ABSTRACT
The absence of dystrophin protein causes cardiac dysfunction in boys with Duchenne Muscular Dystrophy (DMD). However, the common mouse model of DMD (B10-mdx) does not manifest cardiac deficits until late adulthood limiting our understanding of the mechanism and therapeutic approaches to target the pediatric-onset cardiac pathology in DMD. We show the mdx mouse model on the DBA/2J genetic background (D2-mdx) displays juvenile-onset cardiomyopathy. Molecular and histological analysis revealed heightened leukocyte chemotactic signaling and failure to resolve inflammation, leading to chronic inflammation and extracellular matrix (ECM) fibrosis, causing cardiac pathology in juvenile D2-mdx mice. We show that pharmacologically activating the N-formyl peptide receptor 2 (FPR2) - a receptor that physiologically resolves acute inflammation, mitigated chronic cardiac inflammation and fibrosis, and prevented juvenile onset cardiomyopathy in the D2-mdx mice. These studies offer insights into pediatric onset of cardiac damage in DMD, a new therapeutic target, and identify a drug-based potential therapy.
ABSTRACT
This study presents an innovative approach for targeted drug delivery through the development of Glycyrrhizic acid-loaded zein nanoparticles (GA-LNPs) as a proficient carrier system. The juxtaposition of zein, a hydrophobic biological macromolecule as a protein carrier, and Glycyrrhizic acid (GA), a hydrophilic therapeutic compound, exemplifies the adaptability of hydrocolloids within cutting-edge drug delivery systems. The characterization and functional traits of research encompass multifaceted analyses of natural macromolecules, which elucidate the homogeneous and spherical morphology of GA-LNPs with an average size of 170.49 nm. The controlled drug release profile of GA, orchestrated under simulated gastrointestinal conditions, adheres to diffusion-based Higuchi kinetics, reflecting the controlled release of the natural macromolecules. The intermolecular interactions among Zein, GA, and cross-linker EDC, facilitated through molecular dynamics simulations, fortify the structural integrity of the encapsulation matrix. In Vitro studies revealed enhanced cellular uptake of GA-LNPs in MCF-7 breast cancer cells. This cellular internalization was further confirmed through cytotoxicity assessments using MTT and apoptosis assays (fluorescence microscopy), which demonstrated the prominent anticancer effects of GA-LNPs on MCF-7 in time/dose-dependent manner. The successful formulation of GA-LNPs, coupled with their sustained release and potent anticancer properties, makes them a potential platform for advanced targeted therapeutic strategies in biomedical applications.
Subject(s)
Breast Neoplasms , Drug Carriers , Glycyrrhizic Acid , Nanoparticles , Zein , Glycyrrhizic Acid/chemistry , Glycyrrhizic Acid/pharmacology , Zein/chemistry , Humans , Nanoparticles/chemistry , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , MCF-7 Cells , Drug Carriers/chemistry , Drug Delivery Systems , Drug Liberation , Apoptosis/drug effects , Molecular Dynamics Simulation , Female , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Computer Simulation , Cell Survival/drug effectsABSTRACT
Breast cancer is a major cause of death in women worldwide leading to requirement of new therapeutic strategies. Silymarin demonstrated the anti-cancer activity however, due to low bioavailability its use is restricted. This study aimed to improve the solubility of silymarin by developing a silymarin loaded zein nanoparticles (SLNPs) which was stabilized by beta cyclodextrin. Comprehensive physiochemical characterization studies based on DLS, FTIR, UV-Vis Spectroscopy, FE-SEM, TEM, XRD, DSC, NMR and TGA confirmed the successful synthesis of SLNPs via an anti-solvent precipitation method. FE-SEM and TEM images demonstrated the uniform size and spherical shape of nanoparticles with encapsulation and loading efficiencies of 84.32 ± 1.9 % and 15.25 ± 2.4 % respectively. The zein protein interaction with silymarin, and ß-cyclodextrin was shown to be beneficial via the use of molecular simulations and binding energy calculations. Cellular studies demonstrated dose and time dependent cytotoxicity of SLNPs on MCF-7 breast cancer cell. FACS, qRT-PCR and Western blotting showed Bax (pro-apoptotic) upregulation while Bcl-2 (anti-apoptotic) downregulation. Our findings suggest that these loaded nanoparticles are more efficient than pure drug, enhancing its bioavailability and paving the path for developing it as a promising nutraceutical to treat breast cancer.
