Prediction of Preterm Delivery Using Serum Ischemia Modified Albumin, Biglycan, and Decorin Levels in Women with Threatened Preterm Labor / Previsão de parto prematuro usando albumina modificada por isquemia sérica, biglicano e níveis de decorina em mulheres com ameaça de trabalho de parto prematuro

Abstract Objective The serum ischemia modified albumin (IMA), biglycan, and decorin levels of pregnant women who were hospitalized for threatened preterm labor were measured. Methods Fifty-one consecutive pregnant women with a single pregnancy between the 24th and 36th weeks with a diagnosis of threatened preterm labor were included in the present prospective cohort study. Results As a result of multivariate logistic regression analysis for predicting preterm delivery within 24 hours, 48 hours, 7 days, 14 days, ≤ 35 gestational weeks, and ≤ 37 gestational weeks after admission, area under the curve (AUC) (95% confidence interval [CI[) values were 0.95 (0.89-1.00), 0.93 (0.86-0.99), 0.91 (0.83-0.98), 0.92 (0.85-0.99), 0.82 (0.69-0.96), and 0.89 (0.80-0.98), respectively. In the present study, IMA and biglycan levels were found to be higher and decorin levels lower in women admitted to the hospital with threatened preterm labor and who gave preterm birth within 48 hours compared with those who gave birth after 48 hours. Conclusion In pregnant women admitted to the hospital with threatened preterm labor, the prediction preterm delivery of the combined model created by adding IMA, decorin, and biglycan in addition to the TVS CL measurement was higher than the TVS CL measurement alone. Clinical trial registration The present trial was registered at ClinicalTrials.gov, number NCT04451928.

Resumo Objetivo Medir os níveis séricos de albumina modificada por isquemia (IMA), biglicano e decorina de gestantes hospitalizadas por ameaça de parto prematuro. Métodos Cinquenta e uma mulheres grávidas consecutivas com uma única gravidez entre a 24ᵃ e a 36ᵃ semanas com diagnóstico de ameaça de trabalho de parto prematuro foram incluídas no presente estudo de corte prospectivo. Resultados Como resultado da análise de regressão logística multivariada para prever parto prematuro dentro de 24 horas, 48 horas, 7 dias, 14 dias, ≤ 35 semanas gestacionais e ≤ 37 semanas gestacionais após a admissão, área sob a curva (AUC) (95% de confiança os valores de intervalo [CI[) foram 0,95 (0,89-1,00), 0,93 (0,86-0,99), 0,91 (0,83-0,98), 0,92 (0,85-0,99), 0,82 (0,69-0,96) e 0,89 (0,80-0,98), respectivamente. No presente estudo, os níveis de IMA e biglican foram maiores e os níveis de decorin menores em mulheres admitidas no hospital com ameaça de trabalho de parto prematuro e que tiveram parto prematuro em 48 horas em comparação com aquelas que deram à luz após 48 horas. Conclusão Em gestantes admitidas no hospital com ameaça de trabalho de parto prematuro, a predição de parto prematuro do modelo combinado criado pela adição de IMA, decorin e biglican, além da medição do TVS CL, foi maior do que a medição do TVS CL isoladamente. Registro do ensaio clínico O presente ensaio foi registrado em ClinicalTrials.gov, número NCT04451928.

Cerebrospinal fluid levels of sortilin-1, lipocalin-2, autotaxin, decorin and interleukin-33 in patients with idiopathic intracranial hypertension / Níveis de sortilina-1, lipocalina-2, autotaxina, decorina e interleucina-33 no líquido cefalorraquidiano em pacientes com hipertensão intracraniana idiopática

Abstract Background Idiopathic intracranial hypertension (IIH) is characterized by increased cerebrospinal fluid (CSF) pressure of unknown cause. It has been suggested that the inflammatory process plays a role in the pathophysiology of the disease. Sortilin-1, lipocalin-2, autotaxin, decorin, and interleukin-33 (IL-33) are among the factors involved in inflammatory processes. Objective To investigate the CSF levels of sortilin-1, lipocalin-2, autotaxin, decorin, and IL-33 in patients with IIH. Methods A total of 24 IIH patients and 21 healthy controls were included in the study. Demographic characteristics of the patients and of the control group as well as CSF pressures were evaluated. Sortilin-1, lipocalin-2, autotaxin, decorin and IL-33 levels in the CSF were measured. Results The CSF levels lipocalin-2, sortilin-1, autotaxin, IL-33 and CSF pressure were significantly higher in the patients group compared with the control group (p < 0.001). Decorin levels were reduced in patients (p < 0.05). There was no correlation between the autotaxin and IL-33 levels and age, gender, CSF pressure, and body mass index. The results of our study showed that inflammatory activation plays an important role in the development of the pathophysiology of IIH. In addition, the fact that the markers used in our study have never been studied in the etiopathogenesis of IIH is important in explaining the molecular mechanism of this disease. Conclusion Studies are needed to evaluate the role of these cytokines in the pathophysiology of the disease. It is necessary to evaluate the effects of these molecules on this process.

