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Objective To investigate the role and mechanism of SR8278,a synthetic antagonist of nuclear receptor subfamily 1 group D member 1(NR1D1),in alleviating the structural and functional impairment of the extraorbital lacrimal glands induced by jet lag in mice.Methods Totally 36 healthy wild C57BL/6J mice aged 8-10 weeks were randomly divid-ed into 3 groups(normal group,jet-lag group,and jet-lag+SR8278 group)after adapting to a circadian rhythm chamber under the 12 h light/12 h dark(12 h/12 h LD)cycle for 2 weeks,with 12 mice in each group.Mice in the normal group were fed in a circadian rhythm chamber in a 12 h LD cycle,mice in the jet-lag group were fed in a 12 h/12 h LD cycle with an 8-hour advanced LD schedule,and mice in the jet lag+SR8278 group were fed in a 12 h/12 h LD cycle with an 8-hour advanced LD schedule and received 25 mg·kg-1 SR8278.At the end of 5 days of intervention,locomotor activity,core body temperature and tear secretion of mice in each group were collected,and the weight of lacrimal gland tissues and size of lacrimal gland cells were measured.Immunohistochemical methods were used for histological evaluation of the extraor-bital lacrimal glands in mice.Lacrimal ribonucleic acid(RNA)was extracted for high-throughput RNA-sequencing analysis containing NR1D1,and the obtained transcriptomic data were used for KEGG and GO functional enrichment analysis.Re-sults Compared with the normal group,the jet-lag group had higher daytime activity,lower nighttime activity,higher daytime core body temperature,and lower nighttime core body temperature,with statistically significant differences(all P＜0.05).Compared with the jet-lag group,the jet-lag+SR8278 group had lower daytime activity,higher nighttime activi-ty,lower daytime core body temperature,and higher nighttime core body temperature,with statistically significant differ-ences(all P＜0.05).Compared with the normal group,the jet-lag group showed a decrease in lacrimal gland weight and tear secretion and an increase in size of lacrimal gland cells,with statistical significance(all P＜0.05);compared with the jet-lag group,the jet-lag+SR8278 group had an increase in lacrimal gland weight and tear secretion and a decrease in size of lacrimal gland cells,with statistical significance(all P＜0.05).Compared with the normal group,the jet-lag group showed a higher expression of NR1D1 in the lacrimal gland at night;compared with the jet-lag group,the jet-lag+SR8278 group showed a lower expression of NR1 D1 in the lacrimal gland at night(both P＜0.05).Bioinformatics analysis showed 947 significantly different genes in the jet-lag group and the jet-lag+SR8278 group,of which 43 are significantly upregulated genes,and 904 are significantly downregulated genes.The Notch signaling pathway has the most significant difference.Conclusion SR8278 effectively enhances the tear secretion function of jet-lagged mice by targeting NR1D1 inhibition.This process may be completed through the Notch signaling pathway.
Résumé
Objective To compare acoustic radiation force impulse(ARFI)and supersonic shear imaging (SWE) in diagnosis of liver fibrosis in patients with chronic hepatitis B. Methods Eighty patients with chronic hepatitis B having underwent ARFI and SWE examination were enrolled in this study.The elastic modulus E value(EI)was measured by SWE.The liver shear wave velocity(VTQ)was measured by ARFI.All patients underwent liver biopsy.The diagnostic values of SWE and ARFI for liver fibrosis were analyzed with Sperman correlation and the ROC curve.Results The values of EI and VTQ were increased with the pathological stage determined by liver biopsy and there were significantly differences(P<0.01).The correlation coefficient of SWE and ARFI was 0.651,P<0.01.The correlation coefficient of SWE, ARFI and pathological stage determined by liver biopsy were 0.784 and 0.683 and there were significant differences(P<0.01).The areas under ROC for diagnosing liver fibrosis≥S2,≥S3 and =S4 by using SWE were 0.912, 0.934 and 0.955 respectively and those by using ARFI were 0.870, 0.892 and 0.884. The sensitivity of ARFI in diagnosing liver fibrosis was similar with SWE, but SWE showed higher specificity (Z=8.756,P < 0.01; Z=10.802,P < 0.01; Z=15.871,P < 0.01). Conclusions Both SWE and ARFI can be effectively used in the evaluation of liver fibrosis in patients with chronic hepatitis B.The SWE technology has more advantages.
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Objective:To make an assessment on the genotoxicity caused by black carbon ( BC ) and ozonized black carbon (O3-BC).Methods: In this study, 74 healthy male ICR mice [weighed (28 ± 1.5) g] were randomly divided into 7 groups, including one phosphate buffer solution ( PBS) control group and six particles exposed groups by intratracheal instillation with either BC or O 3-BC at the doses of 50, 100, 200 μg/mouse, respectively.There were 12 mice in the groups of 200μg/mouse and 10 mice in others.The mice were sacrificed 24 h after four intratrachealinstillations .The activities of catalase ( CAT) in serum and the levels of malondialdehyde ( MDA) in lung tissue homogenate were measured . As the DNA damage mark , 8-hydroxyguanosine ( 8-OHdG ) in urine and serum were quantified with ELISA method.Micronucleus test was used for potential genotoxicity of BC and O 3-BC.Hematoxylin and eosin staining was used to stain lung paraffin section .Results:The mice were in good condition during instillation , and the liver coefficient of the test groups was significantly lower than that of the control group (P<0.05).The activities of CAT in serum significantly increased in the 100 μg/mouse and 200μg/mouse groups after being exposed to these two kinds of particles .The micronucleus rate in allthe BC and O3-BC exposed groups increased ( P <0.05), but there was no statistically significant difference among the groups in the levels of 8-OHdG in serum and urine and MDA in lung tissue homogenate .In-flammatory response was found in the lung tissue under the microscope after exposure to BC and O 3-BC. Conclusion:Intratracheal instillation of BC and O 3-BC induced increasing of oxidative stress and genetic damage in mice .But there was no significant difference between these two particles in toxicity .Whether the genotoxicity of O 3-BC is higher than that of BC or not is uncertain .Further research is needed .