Progresses of cathepsin S in kidney and rheumatic diseases / 国际儿科学杂志

Cathepsin S (Cat S) is an important member of the cysteine cathepsin protease family.It is a lysosomal protease,which has been shown to be expressed in inflammatory conditions and autoimmune diseases.It has more specific roles such as antigen presentation,tissue repair,cell proliferation and apoptosis.It contributes to a variety of clinical diseases.In this review,we summarize the structure,characteristics and functions of cathepsin S in kidney and rheumatic diseases.

Virtual screening study of cathepsin S natural inhibitor / 中国中药杂志

Cathepsin S is a cysteine protease which is closely related to autoimmune diseases,psoriasis and other diseases. In this study,we used virtual screening method to screen compounds,which from the natural product library of traditional Chinese medicine,with potential inhibitory effect on cathepsin S. The work involved in study on inhibitory mechanism of representative compounds,then analysis of the distribution of these compounds in traditional Chinese medicine and the correlation with disease,so as to provide a new drug research and data-base for cathepsin S. The complex crystal structure of cathepsin S,2FQ9,was used to establish the pharmacophore model of cathepsin S inhibitor,and the best pharmacophore model was selected. As a result,fifty compounds were selected from TCMD database. After molecular docking,65 potential inhibitors were identified. Potential inhibitors can produce multiple intermolecular interactions with targets,resulting in inhibition. There are 58 kinds of traditional Chinese medicines which include 65 natural inhibitors. Data collection and analysis of the nature,flavor xing,channel entry and modern pharmacological effects of these traditional Chinese medicines showed that most of them were related to the biological activity of cathepsin S,which supported the validity of the screening results. Cathepsin S has a certain correlation with autoimmune diseases and can be used as a target for further study of traditional Chinese medicine.

Progresses of cathepsin S in kidney and rheumatic diseases / 国际儿科学杂志

Cathepsin S(Cat S) is an important member of the cysteine cathepsin protease family.It is a lysosomal protease, which has been shown to be expressed in inflammatory conditions and autoimmune diseases.It has more specific roles such as antigen presentation, tissue repair, cell proliferation and apoptosis.It contributes to a variety of clinical diseases.In this review, we summarize the structure, characteristics and functions of cathepsin S in kidney and rheumatic diseases.

Clinical Observation of Recipe for Clearing Heat and Removing Dampness Combined with Butyl Flufenamate Ointment in Treating Facial Seborrheic Dermatitis / 广州中医药大学学报

Objective To observe the clinical efficacy of Recipe for Clearing Heat and Removing Dampness combined with Butyl Flufenamate Ointment for the treatment of facial seborrheic dermatitis. Methods A total of 92 patients with facial seborrheic dermatitis were randomly divided into treatment group and control group,46 cases in each group. The treatment group was treated with oral use of Recipe for Clearing Heat and Removing Dampness combined with external use of Butyl Flufenamate Ointment, and the control group was only treated with external use of Butyl Flufenamate Ointment. The treatment for the two groups covered 4 weeks. Before treatment and on treatment day 7, 14 and 28, scores of clinical symptoms, related skin barrier function indexes,and the serum level of cathepsin S(Cat S)in the two groups were observed. Results(1)On treatment day 14,28,the total effective rate in the treatment group was 84.8％, 89.1％,and that in the control group was 65.2％,71.7％ respectively,the difference being significant(P < 0.05).(2)On treatment day 7,14,28, the scores of clinical symptoms in the two groups were obviously decreased(P < 0.05 compared with those before treatment),and the decrease in the treatment group was superior to that in the control group (P < 0.05).(3) On treatment day 7,14,28,facial sebum secretin,skin water content,and transepidermal water loss(TEWL) of the treatment group were improved to various degrees compared with those of the control group,the differences being significnat(P < 0.05 or P < 0.01).(4)On treatment day 28,serum Cat S of the two groups was markedly decreased(P < 0.01 compared with that before treatment),and the decrease in the treatment group was superior to that in the control group (P < 0.01). Conclusion Recipe for Clearing Heat and Removing Dampness combined with Butyl Flufenamate Ointment exerts certain effect for the treatment of facial seborrheic dermatitis.

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.

