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Topic Review
Biography
Topic Review
Molecular Mechanism of Ferroptosis in Orthopedic Diseases
Programmed Cell Death (PCD) is an active and orderly process of cell death, which plays an important role in the evolution of living organisms, the stability of the internal environment, and the development of multiple systems. PCD includes cell apoptosis, necrosis, pyroptosis, ferroptosis, and autophagy. Apoptosis is characterized by nuclear fragmentation, the formation of apoptotic bodies, and the activation of proteins such as pro-apoptotic B cell lymphoma-2 (BCL-2). It leads to the increase of mitochondrial outer membrane permeabilization (MOMP) and the production of reactive oxygen species (ROS), thereby releasing apoptotic factors and promoting cysteine cascade activation. During necrosis, the plasma membrane rupture, cytoplasmic organelle swelling, internucleosomal DNA fragmentation deficiency, ATP consumption, and damage-associated molecular patterns (DAMPs) release. When pyroptosis occurs, the plasma membrane ruptures, the inflammation-related active IL-1β and IL-18 are released, and the caspase-1 and gasdermin D (GSDMD) are activated by hydrolysis. Autophagy is characterized by the accumulation of autophagic vacuoles, cytoplasmic vacuolation, non-condensation of chromatin, the transformation of microtubule-associated protein light chain 3 (LC3)-I to LC3-II, and p62-cleaved.
342
19 Oct 2022
Topic Review
Mechanism of Action of circRNAs in Cancer Cells
The ever-increasing number of cancer cases and persistently high mortality underlines the urgent need to acquire new perspectives for developing innovative therapeutic approaches. As the research on protein-coding genes brought significant yet only incremental progress in the development of anticancer therapy, much attention is now devoted to understanding the role of non-coding RNAs (ncRNAs) in various types of cancer. The ncRNAs recognized previously as “dark matter” are, in fact, key players in shaping cancer development. Moreover, breakthrough discoveries concerning the role of a new group of ncRNAs, circular RNAs, have evidenced their high importance in many diseases, including malignancies.
342
17 Feb 2023
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.
341
19 Jul 2021
Topic Review
Let-7e Differentiates Stress-Resilient from Susceptible
Three strains of mice with various susceptibilities to restraint stress (RS), i.e., mice with a knocked out norepinephrine transporter gene (NET-KO), SWR/J and C57BL/6J (WT) mice were shown to serve as a good model to study the molecular mechanisms underlying different stress-coping strategies. We identified 14 miRNAs that were altered by RS in the PFC of these mice in a genotype-dependent manner, where the most interesting was let-7e. Further in silico analysis of its potential targets allowed us to identify five mRNAs (Bcl2l11, Foxo1, Pik3r1, Gab1 and Map2k4), and their level alterations were experimentally confirmed. A next-generation sequencing (NGS) approach, which was employed to find transcripts differentially expressed in the PFC of NET-KO and WT mice, showed that, among others, two additional mRNAs were regulated by mmu-let-7e, i.e., mRNAs that encode Kmt2d and Inf2. Since an increase in Bcl2l11 and Pik3r1 mRNAs upon RS in the PFC of WT mice resulted from the decrease in mmu-let-7e and mmu-miR-484 regulations, we postulated that MAPK, FoxO and PI3K-Akt signaling pathways were associated with stress resilience, although via different, genotype-dependent regulation of various mRNAs by let-7e and miR-484. However, a higher level of Kmt2d mRNA (regulated by let-7e) that was found with NGS analysis in the PFC of NET-KO mice indicated that histone methylation was also important for stress resilience.
341
22 Sep 2021
Topic Review
Vascular Inflammatory Diseases and Endothelial Phenotypes
The physiological functions of endothelial cells control vascular tone, permeability, inflammation, and angiogenesis, which significantly help to maintain a healthy vascular system. Several cardiovascular diseases are characterized by endothelial cell activation or dysfunction triggered by external stimuli such as disturbed flow, hypoxia, growth factors, and cytokines in response to high levels of low-density lipoprotein and cholesterol, hypertension, diabetes, aging, drugs, and smoking. Increasing evidence suggests that uncontrolled proinflammatory signaling and further alteration in endothelial cell phenotypes such as barrier disruption, increased permeability, endothelial to mesenchymal transition (EndMT), and metabolic reprogramming further induce vascular diseases, and multiple studies are focusing on finding the pathways and mechanisms involved in it.
