scholarly journals Assessment of Paroxetine Molecular Interactions with Selected Monoamine and γ-Aminobutyric Acid Transporters

2021 ◽  
Vol 22 (12) ◽  
pp. 6293
Author(s):  
Magdalena Kowalska ◽  
Łukasz Fijałkowski ◽  
Alicja Nowaczyk
Keyword(s):  
Stem Cells ◽  
Molecular Interactions ◽  
Mechanism Of Action ◽  
In Silico ◽  
Aminobutyric Acid ◽  
Mammalian Brain ◽  
Monoamine Transporters ◽  
In Vitro Methods ◽  
Proliferation And Differentiation

Thus far, many hypotheses have been proposed explaining the cause of depression. Among the most popular of these are: monoamine, neurogenesis, neurobiology, inflammation and stress hypotheses. Many studies have proven that neurogenesis in the brains of adult mammals occurs throughout life. The generation of new neurons persists throughout adulthood in the mammalian brain due to the proliferation and differentiation of adult neural stem cells. For this reason, the search for drugs acting in this mechanism seems to be a priority for modern pharmacotherapy. Paroxetine is one of the most commonly used antidepressants. However, the exact mechanism of its action is not fully understood. The fact that the therapeutic effect after the administration of paroxetine occurs after a few weeks, even if the levels of monoamine are rapidly increased (within a few minutes), allows us to assume a neurogenic mechanism of action. Due to the confirmed dependence of depression on serotonin, norepinephrine, dopamine and γ-aminobutyric acid levels, studies have been undertaken into paroxetine interactions with these primary neurotransmitters using in silico and in vitro methods. We confirmed that paroxetine interacts most strongly with monoamine transporters and shows some interaction with γ-aminobutyric acid transporters. However, studies of the potency inhibitors and binding affinity values indicate that the neurogenic mechanism of paroxetine’s action may be determined mainly by its interactions with serotonin transporters.

In Vitro Proliferation and Differentiation of Human Hair Follicle Stem Cells on Chitosan-Skin Regenerating Template

2015 ◽  
Vol 05 (999) ◽  
pp. 1-1
Author(s):  
Abu Bakar Mohd Hilmi ◽  
Mohd Noor Norhayati ◽  
Ahmad Sukari Halim ◽  
Chin Keong Lim ◽  
Zulkifli Mustafa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hair Follicle ◽  
Human Hair ◽  
Human Hair Follicle ◽  
In Vitro Proliferation ◽  
Proliferation And Differentiation ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

In Vitro Methods for the Assessment of L-Cysteine Conjugate Toxicity

1994 ◽  
Vol 22 (2) ◽  
pp. 72-80
Author(s):  
Lorraine D. Buckberry ◽  
Harriet J. Adcock ◽  
Jeremy Adler ◽  
Ian S. Blagbrough ◽  
Peter J. Gaskin ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Mammalian Species ◽  
Mercapturic Acid ◽  
Assay Method ◽  
Cellular Toxicity ◽  
In Vitro Methods ◽  
Metabolic Route ◽  
Assay Methods ◽  
Chang Liver

L-Cysteine conjugates are normally metabolised via N-acetylation to produce a mercapturic acid. However, a recently identified metabolic route (C-S lysis) may lead to the generation of an unstable thiol which has been demonstrated to be responsible for toxicity in various mammalian species. Human Chang liver cells were challenged with a number of established L-cysteine conjugates. The cellular toxicity of these compounds was determined using a range of assay procedures, which provided differing information, depending on the assay method used. These observations were then investigated in order to establish which system would provide the most reliable indication of C-S lyase toxicity and whether any information on the mechanism of action could be obtained by these assay methods.

scholarly journals Mechanism of Action of Diallyl Sulphide in Ameliorating the Hematopoietic Radiation Injury

2021 ◽  
Author(s):  
Omika Katoch ◽  
Mrinalini Tiwari ◽  
Namita Kalra ◽  
Paban K. Agrawala
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Proliferation And Differentiation ◽  
Stem And Progenitor Cells ◽  
Radiation Induced ◽  
Medicinal Properties ◽  
Marrow Cellularity

AbstractDiallyl sulphide (DAS), the pungent component of garlic, is known to have several medicinal properties and has recently been shown to have radiomitigative properties. The present study was performed to better understand its mode of action in rendering radiomitigation. Evaluation of the colonogenic ability of hematopoietic progenitor cells (HPCs) on methocult media, proliferation and differentiation of hematopoietic stem cells (HSCs), and transplantation of stem cells were performed. The supporting tissue of HSCs was also evaluated by examining the histology of bone marrow and in vitro colony-forming unit–fibroblast (CFU-F) count. Alterations in the levels of IL-5, IL-6 and COX-2 were studied as a function of radiation or DAS treatment. It was observed that an increase in proliferation and differentiation of hematopoietic stem and progenitor cells occurred by postirradiation DAS administration. It also resulted in increased circulating and bone marrow homing of transplanted stem cells. Enhancement in bone marrow cellularity, CFU-F count, and cytokine IL-5 level were also evident. All those actions of DAS that could possibly add to its radiomitigative potential and can be attributed to its HDAC inhibitory properties, as was observed by the reversal radiation induced increase in histone acetylation.

