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OBJECTIVE: observe the changes of localization and expression of acetylated tubulin alpha( Ac-tubulin α) in fibroblasts of silicosis fibrosis. METHODS: i) A total of 22 autopsy case with coal workers' pneumoconiosis( CWP) was selected as CWP group( autopsy lesion lung tissue) and their adjacent normal lung tissues surrounding fibrotic regions were selected as the control group using typical sampling method. ii) Specific pathogens free healthy male rats were randomly divided into control group and 5 dust-exposed groups with 10 rats in each group. In dust-exposed group,the rats were exposed to 2 000 mg/m~3 of silica dust for 0,2,4,8,12 and 16 weeks respectively by dynamic inhalation. The rats in control group were given no treatment. iii) Primary cultured rat lung fibroblasts were induced by Ang Ⅱ at a concentration of 100 nmol/L at different time points( 0,5,15 and 30 min,1,3,6,12,24 and 48 hours). iv) The expression of Ac-tubulin α and α-smooth muscle actin( α-SMA) were detected by immunohistochemical staining. The expression of Ac-tubulinα/Vimentin and Ac-tubulin α/α-SMA were observed by immunofluorescence staining. The relative expression ofα-SMA and Ac-tubulin α protein was detected by Western blot. RESULTS: The positive expression of Ac-tubulin α in lung tissue of CWP group was down-regulated while that of α-SMA was up-regulated compared with the control group( P < 0. 01). Immunofluorescence results showed that Vimentin positive expression in the CWP group was significantly increased in the lesion fibrosis area,while Ac-tubulin α expression was absent. The co-expression of Ac-tubulin α and Vimentin was detected in normal lung tissue of control group. The animal experiment results showed that the expression of Ac-tubulin αin lung tissue of rats was down-regulated and that of α-SMA was up-regulated with the prolongation of dust exposure time( P < 0. 01). The Ang Ⅱ induced the differentiation of fibroblasts into myofibroblasts,and the expression of Ac-tubulin α in fibroblasts gradually decreased and the expression of α-SMA gradually increased with the prolongation of Ang Ⅱ induction time( P < 0. 05). CONCLUSION: The lack of expression of Ac-tubulin α may be involved in the occurrence and development of silicotic fibrosis.
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<p><b>OBJECTIVE</b>To explore the inhibition effect and mechanism of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP)on myofibroblast differentiation via regulating acetylated tubulin α (Ac-Tub α)in vivo and in vitro.</p><p><b>METHODS</b>Silicotic model were made by SiO2 douched and divided into 6 groups as follows: control (4w, 8w)group, silicotic model (4w, 8w)group and post-or pre-treatment by Ac-SDKP group. Pulmonary fibroblasts were divided into 5 groups: (1) control; (2) Ang II; (3) Ang II+Ac-SDKP; (4) Ang II+Valsartan; (5) Ang II+TCS histone deacetylase (HDAC)6 20b. The localization of Ac-Tub α and α-smooth muscle actin (SMA) were observed by immunohistochemical (IHC) and immunofluorescence staining. The protein levels of Ac-Tub α, α-SMA, collagen type I (col I) and HDAC6 were measured by western blot.</p><p><b>RESULTS</b>In silicotic nodules and interstitial fibrosis area, positive expression of α-SMA, a classical marker of myofibroblast, was ob-served by IHC, accompanied with absence expression of Ac-Tub α. Furthermore, Ac-SDKP post-treatment could attenuate the levels of col I, α-SMA and HDAC6 to 48.39%, 52.63% and 70.18% compared with the silicotic 8w group respectively. And in Ac-SDKP pre-treatment group, compared with the silicotic 8w group, these protein levels were decreased to 32.26%, 64.91% and 54.39% respectively (P<0.05). The up-regulation of Ac-Tub α was found in Ac-SDKP post-and pre-treatment and increased to 3.00 and 2.90 folds compared with the silicotic 8w group. Compared with control group, the levels of α-SMA, HDAC6 and col I in Ang II group were up-regulated to 1.66, 3.56 and 4.00 folds accompanied with down-regulation of Ac-Tub by 44.44% (P<0.05). Pre-treatment with Valsartan, TCS HDAC6 20b or Ac-SDKP could inhibited all this changes induced by Ang II in vitro.</p><p><b>CONCLUSION</b>Ac-SDKP can inhibit the myofibroblast differentiation and collagen deposition via sup-press HDAC6 and up-regulate the expression of Ac-Tub α in vivo and in vitro.</p>
