Epicoccanes A-D, Four Oxidative Dimers of Pyrogallol Analogues from Epicoccum nigrum.

Epicoccanes A-D (1-4) are four novel metabolites of an endophytic fungus Epicoccum nigrum. Their distinct unprecedented structures are hypothesized as oxidative dimers of pyrogallol analogues. Compounds 1 and 2 possess a novel spirobicyclo[3.2.1]octane-6,1'-cyclopentane or -cyclohexane core skeleton. Compound 3 is of a unique cage-like pentacyclic system, which unusually contained three continuous spiro-carbons. Compound 4 is a highly rearranged dimer with five contiguous chiral centers. The absolute structures of 1 and 2 were deduced by electronic circular dichroism (ECD) calculations, and those of 3 and 4 were determined by X-ray crystallography. Compounds 1 and 4 showed potential antiliver fibrosis activity.

Role of psychotherapy strategy for the management of patients with Tourette syndrome - A Bayesian network meta-analysis.

Tourette's syndrome (TS) is a complex neurodevelopmental disorder characterized by high comorbidity. Treatment with psychotherapy is highly recommended, however, there exists limited available evidence on the use and the optimal psychotherapeutic outcome is debatable. We performed a systematic search on several bibliographic databases for randomized controlled trials (RCTs) reporting the use of psychotherapy treatment in TS patients, from inception to August 1st, 2020, and without language restrictions. Outcome measures were measured by the Yale global tic severity scale (YGTSS) to determine the efficacy of psychotherapy. Data were pooled as Standard mean difference (SMD) in the Bayesian analysis of the random effect model. A total of 17 RCTs with 9 treatments and 1042 participants were included from an initial 4901 records. The primary outcome including, Comprehensive behavioral intervention (CBIT) [SMD = -1.43, 95%Credible interval (CrI): -2.39, -0.44], Exposure with response prevention (ERP) [SMD = -1.37, 95%CrI: -2.62, -0.13], Habit reversal therapy (HRT) [SMD = -0.93, 95%CrI: 1.83, -0.05], and Behavior therapy (BT) [SMD = -0.85, 95%CrI: 1.51, -0.18], were found to be significantly lower in the TS group compared with the control group (including wait-list, treatment-as-usual or other named control group). Based on the Surface under the cumulative ranking curve (SUCRA), CBIT (SUCRA value = 86.97%, 95%CrI: 44%, 100%) was found to be a suitable psychotherapeutic treatment for TS patients. High-quality RCTs on psychotherapy are needed to perform for establishing the foundation of the generation of evidence-based guidelines.

Long-term exposure to ambient air pollution and metabolic syndrome in children and adolescents: A national cross-sectional study in China.

BACKGROUND: The prevalence of metabolic syndrome (MetS) rapidly increased over the past decades. However, little evidence exists about the effects of long-term exposure to ambient air pollution on MetS in children and adolescents. OBJECTIVE: This study aims to assess the association between long-term ambient air pollution and the prevalence of MetS in a large population of Chinese children and adolescents. METHODS: In 2013, a total of 9,897 children and adolescents aged 10 to 18 years were recruited from seven provinces/municipalities in China. MetS was defined based on the recommendation by the International Diabetes Federation (IDF). Satellite based spatio-temporal models were used to estimate exposure to ambient air pollution (including particles with diameters ≤1.0 µm (PM1), ≤2.5 µm (PM2.5), and ≤10 µm (PM10), and nitrogen dioxide (NO2)). Individual exposure was calculated according to 94 schools addresses. After adjustment for a range of covariates, generalized linear mixed-effects models were utilized to evaluate the associations between air pollutants and the prevalence of MetS and its components. In addition, several stratified analyses were examined according to sex, weight status, outdoor physical activity time, and sugar-sweetened beverages (SSBs) intake. RESULTS: The prevalence of MetS was 2.8%. The odds ratio of MetS associated with a 10 µg/m3 increase in PM1, PM2.5, PM10 and NO2 was 1.20 (95%CI: 0.99, 1.46), 1.31 (95%CI: 1.05, 1.64), 1.32 (95%CI: 1.08, 1.62), and 1.33 (95%CI: 1.03, 1.72), respectively. Regarding the MetS components, we observed associations between all pollutants and abdominal obesity. In addition, long-term PM1 and NO2 exposures were associated with the prevalence of elevated fasting blood glucose. Stratified analyses detected that the associations between air pollutants and the prevalence of MetS were stronger in boys (Pinteraction < 0.05). CONCLUSIONS: We found that long-term exposure to PM2.5, PM10, and NO2 were positively associated with the prevalence of MetS in children and adolescents. Our findings may have certain public health implications for some comprehensive strategy of environment improvement and lifestyles changes in order to reduce the burden of non-communicable disease.

