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Topic Review
RET Receptor Tyrosine Kinase
Rearranged during transfection (RET) is the tyrosine kinase receptor that under normal circumstances binds ligand at the cell surface and mediates various essential roles in a variety of cellular processes such as proliferation, differentiation, survival, migration, and metabolism. RET plays a pivotal role in the development of both peripheral and central nervous systems. RET is expressed from early stages of embryogenesis and remains expressed throughout all life stages. Mutations either activating or inhibiting RET result in several aggressive diseases, namely cancer and Hirschsprung disease. However, the physiological ligand-dependent activation of RET receptor is important for the survival and maintenance of several neuronal populations, appetite, and weight gain control, thus providing an opportunity for the development of disease-modifying therapeutics against neurodegeneration and obesity. In this review, we describe the structure of RET, its signaling, and its role in both normal development as well as in developmental disorders. We highlight the differences in the signaling and outcomes of constitutive and ligand-induced RET activation. Finally, we review the data on recently developed small molecular weight RET agonists and their potential for the treatment of various diseases.
  • 1.6K
  • 26 Oct 2020
Topic Review
Insight into Phloem Sap Metabolomics
Phloem sap transport is essential for plant nutrition and development since it mediates redistribution of nutrients, metabolites and signaling molecules. However, its biochemical composition is not so well-known because phloem sap sampling is difficult and does not always allow extensive chemical analysis. Efforts have been devoted to metabolomics analyses of phloem sap using either liquid chromatography or gas chromatography coupled with mass spectrometry. Phloem sap metabolomics is of importance to understand how metabolites can be exchanged between plant organs and how metabolite allocation may impact plant growth and development.
  • 1.6K
  • 13 Apr 2023
Topic Review
mTOR in the Brain under Physiological Conditions
ammalian/mechanistic target of rapamycin (mTOR) is a 289 kDa serine–threonine kinase and a key element of two mTOR complexes called mTORC1 and mTORC2 (mTORCs). Furthermore, mTOR is highly conserved and is the center of multiples signaling pathways and coordinates important cellular processes such as cell growth and metabolism. Although mTOR is ubiquitously expressed, it is especially abundant in the brain. Therefore, mTOR dysfunction profoundly affects the central nervous system (CNS).
  • 1.6K
  • 05 May 2022
Topic Review
HSP in Diabetes and Alzheimer
Type 2 diabetes (T2D) and Alzheimer’s disease (AD) are growing in prevalence worldwide. The development of T2D increases the risk of AD disease, while AD patients can show glucose imbalance due to an increased insulin resistance. T2D and AD share similar pathological features and underlying mechanisms, including the deposition of amyloidogenic peptides in pancreatic islets (i.e., islet amyloid polypeptide; IAPP) and brain (β-Amyloid; Aβ). Both IAPP and Aβ can undergo misfolding and aggregation and accumulate in the extracellular space of their respective tissues of origin. As a main response to protein misfolding, there is evidence of the role of heat shock proteins (HSPs) in moderating T2D and AD. HSPs play a pivotal role in cell homeostasis by providing cytoprotection during acute and chronic metabolic stresses. In T2D and AD, intracellular HSP (iHSP) levels are reduced, potentially due to the ability of the cell to export HSPs to the extracellular space (eHSP). The increase in eHSPs can contribute to oxidative damage and is associated with various pro-inflammatory pathways in T2D and AD.
  • 1.6K
  • 27 Jan 2021
Topic Review
Receptor-Dependent Apoptotic Pathway
Apoptosis is a process of programmed cell death which has an important role in tissue and organ homeostasis and in the control of organism development. Two main signaling pathways are involved in regulation of apoptosis: the mitochondrial dependent intrinsic pathway and death receptor dependent extrinsic pathway. The receptors are members of the tumor necrosis factor receptor superfamily (TNFRSF).The extrinsic apoptotic pathway triggers apoptosis by binding of ligands to death receptors, which leads to formation of a death-inducing signaling complex (DISC) and in consequence, caspase activation. This pathway and its subpathways and regulatory factors and linkages to the other cellular signaling events are briefly presented.
  • 1.6K
  • 30 Oct 2020
Topic Review
Osteoclast Multinucleation
       Osteoclasts  are derived from hemopoietic progenitors of the monocyte-macrophage lineage. They differentiate upon exposure to macrophage colony stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL), which are presented by osteoblasts and osteocytesare. Multinucleation in a late phase of osteoclastogenesis is a hallmark of osteoclast maturation. The unique and dynamic multinucleation process not only increases cell size but causes functional alterations through reconstruction of the cytoskeleton, creating the actin ring and ruffled border that enable efficient bone resorption.  The process of osteoclast multinucleation is dynamic, complicated and finely controlled by multiple entangled factors. At the beginning of the 21st century, two master fusogens, DC-STAMP and OC-STAMP, had been identified that directly regulate osteoclast multinucleation.
