Quantitative iTRAQ proteomics reveal the proteome profiles of bone marrow mesenchymal stem cells after cocultures with Schwann cells in vitro.

Background: Bone marrow mesenchymal stem cells (BMSCs) combined with Schwann cells (SCs) represent a better therapeutic cell transplantation strategy for treating spinal cord injury (SCI) than transplantation with BMSCs or SCs alone. In previous studies, we demonstrated that BMSCs are able to differentiate in neuron-like cells when cocultured with SCs. The detailed mechanism underlying SCI repair that occurs during the combined transplantation of BMSCs and SCs has not yet been studied. In this study, we adopted an isobaric tag for relative and absolute quantitation (iTRAQ)-based protein identification/quantification approach to examine the effects of the SC and BMSC coculture process on the BMSCs and then obtained and analyzed the differentially expressed proteins (DEPs) and their possible related pathways. Methods: This study included three groups based on the number of coculture days (i.e., 0, 3, and 7 days). Changes in BMSC protein expression levels were measured using the iTRAQ technique. A bioinformatics analysis of all the data was performed. Results: In total, 6,760 types of proteins were detected, corresponding to 5,181 data points with quantitative information. Of these, a total of 243 DEPs were identified, of which 169 proteins were upregulated and 74 proteins were downregulated. These DEPs were identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Intercellular adhesion molecule-1 (ICAM-1), integrin, and dioxygenase may play crucial roles in the repair of SCI. The data analysis indicates that the relevant biological processes may be regulated by lysosome function, cell adhesion molecules (CAMs), leukocyte transendothelial migration, and the phosphatidylinositol-3-kinase (PI3K) and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Conclusions: The data provided in this study indicate that several molecular mechanisms and signaling pathways are involved in the BMSC and SC coculture process. This information may be useful for the further identification of specific targets and related mechanisms and guide new directions for SCI treatment.

MicroRNA changes of bone marrow-derived mesenchymal stem cells differentiated into neuronal-like cells by Schwann cell-conditioned medium.

Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and identified differentially expressed microRNAs in bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium, and explored targets and related pathways involved in their differentiation into neuronal-like cells. Primary bone marrow-derived mesenchymal stem cells were isolated from femoral and tibial bones, while primary Schwann cells were isolated from bilateral saphenous nerves. Bone marrow-derived mesenchymal stem cells were cultured in unconditioned (control group) and Schwann cell-conditioned medium (bone marrow-derived mesenchymal stem cell + Schwann cell group). Neuronal differentiation of bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium was observed by time-lapse imaging. Upon induction, the morphology of bone marrow-derived mesenchymal stem cells changed into a neural shape with neurites. Results of quantitative reverse transcription-polymerase chain reaction revealed that nestin mRNA expression was upregulated from 1 to 3 days and downregulated from 3 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. Compared with the control group, microtubule-associated protein 2 mRNA expression gradually increased from 1 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. After 7 days of induction, microRNA analysis identified 83 significantly differentially expressed microRNAs between the two groups. Gene Ontology analysis indicated enrichment of microRNA target genes for neuronal projection development, regulation of axonogenesis, and positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that Hippo, Wnt, transforming growth factor-beta, and Hedgehog signaling pathways were potentially associated with neural differentiation of bone marrow-derived mesenchymal stem cells. This study, which carried out successful microRNA analysis of neuronal-like cells differentiated from bone marrow-derived mesenchymal stem cells by Schwann cell induction, revealed key microRNAs and pathways involved in neural differentiation of bone marrow-derived mesenchymal stem cells. All protocols were approved by the Animal Ethics Committee of Institute of Radiation Medicine, Chinese Academy of Medical Sciences on March 12, 2017 (approval number: DWLI-20170311).

Proteomics analysis of Schwann cell-derived exosomes: a novel therapeutic strategy for central nervous system injury.

Exosomes are nanometer-sized vesicles involved in intercellular communication, and they are released by various cell types. To learn about exosomes produced by Schwann cells (SCs) and to explore their potential function in repairing the central nervous system (CNS), we isolated exosomes from supernatants of SCs by ultracentrifugation, characterized them by electron microscopy and immunoblotting and determined their protein profile using proteomic analysis. The results demonstrated that Schwann cell-derived exosomes (SCDEs) were, on average, 106.5 nm in diameter, round, and had cup-like concavity and expressed exosome markers CD9 and Alix but not tumor susceptibility gene (TSG) 101. We identified a total of 433 proteins, among which 398 proteins overlapped with the ExoCarta database. According to their specific functions, we identified 12 proteins that are closely related to CNS repair and classified them by different potential mechanisms, such as axon regeneration and inflammation inhibition. Gene Oncology analysis indicated that SCDEs are mainly involved in signal transduction and cell communication. Biological pathway analysis showed that pathways are mostly involved in exosome biogenesis, formation, uptake and axon regeneration. Among the pathways, the neurotrophin, PI3K-Akt and cAMP signaling pathways played important roles in CNS repair. Our study isolated SCDEs, unveiled their contents, presented potential neurorestorative proteins and pathways and provided a rich proteomics data resource that will be valuable for future studies of the functions of individual proteins in neurodegenerative diseases.

