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Topic Review
Cholestatic Diseases
Cholestatic diseases are based on bile dysfunction due to defects affecting bile synthesis or secretion. These processes involve a wide range of enzymes and membrane transporters involved in hepatobiliary circulation. According to its origin, cholestasis can be classified into two main groups: acquired cholestasis and genetic cholestasis.
  • 685
  • 10 Jun 2022
Topic Review
Non-alcoholic Fatty Liver Disease Pathogenesis and Oxidative Stress
Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it still remains an orphan of adequate therapies. It highlights the interaction between oxidative stress (OS) and disturbed lipid metabolism. Several reactive oxygen species generators, including those produced in the gastrointestinal tract, contribute to the lipotoxic hepatic (and extrahepatic) damage by fatty acids and a great variety of their biologically active metabolites in a “multiple parallel-hit model”. This leads to inflammation and fibrogenesis and contributes to NAFLD progression. The alterations of the oxidant/antioxidant balance affect also metabolism-related organelles, leading to lipid peroxidation, mitochondrial dysfunction, and endoplasmic reticulum stress. This OS-induced damage is at least partially counteracted by the physiological antioxidant response. Therefore, modulation of this defense system emerges as an interesting target to prevent NAFLD development and progression. For instance, probiotics, prebiotics, diet, and fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. The OS and its counter-regulation are under the influence of individual genetic and epigenetic factors as well.
  • 682
  • 14 Feb 2022
Topic Review
ICI-Based Combination Therapy for HCC
Advanced, unresectable hepatocellular carcinoma has a dismal outcome. Multiple immune checkpoint inhibitors (ICIs) targeting the programmed-cell death 1 pathway (PD-1/L1) have been approved for the treatment of advanced HCC. However, outcomes remain undesirable and unpredictable on a patient-to-patient basis. The combination of anti-PD-1/L1 with alternative agents, chiefly cytotoxic T-lymphocyte antigen-4 (CTLA-4) ICIs or agents targeting other oncogenic pathways such as the vascular endothelial growth factor (VEGF) pathway and the c-MET pathway, has, in addition to the benefit of directly targeting alterative oncogenic pathways, in vitro evidence of synergism through altering the genomic and function signatures of T cells and expression of immune checkpoints. Several trials have been completed or are underway evaluating such combinations. Finally, studies utilizing transcriptomics and organoids are underway to establish biomarkers to predict ICI response. 
  • 681
  • 06 May 2021
Topic Review
Liver Injury and Macrophage Issue
The liver is an essential immunological organ due to its gatekeeper position to bypassing antigens from the intestinal blood flow and microbial products from the intestinal commensals. The tissue-resident liver macrophages, termed Kupffer cells, represent key phagocytes that closely interact with local parenchymal, interstitial and other immunological cells in the liver to maintain homeostasis and tolerance against harmless antigens. Upon liver injury, the pool of hepatic macrophages expands dramatically by infiltrating bone marrow-/monocyte-derived macrophages. The interplay of the injured microenvironment and altered macrophage pool skews the subsequent course of liver injuries. It may range from complete recovery to chronic inflammation, fibrosis, cirrhosis and eventually hepatocellular cancer.
  • 681
  • 29 Jul 2021
Topic Review
Molecular Classification of Colorectal Cancer
Colorectal cancer, being mostly colorectal carcinomas (CRC), represents the third most diagnosed cancer and the second cause of cancer-related death. Molecular classification serves as indicator of targeted therapy
  • 680
  • 24 Aug 2022
Topic Review
OCT Applications in GI Tract
Optical coherence tomography (OCT) is uniquely poised for advanced imaging in the gastrointestinal (GI) tract as it allows real-time, subsurface and wide-field evaluation at near-microscopic resolution, which may improve the current limitations or even obviate the need of superficial random biopsies in the surveillance of early neoplasias in the near future. OCT’s greatest impact so far in the GI tract has been in the study of the tubular esophagus owing to its accessibility, less bends and folds and allowance of balloon employment with optimal contact to aid circumferential imaging. Moreover, given the alarming rise in the incidence of Barrett's esophagus and its progression to adenocarcinoma in the U.S., OCT has helped identify pathological features that may guide future therapy and follow-up strategy. This review will explore the current uses of OCT in the gastrointestinal tract and future directions, particularly with non-endoscopic office-based capsule OCT and the use of artificial intelligence to aid in diagnoses.
  • 679
  • 06 Nov 2020
Topic Review
Enteric Glial Cells
 At first, enteric glial cells were considered to be just a structural support for neurons, but recent findings emphasized more on their functions, and they turned out to be equally as important as neural cells, due to their involvement in all aspects of neural functions for both the central and peripheral nervous system, including the ENS.They have been mostly underestimated, particularly regarding the modulation of their functions by nutraceuticals.
  • 679
  • 09 Nov 2021
Topic Review
Pathogenesis of Choledochal Cyst
Choledochal cysts (CC) is characterized by extra- and/or intra-hepatic b\ile duct dilations. There are two main theories, “pancreaticobiliary maljunction” and “congenital stenosis of bile ducts” proposed for the pathogenesis of CC. Although family cases or CC associated with other anomalies have been reported, the molecular pathogenesis of CC is still poorly understood. Advances in transcriptomics and genomics analysis platforms have unveiled key expression signatures/genes/signaling pathways in the pathogenesis of human diseases including CC.
  • 678
  • 24 Jun 2022
Topic Review
Acute Pancreatitis
The incidence of acute and chronic pancreatitis is increasing in the United States. Rates of acute pancreatitis (AP) are similar in both sexes, but chronic pancreatitis (CP) is more common in males. When stratified by etiology, women have higher rates of gallstone AP, while men have higher rates of alcohol- and tobacco-related AP and CP, hypercalcemic AP, hypertriglyceridemic AP, malignancy-related AP, and type 1 autoimmune pancreatitis (AIP). 
  • 678
  • 27 Jan 2021
Topic Review
Hepatic Lipotoxicity in Acute Fatty Liver of Pregnancy
Acute fatty liver of pregnancy (AFLP), a catastrophic illness for both the mother and the unborn offspring, develops in the last trimester of pregnancy with significant maternal and perinatal mortality. AFLP is also recognized as an obstetric and medical emergency. Maternal AFLP is highly associated with a fetal homozygous mutation (1528G>C) in the gene that encodes for mitochondrial long-chain hydroxy acyl-CoA dehydrogenase (LCHAD). The mutation in LCHAD results in the accumulation of 3-hydroxy fatty acids, such as 3-hydroxy myristic acid, 3-hydroxy palmitic acid and 3-hydroxy dicarboxylic acid in the placenta, which are then shunted to the maternal circulation leading to the development of acute liver injury observed in patients with AFLP. 
  • 678
  • 17 Mar 2022
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