Resumo Antecedentes A hipertensão intracraniana idiopática (HII) é caracterizada pelo aumento da pressão do líquido cefalorraquidiano (LCR) de causa desconhecida. Tem sido sugerido que o processo inflamatório desempenha um papel na fisiopatologia da doença. Sortilina-1, lipocalina-2, autotaxina, decorina e interleucina-33 (IL-33) estão entre os fatores envolvidos nos processos inflamatórios. Objetivo Investigar os níveis de sortilina-1, lipocalina-2, autotaxina, decorina e IL-33 no LCR de pacientes com HII. Métodos Um total de 24 pacientes com HII e 21 controles saudáveis foram incluídos no estudo. Foram avaliadas as características demográficas dos pacientes e do grupo controle, bem como as pressões liquóricas. Os níveis de sortilina-1, lipocalina-2, autotaxina, decorina e IL-33 no LCR foram medidos. Resultados Os níveis no líquido cefalorraquidiano lipocalina-2, sortilina-1, autotaxina, IL-33 e pressão liquórica foram significativamente maiores no grupo de pacientes em comparação com o grupo controle (p < 0,001). Os níveis de decorina foram reduzidos nos pacientes (p < 0,05). Não houve correlação entre os níveis de autotaxina e IL-33 e idade, sexo, pressão liquórica e índice de massa corporal. Os resultados do nosso estudo mostraram que a ativação inflamatória desempenha um papel importante no desenvolvimento da fisiopatologia da HII. Além disso, o fato de os marcadores utilizados em nosso estudo nunca terem sido estudados na etiopatogenia da HII é importante para explicar o mecanismo molecular dessa doença. Conclusão Estudos são necessários para avaliar o papel dessas citocinas na fisiopatologia da doença. É necessário avaliar os efeitos dessas moléculas nesse processo

Effects of decorin on proliferation, migration and invasion of bladder cancer cells / 国际肿瘤学杂志

Objective:To investigate the effects of decorin (DCN) on the proliferation, migration and invasion of bladder cancer cells.Methods:Bladder cancer T24 cell line was used as the research object. MTT assay was used to detect the inhibitory effect of DCN at different concentrations (0, 5, 10, 20, 30, 40, 50 mg/L) on T24 cell proliferation at 24, 48, 72 and 96 h. The effects of DCN on T24 cell cycle and apoptosis were analyzed by flow cytometry. MTT assay, Transwell migration and invasion experiments were used to detect the effects of DCN on the adhesion, migration and invasion ability of T24 cells. The effects of DCN on TGF-β1 and P21 protein expression were detected by ELISA and Western blotting.Results:T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN at 24, 48, 72 and 96 h, and there were statistically significant diffe-rences in cell proliferation activity ( F=168.64, P<0.001; F=165.81, P<0.001; F=291.02, P<0.001; F=148.93, P<0.001). T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN for 72 h, and the cell proliferation activities were (60.71±3.03)%, (40.82±2.09)%, (37.24±1.63)%, (25.65±2.55)%, (23.00±2.67)%, (10.78±1.17)%, (11.04±0.96)%, respectively, and there was a statistically significant difference. At the concentration of 40 mg/L, the proliferation activity reached the lowest level, and the inhibitory effect on cell proliferation was the strongest. At concentrations of 40 and 50 mg/L, the cells in G 1 phase reached the peak value, while the cells in S phase reached the lowest value, and the cells in G 2 phase remained unchanged throughout the treatment process. T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN for 72 h, and the apoptosis rates of cells were (12.18±1.17)%, (21.24±1.05)%, (19.80±1.20)%, (26.52±1.40)%, (30.86±1.40)%, (52.99±1.22)%, (43.04±2.16)%, respectively, and there was a statistically significant difference ( F=178.54, P<0.001). The differences between 5, 10, 20, 30, 40, 50 mg/L DCN and 0 mg/L DCN were all statistically significant (all P<0.001). When T24 cells were treated with 0, 40 mg/L DCN for 72 h, the cell adhesion rates were (37.14±1.35)% and (59.86±1.95)%, the numbers of migrated cells were 53.86±3.18 and 12.86±1.35, and there were statistically significant differences ( t=25.25, P<0.001; t=31.36, P<0.001). When DCN was applied to T24 cells for 48 h, the numbers of invasion at 0, 40 mg/L were 235.14±3.44 and 160.86±3.13, and there was a statistically significant difference ( t=2.27, P<0.001). When T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN for 72 h, the relative expression levels of TGF-β1 were 85.67±3.35, 45.51±1.19, 49.93±4.15, 47.64±3.53, 46.05±3.18, 25.54±2.25, 33.44±4.05, and there was a statistically significant difference ( F=324.58, P<0.001). Compared with 0 mg/L DCN, 5, 10, 20, 30, 40 and 50 mg/L DCN could significantly inhibited the expression of TGF-β1 (all P<0.001). Compared with 0 mg/L DCN, P21 protein was upregulated 72 h after treatment with 40 mg/L DCN. Conclusion:DCN can inhibit proliferation and induce apoptosis of T24 cells in vitro, and has the effect of anti-metastasis of T24 cells.

