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Topic Review
Inflammatory Bowel Disease-Associated Colorectal Cancer
Colonic inflammatory bowel disease (IBD) encompasses ulcerative colitis (UC) and Crohn’s colitis (CC). Patients with IBD are at increased risk for colitis-associated colorectal cancer (CACRC) compared to the general population. CACRC is preceded by IBD, characterized by highly heterogenous, pharmacologically incurable, pertinacious, worsening, and immune-mediated inflammatory pathologies of the colon and rectum. The molecular and immunological basis of CACRC is highly correlated with the duration and severity of inflammation, which is influenced by the exogenous free hemoglobin alpha chain (HbαC), a byproduct of infiltrating immune cells; extravasated erythrocytes; and macrophage erythrophagocytosis. The exogenous free HbαC prompts oxygen free radical-arbitrated DNA damage (DNAD) through increased cellular reactive oxygen species (ROS), which is exacerbated by decreased tissue antioxidant defenses. Mitigation of the Fenton Reaction via pharmaceutical therapy would attenuate ROS, promote apoptosis and DNAD repair, and subsequently prevent the incidence of CACRC. Three pharmaceutical options that attenuate hemoglobin toxicity include haptoglobin, deferoxamine, and flavonoids (vitamins C/E). Haptoglobin’s clearance rate from plasma is inversely correlated with its size; the smaller the size, the faster the clearance. Thus, the administration of Hp1-1 may prove to be beneficial.
  • 983
  • 13 Jul 2023
Topic Review
Transarterial Chemoembolization for Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. It is principally associated with liver cirrhosis and chronic liver disease. The major risk factors for the development of HCC include viral infections (HBV, HCV), alcoholic liver disease (ALD,) and non-alcoholic fatty liver disease (NAFLD). The optimal treatment choice is dictated by multiple variables such as tumor burden, liver function, and patient’s health status. Surgical resection, transplantation, ablation, transarterial chemoembolization (TACE), and systemic therapy are potentially useful treatment strategies. TACE is considered the first-line treatment for patients with intermediate stage HCC. 
  • 976
  • 24 Mar 2022
Topic Review
Pathophysiology of NAFLD
Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is a growing cause of liver cirrhosis and liver cancer worldwide because of the global increases in obesity, dyslipidemia, hypertension, and type 2 diabetes mellitus.
  • 970
  • 27 Apr 2022
Topic Review
Alcohol Consumption and Pancreatitis
Pancreatitis is a common inflammatory disorder of the pancreas, associated with high mortality and healthcare burdens worldwide. It mainly consists of two forms: acute pancreatitis (AP) and chronic pancreatitis (CP). Alcohol exposure is a known etiological factor for both AP and CP.
  • 959
  • 19 Apr 2022
Topic Review
Molecular Pathology and Biomarkers of Pancreatic Ductal Adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis due to the lack of methods or biomarkers for early diagnosis and its resistance to conventional treatment modalities, targeted therapies, and immunotherapies. PDACs are a heterogenous group of malignant epithelial neoplasms with various histomorphological patterns and complex, heterogenous genetic/molecular landscapes. The newly proposed molecular classifications of PDAC based on extensive genomic, transcriptomic, proteomic and epigenetic data have provided significant insights into the molecular heterogeneity and aggressive biology of this deadly disease. Studies characterizing the tumor microenvironment (TME) have shed light on the dynamic interplays between the tumor cells and the immunosuppressive TME of PDAC, which is essential to disease progression, as well as its resistance to chemotherapy, newly developed targeted therapy and immunotherapy. There is a critical need for the development of predictive markers that can be clinically utilized to select effective personalized therapies for PDAC patients.
  • 959
  • 02 Dec 2022
Topic Review
The Role of Immune Cells in Ulcerative Colitis
Ulcerative colitis (UC) is a chronic inflammatory disease with an underlying excessive immune response directed against resident microbiota and/or dietary antigens. The condition is diagnosed mostly between the ages of 20 to 40, however it can occur at every age. Characteristic of UC are alternating periods of clinical relapse and remission.
