Downregulation of miR-337-3p in hypoxia/reoxygenation neuroblastoma cells increases KCTD11 expression.

Neurodegeneration is linked to the progressive loss of neural function and is associated with several diseases. Hypoxia is a hallmark in many of these diseases, and several therapies have been developed to treat this disease, including gene expression therapies that should be tightly controlled to avoid side effects. Cells experiencing hypoxia undergo a series of physiological responses that are induced by the activation of various transcription factors. Modulation of microRNA (miRNA) expression to alter transcriptional regulation has been demonstrated to be beneficial in treating multiple diseases, and in this study, we therefore explored potential miRNA candidates that could influence hypoxia-induced nerve cell death. Our data suggest that in mouse neuroblasts Neuro-2a cells with hypoxia/reoxygenation (H/R), miR-337-3p is downregulated to increase the expression of Potassium channel tetramerization domain containing 11 (KCTD11) and subsequently promote apoptosis. Here, we demonstrate for the first time that KCTD11 plays a role in the cellular response to hypoxia, and we also provide a possible regulatory mechanism by identifying the axis of miR-337-3p/KCTD11 as a promising candidate modulator of nerve cell survival after H/R exposure.

Porous Cr2O3 Architecture Assembled by Nano-Sized Cylinders/Ellipsoids for Enhanced Sensing to Trace H2S Gas.

How to achieve high sensing of Cr2O3-based sensors for harmful inorganic gases is still a challenge. To this end, Cr2O3 nanomaterials assembled from different building blocks were simply prepared by chromium salt immersion and air calcination with waste scallion roots as the biomass template. The hierarchical architecture calcined at 600 °C is constructed from nanocylinders and nanoellipsoids (named as Cr2O3-600), and also possesses multistage pore distribution for target gas accessibility. Interestingly, the synergism of two shapes of nanocrystals enables the Cr2O3-based sensor to realize highly sensitive detection of trace H2S gas. At 170 °C, Cr2O3-600 exhibits a high response of 42.8 to 100 ppm H2S gas, which is 3.45 times larger than that of Cr2O3-500 assembled from nanocylinders. Meanwhile, this sensor has a low detection limit of 1.0 ppb (S = 1.4), good selectivity, stability, and moisture resistance. These results show that the combination of nanosized cylinders/ellipsoids together with exposed (104) facet can effectively improve the sensing performance of the p-type Cr2O3 material. In addition, the Cr2O3-600 sensor shows satisfactory results for actual monitoring of the corruption process of fresh chicken.

[Effects of Butylphthalide on airway mucus hypersecretion, IL-13 and TNF-α in asthmatic mice].

Objective: To investigate the effects of Butylphthalide (NBP) on airway mucus hypersecretion, interleukin-13 (IL-13) and tumor necrosis factor-α (TNF-α) in asthmatic mice. Methods: The mice were randomly divided into control group, asthma group, DEX group and high, medium and low doses of NBP (100, 50, 25 mg/kg) groups (n=12). Ovalbumin (OVA) injection was sensitized on the 1st, 8th, and 15th day of the experiment, and OVA was inhaled on the 22nd day to stimulate for 5 weeks to replicate the asthma model, and 20 mg/kg of NBP was given for intervention before the challenge. Finally, the asthma behavior, the secretion of goblet cells and Mucin 5ac (Muc5ac)were observed, and meanwhile the viscosity of bronchoalveolar lavage fluid (BALF) and the levels of Muc5ac, IL-13 and TNF-α in BALF were measured by ELISA. Results: Compared with the control group, the degree of sneezing, nose scratching and asthma, the proliferation of airway epithelial goblet cells and secretion of Muc5ac in the asthma group were increased significantly (P＜0.01), meanwhile, the viscosity of BALF and the contents of Muc5ac, IL-13 and TNF-α were also increased significantly (P＜0.01). Compared with the asthma group, the above behavioral scores of asthma were decreased significantly (P＜0.01) after the intervention of 25, 50 and 100 mg/kg NBP, as well as the proliferation of airway epithelial goblet cells, secretion of Muc5ac, the viscosity of BALF and the contents of Muc5ac, IL-13 and TNF-α were significantly lower than those of the asthma group (P＜0.05, 0.01). Conclusion: NBP has the effect of anti-asthma by inhibiting mucus hypersecretion, and one of its mechanisms is to alleviate the abnormal expressions of IL-13 and TNF-α.

