Salidroside ameliorated hypoxia-induced tumorigenesis of BxPC-3 cells via downregulating hypoxia-inducible factor (HIF)-1α and LOXL2.

Herein, we found that salidroside suppressed hypoxia-inducible factor 1 alpha (HIF-1α) and lysyl oxidase-like protein 2 (LOXL2) within human pancreatic cancer BxPC-3 cells cultured both under normoxia and hypoxia condition. To investigate the effect of salidroside on tumorigenesis of BxPC-3 cells and whether HIF-1α and LXCL2 were involved in this process, cells transfected with or without LOXL2 overexpression vector, were treated with 50 µg/mL of salidroside or 50 µM of KC7F2 (a HIF-1α inhibitor) under hypoxia. Cell viability and invasion were assessed using CCK-8 and Transwell chamber assay, respectively. Expression of E-cadherin and matrix metalloproteinase 2/9 (MMP 2/9) was determined, by Western blot analysis, to assess cell mobility at molecular levels. We confirmed that hypoxia increased LOXL2 and induced tumorigenesis of BxPC-3 cells, as evidenced by promoted cell proliferation and invasion, enhanced MMP2/9 while reduced E-cadherin. Interestingly, hypoxia-induced carcinogenesis was significantly retarded by both salidroside and KC7F2, however, enhanced with LOXL2 overexpression. Besides, salidroside and KC7F2 reduced LOXL2, and reversed the tumorigenesis of BxPC-3 cells induced by LOXL2 overexpression. Given the inhibitory effect of salidroside on HIF-1α expression, our data suggested that: (1) LOXL2 was the mechanism, whereby salidroside and KC7F2 showed inhibitory effect on cancer progression of BxPC-3 cells; (2) salidroside exerted its anticancer effect, most likely, by a HIF-1α/LOXL2 pathway. In conclusion, salidroside was a novel therapeutic drug in pancreatic cancer, and downregulation of HIF-1α and LXCL2 was the underlying mechanism.

MicroRNA profiling in the dentate gyrus in epileptic rats: The role of miR-187-3p.

This study aimed to explore the role of aberrant miRNA expression in epilepsy and to identify more potential genes associated with epileptogenesis.The miRNA expression profile of GSE49850, which included 20 samples from the rat epileptic dentate gyrus at 7, 14, 30, and 90 days after electrical stimulation and 20 additional samples from sham time-matched controls, was downloaded from the Gene Expression Omnibus database. The significantly differentially expressed miRNAs were identified in stimulated samples at each time point compared to time-matched controls, respectively. The target genes of consistently differentially expressed miRNAs were screened from miRDB and microRNA.org databases, followed by Gene Ontology (GO) and pathway enrichment analysis and regulatory network construction. The overlapping target genes for consistently differentially expressed miRNAs were also identified from these 2 databases. Furthermore, the potential binding sites of miRNAs and their target genes were analyzed.Rno-miR-187-3p was consistently downregulated in stimulated groups compared with time-matched controls. The predicted target genes of rno-miR-187-3p were enriched in different GO terms and pathways. In addition, 7 overlapping target genes of rno-miR-187-3p were identified, including NFS1, PAQR4, CAND1, DCLK1, PRKAR2A, AKAP3, and KCNK10. These 7 overlapping target genes were determined to have a different number of matched binding sites with rno-miR-187-3p.Our study suggests that miR-187-3p may play an important role in epilepsy development and progression via regulating numerous target genes, such as NFS1, CAND1, DCLK1, AKAP3, and KCNK10. Determining the underlying mechanism of the role of miR-187-3p in epilepsy may make it a potential therapeutic option.

Gene expression profile analysis of colorectal cancer to investigate potential mechanisms using bioinformatics.

