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Topic Review
Potassium Channels in PAH
Pulmonary arterial hypertension (PAH) is a rare and severe cardiopulmonary disease without curative treatments. PAH is a multifactorial disease that involves genetic predisposition, epigenetic factors, and environmental factors (drugs, toxins, viruses, hypoxia, and inflammation), which contribute to the initiation or development of irreversible remodeling of the pulmonary vessels. The recent identification of loss-of-function mutations in KCNK3 (KCNK3 or TASK-1) and ABCC8 (SUR1), or gain-of-function mutations in ABCC9 (SUR2), as well as polymorphisms in KCNA5 (Kv1.5), which encode two potassium (K+) channels and two K+ channel regulatory subunits, has revived the interest of ion channels in PAH. This entry focuses on KCNK3, SUR1, SUR2, and Kv1.5 channels in pulmonary vasculature and discusses their pathophysiological contribution to and therapeutic potential in PAH.
  • 1.7K
  • 28 Sep 2020
Topic Review
Aryl Hydrocarbon Receptor(AhR)
The aryl hydrocarbon receptor (AhR) is a member of the family of basic helix-loop-helix transcription factors and well-known for its role in xenobiotic metabolism and detoxification.
  • 1.7K
  • 01 Mar 2021
Topic Review
Lamin-A/C expression in immune cells
Nuclear envelope lamin A/C type-V intermediate filaments are a major constituent of the mammalian nuclear lamina, a dense fibrous protein meshwork located in the nuclear interior. Lamin A/C proteins control nuclear mechanics and structure and modify cellular signaling, gene transcription, epigenetic regulation, cell cycle progression, cell differentiation, and cell migration. The immune system is constituted by the innate and adaptive immunity. Innate immune response is mediated by myeloid cells such as neutrophils, macrophages, and dendritic cells. These cells produce a rapid and nonspecific response through phagocytosis, cytokine production, and complement activation, as well as activating adaptive immunity. Specific adaptive immune response is provoked by antigen presentation by antigen presenting cells (APCs) and the cytokine milieu, and is mainly mediated by the cellular functions of T cells and the production of antibodies by B cells. Unlike most cell types, immune cells regulate their lamin A/C protein expression relatively rapidly to exert their functions, with expression increasing in macrophages, reducing in neutrophils, and increasing transiently in T cells. In this article, it is discussed and summarized studies that have addressed the regulation of the expression of lamin A/C in cells of the innate and adaptive immune system.
  • 1.7K
  • 27 Oct 2020
Topic Review
Cell Membrane Theory of Senescence
Lipids are an essential constituent of the cell membrane of which polyunsaturated fatty acids (PUFAs) are the most important component. Activation of phospholipase A2 (PLA2) induces the release of PUFAs from the cell membrane that form precursors to both pro- and ant-inflammatory bioactive lipids that participate in several cellular processes. PUFAs GLA (gamma-linolenic acid), DGLA (dihomo-GLA), AA (arachidonic acid), EPA (eicosapentaenoic acid) and DHA (do-cosahexaenoic acid) are derived from dietary linoleic acid (LA) and alpha-linolenic acid (ALA) by the action of desaturases whose activity declines with age. Consequently, aged cells are deficient in GLA, DGLA, AA, AA, EPA and DHA and their metabolites. LA, ALA, AA, EPA and DHA can also be obtained direct from diet and their deficiency (fatty acids) may indicate malnutrition and deficiency of several minerals, trace elements and vitamins some of which are also much needed co-factors for the normal activity of desaturases. In many instances (patients) the plasma and tissue levels of GLA, DGLA, AA, EPA and DHA are low (as seen in patients with hyperten-sion, type 2 diabetes mellitus) but they do not have deficiency of other nutrients. Hence, it is reasonable to consider that the deficiency of GLA, DGLA, AA, EPA and DHA noted in these condi-tions are due to the decreased activity of desaturases and elongases. PUFAs stimulate SIRT1 through protein kinase A-dependent activation of SIRT1-PGC1α complex and thus, increase rates of fatty acid oxidation and prevent lipid dysregulation associated with aging. 