Synthesis and Cytotoxic Property of Annonaceous Acetogenin Glycoconjugates.

BACKGROUND: Annonaceous acetogenins (ACGs) are secondary metabolites produced by the Annonaceae family and display potent anticancer activity against various cancer cell lines. Squamocin and bullatacin are two examples of ACGs that show promising antitumor activity; however, preclinical data are not sufficient partly due to their being highly lipophilic and poorly soluble in water. These compounds also display high toxicity to normal cells. Due to these disadvantageous properties, the therapeutic potential of squamocin and bullatacin as antitumor agents has not been fully evaluated. METHODS: In order to enhance their water solubility and potentially improve their cancer targeting, squamocin and bullatacin were conjugated to a glucose or galactose to yield glycosylated derivatives by direct glycosylation or the Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reaction (the click reaction). The synthesized compounds were evaluated for their anticancer property against HeLa, A549 and HepG2 cancer cell lines using MTT assay. RESULTS: Nine glycosyl derivatives were synthesized and structurally characterized. Most of them show comparable in vitro cytotoxicity against HeLa, A549 and HepG2 cancer cell lines as their parent compounds squamocin and bullatacin. It appears that the type of sugar residue (glucose or galactose), the position at which the sugar residue is attached, and whether or not a linking spacer is present do not affect the potency of these derivatives much. The solubility of galactosylated squamocin 13 in phosphate buffer saline (PBS, pH = 7) is greatly improved (1.37 mg/mL) in comparison to squamocin (not detected in PBS). CONCLUSION: The conjugation of a glucose or galactose to squamocin and bullatacin yields glycosyl derivatives with similar level of anticancer activity in tested cell lines. Further studies are needed to demonstrate whether or not these compounds show reduced toxicity to normal cells and their therapeutic potential as antitumor agents.

[Effects of Radix Angelicae Sinensis on airway mucus hypersecretion and the TNF-α/NF-κB signaling pathway in Yin-deficiency asthmatic mice].

Objective: To investigate the therapeutic effects of Radix Angelicae Sinensis (RADA) on airway mucus hypersecretion and the tumor necrosis factor-α/ nuclear factor- κB (TNF-α/NF-κB) signaling pathway in Yin-deficiency asthma mice. Methods: KM mice were randomly divided into control group, model group, ambroxol group and RADA low, medium and high dose (2, 4 and 8 g/kg) group(n=12). Ovalbumin and the thyroid gland were used to replicate the model of Yin-deficiency asthma. Asthma symptoms in mice , immune globulin E (IgE) , TNF-α , and the expressions of Mucin 5ac (Muc5ac) and NF- κB in lung tissue were observed under the intervention of RADA. Results: RADA at the doses of 2,4 and 8 g/kg could alleviate the asthma symptoms of Yin-deficiency asthma mice significantly, reduce the levels of IgE in serum and TNF-α in bronchoalveolar lavage fluid (BALF), and inhibite the overexpressions of Muc5ac and NF- κB in lung tissue. Conclusion: RADA has significant anti-asthmatic effect. One of its mechanisms is to inhibit TNF-α/NF- κB signaling pathway and to alleviate airway mucus hypersecretion.

Gastric adenocarcinoma mimicking a submucosal tumor: A case report.

BACKGROUND: Submucosal tumor (SMT)-like early-stage gastric cancer (GC) has rarely been reported. It is difficult to consider the possibility of GC and differentiate it from other submucosal lesions. CASE SUMMARY: We present the case of a 50-year-old male patient with a 1.6 cm SMT-like flat elevated lesion covered by congested mucosa on the gastric angle. Magnifying endoscopy with narrow-band imaging, endoscopic biopsy, endoscopic ultrasound, and computed tomography were performed for diagnosis. Endoscopic submucosal dissection and gastrectomy with lymph node dissection were performed. The post-resection pathological analysis led to a final diagnosis of GC (Bormann type I, T1bN2M0). CONCLUSION: GC should be considered when detecting an SMT-like lesion in the stomach.

The HO-1-expressing bone mesenchymal stem cells protects intestine from ischemia and reperfusion injury.

