SKI306X inhibition of glycosaminoglycan degradation in human cartilage involves down-regulation of cytokine-induced catabolic genes

BACKGROUND/AIMS: SKI306X, a mixed extract of three herbs, Clematis mandshurica (CM), Prunella vulgaris (PV), and Trichosanthes kirilowii (TK), is chondroprotective in animal models of osteoarthritis (OA). The objectives of this study were to investigate its effect on interleukin (IL)-1beta-induced degradation of glycosaminoglycan (GAG) and the basis of its action in human OA cartilage, as well as to screen for the presence of inhibitors of matrix metalloproteinase (MMP)-13 and a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-4 in SKI306X and its component herbs, as well as in fractions from SKI306X. METHODS: Human OA chondrocytes and cartilage explants were obtained during total knee replacements and incubated with IL-1beta +/- oncostatin M with or without SKI306X or its component herb extracts. GAG degradation was assayed in cartilage explants using a commercial kit. Expression of genes involved in cartilage destruction was measured by real-time polymerase chain reaction using chondrocyte RNA. SKI306X was fractionated by preparative liquid chromatography to test for the presence of inhibitors of MMP-13 and ADAMTS-4. RESULTS: SKI306X and PV inhibited IL-1beta-induced GAG release from cartilage explants, and SKI306X, CM, PV, and TK inhibited IL-1beta-induced MMP gene expression. Unexpectedly, SKI306X greatly stimulated IL-1beta + oncostatin M-induced ADAMTS-4 gene expression, probably due to its TK component. Some fractions of SKI306X also inhibited ADAMTS-4 activity. CONCLUSIONS: SKI306X and its herbal components inhibit GAG degradation and catabolic gene expression in human OA chondrocytes and cartilage explants. SKI306X likely also contains one or more ADAMTS-4 inhibitor.

Expression of ADAMTS-2 and TGF-β1 in cirrhotic liver / 中南大学学报(医学版)

OBJECTIVE@#To explore the expression and distribution of a disintegrin and metalloprotease with thrombospondin motif (ADAMTS)-2 and transforming growth factor (TGF) -β1 in patients with or without cirrhosis, and to determine their relation.@*METHODS@#The liver tissues from 16 patients with cirrhotic portal hypertensive and 8 patients with liver injury were collected in Wuhan General Hospital from March to June, 2010. Immunohistochemistry and Western blot were applied to detect the protein expression of ADAMTS-2 and TGF-β1.@*RESULTS@#Immunohistochemistry showed that the expression of ADAMTS-2 and TGF-β1 was significantly higher in the cirrhotic tissues than that in normal tissues (P<0.05). Western blot also showed the expression of ADAMTS-2 and TGF-β1 in the cirrhosis tissues was significantly higher than that in normal tissues (P<0.05). There was a positive correlation between ADAMTS-2 and TGF-β1 (r=0.862, P<0.01).@*CONCLUSION@#ADAMTS-2 and TGF-β1 may have a synergistic reaction in promoting liver cirrhosis.

Effects of RNA interference against aggrecanase 1 gene on extracellular matrix metabolism of cultured chondrocytes in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of RNA interference (RNAi)-mediated aggrecanase-1 gene silencing on extracellular matrix metabolism of cultured rat costochondral chondrocytes.</p><p><b>METHODS</b>Rat costochondral chondrocyte monolayers were obtained by microdissection and digestion. The growth and morphological changes of the chondrocytes were observed after RNAi of aggrecanase-1 gene. The mRNA expression of aggrecanase-1 was detected by RT-PCR method, and aggrecan content was determined by Western blotting.</p><p><b>RESULTS</b>The specific inhibition of aggrecanase-1 by RNAi produced no adverse effect on the morphology and growth of the chondrocytes. The mRNA of aggrecanase-1 decreased and aggrecan content increased significantly after transfection of the chondrocytes.</p><p><b>CONCLUSION</b>Inhibition of aggrecanase-1 decreases aggrecan degradation in cultured rat chondrocytes. RNAi technique can be a useful means for studying extracellular matrix metabolism in the cartilage.</p>

