The antichlamydial activity of 1, 2-disubstituted pyrrole derivatives in vitro / 中国药理学通报

Aim To evaluate the antichlamydial activity of our previously synthesized sixteen 1, 2-disubstituted pyrroles in vitro, providing candidate for the development of novel agents against Chlamydia. Methods Firstly, the inhibitory effect of compounds on the generation of infectious progeny EBs at different concentrations was analyzed for Chlamydia trachomatis L2 (Ct L2), C. muridarum (Nigg II strain, known as MoPn) and C. pneumonia (Cpn AR39). The IC

The Joubert Syndrome Gene arl13b is Critical for Early Cerebellar Development in Zebrafish / 神经科学通报·英文版

Joubert syndrome is characterized by unique malformation of the cerebellar vermis. More than thirty Joubert syndrome genes have been identified, including ARL13B. However, its role in cerebellar development remains unexplored. We found that knockdown or knockout of arl13b impaired balance and locomotion in zebrafish larvae. Granule cells were selectively reduced in the corpus cerebelli, a structure homologous to the mammalian vermis. Purkinje cell progenitors were also selectively disturbed dorsomedially. The expression of atoh1 and ptf1, proneural genes of granule and Purkinje cells, respectively, were selectively down-regulated along the dorsal midline of the cerebellum. Moreover, wnt1, which is transiently expressed early in cerebellar development, was selectively reduced. Intriguingly, activating Wnt signaling partially rescued the granule cell defects in arl13b mutants. These findings suggested that Arl13b is necessary for the early development of cerebellar granule and Purkinje cells. The arl13b-deficient zebrafish can serve as a model organism for studying Joubert syndrome.

The Joubert Syndrome Gene arl13b is Critical for Early Cerebellar Development in Zebrafish / 神经科学通报·英文版

Joubert syndrome is characterized by unique malformation of the cerebellar vermis. More than thirty Joubert syndrome genes have been identified, including ARL13B. However, its role in cerebellar development remains unexplored. We found that knockdown or knockout of arl13b impaired balance and locomotion in zebrafish larvae. Granule cells were selectively reduced in the corpus cerebelli, a structure homologous to the mammalian vermis. Purkinje cell progenitors were also selectively disturbed dorsomedially. The expression of atoh1 and ptf1, proneural genes of granule and Purkinje cells, respectively, were selectively down-regulated along the dorsal midline of the cerebellum. Moreover, wnt1, which is transiently expressed early in cerebellar development, was selectively reduced. Intriguingly, activating Wnt signaling partially rescued the granule cell defects in arl13b mutants. These findings suggested that Arl13b is necessary for the early development of cerebellar granule and Purkinje cells. The arl13b-deficient zebrafish can serve as a model organism for studying Joubert syndrome.

Changes of apoE protein expression in lung of mice with hypoxic pulmonary arterial hypertension / 中国应用生理学杂志

OBJECTIVE@#To observe the changes of apolipoprotein E (apoE) protein expression of pulmonary tissue in mice with pulmonary hypertension induced by hypoxia.@*METHODS@#The animal model of hypoxic pulmonary hypertension was established by exposing the mice to isobaric hypoxic chamber for 3 weeks (23 h/d, regular chow feed).Twenty male wild type (WT) C57BL/6 mice and twenty apoE gene knockout (apoE-KO) mice were randomly divided into normoxia group and hypoxia group. The plasma concentrations of low density lipoprotein (LDL), high density lipoprotein (HDL) and total cholesterol were detected by ELISA method. The protein expression of apoE in lung and liver, and peroxisome proliferators-activated receptor gamma (PPARγ) in lung were measured by Western blot.@*RESULTS@#①In WT mice, the right ventricular systolic pressure (RVSP) and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV+S) of hypoxia group were significantly higher than those of normoxia group by 68% and 59% (<0.05), respectively. The plasma concentration of HDL and HDL/LDL of hypoxia group were significantly lower than those of normoxia group by 17% and 40% (<0.05), respectively.The protein expression of apoE in lung and in liver of hypoxia group were significantly down-regulated than those of normoxia group by 48% and 52% (<0.05), respectively.The protein expression of PPARγ in lung was significantly down-regulated than that of normoxia group by 37%(<0.05).RVSP were significantly negative correlated with the protein levels of apoE and PPARγ in lung (<0.01).② In apoE-KO mice, RVSP and the weight ratio of RV to LV+S of hypoxia group were significantly higher than those of normoxia group by 96% and 86% (<0.05), respectively.RVSP and RV to (LV+S) of hypoxia group in apoE-KO mice were significantly higher than those of hypoxia group in WT mice by 29% and 24% (<0.05), respectively.@*CONCLUSIONS@#Down-regulated expression of apoE in lung tissue participates in the pathological proceeding of pulmonary hypertension induced by hypoxia.

Gene silencing of indoleamine 2,3-dioxygenase 2 influences proliferation,migration and invasion of B16-BL6 melanoma cells / 中国病理生理杂志

AIM:To investigate the effects of indoleamine 2,3-dioxygenase 2 (IDO2) silencing on proliferation,migration and invasion of B16-BL6 melanoma cells.METHODS:IDO2-siRNA was transfected into the B16-BL6 melanoma cells in vitro.The expression of IDO2 or IDOl at mRNA and protein levels was detected by real-time PCR and Western blot.Colony formation assay was performed to analyze the proliferation of IDO2-silencing tumor cells.The migration ability of B16-BL6 cells after silencing of IDO2 was measured by wound healing assay and Transwell cell migration assay.The invasion ability of the tumor cells was detected by Transwell cell invasion assay.RESULTS:IDO2-siRNA significantly down-regulated IDO2 expression in B16-BL6 melanoma cells,and did not affect IDO1 expression.Compared with control group,the colony formation ability,the migratory distance measured by wound healing assay,and the migration and the invasion cell numbers detected by Transwell assay all remarkably decreased in the IDO2-silencing cells.CONCLUSION:IDO2 silencing affects the proliferation,migration and invasion abilities of the R16-BL6 melanoma cells.

Gene silencing of indoleamine 2,3-dioxygenase 2 influences proliferation,migration and invasion of B16-BL6 melanoma cells / 中国病理生理杂志

AIM:To investigate the effects of indoleamine 2,3-dioxygenase 2 (IDO2) silencing on proliferation,migration and invasion of B16-BL6 melanoma cells.METHODS:IDO2-siRNA was transfected into the B16-BL6 melanoma cells in vitro.The expression of IDO2 or IDOl at mRNA and protein levels was detected by real-time PCR and Western blot.Colony formation assay was performed to analyze the proliferation of IDO2-silencing tumor cells.The migration ability of B16-BL6 cells after silencing of IDO2 was measured by wound healing assay and Transwell cell migration assay.The invasion ability of the tumor cells was detected by Transwell cell invasion assay.RESULTS:IDO2-siRNA significantly down-regulated IDO2 expression in B16-BL6 melanoma cells,and did not affect IDO1 expression.Compared with control group,the colony formation ability,the migratory distance measured by wound healing assay,and the migration and the invasion cell numbers detected by Transwell assay all remarkably decreased in the IDO2-silencing cells.CONCLUSION:IDO2 silencing affects the proliferation,migration and invasion abilities of the R16-BL6 melanoma cells.