjected to stroma-depleting agents,there was no effect on cancer cell ***,targeting stroma in our tumor-chip model resulted in a significant increase in the chemotherapy effect on cancer cells,thus validating the use of this tumor-chip device for drug testing.

关键词： cancer chemotherapy adenocarcinoma

Compensation for Neurodegeneration by Hippocampal Neurogenesis in Alzheimer’s Disease: Where is the way?

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Neuroscience Bulletin 2021年第6期37卷 885-888页

作者： Jie Zheng Yawen Li Department of Pharmacology Key Laboratory of Basic Pharmacology of Ministry of EducationJoint International Research Laboratory of Ethnomedicine of Ministry of EducationKey Laboratory of Basic Pharmacology of Guizhou ProvinceZunyi Medical UniversityZunyi 563000China digestive Disease institute of Guizhou Province Clinical Medical Research Center of Digestive Diseases of Guizhou ProvinceDepartment of GastroenterologyAffiliated Hospital of Zunyi Medical UniversityZunyi 563000China

Neurodegeneration,a defining hallmark of Alzheimer's disease(AD),features the progressive loss of neuronal structure and *** approaches to AD show limited efficiency in halting the neurodegeneration to *** the lack of neuronal renewability in most subareas of the adult brain,symptomatic drugs or treatments cannot repopulate neurons and rewire the degenerated neuronal circuits in AD.

关键词： degeneration Alzheimer drugs

Modalities of testing Helicobacter pylori in patients with nonmalignant bile duct diseases

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World Journal of Gastroenterology 2002年第2期8卷 301-304页

作者： Milutin Bulajic Bojan Stimec Miroslav Milicevic Matthias Loehr Petra Mueller Ivan Boricic Nada Kovacevic Mirko Bulajic Department of Internal Medicine Clinical Center"Dr Dragisa Misovic"-DedinjeBelgradeYugoslavia institute for Anatomy School of MedicineBelgrade Yugoslavia First Surgical Clinic Institute for digestive DiseasesUniversity Clinical CenterBelgradeYugoslavia Department of Medicine Ⅱ Medical Faculty MannheimUniversity of HeidelbergGermany Department of Medicine University of RostockGermany institute for Pathology School of Medicine BelgradeYugoslavia Clinic for Gastroenterology and Hepatology Institute for Digestive DiseasesUniversity Clinical CenterBelgradeYugoslavia

AIM:This paper describes the procedure of detection of Helicobacter pylori(***)in bile specimens in patients suffering from benign diseases of biliary ducts(lithiasis with/without nonspecific cholangitis). METHODS:The group of 72 patients entering the study consisted of 32 male and 40 female(45 % and 55 %, respectively).Bile was obtained during ERCP in 68 patients, and during cholecystectomy in 4 patients.A fast urease test (FUT)to determine the existence of *** in gastric mucosa was carried out for all the patients during the endoscopic *** existence of genetic material of *** was determined by detection of ure A gene by the method of nested *** results of this reaction were shown by electrophoresis on 10 g·L^(-1)agarose gel in a band of 256 bp. RESULTS:The majority of the patients included in our study had biliary lithiasis without signs of cholangitis(48 patients, 67 %),whereas other patients were complicated by cholangitis(17 patients,24 %).Seven patients(9 %)had normal ERCP,forming thus the control *** the group of patients with lithiasis 26 patients(24.2 %)had positive PCR of *** in bile and among the patients with associated cholangitis positive PCR was detected in 9 patients(52.9 %).Among the seven patients with normal ERCP only one(14 %)had positive PCR of ***.A high percentage of *** infection of gastric mucosa was observed(57 patients,79 %).It was also observed that its slightly higher positivity was in the patients with distinct bile pathology:81% FLIT positive patients in the group with choledocholithiasis alone and 76 % in the group with choledocholithiasis associated with ***-one percent of the patients with regular findings had positive ***: The prevalence of H. pylori infection both in bile and in gastric mucosa in patients with benign diseases of biliary ducts does not show a statistically significant difference in relation to the prevalence of the same with the patients

关键词： Adolescent Adult Aged Aged, 80 and over Bile Bile Ducts Child Cholangiopancreatography, Endoscopic Retrograde Cholangitis Cholelithiasis Female Gastric Mucosa Helicobacter Infections Helicobacter pylori purification Humans Male Middle Aged Research Support, Non-U.S. Gov't Urease

