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Background α-1-syntrophin (SNTA1), a protein encoded by SNTA1, is highly expressed in human cardiomyocytes. Mutations in SNTA1 are associated with arrhythmia and cardiomyopathy. Previous research on SNTA1 has been based on non-human cardiomyocytes. This study was designed to identify the phenotype of SNTA1-deficiency using human cardiomyocytes. Methods SNTA1 was knocked out in the H9 embryonic stem cell line using the CRISPR-Cas9 system. H9SNTA1KO cells were then induced to differentiate into cardiomyocytes using small molecule inhibitors. The phenotypic discrepancies associated with SNTA1-deficient cardiomyocytes were investigated. Results SNTA1 was truncated at the 149th amino acid position of PH1 domain by a stop codon (TGA) using the CRISPR-Cas9 system. SNTA1-deficiency did not affect the pluripotency of H9SNTA1KO, and they retain their in vitro ability to differentiate into cardiomyocytes. However, H9SNTA1KO derived cardiomyocytes exhibited hypertrophic phenotype, lower cardiac contractility, weak calcium transient intensity, and lower level of calcium in the sarcoplasmic reticulum. Early treatment of SNTA1-deficient cardiomyocytes with ranolazine improved the calcium transient intensity and cardiac contractility. Conclusion SNTA1-deficient cardiomyocytes can be used to research the etiology, pathogenesis, and potential therapies for myocardial diseases. The SNTA1-deficient cardiomyocyte model suggests that the maintenance of cardiac calcium homeostasis is a key target in the treatment of myocardial-related diseases.

Background: In 2010, undifferentiated early-stage gastric cancers (EGCs; ≤1 cm and confined to the mucosa) were included in the expanded criteria for endoscopic submucosal dissection (ESD), as established by the Japanese Gastric Cancer Association. Objective: To evaluate the safety and efficacy of the newly expanded criteria of ESD for EGCs. Methods: PubMed, Embase, and the Cochrane Library were searched for relevant studies published between January 1, 2010 and July 10, 2014. These studies were collected by 2 authors and then analyzed with RevMan 5.0. Results: Six studies including 6,687 patients were identified. Compared to the standard group (SG), the expanded group (EG) had higher bleeding (OR 1.66; 95% CI 1.02-2.68), perforation (OR 2.03; 95% CI 1.25-3.31), positive lateral margin rates (OR 16.88; 95% CI 3.83-74.5) and lower en bloc resection rate (OR 0.48; 95% CI 0.34-0.70). The local recurrence (OR 2.46; 95% CI 0.31-19.23) and total survival rates (OR 0.92; 95% CI 0.76-1.12) between the 2 groups were not statistically different. Conclusions: Considering the similar rates of local recurrence and total survival between the SG and EG, the use of ESD for the management of EGCs that meet the expanded criteria could be considered a safe and effective treatment method.

To investigate the effects and possible mechanisms of action of Curcuma wenyujin Y. H. Chen et C. Ling n-Butyl alcohol extract (CWNAE) on repression of human gastric cancer (GC) AGS cell invasion induced by co-culturing with Helicobacter pylori (HP).AGS cells were cultured with HP of positive or negative cytotoxin-associated gene A (CagA) and vacuolating cytotoxin gene A (VacA) expression (CagA+/- or VacA+/-) and divided into 5 group. Group A was cultured without HP as a control, Group B with HPThe 10% inhibitory concentration of CWNAE against AGS cells after a 48 h incubation was 19.73±1.30 μg/mL. More AGS cells were elongated after co-culturing with HPHP

To study the role of nuclear factor (NF)-kappaB pathway with p38MAPK in Curcuma wenyujin diterpenoid compound C (CDCC) fighting against inflammation and inducing gastric cancer cell apoptosis by stimulating gastric cell SGC7901 with tumor necrosis factor-alpha (TNF-alpha).Human umbilical vein endothelial cells (HUVECs) and human gastric cancer SGC-7901 cells were in vitro acted by CDCC in different concentrations at different time points. Their growth inhibition ratios were measured by MTT assay. The apoptosis rate of gastric cancer cells was detected by Annexin V-FITC/PI double staining. Nuclear translocation of p65 was detected by cell immunofluorescence. Expression levels of p38MAPK/P-p38MAPK, p65/P-p65, and Caspase 3/P-Caspase 3 were measured by Western blot.CDCC had significant inhibitory effect on the proliferation of SGC-7901. It also could effectively induce the apoptosis of gastric cancer cell SGC-7901. It also could reduce nuclear translocation of p65 in gastric cancer cell SGC-7901. Results of Western blot indicated that expression levels of p38MAPK and p65 were reduced and the expression level of Caspase-3 was elevated along with increased concentrations of CDCC (P0.05).Apoptosis executive protein Caspase 3 activated by regulating p65 via p38MAPK might be one of possible mechanisms for CDCC fighting against inflammation and gastric cancer.