BACKGROUND: Bone mesenchymal stromal cells (BMSC) showed protective potential against intestinal ischemia. Oxygenase-1(HO-1) could alleviate oxidative stress. In the present study, we constructed HO-1-expressing BMSC and detected the effects of it on survival, intestinal injury and inflammation following intestinal ischemia and reperfusion injury (I/R). METHODS: In this experiment, eighty adult male mice were divided into Sham, I/R, I/R + BMSC, I/R + BMSC/HO-1 groups. Mice were anesthetized and intestinal I/R model were established by temporarily occluding the superior mesenteric artery for 60 min with a non-crushing clamp. Following ischemia, the clamp was removed and the intestines were allowed for reperfusion. Prior to abdominal closure, BMSC/ HO-1 (2 × 106 cells) or BMSC (2 × 106 cells) were injected into the peritoneum of I/R mice respectively. Mice were allowed to recover for 24 h and then survival rate, intestinal injury and inflammation were determined. Reactive oxygen species (ROS) was assayed by fluorescent probe. TNFα and IL-6 were assayed by ELISA. RESULTS: BMSC/HO-1 increased seven day survival rate, improved intestinal injury and down-regulated inflammation after intestinal I/R when compared with sole BMSC (p < 0.05 respectively). Multiple pro-inflammatory media were also decreased following application of BMSC/HO-1, when compared with sole BMSC (p < 0.05) respectively, suggesting that BMSC /HO-1 had a better protection to intestinal I/R than BMSC therapy. CONCLUSION: Administration of BMSC/HO-1 following intestinal I/R, significantly improved intestinal I/R by limiting intestinal damage and inflammation.

Protective effects of GPR120 agonist-programmed macrophages on renal interstitial fibrosis in unilateral ureteral obstruction (UUO) rats.

Macrophages in the kidney play different roles in renal interstitial fibrosis (RIF) depending on their phenotypes. M2 phenotype macrophages are believed to protect the kidney against RIF. Free fatty acid receptor GPR120 is expressed in macrophages, and its activation induces macrophage transition to M2 phenotype. In this study, the effects of GPR120 agonist-programmed macrophages on RIF were investigated. The peritoneal macrophages collected from rats were incubated with GPR120 agonist TUG891 in vitro for 24 h, and then they were transplanted autologously to the kidney with ureteral obstruction by intrarenal injection for 7 days on the same day following unilateral ureteral obstruction (UUO) operation. RIF was identified by Masson trichrome histological staining, and the expression of RIF-related proteins was analyzed by immunohistochemistry and western blot. It was observed that TUG891-programmed macrophages up-regulated the expression of CD206 and arginase-1 while the expression of interleukin-6 and tumor necrosis factor-α were down-regulated. RIF in rats was significantly increased following UUO, which was markedly alleviated by TUG891-programmed macrophages but not untreated macrophages. TUG891-programmed macrophages inhibited the abnormal expression of TGF-ß1 and SMAD2. The abnormal expression of epithelial-mesenchymal transition (EMT)-related proteins including vimentin, α-SMA and ß-catenin was also significantly decreased in rats with transplantation of TUG891-programmed macrophages as compared to UUO rats. This study suggests that autologous administration of peritoneal macrophages programmed in vitro by GPR120 agonist to kidney has a protective effect against RIF following UUO.

SP1, MYC, CTNNB1, CREB1, JUN genes as potential therapy targets for neuropathic pain of brain.

Neuropathic pain (NP) may cause serious brain diseases, but the genes associated with the metabolic pathway and transcript factors of NP remain unclear. This study is aimed to identify the therapy target genes for NP and to investigate the metabolic pathways and transcript factors associated with NP. The differentially expressed genes of three brain tissues (nucleus accumbens, periaqueductal gray, and prefrontal cortex) dealt with NP stimulation were analyzed. Besides, The Database for Annotation, Visualization, and Integrated Discovery and Tfacts datasets were used in the analysis of the genes related to the metabolic pathway and transcript factors of the brain. Eight genes were found to coexpress in all three tissues. A functional enrichment analysis showed that the upregulated genes were mostly enriched in pathways as inflammatory response, calcium-mediated signaling, cytokine-cytokine receptor interaction, and extracellular matrix (ECM)-receptor interaction, whereas the downregulated genes were mostly enriched in pathways as phospholipid metabolic processes, positive regulation of protein kinase B signaling, and metabolism of xenobiotics by cytochrome P450. Finally, 135 and 98 transcript factors genes were upregulated and downregulated, among which SP1, MYC, CTNNB1, CREB1, JUN were identified as the most critical genes because the number of up- and downregulated gene ranked at the top. In conclusion, the pathways of immune response and cytokine-cytokine receptor interaction were determined as the main metabolic pathways of NP affecting the brain, and SP1, MYC, CTNNB1, CREB1, JUN genes were recognized as the most enriched genes in this process, which may provide evidence for the diagnosis and treatment research of neuropathic pain.

