ABSTRACT
This study explored whether Sagittaria sagittifolia polysaccharides(SSP) activates the nuclear factor erythroid-2-related factor2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway to protect against liver damage jointly induced by multiple heavy metals. First, based on the proportion of dietary intake of six heavy metals in rice available in Beijing market, a heavy metal mixture was prepared for inducing mouse liver injury and HepG2 cell injury. Forty male Kunming mice were divided into five groups: control group, model group, glutathione positive control group, and low-and high-dose SSP groups, with eight mice in each group. After 30 days of intragastric administration, the liver injury in mice was observed by HE staining. In the in vitro experiment, MTT assay was conducted to detect the effects of SSP at 0.25, 0.5, 1, and 2 mg·mL~(-1) on HepG2 cell survival at different time points. The content of alanine transaminase(ALT) and aspartate aminotransferase(AST) in the 48-h cell culture fluid was measured using micro-plate cultivation method, followed by the detection of the change in reactive oxygen species(ROS) content by flow cytometry. The mRNA expression levels of Nrf2 and HO-1 in cells were determined by RT-PCR, and their protein expression by Western blot. HE staining results showed that compared with the model group, the SSP administration groups exhibited significantly alleviated inflammatory cell infiltration and fatty infiltration in the liver, with better outcomes observed in the high-dose SSP group. In the in vitro MTT assay, compared with the model group, SSP at four concentrations all significantly increased the cell survival rate, decreased the ALT, AST, and ROS content(P<0.05), and down-regulated Nrf2 and HO-1 mRNA and protein expression(P<0.05). SSP significantly improves inflammatory infiltration in the liver tissue of mice exposed to a variety of heavy metals and corrects the liver fat degeneration, which may be related to its regulation of the Nrf2/HO-1 signaling pathway, reduction of ROS, and alleviation of oxidative damage.
Subject(s)
Animals , Male , Mice , Heme Oxygenase-1/metabolism , Liver , Metals, Heavy/metabolism , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Polysaccharides/pharmacology , RNA, Messenger/metabolism , Reactive Oxygen Species/metabolism , Sagittaria/metabolismABSTRACT
Objective:To explore the protective effect of Gegen Qinliantang on the intestinal mucosal epithelial barrier function of ulcerative colitis （UC） mice， and to explore its mechanism of action in the treatment of ulcerative colitis via matrix metallopeptidase-9 （MMP-9）/p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. Method:The 48 female C57BL/6 mice were randomly divided into normal group， model group， sulfasalazine group （0.3 g·kg<sup>-1</sup>） and Gegen Qinliantang high， medium and low dose groups （2.84，1.42，0.71 g·kg<sup>-1</sup>）. The UC murine model was established by 3% dextran sulfate sodium （DSS）. Gegen Qinliantang and sulfasalazine were intragastrically administered on the 8<sup>th</sup> day after the model was established for 7 days， and the normal group was treated with the same amount of normal saline. Colon tissues were collected after the last administration， and the pathological changes of colon tissues were detected by hematoxylin-eosin （HE） staining. The expression of tight junction （TJ） proteins such as Occludin and zonula occludens-1（ZO-1） in colon tissues was detected by immunohistochemistry （IHC）， and the expression levels of tumor necrosis factor-alpha （TNF-<italic>α</italic>）， interleukin-1<italic>β</italic> （IL-1<italic>β</italic>）， and MMP-9 mRNA in colon tissues were detected by Real-time polymerase chain reaction （Real-time PCR）. The expression of phosphorylated p38 MAPK （p-p38 MAPK）， p38 MAPK and MMP-9 protein in colon tissues was detected by Western blot. Result:Compared with normal group， the body weight of mice decreased （<italic>P</italic><0.01） and disease activity index （DAI） score increased significantly （<italic>P</italic><0.01） in model group， the colon tissues of the model group were damaged more obviously， the expression of occludin and ZO-1 proteins in model group was significantly reduced （<italic>P</italic><0.01）， and the relative expression levels of TNF-<italic>α</italic>， IL-1<italic>β</italic>， and MMP-9 mRNA in model group were significantly increased （<italic>P</italic><0.01）， the expression of p-p38 MAPK and MMP-9 in model group was significantly increased （<italic>P</italic><0.01）. Compared with model group， the body mass and DAI score of the sulfasalazine group and Gegen Qinliantang group were significantly improved （<italic>P</italic><0.05，<italic>P</italic><0.01）， the colonic tissues damage were significantly improved， and the expression of Occludin and ZO-1 protein was significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01）， the relative expression levels of TNF-<italic>α</italic>， IL-1<italic>β</italic>， and MMP-9 mRNA were significantly decreased （<italic>P</italic><0.01）， and the expression of p-p38 MAPK and MMP-9 was significantly decreased （<italic>P</italic><0.01）. The changes in the middle dose group were the most obvious among the various dose groups of Gegen Qinliantang. Conclusion:Gegen Qinliantang repairs the intestinal mucosal barrier function by inhibiting the expressions of MMP-9 and inflammatory cytokines such as TNF-<italic>α</italic> and IL-1<italic>β</italic>， blocking the activation of the p38 MAPK signaling pathway， and increasing the expressions of tight junction protein.
