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1.
Artigo em Inglês | MEDLINE | ID: mdl-38584562

RESUMO

BACKGROUND: Plant species of the genus Daphne clasps a historical background with a potential source of bioactive phytochemicals such as flavonoids and daphnodorins. These compounds manifest a significant chemotaxonomic value in drug discovery. Their flair comprehensive pharmacological, phytochemical, biological, catalytic, and clinical utilities make them exclusively unique. This study was conducted to investigate the optimization and structure-based virtual screening of these peculiar analogs. The majority of the active constituents of medicines are obtained from natural products. Previously, before the invention of virtual screening methods or techniques, almost 80% of drugs were obtained from natural resources. Comparing reported data to drug discovery from 1981 to 2007 signifies that half of the FDA-approved drugs are obtained from natural resources. It has been reported that structures of natural products that have particularities of structural diversity, biochemical specification, and molecular properties make them suitable products for drug discovery. These products basically have unique chiral centers which increase their structural complexity than the synthesized drugs. METHOD: This work aimed to probe the use of daphnodorins analogs for the first time as antidiabetic inhibitors based on significant features and to determine the potential of daphnodorin analogs as antidiabetic inhibitors through computational analysis and structure-based virtual screening. A dataset of 38 compounds was selected from different databases, including PubChem and ZINC, for computational analysis, and optimized compounds were docked against various co-crystallized structures of inhibitors, antagonists, and receptors which were downloaded from PDB by using AutoDock Vina (by employing Broyden-Fletcher-Goldfarb-Shanno method), Discovery studio visualizer 2020, PYMOL (Schrodinger). Docking results were further validated by Molecular dynamic simulation and MM-GBSA calculation. Quantitative structure-activity relationship (QSAR) was reported by using Gaussian 09W by intimating Density Functional Theory (DFT). Using this combination of multi-approach computational strategy, 14 compounds were selected as potential exclusive lead compounds, which were analyzed through ADMET studies to pin down their druglike properties and toxicity. RESULT: At significant phases of drug design approaches regular use of molecular docking has helped to promote the separation of important representatives from 38 pharmaceutically active compounds by setting a threshold docking score of -9.0 kcal/mol which was used for their exposition. Subsequently, by employing a threshold it was recognized that 14 compounds proclaimed this threshold for antidiabetic activity. Further, molecular dynamic simulation, MM-GBSA, ADMET, and DFT results screened out daphnegiralin B4 (36) as a potential lead compound for developing antidiabetic agents. CONCLUSION: Our analysis took us to the conclusion that daphnegiralin B4 (36) among all ligands comes out to be a lead compound having drug-like properties among 38 ligands being non-carcinogenic and non-cytotoxic which would benefit the medical community by providing significant drugs against diabetes. Pragmatic laboratory investigations identified a new precursor to open new doors for new drug discovery.

2.
J Biomol Struct Dyn ; : 1-23, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38334277

RESUMO

Flavonoids demonstrate beneficial effects on human health because flavonoids contain important biological properties. Kaempferol is a flavonol, type of flavonoid found in eatable plants and in plants usually employed in ancient drugs (Moringa oleifera, Tilia spp., fern genus spp. and gingko etc.). Some medicinal studies have shown that the use of foods full of kaempferol decreases the risk of many (cancer, vascular) diseases. All the data of 50 kaempferol derivatives were collected from PubChem database. Through Schrödinger software, 3D-QSAR study was performed for 50 compounds by using method of field base. Conformer of kaempferol derivatives was docked against anti-diabetic, anti-microbial co-crystal structures and protein. To monitor the best anti-diabetic and antibacterial agent, particular kaempferol derivatives were downloaded from PubChem database. Virtual screening by molecular docking provided four lead compounds with four different proteins. These hit compounds were found to be potent inhibitor for diabetic enzymes alpha-amylase and DPP IV and had the potential to suppress DNA gyrase and dihydrofolate reductase synthesis. Molecular dynamic simulation of docked complexes evaluates the value of root mean square fluctuation by iMOD server. Kaempferol 3-O-alpha-L-(2, 3-di-Z-p-coumaroyl) rhamnoside (42) compound used as anti-diabetic and kaempferol 3-O-gentiobioside (3) as antibacterial with good results can be used for drug discovery.Communicated by Ramaswamy H. Sarma.