This study aimed to explore the underlying molecular mechanisms of colorectal cancer (CRC) using bioinformatics analysis. Using GSE4107 datasets downloaded from the Gene Expression Omnibus, the differentially expressed genes (DEGs) were screened by comparing the RNA expression from the colonic mucosa between 12 CRC patients and ten healthy controls using a paired t-test. The Gene Ontology (GO) functional and pathway enrichment analyses of DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) software followed by the construction of a protein-protein interaction (PPI) network. In addition, hub gene identification and GO functional and pathway enrichment analyses of the modules were performed. A total of 612 up- and 639 downregulated genes were identified. The upregulated DEGs were mainly involved in the regulation of cell growth, migration, and the MAPK signaling pathway. The downregulated DEGs were significantly associated with oxidative phosphorylation, Alzheimer's disease, and Parkinson's disease. Moreover, FOS, FN1, PPP1CC, and CYP2B6 were selected as hub genes in the PPI networks. Two modules (up-A and up-B) in the upregulated PPI network and three modules (d-A, d-B, and d-C) in the downregulated PPI were identified with the threshold of Molecular Complex Detection (MCODE) Molecular Complex Detection (MCODE) score ≥4 and nodes ≥6. The genes in module up-A were significantly enriched in neuroactive ligand-receptor interactions and the calcium signaling pathway. The genes in module d-A were enriched in four pathways, including oxidative phosphorylation and Parkinson's disease. DEGs, such as FOS, FN1, PPP1CC, and CYP2B6, may be used as potential targets for CRC diagnosis and treatment.

Knockdown of HMGB1 inhibits growth and invasion of gastric cancer cells through the NF-κB pathway in vitro and in vivo.

High mobility group box 1 (HMGB1) as a novel inflammatory molecule has been shown to be involved in a variety of cell physiological and pathological behaviors including immune response, inflammation and cancer. Evidence suggests that HMGB1 plays a critical role in the development and progression of multiple malignancies. However, the underlying molecular mechanisms for the HMGB1-mediated growth and invasion of gastric cancer have not yet been elucidated. The present study investigated the expression of HMGB1 in gastric adenocarcinoma (GAC) and the mechanisms by which it contributes to tumor growth and invasion. The correlation between HMGB1 expression and clinicopathological characteristics of GAC patients was assessed by immunohistochemical assay through tissue microarray procedures. The RNA and protein expressions of HMGB1 and downstream factors were detected by quantitative PCR and western blot assays; cell proliferation and invasion were determined by MTT, wound-healing and 3D-Matregel assays, subcutaneous SGC-7901 tumor models were established to verify tumor growth in vivo. We demonstrated that, the expression of HMGB1 was significantly increased in the nucleus of GAC tissues compared with that in adjacent non-cancer tissues (88.6 vs.70.5%, P<0.001), and correlated with the metastatic lymph node of GAC (P=0.018). Furthermore, knockdown of HMGB1 by shRNA inhibited cell proliferative activities and invasive potential, and downregulated the expression of NF-κB p65, PCNA and MMP-9 in GAC cells (SGC-7901 and AGS). The tumor volumes in SGC7901 subcutaneous nude mouse models treated with Lv-shHMGB1 was significantly smaller than those of the nonsense sequence group. Taken together, these findings suggest that increased expression of HMGB1 is associated with tumor metastasis of GAC, and knockdown of HMGB1 suppresses growth and invasion of GAC cells through the NF-κB pathway in vitro and in vivo, suggesting that HMGB1 may serve as a potential therapeutic target for GAC.

[Diagnosis and treatment of postoperative complications after laparoscopic adjustable gastric banding procedure].

OBJECTIVE: To investigate the diagnosis and treatment of the complications in patients after laparoscopic adjustable gastric banding (LAGB) procedure. METHODS: Retrospectively analyze the data of the 23 patients who received the LAGB procedure from June 2003 to November 2004. RESULTS: Of the 23 LAGB operations, 3 (13%) cases of vomiting and nausea, 1 (4.3%) case of access-port infection and 5 (21.4%) cases of food intolerance occurred. One band (4.3%) and one injection reservoir (4.3%) displaced and were removed by laparoscopy. No death and thrombo-embolism occurred. CONCLUSIONS: The diagnosis and treatment of complications after LAGB in morbid obesity was special, if managed properly, the result would be satisfactory.