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Background: Small extracellular vesicles (sEVs) obtained from human umbilical cord mesenchymal stromal cells (MSCs) have shown cardioprotective efficacy in doxorubicin-induced cardiotoxicity (DIC). However, their clinical application is limited due to the low yield and high consumption. This study aims to achieve large-scale production of sEVs using a three-dimensional (3D) bioreactor system. In addition, sEVs were developed to deliver Ginsenoside Rg1 (Rg1), a compound derived from traditional Chinese medicine, Ginseng, that has cardioprotective properties but limited bioavailability, to enhance the treatment of DIC. Methods: The 3D bioreactor system with spinner flasks was used to expand human umbilical cord MSCs and collect MSC-conditioned medium. Subsequently, sEVs were isolated from the conditioned medium using differential ultra-centrifugation (dUC). The sEVs were loaded with Ginsenoside Rg1 by electroporation and evaluated for cardioprotective efficacy using Cell Counting Kit-8 (CCK-8) analysis, Annexin V/PI staining and live cell count of H9c2 cells under DIC. Results: Using the 3D bioreactor system with spinner flasks, the expansion of MSCs reached ~600 million, and the production of sEVs was up to 2.2 × 1012 particles in five days with significantly reduced bench work compared to traditional 2D flasks. With the optimized protocol, the Ginsenoside Rg1 loading efficiency of sEVs by electroporation was ~21%, higher than sonication or co-incubation. Moreover, Rg1-loaded sEVs had attenuated DOX-induced cardiotoxicity with reduced apoptosis compared to free Ginsenoside Rg1 or sEVs. Conclusions: The 3D culture system scaled up the production of sEVs, which facilitated the Rg1 delivery and attenuated cardiomyocyte apoptosis, suggesting a potential treatment of DOX-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) and transfer RNA-derived small RNAs (tsRNAs) play critical roles in the regulation of different biological processes, but their underlying mechanisms in diabetes mellitus (DM) are still largely unknown. This study aimed to gain a better understanding of the functions of miRNAs and tsRNAs in the pathogenesis of DM. A high-fat diet (HFD) and streptozocin (STZ)-induced DM rat model was established. Pancreatic tissues were obtained for subsequent studies. The miRNA and tsRNA expression profiles in the DM and control groups were obtained by RNA sequencing and validated with quantitative reverse transcription-PCR (qRT-PCR). Subsequently, bioinformatics methods were used to predict target genes and the biological functions of differentially expressed miRNAs and tsRNAs. We identified 17 miRNAs and 28 tsRNAs that were significantly differentiated between the DM and control group. Subsequently, target genes were predicted for these altered miRNAs and tsRNAs, including Nalcn, Lpin2 and E2f3. These target genes were significantly enriched in localization as well as intracellular and protein binding. In addition, the results of KEGG analysis showed that the target genes were significantly enriched in the Wnt signaling pathway, insulin pathway, MAPK signaling pathway and Hippo signaling pathway. This study revealed the expression profiles of miRNAs and tsRNAs in the pancreas of a DM rat model using small RNA-Seq and predicted the target genes and associated pathways using bioinformatics analysis. Our findings provide a novel aspect in understanding the mechanisms of DM and identify potential targets for the diagnosis and treatment of DM. [ABSTRACT FROM AUTHOR]

Montmorillonite has been refined to overcome uncertainties originating from different sources, which offers opportunities for addressing various health issues, e.g., cosmetics, wound dressings, and antidiarrheal medicines. Herein, three commercial montmorillonite samples were obtained from different sources and labeled M1, M2, and M3 for Ca-montmorillonite, magnesium-enriched Ca-montmorillonite, and silicon-enriched Na-montmorillonite, respectively. Commercial montmorillonite was refined via ultrasonic scission-differential centrifugation and labeled S, M, or L according to the particle sizes (small, medium, or large, respectively). The size distribution decreased from 2000 nm to 250 nm with increasing centrifugation rates from 3000 rpm to 12,000 rpm. Toxicological evaluations with human colon-associated cells and human skin-associated cells indicated that side effects were correlated with excess dosages and silica sand. These side effects were more obvious with human colon-associated cells. The microscopic interactions between micro/nanosized montmorillonite and human colon-associated cells or human skin-associated cells indicated that those interactions were correlated with the size distributions. The interactions of the M1 series with the human cells were attributed to size effects because montmorillonite with a broad size distribution was stored in the M1 series. The M2 series interactions with human cells did not seem to be correlated with size effects because large montmorillonite particles were retained after refining. The M3 series interactions with human cells were attributed to size effects because small montmorillonite particles were retained after refining. This illustrates that toxicological evaluations with refined montmorillonite must be performed in accordance with clinical medical practices. [ABSTRACT FROM AUTHOR]