Subject(s)
Animals , Rats , Actins , Metabolism , Cell Differentiation , Collagen Type I , Metabolism , Disease Models, Animal , Fibroblasts , Cell Biology , Lung , Pathology , Myofibroblasts , Cell Biology , Oligopeptides , Pharmacology , Silicon Dioxide , Toxicity , Silicosis , Drug Therapy , Tubulin , MetabolismABSTRACT
Objective To develop social integration scale of the disabled,and to test the reliability and validity of the scale.Methods 511 disabled persons were investigated by self-made social integration scale and Chinese version of positive and negative affect schedule (PANAS-C).Results The Scale was composed of three factors:self integration,relationship integration and affection integration,and they explained 47.39% of variance.The theoretical model fit could be accepted (x2/df =2.051,P<0.001;RMSEA =0.046;GFI =0.884;CFI =0.926;IFI =0.927).The factors had significant correlated with positive affect (r=0.34-0.55,P<0.01)and positive affect (r=-0.12--0.32,P<0.01).The high score group and low score group of social integration had significant differences in positive affect (t=13.77,P<0.01)and negative affect(t=-7.58,P<0.01).The cronbach's alpha coefficients of the scale and the three factors were 0.94,0.92,0.87 and 0.89 respectively,and the seven sub-factors'cronbach 's alpha coefficients were from 0.76 to 0.87.Conclusion The theory construct of social integration of the disabled is multi-hierarchical and multi-dimensional.The scale has acceptable reliability and validity,and can be used to assess the degree of social integration of the disabled.
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Objective To explore the relationship between resilience and personality among the physically disabled people.Methods A total of 668 disabled persons were tested by Connor-Davidson Resilience Scale(CD-RISC), Eysenck Personality Questionnaire Short Scale (EPQ-RSC), Rosenberg Self-Esteem Scale (SES).Results The score of resilience of disabled people(53.42± 18.18) was than lower Chinese community people (65.4 ± 13.9, t =-16.83, P< 0.05).The scores of the three sub-factors were tenacity (27.19 ± 10.23), strength (18.11 ±6.42) ,optimism(8.09±3.00).The disabled persons' resilience was positively correlated with self-esteem(r=0.52,P<0.01) ,extraversion(r=0.47, P<0.01) ,and negatively correlated with psychoticism(r=-0.34, P<0.01), neuroticism(r=-0.32, P<0.01).Self-esteem and extraversion could make positive predictions,while psychoticism and neuroticism could make negative predictions to the resilience of disabled persons.Conclusion The disabled Persons' personality is closely related with resilience and has significant predictions to resilience.
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Objective To explore the characteristics of resilience and the relationships between resilience and social integration of disabled people.Methods By convenient sampling,a total of 702 disabled people were investigated by Connor-Davidson Resilience Scale,Social Integration Scale of the Disabled and self-made general questionnaire.Results The score of resilience of disabled people(53.27± 18.21) was lower than chinese community people(65.4± 13.9,t=-13.19,P<0.01).The resilience scores were significantly lower of the disabled people who came from rural areas,younger(≤ 24 years old) or older(≥ 60 years old),and were disabled from birth had poor family economic conditions,and had no insurances(P<0.05,P<0.01).But the disabled people who had university degree or above,married,working,and had warm and harmonious family atmosphere,had significantly higher resilience scores (P<0.05,P<0.01).The vesilience and three sub-factors were significantly correlated with social integration (r=0.38-0.66,P<0.01).The high resilience group had higher score in integration and three dimensions compared with the low resilience group(t=11.60-19.02,P<0.01).Tenacity and strength directly influenced the three dimensions of social integration (the path coefficient were 0.18-0.46,P<0.01).Conclusion The resilience of the disabled people is lower,and there are close relationships between resilience and social integration.The training of tenacity and strength is beneficial to social integration of the disabled people.
