Repair mechanism of human umbilical cord mesenchymal stem cell-derived exosome on neuronal ischemia and hypoxia injury / 中华急诊医学杂志

Objective:To investigate the effects of human umbilical cord mesenchymal stem cell-derived exosome (hucMSC-ex) on proliferation, migration, apoptosis and autophagy in ischemia-anoxia neurons, and to provide a theoretical study for clinical research on stroke.Methods:Primary glial cells were cultured and OGD model was established. Then, these cells were incubated with huMSC-exosome. The inhibition rate of proliferation was detected by MTT assay. Apoptosis was observed by flow cytometry. The expressions of apoptosis related proteins were confirmed by RT-PCR and Western blot. The expressions of autophagy related proteins and PI3K/Akt signal were observed by Western blot. The data were analyzed using SPSS 17.0 software, multiple-group comparisons were performed using one-way ANOVA, and SNK- q test was used for pairwise comparison between groups. Results:MTT assay showed that OGD could inhibit cell proliferation of primary glial cells. After incubation with hucMSC-ex for 2 h, the inhibition rate of cell proliferation was lower than that of the control. The flow cytometry technology showed that hucMSC-ex reduced cell apoptosis. The cell migration experiments showed that OGD reduced cell migration capacity, but cell migration increased after exosomal incubation. RT-PCT and Western blot showed that OGD induced autophagy and apoptosis, hucMSC-ex activated PI3K/Akt signaling pathway, inhibited the expression of Bax and Caspase-3 (both P<0.05), and promoted the expression of Bcl-2 ( P<0.05). hucMSC-ex inhibited the expression of Beclin-1, Atg3 and LC3-Ⅱ(al l P<0.01). Conclusions:huMSC-exosome promote the proliferation and migration in ischemia-anoxia-injured neurons and inhibit the apoptosis and autophagy. The mechanism that hucMSC-ex repaired the injured nerve cells might be associated with PI3K/Akt signaling pathway.

Metabolomic screening for diagnostic biomarkers of drug-induced chronic liver injury related cirrhosis / 药学学报

About 15%-20% of drug-induced liver injury (DILI) will progress to chronic manifestation (CH-DILI), which sometimes advances rapidly to liver cirrhosis (LC-DILI) within 0.5-1 year with deteriorative clinical prognosis. Therefore, it is important to find a non-invasive diagnosis for early detection of liver cirrhosis. In this study, the metabolomic profiles revealed significant differences in the metabolites from the plasma of LC-DILI versus CH-DILI. We found 35 differential metabolites through principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Through pathway enrichment analysis, some up-regulated metabolic pathways reflected impaired liver functions such as bile acid, lipid synthesis and decomposition during cirrhosis. Five biomarkers were found to exhibit effective diagnosis value (AUC > 0.6), including phosphatidylcholine, lysoPC (18:1 (9Z)), creatine, taurochenodeoxycholic acid and taurocholic acid. Furthermore, we found that the relative content ratio between phosphatidylcholine and lysoPC (18:1 (9Z)) had a better distinguishing ability (AUC = 0.867). The relative content ratio also had the feature to reduce systematic errors of sample processing and instrument detection, therefore having a greater value for clinical application.

Metabolomic study on the hepatotoxic or hepatoprotective effects of rhubarb to normal or hepatic fibrosis rats / 药学学报

Focusing on the TCM-related adverse drug reactions, especially those conventionally non-toxic TCM induced hepatotoxicity, this paper has proposed and established the disease-syndrome-based toxicology evaluation pattern and approach for TCM, not only the normal rats, but the hepatic fibrosis model rat were studied hepatotoxic or hepatoprotective effects of rhubarb, meanwhile liver histopathology changes by histological tests such as HE and TUNEL staining. The metabolomics analysis method will be employed to screen the key metabolites and possible metabolic pathway of the dual effects of rhubarb in rats. The results showed that rhubarb could result in significant liver injury in normal rats, indicated by the elevation of plasma serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities (P L-arginine, creatine, L-valine, retinyl ester, and prostaglandin F2α were confirmed by multivariate statistical analysis and metabolic pathways enrichment analysis linked to six metabolic pathways, including taurine and hypotaurine metabolism, primary bile acid biosynthesis, arginine and proline metabolism, arachidonic acid metabolism, retinol metabolism and valine, leucine and isoleucine biosynthesis. In summary, the results suggested the dual effects of rhubarb screened by taurine and hypotaurine metabolism, primary bile acid biosynthesis and arginine and proline metabolism may be the key metabolic pathway related to You Gu Wu Yun phenomenon of rhubarb. This study will provide new vision and illustration of scientific evidences for the hepatotoxicity assessment and rational use of those drugs containing anthraquinones.