Subject(s)
Breast Neoplasms , Nanoparticles , Silymarin , Zein , Female , Humans , Silymarin/pharmacology , Silymarin/chemistry , Zein/chemistry , Molecular Docking Simulation , Breast Neoplasms/drug therapy , Nanoparticles/chemistry , Particle SizeABSTRACT
Annexins are cytosolic proteins with conserved three-dimensional structures that bind acidic phospholipids in cellular membranes at elevated Ca2+ levels. Through this they act as Ca2+-regulated membrane binding modules that organize membrane lipids, facilitating cellular membrane transport but also displaying extracellular activities. Recent discoveries highlight annexins as sensors and regulators of cellular and organismal stress, controlling inflammatory reactions in mammals, environmental stress in plants, and cellular responses to plasma membrane rupture. Here, we describe the role of annexins as Ca2+-regulated membrane binding modules that sense and respond to cellular stress and share our view on future research directions in the field.
Subject(s)
Annexins , Taste , Animals , Annexins/chemistry , Cell Membrane/metabolism , Signal Transduction , Biological Transport , Calcium/metabolism , Mammals/metabolismABSTRACT
Cyanobacteria are photosynthetic organisms and challenged by large number of stresses, especially by ultraviolet radiation (UVR). UVR primarily impacts lipids, proteins, DNA, photosynthetic performance, which lowers the fitness and production of cyanobacteria. UVR has a catastrophic effect on cyanobacterial cells and eventually leads to cell death. UVR tolerance in the Synechocystis was poorly studied. Therefore, we irradiated Synechocystis sp. PCC 6803 to varying hours of photosynthetically active radiations (PAR), PAR + UV-A (PA), and PAR + UV-A + UV-B (PAB) for 48 h. To study the tolerance of Synechocystis sp. PCC 6803 against different UVR. The study shows that Chl a and total carotenoids content increased up to 36 h in PAR and PA, after 36 h a decrease was observed. PC increased up to 4-fold in 48 h of PA irradiation compared to 12 h. Maximum increase in ROS was observed under 48 h PAB i.e., 5.8-fold. Flowcytometry (FCM) based analysis shows that 25% of cells do not give fluorescence of Chl a and H2DCFH. In case of cell viability 10% cells were found to be non-viable in 48 h of PAB irradiance compared to 12 h. From the above study it was found that FCM-based approaches would provide a better understanding of the variations that occurred within the Synechocystis cells compared to fluorescence microscopy-based methods.
Subject(s)
Synechocystis , Ultraviolet Rays , Photosynthesis/radiation effects , Microscopy, FluorescenceABSTRACT
Environmental variation has a significant impact on how organisms, including cyanobacteria, respond physiologically and biochemically. Salinity and ultraviolet radiation (UVR)-induced variations in the photopigments of the rice-field cyanobacterium Nostochopsis lobatus HKAR-21 and its photosynthetic performance was studied. We observed that excessive energy dissipation after UVR is mostly caused by Non-Photochemical Quenching (NPQ), whereas photochemical quenching is important for preventing photoinhibition. These findings suggest that ROS production may play an important role in the UVR-induced injury. To reduce ROS-induced oxidative stress, Nostochopsis lobatus HKAR-21 induces the effective antioxidant systems, which includes different antioxidant compounds like carotenoids and enzymes such as superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX). The study indicates that Nostochopsis lobatus HKAR-21 exposed to photosynthetically active radiation + UV-A + UV-B (PAB) and PAB + NaCl (PABN) had significantly reduced photosynthetic efficiency. Furthermore, maximum ROS was detected in PAB exposed cyanobacterial cells. The induction of lipid peroxidation (LPO) has been investigated to evaluate the impact of UVR on the cyanobacterial membrane in addition to enzymatic defensive systems. The maximal LPO level was found in PABN treated cells. Based on the findings of this research, it was concluded that salinity and UVR had collegial effects on the major macromolecular components of the rice-field cyanobacterium Nostochopsis lobatus HKAR-21.
