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Topic Review
Alternatively Spliced Isoforms in MAPK Signaling
The mitogen-activated protein kinase (MAPK) cascades are key signaling components  that transmit signals to many cellular processes. Each of the cascades operates by a sequential activation of protein kinases organized in three or more tiers that provide a seemingly linear signal transmission. However, the cellular effects regulated by each cascade may vary significantly. To achieve these diverse effects, the specificity of each cascade is extended by distinct regulators.  Here we describe the importance of having distinct components in each tier of the cascades, particularly alternatively spliced isoforms of the MAPK components. This mode of regulation extends the cascade’s specificity and allows accurate, fine-tuned signaling outcomes that lead to proper cell fates. 
  • 1.2K
  • 28 Jan 2022
Topic Review
Matrix Metallopeptidase
Matrix metallopeptidases (MMPs), also known as matrix metalloproteinases or matrixins, are metalloproteinases that are calcium-dependent zinc-containing endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily. Collectively, these enzymes are capable of degrading all kinds of extracellular matrix proteins, but also can process a number of bioactive molecules. They are known to be involved in the cleavage of cell surface receptors, the release of apoptotic ligands (such as the FAS ligand), and chemokine/cytokine inactivation. MMPs are also thought to play a major role in cell behaviors such as cell proliferation, migration (adhesion/dispersion), differentiation, angiogenesis, apoptosis, and host defense. They were first described in vertebrates (1962), including humans, but have since been found in invertebrates and plants. They are distinguished from other endopeptidases by their dependence on metal ions as cofactors, their ability to degrade extracellular matrix, and their specific evolutionary DNA sequence. Recently matrix metalloproteinases have been proposed as markers of many pathological conditions for their ability to degrade extracellular matrix components and remodel tissues. Herein, MMPs have been reported as one of the main factors of cancer progression and metastasis formation. This led to the emerging research field in biosensors development for the detection of such enzymes.
  • 1.2K
  • 23 Nov 2022
Topic Review
Wall-Associated Kinase
Wall-Associated Kinase (WAKs) are one of many classes of plant proteins known to serve as a medium between the extracellular matrix (ECM) and cytoplasm of cell walls. They are serine-threonine kinases that contain epidermal growth factor (EGF) repeats, a cytoplasmic kinase and are located in the cell walls. They provide a linkage between the inner and outer surroundings of cell walls. WAKs are under a group of receptor-like kinases (RLK) that are actively involved in sensory and signal transduction pathways especially in response to foreign attacks by pathogens and in cell development. On the other hand, pectins are an abundant group of complex carbohydrates present in the primary cell wall that play roles in cell growth and development, protection, plant structure and water holding capacity. Pectins are rich in galacturonic acids (OGs) and present in the middle lamellae in plant tissues where they provide strength, flexibility and adhesion between plant cells. Commercially and within the food industry, they are used as gels and stabilizers for desserts and juices. The role of WAKs in cell walls as pectin receptors is vital to a variety of functions involved with cell differentiation, form and host-pathogen relations.
  • 1.2K
  • 25 Nov 2022
Topic Review Peer Reviewed
Phosphatidyl Inositol 4-Kinases
In recent decades, phosphoinositides (or PIs) have emerged as essential signaling molecules. Despite their low cellular abundance, PIs are found to be involved in various cellular processes, including cell migration, vesicular trafficking, cell cycle regulation, metabolism, cytoskeletal remodeling, autophagy, aging, apoptosis, and cell signaling. Recent studies have shown that aberrant activity of either lipid kinases or phosphatases leads to various medical implications like cancer, diabetes, and microbial infections, suggesting an essential role for these lipid molecules and enzymes in their metabolism. This entry focused on one of the critical enzymes involved in phosphoinositide metabolism: phosphatidyl inositol 4-kinase (PI4-Kinase).