Correlation between carotid arterial plaque property with Cat S and Cys C in patients with ischemic stroke / 重庆医学

Objective To investigate the relationship between serum cathepsin S (Cat S) and cystatin C(Cys C) expression levels with carotid arterial plaque property in the patients with ischemic stroke(IS).Methods A total of 336 cases of atherosclerotic cerebral infarction were divided into the stable plaque and unstable plaque group according to the carotid arterial ultrasound.Contemporaneous 114 individuals undergoing healthy physical examination served as the control group.Fasting blood was collected from all subjects entering the groups for detecting serum Cat S and Cys C.Results The serum Cat S and Cys C levels and Cat S/Cys C ratio (Cat S/Cys C) had statistically significant difference between the two groups (P＜0.05),moreover the Cat S level in the unstable plaque group of the patients with cerebral infarction was increased compared with that in the stable plaque group,while serum Cys C level was decreased compared with that in the stable plaque group (P＜0.05).The Cat S levels were (75.34-±-15.45)pg/mL and (60.12±18.53)pg/mL and the Cys C levels were (0.73±0.62)mg/L and (0.93±0.53)mg/L,the Cat S/Cys C ratios were (103.68±2.52) and (64.64± 9.24) respectively,the difference between the two groups had statistical significance (P＜0.05).The Spearman correlation analysis showed that the serum Cat S level and Cat S/Cys C ratio had obviously positive correlation with carotid arterial unstable plaque (r=0.498,P＜0.05;r=0.753,P＜0.01);while the level of serum Cys C was negatively correlated with the unstable plaque (r=-0.213,P＜0.05).Conclusion Serum Cat S/Cys C level has a certain correlation with carotid arterial plaque property in ischemic stroke patients,which may become the serological indicators for predicting carotid arterial plaque.

Influence of cathepsin S deficiency on development of communicating hydrocephalus in mice induced by kaolin / 上海交通大学学报（医学版）

Objective · To evaluate the influence of cathepsin S(CatS) on the severity of communicating hydrocephalus in a kaolin injected mouse model.Methods · Kaolin suspension was injected to 8 CatS knock-out (CatS -/-) mice and 12 wild type (WT) C57BL/6 mice through cisterna magna to establish communicating hydrocephalus mouse model. Cerebral magnetic resonance imaging (MRI) was used before and 1 week after kaolin injection to compare lateral ventricular volume. Lateral ventricular index was calculated to analyze the severity of hydrocephalus. Results · One week after kaolin injection,1 in CatS -/- group and 2 in WT group died. The mortality rate was 12.5% each and there was no significant difference (P=1.000). MRI results showed varying degrees of ventriculomegaly in both groups. Lateral ventricular index of CatS -/-group (n=8) and WT group (n=16) before kaolin injection was 0.05±0.01 and 0.04±0.01 respectively (P=0.720). One week after kaolin injection, lateral ventricular index of CatS-/- group (n=7) and WT group (n=14)was 0.13±0.02 and 0.11±0.01 respectively (P=0.950). In each group, in 71.4% of mice, lateral ventricular index enlarged twice or more. Conclusion · One week after kaolin injection into cisterna magna, lateral ventricles enlarges obviously, indicating hydrocephalus occurs, with high success rate. CatS gene deficiency has no significant influence on the development of communicating hydrocephalus.

Influence of cathepsin S deficiency on development of communicating hydrocephalus in mice induced by kaolin / 上海交通大学学报（医学版）

Objective · To evaluate the influence of cathepsin S(CatS) on the severity of communicating hydrocephalus in a kaolin injected mouse model.Methods · Kaolin suspension was injected to 8 CatS knock-out (CatS -/-) mice and 12 wild type (WT) C57BL/6 mice through cisterna magna to establish communicating hydrocephalus mouse model. Cerebral magnetic resonance imaging (MRI) was used before and 1 week after kaolin injection to compare lateral ventricular volume. Lateral ventricular index was calculated to analyze the severity of hydrocephalus. Results · One week after kaolin injection,1 in CatS -/- group and 2 in WT group died. The mortality rate was 12.5% each and there was no significant difference (P=1.000). MRI results showed varying degrees of ventriculomegaly in both groups. Lateral ventricular index of CatS -/-group (n=8) and WT group (n=16) before kaolin injection was 0.05±0.01 and 0.04±0.01 respectively (P=0.720). One week after kaolin injection, lateral ventricular index of CatS-/- group (n=7) and WT group (n=14)was 0.13±0.02 and 0.11±0.01 respectively (P=0.950). In each group, in 71.4% of mice, lateral ventricular index enlarged twice or more. Conclusion · One week after kaolin injection into cisterna magna, lateral ventricles enlarges obviously, indicating hydrocephalus occurs, with high success rate. CatS gene deficiency has no significant influence on the development of communicating hydrocephalus.