  • 1.7K
  • 19 Mar 2021
Topic Review
Structure, Expression Regulation, and Subcellular Localization of USP16
Ubiquitin-specific peptidase 16 (USP16) is a deubiquitinase that plays a role in the regulation of gene expression, cell cycle progression, and various other functions. It was originally identified as the major deubiquitinase for histone H2A and has since been found to deubiquitinate a range of other substrates, including proteins from both the cytoplasm and nucleus. USP16 is phosphorylated when cells enter mitosis and dephosphorylated during the metaphase/anaphase transition. While much of USP16 is localized in the cytoplasm, separating the enzyme from its substrates is considered an important regulatory mechanism. Some of the functions that USP16 has been linked to include DNA damage repair, immune disease, tumorigenesis, protein synthesis, coronary artery health, and male infertility. The strong connection to immune response and the fact that multiple oncogene products are substrates of USP16 suggests that USP16 may be a potential therapeutic target for the treatment of certain human diseases.
  • 1.7K
  • 06 Apr 2023
Topic Review
ATF5 Function in Regulating Cell Stress and Survival
Activating transcription factor 5 (ATF5) belongs to the activating transcription factor/cyclic adenosine monophosphate (cAMP) response element-binding protein family of basic region leucine zipper transcription factors. ATF5 plays an important role in cell stress regulation and is involved in cell differentiation and survival, as well as centrosome maintenance and development. 
  • 1.7K
  • 27 Jul 2022
Topic Review
The Dual Role of Reactive Oxygen Species
The phrase “reactive oxygen species” (ROS) is commonly used to describe the highly reactive free radicals and molecules originating from molecular oxygen. This so-called bi-radical state of oxygen explains its reactivity: one of its electrons can be paired with an external electron with an antiparallel spin, resulting in the production of the highly reactive superoxide radical (O2·−). Since the superoxide radical is weakly basic and highly soluble in water at physiological pH, cellular membranes are relatively impermeable to it. However, O2·− can be converted into membrane-permeable H2O2 by superoxide dismutase (SOD) or protonated to hydroperoxyl radicals (HOO·). Furthermore, O2·− reacts with H2O2 through the Haber–Weiss reaction using iron catalysis, resulting in the formation of highly reactive and cytotoxic hydroxyl radicals (HO·). Furthermore, during the hydroperoxide and polyunsaturated fatty acid metabolism, other types of ROS, namely the peroxyl (ROO·) and alkoxyl (RO·) radicals, are formed as intermediates. On the one hand, high amounts of ROS may damage biomolecules due to their high reactivity. On the other hand—at strictly regulated levels—ROS are essential to maintaining the redox homeostasis of the cells, and they are engaged in many cellular signalling pathways, so their total elimination by the antioxidant system is not expedient.
  • 1.7K
  • 13 May 2022
Topic Review
Glycosylation
Post-translational modifications are one way that biomineral-associated cells control the function and fate of proteins. Of the ten different types of post-translational modifications, one of the most interesting and complex is glycosylation, or the covalent attachment of carbohydrates to amino acid sidechains Asn, Ser, and Thr of proteins. There are several biomineral-associated glycoproteins that have been characterized, and a subset of these have been the subject of intensive in vitro experimentation.  These studies indicate that glycosylation does not alter the inherent function of the biomineralization protein; rather, it either accentuates or attenuates protein functionality. In essence, glycosylation gives the cell the “last word” as to what degree a biomineralization protein will participate in the biomineralization process.
  • 1.7K
  • 25 Sep 2020
Topic Review
PI3K/AKT/mTOR Signaling Pathway
The PI3K/AKT/mTOR complex is a signaling pathway with a major role in essential cellular activities, such as: cell metabolism, cell growth, cell proliferation, apoptosis, and angiogenesis.