Subject(s)
Cyanobacteria , Oryza , Ultraviolet Rays , Antioxidants/pharmacology , Oryza/radiation effects , Sodium Chloride/pharmacology , Reactive Oxygen Species , Cyanobacteria/metabolism , Photosynthesis/radiation effects , Superoxide Dismutase/metabolismABSTRACT
This study summarizes the response of cyanobacterium Spirulina subsalsa HKAR-19 under simulated light conditions of photosynthetically active radiation (PAR), PAR+UV-A (PA), and PAR+UV-A+UV-B (PAB). Exposure to UV radiation caused a significant (P < 0.05) decrease in chlorophyll a, phycocyanin, and total protein. In contrast, total carotene content increased significantly (P < 0.05) under PA and PAB with increasing irradiation time. The photosynthetic efficiency of photosystem II also decreased significantly in PA and PAB radiation. We have also recorded a decrease in the fluorescence emission intensity of phycocyanin under PA and PAB exposure. The phycocyanin fluorescence shifted towards shorter wavelengths (blue-shift) after 72 h of PA and PAB exposure. Intracellular reactive oxygen species (ROS) levels increased significantly in PA and PAB. Fluorescence microscopic images showed an increase in green fluorescence, indicating ROS generation in UV radiation. We have also quantified ROS generation using green and red fluorescence ratio represented as G/R ratio. A 2-6-fold increase in antioxidative enzymes activity was observed to overcome the damaging effects caused by UV stress as compared to untreated control cultures. The lipid peroxidation was assessed in terms of malondialdehyde content which increases significantly (P < 0.05) as the duration of exposure increases. These results suggest that a combined effect of PAR, UV-A, and UV-B was more deleterious than an individual one.
ABSTRACT
Thymic stromal lymphopoietin (TSLP) is a primarily epithelial-derived cytokine that drives type 2 allergic immune responses. Early life viral respiratory infections elicit high TSLP production, which leads to the development of type 2 inflammation and airway hyperreactivity. The goal of this study was to examine in vivo and in vitro the human airway epithelial responses leading to high TSLP production during viral respiratory infections in early infancy. A total of 129 infants (<1-24 m, median age 10 m) with severe viral respiratory infections were enrolled for in vivo (n = 113), and in vitro studies (n = 16). Infants were classified as 'high TSLP' or 'low TSLP' for values above or below the 50th percentile. High versus low TSLP groups were compared in terms of type I-III IFN responses and production of chemokines promoting antiviral (CXCL10), neutrophilic (CXCL1, CXCL5, CXCL8), and type 2 responses (CCL11, CCL17, CCL22). Human infant airway epithelial cell (AEC) cultures were used to define the transcriptomic (RNAseq) profile leading to high versus low TSLP responses in vitro in the absence (baseline) or presence (stimulated) of a viral mimic (poly I:C). Infants in the high TSLP group had greater in vivo type III IFN airway production (median type III IFN in high TSLP 183.2 pg/mL vs. 63.4 pg/mL in low TSLP group, p = 0.007) and increased in vitro type I-III IFN AEC responses after stimulation with a viral mimic (poly I:C). At baseline, our RNAseq data showed that infants in the high TSLP group had significant upregulation of IFN signature genes (e.g., IFIT2, IFI6, MX1) and pro-inflammatory chemokine genes before stimulation. Infants in the high TSLP group also showed a baseline AEC pro-inflammatory state characterized by increased production of all the chemokines assayed (e.g., CXCL10, CXCL8). High TSLP responses in the human infant airways are associated with pre-activated airway epithelial IFN antiviral immunity and increased baseline AEC production of pro-inflammatory chemokines. These findings present a new paradigm underlying the production of TSLP in the human infant airway epithelium following early life viral exposure and shed light on the long-term impact of viral respiratory illnesses during early infancy and beyond childhood.