CircRNA_0084927 promotes colorectal cancer progression by regulating miRNA-20b-3p/glutathione S-transferase mu 5 axis

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World Journal of Gastroenterology 2021年第36期27卷 6064-6078页

作者： Feng Liu Xiao-Li Xiao Yu-Jing Liu Ruo-Hui Xu Wen-Jun Zhou Han-Chen Xu Ai-Guang Zhao Yang-Xian Xu Yan-Qi Dang Guang Ji institute of digestive diseases Longhua HospitalChina-Canada Center of Research for Digestive Diseases(ccCRDD)Shanghai University of Traditional Chinese MedicineShanghai 200032China Department of Oncology Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Department of General Surgery Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and the second most common cause of cancer-related death *** 5-year survival rate of patients with early-stage CRC could reach 90%,but it is very low in patients with advanced-stage *** studies have shown that circular RNAs play important roles in regulating the migration and invasion of CRC *** To elucidate the role of circRNA_0084927(circ_0084927)in the migration and invasion of CRC cells and its underlying *** clinical tissue samples and cells were collected,and the expression of circ_0084927 was detected by quantitative polymerase chain reaction(qPCR).The diagnostic performance of circ_0084927 was assessed by receiver operating characteristic curve *** role of circ_0084927 in CRC cell proliferation,migration,and invasion was determined using cell counting kit-8 assay,wound healing assay,and transwell assay,*** regulatory relationship among circ_0084927,miRNA-20b-3p(miR-20b-3p),and glutathione S-transferase mu 5(GSTM5)was identified using databases,luciferase reporter assay,qPCR,and Western blot ***-mTOR signaling was also verified after circ_0084927 knockdown or miR-20b-3p mimic *** The expression of circ_0084927 was significantly increased in CRC tissues and cells,and it was higher in advanced-stage CRC compared with early-stage *** area under the curve(AUC)of circ_0084927 was 0.806[95%confidence interval(CI):0.683-0.896].In addition,the AUC was 0.874(95%CI:0.738-0.956)in patients with advanced-stage CRC and 0.713(95%CI:0.555-0.840)in those with early-stage *** of circ_0084927 inhibited the migration and invasion of HCT116 ***,circ_0084927 was found to act as a sponge of ***-20b-3p activation reduced the circ_0084927 level,whereas miR-20b-3p inhibition increased the circ_0084927 *** the effect was not found after circ_0084927 *** addition,miR-20b-3p expression in CRC

关键词： Colorectal cancer CircRNA_0084927 MiRNA-20b-3p Glutathione Stransferase mu 5 Migration Invasion

Computed tomographic colonography:Hope or hype?

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World Journal of Gastroenterology 2010年第8期16卷 915-920页

作者： Otto Schiueh-Tzang Lin digestive diseases institute Virginia Mason Medical Center Department of Medicine University of Washington School of Medicine

Computed tomographic colonography (CTC) is a promising emerging technology for imaging of the colon. This concise review discusses the currently available data on CTC technique,test characteristics,acceptance,safety,cost-effectiveness,follow-up strategy,and extracolonic findings. In summary,CTC technique is still evolving,and further research is needed to clarify the role of automated colonic insufflation,smooth-muscle relaxants,intravenous and oral contrast,soft-ware rendering,and patient positioning. Currently,full bowel preparation is still required to achieve optimal results. The sensitivity for detecting large polyps (> 1 cm) can be as high as 85%,with specificity of up to 97%. These test characteristics are almost comparable to those of conventional colonoscopy. Patient acceptance of CTC is generally higher than that for colonoscopy,especially in patients who have never undergone either procedure. CTC is generally safe,although uncommon instances of colonic perforation have been documented. In terms of cost-effectiveness,most decision analyses have concluded that CTC would only be cost-effective if it were considerably cheaper than conventional colonoscopy. The proper follow-up strategy for small polyps or incidental extracolonic findings discovered during CTC is still under debate. At present,the exact clinical role of virtual colonoscopy still awaits determination. Even though widespread CTC screening is not available today,in the future there may eventually be a role for this technology. Technological advances in this area will undoubtedly continue,with multi-detector row CT scanners allowing thinner collimation and higher reso-lution images. Stool-tagging techniques are likely to evolve and may eventually allow for low-preparation CTC. Perceptual and fatigue-related reading errors can potentially be minimized with the help of computer-aided detection software. Further research will define the exact role of this promising technology in our diagnostic armame