  • 1.2K
  • 02 Jul 2024
Topic Review
Astrocyte–Neuron Crosstalk
Astrocyte-neuron crosstalk is a phenomenon in which both of those cell types depend on each other and support their development, genes expression, metabolism, excitability and plasticity. Astrocyte–neuron crosstalk incontrovertibly plays a crucial role in shaping neuronal metabolism. It has been shown that it substantially affects the expression of basal metabolic enzymes in both types of cells, by essentially unknown factor(s) which are released to extracellular space directly and using extracellular vesicles-packed molecules and by cell-to-cell contacts. Additionally, astrocytes support neurons with lactate, which (when secreted during enhanced neuronal activity events) stimulates a formation and maintenece of long-term plastycity phenomena in neurons.
  • 1.2K
  • 29 Sep 2020
Topic Review
3C Protease as Ferroptosis Inducer
Regulated cell death (RCD) is a fundamental process common to nearly all living beings and essential for the development and tissue homeostasis in animals and humans. A wide range of molecules can induce RCD including a number of viral proteolytic enzymes. To date, numerous data indicate that picornaviral 3C proteases can induce RCD. In most reported cases, these proteases induce classical caspase-dependent apoptosis. In contrast, the human hepatitis A virus 3C protease (3Cpro) has recently been shown to cause caspase-independent cell death accompanied by previously undescribed features. In the current topic the results of the study where 3Cpro-induced cell death was characterized morphologically and biochemically are presented. It was found that dead cells demonstrated necrosis-like morphological changes including permeabilization of plasma membrane, loss of mitochondrial potential, as well as mitochondria and nuclei swelling. Additionally, it was shown that 3Cpro-induced cell death was efficiently blocked by ferroptosis inhibitors and was accompanied by intense lipid peroxidation. Taken together, these results indicate that 3Cpro induces ferroptosis upon its individual expression in human cells. This is the first demonstration that a proteolytic enzyme can induce ferroptosis, the recently discovered and actively studied type of RCD.
  • 1.2K
  • 22 Sep 2021
Topic Review
Diagnosis of Hepatocellular Carcinoma
There are several risk factors of HCC such as viral hepatitis (B, C), cirrhosis, tobacco and alcohol use, aflatoxin-contaminated food, pesticides, diabetes, obesity, nonalcoholic fatty liver disease (NAFLD), and metabolic and genetic diseases. Diagnosis of HCC is based on different methods such as imaging ultrasonography (US), multiphasic enhanced computed tomography (CT), magnetic resonance imaging (MRI), and several diagnostic biomarkers.
  • 1.2K
  • 17 Jul 2023
Topic Review
Extracellular Vesicles in Idiopathic Pulmonary Fibrosis Progression
Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease of unknown etiology. Different types of cells are involved in fibrogenesis, which is persistently physical and molecular stimulation, either directly or by interacting with bioactive molecules and extracellular vesicles (EVs). Current evidence suggests that EVs play an essential role in IPF development. EVs are released by a variety of cells, including fibroblasts, epithelial cells, and alveolar macrophages. In addition, EVs can transport bioactive molecules, such as lipids, proteins, and nucleic acids, which play a pivotal role in cellular communication. Several proposed mechanisms show that an acceptor cell can capture, absorb, or interact with EVs through direct fusion with the plasma membrane, ligand–receptor interaction, and endocytotic process, modifying the target cell. During fibrogenesis, the release of EVs is deregulated, increases the EVs amount, and the cargo content is modified. This alteration is closely associated with the maintenance of the fibrotic microenvironment. 
  • 1.2K
  • 23 Feb 2022
Topic Review
Cell Signaling Pathways and Radioresistance of Cancer Cells
Radiation eradicates cancer cells mainly by causing DNA damage. However, radiation also concomitantly activates multiple prosurvival signaling pathways, which include those mediated by ATM, ATR, AKT, ERK, and NF-κB that promote DNA damage checkpoint activation/DNA repair, autophagy induction, and/or inhibition of apoptosis. Furthermore, emerging data support the role of YAP signaling in promoting the intrinsic radioresistance of cancer cells, which occurs through its activation of the transcription of many essential genes that support cell survival, DNA repair, proliferation, and the stemness of cancer stem cells. Together, these signaling pathways protect cancer cells by reducing the magnitude of radiation-induced cytotoxicity and promoting radioresistance. 
