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Topic Review
Endoglin
Endoglin is a class I, single-membrane spanning receptor with an apparent molecular weight of 95 kDa containing a short cytoplasmic and a modular extracellular domain. This domain contains attachment sites for N- and O-dependent glycosylation and ligand binding residues.
  • 1.3K
  • 16 Apr 2021
Topic Review
IRDS Genes: Interfaces and Pathways
Interferon (IFN)-related DNA damage resistant signature (IRDS) genes are a subgroup of interferon-stimulated genes (ISGs) found upregulated in different cancer types, which promotes resistance to DNA damaging chemotherapy and radiotherapy.
  • 1.3K
  • 27 Apr 2021
Topic Review
Computational Drug Design of TB
Developing new, more effective antibiotics against resistant Mycobacterium tuberculosis that inhibit its essential proteins is an appealing strategy for combating the global tuberculosis (TB) epidemic. Finding a compound that can target a particular cavity in a protein and interrupt its enzymatic activity is the crucial objective of drug design and discovery. Such a compound is then subjected to different tests, including clinical trials, to study its effectiveness against the pathogen in the host. In recent times, new techniques, which involve computational and analytical methods, enhanced the chances of drug development, as opposed to traditional drug design methods, which are laborious and time-consuming. The computational techniques in drug design have been improved with a new generation of software used to develop and optimize active compounds that can be used in future chemotherapeutic development to combat global tuberculosis resistance.
  • 1.3K
  • 17 Dec 2021
Topic Review
DNA Dyes
Cell quantification is widely used both in basic and applied research. A typical example of its use is drug discovery research. Presently, plenty of methods for cell quantification are available. In this review, the basic techniques used for cell quantification, with a special emphasis on techniques based on fluorescent DNA dyes, are described. 
  • 1.3K
  • 23 Sep 2021
Topic Review
Semaphorins Effects in Metabolic Disorders
       Semaphorins are a family originally identified as axonal guidance molecules. They are also involved in tumor growth, angiogenesis, immune regulation, as well as other biological and pathological processes. Recent studies have shown that semaphorins play a role in metabolic diseases including obesity, adipose inflammation, and diabetic complications, including diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, diabetic wound healing, and diabetic osteoporosis. Evidence provides mechanistic insights regarding the role of semaphorins in metabolic diseases by regulating adipogenesis, hypothalamic melanocortin circuit, immune responses, and angiogenesis. In this review, we summarize recent progress regarding the role of semaphorins in obesity, adipose inflammation, and diabetic complications.
  • 1.3K
  • 28 Aug 2020
Topic Review
Histone H1 post-translational modifications
Protein molecules can be further modified after translation. Post-translational modifications (PTMs) are responsible for most of the proteome diversity and often modulate critical protein functions in health and disease. Histone H1 is a chromatin structural protein, which contains many PTMs that may alter chromatin structure and function. In this entry, we present a summary of the post-translational modifications (PTMs) identified, up to date, in histone H1 from lower eukaryotes to humans. We also highlight the use of different proteomic strategies, as well as the technical challenges involved in mapping H1 PTMs.
  • 1.3K
  • 26 Aug 2020
Topic Review
Mammalian Aquaporins
Mammalian aquaporins (AQPs) are transmembrane channels expressed in a large variety of cells and tissues throughout the body. They are known as water channels, but they also facilitate the transport of small solutes, gasses, and monovalent cations. To date, 13 different AQPs, encoded by the genes AQP0–AQP12, have been identified in mammals, which regulate various important biological functions in kidney, brain, lung, digestive system, eye, and skin. Consequently, dysfunction of AQPs is involved in a wide variety of disorders. AQPs are also present in the heart, even with a specific distribution pattern in cardiomyocytes, but whether their presence is essential for proper (electro)physiological cardiac function has not intensively been studied. In a recent review published in Int. J. Mol. Sci. (https://doi.org/10.3390/ijms20082039), we summarizes recent findings and highlights the involvement of AQPs in normal and pathological cardiac function. We conclude that AQPs are at least implicated in proper cardiac water homeostasis and energy balance as well as heart failure and arsenic cardiotoxicity. However, our review also demonstrates that many effects of cardiac AQPs, especially on excitation-contraction coupling processes, are virtually unexplored.
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  • 06 Sep 2021
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. 
  • 1.3K
  • 19 Mar 2021
Topic Review
cAMP-Response Element Modulator in Spermatogenesis and Male Fertility
Spermatogenesis is a very complex process with an intricate transcriptional regulation. The transition from the diploid to the haploid state requires the involvement of specialized genes in meiosis, among other specific functions for the formation of the spermatozoon. The transcription factor cAMP-response element modulator (CREM) is a key modulator that triggers the differentiation of the germ cell into the spermatozoon through the modification of gene expression. CREM has multiple repressor and activator isoforms whose expression is tissue-cell-type specific and tightly regulated by various factors at the transcriptional, post-transcriptional and post-translational level. The activator isoform CREMτ controls the expression of several relevant genes in post-meiotic stages of spermatogenesis. In addition, exposure to xenobiotics negatively affects CREMτ expression, which is linked to male infertility. On the other hand, antioxidants could have a positive effect on CREMτ expression and improve sperm parameters in idiopathically infertile men.
  • 1.3K
  • 01 Nov 2023
Topic Review
Mast Cells
Mast Cells (MCs), from the German mast meaning well-fed, were first described by Paul Ehrlich in 1878 based on the unique color-changing granules within these cells. In fact, MCs are easily recognizable with characteristic toluidine blue-positive granules in the cytoplasm. Their granules contain several elements, such as histamine, serotonin, heparin, proteases (chymase, tryptase, carboxypeptidase), cytokines and other growth factors (vascular endothelial growth factor, VEGF; fibroblast growth factor-2, FGF-2). Tryptases and chymases are considered MC-specific proteases, but the granules also contain some non-specific enzymes, such as metalloproteinase-9.
