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Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.
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Objective To investigate the expression of hepatic glucose transporter-2 ( GLUT-2 ) and glu-cokinase(GCK)after gastric bypass(GBP)in type 2 diabetes mellitus(T2DM)GK rats and to discuss the mecha-nism of GBP improving insulin resistance .Methods 30 male GK rats aged 8 weeks were randomly divided into 3 groups:the operation group(10 rats), the sham operation group(10 rats)and the diet control group(10 rats), and 10 male SD rats aged 8 weeks were made as blank control group .The levels of fasting plasma glucose ( FPG) and fasting insulin(FINS)were measured and compared among the 4 groups before and 1,2 and 4 weeks after the operation and then the rats were sacrificed to retrieve the liver .The expressions of GLUT-2 and GCK mRNA and protein were detected by PT-PCR and Western blot respectively .Results As for GK operation group ,FPG levels at the 1st, 2nd,and 4th week after surgery ((11.06 ±0.52) mmol/L,(7.49 ±0.34) mmol/L,(5.20 ±0.08) mmol/L)respectively)were all lower than that before surgery (all P<0.05),and FINS level at the 4th week after surgery increased from(11.90 ±0.75)mmol/L to(14.20 ±1.23)mmol/L(P<0.05).The expressions of GLUT-2 and GCK mRNA and protein significantly increased in GK operation group 4 weeks after surgery ( P<0.01 ) . Conclusion The expressions of hepatic GLUT-2 and GCK in insulin signal transmission in T2DM rats are up-regu-lated after GBP , which enhance the signal transmission of insulin receptor , and improves the insulin sensibility .
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To develop standard in vitro chondrosarcoma models, we synthesized three hydrogels (i. e., PDMAAm, PNaAMPS and PMETAC) and investigated the influence of Young's modulus, swelling ratio and electric charges on the behavior of chondrosarcoma cells seeded on the hydrogels, including morphology, adhesion and aggregation. Results showed that the morphology of chondrosarcoma cells at 6h was dependent on the charges of hydrogels; cells present spindle-shaped and round-shaped morphology on negative charged and neutral hydrogel, respectively, while no cells spreaded on positive charged hydrogel. Chondrosarcoma cells formed aggregates on neutral PDMAAm after further culture. The hydrogels can be synthesized easily and has the characteristics of ease at use with defined components, which holds great potential for developing standard chondrosarcoma models in vitro.
Subject(s)
Humans , Bone Neoplasms , Pathology , Cell Line, Tumor , Cell Proliferation , Chondrosarcoma , Pathology , Hydrogels , Chemistry , Pharmacology , Methacrylates , Pharmacology , Nylons , Pharmacology , Static ElectricityABSTRACT
Objective To evaluate the clinical application of gastric tube in radical operation for patients with esophageal or cardial carcinoma. Methods From January 2007 to June 2010,50 patients with esophageal or cardial carcinoma were enrolled. Based on surgical methods, they were divided into the gastric tube group (26 cases) and the traditional way group (24 cases). Among the gastric tube group, 21 patients had esophageal carcinoma,and the other 5 patients had cardial carcinoma,and 1 patient was treated with anastomosis in the left neck, 11 patients with anastomosis in upper aortic arch,9 patients with anastomosis in lower aortic arch and 5 cardial carcinoma patients underwent radical resection. Among the traditional way group, 20 patients had esophageal carcinoma,and the other 4 patients had cstdial carcinoma, 1 patient wastreated with anastomosis in the left neck, 11 patients with anastomosis in upper aortic arch, 8 patients with anastomosis in lower aortic arch and 4 cardial carcinoma patients underwent radical resection. The rate of anastomotic leakage, operation time, and length of stay in hospital of the two groups were observed. Results All surgeries were successfully performed. There was no anastomotic leakage case in the two groups, while there were 3 cases pulmonary infection and 1 case death in the traditional way group. There was no statistical difference in operation time [(175 ± 11) min vs. (182±6) min, t = 1.556, P = 0.072] and length of stay in hospital [(16.8 ±9.8) d vs.(17.0 ± 11.3) d,t = 1.495,P= 0.068] between the gastric tube group and the traditional way group. Conclusion Gastric tube has good value in clinical application with fewer complications and without prolonging operation and hospitalization time, which can surely ameliorate quality of life.
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Objective To investigate the effects of diagnosis,surgical treatment of giant esophageal leiomyoma. Method The clinical data of 13 patients with giant esophageal leiomyoma treated by surgical operation from April 2001 to March 2009 were retrospectively analyzed. Results Twelve cases were preoperatively diagnosed by esophagogram and esophagoscopy, 1 case was misdiagnosed. Surgical resection was performed successfully in all 13 patients and no complications such as esophageal fistula and esophageal stenosis were found. Followed up 6 months to 3 years, no recurrence was found among 12 patients with giant esophageal leiomyoma, 1 case with esophageal leiomyosarcoma died of tumor recurrence 10 months after operation. Conclusions Surgical resection is the only effective treatment of giant esophageal leiomyoma.Enucleation of tumor extra-mucosa can be used in most cases. Esophagectomy is available for large tumor or malignant tumor. Treatment by endoscopic and thoracoscopic surgery has some limitations and the indications should be considered strictly.