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Topic Review
Non-Invasive Pulsatile Shear Stress Modifies Endothelial Activation
The luminal surface of all the vasculature and the heart is lined by endothelial cells (EC), encompassing more than 5000 m2. Furthermore, the response of EC to external signals and the synthesis and production of various mediators is heterogeneous and adaptive based on location and signals. EC membranes are the sensing mechanism, responsive to mechanical (shear stress) and biochemical signaling (chemosensor). EC output is important for blood fluidity, coagulation, vasoreactivity, vasculogenesis, barrier function, and inflammation. Endothelial cell activation is the process by which EC changes from a quiescent cell phenotype, which maintains cellular integrity, antithrombotic, and anti-inflammatory properties, to a prothrombotic, pro-inflammatory, and permeable phenotype, also at the site of injury or infection, involved in repair and leukocyte trafficking. Endothelial activation is triggered by a multitude of stimuli that include inflammatory cytokines (interleukins, tumor necrosis factor, and interferon-γ), bacterial endotoxins, and pattern recognition receptor activation (PRR) after recognition of pathogen-associated molecular patterns (PAMP) or damage-associated molecular patterns (DAMP). Pathological activation of EC leads to increased vascular permeability, thrombosis, and an uncontrolled inflammatory response leading to endothelial dysfunction; the latter can be contained at the local level or participate in a more profound systemic response leading to multiorgan dysfunction and death.
  • 1.5K
  • 06 Dec 2022
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
Zinc Oxide Nanoparticles and Their Physiochemical Properties
Zinc oxide nanomaterials have been the cynosure of this decade because of their immense potential in different biomedical applications. It includes their usage in the prognosis and treatment of different infectious and cellular diseases, owing to their peculiar physiochemical properties such as variable shape, size, and surface charge etc. Increasing demand and usage of the ZnO nanomaterials raise concerns about their cellular and molecular toxicity and their biocompatibility with human cells.
  • 1.5K
  • 12 Jul 2023
Topic Review
Bacterial Virulence Factors
There are several levels to influence the expression of eukaryotic genes. A first level of interference is changing of the DNA’s structure on the chromatin level. Epigenetic modulation enables remodelling of the chromatin to transfer heterochromatin into euchromatin allowing transcription or vice versa. In addition, the affinity of promotors and other regulatory DNA sequences for RNA polymerases and transcription factors (TFs) can be influenced by cytosine or adenine methylation. Only a minor portion (fewer than 2%) of genes is transcribed into mRNAs, instead the majority is transferred into so called non-coding RNAs (ncRNAs). Certain long ncRNAs (lncRNAs) are also involved in epigenetic regulations. Epigenetic mechanisms are used for manipulation of gene expression in the course of several cellular processes. Here, we give an overview on the epigenetic control of gene expression by bacterial virulence factors during host cell infection.
  • 1.5K
  • 27 Oct 2020
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
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)).
  • 1.5K
  • 26 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
Exercise Interventions in Cancer-Related Cachexia
Cancer-related cachexia is a complex multifactorial phenomenon in which systemic inflammation plays a key role in the development and maintenance of the symptomatology. Pharmacological interventions seem to produce a positive effect on inflammatory state and cachexia. Nutritional interventions are focused on a high-energy diet with high-density foods and the supplementation with antioxidants, while physical activity is focused on strength-based training. The implementation of multidisciplinary non-pharmacological interventions in cancer-related cachexia could be an important tool to improve traditional treatments and improve patients’ quality of life.
  • 1.5K
  • 14 Jun 2022
Topic Review
Protein Phase Separation
Phase separation is a process by which a well-mixed solution of macromolecules such as proteins or nucleic acids spontaneously separates into two phases: a dense phase and a dilute phase.
  • 1.5K
  • 06 Dec 2022
Topic Review
Copy-number Variation
Copy number variation (CNV) is a phenomenon in which sections of the genome are repeated and the number of repeats in the genome varies between individuals. Copy number variation is a type of structural variation: specifically, it is a type of duplication or deletion event that affects a considerable number of base pairs. Approximately two-thirds of the entire human genome may be composed of repeats and 4.8–9.5% of the human genome can be classified as copy number variations. In mammals, copy number variations play an important role in generating necessary variation in the population as well as disease phenotype. Copy number variations can be generally categorized into two main groups: short repeats and long repeats. However, there are no clear boundaries between the two groups and the classification depends on the nature of the loci of interest. Short repeats include mainly bi-nucleotide repeats (two repeating nucleotides e.g. A-C-A-C-A-C...) and tri-nucleotide repeats. Long repeats include repeats of entire genes. This classification based on size of the repeat is the most obvious type of classification as size is an important factor in examining the types of mechanisms that most likely gave rise to the repeats, hence the likely effects of these repeats on phenotype.
  • 1.5K
  • 02 Nov 2022
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
Bone Morphogenetic Protein 7
Bone morphogenetic protein-7 is (BMP-7) is a potent anti-inflammatory growth factor belonging to the Transforming Growth Factor Beta (TGF-β) superfamily. It plays an important role in various biological processes, including embryogenesis, hematopoiesis, neurogenesis and skeletal morphogenesis. BMP-7 stimulates the target cells by binding to specific membrane-bound receptor BMPR 2 and transduces signals through mothers against decapentaplegic (Smads) and mitogen activated protein kinase (MAPK) pathways. To date, rhBMP-7 has been used clinically to induce the differentiation of mesenchymal stem cells bordering the bone fracture site into chondrocytes, osteoclasts, the formation of new bone via calcium deposition and to stimulate the repair of bone fracture. However, its use in cardiovascular diseases, such as atherosclerosis, myocardial infarction, and diabetic cardiomyopathy is currently being explored. More importantly, these cardiovascular diseases are associated with inflammation and infiltrated monocytes where BMP-7 has been demonstrated to be a key player in the differentiation of pro-inflammatory monocytes, or M1 macrophages, into anti-inflammatory M2 macrophages, which reduces developed cardiac dysfunction. 
  • 1.5K
  • 14 May 2021
Topic Review
α-Synuclein in Gene Expression
α-Synuclein (α-Syn) is a small cytosolic protein associated with a range of cellular compartments, including synaptic vesicles, the nucleus, mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosomes. In addition to its physiological role in regulating presynaptic function, the protein plays a central role in both sporadic and familial Parkinson’s disease (PD) via a gain-of-function mechanism. Because of this, several recent strategies propose to decrease α-Syn levels in PD patients.
  • 1.5K
  • 13 Aug 2021
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
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
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
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
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
Bone Morphogenetic Proteins
Bone morphogenetic proteins (BMPs) were originally identified as the active components in bone extracts that can induce ectopic bone formation. In recent decades, their key role has broadly expanded beyond bone physiology and pathology. Nowadays, the BMP pathway is considered an important player in vascular signaling. Indeed, mutations in genes encoding different components of the BMP pathway cause various severe vascular diseases. Their signaling contributes to the morphological, functional and molecular heterogeneity among endothelial cells in different vessel types such as arteries, veins, lymphatic vessels and capillaries within different organs. The BMP pathway is a remarkably fine-tuned pathway. As a result, its signaling output in the vessel wall critically depends on the cellular context, which includes flow hemodynamics, interplay with other vascular signaling cascades and the interaction of endothelial cells with peri-endothelial cells and the surrounding matrix.
  • 1.5K
  • 27 Jul 2021
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. 
  • 1.5K
  • 28 May 2021
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