3.
J Biomol Struct Dyn ; : 1-22, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38299565

RESUMO

Breast cancer is a major issue of investigation in drug discovery due to its rising frequency and global dominance. Plants are significant natural sources for the development of novel medications and therapies. Medicinal mushrooms have many biological response modifiers and are used for the treatment of many physical illnesses. In this research, a database of 89 macro-molecules with anti-breast cancer activity, which were previously isolated from the mushrooms in literature, has been selected for the three-dimensional quantitative structure-activity relationships (3D-QSAR) studies. The 3D-QSAR model was necessarily used in Pharmacopoeia virtual evaluation of the database to develop novel MCF-7 inhibitors. With the known potential targets of breast cancer, the docking studies were achieved. Using molecular dynamics simulations, the targets' stability with the best-chosen natural product molecule was found. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity of three compounds, resulting after the docking study, were predicted. The compound C1 (Pseudonocardian A) showed the features of effective compounds because it has bioavailability from different coral species and is toxicity-free for the prevention of many dermatological illnesses. C1 is chemically active and possesses charge transfer inside the monomer, as seen by the band gaps of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) electrons. The reactivity descriptors ionization potential, electron affinity, chemical potential (µ), hardness (η), softness (S), electronegativity (χ), and electrophilicity index (ω) have been estimated using the energies of frontier molecular orbitals (HOMO-LUMO). Additionally, molecular electrostatic potential maps were created to show that the C1 is reactive.Communicated by Ramaswamy H. Sarma.


The selected compounds from the mushroom were evaluated as potential breast cancer MCF-7 cell line inhibitor.Ligand-based 3D-QSAR study to analyze the structurally diverse compounds with experimentally reported IC50.Pharmacophore-based virtual screening of compounds.Molecular docking analysis pointed out the vital interaction of the hit with the protein's amino acids.Absorption, distribution, metabolism, and excretion (ADME) and toxicity properties of the lead compounds were examined.

4.
ACS Omega ; 9(2): 2161-2182, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38250382

RESUMO

BACKGROUND: Structure-activity relationship (SAR) is considered to be an effective in silico approach when discovering potential antagonists for breast cancer due to gene mutation. Major challenges are faced by conventional SAR in predicting novel antagonists due to the discovery of diverse antagonistic compounds. Methodologyand Results: In predicting breast cancer antagonists, a multistep screening of phytochemicals isolated from the seeds of the Citrus sinensis plant was applied using feasible complementary methodologies. A three-dimensional quantitative structure-activity relationship (3D-QSAR) model was developed through the Flare project, in which conformational analysis, pharmacophore generation, and compound alignment were done. Ten hit compounds were obtained through the development of the 3D-QSAR model. For exploring the mechanism of action of active compounds against cocrystal inhibitors, molecular docking analysis was done through Molegro software (MVD) to identify lead compounds. Three new proteins, namely, 1T15, 3EU7, and 1T29, displayed the best Moldock scores. The quality of the docking study was assessed by a molecular dynamics simulation. Based on binding affinities to the receptor in the docking studies, three lead compounds (stigmasterol P8, epoxybergamottin P28, and nobiletin P29) were obtained, and they passed through absorption, distribution, metabolism, and excretion (ADME) studies via the SwissADME online service, which proved that P28 and P29 were the most active allosteric inhibitors with the lowest toxicity level against breast cancer. Then, density functional theory (DFT) studies were performed to measure the active compound's reactivity, hardness, and softness with the help of Gaussian 09 software. CONCLUSIONS: This multistep screening of phytochemicals revealed high-reliability antagonists of breast cancer by 3D-QSAR using flare, docking analysis, and DFT studies. The present study helps in providing a proper guideline for the development of novel inhibitors of BRCA1 and BRCA2.

