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Topic Review
Ran GTPase and Its Importance in Malignant Phenotype
Ran is a member of the Ras superfamily of proteins, which primarily regulates nucleocytoplasmic trafficking and mediates mitosis by regulating spindle formation and nuclear envelope (NE) reassembly. Therefore, Ran is an integral cell fate determinant. It has been demonstrated that aberrant Ran expression in cancer is a result of upstream dysregulation of the expression of various factors, such as osteopontin (OPN), and aberrant activation of various signaling pathways, including the extracellular-regulated kinase/mitogen-activated protein kinase (ERK/MEK) and phosphatidylinositol 3-kinase/Protein kinase B (PI3K/Akt) pathways.
  • 894
  • 20 Apr 2023
Topic Review
Healthy Effects of Plant Polyphenols
Natural biophenols are a wide group of molecules (over 8000 described so far) found only in the plant kingdom; their molecules display one or more aromatic rings carrying one or more hydroxyl groups; these molecules display remarkable antioxidant power and are produced as secondary metabolites by the plant for protection against the attack by bacteria, fungi, and insects (phytoalexins). Plant polyphenols include non-flavonoids or flavonoids; the latter are further divided into flavonols, flavononols, flavones, anthocyanins, procyanidins, phenolic acids, stilbenes, and tannins depending on the number of hydroxyls in the molecule and on the nature and the position of other substituents.
  • 893
  • 12 Apr 2021
Topic Review
Dietary Lipids on Bone Health
Age-related bone disorders such as osteoporosis or osteoarthritis are a major public health problem due to the functional disability for millions of people worldwide. Furthermore, fractures are associated with a higher degree of morbidity and mortality in the long term, which generates greater financial and health costs. As the world population becomes older, the incidence of this type of disease increases and this effect seems notably greater in those countries that present a more westernized lifestyle. Thus, increased efforts are directed toward reducing risks that need to focus not only on the prevention of bone diseases, but also on the treatment of persons already afflicted. Evidence is accumulating that dietary lipids play an important role in bone health which results relevant to develop effective interventions for prevent bone diseases or alterations, especially in the elderly segment of the population.
  • 893
  • 28 Jun 2021
Topic Review
Adult Fragile X-Associated Syndromes
Expansions of the CGG-repeats stretch at the 5'-UTR of the Fragile X Mental Retardation 1 (FMR1) gene have pleiotropic effects that lead to a variety of Fragile X-associated syndromes: the neurodevelopmental Fragile X syndrome (FXS) in children, the late-onset neurodegenerative disorder Fragile X-associated tremor-ataxia syndrome (FXTAS) that mainly affects adult men, the Fragile X-associated primary ovarian insufficiency (FXPOI) in adult women, and a variety of psychiatric and affective disorders that are under the term of Fragile X-associated neuropsychiatric disorders (FXAND). In the adult syndromes, the pathological mechanisms are primarily caused by a gain-of-function due to the toxic actions of CGG RNA and FMRpolyG peptide. 
  • 893
  • 26 Aug 2021
Topic Review
Mitogen-Activated Protein Kinases (MAPKs) and Cholangiocarcinoma
Cholangiocarcinoma (CCA) is a malignant adenocarcinoma characterized by biliary tract differentiation and is the second most common primary liver tumor. 
  • 893
  • 19 Apr 2022
Topic Review
DNA Supercoiling and Genomic Sequence Organization
The bacterial growth cycle was described  as a closed, self-reproducing, or autopoietic circuit, reestablishing the physiological state of stationary cells initially inoculated in the growth medium. In batch culture, this process of self-reproduction is associated with the gradual decline in available metabolic energy and corresponding change in the physiological state of the population as a function of “travelled distance” along the autopoietic path. This directional alteration of cell physiology is both reflected in and supported by sequential gene expression along the chromosomal OriC-Ter axis. During the E. coli growth cycle, the spatiotemporal order of gene expression is established by coupling the temporal gradient of supercoiling energy to the spatial gradient of DNA thermodynamic stability along the chromosomal OriC-Ter axis.
  • 893
  • 15 Aug 2022
Topic Review
TRPV3 Ion Channel
Transient receptor potential vanilloid subtype 3 (TRPV3) is an ion channel with a sensory function that is most abundantly expressed in keratinocytes and peripheral neurons. TRPV3 plays a role in Ca2+ homeostasis due to non-selective ionic conductivity and participates in signaling pathways associated with itch, dermatitis, hair growth, and skin regeneration. TRPV3 is a marker of pathological dysfunctions, and its expression is increased in conditions of injury and inflammation.