  • 1.3K
  • 28 Sep 2021
Topic Review
Delivery Platforms for miRNA-Based Cancer Therapeutics
Restoration of microRNA (miRNA) expression or downregulation of aberrantly expressed miRNAs using miRNA mimics or anti-miRNA inhibitors (anti-miRs/antimiRs), respectively, continues to show therapeutic potential for the treatment of cancer. Although the manipulation of miRNA expression presents a promising therapeutic strategy for cancer treatment, it is predominantly reliant on nucleic acid-based molecules for their application, which introduces an array of hurdles, with respect to in vivo delivery. Because naked nucleic acids are quickly degraded and/or removed from the body, they require delivery vectors that can help overcome the many barriers presented upon their administration into the bloodstream.
  • 1.3K
  • 25 Aug 2022
Topic Review
Chemical Speciation of Iodine and Practical Applications
Iodine is one of the 30 essential elements for life, and its chemical speciation defines its biological activities. Both inorganic and organic chemical species have crucial roles in the biology of most living organisms. The most relevant inorganic species are iodate (IO3−) and iodide (I−), as the major sources of iodine for living beings, together with molecular iodine (I2) and hypoiodous acid (HIO) as the most reactive performing catalytic activities. Conversely, Thyroid Hormones (THs) are the master regulators of the metabolism of vertebrates and the representative organic species. Mainly inorganic species are exploited in the health science industry to produce disinfectants, supplements, medicines, and X-ray contrast media. 
  • 1.3K
  • 25 Oct 2022
Topic Review
Glutathione-Mediated Conjugation of Anticancer Drugs
The effectiveness of many anticancer drugs depends on the creation of specific metabolites that may alter their therapeutic or toxic properties. One significant route of biotransformation is a conjugation of electrophilic compounds with reduced glutathione, which can be non-enzymatic and/or catalyzed by glutathione-dependent enzymes. Glutathione usually combines with anticancer drugs and/or their metabolites to form more polar and water-soluble glutathione S-conjugates, readily excreted outside the body. In this regard, glutathione plays a role in detoxification, decreasing the likelihood that a xenobiotic will react with cellular targets.
  • 1.3K
  • 26 Aug 2022
Topic Review
Alternative Splicing
Alternative splicing (AS) is a critical post-transcriptional regulatory mechanism used by more than 95% of transcribed human genes and responsible for structural transcript variation and proteome diversity.
  • 1.3K
  • 18 Mar 2021
Topic Review
Development of CDK4/6 Inhibitors
CDKs, a family of serine/threonine kinases, regulate cell cycle progression into the four distinct phases G1, S (DNA synthesis), G2 and M, and are crucially involved in the regulation of cell division and proliferation.
  • 1.3K
  • 23 Apr 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.
  • 1.3K
  • 27 Oct 2020
Topic Review
The Key Precursors of Brain Acetyl-CoA
Acetyl-CoA  is a principal substrate feeding tricarboxylic acid (TCA). cycle  and energy production. Brain displays high demand for energy due to high frequency of neuronal depolarizatio-repolarization cycles. Therefore, adequate provision of acetyl-CoA precursors is critical factor for proper neuronal activity and survival. 
  • 1.3K
  • 22 Sep 2022
Topic Review
Connexin 26
Connexin 26, one of the smallest connexins, is expressed in diverse epithelial tissue and mutations in this protein are associated with hearing loss, skin and eye conditions of differing severity.
  • 1.3K
  • 26 Jan 2021
Topic Review
PDE4 as Therapeutic Targets in Different Diseases
Cyclic nucleotides (cAMP, cGMP) play a major role in normal and pathologic signaling. Beyond receptors, cyclic nucleotide phosphodiesterases; (PDEs) rapidly convert the cyclic nucleotide in its respective 5′-nucleotide to control intracellular cAMP and/or cGMP levels to maintain a normal physiological state. However, in many pathologies, dysregulations of various PDEs (PDE1-PDE11) contribute mainly to organs and tissue failures related to uncontrolled phosphorylation cascade. Among these, PDE4 represents the greatest family, since it is constituted by 4 genes with multiple variants differently distributed at tissue, cellular and subcellular levels, allowing different fine-tuned regulations.
  • 1.3K
  • 11 Oct 2022
Topic Review
Chemical Enzymology of Monoamine Oxidase
Monoamine oxidase (E.C. 1.4.3.4) enzymes MAO A and MAO B are FAD-containing proteins located on the outer face of the mitochondrial inner membrane, retained there by hydrophobic interactions and a transmembrane helix. The redox co-factor (FAD) is covalently attached to a cysteine and buried deep inside the protein behind an aromatic cage that aligns substrates towards the flavin. MAO metabolizes neurotransmitters such as dopamine and serotonin in the nervous system so is a target for drugs to modify amine levels. MAO also metabolizes a wide range of biogenic amines in all tissues. Current accumulated evidence, particularly from theoretical modelling, supports hydride transfer as the chemical mechanism. The long active site cavity accommodates a wide chemical variety of small molecules designed as inhibitors, including coumarins, chromones, triazoles, and more. Inactivators that bind covalently to MAO include hydrazines, cyclopropylamines and propargylamines. This entry is an extract adapted from a review outlining the remaining uncertainties in the understanding of this key drug target.
  • 1.3K
  • 19 Oct 2021
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