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Topic Review
Mitochondrial Redox Metabolism
Mitochondrial redox metabolism is the central component in the cellular metabolic landscape, where anabolic and catabolic pathways are reprogrammed to maintain optimum redox homeostasis. During different stages of cancer, the mitochondrial redox status plays an active role in navigating cancer cells’ progression and regulating metabolic adaptation according to the constraints of each stage. Mitochondrial reactive oxygen species (ROS) accumulation induces malignant transformation. Once vigorous cell proliferation renders the core of the solid tumor hypoxic, the mitochondrial electron transport chain mediates ROS signaling for bringing about cellular adaptation to hypoxia. Highly aggressive cells are selected in this process, which are capable of progressing through the enhanced oxidative stress encountered during different stages of metastasis for distant colonization. Mitochondrial oxidative metabolism is suppressed to lower ROS generation, and the overall cellular metabolism is reprogrammed to maintain the optimum NADPH level in the mitochondria required for redox homeostasis. After reaching the distant organ, the intrinsic metabolic limitations of that organ dictate the success of colonization and flexibility of the mitochondrial metabolism of cancer cells plays a pivotal role in their adaptation to the new environment.
  • 892
  • 24 Nov 2021
Topic Review
γ-Secretase
γ-Secretase is an aspartyl protease.
  • 891
  • 30 Mar 2021
Topic Review
Skeletal Muscle Pathogenesis in Polyglutamine Diseases
Polyglutamine diseases are characterized by selective dysfunction and degeneration of specific types of neurons in the central nervous system. In addition, nonneuronal cells can also be affected as a consequence of primary degeneration or due to neuronal dysfunction. Skeletal muscle is a primary site of toxicity of polyglutamine-expanded androgen receptor, but it is also affected in other polyglutamine diseases, more likely due to neuronal dysfunction and death. Nonetheless, pathological processes occurring in skeletal muscle atrophy impact the entire body metabolism, thus actively contributing to the inexorable progression towards the late and final stages of disease. 
  • 891
  • 28 Jul 2022
Topic Review
LCA, DCA, and Their Derivatives from Gut Microbiota
A wide variety and large number of bacterial species live in the gut, forming the gut microbiota. Gut microbiota not only coexist harmoniously with their hosts, but they also induce significant effects on each other. The composition of the gut microbiota can be changed due to environmental factors such as diet and antibiotic intake. In contrast, alterations in the composition of the gut microbiota have been reported in a variety of diseases, including intestinal, allergic, and autoimmune diseases and cancer. The gut microbiota metabolize exogenous dietary components ingested from outside the body to produce short-chain fatty acids (SCFAs) and amino acid metabolites. Unlike SCFAs and amino acid metabolites, the source of bile acids (BAs) produced by the gut microbiota is endogenous BAs from the liver. The gut microbiota metabolize BAs to generate secondary bile acids, such as lithocholic acid (LCA), deoxycholic acid (DCA), and their derivatives, which have recently been shown to play important roles in immune cells. 
  • 891
  • 22 Nov 2023
Topic Review
Astroglial sncRNA Relevance on Early Neurodegeneration Stages
Astrocyte dysfunction with consequential neuronal microenvironment dysregulation (astrocytopathy) has been involved in processes of early neurodegenerative disease. Small non-coding RNA (sncRNA) vary in different detrimental conditions of Central Nervous System (CNS), and sustained changes in sncRNA astrocyte expression profile can be the consequence of these conditions. sncRNA signatures derived from astrocytes, could therefore be a key to reveal early neurodegenerative disease, helping to unravel the astrocyte role in neurodegenerative disease. Current biomarkers for neurodegenerative disease, face strong challenges such as high variability, negative cost-effectiveness, low availability, or invasiveness. For example, cerebrospinal fluid evaluation (CSF tests) is a highly invasive, expensive, risky procedure, often used in the diagnosis of neurodegenerative disease. The alternative to CSF tests, which is neuroimaging requires especial equipment, long operating time and it is highly expensive making their widespread use prohibitive. Still, misdiagnosis could occur after the use of these powerful tools. Therefore, new methods are needed to assess neurodegeneration, and extracellular vesicles from astrocytes (ADEV) represent and interesting target of research. ADEV cross blood brain-barrier (BBB) carrying sncRNA from astrocytes and cell-specific membrane surface proteins, which can be used to allow ADEV separation from vesicles of other sources and other contaminants. This approach could be useful for the analysis of a less invasive, simpler, peripheral sample of blood origin. sncRNA dysregulated in conditions associated with increased risk of neurodegenerative disease and their possible effects on target cells is shown.
