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β-elemene prevents monocyte-endothelial tissue interactions via sensitive air species/MAPK/NF-κB signaling path inside vitro.
Experimental rabbits provide evidence for translational research regarding the pathogenies or treatment of human diseases. We developed a novel method for regenerating the middle ear mucosa using autologous cultured nasal mucosal epithelial cell sheets, and evaluated the wound healing process in the middle ear mucosa of experimental rabbits. Nonetheless, vigilant microbiological monitoring of experimental animals is essential to effectively prevent a decline in their health conditions, which may affect the research results. Ruxotemitide solubility dmso We experimented with contamination of Pasteurella multocida in non-specific-pathogen-free (SPF) rabbits (without microbiological monitoring). Most non-SPF rabbits had otitis media, whereas SPF rabbits did not, which affected their results during the mucosal regeneration study. The contamination was resolved by changing the experimental design from using non-SPF rabbits to that using SPF rabbits. It is crucial to use the SPF animals for any surgical intervention studies.Introduction Mesenchymal stem cells (MSCs) have always been the center of the experimental exploration of regenerative therapy together with other stem cells. Among with, peripheral blood-derived mesenchymal stem cells (PBMSCs) have been regarded as promising in clinical applications for its convenience of acquisition from peripheral blood. However, few reported experiments so far to elucidate the exact mechanisms of how PBMSC influence regeneration. As the ability of immunomodulatory is one of the crucial features that influence MSC to reconstruct impaired tissue, we decided to focus on the immunomodulatory abilities of PBMSCs and conducted experiments associated with macrophages and T lymphocytes, which are two main cell types that dominate the innate and acquired immunity. Therefore, a basis can be made from these experiments for applications of PBMSCs in regenerative therapy in the future. Methods A Transwell system was used for the coculturing of PBMSCs with macrophages. T lymphocytes were cultured directly with PBMSCs. Flow cytometry and immunochemistry were conducted for identifying the phenotypes. Immunomagnetic microspheres, ELISA and RT-qPCR were used to detect the expressions of relevant molecules or mRNAs. Results After coculturing PBMSCs with M0, the anti-inflammatory IL-10 was increased whereas the proinflammatory TNF-α decreased; the expression of CD11b, CD68, CD206, Arg-1, IL-10 and CCL-22 was up-regulated whereas IL-1β down-regulated. The expression of TGF-β, RORγt, Foxp3 and IL-10 was increased in the cocultured lymphocytes whereas IL-17 and IL-6 decreased; the ratio of CD4+IL-17+ Th17/CD25+Foxp3+ Treg was reduced. Conclusion The findings demonstrated that PBMSCs promoted the anti-inflammatory features of macrophages and the Th17/Treg system. PBMSCs are able to inhibit inflammation associated with these two immune cell systems, and thus provide insight into how PBMSCs achieve their immunomodulatory ability.The adoptive transfer of CAR-T cells, which are modified T cells expressing chimeric antigen receptors (CARs), to target B cell maturation antigen (BCMA) has demonstrated impressive results in treating relapsed/refractory multiple myeloma. Although BCMA CAR-T therapy induces certain complications in some patients, idiopathic thrombocytopenic purpura (ITP) has not been reported as one of them. To the best of our knowledge, this is the first report of the successful treatment of ITP that arose in a relapsed/refractory multiple myeloma patient following anti-BCMA CAR-T cell infusion. Herein, we describe this relatively uncommon complication and provide guidance on its treatment.Introduction Researchers have investigated the use of platelet-rich plasma (PRP) therapy. However, the mechanisms through which PRP affects tissue repair remain unclear. We hypothesize that PRP promotes tissue repair through not only via direct manner on the local cells but also via indirect manner that encourage the recruitment of reparative cells such as macrophages (MPs), and it depends on the quality of PRP including the concentration of leukocytes. The aim of this study is to elucidate the actions of the MPs in the mechanisms of PRP on tissue repair processes. Methods Leukocyte-rich (LR) PRP and leukocyte-poor (LP) PRP were prepared from 12-week-old C57BL6 mice. Full-thickness defects were created in central third of patellar tendons of 12-week-old C57BL/6 mice for histologic analysis (n = 36) and 12-week-old B6.129P-Cx3cr1tm1Litt/J mice for flow cytometry analysis (n = 108). B6.129P-Cx3cr1tm1Litt/J mouse is GFP-positive only in the MP-linage cells thus MPs recruited to the repair tissue can be distinguiin the LP-PRP group than those in the control group (P less then 0.05). Conclusions This study demonstrated that PRP enhanced the tendon healing and promoted the recruitment of MPs to the injured tissue. The subtypes of MPs were different depends on the types of PRPs, suggesting that leukocytes in PRP influence the effect of PRP therapy.Introduction Currently, there are no approved drugs for treating non-alcoholic steatohepatitis (NASH); however, mesenchymal stem cells (MSCs) and their small extracellular vesicles (sEVs), which possess immunomodulatory activities, are potential candidates. This study aimed to develop a mouse model of NASH with rapid accumulation of fibrosis using the pre-established melanocortin type-4 receptor knockout (Mc4r-KO) NASH mouse model and lipopolysaccharide (LPS), and to evaluate the therapeutic effect of MSCs and their sEVs. Methods Mc4r-KO mice (8 weeks old, male) were fed a western diet (WD) for 8 weeks. Next, the mice were intraperitoneally injected with lipopolysaccharide (LPS) twice a week for 4 weeks while continuing the WD. To confirm the therapeutic effect of MSCs and sEVs, human adipose tissue-derived MSCs or their sEVs were administered 12 weeks after initiation of the WD, and serum testing, quantitative analysis of fibrosis, and quantitative reverse transcription-polymerase chain reaction qRT-PCR were performed. Results By providing a WD combined with LPS treatment, we successfully developed a NASH model with rapid accumulation of fibrosis. Both human MSCs and their sEVs decreased serum alanine transaminase levels and inflammatory markers based on qRT-PCR. Histological analysis showed that MSC or sEV treatment did not affect fat accumulation. However, an improvement in fibrosis in the groups treated with MSCs and their sEVs was observed. Furthermore, after administering MSCs and sEVs, there was a significant increase in anti-inflammatory macrophages in the liver. Conclusion We successfully developed a NASH model with rapid accumulation of fibrosis and confirmed the anti-inflammatory and anti-fibrotic effects of MSCs and their sEVs, which may be options for future therapy.
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