ABSTRACT
Background Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. Results Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. Conclusions In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment.
ABSTRACT
Objective@#To investigate the change in intestinal flora in Mongolian students with anxiety,so as to provide basis for exploring the relationship between flora and secretion expression in vivo.@*Methods@#The Self rating Anxiety Scale(SAS)was used to assess anxiety in medical college students; then a semi structured interview was administered. Fecal samples that met the inclusion criteria were collected and divided into anxiety (SAS score≥50) and control groups (no anxiety, SAS score<50) according to the standard score of SAS. Samples provided by Mongolian female students were selected from each group. The total bacterial DNA was extracted from the fecal samples for PCR amplification and NovaSeq 2x250bp high throughput sequencing was performed for the V3- V4 region of 16S rDNA gene to obtain the biological information of the intestinal flora. The intergroup OTU, structural diversity, significant difference, and LEfSe analyses were performed with information mining of the literature think tanks.@*Results@#Anxiety existed in 23.86% of the Mongolian students,and 16.96% of the Han people. A Chi square test showed no significant difference in detection of anxiety between Mongolian and Han college students ( P =0.07). Analysis of the alpha diversity index showed that the Shannon index, Simpson index, Chao1 index, and Observed species did not differed significantly between the two groups( t =8.0， 9.0 ，6.0，6.5). The difference in abundance of some bacteria was significant at the Class, Order, Family, and Genus levels between the two groups( t =-2.26-2.57，-5.08-3.58，-2.65-2.09， P <0.05).@*Conclusion@#The alpha diversity index showed that there was no significant difference in the abundance and diversity of intestinal flora between the two groups. While there were significant differences at different classification levels, the results suggest that the structure of intestinal flora can change in students with anxiety.
ABSTRACT
To character a novel chimera(1b/2a) hepatitis C virus cell culture (HCVcc) system carrying envelope E1E2 coding gene from Hebei strain of China, chimera HCVcc (cHCVcc) was developed from Huh7.5-CD81 cells after transfection with in vitro transcribed full-length 1b/2a chimera RNA, which carrying envelope E1E2 coding gene from Hebei strain of China. Then the replication, expression and infectious titer of serial passage HCVcc were assessed by Real Time RT-PCR, indirect immunofluorescence assay (IFA) and Western blotting (WB). In addition, chimeric envelope gene from HCVcc was sequenced after serial passage. We found that the number of HCV positive focus increased gradually in cell post-transfection with chimera HCVcc (1b/2a) RNA and reach a peak platform (80% to 90%) at 41 days post-transfection; the expression of HCV protein was also confirmed by WAB during serial passage. At meantime, HCV RNA copy number in the supernatant peaked at 10(4)-10(7) copies/mL and the highest infectious titer of this 1b/2a cHCVcc reinfection were tested as 10(4) ffu/mL. Sequence analysis indicated 6 of adaptive amino acid substitutes occur among chimeric envelope E1E2 during serial passages. We con:luded that a novel 1b/2a chimera HCVcc carrying envelope E1E2 coding gene from Hebei strain of China was developed and its infectious titer increased after serial passage of HCVcc. This novel cHCVcc will be an effective tool for further evaluation of anti-virus drugs and immune effects against the major genotype from Chinese.