Marcadores de fibrogénesis hepática en pacientes alcohólicos / Hepatic fibrogenesis markers in alcoholic patients

Serum P-III-P and laminim levels were measured in asymptomatic alcoholics during detoxication treatment. Liver biopsies were obtained, in order to detect liver damage, which was graded with a numeric score, considering values over 6 as severe damage. Serum fibrogenesis markers were also measured in a group of decompensated alcoholic cirrhotics. P-III-P levels were significantly higher in cirrhotic patients compared to alcoholics with or without liver damage and to normal controls. Laminin was not different between groups. P-III-P did not correlate with histological score in asymptomatic patients. In this study P-III-P and P1 laminin were not usefull discriminators of severe liver damage among asymptomatic alcoholics; their levels were found to rises significantly only when liver disease has become clinically evident

Mini-review: the ultrasonographical and serological chanbges and their improvement after praziquantel treatment Schistosoma japonicum infected patients in Leyete, Philippines

We have identified the specific ultrasonographical (US) changes in Schistosoma japonicum infected patients with the serological changes in general liver function markers. The US examination with the following haematological and biochemical serum analysis was performed on 102 patients in Shistosomiasis Hospital, Leyte, Philippines. The US liver images were classified into 4 patterns according to the development of periportal fibrosis and the patterns of echogenic bands. Among various haematological and biochemical serum parameters of liver damage. The serum levels of total bile acid (TBA) and procollagen-III-peptide (P-III-P) correlated well with the development of hepatic fibrosis and the portal hypertension. These patients were subsequently treated with praziquantel (3 x 20 mg/kg), and improvement of the thickening of the portal vein wall and the dintensity of the echogenic band formation was detected 6 months after treatment. The significant US changes could not be detected in the patients with severe hepatic fibrosis caused in the long term infection. The results revealed that the US examination with the serum TBa level would provider a sensitive tool monitor the severity of the infection and also the improvement occured shortly after praziquantel treatment

Peptídios séricos do procolágeno tipo III: novo teste para o estudo da hepatite alcoólica? / Serum type III procolagen peptide: a new test for the study of alcoholic hepatitis?

A hepatite alcoólica é uma das lesöes que compöem o espectro morfológico da doença hepática alcoólica. O se estudo é particularmente importante pois está demonstrado que é lesäo pré-cirrótica. Os dados clínico e laboratoriais näo detectam por vezes a presença dessa lesäo. A determinaçäo dos peptídios séricos do procolágeno tipo III parece constitutir grande avanço para o diagnóstico de hepatite alcoólica, em estilistas sem ou com cirrose. A presença de níveis séricos significantemente elevados daqueles peptídios em paciente alcoólatra justificaria indicaçäo para biópsia hepática

Serum type III procollagen peptides in patients with hepatointestinal and compensated hepatoesplenic schistosomiasis forms

Os níveis dos peptídios séricos do procolágeno tipo III (PSPC III) foram determinados em 35 indivíduos: 25 esquistossomóticos näo tratados da parasitose, sendo 16 da forma hepatointestinal (HI) e nove da hepatoesplênica compensada (HEC) e dez sadios. Para a dosagem dos PSPC III foram utilizados kits de radioimunoensaio. Procurou-se demonstrar a correlaçäo entre os níveis dos PSPC III e as atividades séricas das enzimas aminotransferase da alanina (ALT), aminotransferase do aspartato (AST), fosfatase alcalina (FA) e gamaglutamiltranspeptidase (GGTP). As médias dos valores dos PSPC III nas formas HI (13 ng/ml) e HEC (17 ng/ml) foram significantemente maiores do que as do grupo controle (9,0 ng/ml) (p < 0,05). Näo se observou diferença significante quanto aos valores dos PSPC III entre os grupos de pacientes das formas HI e HEC. Näo houve correlaçäo entre os aumentos dos PSPC III e os da atividade sérica da ALT, AST, FA e GGPT. Os autores discutem aspectos sobre eventual aplicabilidade da determinaçäo dos PSPC III em pacientes com esquistossomose