Potential regulatory effects of stem cell exosomes on inflammatory response in ischemic stroke treatment.

The high incidence and disability rates of stroke pose a heavy burden on society. Inflammation is a significant pathological reaction that occurs after an ischemic stroke. Currently, therapeutic methods, except for intravenous thrombolysis and vascular thrombectomy, have limited time windows. Mesenchymal stem cells (MSCs) can migrate, differentiate, and inhibit inflammatory immune responses. Exosomes (Exos), which are secretory vesicles, have the characteristics of the cells from which they are derived, making them attractive targets for research in recent years. MSC-derived exosomes can attenuate the inflammatory response caused by cerebral stroke by modulating damage-associated molecular patterns. In this review, research on the inflammatory response mechanisms associated with Exos therapy after an ischemic injury is discussed to provide a new approach to clinical treatment.

PERK activator CCT020312 prevents inflammation-mediated osteoporosis in the ovariectomized rats.

OBJECTIVE: To investigate the therapeutic effects of PERK activator CCT020312 (CCT) on inflammation-mediated osteoporosis (IMO) in ovariectomized rats. METHODS: Rats were divided into Sham, IMO, IMO + 1 mg/kg CCT and IMO + 2 mg/kg CCT groups. IMO models were constructed by bilateral ovariectomy (OVX) on 1st day followed by injection with magnesium silicate (Talc) on the 59th day. Sham rats did not undergo OVX surgery and were injected with saline instead of Talc. From 60th to 79th day, rats were treated with DMSO (vehicle control) in the Sham and IMO groups, and 1 or 2 mg/kg CCT020312 in treatment groups. Osteopontin (OPN), osteocalcin (OCN), tartrate-resistant acid phosphatase (TRAP), C-terminal telopeptide of type I collagen (CTX-I), and pro-inflammatory factors were measured on the 80th day. ProdigyDEXA was used to evaluate bone mineral density and content (BMD/BMC). Bone volume/total volume (BV/TV), connectivity density (Conn.D), trabecular number (Tb.N), and trabecular separation (Tb.Sp) was assessed using 3D micro-CT scanner. RESULTS: CCT up-regulated Conn.D, BV/TV, and Tb.N, but down-regulated Tb.Sp in IMO rats. Besides, the declined femoral BMD and BMC in IMO rats were elevated after CCT treatment. Besides, IMO rats represented declined OPN and OCN, as well as increased TRAP, CTX-I, and pro-inflammatory factors, whereas those in the treatment groups were ameliorated regarding these indexes, with 2 mg/kg CCT showing better effect. CONCLUSION: PERK activator CCT020312 can be served as a new therapeutic option for the protection against bone loss in the OVX rat model associated with inflammation probably by manipulating inflammatory factors.

One-for-All Nanoplatform for Synergistic Mild Cascade-Potentiated Ultrasound Therapy Induced with Targeting Imaging-Guided Photothermal Therapy.

Ameliorated therapy based on the tumor microenvironment is becoming increasingly popular, yet only a few methods have achieved wide recognition. Herein, targeting multifunctional hydrophilic nanomicelles, AgBiS2@DSPE-PEG2000-FA (ABS-FA), were obtained and employed for tumor treatment. In a cascade amplification mode, ABS-FA exhibited favorable properties of actively enhancing computed tomography/infrared (CT/IR) imaging and gently relieving ambient oxygen concentration by cooperative photothermal and sonodynamic therapy. Compared with traditional Bi2S3 nanoparticles, the CT imaging capability of the probe was augmented (43.21%), and the photothermal conversion efficiency was increased (33.1%). Furthermore, remarkable ultrasonic dynamic features of ABS-FA were observed, with increased generation of reactive oxygen species (24.3%) being obtained compared to Ce6, a commonly used sonosensitizer. Furthermore, ABS-FA exhibited obvious inhibitory effects on HeLa cell migration at 6 µg/mL, which to some extent, demonstrated its suppressive effect on tumor growth. A lower dose, laser and ultrasonic power, and shorter processing time endowed ABS-FA with excellent photothermal and sonodynamic effects. By mild cascade mode, the hypoxic condition of the tumor site was largely improved, and a suitable oxygen-rich environment was provided, thereby endowing ABS-FA with a superior synergistically enhanced treatment effect compared with the single-mode approach, which ultimately realized the purpose of "one injection, multiple treatment". Moreover, our data showed that ABS-FA was given with a biological safety profile while harnessing in vivo. Taken together, as a synergistically enhanced medical diagnosis and treatment method, the one-for-all nanoplatform will pave a new avenue for further clinical applications.