关键词： Computed tomographic colonography Colonoscopy Colonic neoplasms Cancer screening Colonic polyps

Awareness and attitude of fecal microbiota transplantation through transendoscopic enteral tubing among inflammatory bowel disease patients

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World Journal of clinical Cases 2020年第17期8卷 3786-3796页

作者： Min Zhong Yang Sun Hong-Gang Wang Cicilia Marcella Bo-Ta Cui Ying-Lei Miao Fa-Ming Zhang Medical center for digestive diseases The Second Affiliated Hospital of Nanjing Medical UniversityNanjing 210011Jiangsu ProvinceChina Key Lab of Holistic Integrative Enterology Nanjing Medical UniversityNanjing 210011Jiangsu ProvinceChina Department of Gastroenterology The First Affiliated Hospital of Kunming Medical UniversityYunnan Institute of Digestive DiseaseKunming 650032YunnanChina Medical center for digestive diseases The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical UniversityHuaian 223300Jiangsu ProvinceChina

BACKGROUND Transendoscopic enteral tubing(TET)has been used in China as a novel delivery route for fecal microbiota transplantation(FMT)into the whole colon with a high degree of patient satisfaction among *** To explore the recognition and attitudes of FMT through TET in patients with inflammatory bowel disease(IBD).METHODS An anonymous questionnaire,evaluating their awareness and attitudes toward FMT and TET was distributed among IBD patients in two provinces of Eastern and Southwestern *** formats included single-choice questions,multiple-choice questions and sorting *** who had not undergone FMT were mainly investigated for their cognition and acceptance of FMT and *** who had experience of FMT,the way they underwent FMT and acceptance of TET were the main *** all the patients were asked whether they would recommend FMT and *** study also analyzed the preference of FMT delivery in IBD patients and the patient-related factors associated with *** A total of 620 eligible questionnaires were included in the *** survey showed that 44.6%(228/511)of patients did not know that FMT is a therapeutic option in IBD,and 80.6%(412/511)of them did not know the concept of *** than half(63.2%,323/511)of the participants stated that they would agree to undergo FMT through *** the patients who underwent FMT via TET[62.4%(68/109)],the majority[95.6%(65/68)]of them were satisfied with *** who had undergone FMT and TET were more likely to recommend FMT than patients who had not(94.5%vs 86.3%,P=0.018 and 98.5%vs 87.8%,P=0.017).Patients’choice for the delivery way of FMT would be affected by the type of disease and whether the patient had the experience of *** compared to patients without experience of FMT,Crohn’s disease and ulcerative colitis patients who had experience of FMT preferred mid-gut TET(P<0.001)and colonic TET(P<0.001),*** Patients’experience of FMT through T

关键词： Recognition Fecal microbiota transplant Washed microbiota transplantation Transendoscopic enteral tubing Attitude

Inhibition of M2 tumor-associated macrophages polarization by modulating the Wnt/β-catenin pathway as a possible liver cancer therapy method

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World Journal of Gastroenterology 2024年第40期30卷 4399-4403页

作者： Vladislav V Tsukanov Julia L Tonkikh Edward V Kasparov Alexander V Vasyutin clinical Department of the digestive System Pathology of Adults and Children Federal Research Center“Krasnoyarsk Science Center”of the Siberian Branch of the Russian Academy of SciencesScientific Research Institute of Medical Problems of the NorthKrasnoyarsk 660022Russia

The problem of liver cancer is becoming increasingly important due to the epi-demic of metabolic diseases and persistent high alcohol *** deter-mines great attention to the development and improvement of methods for early diagnosis and treatment of liver *** et al presented a study in the World Journal of Gastroenterology,in which they showed that the use of the traditional Chinese medicine Calculus bovis(CB)can suppress tumor growth in mice by inhibiting M2 tumor-associated macrophages(TAM)through modulating the activity of the Wnt/β-catenin *** interaction of CB components with the Wnt/β-catenin pathway,M2 TAM polarization,and tumor dynamics were studied using network pharmacology,transcriptomics,and molecular *** is now generally accepted that the polarization of TAM and the differentiation of the functions of M1 and M2 phagocytes are of great importance for the progression of *** is assumed that M2 TAM promote proliferation and migration of tumor *** to medicinally influence the Wnt/β-catenin pathway in order to modulate phagocyte polarization now belong to one of the most promising areas of immunotherapy of oncological ***,the work of the Chinese authors deserves attention and further development.

