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Topic Review
K+-2Cl− cotransporter 2 (KCC2)
Intracellular chloride levels in the brain are regulated primarily through the opposing effects of two cation-chloride co-transporters (CCCs), namely K+-Cl− co-transporter-2 (KCC2) and Na+-K+-Cl− co-transporter-1 (NKCC1). These CCCs are differentially expressed throughout the course of development, thereby determining the excitatory-to-inhibitory γ-aminobutyric acid (GABA) switch. GABAergic excitation (depolarisation) is important in controlling the healthy development of the nervous system; as the brain matures, GABAergic inhibition (hyperpolarisation) prevails. This developmental switch in excitability is important, as uncontrolled regulation of neuronal excitability can have implications for health.
  • 1.2K
  • 22 Jan 2021
Topic Review
PKCtheta in Cancer
Protein Kinase C theta (PKCθ) is a serine/threonine kinase that belongs to the novel PKC sub-family. PKCθ has been extensively studied for its role in the immune system where it plays a critical role in T cell activation. Beyond its physiological role in immune responses, increasing evidence implicates PKCθ in the pathology of various diseases, especially autoimmune disorders and cancers. Particularly, in various types of cancers, the high PKCθ expression leads to aberrant cell proliferation, migration and invasion, thereby promoting cancer aggressiveness. The recent development and application of PKCθ inhibitors in the context of auto-immune diseases could benefit the emergence of treatment for cancers in which PKCθ has been implicated.
  • 1.2K
  • 20 Feb 2021
Topic Review
5-10-Methylenetetrahydrofolate Reductase
The 5-10-methylenetetrahydrofolate reductase (MTHFR) enzyme is vital for cellular homeostasis due to its key functions in the one-carbon cycle, which include methionine and folate metabolism, and protein, DNA, and RNA synthesis. 
  • 1.2K
  • 14 Feb 2022
Topic Review
Small Peptides of Marine Origin
Cancer is one of the leading causes of death in the world, and antineoplastic drug research continues to be a major field in medicine development. The marine milieu has thousands of biological species that are a valuable source of novel functional proteins and peptides, which have been used in the treatment of many diseases, including cancer. In contrast with proteins and polypeptides, small peptides (with a molecular weight of less than 1000 Da) have overwhelming advantages, such as preferential and fast absorption, which can decrease the burden on human gastrointestinal function. Besides, these peptides are only connected by a few peptide bonds, and their small molecular weight makes it easy to modify and synthesize them. Specifically, small peptides can deliver nutrients and drugs to cells and tissues in the body. These characteristics make them stand out in relation to targeted drug therapy. Nowadays, the anticancer mechanisms of the small marine peptides are still largely not well understood; however, several marine peptides have been applied in preclinical treatment. 
  • 1.2K
  • 10 Mar 2021
Topic Review
Antimicrobial Lipids from Plants and Marine Organisms
Medicinal plants and marine organisms are natural sources of many antimicrobial compounds. Plant components with antimicrobial activity include alkaloids, sulfur-containing compounds, diterpenes/terpenoids, fatty acids (FA), some carbohydrates, steroidal glycosides, and phenolic compounds. Both primary and secondary metabolites are “generally recognized as safe” (GRAS) substances and the chance of triggering antimicrobial resistance is low. The most studied antimicrobial compounds of marine origin are peptides and alkaloids, contrarily to lipids. However, lipids are ubiquitously distributed in the different marine phyla, being quite abundant in some of them. Besides, several lipid classes from marine organisms have been recognized by their biological activity with a high potential to discover new antimicrobial compounds.
  • 1.2K
  • 15 Dec 2021
Topic Review
Targeting Tryptophan Metabolism to Treat Cancers
Major hallmarks of cancers are connected to dysfunctions in many metabolic pathways aiming at providing the energetic needs and the raw material for cellular growth and the signaling molecules needed for oncogenesis. Tryptophan (TRP) catabolism through the kynurenine (KYN) pathway was reported to play immunosuppressive actions across many types of cancer. However, results from clinical trials assessing the benefit of inhibiting key limiting enzymes of this pathway such as indoleamine 2,3-dioxygenase (IDO1) or tryptophan 2,3-dioxygenase (TDO2) failed to meet the expectations. Bearing in mind the complexity of the tumoral terrain and the existence of different cancers with IDO1/TDO2 expressing and non-expressing tumoral cells, here we present a comprehensive analysis of the TRP global metabolic hub and the approach of inhibiting these pathways as a potential therapeutic option to treat cancers such as liver cancers. 
  • 1.2K
  • 29 Mar 2022
Topic Review
TRPC, TRPV and Vascular Disease
Ion channels play an important role in vascular function and pathology. In this review we gave an overview of recent findings and discussed the role of TRPC and TRPV channels as major regulators of cellular remodeling and consequent vascular disorders. Here, we focused on their implication in 4 relevant vascular diseases: systemic and pulmonary artery hypertension, atherosclerosis and restenosis.  
