Research on effect of the extract of Caulis Sinomenii on the expression of TNF-α, Cat-G and Cat-S in collagen induced arthritis rats / 国际中医中药杂志

Objective To explore the effect of sinomenine on the expression of tumor necrosis factor-α (TNF-α),cathepsin G (Cat-G) and cathepsin S (Cat-S) in rats with collagen induced arthritis (CIA).Methods The 60 SPF male Wistar rats were randomly divided into normal group,model group,high dose group,medium dose group,low dose group,and dexamethasone group (with 1 0 in each group).In the normal control group,the rats were given ordinary feed.For the other five groups,the rats were used to build a CIA model and give pharmacologic intervention in the following 20 days.After 20 days of inflammation,sinomenine would be divided into three different dose groups,with 120 mg/kg,90 mg/kg and 60 mg/kg,respectively,and each group was given a gavage daily.For the dexamethasone group,7.5 mg/kg dexamethasone was given for gavage once a day.In terms of the model group and normal group,the rats were perfused with the same volume of saline once daily.Then,taken the pictures of foot paw X-ray and foot paw pictures of rats in each group,measured the content of TNF-α,Cat-G,Cat-S in blood serum,observed the pathological changes in the synovial tissue of rats in each group by tissue section,measured the content of TNF-α,Cat-G,Cat-S in in spleen of rats by Immunohistochemical staining.Results The results of X-ray showed that there were obvious soft tissue swelling,joint deformity and osteolysis in the paws of the model group,and the above symptoms were alleviated in different degrees in each treatment group compared with the model group.Compared with the model group,the expression of TNF-α (376.48 ± 22.21 pg/ml,369.45 ± 82.68 pg/ml,425.17 ± 153.51 pg/ml vs.457.63 ± 152.67 pg/ml),Cat-G (1 398.05 ± 167.32 pg/ml,1 337.65 ± 209.34 pg/ml,1 412.78 ± 67.65 pg/ml vs.2 283.03 ± 185.21 pg/ml),and Cat-S (662.18 ± 169.66 pg/ml,406.80 ± 41.93 pg/ml,452.76 ± 50.49 pg/ml vs.838.11 ± 141.86 pg/ml) in blood serum of sinomenine high dose group,medium dose group and low dose group significantly decreased (P＜0.05).The expression of TNF-α (0.28 ± 0.05,0.21 ± 0.03,0.34 ± 0.04 vs.0.50 ± 0.04),Cat-G (0.28 ± 0.02,0.18 ± 0.06,0.27 ± 0.02 vs.0.37 ± 0.03),and Cat-S (0.22 ± 0.02,0.18 ± 0.03,0.27 ± 0.02 vs.0.35 ± 0.03) in spleen tissue significantly decreased (P＜0.05).The results of HE staining showed that the synovial tissue of normal rats was normal,the synovial tissue cells of model rats were damaged,the expression of inflammatory cells was significantly increased,and pannus hyperplasia was observed.Inflammatory cell infiltration and pannus hyperplasia were decreased in each group after administration.Conclusions Sinomenine has a sound and comprehensive intervention effect on rheumatoid arthritis,and the mechanism may be related to the inhibition of the expression ofTNF-α,Cat-G and Cat-S.

Terminally Differentiating Eosinophils Express Neutrophil Primary Granule Proteins as well as Eosinophil-specific Granule Proteins in a Temporal Manner