The inhibitory effect of decorin on apoptosis of human lens epithelial cells under high glucose condition and its mechanism / 中华实验眼科杂志

Objective To investigate the effects of decorin (DCN) on apoptosis and oxidative stress in human lens epithelial cells (LECs) under high glucose condition.Methods HLE-B3 cells were cultured in vitro and the effect of DCN with different concentrations on HLE-B3 viability was determined by using cell counting kit-8 (CCK-8).The cultured cells were divided into normal control group,DCN group,high glucose group and DCN + high glucose group.Flow cytometry was used to detect the apoptosis rate and the expression of reactive oxygen species (ROS) in the cells.Microplate spectrophotometer was used to measure total superoxide dismutase (SOD) enzyme activity and the radio of glutathione (GSH)/glutathione disulfide (GSSG).Western blot was used to detect the expressions of bax and bcl-2 proteins.Results HLE-B3 cells were spindle shaped,with centered and clearly visible nuclei and neatly cell arrangment.According to CCK-8 method,survival rates of HLE-B3 in all groups were more than 90％.Different concentrations of DCN showed no significant effect on HLEoB3 survival rate (all at P＞0.05).After 48 hours of cell culture,the apoptosis rate of high glucose group was significantly higher than that of normal control group,and the apoptosis rate of DCN+high glucose group was significantly lower than that of high glucose group (both at P =0.000).The mean fluorescence intensity of intracellular ROS in the high-glucose group was significantly higher than that in the normal control group,and the mean fluorescence intensity of ROS in the DCN group was significantly higher than that in the high glucose group (both at P=0.000).The total SOD activity in the high glucose group was significantly lower than that in the normal control group and DCN group (P =0.007,0.004).The GSH/GSSG ratio of the high-glucose group was significantly lower than that of the normal control group and DCN group (both at P=0.000).Conclusions DCN can inhibit the apoptosis and oxidative stress of HLE-B3 under high glucose,which provides the basis for the treatment of diabetic cataract.

Acetylation of decorin can enhance the stability and function of decorin protein in renal mesangial cells of rats / 复旦学报（医学版）

Objective To detect the acetylation of decorin (DCN) and its influence on DCN ubiquitination in mesangial cells in rats.Methods Mesangial cells of rats were cultured in vitro.The immunoprecipitation,Western blot assay and RT-PCR were used to determine the acetylation of DCN.Results DCN was acetylated in renal mesangial cells in rats.The acetylated DCN promoted its stability via inhibiting of its degradation through polyubiquitination.Moreover,transforming growth factor-β1 (TGF-β1) and type Ⅳ collagen expression of mesangial cells decreased,and cell growth was inhibited when acetylation of DCN was enhanced in mesangial cells.Conclusions Acetylation of DCN inhibited DCN ubiquitination degradation,which enhances DCN's antagonistic effect against nephritis.These results may provide a potential target for further study of prevention and treatment of mesangial cell proliferative glomerulonephritis.

Correlation be tween serum expression levels of decorin, chondroitin sulfate and C-terminal crosslinking telopeptide of type Ⅱ collagen and clinical features in arthritis patients / 中华风湿病学杂志