[Diversity, antibacterial activites and growth promoting characteristics of endophytic fungi from sandal (Santalum album)].

The aim of this study was to investigated the biological diversity, antibacterial activites and the plant growth-promoting traits of endophytic fungi of sandal (Santalum album), and to assess their potential in the development of antibacterial substances and rapid cultivation of sandal. The results of isolation and taxa analysis of endophytic fungi from sandal showed that 325 strains of endophytic fungi belonging to 16 genera of endophytic fungi were isolated from sandal (of which 86 from roots, 105 from stems and 134 from leaves). The isolation rate and colonization rate of endophytic fungi in different sandal parts showed the same pattern of change: leave>stems>roots. The diversity index of endophytic fungi in sandal roots was significantly higher than that of stems and leaves. The dominant endophytic fungi of sandal roots, stems and leaves showed significant differences. The dominant endophytic fungi of roots were Fusarium (50.00%) and Alternaria (10.47%), Alternaria (58.11%) and Acremonium (20.00%) for stems, and Pantoea (74.63%) for leaves. The antibacterial activity of 40 representative strains of sandal endophytic fungi were analyzed and the results showed that 90% of endophytic fungi exhibited inhibitory activity against at least one of the tested bacteria strains, and the strains with inhibitory activity to Escherichia coli, Enterobacter aerogenes, Shigella dysenteriae, Salmonella typhimurium, Staphylococcus aureus, and Bacillus subtilis accounted for 45.0%, 30%, 47.5%, 55%, 72.5%, and 62.5%, respectively. The sandal fungal endophytes with plant growth-promoting characteristics were screened, and 5 strains of endophytic fungi with phosphorus-solubilizing activity, 8 strains of endophytic fungi producing IAA, and 4 strains of endophytic fungi producing siderophores were found. Among them, endophytic fungus Monilia sp TXRF45 clould produced IAA and siderophores, and also show phosphate-solubilizing activity. The results indicated that the endophytic fungi of Sandal were rich in species diversity and their distribution had a certain tissue specificity. Some strains showed good antibacterial activity and growth-promoting properties, which could potentially applicable for the development of antibacterial substances and rapid cultivation of sandal.

Integrated microRNA and mRNA sequencing analysis of age-related changes to mouse thymic epithelial cells.

MicroRNAs (miRNAs) play key roles in the regulation of gene expression during multiple physiological processes, including early development, differentiation, and ageing. However, their involvement in age-related thymic involution is not clear. In this study, we profiled the global transcriptome and miRNAome of thymic epithelial cells in 1- and 3-month-old male and female mice, and predicted the possible transcription factors and target genes of the four most significantly differentially expressed miRNAs (DEMs) (miR-183-5p, miR-199b-5p, miR-205-5p, and miR-200b-3p) by performing bioinformatics analyses. We also evaluated the relationships between the significantly DEMs and mRNAs. We performed quantitative polymerase chain reaction to confirm the changes in the expression of the miRNAs and their predicted target genes. We found that miR-183-5p, miR-199b-5p, miR-205-5p, and miR-200b-3p can be used as a biomarker group for mouse thymus development and involution. In addition, the predicted target genes (Ptpn4, Slc2a9, Pkib, Pecam1, and Prkdc), which were identified by mRNA sequencing analysis, were mainly involved in growth, development, and accelerated senescence. In conclusion, miRNAs and their predicted target genes likely play important roles in thymus development and involution. To the best of our knowledge, this is the first study to systematically analyze the relevance of miRNAs and their targets by mRNA sequencing in mouse thymic epithelial cells. © 2018 IUBMB Life, 70(7):678-690, 2018.