Preparation and properties of heparosan polysaccharide-vitamin E succinate polymer micelles / 药学学报

Due to the advantages of polymer micelles and the anticancer activity of doxorubicin (DOX), the polymer micelle of DOX is expected to be used for drug delivery in anticancer applications. As a biocompatible and biodegradable polymer, amphiphilic copolymer heparosan-adipic dihydrazide-vitamin E succinate (KV) can be self-assembled to form micelles with core-shell structure in aqueous phase. In this article, KV conjugates with two different degrees of substitution (DS) were synthesized to load DOX and were characterized by 1H NMR. The size distribution, morphology, zeta potential and release behavior in vitro of the DOX-loaded micelles were studied. In vitro cytotoxicity was investigated by MTT assay against MGC80-3 and COS7 cells. The cellular uptake of the DOX-loaded micelles was observed by fluorescence microscopy and flow cytometry. The 1H NMR spectra results confirmed the KV polymers were successfully conjugated and the degree of VES grafted on heparosan polysaccharide were 12% and 25%. Briefly, the micelles with two different DS were expressed as KV12 and KV25. The DOX-loaded micelles could resist serum adsorption because of the negative charge on the surface. The average particle size measured by dynamic light scattering (DLS) method was 140-150 nm and the TEM results indicated that the morphology of DOX-loaded micelles were spherical. The encapsulation efficiency and drug loading were 80% and 10%-15%, respectively. The DOX-loaded micelles had sustained release behavior and the cumulative release of DOX/KV12 was slightly higher than DOX/KV25. Moreover, the viabilities of cells which were co-incubated with blank micelles were greater than 90%. It is clear that the blank micelles almost non-toxic to both cells. The IC50 of drug-loaded micelles against COS7 cells was much higher than that of MGC80-3 cells and the DOX/KV12 exhibited greater cytotoxicity. The cellular uptake of DOX/KV on MGC80-3 was greater than COS7 cells. In this study, KV polymer micelles have a sustained drug release activity and have a good selectivity to tumor cells, so it would be a potential carrier in drug delivery.

Evaluating the effect and safety of treating thyroid multiple-nodule by Ultrasound-guided microwave ablation in one-session / 实用医学杂志

Objective To investigate the short-term efficacy of treating thyroid multiple-nodule by Ultrasound-guided microwave ablation in one-session,and to evaluate its safety and effect.Methods Treatment and follow-up data of 85 patients with benign thyroid nodules underwent tUltrasound-guided microwave ablation in one-session were retrospectively analyzed.Results Symptom scores and cosmetic scores increased with the increasing number of nodules ablated before ablation (P ＜ 0.001),as well as the ablation time (P ＜ 0.001).However,there was no significant difference in the amount of isolation belt and intraoperative pain score between the groups.There were no serious complications such as recurrent laryngeal nerve injury and massive hemorrhage in 85 cases underwent tUltrasound-guided microwave ablation in one-session.Compared with the thyroid function,there was no significant difference on before the ablation and 1,3,6 months after ablation.Postoperative 6 months,the maximum volume of nodule and the total volume of the nodules were reduced 63％ and 69.5％,respectively.After ablation,both the symptom scores and cosmetic scores were improved significantly.On 6 months after ablation,the symptom scores decreased from (4.41 ± 1.75) cm to (1 ± 0.76) cm,and the cosmetic score3 decreased from 2.27 ± 0.81 to 1.25 ± 0.43.Conclusion Ultrasound-guided microwave ablation could treat multiple thyroid nodules effectively and protect the physiological function of thyroid,which was worthy of further promotion in clinical application.

Study on the dynamic changing profiles of telomeric restricted fragment length among sex balanced different age groups / 法医学杂志

OBJECTIVE@#In human, both in vivo and in vitro, telomere shortening appears to be a major component of cell senescence and aging. The detailed telomere shortening status and mechanism in peripheral blood cell is needed to be further characterized.@*METHODS@#One hundred and twenty three peripheral blood samples were collected from healthy individuals of different age groups and the mean telomeric restricted fragment (TRF) was measured using Southern Blotting with Dig labeled probe. The samples of different groups were homogenized in sex components as indicated by chi 2 test of sex ratio of different test groups (P > 0.05).@*RESULTS@#The average length of TRF is shortening with aging and distinguished shortening dynamic profiles could be observed. Further analysis showed that there might be a shortening peak near the age of 5.@*CONCLUSION@#There are distinguished dynamics profiles of telomere shortening among different age groups. Thus, the results indicate that it might be possible to infer individual age by telomeric restricted fragment length assay.

Gender specific profiles of human telomere shortening during aging / 中国法医学杂志

Objective In human,both in vivo and in vitro,telomere shortening appears to be a major component of cell senescence and aging. However, gender specific human telomere shortening needs to be further characterized. Therefore our study is aimed at clarifying gender-dependent profiles of telomere shortening. Methods 123 peripheral blood samples were collected from healthy individuals of different ages. The mean telomeric restricted fragment (TRF) was measured using Southern Blotting with Dig-labeled probe. Results Distinguished dynamics profiles of telomere shortening were observed among different age groups. Conclusion The result indicates that there are gender specific dynamic profiles of telomere shortening. Therefore, the gender must be considered when an individual age is estimated by telomeric restricted fragment length assay.