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Topic Review
Tyrosine Kinase Syk
Platelet-rich thrombi formed in vivo in mice have been shown to be composed of a core and shell region. Different pathways regulate the formation and stability of these two regions and understanding them may result in new ways to treat arterial thrombosis. The distinguishing feature between these two regions is the absence of fibrin in the shell, which indicates that in-vitro flow-based assays over thrombogenic surfaces, in the absence of coagulation, can be used to resemble this region.  Glycoprotein VI (GPVI) is a platelet immunoglobulin receptor which is known as a receptor for collagen and has been shown to contribute to the stability of platelet aggregates on collagen at high shear. In recent years GPVI has also been shown to be a receptor for fibrin and fibrinogen. Since the activation of GPVI by fibrinogen is also dependent on integrin αIIbβ3, with the interplay of the two receptors driving platelet adhesion and activation, blocking signalling pathways common to both receptors may have a greater antithrombotic effect than blocking GPVI alone. Therefore in this study, we have investigated the contribution of Syk tyrosine kinase, which plays a critical role in signalling by integrin αIIbβ3 and GPVI, in the stability of platelet aggregates formed on collagen or atherosclerotic plaque homogenate at arterial shear (1000 s-1). The results show that Syk regulates thrombus stability in the absence of fibrin. The fact that inhibitors of Syk are currently used for the treatment of patients with refractory immune thrombocytopenia (ITP) without increasing the risk of bleeding, indicate that Syk inhibitors may represent a new class of antiplatelet agent with reduced bleeding risk compared to current drugs.
  • 897
  • 17 Jan 2022
Topic Review
MicroRNAs and Oxidative Stress
Emerging evidence reveals that oxidative stress has a critical role in the development of type 2 diabetes. Overproduction of reactive oxygen species can promote an imbalance between the production and neutralization of antioxidant defence systems, thus favoring lipid accumulation, cellular stress, and the activation of cytosolic signaling pathways, and inducing β-cell dysfunction, insulin resistance, and tissue inflammation. Over the last few years, microRNAs (miRNAs) have attracted growing attention as important mediators of diverse aspects of oxidative stress. These small endogenous non-coding RNAs of 19–24 nucleotides act as negative regulators of gene expression, including the modulation of redox signaling pathways. 
  • 893
  • 03 Jun 2021
Topic Review
Corneous ß-proteins
The epidermal appendages of birds and reptiles (the sauropsids) include claws, scales, and feathers. Each has specialized physical properties that facilitate movement, thermal insulation, defence mechanisms, and/or the catching of prey. The mechanical attributes of each of these appendages originate from its fibril-matrix texture, where the two filamentous structures present, i.e., the corneous ß-proteins (CBP or ß-keratins) that form 3.4 nm diameter filaments and the α-fibrous molecules that form the 7–10 nm diameter keratin intermediate filaments (KIF), provide much of the required tensile properties. The matrix, which is composed of the terminal domains of the KIF molecules and the proteins of the epidermal differentiation complex (EDC) (and which include the terminal domains of the CBP), provides the appendages, with their ability to resist compression and torsion. 
  • 893
  • 05 Jul 2021
Topic Review
Levodopa/Receptor Ligands in Parkinson’s Disease
Levodopa (LD) is the most effective drug in the treatment of Parkinson’s disease (PD). However, although it represents the “gold standard” of PD therapy, LD can cause side effects, including gastrointestinal and cardiovascular symptoms as well as transient elevated liver enzyme levels. Moreover, LD therapy leads to LD-induced dyskinesia (LID), a disabling motor complication that represents a major challenge for the clinical neurologist. Due to the many limitations associated with LD therapeutic use, other dopaminergic and non-dopaminergic receptor drugs, including serotoninergic, gluamatergic and noradrenergic receptor ligands, are being developed to optimize the treatment response.
  • 893
  • 01 Sep 2021
Topic Review
The Immune System in Brief
The immune system is the body's intricate defense mechanism against infections and diseases. It is composed of a vast network of cells, tissues, and molecules working in harmony to protect us. Two main branches, the innate and adaptive immune systems, work together to differentiate between "self" and "non-self" entities. Innate immunity provides immediate but nonspecific protection, employing barriers like the skin and various white blood cells to quickly respond to threats. Adaptive immunity, on the other hand, takes time to develop and is highly specific. It relies on the production of antibodies and memory cells to remember and target specific pathogens for future encounters. The immune system's functionality revolves around recognizing foreign invaders, launching targeted responses, and forming immunological memory. It also requires tight regulation to prevent overactive responses or autoimmune disorders. Recent breakthroughs in immunology, such as immunotherapy and mRNA vaccines, highlight the ever-evolving understanding and harnessing of the immune system's capabilities, promising a brighter future in the fight against diseases.