  • 1.2K
  • 22 Apr 2021
Topic Review
S-Glutathionylation and S-Nitrosylation in Mitochondria: Homeostasis and Neurodegeneration
Redox post-translational modifications are derived from fluctuations in the redox potential and modulate protein function, localization, activity and structure. Amongst the oxidative reversible modifications, the S-glutathionylation of proteins was the first to be characterized as a post-translational modification, which primarily protects proteins from irreversible oxidation. S-nitrosylation, another post-translational modification, was identified in the past, but it was re-introduced as a prototype cell-signaling mechanism, one that tightly regulates core processes within the cell’s sub-compartments, especially in mitochondria. S-glutathionylation and S-nitrosylation are modulated by fluctuations in reactive oxygen and nitrogen species and, in turn, orchestrate mitochondrial bioenergetics machinery, morphology, nutrients metabolism and apoptosis.
  • 1.2K
  • 26 Dec 2022
Topic Review
Arbuscular Mycorrhizal Fungi and Strigolactone
Plants, the cornerstone of life on Earth, are constantly struggling with a number of challenges arising from both biotic and abiotic stressors. To overcome these adverse factors, plants have evolved complex defense mechanisms involving both a number of cell signaling pathways and a complex network of interactions with microorganisms. Among these interactions, the relationship between symbiotic arbuscular mycorrhizal fungi (AMF) and strigolactones (SLs) stands as an important interplay that has a significant impact on increased resistance to environmental stresses and improved nutrient uptake and the subsequent enhanced plant growth.
  • 1.2K
  • 06 Dec 2023
Topic Review
RBM10−a New Regulator of p53
The tumor suppressor p53 acts as a transcription factor that regulates the expression of a number of genes responsible for DNA repair, cell cycle arrest, metabolism, cell migration, angiogenesis, ferroptosis, senescence, and apoptosis. It is the most commonly silenced or mutated gene in cancer, as approximately 50% of all types of human cancers harbor TP53 mutations. Activation of p53 is detrimental to normal cells, thus it is tightly regulated via multiple mechanisms. One of the recently identified regulators of p53 is RNA-binding motif protein 10 (RBM10). RBM10 is an RNA-binding protein frequently deleted or mutated in cancer cells. Its loss of function results in various deformities, such as cleft palate and malformation of the heart, and diseases such as lung adenocarcinoma. In addition, RBM10 mutations are frequently observed in lung adenocarcinomas, colorectal carcinomas, and pancreatic ductal adenocarcinomas. RBM10 plays a regulatory role in alternative splicing. Several recent studies not only linked this splicing regulation of RBM10 to cancer development, but also bridged RBM10′s anticancer function to the p53 pathway.
  • 1.2K
  • 09 Oct 2020
Topic Review
Amyloidogenic Regions in bPaS1
Bacterial S1 protein is a functionally important ribosomal protein. It is a part of the 30S ribosomal subunit and is also able to interact with mRNA and tmRNA. An important feature of the S1 protein family is a strong tendency towards aggregation. 
  • 1.2K
  • 20 Jul 2021
Topic Review
Selenium and Ageing
Selenium (Se) is an essential dietary trace element that plays an important role in the prevention of inflammation, cardiovascular diseases, infections, and cancer. Selenoproteins contain selenocysteine in the active center and include, i.a., the enzymes thioredoxin reductases (TXNRD1–3), glutathione peroxidases (GPX1–4 and GPX6) and methionine sulfoxide reductase, involved in immune functions, metabolic homeostasis, and antioxidant defense. Ageing is an inevitable process, which, i.a., involves an imbalance between antioxidative defense and reactive oxygen species (ROS), changes in protein and mitochondrial renewal, telomere attrition, cellular senescence, epigenetic alterations, and stem cell exhaustion. These conditions are associated with mild to moderate inflammation, which always accompanies the process of ageing and age-related diseases. In older individuals, Se, by being a component in protective enzymes, operates by decreasing ROS-mediated inflammation, removing misfolded proteins, decreasing DNA damage, and promoting telomere length. Se-dependent GPX1–4 and TXNRD1–3 directly suppress oxidative stress. Selenoprotein H in the cell nucleus protects DNA, and selenoproteins residing in the endoplasmic reticulum (ER) assist in the removal of misfolded proteins and protection against ER stress.
  • 1.2K
  • 11 Nov 2021
Topic Review
Didymo
Didymosphenia geminata diatoms, or Didymo, was first found to be an invasive species that could have negative impacts on the environment due to the aggressive growth of its polysaccharide-based stalks.
  • 1.2K
  • 08 Nov 2021
Topic Review
Protein Tyrosine Phosphatases
Protein tyrosine kinases, especially receptor tyrosine kinases, have dominated the cancer therapeutics sphere as proteins that can be inhibited to selectively target cancer. However, protein tyrosine phosphatases (PTPs) are also an emerging target. Though historically known as negative regulators of the oncogenic tyrosine kinases, PTPs are now known to be both tumor-suppressive and oncogenic.
