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Topic Review
Tackling Chronic Inflammation with Withaferin
Chronic inflammatory diseases are considered to be one of the biggest threats to human health. Most prescribed pharmaceutical drugs aiming to treat these diseases are characterized by side-effects and negatively affect therapy adherence. Finding alternative treatment strategies to tackle chronic inflammation has therefore been gaining interest over the last few decades. In this context, Withaferin A (WA), a natural bioactive compound isolated from Withania somnifera, has been identified as a promising anti-cancer and anti-inflammatory compound. Although the majority of studies focus on the molecular mechanisms of WA in cancer models, recent evidence demonstrates that WA also holds promise as a new phytotherapeutic agent against chronic inflammatory diseases. By targeting crucial inflammatory pathways, including NF-kB and Nrf2 signaling, WA suppresses the inflammatory disease state in several in vitro and preclinical in vivo models of diabetes, obesity, neurodegenerative disorders, cystic fibrosis, and osteoarthritis. This review provides a concise overview of the molecular mechanisms by which WA orchestrates its anti-inflammatory effects to restore immune homeostasis. 
  • 684
  • 10 Aug 2021
Topic Review
Dystrophin Node
Dystrophin isoform Dp427-M is tightly associated with a variety of glycoproteins at the muscle sarcolemma membrane. The core dystrophin-glycoprotein complex forms a variety of links to components of the extracellular matrix and the intracellular cytoskeleton. The wider dystrophin complexome plays a crucial functional role as an integrative node of the skeletal muscle periphery. The sarcolemmal dystrophin node is involved in the maintenance of fiber stability, the provision of cellular signaling cascades, organizer of cytoskeletal networks and costameric anchor for lateral force transmission.
  • 684
  • 19 Feb 2021
Topic Review
Trans-Synaptic Neurexin–Neuroligin Interaction
Synapses serve as the interface for the transmission of information between neurons in the central nervous system. The structural and functional characteristics of synapses are highly dynamic, exhibiting extensive plasticity that is shaped by neural activity and regulated primarily by trans-synaptic cell-adhesion molecules (CAMs). Prototypical trans-synaptic CAMs, such as neurexins (Nrxs) and neuroligins (Nlgs), directly regulate the assembly of presynaptic and postsynaptic molecules, including synaptic vesicles, active zone proteins, and receptors. Therefore, the trans-synaptic adhesion mechanisms mediated by Nrx–Nlg interaction can contribute to a range of synaptopathies in the context of pathological pain and other neurological disorders.
  • 684
  • 01 Jul 2022
Topic Review
Tuning between Nuclear Organization and Functionality in Health
The organization of eukaryotic genome in the nucleus, a double-membraned organelle separated from the cytoplasm, is highly complex and dynamic. The functional architecture of the nucleus is confined by the layers of internal and cytoplasmic elements, including chromatin organization, nuclear envelope associated proteome and transport, nuclear–cytoskeletal contacts, and the mechano-regulatory signaling cascades. The size and morphology of the nucleus could impose a significant impact on nuclear mechanics, chromatin organization, gene expression, cell functionality and disease development. The maintenance of nuclear organization during genetic or physical perturbation is crucial for the viability and lifespan of the cell. Abnormal nuclear envelope morphologies, such as invagination and blebbing, have functional implications in several human disorders, including cancer, accelerated aging, thyroid disorders, and different types of neuro-muscular diseases. 
  • 684
  • 07 Mar 2023
Topic Review
Omega-3 Fatty Acids on Insulin Resistance
Insulin resistance is a critical pathophysiological process in the onset and advancement of type 2 diabetes mellitus. It is well-recognized that alterations in the metabolism of lipids and aberrant fat buildup effectively trigger the development of resistance to insulin. Adjusting one’s eating habits and managing weight appropriately are crucial for treating, controlling, and reducing the risk of T2DM because obesity and a lack of physical exercise are the primary factors responsible for the worldwide rise in T2DM. Omega-3 fatty acid is one of the polyunsaturated fatty acids (PUFA) that include long-chain omega-3 fatty acids such as eicosapentaenoic acid and docosahexaenoic acid, commonly found in fish oils.
  • 684
  • 21 Jun 2023
Topic Review
AztABCD Zinc Transporter System
Zinc is an essential trace nutrient. In bacteria, its import into the cell is largely mediated by ATP binding cassette (ABC) transporters, which rely on extracellular solute binding proteins (SBP) to bind the metal with high affinity and specificity. In some cases, the SBPs work with other extracellular zinc binding proteins known as metallochaperones. The mechanisms of zinc transport in these systems is of interest because zinc ABC transporters have been shown to be essential for virulence in a number of pathogenic bacteria. This entry describes several structural features of a zinc SBP and related metallochaperone and their role in zinc binding and transfer. 