XIST accelerates neuropathic pain progression through regulation of miR-150 and ZEB1 in CCI rat models.

LncRNAs are reported to participate in neuropathic pain development. LncRNA X-inactive specific transcript (XIST) is involved in the progression of various cancers. However, the role of XIST in neuropathic pain remains unclear. In our present study, we established a chronic constriction injury (CCI) rat model and XIST was found to be greatly upregulated both in the spinal cord tissues and in the isolated microglias of CCI rats. Inhibition of XIST inhibited neuropathic pain behaviors including mechanical and thermal hyperalgesia. Moreover, decrease of XIST repressed neuroinflammation through inhibiting COX-2, tumor necrosis factor (TNF)-α and IL-6 and in CCI rats. Previously, miR-150 has been reported to restrain neuropathic pain by targeting TLR5. Currently, miR-150 was predicted to be a microRNA target of XIST, which indicated a negative correlation between miR-150 and XIST. miR-150 was remarkably decreased in CCI rats and overexpression of miR-150 can significantly suppress neuroinflammation-related cytokines. Furthermore, ZEB1 was exhibited to be a direct target of miR-150 and we found it was overexpressed in CCI rats. Silencing ZEB1 was able to inhibit neuropathic pain in vivo and downreguation of XIST decreased ZEB1, which can be reversed by miR-150 inhibitors. Taken these together, we indicated that XIST can induce neuropathic pain development in CCI rats via upregulating ZEB1 by acting as a sponge of miR-150. It was revealed that XIST/miR-150/ZEB1 axis can be provided as a therapeutic target in neuropathic pain.

Clustering of disulfide-rich peptides provides scaffolds for hit discovery by phage display: application to interleukin-23.

BACKGROUND: Disulfide-rich peptides (DRPs) are found throughout nature. They are suitable scaffolds for drug development due to their small cores, whose disulfide bonds impart extraordinary chemical and biological stability. A challenge in developing a DRP therapeutic is to engineer binding to a specific target. This challenge can be overcome by (i) sampling the large sequence space of a given scaffold through a phage display library and by (ii) panning multiple libraries encoding structurally distinct scaffolds. Here, we implement a protocol for defining these diverse scaffolds, based on clustering structurally defined DRPs according to their conformational similarity. RESULTS: We developed and applied a hierarchical clustering protocol based on DRP structural similarity, followed by two post-processing steps, to classify 806 unique DRP structures into 81 clusters. The 20 most populated clusters comprised 85% of all DRPs. Representative scaffolds were selected from each of these clusters; the representatives were structurally distinct from one another, but similar to other DRPs in their respective clusters. To demonstrate the utility of the clusters, phage libraries were constructed for three of the representative scaffolds and panned against interleukin-23. One library produced a peptide that bound to this target with an IC50 of 3.3 µM. CONCLUSIONS: Most DRP clusters contained members that were diverse in sequence, host organism, and interacting proteins, indicating that cluster members were functionally diverse despite having similar structure. Only 20 peptide scaffolds accounted for most of the natural DRP structural diversity, providing suitable starting points for seeding phage display experiments. Through selection of the scaffold surface to vary in phage display, libraries can be designed that present sequence diversity in architecturally distinct, biologically relevant combinations of secondary structures. We supported this hypothesis with a proof-of-concept experiment in which three phage libraries were constructed and panned against the IL-23 target, resulting in a single-digit µM hit and suggesting that a collection of libraries based on the full set of 20 scaffolds increases the potential to identify efficiently peptide binders to a protein target in a drug discovery program.

Association of genetic polymorphisms in PRKDC and XRCC4 with risk of ESCC in a high-incidence region of North China.