关键词： Liver cancer Treatment Calculus bovis Tumor-associated macrophages M2 tumor Macrophage polarization Wnt/β-catenin pathway

Integrated miRNA and mRNA Analysis Identified Potential Mechanisms and Targets of Qianggan Extracts in Preventing Nonalcoholic Steatohepatitis

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World Journal of Traditional Chinese Medicine 2022年第1期8卷 77-86页

作者： Jie Huang Meng Li Wen-Jun Zhou Ze-Min Yao Guang Ji Li Zhang Ming-Zhe Zhu China-Canada center of Research for digestive diseases Institute of Digestive DiseasesLonghua HospitalShanghai University of Traditional Chinese MedicineShanghaiChina Department of Biochemistry Microbiology and ImmunologyOttawa Institute of Systems BiologyUniversity of OttawaOttawaCanada School of Public Health Shanghai University of Traditional Chinese MedicineShanghaiChina

Objective: Qianggan(QG) extract is a patented traditional Chinese medicine that has been widely used for the clinical treatment of nonalcoholic steatohepatitis(NASH). However, its mechanism remains unclear. Methods: The efficacy of QG was evaluated in mice with methionine-and-choline-deficient diet-induced NASH by measuring serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels and by H and E staining of liver sections. Microarray and bioinformatics analyses were performed to obtain hepatic micro RNA(mi RNA) and m RNA expression profiles and to mine potential mechanisms and therapeutic targets. Furthermore, representative mi RNA and m RNA expression levels were validated by quantitative real-time polymerase chain reaction(q RT-PCR). Results: QG extract significantly improved NASH. Twelve differentially expressed mi RNAs and 1124 differentially changed m RNAs were identified as potential targets of QG extract. Integrated analysis detected 976 mi RNA–m RNA regulatory pairs, and networks including 11 mi RNAs and 427 m RNAs were constructed by Cytoscape. Hub nodes including mi R-7050-5p, mi R-212-3p, Bcl2l11, and Kras were filtered out. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that 427 m RNAs were enriched in pathways including apoptotic process, immune response, Fox O signaling pathway, and natural killer cell-mediated cytotoxicity. We also constructed a protein–protein interaction network with 254 nodes, and identified hub genes including Kras, Fasl, and Ncam1. Finally, the results of q RT-PCR were in good accordance with microarray data. Conclusion: This study identified important hub mi RNAs and m RNAs involved in the mechanism of QG extract and which might provide potential therapeutic targets for patients with NASH.

关键词： Fatty liver gene regulatory networks microarray analysis Qianggan extract Traditional Chinese Medicine

Liver-inclusive intestinal transplantation results in decreased alloimmune-mediated rejection but increased infection

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Gastroenterology Report 2018年第1期6卷 29-37,I0001,I0002页

作者： Guosheng Wu Ruy J.Cruz Jr Department of Gastrointestinal Surgery Xijing Hospital of Digestive DiseasesThe Fourth Military Medical UniversityXi’anShannxiChina Thomas E.Starzl Transplantation institute University of Pittsburgh Medical CenterPittsburghPAUSA

Background and aims:A co-transplanted liver allograft has been thought to protect other organs from rejection-mediated injury;however,detailed analyses of co-transplanted liver on intestinal allograft outcomes have not been conducted to *** aimof the study was to compare immune-mediated injury,causes of graft failure and clinical outcomes between recipients who underwent either a liver-inclusive intestinal transplant(LITx)or liver-exclusive intestinal transplant(LETx).Methods:Between May 2000 and May 2010,212 adult patients undergoing LITx(n¼76)and LETx(n¼136)were *** underwent either liver combined intestinal or full multivisceral *** underwent either isolated intestinal or modified multivisceral ***:During 44.9631.4 months of follow-up,death-censored intestinal graft survival was significantly higher for LITx than LETx(96.9%,93.2%and 89.9%vs 91.4%,69.3%and 60.0%at 1,3 and 5 years;p¼0.0001).Incidence of graft loss due to rejection was higher in LETx than in LITx(30.9%vs 6.6%;pclinical *** immunosuppression may need to be considered for patients who undergo LITx to attenuate increased risk of infection.

关键词： Intestinal transplant immunosuppression rejection infection