  • 892
  • 28 Sep 2023
Topic Review
ROS in External Digestion by Carnivorous Plants
Carnivorous plants attract animals, trap and kill them, and absorb nutrients from the digested bodies. This unusual (for autotrophs) type of nutrient acquisition evolved through the conversion of photosynthetically active leaves into specialised organs commonly called traps. The genus Nepenthes (pitcher plants) consists of approximately 169 species belonging to the group of carnivorous plants. Pitcher plants are characterised by specialised passive traps filled with a digestive fluid. The digestion that occurs inside the traps of carnivorous plants depends on the activities of many enzymes. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) also participate in the digestive process.
  • 892
  • 10 Nov 2023
Topic Review
Superoxide Dismutases
Several enzymes exist that can convert or degrade reactive oxygen species (ROS); among them are the superoxide dismutases (SODs). SODs are responsible for converting superoxide anions to hydrogen peroxide by dismutation, therefore participating in the ROS detoxification. Here a short overview on the role of SODs in development and pathogenicity of fungi like Podospora anserina and Aspergillus spp. is given. 
  • 890
  • 06 Feb 2022
Topic Review
OGG1 in Lung
As the organ executing gas exchange and directly facing the external environment, the lungs are challenged continuously by various stimuli, causing the disequilibration of redox homeostasis and leading to pulmonary diseases. The breakdown of oxidants/antioxidants system happens when the overproduction of free radicals results in an excess over the limitation of cleaning capability, which could lead to the oxidative modification of macromolecules including nucleic acids. The most common type of oxidative base, 8-oxoG, is considered the marker of DNA oxidative damage. The appearance of 8-oxoG could lead to base mismatch and its accumulation might end up as tumorigenesis. The base 8-oxoG was corrected by base excision repair initiated by 8-oxoguanine DNA glycosylase-1 (OGG1), which recognizes 8-oxoG from the genome and excises it from the DNA double strand, generating an AP site for further processing. Aside from its function in DNA damage repairment, it has been reported that OGG1 takes part in the regulation of gene expression, derived from its DNA binding characteristic, and showed impacts on inflammation. 
  • 889
  • 25 May 2022
Topic Review
Tooth Cementum Annulation
Tooth Cementum Annulation (or TCA) is a technique that relies on the analysis of the incremental growth of dental cementum for age and season at death estimation.
  • 889
  • 27 Jul 2022
Topic Review
Non-Classical Exosomes for Osteoarthritis Treatment
Osteoarthritis of the knee is one of the most common chronic, debilitating musculoskeletal conditions. Exosomes derived from non-classical sources (not bone marrow or adipose derived MSCs derived MSCs) for osteoarthritis of the knee have potential clinical use.
  • 886
  • 18 Jun 2021
Topic Review
Yes-Associated Protein in Psoriasis and Skin Tumor Pathogenesis
Psoriasis and skin tumors (such as basal cell carcinoma, squamous cell carcinoma, and melanoma) are chronic diseases that endanger physical and mental health, and yet the causes are largely unknown and treatment options limited. Yes-associated protein (YAP) is a key member of the Hippo signaling pathway. It was originally identified in Drosophila, with a molecular weight of 65 kDa, and is also known as YAP65.
  • 886
  • 28 Jun 2022
Topic Review
Antiparasitic Activity of Betulinic Acid and Its Derivatives
Betulinic acid (BA) is a triterpene natural product which has shown antiparasitic activity against Leishmania, Trypanosoma cruzi, and Plasmodium. 
  • 884
  • 31 May 2022
Topic Review
Pathophysiology of Sickle Cell Disease
Sickle cell disease (SCD) is the most common hemoglobinopathy worldwide. It is characterized by an impairment of shear stress-mediated vasodilation, a pro-coagulant, and a pro-adhesive state orchestrated among others by the depletion of the vasodilator nitric oxide, by the increased phosphatidylserine exposure and tissue factor expression, and by the increased interactions of erythrocytes with endothelial cells that mediate the overexpression of adhesion molecules such as VCAM-1, respectively. Extracellular vesicles (EVs) have been shown to be novel actors involved in SCD pathophysiological processes. Medium-sized EVs, also called microparticles, which exhibit increased plasma levels in this pathology, were shown to induce the activation of endothelial cells, thereby increasing neutrophil adhesion, a key process potentially leading to the main complication associated with SCD, vaso-occlusive crises (VOCs). Small-sized EVs, also named exosomes, which have also been reported to be overrepresented in SCD, were shown to potentiate interactions between erythrocytes and platelets, and to trigger endothelial monolayer disruption, two processes also known to favor the occurrence of VOCs.