Objective To investigate changes in the serum expression levels of decorin (DCN),chondroitin sulfate (CS) and C-terminal crosslinking telopeptide of type Ⅱ collagen (CTX-Ⅱ) and analyze the relationship between the expression levels and clinical characteristics,aiming to provide evidence for clinical diagnosis and treatment of arthritis.Methods Ninety subjects were divided into the osteoarthritis (OA),rheumatoid arthritis (RA) and control groups (n=30 for each group).The OA and RA patients were diagnosed in Department of Rheumatism Immunity of Shanxi Dayi Hospital,and the healthy volunteers who were doing physical check-up in the Physical Check-up Center of Shanxi Dayi Hospital were recruited as the control subjects.Visual analogue scale (VAS) was utilized to evaluate the degree of pain.X-ray was performed to assess the severity of joint lesions.Enzyme linked immunosorbent assay (ELISA) was adopted to quantitatively measure the serum expression levels of DCN,CS and CTX-Ⅱ.The correlation among these parameters was statistically analyzed.Measurement data among different groups were statistically compared by one-way analysis of variance (ANOVA)and comparison between two groups was conducted by Tambane's T2.The correlation between two factors was analyzed by using Spearman correlation analysis.Results The difference of the serum expression levels of DCN in the OA,RA and control groups [(3.19±1.38) ng/ml,(1.90±0.62) ng/ml,(1.33 ±0.33) ng/ml] was statistically significant,which of the OA group was higher than the control group (P＜0.01),which of the RA group was higher than control group (P＜0.01),which of the OA group was higher than the RA group (P＜0.001).The difference of the serum expression levels of CS in the OA,RA and control groups [(0.57±0.12) ng/ml,(0.95±0.47) ng/ml,(0.36±0.09) ng/ml] was statistically significant,in which,the OA group was higher than the control group (P＜0.01),RA group was higher than control group (P＜0.01),OA group was lower than RA group (P＜0.01).The serum expression levels of CTX-Ⅱ in the OA and RA groups [(3.08±0.86) ng/ml,(3.03±1.14) ng/ml] were significantly up-regulated compared with those in the control group [(2.17±0.82) ng/ml](P＜0.001,P=0.005).The expression level of CTX-Ⅱ did not significantly different between the OA and RA groups (P=0.996).In the OA and RA groups,the serum levels of DCN,CS,CTX-Ⅱ were po-sitively related to X-ray and VAS,the correlation of DCN was the highest,the correlation was high in both OA (r=0.777,P＜0.01;r=0.622,P＜0.01) and RA (r=0.640,P＜0.01;r=0.493,P=0.006).Conclusion The serum levels of DCN,CS and CTX-Ⅱ in arthritis patients are significantly up-regulated compared with those in healthy controls,which are positively correlated with the degree of pain,and the severity of cartilage and bone defects.DCN is probably valuablein the differential diagnosis of early OA and RA.However,the clinical application remains to be further validated by evidence-based studies.

Correlation of the serum decorin levels and the cognitive function in first-episode drug-native patients with schizophrenia / 中华行为医学与脑科学杂志

Objective To explore the role of decorin (DCN) on the pathogenesis of schizophrenia by analyzing the correlation between serum DCN levels and cognitive impairment in the first-episode drug-native (FEDN) patients with schizophrenia.Methods 30 FEDN patients with schizophrenia and 30 age and gender matched healthy volunteers (control group) were enrolled.The psychopathological symptoms were assessed by the PANSS and the cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB).The serum DCN levels were measured by using enzyme linked immunosorbent assay (ELISA).The difference of DCN levels between the two groups were compared and the correlations of serum DCN levels to age,sex,the score of the MCCB and PANSS were analyzed.Results The serum DCN levels were lower in patients with schizophrenia than those in control group ((1.56±0.96) ng/ml vs (3.35± 1.71) ng/ml,P＜ 0.01).The serum DCN levels were positively correlated with the positive symptom score (r=0.41,P=0.03).The serum DCN levels were significantly negatively correlated with MCCB verbal fluency (r =-0.40,P =0.04),verbal memory (r=-0.42,P=0.02),visual memory (r=-0.39,P=0.04),continuous operation (r=-0.41,P=0.03),encoding symbols (r=-0.49,P=0.01),T line (r=-0.42,P=0.02) and total score (r=-0.55,P＜0.01),and after controlling the age and gender,the relationships were still exist.Conclusion It suggests that serum DCN levels are associated with cognitive function in first-episode patients with schizophrenia,and that DCN may be involved in the pathogenesis of schizophrenia.

Protective effects of decorin on blood-retinal barrier function under high-glucose plus hypoxia conditions / 眼科新进展

