PurposeCarcinoma of the breast is the most prevalent cancer among Egyptian women and constitutes 29% of National Cancer Institute cases. The aim of this study was to determine the effect of breast cancer on oxidative stress, cardiac markers and liver function tests, moreover the role of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) in the treatment of breast cancer and its mechanism through changing the measured markers.MethodsForty female breast cancer patients who were admitted to the Department of Oncology of the Beni-Suef University Hospital were enrolled in the study. This study included three arms: a control group of healthy age-matched females (n=20), breast cancer patients who weren't receiving treatment (n=20), and patients undergoing treatment with anticancer combination drugs FAC (n=20). Blood samples collected from the control subjects and patients were analysed to determine levels of catalase, reduced glutathione (GSH), uric acid, nitric oxide (NO), malondialdehyde, creatine kinase (CK), lactate dehydrogenase (LDH), liver enzymes (alanine aminotransferase and aspartate aminotransferase), and creatinine.ResultsThe levels of catalase and GSH were significantly reduced (p<0.05) in breast carcinoma and FAC treated breast cancer patients. The lipid peroxidation and NO levels were significantly enhanced in both untreated and FAC treated breast cancer patients. The CK and LDH were significantly enhanced (p<0.05) in the FAC group.ConclusionThe results from the present study show that oxidative stress is implicated in breast carcinoma and chemotherapy aggravates this oxidative stress which causes damage to many cellular targets and has the main side effect of cardiotoxicity.
Background Several coronavirus vaccine have been fast-tracked to halt the pandemic, the usage of immune adjuvants that can boost immunological memory has come up to the surface. This is particularly of importance in view of the rates of failure of seroconversion and re-infection after COVID-19 infection, which could make the vaccine role and response debatable. Peroxisome proliferator-activated receptors (PPARs) have an established immune-modulatory role, but their effects as adjuvants to vaccination have not been explored to date. Main body of the abstract It is increasingly recognized that PPAR agonists can upregulate the levels of anti-apoptotic factors such as MCL-1. Such effect can improve the results of vaccination by enhancing the longevity of long-lived plasma cells (LLPCs). The interaction between PPAR agonists and the immune system does not halt here, as T cell memory is also stimulated through enhanced T regulatory cells, antagonizing PD-L1 and switching the metabolism of T cells to fatty acid oxidation, which has a remarkable effect on the persistence of T memory cells. What is even of a more significant value is the effect of PPAR gamma on ensuring a profound secretion of antibodies upon re-exposure to the offending antigen through upregulating lipoxin B4, therefore potentially assisting the vaccine response and deterring re-infection. Short conclusion In view of the above, we suggest the use of PPAR as adjuvants to vaccines in general especially the emerging COVID-19 vaccine due to their role in enhancing immunologic memory through DNA-dependent mechanisms.
D oxorubicin (Adriamycin) is an anthracycline anticancer drug that is commonly applied for the chemotherapy of solid and hematological tumors such as breast cancer, soft-tissue sarcomas, osteosarcomas, leukemia and lymphomas (Cappetta et al., 2017). However, its clinical use may be restricted due to its severe toxicological history in various organs including kidneys and heart (
Background Cerium-containing materials have wide applications in the biomedical field, because of the mimetic catalytic activities of cerium. The study aims to deeply estimate the biocompatibility of different scaffolds based on Ce-doped nanobioactive glass, collagen, and chitosan using the first passage of rabbit bone marrow mesenchymal stem cells (BM-MSCs) directed to osteogenic lineage by direct and indirect approach. One percentage of glass filler was used (30 wt. %) in the scaffold, while the percentage of CeO2 in the glass was ranged from 0 to 10 mol. %. Cytotoxicity was evaluated by monitoring of cell morphological changes and reduction in cell proliferation activity of BMMSCs maintained under osteogenic condition using proliferation assays, MTT assay for the direct contact of cells/scaffolds twice in a week, trypan blue and hemocytometer cell counting for indirect contact of cells/scaffolds extracts at day 7. Cell behaviors growth, morphology characteristics were monitored daily under a microscope and cell counting were conducted after 1 week of the incubation of the cells with the extracts of the four composite scaffolds in the osteogenic medium at the end of the week. Results Showed that at 24 h after direct contact with composite scaffold, all scaffolds showed proliferation of cells > 50% and increased in cell density on day 7. The scaffold of the highest percentage of CeO2 in bioactive glass nanoparticles (sample CL/CH/C10) showed the lowest inhibition of cell proliferation (< 25%) at day 7. Moreover, the indirect cell viability test showed that all extracts from the four composite scaffolds did not demonstrate a toxic effect on the cells (inhibition value < 25%). Conclusion The addition of CeO2 to the glass composition improved the biocompatibility of the composite scaffold for the proliferation of rabbit bone marrow mesenchymal stem cells directed to osteogenic lineage.