  • 1.6K
  • 17 Aug 2020
Topic Review
Direct Arylation in Pincer Complexes
Direct arylation is an atom-economical alternative to more established procedures such as Stille, Suzuki or Negishi arylation reactions. In comparison with other palladium sources and ligands, the use of palladium pincer complexes as catalysts or pre-catalysts for direct arylation has resulted in improved efficiency, higher reaction yields, and advantageous reaction conditions. In addition to a revision of the literature concerning intra- and intermolecular direct arylation reactions performed in the presence of palladium pincer complexes, the role of these remarkably active catalysts will also be discussed.
  • 1.6K
  • 09 Aug 2021
Topic Review
Gliotoxins
Gliotoxin is a kind of epipolythiodioxopiperazine derived from different fungi that is characterized by a disulfide bridge. Gliotoxins can be biosynthesized by a gli gene cluster and regulated by a positive GliZ regulator. Gliotoxins show cytotoxic effects via the suppression the function of macrophage immune function, inflammation, antiangiogenesis, DNA damage by ROS production, peroxide damage by the inhibition of various enzymes, and apoptosis through different signal pathways. In the other hand, gliotoxins can also be beneficial with different doses. Low doses of gliotoxin can be used as an antioxidant, in the diagnosis and treatment of HIV, and as an anti-tumor agent in the future. Gliotoxins have also been used in the control of plant pathogens, including Pythium ultimum and Sclerotinia sclerotiorum.
  • 1.6K
  • 23 Dec 2021
Topic Review
Natural Compounds in Thromboembolism Treatment
Venous thromboembolism (VTE) refers to deep vein thrombosis (DVT), whose consequence may be a pulmonary embolism (PE). Thrombosis is associated with significant morbidity and mortality and is the third most common cardiovascular disease after myocardial infarction and stroke. DVT is associated with the formation of a blood clot in a deep vein in the body. Thrombosis promotes slowed blood flow, hypoxia, cell activation, and the associated release of many active substances involved in blood clot formation. All thrombi which adhere to endothelium consist of fibrin, platelets, and trapped red and white blood cells.
  • 1.6K
  • 11 Nov 2020
Topic Review
L19-TNF
Tumor necrosis factor (TNF) is used as a pro-inflammatory payload to trigger haemorrhagic necrosis and boost anti-cancer immunity at the tumor site. There is  a depotentiated version of TNF (carrying the single point mutation I97A), which displayed reduced binding affinity to its cognate receptor tumor necrosis factor receptor 1 (TNFR-1) and lower biocidal activity. 
  • 1.6K
  • 29 Mar 2022
Topic Review
Sweet Taste Signaling
Sweet taste, a proxy for sugar-derived calories, is an important driver of food intake, and animals have evolved robust molecular and cellular machinery for sweet taste signaling. The below is a description of the mechanisms underlying sweet taste signaling in the periphery, and the factors regulating them.
  • 1.6K
  • 09 Aug 2022
Topic Review
Mammalian Aquaporins
Mammalian aquaporins (AQPs) are transmembrane channels expressed in a large variety of cells and tissues throughout the body. They are known as water channels, but they also facilitate the transport of small solutes, gasses, and monovalent cations. To date, 13 different AQPs, encoded by the genes AQP0–AQP12, have been identified in mammals, which regulate various important biological functions in kidney, brain, lung, digestive system, eye, and skin. Consequently, dysfunction of AQPs is involved in a wide variety of disorders. AQPs are also present in the heart, even with a specific distribution pattern in cardiomyocytes, but whether their presence is essential for proper (electro)physiological cardiac function has not intensively been studied. In a recent review published in Int. J. Mol. Sci. (https://doi.org/10.3390/ijms20082039), we summarizes recent findings and highlights the involvement of AQPs in normal and pathological cardiac function. We conclude that AQPs are at least implicated in proper cardiac water homeostasis and energy balance as well as heart failure and arsenic cardiotoxicity. However, our review also demonstrates that many effects of cardiac AQPs, especially on excitation-contraction coupling processes, are virtually unexplored.
  • 1.6K
  • 06 Sep 2021
Topic Review
Hydroxyapatite in Oral Care Products
Calcium phosphate compounds form the inorganic phases of our mineralised tissues such as bone and teeth, playing an important role in hard tissue engineering and regenerative medicine. In dentistry and oral care products, hydroxyapatite (HA) is a stable and biocompatible calcium phosphate with low solubility being used for various applications such as tooth remineralisation, reduction of tooth sensitivity, oral biofilm control, and tooth whitening. 
