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World Journal of Gastroenterology Aug 2018() infection is very common and affects approximately half of the world population. It causes gastric diseases, but some authors have reported an association of... (Review)
Review
() infection is very common and affects approximately half of the world population. It causes gastric diseases, but some authors have reported an association of infection with other systemic manifestations beginning in 1994. The list of potential effects of outside the stomach includes a number of extragastric manifestations and we focused on neurological, dermatological, hematologic, ocular, cardiovascular, metabolic, allergic, and hepatobiliary diseases. This review discusses these important reported manifestations that are not related to the gastrointestinal tract.
Topics: Anti-Bacterial Agents; Cardiovascular Diseases; Eye Diseases; Helicobacter Infections; Helicobacter pylori; Hematologic Diseases; Humans; Hypersensitivity; Metabolic Diseases; Nervous System Diseases; Risk Factors; Skin Diseases; Treatment Outcome
PubMed: 30090002
DOI: 10.3748/wjg.v24.i29.3204 -
Hepatology (Baltimore, Md.) Jan 2023The burden of liver diseases is increasing worldwide, with liver transplantation remaining the only treatment option for end-stage liver disease. Regenerative medicine...
The burden of liver diseases is increasing worldwide, with liver transplantation remaining the only treatment option for end-stage liver disease. Regenerative medicine holds great potential as a therapeutic alternative, aiming to repair or replace damaged liver tissue with healthy functional cells. The properties of the cells used are critical for the efficacy of this approach. The advent of liver organoids has not only offered new insights into human physiology and pathophysiology, but also provided an optimal source of cells for regenerative medicine and translational applications. Here, we discuss various historical aspects of 3D organoid culture, how it has been applied to the hepatobiliary system, and how organoid technology intersects with the emerging global field of liver regenerative medicine. We outline the hepatocyte, cholangiocyte, and nonparenchymal organoids systems available and discuss their advantages and limitations for regenerative medicine as well as future directions.
Topics: Humans; Gastroenterology; Organoids; Liver; Regenerative Medicine; Hepatocytes
PubMed: 35596930
DOI: 10.1002/hep.32583 -
World Journal of Gastroenterology Oct 2021The development of artificial intelligence (AI) has increased dramatically in the last 20 years, with clinical applications progressively being explored for most of the... (Review)
Review
The development of artificial intelligence (AI) has increased dramatically in the last 20 years, with clinical applications progressively being explored for most of the medical specialties. The field of gastroenterology and hepatology, substantially reliant on vast amounts of imaging studies, is not an exception. The clinical applications of AI systems in this field include the identification of premalignant or malignant lesions (, identification of dysplasia or esophageal adenocarcinoma in Barrett's esophagus, pancreatic malignancies), detection of lesions (, polyp identification and classification, small-bowel bleeding lesion on capsule endoscopy, pancreatic cystic lesions), development of objective scoring systems for risk stratification, predicting disease prognosis or treatment response [, determining survival in patients post-resection of hepatocellular carcinoma), determining which patients with inflammatory bowel disease (IBD) will benefit from biologic therapy], or evaluation of metrics such as bowel preparation score or quality of endoscopic examination. The objective of this comprehensive review is to analyze the available AI-related studies pertaining to the entirety of the gastrointestinal tract, including the upper, middle and lower tracts; IBD; the hepatobiliary system; and the pancreas, discussing the findings and clinical applications, as well as outlining the current limitations and future directions in this field.
Topics: Artificial Intelligence; Barrett Esophagus; Diagnostic Imaging; Endoscopy; Gastroenterology; Humans
PubMed: 34790008
DOI: 10.3748/wjg.v27.i40.6794 -
Advanced Science (Weinheim,... Jun 2021Molecular heterogeneity of hepatobiliary tumor including intertumoral and intratumoral disparity always leads to drug resistance. Here, seven hepatobiliary tumor...