Background: Hepatotoxicity was one of the major side effects associated with doxorubicin treatment in cancer chemotherapy. The synthesized silver nanoparticles (AgNPs) from natural products such as algae especially green algae is one of the favorable means to minimize the deleterious effects of the chemotherapy. Thus, this study aimed to evaluate the preventive role of AgNPs synthesized by Ulva fasciata (U. fasciata) against doxorubicin-induced hepatotoxicity and oxidative stress in the liver of male Wistar rats. Materials and Methods: In the present study, the green macroalga U. fasciata ethanolic extract was used as reducing agents to reduce Ag ions to Ag0. Doxorubicin-injected male Wistar rats were concomitantly treated with U. fasciata ethanolic extract and AgNPs synthesized by U. fasciata extract (AgNPs/U. fasciata) 3 times/week by oral gavage for 6 weeks. Results: The results showed that male Wistar rats injected with doxorubicin showed a significant increase in ALT, ALP and GGT activities and total bilirubin level as well as a reduction in the serum albumin level. The concurrent treatments of doxorubicin-injected rats with U. fasciata ethanolic extract and AgNPs/U. fasciata significantly abrogate these alterations. The altered levels of tumor biomarkers CA19.9 and AFP as well as pro-inflammatory cytokine, TNF-α, and anti-inflammatory cytokine, IL-4, in doxorubicin-injected animals were significantly ameliorated by concurrent treatment with U. fasciata and AgNPs/U. fasciata. Moreover, the elevated mRNA expression of p53 significantly decreased by treatment. In association, the doxorubicin-induced deleterious histological changes represented by severe hydropic degenerative changes, steatosis, inflammatory cell infiltration, Kupffer cell proliferation and apoptosis were remarkably improved by concurrent treatment with U. fasciata extract and AgNPs/U. fasciata which was more potent. Conclusion: Based on results of this study, it can be concluded that U. fasciata extract and AgNPs/U. fasciata counteracts doxorubicin-induced toxicity by suppression of inflammation, oxidative stress and apoptosis. AgNPs/U. fasciata was the most potent in improving hepatocyte integrity and liver histological architecture. Graphical Abstract
Pyrazolo[1,5-a]pyrimidines were synthesised from the the reaction of b-diketone, b-keto ester, 1,2-disubstituted acrylonitrile or sodium (3-oxocycloalkylidene) methenolate. Elemental analysis, spectral data and alternative synthesis route elucidated structures of the newly synthesised compounds.
This research aims to evaluate cerium-doped nanobioactive glass/collagen/chitosan composites scaffolds with osteoblast mineralization of normal rabbit bone marrow mesenchymal stem cells (rBM-MSCs) and cancer osteosarcoma cells. The non-cellular in vitro bioactivity test was performed in simulated body fluids for periods 1, 3, 10, 20 and 30 d by measuring the calcium and phosphate ion concentrations by SEM/EDX analysis. While, the bioactivity of expanded and differentiated osteoblast cells derived from isolated rBM-MSCs by flowcytometric analysis was studied by histochemical staining with Alizarin Red and von Kossa to confirm the osteogenic differentiation process. Also, cell viability assay by MTT was used to measure the number of viable osteoblast cells cultured with scaffolds extracts. Also, the antitumor activity of the scaffolds was studied against cancer osteosarcoma cell lines using Sulforhodamine B (SRB) assay. The results showed that addition of cerium-doped nanobioactive glass to the composite scaffolds was triggered an increase in cell growth, proliferation and mineralization markers of osteoblast cells that increased with time as the highest concentrations of CeO 2 in nanobioactive glass (sample CL/CH/C10). Cell viability proved also that all scaffolds and their extracts showed proliferation inhibition with time < 25% reference to final cell number of control cells. Among the composites, having CL/CH/C5 showed the highest cytotoxic effect and reduced survival rate of osteosarcoma cells to 75.68% after 24 h. The subsequent increase of CeO 2 concentration was also effective but its effect was less than CL/CH/C5 sample. Finally, cerium-doped nanobioactive glass/collagen/chitosan composites scaffolds were exhibited good biocompatibility on normal cells and increased cytotoxicity on cancer osteosaroma cells.
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