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Topic Review
Secreted Frizzled-Related Protein 5
Secreted frizzled-related protein 5 (SFRP5) is an anti-inflammatory adipocytokine member of the SFRP family that is an antagonist of the WNT (wingless-MMTV integration site) family member 5a (WNT5A), a ligand of WNT pathway. There are two types of WNT signaling pathways: canonical and noncanonical, but SFRP5 is implicated only in the last one. The noncanonical pathway is activated by WNT ligands that bind to the frizzled receptors, followed by the phosphorylation of Jun N-terminal kinase (JNK) that triggers proinflammatory and proliferative processes. The SFRP5/WNT5A-mediated noncanonical pathways are associated with the pathogenesis of many inflammation-related diseases. However, SFRP5 has a controversial role in liver disease.
  • 708
  • 05 Jul 2021
Topic Review
Ngn3-Positive Cell Detection from Duct
The production of pancreatic β cells is the most challenging step for curing diabetes using next-generation treatments. Adult pancreatic endocrine cells are thought to be maintained by the self-duplication of differentiated cells, and pancreatic endocrine neogenesis can only be observed when the tissue is severely damaged. Experimentally, this can be performed using a method named partial duct ligation (PDL). We performed PDL on neurogenin3 (Ngn3)-GFP transgenic mice to determine the origin of endocrine precursor cells and evaluate their potential to differentiate into multiple cell types. Ngn3-expressing cells, which were marked with GFP, appeared after PDL operation. Because some GFP-positive cells were found proximally to the duct, we hypothesized that Ngn3-positive cells arise from the pancreatic duct. Therefore, we next developed an in vitro pancreatic duct culture system using Ngn3-GFP mice and examined whether Ngn3-positive cells emerge from this duct. Our results demonstrate that in adult mice, Ngn3-positive endocrine precursor cells arise from the pancreatic ducts both in vivo and in vitro experiments indicating that the pancreatic duct could be a potential donor for therapeutic use.
  • 708
  • 22 Sep 2021
Topic Review
Site-Search Process for Synaptic Protein-DNA Complexes
The assembly of synaptic protein-DNA complexes by specialized proteins is critical for bringing together two distant sites within a DNA molecule or bridging two DNA molecules. The assembly of such synaptosomes is needed in numerous genetic processes requiring the interactions of two or more sites. The molecular mechanisms by which proteins bring the sites together, enabling the assembly of synaptosomes, remain unknown. Such proteins can utilize sliding, jumping, and segmental transfer pathways for the single-site search process, but none of these pathways explains how the synaptosome assembles. Here we used restriction enzyme SfiI, that requires the assembly of synaptosome for DNA cleavage, as our experimental system and applied time-lapse high-speed AFM (HS-AFM) to directly visualize the site search process accomplished by the SfiI enzyme.
  • 708
  • 17 Jan 2022
Topic Review
Influence of DDP Chemotherapy on miRNA Expression
Platinum-based chemotherapy, cisplatin (DDP) specifically, is the main strategy for treating lung cancer (LC). However, there is a lack of predictive drug-resistance markers, and there is increased interest in the development of a reliable and sensitive panel of markers for DDP chemotherapy-effectiveness prediction. MicroRNAs represent a perspective pool of markers for chemotherapy effectiveness.
  • 708
  • 17 Aug 2022
Topic Review
Actions of Insulin Expressed in the CNS
The expression of insulin receptors (IR) in the central nervous system (CNS) was first documented almost half a century ago. It is now known that both short (IR-A) and long (IR-B) isoform of this receptor is expressed in the hypothalamus, hippocampus, cerebral cortex, and cerebellum, the brain regions also associated with the production of insulin. In regard to the IR expression at the cellular level, it was shown that, unlike neurons that only express IR-A, astrocytes express both IR-A and IR-B. Ever since the transport of insulin across the BBB and the expression of functional IR in the CNS was documented, attempts have been made to learn more about the effects of insulin on the brain. In line with that, numerous actions of insulin in the CNS have been described so far. It has been known that insulin takes part in controlling food intake and body weight. In addition to that, insulin actions are also essential for proper neuronal development and survival, cognition, brain cholesterol synthesis, hepatic glucose production, lipolysis and lipogenesis, and even reproductive competence. Moreover, it was also shown that impairment in insulin signaling could trigger depression- and anxiety-like behaviors. Although new roles of insulin keep emerging, it is still mainly unknown which of them can be attributed to brain-derived and which to pancreatic insulin, or whether their actions in the CNS overlap and to what extent.
