Therapeutic properties, biological effects, antiliver cancer, and anticolon cancer effects of some natural compounds: A biochemical approach.

Natural compounds, such as carotenoids, flavonoids, anthocyanins, or terpenoids, are physiologically active components found in plants (pigments), often known as phytochemicals or phytonutrients. The in vitro cytotoxic and anticolon cancer effects of biologically bavachin, bavachinin, artepillin C, and aromadendrin compounds against SW48, SNU-C1, COLO 205, RKO, LS411N, and SW1417 cancer cell lines were assessed. Results of enzymes and antibacterial, antifungal were in level of micromolar that is good impacts. These natural compounds may be antidiabetic, anticancer, and antibacterial candidates for drug design. IC50 results were obtained between 14-19 and 5-119 µM for α-amylase and α-glucosidase, respectively. Good inhibitor Bavachinin was detected for both enzymes (IC50 for α-amylase: 14.37 µM and IC50 for α-glucosidase: 5.27 µM). The chemical activities of aromadendrin, artepillin C, bavachin, and bavachinin against pancreatic α-amylase and α-glucosidase were assessed by conducting the molecular docking study. The chemical activities of aromadendrin, artepillin C, bavachin, and bavachinin against some of the expressed surface receptor proteins (CD44, CD47, CXCR4, EGFR, folate receptor, HER2, and endothelin receptor) in the mentioned cell lines were investigated using the molecular docking calculations. The results illustrated the atomic-level properties and potential interactions. These chemicals have high binding affinities to the enzymes and proteins, according to the docking scores. In addition, the compounds formed strong contacts with the enzymes and receptors. Thus, these compounds could be potential inhibitors for enzymes and cancer cells.

CircRNA circPDSS1 promotes the gastric cancer progression by sponging miR-186-5p and modulating NEK2.

The aim of this study is to investigate the regulatory mechanism of circPDSS1/miR-186-5p/NEK2 axis on the viability and proliferation in gastric cancer (GC) cell line. Differentially expressed circRNAs, miRNAs, and mRNAs in GC tissues and paracarcinoma tissues were analyzed using gene chips GSE83521, GSE89143, and GSE93415. Then, the expression of circPDSS1, miR-186-5p, and NEK2 was analyzed via quantitative real-time polymerase chain reaction (qRT-PCR). Survival analysis was adopted to explore the association between the circPDSS1 expression and the prognosis of GC. The effect of circPDSS1 on GC cell cycle and apoptosis was verified with the flow cytometry. Targeting relationships among circPDSS1, miR-186-5p, and NEK2 were predicted via bioinformatics analysis and demonstrated by the dual-luciferase reporter assay. Our results showed that circPDSS1 and NEK2 were high-expressed whereas miR-186-5p was low-expressed in GC tissues and cells. CircPDSS1 promoted GC cell cycle and inhibited apoptosis by sponging miR-186-5p, while miR-186-5p inhibited cell cycle and promoted apoptosis by targeting NEK2. Thus, circPDSS1 acts as a tumor promoter by regulating miR-186-5p and NEK2, which could be a potential biomarker and therapeutic target for the management of GC.

Long non-coding RNA MIF-AS1 promotes gastric cancer cell proliferation and reduces apoptosis to upregulate NDUFA4.

Long non-coding RNA MIF-AS1 (lncMIF-AS1) has been found to be upregulated in the tumor tissues of gastric cancer; however, its importance for the progression of gastric cancer remains unknown. Thus, the present study was designed to determine the role of the lncMIF-AS1-based signal transduction pathway in mediating the proliferation and apoptosis of gastric cancer cells. Differentially expressed lncRNAs and mRNAs were screened out using microarray analysis, based on the published data (GSE63288), and validated using quantitative RT-PCR. Target relationships between lncRNA-micro RNA (miRNA) and miRNA-mRNA were predicted by bioinformatics analysis and verified by dual-luciferase reporter assay. Protein expression of NDUFA4, COX6C and COX5B was detected by western blot. Cell proliferation, cell cycle and apoptosis were determined using colony formation assay and flow cytometry analysis. Oxidative phosphorylation in gastric cancer cells was assessed by levels of oxygen consumption and ATP synthase activity. Expression of lncMIF-AS1 and NDUFA4 were upregulated in gastric cancer tissues and cells as compared with non-cancerous gastric tissues and cells (P < .05). MiR-212-5p was identified as the most important miRNA linker between lncMIF-AS1 and NDUFA4, which was negatively regulated by lncMIF-AS1 and its depletion is the main cause of NDUFA4 overexpression (P < .01). The upregulated expression of NDUFA4 then greatly promoted the proliferation and decreased the apoptosis of gastric cancer cells through activation of the oxidative phosphorylation pathway. Taken together, the present study implies that inhibition of lncMIF-AS1/miR-212-5p/NDUFA4 signal transduction may provide a promising therapeutic target for the treatment of gastric cancer.

Visfatin inhibits colon cancer cell apoptosis and decreases chemosensitivity to 5­FU by promoting the SDF­1/CXCR4/Akt axis.