  • 1.7K
  • 12 Jan 2021
Topic Review
Regulation of Membrane Fluidity in Cold Environments
Temperature changes and periods of detrimental cold occur frequently for many organisms in their natural habitats. Homeothermic animals have evolved metabolic adaptation strategies to increase mitochondrial-based energy expenditure and heat production, largely relying on fat as a fuel source. Alternatively, certain species are able to repress their metabolism during cold periods and enter a state of decreased physiological activity known as torpor. By contrast, poikilotherms, which are unable to maintain their internal temperature, predominantly increase membrane fluidity to diminish cold-related damage from low-temperature stress.
  • 1.7K
  • 05 Jun 2023
Topic Review
Telocytes
Telocytes/CD34+ stromal cells in the normal and pathological peripheral nervous system (PNS). We consider the following aspects: (A) general characteristics of telocytes; (B) the presence, characteristics and arrangement of telocytes in the normal PNS, including i) nerve epi-perineurium and endoneurium (e.g., telopodes extending into the endoneurial space); ii) sensory nerve endings (e.g., Meissner and Pacinian corpuscles, and neuromuscular spindles); iii) ganglia; and iv) the intestinal autonomic nervous system; (C) the telocytes in the pathologic PNS, encompassing (i) hyperplastic neurogenic processes (neurogenic hyperplasia of the appendix and gallbladder), highly demonstrative of telocyte characteristics and relations, (ii) PNS tumours, such as neurofibroma, schwannoma and granular cell tumour. 
  • 1.7K
  • 26 Oct 2020
Topic Review
The Synthesis Pathway of L-Theanine in Microorganisms
Theanine, a representative non-protein amino acid in tea, is one of the umami components of tea and a major factor in the formation of the unique flavor of tea leaves. In addition to its delicious taste, theanine has a variety of health functions and is used in the food supplement, pharmaceutical, nutraceutical, and cosmetic industries. 
  • 1.7K
  • 30 Jun 2023
Topic Review
Reactive Oxygen Species in Malaria Treatment
Malaria is a vector-transmitted parasite disease that continues to plague mankind. It is caused in humans by five main species of Plasmodium. The majority of conventional antimalarials kill parasites via direct or indirect overproduction of reactive oxygen species (ROS). Even when some parasites try to manage these ROS, over production of the ROS still leads to parasite death. This therefore underscores the role of ROS in the antiplasmodial activity of different antimalarials.
  • 1.7K
  • 04 Mar 2022
Topic Review
Chemical and Cell-Based Antioxidant Assays
Antioxidants remain interesting molecules of choice for suppression of the toxic effects of free radicals in foods and human systems. The current practice involves the use of mainly synthetic molecules as potent antioxidant agents. However, due to the potential negative impact on human health, there is an intensive effort within the research community to develop natural alternatives with similar antioxidant efficacy but without the negative side effects of synthetic molecules. Still, the successful development of new molecules depends on the use of reliable chemical or cell culture assays to screen antioxidant properties. Chemical antioxidant assays include the determination of scavenging ability against free radicals such as DPPH, superoxide anion radicals, hydroxyl radicals, hydrogen peroxide, and nitric oxide. Other antioxidant tests include the ability of compounds to bind and sequester prooxidant metal cations, reduce ferric iron, and attenuate the rate of lipid oxidation. Ex vivo tests utilize cell cultures to confirm entry of the molecules into cells and the ability to quench synthetic intracellular free radicals or to stimulate the increased biosynthesis of endogenous antioxidants.
  • 1.7K
  • 19 Aug 2021
Topic Review
ANO1 in Cystic Fibrosis
Cystic fibrosis (CF) is the most common of rare hereditary diseases in Caucasians, and it is estimated to affect 75,000 patients globally. CF is a complex disease due to the multiplicity of mutations found in the CF transmembrane conductance regulator (CFTR) gene causing the CFTR protein to become dysfunctional. Although CFTR is the main chloride channel in the lungs, others could, e.g., anoctamin-1 (ANO1 or TMEM16A), compensate for the deficiency of CFTR. 