  • 683
  • 18 Aug 2020
Topic Review
GPCR signaling in the carotid-body
       The carotid body (CB) is a vital sensory organ, located near the carotid bifurcation, that constantly monitors blood supplying the brain. The CB is stimulated by acute hypoxia, upon which it rapidly activates vital cardiovascular and respiratory reflexes, including peripheral vasoconstriction, elevated heart rate and increased breathing. These ensure that sufficient blood-oxygen is delivered to the brain to support survival. It is now apparent that there are numerous G-protein-coupled receptors (GPCRs) expressed in the CB, and that modulation of these receptors is able to alter baseline CB activity and the sensitivity to hypoxia. Indeed, components of GPCR signaling pathways represent some of the most highly expressed genes in the rodent CB.
  • 682
  • 25 Aug 2020
Topic Review
The Main Protease of SARS-CoV-2 and its inhibitors
Mpro, also known as 3-chymotrypsin-like protease (3CLpro), is a 33.8 kDa, three-domain cysteine protease, essential for proteolytic maturation and viral replication of coronaviruses. This enzyme is an excellent target for a potential drug, as it is essential for viral replication and has no closely related homologues in humans, making its inhibitors unlikely to be toxic. 
  • 682
  • 08 Aug 2022
Topic Review
MicroRNAs Responding to Space Radiation
High-energy and high-atom-number (HZE) space radiation poses an inevitable potential threat to astronauts on deep space exploration missions. In addition to inducing damage at the DNA level, space radiation also causes epigenetic changes, such as microRNAs, which is important to understanding of the machanisms underlying space radiobiological effects.
  • 681
  • 22 Sep 2020
Topic Review
miR-944 in Cancer
miR-944 is localized in intron 4 of TP63. ΔNp63 in intron 3 of TP63 recruits the transcription factor AP-2 to promote miR-944 gene expression, which mediates epidermal differentiation induction by ΔNp63. miR-944 is dysregulated in various cancers. In squamous cell carcinoma. miR-944 can target and inhibit 27 protein-coding genes, thereby regulating cell cycle, proliferation, apoptosis, epithelial mesenchymal transition, cancer cell invasion and migration, and other cell behaviors. The genes targeted by miR-944 are involved in three signaling pathways, including the Wnt/β-catenin pathway, Jak/STAT3 pathway, and PI3K/AKT pathway. miR-944 was regulated by a total of 11 competing endogenous RNAs, including 6 circular RNAs and 5 long non-coding RNAs. Abnormally expressed miR-944 can act as an independent prognostic factor and is closely related to tumor invasion, lymph node metastasis, TNM staging, and drug resistance. miR-944 is expected to become a critical biomarker with great clinical application value in cancer.
  • 681
  • 15 Sep 2022
Topic Review
Tyrp1 Mutant Variants and OCA3
Oculocutaneous albinism type 3 (OCA3) is an autosomal recessive disorder caused by mutations in the TYRP1 gene. Tyrosinase-related protein 1 (Tyrp1) is involved in eumelanin synthesis, catalyzing the oxidation of 5,6-dihydroxyindole-2-carboxylic acid oxidase (DHICA) to 5,6-indolequinone-2-carboxylic acid (IQCA).
  • 681
  • 29 Oct 2021
Topic Review
Carbon Dots-Based Logic Gates
Carbon dots (CDs)-based logic gates are smart nanoprobes that can respond to various analytes such as metal cations, anions, amino acids, pesticides, antioxidants, etc. Most of these logic gates are based on fluorescence techniques because they are inexpensive, give an instant response, and highly sensitive
  • 680
  • 24 Apr 2022
Topic Review
Dermal Aging and Antiaging Approaches
The dermis is primarily composed of the extracellular matrix (ECM) and fibroblasts. During the aging process, the dermis undergoes significant changes. Collagen, which is a major component of ECM, becomes fragmented and coarsely distributed, and its total amount decreases. This is mainly due to increased activity of matrix metalloproteinases, and impaired transforming growth factor-β signaling induced by reactive oxygen species generated during aging. The reduction in the amount of collagen hinders the mechanical interaction between fibroblasts and the ECM, and consequently leads to the deterioration of fibroblast function and further decrease in the amount of dermal collagen. Other ECM components, including elastic fibers, glycosaminglycans (GAGs), and proteoglycans (PGs), also change during aging, ultimately leading to a reduction in the amount of functional components. Elastic fibers decrease in intrinsically aged skin, but accumulate abnormally in photoaged skin. A reduction in the levels of functional dermal components results in the emergence of clinical aging features, such as wrinkles and reduced elasticity. Various antiaging approaches, including topicals, energy-based procedures, and dermal fillers, can restore the molecular features of dermal aging with clinical efficacy. 
