FGD5­AS1 is an oncogenic lncRNA in pancreatic cancer and regulates the Wnt/ß­catenin signaling pathway via miR­577.

The objective of the present study was to clarify the expression characteristics of long non­coding RNA (lncRNA) FGD5 antisense RNA 1 (FGD5­AS1) in pancreatic cancer, as well as its biological function and underlying mechanism. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was utilized for the detection of FGD5­AS1 and microRNA (miR)­577 expression levels in pancreatic cancer tissues. Transfection was performed to upregulate or downregulate FGD5­AS1 in pancreatic cancer cell lines. MTT and Transwell assays were then utilized to detect the proliferation, migration and invasion of cancer cells, respectively. Subsequently, dual­luciferase reporter gene assay, RNA immunoprecipitation assay, RNA pull­down assay, RT­qPCR, western blotting, and Pearson's correlation analysis were employed to confirm the regulatory relationships among FGD5­AS1, miR­577, low­density lipoprotein receptor­related protein 6 (LRP6) and ß­catenin. Western blotting was employed to determine the expression levels of Axin2, cyclin D1 and c­Myc. The expression level of FGD5­AS1 was upregulated in pancreatic cancer tissues and cell lines. FGD5­AS1 knockdown inhibited pancreatic cancer cell proliferation, migration and invasion. By contrast, miR­577 was significantly inhibited in pancreatic cancer cells and tissues; its downregulation promoted pancreatic cancer cell proliferation, migration and invasion, and reversed the effects of FGD5­AS1 knockdown on pancreatic cancer cells. In addition, it was revealed that miR­577 was a target of FGD5­AS1, and FGD5­AS1 could modulate the expression levels of LRP6, ß­catenin, Axin2, cyclin D1 and c­Myc via suppressing miR­577. In conclusion, in pancreatic cancer, highly expressed FGD5­AS1 activated the Wnt/ß­catenin signaling and promoted cancer cell proliferation, migration and invasion via suppression of miR­577.

A Bifunctional Coordination Polymer for Al3+ Ion Detection and its Treatment Effect on Nonalcoholic Fatty Liver Disease by Promoting Lipoxygenases and Reducing Intrahepatic Triglyceride Content.

In this study, a new Cd(II)-bearing coordination polymer with the chemical formula of {[Cd4(meda)3(dpe)4(H2O)4]·(NO3)2·2(H2O)}n (1, H2meda = 3,3'-methylenedibenzoic acid, dpe = 1,2-di(pyridin-4-yl)ethane) has been successfully prepared by reaction of Cd(NO3)·4H2O with a V-shape carboxyl ligand H2meda along with the linear dipyridine ligand dpe under the hydrothermal conditions. Due to its intensive luminescence, complex 1 could be utilized as the sensor of detecting Al3+ ion, and its detection limit is 4 × 10-6 M. Firstly, the toxicity of the compound on the normal liver cells was determined with Cell Counting Kit-8 detection kit. The triglyceride in liver cells was detected by detection kit after compound treatment and the relative expression of 15-lox and 12-lox in L02 cells was also measured by RT-PCR after compound treatment. In addition, multiple functional groups that provided by the synthesized Cd(II) complex have been studied by using molecular docking simulation for the confirmation of possible binding modes that formed between ligand and receptor.

Diabetes mellitus and risk of pancreatic cancer in China: A meta-analysis based on 26 case-control studies.

