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Topic Review
The Astrocytes in Brain Ischemia-Reperfusion Injury
Astrocytes account for 50% of the human brain volume and are normally classified into two mayor types according to morphological and spatial criteria: fibrous astrocytes in the white matter and protoplasmic astrocytes predominant in the grey matter. Astrocytes are the main glia of the central nervous system and play an important role both in brain physiology and in the response to damage. This article summarizes the most important evidence related to astrocytes and their response to cerebral ischemia. 
  • 953
  • 27 Jun 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. 
  • 953
  • 01 Mar 2023
Topic Review
CD36 in Pancreatic β-Cell Pathophysiology
CD36 is a transmembrane glycoprotein found in platelets, mononuclear phagocytes, adipocytes, hepatocytes, myocytes, taste bud cells, and a variety of other cell types. 
  • 952
  • 28 Sep 2021
Topic Review
Major Components of Air Pollution Affecting Skin Appearance
The human skin is exposed daily to different environmental factors such as air pollutants and ultraviolet (UV) light. Air pollution is considered a harmful environmental risk to human skin and is known to promote aging and inflammation of this tissue, leading to the onset of skin disorders and to the appearance of wrinkles and pigmentation issues. Besides this, components of air pollution can interact synergistically with ultraviolet light and increase the impact of damage to the skin. 
  • 951
  • 19 Jul 2022
Topic Review
Manganese Superoxide Dismutase in Diseases
Redox equilibria and the modulation of redox signalling play crucial roles in physiological processes. Overproduction of reactive oxygen species (ROS) disrupts the body’s antioxidant defence, compromising redox homeostasis and increasing oxidative stress, leading to the development of several diseases. Manganese superoxide dismutase (MnSOD) is a principal antioxidant enzyme that protects cells from oxidative damage by converting superoxide anion radicals to hydrogen peroxide and oxygen in mitochondria. Systematic studies have demonstrated that MnSOD plays an indispensable role in multiple diseases. 
  • 951
  • 03 Jan 2023
Topic Review
P-21 Activated Kinases in Liver Disorders
The p21 Activated Kinases (PAKs) are serine threonine kinases and play important roles in many biological processes, including cell growth, survival, cytoskeletal organization, migration, and morphology. PAKs have emerged in the process of liver disorders, including liver cancer, hepatic ischemia-reperfusion injury, hepatitis, and liver fibrosis, owing to their effects in multiple signaling pathways in various cell types. Activation of PAKs promotes liver cancer growth and metastasis and contributes to the resistance of liver cancer to radiotherapy and chemotherapy, leading to poor survival of patients. PAKs also play important roles in the development and progression of hepatitis and other pathological processes of the liver such as fibrosis and ischemia-reperfusion injury.
  • 951
  • 10 Mar 2023
Topic Review
Multidrug Resistance Mechanisms and Nano-Treatments
The cellular mechanisms of drug resistance prevent the correct efficacy of the therapies used in various types of cancer and nanotechnology has been postulated as a possible alternative to avoid them. This entry focuses on describing the different mechanisms of drug resistance and dis-covering which nanotechnology-based therapies have been used in recent years to evade them in colon (CRC) and pancreatic cancer (PAC). Here we summarize the use of different types of nanotechnology (mainly nanoparticles) that have shown efficacy in vitro and in vivo in preclinical phases, allowing future in-depth research in CRC and PAC and its translation to future clinical trials.
  • 950
  • 02 May 2021
Topic Review
Cripto in scientific literature
Cripto is a small glycosylphosphatidylinisitol (GPI)-anchored and secreted oncofetal protein that plays important roles in regulating normal physiological processes, including stem cell differentiation, embryonal development, and tissue growth and remodeling, as well as pathological processes such as tumor initiation and progression. Cripto functions as a co-receptor for TGF-β ligands such as Nodal, GDF1, and GDF3. Soluble and secreted forms of Cripto also exhibit growth factor-like activity and activate SRC/MAPK/PI3K/AKT pathways. Glucose-Regulated Protein 78 kDa (GRP78) binds Cripto at the cell surface and has been shown to be required for Cripto signaling via both TGF-β and SRC/MAPK/PI3K/AKT pathways.