ABSTRACT
Cells are routinely exposed to agents that cause plasma membrane (PM) injury. While pore-forming toxins (PFTs), and chemicals cause nanoscale holes dispersed throughout the PM, mechanical trauma causes focal lesions in the PM. To examine if these distinct injuries share common repair mechanism, membrane trafficking is monitored as the PM repairs from such injuries. During the course of repair, dispersed PM injury by the PFT Streptolysin O activates endocytosis, while focal mechanical injury to the PM inhibits endocytosis. Consequently, acute block of endocytosis prevents repair of diffuse, but not of focal injury. In contrast, a chronic block in endocytosis depletes cells of early endosomes and inhibits repair of focal injury. This study finds that both focal and diffuse PM injury activate Ca2+ -triggered exocytosis of early endosomes. The use of markers including endocytosed cargo, Rab5, Rab11, and VAMP3, all reveal injury-triggered exocytosis of early endosomes. Inhibiting Rab5 prevents injury-triggered early endosome exocytosis and phenocopies the failed PM repair of cells chronically depleted of early endosomes. These results identify early endosomes as a Ca2+ -regulated exocytic compartment, and uncover the requirement of their dual functions - endocytosis and regulated exocytosis, to differentially support PM repair based on the nature of the injury.
Subject(s)
Calcium , Endosomes , Endosomes/metabolism , Calcium/metabolism , Cell Membrane/metabolism , Endocytosis , ExocytosisABSTRACT
Cordycepin gets rapidly metabolized in the body into inactive form due to its structural similarity to adenosine, thus inhibiting its development as a medicinal agent. This study was aimed to improve the solubility and stability of cordycepin, a potential drug with known antiproliferative activity, by encapsulating it in bovine serum albumin: ß-cyclodextrin nanoparticles. Cordycepin-loaded nanoparticles (CLNPs) were synthesized using the antisolvent method and characterized thoroughly using various techniques. Our dynamic light scattering measurement showed a particle size and zeta potential of 160 ± 2.75 nm and -20.21 ± 2.1 mV, respectively, for CLNPs. Transmission electron microscopy studies revealed that particles were spherical in morphology. These CLNPs showed sustained release of cordycepin with encapsulation and loading efficiency of 81.62 ± 1.5 and 27.02 ± 2.0%, respectively, based on high-performance liquid chromatography and UV-vis studies. Based on differential scanning calorimetry and zeta potential studies, CLNPs improve cordycepin stability and solubility. Our molecular simulations and binding energy calculation also showed favorable protein interaction between cordycepin, bovine serum albumin, and ß-cyclodextrin, further supporting the notion of improved stability. In vitro cytotoxicity, apoptosis, and cellular uptake studies on breast cancer cells showed that the synthesized nanoparticles had greater cytotoxicity as compared to free cordycepin.