5.
ACS Omega ; 9(1): 730-740, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38222607

RESUMO

This review deals with computational study of polyphenolic compounds of medicinal importance and interest for drug development. Herein, four polyphenolic compounds comprising catechol (1), caffeic acid (II), gallic acid (III), and pyrogallol (IV) have been isolated from a medicinal specie, Fagonia indica, by applying silica gel column chromatography. These compounds were identified by using gas chromatography-mass spectrometry (GC-MS) analysis and confirmed by geometric computational analysis. According to computational results, caffeic acid has shown the highest biological activation due to higher chemical softness, electronegativity (χ (eV) = -648.644), and electrostatic potential value (-8.424 × 10-2 to +8.424 × 10-2), while smaller values of chemical potential (-0.269), ELUMO (-0.080), and energy gap (ΔE = 0.149). The Mulliken atomic charges were calculated by using DFT/B3LYP with basis set 6-311G for the determination of active sites. The oxygen atom of catechol showed highest nucleophilic characteristic with a more negative charge (08 = -0.695), and pyrogallol indicated a strong electrophilic center at C14 = 0.415 with a higher positive charge. Moreover, UV-visible absorption spectra and a detailed study of vibrational frequencies for all phenolic compounds by employing the DFT approach with 3-21G, 6-31G, and 6-311G basis sets at the ground-state level showed the great agreement with experimental results. ANOVA has been applied to validate the theoretical data. Results suggest that compounds I-IV are suitable in diverse fields.

6.
J Steroid Biochem Mol Biol ; 237: 106427, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38008365

RESUMO

Ecdysteroids, a class of naturally isolated polyhydroxylated sterols, stands at a very good place in the pharmaceutical industry from their medicinal point of views like anti-inflammatory, neuroprotective, anti-microbial, anti-diabetic, antioxidant, and anti-tumor effects. Due to their excellent antioxidant and anti-microbial potential, ecdysteroids have extensive use in skin products, especially derma creams. To monitor the best anti-acne phytoecdysteroids, here made use of different computational approaches, by using the rapid, easy, cost-effective and high throughput method to screen and identify ecdysteroids as androgen receptor inhibitors. 3D-QSAR study was carried out on a dataset of ecdysteroids by using comparative molecular field analysis (CoMFA) to determine the factors responsible for the activity of compounds. Statistically a cross-validated (q2) 0.1457 and regression coefficient (r2) 0.9713 indicated the best model. Contour map results showed the influence of steric effect to enhance activity. A molecular docking analysis was done to further find out the binding sites and their anti-acne potential against three crystal structured macromolecules (PDB ID: 2REQ, 2BAC, 4EM0). Docking results were further evaluated by prime MM-GBSA analysis and findings confirmed the accuracy. Toxicity by ADMET assessment was carried out and M2 was found as lead druglike with best anti-acne activity against Propionium acnes GehA lipase bacteria after passing all filters. This research study is novel because it is representing first effort to explore ecdysteroids class for their high therapeutic output as androgen receptor inhibitor by using computational tools and expectedly led to novel scaffold for androgen receptor inhibitor. This is a novel and new approach to investigate the ecdysteroids for first time for their practical applications.