In silico screening of phytoconstituents with antiviral activities against SARS-COV-2 main protease, Nsp12 polymerase and Nsp13 helicase proteins

2021 ◽  
Vol 18 ◽  
Author(s):  
Jainey James ◽  
Divya Jyothi ◽  
Sneh Priya
Keyword(s):  
Antiviral Activity ◽  
Molecular Interactions ◽  
In Silico ◽  
Antiviral Treatment ◽  
In Vivo Studies ◽  
Main Protease ◽  
Hypothesis Model ◽  
Antiviral Activities ◽  
Pharmacophore Hypothesis

Aims: The present study aim was to analyse the molecular interactions of the phytoconstituents known for their antiviral activity with the SARS-CoV-2 nonstructural proteins such as main protease (6LU7), Nsp12 polymerase (6M71), and Nsp13 helicase (6JYT). The applied in silico methodologies was molecular docking and pharmacophore modeling using Schrodinger software. Methods: The phytoconstituents were taken from PubChem, and SARS-CoV-2 proteins were downloaded from the protein data bank. The molecular interactions, binding energy, ADMET properties and pharmacophoric features were analysed by glide XP, prime MM-GBSA, qikprop and phase application of Schrodinger respectively. The antiviral activity of the selected phytoconstituents was carried out by PASS predictor, online tools. Results: The docking score analysis showed that quercetin 3-rhamnoside (-8.77 kcal/mol) and quercetin 3-rhamnoside (-7.89 kcal/mol) as excellent products to bind with their respective targets such as 6LU7, 6M71 and 6JYT. The generated pharmacophore hypothesis model validated the docking results, confirming the hydrogen bonding interactions of the amino acids. The PASS online tool predicted constituent's antiviral potentials. Conclusion: The docked phytoconstituents showed excellent interactions with the SARS-CoV-2 proteins, and on the outset, quercetin 3-rhamnoside and quercetin 7-rhamnoside have well-interacted with all the three proteins, and these belong to the plant Houttuynia cordata. The pharmacophore hypothesis has revealed the characteristic features responsible for their interactions, and PASS prediction data has supported their antiviral activities. Thus, these natural compounds could be developed as lead molecules for antiviral treatment against SARS-CoV-2. Further in-vitro and in-vivo studies could be carried out to provide better drug therapy.

Combined use of NGF/BDNF/bFGF promotes proliferation and differentiation of neural stem cells in vitro

2014 ◽  
Vol 38 (1) ◽  
pp. 74-78 ◽  
Author(s):  
Shuang‐Qing Chen ◽  
Qing Cai ◽  
Yu‐Ying Shen ◽  
Xiu‐Ying Cai ◽  
Hai‐Ying Lei
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Combined Use ◽  
Proliferation And Differentiation

scholarly journals Effects of Naringin on Proliferation and Osteogenic Differentiation of Human Periodontal Ligament Stem Cells In Vitro and In Vivo

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Lihua Yin ◽  
Wenxiao Cheng ◽  
Zishun Qin ◽  
Hongdou Yu ◽  
Zhanhai Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Periodontal Ligament ◽  
Trabecular Structure ◽  
Control Group ◽  
Periodontal Ligament Stem Cells ◽  
Expression Levels ◽  
Proliferation And Differentiation

This study is to explore the osteogenesis potential of the human periodontal ligament stem cells (hPDLSCs) induced by naringin in vitro and in vitro. The results confirmed that 1 μM naringin performs the best effect and a collection of bone-related genes (RUNX2,COL1A2, OPN, and OCN) had significantly higher expression levels compared to the control group. Furthermore, a typical trabecular structure was observed in vivo, surrounded by a large amount of osteoblasts. These results demonstrated that naringin, at a concentration of 1 μM, can efficiently promote the proliferation and differentiation of hPDLSCs both in vitro and in vivo.

scholarly journals Accumulation of DNA methylation alterations in paediatric glioma stem cells following fractionated dose irradiation

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Anna Danielsson ◽  
Kristell Barreau ◽  
Teresia Kling ◽  
Magnus Tisell ◽  
Helena Carén
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Cellular Response ◽  
Glioma Stem Cells ◽  
Proliferation And Differentiation ◽  
Radiation Resistant ◽  
Radiation Induced ◽  
Induced Changes ◽  
Regulatory Functions

Abstract Background Radiation is an important therapeutic tool. However, radiotherapy has the potential to promote co-evolution of genetic and epigenetic changes that can drive tumour heterogeneity, formation of radioresistant cells and tumour relapse. There is a clinical need for a better understanding of DNA methylation alterations that may follow radiotherapy to be able to prevent the development of radiation-resistant cells. Methods We examined radiation-induced changes in DNA methylation profiles of paediatric glioma stem cells (GSCs) in vitro. Five GSC cultures were irradiated in vitro with repeated doses of 2 or 4 Gy. Radiation was given in 3 or 15 fractions. DNA methylation profiling using Illumina DNA methylation arrays was performed at 14 days post-radiation. The cellular characteristics were studied in parallel. Results Few fractions of radiation did not result in significant accumulation of DNA methylation alterations. However, extended dose fractionations changed DNA methylation profiles and induced thousands of differentially methylated positions, specifically in enhancer regions, sites involved in alternative splicing and in repetitive regions. Radiation induced dose-dependent morphological and proliferative alterations of the cells as a consequence of the radiation exposure. Conclusions DNA methylation alterations of sites with regulatory functions in proliferation and differentiation were identified, which may reflect cellular response to radiation stress through epigenetic reprogramming and differentiation cues.

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