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Topic Review
Chemical and Biological Characteristics of Hydrogen Sulfide
Hydrogen sulfide (H2S), as an environmental toxin, is now confirmed to be a biological mediator and plays essential roles in normal physiology and in the responses to different stresses. H2S also regulates the responses to oxidative stress by interplaying with reactive oxygen species (ROS) at multiple levels and protects mitochondrial function, maintaining mitochondrial homeostasis.
  • 944
  • 12 Oct 2023
Topic Review
RhoH in TCR Signalling
As an atypical member of the Rho family small GTPases, RhoH shares less than 50% sequence similarity with other members, and its expression is commonly observed in the haematopoietic lineage. To date, RhoH function was observed in regulating T cell receptor signalling, and less is known in other haematopoietic cells. Its activation may not rely on the standard GDP/GTP cycling of small G proteins and is thought to be constitutively active because critical amino acids involved in GTP hydrolysis are absent. Alternatively, its activation can be regulated by other types of regulation, including lysosomal degradation, somatic mutation and transcriptional repressor, which also results in an altered protein expression. Aberrant protein expression of RhoH has been implicated not only in B cell malignancies but also in immune-related diseases, such as primary immunodeficiencies, systemic lupus erythematosus and psoriasis, wherein its involvement may provide the link between immune-related diseases and cancer.
  • 943
  • 27 May 2021
Topic Review
Lemur Tyrosine Kinases
The members of the Lemur Tyrosine Kinases (LMTK1-3) subfamily constitute a group of three membrane-anchored kinases. They are known to influence a wide variety of key cellular events, often affecting cell proliferation and apoptosis. They have been discovered to be involved in cancer, in that they impact various signalling pathways that influence cell proliferation, migration, and invasiveness. 
  • 943
  • 04 Jun 2021
Topic Review
Parasporins, Bacillus thuringiensis Proteins
Bacillus thuringiensis (Bt) is a bacterium capable of producing Cry toxins, which are recognized for their bio-controlling actions against insects. However, a few Bt strains encode proteins lacking insecticidal activity but showing cytotoxic activity against different cancer cell lines and low or no cytotoxicity toward normal human cells. 
  • 943
  • 29 Mar 2022
Topic Review
Preserving Adult Endothelium Health and Reversing Its Dysfunction
The endothelium has multiple functions, ranging from maintaining vascular homeostasis and providing nutrition and oxygen to tissues to evocating inflammation under adverse conditions and determining endothelial barrier disruption, resulting in dysfunction. Endothelial dysfunction represents a common condition associated with the pathogenesis of all diseases of the cardiovascular system, as well as of diseases of all of the other systems of the human body, including sepsis, acute respiratory distress syndrome, and COVID-19 respiratory distress. Such evidence is leading to the identification of potential biomarkers and therapeutic targets for preserving, reverting, or restoring endothelium integrity and functionality by promptly treating its dysfunction.
  • 943
  • 14 Jul 2022
Topic Review
Mining the Immunopeptidome for Antigenic Peptides in Cancer
Harnessing the immune system for cancer therapy has shown success, however the response to immunotherapy has been limited. Deciphering the immunopeptidome repertoire of cancer cells is crucial for identifying neoantigens. To date the emphasis has been on mutations. However, there is more to neoantigens than mutations. Thus, there is a need to identify other types of neoantigens that are commonly expressed in a cancer type that are presented by MHC class I and class II, to induce a cytotoxic CD8+ T and CD4+ T response, respectively. The immunopeptidome encompasses protein post-translation modifications (PTMs), which are overlooked by genome or transcriptome profiling. This entry covers how the immunopeptidome can yield novel cancer-specific antigens, focusing on PTMs and their applications.
  • 943
  • 26 Oct 2022
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.
  • 942
  • 25 Aug 2020
Topic Review
LRRFIP1 is a DAPK1 Interactor
Death-associated protein kinase 1 (DAPK1) is a pleiotropic hub of a number of networked distributed intracellular processes. Among them, DAPK1 is known to interact with the excitotoxicity driver NMDA receptor (NMDAR), and in sudden pathophysiological conditions of the brain, e.g., stroke, several lines of evidence link DAPK1 with the transduction of glutamate-induced events that determine neuronal fate. In turn, DAPK1 expression and activity are known to be affected by the redox status of the cell. To delineate specific and differential neuronal DAPK1 interactors in stroke-like conditions in vitro, we exposed primary cultures of rat cortical neurons to oxygen/glucose deprivation (OGD), a condition that increases reactive oxygen species (ROS) and lipid peroxides. OGD or control samples were co-immunoprecipitated separately, trypsin-digested, and proteins in the interactome identified by high-resolution LC-MS/MS. Data were processed and curated using bioinformatics tools. OGD increased total DAPK1 protein levels, cleavage into shorter isoforms, and dephosphorylation to render the active DAPK1 form. The DAPK1 interactome comprises some 600 proteins, mostly involving binding, catalytic and structural molecular functions. OGD up-regulated 190 and down-regulated 192 candidate DAPK1-interacting proteins. Some differentially up-regulated interactors related to NMDAR and specially the interaction of DAPK1 with the protein leucine-rich repeat of flightless interacting protein 1 (LRRFIP1), that we observed upregulated during OGD and ferroptosis , were validated by WB.