Objeetive To evaluate the protective effects of decorin on the inner blood-retinal barrier function under high-glucose plus hypoxia conditions,and explore its potential mechanism.Methods The human umbilical vein endothelial cells (HUVEC) were cultured,and the effect of decorin with different concentrations on HUVEC viability was determined by using the cell counting kit-8 assay (CCK-8).At different hours after incubation under high-glucose plus hypoxia conditions (25 mmol · L-1 D-glucose + 100 μmol · L-1 CoCl2),the suppression effects of various concentrations of decorin on the vascular endothelial growth factor (VEGF) expression of HUVEC was detected by enzyme-linked immunosorbent assay (ELISA).HUVEC were divided into normal control group (5.5 mmol · L-1 D-glucose),high-glucose plus hypoxia group (25 mmol · L-1 D-glucose + 100 μmol · L-1 CoCl2),mannitol control group(5.5 mmol· L-1 D-glucose +19.5 mmol · L-1 mannitol) and decorin treatment group (25 mmol · L-1 D-glucose+ 100 μmol · L-1 CoCl2 + 100 nmol · L-1 decorin).HUVEC barrier function was evaluated by detecting transepithelial electrical resistance (TER) and permeability of fluorescein isothiocyanate-dextran (FITC-dextran).The content of tight junction proteins (claudin-5,occludin,and ZO-1) and p38 mitogen-activated protein kinase (MAPK) phosphorylation were examined by Western blotting.Results According to the results of CCK-8,the survival rates of HUVEC in all groups were more than 90％,different concentrations of decorin showed no significant effect on HUVEC survival (all P ＞ 0.05).According to the results of CCK-8 and ELISA,the stimulation of hypoxia for 48 hours and 100 nmol · L-1 decorin was taken as the condition of further experiment.At 14 days,TER of HUVEC reached its peak of (170.67 ±9.07) Ω.TER of high-glucose plus hypoxia group (97.33 ±6.11)Ω was significantly lower than that of decorin treatment group (157.67 ± 11.72)Ω (P ＜0.05).The FITC-dextran permeability of high-glucose plus hypoxia group increased to (2.12 ±0.07) times of normal control group(P ＜0.05).Decorin reversed this effect to (1.16 ± 0.03) times of normal control group (P ＜ 0.05).The expression of claudin-5,occludin and ZO-1 in high-glucose plns hypoxia group were 0.38 ±0.05,0.43 ±0.02,0.25 ± 0.02,compared to the normal control group (0.72 ±0.05,0.90 ±0.01,0.75 ±0.02),there were statistical differences (all P ＜0.05).The expression of claudin-5,occludin and ZO-1 m decorin treatment group were 0.65 ±0.08,0.87 ±0.03,0.60 ±0.01,there were statistical differences compared with high-glucose plns hypoxia group (all P ＜0.05).The ration of p-p38 MAPK/p38 MAPK in high-glucose plus hypoxia group (0.88 ± 0.02) was increased,while the decorin treatment group (0.58 ± 0.04) reached the level of the normal control group (0.56 ±0.02),there was statistical difference compared with high-glucose plns hypoxia group (P ＜0.05).Conclusion Decorin can protect the HUVEC barrier function under high-glucose plus hypoxia conditions and inhibit the activation of p38 MAPK signaling pathway.So it may be used to treat diabetic retinopathy.

Inhibitory effect of decorinon invasion of colorectal adenocarcinoma cell line HCT116 in vitro / 基础医学与临床

Objective To investigate the effect and mechanism of decorin (DCN) on invasion of colorectal cancer cell line HCT116 in vitro.Methods Transwell assay was employed to detect the invasion of HCT116 cells;Real-time PCR was used to detect the expression of CD133 and TIMP-2 mRNA of HCT116 cells;Western blot method was used to detect the expression of HIF-1α, CD133 and TIMP-2 protein of HCT116 cells.Results 1) When the concentrations of DCN was 0, 1 and 3 mg/L, under the conditions of normal oxygen and hypoxia, the numbers of invasive cells were (241±46), (168±46), (51±17) fields in each well (P<0.01) and (207±61), (213±64), (156±54), (44±17) fields in each well (P<0.01).2) Under the normoxic conditions, the TIMP-2 mRNA and protein in HCT116 cells were increased by DCN (3 mg/L) (P<0.01), but that of CD133 were not affected.3) DCN (3 mg/L) significantly decreased the expression of HIF-1α/CD133/TIMP-2 protein in HCT116 cells under hypoxia (P<0.01), but had no significant effect on the expression of CD133 mRNA.ConclusionsUnder the conditions of hypoxia and normal oxygen, DCN may function through different mechanisms to inhibit the invasion of colorectal adenocarcinoma cell line HCT116 in vitro.

The influences of Decorin gene on biological behavior in human lung adenocarcinoma A549 cell line / 实用肿瘤学杂志

Objective To explore the influences of decorin ( DCN) gene down-regulating on biological behavior in human lung adenocarcinoma A 549 cell line.Methods Chemically synthesis in vitro targeting DCN -siRNA was transfected into human lung adenocarcinoma A 549 cells by LipofectamineTM 2000 .The gene expres-sion of DCN was detected using Real-Time PCR ;The protein expression of DCN was investigated using Western blot;Checkout DCN-siRNA effects on lung adenocarcinoma cancer cell proliferation was detected by CCK -8;The migration and invasion ability were determined by Transwell assay .Results DCN-siRNA was successfully transfected into human lung adenocarcinoma A 549 cells.Real-Time PCR results showed that DCN mRNA ex-pression level significantly decreased ,compared with untransfected group ,negative control group .Western blot re-sults showed that DCN-siRNA transfection inhibited DCN protein expression level;CCK-8 results showed that the proliferation was enhanced in the DCN -siRNA group as compared with untransfected group ,as well as the negative control group and empty vector group .Transwell assay results showed the invasion of A 549 cells in DCN-siRNA group was significantly enhanced as compared with untransfected group [(22.6 ±1.14) vs.(5.2 ± 0.84)].Wound-Healing assay results revealed that the cell repairing rate was markedly increased in DCN -siRNA group.A549 cells were close to complete repair after 48 hours.Apoptosis was not significant in DCN -siR-NA group as compared with untransfected group (P=0.214).Conclusion Down-regulation the expression of DCN gene by DCN-siRNA may enhance the ability of invasion ,migration and proliferation of A 549 cells without affecting apoptosis ,which provides a new evidence of function for advancing research of lung cancer .

