[Metabolomics study of Berberidis Radix in intervening ulcerative colitis based on UPLC-Q-TOF-MS].

The effect of Tujia medicine Berberidis Radix on endogenous metabolites in the serum and feces of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) was analyzed by metabolomics technology to explore the metabolic pathway and underlying mechanism of Berberidis Radix in the intervention of UC. The UC model was induced in mice by DSS. Body weight, disease activity index(DAI), and colon length were recorded. The levels of tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in colon tissues were determined by ELISA. The levels of endogenous metabolites in the serum and feces were detected by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to characterize and screen differential metabolites. The potential metabolic pathways were analyzed by MetaboAnalyst 5.0. The results showed that Berberidis Radix could significantly improve the symptoms of UC mice and increase the level of the anti-inflammatory factor IL-10. A total of 56 and 43 differential metabolites were identified in the serum and feces, respectively, belonging to lipids, amino acids, fatty acids, etc. After the intervention by Berberidis Radix, the metabolic disorder gradually recovered. The involved metabolic pathways included biosynthesis of phenylalanine, tyrosine, and tryptophan, linoleic acid metabolism, phenylalanine metabolism, and glycerophospholipid metabolism. Berberidis Radix can alleviate the symptoms of mice with DSS-induced UC, and the mechanism may be closely related to the re-gulation of lipid metabolism, amino acid metabolism, and energy metabolism.

Association of Single-Nucleotide Polymorphisms in Monoubiquitinated FANCD2-DNA Damage Repair Pathway Genes With Breast Cancer in the Chinese Population.

OBJECTIVE: The aim of the study was to estimate breast cancer risk conferred by individual single-nucleotide polymorphisms of breast cancer susceptibility genes. METHODS: We analyzed the 48 tagging single-nucleotide polymorphisms of 8 breast cancer susceptibility genes involved in the monoubiquitinated FANCD2-DNA damage repair pathway in 734 Chinese women with breast cancer and 672 age-matched healthy controls. RESULTS: Forty-five tagging single-nucleotide polymorphisms were successfully genotyped by SNPscan, and the call rates for each tagging single-nucleotide polymorphisms were above 98.9%. We found that 13 tagging single-nucleotide polymorphisms of 5 genes ( Parter and localizer of Breast cancer gene2 ( PALB2), Tumour protein 53 ( TP53), Nijmegen breakage syndrome 1, Phosphatase and tensin homolog deleted from chromosome 10 ( PTEN), and Breast cancer gene 1 ( BRCA1-interacting protein 1)) were significantly associated with breast cancer risk. A total of 5 tagging single-nucleotide polymorphisms (rs2299941 of PTEN, rs2735385, rs6999227, rs1805812, and rs1061302 of Nijmegen breakage syndrome 1) were tightly associated with breast cancer risk in sporadic cases, and 5 other tagging single-nucleotide polymorphisms (rs1042522 of TP53, rs2735343 of PTEN, rs7220719, rs16945628, and rs11871753 of BRCA1-interacting protein 1) were tightly associated with breast cancer risk in familial and early-onset cases. CONCLUSIONS: Some of the tagging single-nucleotide polymorphisms of 5 genes ( PALB2, TP53, Nijmegen breakage syndrome 1, PTEN, and BRCA1-interacting protein 1) involved in the monoubiquitinated FANCD2-DNA damage repair pathway were significantly associated with breast cancer risk.

Routine Hemostasis and Hemogram Parameters: Valuable Assessments for Coagulation Disorder and Chemotherapy in Cancer Patients.

BACKGROUND: The clotting system abnormalities are the common complication in cancer patients. The aim of this retrospective study was to evaluate the coagulation state, clinical features, and treatment in cancer patients by routine tests. METHODS: A total of 2328 patients with different types of cancer were classified as the positive group (n = 1419, including 53 patients with thrombosis) and the negative group (n = 909) based on D-dimer (DD) value. Of the 2328 cases, 354 were admitted for chemotherapy. Hemostasis test and complete blood count (CBC) were performed during treatment or following-up. RESULTS: This study showed that the hypercoagulable state was affected not only by clinical staging (P < 0.0001) but also by metastasis site (P < 0.0001 for bone vs. lung). Compared to negative DD group, the higher fibrinogen level, the extended activated partial thromboplastin time, and prothrombin time interacted markedly with disease clinical stage (P < 0.05) in the positive group. Between positive DD groups with and without thrombus, the significantly statistic difference in white blood cell (WBC) and DD (P < 0.05) rather than in red blood cell (RBC) and platelet count was observed. However, the higher DD level was not correlated with WBC, RBC, and platelet count in the positive DD group. Furthermore, the hypercoagulable plasma profile in cancer patients was moderated 2-3 weeks after chemotherapy (P < 0.05 for first six cycles). CONCLUSIONS: The routine hemostatic parameters and CBC are valuable to assessment for thrombosis and chemotherapy even for disease prognosis.

[Land use pattern of Dalian City, Liaoning Province of Northeast China based on CA-Markov model and multi-objective optimization].

Based on the land use/cover maps of 1990, 2000, and 2010, topographic factors, and geographic elements, a CA-Markov model consisting of Markov transition matrix, multi-criteria evaluation, and cellular automata was developed to simulate the change trends of the future land use and landscape patterns of Dalian, Liaoning Province. The future land use pattern of Dalian was optimally allocated by the method of fuzzy multi-objective programming, based on the characters of land use structure, society, economy, and natural environment. The results indicated that in 1990-2010, the rapid development of Dalian showed the characteristics of the continued expansion of urban area and the reduction of cropland and woodland area. With the present speed of urban development, the landscape pattern and land use cover would have a great change, and the landscape fragmentation would be exacerbated. To optimize the land use structure could meet the demand of the future sustainable development of Dalian.

