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.
  • 683
  • 14 Feb 2022
Topic Review
Non-Alcoholic Fatty Liver Disease Patients
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disorders ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Hepatic steatosis may result from the dysfunction of multiple pathways and thus multiple molecular triggers involved in the disease have been described. The development of NASH entails the activation of inflammatory and fibrotic processes. Furthermore, NAFLD is also strongly associated with several extra-hepatic comorbidities, i.e., metabolic syndrome, type 2 diabetes mellitus, obesity, hypertension, cardiovascular disease and chronic kidney disease. Due to the heterogeneity of NAFLD presentations and the multifactorial etiology of the disease, clinical trials for NAFLD treatment are testing a wide range of interventions and drugs, with little success. A review is given to the different phenotypic characteristics of NAFLD patients, whose disease may be triggered by different agents and driven along different pathophysiological pathways. Thus, correct phenotyping of NAFLD patients and personalized treatment is an innovative therapeutic approach that may lead to better therapeutic outcomes.
  • 208
  • 14 Jul 2023
Topic Review
Non-Alcoholic Steatohepatitis-Driven Hepatocarcinogenesis
Non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (NASH) are chronic hepatic conditions leading to hepatocellular carcinoma (HCC) development. According to the recent “multiple-parallel-hits hypothesis”, NASH could be caused by abnormal metabolism, accumulation of lipids, mitochondrial dysfunction, and oxidative and endoplasmic reticulum stresses and is found in obese and non-obese patients.
  • 119
  • 27 Sep 2023
Topic Review
Non-Canonical Programmed Cell Death in Colon Cancer
Programmed cell death (PCD) is an evolutionarily conserved process of cell suicide that is regulated by various genes and the interaction of multiple signal pathways. Non-canonical programmed cell death (PCD) represents different signaling excluding apoptosis. Colon cancer is the third most incident and the fourth most mortal worldwide. Multiple factors such as alcohol, obesity, and genetic and epigenetic alternations contribute to the carcinogenesis of colon cancer. The emerging evidence has suggested that diverse types of non-canonical programmed cell death are involved in the initiation and development of colon cancer, including mitotic catastrophe, ferroptosis, pyroptosis, necroptosis, parthanatos, oxeiptosis, NETosis, PANoptosis, and entosis.
  • 520
  • 14 Jul 2022
Topic Review
Non-Coding RNAs in Hepatocellular Carcinoma Progression
Hepatocellular carcinoma (HCC) is a predominant malignancy with increasing incidences and mortalities worldwide. In Western countries, the progressive affirmation of Non-alcoholic Fatty Liver Disease (NAFLD) as the main chronic liver disorder in which HCC occurrence is appreciable even in non-cirrhotic stages, constitutes a real health emergency. In light of this, a further comprehension of molecular pathways supporting HCC onset and progression represents a current research challenge to achieve more tailored prognostic models and appropriate therapeutic approaches. RNA non-coding transcripts (ncRNAs) are involved in the regulation of several cancer-related processes, including HCC. When dysregulated, these molecules, conventionally classified as “small ncRNAs” (sncRNAs) and “long ncRNAs” (lncRNAs) have been reported to markedly influence HCC-related progression mechanisms. 
  • 266
  • 01 Nov 2023
Topic Review
Non-Invasive Biomarkers for Immunotherapy with Hepatocellular Carcinoma
Tumor biomarkers are cellular and molecular products linked directly or indirectly to the presence of cancer cells that are an expression of the tumor’s intrinsic characteristics and can be identified, measured, and analyzed by specific tests.  Currently, there is an increasing interest in developing novel techniques to extract information on tumor biology directly from patient’s body fluids in a non-invasive way. Liquid biopsy, a non-invasive approach of tumor biomarkers detection, permits a dynamic picture of HCC’s evolution and response to therapy. 
  • 496
  • 20 Oct 2022
Topic Review
Non-Steroid Anti-Inflammatory Drugs/Acetylsalicylic Acid-Associated Gastropathy
Drugs are widely used to treat different diseases in modern medicine, but they are often associated with adverse events. Those located in the gastrointestinal tract are common and often mild, but they can be serious or life-threatening and determine the continuation of treatment. The stomach is often affected not only by drugs taken orally but also by those administered parenterally. The first description of the endoscopic picture of the damage to the gastric mucosa associated with the use of aspirin was published by A. Douthwait and J. Lintoff in 1938.
  • 414
  • 18 Jul 2023
Topic Review
Nonalcoholic Fatty Liver Disease and Peripheral Diabetic Polyneuropathy
Peripheral diabetic polyneuropathy (DPN) is a microvascular complication of diabetes mellitus (DM), representing the most clinically relevant manifestation of typical forms of diabetic neuropathy (DN). DPN has been associated with another pathological condition linked to DM and obesity, the nonalcoholic fatty liver disease (NAFLD). NAFLD is a metabolically derangement-based liver disease, defined by the presence of steatosis in more than 5% of hepatocytes, in association with metabolic risk factors (such as obesity, diabetes, and dyslipidemia) and in the absence of excessive alcohol consumption or other chronic liver diseases.
  • 504
  • 21 Oct 2021
Topic Review
Nonalcoholic Fatty Liver Disease Management
Nonalcoholic fatty liver disease (NAFLD) is a rising epidemic worldwide, involving more than a quarter of the world's population. A sedentary lifestyle and consuming a Western diet have led to substantial challenges in managing NAFLD patients. With no curative pharmaceutical therapies, lifestyle modifications, including dietary changes and exercise, that ultimately lead to weight loss remain the only effective therapy for NAFLD. 
  • 433
  • 09 Dec 2021
Topic Review
Noninvasive Indices for Hepatic Fibrosis in Hemodialysis Patients
Hepatitis C virus (HCV) is a major health problem in hemodialysis patients, which leads to significant morbidity and mortality through progressive hepatic fibrosis or cirrhosis. Percutaneous liver biopsy is the gold standard to stage hepatic fibrosis. However, it is an invasive procedure with postbiopsy complications. Because uremia may significantly increase the risk of fatal and nonfatal bleeding events, the use of noninvasive means to assess the severity of hepatic fibrosis is particularly appealing to hemodialysis patients.
  • 362
  • 29 Sep 2022
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