Research progress of decorin gene in oncology / 实用肿瘤学杂志

Decorin( DCN) is one of the leucine-rich proteoglycan family of small molecules.It is recog-nized as a tumor suppressor gene.DCN can inhibit tumor cell proliferation and metastasis by binding and inactiva-tion of transforming growth factor beta( TGF-β) and inhibiting the expression of vascular endothelial growth fac-tor or by activating the signaling pathway that promotes cell proliferation by EGFR/MAPK/p21.it plays an impor-tant effect on tumor development,angiogenesis and metastasis.DCN is expressed in various malignant tumors,By up or down regulation,DCN can exert its anti tumor activity,as well as reducing or delaying the occurrence and development of many kinds of malignant tumor.DCN gene may be a potential target for the treatment of many kinds of malignant tumors.

NecroX-5 exerts anti-inflammatory and anti-fibrotic effects via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway in hypoxia/reoxygenation-treated rat hearts

Inflammatory and fibrotic responses are accelerated during the reperfusion period, and excessive fibrosis and inflammation contribute to cardiac malfunction. NecroX compounds have been shown to protect the liver and heart from ischemia-reperfusion injury. The aim of this study was to further define the role and mechanism of action of NecroX-5 in regulating infl ammation and fi brosis responses in a model of hypoxia/reoxygenation (HR). We utilized HR-treated rat hearts and lipopolysaccharide (LPS)-treated H9C2 culture cells in the presence or absence of NecroX-5 (10 µmol/L) treatment as experimental models. Addition of NecroX-5 signifi cantly increased decorin (Dcn) expression levels in HR-treated hearts. In contrast, expression of transforming growth factor beta 1 (TGFβ1) and Smad2 phosphorylation (pSmad2) was strongly attenuated in NecroX-5-treated hearts. In addition, signifi cantly increased production of tumor necrosis factor alpha (TNFα), TGFβ1, and pSmad2, and markedly decreased Dcn expression levels, were observed in LPS-stimulated H9C2 cells. Interestingly, NecroX-5 supplementation effectively attenuated the increased expression levels of TNFα, TGFβ1, and pSmad2, as well as the decreased expression of Dcn. Thus, our data demonstrate potential antiinflammatory and anti-fibrotic effects of NecroX-5 against cardiac HR injuries via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway.

Effect of decorin on proliferation and collagen type I synthesis of stiff knee joint synovial type B cells / 中国病理生理杂志

AIM:To explore the effects of decorin on procollagen type I (PcI), mRNA expression,collagen type I synthesis and proliferation of synovial type B cells of stiff knee joint synovial membrane.METHODS:Type B cells of synovial membrane were isolated from the stiff knee joint synovial membrane and cultured in vitro.The cells were treated with decorin at concentrations of 0.1 mg/L, 5 mg/L and 10 mg/L.After cultured for 24 h, 48 h and 72 h, the cell proli-feration rates were measured by MTT colorimetric determination.Cell cycle distribution and apoptosis were analyzed by flow cytometry.The mRNA level of Pc I was detected by RT-PCR, while collagen type I was measured by Western blot.RE-SULTS:The proliferation of synovial type B cells was significantly inhibited, the percentage of synovial type B cells at G1 phase was significantly increased by 5 mg/L and 10 mg/L decorin (P<0.05), and PcⅠmRNA expression and collagen type I synthesis were significantly decreased.The cells with late apoptosis were not found in control group and experimental groups.CONCLUSION:Recombinant human decorin inhibits synovial type B cell proliferation and decreases PcⅠmRNA expression and collagen type I synthesis in synovial type B cells of stiff knee joint synovial membrane in vitro, suggesting that decorin potentially contributes to the therapy of human knee stiffness.

Study on the synergistic proliferation-inhibiting and apoptosis-inducing effects of recombinant human-derived interleukin-24 and recombinant human-derived decorin on human hepatocellular carcinoma cells HepG2 / 肿瘤研究与临床

