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Abstract Toxoplasmosis induced by Toxoplasma gondii is a well-known health threat, that prompts fatal encephalitis increased with immunocompromised patients, in addition, it can cause chorioretinitis, microcephaly, stillbirth in the fetus and even led to death. Standard therapy uses sulfadiazine and pyrimethamine drugs revealed beneficial results during the acute stage, however, it has severe side effects. UPLC-ESI-MS/MS used to explore C. limon MeOH ext. constituents, which revealed a list of 41 metabolites of different classes encompasses; unsaturated fatty acid, tricarboxylic acids, phenolic aldehyde, phenolic acids, phenolic glycosides, coumarins, sesquiterpene lactone, limonoid, steroid and flavonoids. C. limon MeOH ext. and the isolates reduced significantly the number of T. gondii tachyzoites. Consequently, histopathological examination, proved significant reduction in the number of mononuclear inflammatory cells in the kidney and liver sections, besides, lowering the number of shrunken and degenerative neurons in the brain sections of infected mice. Molecular docking study was performed targeted certain receptors, which are important for the life cycle fundamentals for the parasite mobility including invasion and egress, and further molecular dynamics simulation was conducted to get insights into the structural changes of the formed complexes, along with a pharmacophoric mapping approach, that confirmed the need for a free hydroxyl group and/or a phenolic substituted one, in order to form HB, Hyd/Aro and ML interactions, through which, cell cycle disruption via iron chelation, could be achieved. In addition, the ADMIT properties of all identified metabolites were predicted.

Abstract Background Coronavirus disease 2019 (COVID-19) has created a global pandemic with significant morbidity and mortality. SARS-CoV-2 primarily infects the lungs and is associated with various organ complications. Therapeutic approaches to combat COVID-19, including convalescent plasma and vaccination, have been developed. However, the high mutation rate of SARS-CoV-2 and its ability to inhibit host T-cell activity pose challenges for effective treatment. Mesenchymal stem cells (MSCs) and their extracellular vesicles (MSCs–EVs) have shown promise in COVID-19 therapy because of their immunomodulatory and regenerative properties. MicroRNAs (miRNAs) play crucial regulatory roles in various biological processes and can be manipulated for therapeutic purposes. Objective We aimed to investigate the role of lyophilized MSC–EVs and their microRNAs in targeting the receptors involved in SARS-CoV-2 entry into host cells as a strategy to limit infection. In silico microRNA prediction, structural predictions of the microRNA–mRNA duplex, and molecular docking with the Argonaut protein were performed. Methods Male Syrian hamsters infected with SARS-CoV-2 were treated with human Wharton’s jelly-derived Mesenchymal Stem cell-derived lyophilized exosomes (Bioluga Company)via intraperitoneal injection, and viral shedding was assessed. The potential therapeutic effects of MSCs–EVs were measured via histopathology of lung tissues and PCR for microRNAs. Results The results revealed strong binding potential between miRNA‒mRNA duplexes and the AGO protein via molecular docking. MSCs–EVs reduced inflammation markers and normalized blood indices via the suppression of viral entry by regulating ACE2 and TMPRSS2 expression. MSCs–EVs alleviated histopathological aberrations. They improved lung histology and reduced collagen fiber deposition in infected lungs. Conclusion We demonstrated that MSCs–EVs are a potential therapeutic option for treating COVID-19 by preventing viral entry into host cells.

Climate change has led to increased and varying pest infestation patterns, triggering a rise in pesticide usage and exposure. The effects of oxamyl, a widely used nematicide in Egypt, encompasses typical signs of carbamate intoxication; nevertheless, long-term effects of oxamyl exposure, particularly on the nervous system, require further elucidation. This study systematically investigated the mechanism and manifestations of repeated subacute exposure to sublethal doses of oxamyl in male SD rats. Data showed a dose-dependent genotoxic effect, manifested as increased bone marrow micronuclei and decreased brain expression of key genes involved in neurogenesis and neuronal development. Coincidently, brain histopathology showed dose-dependent neurodegeneration in various regions, associated with a significant increase in GFAP immunoreactivity, indicative of neuroinflammation. Biochemical examination revealed a typical pattern of cholinesterase inhibition by carbamates in serum and brain tissue, as well as increased oxidative stress markers in the brain such as SOD activity reduction, alongside an increase in NO and MDA. The ability of Ginseng at a 100 mg/Kg dose to ameliorate the effects of oxamyl exposure was investigated. Ginseng use, either as a protective or therapeutic regimen, attenuated the observed genotoxic, neuroinflammatory, and biochemical alterations. Our results indicate that repeated exposure to oxamyl triggers an integrative neurotoxic response, driven by genotoxicity, oxidative stress, and neuroinflammation, that could trigger an increase in neurological and cognitive disorders. These findings emphasize the urgent need for confirmatory translational studies in human subjects to assess these changes and inform policy decisions regarding safe levels of usage and appropriate agricultural and public health practices.

Abstract This study aimed to evaluate the efficacy of calcium carbonate nanoparticles (CCNPs) to induce new bone formation in a critical size segmental bone defect in rabbit’s radius when used alone, combined with silver nanoparticles (AgNPs) as a paste, or as a composite containing CCNPs, AgNPs, and advanced platelet-rich fibrin (A-PRF). Thirty-six adult apparently healthy male New Zealand White rabbits aging from 5 to 6 months and weighting 3.5 ± 0.5 kg were used. The animals were divided into four groups; control group, CCNPs group, CCNPs/AgNPs paste group, and CCNPs/AgNPs/A-PRF composite group. The animals were investigated at 4, 8, and 12 weeks post-implantation in which the healing was evaluated using computed tomographic (CT) and histopathological evaluation. The results revealed that CCNPs/AgNPs paste and CCNPs/AgNPs/A-PRF composite has a superior effect regarding the amount and the quality of the newly formed bone compared to the control and the CCNPs alone. In conclusion, addition of AgNPs and/or A-PRF to CCNPs has reduced its resorption rate and improved its osteogenic and osteoinductive properties.