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Topic Review
VDAC1
The voltage-dependent anion channel 1 (VDAC1) protein, is an important regulator of mitochondrial function, and serves as a mitochondrial gatekeeper, with responsibility for cellular fate.
  • 1.8K
  • 26 Nov 2020
Topic Review
Tumor Necrosis Factor -Related Apoptosis-Inducing Ligand Signaling Pathways
The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein that undergoes proteolytic cleavage to produce an extracellular ligand. TRAIL can bind to decoy receptor 1 (DcR1) which lacks a death domain (DD) altogether, and DcR2 which has a truncated DD. These decoy receptors are unable to induce DISC (death-inducing signaling complex) formation and act as negative regulators of the apoptotic signaling by competitively binding TRAIL. The canonical TRAIL-induced apoptotic signaling pathway is an example of apoptosis mediated through the extrinsic death pathway, which entails activation of cell-surface receptors by a ligand to induce activation of downstream caspases.
  • 1.8K
  • 30 Nov 2022
Topic Review
Transcriptionally Active Chromatin Structure
Chromatin structure can either positively or negatively regulates transcription and plays an essential role in eukaryotic gene expression and cell identity. 
  • 1.8K
  • 13 May 2021
Topic Review
Bisphenol A-Induced Male Infertility
Bisphenol A (BPA) is a well-known endocrine disruptor present in epoxy resins and polycarbonate plastics, which negatively disturbs the male reproductive system affecting male fertility. In vivo studies showed that BPA exposure has deleterious effects on spermatogenesis by disturbing the hypothalamic-pituitary-gonadal axis and inducing oxidative stress in the testis. This compound seems to disrupt hormone signalling even at low concentrations, modifying the levels of inhibin B, oestradiol, and testosterone. The adverse effects on seminal parameters are mainly supported by studies based on urinary BPA concentration, showing a negative association between BPA levels and sperm concentration, motility, normal morphology and sperm DNA damage.
  • 1.8K
  • 01 Apr 2021
Topic Review
Mitophagy
Mitophagy is a selective autophagic process that eliminates unnecessary and/or damaged mitochondria. Therefore, it is a central hormetic mechanism of mitochondrial quality and quantity control, essential for cellular homeostasis. Its dysregulation has been shown to be a key event in metabolic related diseases and it is the target of emerging therapeutical approaches in this field.
  • 1.8K
  • 28 May 2021
Topic Review
Neutrophil Apoptosis as A Powerful Anti-Inflammatory Signal
Neutrophils are highly abundant circulating leukocytes that are amongst the first cells to be recruited to sites of infection or sterile injury. Their ability to generate and release powerful cytotoxic products ties with their role in host defence from bacterial and fungal infections. Neutrophilic inflammation is tightly regulated to limit the amount of ‘bystander injury’ caused. Neutrophils were in the past regarded as short-lived, indiscriminate killers of invading microorganisms. Neutrophils are recognised to also have important anti-inflammatory functions that are critical for the resolution of inflammation and return to homeostasis.
  • 1.8K
  • 30 Dec 2022
Topic Review
Endoplasmic Reticulum-Related Protein Targeting and Protein Transport
Cells use an impressive array of components to enable the safe transport of protein cargo from the cytosolic ribosomes to the endoplasmic reticulum. Safety during the transit is warranted by the interplay of cytosolic chaperones, membrane receptors, and protein translocases that together form functional networks and serve as protein targeting and translocation routes. While two targeting routes to the endoplasmic reticulum, SRP (signal recognition particle) and GET (guided entry of tail-anchored proteins), prefer targeting determinants at the N- and C-terminus of the cargo polypeptide, respectively, the discovered SND (SRP-independent) route seems to preferentially cater for cargos with non-generic targeting signals that are less hydrophobic or more distant from the termini. 
  • 1.8K
  • 19 Mar 2022
Topic Review
Intracellular Signalling in Wound Healing
The cells response to injury is initiated by growth factors and cytokines that play a key role in wound restoration, and their biological action is achieved via signal transduction. Growth factors and cytokines play distinct roles through all phases of wound healing. In response to injury, they can trigger several strategic signalling transduction pathways that are mostly activated during embryonic skin development. Extracellular signal-regulated kinases (ERKs) and calcium (Ca2+) are the first intracellular signalling molecules for tissue repair response. These signalling molecules regulate several biological activities including cellular migration, proliferation, contractility, survival and many more related to different transcription factors that are usually induced by several other intracellular signalling pathways. This phenomenon makes it difficult to link a specific signalling response to injury.