Greenness surrounding schools and adiposity in children and adolescents: Findings from a national population-based study in China.

BACKGROUND: Previous studies have indicated that exposure to green space may benefit human health. However, the available evidence concerning the effects of greenness, especially school-based greenness, on pediatric obesity is scarce. OBJECTIVE: To explore the association between school-based greenness and adiposity in children and adolescents in China. METHOD: We conducted a nationwide cross-sectional study of 56,620 children and adolescents (aged 6-18 years) in seven provinces/municipalities across China. School-based greenness was assessed using satellite-derived Normalized Difference Vegetation Index (NDVI) and Soil Adjusted Vegetation Index (SAVI) within 100-, 500-, and 1000-m circular buffers around each school's address. Generalized linear mixed regression models were used to estimate associations of greenness with BMI z-scores (zBMI), waist circumference, and prevalent overweight/obesity. We also explored the potential mediating role of ambient air pollution and physical activity in the greenness-adiposity associations. RESULT: In the adjusted model, an IQR increase in NDVI-1000m was associated with lower zBMI (ß: -0.11, 95% confidence interval[CI]: -0.13,-0.09) and waist circumference (ß: -0.64, 95%CI: -0.78,-0.50). Consistently, an IQR increase in NDVI-100m, NDVI-500m, NDVI-1000m was associated with 7-20% lower odds of overweight/obesity in the adjusted models. Air pollutants mediated 6.5-29.1% of the association between greenness and zBMI. No significant mediation effect was observed for physical activity. CONCLUSION: Higher school-based greenness levels were associated with lower zBMI, waist circumference, and lower odds of overweight and obesity in children and adolescents. Ambient air pollutants may partially mediate the greenness-adiposity associations.

Gender differences in self-harm and drinking behaviors among high school students in Beijing, China.

BACKGROUND: Self-harm and drinking are both serious problems in adolescents and many studies presented evidence of their association. However, gender differences in this association are seldom deeply discussed. Our study aimed to evaluate the prevalence of self-harm and explore its association with drinking behaviors by gender and investigate the extent to which the gender differences exist in the association between self-harm and drinking. METHODS: A total of 32,362 students in grades 7 to 12 in Beijing, China were anonymously surveyed and included in our study using two-stage, stratified probability proportion sampling. Self-harm, drinking behaviors and other basic information were obtained from an anonymous questionnaire. Demographic variables, self-harm and drinking behaviors were analyzed using the Chi-square test and the Gamma test between genders and the gender differences in this association were analyzed by Log-binomial regression. RESULTS: The total prevalence of self-harm was 13.7% with no significant gender difference (χ2 =0.352, P = 0.553). The prevalence of self-harm in girls decreased with age (G = -0.163, P < 0.001). Self-harm was associated with drinking behaviors in both boys and girls. The Log-binomial regression demonstrated that girls in the 16-19 years old group were at lower risk of self-harm than girls in the 12-15 years old group while this association was weaker in boys (1.493 vs 1.128). The higher OR for self-harm was found among girls with early drinking experiences compared with boys (2.565 vs 1.863). Girls who had previously drunk (i.e. drunk at least once) (2.211 vs 1.636), were currently drinking (3.400 vs 2.122) and performed binge drinking (6.357 vs 3.924) were at greater risk of self-harm than boys. CONCLUSION: Among high school students, self-harm has a significant positive association with drinking and girls with drinking behaviors are at higher risk of suffering self-harm. Identifying adolescents' drinking behaviors is of vital importance to self-harm prevention and special attention should be focused on younger girls.