  • 942
  • 04 Dec 2020
Topic Review
ClpB's Function in Bacterial Virulence
The molecular chaperone ClpB belongs to the Hsp100/Clp subfamily of the AAA+ ATPases. It has been established that ClpB disaggregates and reactivates aggregated cellular proteins. It has been postulated that ClpB’s protein disaggregation activity supports the survival of pathogenic bacteria under host-induced stresses (e.g., high temperature and oxidative stress), which allows them to rapidly adapt to the human host and establish infection. Interestingly, ClpB may also perform other functions in pathogenic bacteria, which are required for their virulence. Since ClpB is not found in human cells, this chaperone emerges as an attractive target for novel antimicrobial therapies in combating bacterial infections. 
  • 942
  • 11 Jun 2021
Topic Review
GM1 Ganglioside and Parkinson’s Disease
GM1 (monosialotetrahexosylganglioside) the "prototype" ganglioside, is a member of the ganglio series of gangliosides which contain one sialic acid residue. GM1 has important physiological properties and impacts neuronal plasticity and repair mechanisms, and the release of neurotrophins in the brain.
  • 942
  • 18 Feb 2022
Topic Review
TGF-β1 Signaling in Kidney Diseases
Transforming growth factor-β (TGF-β) is a crucial pathogenic mediator of inflammatory diseases. In tissue fibrosis, TGF-β regulates the pathogenic activity of infiltrated immunocytes and promotes extracellular matrix production via de novo myofibroblast generation and kidney cell activation. However, TGF-β is highly pleiotropic in tissue fibrosis, and thus, direct targeting of TGF-β may also block its protective anti-inflammatory effects, resulting in undesirable outcomes. Increasing evidence suggests the involvement of long non-coding RNAs (lncRNAs) in TGF-β-driven tissue fibrosis with a high cell-type and disease specificity, serving as an ideal target for therapeutic development.
  • 942
  • 01 Jun 2022
Topic Review
Flavonoids-Based Delivery Systems towards Cancer Therapies
Cancer is the second leading cause of death worldwide. Cervical cancer, for instance, is considered a major scourge in low-income countries. Its development is mostly associated with the human papillomavirus persistent infection and despite the availability of preventive vaccines, they are only widely administered in more developed countries, thus leaving a large percentage of unvaccinated women highly susceptible to this type of cancer. The treatments are based on invasive techniques, being far from effective. Therefore, the search for novel, advanced and personalized therapeutic approaches is imperative. Flavonoids belong to a group of natural polyphenolic compounds, well recognized for their great anticancer capacity, thus promising to be incorporated in cancer therapy protocols. However, their use is limited due to their low solubility, stability and bioavailability. Several types of flavonoid-based delivery systems are being developed for anticancer therapy, namely for cervical cancer. The consideration of these new forms of delivery systems allows for the use of fewer flavonoids as well as permits the use of ligands that efficiently target these systems to cancer cells, therefore reducing the risk of toxicity in healthy cells and improving their therapeutic effect. A variety of delivery systems for the encapsulation of these drugs can be explored, depending on the material considered and the properties exhibited by the drug.
  • 941
  • 08 Jul 2022
Topic Review
Mechanism of TGF-β Functions in mCRC
Colorectal cancer (CRC) is a serious public health issue, and it has the leading incidence and mortality among malignant tumors worldwide. CRC patients with metastasis in the liver, lung or other distant sites always have poor prognosis. CRC metastasis is a dynamic, multistep and multifactorial process, which includes the following successive steps: detachment from the primary CRC site, infiltration into adjacent tissues, invasion into blood/lymphatic circulation, transportation through the circulatory system, intravasation from vasculature and formation of CRC colonies in distant sites. Three critical factors contribute to CRC cells migration (pivotal for early metastasis): regulating the epithelial–mesenchymal transition (EMT) process, stemness and the microenvironment of CRC cells. Additionally, angiogenesis facilitates CRC cell transportation to distal locations. TGF-β signaling contributes to mCRC mainly through the following four mechanisms: promoting EMT, facilitating angiogenesis, creating an immunosuppressive microenvironment and regulating the stemness of mCRC .