ABSTRACT
ObjectiveThere are many methods for the detection of hydroxyproline (HYP), but few of them are suitable for the detection of lung tissue in mice. We intend to establish an accurate and reliable method for measuring HYP levels based on mouse lung tissues to assess the degree of fibrosis development more effectively.MethodsBased on the alkali hydrolysis method, the effects of the concentration of alkali hydrolysate and hydrolysis time on the determination results of HYP level in mice lung tissue were compared; the effects of the changes of experimental conditions on the determination results of HYP standard were compared; and the results of the determination of HYP level in mice lung tissue under dry and wet conditions were compared on the basis of the above experimental results.ResultsThe optimum concentration of alkali hydrolysate is 2 mol/L and the optimum hydrolysis time is 20 min. The optimum pH value of citric acid buffer is 6.0-6.5. The optimum solvent for chloramine T is methanol, the optimum reaction time for chloramine T solution is 15 min, the optimum reaction time for perchloric acid solution is 5 min, and the optimum reaction time for 4-(dimethylamino) benzoyl toluene is 5 min. The optimum condition of aldehyde solution color development is that it is bathed in water at 85 for 3 minutes. Some related reagents are stored in suitable environment after preparation, and the experimental data will not be affected within 7 days. Dry lung tissue of mice can improve the detection level of HYP. The improved experimental protocol was applied to the bleomycin-induced mouse pulmonary fibrosis model, and the HYP measurement results were significantly higher than that of the original protocol.ConclusionAn accurate and reliable method for the determination of hydroxyproline in lung tissue of mice was established.
ABSTRACT
Background@#The development of auditory and speech perception ability of children with hearing loss is affected by many factors after they undergo cochlear implantation (CI). Age at CI (CI age) appears to play an important role among these factors. This study aimed to evaluate the development of auditory and speech perception ability and explore the impact of CI age on children with prelingual deafness present before 3 years of age.@*Methods@#Two hundred and seventy-eight children with pre-lingual deafness (176 boys and 102 girls) were included in this study, and the CI age ranged from 6 to 36 months (mean age, 19 months). Categorical auditory performance (CAP) was assessed to evaluate auditory ability, and the speech intelligibility rating was used to evaluate speech intelligibility. The evaluations were performed before CI and 1, 3, 6, 12, 18, 24, 36, 48, and 60 months after CI.@*Results@#The auditory ability of the pre-lingually hearing-impaired children showed the fastest development within 6 months after CI (k = 0.524, t = 30.992, P < 0.05); then, the progress started to decelerate (k = 0.14, t = 3.704, P < 0.05) and entered a plateau at the 24th month (k = 0.03, t = 1.908, P < 0.05). Speech intelligibility showed the fastest improvement between the 12th and 24th months after CI (k = 0.138, t = 5.365, P < 0.05); then, the progress started to decelerate (k = 0.026, t = 1.465, P < 0.05) and entered a plateau at the 48th month (k = 0.012, t = 1.542, P < 0.05). The CI age had no statistical significant effect on the auditory and speech abilities starting at 2 years after CI (P < 0.05). The optimal cutoff age for CI was 15 months.@*Conclusions@#Within 5 years after CI, the auditory and speech ability of young hearing-impaired children continuously improved, although speech development lagged behind that of hearing. An earlier CI age is recommended; the optimal cutoff age for CI is at 15 months.
ABSTRACT
Objective: To explore the effect of Da Chengqitang on the lung index,lung index inhibition rate,lung histological morphology,classification changes of inflammatory cells and mitogen-activated protein kinase (MAPK) signal pathway in mice with allergic asthma.Method: Forty female C57BL/6 mice were randomly divided into normal control group,model group,dexamethasone group (0.005 g·kg-1) and Da Chengqitang group (19 g·kg-1).Murine allergic asthma model was established by sensitization and nebulization of ovalbumin (OVA).In brief,asthmatic mice were first sensitized by OVA and Al (OH)3 mixture ip on day 0 and day 14,and then nebulized by OVA from day 21 to 27.At the same time,each mouse in the dexamethasone and Da Chengqitang groups were intragastrically administered with 0.2 mL corresponding medicine one hour before the nebulization challenge,while the normal control group was given with the same amount of normal saline.On day 28,pulmonary morphology was detected by htoxylin eosin (HE) staining and inflammatory cells from the brachial alveolar lavage fluid were counted by Diff staining.The expression levels of key proteins in MAPK signaling pathway were detected by Western blot.Result: As compared with the normal control group,the lung indexes were significantly increased in model group (PP0.01),with a predominant percentage of eosinophils,moreover,the expression levels of phosphorylated p38 MAPK and extracellular signal-regulated kinase 1/2(ERK1/2) were increased obviously in asthmatic mice.After treatment by Da Chengqitang,lung indexes and pulmonary inflammation were significantly decreased,with an inhibitory rate of 68.4% for lung indexes,and inflammatory pathology of lung tissues was obviously improved and inflammatory cell exudation was alleviated,with the obviously lower levels of phosphorylated p38 MAPK and ERK1/2 protein.Conclusion: Da Chengqitang based on "Pulmonary Intestinal Treatment" can effectively improve lung inflammation in mice with allergic asthma,which may be related to the expression of phosphorylated p38 MAPK and ERK1/2 protein.
