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Topic Review
Alternate Causes for Pathogenesis of Exfoliation Glaucoma
Exfoliation glaucoma (XFG) is the most recognizable form of secondary open-angle glaucoma associated with a high risk of blindness. This disease is characterized by white flaky granular deposits in the anterior chamber that leads to the elevation of intraocular pressure (IOP) and subsequent glaucomatous optic nerve damage. Conventionally, XFG is known to respond poorly to medical therapy, and surgical intervention is the only management option in most cases.
  • 691
  • 11 Mar 2022
Topic Review
Evolutionary Medicine
Evolutionary medicine is a rapidly developing field. There are two polyploidy-related aspects of it. Firstly, mutations and changes in expression patterns of many ohnologs are associated with various diseases and developmental disorders. Secondly (and probably more important), cancer is now interpreted as an evolutionary phenomenon, and polyploidy often arises in cancer.
  • 691
  • 11 Apr 2022
Topic Review
Two-Pore Channels and Ca2+ Homeostasis in Immune Cells
Two-pore channels (TPCs) are ligand-gated cation-selective ion channels that are preserved in plant and animal cells. In the latter, TPCs are located in membranes of acidic organelles, such as endosomes, lysosomes, and endolysosomes. Mast cells, along with basophil granulocytes, play an essential role in anaphylaxis and allergic reactions by releasing inflammatory mediators. Signaling in mast cells is mainly regulated via the release of Ca2+ from the endoplasmic reticulum as well as from acidic compartments, such as endolysosomes. For the crosstalk of these organelles TPCs seem essential. Allergic reactions and anaphylaxis were previously shown to be associated with the endolysosomal two-pore channel TPC1. The release of histamine, controlled by intracellular Ca2+ signals, was increased upon genetic or pharmacologic TPC1 inhibition. Conversely, stimulation of TPC channel activity by one of its endogenous ligands, namely nicotinic adenine dinucleotide phosphate (NAADP) or phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), were found to trigger the release of Ca2+ from the endolysosomes; thereby improving the effect of TPC1 on regulated mast cell degranulation. 
  • 691
  • 16 May 2022
Topic Review
CK2 in Musculoskeletal Disorders
Protein kinase CK2 (CK2) influences one-fifth of the cellular phosphoproteome. It regulates almost all cellular pathways and is thus a critical switch between biological processes within a cell. Inhibition of CK2 reverses oncogene addiction of tumor and alters tumor microenvironment.
  • 691
  • 07 Feb 2024
Topic Review
Testicular Germ-Cell Tumours (TGCT)
Testicular Germ Cell Tumors (TGCTs) are the second most common form of Germ Cell Tumour after benign ovarian teratomas. They are considered a “curable cancer” due to their exceptionally high survival rate of their patients: young caucasian men mostly. A better stratification of those patients would mean an improvement in their quality of life, which is currently diminished by the aggressiveness of prognostic treatments. The knowledge about the relation between TGCTs and the immune system could give keys to improve prognosis, diagnosis and treatment of this cancer.
  • 690
  • 24 May 2022
Topic Review
Coordination between Rac1 and Rab Proteins
Ras-related C3 botulinum toxin substrate 1 (Rac1) is a member of the family of the typical Rho guanosine triphosphate phosphohydrolases (GTPases), which are known for their role in several cellular processes such as cytoskeleton organization, gene expression regulation, and cell migration. The small GTPases of the Rho family regulate many aspects of actin dynamics, but are functionally connected to many other cellular processes. Rac1, a member of this family, besides its known function in the regulation of actin cytoskeleton, plays a key role in the production of reactive oxygen species, in gene transcription, in DNA repair, and also has been proven to have specific roles in neurons. 
  • 689
  • 19 May 2022
Topic Review
RUNX2 and Cancer
Runt-related transcription factor 2 (RUNX2) is critical for the modulation of chondrocyte osteoblast differentiation and hypertrophy. Recently discovered RUNX2 somatic mutations, expressional signatures of RUNX2 in normal tissues and tumors, and the prognostic and clinical significance of RUNX2 in many types of cancer have attracted attention and led RUNX2 to be considered a biomarker for cancer. Many discoveries have illustrated the indirect and direct biological functions of RUNX2 in orchestrating cancer stemness, cancer metastasis, angiogenesis, proliferation, and chemoresistance to anticancer compounds, warranting further exploration of the associated mechanisms to support the development of a novel therapeutic strategy. 
  • 687
  • 25 Apr 2023
Topic Review
Lipid Metabolic Alterations in KRAS Mutant Tumors
KRAS is one of the most commonly mutated genes, an event that leads to development of highly aggressive and resistant to any type of available therapy tumors. Mutated KRAS drives a complex network of lipid metabolic rearrangements to support the adaptation of cancer cells to harsh environmental conditions and ensure their survival. Because there has been only a little success in the continuous efforts of effectively targeting KRAS-driven tumors, it is of outmost importance to delineate the exact mechanisms of how they get rewired, leading to this distinctive phenotype.