Effect of magnesium gluconate administration on lipid metabolism, antioxidative status, and related gene expression in rats fed a high-fat diet.

To explore the effect of magnesium gluconate (MgG) on lipid metabolism and its regulation mechanism through animal experiments, and to provide basis for MgG dietary intervention in hyperlipidemia. The first four weeks was hyperlipidemia-inducing period through high-fat diet and the following eight weeks was the MgG supplementation. At the end of the experiment, blood and liver samples were collected for the measurements of lipid profile, antioxidative indexes, pathological examination, and cholesterol metabolism-related gene expression. Oral administration of MgG notably decreased the blood levels of TC, TG, LDL-C and liver function index ALT and AST of hyperlipidemic rats. The rats supplemented with magnesium showed a huge increase in the GSH-Px and SOD activities, and reduced the heart weight and liver lipid accumulation of high-fat diet fed rats. MgG remarkably up-regulated the mRNA expression levels of LDLR and CYP7A1 of liver enzymes related to cholesterol metabolism. Oral magnesium supplementation inhibited an increase in lipid profile and liver function index by a high-fat diet, and enhanced the activity of the antioxidant enzymes. Magnesium has lipid-lowering and antioxidative effects that protect the liver against hyperlipidemia.

miR-873 suppresses H9C2 cardiomyocyte proliferation by targeting GLI1.

MicroRNAs (miRNAs) are a class of endogenous, non-coding small RNAs that regulate the expression of target genes. Previous studies have suggested that miRNAs are key regulators in cardiovascular systems. This study investigated the role of miR-873 in H9C2 cardiomyocytes by targeting glioma-associated oncogene 1 (GLI1). miR-873 was significantly up-regulated in serum samples from congenital heart disease (CHD) patients compared with those from normal individuals. Furthermore, miR-873 over-expression suppressed H9C2 proliferation and induced cell cycle arrest. Bioinformatic algorithms revealed a predicted target site for miR-873 in the 3'-untranslated region (3'UTR) of GLI1, which was verified using a dual-luciferase reporter assay. qPCR and western blot analysis also showed that miR-873 negatively regulated GLI1 mRNA and protein expression in H9C2 cells. Conversely, GLI1 over-expression partially reversed the growth-inhibitory effect of miR-873. To summarize, our data suggest that miR-873 is a novel miRNA that regulates H9C2 cell proliferation via targeting GLI1, and miR-873 may serve as a new potential biomarker diagnosis in CHD in the future.

Tocotrienol-rich fraction (TRF) suppresses the growth of human colon cancer xenografts in Balb/C nude mice by the Wnt pathway.

Tocotrienols have been shown many biologic functions such as antioxidant, anti-cancer, maintaining fertility and regulating the immune system and so on. In this study, after feeding with tocotrienol-rich fraction from palm oil (TRF) for 2 weeks, Balb/c nude mice were inoculated human colon SW620 cancer cell and then continued to feed TRF for 4 weeks. At termination of experiments, xenografts were removed and determined the expression of Wnt-pathways related protein by immunohistochemistry or western blotting. Liver tissues were homogenated for determining the levels of antioxidative enzymes activity or malondialdehyde (MDA). The results showed that TRF significantly inhibited the growth of xenografts in nude mice. TRF also affected the activity of antioxidative enzymes in the liver tissue of mice. These changes were partly contributed to activation of wnt pathways or affecting their related protein. Thus, these finding suggested that the potent anticancer effect of TRF is associated with the regulation of Wnt signal pathways.