  • 1.8K
  • 28 Apr 2022
Topic Review
Cardiovascular Diseases and Stem Cells
This entry provides an update on previous and current research in the field of Cardiovascular diseases (CVDs), a class of disorders affecting the heart or blood vessels. Despite progress in clinical research and therapy, CVDs still represent the leading cause of mortality and morbidity worldwide. The hallmarks of cardiac diseases include inflammation, fibrosis, scar tissue, hyperplasia, hypertrophy, abnormal ventricular remodeling, and cardiomyocyte death, which is an irreversible process that induces heart failure with progressive and dramatic consequences. Both genetic and environmental factors pathologically contribute to the development of CVDs, but the precise causes that trigger cardiac diseases and their progression are still largely unknown. In this scenario, the possibility to generate patient-specific cardiac cells from induced pluripotent stem cells (iPSCs) represents a powerful platform for the investigation of these life-threatening disorders.
  • 1.8K
  • 26 Oct 2020
Topic Review
Changes in Homeostasis of the Dermal Extracellular Matrix
Skin aging is a multi-factorial process that affects nearly every aspect of skin biology and function. With age, an impairment of structures, quality characteristics, and functions of the dermal extracellular matrix (ECM) occurs in the skin, which leads to disrupted functioning of dermal fibroblasts (DFs), the main cells supporting morphofunctional organization of the skin. The DF functioning directly depends on the state of the surrounding collagen matrix (CM). The intact collagen matrix ensures proper adhesion and mechanical tension in DFs, which allows these cells to maintain collagen homeostasis while ECM correctly regulates cellular processes. When the integrity of CM is destroyed, mechanotransduction is disrupted, which is accompanied by impairment of DF functioning and destruction of collagen homeostasis, thereby contributing to the progression of aging processes in skin tissues. 
  • 1.8K
  • 21 Jun 2022
Topic Review
Factor V Leiden
Factor V Leiden (rs6025 or F5 p.R506Q) is a variant (mutated form) of human factor V (one of several substances that helps blood clot), which causes an increase in blood clotting (hypercoagulability). Due to this mutation, protein C, an anticoagulant protein that normally inhibits the pro-clotting activity of factor V, is not able to bind normally to factor V, leading to a hypercoagulable state, i.e., an increased tendency for the patient to form abnormal and potentially harmful blood clots. Factor V Leiden is the most common hereditary hypercoagulability (prone to clotting) disorder amongst ethnic Europeans. It is named after the Dutch city of Leiden, where it was first identified in 1994 by Rogier Maria Bertina under the direction of (and in the laboratory of) Pieter Hendrick Reitsma. Despite the increased risk of venous thromboembolisms, people with one copy of this gene have not been found to have shorter lives than the general population.
  • 1.8K
  • 07 Nov 2022
Topic Review
Molecular Mechanisms of Parthanatos
Differential evolution of apoptosis, programmed necrosis, and autophagy, parthanatos is a form of cell death mediated by poly(ADP-ribose) polymerase 1 (PARP1), which is caused by DNA damage. PARP1 hyper-activation stimulates apoptosis-inducing factor (AIF) nucleus translocation, and accelerates nicotinamide adenine dinucleotide (NAD+) and adenosine triphosphate (ATP) depletion, leading to DNA fragmentation. The mechanisms of parthanatos mainly include DNA damage, PARP1 hyper-activation, PAR accumulation, NAD+ and ATP depletion, and AIF nucleus translocation. Parthanatos, a kind of new programmed death mode, has been put forward by Professors Ted and Valina Dawson to indicate a caspase-independent cell death subroutine that critically relies on the hyper-activation of poly(ADP-ribose) polymerase 1 (PARP1).
  • 1.8K
  • 18 Jul 2022
Topic Review
Extracellular Vesicles Mediated Regulation
Small noncoding RNAs (sRNA) appear to play a key role in extracellular vesicle (EV)-mediated information transfer. Within the vesicular envelope, RNAs are well protected from degradation and can be shuttled between individuals from one and the same species and beyond. Various communication routes have been discovered such as mother-infant-interaction via breast milk, diverse host-pathogen-relations, and dietary uptake of food derived EVs, proving that EV-mediated inter-kingdom regulation is more than a random event.