Haplotype analysis of eight genes of the monoubiquitinated FANCD2-DNA damage-repair pathway in breast cancer patients.

BACKGROUND: Ten genes are associated with increased susceptibility to inherited breast cancer have also been associated with population breast cancer risk, and all are involved directly or indirectly in the monoubiquitinated FANCD2-DNA damage repair pathway. We analyzed 13 haplotype blocks in eight of these genes to estimate the breast cancer risk conferred by individual haplotypes. METHODS: Haplotype blocks were constructed with 48 tag single-nucleotide polymorphisms (tSNPs) identified in eight breast cancer susceptibility genes, TP53, PTEN, CHEK2, ATM, NBS1, RAD50, BRIP1, and PALB2. Genotyping was performed by SNPscan on 734 female patients and 672 female age-matched controls. RESULTS: Forty-five tSNPs were successfully genotyped by SNPscan, and call rates for each tSNP were above 98.9%. Thirteen haplotype blocks of eight genes were constructed with 41 successfully genotyped tSNPs. We found that seven haplotypes from four haplotype blocks located within three genes (NBS1, PTEN, and BRIP1) were significantly associated with breast cancer risk. Among these, four haplotypes (ATC in block 1 of NBS1, GCCCC and GCCCT in block 2 of NBS1, and GCT in block 2 of BRIP1) were correlated with breast cancer risk in sporadic cases (OR (95% CI) 1.350(1.124-1.623), 0.752(0.584-0.969), 0.803(0.649-0.993), and 0.776(0.604-0.997), respectively), and only one haplotype (GGCCT in block 2 of NBS1) was significantly associated with breast cancer risk in familial and early-onset cases (OR(95% CI) 1.902(1.134-3.191)). CONCLUSIONS: Four haplotypes within two genes (NBS1 and BRIP1) involved in the monoubiquitinated FANCD2-DNA damage-repair pathway are significantly associated with increased sporadic breast cancer risk, while one haplotype within NBS1 is correlated with an increased risk of familial or early-onset breast cancer, indicating that specific haplotypes may be distinct predictors of breast cancer.

[Effects of soluble egg antigen and adult worm antigen of Schistosoma japonicum on differentiation of effector B cells of mice].

OBJECTIVE: To observe the differentiation ability of effector B cells induced by soluble egg antigen (SEA) and soluble adult worm antigen (SWAP) of Schistosoma japonicum. METHODS: The mouse spleen mononuclear cells and CDl9+ B cells sorted by beadg were stimulated by SEA, SWAP and lipopolysaccharide (LPS), respectively. The ratios of CD19+ IL-6+ cells and CD19+ IFN-gamma+ cells were analyzed by flow cytometry after 72 hours. At the same time, the cytokines IL-6 and IFN-gamma levels in the cultured supernatants were detected by ELISA. The mouse was immunized with the mixture of SEA or SWAP or LPS and the incomplete Freund' s adjuvant for three times, respectively. The mouse spleen mononuclear cells were isolated at the seventh day after the last immunization. The ratios of CD19+ IL-6+ cells and CD19 IFN-gama+ cells were analyzed, and the cytokines IL-6 and IFN-gamma+ levels in the culture supernatants were detected. RESULTS: The ratio of CD19 IL-6+ cells in spleen mononuclear cells and splenic B cells was significantly increased in the groups stimulated by SEA and LPS (P < 0.05), and the cytokines IL-6 level in the CD193 cells culture supernatants were significantly increased (P < 0.01). Furthermore, the ratio of CD19+ IL-6+ cells and the cytokines IL-6 level were significantly increased in the SEA immunized group (P < 0.01). SWAP could induce a significantly higher ratio of the CD19+ IFN-gamma+ cells in spleen cells, instead of in splenic CD19+ B cells (P < 0.05). The CD19+ IFN-gamma+ cells and the cytokine IFN-gamma level in the culture supernatants in the SWAP immunized group were significantly higher than those in the SEA and PBS immunized groups (P C 6.01). CONCLUSIONS: SEA preferentially induces the increase of CDl9+ IL-6+ cells in mouse spleen cells; while SWAP preferentially induces the CD19 + IFN-gamma+ cells' production of mouse spleen cells, depending on the effects of other immune cells.

Inhibition of renal cancer cell growth by oncolytic adenovirus armed short hairpin RNA targeting hTERT gene.

RNA interference (RNAi) has been proved to be a powerful tool for gene knockdown purpose and holds a great promise for the treatment of cancer. Our previous study demonstrated that the reduction of hTERT expression by means of chemically synthesized siRNAs and shRNAs expressed from plasmid resulted in proliferation inhibition in human renal carcinoma cells. In this study, we constructed a novel oncolytic adenovirus-based shRNA expression system, ZD55-hTERT, and to explore ZD55-hTERT-mediated RNAi for hTERT gene silencing. Our results showed that ZD55-hTERT could induce silencing of hTERT gene effectively, allow for efficient tumor-specific viral replication and induce the apoptosis of tumor cells effectively in vitro and in nude mice. We conclude that combining shRNA gene therapy and oncolytic virotherapy can enhance antitumor efficacy as a result of synergism between CRAd oncolysis and shRNA antitumor responses.