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Topic Review
Biography
Topic Review
Bicarbonate Transport in Cystic Fibrosis and Pancreatitis
CFTR, the cystic fibrosis (CF) gene-encoded epithelial anion channel, has a prominent role in driving chloride, bicarbonate and fluid secretion in the ductal cells of the exocrine pancreas. Here, we summarize recent insights into the mechanism and regulation of CFTR-mediated and modulated bicarbonate secretion in the pancreatic duct, including the role of the osmotic stress/chloride sensor WNK1 and the scaffolding protein IRBIT, and current knowledge about the role of CFTR in genetic and acquired forms of pancreatitis. Furthermore, we discuss the perspectives for CFTR modulator therapy in the treatment of exocrine pancreatic insufficiency and pancreatitis and introduce pancreatic organoids as a promising model system to study CFTR function in the human pancreas, its role in the pathology of pancreatitis and its sensitivity to CFTR modulators on a personalized basis.
418
19 Apr 2022
Topic Review
Bile Acid Diarrhoea
Bile acid diarrhoea (BAD) is a widespread gastrointestinal disease that presents as chronic watery diarrhoea as well as bloating and abdominal pain. This condition is often misdiagnosed as irritable bowel syndrome and is estimated to affect 1% of the United Kingdom population alone. BAD is associated with excessive bile acid synthesis secondary to a gastrointestinal or idiopathic disorder (also known as primary BAD). Current treatment includes diet changes and bile acid sequestrant medication.
628
19 May 2021
Topic Review
Bile Acid Malabsorption
Bile acid malabsorption (BAM), known also as bile acid diarrhea, is a cause of several gut-related problems, the main one being chronic diarrhea. It has also been called bile acid-induced diarrhea, cholerheic or choleretic enteropathy, bile salt diarrhea or bile salt malabsorption. It can result from malabsorption secondary to gastrointestinal disease, or be a primary disorder, associated with excessive bile acid production. Treatment with bile acid sequestrants is often effective.
717
09 Oct 2022
Topic Review
Bile Acids in Alcohol-Associated Liver Disease
Alcohol-associated liver disease (ALD) is a spectrum of diseases, the onset and progression of which are due to chronic alcohol use. ALD ranges, by increasing severity, from hepatic steatosis to alcoholic hepatitis (AH) and alcohol-associated cirrhosis (AC), and in some cases, can lead to the development of hepatocellular carcinoma (HCC). ALD continues to be a significant health burden and is now the main cause of liver transplantations in the United States. ALD leads to biological, microbial, physical, metabolic, and inflammatory changes in patients that vary depending on disease severity. ALD deaths have been increasing in recent years and are projected to continue to increase. Current treatment centers focus on abstinence and symptom management, with little in the way of resolving disease progression. Due to the metabolic disruption and gut dysbiosis in ALD, bile acid (BA) signaling and metabolism are also notably affected and play a prominent role in disease progression in ALD, as well as other liver disease states, such as non-alcoholic fatty liver disease (NAFLD).
540
11 May 2022
Topic Review
Bile Acids in the Liver and Gut Metabolism
Bile acids (BAs) represent heterogeneous amphipathic molecules that have both polar (water-soluble or hydrophilic) and apolar (water-insoluble or hydrophobic) parts, and therefore they can dissolve in water as well as in fat. The regulation of cholesterol homeostasis remains their main role in the host. The better water solubility in comparison with their precursor promotes cholesterol removal from the human body. The proper bile ratio of BAs and cholesterol prevents cholesterol precipitation and further formation of gallstones; therefore, the loss of BAs increases the risk of cholesterol stone development.
1.3K
08 Feb 2023
Topic Review
Biliary Atresia Animal Models
Biliary atresia (BA) is a progressive fibro-obliterative process with a variable degree of inflammation involving the hepatobiliary system. Its consequences are incalculable for the patients, the affected families, relatives, and the healthcare system. Scientific communities have identified a rate of about 1 case per 10,000–20,000 live births, but the percentage may be higher, considering the late diagnoses. The etiology is heterogeneous. BA, which is considered in half of the causes leading to orthotopic liver transplantation, occurs in primates and non-primates. To consolidate any model, (1) more transport and cell membrane studies are needed to identify the exact mechanism of noxa-related hepatotoxicity; (2) an online platform may be key to share data from pilot projects and new techniques; and (3) the introduction of differentially expressed genes may be useful in investigating the liver metabolism to target the most intricate bilio-toxic effects of pharmaceutical drugs and toxins.
754
19 Jul 2022
Topic Review
Biliopancreatic Endoscopy in Altered Anatomy
Anatomical post-surgical alterations of the upper gastrointestinal (GI) tract have always been challenging for performing diagnostic and therapeutic endoscopy, especially when biliopancreatic diseases are involved. Esophagectomy, gastrectomy with various reconstructions and pancreaticoduodenectomy are among the most common surgeries causing upper GI tract alterations. Several different techniques developed over the years for biliopancreatic diseases in altered anatomy, in order to perform both endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP). They included enteroscopy-assisted ERCP (double and single balloon enteroscopy-ERCP, spiral enteroscopy-ERCP) laparoscopic assisted ERCP, EUS-Directed transgastric ERCP, EUS-directed transgastric intervention, gastric access temporary for endoscopy, and percutaneous assisted trans prosthetic endoscopic therapy.
552
26 Oct 2021
Topic Review
Biologic Therapy for Inflammatory Bowel Disease Patients
Many patients with inflammatory bowel disease (IBD) experience a loss of effectiveness to biologic therapy (i.e., anti-TNF therapy, etc.). Therefore, in addition to the adverse effects of the treatment, these patients also face failure to achieve and maintain remission. Immunogenicity, the process of production of antibodies to biological agents, is fundamental to the evolution of loss of response to treatment in IBD patients.
124
07 Mar 2024
Topic Review
Biological Drugs in EoE and Their Targets
Eosinophilic esophagitis (EoE) is a multifaceted disease characterized by a wide heterogeneity of clinical manifestations, endoscopic and histopathologic patterns, and responsiveness to therapy. From the perspective of an effective approach to the patient, the different inflammatory mechanisms involved in the pathogenesis of EoE and biologics, in particular monoclonal antibodies (mAbs), targeting these pathways are needed. Currently, the most relevant is dupilumab, which interferes with both interleukin (IL)-4 and IL-13 pathways by binding IL-4 receptor α, and is the only mAb approved by the European Medicine Agency and US Food and Drug Administration for the treatment of EoE. Other mAbs investigated include mepolizumab, reslizumab, and benralizumab (interfering with IL-5 axis), cendakimab and dectrekumab (anti-IL-13s), tezepelumab (anti-TSLP), lirentelimab (anti-SIGLEG-8), and many others.
158
08 Feb 2024
Topic Review
Biomarkers for Esophageal Cancers
Esophageal cancer (EC) is the deadliest cancer worldwide, with a 92% annual mortality rate per incidence. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two major types of ECs, with EAC having one of the worst prognoses in oncology. Limited screening techniques and a lack of molecular analysis of diseased tissues have led to late-stage presentation and very low survival durations.
814
15 May 2023
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