Assuntos
Relação Quantitativa Estrutura-Atividade , Receptores Androgênicos , Simulação de Acoplamento Molecular , Ecdisteroides , Antioxidantes
7.
Future Med Chem ; 15(12): 1069-1089, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37503685

RESUMO

Background: Due to the close relationship of diabetes with hypertension reported in various research, a set of pyridine derivatives with US FDA-approved drug cores were designed and integrated by artificial intelligence. Methods: Novel pyridines were designed and synthesized. Compounds MNS-1-MNS-4 were evaluated for their structure and were screened for their in vitro antidiabetic (α-amylase) activity and anticancer (HepG2) activity by methyl thiazolyl tetrazolium assay. Comparative 3D quantitative structure-activity relationship analysis and pharmacophore generation were carried out. Results: The study revealed MNS-1 and MNS-4 as good alternatives to acarbose as antidiabetic agents, and MNS-2 as a more viable, better alternative to doxorubicin in the methyl thiazolyl tetrazolium assay. Conclusion: This combination of studies identifies new and more active analogs of existing FDA-approved drugs for the treatment of diabetes.


Assuntos
Inteligência Artificial , Hipoglicemiantes , Hipoglicemiantes/farmacologia , Simulação de Acoplamento Molecular , Piridinas/química , Relação Estrutura-Atividade , Estrutura Molecular
8.
Front Chem ; 11: 1197665, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37441272

RESUMO

Breast cancer covers a large area of research because of its prevalence and high frequency all over the world. This study is based on drug discovery against breast cancer from a series of imidazole derivatives. A 3D-QSAR and activity atlas model was developed by exploring the dataset computationally, using the machine learning process of Flare. The dataset of compounds was divided into active and inactive compounds according to their biological and structural similarity with the reference drug. The obtained PLS regression model provided an acceptable r 2 = 0.81 and q2 = 0.51. Protein-ligand interactions of active molecules were shown by molecular docking against six potential targets, namely, TTK, HER2, GR, NUDT5, MTHFS, and NQO2. Then, toxicity risk parameters were evaluated for hit compounds. Finally, after all these screening processes, compound C10 was recognized as the best-hit compound. This study identified a new inhibitor C10 against cancer and provided evidence-based knowledge to discover more analogs.

9.
Nat Prod Res ; 37(11): 1822-1828, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36008875

RESUMO

Plant-derived compounds represent an important source for developing innovative drugs. One of the widely distributed plants, especially in Afghanistan and Pakistan, Seriphidium stenocephalum, was investigated in this study to identify bioactive compounds. The plant extract was subjected to silica gel column chromatography, four phenolic acid derivatives were isolated, while stenocephol was obtained by ethyl acetate fraction. Stenocephol was subjected to experimental screening for anti-diabetic and anti-cancer activities, measuring its inhibitory potency against glycogen phosphorylase, and its cytotoxicity against HepG2 cells. Further insights into the mechanism of action of stenocephol were obtained from a computational investigation. Stenocephol showed a dose-dependent manner of inhibition against glycogen phosphorylase and HepG2 cells in the low micromolar range. Notably, coupling in vitro and computational investigation, we identified the natural product stenocephol as a possible anti-diabetic and anti-cancer agent, representing a possible starting point for developing novel therapeutics, enriching the armamentarium against the mentioned diseases.


Assuntos
Artemisia , Diabetes Mellitus , Humanos , Células Hep G2 , Fenóis , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Glicogênio Fosforilase
10.
CNS Neurol Disord Drug Targets ; 21(1): 62-76, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33719979

RESUMO

Parkinson's Disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Though significant insights into the molecular-biochemical-cellular-behavioral basis of PD have been understood, there is no appreciable treatment available till date. Current therapies provide symptomatic relief without any influence on the progression of the disease. Stem cell therapy has been vigorously explored to treat PD. In this comprehensive review, we analyze various stem cell candidates for treating PD and discuss the possible mechanisms. We advocate the advantage of using neural crest originated Dental Pulp Stem Cells (DPSC) due to their predisposition towards neural differentiation and their potential to regenerate neurons far better than commonly used bone marrow derived mesenchymal stem cells (BM-MSCs). Eventually, we highlight the current challenges in the field and the strategies, which may be used for overcoming the impediments.


