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Topic Review
Neuroprotective Effects of Epigallocatechin-3-Gallate in Alzheimer’s Disease
Alzheimer’s disease (AD) is the most common cause of dementia, characterised by a marked decline of both memory and cognition, along with pathophysiological hallmarks including amyloid beta peptide (Aβ) accumulation, tau protein hyperphosphorylation, neuronal loss and inflammation in the brain. Additionally, oxidative stress caused by an imbalance between free radicals and antioxidants is considered one of the main risk factors for AD, since it can result in protein, lipid and nucleic acid damage and exacerbate Aβ and tau pathology. Green tea, and its main bioactive compound, epigallocatechin-3-gallate (EGCG), have been targeted as a plausible option for the modulation of AD. Specifically, EGCG acts as an antioxidant by regulating inflammatory processes involved in neurodegeneration such as ferroptosis and microglia-induced cytotoxicity and by inducing signalling pathways related to neuronal survival. Furthermore, it reduces tau hyperphosphorylation and aggregation and promotes the non-amyloidogenic route of APP processing, thus preventing the formation of Aβ and its subsequent accumulation.
  • 1.3K
  • 20 Oct 2023
Topic Review
GABAergic pain modulation
GABAA receptors (GABAARs) are ligand-gated heteropentameric ion channels, most commonly formed by 2α, 2β, and 1γ subunit. They are expressed in spinal cord dorsal horn, both at the pre- and postsynaptic site, controlling the transmission of pain, itch, touch and proprioception.
  • 1.3K
  • 19 Jan 2021
Topic Review
Immune Checkpoints Inhibitors in the Treatment of Melanoma
Metastatic melanoma is a highly immunogenic tumor with very poor survival rates due to immune system escape-mechanisms. Immune checkpoint inhibitors (ICIs) targeting the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and the programmed death-1 (PD1) receptors, are being used to impede immune evasion. 
  • 1.3K
  • 04 Nov 2022
Topic Review
Lactoferrin and Its Derived Peptides
Lf is bacteriostatic and/or bactericidal, can stimulate cell proliferation and differentiation, facilitate iron absorption, improve neural development and cognition, promote bone growth, prevent cancer and exert anti-inflammatory and immunoregulatory effects.
  • 1.3K
  • 29 Dec 2020
Topic Review
Nociceptive TRP Channel
Transient receptor potential (TRP) channels have emerged as key molecular identities in the sensory transduction of pain-producing stimuli. The ability of nociceptors to behave as noxious stimuli detectors relies on the presence of specialized transducing molecules at their peripheral nerve terminals capable of transforming the harmful physical (thermal and mechanical) and chemical stimuli into generator potentials. Upon nerve terminal stimulation, the output signal conveying to the central nervous system depends on the properties of transducer channels which produce generator potentials. Voltage-gated channels subsequently translate it into action potential firing. Nociceptive TRP channels are among the most studied transducer channels expressed in nociceptors and play a pivotal role in the study of pain.
  • 1.3K
  • 09 Feb 2021
Topic Review
ZMYND8
Zinc finger myeloid, nervy, and deformed epidermal autoregulatory factor 1-type containing 8 (Zinc finger MYND-type containing 8, ZMYND8) is a transcription factor, a histone H3-interacting protein, and a putative chromatin reader/effector that plays an essential role in regulating transcription during normal cellular growth. Mutations and altered expression of ZMYND8 are associated with the development and progression of cancer. Increased expression of ZMYND8 is linked to breast, prostate, colorectal, and cervical cancers. It exerts pro-oncogenic effects in breast and prostate cancers, and it promotes angiogenesis in zebrafish, as well as in breast and prostate cancers. In contrast, downregulation of ZMYND8 is also reported in breast, prostate, and nasopharyngeal cancers. ZMYND8 acts as a tumor suppressor in breast and prostate cancers, and it inhibits tumor growth by promoting differentiation; inhibiting proliferation, cell-cycle progression, invasiveness, and metastasis; and maintaining the epithelial phenotype in various types of cancers. These data together suggest that ZMYND8 is important in tumorigenesis; however, the existing data are contradictory. More studies are necessary to clarify the exact role of ZMYND8 in tumorigenesis. In the future, regulation of expression/activity of ZMYND8 and/or its binding partners may become useful in treating cancer.
