Background: Hepatic stellate cells (HSCs) are the primary collagen-secreting cells in the liver. While HSCs are the major cell type involved in the pathogenesis of liver fibrosis, hepatic macrophages also play an important role in mediating fibrogenesis and fibrosis resolution. Previously, we observed a reduction in HSC activation, proliferation, and collagen synthesis following exposure to human amnion epithelial cells (hAEC) and hAEC-conditioned media (hAEC-CM). This suggested that specific factors secreted by hAEC might be effective in ameliorating liver fibrosis. hAEC-derived extracellular vesicles (hAEC-EVs), which are nanosized (40–100 nm) membrane bound vesicles, may act as novel cell–cell communicators. Accordingly, we evaluated the efficacy of hAEC-EV in modulating liver fibrosis in a mouse model of chronic liver fibrosis and in human HSC.Methods: The hAEC-EVs were isolated and characterized. C57BL/6 mice with CCl4-induced liver fibrosis were administered hAEC-EV, hAEC-CM, or hAEC-EV depleted medium (hAEC-EVDM). LX2 cells, a human HSC line, and bone marrow-derived mouse macrophages were exposed to hAEC-EV, hAEC-CM, and hAEC-EVDM. Mass spectrometry was used to examine the proteome profile of each preparation.Results: The extent of liver fibrosis and number of activated HSCs were reduced significantly in CCl4-treated mice given hAEC-EVs, hAEC-CM, and hAEC EVDM compared to untreated controls. Hepatic macrophages were significantly decreased in all treatment groups, where a predominant M2 phenotype was observed. Human HSCs cultured with hAEC-EV and hAEC-CM displayed a significant reduction in collagen synthesis and hAEC-EV, hAEC-CM, and hAEC-EVDM altered macrophage polarization in bone marrow-derived mouse macrophages. Proteome analysis showed that 164 proteins were unique to hAEC-EV in comparison to hAEC-CM and hAEC-EVDM, and 51 proteins were co-identified components with the hAEC-EV fraction.Conclusion: This study provides novel data showing that hAEC-derived EVs significantly reduced liver fibrosis and macrophage infiltration to an extent similar to hAEC-EVDM and hAEC-CM. hAEC-EV-based therapy may be a potential therapeutic option for liver fibrosis.
Coronavirus disease-19 (COVID-19) is a highly contagious infection that mainly affects the respiratory system of patients. To date, more than 10 million people have been affected by this virus, and Saudi Arabia has also reported over 210 million cases. At present, there is no established treatment for COVID-19. Vaccination is one of the ways to defeat the pandemic. Recent reports have indicated rare but serious adverse events after vaccination, causing an anxious response from the general public worldwide. Therefore, this study was aimed at evaluating the knowledge, attitude, and perception of the COVID-19 vaccine among the Saudi population. This study is a cross-sectional, web-based online survey conducted using a snowball sampling technique. A self-administered questionnaire prepared in Arabic and English was used to collect feedback from the general population on their knowledge, attitudes, and perceptions about the COVID-19 vaccine. Participants (n = 2022) from different regions of the country replied to the questions. The responses to the questions were recorded on a spreadsheet and analyzed using the SPSS software. Statistical analysis was performed using one-way ANOVA and non-parametric tests to draw conclusions about the results. Multivariate stepwise regression analysis was performed to determine the association between the knowledge, attitude, and perception scores and the demographic variables. p < 0.05 was used to indicate the significance of the data. The data from the study indicated that most of the participants were males (81%), between 18 and 59 years of age (85.9%), Saudi nationals (98.3%), and possessed graduation or above as a qualification (62.9%). The results suggest that a major portion of respondents have satisfactory knowledge (76%), a positive attitude (72.4%), and perception (71.3%) towards the use of COVID-19 vaccines. Their responses can be categorized as between ‘good’ and ‘fair’. However, 30–40% of respondents lacked information about COVID-19 vaccination availability for under 18-year-olds as well as for pregnant women, in addition to the lack of knowledge about the serious unreported adverse reactions and long-term protection offered by the vaccine against coronavirus. The correlation analysis between the variables (p > 0.05) indicated that the response to the KAP domains has no direct relationship. The survey results suggest that most of the Saudi population has sound knowledge and a positive attitude and perception. Since the COVID-19 vaccines have been approved for use in pregnancy and above 12-year-old children by health authorities, the lack of information shown by a significant percentage of participants requires strategies to update this information. Awareness programs targeting all sections of the population must be continued to provide all the updates, including vaccinations for pregnant women and children.
Herein, we report the synthesis of eight new mononuclear and binuclear Co2+, Ni2+, Cu2+, and Zn2+ methoxy thiosemicarbazone (MTSC) complexes aiming at obtaining thiosemicarbazone complex with potent biological activity. The structure of the MTSC ligand and its metal complexes was fully characterized by elemental analysis, spectroscopic techniques (NMR, FTIR, UV-Vis), molar conductivity, thermogravimetric analysis (TG), and thermal differential analysis (DrTGA). The spectral and analytical data revealed that the obtained thiosemicarbazone-metal complexes have octahedral geometry around the metal center, except for the Zn2+-thiosemicarbazone complexes, which showed a tetrahedral geometry. The antibacterial and antifungal activities of the MTSC ligand and its (Co2+, Ni2+, Cu2+, and Zn2+) metal complexes were also investigated. Interestingly, the antibacterial activity of MTSC- metal complexes against examined bacteria was higher than that of the MTSC alone, which indicates that metal complexation improved the antibacterial activity of the parent ligand. Among different metal complexes, the MTSC- mono- and binuclear Cu2+ complexes showed significant antibacterial activity against Bacillus subtilis and Proteus vulgaris, better than that of the standard gentamycin drug. The in silico molecular docking study has revealed that the MTSC ligand could be a potential inhibitor for the oxidoreductase protein.
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