Liensinine inhibited gastric cancer cell growth through ROS generation and the PI3K/AKT pathway.

Liensinine, an isoquinoline alkaloid extracted from the seed embryo of Nelumbo nucifera Gaertn, has been shown to exhibit various phrenological effects, including anti­cancer activity. The aim of this study is to investigate the effects and mechanisms of liensinine in human gastric cancer cells. In this study, we found liensinine can significantly inhibit gastric cancer cell proliferation in vitro and in vivo. Liensinine inducedgastric cancer cell apoptosis by increasing cleaved PARP, caspased 3 and caspased 9. Moreover, liensinine induced cycle arrest by downregulatingcyclinD1/cyclin­dependent kinase4 and phosphorylated protein kinase B. Furthermore, we found liensinine increases ROS levels and inhibits the PI3K/AKT pathway. These data suggested that liensinine might represent a novel and effective agent against gastric cancer.

Efficacy and Safety of Therapeutic ERCP in the Elderly: A Single Center Experience.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has been an important therapeutic measure for the treatment of pancreatobiliary diseases in the elderly, but limited data on the use of ERCP in the super-aged elderly are available. This study aimed to evaluate the efficacy and safety of ERCP in patients 80 years of age or older. METHODS: All therapeutic ERCPs performed from January 2012 to December 2015 at our endoscopy unit were retrospectively reviewed to evaluate the clinical outcomes and ERCP-related complications in patients 80 years of age or older (group A) and in patients younger than 65 years of age (group B). RESULTS: A total of 141 patients (182 procedures) were 80 years of age or older (group A), and 513 patients (610 procedures) were 65 years old or younger (group B). Chronic concomitant diseases (73.05% vs. 31.19%, P<0.01) and the use of antithrombotic drugs (25.53% vs. 15.01%, P<0.01) were more frequent in group A than in group B. Common bile duct (CBD) stones were the most common indication for ERCP in both groups. The rate of a difficult cannulation was higher in group A than in group B (23.63% vs. 16.56%, P<0.01). The mean procedure time was longer, and second ERCPs were performed more frequently in group A than in group B. In addition, periampullary diverticulum was observed significantly more frequently in group A (30.22% vs. 20%, P<0.01) than in group B. The overall success rate (92.31% vs. 93.93%, P>0.05) and the complication rate (6.59% vs. 5.25%, P>0.05) were not significantly different between the 2 groups. CONCLUSIONS: ERCP is a safe and effective intervention in patients 80 years of age or older, although elderly patients had a high rate of concomitant chronic diseases and used antithrombotic drugs more frequently.

[Study of TGF-ß1 phage model peptides on inhibiting keloid fibroblasts proliferation].

OBJECTIVE: To isolate the transforming growth factor-beta 1 (TGF-ß1) phage model peptides from phage 12-mer display peptide library to inhibit the proliferation of keloid fibroblasts. METHODS: The phage display 12-mer peptide library was screened for 4 rounds with monoclonal anti-human TGF-ß1 as the target to yield the specific phage model peptides. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used for the quantitative determination of cellular proliferation. Apoptosis was detected by the Annexin V-FITC/PI apoptosis detection kit and the cells were analyzed with flow cytometry. Immunofluorescent assay was employed to show the binding affinity of model peptides for keloid fibroblasts. Quantitative real-time polymerase chain reaction (PCR) was performed to detect the expressions of nuclear factor kappa B (NF-κB) and connective tissue growth factor (CTGF). RESULTS: Ten phage model peptides were obtained and they were similar to TGF-ß1, TGF-ß2, TGF-ß receptor II (TßRII), TGF-ß-induced factor, NF-κB or mitogen-activated protein kinase (MAPK). The results of MTT showed that four phage model peptides (No. 7 - 10) could inhibit the proliferation of keloid fibroblasts (P < 0.05). The results of apoptotic assessment showed that phage model peptides (No. 7 - 10) could slightly trigger the late apoptotic stage of keloid fibroblasts. The data of immunofluorescence assay revealed that the model peptides on phages rather than phages could bind to keloid fibroblasts. The findings of quantitative real-time PCR analysis suggested that the relative expression of NF-κB decreased in phage model peptides groups (No. 7 - 10). The quantitative expression was 0.28, 0.26, 0.46 and 0.30 respectively versus the negative control group. The relative expression of CTGF decreased in phage model peptides groups (No. 7 - 10). The quantitative expression was 0.26, 0.60, 0.34 and 0.17 respectively versus the negative control group. CONCLUSION: Four phage model peptides (No. 7 - 10) isolated from phage display 12-mer peptide library can inhibit the proliferation of keloid fibroblasts via regulating the expressions of NF-κB and CTGF.

[Expression and function of sphingosine kinases 1 and 2 in human keloid fibroblasts].

OBJECTIVE: To study the expression and function of sphingosine kinase (SphK) 1 and SphK2 in human keloid fibroblasts. METHODS: Specimens of keloid and surrounding normal skin were collected from 12 patients with keloid during operation. Primary fibroblasts were isolated, cultured, and randomly divided into 3 groups: normal skin group, keloid group, and keloid with transforming growth factor (TGF)-beta1 group cultured with TGF-beta1 for 48 h. Immunofluorescence technique was used to detect the location of SphK1 and SphK2 protein. Real-time PCR and Western blotting were used to measure the mRNA and protein expression levels of SphK1 and SphK2. RESULTS: Sphk1 protein was localized primarily in the nuclei of the fibroblasts, and Sphk2 protein was detected both in the cytoplasm and nuclei in the 3 groups. The mRNA and protein levels of Sphk1 in the keloid group were (0.0608 +/- 0.0190) and (0.8308 +/- 0.1093) respectively, both significantly higher than those of the normal skin group [(0.0383 +/- 0.0147) and (0.6800 +/- 0.1126) respectively, both P < 0.05], but significantly lower than those of the keloid fibroblasts with TGF-beta1 group [(0.0790 +/- 0.0280), P < 0.05, and (1.4267 +/- 0.1938), P < 0.01]. There was no significant differences in the Sphk2 mRNA and protein levels among these 3 groups (all P > 0.05). CONCLUSIONS: Sphk1 plays a leading role in keloid pathogenesis. The SphK1 mRNA and protein levels are increased by TGF-beta1 stimulation in keloid fibroblasts, perhaps indicating that Sphk1 is involved in TGF-beta signal transduction pathway.