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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
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
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
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
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
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
Dystroglycanopathy
Dystroglycanopathy is a collective term referring to muscular dystrophies with abnormal glycosylation of dystroglycan. At least 18 causative genes of dystroglycanopathy have been identified, and its clinical symptoms are diverse, ranging from severe congenital to adult-onset limb-girdle types. 
  • 1.2K
  • 12 Jan 2022
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
Thrombospondin-1 CD47 Signalling
Recent advances provide evidence that the cellular signalling pathway comprising the ligand-receptor duo of thrombospondin-1 (TSP1) and CD47 is involved in mediating a range of diseases affecting renal, vascular, and metabolic function, as well as cancer. In several instances, research has barely progressed past pre-clinical animal models of disease and early phase 1 clinical trials, while for cancers, anti-CD47 therapy has emerged from phase 2 clinical trials in humans as a crucial adjuvant therapeutic agent. This has important implications for interventions that seek to capitalize on targeting this pathway in diseases where TSP1 and/or CD47 play a role. Despite substantial progress made in our understanding of this pathway in malignant and cardiovascular disease, knowledge and translational gaps remain regarding the role of this pathway in kidney and metabolic diseases, limiting identification of putative drug targets and development of effective treatments. This review considers recent advances reported in the field of TSP1-CD47 signalling, focusing on several aspects including enzymatic production, receptor function, interacting partners, localization of signalling, matrix-cellular and cell-to-cell cross talk. The potential impact that these newly described mechanisms have on health, with a particular focus on renal and metabolic disease, is also discussed.
  • 1.2K
  • 02 Jul 2021
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
ADAM9 in Cancers
ADAM9 plays an important role in tumor biology. It is overexpressed in several cancer types and is correlated with tumor aggressiveness and poor prognosis. Through either proteolytic or non-proteolytic pathways, ADAM9 promotes tumor progression, therapeutic resistance, and metastasis of cancers. Therefore, comprehensively understanding the mechanism of ADAM9 is crucial for the development of therapeutic anti-cancer strategies.
  • 1.2K
  • 13 Jan 2021
Topic Review
Heat Shock Protein 90
Heat shock protein 90 (Hsp90) is a molecular chaperone that could modulate the pain signaling.
  • 1.2K
  • 08 Jan 2021
Topic Review
Cancer Chemoprevention
Carcinogenesis is a multistep process characterized by a progression of molecular changes that ultimately transform a cell to undergo uncontrolled proliferation.
  • 1.2K
  • 02 Apr 2021
Topic Review
Metabolic Reprogramming in Tumor Endothelial Cells
The dynamic crosstalk between the different components of the tumor microenvironment is critical to determine cancer progression, metastatic dissemination, tumor immunity, and therapeutic responses. Angiogenesis is critical for tumor growth, and abnormal blood vessels contribute to hypoxia and acidosis in the tumor microenvironment. In this hostile environment, cancer and stromal cells have the ability to alter their metabolism in order to support the high energetic demands and favor rapid tumor proliferation. 
  • 1.2K
  • 12 Oct 2022
Topic Review
Gene annotation for 'Flaviviridae' genomes
Responding to the ongoing and severe public health threat of viruses of the family Flaviviridae, including dengue, hepatitis C, West Nile, yellow fever, and Zika, demands a greater understanding of how these viruses emerge and spread. Updated phylogenies are central to this understanding. Most cladograms of Flaviviridae focus on specific lineages and ignore outgroups, thus hampering the efficacy of the analysis to test ingroup monophyly and relationships. This is due to the lack of annotated Flaviviridae genomes, which has gene content variation among genera. This variation makes analysis without partitioning difficult. Therefore, we developed an annotation pipeline for the genera of Flaviviridae (Flavirirus, Hepacivirus, Pegivirus, and Pestivirus), named “Fast Loci Annotation of Viruses” (FLAVi: flavi-web.com), that combines ab initio and homology-based strategies. FLAVi recovered 100% of the genes in Flavivirus and Hepacivirus genomes. In Pegivirus and Pestivirus, annotation efficiency was 100% except for one partition each. There were no false positives. The combined phylogenetic analysis of multiple genes made possible by annotation has clear impacts over the tree topology compared to phylogenies that we inferred without outgroups or data partitioning. The final tree is largely congruent with previous hypotheses and adds evidence supporting the close phylogenetic relationship between dengue and Zika.
  • 1.2K
  • 27 Oct 2020
Topic Review
Biomarker Studies in Stress Biology
Endpoints assessed at the population or community level are most often the result of the sum of effects on individuals, arising from the effects at the cellular and molecular levels. Within this framework, these lower biological level endpoints are more responsive at an early stage of exposure, making them potential toolboxes to be used as early-warning markers to address stress. Given this, by linking responses and understanding organisms’ metabolism and physiology, the possibilities for the use of biomarkers in stress biology are vast.
  • 1.2K
  • 10 Jan 2022
Topic Review
EVs, Substance Abuse, and HIV
While extracellular vesicles (EVs) have been shown to play a role in CNS disorders, the intersection of EVs, drug use, and HIV is of particular interest. The interactions of HIV and drugs of abuse are a growing concern given the increasing incidence of HIV transmission via shared needles in illicit drug use. As a drug commonly taken through shared needles, METH is being investigated due to its role in exacerbating HIV-mediated inflammation through both increased vesicular shedding and extracellular release. In vivo experiments have shown that cocaine-induced EV release impacts synaptic plasticity through noncoding RNA. Nicotine studies have also highlighted how the differential packaging of antioxidant enzyme cargoes into EVs affects nicotine-mediated HIV pathogenesis. Additionally, studies of both morphine and heroin have demonstrated differences in the miRNA cargoes of EVs, potentially impacting gene expression and exacerbating HIV. Studies of alcohol use in combination with HIV have shown that EV cargoes such as cytokines are affected in HIV-infected subjects who use alcohol. Investigating EV cargo alterations in all forms of substance abuse studies may allow the EV, HIV, and addiction fields to progress towards diagnosis and remedies for substance-abuse-induced toxicity in HIV patients.
  • 1.2K
  • 27 Sep 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
Peretinoin
Peretinoin, an retinoid acid (RA), a metabolite of vitamin A and its related analogues (termed retinoids) has been suggested as a promising chemotherapeutic agent in cancer treatment. The synthetic oral retinoid peretinoin is the only agent for the secondary chemoprevention of HCC after curative therapy that is currently well applied into clinical development.
  • 1.2K
  • 12 Oct 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
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