BACKGROUND: The nonhomologous end-joining (NHEJ) pathway is the main mechanism repairing DNA double-strand breaks (DSBs) in human cells. This research was designed to study the association between selected variants in NHEJ members and esophageal squamous cell carcinoma (ESCC). METHODS: Two single nucleotide polymorphisms (SNPs), PRKDC (rs7003908) and X-ray repair cross complementing group 4 (XRCC4; rs1805377), were genotyped in a total of 189 patients with ESCC and 189 unrelated control individuals in a high-risk area for ESCC in North China, and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied. RESULTS: A significantly different distribution was found in the frequency of PRKDC (rs7003908) genotype between the ESCC group and controls. Individuals homozygous for the C allele had a significant (3.185-fold) increased risk of ESCC. As for XRCC4 (rs1805377) polymorphism, no difference was found in distribution between the ESCC and control groups. CONCLUSIONS: Our results suggest that variation in DNA repair genes may be associated with risk of ESCC.

[Effect of Volatile Oil of Radix Angelicae Sinensis on experimental asthma in rats].

OBJECTIVE: To study the effects of Volatile Oil of Radix Angelicae Sinensis (VOA) on experimental asthma in rat model based on abnormal immune functions of Treg cells. METHODS: After grouping, the asthmatic rats were developed through injecting OVA and AI(OH)3 for sensitization and then administering OVA aerosol for challenge, and the respiratory functions, asthmatic behaviors, IL-10 levels in bronchoalveolar lavage fluid (BALF) (ELISA) and Foxp3 expression (immunohistochemistry) in lung of asthmatic rats were observed. RESULTS: VOA at the doses of 40-160 mg/kg could improve the respiratory functions and the asthmatic behaviors, and upgrade IL-10 levels in BALF and Foxp3 expression in lung of asthmatic rats. CONCLUSION: VOA has some effects of anti-asthma and one of the mechanisms is to improving the lower immune functions of Treg cells.

Tumor inhibition effects and mechanisms of Angelica sinensis and Sophorae flavescentis ait decoction combined with cisplatin in xenograft mice.

BACKGROUND: To investigate tumor inhibition effects and mechanisms of Angelica sinensis and Sophorae flavescentis ait decoction (ASSF) combined with diamine-dichloroplatinum (DDP). MATERIALS AND METHODS: Bodyweight, tumor inhibition rate and q value were calculated for single ASSF or ASSF combined with DDP on H22 carcinoma xenograft KM mice. Biochemical methods for serum LDH, AST, ALT, and AKP, ELISA method for serum HIF-1α, pathological assessemnt of thymus, immunohistochemistry detection of tumor tissue caspase3 and mutant p53 protein, and qRT-PCR detection of bax/ bcl-2 mRNA were applied. RESULTS: Compared with DDP control group, the bodyweight increased in ASSF-DDP group (p<0.01). Tumor inhibition rates for DDP, ASSF, ASSF-DDP were 62.7%. 43.7% and 71.0% respectively, with a q value of 0.90. Compared with other groups, thymus of DDP control group had obvious pathological injury (p<0.01), serum LDH, AST, ALT, AKP increased significantly in DDP control group (p<0.01), while serum HIF-1α was increased in the model control group. Compared with this latter, the expression of mutant p53 protein and bcl-2 mRNA were decreased in all treatment groups (p<0.01), but there were no statistical difference between DDP control p and ASSF-DDP groups. The expression of caspase3 protein and bax mRNA was increased in all treatment groups, with statistical differences between the DDP and ASSF-DDP groups (p<0.01). CONCLUSIONS: ASSF can inhibit bodyweight decrease caused by DDP, can inhibit tumor growth synergistically with DDP mainly through increasing serum HIF-1α and pro-apoptotic molecules such as caspase 3 and bax, rather than through decreasing anti-apoptotic mutant p53 and bcl-2. ASSF can reduce DDP toxicity due to decreasing the release of LDH, AST, ALT, AKP into blood and enhancing thymus protection.

Effects of small interfering RNA inhibit Class I phosphoinositide 3-kinase on human gastric cancer cells.

