Repair effect of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles on ovarian injury induced by cisplatin.

Small extracellular vesicles (sEVs) secreted by human umbilical cord have therapeutic effects on various degenerative diseases. However, the characteristics and potential functions of human umbilical cord mesenchymal stem cells (huMSCs)-derived sEVs, especially the role of premature ovarian failure (POF), are poorly understood. Here, we isolated and characterized huMSCs and their sEVs. huMSCs highly expressed CD73, CD90, and CD105. huMSC-sEVs showed typical exosomal features, highly expressing CD9, TSG101, and CD63. It was shown that huMSC-sEVs could be taken up by granulosa cells (GCs) and damaged ovarian tissue, which increased the levels of hormone secretion and reduced GCs apoptosis. We further confirmed that the levels of follicle-stimulating hormone in rat serum decreased dramatically, while the levels of estrogen (E2）and anti-mullerian hormone (AMH) increased significantly with the treatment of huMSC-sEVs. Meanwhile, huMSC-sEVs treatment greatly reduced cell apoptosis and autophagy, while increased the phosphorylation levels of p-PI3K and p-Akt. Therefore, treatment with huMSC-sEVs significantly inhibited GCs apoptosis, improved ovarian morphology, promoted follicular development, inhibited follicular over-atresia, and improved ovarian reserve capacity in POF rats. Our study verified that activation of PI3K/Akt signaling pathway and regulation of cellular autophagy, thus reducing GCs death, are the mechanisms by which huMSC-sEVs restore ovarian tissue function.

Potential Value of Probiotics on Lipid Profiles in Hyperlipidemia and Healthy Participants: Systematic Review and Meta-Analysis.

Objective: Many randomized controlled trials (RCTs) have reported the effect of probiotics on reducing plasma lipids with inconsistent results. An explicit systematic review and meta-analysis were conducted in this study to evaluate the effect of probiotics on the lipid profile of healthy and hyperlipidemia participants. Methods: A comprehensive literature search of RCTs was conducted using PubMed, Embase, World Health Organization (WHO) Global Index Medicus, WHO clinical trial registry, and Clinicaltrials.gov. Inclusion criteria included RCTs comparing the use of any strain of a specified probiotic with the placebo control group. The change in lipid profiles was analyzed. Results: The probiotics can decrease the total cholesterol (TC) level in hyperlipidemia participants but not healthy persons (MD = -0.43, 95% CI -0.60 - -0.25, P < .01; MD = -0.09, 95% CI -0.26 - 0.08, P > .05). Probiotics did not reduce high-density lipoprotein cholesterol (HDL-C) in patients with hyperlipidemia or healthy people (MD = -0.01, 95% CI -0.09 - 0.07, P > .05; MD = 0.02, 95% CI -0.04 - 0.09, P > .05). Furthermore, probiotics can reduce the low-density lipoprotein cholesterol (LDL-C) level both in hyperlipidemia and healthy persons (MD = -0.34, 95% CI -0.43 - -0.26, P < .01; MD = -0.15, 95% CI -0.28 - -0.02, P < .05). Lastly, the effect of probiotics on reducing triglyceride (TG) levels was significant in hyperlipidemia persons but not in the healthy population (MD = -0.20, 95% CI -0.37 - -0.04, P < .01; MD = -0.01, 95% CI -0.02 - 0.04, P > .05). Conclusions: Through our analysis, the effect of probiotics on lowering plasma lipid was more obvious in hyperlipidemia participants than healthy population. However, further studies are required to confirm the findings due to pronounced clinical heterogeneity.

Unraveling the molecular mechanisms of hyperlipidemia using integrated lncRNA and mRNA microarray data.

Long non-coding RNAs (lncRNAs) have key roles in various diseases; however, their functions in hyperlipidemia (HLP) have remained elusive. In the present study, microarray technology was utilized to analyze the differential expression of lncRNAs and mRNAs in liver tissues of apolipoprotein E-/- mice as a model of HLP compared with control mice. A total of 104 and 96 differentially expressed lncRNAs and mRNAs, respectively, were identified. Differentially expressed genes were significantly enriched in biological processes such as nitric oxide biosynthesis, innate immune response and inflammatory response. Finally, two pairs of target genes and 38 transcription factors with regulatory functions in HLP were predicted based on the lncRNA and mRNA co-expression network. The lncRNA expression profile was significantly altered in liver tissues of the mouse model of HLP and may provide novel targets for research into treatments.

Exosomes derived from mesenchymal stem cells repair a Parkinson's disease model by inducing autophagy.

Parkinson's disease (PD) is a progressively debilitating neurodegenerative condition that leads to motor and cognitive dysfunction. At present, clinical treatment can only improve symptoms, but cannot effectively protect dopaminergic neurons. Several reports have demonstrated that human umbilical cord mesenchymal stem cells (hucMSCs) afford neuroprotection, while their application is limited because of their uncontrollable differentiation and other reasons. Stem cells communicate with cells through secreted exosomes (Exos), the present study aimed to explore whether Exos secreted by hucMSCs could function instead of hucMSCs. hucMSCs were successfully isolated and characterized, and shown to contribute to 6-hydroxydopamine (6-OHDA)-stimulated SH-SY5Y cell proliferation; hucMSC-derived Exos were also involved in this process. The Exos were purified and identified, and then labeled with PKH 26, it was found that the Exos could be efficiently taken up by SH-SY5Y cells after 12 h of incubation. Pretreatment with Exos promoted 6-OHDA-stimulated SH-SY5Y cells to proliferate and inhibited apoptosis by inducing autophagy. Furthermore, Exos reached the substantia nigra through the blood-brain barrier (BBB) in vivo, relieved apomorphine-induced asymmetric rotation, reduced substantia nigra dopaminergic neuron loss and apoptosis, and upregulated the level of dopamine in the striatum. These results demonstrate that hucMSCs-Exos have a treatment capability for PD and can traverse the BBB, indicating their potential for the effective treatment of PD.