Molecular heterogeneity of hepatobiliary tumor including intertumoral and intratumoral disparity always leads to drug resistance. Here, seven hepatobiliary tumor organoids are generated to explore heterogeneity and evolution via single-cell RNA sequencing. HCC272 with high status of epithelia-mesenchymal transition proves broad-spectrum drug resistance. By examining the expression pattern of cancer stem cells markers (e.g., PROM1, CD44, and EPCAM), it is found that CD44 positive population may render drug resistance in HCC272. UMAP and pseudo-time analysis identify the intratumoral heterogeneity and distinct evolutionary trajectories, of which catenin beta-1 (CTNNB1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and nuclear paraspeckle assembly transcript 1 (NEAT1) advantage expression clusters are commonly shared across hepatobiliary organoids. CellphoneDB analysis further implies that metabolism advantage organoids with enrichment of hypoxia signal upregulate NEAT1 expression in CD44 subgroup and mediate drug resistance that relies on Jak-STAT pathway. Moreover, metabolism advantage clusters shared in several organoids have similar characteristic genes (GAPDH, NDRG1 (N-Myc downstream regulated 1), ALDOA, and CA9). The combination of GAPDH and NDRG1 is an independent risk factor and predictor for patient survival. This study delineates heterogeneity of hepatobiliary tumor organoids and proposes that the collaboration of intratumoral heterogenic subpopulations renders malignant phenotypes and drug resistance.
Topics: Antigens, Neoplasm; Carbonic Anhydrase IX; Cell Cycle Proteins; Digestive System Diseases; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Fructose-Bisphosphate Aldolase; Gastrointestinal Neoplasms; Gene Expression Regulation, Neoplastic; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); Humans; Hyaluronan Receptors; Intracellular Signaling Peptides and Proteins; Janus Kinases; Neoplastic Stem Cells; Organoids; RNA, Long Noncoding; RNA-Seq; STAT Transcription Factors; Single-Cell Analysis; Transcriptome; beta Catenin
PubMed: 34105295
DOI: 10.1002/advs.202003897 -
ELife Oct 2022As the most aggressive tumor, the outcome of pancreatic cancer (PACA) has not improved observably over the last decade. Anatomy-based TNM staging does not exactly...
As the most aggressive tumor, the outcome of pancreatic cancer (PACA) has not improved observably over the last decade. Anatomy-based TNM staging does not exactly identify treatment-sensitive patients, and an ideal biomarker is urgently needed for precision medicine. Based on expression files of 1280 patients from 10 multicenter cohorts, we screened 32 consensus prognostic genes. Ten machine-learning algorithms were transformed into 76 combinations, of which we selected the optimal algorithm to construct an artificial intelligence-derived prognostic signature (AIDPS) according to the average C-index in the nine testing cohorts. The results of the training cohort, nine testing cohorts, Meta-Cohort, and three external validation cohorts (290 patients) consistently indicated that AIDPS could accurately predict the prognosis of PACA. After incorporating several vital clinicopathological features and 86 published signatures, AIDPS exhibited robust and dramatically superior predictive capability. Moreover, in other prevalent digestive system tumors, the nine-gene AIDPS could still accurately stratify the prognosis. Of note, our AIDPS had important clinical implications for PACA, and patients with low AIDPS owned a dismal prognosis, higher genomic alterations, and denser immune cell infiltrates as well as were more sensitive to immunotherapy. Meanwhile, the high AIDPS group possessed observably prolonged survival, and panobinostat may be a potential agent for patients with high AIDPS. Overall, our study provides an attractive tool to further guide the clinical management and individualized treatment of PACA.
Topics: Humans; Gene Expression Profiling; Consensus; Artificial Intelligence; Panobinostat; Pancreatic Neoplasms; Machine Learning; Biomarkers
PubMed: 36282174
DOI: 10.7554/eLife.80150 -
Journal of Hepatology Jun 2019Human induced pluripotent stem cell (hiPSC)-derived liver modeling systems have the potential to overcome the shortage of donors for clinical application and become a...
BACKGROUND & AIMS
Human induced pluripotent stem cell (hiPSC)-derived liver modeling systems have the potential to overcome the shortage of donors for clinical application and become a model for drug development. Although several strategies are available to generate hepatic micro-tissues, few have succeeded in generating a liver organoid with hepatobiliary structure from hiPSCs.
