Dalian Medical University

About: Dalian Medical University is a education organization based out in Dalian, China. It is known for research contribution in the topics: Cancer & Apoptosis. The organization has 15623 authors who have published 9993 publications receiving 164145 citations.

Protective Effects of Fucoidan on Aβ25-35 and d-Gal-Induced Neurotoxicity in PC12 Cells and d-Gal-Induced Cognitive Dysfunction in Mice.

Abstract: Alzheimer’s disease (AD) is a chronic neurodegenerative disease which contributes to memory loss and cognitive decline in the elderly. Fucoidan, extracted from brown algae, is a complex sulfated polysaccharide and potential bioactive compound. In this study, we investigated whether fucoidan protects PC12 cells from apoptosis induced by a combination of beta-amyloid 25–35 (Aβ25–35) and d-galactose (d-Gal), and improves learning and memory impairment in AD model mice. The results indicated that fucoidan could inhibit the release of cytochrome c from the mitochondria to cytosol and activation of caspases, and increase the expression of apoptosis inhibitor proteins (IAPs), including livin and X-linked IAP (XIAP) in PC12 cells damaged by Aβ25–35 and d-Gal-induction. Fucoidan reversed the decreased activity of acetylcholine (ACh) and choline acetyl transferase (ChAT), as well as the increased activity of acetylcholine esterase (AChE), in AD model mice induced by infusion of d-Gal. Furthermore, fucoidan improved antioxidant activity in vitro and in vivo by activation of superoxide dismutase (SOD) and glutathione (GSH). These results suggested that fucoidan could protect PC12 cells from apoptosis and ameliorate the learning and memory impairment in AD model mice, which appeared to be due to regulating the cholinergic system, reducing oxidative stress, and inhibiting the caspase-dependent apoptosis pathway.

Lixisenatide treatment improves glycaemic control in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin with or without sulfonylurea: a randomized, double-blind, placebo-controlled, 24-week trial (GetGoal-M-Asia).

Abstract: Background This study assessed the efficacy and safety of the once-daily glucagon-like peptide-1 receptor agonist, lixisenatide, in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin ± sulfonylurea. Methods In this 24-week, double-blind, placebo-controlled, multinational study, patients were randomized to lixisenatide 20 µg once daily or placebo. The primary endpoint was absolute change in glycated haemoglobin (HbA1c) from baseline to week 24. Results A total of 391 patients were randomized. Lixisenatide significantly reduced HbA1c levels compared with placebo (LS mean difference: −0.36%, p = 0.0004). A significantly higher proportion of lixisenatide-treated patients achieved HbA1c targets of <7% (p = 0.003) and ≤6.5% (p = 0.001) versus placebo. Lixisenatide was associated with a statistically significant reduction in 2-h postprandial plasma glucose after a standardized breakfast versus placebo (LS mean difference: −4.28 mmol/L, p < 0.0001) and a significant reduction in fasting plasma glucose (p = 0.0109). There was no difference in weight loss versus placebo, with a modest reduction in body weight reported for both groups (lixisenatide: −1.50 kg, placebo: −1.24 kg; p = 0.296). The incidence of treatment-emergent adverse events (TEAEs) was 64.3% with lixisenatide versus 47.4% with placebo, with serious TEAEs reported in 1.5% versus 2.1% of patients, respectively. The most common TEAE in the lixisenatide group was nausea (16.3% vs 2.6% with placebo). The incidence of symptomatic hypoglycaemia was 5.6% with lixisenatide treatment and 2.6% with placebo (p = 0.1321), with no severe symptomatic hypoglycaemia events reported. Conclusions In Asian patients with type 2 diabetes mellitus insufficiently controlled on metformin ± sulfonylurea, lixisenatide significantly improved glycaemic control and was well tolerated during the 24-week study. © 2014 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons, Ltd.

The expression and functional role of a FOXC1 related mRNA-lncRNA pair in oral squamous cell carcinoma.