Assuntos
Polpa Dentária/transplante , Doença de Parkinson/terapia , Transplante de Células-Tronco/métodos , Células-Tronco , Animais , Diferenciação Celular , Células Cultivadas , Exossomos , Humanos , Neurônios , Ratos
11.
Molecules ; 26(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34361577

RESUMO

OBJECTIVE: In this study, small molecules possessing tetrahydropyrimidine derivatives have been synthesized having halogenated benzyl derivatives and carboxylate linkage. As previously reported, FDA approved halogenated pyrimidine derivatives prompted us to synthesize novel compounds in order to evaluate their biological potential. METHODOLOGY: Eight pyrimidine derivatives have been synthesized from ethyl acetoacetate, secondary amine, aromatic benzaldehyde by adding catalytic amount of CuCl2·2H2O via solvent less Grindstone multicomponent reagent method. Molecular structure reactivity and virtual screening were performed to check their biological efficacy as an anti-oxidant, anti-cancer and anti-diabetic agent. These studies were supported by in vitro analysis and QSAR studies. RESULTS: After combined experimental and virtual screening 5c, 5g and 5e could serve as lead compounds, having low IC50 and high binding affinity.


Assuntos
Antineoplásicos , Antioxidantes , Hipoglicemiantes , Simulação de Acoplamento Molecular , Pirimidinas , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/síntese química , Antioxidantes/química , Antioxidantes/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Pirimidinas/síntese química , Pirimidinas/química , Pirimidinas/farmacologia
12.
Environ Sci Pollut Res Int ; 28(2): 2082-2096, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32869181

RESUMO

Biomass is one of the prime domestic energy sources in the kitchens and about 60% of households are still using biomass and kerosene for cooking in India. These traditional cooking practices are incompetent as the use of biomass in traditional cookstove produces an enormous amount of carbonaceous aerosols that lead to indoor and outdoor air pollution. Emissions of various pollutants like black carbon (BC), PM10 and PM2.5 from burning of biomass cause serious health impacts like respiratory illness, lung cancer, watering of eyes, coughing, asthma and heart problems especially in women due to higher rate of inhalation of these fine particulate matters during the cooking period. Quantification of BC, PM2.5 and PM10 emissions from a different type of biomass in various types of kitchen arrangements and its associated impacts are poorly examined in India. Hence, daily concentrations of BC, PM2.5 and PM10 were monitored from different types of biomass user's households during January 2018 to December 2019 to assess indoor air quality by using aethalometer and nephelometer (pDR-1500) in three districts (Sitapur, Patna and Murshidabad) of Indo-Gangetic Plains (IGP) where approximately, 96% of rural families rely on biomass cooking. The highest mass concentrations were observed in biomass user's households and cow-dung cake users due to low calorific value. About 30.13% of PM10 and 35.89% of PM2.5 data exceeded the national ambient air quality standard on a daily basis in biomass user's households. A cancer risk assessment was also conducted in terms of mass concentration of these pollutants. The lifespan danger from exposure to BC was 4.33 × 10-7 in indoor for non-ventilated kitchens, 2.63 × 10-7 in indoor for ventilated kitchens, 3.98 × 10-7 in outdoor for separated kitchen, 3.22 × 10-7 for semi-open kitchen and 1.78 × 10-7 for open kitchen. The vulnerability assessment for cancer mortality under exposure of pollution was estimated to be highest for the age group of more than 50 years whereas lowest for the age group of 0-4 years for all kinds of kitchens in the study area.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Biomassa , Carbono , Pré-Escolar , Culinária , Monitoramento Ambiental , Feminino , Humanos , Índia , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Material Particulado/análise
13.
Indian J Pharmacol ; 52(5): 372-377, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33283768

