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Topic Review
Engineering Plastic Eating Enzymes Using Structural Biology
Plastics are polymers composed of repeating units of small organic molecules with the majority manufactured from non-renewable fossil fuels. The potential interactions between the enzymes and plastic substrates have also been identified and this knowledge leveraged to engineer improved variants of cutinases with enhanced plastic degradation capabilities.
  • 1.3K
  • 07 Oct 2023
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
Nanobody in CAR-T Therapy
Chimeric antigen receptor (CAR) T therapy represents a form of immune cellular therapy with clinical efficacy and a specific target. A typical chimeric antigen receptor (CAR) construct consists of an antigen binding domain, a transmembrane domain, and a cytoplasmic domain. Nanobod-ies have been widely applied as the antigen binding domain of CAR-T due to their small size, optimal stability, high affinity, and manufacturing feasibility. The nanobody-based CAR struc-ture has shown a proven function in more than ten different tumor-specific targets. After being transduced in Jurkat cells, natural killer cells, or primary T cells, the resulting nanobody-based CAR-T or CAR-NK cells demonstrate anti-tumor effects both in vitro and in vivo. Interestingly, anti-BCMA CAR-T modulated by a single nanobody or bi-valent nanobody displays comparable clinical effects with that of single-chain variable fragment (scFv)-modulated CAR-T. The applica-tion of nanobodies in CAR-T therapy has been well demonstrated from bench to bedside and displays great potential in forming advanced CAR-T for more challenging tasks.
  • 1.3K
  • 21 Feb 2021
Topic Review
Aging Stress Response
Aging induces several stress response pathways to counterbalance detrimental changes associated with this process. These pathways include nutrient signaling, proteostasis, mitochondrial quality control and DNA damage response. At the cellular level, these pathways are controlled by evolutionarily conserved signaling molecules, such as 5'AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), insulin/insulin-like growth factor 1 (IGF-1) and sirtuins, including SIRT1. Peroxisome proliferation-activated receptor coactivator 1 alpha (PGC-1α), encoded by the PPARGC1A gene, playing an important role in antioxidant defense and mitochondrial biogenesis, may interact with these molecules influencing lifespan and general fitness. Perturbation in the aging stress response may lead to aging-related disorders, including age-related macular degeneration (AMD), the main reason for vision loss in the elderly. This is supported by studies showing an important role of disturbances in mitochondrial metabolism, DDR and autophagy in AMD pathogenesis. In addition, disturbed expression of PGC-1α was shown to associate with AMD. Therefore, the aging stress response may be critical for AMD pathogenesis, and further studies are needed to precisely determine mechanisms underlying its role in AMD.
  • 1.3K
  • 28 Sep 2021
Topic Review
Nucleotide-binding oligomerization domain 2
Nucleotide-binding oligomerization domain 2 (NOD2) is a cytoplasmic receptor that recognizes invading molecules and danger signals inside the cells.
  • 1.3K
  • 17 Aug 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
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
Targeted Cytokine Delivery for Cancer Treatment
Anti-tumor properties of several cytokines have already been investigated in multiple experiments and clinical trials. However, those studies evidenced substantial toxicities, even at low cytokine doses, and the lack of tumor specificity. These factors significantly limit clinical applications. Due to their high specificity and affinity, tumor-specific monoclonal antibodies or their antigen-binding fragments are capable of delivering fused cytokines to tumors and, therefore, of decreasing the number and severity of side effects, as well as of enhancing the therapeutic index. Targeted cytokine-mediated activation of the immune cells may trigger massive cytokine production at the disease site, making the local environmental conditions more favorable for local immune system cell functioning.
  • 1.3K
  • 10 Feb 2023
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
Ionic Liquids in Drug Delivery Systems
Advancements in the fields of ionic liquids (ILs) broaden its applications not only in traditional use but also in different pharmaceutical and biomedical fields. Ionic liquids “Solutions for Your Success” have received a lot of interest from scientists due to a myriad of applications in the pharmaceutical industry for drug delivery systems as well as targeting different diseases. Solubility is a critical physicochemical property that determines the drug’s fate at the target site. Many promising drug candidates fail in various phases of drug research due to poor solubility.
  • 1.3K
  • 08 Mar 2023
Topic Review
Antioxidant Compounds of Mushrooms as Neuroprotective Agents
Mushrooms have been used for their nutritional value and medicinal properties. They therefore represent not only a food but also a precious source of biologically active compounds that act as nutraceuticals. Numerous studies have shown that edible mushrooms possess anticancer, anti-atherosclerotic, hypocholesterolemic, hypolipidemic, antiviral, antimicrobial, immunostimulant, anti-inflammatory, antioxidant, and anti-aging effects. The antioxidant properties of edible mushrooms are mainly related to their content in phenolic compounds and polysaccharides. Among polyphenol groups, phenolic acids are the main antioxidants, whereas the major antioxidant effects of polysaccharides are attributed to beta-glycans. These compounds show significant reactive oxygen species (ROS) scavenging activity and are also able to stimulate the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) enzymes.
  • 1.3K
  • 27 Jun 2023
Topic Review
Insights into HP1a-Chromatin Interactions
     Understanding the packaging of DNA into chromatin is essential for the study of gene expression regulatory mechanisms. Heterochromatin establishment and maintenance dynamics have emerged as key features involved in genome stability, cellular growth, and disease. The heterochromatin protein HP1a is the most extensively studied factor that has both establishment and heterochromatin maintenance activities. This protein has two primary domains, namely the chromoshadow and the chromodomain, separated by a hinge region. Several works have taken place over the years, taking the challenge of defining HP1a partners using diverse experimental approaches. We revised and assemble on explaining these interactions and the potential complexes and subcomplexes associated formed with this essential protein. Characterization of these complexes will allow us to clearly understand the consequences of HP1a interactions in heterochromatin in maintenance, heterochromatin dynamics, and the direct relationship of heterochromatin with gene regulation.
  • 1.3K
  • 03 Apr 2021
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
BET Family Proteins
The BET family of proteins consists of a series of proteins with two N-terminal tandem bromodomains and an exclusive extra terminal domain (ET) that play an important role in gene transcription through epigenetic regulation, with a prominent impact in the control of cell growth and differentiation.
  • 1.3K
  • 05 Aug 2021
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
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
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
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
Usefulness of Microbiome for Forensic Geolocation
Forensic microbiomics is a promising tool for crime investigation. Geolocation connects an individual to a certain place or location by microbiota.
  • 1.3K
  • 16 Dec 2021
Topic Review
Role of Proteins and Divalent Ions in LLPS
Liquid–liquid phase separation (LLPS) is one of the key mechanisms affecting how macromolecular assemblies, including membrane-less organelles (MLOs), are formed and regulated. The molecular and biochemical mechanisms involved in the biomineralization pathway remain puzzling. Additionally, the significance of intrinsically disordered proteins (IDPs), which are an abundant organic component of hard tissues, in the formation of liquid precursors of biominerals remains to be solved. Research on the interactions between proteins and divalent cations is essential for understanding the resulting liquid precursors.
  • 1.3K
  • 21 Sep 2022
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