Docetaxel versus docetaxel plus cisplatin for non-small-cell lung cancer: a meta-analysis of randomized clinical trials.

OBJECTIVE: To compare the activity, efficacy and toxicity of docetaxel versus docetaxel plus cisplatin in patients with non-small-cell lung cancer. METHODS: A literature search was performed in the EMBASE, Medline, Cochrane Library, Web of Science, China National Knowledge Internet, Wan-fang databases. The trials that were found were then evaluated for eligibility. The Cochrane Collaboration's Review Manager software was used to perform the meta-analyses. RESULTS: Nine clinical trials including 1257 patients were included. The docetaxel plus cisplatin regimens had higher overall response rates compared with the docetaxel regimen (RR = 0.70; 95% CI, 0.61 to 0.80; P < 0.00001). No statistically significant difference was observed between the two regimens with respect to the one-year survival rate (RR = 1.04; 95% CI, 0.90 to 1.19; P = 0.62). Patients treated with the DP regimen were more likely to experience anemia, thrombocytopenia, nausea/vomiting, nephrotoxicity, hyponatremia, mucositis and treatment-related deaths compared with patients treated with docetaxel alone. No significant difference was observed between the two regimens with respect to the occurrence of neurotoxicity, diarrhea, fatigue, pneumonitis, neutropenia and leucopenia. CONCLUSIONS: The docetaxel plus cisplatin combination regimen resulted in a high response rate and a high adverse effect rate compared with docetaxel monochemotherapy for non-small-cell lung cancer.

Ropivacaine versus levobupivacaine in peripheral nerve block: A PRISMA-compliant meta-analysis of randomized controlled trials.

BACKGROUND: To determine which is more potent in peripheral nerve block between ropivacaine and levobupivacaine. METHODS: A literature search was performed in the EMBASE, Medline, the Cochrane Library, and the Web of Science. The trials that were found were then evaluated for eligibility. The Cochrane Collaboration's Review Manager software was used to perform the meta-analyses. RESULTS: Twelve studies including 556 patients were included for final analysis. No statistically significant difference was observed between the 2 drugs with respect to onset time of surgical anesthesia, onset time of sensory block, onset time of motor block, duration of motor block, and patients overall satisfaction. Levobupivacaine provided more long-term anesthesia (weighted mean difference [WMD], -2.94; 95% confidence interval [CI], -5.56 to -0.32; I = 93%) and significantly lower incidence of postoperative rescue analgesia (odds ratio [OR], 2.11; 95% CI 1.18-3.74; I = 21%) than ropivacaine. There was a trend toward greater duration of sensory block in the levobupivacaine group (WMD, -1.16; 95% CI, -1.89 to -0.43; I = 14%). CONCLUSION: Levobupivacaine is more potent than ropivacaine in peripheral nerve block to some extent. Otherwise, more rigorous randomized control trials are required in the future.

Minimally invasive percutaneous plates versus conventional fixation techniques for distal tibial fractures: A meta-analysis.

OBJECTIVE: This meta-analysis was performed to determine the effects of minimally invasive percutaneous plate osteosynthesis (MIPO) versus conventional fixation techniques (CFT) for treating distal tibial fractures. METHODS: A literature search was performed in EMBASE, Medline, the Cochrane Library, and Web of Science. The trials searched were evaluated for eligibility. The Cochrane Collaboration's Review Manager software was used to perform meta-analyses. RESULTS: Eight studies were enrolled, including five randomized controlled trials, one control-matched trial and two retrospective cohort trials. The meta-analysis revealed that MIPO has a longer operating time, longer radiation time and higher incidence rate of soft tissue irritation symptoms than those of CFT. There was no significant difference between the two techniques with regard to union time, the American Orthopedic Foot and Ankle Society (AOFAS), infection rate and various other complications. CONCLUSIONS: The present meta-analysis showed that MIPO did not have obvious advantages over CFT in the treatment of distal tibia fracture. However, more rigorous randomized controlled trials are required in the future.