  • 890
  • 05 Dec 2022
Topic Review
Applications of Acyl-Homoserine Lactone-Dependent Quorum Sensing
Several clinically and industrially relevant microorganisms employ acyl-homoserine lactone (AHL)-dependent quorum sensing (QS) to communicate and control phenotypic variations. The AHL-QS biomolecule is now being used to develop biosensor assays, anti-virulent compounds, and even anti-cancer therapeutics. QS applications have thrived in agriculture, aquaculture, energy, bioremediation, and health research.
  • 890
  • 21 Nov 2022
Topic Review
CMGC Kinases in Health and Cancer
CMGC kinases, encompassing cyclin-dependent kinases (CDKs), mitogen-activated protein kinases (MAPKs), glycogen synthase kinases (GSKs), and CDC-like kinases (CLKs), play pivotal roles in cellular signaling pathways, including cell cycle regulation, proliferation, differentiation, apoptosis, and gene expression regulation. The dysregulation and aberrant activation of these kinases have been implicated in cancer development and progression, making them attractive therapeutic targets. Kinase inhibitors targeting CMGC kinases, such as CDK4/6 inhibitors and BRAF/MEK inhibitors, have demonstrated clinical success in treating specific cancer types.
  • 890
  • 01 Aug 2023
Topic Review
Viral Ejection Proteins
Genes encoding ejection proteins are commonly found in Podoviridae phages that infect Gram-negative bacteria, including Enterobacteriaceae, Mycobacteria, Pseudomonadaceae, and Cyanobacteria.
  • 889
  • 11 Mar 2022
Topic Review
Histone Demethylases: Insights into Human
Histone methylation is a three-step process that includes the integral roles of “writers”, or histone methyltransferases (HMTs), “readers,” or histone methylation-recognizing proteins, and “erasers,” or histone demethylases (HDMs). Histone methylation and demethylation regulate genes, either by relaxing histone tails to permit transcription factors and other proteins to contact the DNA, or by wrapping histone tails around the DNA, thereby blocking access. These changes impact nucleosomal characteristics and, henceforth, their interactions with other proteins.
  • 889
  • 25 Jun 2023
Topic Review
Interleukin-4 and -13 Receptors
Interleukin (IL)-4 and -13 are structurally and functionally related cytokines sharing common receptor subunits. They regulate immune responses and, moreover, are involved in the pathogenesis of a variety of human neoplasms. In this entry, their possible roles in gastric cancer were shown as an example.
  • 888
  • 12 Oct 2021
Topic Review
PKGIβ/IRAG1 Signaling
Inositol 1,4,5-triphosphate receptor-associated cGMP kinase substrate 1 (IRAG1) is a substrate protein of the NO/cGMP-signaling pathway and forms a ternary complex with the cGMP-dependent protein kinase Iβ (PKGIβ) and the inositol triphosphate receptor I (IP3R-I).
  • 888
  • 11 Oct 2021
Topic Review
Inorganic Nanoparticle-Loaded Exosomes
Exosomes are intrinsic cell-derived membrane vesicles in the size range of 40–100 nm, serving as great biomimetic nanocarriers for biomedical applications. These nanocarriers are known to bypass biological barriers, such as the blood–brain barrier, with great potential in treating brain diseases. Exosomes are also shown to be closely associated with cancer metastasis, making them great candidates for tumor targeting. However, the clinical translation of exosomes are facing certain critical challenges, such as reproducible production and in vivo tracking of their localization, distribution, and ultimate fate. Recently, inorganic nanoparticle-loaded exosomes have been shown great benefits in addressing these issues.
  • 885
  • 10 Mar 2021
Topic Review
Macrophages in Diabetic Wounds Healing
Macrophages play a prominent role in wound healing. In the early stages, they promote inflammation and remove pathogens, wound debris, and cells that have apoptosed. Later in the repair process, they dampen inflammation and secrete factors that regulate the proliferation, differentiation, and migration of keratinocytes, fibroblasts, and endothelial cells, leading to neovascularisation and wound closure. The macrophages that coordinate this repair process are complex: they originate from different sources and have distinct phenotypes with diverse functions that act at various times in the repair process. Macrophages in individuals with diabetes are altered, displaying hyperresponsiveness to inflammatory stimulants and increased secretion of pro-inflammatory cytokines. They also have a reduced ability to phagocytose pathogens and efferocytose cells that have undergone apoptosis. This leads to a reduced capacity to remove pathogens and, as efferocytosis is a trigger for their phenotypic switch, it reduces the number of M2 reparative macrophages in the wound. This can lead to diabetic foot ulcers (DFUs) forming and contributes to their increased risk of not healing and becoming infected, and potentially, amputation. 
