Suppressive effect of YY1-mediated RGS22 regulation on the proliferation, migration and invasion of pancreatic ductal adenocarcinoma.

Regulator of G-protein signaling 22 (RGS22) is specifically expressed in the testis and in tumors of epithelial origin, but the expression and role of RGS22 in pancreatic cancer are unclear. In this study, 52 pairs of pancreatic ductal adenocarcinoma (PDAC) and adjacent non-neoplastic tissue samples with the corresponding clinical data were used to examine the expression of RGS22 and its relationship with PDAC prognosis. The findings showed that the expression of RGS22 was higher in the PDAC tissues than in the adjacent non-tumorous tissues and its expression was associated with the degree of blood vessel invasion. The in vitro experiments with PDAC cell lines and a normal control cell line showed that the proliferation, invasion, and metastasis of PDAC cells were suppressed by RGS22 overexpression and enhanced by RGS22 knockdown. The in vivo effect of RGS22 on PDAC xenografts was studied using subcutaneous implantation of tumor cells in BALB/cA-nu mice, and the results corroborated the in vitro findings. Analysis of the regulators of RGS22 showed that it was positively regulated by the transcription factor Yin Yang-1 (YY1). Thus, YY1-mediated RGS22 regulation suppressed the proliferation, migration, and invasion of PDAC.

Design, synthesis and herbicidal activities of p-menth-3-en-1-amine thiourea derivatives.

An efficient method for the synthesis of 1-isopropyl-4-isothiocyanato-4-methylcyclohex-1-ene has been developed with p-menth-3-en-1-amine as raw material. Next, a number of p-menth-3-en-1-amine thiourea derivatives (4a-f) have been obtained from the reactions between 1-isopropyl-4-isothiocyanato-4-methylcyclohex-1-ene and cyclohexylamine or the reactions between p-menth-3-en-1-amine and different isothiocyanates. Then, the herbicidal activities of these compounds were evaluated. The result indicated that some of these newly synthesised compounds displayed remarkable herbicidal activities against annual ryegrass. In addition, the derivative containing cyclohexane ring (4a) displayed much higher herbicidal activity against annual ryegrass than the derivatives containing benzene ring.

Constructing a Predictive Model of Depression in Chemotherapy Patients with Non-Hodgkin's Lymphoma to Improve Medical Staffs' Psychiatric Care.

OBJECTIVES: Depression is highly prevalent in non-Hodgkin's lymphoma (NHL) patients undergoing chemotherapy. The social stress associated with malignancy induces neurovascular pathology promoting clinical levels of depressive symptomatology. The purpose of this study was to establish an effective depressive symptomatology risk prediction model to those patients. METHODS: This study included 238 NHL patients receiving chemotherapy, 80 of whom developed depressive symptomatology. Different types of variables (sociodemographic, medical, and psychosocial) were entered in the models. Three prediction models (support vector machine-recursive feature elimination model, random forest model, and nomogram prediction model based on logistic regression analysis) were compared in order to select the one with the best predictive power. The selected model was then evaluated using calibration plots, ROC curves, and C-index. The clinical utility of the nomogram was assessed by the decision curve analysis (DCA). RESULTS: The nomogram prediction has the most efficient predictive ability when 10 predictors are included (AUC = 0.938). A nomogram prediction model was constructed based on the logistic regression analysis with the best predictive accuracy. Sex, age, medical insurance, marital status, education level, per capita monthly household income, pathological stage, SSRS, PSQI, and QLQ-C30 were included in the nomogram. The C-index was 0.944, the AUC value was 0.972, and the calibration curve also showed the good predictive ability of the nomogram. The DCA curve suggested that the nomogram had a strong clinical utility. CONCLUSIONS: We constructed a depressive symptomatology risk prediction model for NHL chemotherapy patients with good predictive power and clinical utility.

Roundabout homolog 1 inhibits proliferation via the YY1-ROBO1-CCNA2-CDK2 axis in human pancreatic cancer.