  • 955
  • 29 Jan 2022
Topic Review
Esophageal Vagal afferent C-fibers' Functions
Heartburn and non-cardiac chest pain are the predominant symptoms in many esophageal disorders, such as gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD), functional heartburn and chest pain, and eosinophilic esophagitis (EoE). At present, neuronal mechanisms underlying the process of interoceptive signals in the esophagus are still less clear. Noxious stimuli can activate a subpopulation of primary afferent neurons at their nerve terminals in the esophagus. The evoked action potentials are transmitted through both the spinal and vagal pathways to their central terminals, which synapse with the neurons in the central nervous system to induce esophageal nociception. Over the last few decades, progress has been made in our understanding on the peripheral and central neuronal mechanisms of esophageal nociception. In this review, we focus on the roles of capsaicin-sensitive vagal primary afferent nodose and jugular C-fiber neurons in processing nociceptive signals in the esophagus. We briefly compare their distinctive phenotypic features and functional responses to mechanical and chemical stimulations in the esophagus. Then, we summarize activation and/or sensitization effects of acid, inflammatory cells (eosinophils and mast cells), and mediators (ATP, 5-HT, bradykinin, adenosine, S1P) on these two nociceptive C-fiber subtypes. Lastly, we discuss the potential roles of capsaicin-sensitive esophageal afferent nerves in processing esophageal sensation and nociception. A better knowledge of the mechanism of nociceptive signal processes in primary afferent nerves in the esophagus will help to develop novel treatment approaches to relieve esophageal nociceptive symptoms, especially those that are refractory to proton pump inhibitors.
  • 934
  • 16 Jul 2021
Topic Review
Microbial Metabolites in Colorectal Cancer
Colorectal cancer (CRC) is one of the leading cancers that cause cancer-related deaths worldwide. The gut microbiota has been proved to show relevance with colorectal tumorigenesis through microbial metabolites. By decomposing various dietary residues in the intestinal tract, gut microbiota harvest energy and produce a variety of metabolites to affect the host physiology. However, some of these metabolites are oncogenic factors for CRC.
  • 932
  • 27 Apr 2021
Topic Review
Interferon Regulatory Factors in NAFLD and NASH
Interferon regulatory factors (IRFs), a family of transcription factors that regulate Interferon (IFN) expression, play important roles in both innate and adaptive immune responses. IRF-involved signaling pathways contribute to hepatic inflammation, insulin resistance, and immune cell activation, such as macrophage polarization, playing critical roles in non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) pathogenesis. Treatments such as microRNAs, PPAR modulators, anti-inflammatory agents, and TLR agonists or antagonists that modulate IRF-mediated signaling pathways can ameliorate the progression of NAFLD to NASH. 
  • 932
  • 06 May 2022
Topic Review
Gut Microbiome and Liver Diseases
The important role of human gut microbiota in liver diseases has long been recognized as dysbiosis and the translocation of certain microbes from the gut to liver. With the development of high-throughput DNA sequencing, the complexity and integrity of the gut microbiome in the whole spectrum of liver diseases is emerging. Specific patterns of gut microbiota have been identified in liver diseases with different causes, including alcoholic, non-alcoholic, and virus induced liver diseases, or even at different stages, ranging from steatohepatitis, fibrosis, cirrhosis, to hepatocellular carcinoma. At the same time, the mechanism of how microbiota contributes to liver diseases goes beyond the traditional function of the gut–liver axis which could lead to liver injury and inflammation.
  • 924
  • 11 May 2021
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.
  • 907
  • 15 May 2023
Topic Review
Targeting Chemosensitive Channels for Dysphagia
Swallowing is a physiological process that transports ingested foods, liquids, and saliva from the oral cavity into the stomach. Difficulty in the oropharyngeal swallowing process or oropharyngeal dysphagia is a major health problem. There is no established pharmacological therapy for the management of oropharyngeal dysphagia. Studies have suggested that the current clinical management of oropharyngeal dysphagia has limited effectiveness for recovering swallowing physiology and for promoting neuroplasticity in swallowing-related neuronal networks. The peripheral chemical neurostimulation strategy is one of the innovative strategies, and targets chemosensory ion channels expressed in peripheral swallowing-related regions. A considerable number of animal and human studies, including randomized clinical trials in patients with oropharyngeal dysphagia, have reported improvements in the efficacy, safety, and physiology of swallowing using this strategy. There is also evidence that neuroplasticity is promoted in swallowing-related neuronal networks with this strategy. The targeting of chemosensory ion channels in peripheral swallowing-related regions may therefore be a promising pharmacological treatment strategy for the management of oropharyngeal dysphagia.
  • 905
  • 27 Oct 2020
Topic Review
NAFLD
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and may progress to cirrhosis or even hepatocellular carcinoma. A number of steroid hormones are important regulators of lipid homeostasis through fine tuning the expression of genes related to lipid synthesis, export, and metabolism. Dysregulation of such pathways has been implicated in the pathogenesis of NAFLD. 