Subject(s)
Nanoparticles , Serum Albumin, Bovine , Serum Albumin, Bovine/chemistry , Drug Carriers/chemistry , Deoxyadenosines/pharmacology , Nanoparticles/chemistry , Particle SizeABSTRACT
Fibro/adipogenic progenitors (FAPs) are skeletal muscle stromal cells that support regeneration of injured myofibers and their maintenance in healthy muscles. FAPs are related to mesenchymal stem cells (MSCs/MeSCs) found in other adult tissues, but there is poor understanding of the extent of similarity between these cells. Using single-cell RNA sequencing (scRNA-seq) datasets from multiple mouse tissues, we have performed comparative transcriptomic analysis. This identified remarkable transcriptional similarity between FAPs and MeSCs, confirmed the suitability of PDGFRα as a reporter for FAPs, and identified extracellular proteolysis as a new FAP function. Using PDGFRα as a cell surface marker, we isolated FAPs from healthy and dysferlinopathic mouse muscles and performed scRNA-seq analysis. This revealed decreased FAP-mediated Wnt signaling as a potential driver of FAP dysfunction in dysferlinopathic muscles. Analysis of FAPs in dysferlin- and dystrophin-deficient muscles identified a relationship between the nature of muscle pathology and alteration in FAP gene expression.
ABSTRACT
Lack of dystrophin expression is the underlying genetic basis for Duchenne muscular dystrophy (DMD). However, disease severity varies between patients, based on specific genetic modifiers. D2-mdx is a model for severe DMD that exhibits exacerbated muscle degeneration and failure to regenerate even in the juvenile stage of the disease. We show that poor regeneration of juvenile D2-mdx muscles is associated with an enhanced inflammatory response to muscle damage that fails to resolve efficiently and supports the excessive accumulation of fibroadipogenic progenitors (FAPs), leading to increased fibrosis. Unexpectedly, the extent of damage and degeneration in juvenile D2-mdx muscle is significantly reduced in adults, and is associated with the restoration of the inflammatory and FAP responses to muscle injury. These improvements enhance regenerative myogenesis in the adult D2-mdx muscle, reaching levels comparable to the milder B10-mdx model of DMD. Ex vivo co-culture of healthy satellite cells (SCs) with juvenile D2-mdx FAPs reduces their fusion efficacy. Wild-type juvenile D2 mice also manifest regenerative myogenic deficit and glucocorticoid treatment improves their muscle regeneration. Our findings indicate that aberrant stromal cell responses contribute to poor regenerative myogenesis and greater muscle degeneration in juvenile D2-mdx muscles and reversal of this reduces pathology in adult D2-mdx muscle, identifying these responses as a potential therapeutic target for the treatment of DMD.
ABSTRACT
Macrophages are essential for skeletal muscle homeostasis, but how their dysregulation contributes to the development of fibrosis in muscle disease remains unclear. Here, we used single-cell transcriptomics to determine the molecular attributes of dystrophic and healthy muscle macrophages. We identified six clusters and unexpectedly found that none corresponded to traditional definitions of M1 or M2 macrophages. Rather, the predominant macrophage signature in dystrophic muscle was characterized by high expression of fibrotic factors, galectin-3 (gal-3) and osteopontin (Spp1). Spatial transcriptomics, computational inferences of intercellular communication, and in vitro assays indicated that macrophage-derived Spp1 regulates stromal progenitor differentiation. Gal-3+ macrophages were chronically activated in dystrophic muscle, and adoptive transfer assays showed that the gal-3+ phenotype was the dominant molecular program induced within the dystrophic milieu. Gal-3+ macrophages were also elevated in multiple human myopathies. These studies advance our understanding of macrophages in muscular dystrophy by defining their transcriptional programs and reveal Spp1 as a major regulator of macrophage and stromal progenitor interactions.
