scholarly journals Noscapine, an Emerging Medication for Different Diseases: A Mechanistic Review

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Pouria Rahmanian-Devin ◽  
Vafa Baradaran Rahimi ◽  
Mahmoud Reza Jaafari ◽  
Shiva Golmohammadzadeh ◽  
Zahra Sanei-far ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Dynamic Properties ◽  
Cell Types ◽  
Endothelial Cell Migration ◽  
Antioxidant Defences ◽  
Benzylisoquinoline Alkaloid ◽  
Cancerous Cell ◽  
M Phase ◽  
Resistant Strains ◽  
Drug Resistant Strains

Noscapine is a benzylisoquinoline alkaloid isolated from poppy extract, used as an antitussive since the 1950s, and has no addictive or euphoric effects. Various studies have shown that noscapine has excellent anti-inflammatory effects and potentiates the antioxidant defences by inhibiting nitric oxide (NO) metabolites and reactive oxygen species (ROS) levels and increasing total glutathione (GSH). Furthermore, noscapine has indicated antiangiogenic and antimetastatic effects. Noscapine induces apoptosis in many cancerous cell types and provides favourable antitumour activities and inhibitory cell proliferation in solid tumours, even drug-resistant strains, via mitochondrial pathways. Moreover, this compound attenuates the dynamic properties of microtubules and arrests the cell cycle in the G2/M phase. Noscapine can reduce endothelial cell migration in the brain by inhibiting endothelial cell activator interleukin 8 (IL-8). In fact, this study aimed to elaborate on the possible mechanisms of noscapine against different disorders.

scholarly journals Hyaluronan-binding protein in endothelial cell morphogenesis.

1992 ◽  
Vol 119 (3) ◽  
pp. 643-652 ◽  
Author(s):  
S D Banerjee ◽  
B P Toole
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Type I Collagen ◽  
Binding Protein ◽  
Cell Types ◽  
Endothelial Cell Migration ◽  
Type I ◽  
Tubule Formation ◽  
High Concentrations ◽  
Membrane Components

Previous studies from several laboratories have provided evidence that interaction of hyaluronan (HA) with the surface of endothelial cells may be involved in endothelial cell behavior. We have recently characterized a mAb, mAb IVd4, that recognizes and neutralizes HA-binding protein (HABP) from a wide variety of cell types from several different species (Banerjee, S. D., and B. P. Toole. 1991. Dev. Biol. 146:186-197). In this study we have found that mAb IVd4 inhibits migration of endothelial cells from a confluent monolayer after "wounding" of the monolayer. HA hexasaccharide, a fragment of HA with the same disaccharide composition as polymeric HA, also inhibits migration. In addition, both reagents inhibit morphogenesis of capillary-like tubules formed in gels consisting of type I collagen and basement membrane components. Immunocytology revealed that the antigen recognized by mAb IVd4 becomes localized to the cell membrane of migrating cells, including many of their lamellipodia. Treatment with high concentrations of HA hexamer causes loss of immunoreactivity from these structures. We conclude that HABP recognized by mAb IVd4 is involved in endothelial cell migration and tubule formation.

An in vitro model for investigation of vitamin A effects on wound healing

2021 ◽  
pp. 1-6
Author(s):  
Hoda Keshmiri Neghab ◽  
Mohammad Hasan Soheilifar ◽  
Gholamreza Esmaeeli Djavid
Keyword(s):  
Wound Healing ◽  
Endothelial Cell ◽  
Vitamin A ◽  
In Vitro Model ◽  
Cellular Proliferation ◽  
Endothelial Cell Migration ◽  
Normal Fibroblast ◽  
Anti Inflammatory ◽  
Vitro Model

Abstract. Wound healing consists of a series of highly orderly overlapping processes characterized by hemostasis, inflammation, proliferation, and remodeling. Prolongation or interruption in each phase can lead to delayed wound healing or a non-healing chronic wound. Vitamin A is a crucial nutrient that is most beneficial for the health of the skin. The present study was undertaken to determine the effect of vitamin A on regeneration, angiogenesis, and inflammation characteristics in an in vitro model system during wound healing. For this purpose, mouse skin normal fibroblast (L929), human umbilical vein endothelial cell (HUVEC), and monocyte/macrophage-like cell line (RAW 264.7) were considered to evaluate proliferation, angiogenesis, and anti-inflammatory responses, respectively. Vitamin A (0.1–5 μM) increased cellular proliferation of L929 and HUVEC (p < 0.05). Similarly, it stimulated angiogenesis by promoting endothelial cell migration up to approximately 4 fold and interestingly tube formation up to 8.5 fold (p < 0.01). Furthermore, vitamin A treatment was shown to decrease the level of nitric oxide production in a dose-dependent effect (p < 0.05), exhibiting the anti-inflammatory property of vitamin A in accelerating wound healing. These results may reveal the therapeutic potential of vitamin A in diabetic wound healing by stimulating regeneration, angiogenesis, and anti-inflammation responses.