  • 885
  • 20 Aug 2021
Topic Review
Targeting of Signaling Pathways by Thymoquinone in Cancer
Thymoquinone is isolated from Nigella sativa with a molecular weight of 164.2 g/mol. A series of cutting-edge research works have demonstrated the health-promoting and disease-ameliorating roles of thymoquinone.
  • 885
  • 13 Jun 2022
Topic Review
Molecular Landscape of Pediatric Thyroid Cancer
Thyroid carcinomas (TC) are rare in the pediatric population; however, they constitute the most common endocrine malignancy. Despite some similarities with adult carcinomas, they have distinct clinical behavior and responses to therapy due to their unique pathology and molecular characteristics. The age cut-off used for defining the pediatric age group has been variable across different studies, and the universally accepted recommendations influence accurate interpretation of the available data. Moreover, factors such as radiation exposure and germline mutations have greater impact in children than in adults. 
  • 885
  • 30 Dec 2022
Topic Review
Asparagine Endopeptidase in Tumors Progression
Asparagine endopeptidase (AEP), also called legumain, is currently the only known cysteine protease that specifically cleaves peptide bonds in asparaginyl residue in the mammalian genome. Since 2003, AEP has been reported to be widely expressed in a variety of carcinomas and is considered a potential therapeutic target. In the following years, researchers intensively investigated the substrates of AEP and the mechanism of AEP in partial tumors. With the identification of substrate proteins such as P53, integrin αvβ3, MMP-2, MMP-9, the biochemical mechanism of AEP in carcinomas is also more precise. This review will clarify the probable mechanisms of AEP in the progression of breast carcinoma, glioblastoma, gastric carcinoma, and epithelial ovarian carcinoma.  This review will also discuss the feasibility of targeted therapy with AEP inhibitor (AEPI) in these carcinomas.
  • 884
  • 20 May 2021
Topic Review
MERCs in Glioblastoma
Glioblastoma (GB), also known as glioblastoma multiforme, is the most aggressive type of astrocytoma. GB derives both from glial and glioma stem cells and affects glia and astrocytes. Gliomas are heterogeneous neoplasms, classified into grade I to IV according to their malignancy and the presence of specific histological/molecular hallmarks. The higher grade of glioma is known as glioblastoma (GB). Although progress has been made in surgical and radiation treatments, its clinical outcome is still unfavorable. The invasive properties of GB cells and glioma aggressiveness are linked to the reshaping of the cytoskeleton. Recent works suggest that the different susceptibility of GB cells to antitumor immune response is also associated with the extent and function of mitochondria–ER contact sites (MERCs). 
  • 884
  • 29 Apr 2022
Topic Review
GNL3 and PA2G4 as Prostate Cancer Prognostic Biomarkers
Guanine nucleotide-binding protein-like 3 (GNL3) and proliferation-associated protein 2G4 (PA2G4) are molecules involved during metaphase-to-anaphase transition and growth regulation. GNL3 and PA2G4 have been found to be overexpressed in several human cancers, including prostate cancer. Clinical data suggest that GNL3 and PA2G4 could be developed as prognostic biomarkers of clinical significance in prostate cancer.
  • 884
  • 03 Jul 2023
Topic Review
Adult Fragile X-Associated Syndromes
Expansions of the CGG-repeats stretch at the 5'-UTR of the Fragile X Mental Retardation 1 (FMR1) gene have pleiotropic effects that lead to a variety of Fragile X-associated syndromes: the neurodevelopmental Fragile X syndrome (FXS) in children, the late-onset neurodegenerative disorder Fragile X-associated tremor-ataxia syndrome (FXTAS) that mainly affects adult men, the Fragile X-associated primary ovarian insufficiency (FXPOI) in adult women, and a variety of psychiatric and affective disorders that are under the term of Fragile X-associated neuropsychiatric disorders (FXAND). In the adult syndromes, the pathological mechanisms are primarily caused by a gain-of-function due to the toxic actions of CGG RNA and FMRpolyG peptide. 
  • 883
  • 26 Aug 2021
Topic Review
CELF Family Proteins in Cancer
CELF (CUGBP Elav-like family) proteins are RBPs (RNA-binding proteins) with pleiotropic capabilities in RNA processing. Their responsibilities extend from alternative splicing and transcript editing in the nucleus to mRNA stability, and translation into the cytoplasm. In this way, CELF family members have been connected to global alterations in cancer proliferation and invasion, leading to their identification as potential tumor suppressors or even oncogenes. Notably, genetic variants, alternative splicing, phosphorylation, acetylation, subcellular distribution, competition with other RBPs, and ultimately lncRNAs, miRNAs, and circRNAs all impact CELF regulation. 
  • 882
  • 25 Oct 2021
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