Subject(s)
Macrophages , Transcriptome , Mice , Animals , Humans , Mice, Inbred C57BL , Macrophages/metabolism , Muscle, Skeletal/metabolism , Galectin 3/genetics , Galectin 3/metabolism , FibrosisABSTRACT
The monocytic/macrophage system is essential for skeletal muscle homeostasis, but its dysregulation contributes to the pathogenesis of muscle degenerative disorders. Despite our increasing knowledge of the role of macrophages in degenerative disease, it still remains unclear how macrophages contribute to muscle fibrosis. Here, we used single-cell transcriptomics to determine the molecular attributes of dystrophic and healthy muscle macrophages. We identified six novel clusters. Unexpectedly, none corresponded to traditional definitions of M1 or M2 macrophage activation. Rather, the predominant macrophage signature in dystrophic muscle was characterized by high expression of fibrotic factors, galectin-3 and spp1. Spatial transcriptomics and computational inferences of intercellular communication indicated that spp1 regulates stromal progenitor and macrophage interactions during muscular dystrophy. Galectin-3 + macrophages were chronically activated in dystrophic muscle and adoptive transfer assays showed that the galectin-3 + phenotype was the dominant molecular program induced within the dystrophic milieu. Histological examination of human muscle biopsies revealed that galectin-3 + macrophages were also elevated in multiple myopathies. These studies advance our understanding of macrophages in muscular dystrophy by defining the transcriptional programs induced in muscle macrophages, and reveal spp1 as a major regulator of macrophage and stromal progenitor interactions.
ABSTRACT
In spite of various reports on perinatal outcomes of coronavirus disease 2019 (COVID-19) during pregnancies, the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on unborn babies and pregnant mothers are still mysterious. The goal of our research is to examine the perceived fetomaternal outcomes of COVID-19 during pregnancy. A total of 396 pregnant women were admitted to the Department of Gynaecology and Obstetrics, Pt. JNM Medical College, Raipur, Chhattisgarh, India, during the period from July 20, 2020 to January 6, 2021. The presence of SARS-CoV-2 in different biological samples was recorded via positive quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) test results. All the newborns delivered from the infected pregnant mothers were tested as RT-PCR negative. Negative findings of RT-PCR for respiratory swabs of newborns, amniotic fluid, placental tissue, breast milk, vaginal swabs, and cord blood indicated no transmission of the virus from mother to baby. However, maternal outcomes, such as hospitalization (46.96%), preeclampsia (13.88%), pre-term birth (14.39%), prelabor rupture of membranes (PROM) before 34 weeks (3.78%), PROM before 37 weeks (2.77%), vaginal bleeding (4.29%), postpartum hemorrhage (2.52%), pregnancy-induced hypertension (1.51%), and neonatal outcomes such as low birth weight ≤1.5 kg (6.59) and 1.6-2.4 kg (39.34%), intrauterine deaths (IUD) (0.50%), fetal distress (22.33%), NICU admission (5.58%), meconium-stained liquor (14.46%), diarrhea (0.25%), and low APGAR score 4-6 at 1 min (20.54%), were observed. The results of the present study indicate that SARS-CoV-2-induced complications during pregnancy must be taken seriously. Intrauterine fetal deaths occurred at lower rates. There is no substantial proof of vertical perinatal transmission of the virus, as none of the neonates had tested positive for COVID-19.
ABSTRACT
Lack of dystrophin is the genetic basis for the Duchenne muscular dystrophy (DMD). However, disease severity varies between patients, based on specific genetic modifiers. D2- mdx is a model for severe DMD that exhibits exacerbated muscle degeneration and failure to regenerate even in the juvenile stage of the disease. We show that poor regeneration of juvenile D2- mdx muscles is associated with enhanced inflammatory response to muscle damage that fails to resolve efficiently and supports excessive accumulation of fibroadipogenic progenitors (FAPs). Unexpectedly, the extent of damage and degeneration of juvenile D2- mdx muscle is reduced in adults and is associated with the restoration of the inflammatory and FAP responses to muscle injury. These improvements enhance myogenesis in the adult D2- mdx muscle, reaching levels comparable to the milder (B10- mdx ) mouse model of DMD. Ex vivo co-culture of healthy satellite cells (SCs) with the juvenile D2- mdx FAPs reduced their fusion efficacy and in vivo glucocorticoid treatment of juvenile D2 mouse improved muscle regeneration. Our findings indicate that aberrant stromal cell response contributes to poor myogenesis and greater muscle degeneration in dystrophic juvenile D2- mdx muscles and reversal of this reduces pathology in adult D2- mdx mouse muscle, identifying these as therapeutic targets to treat dystrophic DMD muscles.