Design, Synthesis and Antiplasmodial Evaluation of Sulfoximine-triazole Hybrids as Potential Antimalarial Prototypes

2019 ◽  
Vol 15 (6) ◽  
pp. 685-692 ◽  
Author(s):  
Tommy F. Mabasa ◽  
Babatunde Awe ◽  
Dustin Laming ◽  
Henok H. Kinfe
Keyword(s):  
Alkyl Substituent ◽  
Antimalarial Drugs ◽  
Significant Activity ◽  
Design Synthesis ◽  
Antimalarial Agents ◽  
Falciparum Strain ◽  
Physiological Properties ◽  
Resistant Strains ◽  
Cytotoxicity Activities ◽  
Drug Resistant Strains

Background:Malaria, caused by the deadly Plasmodium falciparum strain, claims the lives of millions of people annually. The emergence of drug-resistant strains of P. falciparum to the artemisinin-based combination therapy (ACT), the last line of defense against malaria, is worrisome and urges for the development of new chemo-types with a new mode of action. In the search of new antimalarial agents, hybrids of triazoles and other known antimalarial drugs have been reported to possess better activity than either of the parent compounds administered individually. Despite their better activity, no hybrid antimalarial drugs have been developed so far.Objective:In the hope of developing new antimalarial prototypes, we propose the design, synthesis and antimalarial evaluation of novel sulfoximine-triazole hybrids owing to their interesting biological and physiological properties.Methods:The sulfoximine part of the hybrid will be synthesized via imidation of the corresponding sulfoxide. Propargylation of the NH moiety of the sulfoximine followed by copper-catalyzed click chemistry with benzyl azide was envisaged to provide the target sulfoximine-triazole hybrids.Results:Five novel sulfoximine-triazole hybrids possessing various substituents on the sulfoximine moiety have been successfully synthesized and evaluated for their antiplasmodial and cytotoxicity activities. The results revealed that the co-presence of the sulfoximine and triazole moieties along with a lipophilic alkyl substituent on the sulfur atom impart significant activity.Conclusion:Sulfoximine-triazole hybrids could be used as a prototype for the synthesis of new derivatives with better antiplasmodial activities.

scholarly journals Interactome Analysis of KIN (Kin17) Shows New Functions of This Protein

2021 ◽  
Vol 43 (2) ◽  
pp. 767-781
Author(s):  
Vanessa Pinatto Gaspar ◽  
Anelise Cardoso Ramos ◽  
Philippe Cloutier ◽  
José Renato Pattaro Junior ◽  
Francisco Ferreira Duarte Junior ◽  
...  
Keyword(s):  
Dna Replication ◽  
Protein Interactions ◽  
Ribosome Biogenesis ◽  
Cell Metabolism ◽  
Cell Types ◽  
Protein Protein Interactions ◽  
Cellular Mechanisms ◽  
Cancerous Cell ◽  
First Time

KIN (Kin17) protein is overexpressed in a number of cancerous cell lines, and is therefore considered a possible cancer biomarker. It is a well-conserved protein across eukaryotes and is ubiquitously expressed in all cell types studied, suggesting an important role in the maintenance of basic cellular function which is yet to be well determined. Early studies on KIN suggested that this nuclear protein plays a role in cellular mechanisms such as DNA replication and/or repair; however, its association with chromatin depends on its methylation state. In order to provide a better understanding of the cellular role of this protein, we investigated its interactome by proximity-dependent biotin identification coupled to mass spectrometry (BioID-MS), used for identification of protein–protein interactions. Our analyses detected interaction with a novel set of proteins and reinforced previous observations linking KIN to factors involved in RNA processing, notably pre-mRNA splicing and ribosome biogenesis. However, little evidence supports that this protein is directly coupled to DNA replication and/or repair processes, as previously suggested. Furthermore, a novel interaction was observed with PRMT7 (protein arginine methyltransferase 7) and we demonstrated that KIN is modified by this enzyme. This interactome analysis indicates that KIN is associated with several cell metabolism functions, and shows for the first time an association with ribosome biogenesis, suggesting that KIN is likely a moonlight protein.

scholarly journals Inhibition of MMP2-PEX by a novel ester of dihydroxy cinnamic and linoleic acid from the seagrass Cymodocea serrulata

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
V. S. Christina ◽  
R. Lakshmi Sundaram ◽  
V. Sivamurugan ◽  
D. Thirumal Kumar ◽  
C. D. Mohanapriya ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Ovarian Cancer Cell Line ◽  
Cancer Cell Line ◽  
Md Simulations ◽  
Cell Types ◽  
Structural Details ◽  
M Phase ◽  
Ft Ir ◽  
Target Binding ◽  
Cymodocea Serrulata