  • 892
  • 24 May 2023
Topic Review
Elucidating Selenoprotein M Function from Structure
Selenocysteine (Sec), the 21st amino acid, is structurally similar to cysteine but with a sulfur to selenium replacement. This single change retains many of the chemical properties of cysteine but often with enhanced catalytic and redox activity. Incorporation of Sec into proteins is unique, requiring additional translation factors and multiple steps to insert Sec at stop (UGA) codons. These Sec-containing proteins (selenoproteins) are found in all three domains of life where they often are involved in cellular homeostasis (e.g., reducing reactive oxygen species). The essential role of selenoproteins in humans requires us to maintain appropriate levels of selenium, the precursor for Sec, in our diet. Too much selenium is also problematic due to its toxic effects. Deciphering the role of Sec in selenoproteins is challenging for many reasons, one of which is due to their complicated biosynthesis pathway. However, clever strategies are surfacing to overcome this and facilitate production of selenoproteins.
  • 892
  • 01 Nov 2023
Topic Review
Gut dysbiosis by HFD: Effect on Distant Organs
The gastrointestinal (GI) tract protects the body from environmental challenges by blocking access to the host’s blood circulation for many pathogens, including fungi, bacteria, and parasites. This GI firewall comprises various structures and shielding mechanisms to fulfil its protective function, constituting an intestinal barrier (IB). The IB includes mucosal and submucosal layers, tight junctions (TJ), continuously renewing epithelium, and microbiota. The intestinal epithelial cells (IECs) are a barrier between the immune system and GI lumen, maintaining a limited IB permeability. Nonetheless, the GI tract has an arduous task. The constantly changing environment requires the IB to continually respond to new challenges, yet maintain its integrity while protecting the host from pathogens. Failure of the IB leads to intestinal hyperpermeability (leaky gut), allowing pathogens and their metabolites to enter the bloodstream. The metabolites then can affect distant organs, such as brain and inner ear.
  • 891
  • 26 Jan 2022
Topic Review
Polymyxin B Immobilized Fiber Column
Endotoxin removal therapy with polymyxin B immobilized fiber column (PMX) has been clinically applied for sepsis and septic shock patients since 1994. The effectiveness and usefulness of this therapy have been demonstrated for more than a quarter of a century. However, a documented survival benefit has not yet been demonstrable in a large, multicenter, randomized and controlled trial. Following the findings derived from a large sepsis clinical trial with PMX in North America, a new trial is ongoing to determine if PMX has a long-term survival benefit when administered to septic patients. Another approach to support a survival benefit from intervention with PMX is to utilize a detailed analysis available from a large clinical data base. The endotoxin adsorption capacity of PMX columns in vitro and the effectiveness of PMX columns can be further demonstrable in animal models. The capability of PMX and details of its mechanism of action to intervene in the sepsis cascade and impede organ dysfunction in septic patients is not fully understood. The surface antigen expression in monocytes and neutrophils are improved after PMX therapy. Immunomodulatory effects as a result of endotoxin removal and/or other mechanisms of action have been suggested. These effects and other potential immune effects may explain some of the improved effects upon organ dysfunction of sepsis and septic shock patients. Endotoxemia may be involved in the pathophysiology of other diseases than sepsis. A rapid diagnostic method to detect and target endotoxemia could allow us to practice precision medicine and expand the clinical indications of endotoxin removal therapy.
  • 890
  • 10 Mar 2021
Topic Review
ABCC6 Transporter in Hepatic Cells
Pseudoxanthoma elasticum (PXE) is a complex autosomal recessive disease caused by mutations of ABCC6 transporter and characterized by ectopic mineralization of soft connective tissues.
  • 890
  • 20 May 2021
Topic Review
Bispecific Antibodies for IFN-β Delivery to ErbB2+ Tumors
The main aim of this work was to create a full-length bispecific antibody (BsAb) as a vehicle for the targeted delivery of interferon-beta (IFN-β) to ErbB2+ tumor cells in the form of non-covalent complex of BsAb and IFN-β. Such a construct is a CrossMab-type BsAb, consisting of an ErbB2-recognizing trastuzumab moiety, a part of chimeric antibody to IFN-β, and human IgG1 Fc domain carrying knob-into-hole amino acid substitutions necessary for the proper assembly of bispecific molecules. The IFN-β- recognizing arm of BsAb not only forms a complex with the cytokine but neutralizes its activity, thus providing a mechanism to avoid the side effects of the systemic action of IFN-β by blocking IFN-β Interaction with cell receptors in the process of cytokine delivery to tumor sites. Enzyme sandwich immunoassay confirmed the ability of BsAb to bind to human IFN-β comparable to that of the parental chimeric mAb.