342
27 Jun 2023
Topic Review
Structure and Architecture of BRCT Domains
The human BRCT domain was first resolved from the crystal structure of the N-terminal BRCT of the X-ray repair cross-complementing protein 1 (XRCC1), determined by X-ray crystallography to a 3.2 Å resolution. Its tertiary structure features a central core of four-stranded parallel β-sheet (β1, β2, β3, and β4) flanked by two α-helices (α1 and α3) on the C-terminal end, a single α-helix (α2) on the N-terminal end, and two surface loops connecting β1 with α1 and α2 with β3 (the overall structure being β1-α1-β2-β3-α2-β4-α3). BRCT domains have been identified in a wide group of living organisms (from bacteria, parasites to mammals) and viruses. As mentioned above, those domains take part in a variety of important cell processes including DDR and cell cycle control. In addition, a few of these protein modules have been shown to be involved in pathologies such as cancer or infectious diseases including leishmaniasis. Therefore, significant efforts have been made towards finding compounds able to specifically inhibit the functions of these protein domains.
341
24 Jul 2023
Topic Review
Pluripotent Organ-Specific Pericytes in Growth and Maturation
Cells fitting the description of Mesenchymal Stem/Signaling Cells (MSC) have been isolated from a large number of adult tissues. The original characteristics of MSC as defined by Caplan’s group were adherence to plastic, expression of a subset of cell surface antigens, and the cells could be induced in vitro to differentiate towards different cell lineages, including chondrocytes, bone cells, and adipocytes. It has been noted that MSC from most tissues or fluids are very heterogeneous, and some sources appear to have unique features, including unique lectin-binding phenotypes. Interestingly, MSC from bone marrow appear to preferentially respond to osteogenic stimuli, while MSC from synovium respond well to chondrogenic stimuli. Thus, different locations may reflect the needs of different environments.
340
25 May 2022
Topic Review
Cysteine Modification in Aurora Kinase A
Aurora kinase A (AURKA), which is a member of serine/threonine kinase family, plays a critical role in regulating mitosis. AURKA has drawn much attention as its dysregulation is critically associated with various cancers, leading to the development of AURKA inhibitors, a new class of anticancer drugs. As the spatiotemporal activity of AURKA critically depends on diverse intra- and inter-molecular factors, including its interaction with various protein cofactors and post-translational modifications, each of these pathways should be exploited for the development of a novel class of AURKA inhibitors other than ATP-competitive inhibitors.
338
05 Jun 2023
Topic Review
Mycolactone Targets the Sec61 Translocon
“Recognizing a surprising fact is the first step towards discovery.” This famous quote from Louis Pasteur is particularly appropriate to describe what led us to study mycolactone, a lipid toxin produced by the human pathogen Mycobacterium ulcerans. M. ulcerans is the causative agent of Buruli ulcer, a neglected tropical disease manifesting as chronic, necrotic skin lesions with a “surprising” lack of inflammation and pain. Decades after its first description, mycolactone has become much more than a mycobacterial toxin. This uniquely potent inhibitor of the mammalian translocon (Sec61) helped reveal the central importance of Sec61 activity for immune cell functions, the spread of viral particles and, unexpectedly, the viability of certain cancer cells.
338
20 Jun 2023
Topic Review
Basophils in Brief
Basophils are a type of white blood cell that play a multifaceted role in the immune system. These enigmatic cells, constituting a mere 0.5% or less of the total white blood cell population, originate in the bone marrow and mature under the influence of various growth factors and cytokines. Traditionally known for their involvement in allergic reactions, basophils are equipped with high-affinity IgE receptors (FcεRI) that bind to allergens. Upon allergen exposure, basophils release histamine and other inflammatory mediators, triggering the hallmark symptoms of allergies. Beyond allergies, basophils are integral in the body's defense against parasitic infections. When they encounter parasitic antigens, they release cytokines like IL-4 and IL-13, promoting a Th2 immune response that helps eliminate parasites. Basophils also have a less explored role as regulators of the immune system, potentially influencing T cell differentiation and acting as antigen-presenting cells (APCs). Additionally, they contribute to tissue repair and wound healing by releasing factors that stimulate angiogenesis and tissue regeneration. In clinical settings, basophils serve as valuable biomarkers for allergic diseases, parasitic infections, and certain hematological disorders. Ongoing research continues to unveil the diverse functions of basophils, highlighting their importance in immunology and beyond.
338
07 Oct 2023
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