  • 1.3K
  • 10 Mar 2021
Topic Review
CD38–Cyclic ADP-Ribose Signal System
Calcium (Ca2+) is a ubiquitous and fundamental signaling component that is utilized by cells to regulate a diverse range of cellular functions, such as insulin secretion from pancreatic β-cells of the islets of Langerhans. Cyclic ADP-ribose (cADPR), synthesized from NAD+ by ADP-ribosyl cyclase family proteins, such as the mammalian cluster of differentiation 38 (CD38), is important for intracellular Ca2+ mobilization for cell functioning. cADPR induces Ca2+ release from endoplasmic reticulum via the ryanodine receptor intracellular Ca2+ channel complex, in which the FK506-binding protein 12.6 works as a cADPR-binding regulatory protein.
  • 1.3K
  • 20 Apr 2022
Topic Review
Connexins in Cancer
The expression, localization, and function of connexins, the protein subunits that comprise gap junctions, are often altered in cancer. In addition to cell–cell coupling through gap junction channels, connexins also form hemichannels that allow communication between the cell and the extracellular space and perform non-junctional intracellular activities. Historically, connexins have been considered tumor suppressors; however, they can also serve tumor-promoting functions in some contexts. Here, we review the literature surrounding connexins in cancer cells in terms of specific connexin functions and propose that connexins function upstream of most, if not all, of the hallmarks of cancer. The development of advanced connexin targeting approaches remains an opportunity for the field to further interrogate the role of connexins in cancer phenotypes, particularly through the use of in vivo models. More specific modulators of connexin function will both help elucidate the functions of connexins in cancer and advance connexin-specific therapies in the clinic.
  • 1.3K
  • 24 Dec 2020
Topic Review
Biopesticides
Biopesticides are a type of pesticides derived from natural materials including plants and bacteria. In this entry, we reviewed the structural and biological features of Jaburetox and Soyuretox, two plant urease-derived recombinant peptides that present entomotoxic and fungitoxic effects without harming beneficial species or the environment. We also discussed other bioactive peptides in the context of their action mechanism.
  • 1.3K
  • 15 Dec 2020
Topic Review
Protein Arginine Methyltransferase PRMT7
PRMT7 is a member of the protein arginine methyltransferase (PRMT) family, which methylates a diverse set of substrates. Arginine methylation as a posttranslational modification regulates protein–protein and protein–nucleic acid interactions, and as such, has been implicated in various biological functions. PRMT7 is a unique, evolutionarily conserved PRMT family member that catalyzes the mono-methylation of arginine. The structural features, functional aspects, and compounds that inhibit PRMT7 are discussed here. Several studies have identified physiological substrates of PRMT7 and investigated the substrate methylation outcomes which link PRMT7 activity to the stress response and RNA biology. PRMT7-driven substrate methylation further leads to the biological outcomes of gene expression regulation, cell stemness, stress response, and cancer-associated phenotypes such as cell migration. Furthermore, organismal level phenotypes of PRMT7 deficiency have uncovered roles in muscle cell physiology, B cell biology, immunity, and brain function. 
  • 1.3K
  • 10 Aug 2021
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.
  • 1.3K
  • 15 Sep 2022
Topic Review
Chitosan-Based Delivery Systems for Carotenoids
Carotenoids are secondary metabolites present in microorganisms (bacteria, yeast, fungi, and microalgae) and higher plants. They cannot be produced by the human organism. In nature, their principal role is to attract different light wavelengths and transfer their energy to chlorophylls, a function occurring mainly in photosynthetic organisms. Moreover, they can act as photo-protectors, precursors of hormonal substances, antistress secondary metabolites, and attractive agents in plant–insect interaction.
  • 1.3K
  • 27 Sep 2023
Topic Review
Oxidative-Stress Modulators in Hematological Malignancies
Among the different mechanisms involved in oxidative stress, protein carbonylation and lipid peroxidation are both important modifications associated with the pathogenesis of several diseases, including cancer. Hematopoietic cells are particularly vulnerable to oxidative damage, as the excessive production of reactive oxygen species and associated lipid peroxidation suppress self-renewal and induce DNA damage and genomic instability, which can trigger malignancy. A richer understanding of the clinical effects of oxidative stress might improve the prognosis of these diseases and inform therapeutic strategies. The most common protein carbonylation and lipid peroxidation compounds, including hydroxynonenal, malondialdehyde, and advanced oxidation protein products, have been investigated for their potential effect on hematopoietic cells in several studies.
