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131.
Samia E. Omer Tawasol M. Ibrahim Omer A. Krar Amna M. Ali Alaa A. Makki Walaa Ibraheem Abdulrahim A. Alzain 《Biochemistry and Biophysics Reports》2022
The current novel corona virus illness (COVID-19) is a developing viral disease that was discovered in 2019. There is currently no viable therapeutic strategy for this illness management. Because traditional medication development and discovery has lagged behind the threat of emerging and re-emerging illnesses like Ebola, MERS-CoV, and, more recently, SARS-CoV-2. Drug developers began to consider drug repurposing (or repositioning) as a viable option to the more traditional drug development method. The goal of drug repurposing is to uncover new uses for an approved or investigational medicine that aren't related to its original use. The main benefits of this strategy are that there is less developmental risk and that it takes less time because the safety and pharmacologic requirements are met. The main protease (Mpro) of corona viruses is one of the well-studied and appealing therapeutic targets. As a result, the current research examines the molecular docking of Mpro (PDB ID: 5R81) conjugated repurposed drugs. 12,432 approved drugs were collected from ChEMBL and drugbank libraries, and docked separately into the receptor grid created on 5R81, using the three phases of molecular docking including high throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP). Based on docking scores and MM-GBSA binding free energy calculation, top three drugs (kanamycin, sulfinalol and carvedilol) were chosen for further analyses for molecular dynamic simulations. 相似文献
132.
Nivitchanyong T Martinez A Ishaque A Murphy JE Konstantinov K Betenbaugh MJ Thrift J 《Biotechnology and bioengineering》2007,98(4):825-841
The engineering of production cell lines to express anti-apoptotic genes has been pursued in recent years due to potential process benefits, including enhanced cell survival, increased protein expression, and improved product quality. In this study, a baby hamster kidney cell line secreting recombinant factor VIII (BHK-FVIII) was engineered to express the anti-apoptotic genes Aven and E1B-19K. In high cell density shake flask culture evaluation, 11 clonal cell lines expressing either E1B-19K or a combination of Aven and E1B-19K showed improved survival compared to both parental and blank vector cell line controls. These cell lines exhibited lower caspase-3 activation and reduced Annexin-V binding compared to the controls. Parental and blank vector cell lines were less than 50% viable after 48 h of exposure to thapsigargin while cell lines expressing E1B-19K with or without Aven maintained viabilities approaching 90%. Subsequently, the best Aven-E1B-19K candidate cell line was compared to the parental cell line in 12-L perfusion bioreactor studies. Choosing the appropriate perfusion rates in bioreactors is a bioprocess optimization issue, so the bioreactors were operated at sequentially lower specific perfusion rates, while maintaining a cell density of 2 x 10(7) viable cells/mL. The viability of the parental cell line declined from nearly 100% at a perfusion rate of 0.5 nL/cell/day to below 80% viability, with caspase-3 activity exceeding 15%, at its lower perfusion limit of 0.15 nL/cell/day. In contrast, the Aven-E1B-19K cell line maintained an average viability of 94% and a maximum caspase-3 activity of 2.5% even when subjected to a lower perfusion minimum of 0.1 nL/cell/day. Factor VIII productivity, specific growth rate, and cell size decreased for both cell lines at lower perfusion rates, but the drop in all cases was larger for the parental cell line. Specific consumption of glucose and glutamine and production of lactate were consistently lower for the Aven-E1B-19K culture. Furthermore, the yield of ammonia from glutamine increased for the Aven-E1B-19K cell line relative to the parent to suggest altered metabolic pathways following anti-apoptosis engineering. These results demonstrate that expression of anti-apoptotic genes Aven and E1B-19K can increase the stability and robustness of an industrially relevant BHK-FVIII mammalian cell line over a wide range of perfusion rates. 相似文献
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To investigate the effect of cell cycle inhibitor p19ARF on replicative senescence of human diploid cell, recombinant p19ARF eukaryotic expression vector was constructed and p19ARF gene was transfected into human diploid fibroblasts (WI-38 cells) by liposome-mediated transfection for overexpression. Then, the effects of p19ARF on replicative senescence of WI-38 cells were observed. The results re- vealed that, compared with control cells, the WI-38 cells in which p19ARF gene was introduced showed significant up-regulation of p53 and p21 expression level, decrease of cell generation by 10 12 generations, decline of cell growth rate with cell cycle being arrested at G1 phase, increase of positive rate of senescent marker SA-β-gal staining, and decrease of mitochondrial membrane potential. The morphology of the transfected fibroblasts presented the characteristics changes similar to senescent cells. These results indicated that high expression of p19ARF may promote the senescent process of human diploid cells. 相似文献
136.