  • 948
  • 19 Oct 2020
Topic Review
Deubiquitinases in Regulated Cell Death
The mechanisms and physiological implications of regulated cell death (RCD) have been extensively studied. Among the regulatory mechanisms of RCD, ubiquitination and deubiquitination enable post-translational regulation of signaling by modulating substrate degradation and signal transduction. Deubiquitinases (DUBs) are involved in diverse molecular pathways of RCD. Some DUBs modulate multiple modalities of RCD by regulating various substrates and are powerful regulators of cell fate.
  • 948
  • 05 May 2021
Topic Review
Secretory Autophagy Forges Therapy Resistant Microenvironment in Melanoma
Tumor microenvironment (TME) is a complex of many cell types and extracellular matrix that play an active role in regulating and sustaining melanoma tumor progression. The secretion of several molecules, by secretory autophagy or exosome release, stimulates the intercellular communication between the different components of the TME modulating tumor response.
  • 947
  • 15 Feb 2022
Topic Review
Autophagy in Cell Survival and Cell Death
Autophagy is a process conserved from yeast to humans. Since the discovery of autophagy, its physiological role in cell survival and cell death has been intensively investigated. The inherent ability of the autophagy machinery to sequester, deliver, and degrade cytoplasmic components enables autophagy to participate in cell survival and cell death in multiple ways. The primary role of autophagy is to send cytoplasmic components to the vacuole or lysosomes for degradation. By fine-tuning autophagy, the cell regulates the removal and recycling of cytoplasmic components in response to various stress or signals. Autophagy also facilitates certain forms of regulated cell death. In addition, there is complex crosstalk between autophagy and regulated cell death pathways, with a number of genes shared between them, further suggesting a deeper connection between autophagy and cell death. Finally, the mitochondrion presents an example where the cell utilizes autophagy to strike a balance between cell survival and cell death.
  • 947
  • 22 Jul 2022
Topic Review
Breast carcinoma eukaryotic initiation factors
Breast cancer is the most frequent neoplasm in females. It is a heterogenous entity, classified into intrinsic subtypes based on gene expression data and in corresponding clinical subtypes based on the determination of hormone receptor expression and proliferative activity estimated from ki67 by immunohistochemistry. As for other tumors, the metabolism of breast tumors depends on aerobic glycolysis ("Warburg-effect") and the capability for effective biosynthesis of proteins. Quantity and quality of protein biosynthesis is mainly controlled in the initiation phase of translation, which is characterized by a complex interaction of eucaryotic initiation factors with the mRNA and ribosomal proteins to form a translationally active ribosome. Thus the eIF subunit composition varies from cancer to cancer and is a key factor for determining the cancer cell´s proteome. eIFs can therefore become a suitable anti-cancer drug target. We here summarize the current knowledge on eIF expression and prognostic impact in breast cancer.
  • 946
  • 11 Aug 2020
Topic Review
Tumor-derived exosomes in tumor-induced immune suppression
Exosomes are a class of small membrane-bound extracellular vesicles released by almost all cell types and present in all body fluids. Based on the studies of exosome content and their interactions with recipient cells, exosomes are now thought to mediate “targeted” information transfer. Tumor-derived exosomes (TEX) carry a cargo of molecules different from that of normal cells-derived exosomes. TEX functions to mediate distinct biological effects such as receptor discharge and intercellular cross-talk. The immune system defenses, which may initially restrict tumor progression, are progressively blunted by the broad array of TEX molecules that activate suppressive pathways in different immune cells. Herein, we provide a review of the latest research progress on TEX in the context of tumor-mediated immune suppression, and discuss the potential as well as challenges of TEX as a target of immunotherapy. 
  • 946
  • 29 Mar 2022
Topic Review
Tour of the Nuclear Pore Complex Architecture
Nuclear pore complexes (NPCs) are the only transport channels that cross the nuclear envelope. Constructed from ~500–1000 nucleoporin proteins each, they are among the largest macromolecular assemblies in eukaryotic cells. Thanks to advances in structural analysis approaches, the construction principles and architecture of the NPC have recently been revealed at submolecular resolution. Although the overall structure and inventory of nucleoporins are conserved, NPCs exhibit significant compositional and functional plasticity even within single cells and surprising variability in their assembly pathways. Once assembled, NPCs remain seemingly unexchangeable in post-mitotic cells. 