  • 905
  • 12 Oct 2021
Topic Review
Quercetin in Hepatocellular Carcinoma
Quercetin is a flavonoid present in fruits, vegetables and plants with beneficial effects in several human disorders, including liver cancer. The antioxidant and anti-inflammatory properties make quercetin an interesting drug to be evaluated in hepatocarcinoma (HCC), the major primary liver tumor with a high mortality rate. Moreover, increasing number of studies reported a high variety of antitumor actions which places quercetin as a promising antitumor agent, not only as single treatment but also improving current therapeutic options against advanced HCC.
  • 900
  • 12 Oct 2021
Topic Review
Achalasia
Achalasia is an esophageal motor disease characterized by the lack of relaxation of the lower esophageal sphincter (LES) and aperistalsis. The first time this condition was described was in 1672 by Sir Thomas Willis, but the "achalasia" term was only created in 1929 by Hurst and Rake, meaning "no relaxation".
  • 900
  • 31 May 2021
Topic Review
Colorectal Adenomas
Colorectal cancer (CRC) is a malignant disease with an incidence of over 1.8 million new cases per year worldwide. CRC outcome is closely related to the respective stage of CRC and is more favorable at less advanced stages. Detection of early colorectal adenomas is the key to survival. In spite of implemented screening programs showing efficiency in the detection of early precancerous lesions and CRC in asymptomatic patients, a significant number of patients are still diagnosed in advanced stages. Research on CRC accomplished during the last decade has improved our understanding of the etiology and development of colorectal adenomas and revealed weaknesses in the general approach to their detection and elimination. Recent studies seek to find a reliable non-invasive biomarker detectable even in the blood.
  • 896
  • 30 Oct 2020
Topic Review
Mitochondrial Dysfunction in Nonalcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) is a global pandemic that affects one-quarter of the world’s population. NAFLD includes a spectrum of progressive liver disease from steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis and can be complicated by hepatocellular carcinoma. It is strongly associated with metabolic syndromes, obesity, and type 2 diabetes, and it has been shown that metabolic dysregulation is central to its pathogenesis. It has been suggested that metabolic- (dysfunction) associated fatty liver disease (MAFLD) is a more appropriate term to describe the disease than NAFLD, which puts increased emphasis on the important role of metabolic dysfunction in its pathogenesis. There is strong evidence that mitochondrial dysfunction plays a significant role in the development and progression of NAFLD. Impaired mitochondrial fatty acid oxidation and, a reduction in mitochondrial quality, have been suggested to play a major role in NAFLD development and progression. 
  • 893
  • 11 Jul 2022
Topic Review
Helicobacter pylori in Gastric Cancer
The H. pyloriinfection generates an inflammatory reaction in the stomach, resulting in the loss of parietal cells and an elevation in gastric pH. H. pylorimay contribute to microbial dysbiosis, and effective eradication can restore the gut microbiota to a state comparable to that of uninfected people.
  • 888
  • 02 Sep 2021
Topic Review
PD-L1
The gastrointestinal (GI) mucosa is among the most complex systems in the body. It has a diverse commensal microbiome challenged continuously by food and microbial components while delivering essential nutrients and defending against pathogens. For these reasons, regulatory cells and receptors are likely to play a central role in maintaining the gut mucosal homeostasis. Recent lessons from cancer immunotherapy point out the critical role of the B7 negative co-stimulator PD-L1 in mucosal homeostasis. In this entry, we summarize the current knowledge supporting the critical role of PD-L1 in gastrointestinal mucosal tolerance and how abnormalities in its expression and signaling contribute to gut inflammation and cancers. Abnormal expression of PD-L1 and/or the PD-1/PD-L1 signaling pathways have been observed in the pathology of the GI tract. We also discuss the current gap in our knowledge with regards to PD-L1 signaling in the GI tract under homeostasis and pathology. Finally, we summarize the current understanding of how this pathway is currently targeted to develop novel therapeutic approaches.
  • 883
  • 22 Dec 2020
Topic Review
Macrophages as Key Players in Intestinal Fibrogenesis
Intestinal fibrosis is a common complication in inflammatory bowel disease (IBD) without specific treatment. Macrophages are the key actors in inflammatory responses and the wound healing process. By their exceptional ability to integrate diverse stimuli in their surrounding environment, macrophages display a multitude of phenotypes to underpin a broad spectrum of functions, from the initiation to the resolution of inflammation following injury. The hypothesis that distinct macrophage subtypes could be involved in fibrogenesis and wound healing is emerging and could open up new therapeutic perspectives in the treatment of intestinal fibrosis. 
  • 876
  • 11 Mar 2022
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