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Topic Review
Huntingtin and Other Neurodegeneration-Associated Proteins in Intracellular Pathologies
Neurodegenerative diseases are currently incurable. Numerous experimental data accumulated over the past fifty years have brought us closer to understanding the molecular and cell mechanisms responsible for their development. It is known that the basis of neurodegenerations are proteinopathies, disorders in the structure and function of various proteins that lead to their aggregation and toxic effects on cells. The most common neurodegenerative proteinopathies are amyloidosis (amyloid extracellular plaques in AD), tauopathy (various dementias), α-synucleopathy (Lowy bodies in PD), prionopathy, and TDP-43 proteinopathy (in amyotrophic lateral sclerosis (ALS)).
  • 1.6K
  • 26 Dec 2022
Topic Review
Oral Submucous Fibrosis
Betel quid (BQ) chewing increased the risk of oral cancer and oral submucous fibrosis (OSMF), an oral premalignant disorder (OPMD) with malignant transformation potential. BQ components such as areca nut (AN), trauma by coarse AN fiber, catechin, copper, alkaloids, stimulated reactive oxygen species (ROS), inflammation and cytotoxicity are suggested to be the contributing factors. In this review, the expression of extracellular matrix (ECM) turnover related genes and proteins in OSMF and the relation to betel quid chewing habit is discussed. Genetic susceptibility of ECM-related genes to OSMF is also mentioned. These results can facilitate our understanding the pathogenesis of OSMF and its possible prevention/treatment in the future.
  • 1.6K
  • 08 Dec 2020
Topic Review
Hematopoietic Stem Cells (HSCs)
Hematopoietic stem cells (HSCs) and their offspring, the hematopoietic progenitor cells (HPCs), are highly sociable. Their capacity to interact with bone marrow niche cells and respond to environmental cytokines orchestrates the generation of the different types of blood and immune cells. 
  • 1.6K
  • 28 May 2021
Topic Review
KRAS
The RAS family consists of membrane-associated small GTPases which play essential roles in cell survival, proliferation, and differentiation. There are four RAS protein isoforms in humans: HRAS, NRAS, and two splice variants, KRAS4A and KRAS4B. 
  • 1.6K
  • 12 Oct 2021
Topic Review
Role of Immunoproteasome Subunits in Cancer
Cell-mediated immunity is driven by antigenic peptide presentation on major histocompatibility complex (MHC) molecules. Specialized proteasome complexes called immunoproteasomes process viral, bacterial, and tumor antigens for presentation on MHC class I molecules, which can induce CD8 T cells to mount effective immune responses. Immunoproteasomes are distinguished by three subunits that alter the catalytic activity of the proteasome and are inducible by inflammatory stimuli such as interferon-γ (IFN-γ). This inducible activity places them in central roles in cancer, autoimmunity, and inflammation. 
  • 1.5K
  • 29 Mar 2022
Topic Review
Aprotinin
The drug aprotinin (Trasylol, previously Bayer and now Nordic Group pharmaceuticals), is a small protein bovine pancreatic trypsin inhibitor (BPTI), or basic trypsin inhibitor of bovine pancreas, which is an antifibrinolytic molecule that inhibits trypsin and related proteolytic enzymes. Under the trade name Trasylol, aprotinin was used as a medication administered by injection to reduce bleeding during complex surgery, such as heart and liver surgery. Its main effect is the slowing down of fibrinolysis, the process that leads to the breakdown of blood clots. The aim in its use was to decrease the need for blood transfusions during surgery, as well as end-organ damage due to hypotension (low blood pressure) as a result of marked blood loss. The drug was temporarily withdrawn worldwide in 2007 after studies suggested that its use increased the risk of complications or death; this was confirmed by follow-up studies. Trasylol sales were suspended in May 2008, except for very restricted research use. In February 2012 the European Medicines Agency (EMA) scientific committee reverted its previous standpoint regarding aprotinin, and has recommended that the suspension be lifted. Nordic became distributor of aprotinin in 2012.
  • 1.5K
  • 20 Oct 2022
Topic Review
Selenomethionine
Selenium is an essential trace element. Although this chalcogen forms a wide variety of compounds, there are surprisingly few small-molecule organic selenium compounds (OSeCs) in biology. Besides its more prominent relative selenocysteine (SeCys), the amino acid selenomethionine (SeMet) is one example. SeMet is synthesized in plants and some fungi and, via nutrition, finds its way into mammalian cells. In contrast to its sulfur analog methionine (Met), SeMet is extraordinarily redox active under physiological conditions and via its catalytic selenide (RSeR’)/selenoxide (RSe(O)R’) couple provides protection against reactive oxygen species (ROS) and other possibly harmful oxidants. In contrast to SeCys, which is incorporated via an eloquent ribosomal mechanism, SeMet can enter such biomolecules by simply replacing proteinogenic Met. Interestingly, eukaryotes, such as yeast and mammals, also metabolize SeMet to a small family of reactive selenium species (RSeS). Together, SeMet, proteins containing SeMet and metabolites of SeMet form a powerful triad of redox-active metabolites with a plethora of biological implications. In any case, SeMet and its family of natural RSeS provide plenty of opportunities for studies in the fields of nutrition, aging, health and redox biology. 