  • 941
  • 01 Dec 2022
Topic Review Peer Reviewed
Tissue Integrity and COVID-19
Tissue integrity depends on biological tissue stiffness. Tissue integrity can protect both against age-related diseases and against severity of COVID-19. The disruption of tight junctions and increase of tissue permeability with advancing age can be related with age-related diseases as well as with age-dependent COVID-19. Release of tightly bound water from collagen fibrils leads to the increase of extracellular matrix stiffness and to the associated with matrix stiffness increased tissue permeability. The link between arterial stiffness and oxidative stress has been reported and is expected to be studied in more detail in the future. Trehalose can be suggested for retardation of tightly bound water release and subsequent extracellular matrix crosslinking by advanced glycation end products. Increase in tissue permeability can be blocked by polyphenols that inhibit ICAM-1 expression and mitigate cytoskeleton reorganization. NF-κB activation as a result of increased stiffness and cytoskeleton reorganization can cause both cardiovascular pathologies and COVID-19. Increased cholesterol content in cell membrane leads to increased virus entry into cell and increase of cholesterol is linked with cardiovascular diseases. Statins and chitosan are known as cholesterol-lowering substances. Nrf2 inhibits NF-κB activation and NF-κB inhibits Nrf2 pathway.
  • 940
  • 13 Apr 2022
Topic Review
Myzus persicae Sulzer
The green peach aphid (Myzus persicae Sulzer), a major and harmful chili aphid usually managed using chemical pesticides, is responsible for massive annual agricultural losses. The efficacy of two protein elicitors, PeaT1 and PeBC1, to stimulate a defensive response against M. persicae in chili was studied in this study.
  • 940
  • 11 Nov 2021
Topic Review
Whole Genome Amplification and the appropriate DNA polymerases
In the same way that specialized DNA polymerases (DNAPs) replicate cellular and viral genomes, only a handful of dedicated proteins from various natural origins as well as engineered versions are appropriate for competent exponential amplification of whole genomes and metagenomes (WGA). Different applications have led to the development of diverse protocols, based on various DNAPs. Isothermal whole genomes and metagenomes (WGA) is currently widely used due to the high performance of Φ29 DNA polymerase, but polymerase chain reaction (PCR)-based methods are also available and can provide competent amplification of certain samples. Replication fidelity and processivity must be considered when selecting a suitable enzyme for WGA. However, other properties, such as thermostability, capacity to couple replication, and double helix unwinding, or the ability to maintain DNA replication opposite to damaged bases, are also very relevant for some applications.
  • 940
  • 29 Jun 2023
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. 
  • 939
  • 10 Aug 2021
Topic Review
High-Density Lipoproteins
The quantity of high-density lipoproteins (HDL) is represented as the serum HDL-C concentration (mg/dL), while the HDL quality manifests as the diverse features of protein and lipid content, extent of oxidation, and extent of glycation. The HDL functionality represents several performance metrics of HDL, such as antioxidant, anti-inflammatory, and cholesterol efflux activities. The quantity and quality of HDL can change during one’s lifetime, depending on infection, disease, and lifestyle, such as dietary habits, exercise, and smoking. The quantity of HDL can change according to age and gender, such as puberty, middle-aged symptoms, climacteric, and the menopause. HDL-C can decrease during disease states, such as acute infection, chronic inflammation, and autoimmune disease, while it can be increased by regular aerobic exercise and healthy food consumption. Generally, high HDL-C at the normal level is associated with good HDL quality and functionality. 
  • 939
  • 16 May 2022
Topic Review
Quercetin in Age-Related Diseases
Polyphenols are the known group of phytochemicals that essentially consists of phenolic rings. These are the plant product present in varied fruits and vegetables. These secondary metabolites perform a protective function in plants from environmental and biological stress. When consumed as a human diet these are also known to prevent various age-associated diseases. Polyphenols are known to possess antioxidant properties and protect against oxidative stress. Quercetin is among the widely occurring polyphenol, found abundantly in nature. It is commonly present in different plant products. Onion is known to have the highest quantity of quercetin. This plant compound is possessed antioxidant properties and is considered to have a protective function against aging. It is known to be present in both free and conjugated forms. Quercetin has anti-oxidative, anti-inflammatory, anti-proliferative, anti-carcinogenic, anti-diabetic, and anti-viral properties.
  • 939
  • 11 May 2022
Topic Review
3,7-Dioleylquercetin
Quercetin is a well-known plant flavonol and antioxidant; however, there has been some debate regarding the efficacy and safety of native quercetin as a skin-whitening agent via tyrosinase inhibition. Several researchers have synthesized quercetin derivatives as low-toxicity antioxidants and whitening agents. However, no suitable quercetin derivatives have been reported to date. In this study, a novel quercetin derivative was synthesized by the SN2 reaction using quercetin and oleyl bromide. The relationship between the structures and activities of quercetin derivatives as anti-melanogenic agents was assessed using in vitro enzyme kinetics, molecular docking, and quenching studies; cell line experiments; and in vivo zebrafish model studies. Novel 3,7-dioleylquercetin (OQ) exhibited a low cytotoxic concentration level at >100 µg/mL (125 µM), which is five times less toxic than native quercetin.
  • 938
  • 06 May 2021
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