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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
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
M1 Family of Metalloaminopeptidases
Proteolytic enzymes, also known as peptidases, are one of the most abundant groups of enzymes in living organisms. They control the activation, synthesis and turnover of proteins, and regulate most biochemical and physiological processes, such as digestion, fertilization, growth, differentiation, cell signaling/migration, immunological defense, wound healing, and apoptosis. They are consequently major regulators of homeostasis, ageing, and different human diseases like cancer, hypertension, diabetes, inflammation, neurodegeneration, Alzheimer among others. Proteases are also essential for propagation of infectious agents, being major contributors of pathogenesis in several infectious diseases, including the current coronavirus emergent pandemic SARS COVID 19. Among peptidases, aminopeptidases catalyze the cleavage of the N-terminal amino acids of proteins or peptide substrates. They are distributed in many phyla and play critical roles in physiology and pathophysiology. Many of them are metallopeptidases belonging to the M1 and M17 families, among others. Some, such as M1 aminopeptidases N and A, thyrotropin-releasing hormone-degrading ectoenzyme, and M17 leucyl aminopeptidase, are targets for the development of therapeutic agents for human diseases, including cancer, hypertension, central nervous system disorders, inflammation, immune system disorders, skin pathologies, and infectious diseases, such as malaria. 
  • 1.3K
  • 23 May 2023
Topic Review
IL-6 Signaling in colorectal cancer onset and progression
IL-6 is a pleiotropic cytokine showing both pro- and anti-inflammatory roles.
  • 1.3K
  • 10 Dec 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
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
Insights into the Pharmacological Effects of Flavonoids
Flavonoids are widely occurring secondary metabolites of plants. Currently, there is a trend of article numbers increasing, which focuses on the computer modeling of flavonoid interactions with biological targets. Such studies help to accumulatethe data on lead compounds that can find medicinal implementation, including COVID-19. Flavanonol taxifolin demonstrated wound-healing activity. Luteolin, apigenin, and wogonin, which can be classified as flavones, show induced neutrophil apoptosis and have potential as neutrophil apoptosis-inducing anti-inflammatory, proresolution agents.
  • 1.3K
  • 10 Jun 2022
Topic Review
Nasal Air Conditioning and SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as with the influenza virus, has been shown to spread more rapidly during winter. Severe coronavirus disease 2019 (COVID-19), which can follow SARS-CoV-2 infection, disproportionately affects older persons and males as well as people living in temperate zone countries with a tropical ancestry. The available data are consistent with optimal warming and humidifying of inspired air by the nose (nasal air conditioning) being essential for minimising SARS-CoV-2 infectivity of the upper respiratory tract (URT)  and, as a consequence, severe COVID-19. 
  • 1.3K
  • 04 Jan 2022
Topic Review
Application of Sygen® in Diabetic Peripheral Neuropathies
Diabetic peripheral neuropathies (DPNs) are conditions that impair the peripheral nervous system (PNS) component. These disorders may have numerous causes and are often presented in various forms. The monosialotetrahexosylganglioside (GM1) ganglioside, popularly known as Sygen, provides beneficial effects such as enhanced neuritic sprouting, neurotrophism, neuroprotection, anti-apoptosis, and anti-excitotoxic activity, being particularly useful in the treatment of neurological complications that arise from diabetes.
  • 1.3K
  • 10 Jun 2022
Topic Review
Adipokines, Myokines, and Hepatokines
Adipose, skeletal, and hepatic muscle tissues are the main endocrine organs that produce adipokines, myokines, and hepatokines. These biomarkers can be harmful or beneficial to an organism and still perform crosstalk, acting through the endocrine, paracrine, and autocrine pathways. Far beyond understanding the actions of each biomarker alone, it is important to underline that these cytokines act together in the body, resulting in a complex network of actions in different tissues, which may have beneficial or non-beneficial effects on the genesis of various physiological disorders and their respective outcomes, such as type 2 diabetes mellitus (DM2), obesity, metabolic syndrome, and cardiovascular diseases (CVD). Overweight individuals secrete more pro-inflammatory adipokines than those of a healthy weight, leading to an impaired immune response and greater susceptibility to inflammatory and infectious diseases. Myostatin is elevated in pro-inflammatory environments, sharing space with pro-inflammatory organokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), resistin, and chemerin. Fibroblast growth factor FGF21 acts as a beta-oxidation regulator and decreases lipogenesis in the liver. The crosstalk mentioned above can interfere with homeostatic disorders and can play a role as a potential therapeutic target that can assist in the methods of diagnosing metabolic syndrome and CVD.
  • 1.3K
  • 25 Mar 2021
Topic Review
Vitamin C Anticancer Action
Vitamin C is an indispensable micronutrient in the human diet due to the multiple functions it carries out in the body. Reports of clinical studies have indicated that, when administered at high dosage by the intravenous route, vitamin C may exert beneficial antitumor effects in patients with advanced stage cancers, including those refractory to previous treatment with chemotherapy. 
  • 1.3K
  • 19 May 2021
Topic Review
Resveratrol in Aging COVID-19 Patients
COVID-19 symptoms are highly heterogeneous, and the patient may be asymptomatic or may present with mild to severe or fatal symptoms. Factors, such as age, sex, and comorbidities, are key determinants of illness severity and progression. Aging is accompanied by multiple deficiencies in interferon production by dendritic cells or macrophages in response to viral infections, resulting in dysregulation of inflammatory immune responses and excess oxidative stress. Age-related dysregulation of immune function may cause a more obvious pathophysiological response to SARS-CoV-2 infection in elderly patients and may accelerate the risk of biological aging, even after recovery. Resveratrol is a potent antioxidant with antiviral activity. 