  • 680
  • 01 Aug 2021
Topic Review
Bio-Photonic Cavities
An eco-friendly approach to usual optical cavities, in which an electromagnetic radiation can release energy to matter by interacting with its molecular or atomic structure. Based on bio-inspired and biodegradable meta-surfaces, able to behave as a resonator for light, their optical response can be engineered at will to accomplish a particular optical task.  
  • 680
  • 24 Nov 2021
Topic Review
Starvation-Induced Autophagy in Saccharomyces cerevisiae in Metabolomics Perspectives
The application of metabolomics has extended the scope of autophagy and provided newer intervention targets against cancer as well as neurodegenerative diseases in which autophagy is implicated. 
  • 680
  • 02 Dec 2021
Topic Review
5-10-Methylenetetrahydrofolate Reductase
The 5-10-methylenetetrahydrofolate reductase (MTHFR) enzyme is vital for cellular homeostasis due to its key functions in the one-carbon cycle, which include methionine and folate metabolism, and protein, DNA, and RNA synthesis. 
  • 679
  • 14 Feb 2022
Topic Review
Transcriptomic Harmonization
Emergence of methods interrogating gene expression at high throughput gave birth to quantitative transcriptomics, but also posed a question of inter-comparison of expression profiles obtained using different equipment and protocols and/or in different series of experiments. Addressing this issue is challenging, because all of the above variables can dramatically influence gene expression signals and, therefore, cause a plethora of peculiar features in the transcriptomic profiles. Millions of transcriptomic profiles were obtained and deposited in public databases of which the usefulness is however strongly limited due to the inter-comparison issues. Platform/protocol/batch bias can be efficiently reduced not only for the comparisons of limited transcriptomic datasets. Instead, instruments were proposed for transforming gene expression profiles into the universal, uniformly shaped format that can support multiple inter-comparisons for reasonable calculation costs. This forms a basement for universal indexing of all or most of all types of RNA sequencing and microarray hybridization profiles.
  • 679
  • 02 Dec 2022
Topic Review
FLT3 Tyrosine Kinase Inhibitors
FLT3 is a member of the class III receptor tyrosine kinase family that exerts a key role in the proliferation and differentiation of hematopoietic progenitor cells. FLT3 inhibitors have dramatically altered the prognosis of the FLT3 mutant AML.
  • 678
  • 10 Jun 2021
Topic Review
Curcumin Targeting Non-Coding RNAs in Colorectal Cancer
Colorectal cancer is one of the most common gastrointestinal malignancies, with high incidence rates, a low rate of early diagnosis, and complex pathogenesis. In recent years, there has been progress made in its diagnosis and treatment methods, but tumor malignant proliferation and metastasis after treatment still seriously affect the survival and prognosis of patients. Therefore, it is an extremely urgent task of current medicine to find new anti-tumor drugs with high efficiency and safety and low toxicity. Curcumin has shown potent anti-tumor and anti-inflammatory effects and is considered a hot spot in the research and development of anti-tumor drugs due to its advantages of precise efficacy, lower toxic side effects, and less drug resistance. Recent studies have revealed that curcumin has anti-tumor effects exerted on the epigenetic regulation of tumor-promoting/tumor-suppressing gene expression through the alteration of expression levels of non-coding RNAs (e.g., lncRNAs, miRNAs, and circRNAs). The interaction between curcumin and non-coding RNAs on the occurrence and development of colorectal cancer is summarized herein.
  • 678
  • 14 Oct 2022
Topic Review
Heteroelement Analogues of Benzoxaborole
Heteroelement analogues of benzoxaboroles constitute an interesting class of boracyclic compounds and may offer the opportunity for various applications while retaining high stability arising from the presence of a strong B-O bond in the ring structure. The replacement of a carbon atom in the boracycle or an adjacent benzene ring with a heteroatom may result in a significant change of structural behaviour. Moreover,  physicochemical properties, including solubility, lipophilicity, hydrolytic stability, boron Lewis acidity, and others, can be modified. The aim of this review is to highlight several emerging groups of boracyclic systems which comprise various heteroelement atoms such as another boron, silicon, tin, nitrogen, phosphorus, and iodine. The information on synthesis and properties of such systems is complemented by presentation of their practical potential encompassing especially organic synthesis and catalysis as as medicinal chemistry. 
  • 677
  • 22 Sep 2021
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