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Topic Review
Treatments for Acute Intermittent Porphyria
Rare diseases, especially monogenic diseases, which usually affect a single target protein, have attracted growing interest in drug research by encouraging pharmaceutical companies to design and develop therapeutic products to be tested in the clinical arena. Acute intermittent porphyria (AIP) is one of these rare diseases. AIP is characterized by haploinsufficiency in the third enzyme of the heme biosynthesis pathway. Identification of the liver as the target organ and a detailed molecular characterization have enabled the development and approval of several therapies to manage this disease.
  • 597
  • 22 Dec 2022
Topic Review
Chitosan-Based Nanomaterials and its Applications
The small intestine provides the major site for the absorption of numerous orally administered drugs. However, before reaching to the systemic circulation to exert beneficial pharmacological activities, the oral drug delivery is hindered by poor absorption/metabolic instability of the drugs in gastrointestinal (GI) tract and the presence of the mucus layer overlying intestinal epithelium. Therefore, a polymeric drug delivery system has emerged as a robust approach to enhance oral drug bioavailability and intestinal drug absorption. Chitosan, a cationic polymer derived from chitin, and its derivatives have received remarkable attention to serve as a promising drug carrier, chiefly owing to their versatile, biocompatible, biodegradable, and non-toxic properties. Several types of chitosan-based drug delivery systems have been developed, including chemical modification, conjugates, capsules, and hybrids. They have been shown to be effective in improving intestinal assimilation of several types of drugs, e.g., antidiabetic, anticancer, antimicrobial, and anti-inflammatory drugs. In this review, the physiological challenges affecting intestinal drug absorption and the effects of chitosan on those parameters impacting on oral bioavailability are summarized. More appreciably, types of chitosan-based nanomaterials enhancing intestinal drug absorption and their mechanisms, as well as potential applications in diabetes, cancers, infections, and inflammation, are highlighted. The future perspective of chitosan applications is also discussed. 
  • 596
  • 13 Jul 2021
Topic Review
Clinical Presentation of Wilson’s Disease
Wilson’s disease can appear at any age, although it is most prevalent in patients before the age of 40. Most cases are diagnosed between 5 and 35 years of age. Clinical signs and symptoms of the disease may vary considerably but the most common are hepatic (including cirrhosis), neurologic, and psychiatric disorders; ophthalmic signs (Kayser–Fleischer rings); and episodes of hemolysis coexisting with acute liver failure. Due to its heterogeneous presentation, Wilson’s disease has been referred to as “the great masquerader”
  • 596
  • 01 Dec 2021
Topic Review
New-Onset Liver Injuries Due to COVID-19
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted the world and caused the 2019 coronavirus disease (COVID-19) pandemic. The clinical manifestations of the virus can vary from patient to patient, depending on their respective immune system and comorbidities. SARS-CoV-2 can affect patients through two mechanisms: directly by targeting specific receptors or by systemic mechanisms.
  • 596
  • 17 Mar 2023
Topic Review
Pathophysiology of Nitrergic Enteric Neurons
Nitrergic enteric neurons are key players of the descending inhibitory reflex of intestinal peristalsis, therefore loss or damage of these neurons can contribute to developing gastrointestinal motility disturbances suffered by patients worldwide. There is accumulating evidence that the vulnerability of nitrergic enteric neurons to neuropathy is strictly region-specific and that the two main enteric plexuses display different nitrergic neuronal damage. Alterations both in the proportion of the nitrergic subpopulation and in the total number of enteric neurons suggest that modification of the neurochemical character or neuronal death occurs in the investigated gut segments. 
  • 595
  • 23 Jun 2021
Topic Review
FOXO3 as a Novel Biomarker in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) represents one of the main causes of cancer-related death worldwide. The transcription factor forkhead box O3 (FOXO3) has been related to hepatic diseases and tumor progression, but the exact role played by FOXO3 on HCC still remains unclear. Recently, a novel systematic review with meta-analysis revealed the potential diagnostic and prognostic value of FOXO3 in this primary liver cancer type.