  • 1.2K
  • 07 Dec 2021
Topic Review
Non-Coding RNAs in Nervous System
Oxidative stress (OS) is defined as an imbalance between free radicals biogenesis and the cell antioxidant capacity to eliminate them. In neurodegenerative diseases, OS play a central role altering mitochondrial metabolism, protein synthesis, and inducing cellular malfunctioning. Most part of the human genome encodes for non-coding protein genes, which are transcribed into non-coding RNA (ncRNA). Most of these ncRNAs are involved transcriptional and post-transcriptional regulation of gene and their deregulation has been linked to diverse neurodegenerative disorders. In this review we compiled most recent evidences reporting a role of main types of ncRNAs in the regulation and management of oxidative stress in Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic Lateral Sclerosis. 
  • 1.2K
  • 19 Nov 2020
Topic Review
Epidermal Stem Cells
The skin surface is modified by numerous appendages. These structures arise from epithelial stem cells (SCs) through the induction of epidermal placodes as a result of local signalling interplay with mesenchymal cells based on the Wnt–(Dkk4)–Eda–Shh cascade. Slight modifications of the cascade, with the participation of antagonistic signalling, decide whether multipotent epidermal SCs develop in interfollicular epidermis, scales, hair/feather follicles, nails or skin glands. 
  • 1.2K
  • 05 Jan 2021
Topic Review
Tumor-Associated Macrophages (TAMs)
Tumor-associated macrophages (TAMs) are a major component of the immune cells of the TME. They play a prominent role by secreting cytokines and chemokines and coordinating with inflammatory mechanisms to promote tumor development, invasion, metastasis, immunosuppression, angiogenesis, and drug tolerance. Different subtypes of TAMs have different functions, which can be dynamically changed in response to various signals from cancer cells or the TME.
  • 1.2K
  • 18 Aug 2021
Topic Review
Mesenchymal Stem Cells in Targeting Triple-Negative Breast Cancer
Triple-negative breast cancer (TNBC) lacks estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expressions, making targeted therapies ineffective. Mesenchymal stem cells (MSCs) have emerged as a promising approach for TNBC treatment by modulating the tumor microenvironment (TME) and interacting with cancer cells.
  • 1.2K
  • 08 May 2023
Topic Review
Molecular concepts in vascular disorders
In physiology and pathophysiology the molecules involved in blood cell–blood cell and blood cell–endothelium interactions have been identified. Platelet aggregation and adhesion to the walls belonging to vessels involve glycoproteins (GP), GP llb and GP llla and the GP Ib–IX–V complex. Red blood cells (RBCs) in normal situations have little interaction with the endothelium. Abnormal adhesion of RBCs was first observed in sickle cell anemia involving vascular cell adhesion molecule (VCAM)-1, α4β1, Lu/BCAM, and intercellular adhesion molecule (ICAM)-4. More recently RBC adhesion was found to be increased in retinal-vein occlusion (RVO) and in polycythemia vera (PV). The molecules which participate in this process are phosphatidylserine and annexin V in RVO, and phosphorylated Lu/BCAM and α5 laminin chain in PV. The additional adhesion in diabetes mellitus occurs due to the glycated RBC band 3 and the advanced glycation end-product receptors. The multiligand receptor binds advanced glycation end products (AGEs) or S100 calgranulins, or β-amyloid peptide. This receptor for advanced glycation end products is known as RAGE. The binding to RAGE-activated endothelial cells leads to an inflammatory reaction and a prothrombotic state via NADPH activation and altered gene expression. RAGE blockade is a potential target for drugs preventing the deleterious consequences of RAGE activation.
  • 1.2K
  • 28 Sep 2021
Topic Review
EVs as Potential-Biomarkers in MS
       Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and its pathophysiology is characterized by a progressive blood-brain barrier dysfunction accompanied by infiltration in the central nervous system of peripheral pathogenic immune cells and inflammatory mediators leading to demyelination, axonal damage, and dysfunction and/or loss of synapses. Accumulating evidence highlights blood and cerebrospinal fluid (CSF) derived extracellular vesicles (EVs) as potential biomarkers of MS disease stages and of response to treatment. In particular, EVs released from blood–brain barrier (BBB) endothelial cells, platelets, leukocytes, myeloid cells, astrocytes, and oligodendrocytes seem to be involved in the pathogenesis of MS and of its rodent model experimental autoimmune encephalomyelitis. Further research is necessary to validate these observations and the screening of specific EVs subsets based on their cargo and membrane compositions associated to specific MS pathophysiological mechanisms might help guiding MS diagnosis, prognosis, and response to therapy. 
  • 1.2K
  • 28 Sep 2021
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