KDEL Receptors Assist Dengue Virus Exit from the Endoplasmic Reticulum.

Membrane receptors at the surface of target cells are key host factors for virion entry; however, it is unknown whether trafficking and secretion of progeny virus requires host intracellular receptors. In this study, we demonstrate that dengue virus (DENV) interacts with KDEL receptors (KDELR), which cycle between the ER and Golgi apparatus, for vesicular transport from ER to Golgi. Depletion of KDELR by siRNA reduced egress of both DENV progeny and recombinant subviral particles (RSPs). Coimmunoprecipitation of KDELR with dengue structural protein prM required three positively charged residues at the N terminus, whose mutation disrupted protein interaction and inhibited RSP transport from the ER to the Golgi. Finally, siRNA depletion of class II Arfs, which results in KDELR accumulation in the Golgi, phenocopied results obtained with mutagenized prME and KDELR knockdown. Our results have uncovered a function for KDELR as an internal receptor involved in DENV trafficking.

Interaction between Tbx1 and Hoxd10 and connection with TGFß-BMP signal pathway during kidney development.

Renal malformations are commonly found among patients carrying a 22q11 deletion which renders loss of Tbx1 gene, an important transcriptional factor implicated in a number of developmental processes. Smad1 is known to interact with Tbx1, but the exact mechanism remains unknown. In this study, we have measured the expression of Tbx1 in both murine and human tissues using RT-PCR, and analyzed its protein product and protein-protein interactions with Western blotting and immunoprecipitation assays. Precipitated proteins were verified with mass spectrometry. As discovered, Tbx1 binds with Hoxd10. Tbx1 and Hoxd10 genes also have similar expression profiles during murine kidney development. Based on homology between mouse and human, we hypothesized that such interaction also exists in human. Through a RNA interference experiment using a human embryonic kidney HEK293 cell line, we demonstrated that TBX1 can alter TGF-ß/BMP, an important signaling pathway, through interacting with HOXD10. Above findings may shed light on the mechanism of TBX1 mutations leading to renal malformations found in patients carrying a 22q11 deletion.

[The effect of suppressive oligodeoxynucleotides on interferon-γ and phosphorylation of signal transducers and activators of transcription 4 expression of silica-induced pulmonary inflammation in mice].

OBJECTIVE: To investigate the protective effect of suppressive oligodeoxynucleotides (Sup ODN) on interferon-γ (IFN-γ) and signal transducers and activators of transcription (pSTAT4) expression of Silica-induced pulmonary inflammation in Mice. METHODS: Sixty Balb/c mice were randomly divided into 4 groups, normal control group, silicious group, suppressive oligodeoxynucleotides (Sup ODN) group, control oligodeoxynucleotides (Con ODN) group. Except the normal control group injected normal saline, the rest groups were induced by the intratracheal instillation of 0.1 ml (5 g/L) of sterilized silica suspension. Sup ODN group and Con ODN group were treated by i.p. injection of 0.3 ml (1mg/mL) of suppressive or control ODN 3 h before silica administration. After 7 days, the animals were killed and levels of IFN-γ were detected by ELISA. The pathologic changes in lung tissues of mice were observed with HE staining. Expressions of IFN-γ and pSTAT4 in lung tissue were detected with immunohistochemistry and quantified by Image-Pro Plus 7.0. RESULTS: HE staining showed that the lung tissue of silicious group were damaged seriously than Sup ODN group. Compared with the normal control group (serum: (280.1±41.3) pg/ml, lung tissue: (0.249±0.373), IFN-γ increased in silicious group (serum: (886.3±81.7) pg/ml, lung tissue: (0.270±0.300) (P < 0.05). Compared with the normal control group and Con ODN group [(894.5±91.6) pg/ml], IFN-γ in the serum of Sup ODN group decreased significantly (P < 0.01). Compared with the silicious group , IFN-γ in lung tissue decreased in Sup ODN group (0.241±0.250) (P < 0.05). Compared with the normal control group (0.279±0.353), pSTAT4 in lung tissue increased significantly in silicious group (0.313±0.231) (P < 0.01). Compared with the silicious group, pSTAT4 in lung tissue decreased significantly in Sup ODN group (0.269±0.523) (P < 0.01). CONCLUSION: Sup ODN attained protective effect on Silica treated mice by suppressing expression of IFN-γ and pSTAT4.