  • 595
  • 05 Nov 2021
Topic Review
Impact of Female Gender in Inflammatory Bowel Diseases
Inflammatory bowel diseases show a gender bias, as reported for several other immune-mediated diseases. Female-specific differences influence disease presentation and activity, leading to a different progression between males and females. Women show a genetic predisposition to develop inflammatory bowel disease related to the X chromosome. Female hormone fluctuation influences gastrointestinal symptoms, pain perception, and the state of active disease at the time of conception could negatively affect the pregnancy. Women with inflammatory bowel disease report a worse quality of life, higher psychological distress, and reduced sexual activity than male patients. 
  • 595
  • 13 Feb 2023
Topic Review
Microbiota, Diet and Mucus in Inflammatory Bowel Disease
The gastrointestinal tract is optimized to efficiently absorb nutrients and provide a competent barrier against a variety of lumen environmental compounds. Different regulatory mechanisms jointly collaborate to maintain intestinal homeostasis, but alterations in these mechanism lead to a dysfunctional gastrointestinal barrier and are associated to several inflammatory conditions usually found in chronic pathologies such as inflammatory bowel disease (IBD). The gastrointestinal mucus, mostly composed of mucin glycoproteins, covers the epithelium and plays an essential role in digestive and barrier functions. However, its regulation is very dynamic and is still poorly understood. This review presents some aspects concerning the role of mucus in gut health and its alterations in IBD. In addition, the impact of gut microbiota and dietary compounds as environmental factors modulating the mucus layer is addressed. To date, studies have evidenced the impact of the three-way interplay between the microbiome, diet and the mucus layer on the gut barrier, host immune system and IBD. This review emphasizes the need to address current limitations on this topic, especially regarding the design of robust human trials and highlights the potential interest of improving our understanding of the regulation of the intestinal mucus barrier in IBD.
  • 594
  • 21 Oct 2021
Topic Review
Eating Disorders and Gastrointestinal Diseases
Eating disorders (ED) are frequently associated with a wide range of psychiatric or somatic comorbidities. The most relevant ED are anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorders (BED). Patients with ED exhibit both upper and lower gastrointestinal (GI) symptoms. Evidence of alterations throughout the GI tract in ED will be analyzed given the role of the GI tract in food intake and its regulation. It remains a matter of debate whether GI disorders are inherent manifestations of ED or the results of malnutrition occurring from ED. Moreover, recent clinical studies have highlighted the growing role of intestinal microbiota in the pathogenesis of ED, making it possible to hypothesize a modulation of intestinal microbiota as a co-adjuvant to standard therapy. 
  • 593
  • 28 Jul 2021
Topic Review
The Gut Microbiome and Female Health
Given that females may be more likely to be affected by some ailments such as osteoarthritis, heart disease, cancer, and anxiety, it is imperative to study the effect of the gut microbiome and its role in female health. It is evident that the presence/ratio of microbial species is altered in polycystic ovarian syndrome, cancer, pregnancy, and menopause. Thus, potential probiotics should be developed and the administration of certain bacterial species should be considered, as novel independent or adjunct therapies for various female-related pathologies.
  • 593
  • 30 Nov 2022
Topic Review
TGR5
Takeda G protein-coupled receptor (TGR5) is a metabolic regulator, which is also involved in inflammatory responses. TGR5 belongs to the G protein-coupled receptor (GPCR) superfamily.
  • 593
  • 02 Aug 2021
Topic Review
FOXO3, Autophagy and Sorafenib Resistance in Human Hepatocarcinoma
Early development of resistance to sorafenib accounts for the poor prognosis of advanced hepatocarcinoma (HCC). Autophagy, a double-edge autodegradative and recycling process, has been related to the modulation of drug sensitivity in cancer cells. The transcription factor forkhead box O3 (FOXO3) has been associated with the pathogenesis of HCC, but the involvement of FOXO3 on autophagy-related sorafenib resistance in HCC needs to be further investigated. A recent research verified that HCC cells are able to surpass sorafenib effects during chemoresistance acquisition via the upregulation of FOXO3 and the subsequent induction of a pro-survival autophagy. Hence, FOXO3-associated autophagy could constitute a novel therapeutic target in the advanced HCC landscape.