Neutrophils and eosinophils, 2 prominent granulocytes, are commonly derived from myelocytic progenitors through successive stages in the bone marrow. Our previous genome-wide transcriptomic data unexpectedly showed that genes encoding a multitude of neutrophil primary granule proteins (NPGPs) were markedly downregulated during the end period of eosinophilic terminal differentiation when cord blood (CB) cluster of differentiation (CD) 34+ cells were induced to differentiate toward the eosinophil lineage during a 24-day culture period. Accordingly, this study aimed to examine whether NPGP genes were expressed on the way to eosinophil terminal differentiation stage and to compare their expression kinetics with that of genes encoding eosinophil-specific granule proteins (ESGPs). Transcripts of all NPGP genes examined, including proteinase 3, myeloperoxidase, cathepsin G (CTSG), and neutrophil elastase, reached a peak at day 12 and sharply declined thereafter, while transcript of ESGP genes including major basic protein 1 (MBP1) attained maximum expression at days 18 or 24. Growth factor independent 1 (GFI1) and CCAAT/enhancer-binding protein α (C/EBPA), transactivators for the NPGP genes, were expressed immediately before the NPGP genes, whereas expression of C/EBPA, GATA1, and GATA2 kinetically paralleled that of eosinophil granule protein genes. The expression kinetics of NPGPs and ESGPs were duplicated upon differentiation of the eosinophilic leukemia cell line (EoL-1) immature eosinophilic cells. Importantly, confocal image analysis showed that CTSG was strongly coexpressed with MBP1 in differentiating CB eosinophils at days 12 and 18 and became barely detectable at day 24 and beyond. Our results suggest for the first time the presence of an immature stage where eosinophils coexpress NPGPs and ESGPs before final maturation.

The role of cathepsin G in the diagnosis and immunotherapy of acute myeloid leukemia / 白血病·淋巴瘤

Cathepsin G (CG) is one of the serine proteases of neutrophils,and its mRNA is specifically increased in the promyelomonocytic stage of neutrophils and abnormal in several acute myeloid leukemias (AML).Meanwhile,CG is one of AML-associated antigens with strong immunocompetence,it is an important target of immunotherapy in AML.In this paper,the role of CG in the diagnosis and immunotherapy of AML were reviewed.

Sunburn (fohia) Healing Effects of Noni: Is it a Mechanism Involving Its Inhibitory Effects on MMP, COX-2 and Cat-G Enzymes.

The aim of the present investigation was to evaluate whether extracts and preparations of noni fruit and leaf, a Polynesian traditional herbal medicine, inhibit MMP, COX-2 and Cat-G enzymes in vitro, as its mechanism of action for healing sun-burn known as fohia in Tonga. Noni leaf ethanolic extract (NLEE) inhibited MMP-1, -2, -3, and -9 enzymes concentration dependently with 0.517, 0.234, 0.184, and 0.302 mg/mL IC50, respectively. Noni fruit juice concentrates (NFJC) in 1 and 5 mg/mL concentrations, inhibited MMP-12 enzymes by 102, and 99%, respectively. NFJC and NLEE inhibited Cat-G enzymes concentration-dependently with 0.125, <0.1, and 0.41 mg/mL IC50, respectively. Noni fruit juice fractions 4 and 6 inhibited COX-2 and Cat-G enzymes by 85 and 89%, and 89 and 78%, respectively. Additionally, the noni fruit puree and noni leaf has 1.91 mg/g and 5.77 mg/g of ursolic acid, respectively. NFJC, and NLEE inhibitory effects on MMP, COX-2 and Cat-G enzymes might help explain the traditional usage of the noni fruits and leaves for treatment of fohia skin as alluded to by Polynesian traditional healers. These results warrant further studies into the skin health benefits of noni fruit and leaf to further assess their efficacies and dosages in human subjects suffering from photoaging.

Expression of cathepsin G in photoaged fibroblasts / 中华医学美学美容杂志

Objective To investigate the role of cathepsin G in photoaged fibroblasts. Methods Human fibroblasts were cultured and induced to premature senescence using UVA + MOP methods. Senescence-associated-β-galactosidase (SA-β-gal) stain was used to evaluate the positive rate of aged cells. The mRNA and protein expression of cathepsin G in photoaged fibroblasts were detected by real-time RT-PCR and Western blot techniques. Results Over 98 % induced cells presented a positive SA-β-gal straining. The expression of cathepsin G, detected by Western blot, was increased to (1. 70±0. 028) times of the control. And RT-PCR revealed that the synthesis of cathepsin G mRNA was also up-regulated to 1. 42±0. 09. Conclusion The results of our study demonstrates a significant correlation between photoaged fibroblasts and cathepsin G. The up-regulation of cathepsin G may play an important role in the damages of extracellular matrix and activation of MMPS in photoaged human skin.