  • 884
  • 26 Sep 2022
Topic Review
Neuraminidases
Neuraminidases (NEUs) are able to cleave off sugars termed sialic acids, which are terminally attached to glycolipids and -proteins. Glycoproteins and glycolipids on the cell surfaces of vertebrates and higher invertebrates contain α-keto acid sugars called sialic acids, terminally attached to their glycan structures. The actual level of sialylation, regulated through enzymatic removal of the latter ones by NEU enzymes, highly affects protein-protein, cell-matrix and cell-cell interactions. Thus, their regulatory features affect a large number of different cell types, including those of the immune system.
  • 881
  • 05 Sep 2022
Topic Review
Pepsin Hydrolysis of Orange By-Products
The orange seed is an important by-product obtained from the juice production industry. The juice industry considers seed as a by-product that contains between 17.9% to 26.5% of protein [18]. In fact, the protein obtained from defatted flour can be used as a low-cost source for the generation of peptides through hydrolysis that could have an important role as antioxidant, anticancer, antidiabetic, or antihypertensive peptides.
  • 880
  • 28 May 2021
Topic Review
Matrix Metalloproteinases Inhibition
Matrix metalloproteinases are enzymes that degrade the extracellular matrix. They have different substrates but similar structural organization. Matrix metalloproteinases are involved in many physiological and pathological processes and there is a need to develop inhibitors for these enzymes in order to modulate the degradation of the extracellular matrix (ECM). There exist two classes of inhibitors: endogenous and synthetics. The development of synthetic inhibitors remains a great challenge due to the low selectivity and specificity, side effects in clinical trials, and instability. 
  • 877
  • 30 Jun 2021
Topic Review
Application of Barley Tweaky Spike Mutants
Barley developmental mutants tweaky spike (tw) with disturbed auxin pathways possess a unique feature of an increased level of mouldy germinating grains (MGG), which serves as a convenient model to investigate the effects of plant immunity-related substances. The effects of the auxin 2,4-dichlorophenoxyacetic acid (2,4-D), auxin inhibitors, salicylic acid (SA), and trans-cinnamic acid (TCA) were studied using the tw-WT system in surface-sterilized and unsterilized germinating grains under high rates of natural infection. Significant differences among the allelic tw mutants were revealed at the natural MGG level and in response to 2,4-D, SA, and TCA. The most effective means against MGG were sterilization and TCA. 2,4-D inhibited root growth in tw and tw2 mutants, occurring only in unsterilized and not sterilized germinating grains, while the opposite was observed for TCA and SA. The tw mutations influenced variations in the seed-borne fungal spectra, decreasing the frequency of Bipolaris sorokiniana and increasing Fusarium spp. Hypochlorite-based surface sterilization methods should be used with caution in studies where the action of exogenous 2,4-D will be analysed in germinating grains. Auxin pathway disturbances specific for pleiotropic tw mutants are generally restricted to organogenesis but not to germination events. 
  • 877
  • 29 Oct 2021
Topic Review
Genetic Mutations Associated with TOF
Perturbed cardiac fetal blood flow and congenital heart disease are intrinsically interlinked. The presence of subtle or overt structural heart defects induces blood flow conditions that differ from normal. Because blood flow provides important mechanical feedback during heart development, mutations in genes that are responsive to flow (such as the vascular endothelial growth factor family) or perturbations in blood flow itself both lead to congenital heart defects. In particular tetralogy of Fallot (TOF) is associated with perturbations in early embryonic blood flow as well as genetic mutations.
  • 875
  • 03 Sep 2021
Topic Review
Epo1-Bem3
Tubules of the endoplasmic reticulum (ER) spread into the buds of yeast by an actin-based mechanism and, upon entry, become attached to the polarisome, a proteinaceous micro-compartment below the tip of the bud. The minimal tether between polarisome and cortical ER is formed by a protein complex consisting of Epo1, a member of the polarisome, Scs2, a membrane protein of the ER and Cdc42 guanosine triphosphatase-activating protein Bem3. Here, we report the crystal structure of a complex between Epo1 and Bem3.
  • 874
  • 06 May 2021
Topic Review
Discovery of NPs by Genomics/Metabolomics
Natural products (NPs) are evolutionarily optimized as drug-like molecules and remain the most consistently successful source of drugs and drug leads. Due to traditional discovery approaches’ limitations relying on untargeted screening methods, there is a growing trend to employ unconventional secondary metabolomics techniques.
  • 872
  • 13 Jul 2021
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