  • 1.3K
  • 17 Jan 2021
Topic Review
YAP-TEAD Interaction Disruptors
This a entry that comprehensively covers the modalities that act as disruptors of the YAP-TEAD interaction. The transcriptional co-activator YAP (Yes-associated protein) by pairing with the transcription factor TEAD (TEA domain) orchestrates the expression of several oncogenic transcriptional programs. These programs are seen in a proportion of all solid tumors. Therefore, the disruption of YAP-TEAD interaction is proposed as an attractive option to target cancers.
  • 1.3K
  • 11 Jan 2021
Topic Review
KRAS and the Inflammatory Tumor Microenvironment Modulation
The TME is a dynamic network composed, not only by tumor cells, but also by several non-tumor cell types, including stromal cells as immune cells (macrophages, neutrophils, dendritic and natural killer cells, myeloid-derived suppressor cells (MDSCs), B and T cells), fibroblasts, adipocytes, endothelial cells, neurons, osteoblasts, osteoclasts, and the extracellular matrix (ECM). This non-cellular component, together with the tumor and the non-tumor cells, establish a dynamic, challenging microenvironment that can be modulated, but especially modulates cancer cell activities, dictating the success of tumor progression. Inflammation has been gradually recognized as a key initiator and contributor for tumorigenesis by orchestrating the immune surveillance and the immune escape, but also by affecting treatment response. Interestingly, the concept of tumor-promoting inflammation has been tightly associated with KRAS mutations. In fact, in colorectal cancers, the majority of the cases with a high prevalence of KRAS mutations correlate with chronic inflammatory diseases. KRAS and its downstream interactors are described as capable of shaping the immune microenvironment through the induction of the nuclear factor kappa light chain enhancer of activated B cells (NF)-kB signaling, which in turn promotes the transcription of several cytokines and chemokines, including interleukin (IL)-1α/β, IL-6, tumor necrosis factor α (TNF-α), Cys-X-Cys Chemokine (CXCL)-1, 2, 5, and 8, monocyte chemoattractant protein 1 (MCP-1 or CCL2), inducible nitric oxide synthase (iNOS), intracellular adhesion molecule 1 (ICAM-1), and endothelial leukocyte adhesion molecule 1 (ELAM1). Independently of NF-kB, KRAS-downstream partners, such as RAF/MAPK and PI3K, may also induce IL-10, transforming growth factor β (TGF-β) and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression. Several studies already reported that KRAS mutations could drive the secretion of anti-inflammatory cytokines, such as IL-10 and TGF-β, with the ability to sustain an immunosuppressive TME, whereas other studies verified that KRAS mutations could interfere with the secretion of pro-inflammatory cytokines, such as ICAM-1, TNF-α, IL-1β, IL-6, and IL-18. Thus, KRAS seems to act as a modulator of both an anti-inflammatory and a pro-inflammatory TME.
  • 1.3K
  • 22 Feb 2022
Topic Review
BAZ1B the Protean Protein
The bromodomain adjacent to the zinc finger domain 1B (BAZ1B) or Williams syndrome transcription factor (WSTF) are just two of the names referring the same protein that is encoded by the WBSCR9 gene and is among the 26–28 genes that are lost from one copy of 7q11.23 in Williams syndrome (WS: OMIM 194050). Patients afflicted by this contiguous gene deletion disorder present with a range of symptoms including cardiovascular complications, developmental defects as well as a characteristic cognitive and behavioral profile. Studies in patients with atypical deletions and mouse models support BAZ1B hemizygosity as a contributing factor to some of the phenotypes. Focused analysis on BAZ1B has revealed this to be a versatile nuclear protein with a central role in chromatin remodeling through two distinct complexes as well as being involved in the replication and repair of DNA, transcriptional processes involving RNA Polymerases I, II, and III as well as possessing kinase activity. 
