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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
Decoding CD271 in melanoma
The evolution of melanoma, the most aggressive type of skin cancer, is triggered bydriver mutations that are acquired in the coding regions of particularly BRAF (rat fibrosarcomaserine/threonine kinase, isoform B) or NRAS (neuroblastoma-type ras sarcoma virus) in melanocytes.Although driver mutations strongly determine tumor progression, additional factors are likelyrequired and prerequisite for melanoma formation. Melanocytes are formed during vertebratedevelopment in a well-controlled di erentiation process of multipotent neural crest stem cells(NCSCs). However, mechanisms determining the properties of melanocytes and melanoma cellsare still not well understood. The nerve growth factor receptor CD271 is likewise expressed inmelanocytes, melanoma cells and NCSCs and programs the maintenance of a stem-like and migratoryphenotype via a comprehensive network of associated genes. Moreover, CD271 regulates phenotypeswitching, a process that enables the rapid and reversible conversion of proliferative into invasive ornon-stem-like states into stem-like states by yet largely unknown mechanisms. Here, we summarizecurrent findings about CD271-associated mechanisms in melanoma cells and illustrate the role ofCD271 for melanoma cell migration and metastasis, phenotype-switching, resistance to therapeuticinterventions, and the maintenance of an NCSC-like state.
  • 1.3K
  • 28 Oct 2020
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
Anti-Lipopolysaccharide Factor
Sepsis is a life-threatening complication of an infectious process that results from the excessive and uncontrolled activation of the host’s pro-inflammatory immune response to a pathogen. Lipopolysaccharide (LPS), also known as endotoxin, which is a major component of Gram-negative bacteria’s outer membrane, plays a key role in the development of Gram-negative sepsis and septic shock in humans. To date, no specific and effective drug against sepsis has been developed.
  • 1.3K
  • 22 Nov 2023
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
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
Signal Transduction by VIP and PACAP Receptors
Homeostasis of the human immune system is regulated by many cellular components, including two neuropeptides, VIP and PACAP, primary stimuli for three class B G protein-coupled receptors, VPAC1, VPAC2, and PAC1. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) regulate intestinal motility and secretion and influence the functioning of the endocrine and immune systems. Inhibition of VIP and PACAP receptors is an emerging concept for new pharmacotherapies for chronic inflammation and cancer, while activation of their receptors provides neuroprotection. Major molecular switches of VPAC1, VPAC2, and PAC1 may act as triggers for receptor activation and compare them with similar non-covalent interactions changing upon activation that were observed for other GPCRs. Interhelical interactions in VIP and PACAP receptors that are important for agonist binding and/or activation provide a molecular basis for the design of novel selective drugs demonstrating anti-inflammatory, anti-cancer, and neuroprotective effects. As to the genetic variants of VIP, PACAP, and their receptors on signalling mediated by endogenous agonists, this sequence diversity resulting from gene splicing has a significant impact on agonist selectivity and potency as well as on the signalling properties of VIP and PACAP receptors. 
  • 1.3K
  • 28 Mar 2022
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
Topic Review
Ribonucleoside Hydrolase Structure
Ribonucleoside hydrolases are enzymes that catalyze the cleavage of ribonucleosides to nitrogenous bases and ribose. These enzymes are found in many organisms: bacteria, archaea, protozoa, metazoans, yeasts, fungi and plants.
  • 1.3K
  • 20 Sep 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
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
Biosynthesis of Non-Canonical Amino Acids
The functional pool of canonical amino acids (cAAs) has been enriched through the emergence of non-canonical amino acids (ncAAs). NcAAs play a crucial role in the production of various pharmaceuticals. The biosynthesis of ncAAs has emerged as an alternative to traditional chemical synthesis due to its environmental friendliness and high efficiency.
  • 1.3K
  • 10 Oct 2023
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
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
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
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
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
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
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
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