Păunescu V Deak E Herman D Siska IR Tănasie G Bunu C Anghel S Tatu CA Oprea TI Henschler R Rüster B Bistrian R Seifried E 《Journal of cellular and molecular medicine》2007,11(3):502-508
Our study examined whether human bone marrow-derived MSCs are able to differentiate, in vitro, into functional epithelial-like cells. MSCs were isolated from the sternum of 8 patients with different hematological disorders. The surface phenotype of these cells was characterized.To induce epithelial differentiation, MSCs were cultured using Epidermal Growth Factor, Keratinocyte Growth Factor, Hepatocyte Growth Factor and Insulin-like growth Factor-II. Differentiated cells were further characterized both morphologically and functionally by their capacity to express markers with specificity for epithelial lineage. The expression of cytokeratin 19 was assessed by immunocytochemistry, and cytokeratin 18 was evaluated by quantitative RT-PCR (Taq-man). The data demonstrate that human MSCs isolated from human bone marrow can differentiate into epithelial-like cells and may thus serve as a cell source for tissue engineering and cell therapy of epithelial tissue. 相似文献
137.
The epidemiological literature has widely documented the importance of social distancing interventions in containing the spread of the COVID-19 pandemic. However, the epidemiological measure of virus reproduction, R0, provides a myopic view of containment, especially when the absolute number of cases is still high. The paper investigates cross-country variations concerning the impact of social distancing interventions on COVID-19 incidence by employing a statistical measure of containment, which models the daily number of cases as a structural time-series, state-space vector. Countries that adopt strict lockdown policies and provide economic support in the form of income augmentations and debt relief improve the response towards the pandemic. Countries like China and South Korea have been most influential in containing the spread of infections. European nations of France, Italy, Spain and the UK are witnessing a second wave of the virus, indicating that re-opening the European economy perhaps has instigated an exponential spread. 相似文献
138.
This paper studies the impact on reported coronavirus 2019 (COVID-19) cases and deaths in Spain resulting from large mass gatherings that occurred from March 6 to March 8, 2020. To study these outcomes, the geographic differences in the planned pre-pandemic major events that took place on these dates were exploited, which is a quasi-random source of variation for identification purposes. We collected daily and detailed information about the number of attendees at football (soccer) and basketball matches in addition to individuals participating in the Women’s Day marches across Spain, which we merged with daily data on reported COVID-19 cases and deaths at the provincial level. Our results reveal evidence of non-negligible COVID-19 cases related to the differences in the percentage of attendees at these major events from March 6 to March 8. In a typical province, approximately 31% of the average daily reported COVID-19 cases per 100,000 inhabitants between mid-March and early April 2020 can be explained by the participation rate in those major events. A back-of-the-envelope calculation suggests that this implies almost five million euros (169,000 euros/day) of additional economic cost in the health system of a typical province with one million inhabitants in the period under consideration. Several mechanisms behind the spread of COVID-19 are also examined. 相似文献
139.
In the first year of the COVID-19 pandemic, Spain was one of the worst-hit countries, although not all areas and social groups were affected equally. This study focuses on Malaga, a cosmopolitan tourist destination located on the southern Mediterranean coast that has the sixth largest population in Spain. Specifically, it examines the relationship between multidimensional vulnerability and COVID-19 infection rates across the city’s census tracts for the period February 2020 to February 2021. The analysis uses high frequency (daily) data on the accumulated incidence of the disease at 14 days and shows that COVID-19 did not spread symmetrically across the census tracts of Malaga but had a greater impact on the most vulnerable neighbourhoods. However, the pattern of this relationship was not uniform in the period examined, with specific contextual factors driving the higher infection rates across time. Our findings show that pandemic containment regulations cannot overlook vulnerability considerations and universal restrictions to reduce the spread of disease should be supplemented by targeted regulations for specific areas. 相似文献
140.