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Topic Review
BRAF and MEK Inhibitors in Pediatric CNS Tumors
BRAF is a component of the MAPK and PI3K/AKT/mTOR pathways that play a crucial role in cellular proliferation, differentiation, migration, and angiogenesis. Pediatric central nervous system tumors very often show mutations of the MAPK pathway, as demonstrated by next-generation sequencing (NGS), which now has an increasing role in cancer diagnostics.
  • 463
  • 13 Sep 2022
Topic Review
The Role of Formins in Wound Repair
The restoration of an intact epidermal barrier after wound injury is the culmination of a highly complex and exquisitely regulated physiological process involving multiple cells and tissues, overlapping dynamic events and protein synthesis and regulation. Central to this process is the cytoskeleton, a system of intracellular proteins that are instrumental in regulating important processes involved in wound repair including chemotaxis, cytokinesis, proliferation, migration, and phagocytosis. One highly conserved family of cytoskeletal proteins that are emerging as major regulators of actin and microtubule nucleation, polymerization, and stabilization are the formins. The formin family includes 15 different proteins categorized into seven subfamilies based on three formin homology domains (FH1, FH2, and FH3). The formins themselves are regulated in different ways including autoinhibition, activation, and localization by a range of proteins, including Rho GTPases
  • 463
  • 04 Oct 2022
Topic Review
Lysosomes in Regulating Metabolism of Hematopoietic Stem Cells
Hematopoietic stem cells (HSCs) have the capacity to renew blood cells at all stages of life and are largely quiescent at a steady state. It is essential to understand the processes that govern quiescence in HSCs to enhance bone marrow transplantation. It is hypothesized that in their quiescent state, HSCs primarily use glycolysis for energy production rather than mitochondrial oxidative phosphorylation (OXPHOS). In addition, the HSC switch from quiescence to activation occurs along a continuous developmental path that is driven by metabolism. Specifying the metabolic regulation pathway of HSC quiescence will provide insights into HSC homeostasis for therapeutic application. Therefore, understanding the metabolic demands of HSCs at a steady state is key to developing innovative hematological therapeutics. Lysosomes are the major degradative organelle in eukaryotic cells. Catabolic, anabolic, and lysosomal function abnormalities are connected to an expanding list of diseases.
  • 463
  • 27 Dec 2022
Topic Review
Cytochrome P450 1B1 in Ocular Iron Homeostasis Regulation
Cytochrome P450 (CYP) 1B1 belongs to the superfamily of heme-containing monooxygenases. Unlike other CYP enzymes, which are highly expressed in the liver, CYP1B1 is predominantly found in extrahepatic tissues, such as the brain, and ocular tissues including retina and trabecular meshwork. CYP1B1 metabolizes exogenous chemicals such as polycyclic aromatic hydrocarbons. CYP1B1 also metabolizes endogenous bioactive compounds including estradiol and arachidonic acid. These metabolites impact various cellular and physiological processes during development and pathological processes.
  • 462
  • 01 Dec 2022
Topic Review
ZIP9
Zinc transporter ZIP9 also known as Zrt- and Irt-like protein 9 (ZIP9) and solute carrier family 39 member 9 (SLC39A9) is a protein that in humans is encoded by the SLC39A9 gene. This protein is the 9th member out of 14 ZIP family proteins, which is a membrane androgen receptor (mAR) coupled to G proteins, and also classified as a zinc transporter protein. ZIP family proteins transport zinc metal from the extracellular environment into cells through cell membrane.
  • 462
  • 21 Nov 2022
Topic Review
DNA Methylation in Low-Grade Gliomas
Gliomas, the most common type of malignant primary brain tumor, were conventionally classified through WHO Grades I–IV (now 1–4), with low-grade gliomas being entities belonging to Grades 1 or 2. While the focus of the WHO Classification for Central Nervous System (CNS) tumors had historically been on histopathological attributes, the recently released fifth edition of the classification (WHO CNS5) characterizes brain tumors, including gliomas, using an integration of histological and molecular features, including their epigenetic changes such as DNA methylation which are increasingly being used for the classification of low-grade gliomas. 
  • 462
  • 01 Mar 2023
Topic Review
Post-Translational Modifications
The healthy state is guaranteed by the fine-tuning of genes controlling cell proliferation, differentiation, and development, whose alteration induces cellular behavioral changes finally leading to cancer. A major challenge to the cell is to guarantee that proteins are made, folded, assembled and delivered to function properly, like and even more when referring to oncogenes and onco-suppressors products. Ubiquitination and ubiquitin-like modifications modulate the stability and control the activity of most of the proteins that manage cell cycle, immune responses, apoptosis, and senescence.
  • 461
  • 07 Feb 2023
Topic Review
Post-Translational Modifications in Regulation of NLRP3 Inflammasome Activation
Pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) induce NLRP3 inflammasome activation, and subsequent formation of active caspase-1 as well as the maturation of interleukin-1β (IL-1β) and gasdermin D (GSDMD), mediating the occurrence of pyroptosis and inflammation. Aberrant NLRP3 inflammasome activation causes a variety of diseases. Therefore, the NLRP3 inflammasome pathway is a target for prevention and treatment of relative diseases. 
  • 461
  • 26 Apr 2023
Topic Review
PE_PGRS33 and humoral immune response
PE_PGRS proteins are surface antigens of Mycobacterium tuberculosis (Mtb) and a few other pathogenic mycobacteria. The PE_PGRS33 protein is among the most studied PE_PGRSs. It is known that the PE domain of PE_PGRS33 is required for the protein translocation through the mycobacterial cell wall, where the PGRS domain remains available for interaction with host receptors. Interaction with Toll like receptor 2 (TLR2) promotes secretion of inflammatory chemokines and cytokines, which are key in the immunopathogenesis of tuberculosis (TB). Here, we address key challenges in the development of a TB vaccine and attempt to provide a rationale for the development of new vaccines aimed at fostering a humoral response against Mtb. We show that the PGRS domain of PE_PGRS33 exposes four PGII sandwiches on the outer surface, which we propose to be directly involved through their loops in the interactions with the host receptors and as such are promising targets for a vaccination strategy aimed at inducing a humoral response. 
  • 460
  • 27 Jan 2021
Topic Review
CAF partners with Endometrial Tumor-Cells
A tumor cell carrying characteristic genomic alteration(s) exists within its host’s microenvironment. The tempero-spatial interaction of tumor cells with its microenvironment is the deterministic factor for tumor growth, progression, resistance to therapy, and its outcome in clinics. This manuscript presents a systemic review of the role of CAF in endometrial cancers. Here we present the functional characteristics of CAF in the context of endometrial cancers. We review (1) the characteristics of CAF, (2) their evolution from being anti-tumor to pro-tumor, (3) their involvement in regulating growth and several metastasis-associated phenotypes of tumor cells, (4) their participation in perturbing immune defense and evading immune surveillance, and (5) their role in mediating drug resistance via tumor-CAF cross-talk with particular reference to endometrial cancers. We interrogate the functional characteristics of CAF in the light of its dialogue with tumor cells and other components of TME towards developing a CAF-based strategy for precision therapy to supplement tumor-based therapy. The purpose of the review is to present a new vision and initiate a thought process which recognizes the importance of CAF in a tumor, thereby resulting in a novel approach to the design and management of the disease in endometrial cancers.
  • 460
  • 29 Mar 2022
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