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Abstract Chemotherapy detrimentally impacts fertility via depletion of follicular reserves in the ovaries leading to ovarian failure (OF) and development of estrogen deficiency-related complications. The currently proposed options to preserve fertility such as Oocyte or ovarian cortex cryopreservation are faced with many technical obstacles that limit their effective implementation. Therefore, developing new modalities to protect ovarian function remains a pending target. Exosomes are nano-sized cell-derived extracellular vesicles (EVs) with documented efficacy in the field of regenerative medicine. The current study sought to determine the potential beneficial effects of mesenchymal stem cells (MSCs)-derived EVs in experimentally induced OF. Female albino rats were randomly allocated to four groups: control, OF group, OF + MSCs-EVs group, OF + Rapamycin (mTOR inhibitor) group, and OF + Quercetin (PI3K/AKT inhibitor) group. Follicular development was assessed via histopathological and immunohistochemical examination, and ovarian function was evaluated by hormonal assay. PI3K/Akt/mTOR signaling pathway as a key modulator of ovarian follicular activation was also assessed. MSCs-EVs administration to OF rats resulted in restored serum hormonal levels, preserved primordial follicles and oocytes, suppressed ovarian PI3K/AKT axis and downstream effectors (mTOR and FOXO3), modulated miRNA that target this axis, decreased expression of ovarian apoptotic markers (BAX, BCl2) and increased expression of proliferation marker Ki67. The present study validated the effectiveness of MSCs-EVs therapy in preventing ovarian insufficiency induced by chemotherapy. Concomitant MSCs-EVs treatment during chemotherapy could significantly preserve ovarian function and fertility by suppressing the PI3K/Akt axis, preventing follicular overactivation, maintaining normal ovarian cellular proliferation, and inhibiting granulosa cell apoptosis.

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.

Human milk comprises a diverse array of microbial communities with health-promoting effects, including colonization and development of the infant’s gut. In this study, we characterized the bacterial communities in the Egyptian mother–infant pairs during the first year of life under normal breastfeeding conditions. Out of one hundred isolates, forty-one were chosen for their potential probiotic properties. The selected isolates were profiled in terms of morphological and biochemical properties. The taxonomic evidence of these isolates was investigated based on 16S rRNA gene sequence and phylogenetic trees between the isolates’ sequence and the nearest sequences in the database. The taxonomic and biochemical evidence displayed that the isolates were encompassed in three genera: Lactobacillus, Enterococcus, and Lactococcus. The Lactobacillus was the most common genus in human milk and feces samples with a high incidence of its different species (Lacticaseibacillus paracasei, Lactobacillus delbrueckii, Lactiplantibacillus plantarum, Lactobacillus gasseri, and Lacticaseibacillus casei). Interestingly, BlastN and Jalview alignment results evidenced a low identity ratio of six isolates (less than 95%) with database sequences. This divergence was supported by the unique physiological, biochemical, and probiotic features of these isolates. The isolate L. delbrueckii, ASO 100 exhibited the lowest identity ratio with brilliant probiotic and antibacterial features suggesting the high probability of being a new species. Nine isolates were chosen and subjected to probiotic tests and ultrastructural analysis; these isolates exhibited antibiotic resistance and antibacterial activity with high probiotic characteristics, and high potentiality to be used as prophylactic and therapeutic agents in controlling intestinal pathogens.