RESUMO

BACKGROUND AND OBJECTIVE: Chronic hepatitis, cirrhosis, and hepatocellular carcinoma are mainly caused by hepatitis C infection. It is a worldwide predominant pathogen and is one of the main causes of healthcare problem in Asia. In the last few decades, there has been a considerable change in the treatment regimen for hepatitis C virus. The objective of this research was to relate the treatment response with sustained viral response in various therapies which have been the standard of care from time to time. MATERIALS AND METHODS: This hospital-based, retrospective-cum-prospective research span over a period of 2 years; we enrolled hepatitis C patients who attended the Department of Gastroenterology and Hepatology, Government Medical College, Srinagar, since June 2015 till May 2017. Subsequently, the database was prepared, containing all the relevant information about these patients. CONCLUSIONS: (i) In retrospective group: The overall efficacy (sustained viral response at 24 weeks [SVR-24]) of pegylated interferon a2a and ribavirin regimen was 90.96%. (ii) In prospective group: The efficacy (SVR) of different regimens was found to be as: sofosbuvir + ribavirin + daclatasvir (SVR-24, 83.33%); sofosbuvir + ribavirin (SVR-12, 94.57%); and sofosbuvir + daclatasvir (SVR-12, 98.00%).


Assuntos
Antivirais/administração & dosagem , Hepacivirus/isolamento & purificação , Hepatite C/tratamento farmacológico , Adulto , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Resposta Viral Sustentada , Resultado do Tratamento , Adulto Jovem
14.
Neurotoxicology ; 81: 89-100, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32905802

RESUMO

Stem cell therapy provides a ray of hope for treating neurodegenerative diseases (ND). Bone marrow mesenchymal stem cells (BM-MSC) were extensively investigated for their role in neuroregeneration. However, drawbacks like painful bone marrow extraction, less proliferation and poor CNS engraftment following systemic injections of BM-MSC prompt us to search for alternate/appropriate source of MSC for treating ND. In this context, dental pulp stem cells (DPSC) could be an alternative to BM-MSC as it possess both mesenchymal and neural characteristic features due to its origin from ectoderm, ease of isolation, higher proliferation index and better neuroprotection. A study on the migration potential of DPSC compared to BM-MSC in a neurodegenerative condition is warranted. Given the neural crest origin, we hypothesize that DPSC possess better migration towards neurodegenerative milieu as compared to BM-MSC. In this prospect, we investigated the migration potential of DPSC in an in vitro neurodegenerative condition. Towards this, transwell, Matrigel and chorioallantoic membrane (CAM) migration assays were carried-out by seeding hippocampal neurons in the lower chamber and treated with 300 µM kainic acid (KA) for 6 h to induce neurodegeneration. Subsequently, the upper chamber of transwell was loaded with DPSC/BM-MSC and their migration potential was assessed following 24 h of incubation. Our results revealed that the migration potential of DPSC/BM-MSC was comparable in non-degenerative condition. However, following injury the migration potential of DPSC towards the degenerating site was significantly higher as compared to BM-MSC. Furthermore, upon exposure of naïve DPSC/BM-MSCs to culture medium derived from neurodegenerative milieu resulted in significant upregulation of homing factors like SDF-1alpha, CXCR-4, VCAM-1, VLA-4, CD44, MMP-2 suggesting that the superior migration potential of DPSC might be due to prompt expression of homing factors in DPSC compared to BM-MSCs.


Assuntos
Quimiotaxia , Polpa Dentária/citologia , Hipocampo/patologia , Degeneração Neural , Comunicação Parácrina , Células-Tronco/fisiologia , Animais , Células Cultivadas , Técnicas de Cocultura , Meios de Cultivo Condicionados/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Ácido Caínico/toxicidade , Células-Tronco Mesenquimais/fisiologia , Camundongos , Fenótipo , Células-Tronco/metabolismo
15.
In Vitro Cell Dev Biol Anim ; 55(4): 272-284, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30798515