METHODS
At differentiation stages I and II (day 1-15), 25% of mTeSR™ culture medium was added to hepatic differentiation medium to induce endodermal and mesodermal commitment and thereafter hepatic and biliary co-differentiation. At stage III (day 15-45), 10% cholesterol MIX was added to the maturation medium to promote the formation and maturation of the hepatobiliary organoids. Phenotypes and functions of organoids were determined by specific markers and multiple functional assays both in vitro and in vivo.
RESULTS
In this system, hiPSCs were induced to form 3D hepatobiliary organoids and to some extent recapitulated key aspects of early hepatogenesis in a parallel fashion. The organoids displayed a series of functional attributes. Specifically, the induced hepatocyte-like cells could take up indocyanine green, accumulate lipid and glycogen, and displayed appropriate secretion ability (albumin and urea) and drug metabolic ability (CYP3A4 activity and inducibility); the biliary structures in the system showed gamma glutamyltransferase activity and the ability to efflux rhodamine and store bile acids. Furthermore, after transplantation into the immune-deficient mice, the organoids survived for more than 8 weeks.
CONCLUSION
This is the first time that functional hepatobiliary organoids have been generated from hiPSCs. The organoid model will be useful for in vitro studies of the molecular mechanisms of liver development and has important potential in the therapy of liver diseases.
LAY SUMMARY
Herein, we established a system to generate human induced pluripotent stem cell-derived functional hepatobiliary organoids in vitro, without any exogenous cells or genetic manipulation. To some extent this model was able to recapitulate several key aspects of hepatobiliary organogenesis in a parallel fashion, holding great promise for drug development and liver transplantation.
Topics: Bile Ducts; Cell Differentiation; Cells, Cultured; Humans; Induced Pluripotent Stem Cells; Liver; Organogenesis; Organoids
PubMed: 30630011
DOI: 10.1016/j.jhep.2018.12.028 -
Seminars in Interventional Radiology Aug 2021The hepatobiliary system is known to have high anatomic variability, as studies have shown variant rates of over 40% among individuals. This review will describe biliary... (Review)
Review
The hepatobiliary system is known to have high anatomic variability, as studies have shown variant rates of over 40% among individuals. This review will describe biliary anatomy and the most common anatomic variants, knowledge of which is critical to ensuring safe and effective biliary interventions.
PubMed: 34393334
DOI: 10.1055/s-0041-1731085 -
World Journal of Gastroenterology Sep 2016Hepatobiliary and pancreatic ascariasis (HPA) was described as a clinical entity from Kashmir, India in 1985. HPA is caused by invasion and migration of nematode,... (Review)
Review
Hepatobiliary and pancreatic ascariasis (HPA) was described as a clinical entity from Kashmir, India in 1985. HPA is caused by invasion and migration of nematode, Ascaris lumbricoides, in to the biliary tract and pancreatic duct. Patients present with biliary colic, cholangitis, cholecystitis, hepatic abscesses and acute pancreatitis. Ascarides traverse the ducts repeatedly, get trapped and die, leading to formation of hepatolithiasis. HPA is ubiquitous in endemic regions and in Kashmir, one such region, HPA is the etiological factor for 36.7%, 23%, 14.5% and 12.5% of all biliary diseases, acute pancreatitis, liver abscesses and biliary lithiasis respectively. Ultrasonography is an excellent diagnostic tool in visualizing worms in gut lumen and ductal system. The rational treatment for HPA is to give appropriate treatment for clinical syndromes along with effective anthelmintic therapy. Endotherapy in HPA is indicated if patients continue to have symptoms on medical therapy or when worms do not move out of ductal lumen by 3 wk or die within the ducts. The worms can be removed from the ductal system in most of the patients and such patients get regression of symptoms of hepatobiliary and pancreatic disease.
Topics: Algorithms; Animals; Ascariasis; Ascaris lumbricoides; Biliary Tract; Biliary Tract Diseases; Cholangitis; Cholecystitis; Humans; India; Liver Diseases, Parasitic; Pancreatitis; Prevalence
PubMed: 27672273
DOI: 10.3748/wjg.v22.i33.7507