Pancreatic cancer (PC) is highly malignant and has a high mortality with a 5-year survival rate of less than 8%. As a member of the roundabout immunoglobulin superfamily of proteins, ROBO1 plays an important role in embryogenesis and organogenesis and also inhibits metastasis in PC. Our study was designed to explore whether ROBO1 has effects on the proliferation of PC and its specific mechanism. The expression of ROBO1 was higher in cancer tissues than in matched adjacent tissues by immunohistochemistry (IHC) and qRT-PCR. Low ROBO1 expression is associated with PC progression and poor prognosis. Overexpression of ROBO1 can inhibit the proliferation of PC cells in vitro, and the S phase fraction can also be induced. Further subcutaneous tumor formation in nude mice showed that ROBO1 overexpression can significantly inhibit tumor growth. YY1 was found to directly bind to the promoter region of ROBO1 to promote transcription by a luciferase reporter gene assay, a chromatin immunoprecipitation (ChIP) and an electrophoretic mobility shift assay (EMSA). Mechanistic studies showed that YY1 can inhibit the development of PC by directly regulating ROBO1 via the CCNA2/CDK2 axis. Taken together, our results suggest that ROBO1 may be involved in the development and progression of PC by regulating cell proliferation and shows that ROBO1 may be a novel and promising therapeutic target for PC.

DUOX2 As a Potential Prognostic Marker which Promotes Cell Motility and Proliferation in Pancreatic Cancer.

DUOX2 has been reported to highly express in several types of cancers. However, the prognostic significance and the biological function of DUOX2 expression with pancreatic cancer (PC) still remain unclear. The present study is aimed at investigating whether DUOX2 could act as a novel biomarker of prognosis and evaluating its effect on PC cell progression. The mRNA and protein expression of DUOX2 in PC cells and tissues were assessed by quantitative real-time PCR (RT-qPCR) and immunohistochemistry. The effect of DUOX2 expression on PC cell motility and proliferation was evaluated in vitro. The correlation between DUOX2 mRNA expression and clinicopathological features and its prognostic significance were analyzed according to the Gene Expression Profiling Interactive Analysis (GEPIA) website based on The Cancer Genome Atlas (TCGA) and the GTEx databases combined with our clinical information. According to bioinformatics analysis, we forecasted the upstream transcription factors (TFs) and microRNA (miRNA) regulatory mechanism of DUOX2 in PC. The expression of DUOX2 at transcriptional and protein level was dramatically increased in PC specimens when compared to adjacent nontumor specimens. Functionally, DUOX2 knockdown inhibited cell motility and proliferation activities. Our clinical data revealed that the patients had better postoperative overall survival (OS) with lower expression of DUOX2, which is consistent with GEPIA data. Multivariate analysis revealed that high DUOX2 expression was considered as an independent prognostic indicator for OS (P = 0.031). Based on Cistrome database, the top 5 TFs of each positively and negatively association with DUOX2 were predicted. hsa-miR-5193 and hsa-miR-1343-3p targeting DUOX2 were forecasted from TargetScan, miRDB, and DIANA-TarBase databases, which were negatively correlated with OS (P = 0.043 and P = 0.0088, respectively) and DUOX2 expression (P = 0.0093 and P = 0.0032, respectively) in PC from TCGA data. These findings suggest that DUOX2 acts as a promising predictive biomarker and an oncogene in PC, which could be a therapeutic target for PC.

Linc01232 promotes the metastasis of pancreatic cancer by suppressing the ubiquitin-mediated degradation of HNRNPA2B1 and activating the A-Raf-induced MAPK/ERK signaling pathway.

Pancreatic cancer (PC) is a malignant cancer with high mortality and poor prognosis. In this study, we found that Linc01232 was significantly upregulated in PC tissues and cells and higher Linc01232 expression was associated with poorer prognosis. Linc01232 overexpression promoted and Linc01232 knockdown inhibited the migration and invasion of PC cells. The results of RNA pull-down, RNA Binding Protein Immunoprecipitation (RIP) assays revealed that Linc01232 physically interacted with Heterogeneous Nuclear Ribonucleoprotein A2/B1 (HNRNPA2B1) (680-890 nt fragment with the RNA recognition motif 2 domain) to inhibit its ubiquitin-mediated degradation in PC cells. RNA sequencing was performed to obtain the transcriptional profiles regulated by Linc01232 and we further demonstrated that Linc01232 participated in the alternative splicing of A-Raf by stabilizing HNRNPA2B1 and subsequently regulated the MAPK/ERK signaling pathway. Collected, our study showed that Linc01232/HNRNPA2B1/A-Raf/MAPK axis participated in the progression of PC and provided a potential therapeutic target for PC.