  • 1.3K
  • 14 Sep 2021
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
The Response of Primary Metabolites to Abiotic Stresses
Several environmental stresses, including biotic and abiotic factors, adversely affect the growth and development of crops, thereby lowering their yield. However, abiotic factors, e.g., drought, salinity, cold, heat, ultraviolet radiations (UVr), reactive oxygen species (ROS), trace metals (TM), and soil pH, are extremely destructive and decrease crop yield worldwide. The response of different plant species to such stresses is a complex phenomenon with individual features for several species. Metabolomics is a promising way to interpret biotic and abiotic stress tolerance in plants. The study of metabolic profiling revealed different types of metabolites, e.g., amino acids, carbohydrates, phenols, polyamines, terpenes, etc, which are accumulated in plants. Among all, primary metabolites, such as amino acids, carbohydrates, lipids polyamines, and glycine betaine, are considered the major contributing factors that work as osmolytes and osmoprotectants for plants from various environmental stress factors. Therefore, metabolomics practices are becoming essential and influential in plants by identifying different phytochemicals that are part of the acclimation responses to various stimuli.
  • 1.3K
  • 28 Mar 2023
Topic Review
CRISPR/Cas-Based Gene Editing
There is a growing need for a molecular vehicle that can successfully load and deliver CRISPR/Cas ribonucleoprotein complexes (and other gene editing systems) into target tissues. Synthetic delivery vehicles are being developed but so far have been only moderately successful. Extracellular vesicles are ideal candidates for a universal biological platform to produce ready-to-use, programmable, and highly biocompatible CRISPR therapeutics. Using extracellular vesicles in the CRISPR/Cas research and, ultimately, in the clinic, demands novel, advanced techniques for protein/RNA loading, surface engineering, and manufacturing. Safety of CRISPR/Cas systems and EVs also need to be tested extensively for every particular application.
  • 1.3K
  • 03 Nov 2020
Topic Review
Relationship between D-Amino Acids and Schizophrenia
D-amino acids may play key roles for specific physiological functions in different organs including the brain. Importantly, D-amino acids have been detected in several neurological disorders such as schizophrenia, amyotrophic lateral sclerosis, and age-related disorders, reflecting the disease conditions. Relationships between D-amino acids and neurophysiology may involve the significant contribution of D-Serine or D-Aspartate to the synaptic function, including neurotransmission and synaptic plasticity. Gut-microbiota could play important roles in the brain-function, since bacteria in the gut provide a significant contribution to the host pool of D-amino acids. In addition, the alteration of the composition of the gut microbiota might lead to schizophrenia. Furthermore, D-amino acids are known as a physiologically active substance, constituting useful biomarkers of several brain disorders including schizophrenia.
  • 1.3K
  • 17 May 2022
Topic Review
Epigenomic Dysregulation in Schizophrenia
       Schizophrenia is a severe psychiatric disorder with a complex array of signs and symptoms that causes very significant disability in young people. While schizophrenia has a strong genetic component, with heritability around 80%, there is also a very significant range of environmental exposures and stressors that have been implicated in disease development and neuropathology, such as maternal immune infection, obstetric complications, childhood trauma and cannabis exposure. It is postulated that epigenetic factors, as well as regulatory non-coding RNAs, mediate the effects of these environmental stressors. In this review, we explore the most well-known epigenetic marks, including DNA methylation and histone modification, along with emerging RNA mediators of epigenomic state, including miRNAs and lncRNAs, and discuss their collective potential for involvement in the pathophysiology of schizophrenia implicated through the postmortem analysis of brain tissue. Given that peripheral tissues, such as blood, saliva, and olfactory epithelium have the same genetic composition and are exposed to many of the same environmental exposures, we also examine some studies supporting the application of peripheral tissues for epigenomic biomarker discovery in schizophrenia. Finally, we provide some perspective on how these biomarkers may be utilised to capture a signature of past events that informs future treatment.
  • 1.3K
  • 27 Aug 2020
Topic Review
Rumex Species
Today, more than ever, the search for non-trivial sources of biologically active substances is critical. Plants of the genus Rumex are noteworthy. Plants of this genus stand out for a number of advantages from the dominant plant core of meadow phytocenoses of the temperate climatic zone: a short growing season, an intensive increase in biomass, and undemanding growth conditions. In addition, this plant genus is known as a super-producer of secondary phenolic compounds.
  • 1.3K
  • 02 Mar 2022
Topic Review
Redox Potential Features of Laccase
Laccase, one of the metalloproteins, belongs to the multicopper oxidase family. It oxidizes a wide range of substrates and generates water as a sole by-product. The engineering of laccase is important to broaden their industrial and environmental applications. The general assumption is that the low redox potential of laccases is the principal obstacle, as evidenced by their low activity towards certain substrates. Therefore, the primary goal of engineering laccases is to improve their oxidation capability, thereby increasing their redox potential. Even though some of the determinants of laccase are known, it is still not entirely clear how to enhance its redox potential. However, the laccase active site has additional characteristics that regulate the enzymes’ activity and specificity. These include the electrostatic and hydrophobic environment of the substrate binding pocket, the steric effect at the substrate binding site, and the orientation of the binding substrate with respect to the T1 site of the laccase. 
  • 1.3K
  • 01 Sep 2023
Topic Review
Synthetic Oleanolic Acid Derivatives
Oleanolic acid (3β-hydroxyolean-12-en-28-oic acid) is a pentacyclic triterpenoid, widely occurring in the plant kingdom, which includes edible and medicinal plants. The richest source of oleanolic acid (OA) are the leaves of the olive plant. Common culinary spices such as garden thyme and clove plants, as well as fruits, are also sources of OA.
  • 1.3K
  • 22 Sep 2021
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