ABSTRACT
Cyanobacteria have been recognized as a rich source of bioactive metabolites with potential biotechnological applications in the pharmacological industry. The chemically diverse natural compounds or their analogues cause cytotoxicity. They may kill various cancer cells by inducing apoptosis or changing the activation of cell signaling, particularly involving the protein kinase-C family of enzymes, mitochondrial dysfunctions, and oxidative damage. B cell lymphoma 2 (Bcl-2) is an essential component of apoptosis and is an antiapoptotic molecule. The key apoptotic regulators associated with cancer are members of the Bcl-2 protein family, the key member of which is Bcl-2. The Bcl-2 protein is a promising target for the emergence of new anti-tumor therapies because of its critical role in controlling apoptosis. This review explores the significance of Bcl-2 in the onset of cancer; it may be used as a target for developing high-quality drug therapies to treat various tumors. In addition, a number of computational techniques were used to identify novel hit compounds that may act as inhibitors of the apoptotic protein Bcl-2, including virtual screening, toxicity prediction, and drug-likeness analysis. Twenty-three compounds were assessed as potential hits against Bcl-2, and these compounds were subjected to ADMET property prediction. Dendroamide A and Welwitindolinone A appear to be the most stable and effective drugs against Bcl-2 out of all those evaluated. This article gives an overview of the bioactive compounds produced by cyanobacteria that have anticancer properties and may be exploited to create novel anticancer medications in the future.
Subject(s)
Antineoplastic Agents , Cyanobacteria , Neoplasms , Humans , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Apoptosis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry , Apoptosis Regulatory Proteins/pharmacology , Neoplasms/drug therapy , Cell Line, TumorABSTRACT
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) affects human respiratory function that causes COVID-19 disease. COVID-19 has spread rapidly all over the world and became a pandemic within no time. Therefore, it is the need of hour to screen potential lead candidates from natural resources like edible mushrooms and marine fungi. These natural resources are very less explored till now and known to be the source for many medicinal compounds with several health benefits. These medicinal compounds can be easily exploited for the faster development of nutraceuticals for controlling SARS-CoV-2 infections. Our Insilico research suggests, bioactive compounds originating from mushroom and marine fungi shows strong potential to interact with ACE2 receptor or main protease of SARS-CoV-2, showing the inhibition activity towards the enzymatic protease. We performed a series of Insilico studies for the validation of our results, which includes Molecular docking, drug likeness property investigation by Swiss ADME tools, MD simulation, and thermodynamically stable free binding energy calculation. Overall, these results suggest that Ganodermadiol and Heliantriol F bioactive compounds originating from edible mushroom has strong potential to be developed as low-cost nutraceutical against SARS-CoV-2 viral infection. The drug candidate isolated from marine fungi and edible mushroom are highly unexplored for the development of potential alternative drug against SARS-CoV-2 virus with minimum side effects. Though our in silico studies of these compounds are showing a promising results against SARS-CoV-2 main protease and ACE2 receptor binding domain, the effectiveness of these bioactive compounds should be further validated by proper clinical trials.Communicated by Ramaswamy H. Sarma.
Subject(s)
Agaricales , COVID-19 , Humans , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Bioprospecting , Molecular Docking Simulation , Antiviral Agents/pharmacology , Dietary Supplements , Protease Inhibitors , Molecular Dynamics SimulationABSTRACT
Plasma membrane injury activates membrane trafficking and remodeling events that are required for the injured membrane to repair. With the rapidity of the membrane repair process, the repair response needs to be monitored at high temporal and spatial resolution. In this chapter, we describe the use of live cell optical imaging approaches to monitor injury-triggered bulk and individual vesicle endocytosis. Use of these approaches allows quantitatively assessment of the rate of retrieval of the injured plasma membrane by bulk endocytosis as well as by endocytosis of individual caveolae following plasma membrane injury.