5­Fluorouracil (5­FU) is the preferred chemotherapeutic drug used in the treatment of colon cancer; however, drug resistance affects its clinical efficacy. Visfatin, an adipokine that promotes tumour development, has the potential to increase resistance to chemotherapy. The present study aimed to verify the effects of visfatin on the sensitivity of colon cancer cells to 5­FU and to elucidate the potential mechanisms involved. Tissue microarrays (TMAs) were used to analyse visfatin differential expression in normal colon and colon cancer tissues, and the data were further validated in vitro. Cell Counting Kit­8, clone formation, caspase­3/7 activity assays, as well as other analyses were used to verify the effects of visfatin on sensitivity to 5­FU. TMA and correlation analyses were used to predict and verify the correlation between visfatin and stromal cell­derived factor­1 (SDF­1). Rescue experiments and PI3K/Akt inhibitors were used to verify the role of the visfatin/SDF­1/Akt axis in the sensitivity of colon cancer cells to 5­FU. Visfatin was found to be highly expressed in colon cancer tissues and cell lines. Moreover, visfatin knockdown increased apoptosis, reduced cell proliferation and enhanced the chemosensitivity of DLD­1 and SW48 cells to 5­FU. A positive correlation between visfatin and SDF­1 was observed, with the knockdown of visfatin enhancing cell sensitivity to 5­FU chemotherapy by targeting the SDF­1/C­X­C chemokine receptor type 4 (CXCR4) axis. Furthermore, the Akt signalling pathway downstream of SDF­1/CXCR4 proved to be critical in the decreased sensitisation of colon cancer cells to 5­FU induced by visfatin. On the whole, the present study demonstrates that visatin can potentially decrease colon cancer cell apoptosis, promote proliferation and decrease colon cancer cell sensitivity to 5­FU via the visfatin/SDF­1/Akt axis.

RNF38 enhances 5-Fluorouracil resistance in colorectal cancer by activating the Wnt pathway.

PURPOSE: Colorectal cancer (CRC) is a frequent fatal cancer worldwide. 5-Fluorouracil (5-FU) is extensively used in its chemotherapy. This drug resistance, however, should be well concerned. Ring finger proteins (RNF) are vital regulators involved in CRC development. In this article, HCT116R cells were first established. The roles of RNF38 and Wnt signaling in 5-FU-resistant CRC were further illustrated. Our study provides novel evidence for improving 5-FU chemotherapy outcome in CRC patients. METHODS: The phenotype of established HCT116R cells was first examined. Next, the regulatory effect of RNF38 on 5-FU resistance in CRC was mainly explored. Nude mice bearing CRC were treated with 5-FU and in vivo overexpression of RNF38. RESULTS: 5-FU-resistant HCT-116 cells (HCT116R) were first established. 5-FU treatment markedly killed survival and induced apoptosis in HCT-116 cells. P53 was downregulated in HCT116R cells. Through microarray analysis, RNF38 was found to be upregulated in HCT116R cells compared to parental cells. CONCLUSIONS: Overexpression of RNF38 enhanced 5-FU resistance in CRC. Furthermore, Wnt signaling was activated by RNF38 and involved in 5-FU resistance in CRC.

[Treatment on post-operational complications of aortic endovascular grafting exclusion].

OBJECTIVE: To investigate the post-operative complications of aortic endovascular grafting exclusion (EVGE) and its reasons and treatments. METHODS: Clinical data of 82 cases received aortic endovascular grafting exclusion from January 2002 to October 2008 were retrospectively analyzed. Seventy-one cases were male and 11 cases were female with the age of 33 to 78 years and the average age of 49.2 years. There were 66 cases of thoracic aortic dissecting aneurysms and 16 cases of abdominal aortic aneurysm. The effect, post-operational complications and its treatment were investigated. RESULTS: There were 90.1% patients had been followed up with the time of 3 to 78 months with technical success of 90.3%, clinical success of 94.1%, peri-operational mortality of 2.4%, total mortality of 6.1% and mortality associated with EVGE of 2.4%. Twenty-one cases underwent complications including type I endoleak (13 cases), abdominal aortoduodenal fistula (1 case), narrow true lumen (2 cases), reverse Stanford A dissection (2 cases), post EVGE syndrome (12 cases), delayed healing of inguinal incision (5 cases), constipation (3 cases), cerebral infarction (1 case). No paraplegia, left subclavian artery ischemia, contrast media associated nephrosis, ischemic colitis, ischemic neurologic injury, and artery embolism occurred. Post operation 4 cases had the second intervention including 2 type I endoleak and 2 narrow true lumen. CONCLUSIONS: The technique-related complications still hinder the long-term effect of EVGE. It needs to be further investigated on technique improvement and treatment standardization.

Effects of high-fat diet-induced adipokines and cytokines on colorectal cancer development.

Colorectal cancer (CRC) is the third most common tumor worldwide, and recent epidemiological studies have indicated that obesity contributes to the morbidity and mortality of CRC. Furthermore, obesity-related adipokines have been shown to be closely related to the incidence of CRC, but the underlying mechanisms are unclear. Here, we investigated the effects of high-fat diet-induced adipokines and cytokines on the development of CRC in vitro and in vivo. For the in vivo assays, we divided 2-week-old C57BL/6J-ApcMin/J male mice into three groups: normal-fat diet (ND), high-fat and high-sugar feed (HFHS), and high-fat and low-sugar feed (HFLS). After 1 week, all mice were injected with 20 mg·kg-1 1,2-dimethylhydrazine once weekly for 10 consecutive weeks. Body weight, liver weight, epididymal fat weight and blood glucose levels were greatly increased in HFHS and HFLS groups compared with the ND group, and the expression levels of some adipokines and cytokines were obviously higher in HFHS or HFLS mice compared with ND mice. For the in vitro assays, HCT116 CRC cells were treated with sera of ND, HFHS or HFLS groups, or serum-free media as a negative control. We observed that sera derived from HFHS or HFLS mice that contain excess adipokines and cytokines promoted the proliferation, migration and invasion of HCT116 cells compared with the ND sera-conditioned medium or serum-free medium group. Therefore, high-fat diet-induced adipokines and cytokines may promote the progression of CRC in vivo and in vitro.