AIMS: The relationship between diabetes mellitus and pancreatic cancer risk from is uncertain based on the results of existing publications. The current report updated and re-evaluated the possible association between diabetes mellitus and pancreatic cancer risk in China. METHODS: Six databases (PubMed, Embase, Web of Science, the Cochrane Library, the Chinese Biomedical Database, and the Chinese National Knowledge Infrastructure) were used for the literature search up to October 2017. RESULTS: Twenty-six case-control studies involving 7702 pancreatic cancer cases and 10186 controls were screened out. The overall summary estimate for the relationship between diabetes and pancreatic cancer was 3.69 (95% CI, 3.12-4.37). The subgroup analysis indicated positive associations among northern and southern Chinese, as well as studies with healthy population or hospital controls. In addition, the risk of developing pancreatic cancer was inversely associated with the duration of diabetes, with the highest risk of pancreatic cancer occurring among patients with diabetes <2years. Individuals who had diabetes <2years had a >2-fold higher risk of developing pancreatic cancer than individuals who had diabetes for 2-4years or 5-10years (OR, 4.92; 95% CI, 4.16-5.80 vs. OR, 1.92; 95% CI, 1.30-2.85/OR, 2.14; 95% CI, 1.49-3.09). CONCLUSIONS: This meta-analysis strongly supports that an association exists between diabetes and an increased risk of pancreatic cancer in China, which should be confirmed with other ethnic groups.

4E-BP1 regulates the sensitivity of human glioma cells to chemotherapy through PI3K/Akt/mTOR-independent pathway.

Drug resistance is one of the most formidable obstacles for treatment of glioma. Eukaryotic initiation factor 4E-binding protein (4E-BP1), a key component in the rate-limiting step of protein translation initiation, is closely associated with poor prognosis in multiple tumor types. However, it is unclear whether 4E-BP1 is involved in the drug resistance of human glioma. Herein we show that the expression of 4E-BP1 in human SWOZ2-BCNU drug-resistant glioma cells is significantly lower than that of the parent SWOZ2 cell line. Moreover, down-regulation of 4E-BP1 by short interfering RNA significantly impaired the sensitivity of SWOZ2 and U251 cells to carmustine (BCNU). Furthermore, overexpression of 4E-BP1 with plasmid transfection regained this sensitivity. Clinical studies showed that the expression levels of 4E-BP1 in primary glioma tissues were markedly higher than those of recrudescent glioma tissues. Taken together, our results suggest that 4E-BP1 is a novel protein that contributes to acquired drug resistance and it may be a potential target for reversing drug resistance in human glioma.

Role of PTEN in cholera toxin-induced SWO­38 glioma cell differentiation.

Malignant gliomas persist as a major disease responsible for high morbidity and mortality rates in adults. Differentiation therapy has emerged as a promising treatment modality. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene function is commonly lost in primary gliomas, particularly in glioblastomas, and this is associated with tumor differentiation. PTEN gene deletion is one of the main molecular events in gliomas. In this study, we aimed to explore the effect and mechanisms of PTEN on cholera toxin (CT)­induced SWO-38 glioma cell differentiation. It has been shown that transfection of the exogenous PTEN gene induces glioma cell differentiation; however, the underlying mechanism remains to be elucidated. Results of the present study showed that CT-induced SWO-38 glioma cell differentiation was characterized by morphological changes, the increased expression of glial fibrillary acidic protein (GFAP), an accumulation of cells in the G0/G1 phase of the cell cycle, the decreased expression of cyclin D1 and a decreased invasion and migration capacity. Silencing of the PTEN protein using RNA interference resulted in suppressed cell differentiation. Furthermore, inhibition of the PI3K/AKT pathway by the inhibitor LY294002 led to attenuated differentiation, while differentiation remained stable with the inhibition of the MAPK/ERK pathway by PD0325901. Thus, PTEN may be important in glioma cell differentiation.

[The experimental study of suppressing silicosis fibrosis].