Objective To investigate the synergistic proliferation-inhibiting and apoptosis-inducing effects of recombinant human-derived interleukin-24 (rhIL-24) and recombinant human-derived decorin (rhDCN) on human hepatocellular carcinoma cells HepG2.Methods Cellular growth and morphological changes of HepG2 cells were observed under the inverted microscope at 48 h after being transiently transfected with pcDNA3.1 (+)-IL-24 and pcDNA3.1 (+)-DCN by Lipofectamine.The proliferation-inhibiting effects of IL-24 and DCN on HepG2 cells,respectively and jointly,were observed with MTT assay at 24 h,48 h and 72 h post-transfection.Apoptosis and cell-cycle of HepG2 cells were analyzed by flow cytometry at 48 h post-transfection.Results Compared to control groups,the cells of target gene groups presented typically changes of proliferation inhibition and apoptotic morphology,which occurred obviously in co-transfection group.The results of MTT assay showed that at 48 h and 72 h post-transfection,the profiferation-inhibiting rates in the group of cells co-transfected with IL-24 and DCN were (31.88±6.57) ％ and (36.83±3.76) ％,respectively,displaying significant difference with those of other groups (P ＜ 0.01).The results of flow cytometry showed that IL-24 and DCN can induce HepG2 cells apoptosis to some extent.Compared to the early apoptosis rate of cells of control groups,plasmid (2.98±0.72) ％,blank cell (3.50±0.92) ％,IL-24 (20.01±1.08) ％ and DCN (22.20±0.91) ％,a statistically remarkable apoptosis rate,(32.56±0.90) ％,can be seen in the group of cells treated with IL-24 and DCN jointly (P ＜ 0.01).The result of cell cycle analysis revealed that,compared to control groups,the proportion of cells was higher in the phase of G2/M in the IL-24 group (11.24±0.35) ％ and in the phase of G0/G1 in the DCN group (77.93±0.67) ％.The proportions of cells in the phases of G2/M increased to (71.36±0.60) ％ and that of G0/G1 statistically increased to (10.39±0.67) ％ in the group of cells co-transfected with IL-24 and DCN (P ＜ 0.01).Conclusions Combinatorial treatment of HepG2 cells with IL-24 and DCN can exert stronger synergistic proliferation-inhibiting effect and apoptosisinducing activity-in comparison to single therapies.IL-24 and DCN can induce cell cycle arrest on HepG2 cells,occurred in the phase of G2/M and G0/G1,respectively.Promoting effect of cell cycle arrest in the phase of both G2/M and G0/G1 can be seen on HepG2 cells co-transfected with IL-24 and DCN,which maybe the possible mechanism of the synergistic proliferation-inhibiting and apoptosis-inducing effect.

Molecular and phenotypic expression of decorin as modulator of angiogenesis in human potentially malignant oral lesions and oral squamous cell carcinomas.

Background: Decorin is an extracellular matrix, multifunctional small proteoglycan molecule in tumor stroma that has been shown to be modulator of angiogenesis. No clinical data is available so far on decorin expression and survival outcome of oral cancer. Aim: The aim of the present study was to examine molecular and phenotypic expression of two angiogenesis modulators viz. decorin and vascular endothelial growth factor-A (VEGF-A) in human potentially malignant oral lesions (PMOLs) and oral squamous cell carcinomas (OSCC) in relation to clinico-pathological variables and survival outcome. Materials and Methods: Tissue biopsies were obtained from 72 PMOLs, 108 OSCC and 52 healthy controls. The PMOLs included cases of leukoplakias and oral submucous fi brosis. Immunohistochemistry was performed using antibodies against decorin, VEGF-A and CD-31. Messenger-ribonucleic acid (mRNA) expression was analyzed by using real-time polymerase chain reaction. Results: Cytoplasmic staining of decorin was observed in the basal layer of epithelium in 53 (73.61%) cases of PMOLs and in peritumoral stroma in 55 (50.92%) cases of OSCC. None of the cases showed nuclear expression of decorin. Decorin expression both at phenotypic and molecular level was found to be down-regulated from PMOLs to OSCC. Lymph node metastasis and reduced decorin expression independently correlated with overall survival in OSCC. VEGF-A expression had no signifi cant impact on survival outcome. Conclusion: Micro vessel density and VEGF-A expression were signifi cantly associated with reduced decorin expression in tumor stroma suggesting, decorin as angiogenic modulator in OSCC. Down-regulation of decorin expression and the presence of lymph node metastasis were adverse factor independently affecting overall survival in OSCC.

Decorin and TGF-beta Expression after Partial Myotomy of the Extraocular Muscle in Rat

PURPOSE: To report the expression of decorin and TGF-beta in partial myotomy of the extraocular muscle in rats. METHODS: Partial myotomy of the superior rectus muscle was performed on the right eye of 10 Sprague-Dawley rats followed by exposure of the left superior rectus muscle and a simple suture of the conjunctiva. The bilateral superior rectus muscle was obtained from all rats at 2 weeks postoperatively. The tissues were observed under light microscopy with hematoxylin-eosin, Masson's trichrome staining and immunohistochemistry. RESULTS: Histological examinations of the surgical area at 2 weeks after postoperatively showed irregularly concentrated fibrosis on light microscopy with hematoxylin-eosin and Masson's trichrome staining of the experimental eyes. Immnohistochemistry showed that expression of decorin was in the same location as TGF-beta in the experimental group. CONCLUSIONS: The expression of decorin was found in the healing process after partial myotomy of the extraocular muscle in rats. Immunohistochemistry showed that expression of decorin was in the same location as with TGF-beta.