  • 1.2K
  • 24 Mar 2022
Topic Review
Senescent Cells in Cutaneous Wound Healing
Cellular senescence has gained increasing attention in the field of aging research. Senescent cells have been implicated in biological aging processes, tumorigenesis, development, and wound repair amongst other processes and pathologies. Recent findings reveal that senescent cells can both promote and inhibit cutaneous wound healing processes. 
  • 1.2K
  • 26 Dec 2022
Topic Review
MicroRNA-502-3p and Human Diseases: Focus on Alzheimer's Disease
The microRNA-500’s family has five different genotypes: microRNA-362, microRNA-500a, microRNA-500b, microRNA-501, and microRNA-502 (Genesnames.org). All the forms of miR-500 family members are expressed in humans and different animal species. The miR-502-3p sequence is 22 nucleotides long and is found in Homo sapiens (Has-miR-502-3p) as annotated by 7 gene databases such as MalaCards, miRBase, GeneCards, TarBase, ENA, RefSeq, and LncBase. The miR-502 were also found to be conserved in seven different animal species such as Cow (Bos taurus) Bta-miR-502a; Dog (Canis lupus familiaris) Cfa-miR-502; Horse (Equus caballus) Eca-miR-502-3p; Gorilla (Gorilla gorilla) Ggo-miR-502a; Rhesus monkey (Macaca mulatta) Mml-miR-502-3p); Rabbit (Oryctolagus cuniculus) Ocu-miR-502-3p; and Bornean orangutan (Pongo pygmaeus) Ppy-miR-502-3p (https://rnacentral.org/rna) (accessed on 26 February 2023). The miR-502-3p is encoded by the MIR502 gene (ENSG00000272080) which is composed of an 86 base-pairs genomic sequence, a plus stranded RNA orientation starting from 50,014,598, and ending at 50,014,683. The MiR502 gene is located at the Chromosome X genomic location: 50,014,598-50,014,683 forward strands.
  • 1.2K
  • 13 Apr 2023
Topic Review
DNA Homeostasis and Senescence
As we age, our bodies accrue damage in the form of DNA mutations. These mutations lead to the generation of sub-optimal proteins, resulting in inadequate cellular homeostasis and senescence. The build-up of senescent cells negatively affects the local cellular micro-environment and drives ageing associated disease, including neurodegeneration. Therefore, limiting the accumulation of DNA damage is essential for healthy neuronal populations.  
  • 1.2K
  • 17 Jun 2021
Topic Review
ROS in Cancer Progression
Reactive oxygen species (ROS) play a pivotal role in biological processes and continuous ROS production in normal cells is controlled by the appropriate regulation between the silver lining of low and high ROS concentration mediated effects. Interestingly, ROS also dynamically influences the tumor microenvironment and is known to initiate cancer angiogenesis, metastasis, and survival at different concentrations. At moderate concentration, ROS activates the cancer cell survival signaling cascade involving mitogen-activated protein kinase/extracellular signal-regulated protein kinases 1/2 (MAPK/ERK1/2), p38, c-Jun N-terminal kinase (JNK), and phosphoinositide-3-kinase/ protein kinase B (PI3K/Akt), which in turn activate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF). At high concentrations, ROS can cause cancer cell apoptosis. Hence, it critically depends upon the ROS levels, to either augment tumorigenesis or lead to apoptosis.
  • 1.2K
  • 03 Aug 2021
Topic Review
Phenotypical and Functional Polymorphism of Liver Resident Macrophages
Liver diseases are one of the main causes of mortality. In this regard, the development of new ways of reparative processes stimulation is relevant. Macrophages play a leading role in the regulation of liver homeostasis in physiological conditions and in pathology. In this regard, the development of new liver treatment methods is impossible without taking into account this cell population. Resident macrophages of the liver, Kupffer cells, represent a unique cell population, first of all, due to their development. Most of the liver macrophages belong to the self-sustaining macrophage cell population, whose origin is not bone marrow. In addition, Kupffer cells are involved in such processes as regulation of hepatocyte proliferation and apoptosis, remodeling of the intercellular matrix, lipid metabolism, protective function, etc. Such a broad spectrum of liver macrophage functions indicates their high functional plasticity. The Recent data on the development, phenotypic and functional plasticity, and participation in the reparative processes of liver macrophages: resident macrophages (Kupffer cells) and bone marrow-derived macrophages were summarized.