RESUMO

Recent approaches of using decellularized organ matrices for cardiac tissue engineering prompted us to culture human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) on the human amniotic membrane (hAM). Since hAM has been used lately to patch diseased hearts in patients and has shown anti-inflammatory and anti-fibrotic benefits, it qualifies as a cardiac compatible and clinically relevant heart tissue scaffold. The aim of this study was to test the ability of the hAM to support attachment, differentiation, and maturation of hiPSC-derived CMs in vitro. hAMs were prepared from term placenta. An in-house generated hiPSC line was used for CM derivation. hiPSC-derived cardiac progenitors were cultured on the surface of cryopreserved hAMs and in the presence of cytokines promoting cardiac differentiation. CMs grown on hAM and popular basement membrane matrix (BMM) Matrigel™ were compared for the following aspects of cardiac development: the morphology of cardiomyocytes with respect to shape and cellular alignments, levels of cardiac-related gene transcript expression, functionality in terms of spontaneous calcium fluxes and mitochondrial densities and distributions. hAM is biocompatible with hiPSC-derived CMs. hAM increased cardiac transcription regulator and myofibril protein transcript expression, accelerated intracellular calcium transients, and enhanced cellular mitochondrial complexity of its cardiomyocytes in comparison to cardiomyocytes differentiated on Matrigel™. Our data suggests that hAM supports differentiation and improves cardiomyogenesis in comparison to Matrigel™. hAMs are natural, easily and largely available. The method of preparing hAM cardiac sheets described here is simple with potential for clinical transplantation. Graphical abstract A An outline of the differentiation protocol with stage-specific growth factors and culture media used. B Cell fates from pluripotent stem cells to cardiomyocytes during differentiation on the amniotic membrane. C-FPhotomicrographs of cells at various stages of differentiation. Scale bars represent 100 µm.


Assuntos
Âmnio/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Cálcio/metabolismo , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Forma Celular/efeitos dos fármacos , Colágeno/farmacologia , Combinação de Medicamentos , Regulação da Expressão Gênica/efeitos dos fármacos , Coração/fisiologia , Humanos , Laminina/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Proteoglicanas/farmacologia , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Engenharia Tecidual
16.
Stem Cell Res ; 27: 15-20, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29291511

RESUMO

Human term placenta is a bulky organ which harbours abundant mesenchymal stromal cells. This study reports isolation and characterization of placental mesenchymal stromal cells (PMSCs) followed by reprogramming of PMSCs to induced pluripotent stem cells (iPSCs). The placental human iPSC (PhiPSC) line is pluripotent with high telomerase activity, genetically identical to parental PMSCs, transgene free, karyotypically normal and differentiates into ectoderm, mesoderm and endoderm both in vitro and in vivo. Thus PMSCs serve as a unique cell type for human perinatal iPSC derivation from extra embryonic tissue.


Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Mesenquimais/citologia , Placenta/citologia , Diferenciação Celular/fisiologia , Células Cultivadas , Feminino , Humanos , Cariótipo , Gravidez , Teratoma/metabolismo
17.
Braz. arch. biol. technol ; 61: e18170802, 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-974100

RESUMO

ABSTRACT The excessive industrial use of dye producing plants has threatened the existence of these species and biodiversity. Exploration of abundantly available natural dye sources not only provide industrial benefits but also share the load of dye yielding plants. In the present study we used the inflorescence of munj sweet cane (Saccharum bengalense Retz.) to extract natural colorant for textile industry. This easily available plant is cheap source of natural colorants and good alternative of synthetic dyes. The munj sweet cane inflorescence extract and fabric was treated with microwave radiations. The dyeing aspects like temperature, time, fabrics to extract ratio, salt type and salt concentrations were optimized. Pre-and post mordanting was carried out and optimized using copper, iron, moringa and turmeric. All the samples were analyzed by spectra flash D65 10 Deg to determine the color strength (%) value. Results proved inflorescence extract of munj sweet cane (RS, two minutes) using aqueous media as a good source of natural dye. Three grams of sodium chloride as exhaustion agent was observed to be the best while 70 0C temperatures gave best colour strength. Among chemical mordants, iron proved to be good one for producing varying shades and better colour strength. Bio mordanting with turmeric was proved to be more beneficial for getting best color strength and new shades.

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