  • 708
  • 12 Apr 2023
Topic Review
Cancer Cells and Induced Pluripotent Stem Cells
Cancer cells, especially cancer stem cells (CSCs), share many molecular features with induced pluripotent stem cells (iPSCs) that enable the derivation of induced pluripotent cancer cells by reprogramming malignant cells. Conversely, normal iPSCs can be converted into cancer stem-like cells with the help of tumor microenvironment components and genetic manipulation. These CSC models can be utilized in oncogenic initiation and progression studies, understanding drug resistance, and developing novel therapeutic strategies.
  • 708
  • 25 Jan 2024
Topic Review
Clinical Applications of Targeting Exosomes
Breast cancer metastasis is a complicated process involving multiple physiological changes, and lung, brain, bone and liver are the main metastatic targets. Exosomes are membrane-bound extracellular vesicles that contain secreted cellular constitutes. The biogenesis and functions of exosomes in cancer have been intensively studied, and mounting studies have indicated that exosomes play a crucial role in cancer metastasis. 
  • 707
  • 06 Dec 2022
Topic Review
Calcineurin B-like Proteins in Plants under Salt Stress
Salinity stands as a significant environmental stressor, severely impacting crop productivity. Plants exposed to salt stress undergo physiological alterations that influence their growth and development. Meanwhile, plants have also evolved mechanisms to endure the detrimental effects of salinity-induced salt stress. Within plants, Calcineurin B-like (CBL) proteins act as vital Ca2+ sensors, binding to Ca2+ and subsequently transmitting signals to downstream response pathways. CBLs engage with CBL-interacting protein kinases (CIPKs), forming complexes that regulate a multitude of plant growth and developmental processes, notably ion homeostasis in response to salinity conditions.
  • 707
  • 05 Dec 2023
Topic Review
Lipid Droplets, Phospholipase A2, Arachidonic Acid, and Atherosclerosis
Lipid droplets, classically regarded as static storage organelles, are currently considered as dynamic structures involved in key processes of lipid metabolism, cellular homeostasis and signaling. Studies on the inflammatory state of atherosclerotic plaques suggest that circulating monocytes interact with products released by endothelial cells and may acquire a foamy phenotype before crossing the endothelial barrier and differentiating into macrophages. One such compound released in significant amounts into the bloodstream is arachidonic acid, the common precursor of eicosanoids, and a potent inducer of neutral lipid synthesis and lipid droplet formation in circulating monocytes. Members of the family of phospholipase A2, which hydrolyze the fatty acid present at the sn-2 position of phospholipids, have recently emerged as key controllers of lipid droplet homeostasis, regulating their formation and the availability of fatty acids for lipid mediator production.
  • 706
  • 20 Jan 2022
Topic Review
Neuroinflammation in Retinitis Pigmentosa
The retina is a multilayer neuronal tissue located in the back of the eye that transduces the environmental light into a neural impulse. Many eye diseases caused by endogenous or exogenous harm lead to retina degeneration with neuroinflammation being a major hallmark of these pathologies.
  • 706
  • 24 Jan 2022
Topic Review
Differential Intracellular Protein Distribution in Cancer and Cells
It is well-established that cancer and normal cells can be differentiated based on the altered sequence and expression of specific proteins. There are only a few examples, showing that cancer and normal cells can be differentiated based on the altered distribution of proteins within intracellular compartments. there are available data on shifts in the intracellular distribution of two proteins, the membrane associated beta-catenin and the actin-binding protein CapG. Both proteins show altered distributions in cancer cells compared to normal cells. These changes are noted (i) in steady state and thus can be visualized by immunohistochemistry—beta-catenin shifts from the plasma membrane to the cell nucleus in cancer cells; and (ii) in the dynamic distribution that can only be revealed using the tools of quantitative live cell microscopy—CapG shuttles faster into the cell nucleus of cancer cells. Both proteins may play a role as prognosticators in gynecologic malignancies: beta-catenin in endometrial cancer and CapG in breast and ovarian cancer. Thus, both proteins may serve as examples of altered intracellular protein distribution in cancer and normal cells.
  • 706
  • 19 Oct 2022
Topic Review
suPAR in Autoimmune Rheumatic Diseases
The soluble urokinase plasminogen activator receptor (suPAR) is the bioactive form of urokinase plasminogen activator receptor (uPAR), a membrane-bound glycoprotein, and it is primarily expressed on the surface of immunologically active cells. Mirroring local inflammation and immune activation, suPAR has gained interest as a potential prognostic biomarker in several inflammatory diseases. Mirroring immune system activation, suPAR has been associated with many autoimmune rheumatic diseases.