γ-Tocotrienol induces paraptosis-like cell death in human colon carcinoma SW620 cells.

Colorectal cancer is one of the most serious illnesses among diagnosed cancer. As a new type of anti-cancer composition from tocotrienol-rich fraction of palm oil, γ-tocotrienol is widely used in anti-cancer research. The objectives of this study were to investigate the effects of γ-tocotrienol on human colon cancer SW620 and HCT-8 cells. We showed that treatment with different concentrations of γ-tocotrienol resulted in a dose dependent inhibition of cell growth. Cell death induced by γ-tocotrienol was mediated by a paraptosis-like cell death in SW620 and HCT-8 cells. Real-time RT-PCR and western blot analyses showed that γ-tocotrienol inhibited the expression level of ß-catenin, cyclin D1 and c-jun. These data suggest that a paraptosis-like cell death induced by γ-tocotrienol in SW620 cells is associated with the suppression of the Wnt signaling pathway, which offers a novel tool for treating apoptosis-resistance colon cancer.

[Effects of dibutyl phthalate and monobutyl phthalate on testosterone secretion and insulin-like factor 3 expression of Leydig tumor cells in mice].

OBJECTIVE: To observe the effects of dibutyl phthalate (DBP) and monobutyl phthalate (MBP) on the mRNA and protein expression of insulin-like factor 3 (INSL3) in the Leydig tumor cells (MA-10) of mice and the level of testosterone secreted from MA-10 cells. METHODS: The MA-10 cells of mice, used as a cellular model, were exposed to DBP and MBP. The content of testosterone in the supernatant medium was measured by enzyme-linked immunosorbent assay; the mRNA and protein expression levels of INSL3 in MA-10 cells were measured by quantitative PCR and Western Blot. RESULTS: Compared with the control group, MA-10 cells showed increased synthesis of testosterone when exposed to low concentrations of DBP and MBP (10(-9) ∼ 10(-6) mol/L) and inhibited synthesis of testosterone when exposed to high concentrations of DBP and MBP (10(-3) mol/L), and the typical two-way effects became more significant as the time went one and the concentrations increased (P < 0.05). Compared with the control group, MA-10 cells showed significantly lower mRNA and protein expression levels of INSL3 when exposed to 10(-6) and 10(-4) mol/L DBP (P < 0.05); MA-10 cells showed increased protein expression of INSL3 when exposed to 10(-7) mol/L MBP, and the mRNA and protein expression levels of INSL3 decreased as the concentration of MBP increased. CONCLUSION: DBP and MBP can inhibit the secretion of testosterone from MA-10 cells at high concentrations, but stimulate the secretion of testosterone at low concentrations. Both DBP and MBP have inhibitory effects on the mRNA and protein expression of INSL3 in MA-10 cells.

[Effects of lead on protein kinase C expression in U251 cell line].