AIM: To investigate the effects of small interfering RNA (siRNA)-mediated inhibition of Class I phosphoinositide 3-kinase (Class I PI3K) signal transduction on the proliferation, apoptosis, and autophagy of gastric cancer SGC7901 and MGC803 cells. METHODS: We constructed the recombinant replication adenovirus PI3K(I)-RNA interference (RNAi)-green fluorescent protein (GFP) and control adenovirus NC-RNAi-GFP, and infected it into human gastric cancer cells. MTT assay was used to determine the growth rate of the gastric cancer cells. Activation of autophagy was monitored with monodansylcadaverine (MDC) staining after adenovirus PI3K(I)-RNAi-GFP and control adenovirus NC-RNAi-GFP treatment. Immunofluorescence staining was used to detect the expression of microtubule-associated protein 1 light chain 3 (LC3). Mitochondrial membrane potential was measured using the fluorescent probe JC-1. The expression of autophagy was monitored with MDC, LC3 staining, and transmission electron microscopy. Western blotting was used to detect p53, Beclin-1, Bcl-2, and LC3 protein expression in the culture supernatant. RESULTS: The viability of gastric cancer cells was inhibited after siRNA targeting to the Class I PI3K blocked Class I PI3K signal pathway. MTT assays revealed that, after SGC7901 cancer cells were treated with adenovirus PI3K(I)-RNAi-GFP, the rate of inhibition reached 27.48% ± 2.71% at 24 h, 41.92% ± 2.02% at 48 h, and 50.85% ± 0.91% at 72 h. After MGC803 cancer cells were treated with adenovirus PI3K(I)-RNAi-GFP, the rate of inhibition reached 24.39% ± 0.93% at 24 h, 47.00% ± 0.87% at 48 h, and 70.30% ± 0.86% at 72 h (P < 0.05 compared to control group). It was determined that when 50 MOI, the transfection efficiency was 95% ± 2.4%. Adenovirus PI3K(I)-RNAi-GFP (50 MOI) induced mitochondrial dysfunction and activated cell apoptosis in SGC7901 cells, and the results described here prove that RNAi of Class I PI3K induced apoptosis in SGC7901 cells. The results showed that adenovirus PI3K(I)-RNAi-GFP transfection induced punctate distribution of LC3 immunoreactivity, indicating increased formation of autophagosomes. The results showed that the basal level of Beclin-1 and LC3 protein in SGC7901 cells was low. After incubating with adenovirus PI3K(I)-RNAi-GFP (50 MOI), Beclin-1, LC3, and p53 protein expression was significantly increased from 24 to 72 h. We also found that Bcl-2 protein expression down-regulated with the treatment of adenovirus PI3K(I)-RNAi-GFP (50 MOI). A number of isolated membranes, possibly derived from ribosome-free endoplasmic reticulum, were seen. These isolated membranes were elongated and curved to engulf a cytoplasmic fraction and organelles. We used transmission electron microscopy to identify ultrastructural changes in SGC7901 cells after adenovirus PI3K(I)-RNAi-GFP (50 MOI) treatment. Control cells showed a round shape and contained normal-looking organelles, nucleus, and chromatin, while adenovirus PI3K(I)-RNAi-GFP (50 MOI)-treated cells exhibited the typical signs of autophagy. CONCLUSION: After the Class I PI3K signaling pathway has been blocked by siRNA, the proliferation of cells was inhibited and the apoptosis of gastric cancer cells was enhanced.

[Association between ESR1 gene polymorphisms and haplotypes with schizophrenia].

OBJECTIVE: To assess the association between single nucleotide polymorphisms (SNPs) and haplotypes of estrogen receptor 1 (ESR1) gene with schizophrenia. METHODS: Three SNPs (rs2234693, rs9340799 and rs3798759) were determined in 333 schizophrenic patients and 315 healthy subjects with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Allelic and genotypic frequencies and particular haplotypes were compared between the two groups using Chi-square test. RESULTS: The allelic and genotypic frequencies of rs2234693 and rs9340799 showed no significant difference between the two groups (P U+003E 0.05). However, a significant difference was detected in the frequencies of rs3798759 G allele and GG genotype between the two groups (P U+003C 0.01). Single factor analysis stratified by sex also found that frequencies of rs3798759 GG and TG genotypes and G allele were significantly higher in female schizophrenia patients compared with healthy females (P U+003C 0.05). Haplotypes C-A-G and C-G-G were more common in schizophrenia group (P U+003C 0.05). CONCLUSION: polymorphisms of rs3798759 may be a risk factor for female patients with schizophrenia, and haplotypes C-A-G and C-G-G may be risk factors for schizophrenia.

[Sequence analysis and identification of a chloroplast matK gene in Rhei Rhizoma from different botanical origins].