  • 1.3K
  • 22 Oct 2021
Topic Review
A-FABP in Metabolic Diseases
Adipocyte fatty acid-binding protein (A-FABP), which is also known as ap2 or FABP4, is a fatty acid chaperone that has been further defined as a fat-derived hormone. It regulates lipid homeostasis and is a key mediator of inflammation. Circulating levels of A-FABP are closely associated with metabolic syndrome and cardiometabolic diseases with imminent diagnostic and prognostic significance. Numerous animal studies have elucidated the potential underlying mechanisms involving A-FABP in these diseases. Recent studies demonstrated its physiological role in the regulation of adaptive thermogenesis and its pathological roles in ischemic stroke and liver fibrosis. Due to its implication in various diseases, A-FABP has become a promising target for the development of small molecule inhibitors and neutralizing antibodies for disease treatment. This review summarizes the clinical and animal findings of A-FABP in the pathogenesis of cardio-metabolic diseases in recent years.
  • 1.3K
  • 22 Sep 2021
Topic Review
Iron Oxide Nanoparticles in Cancer Diagnostics and Therapy
Cancer theranostics remains a vital research niche as a result of the rising mortality rates caused by various cancers globally. This is excarcebated by challenges related to conventional therapies. Iron-oxide-based NPs that possess characteristically large surface areas, small particle sizes, and superparamagnetism have been cited in applications geared towards diagnosis, and targeted drug delivery. When an external magnetic field is applied to superparamagnetic iron oxide NPs (SPIONs), the domains are aligned to the field. Once the field is removed, they return to a non-magnetic state. The NP magnetic moments turn to flip in the direction of the applied field. This flipping of the magnetic moments generates heat, which forms the basis of tumour ablation therapy through hyperthermia. Substituted iron-oxides or ferrites (MFe2O4) have emerged as interesting magnetic NPs due to their unique and attractive properties such as size and magnetic tunability, ease of synthesis, and manipulatable properties. In recent years, they have been explored for use in targeted therapy and drug delivery for anti-cancer treatment.
  • 1.3K
  • 27 May 2022
Topic Review
Tropomyosin mutation Glu173Ala
Substitution of Glu173 for Ala in Tpm3.12 (E173A) is associated with congenital muscle weakness. It was found that this mutation increases myofilament Ca2+-sensitivity and inhibits in vitro actin-activated ATPase activity of myosin subfragment-1 at high Ca2+. In order to determine the critical conformational changes in myosin, actin and tropomyosin caused by the mutation, we used the polarized fluorimetry technique. We observed changes in the spatial arrangement of actin monomers and myosin heads, and in the position of the mutant tropomyosin on the thin filaments in muscle fibres at various ATPase cycle stages. At low Ca2+ the E173A mutant tropomyosin shifts abnormally towards the inner domains of actin at all stages of the cycle. The number of switched-on actin monomers and strong-binding myosin heads increases even at relaxation. Contrarily, at high Ca2+ the amount of the myosin heads strongly bound with F-actin slightly decreases. The changes in the balance of the strongly bound myosin heads in the ATPase cycle may underlie the occurrence of muscle weakness. W7, an inhibitor of troponin Ca2+-sensitivity, restores the number of strong-binding myosin heads at high Ca2+ and inhibits it at relaxation, suggesting the possibility of using Ca2+-desensitizers to reduce the damaging effect of the E173A mutation on muscle fibre contractility.
  • 1.3K
  • 27 Oct 2020
Topic Review
Bile Salt Hydrolases
Bile salt hydrolase (BSH; EC 3.5.1.24) is an enzyme produced by the intestinal microbiota that catalyzes the hydrolysis of amide bonds in conjugated BAs, resulting in the release of free amino acids. These enzymes belong to the N-terminal nucleophilic (Ntn) hydrolase superfamily and share a similar αββα-core structure to an N-terminal catalytic cysteine residue. This residue is critical to the catalysis mechanism and acts both as a nucleophile and a proton donor. The N-terminal amino group serves as the proton acceptor and activates the nucleophilic thiol group of the cysteine side chain. Besides the cysteine residue, other amino acids conserved in most BSHs are also relevant to the catalytic reaction, including Arg18, Asp21, Asn82, Asn175, and Arg228.
  • 1.3K
  • 27 May 2021
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