  • 890
  • 29 Mar 2022
Topic Review
Circulating Cell-Free DNA Levels in Psychiatric Diseases
The cell-free DNA (cfDNA) levels are known to increase in biological fluids in various pathological conditions. However, the data on circulating cfDNA in severe psychiatric disorders, including schizophrenia, bipolar disorder (BD), and depressive disorders (DDs), is contradictory. The meta-analysis showed that the levels of total cfDNA and genomic cfDNA in patients with schizophrenia are significantly higher than in healthy donors (SMD values of 0.61 and 0.6, respectively; p < 0.00001). Data on mitochondrial cfDNA in schizophrenia were scarce. Meta-analysis in BD and DDs found no significant differences in the level of mitochondrial cfDNA. However, further research on mitochondrial and genomic cfDNA levels in psychiatric disorders is needed due to the data heterogeneity.
  • 890
  • 08 Mar 2023
Topic Review
Anticancer Potentials of the Lignan Magnolin
Magnolin is a compound found in many different plants. It has been demonstrated to have anticancer activity in numerous experimental models by inhibiting the cell cycle (G1 and G2/M phase); inducing apoptosis; and causing antiinvasion, antimetastasis, and antiproliferative effects via the modulation of several pathways.
  • 890
  • 26 Apr 2023
Topic Review
L-Type Ca2+ Channel Regulation by Calmodulin and CaBP1
L-type voltage-gated Ca2+ channels (CaV1.2 and CaV1.3, called CaV) interact with the Ca2+ sensor proteins, calmodulin (CaM) and Ca2+ binding Protein 1 (CaBP1), that oppositely control Ca2+-dependent channel activity. CaM and CaBP1 can each bind to the IQ-motif within the C-terminal cytosolic domain of CaV, which promotes increased channel open probability under basal conditions. At elevated cytosolic Ca2+ levels (caused by CaV channel opening), Ca2+-bound CaM binding to CaV is essential for promoting rapid Ca2+-dependent channel inactivation (CDI). By contrast, CaV binding to CaBP1 prevents CDI and promotes Ca2+-induced channel opening (called CDF). 
  • 889
  • 15 Dec 2021
Topic Review
Tepotinib
Tepotinib (trade name Tepmetko) is a novel c-MET tyrosine kinase inhibitor that was recently approved in Japan for the treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring a MET exon 14 skipping mutation.
  • 889
  • 23 Nov 2021
Topic Review
ACE2 and SARS-CoV-2
Angiotensin-Converting Enzyme 2 (ACE2) is an essential enzyme in the renin-angiotensin system (RAS), effectively maintaining RAS equilibrium. Recently, scientists have also found that through the mediation of the S protein, SARS-CoV-2 can invade host cells using ACE2 as the target.
  • 888
  • 23 Feb 2021
Topic Review
Genomics and Transcriptomics of Myopia
Myopia is a globally emerging concern accompanied by multiple medical and socio-economic burdens with no well-established causal treatment to control thus far. The study of the genomics and transcriptomics of myopia treatment is crucial to delineate disease pathways and provide valuable insights for the design of precise and effective therapeutics. A strong understanding of altered biochemical pathways and underlying pathogenesis leading to myopia may facilitate early diagnosis and treatment of myopia, ultimately leading to the development of more effective preventive and therapeutic measures.
  • 888
  • 27 Mar 2023
Topic Review
Vanadium Effects on Lipid Peroxidation and Disease Processes
Lipid peroxidation (LPO), a process that affects human health, can be induced by exposure to vanadium salts and compounds. LPO is often exacerbated by oxidation stress, with some forms of vanadium providing protective effects. The LPO reaction involves the oxidation of the alkene bonds, primarily in polyunsaturated fatty acids, in a chain reaction to form radical and reactive oxygen species (ROS). The important question is which radical starts the chain first. On the one hand, a radical is needed (oxidative stress environment) while on the other hand, LPO amplifies and contributes to changing the redox state towards oxidation (what was called oxidative stress). 
  • 888
  • 31 Mar 2023
Topic Review
Ultrastructural Features of the Blood-Brain Barrier
The blood-brain barrier (BBB) is a dynamic barrier separating neurocytes and brain tissues from blood that is extremely sealed and strictly regulated by transporters such as aquaporin-4 (AQP-4), glucose transporter (GLUT), and specialized tight junctional complexes (TJCs) including tight junctions (TJs), adherens junctions (AJs), and Zonulae occludens (ZOs). With specifically selective transcellular and paracellular permeability, the BBB maintains a homeostatic microenvironment to protect the central nervous system (CNS).
  • 888
  • 27 Jul 2023
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