  • 1.5K
  • 23 Jun 2021
Topic Review
PTEN Dual Lipid- and Protein-Phosphatase Function in Tumor
Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a multifunctional tumor suppressor with protein- and lipid-phosphatase activities. The inactivation of PTEN is commonly found in all human cancers and is correlated with tumor progression. PTEN-lipid-phosphatase activity has been well documented to dephosphorylate phosphatidylinositol-3, 4, 5-phosphate (PIP3), which hinders cell growth and survival by dampening the PI3K and AKT signaling activity. PTEN-protein-phosphatase activity dephosphorylates the different proteins and acts in various cell functions. 
  • 1.5K
  • 28 Sep 2022
Topic Review
Lactic Acidosis’ Effect on Energy Metabolism
Lactic acidosis, a hallmark of solid tumour microenvironment, originates from lactate hyperproduction and its co-secretion with protons by cancer cells displaying the Warburg effect. Long considered a side effect of cancer metabolism, lactic acidosis is now known to play a major role in tumour physiology, aggressiveness and treatment efficiency. 
  • 1.5K
  • 07 Mar 2023
Topic Review
Function of platelet lipid rafts
Lipid rafts are dynamic assemblies of glycosphingolipids, sphingomyelin, cholesterol, and specific proteins which are stabilized into platforms involved in the regulation of vital cellular processes. Recent reports have demonstrated that lipid rafts are spatially and compositionally heterogeneous in the single-cell membrane. Sphingomyelin-rich rafts that are spatially and functionally distinct from the cholesterol-rich rafts are found at spreading platelets. Fibrin is translocated to sphingomyelin-rich rafts and platelet sphingomyelin-rich rafts act as platforms where extracellular fibrin and intracellular actomyosin join to promote clot retraction.
  • 1.5K
  • 07 Aug 2020
Topic Review
GSK-3 and Tau
Glycogen synthase kinase-3 (GSK-3) is a ubiquitously expressed serine/threonine kinase with a plethora of substrates. As a modulator of several cellular processes, GSK-3 has a central position in cell metabolism and signaling, with important roles both in physiological and pathological conditions. GSK-3 has been associated with a number of human disorders, such as neurodegenerative diseases including Alzheimer’s disease (AD). GSK-3 contributes to the hyperphosphorylation of tau protein, the main component of neurofibrillary tangles (NFTs), one of the hallmarks of AD. GSK-3 is further involved in the regulation of different neuronal processes that are dysregulated during AD pathogenesis, such as the generation of amyloid-β (Aβ) peptide or Aβ-induced cell death, axonal transport, cholinergic function, and adult neurogenesis or synaptic function. In this review, we will summarize recent data about GSK-3 involvement in these processes contributing to AD pathology, mostly focusing on the crucial interplay between GSK-3 and tau protein. We further discuss the current development of potential AD therapies targeting GSK-3 or GSK-3 phosphorylated tau. 
  • 1.5K
  • 11 May 2021
Topic Review
Development of Schwann Cells
Schwann cells are glial cells of the peripheral nervous system. They exist in several subtypes and perform a variety of functions in nerves. Their derivation and culture in vitro are interesting for applications ranging from disease modeling to tissue engineering. Since primary human Schwann cells are challenging to obtain in large quantities, in vitro differentiation from other cell types presents an alternative. To achieve differentiation of Schwann cells from stem cell sources in vitro, cultures are manipulated using molecular factors to emulate developmental signaling events which lead to development of Schwann cells in vivo. Therefore, knowledge of molecular determinants in embryonal development of the Schwann cell fate is key to develop and refine in vitro differentiation protocols.
  • 1.5K
  • 05 Dec 2022
Topic Review
EphA2 Surface Marker for WJ-MSCs
Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) are a valuable tool in stem cell research due to their high proliferation rate, multi-lineage differentiation potential, and immunotolerance properties. However, fibroblast impurity during WJ-MSCs isolation is unavoidable because of morphological similarities and shared surface markers. Here, a proteomic approach was employed to identify specific proteins deferentially expressed by WJ-MSCs in comparison to those by neonatal foreskin and adult skin fibroblasts (NFFs and ASFs, respectively). EphA2, SLC25A4, and SOD2 were predominantly expressed by WJ-MSCs, while CDH2 and Talin2 were specific to NFFs and ASFs, respectively. Here, EphA2 was established as a potential surface-specific marker to distinguish WJ-MSCs from fibroblasts and for prospective use to prepare pure primary cultures of WJ-MSCs for prospective clinical use. Additionally, CDH2 could be used for a negative-selection isolation/depletion method to remove neonatal fibroblasts contaminating preparations of WJ-MSCs.