Rhei Rhizoma is a Chinese medicine with multiple botanical origins. There is a problem to identify it with conventional methods. To compare the characteristics of chloroplast matK gene sequences of different Rheum species and authenticate inspected species, the matK gene sequences of different species from different origins were amplified, cloned, and sequenced. Genomic DNA of Rheum plants was extracted using modified DNA extracted Kit and matK gene sequences were analyzed by ContingExpress, DNAman and MEGA5.0. The length of matK gene sequences of Rheum palmatum, R. tanguticum and R. officinale were 1 518 bp containing 57 variable loci. According to the mutation sites, R. palmatum, R. tanguticum and R. officinale were divided into different genotypes separately. Based on the established method according to the loci 587, 707, 838, we successfully identified the genuine Rheum species from its adulterants.

Haplotype analysis of CTLA4 gene and risk of esophageal squamous cell carcinoma in Anyang area of China.

BACKGROUND/AIMS: To study the effect of cytotoxic T-lymphocyte antigen 4 gene haplotypes to susceptibility of esophageal squamous cell carcinoma. METHODOLOGY: A gender- and age-matched case-control design was used in this study. PCR-RFLP method was used to detect the genotype of CTLA4 in 205 patients and 205 control individuals in the Anyang area. Furthermore, haplotypes were calculated by PHASE2.1 software. Finally, the conditional logistic regression analysis was carried out to analyze the relevance between the risk of ESCC and the genotypes or haplotypes of CTLA4 gene. RESULTS: The CTLA4 rs231775 and rs4553808 genotypes in patients with ESCC were significantly different from controls (p=0.004, p=0.023, respectively). The AG and AA genotypes of rs231775 were highly correlated with the risk of ESCC (Adjusted OR=2.280, 95%CI=1.433-3.629, p=0.001; Adjusted OR=2.192, 95%CI=1.229-3.911, p=0.008, respectively), and AG genotype of rs4553808 also increased the susceptibility of ESCC (Adjusted OR=1.848, 95%CI=1.220-2.800, p=0.004). Further study suggested that AAG haplotype may enhance the risk of ESCC (Adjusted OR=5.035, 95%CI=1.599-15.860, p=0.005), but GAA haplotype played a protective role (Adjusted OR=0.413, 95%CI=0.251-0.680, p=0.001). CONCLUSIONS: Our research confirmed that CTLA4 genetic variation was related to ESCC in the Anyang area and GAA haplotype was the protective factor of ESCC.

Bis(2-amino-pyrazine-κN)tetra-aqua-cadmium(II) bis-(perchlorate)-2-amino-pyrazine (1/4).

In the title compound, [Cd(C(4)H(5)N(3))(2)(H(2)O)(4)](ClO(4))(2)·4C(4)H(5)N(3), the Cd(II) atom (site symmetry ) is coordinated by two N-heterocycles and four water mol-ecules, resulting in a distorted trans-CdN(2)O(4) octa-hedral geometry for the metal. In the crystal, the cation, anion and free N-heterocycle mol-ecules are linked by N-H⋯N, N-H⋯O, O-H⋯N and O-H⋯O hydrogen bonds, forming a three-dimensional network.

Chlorinated river and lake water extract caused oxidative damage, DNA migration and cytotoxicity in human cells.

Consumption of chlorinated drinking water is suspected to be associated with adverse health effects, including mutations and cancer. In the present study, the genotoxic potential of water from Donghu lake, Yangtze river and Hanjiang river in Wuhan, an 8-million metropolis in China, was investigated using HepG2 cells and the alkaline version of the comet assay. It could be shown that all water extracts caused dose-dependent DNA migration in concentrations corresponding to dried extracts of 0.167-167 ml chlorinated drinking water per ml medium. To explore whether the intracellular redox status is regulated by chlorinated drinking water, we determined lipid peroxidation (LPO) and depletion of reduced glutathione (GSH). The malondialdehyde (thiobarbituric acid (TBA)-reactive aldehydes) concentration increased after chlorinated drinking water treatment of HepG2 cells in a dose-dependent manner, the GSH content decreased. The activity of lactate dehydrogenase (LDH) increased in chlorinated drinking water treated HepG2 cells indicating cytotoxicity. In accordance with former studies which dealt with in vivo and in vitro micronucleus induction the present study shows that chlorinated drinking water from polluted raw water may entail genetic risks.