An efficient synthesis method targeted to a novel aziridine derivative of p-menthane from turpentine and its herbicidal activity.

A novel aziridine compound N-acetyl-1,2-azacyclo-p-menthane d was synthesised using turpentine as raw material and characterised by FT-IR, 1H NMR, 13C NMR, ESI+-MS and HRMS. The pre-emergence herbicidal activities of d and its synthetic intermediates cis- and trans-N,N'-diacetyl-p-menthane-1,8-diamine (b2 and b1) were determined. The result showed that d exhibited much higher herbicidal activities against annual ryegrass, Digitaria sanguinalis and Ixeris denticulate than b2 and b1. The IC50 of d against the root and shoot growth of these three plants were lower than 1 mmol L-1. In contrast, the IC50 of b1 and b2 against the root and shoot growth of these plants were more than 10 mmol L-1.

Youhaiella tibetensis gen. nov., sp. nov., isolated from subsurface sediment.

A Gram-reaction-negative bacterial strain, designated fig4(T), was isolated from a subsurface sediment core of Qiangtang Basin permafrost in China. Cells were catalase- and oxidase-positive and rods. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain fig4(T )was a member of the family Hyphomicrobiaceae and was most closely related to members of the genera Pelagibacterium, Vasilyevaea and Devosia with 93.8-96.2% sequence similarities. The major cellular fatty acids were C16 : 0, C18 : 0, 11-methyl C18 : 1 ω7c, C19 : 0 cyclo ω8c and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The major respiratory quinone was Q-10 and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and two unknown glycolipids. The DNA G+C content was 60.7 mol%. Based on the phenotypic, phylogenetic and genotypic data, strain fig4(T) is considered to represent a novel species of a new genus in the family Hyphomicrobiaceae, for which the name Youhaiella tibetensis gen. nov., sp. nov. is proposed. The type strain is fig4(T) ( = CGMCC 1.12719(T) = JCM 19854(T)).

Clinical and prognostic significance of high-mobility group box-1 in human gliomas.

The objective of this study was to explore the expression and the clinical and prognostic significance of high-mobility group box-1 (HMGB1) in human gliomas. The expression of HMGB1 in 15 samples of normal brain tissue and 65 samples of different-grade glioma tissue was assayed using immunohistochemistry and western blot analysis. The associations between the differences in expression and pathology grades were analyzed statistically. Uni- and multivariate analyses were performed to investigate the prognostic value of HMGB1 expression and its expression levels. The positive rates of HMGB1 expression in normal brain and glioma tissue were 20.0% (3/15) and 76.9% (50/65), respectively. The expression of HMGB1 in glioma tissue was higher than that in normal tissue (P<0.05). The positive rates of HMGB1 expression in low-grade gliomas (LGGs, grades I and II) and high-grade gliomas (HGGs, grades III and IV) were 63.0% (17/27) and 86.8% (33/38), respectively, and the positive rates in HGG were higher than those in LGG (P=0.024). Western blot analysis showed that HMGB1 was also expressed in normal brain tissue. The expression levels in HGG were significantly higher than those in LGG (P<0.001). HMGB1-positive patients had significantly shorter overall survival times compared with HMGB1-negative patients (P=0.026). Increasing levels of HMGB1 expression significantly correlated with reduced survival times when all patients with glioma were considered (P=0.045). In conclusion, HMGB1 positivity and protein expression levels are of significant clinical and prognostic value in human gliomas. Detecting HMGB1 in human gliomas may be useful for assessing the degree of malignancy, and HMGB1 would appear to be a promising target in the clinical management of patients with glioma.

Metabolic changes in acute cerebral infarction: Findings from proton magnetic resonance spectroscopic imaging.