OBJECTIVE: To investigate the cytotoxicity of silk fibroin/gelatin (SF/G) composite scaffolds in vitro as well as their biocompatibility and degradation in vivo. METHODS: The proliferation and relative growth rate of human hepatic QZG cells grown on different blends of two-dimensional (2-D) SF/G scaffolds were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry was used to evaluate apoptotic rate of QZG cells on different blends of 2-D SF/G scaffolds. The effect of silk protein materials on cell growth was observed by scanning electron microscopy. Three-dimensional (3-D) SF/G scaffolds of three different ratios (diameter 10 mm, thickness 1 mm) were implanted into subcutaneous pockets on male Sprague–Dawley (SD) rats. On the 7th, 14th and 30th day post-implantation, the rats were sacrificed. The scaffold area including the surrounding tissues was retrieved. Hematoxylin and eosin staining was performed for observation under a light microscope. RESULTS: Significant cell attachment and proliferation on the SF/G scaffolds were observed. As the increased gelatin concentration, SF/G scaffolds became more amenable to cell adhesion. After the subcutaneous implantation of the SF/G scaffolds in SD rats, immunological rejection tests showed only slight inflammation, measured by the presence of inflamed cells on day 7 and 14. By day 30, each scaffold had been completely infiltrated and organized by fibroblasts and inflamed cells. The greater the gelatin concentration in the scaffold, the faster the degradation rate. CONCLUSION: Composite SF/G scaffolds are a promising candidate matrix for implantable bio-artificial livers.

Reprogramming human somatic cells to pluripotency represents a valuable resource for research aiming at the development of in vitro models for human diseases and regenerative medicines to produce patient-specific induced pluripotent stem (iPS) cells. Seeking appropriate cell resources for higher efficiency and reducing the risk of viral transgene activation, especially oncogene activation, are of significance for iPS cell research. In this study, we tested whether human amnion-derived cells (hADCs) could be rapidly and efficiently reprogrammed into iPS cells by the defined factors: OCT4/SOX2/NANOG. hADCs from normal placenta were isolated and cultured. The 3rd passage cells were infected with the lentiviral vectors for the delivery of OCT4, SOX2, and NANOG. Afterwards, the generated iPSCs were identified by morphology, pluripotency markers, global gene expression profiles, and epigenetic status both in vitro and in vivo. The results showed that we were able to reprogram hADCs by the defined factors (OCT4/SOX2/NANOG). The efficiency was significantly high (about 0.1%), and the typical colonies appeared on the 9th day after infection. They were similar to human embryonic stem (ES) cells in morphology, proliferation, surface markers, gene expression, and the epigenetic status of pluripotent cell-specific genes. Furthermore, these cells were able to differentiate into various cell types of all three germ layers both in vitro and in vivo. These results demonstrate that hADCs were an ideal somatic cell resource for the rapid and efficient generation of iPS cells by OCT4/SOX2/NANOG.

To evaluate the preventive potential of intraoperative or early postoperative local administration of peptide PIII into the abdominal cavity against peritoneal carcinomatosis.Human gastric cancer cells of the line GC9811 were inoculated subcutaneously into nude mice to cause subcutaneous carcinoma. The 8th generation cancer was taken out to isolate the cancer cells to be inoculated into the serous membrane at the greater curvature of the stomach. Forty-eight nude BALB/C-nu/nu mice underwent implantation of the 8th generation cancer cells into the serous membrane at the greater curvature of the stomach via minilaparotomy so as to establish models of peritoneal carcinoma The 48 mice were randomly divided into 3 equal groups: Group 1 (control group); Group 2, undergoing intraperitoneal perfusion of 100 microg of peptide PIII, and post-operative intraperitoneal perfusion of 2 mg/kg peptide PIII twice; and Group 3, undergoing post-operative intraperitoneal perfusion of 100 microg/kg peptide PIII twice. Six mice in every group were sacrificed on the day 23 to undergo pathological examination. The other mice in every group were used to evaluate the survival rate. The tumor-bearing mice showing manifestations of failure were killed to undergo pathology.The weight of individual tumor was not significantly different among the 3 groups. The number of peritoneal metastatic nodules of Group 2 was (9.2 +/- 1.3), significantly less than those of Group 1 and 3 [(126.3 +/- 9.6) and (64.2 +/- 8.3) respectively, both P0.01]. The number of metastatic nodules2 mm of Group 2 was 1.6 +/- 0.2, significantly less then those of Groups 1 and 3 [(51.2 +/- 3.6) and (21.7 +/- 4.9) respectively, both P0.01]. The survival rate of Group 2 was significantly longer than those of Groups 1 and 3 (both P0.01).Peptide PIII does not significantly inhibit the growth of GC, but significantly reduce the peritoneal metastasis of GC. An ideal targeting chemotherapy, intra-operative application of peptide PIII into the abdominal cavity plus intraperitoneal perfusion is an attractive and promising strategy to prevent peritoneal metastasis of GC.