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Topic Review
Non-Coding RNAs in Tamoxifen Resistance
Despite the clinical efficacy of Tam, intrinsic or acquired resistance is an important obstacle limiting the success of ER + breast cancer patient treatment. It is a challenge that needs to be overcome to improve the prognosis of these patients. The main mechanisms of resistance to tamoxifen can be divided according to different causes: mechanisms that involve genetic mutations and lead to loss or gain of function of the receptor and mechanisms that modulate other protumorigenic pathways, including other receptors involved in estrogen’s pathway of action.
  • 401
  • 09 Aug 2021
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.
  • 625
  • 14 Feb 2022
Topic Review
Non-Alcoholic Fatty Liver Disease and Cardiovascular Disease
Non-alcoholic fatty liver disease (NAFLD) is a metabolic liver disease, which classically includes a spectrum of progressive pathological conditions, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) with different grades of fibrosis and cirrhosis. NAFLD is also a “multisystemic” disease, NAFLD is independently associated with serious hepatic complications (e.g., hepatic decompensation, hepatocellular carcinoma [HCC]), but also with an increased risk of developing cardiovascular disease (CVD).
  • 460
  • 17 Feb 2022
Topic Review
NO Signaling Pathways in Aging
Nitric Oxide (NO) is a potent signaling molecule involved in the regulation of various cellular mechanisms and pathways under normal and pathological conditions. NO production, its effects, and its efficacy, are extremely sensitive to aging-related changes in the cells. 
  • 440
  • 12 Aug 2021
Topic Review
NLRP3 Inflammasome in Neuromuscular Diseases
Inflammasomes are molecular platforms that are formed and activated by a host in response to pathogen- and damage-associated molecular patterns as well as cellular injury and stress. Inflammasome activation is benefical to the host as it plays a pivotal role in the clearance of the pathogen and restore tissue homeostasis. However, aberrant activation of the NLRP3 inflammasome by a wide variety of sterile triggers, including misfolded protein aggregates drives pathological sterile inflammation and is associated with several neuromuscular diseases. Assembly of the NLRP3 inflammasome leads to the caspase-1-mediated proteolytic cleavage and secretion of key proinflammatory cytokines, interleukin (IL)-1β and IL-18, and a lytic form of cell death known as pyroptosis. These cytokines further amplify inflammatory responses by activating various signaling cascades, leading to the recruitment of immune cells and overproduction of proinflammatory cytokines and chemokines, resulting in a vicious cycle of chronic inflammation and tissue damage.
  • 437
  • 08 Jul 2021
Topic Review
Nitrate in Type 2 Diabetes
Beneficial metabolic effects of inorganic nitrate (NO3−) and nitrite (NO2−) in type 2 diabetes mellitus (T2DM) have been documented in animal experiments; however, this is not the case for humans. Although it has remained an open question, the redox environment affecting the conversion of NO3− to NO2− and then to NO is suggested as a potential reason for this lost-in-translation. Ascorbic acid (AA) has a critical role in the gastric conversion of NO2− to NO following ingestion of NO3−. In contrast to AA-synthesizing species like rats, the lack of ability to synthesize AA and a lower AA body pool and plasma concentrations may partly explain why humans with T2DM do not benefit from NO3−/NO2− supplementation. Rats also have higher AA concentrations in their stomach tissue and gastric juice that can significantly potentiate gastric NO2−-to-NO conversion.
  • 685
  • 11 Oct 2021
Topic Review
Neutropenic Enterocolitis and Sepsis
Neutropenic enterocolitis (NE), which in the past was also known as typhlitis or ileocecal syndrome for the segment of the gastrointestinal tract most affected, is a nosological entity that is difficult to diagnose and whose pathogenesis is not fully known to date. Initially described in pediatric patients with leukemic diseases, it has been gradually reported in adults with hematological malignancies and non-hematological conditions, such as leukemia, lymphoma, multiple myeloma, aplastic anemia, and also myelodysplastic syndromes, as well as being associated with other immunosuppressive causes such as AIDS treatment, therapy for solid tumors, and organ transplantation. Therefore, it is associated with high mortality due to the rapid evolution in worse clinical pictures: rapid progression to ischemia, necrosis, hemorrhage, perforation, multisystem organ failure, and sepsis
  • 495
  • 21 Jun 2021
Topic Review
Neuromyelitis Optica Spectrum Disorder
The term neuromyelitis optica was introduced by Eugène Devic and Fernand Gault in 1894, who first recognized the association of amaurosis and myelitis as a new clinical entity.
  • 378
  • 01 Sep 2021
Topic Review
Neurological Functions of Bile Acids
Bile acids (BA) are amphipathic steroid acids synthesized from cholesterol in the liver. They act as detergents to expedite the digestion and absorption of dietary lipids and lipophilic vitamins. BA are also considered to be signaling molecules, being ligands of nuclear and cell-surface receptors, including farnesoid X receptor and Takeda G-protein receptor 5. Moreover, BA also activate ion channels, including the bile acid-sensitive ion channel and epithelial Na+ channel. BA regulate glucose and lipid metabolism by activating these receptors in peripheral tissues, such as the liver and brown and white adipose tissue. Recently, 20 different BA have been identified in the central nervous system. Furthermore, BA affect the function of neurotransmitter receptors, such as the muscarinic acetylcholine receptor and γ-aminobutyric acid receptor. BA are also known to be protective against neurodegeneration. 
  • 581
  • 31 Aug 2021
Topic Review
Neuroglia in Administrating Nerve Blockers and Anesthesia
Dysfunction of the neuroglia can have profound consequences on the blood–brain barrier (BBB). Studies have shown that the disruption of astrocytic–endothelial interaction can compromise the permeability of BBB and its effectiveness in selectively regulating the exchange of substances. Microglia have been recognized to have a significant role in the initiation of chronic pain and in its interactions with various nerve blockers and anesthetic agents. Microglia have a role in pain resolution via a pathway that involves Cannabinoid receptor type 2 activation and MAP kinase phosphorylation. 
  • 297
  • 26 Feb 2024
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