Abstract: The Fork head box C1 (FOXC1) gene is overexpressed in multiple malignant tumors and is functionally correlated with tumor progression. However, its’ role in oral squamous cell carcinoma (OSCC) is still unclear. Recent studies have revealed that many long non-coding RNA (lncRNAs) cooperate with adjacent coding genes and form a functional “lncRNA-mRNA pair”. In this study, we report a new lncRNA FOXC1 upstream transcript (FOXCUT) that was remarkably overexpressed in 23 OSCC patients, as was the adjacent FOXC1 gene. The expressions of FOXC1 and FOXCUT were positively correlated. When the expression of FOXCUT was down-regulated by small interfering RNA (siRNA), the expression of FOXC1 was also decreased. Moreover, in OSCC cells Tca8113 and SCC-9, down-regulation of either FOXC1 or FOXCUT by siRNA could inhibit cell proliferation and cell migration in vitro and was accompanied with a reduction of MMP2, MMP7, MMP9, and VEGF-A. In conclusion, FOXC1 may be co-amplified with FOXCUT in OSCC, and both of them may be functionally involved in the tumor progression of OSCC. This provides evidence that both FOXC1 and FOXCUT may serve as novel biomarkers and therapeutic targets in OSCC patients who overexpress this “lncRNA-mRNA pair”.

Loss of TDP43 inhibits progression of triple-negative breast cancer in coordination with SRSF3

Abstract: Aberrant alternative splicing has been highlighted as a potential hallmark of cancer. Here, we identify TDP43 (TAR DNA-binding protein 43) as an important splicing regulator responsible for the unique splicing profile in triple-negative breast cancer (TNBC). Clinical data demonstrate that TDP43 is highly expressed in TNBC with poor prognosis. Knockdown of TDP43 inhibits tumor progression, including proliferation and metastasis, and overexpression of TDP43 promotes proliferation and malignancy of mammary epithelial cells. Deep sequencing analysis and functional experiments indicate that TDP43 alters most splicing events with splicing factor SRSF3 (serine/arginine-rich splicing factor 3), in the regulation of TNBC progression. The TDP43/SRSF3 complex controls specific splicing events, including downstream genes PAR3 and NUMB. The effect of reduced metastasis and proliferation upon the knockdown of TDP43 or SRSF3 is mediated by the splicing regulation of PAR3 and NUMB exon 12, respectively. The TDP43/SRSF3 complex and downstream PAR3 isoform are potential therapeutic targets for TNBC.

Anti-tumor effects of dihydroartemisinin on human osteosarcoma.

Abstract: Dihydroartemisinin (DHA) exhibits antitumor activity against a wide spectrum of cancer cells. However, whether DHA has anti-tumor effect on human osteosarcoma cells remains unknown. This study aims to investigate the anti-tumor activity of DHA and the underlying mechanisms in human osteosarcoma cell lines with different p53 mutation statuses. Four human osteosarcoma cell lines were treated with different concentrations of DHA. Then, cell proliferation was determined by the CCK-8 viability assay; apoptosis and cell cycle progression were evaluated by flow cytometry; protein expression was analyzed by western blot assay; and NF-kB activity was examined by luciferase assay. The results demonstrated that DHA treatment could inhibit the proliferation of four osteosarcoma cell lines in a dose-dependent manner. P53 wild-type osteosarcoma cells were more sensitive to DHA. Moreover, the percentage of apoptotic cell and cell arrest in G2/M phase was increased upon DHA treatment in a dose-dependent manner. Mechanistically, DHA activated caspase-3, caspase-8, and caspase-9; upregulated the expression of Bax, FAS, and cyclin D1; downregulated the expression of Bcl-2, Cdc25B, and cyclin B1; and inhibited the activity of NF-кB. In conclusion, DHA has significant anticancer effects against human osteosarcoma cells, which include induction of apoptosis and cell cycle arrest. The p53 gene may play a certain role in the DHA-induced human osteosarcoma apoptosis and cell cycle arrest. DHA is a novel anti-osteosarcoma drug candidate that merits further study.