  • 1.6K
  • 08 Sep 2021
Topic Review
Docking Analysis in Research for Novel Enzyme Inhibitors
Approaches for increasing effectiveness of docking analysis in Prediction of inhibitory potency of small molecules, emphasizing in selection of appropriate enzyme 3D-structure and in calculation of probability of binding factors, based on docking analysis to the target site and to the whole enzyme.
  • 1.6K
  • 22 Jan 2025
Topic Review
Principal Postulates of Centrosomal Biology
The centrosome, which consists of two centrioles surrounded by pericentriolar material, is a unique structure that has retained its main features in organisms of various taxonomic groups from unicellular algae to mammals over one billion years of evolution. In addition to the most noticeable function of organizing the microtubule system in mitosis and interphase, the centrosome performs many other cell functions. In particular, centrioles are the basis for the formation of sensory primary cilia and motile cilia and flagella. Another principal function of centrosomes is the concentration in one place of regulatory proteins responsible for the cell's progression along the cell cycle. Despite the existing exceptions, the functioning of the centrosome is subject to general principles.
  • 1.6K
  • 15 Oct 2020
Topic Review
Glucagon-Like Peptide 1 Receptor Agonists: Sex Differences
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a relatively new class of anti-diabetic medications that have exhibited very promising results in the treatment of type 2 diabetes mellitus (T2DM). According to the 2021 American Diabetes Association guidelines, they constitute one of the preferred add-on agents when metformin monotherapy and lifestyle modifications have failed to achieve adequate glycemic control.
  • 1.6K
  • 06 Apr 2022
Topic Review
Heme Oxgenase-1 in cytoprotection
Heme oxygenase catalyzes the rate-limiting step in heme degradation in order to generate biliverdin, carbon monoxide (CO), and iron. The inducible form of the enzyme, heme oxygenase-1 (HO-1), exerts a central role in cellular protection. The substrate, heme, is a potent pro-oxidant that can accelerate inflammatory injury and promote cell death. HO-1 has been implicated as a key mediator of inflammatory cell and tissue injury, as validated in preclinical models of acute lung injury and sepsis. A large body of work has also implicated HO-1 as a cytoprotective molecule against various forms of cell death, including necrosis, apoptosis and newly recognized regulated cell death (RCD) programs such as necroptosis, pyroptosis, and ferroptosis. While the antiapoptotic potential of HO-1 and its reaction product CO in apoptosis regulation has been extensively characterized, relatively fewer studies have explored the regulatory role of HO-1 in other forms of necrotic and inflammatory RCD (i.e., pyroptosis, necroptosis and ferroptosis). HO-1 may provide anti-inflammatory protection in necroptosis or pyroptosis. In contrast, in ferroptosis, HO-1 may play a pro-death role via enhancing iron release. HO-1 has also been implicated in co-regulation of autophagy, a cellular homeostatic program for catabolic recycling of proteins and organelles. While autophagy is primarily associated with cell survival, its occurrence can coincide with RCD programs. 
  • 1.6K
  • 28 Apr 2021
Topic Review
The Dbf4-Dependent Kinase
The Dbf4-dependent kinase (DDK) is formed by the association of the kinase subunit, cell division cycle 7 (Cdc7), with its activating partner, dumb-bell factor 4 (Dbf4). By analogy with the cyclin-dependent kinases (CDK), Cdc7:Dbf4 is now most often referred to as ‘Dbf4-dependent kinase’ or DDK.
  • 1.6K
  • 27 Jun 2022
Topic Review
EV-Based Vaccines
Extracellular vesicles (EVs) are secreted from almost all human cells and mediate intercellular communication by transferring heterogeneous molecules (i.e., DNA, RNAs, proteins, and lipids). In this way, EVs participate in various biological processes, including immune responses. Viruses can hijack EV biogenesis systems for their dissemination, while EVs from infected cells can transfer viral proteins to uninfected cells and to immune cells in order to mask the infection or to trigger a response. Several studies have highlighted the role of native or engineered EVs in the induction of B cell and CD8(+) T cell reactions against viral proteins, strongly suggesting these antigen-presenting EVs as a novel strategy for vaccine design, including the emerging COVID-19. EV-based vaccines overcome some limitations of conventional vaccines and introduce novel unique characteristics useful in vaccine design, including higher bio-safety and efficiency as antigen-presenting systems and as adjuvants.
  • 1.6K
  • 02 Feb 2021
Topic Review
Crop Resilience to Drought Stress
Among all the abiotic factors, drought is likely to have one of the most detrimental effects on soil organisms and plants. Drought is a major problem for crops because it limits the availability of water, and consequently nutrients which are crucial for plant growth and survival. This results in reduced crop yields, stunted growth, and even plant death, according to the severity and duration of the drought, the plant’s developmental stage, and the plant’s genetic background. The ability to withstand drought is a highly complex characteristic that is controlled by multiple genes, making it one of the most challenging attributes to study, classify, and improve.
  • 1.6K
  • 21 Jun 2023
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