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Aims Alienation towards parents often occurs when parents divorce; however, it can also occur when one or both parents leave for work for more than 6 months. Our previous investigation has confirmed a high level of feelings of alienation towards parents among Chinese left-behind children. However, the longitudinal prediction of alienation on children's mental health outcomes remains largely unknown. This study aims to observe the prediction of alienation towards parents on children's depression 12 months later and potential mediators and moderators. Methods A total of 1090 Chinese left-behind children took part in this 12-month follow-up investigation, using the Chinese version of the Inventory of Alienation towards Parents (IAP), the Children's Depression Inventory (CDI), the Adolescent Self-Rating Life-events Checklist (ASLEC), and the Adolescent Resilience Scale. Results Alienation towards parents was high (16.42 ± 7.27 for mother, 15.63 ± 7.17 for father) in left-behind children, and 21.01% of children reported depression. Alienation towards parents predicted current depression of children directly and later depression indirectly; children's alienation toward their mothers was a stronger predictor of depression than alienation towards fathers. In models, stressful life-events acted as a risk mediator. Previous depression was the strongest risk predictor, resilience was the strongest protective factor, and duration of fathers’ absence and parents’ marital status moderated the predictive effects. Conclusions This study is among the first to longitudinally confirm that alienation towards parents is a predictor of children's later depression. The results provide important suggestions for families and schools; i.e. to prevent depression in left-behind children, parent−child bonds especially alienation towards mothers, should be carefully considered, and individuals with more negative life-events and weaker resilience need further attention.

Flavonols and proanthocyanidins are the major components that determine the black colouration of cucumber fruit spines and their synthesis is regulated by CsMYB60., Spine colour is an important fruit quality trait that influences the commercial value of cucumber (Cucumis sativus). However, little is known about the metabolites and the regulatory mechanisms of their biosynthesis in black spine varieties. In this study, we determined that the pigments of black spines are flavonoids, including flavonols and proanthocyanidins (PAs). We identified CsMYB60 as the best candidate for the previously identified B (Black spine) locus. Expression levels of CsMYB60 and the key genes involved in flavonoid biosynthesis were higher in black-spine inbred lines than that in white-spine lines at different developmental stages. The insertion of a Mutator-like element (CsMULE) in the second intron of CsMYB60 decreased its expression in a white-spine line. Transient overexpression assays indicated that CsMYB60 is a key regulatory gene and Cs4CL is a key structural gene in the pigmentation of black spines. In addition, the DNA methylation level in the CsMYB60 promoter was much lower in the black-spine line compared with white-spine line. The CsMULE insert may decrease the expression level of CsMYB60, causing hindered synthesis of flavonols and PAs in cucumber fruit spines.

MicroRNAs (miRNAs) are increasingly recognized as being involved in pancreatic cancer progression by directly regulating the expression of their targets. In this study, we showed that miR-216b-5p expression was significantly decreased in pancreatic cancer tissues and cell lines. In addition, low miR-216b-5p expression was significantly associated with large tumor size and advanced TNM stage. Meanwhile, both Kaplan-Meier and multivariate survival analysis showed that decreased miR-216b-5p expression was associated with overall survival. miR-216b-5p over-expression repressed pancreatic cancer cell proliferation and induced cell cycle arrest and cell apoptosis in vitro and inhibited tumorigenesis in vivo. The translationally controlled tumor protein (TPT1) was identified as a novel direct target of miR-216b-5p. miR-216b-5p up-regulation suppressed TPT1 expression. Moreover, TPT1 mRNA expression levels were increased in pancreatic cancer tissues, and were inversely correlated with miR-216b-5p expression. TPT1 down-regulation had similar effects as miR-216b-5p up-regulation on pancreatic cancer cell progression. The restoration of TPT1 reversed the effect of miR-216b-5p on pancreatic cancer cell progression. Furthermore, we found that miR-216b-5p up-regulation suppressed Pim-3, Cyclin B1, p-Bad and Bcl-xL protein expression. However, the effect of miR-216b-5p up-regulation was partly reversed by TPT1 up-regulation in vitro. Taken together, our findings suggested that miR-216b-5p functions as a potential tumor suppressor by regulating TPT1 in pancreatic cancer cells, and it may represent a potential therapeutic target for patients with pancreatic cancer.

