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Topic Review
HSP90 inhibitors for IPF/COVID-19
Heat shock protein 90 (HSP90) is an important chaperone that assists the late stage folding of several proteins involved in cell survival in response to environmental stressors. The inhibition of HSP90 is followed by a complex modulation of the proteome and the kinome, that has proved beneficial in cancer and various neurodegenerative diseases. Additionally, accumulating literature suggests that HSP90 may be a key target during the development of pulmonary fibrosis and that its inhibition could serve as a new and exciting therapeutic approach. We have summarized the current evidence about HSP90’s role in Idiopathic Pulmonary Fibrosis (IPF), the results from preclinical studies on its inhibition and the intracellular signaling pathways involved, in a recent review article (Review). In this Article entry, we will introduce the main findings discussed in the review and focus on its translation and possible significance in the era of the SARS-CoV-2 pandemic.
  • 1.4K
  • 07 Aug 2020
Topic Review
Curcuma longa L. Essential Oil
Curcuma longa L. rhizome essential oil is a valuable product in pharmaceutical industry due to its wide beneficial health effects.
  • 1.3K
  • 09 Feb 2021
Topic Review
Heat Shock Proteins
The heat shock proteins (HSPs), are a family of proteins that have been linked to different cellular functions, being activated under conditions of cellular stress, not only imposed by thermal variation but also toxins, radiation, infectious agents, hypoxia, etc. Regarding pathological situations as seen in cardiorenal syndrome (CRS), HSPs have been shown to be important mediators involved in the control of gene transcription and intracellular signaling, in addition to be an important connector with the immune system. Thus, HSPs have been targeted by researchers as important connectors between kidney and heart.
  • 1.3K
  • 26 Nov 2021
Topic Review
Osteosarcoma Pathogenesis
Osteosarcoma (OS) is thought to originate from mesenchymal stem cells and is the primary malignant bone tumor that most commonly affects children, adolescents, and young adults.
  • 1.3K
  • 10 Feb 2021
Topic Review
Bacterial Flagellar Filament
The bacterial flagellum is a complex and dynamic nanomachine that propels bacteria through liquids. It consists of a basal body, a hook, and a long filament. The flagellar filament is composed of thousands of copies of the protein flagellin (FliC) arranged helically and ending with a filament cap composed of an oligomer of the protein FliD. The overall structure of the filament core is preserved across bacterial species, while the outer domains exhibit high variability, and in some cases are even completely absent. Flagellar assembly is a complex and energetically costly process triggered by environmental stimuli and, accordingly, highly regulated on transcriptional, translational and post-translational levels. Apart from its role in locomotion, the filament is critically important in several other aspects of bacterial survival, reproduction and pathogenicity, such as adhesion to surfaces, secretion of virulence factors and formation of biofilms. Additionally, due to its ability to provoke potent immune responses, flagellins have a role as adjuvants in vaccine development.
  • 1.3K
  • 02 Aug 2021
Topic Review
Long Non-coding RNAs
Long noncoding RNAs (lncRNAs) constitute important group of RNA molecules with various biological activities. Despite significant progress in the understanding of lncRNAs, pivotal functions of this class of molecules are emerging. Among these, role in DNA damage response (DDR) seems to be fundamental. Various lncRNAs were found to modulate DNA repair on different levels: through TP53 activity modulation at transcriptional and translational level, through recruitment of chromatin remodelers that modulate the access of DNA repair proteins to the site of damage, and by working as scaffolds and mediators for DNA repair proteins, and acting as sponges for various DNA-damage-associated miRNAs. Considering that, lncRNAs involvement in DDR constitute interesting field of research with numerous future applications, such as development of new targeted anticancer therapies. 
  • 1.3K
  • 22 Jan 2021
Topic Review
Antagonistic Yeasts
Antagonistic yeasts (also known as biocontrol yeasts) are promising substitutes for chemical fungicides in the control of postharvest decay owing to their widespread distribution, antagonistic ability, environmentally friendly nature, and safety for humans.