  • 1.5K
  • 30 Sep 2020
Topic Review
Mechanisms of Cathepsins in Hepatocellular Carcinoma
Cathepsins are lysosomal proteases that are essential to maintain cellular physiological homeostasis and are involved in multiple processes, such as immune and energy regulation. Cathepsins are also involved in pathological situations, especially when they are secreted and enter the extracellular space. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and it is the third leading cause of cancer-related deaths worldwide. Cathepsins are involved in the pathology of HCC through acting in proliferation, apoptosis, angiogenesis, invasion and metastasis, metabolism and immunity. 
  • 1.5K
  • 14 Oct 2022
Topic Review
3D Cell Cultures
The 3D cell cultures allow cells to growth and interact between them and with the extracellular matrix in three dimensions. This conforms a culture structure closer to physiological conditions than the cell monolayers (2D) traditionally employed in cell biology, and it can be achieved by using extracellular matrix hydrogels derived from decellularized tissues, bio-printed scaffolds made of different materials, or by forcing the cells to interact between each other without physical support. 3D culture models provide a powerful tool to understand cell-to-cell interactions when used in co-cultures, and to determine the involvement of extracellular vesicles as major key interactors in cellular crosstalk.
  • 1.5K
  • 23 Feb 2021
Topic Review
Notch Signaling
Roles of Notch signaling in human development and cancer are reviewed herein. The four Notch paralogs along with the five Notch ligands are described. Their structures, mode of activation, and functions are briefly summarized based on published works.
  • 1.5K
  • 21 Oct 2020
Topic Review
Lipid Metabolism and Acylglycerolphosphate Acyltransferases (AGPATs) in Cancer
Alter lipid metabolism is an emerging hallmark of cancer. The conversion of fatty acids to neutral triacylglycerides (TAG), plays a central role in this adaptive process.  Acylglycerolphosphate acyltransferases (AGPATs)/lysophosphatidic acid acyltransferases (LPAATs) are a family of enzymes that catalyze the synthesis of phosphatidic acid (PA), an intermediate in TAG synthesis, a signaling molecule, and a precursor of phospholipids. Importantly, the expression of AGPATs has been linked to diverse physiological and pathological phenotypes, including cancer.
  • 1.5K
  • 20 Jan 2022
Topic Review
Hippo in Gastric Cancer
The Hippo signalling pathway is one of the most crucial and complex ones in physiology, and there is no doubt that the regulatory mechanisms it possesses are various. The role of this signalisation process in tissue homeostasis makes it keen to lead to cancerous processes when dysregulated. 
  • 1.5K
  • 16 May 2022
Topic Review
Hematopoietic Stem Cells
Hematopoietic cells consist of a heterogenous group of cells originating from hematopoietic stem cells (HSCs). HSCs differentiate into multi-potent progenitor cells (MPPs) which further produce circulating and tissue-residing blood cells of specific lineage. The bone marrow (BM) is the main hematopoietic organ in an adult and houses millions of immature and mature hematopoietic cells. HSCs reside as a rare cell population in the BM where they are maintained in quiescence as a reserve pool for hematopoiesis. When hematopoiesis is compromised, HSCs self-renew, proliferate and differentiate to replenish hematopoietic cells. As with all cells in an organism, hematopoietic cells utilize adenosine triphosphate (ATP) as a common energy currency. While it is fundamentally known that ATP is produced anaerobically through glycolysis and aerobically through mitochondrial oxidative phosphorylation (OXPHOS), the contribution of these processes for energy production varies between hematopoietic cell type. While the BM microenvironment is predominantly hypoxic, different hematopoietic cells utilize both glycolysis and OXPHOS at varying degrees for survival.
  • 1.5K
  • 25 May 2021
Topic Review
FTO Intronic SNP
Browning of white adipose tissue shifts adipocytes from energy storage white to energy expenditure beige types. The balance between the two adipocyte populations in white adipose tissue is highly determined by noncoding variants of the Fat mass and obesity-associated (FTO) locus which has the strongest association with obesity. The rs1421085 FTO risk allele results in a loss of ARID5B repression of IRX3 and IRX5 which promotes excess white adipocyte formation. Recent studies have revealed the presence of brown adipose tissues at several anatomical sites in humans including the deep-neck (DN).  We found that the characteristic gene expression profile and associated pathways of DN brown adipocytes were determined by partially overlapping effects of tissue site specific commitments of the stem cells, PPARγ stimulation and the FTO status of donors. The presence of FTO rs1421085 risk alleles had a strong influence, manifested during differentiation, on browning resulting in compromised expression of metabolic and mitochondrial genes as well as pathways which are decisive in thermogenesis.
  • 1.5K
  • 30 Oct 2020
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