Bioassay-guided fractionation of marine-derived fungi revealed that the EtOAc fraction from the fermentation broth of a mutated fungal strain Streptomyces nitrosporeus YBH10-5 had lipid-lowering effects in HepG2 cells. Chromatographic separation of the EtOAc fraction resulted in the isolation of 11 PKS-based derivatives, including a structurally unique meroterpenoid namely nitrosporeunol H (1). The structure of compound 1 was determined by the analysis of spectroscopic data. Further bioassay resulted in farnesylquinone (2) and its analogues to exert in vivo fat-reducing effects in C. elegans worm model. The underlying mode of action of compound 2 in the context of live worms was investigated, uncovering that compound 2 enhanced the mitochondrial &beta, oxidation rate and changed the transcriptional level of energy metabolism genes. Additional experiments revealed that compound 2 exerted its effects in C. elegans partially through repressing FAT-5, an isoform of stearoyl-CoA desaturase (SCD) which catalyzes the conversion of saturated fatty acids to monounsaturated fatty acids, thereafter leading to the modification of the fatty acid profile. Thus, compound 2 was suggested to be a promising lead for further optimization to treat obesity.

// Yu You 1 , Jia-Xin Tan 1 , Hai-Su Dai 1 , Hao-Wei Chen 1 , Xue-Jun Xu 1 , Ai-Gang Yang 1 , Yu-Jun Zhang 1 , Lian-Hua Bai 1 , Ping Bie 1 1 Department of Hepatobiliary Surgery Institute, South Western Hospital, Third Military Medical University, Chongqing 400038, China Correspondence to: Ping Bie, email: bieping@medmail.com.cn Lian-Hua Bai, email: 870426131@qq.com Keywords: hepatocellular carcinoma, hepatic stellate cells, galectin-1, miRNA-22 Received: April 14, 2016 Accepted: July 10, 2016 Published: August 1, 2016 ABSTRACT Hepatic stellate cells (HSCs) induce immune privilege and promote hepatocellular carcinoma (HCC) by suppressing the immune system. On the other hand, galectin-1 and miRNA-22 (miR-22) are dysregulated in HCC and serve as prognostic indicators for patients. In this study, therefore, we measured galectin-1 and miR-22 expression in HSCs isolated from HCC tissues (Ca-HSCs), and in normal liver tissues (N-HSCs) as a control. We also investigated the apoptosis rate among T cells and the production of cytokines (IFN-γ and IL-10) in HSCs co-cultured with T cells. And we used immunohistochemical staining to tested for correlation between galectin-1 expression, CD3 expression and clinicopathological features in 162 HCC patients. Our results showed that galectin-1 expression was much higher in Ca-HSCs than in N-HSCs. Overexpression of galectin-1 promoted HSC-induced T cell apoptosis and cytokine production (IFN-γ and IL-10), while miR-22 expression inhibited it. Galectin-1 expression correlated negatively with miR-22 expression in HSCs. High galectin-1 and low CD3 expression levels were associated with poor prognosis in HCC patients. These results suggest that the immunosuppressive microenvironment promoted by HSC-derived galectin-1 in HCC can be inhibited by miR-22. Galectin-1 and miR-22 could potentially serve as prognostic markers and therapeutic targets in HCC.

Indolocarbazole (ICZ) alkaloid constitutes a group of natural products which manifested powerful biological activity, especially anticancer. However, it was laborious to find ICZs-yield organism when anticancer activity was adopted as selection target. The specificity of 6 primer pairs was detected and the results revealed that primer rebBN1/rebBC1 possessed preferable specificity because indolocarbazole-producers DNA was exclusively amplified and no target fragment was amplified from any of indolocarbazole nonproducers. Therefore, primer rebBN1/rebBC1 could specifically identify indolocarbazole-producers from microorganism strains. Key words: Indolocarbazole, rebBN1/rebBC1, ICZs-producing microorganism screening.

Chemical examination of an arctic actinomycete Streptomyces nitrosporeus resulted in the isolation of two new alkaloids named nitrosporeusines A (1) and B (2), an unprecedented skeleton containing benzenecarbothioc cyclopenta[c]pyrrole-1,3-dione. Their structures were determined through extensive spectroscopic analyses in association with X-ray single crystal diffraction. Both 1 and 2 exhibited inhibitory activities against the H1N1 virus in MDCK cells.