Interferon-γ suppresses the proliferation and migration of human placenta-derived mesenchmal stromal cells and enhances their ability to induce the generation of CD4+CXCR5+Foxp3+Treg subset.

We investigate the effects of interferon (IFN)-γ on human placenta-derived mesenchymal stromal cells (hPMSCs), in particular, their adhesion, proliferation and migration and modulatory effects on the CD4+CXCR5+Foxp3+Treg subset. And we compared hPMSCs ability to induce the generation of different Treg subsets in response to treatment with IFN-γ. We found that IFN-γ suppressed the proliferation and migration for hPMSCs. The ability of hPMSCs to induce the generation of CD4+CXCR5+Foxp3+Treg subset was enhanced by IFN-γ. And maximal effectiveness of IFN-γ treated hPMSCs upon inducing the generation of Treg subsets was for CD4+CXCR5+Foxp3+Treg subset as compared with that of CD4+CD25+Foxp3+, CD8+CD25+Foxp3+, CD4+IL-10+ and CD8+IL-10+Treg subsets. These results have important implications for the development and application of hPMSCs in clinical use.

[Correlation between the Expression of microRNA 451 in Red Blood Cells and Chronic Mountain Sickness].

OBJECTIVE: To investigate the correlation between the expression of microRNA-451 in red blood cells and chronic mountain sickness(CMS). METHODS: Peripheral blood samples were collected from emigrant CMS patients (28 cases), localized CMS patients (12 case), emigrant healthy people (24 case) and localized healthy people (22 case). The microRNA-451 expression in red blood cells was measured by the RT-PCR. The results combined with the clinical data of patients were analysed. RESULTS: The expression of microRNA-451 in emigrant CMS patients was higher than that in emigrant healthy people (P<0.05); the expression of microRNA-451 in localized CMS patients was higher than that in localized healthy people (P<0.05); the microRNA-451 expression had no statistical difference between emargant and localized healthy people. The level of hemoglobin in CMS patients was positively correlated with the expression of microRNA-451 in red cells (r=0.701). CONCLUSION: There is a certain level of microRNA-451 in healthy people, the expression of microRNA-451 in CMS patients is significantly higher than that in healthy people. MicroRNA-451 may play an important role in the process of chronic mountain sickness.

MicroRNA expression profile in exosome discriminates extremely severe infections from mild infections for hand, foot and mouth disease.

BACKGROUND: Changes of miRNAs in exosome have been reported in different disease diagnosis and provided as potential biomarkers. In this study, we compared microRNA profile in exosomes in 5 MHFMD and 5 ESHFMD as well as in 5 healthy children. METHODS: Different expression of miRNAs in exosomes across all the three groups were screened using miRNA microarray method. Further validated test was conducted through quantitative real-time PCR assays with 54 exosome samples (18 ESHFMD, 18 MHFMD, and 18 healthy control). The judgment accuracy was then estimated by the receiver operating characteristic (ROC) curve analysis; and the specificity and sensitivity were evaluated by the multiple logistic regression analysis. RESULTS: There were 11 different miRNAs in exosomes of MHFMD and ESHFMD compared to healthy children, of which 4 were up-regulated and 7 were down-regulated. Further validation indicated that the 4 significant differentially expressed candidate miRNAs (miR-671-5p, miR-16-5p, miR-150-3p, and miR-4281) in exosome showed the same changes as in the microarray analysis, and the expression level of three miRNAs (miR-671-5p, miR-16-5p, and miR-150-3p) were significantly different between MHFMD or ESHFMD and the healthy controls. The accuracy of the test results were high with the under curve (AUC) value range from 0.79 to 1.00. They also provided a specificity of 72%-100% and a sensitivity of 78%-100%, which possessed ability to discriminate ESHFMD from MHFMD with the AUC value of 0.76-0.82. CONCLUSIONS: This study indicated that the exosomal miRNA from patients with different condition of HFMD express unique miRNA profiles. Exosomal miRNA expression profiles may provide supplemental biomarkers for diagnosing and subtyping HFMD infections.