MATERIALS AND METHODS: Silymarin was isolated from seeds of milk thistle. Various genotoxicity bioassays of silymarin were performed using mice. First, the bone marrow cell proliferation was estimated by calculating mitotic index. Second, the chromosomal abnormalities in mice bone marrow cells were studied. Third, micronucleated polychromatic erythrocytes (MPE) test and in vivo activation of sister chromatid exchanges (SCEs) were carried out in mice bone marrow cells. Finally, primary spermatocytes were analyzed to estimate genotoxic effect of silymarin on germ cells.
RESULTS: We found that silymarin is capable of inducing a significant increase (P ≤ 0.05) in cell proliferation of bone marrow cells. There is no increase in chromosomal aberrations following silymarin treatments. Results clearly showed that it significantly (P ≤ 0.05) decreased the MPE. Likewise, it was found to be a negative inducer of SCEs. It decreased in total abnormal metaphase, SCEs, MPE, and aberrant diakinesis.
CONCLUSION: The results demonstrated that silymarin has a strong anticlastogenic activity upon mice genome in somatic and germ cells, indicating its safe use as a medicinal substance. Furthermore, it is not only safe but also has protective effect from clastogens.
MATERIALS AND METHODS: This review utilises three databases (SCOPUS, Science Direct, and PubMed). The search phrases used are (Metabolomic* OR Metabolite*) for metabolomic study, (3T3-L1 OR Adipocyte OR "Adipose Tissue") for experimental design, and (Obesity) for obesity condition. Each of the search keywords was separated by an "AND" term in the databases. Other terms related to obesity, such as insulin resistance, heart disease, type 2 diabetes, muscular disorders, respiratory problems, and psychological problems were omitted because they did not contribute to the total number of studies discovered.
RESULTS: A total of 27 research publications were included in this scoping review. Most of the study focuses on metabolomics in obesity. Metabolites detected were found in various metabolic pathways including amino acids, carbohydrates, lipids as well as other metabolisms. Most of these metabolites discovered in obese conditions showed an alteration when compared to the level of the metabolite in normal conditions.
CONCLUSION: Unfortunately, these studies had some limitations in which the metabolites detected varied between the articles and the information concerning the relationship between the technique or instrument utilised and the metabolites detected in the samples were not well described. Therefore, using the findings obtained in this study, it can help to determine the direction of the study in the future.
Methods: The designed anti-tuberculosis nanodelivery composite, MgLH-PAS, was prepared by a novel co-precipitation method using MgNO3 as well MgO as starting materials.
Results: The designed nano-formulation, PAS-MgLH, showed good antimycobacterial and antimicrobial activities with significant synergistic anti-inflammatory effects on the suppression of lipopolysaccharide (LPS) stimulated inflammatory mediators in RAW 264.7 macrophages. The designed nano-formulation was also found to be biocompatible with human normal lung cells (MRC-5) and 3T3 fibroblast cells. Furthermore, the in vitro release of PAS from PAS-MgLH was found to be sustained in human body simulated phosphate buffer saline (PBS) solutions of pH 7.4 and pH 4.8.
Discussion: The results of the present study are highly encouraging for further in vivo studies. This new nanodelivery system, MgLH, can be exploited in the delivery of other drugs and in numerous other biomedical applications as well.
OBJECTIVES: To assess the psychological distress, anxiety, depression, coping strategies, risk perception, and attitude toward interprofessional teamwork among Egyptian healthcare workers during the COVID-19 pandemic.
METHODS: We conducted a cross-sectional online survey which consisted of five sections. The primary outcomes were anxiety (GAD-7), depression (PHQ-9), risk perception towards COVID-19, interprofessional teamwork attitude, and coping strategies during the Coronavirus disease-19 pandemic. The web-based questionnaire was distributed to Egyptian healthcare workers from the 20th of April 2020 to the 20th of May 2020. A snowball sampling method was used. Regression analysis was conducted to test the relationship between the socioeconomic characteristics and the previously mentioned outcomes.
RESULTS: A total of 403 participants responded to the online questionnaire. The majority were females (70.5%) and within the age group of 26-40 years (77.7%), with 2-5 years of work experience (43.2%). Most participants were pharmacists (33%) and physicians (22.1%). Eighty-two participants (21%) reported moderate to severe anxiety, and 79 participants reported (19.4%) moderate to severe depressive symptoms. In the univariate model, the marital status was associated with depression (OR 0.47, 95% CI 0.28-0.78), anxiety (OR 0.52, 95% CI 0.32-0.85), and an attitude toward interprofessional teamwork (β = -1.96 95% CI -2.72 to -1.2). Providing direct care to the patients was associated with lower anxiety symptoms (AOR 0.256, 95% CI 0.094-0.697). More severe anxiety and depressive symptoms were associated with difficulties in everyday life and the professional work environment (AOR 4.246 and 3.3, P = 0.003 and 0.01, respectively). Availability of mental health facilities at the workplace was associated with a lower risk perception towards COVID-19 (β = -0.79, 95% CI -1.24 to -0.34) and a more positive attitude towards teamwork (β = 2.77 95% CI 1.38-4.15).
CONCLUSIONS: According to our results, the COVID-19 pandemic was associated with mild anxiety and depression among healthcare workers in Egypt, especially pharmacists and physicians. We recommend more research targeting the mental health of healthcare workers in Egypt. If proven cost-effective and needed, wide-scale mental health screening and public health campaigns can facilitate effective prevention and treatment strategies. In addition, the availability of mental health facilities at the workplace could alleviate some of the risk perception associated with health emergencies and improve interprofessional teamwork.
PURPOSE: This study outlines CuE's cytotoxic activity against drug-resistant tumor cell lines. Three members of ABC transporters superfamily, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and ABCB5 were investigated, whose overexpression in tumors is tightly linked to multidrug resistance. Further factors of drug resistance studied were the tumor suppressor TP53 and the epidermal growth factor receptor (EGFR).
METHODS: Cytotoxicity assays (resazurin assays) were used to investigate the activity of Citrullus colocynthis and CuE towards multidrug resistant cancer cells. Molecular docking (In silico) has been carried out to explore the CuE's mode of binding to ABC transporters (P-gp, BCRP and ABCB5). The visualization of doxorubicin uptake was done by a Spinning Disc Confocal Microscope. The assessment of proteins expression was done by western blotting analysis. COMPARE and hierarchical cluster analyses were applied to identify, which genes correlate with sensitivity or resistance to cucurbitacins (CuA, CuB, CuE, CuD, CuI, and CuK).
RESULTS: Multidrug-resistant cells overexpressing P-gp or BCRP were cross-resistant to CuE. By contrast, TP53 knock-out cells were sensitive to CuE. Remarkably, resistant cells transfected with oncogenic ΔEGFR or ABCB5 were hypersensitive (collateral sensitive) to CuE. In silico analyses demonstrated that CuE is a substrate for P-gp and BCRP. Immunoblot analyses highlighted that CuE targeted EGFR and silenced its downstream signaling cascades. The most striking result that emerged from the doxorubicin uptake by ABCB5 overexpressing cells is that CuE is an effective inhibitor for ABCB5 transporter when compared with verapamil. The COMPARE analyses of transcriptome-wide expression profiles of tumor cell lines of the NCI identified common genes involved in cell cycle regulation, cellular adhesion and intracellular communication for different cucurbitacins.
CONCLUSION: CuE represents a potential therapeutic candidate for the treatment of certain types of refractory tumors. To best of our knowledge, this is the first time to identify CuE and verapamil as inhibitors for ABCB5 transporter.