  • 1.7K
  • 26 Oct 2021
Topic Review
Lipid Phosphate Phosphatases
Lipid phosphate phosphatases (LPPs) consist of three enzymes (LPP1–3), which have been classified as phospholipid phosphatases (PLPP). The LPPs dephosphorylate a wide spectrum of bioactive lipid phosphates, among which lysophosphatidate (LPA) and sphingosine 1-phosphate (S1P) are two important extracellular signaling molecules. The LPPs are integral membrane proteins, which are partly localized on plasma membranes. These activities participate in regulating the concentrations of extracellular LPA and S1P and thus signaling through their families of G protein coupled receptors. The expression of the LPPs on intracellular membranes, including endoplasmic reticulum and Golgi net work, are thought to attenuate signaling downstream of the activation of LPA and protease activates receptors. The LPPs differentially regulate signal transduction in cancer cells. LPP1 and LPP3 have decreased expressions in several caners and this is associated with increased tumor growth and metastasis.  Conversely, LPP2 activity is increased in these cancers and this accelerates progression through the cell cycle. Increasing the relative activities of LPP1 and LPP3 and decreasing LPP2 activity, therefore, provides a novel approach to treating some cancers.
  • 1.7K
  • 11 Sep 2020
Topic Review
G-Quadruplexes: Emerging Anticancer Roles
G-quadruplexes, a family of (thermodynamically and kinetically stable) tetraplex helices, are non-canonical secondary structures derived from guanine (G)-rich sequences of nucleic acids. G-quadruplexes were found to occur in functionally-important regions of the human genome, including the telomere tandem sequences, several proto-oncogene promoters and other regulatory regions, ribosomal DNA (rDNA), as well as mRNA sequences encoding for proteins with roles in tumorigenesis, thus establishing a clear connection between G-quadruplexes and known hallmarks of cancer. Stabilization of G-quadruplexes belonging to the above categories, by means of small-molecule intervention, has been correlated with a range of anticancer effects, which has led to classifying G-quadruplexes as novel potential targets in anticancer research. The most common ways in which G-quadruplexes are now understood to serve in an anticancer capacity are presented herein.
  • 1.7K
  • 03 Mar 2021
Topic Review
Yeast Cells in Microencapsulation
Yeasts are uni/multicellular eukaryotic organisms, originally thought to be ascomycetous fungi, but later recognized to also comprise basidiomycetous organisms; more typically, yeasts reproduce asexually (rapid duplication) but can also adopt sexual reproduction.
  • 1.7K
  • 02 Jul 2021
Topic Review
Antimetabolite Drug
Methotrexate (4-{N-[(2,4-diaminopteridin-6-yl) methyl]-N-methylamino} benzoyl)-L-glutamic acid, MTX) is an antimetabolite drug. It is widely used as a chemotherapeutic agent in rheumatoid arthritis (RA), psoriasis and some sorts of leukemia. MTX is a relatively well-known molecule and is a first-line antirheumatic medication because of its efficacy and safety. It decreases the concentration of tetrahydrofolate (THF) in the cells by the inhibition of dihydrofolate reductase (DHFR) enzyme, therefore it reduces the purine nucleotide and DNA synthesis.
  • 1.7K
  • 27 Oct 2020
Topic Review
Curcumin in Chronic Hepatitis
Curcumin, as a natural product, is inexpensive, without side effects, and can stimulate very well certain areas of the human immune system. The cytotoxicity of curcumin as photosensitizer could be expanded by the intravenous blue laser blood irradiation (IVBLBI) or photobiomodulation in patients with chronic hepatitis B infection, Hepatitis B e-antigen (HBeAg)-positive, noncirrhotic, but nonresponsive to classical therapy. 
  • 1.7K
  • 26 May 2021
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