  • 687
  • 06 Mar 2023
Topic Review
Emerging Role of Extracellular Vesicles in Metastasis
Communication between cancer cells and the surrounding stromal cells of the tumor microenvironment (TME) plays a key role in promoting metastasis, which is the major cause of cancer death. Small membrane-bound particles called extracellular vesicles (EVs) are released from both cancer and stromal cells and have a key role in mediating this communication through transport of cargo such as various RNA species (mRNA, miRNA, lncRNA), proteins, and lipids. 
  • 686
  • 04 Jan 2022
Topic Review
SLC26A9 in Cystic Fibrosis Lung Disease
SLC26A9 belongs to the solute carrier family 26 (SLC26), which comprises membrane proteins related to the phylogenetically older SLC26-SulP gene family. On the basis of different preliminary findings, including the phenotype of SlC26A9-deficient mice and its possible role as a gene modifier of the human phenotype and treatment response, SLC26A9 has emerged as one of the most interesting alternative targets for the treatment of cystic fibrosis (CF).
  • 686
  • 18 Feb 2022
Topic Review
Role of TAM Receptors in Bone Remodeling
The TAM (TYRO3, MERTK, and AXL) family of receptor tyrosine kinases are pleiotropic regulators of adult tissue homeostasis maintaining organ integrity and self-renewal. Disruption of their homeostatic balance fosters pathological conditions like autoinflammatory or degenerative diseases including rheumatoid arthritis, lupus erythematodes, or liver fibrosis. Moreover, TAM receptors exhibit prominent cell-transforming properties, promoting tumor progression, metastasis, and therapy resistance in various cancer entities. Emerging evidence shows that TAM receptors are involved in bone homeostasis by regulating osteoblastic bone formation and osteoclastic bone resorption. Therefore, TAM receptors emerge as new key players of the regulatory cytokine network of osteoblasts and osteoclasts and represent accessible targets for pharmacologic therapy for a broad set of different bone diseases, including primary and metastatic bone tumors, rheumatoid arthritis, or osteoporosis.
  • 686
  • 10 Jan 2024
Topic Review
A Journey to Produce Functional Beta Cells
Due to a pressing worldwide situation with diabetes, ideas to use direct differentiation from embryonic stem cells (ESCs) and pluripotent stem cells (PSCs) to produce beta cells have surfaced. Stem cells are thought to be an ideal source of all cell types including pancreatic beta cells. 
  • 685
  • 28 Jun 2022
Topic Review
Extracellular Vesicles of MSCs
Mesenchymal stem cells (MSCs), the cells distributed in the stromas of the body, are known for various properties including replication, the potential of various differentiations, the immune-related processes including inflammation. These cells were shown to play relevant roles in the therapy of numerous diseases, dependent on their immune regulation and their release of cytokines and growth factors, with ensuing activation of favorable enzymes and processes. Soon thereafter, it became clear that therapeutic actions of MSCs are risky, accompanied by serious drawbacks and defects. MSC therapy has been therefore reduced to a few diseases, replaced for the others by their extracellular vesicles, the MSC-EVs. The latter vesicles recapitulate most therapeutic actions of MSCs, with equal or even better efficacies and without the serious drawbacks of the parent cells. In addition, MSC-EVs are characterized by many advantages, among which are their heterogeneities dependent on the stromas of origin, the alleviation of cell aging, the regulation of immune responses and inflammation.
  • 684
  • 26 Jul 2021
Topic Review
Stathmins and Motor Neuron Diseases
Motor neuron diseases (MNDs) are a group of fatal, neurodegenerative disorders with different etiology, clinical course and presentation, caused by the loss of upper and lower motor neurons (MNs). MNs are highly specialized cells equipped with long, axonal processes; axonal defects are some of the main players underlying the pathogenesis of these disorders. Microtubules are key components of the neuronal cytoskeleton characterized by dynamic instability, switching between rapid polymerization and shrinkage. Proteins of the stathmin family affect microtubule dynamics regulating the assembly and the dismantling of tubulin. Stathmin-2 (STMN2) is one of the most abundantly expressed genes in MNs. Following axonal injury, STMN2 expression is upregulated, and the protein is transported toward the growth cones of regenerating axons. STMN2 has a critical role in axonal maintenance, and its dysregulation plays an important role in neurodegenerative processes. Stathmin-1 (STMN1) is a ubiquitous protein that is highly expressed during the development of the nervous system, and its phosphorylation controls microtubule dynamics.
