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Rheumatoid arthritis(RA) is a chronic degenerative joint disease characterized by inflammation. Due to the complex causes, no specific therapy is available. Non-steroidal anti-inflammatory agents and corticosteroids are often used(long-term, oral/injection) to interfere with related pathways for reducing inflammatory response and delaying the progression of RA, which, however, induce many side effects. Microneedle, an emerging transdermal drug delivery system, is painless and less invasive and improves drug permeability. Thus, it is widely used in the treatment of RA and is expected to be a new strategy in clinical treatment. This paper summarized the application of microneedles in the treatment of RA, providing a reference for the development of new microneedles and the expansion of its clinical application.
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Humans , Drug Delivery Systems , Administration, Cutaneous , Pharmaceutical Preparations , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis, Rheumatoid/drug therapy , NeedlesABSTRACT
Chemical investigation of the culture extract of an endophytic Penicillium citrinum from Dendrobium officinale, afforded nine citrinin derivatives (1-9) and one peptide-polyketide hybrid GKK1032B (10). The structures of these compounds were determined by spectroscopic methods. The absolute configurations of 1 and 2 were determined for the first time by calculation of electronic circular dichroism (ECD) data. Among them, GKK1032B (10) showed significant cytotoxicity against human osteosarcoma cell line MG63 with an IC50 value of 3.49 μmol·L-1, and a primary mechanistic study revealed that it induced the apoptosis of MG63 cellsvia caspase pathway activation.
Subject(s)
Humans , Apoptosis , Bone Neoplasms , Caspases , Osteosarcoma/drug therapy , PenicilliumABSTRACT
Objective:To explore the correlation between the efficacy of <italic>Usnea diffracta</italic> in treating atherosclerosis （AS） and the altered microbial flora in rat ileum based on the interior-exterior relationship between heart and small intestine in traditional Chinese medicine （TCM）. Method:Forty-eight SD rats were randomized into a normal group （<italic>n</italic>=8） and a modeling group （<italic>n</italic>=40）. The AS model was established with high-fat diet combined with intraperitoneal injection of vitamin D<sub>3</sub>. The successfully modeled rats were further randomly divided into the model group， positive control （simvastatin， 4 mg·kg<sup>-1</sup>） group， and low- （0.7 g·kg<sup>-1</sup>）， medium- （1.4 g·kg<sup>-1</sup>）， and high-dose （2.8 g·kg<sup>-1</sup>） <italic>U. diffracta</italic> ethanol extract groups， with eight rats in each group. After four weeks of intervention， the blood， aorta， ileum， and ileum content of rats in each group were collected. The levels of serum lipopolysaccharide （LPS）， tumor necrosis factor-<italic>α </italic>（TNF-<italic>α</italic>） and interleukin 6 （IL-6） were measured by enzyme-linked immunosorbent assay （ELISA）， and the pathological changes in rat thoracic aorta was detected by hematoxylin-eosin （HE） staining. Western blot was conducted to determine the protein expression levels of tight junction protein zonula occluden （ZO-1） and Occludin in rat ileum， and the high-throughput 16S rRNA sequencing technology was employed to detect changes in microbial diversity and abundance in rat ileum of each group. Result:Compared with the normal group， the model group exhibited obvious aortic plaque deposition， increased LPS， TNF-<italic>α</italic>， and IL-6 levels （<italic>P</italic><0.01）， but decreased ZO-1 and Occludin protein expression （<italic>P</italic><0.01）. The comparison with the model group revealed that <italic>U. diffracta</italic> significantly ameliorated the aortic plaque deposition of model rats， lowered serum LPS， TNF-<italic>α</italic>， and IL-6 levels （<italic>P</italic><0.05， <italic>P</italic><0.01）， and up-regulated ZO-1 and Occludin protein expression （<italic>P</italic><0.05， <italic>P</italic><0.01）. The abundance of Proteobacteria and Bacteroidetes in the model group changed significantly in contrast to that in the normal group， and the Bacteroidetes/Firmicutes（B/F） value declined （<italic>P</italic><0.05）. Alpha and Beta diversity analysis indicated higher total number of intestinal flora species in the model group， but lower richness and uneven distribution （<italic>P</italic><0.05， <italic>P</italic><0.01）， with a large number of pathogenic bacteria enriched. The ethanol extract of <italic>U. diffracta</italic> significantly increased the B/F value， corrected the structural disorder of microbial flora in ileum， reduced pathogenic bacteria， and increased the relative abundance of probiotics. Conclusion:<italic>U. diffracta</italic> exerts the therapeutic effect against AS possibly by improving the intestinal microbial communities， strengthening the intestinal mucosal barrier function， and reducing the serum LPS and inflammatory factors.