  • 1.3K
  • 26 Oct 2020
Topic Review
Cytoplasmic Actin Mutations
Cytoplasmic actins are abundant molecules in non-muscle cells, including white blood cells. Two forms exist which are referred to as beta- or gamma-cytoplasmic actin encoded by ACTB and ACTG1, respectively. They form the building blocks of the dynamic actin polymers of the cytoskeleton that are involved in migration and motility processes of cells. Whereas mutations in cytoplasmic actins have been discovered in congenital diseases, their prevalence in cancer types has not been studied in detail. We show that within hematological cancer cytoplasmic actin mutations occur with higher frequency in two specific subtypes. Beta-actin mutations occur mainly in the subtype diffuse large B-cell lymphoma or DLBCL whereas gamma-actin mutations occur mainly in multiple myeloma. Mapping these mutations on the three dimensional structure reveals they map to regions of actin that are important in actin polymer formation and, for gamma-actin also for myosin interaction. Given their occurrence in these functionally important regions, their role as potential driver mutations or in disease progression merits further investigation.
  • 1.3K
  • 28 Oct 2020
Topic Review
Updated Understanding of Cancer
       Cancer is a tumorigenesis process that forms a mass of cells that we call a tumor. During tumorigenesis, the cells that compose the tumor can be benign or malignant. When the cells in the tumor are normal but old, the tumor is termed benign. When the cells in the tumor are abnormal and can grow uncontrollably, the tumor is malignant. Sometimes a benign tumor can transform into a malign one if the normal old cells begin to develop abnormalities, such as DNA mutations, and grow rapidly. - by Cristian Muresanu
  • 1.3K
  • 30 Oct 2020
Topic Review
Von Willebrand Factor
The von Willebrand factor (vWF) is a plasma protein that mediates platelet adhesion and leukocyte recruitment to vascular injury sites and carries coagulation factor VIII, a building block of the intrinsic pathway of coagulation. A steep rise in shear rates, which may occur at sites of arterial stenosis and injury, is crucial for unfolding and activation of vWF. The hemostatic activity of vWF is counterbalanced by ADAMTS-13, a vWF-cleaving protease. The presence of ultra-large multimers of vWF in the bloodstream is associated with spontaneous thrombosis, whereas its deficiency leads to bleeding.
  • 1.3K
  • 12 Nov 2020
Topic Review
Coriandrum sativum L.
Coriandrum sativum (C. sativum), belonging to the Apiaceae (Umbelliferae) family, is widely recognized for its uses in culinary and traditional medicine. C. sativum contains various phytochemicals such as polyphenols, vitamins, and many phytosterols, which account for its properties including anticancer, anti-inflammatory, antidiabetic, and analgesic effects.
  • 1.3K
  • 13 Jan 2022
Topic Review
CRISPR-Cas Genome Editing Components in C. elegans
CRISPR-Cas allows us to introduce desired genome editing, including mutations, epitopes, and deletions, with unprecedented efficiency. The development of CRISPR-Cas has progressed to such an extent that it is now applicable in various fields, with the help of model organisms. C. elegans is one of the pioneering animals in which numerous CRISPR-Cas strategies have been rapidly established. Ironically, the emergence of numerous methods makes the choice of the correct method difficult. Choosing an appropriate selection or screening approach is the first step in planning a genome modification.
  • 1.3K
  • 30 Dec 2022
Topic Review
Therapeutic miRNA-Enriched Extracellular Vesicles
Extracellular vesicles (EVs) are 50–300 nm vesicles secreted by eukaryotic cells. They can carry cargo (including miRNA) from the donor cell to the recipient cell. miRNAs in EVs can change the translational profile of the recipient cell and modulate cellular morphology. This endogenous mechanism has attracted the attention of the drug-delivery community in the last few years. EVs can be enriched with exogenous therapeutic miRNAs and used for treatment of diseases by targeting pathological recipient cells. However, there are some obstacles that need to be addressed before introducing therapeutic miRNA-enriched EVs in clinics.
  • 1.3K
  • 19 Oct 2020
Topic Review
Transcription Factors
Transcription factors (TFs) are regulatory proteins that are responsible for the mechanistic control of gene transcription.
  • 1.3K
  • 25 Jan 2021
Topic Review
Potassium Channels in PAH
Pulmonary arterial hypertension (PAH) is a rare and severe cardiopulmonary disease without curative treatments. PAH is a multifactorial disease that involves genetic predisposition, epigenetic factors, and environmental factors (drugs, toxins, viruses, hypoxia, and inflammation), which contribute to the initiation or development of irreversible remodeling of the pulmonary vessels. The recent identification of loss-of-function mutations in KCNK3 (KCNK3 or TASK-1) and ABCC8 (SUR1), or gain-of-function mutations in ABCC9 (SUR2), as well as polymorphisms in KCNA5 (Kv1.5), which encode two potassium (K+) channels and two K+ channel regulatory subunits, has revived the interest of ion channels in PAH. This entry focuses on KCNK3, SUR1, SUR2, and Kv1.5 channels in pulmonary vasculature and discusses their pathophysiological contribution to and therapeutic potential in PAH.