  • 946
  • 17 Jun 2022
Topic Review
High-Throughput Screening Methods for Radiosensitivity and Resistance
The biological impact of ionizing radiation (IR) on humans depends not only on the physical properties and absorbed dose of radiation but also on the unique susceptibility of the exposed individual. A critical target of IR is DNA, and the DNA damage response is a safeguard mechanism for maintaining genomic integrity in response to the induced cellular stress. Unrepaired DNA lesions lead to various mutations, contributing to adverse health effects.
  • 946
  • 19 Aug 2022
Topic Review
CD133
Prostate cancer stem cells (PCSCs), possessing self-renewal properties and resistance to anticancer treatment, are possibly the leading cause of distant metastasis and treatment failure in prostate cancer (PC). CD133 is one of the most well-known and valuable cell surface markers of cancer stem cells (CSCs) in many cancers, including PC. CSCs refer to a small subset of cancer cells, theoretically, this can be even a single cancer cell, which can differentiate into a heterogeneous and hierarchy of cancer cells. Sharing a number of characteristics with normal somatic stem cells, CSCs are capable of self-renewing, asymmetric division, generation of heterogeneous lineage, differentiation into various cancer cells which make up the tumor bulk, manifesting more aggressive phenotypes and exhibiting resistance to anticancer treatment. The existence of CSCs was first reported in acute myeloid leukemia in 1997 and later in a broad spectrum of common solid tumors, including PC.
  • 945
  • 18 Nov 2022
Topic Review
Arteriovenous and Cavernous Malformations
Brain arteriovenous malformations (BAVMs) are predominantly congenital vascular disorders that may arise anywhere inside of the central nervous system. They are comprised of one or more arterial feeders supplying a vascular nidus, and one or more draining veins. The nidus itself represents the site where arterial blood is shunted directly into the venous system without an interpolating network of capillaries.
  • 944
  • 18 Jun 2021
Topic Review
Polyphenols in Leukaemia
Leukaemia is a malignant disease of the blood. Current treatments for leukaemia are associated with serious side-effects. Here we discuss the potential therapeutic use of polyphenols in leukaemia. We outline the molecular mechanism of action of polyphenol in leukaemia cell lines, and discuss the pharmacological properties of polyphenols, including their anti-inflammatory, antioxidant, anti-proliferative, and anti-tumour activities, and suggest that polyphenols are potent natural agents that can be useful therapeutically; and discuss why data on bioavailability, toxicity and metabolism is essential to evaluate their clinical use. 
  • 943
  • 22 Sep 2021
Topic Review
Mutations in TSC Genes and Synaptic Transmission
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease featuring localized uncontrolled growth of tissues, known as hamartomas, in many organs, including the central nervous system (CNS). A large proportion of the cases are sporadic mutations (ca. two thirds). The disease results from a loss-of-function mutation in either the TSC1 or TSC2 gene, which encode for hamartin and tuberin proteins, respectively; two proteins that together form the Tsc1–Tsc2 complex. This complex, which is the converging center of several signaling pathways, has GTPase activity and can inhibit the activity of Ras homolog enriched in the brain (Rheb). The complex itself is modulated by phosphorylation via, for example, Akt or AMPK (Figure 1).
  • 943
  • 09 Nov 2021
Topic Review
Xanthohumol Is a Potent Pan-Inhibitor of Coronaviruses
Coronaviruses cause diseases in humans and livestock. The SARS-CoV-2 is infecting millions of human beings, with high morbidity and mortality worldwide. The main protease (Mpro) of coronavirus plays a pivotal role in viral replication and transcription, which, in theory, is an attractive drug target for antiviral drug development. It has been extensively discussed whether Xanthohumol is able to help COVID-19 patients. Here, researchers report that Xanthohumol, a small molecule in clinical trials from hops (Humulus lupulus), was a potent pan-inhibitor for various coronaviruses by targeting Mpro, for example, betacoronavirus SARS-CoV-2 (IC50 value of 1.53 μM), and alphacoronavirus PEDV (IC50 value of 7.51 μM). Xanthohumol inhibited Mpro activities in the enzymatical assays, while pretreatment with Xanthohumol restricted the SARS-CoV-2 and PEDV replication in Vero-E6 cells. Therefore, Xanthohumol is a potent pan-inhibitor of coronaviruses and an excellent lead compound for further drug development.
  • 943
  • 22 Dec 2021
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