OBJECTIVE: To compare the difference of effects on SiO(2)-induced alveolitis and early fibrosis between bone marrow-derived mesenchymal-like stem cells (BM-MSCs) and BM-MSCs transfected by pcDNA3.1-HGF and to explore the mechanism of this effects. METHODS: The Primary BM-MSCs from Wistar male young rats were cultured and labeled by 4, 6-diamidino-2-phenylindole (DAPI). Fifty Wistar rats were randomly divided into 3 groups:model group (10 rats),which was administered with SiO(2) by the trache, the next day,injected PBS via the tail vein; BM-MSCs group (20 rats),which was administered with SiO(2) by the trache, the next day,injected with 1 ml suspension of BM-MSCs via the tail vein; pcDNA3.1-HGF plus BM-MSC group (20 rats),which was administered with SiO(2) by the trache, the next day,injected with 1 ml suspension of BM-MSCs transfected by pcDNA3.1-HGF via the tail vein. On the 14th and 28th days after treatment, half of the animals were sacrificed, respectively, and the lungs were harvested for frozen section to observe the cell marked by DAPI. HE staining under a fluorescent microscope, and to observe the pulmonary alveolitis and fibrosis by HE and Masson staining under a light microscope. Western blot assay was used to detect the expression of HGF in rat lungs. The expression levels of tumor necrosis factor-α (TNF-α) in pulmonary tissues were analyzed quantitatively by ELISA. The contents of HYP in pulmonary tissues were analyzed quantitatively by sample hydrolysis method. RESULTS: On the 14th and 28th days after treatment, the scores of pulmonary alveolitis and early fibrosis in pcDNA3.1-HGF plus BM-MSCs group were 2.36 ± 0.17, 2.8 ± 0.14 and 0.1 ± 0.11, 1.16 ± 0.13, which were significantly lower than those (1.68 ± 0.17, 1.58 ± 0.31 and 0.54 ± 0.15, 1.36 ± 0.13) in BM-MSCs group, also which were significantly lower those (2.36 ± 0.17, 2.80 ± 0.14 and 0.64 ± 0.09, 1.84 ± 0.17) in model group (P < 0.05); On the 14th and 28th days after treatment, the TNF-α contents of pulmonary tissues in pcDNA3.1-HGF plus BM-MSCs group were 280.4 ± 23.11 and 249.78 ± 22.33 pg/mg, which were significantly lower than those (341.58 ± 35.34, 442.29 ± 36.76 pg/mg and 319.51 ± 17.84, 348.53 ± 33.95 pg/mg) in BM-MSCs and model groups (P < 0.05); On the 14th and 28th days after treatment, the HYP contents of pulmonary tissues in pcDNA3.1-HGF plus BM-MSCs group were 0.46 ± 0.04 and 0.65 ± 0.05 µg/mg, which were significantly lower than those (0.63 ± 0.04, 1.04 ± 0.07 µg/mg and 0.72 ± 0.60, 1.39 ± 0.60 µg/mg) in BM-MSCs and model groups (P < 0.05). CONCLUSION: The effects of BM-MSCs transfected by pcDNA3.1-HGF on suppressing pulmonary alveolitis and early fibrosis induced by SiO2 were better than those of BM-MSCs. The mechanism may be associated with the reduced pulmonary inflammation.

[Random amplified polymorphic DNA analysis of the genomes among 7 species of ticks].

OBJECTIVE: To study genomic polymorphic DNA and genetic distance of 7 species of ticks. METHODS: Ticks used in this study were Dermacentor nuttalli, D. silvarum, Haemaphysalis qinghaiensis, H. formosensis, H. punctata, Amblyomma testudinarium, and Ixodes ovatus. DNA extracts of the 7 species of ticks were amplified by random amplified polymorphic DNA (RAPD) and PCR technique using 5 primers with different arbitrary single chain polynucleotide sequences. DNA fingerprint maps were analyzed and the genetic distance among 7 species of ticks were counted. RESULTS: The amplified products of the 7 species of ticks by RAPD all showed their specific DNA band. The average genetic distance among them was 0.71. CONCLUSION: RAPD can differentiate the 7 species of ticks.

[Peroxisome proliferation-activated receptor-gamma ligands ameliorate autoimmune myocarditis associated with inhibition of T cell immunity].