The purpose of this study was to investigate the clinical role of proton magnetic resonance spectroscopy (1H-MRS) in the diagnosis of acute cerebral infarction. Using databases available at the Fifth Affiliated Hospital of Zhengzhou University (Zhengzhou, China), the medical records of 47 patients with acute cerebral infarction treated between April 2010 and March 2012 were retrospectively reviewed. The patients underwent routine magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI) and multiple-voxel 1H-MRS examination within 12 h after the onset of stroke. The patients then received normal medical treatment for 2 weeks and underwent follow-up 1H-MRS examination at 1-2 months after stroke. The concentrations of the main metabolites [N-acetylaspartic acid (NAA), creatine (Cr), choline (Cho) and lactate (Lac)] in the infarct center, the infarction border region and the contralateral brain areas (control) were analyzed. The 47 patients experienced changes in NAA, Cho and Lac levels at different stages after stroke. In the infarction center, the NAA/Cr and NAA/Cho ratios decreased, while the Lac/Cr ratio increased within 12 h compared with those in the contralateral side. Within 6-12 h after stroke, the Lac/Cr ratio increased and the NAA/Cho ratio decreased compared with those <6 h after stroke. During the 1-2 months post-stroke, significant reductions in the NAA/Cr, NAA/Cho, Cho/Cr and Lac/Cr ratios were observed in the infarction center. In the infarction border region, the Lac/Cr ratio increased significantly at 12 h and decreased during the 1-2 months after stroke. The NAA/Cr, NAA/Cho and Cho/Cr ratios were significantly increased in the infarction border regions of patients who received thrombolytic therapy for 1-2 months compared with those in patients who did not undergo thrombolysis. Our results highlight the usefulness of 1H-MRS-based metabolomics as a feasible and efficient prognostic tool for assessing the treatment effect of acute cerebral infarction.

Nucleostemin and ASPP2 expression is correlated with pituitary adenoma proliferation.

Nucleostemin is a GTP-conjugated protein located in the nucleoli of stem cells and certain cancer cells, and maintains cellular self-renewal. The present study aimed to evaluate nucleostemin as a potential target for pituitary adenoma gene therapy by investigating nucleostemin and apoptosis-stimulating of p53 protein 2 (ASPP2) expression and their effect on pituitary adenoma cell proliferation. A total of 71 samples of pituitary adenomas were collected. Semi-quantitative PCR was used to detect the expression of nucleostemin and ASPP2 mRNA in the samples. Immunochemistry techniques were used to examine Ki-67 expression in the paraffin section of the samples. Coherent clinical data were also collected. Nucleostemin and ASPP2 were detectable in all the pituitary adenoma samples. Significant differences were observed in nucleostemin and ASPP2 expression between invasive pituitary adenoma and non-invasive pituitary adenomas (P<0.01) and the Ki-67 labeling index (LI; P>0.05). The difference in the Ki-67 LI between the recurrence and non-recurrence groups was significant (P<0.05). There was positive correlation between nucleostemin gene expression and the Ki-67 LI levels (P<0.05). The correlation between ASPP2 expression and the Ki-67 LI was negative (P<0.05). Negative correlation was demonstrated between nucleostemin and ASPP2 expression (P<0.01). The nucleostemin and ASPP2 genes were expressed in the human pituitary adenoma tissues. The differences in the expression of nucleostemin, ASPP2 and Ki-67 in the various pathological types of pituitary adenomas represented differences in molecular biological character and were associated with invasion. In the pituitary adenomas, the expression of nucleostemin and ASPP2 was correlated with tumor proliferation. Nucleostemin, ASPP2 and Ki-67 may serve as valid clinical detection markers for the invasion of pituitary adenomas.

[The effects of extracts from Arenaria kansuensis on the levels of HBsAG and HBeAg in HepG2.2.15 cells].

OBJECTIVE: To investigate the anti-HBV effects of the extracts with alcohol and water from Arenaria kansuensis in vitro. METHODS: HepG2.2.15 cells were used to estimate the effects of the extracts with alcohol and water from Arenaria kansuensis on the levels of HBsAg and HBeAg in medium by ELISA. RESULTS: Incubation of HepG2.2.15 cells with both the extracts with alcohol and water from Arenaria kansuensis (50-400 mg/L) for 72 and 96h significantly inhibited the levels of HBsAg and HBeAg. The maximum inhibiting rate of HBeAg from the Arenaria kansuensis extracts with alcohol was 63.2% and 90. 8% at 72h and 96h, respectively. Meanwhile, the Arenaria kansuensis extracts with water had obvious inhibitory effects on the levels of HBsAg and HBeAg in HepG2.2.15 cells at 96 h, compared with that of the control group (P < 0.01). The maximum inhibiting rates were 52.5% and 72.8%, respectively. CONCLUSION: The extracts with water from Arenaria kansuensis has obvious anti-HBV effects in vitro.