  • 592
  • 26 Nov 2021
Topic Review
Gastrointestinal Involvement in Extra-Digestive Disease
Calprotectin (CP) is a dimer composed of S100A8 and S100A9, which are calcium and zinc binding proteins. CP is found mainly in neutrophils, where under constitutive conditions, it represents about 45% of the total cytosolic protein. Moreover, calprotectin is constitutively expressed by monocytes, macrophages, dendritic cells oral keratocytes and squamous mucosal epithelium. In inflammation, the expression of calprotectin is increased. CP is released by neutrophils, monocytes, and macrophages during inflammation due to its antimicrobial properties. CP can be detected in serum, urine, cerebrospinal, synovial, and pleural fluids in proportion to the degree of any existing inflammation, but the most useful and widely used form is in stool as a reliable marker of intestinal tissue inflammation. Moreover, CP concentration in feces is approximately six times higher than in plasma.
  • 592
  • 13 Jan 2023
Topic Review
Sleeve Gastrectomy, Roux-En-Y Gastric Bypass
Bariatric/metabolic surgery involves different techniques leading to different effects on pancreatic cell populations. Currently, sleeve gastrectomy (SG) is one of the most performed techniques. A consequence of this procedure is the drastic removal of the gastric fundus and corpus ghrelin-producing cell population.
  • 589
  • 24 Sep 2021
Topic Review
Cellular and Molecular Mechanisms Underlying Liver Fibrosis Regression
Hepatic fibrosis is a scar formation process consisting in altered deposition of extracellular matrix. Progression of fibrosis can lead to impaired liver architecture and function, resulting in cirrhosis and organ failure. In the liver, due to its high regenerative ability, the extent of fibrosis regression and reversion to normal architecture is higher than in other tissues, even in advanced disease. 
  • 589
  • 24 Aug 2022
Topic Review
Artificial Intelligence in Digestive Healthcare
With modern society well entrenched in the digital area, the use of Artificial Intelligence (AI) to extract useful information from big data has become more commonplace in our daily lives than we perhaps realize. A number of medical specialties such as Gastroenterology rely heavily on medical images to establish disease diagnosis and patient prognosis, as well as to monitor disease progression. Moreover, some such imaging techniques have been adapted so that they can potentially deliver therapeutic interventions. The digitalization of medical imaging has paved the way for important advances in this field, including the design of AI solutions to aid image acquisition and analysis.
  • 588
  • 08 May 2023
Topic Review
Pre-biotics, Probiotics and Post-Biotics
Gut microbiota (GM) is a complex ecosystem containing bacteria, viruses, fungi, and yeasts. It has several functions in the human body ranging from immunomodulation to metabolic. GM derangement is called dysbiosis and is involved in several host diseases. Pre-, probiotics, and symbiotics (PRE-PRO-SYMB) have been extensively developed and studied for GM re-modulation.
  • 587
  • 11 Jan 2022
Topic Review
Heterogeneity Sources in Metabolic Dysfunction-Associated Fatty Liver Disease
Non-alcoholic fatty liver disease (NAFLD) is a slowly progressing disease, beginning with isolated liver steatosis that evolves in a subset of patients to non-alcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). It was recently proposed to redefine NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) in which other known causes of liver disease such as alcohol consumption or viral hepatitis do not need to be excluded. Revised nomenclature envisions speeding up and facilitating anti-MAFLD drug development by means of patient stratification whereby each subgroup would benefit from distinct pharmacological interventions. 
  • 587
  • 24 Jan 2022
Topic Review
Effect of COVID-19 on Liver
The gastrointestinal tract plays an important role in the pathogenesis of COVID-19. Most patients present with gastrointestinal symptoms and/or abnormal liver function tests, both of which have been associated with adverse outcomes. The mechanisms of liver damage are currently under investigation, but the damage is usually transient and nonsevere. Liver transplantation is the only definitive treatment for acute liver failure and end-stage liver disease, and unfortunately, because of the need for ventilators during the COVID-19 pandemic, most liver transplant programs were temporarily suspended. 
  • 587
  • 26 Sep 2022
Topic Review
OCA on Different Physiological Processes through FXR Activation
Obeticholic acid (OCA) or 6-alpha-ethyl-chenodeoxycholic acid is a semisynthetic modified bile acid derivative that acts on the farnesoid X receptor (FXR) as an agonist with a higher potency than bile acid. The FXR is a nuclear receptor highly expressed in the liver and small intestine and regulates bile acid, cholesterol, glucose metabolism, inflammation, and apoptosis. 
  • 587
  • 08 Mar 2023
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