OBJECTIVE: To investigate the role of peroxisome proliferator-activated receptor-gamma (PPAR gamma) on autoimmune myocarditis, and to test the hypothesis that PPAR-gamma ligands reduce experimental autoimmune myocarditis (EAM) associated with inhibition of the expansion and activation of self-sensitive T cells. METHODS: EAM was induced in Lewis rats by immunization with porcine cardiac myosin. Then the rats were divided into 3 groups of 9 rats: PPAR-gamma ligand 15-deoxy-(12,14)-PGJ(2) (15d-PGJ(2)) group (15d-PGJ(2) was injected intraperitoneally at the dosage of 200 microg.kg(-1).d(-1)), pioglitazone (PIO) group (PIO was mixed with the food and than fed at the dosage of 10 mg.kg(-1).d(-1)), and positive control group (phosphate-buffered saline was injected intraperitoneally). Nine normal rats were used as normal controls. Three weeks later, the rats underwent thoracotomy to undergo pathologic examination. The numbers of CD4(+) cells, CD8(+) cells, and macrophages were calculated by microscopy. Immunohistochemistry was used to examine the location and expression of PPAR gamma. Western blotting was used to examine the relative amount of PPAR gamma protein. The proliferative response and the cytotoxicity of T cell-enriched splenocytes and lymph node cells were determined. Another rats were killed 12 days after immunization. Their spleens and lymph nodes were taken out. T-cell rich splenocytes and cells from the lymph nodes were cultured. Cardiac myosin and 15d-PGJ(2) were added. [(3)H] thymine was added 72 hours after. ELISA was used to examine the interferon-gamma (IFN-gamma) in the supernatant. 15d-PGJ(2), PIO, or PBS were given to immunize the rats. The rats were killed 12 days after. The lymph nodes were taken out to make single cell suspension. (51)Cr was used to label the cells so as to calculate the %cytotoxicity. RESULTS: All immunized rats showed myocarditis. The numbers of CD4(+) cells, CD8(+) T cells, and macrophages, were 18 +/- 5, 7 +/- 2, and 45 +/- 8/six 0.25 mm x 0.25 mm squares. PPAR gamma was mainly located in the nuclear and perinuclear regions of infiltrating inflammatory cells, such as mononuclear cells and macrophage-like cells. The expression of PPAR gamma in the myocardium of EAM rats was 3.7 times higher than of the normal rats. The heart weight/body weight ratio, pericardial effusion scores, macroscopic scores and microscopic scores of the 15d-PGJ group were significantly lower than those of the positive control group. The numbers of CD4(+) cells of the 15d-PGJ and PIO groups were 8 +/- 2 and 10 +/- 3, both significantly lower than that of the positive control group (both P < 0.01), the numbers of CD8(+) cells of the 15d-PGJ and PIO groups were 3 +/- 1 and 4 +/- 2 respectively, both significantly lower than that of the positive control group (P < 0.01 and P < 0.05), and the numbers of macrophages of the 15d-PGJ and PIO groups were 22 +/- 4 and 26 +/- 6 respectively, both significantly lower than that of the positive control group (both P < 0.01). The myocardiogenicity and the severity of myocarditis of the 15d-PGJ(2)- and PIO-groups were at lower degrees compared with those of the positive control group. The % cytotoxic activity was 10.2% +/- 2.6% in the 15d-PGJ(2) group and was 11.6% +/- 3.7% in the PIO group, both significantly lower than that of the positive control group (37.7% +/- 8.4%, both P < 0.01) Stimulated by cardiac myosin, the T-cell rich splenocytes and cells from lymph nodes showed obvious proliferation and production of IFN-gamma. The cardiac myosin-stimulated cell proliferation and production of IFN-gamma in the 15d-PGJ(2) and PIO groups were significantly reduced in comparison with those in the positive control group. CONCLUSION: PPAR-gamma ligands ameliorate EAM associated with inhibition of expansion and activation of the self-sensitive T cells.