OBJECTIVE: To observe the effects of lead on mRNA and protein expression of PKC in U251 cell line. METHODS: After U251 cells were exposed to 0.05, 0.50, 5.00, 50.00, 500.00, 900.00 and 1000.00 micromol/L Ph(Ac)2 for 24 hours, the cytotoxicity of Pb on U251 cells was measured by MTT assay. RT-PCR and Western blot assay were used to detect the mRNA and protein expression levels of PKC in U251 cells exposed to 0.05, 5.00 and 500.00 micromol/L Ph (Ac), for 24 hours. RESULTS: The survival rates of U251 cells treated with 5.00, 50.00, 500.00, 900.00 and 1000.00 micromol/L Pb (Ac)2 were 84.5%, 78.2%, 76.5%, 50.3% and 43.2%, respectively, which were significantly lower than those of control group (P < 0.01). The PKC mRNA expression level (0.40 +/- 0.01) of U251 cells treated with 500.00 micromol/L Pb (Ac)2 was significantly lower than that (0.51 +/- 0.02) of control group (P < 0.01). The PKC protein expression levels of U251 cells treated with 0.05, 5.00 or 500.00 micromol/L Pb(Ac)2 were 0.68 +/- 0.02, 0.62 +/- 0.01 and 0.33 +/- 0.02, respectively, which were significantly lower (0.98 +/- 0.01) than those of control group (P < 0.01). CONCLUSION: Lead can decline the cell viability, PKC mRNA and protein expression levels of U251 cells.

[The clinical application and value of intra-aortic balloon pump in patients with septic shock].

OBJECTIVE: To investigate the clinical efficacy and value of intra-aortic balloon pump (IABP) with vasoactive drugs for septic shock patients. METHODS: A method of single-centre registry was conducted. Data were collected from 78 consecutive septic shock patients in late stage in intensive care unit (ICU) of Beijing Shijitan Hospital diagnosed between July 2006 and October 2010. With the consent of family members of the patients, they were divided into two groups: group A, in whom only vasoactive drugs were used (dopamine + norepinephrine treatment, n = 39), and group B, in whom vasoactive drugs were used combined with IABP (dopamine + norepinephrine + IABP therapy, n = 39). Before and after treatment of two groups, hemodynamic and tissue perfusion monitoring were executed. At the same time, the shock recovery time, the doses of vasoactive drugs, length of ICU stay, and mortality within 28 days were observed. RESULTS: There was no significant difference in all above parameters between two groups. After treatment, heart rate, blood pressure and heart function parameters were significantly improved compared with those before treatment. In group B, mean arterial pressure (MAP, mm Hg,1 mm Hg = 0.133 kPa) 24 hours and 72 hours after IABP, cardiac index [CI, L×min(-1)× m(-2)] after 48 hours of IABP, and in 2 hours after termination of IABP, dopamine dosage [µg×kg(-1)×min(-1)] in 24, 48, 72 hours after IABP and 2 hours after termination were significantly improved than those in group A (MAP: 53.0 ± 6.3 vs. 52.1 ± 6.2, 65.6 ± 4.3 vs. 65.0 ± 2.1; CI: 3.40 ± 0.20 vs. 3.30 ± 0.50, 3.60 ± 0.30 vs. 3.60 ± 0.30; dopamine dosage: 17.5 ± 1.2 vs. 17.6 ± 1.3, 10.2 ± 1.3 vs. 12.8 ± 1.6, 5.8 ± 1.5 vs. 6.8 ± 1.7, 3.0 ± 0.7 vs. 4.1 ± 1.3, P < 0.05 or P < 0.01). Compared with group A, shock recovery time (days) of group B was significantly shorter (10.4 ± 2.2 vs. 14.1 ± 3.4, P < 0.01) than that of group A; mortality within 28 days was significantly lower (34.1% vs. 45.6%, P < 0.01) in group B; length of ICU stay of two groups showed no significant difference between two groups. CONCLUSIONS: IABP in patients with septic shock significantly improved hemodynamics, increased coronary and systemic tissue perfusion, reduced cardiac afterload, elevated CI, reduced doses of vasoactive drugs, shortened length of ICU stay, improved prognosis, and lowered the mortality rate. IABP had important clinical value, and could be recommended as an additional treatment option in patients with septic shock in whom the effect of drug was poor.

A paraptosis-like cell death induced by δ-tocotrienol in human colon carcinoma SW620 cells is associated with the suppression of the Wnt signaling pathway.