  • 1.2K
  • 29 Jan 2022
Topic Review
Somatic Polyploidy
Somatic polyploidy was found in the tissues of all multicellular organisms (including algae, mosses, lichens, vascular plants, invertebrates, and vertebrates), which points to its adaptive value. In human and warm-blooded animals, polyploidy can be a part of normal postnatal morphogenetic programs and can be a manifestation of response to pathological stimuli and diseases.
  • 1.2K
  • 11 Apr 2022
Topic Review
Proteolysis-Targeting Chimeras
The ubiquitin–proteasome system (UPS) is an essential part of the cellular machinery responsible for maintaining intracellular protein homeostasis. A network of proteins that comprises the proteolytic system and chaperones calculates cellular protein homeostasis. Chaperones are in charge of correcting protein misfolding, but the proteolytic system, which converges on the 26S proteasome, is in charge of removing damaged or unfolded proteins to maintain a healthy environment inside the cell. Using proteolysis-targeting chimera (PROTAC) technology for targeted protein degradation, a novel technique of treatment is emerging that stems from an aberrant expression of a protein that causes disease. PROTAC molecules are tiny, bifunctional molecules that bind an E3-ubiquitin ligase and a target protein at the same time, causing ubiquitination and proteasome destruction of the target protein.
  • 1.2K
  • 22 May 2023
Topic Review
SARS-CoV-2 spike protein
The article by Suresh & Suzuki (2021) describes the finding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein affecting human lung vascular cells and explains how the spike protein possibly increases the incidence of pulmonary arterial hypertension (PAH). Since the SARS-CoV-2 spike protein will be administered to millions of people as vaccines, it is critical to understand the effects of this protein on human cells to ensure that it does not promote long-term adverse health consequences.
  • 1.1K
  • 06 Jan 2021
Topic Review
Autonomy in Stem Cell-Derived Embryoids
The experimental production of complex structures resembling mammalian embryos (e.g., blastoids, gastruloids) from pluripotent stem cells in vitro has become a booming research field. Since some of these embryoid models appear to reach a degree of complexity that may come close to viability, a broad discussion has set in with the aim to arrive at a consensus on the ethical implications with regard to acceptability of the use of this technology with human cells. The present text focuses on developmental autonomy of embryoids which is an aspect of great ethical relevance and must receive increased attention during the preparation of new legal regulations, but which has not been included yet in the recently issued ISSCR Guidelines.  
  • 1.1K
  • 10 Nov 2021
Topic Review
Read
In DNA sequencing, a read is an inferred sequence of base pairs (or base pair probabilities) corresponding to all or part of a single DNA fragment. A typical sequencing experiment involves fragmentation of the genome into millions of molecules, which are size-selected and ligated to adapters. The set of fragments is referred to as a sequencing library, which is sequenced to produce a set of reads.
  • 1.1K
  • 24 Nov 2022
Topic Review
Intestinal Porcine Epithelial Cell Lines
Numerous bioactive plant additives have shown various positive effects in pigs and chickens. The demand for feed additives of natural origin has increased rapidly in recent years to support the health of farm animals and thus minimize the need for antibiotics and other drugs. Although only in vivo experiments can fully represent their effect on the organism, the establishment of reliable in vitro methods is becoming increasingly important in the goal of reducing the use of animals in experiments. The use of cell models requires strict control of the experimental conditions so that reliability and reproducibility can be achieved. In particular, the intestinal porcine epithelial cell line IPEC-J2 represents a promising model for the development of new additives. It offers the possibility to investigate antioxidative, antimicrobial, anti- or pro-proliferative and antiviral effects.
  • 1.1K
  • 22 Apr 2022
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