ABSTRACT
BACKGROUND@#The development of auditory and speech perception ability of children with hearing loss is affected by many factors after they undergo cochlear implantation (CI). Age at CI (CI age) appears to play an important role among these factors. This study aimed to evaluate the development of auditory and speech perception ability and explore the impact of CI age on children with pre-lingual deafness present before 3 years of age.@*METHODS@#Two hundred and seventy-eight children with pre-lingual deafness (176 boys and 102 girls) were included in this study, and the CI age ranged from 6 to 36 months (mean age, 19 months). Categorical auditory performance (CAP) was assessed to evaluate auditory ability, and the speech intelligibility rating was used to evaluate speech intelligibility. The evaluations were performed before CI and 1, 3, 6, 12, 18, 24, 36, 48, and 60 months after CI.@*RESULTS@#The auditory ability of the pre-lingually hearing-impaired children showed the fastest development within 6 months after CI (k = 0.524, t = 30.992, P 0.05). The optimal cutoff age for CI was 15 months.@*CONCLUSIONS@#Within 5 years after CI, the auditory and speech ability of young hearing-impaired children continuously improved, although speech development lagged behind that of hearing. An earlier CI age is recommended; the optimal cutoff age for CI is at 15 months.
ABSTRACT
<p><b>OBJECTIVE</b>To assess the rhythmic and timbral perception ability in musical activities for postlingually deafened adult cochlear implant users.</p><p><b>METHODS</b>Twelve normal-hearing and 12 adult cochlear implant users were recruited in this study. Rhythm discrimination, instrument identification, and instrument number detection measurements in Musical Sounds in Cochlear Implants (MuSIC) test battery were used to assess the rhythmic and timbral perception ability for both normal-hearing and cochlear implant users.</p><p><b>RESULTS</b>Cochlear implant subjects achieved 84.4% correct in rhythm discrimination test on average, which was not significantly different from the performance of normal-hearing subjects (85.1%) (t = 0.116, P > 0.05). The average score of instrument identification and instrument number detection test for cochlear implant subjects were 72.3% and 39.2%, respectively. The performance of cochlear implant subjects in both of two tests were significantly poorer than those of normal-hearing subjects with 88.3% and 73.5% correct, respectively (t = 2.498 and 4.673, P < 0.05).</p><p><b>CONCLUSION</b>Postlingually deafened cochlear implant subjects, on average, performed significantly poorer in timbral perception tasks relative to normal hearing subjects, while close to the ability of normal hearing subjects in rhythmic perception.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Auditory Perception , Case-Control Studies , Cochlear Implantation , Cochlear Implants , Deafness , Rehabilitation , Music , Perception , Periodicity , Pitch PerceptionABSTRACT
<p><b>OBJECTIVE</b>To investigate the reliability and validity of the Chinese version of Nijmegen Cochlear Implant Questionnaire (NCIQ).</p><p><b>METHODS</b>There were six subdomains: basic sound perception, advanced sound perception, speech production, self-esteem, activities and social Interactions. The cross-cultural adaptation measures were used to translate the NCIQ into its Chinese version. Ninety-four cochlear implant users no younger than 18 years old were included. Test-retest analysis was administered randomly to 30 users without significant changes in health and social status during a two weeks' interval between test and retest.</p><p><b>RESULTS</b>(1) Reliability: test-retest reliability of the NCIQ was proved to be satisfactory. All domains had coefficients that exceeded 0.70 (P < 0.01). Except for the subdomain, speech production, whose Cronbach's α score was 0.560, other Cronbach's α scores were greater than 0.700. (2) VALIDITY: The correlation coefficients between overall NCIQ scores and the six subdomains were 0.620 - 0.810 (P < 0.01). There were weak or no correlations among the six subdomains. The evaluation of content validity by expert review showed the questionnaire had good content validity. NCIQ total scores in postlingually deafened users were significantly higher than those in prelingually deafened users (Z = 4.350, P = 0.000). This was also true for scores of the following subdomains:advanced sound perception (Z = 4.774, P = 0.000), speech production (Z = 4.416, P = 0.000), self-esteem (Z = 3.718, P = 0.000), activities (Z = 3.228, P = 0.001) and social interactions (Z = 3.001, P = 0.003). There was no significant difference between scores obtained from the two groups in the subdomain of basic sound perception (Z = 1.943, P = 0.052).</p><p><b>CONCLUSIONS</b>The Chinese version of the NCIQ meets many psychometric criteria of a robust instrument. It possesses appropriate validity and good reliability, and can be used to measure the outcome of cochlear implant adults in China.</p>