Detection of decorin expression in keloid with fluorescent quantitative-PCR / 中华医学美学美容杂志

Objective To detect the expression and content of decorin in fibroblasts of keloid to deeply reveal the mechenism and the role of decorin plays in scar formation.Methods Fibroblasts of keloid,normal scar and normal skin were cultured in vitro,and the morphology,activity,apoptosis of fibroblast were observed under light microscope and electron microscope; the mRNAs of decorin and TGF-β1 were detected and analyzed with real-time fluorescent quantitative-PCR (FQ-PCR).Results Fibroblasts of keloid showed irregular morphology,larger size and disorder arrangement.There were a large number of mitochondria,swelling rough endoplasmic reticulum,and euchromatin-rich in nucleus of fibroblasts,suggesting the protein synthesis of keloid fibroblast was very active.Compared with normal skin,the expression of decorin was significantly lower in keloid fibroblast; On the contrary,the expression of TGF-β1 was significantly higher in keloid fibroblast than in normal scar and normal skin.Conclusions Compared with normal skin,the expression of decorin in keloid fibroblast is significantly lower.Lower content of decorin in early stage of wound healing may induce weakly suppression of proliferation and synthesis of fibroblast,and up-regulate the activity of TGF-β1,which promotes the proliferation,migration and excessive collagen synthesis of the fibroblast of keloid.Thus,decorinis an suppressor factor of keloid formation.

Reduction of plasma decorin following acute ischemic stroke and its clinical significance / 第二军医大学学报

Objective To investigate the changes of plasma decorin in patients with acute ischemic stroke and its clinical significance. Methods The plasma levels of decorin were assessed in 102 patients with acute ischemic stroke (< 7 days) and 120 control subjects using ELISA. Then we evaluated the relationship between decorin level and the TOAST subtypes of stroke, so as to analyze the role of decorin level in diagnosis and treatment of acute ischemic stroke. Results Compared with the control group, the decorin level was significantly decreased in acute ischemic stroke group (P<0. 001), and that in the large-artery atherosclerosis group was lower than those in other groups of the same level. According to the receiver operating characteristic curve, decorin level was a diagnostie marker for acute ischemic stroke (P<0. 001). Decorin levels

A Novel Decorin Gene Mutation in Congenital Hereditary Stromal Dystrophy: A Korean Family

A 43-year-old man developed decreased vision in the right eye that had persisted for seven years. Under slit lamp examination, corneal clouding was noted with normal endothelium and ocular structure. From the clinical evidence, we suspected that the patient had congenital hereditary stromal dystrophy (CHSD). He and his family underwent a genetic analysis. Penetrating keratoplasty was conducted, and the corneal button was investigated for histopathologic confirmation via both light and electron microscopy. The histopathologic results revealed mildly loosened stromal structures, which exhibited an almost normal arrangement and differed slightly from the previous findings of CHSD cases. With regard to the genetic aspects, the patient and his mother harbored a novel point mutation of the decorin gene. This genetic mutation is also distinct from previously described deletion mutations of the decorin gene. This case involved delayed penetration of mild clinical symptoms with the histological feature of a loosened fiber arrangement in the corneal stroma. We concluded that this condition was a mild form of CHSD. However, from another perspective, this case could be considered as "decorin gene-associated corneal dystrophy," which is distinct from CHSD. Further evaluation will be required for appropriate clinical, histopathologic and genetic approaches for such cases.

Effect of rhDCN on proliferation of leukemic cell line K562 / 白血病·淋巴瘤

ObjectiveTo investigate the anti-tumorigenesis function of rhDCN on the leukemia K562 cells in vitro and analyze the possible mechanism.Methods Exponential phase of K562 cells were transfected with pcDNA3.1(+)-DCN,and PBS,liposome alone,and pcDNA3.1(+) vector were as control groups.Morphology change of K562 cells was detected by Wright stain,and cell proliferation activity was detected by MTT. Cell cycle and apoptosis of K562 cells were assessed by FCM. The expression of apoptosis-related protein,including bcl-xl,Mcl-1 and Bax were detected by Western blot.ResultsWright stain showed that typical apoptotic morphology of K562 cells were observed in DCN transfected group.There were no morphological changes of apoptosis in other groups. MTT method results showed that proliferation inhibition rate of the transfected cells [24 h (16.14±1.08) ％,48 h (14.07±1.01) ％,72 h (20.29±1.19) ％]was higher than that of the other control groups (P ＜ 0.05).FCM results showed that the apoptosis index (20.15±1.31) ％of the DCN transfected group was higher than that of the other groups (P ＜ 0.05),and most of cells arrested in the G0/G1 phase (51.15±0.57) ％ (P ＜ 0.05).Western blot results showed the expression levels of Bax were increased while bcl-xl and Mcl-1 were decreased in pcDNA3.1(+)-DCN/K562 group.ConclusionrhDCN can inhibit the growth of K562 cells and induce the apoptosis.The effect of DCN on bcl-xl,Mcl-1,Bax may play a role in its mechanism.