Tocotrienol is considered a beneficial effect agent on inhibition of tumor development. In this study, we focused on the effects of δ-tocotrienol and its possible mechanism on induction of death in human colon cancer SW620 cells. δ-Tocotrienol inhibited proliferation of SW620 cell in a dose-dependent manner. Our findings showed that δ-tocotrienol effectively induced paraptosis-like death in SW620 cells, correlated with the vacuolation that may be from welling and fusion of mitochondria and/or the endoplasmic reticulum (ER) as well as caspase-3 nonactivated. However, there were no changes in apoptosis based on flow cytometry analysis. Of being noted, δ-tocotrienol reduced the expression of ß-catenin and wnt-1 proteins by about 50% at the highest dose (20µmol/L). δ-Tocotrienol also decreased cyclin D1, c-jun and MMP-7 protein levels in SW620 cells. Altogether, these data indicate that δ-tocotrienol induces paraptosis-like cell death, which is associated with the suppression of the Wnt signaling pathway. Thus, our findings may provide a novel application in treatment of human colon carcinoma.

[Genetic analysis of genitourinary malformations].

OBJECTIVE: To analyze the expression of genes from chromosomal region 22q11.2 and assess the association between mutation(s) of particular gene(s) from this region and malformations of the urinary system. METHODS: Expression of rat homologs of 33 genes from above region was determined in kidney tissues derived from rats of different fetal development ages (E13, E15, E19) and adulthood with reverse transcriptase-PCR. Potential mutation(s) in candidate gene SNAP29, whose expression pattern appeared to be unique, was screened in 44 patients and 220 normal controls with PCR-single strand conformation polymorphism (SSCP). Suspected positive regions were sequenced to verify the mutations. RESULTS: Nine genes showed no expression throughout the whole development process; 18 genes with various expression levels showed continuous expression from the beginning of development; 6 genes only expressed for a short time, among which SNAP29 was selected for mutation screening. Upon sequencing, three mutations were identified from the 44 patients, including a G to A transition (GAG to AAG) in exon 2, and two A to G transitions (AGC to GGC) in exon 3. CONCLUSION: Through systematic analysis of the expression of genes from chromosomal region 22q11.2, the SNAP29 gene was found to have a potential role in the development of genitourinary system. Two missense mutations were identified in three patients. These included one in exon 2 (featuring cryptorchidism), and the other in exon 3 (featuring cryptorchidism and hypospadia). Neither of the mutations was found in the normal controls. The results suggested that mutation(s) of gene(s) from chromosomal region 22q11.2 may play an important role in the genesis of genitourinary malformations.

[Effects of lead exposure on protein kinase C and calmodulin expression in hippocampus and neurobehavioral function of baby rats].

OBJECTIVE: To observe the effect of chronic lead contaminant on mRNA expression of protein kinase C (PKC) and calmodulin (CaM) in hippocampus of baby rats. METHODS: The Wistar pregnant rats were randomly divided into 3 groups fed with distilled water and lead contained water (0.2% and 1.0% lead acetate) respectively. The lead exposure period was from the 0 day of pregnancy to the day when the offspring weaned. Then the baby rats were fed with lead water the same as their mothers. The cliff avoidance reflex within postnatal day 8 and step down test at postnatal day 50 were performed. Then pups were killed at postnatal day 8 and 50 respectively. Atomic absorption spectrometry was used to determine lead content of rats' brain. RT-PCR was used to observe mRNA expression of PKC and CaM in hippocampus of baby rats. RESULTS: The brain lead content of test groups were much higher than that of the control group. The completion rate of cliff avoidance reflex and the score of step down test of test groups were lower than those in the control group (P < 0.05). Compared with control group, PKC and CaM mRNA expression of chronic lead exposure baby rats in the hippocampus had the down trend (P < 0.05). CONCLUSION: The decrease of PKC and CaM mRNA expression level in hippocampus has a great link with the impairment of learning and memory induced by lead in baby rats, which might be one of the molecule mechanisms of lead induced impairment of learning and memory.