AbstractMatrix metalloproteinases (MMPs) are pivotal for cancer cell migration and metastasis which are generally over-expressed in such cell types. Many drugs targeting MMPs do so by binding to the conserved catalytic domains and thus exhibit poor selectivity due to domain-similarities with other proteases. We report herein the binding of a novel compound [3-(E-3,4-dihydroxycinnamaoyloxyl)-2-hydroxypropyl 9Z, 12Z-octadeca-9, 12-dienoate; Mol. wt: 516.67 Da], (C1), isolated from a seagrass, Cymodocea serrulata to the unconserved hemopexin-like (PEX) domain of MMP2 (− 9.258 kcal/mol). MD simulations for 25 ns, suggest stable ligand-target binding. In addition, C1 killed an ovarian cancer cell line, PA1 at IC50: 5.8 μM (lesser than Doxorubicin: 8.6 µM) and formed micronuclei, apoptotic bodies and nucleoplasmic bridges whilst causing DNA laddering, S and G2/M phase dual arrests and MMP disturbance, suggesting intrinsic apoptosis. The molecule increased mRNA transcripts of BAX and BAD and down-regulated cell survival genes, Bcl-xL, Bcl-2, MMP2 and MMP9. The chemical and structural details of C1 were deduced through FT-IR, GC–MS, ESI–MS, 1H and 13C NMR [both 1D and 2D] spectra.

Overview of Antiretroviral Agents in 2005

2005 ◽  
Vol 18 (4) ◽  
pp. 228-246 ◽  
Author(s):  
Anela Stanic ◽  
Tulip K. Schneider
Keyword(s):  
Protease Inhibitors ◽  
Transcriptase Inhibitor ◽  
Fixed Dose ◽  
Antiretroviral Agents ◽  
Entry Inhibitors ◽  
Fusion Inhibitors ◽  
Resistant Strains ◽  
Atazanavir Sulfate ◽  
Reverse Transcriptase Inhibitor ◽  
Drug Resistant Strains

To date, 25 antiretroviral agents (including fixed-dose combinations) have gained approval by the Food and Drug Administration and are currently available on the market for the treatment of HIV-1 infection. New protease inhibitors, atazanavir sulfate (Reyataz) and fosamprenavir (Lexiva), were licensed, in addition to the nucleoside analogue reverse transcriptase inhibitor (NRTI) emtricitabine (Emtriva) and 2 fixed-dose NRTI combinations, emtricitabine/tenofovir disoproxil fumarate (Truvada) and lamivudine/abacavir (Epzicom). These newly licensed antiretroviral agents allow for lower pill burden and dosing schedule simplification, and some agents such as atazanavir sulfate are associated with improved lipid profile in comparison to other currently marketed protease inhibitors. In addition, a new class of anti-retroviral agents, entry inhibitors, of which a subclass exists called fusion inhibitors with its representative member, enfuvirtide (Fuzeon), which is currently the only available drug in its class, was marketed almost 2 years ago. Despite a remarkable progress in the treatment of HIV infection noted during the past decade, significant challenges to therapy such as tolerability issues and emergence of drug-resistant strains remain. Therefore, new antiretroviral drug development has focused on a design of drugs that work against the resistant strains of HIV and/or have a novel mechanism of action.

scholarly journals Single cell sequencing reveals endothelial plasticity with transient mesenchymal activation after myocardial infarction

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lukas S. Tombor ◽  
David John ◽  
Simone F. Glaser ◽  
Guillermo Luxán ◽  
Elvira Forte ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Single Cell ◽  
Rna Sequencing ◽  
Endothelial Cell Migration ◽  
Metabolic Adaptation ◽  
Endothelial Cell Proliferation ◽  
Mesenchymal Transition ◽  
Single Cell Rna Sequencing

AbstractEndothelial cells play a critical role in the adaptation of tissues to injury. Tissue ischemia induced by infarction leads to profound changes in endothelial cell functions and can induce transition to a mesenchymal state. Here we explore the kinetics and individual cellular responses of endothelial cells after myocardial infarction by using single cell RNA sequencing. This study demonstrates a time dependent switch in endothelial cell proliferation and inflammation associated with transient changes in metabolic gene signatures. Trajectory analysis reveals that the majority of endothelial cells 3 to 7 days after myocardial infarction acquire a transient state, characterized by mesenchymal gene expression, which returns to baseline 14 days after injury. Lineage tracing, using the Cdh5-CreERT2;mT/mG mice followed by single cell RNA sequencing, confirms the transient mesenchymal transition and reveals additional hypoxic and inflammatory signatures of endothelial cells during early and late states after injury. These data suggest that endothelial cells undergo a transient mes-enchymal activation concomitant with a metabolic adaptation within the first days after myocardial infarction but do not acquire a long-term mesenchymal fate. This mesenchymal activation may facilitate endothelial cell migration and clonal expansion to regenerate the vascular network.

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