  • 684
  • 01 Apr 2022
Topic Review
ABCA1 and Atherogenesis
Atheroprotective properties of human plasma high-density lipoproteins (HDLs) are determined by their involvement in reverse cholesterol transport (RCT) from the macrophage to the liver. ABCA1, ABCG1, and SR-BI cholesterol transporters are involved in cholesterol efflux from macrophages to lipid-free ApoA-I and HDL as a first RCT step. Molecular determinants of RCT efficiency that may possess diagnostic and therapeutic meaning remain largely unknown. Defects in the structure and function of ABCA1, ABCG1, and SR-BI are caused by changes in the gene sequence, such as single nucleotide polymorphism or various mutations. In the transcription initiation of transporter genes, in addition to transcription factors, long noncoding RNA (lncRNA), transcription activators, and repressors are also involved. Furthermore, transcription is substantially influenced by the methylation of gene promoter regions. Post-transcriptional regulation involves microRNAs and lncRNAs, including circular RNAs.
  • 683
  • 06 Jan 2022
Topic Review
Exercise Regulates Microglial Activation by Increasing Anti-Inflammatory Factors
Exercise impacts our body at multiple levels, including the central nervous system (CNS). In responding to exercise-related stress (e.g., hypoxia, heat, free radicals, etc.) and injuries, the body launches multiple endogenous protective and repair systems by altering gene expression and releasing a range of factors that prepare the body for the next challenge. Accumulating evidence indicates that exercise can enhance brain function and attenuate neurodegeneration. Besides improving neuroplasticity by altering the synaptic structure and function in various brain regions, exercise also modulates multiple systems that are known to regulate neuroinflammation and glial activation. Activated microglia and several pro-inflammatory cytokines play active roles in the pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. 
  • 683
  • 17 Jul 2023
Topic Review
Myoglobin in Brown Adipose Tissue: Novel Thermogenic Implications
Brown adipose tissue (BAT) plays an important role in energy homeostasis by generating heat from chemical energy via uncoupled oxidative phosphorylation. Besides its high mitochondrial content and its exclusive expression of the uncoupling protein 1, another key feature of BAT is the high expression of myoglobin (MB), a heme-containing protein that typically binds oxygen, thereby facilitating the diffusion of the gas from cell membranes to mitochondria of muscle cells. In addition, MB also modulates nitric oxide (NO•) pools and can bind C16 and C18 fatty acids, which indicates a role in lipid metabolism. Studies in humans and mice implicated MB present in BAT in the regulation of lipid droplet morphology and fatty acid shuttling and composition, as well as mitochondrial oxidative metabolism. 
  • 683
  • 14 Sep 2023
Topic Review
Hematopoietic Cell Transplant
Following primary infection, herpesviruses establish latency in infected individuals in the host cells and may reactivate upon external stimuli and during periods of immunosuppression.
  • 682
  • 10 Mar 2021
Topic Review
Oral Pathogenic Bacteria-Inducing Neurodegenerative Microgliosis
Porphyromonas gingivalis is a gram-negative bacterium found in the human oral cavity and is responsible for the development of chronic periodontitis as well as neurological diseases, including Alzheimer’s disease (AD). Given the significance of the roles of P. gingivalis in AD pathogenesis, it is critical to understand the underlying mechanisms of P. gingivalis-driven neuroinflammation and their contribution to neurodegeneration. Herein, we hypothesize that P. gingivalis produces secondary metabolites that may cause neurodegeneration through direct or indirect pathways mediated by microglia. To test our hypothesis, we treated human neural cells with bacterial conditioned media on our brain platforms and assessed microgliosis, astrogliosis and neurodegeneration. We found that bacteria-mediated microgliosis induced the production of nitric oxide, which causes neurodegeneration assessed with high pTau level. Our study demonstrated the elevation of detrimental protein mediators, CD86 and iNOS and the production of several pro-inflammatory markers from stimulated microglia. Through inhibition of LPS and succinate dehydrogenase in a bacterial conditioned medium, we showed a decrease in neurodegenerative microgliosis. In addition, we demonstrated the bidirectional effect of microgliosis and astrogliosis on each other exacerbating neurodegeneration. Overall, our study suggests that the mouth-brain axis may contribute to the pathogenesis of AD.
  • 682
  • 19 Jul 2021
Topic Review
Resveratrol-Induced Resensitization of Acquired Drug-Resistant Cancer Cells
Multidrug resistance (MDR) refers to a phenomenon wherein tumors exhibit cross-resistance to an array of drugs with different structures or action mechanisms once they become resistant to one anticancer drug. MDR to anticancer drugs remains a serious obstacle to the success of cancer chemotherapy. Resveratrol, a polyphenol, present in natural products exerts anticancer activity and acts as a potential MDR inhibitor in various drug-resistant cancer cells.
  • 682
  • 03 Mar 2022
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