  • 1.3K
  • 28 Sep 2020
Topic Review
Symmetric and Asymmetric Synapses Driving Neurodegenerative Disorders
In 1959, E. G. Gray described two different types of synapses in the brain for the first time: symmetric and asymmetric. Later on, symmetric synapses were associated with inhibitory terminals, and asymmetric synapses to excitatory signaling. The balance between these two systems is critical to maintain a correct brain function. Likewise, the modulation of both types of synapses is also important to maintain a healthy equilibrium. Cerebral circuitry responds differently depending on the type of damage and the timeline of the injury. For example, promoting symmetric signaling following ischemic damage is beneficial only during the acute phase; afterwards, it further increases the initial damage. Synapses can be also altered by players not directly related to them; the chronic and long-term neurodegeneration mediated by tau proteins primarily targets asymmetric synapses by decreasing neuronal plasticity and functionality. Dopamine represents the main modulating system within the central nervous system. Indeed, the death of midbrain dopaminergic neurons impairs locomotion, underlying the devastating Parkinson’s disease.
  • 1.3K
  • 10 Dec 2021
Topic Review
IP6K
Inositol and its phosphate metabolites play a pivotal role in several biochemical pathways and gene expression regulation: inositol pyrophosphates (PP-IPs) have been increasingly appreciated as key signaling modulators. Fluctuations in their intracellular levels hugely impact the transfer of phosphates and the phosphorylation status of several target proteins. Pharmacological modulation of the proteins associated with PP-IP activities has proved to be beneficial in various pathological settings. IP7 has been extensively studied and found to play a key role in pathways associated with PP-IP activities. Three inositol hexakisphosphate kinase (IP6K) isoforms regulate IP7 synthesis in mammals. Genomic deletion or enzymic inhibition of IP6K1 has been shown to reduce cell invasiveness and migration capacity, protecting against chemical-induced carcinogenesis. IP6K1 could therefore be a useful target in anticancer treatment.
  • 1.3K
  • 14 Oct 2020
Topic Review
Limb Development
The function of retinoic acid (RA) during limb development is still debated, as loss and gain of function studies led to opposite conclusions. With regard to limb initiation, genetic studies demonstrated that activation of FGF10 signaling is required for the emergence of limb buds from the trunk, with Tbx5 and RA signaling acting upstream in the forelimb field, whereas Tbx4 and Pitx1 act upstream in the hindlimb field. Early studies in chick embryos suggested that RA as well as Meis1 and Meis2 (Meis1/2) are required for subsequent proximodistal patterning of both forelimbs and hindlimbs, with RA diffusing from the trunk, functioning to activate Meis1/2 specifically in the proximal limb bud mesoderm. However, genetic loss of RA signaling does not result in loss of limb Meis1/2 expression and limb patterning is normal, although Meis1/2 expression is reduced in trunk somitic mesoderm. More recent studies demonstrated that global genetic loss of Meis1/2 results in a somite defect and failure of limb bud initiation. Other new studies reported that conditional genetic loss of Meis1/2 in the limb results in proximodistal patterning defects, and distal FGF8 signaling represses Meis1/2 to constrain its expression to the proximal limb.
  • 1.3K
  • 19 Jan 2021
Topic Review
Lateral Organization of PI(4,5)P2
Phosphatidylinositol 4,5- bisphosphate (PI(4,5)P2) is a minor but ubiquitous component of the inner leaflet of the plasma membrane of eukaryotic cells. However, due to its particular complex biophysical properties, it stands out from its neighboring lipids as one of the most important regulators of membrane-associated signaling events. Despite its very low steady-state concentration, PI(4,5)P2 is able to engage in a multitude of simultaneous cellular functions that are temporally and spatially regulated through the presence of localized transient pools of PI(4,5)P2 in the membrane.
  • 1.3K
  • 04 Nov 2020
Topic Review
ASIA Syndrome
Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was first introduced in 2011 by Shoenfeld et al. and encompasses a cluster of related immune mediated diseases, which develop among genetically prone individuals as a result of adjuvant agent exposure.
  • 1.3K
  • 20 Feb 2021
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