Structural and functional analysis of cathepsin S of Heterodera spp: A promising candidate for its control.

Cysteine proteinases are required for a wide range of physiological processes in all living organisms. In parasitic nematodes, they are particularly crucial for the digestion of host tissues and evasion of host immune responses. Therefore, in general, these are identified as primary targets for the control of parasitic nematodes. Herein, cathepsin S-like cysteine proteinase of Heterodera avenae (Hacp-s) has been cloned and analysed for the first time. The predicted protein is 298 amino acids long and showed significant similarity with cathepsin S of Heterodera glycines (Hgcp-s). The sequence of cathepsin S contains a signal peptide of 30 amino acids which suggests its role in extracellular functions. Multiple sequence alignment revealed the presence of ERFNIN motif and conserved catalytic residues. Three dimensional structure (3D) of Hgcp-s was modelled using homology modelling. In order to illustrate the plausible mode of interaction of cathepsin S (Hgcp-s), docking analysis was performed with E-64 cysteine proteinase inhibitor. Docking studies revealed the hydrogen bonding of E-64 with Gln153, His299 and Gly203 as well as close interaction with catalytic residues Cys159 and Asn320. Expression analysis of Hacp-s using qRT-PCR showed high expression of cathepsin S in pre parasitic J2s and female stages suggesting its significant role in both pre-parasitic and parasitic stages of the nematode life cycle.

The expression of cathepsin S in human and mouse abdominal aortic aneurysm / 中国基层医药

Objective To observe the expression of Cathepsin S in the human abdominal aortic aneurysm (AAA) and angiotensin Ⅱ(AngⅡ) perfusion induced AAA lesions in apolipoprotein E-deficient(ApoE-/-) mice.Methods AAA specimens of clinical diagnosis patients(AAA group) and the normal blood vessels(control group)were collected.The AAA model was established by infused Ang Ⅱ 1 000ng · kg-1 · d-1 to ApoE-/-mice.Elastic fibersfracture was observed by elastic fiber staining and Cathepsin S expression by immunohistochemistry.Results The elastic fiber staining revealed that the elastic fibers fracture of the human and mouse AAA group increased significantly (P ＜ 0.05) ; Cathepsin S expression significantly increased in the human and mouse AAA group than the control group by immunohistochemistry(P ＜ 0.05).Conclusion Cathepsin S is activated in human and murine AAA lesions and may be involved in the pathogenesis of AAA.

Cathepsin S and atherosclerosis / 国际脑血管病杂志

Cathepsin S is one of the cathepsins that distributes generally at lysosomes of histiocyte in humans body.It has variety of actions when it is unbalancing,including promote inflammation,atherosclerosis,diabetes and obesity,etc.Studies in recent years have demonstrated that there are certain correlations of adiponectin with vascular risk factor and cerebrovascular disease.

Atorvastatin Attenuated Cathepsin S Expression in Neointima after Carotid Artery Balloon Injury in Rats / 中华高血压杂志

Background Neointima formation plays an important role in the pathogenesis of atherosclerosis and restenosis after angioplasty.We hypothesized if atorvastatin inhibits neointima formation mediating decreases in cathepsin S (Cat S) and nuclear factor-?B(NF-?B) expression.Objective The study was aimed to explore the effect of atorvastatin on the neointima formation,Cat S and NF-?B expression in rats after balloon-injured carotid artery.Methods Twenty-four male Sprague-Dawley rats were randomly one of three arms:control group(n=8),surgery group(n=8) and atorvastatin group[10 mg/(kg?d),n=8] for 4 weeks.Surgery and atorvastatin group were performed with balloon angioplasty to the left common carotid artery.The serum levels of IL-1? were measured using enzyme-link-immunosorbent assay(ELISA).Carotid arteries were excised and examined with pathomorphology.The expression of Cat S and NF-?B was measured using using the RT-PCR and immunohistochemistry techniques.Results Compared with surgery group,atorvastatin decreased intima area and intima media ratio(I/M)[intima area:(148.6?8.8)?103 vs (64.8?5.1)?103 ?m2;I/M:(2.1?0.2) vs (0.9?0.1),all P