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[Abstract ] Objective Silicosis is one of the most serious occupational diseases in China .In this study,we explored the reg -ulatory effect of N-acetyl-seryl-aspartyl-lysyl-proline ( Ac-SDKP ) on angiotensin ( Ang ) Ⅱ-induced extracellular signal-regulated ki-nase ( ERK1/2) and Jun N-terminal kinase ( JNK) signals and its inhibitory effect on the differentiation of human embryonic lung MRC-5 fibroblasts to myofibroblasts via Ang Ⅱ-induced ERK1/2 and JNK signals . Methods Human embryonic lung MRC-5 fibro-blasts were induced by Ang Ⅱand pre-treated with the JNK signal inhibitor ( SP600125 ) , the ERK1/2 signal inhibitor ( PD98059 ) or Ac-SDKP.The proliferation of the cells was measured by MTT assay .The expressions of αS-MA, SRF, p-ERK1/2 and p-JNK were determined by immunocytochemical staining , and the expression levels of these proteins and collagen Ⅰwere detected by Western blot .Results The A value of Ang Ⅱ group (0.56 ±0.08) measured by MMT assay was 2.07 fold as control group ( 0.27 ±0.05 ). Pretreatment with SP600125 , PD98059 and Ac-SDKP, the A value were (0.39 ±0.02), (0.40 ±0.03) and (0.36 ±0 0.5) that had a statistical significance with Ang Ⅱgroup.The up-regulation of colla-gen type Ⅰ,α-SMA, SRF were induced by Ang Ⅱ by 4.50, 3.50 and 3.00 fold compared with control group.Moreover, the expression of p-ERK1/2 and p-JNK were increased as 6.71 and 7.90 fold as control. Pre-treatment with Ac-SDKP could inhibit p-JNK and p-ERK1/2 to 29.79% and 46.84% compared with AngⅡ group. Conclusion Ac -SDKP can inhibit the differentiation of human embryonic lung MRC-5 fibroblasts to myofibroblasts by regulating AngⅡ-induced JNK and ERK1/2 signals.
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<p><b>OBJECTIVE</b>To explore the inhibition effect of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on myofibroblast differentiation of MRC-5 human fetal lung fibroblasts induced by angiotensin (Ang) II.</p><p><b>METHODS</b>The study was divided into 2 step: (1) MRC-5 human fetal lung fibroblasts was induced for 48 h at different dose of Ang II and at different time point by 100 nmol/L Ang II. Then the expression of collagen type I and α-smooth muscle actin (α-SMA) were mesaured by western blot. (2) MRC-5 human fetal lung fibroblasts were divided into 4 group: (1) control, (2) Ang II, (3) Ang II+Ac-SDKP, (4) Ang II+8-Me-cAMP (a specific activator of Epac). The α-SMA expression was observed by immnocytochemical stain. The protein expression of collagen type I, α-SMA, serum response factor (SRF), myocardin-related transcription factor (MRTF)-A, exchange protein directly activated by cAMP (Epac) 1, 2 were measured by Westen blot.</p><p><b>RESULTS</b>Myofibroblast differentiation could be induced by Ang II from MRC-5 cells with a dose- and time-dependent manner. The up-regulation of SRF and MRTF-A were observed in MRC-5 cells induced by Ang II and accompanied with collagen I and α-SMA increased. Pre-treatment with 8-Me-cAMP or Ac-SDKP could attenuated all this changes induced by Ang II, and promoted the expression of Epac1.</p><p><b>CONCLUSION</b>Ac-SDKP can inhibit the myofibroblast differentiation of MRC-5 cells induced by Ang II via Epac1 activating.</p>