  • 706
  • 17 May 2023
Topic Review
The Regulatory Roles of PPARs
Peroxisome proliferator-activated receptors (PPARs) are a group of transcription factors implicated in wide-ranging cellular functions, including lipid metabolism, inflammatory responses and cell proliferation and differentiation.
  • 705
  • 13 Dec 2021
Topic Review
Innate Immunity in Disease and Adaptation to Stress
Since first being documented in ancient times, the relation of inflammation with injury and disease has evolved in complexity and causality. Early observations supported a cause (injury) and effect (inflammation) relationship, but the number of pathologies linked to chronic inflammation suggests that inflammation itself acts as a potent promoter of injury and disease. Additionally, results from studies over the last decades point to chronic inflammation and innate immune signaling as a critical link between stress (exogenous and endogenous) and adaptation.
  • 705
  • 06 Jun 2022
Topic Review
Role of Mint3 in Inflammatory Response Cancer
Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that plays a crucial role in cells adapting to a low-oxygen environment by facilitating a switch from oxygen-dependent ATP production to glycolysis. Mediated by membrane type-1 matrix metalloproteinase (MT1-MMP) expression, Munc-18-1 interacting protein 3 (Mint3) binds to the factor inhibiting HIF-1 (FIH-1) and inhibits its suppressive effect, leading to HIF-1α activation. Defects in Mint3 generally lead to improved acute inflammation, which is regulated by HIF-1α and subsequent glycolysis, as well as the suppression of the proliferation and metastasis of cancer cells directly through its expression in cancer cells and indirectly through its expression in macrophages or fibroblasts associated with cancer. Mint3 in inflammatory monocytes enhances the chemotaxis into metastatic sites and the production of vascular endothelial growth factors, which leads to the expression of E-selectin at the metastatic sites and the extravasation of cancer cells. Fibroblasts express L1 cell adhesion molecules in a Mint3-dependent manner and enhance integrin-mediated cancer progression. In pancreatic cancer cells, Mint3 directly promotes cancer progression. Naphthofluorescein, a Mint3 inhibitor, can disrupt the interaction between FIH-1 and Mint3 and potently suppress Mint3-mediated inflammation, cancer progression, and metastasis without causing marked adverse effects. 
  • 705
  • 15 Mar 2023
Topic Review
Ophiobolins in Aspergillus ustus 094102
Ophiobolins are a group of sesterterpenoids with a 5-8-5 tricyclic skeleton. They exhibit a significant cytotoxicity and present potential medicinal prospects. 
  • 704
  • 25 Feb 2022
Topic Review
Hypoxia-Induced circRNAs in Human Diseases
Hypoxia is the driving force that is responsible for the characteristic metabolic switch from the oxidation of fatty acids in a healthy heart to the utilization of glucose in a failing myocardium. It also promotes the reactivation of fetal gene programs, thereby inducing the cardiac hypertrophy response, changing the composition of the extracellular matrix, and affecting mitochondrial biogenesis, as well as myocardial contractility. Hypoxia-related circRNAs may add to the complexities involved in the regulation of hypoxia-mediated effects, and unraveling the roles played by these circRNAs may provide new directions for the treatment of diverse diseases.
  • 704
  • 07 May 2022
Topic Review
C. elegans DMD Mutants
The nematode worm Caenorhabditis elegans has been used extensively to enhance our understanding of the human neuromuscular disorder Duchenne Muscular Dystrophy (DMD).
  • 702
  • 11 May 2021
Topic Review
Molecular Structure of Leucine-Rich-Repeat Kinase 2
Mutations in the multidomain protein Leucine-rich-repeat kinase 2 (LRRK2) have been identified as a genetic risk factor for both sporadic and familial Parkinson’s disease (PD). LRRK2 has two enzymatic domains: a RocCOR tandem with GTPase activity and a kinase domain. In addition, LRRK2 has three N-terminal domains: ARM (Armadillo repeat), ANK (Ankyrin repeat), and LRR (Leucine-rich-repeat), and a C-terminal WD40 domain, all of which are involved in mediating protein–protein interactions (PPIs) and regulation of the LRRK2 catalytic core.
  • 701
  • 25 Apr 2023
Topic Review
mtDNA in Metabolic Syndrome and Obesity
Metabolic syndrome (MetS) is a precursor to the major health diseases associated with high mortality in industrialized countries: cardiovascular disease and diabetes. An important component of the pathogenesis of the metabolic syndrome is mitochondrial dysfunction. The mitochondrial AAA + protease Lon (Lonp1) has a broad spectrum of activities. In addition to its classical function (degradation of misfolded or damaged proteins), enzymatic activity (proteolysis, chaperone activity, mitochondrial DNA (mtDNA) binding) has been demonstrated. 
  • 701
  • 11 Aug 2023
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