  • 1.8K
  • 23 Oct 2020
Topic Review
The ROR Pathway
The WNT pathway is one of the major signaling cascades frequently deregulated in human cancer. Binding of WNT ligands to their respective receptors can trigger various downstream signaling cascades centered around cell proliferation, survival or migration. In particular, WNT signaling via the receptor tyrosine kinase-like orphan receptors (RORs) has gained increasing attention in cancer research due to their overexpression in a multitude of tumor entities.
  • 1.8K
  • 19 Feb 2021
Topic Review
Breast cancer cell growth/motility is influenced by metal compounds
Triple-negative breast cancer (TNBC) is a  highly "aggressive" malignant neoplasm with limited treatment options due to the lack of expression of estrogen and progesterone receptors and HER2/neu. In search of novel molecules displaying anti-TNBC activities, the TNBC cell line MDA-MB231 was exposed to cadmium chloride and/or manganese chloride, and a biological characterization of the effect observed was performed. The data obtained demonstrate a cytotoxic effect exerted by cadmium chloride with drastic changes affecting gene expressions and production of reactive oxygen species. Conversely, manganese chloride was effective in increasing cell number and promoting cell invasive ability.  Such effect was reverted by coexposure with cadmium chloride. Thus, metal compounds appear to be able to modulate the biological behavior of TNBC cells, although addressing them to different fates. The data obtained suggest that high environmental pollution with manganese chloride might increase the risk of breast tumorigenesis. On the other hand, the restraining modulatory property of cadmium chloride looks promising and deserves a more detailed mechanistic study aimed to the identification of possible molecular targets instrumental in inhibiting the expansion of malignant breast cancer.
  • 1.8K
  • 30 Oct 2020
Topic Review
GRKs
G protein-coupled receptor (GPCR) kinases (GRKs) play an important role in the regulation of signaling of GPCRs that bind neurotransmitters. The canonical model of GPCR desensitization posits that GRKs phosphorylate ligand-activated GPCRs, and this phosphorylation prepares receptors for the high-affinity binding of arrestin proteins. Arrestin binding prevents further G protein coupling, promotes receptor internalization, and initiates and/or facilitates specific branches of signaling. Existing data suggest that the role of GPCR phosphorylation by GRKs is distinct in different receptors. The relationship between G protein- and arrestin-mediated signaling on the one hand, and therapeutic and side effects of drugs on the other, is more complex than is widely believed. Also, the relationship between rapid (minutes to hours) GRK/arrestin-mediated regulation and long-term (days to weeks) neural plasticity remains to be elucidated. 
  • 1.8K
  • 19 Jan 2021
Topic Review
Misregulation of Wnt Signaling Pathways
Wnt signaling pathways constitute a group of signal transduction pathways that direct many physiological processes, such as development, growth, and differentiation. Dysregulation of these pathways is thus associated with many pathological processes, including neurodegenerative diseases, metabolic disorders, and cancer. At the same time, alterations are observed in plasma membrane compositions, lipid organizations, and ordered membrane domains in brain and metabolic diseases that are associated with Wnt signaling pathway activation.
  • 1.8K
  • 03 Nov 2021
Topic Review
Medical Applications of Senescence-Associated β-Galactosidase Assay
β-galactosidase is a lysosomal hydrolase, which cleaves terminal β-d-galactose residues. Senescence-associated β-galactosidase (SA-β-gal) assay found its place in the routine work of thousands of biological laboratories. There is a bulk of evidence that supports the future implementation of β-galactosidase detection as a prognostic marker in medical practice as well.
  • 1.8K
  • 11 Oct 2022
Topic Review
The B-cell Activating Factor/A Proliferation-Inducing Ligand System
It cannot present MZ B-cell populations without discussing the B-cell Activating Factor/A Proliferation-Inducing Ligand System (BAFF/APRIL) system. Without a doubt, one of the most important molecules for the survival and differentiation of B-cells is BAFF. BAFF, also known as B lymphocyte stimulator (BLyS), is part of the tumor necrosis factor (TNF) family and is encoded by the TNFSF13B gene.
  • 1.8K
  • 18 Apr 2022
Topic Review
Appendage Regeneration in Vertebrates
Appendage regeneration in vertebrates means the ability to regenerate amputated or injured tissues and organs, which is a fascinating property shared by several invertebrates and, interestingly, some vertebrates.
  • 1.8K
  • 01 Jun 2021
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