A sensitive and reliable bioanalytical method was established for quantitati\ve and pharmacokinetic investigation of nine ginsenosides and seven bufadienolides in rat plasma after the oral administration of Shexiang Baoxin Pill by liquid chromatography-electrospray ionization tandem mass spectrometry, using tinidazole and digoxin as internal standards (ISTDs). All of the analytes and ISTDs obtained satisfactory recoveries by solid-phase extraction using an Oasis HLB μElution Plate, which was eluted with methanol and ethyl acetate successively, and chromatographic separation was achieved on a Shim-pack XR-ODSIIcolumn (75 × 2.0 mm, 2.2 μm) with gradient elution using a mixture of acetonitrile-0.1% formic acid solution (v/v) as the mobile phase at a flow rate of 0.3 mL/min. Detection was carried out by a triple-quadrupole tandem mass spectrometry with positive/negative ion switching multiple reaction monitoring mode. All analytes showed good linearity over a wide concentration range (r2 > 0.99). The lower limit of quantification was in the range 0.625-12.5 ng/mL for bufadienolides and 2-5.5 ng/mL for ginsenosides, and the mean recoveries of all analytes were in the range 78.29-99.35%. The intra- and inter-day precisions (RSD) were in the range 0.08-12.38% with the accuracies between 86.09 and 99.40%. The validated method was then successfully applied to pharmacokinetic study of the above 16 compounds in rat plasma. Pharmacokinetic results indicated that the developed extraction and analytical method could be employed as a rapid, effective technique for pharmacokinetic study of multiple components, especially various polarity that are difficult to extract simultaneously.

Raf kinase inhibitor protein (RKIP) is a tumor suppressor that inhibits cell growth and metastasis of malignant tumors. Pancreatic cancer is a leading cause of cancer death with a low survival rate. RKIP expression and its role in tumorigenesis and metastasis in pancreatic cancer are poorly understood. The aims of our study were to assess the effects of RKIP on pancreatic carcinoma cells in vitro and in tumor tissues in vivo. This study included 84 patients with histologically confirmed pancreatic adenocarcinoma. The expression levels of RKIP were measured in pancreatic cancer tissues and adjacent normal tissues using real-time PCR and immunohistochemistry. Overexpression plasmid of RKIP was transfected into SW1990 and AsPC-1 cell lines, and the effects on cell proliferation were studied using a Cell Counting Kit-8 assay. MEK1/2 and ERK1/2 were detected by Western blot and immunofluorescence assay. Results showed a reduced expression of RKIP in pancreatic carcinoma tissues compared with adjacent normal tissues, which closely correlated with patient outcomes. Overexpression of RKIP suppressed cell proliferation and promoted apoptosis in cultured SW1990 and AsPC-1 cell lines. Transwell assay showed RKIP can inhibit cell migration and invasion, and in vivo RKIP can suppress tumorigenesis by diminishing the volume of the tumors. In conclusion, expression of RKIP is closely correlated with the survival of pancreatic cancer patients. RKIP can inhibit pancreatic adenocarcinoma cells proliferation, activities of migration and invasion, through downregulating Raf-1-MEK1/2-ERK1/2 signaling pathway.

Prenylated indolocarbazoles have been reported neither from natural sources, nor by chemical synthetic approaches. In this Letter, we report a regiospecific prenylation of indolocarbazoles at the para- position of the indole N-atom by two recombinant enzymes from the dimethylallyltryptophan synthase (DMATS) superfamily, that is, 5-DMATS from Aspergillus clavatus and FgaPT2 from Aspergillus fumigatus .

Bioassay-guided fractionation of the fermentation broth of Arctic Streptomyces nitrosporeus YBH10-5 resulted in the isolation of seven new compounds named nitrosporeunols A-G (1-7), together with seven known analogues (8-14). Their structures were determined based on extensive spectroscopic analysis. Compounds 1-14 were evaluated for the lowering lipid effects, while two compounds (10 and 12) remarkably decreased lipid levels including total cholesterol (TC) and triglycerides (TG) in HepG2 cells. Quantitative realtime PCR and Western blot indicated that farnesylquinone (12) increased the expression of the key proteins including peroxisome proliferator-activated receptor-α (PPARα), peroxisome proliferator-activated receptor-γ, and coactivator 1α (PGC-1α), as well as their downstream genes carnitine palmitoyltransterase-1 (CPT-1), acyl-coenzyme A oxidase 1 (ACOX), malonyl CoA decarboxylase 1 (MCD1), pyruvate dehydrogenase kinase 4 (PDK4), and cholesterol 7α -hydroxylase (CYP7A1). Luciferase assay showed that 12 increased the transcriptional activity of PPARα, while its lipid-lowering effect was abolished by PPARα inhibitor, MK886, in HepG2 cells. These findings suggested that 12 is a potent lipid-lowering agent which may decrease lipid levels through upregulation of PPARα pathway.

Chemical examination of an arctic actinomycete Streptomyces nitrosporeus resulted in the isolation of two new alkaloids named nitrosporeusines A (1) and B (2), an unprecedented skeleton containing benzenecarbothioc cyclopenta[c]pyrrole-1,3-dione. Their structures were determined through extensive spectroscopic analyses in association with X-ray single crystal diffraction. Both 1 and 2 exhibited inhibitory activities against the H1N1 virus in MDCK cells.