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Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain-heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain-heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.
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The minimum amount of tooth preparation that can be fully controlled is crucial in achieving long-term, stable, and effective aesthetic restoration, which is also a major difficulty in aesthetic restoration. The tooth preparation can be imple-mented efficiently and accurately through digital technology based on the fixed-deep hole guiding technology. Prior the actual tooth preparation, the technology first designs the virtual contour, layering, and virtual occlusion of the prosthesis on the computer. Then, virtual tooth preparation is carried out by cutting back according to the virtual prosthesis. Next, the virtual drilling operation plan is designed according to the shape of the virtual tooth preparation and the contour of the abutment tooth. Finally, the tooth preparation guide plate is designed and printed in 3D. It realizes the whole process of quantitative and precise guidance of dental preparation, visualizes the restoration space, reduces the clinical operation time, and guarantees the quality of dental preparation. It also promotes the improvement of the teaching quality of digital practical exercises.
Subject(s)
Bone Plates , Esthetics, Dental , Printing, Three-Dimensional , Tooth , Tooth PreparationABSTRACT
This study aims to apply a new expert system to design removable partial denture (RPD) framework. The RPD design is completed in three steps, namely, "selecting missing teeth", "selecting abutment condition", and "selecting personalized clasp". The system can help auxiliary dentists develop personalized treatment plans to reduce their clinical workload. It can also generate a dental preparation guideline for clinical preparation, which can prevent tooth preparation mistakes. By generating the standard electronic drawings of the framework design, the system can reduce the inconvenience caused by manual drawing, thereby facilitating dentist-technician communication and reducing the rate of remade.
Subject(s)
Dental Abutments , Denture Design , Denture, Partial, Removable , Expert Systems , ToothABSTRACT
Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain-heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain-heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.
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OBJECTIVE@#To assess the genotoxicity and embryotoxicity of bicyclol methyl ether (BME), the main impurity in bicyclol.@*METHODS@#Five concentrations of BME (0.5, 5, 50, 500 and 5000 μg/plate) were used in the Ames test to detect gene mutation. In the chromosome aberration test, Chinese hamster lung cells were used to detect chromosomal aberration of BME (15, 30, 60, 120 μg/mL) with or without S9 mixture. Embryotoxicity test was also conducted to determine any embryotoxicity of BME (7.5, 22.5, 67.5 μg/L) using zebrafish embryos.@*RESULTS@#No significant differences were observed in the Ames test and the chromosome aberration test in the BME groups compared with the vehicle control group. The zebrafish embryos toxicity test also showed no embryo development toxicity of BME, including hatching rate, body length, pericardial area and yolk sac area.@*CONCLUSIONS@#Bicyclol methyl ether has no genotoxicity in vitro and embryotoxicity in zebrafish embryos, and the impurity in bicyclol is qualified.
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Objective To investigate whether the metabolite of benzene, 1, 4-benzoquinone (1, 4-BQ) , can activate PINK1/Parkin-mediated mitocphagy and the role of reactive oxygen species (ROS) in 1, 4-BQ induced mitophagy in vitro. Methods Human promyelocytic leukemia cells HL60 were used as the test cells, and were divided into control group, 1, 4-BQ group (10 μM 1, 4-BQ treated cells for 24 h), NAC group (5 mM antioxidant N-acetyl cysteine treated cells for 24 h) and 1, 4-BQ+NAC group (5 mM NAC preincubated for 1 h prior to the treatment with 10 μM 1, 4-BQ for 24 h) . The ultra structure of the cells were observed by transmission electron microscopy (TEM), and the expression of mitophagy related protein LC3, PINK1 and Parkin were detected by Western blot, and the intracellular ROS content was determined by DCFH-DA staining. Results The mitochondria in the control group showed a normal rod-shaped structure with clear mitochondrial cristae, while in the 1, 4-BQ group, the mitochondria showed a swollen structure with less mitochondrial cristae, and typical double-membrane mitophagosomes were observed. LC3-Ⅱ/LC3-Ⅰ ratio, the expression of PINK1, Parkin protein and ROS content in 1, 4-BQ group were increased compared with the control group (P <0.05) , and this increase was markedly blocked by the co-treatment of 1, 4-BQ and NAC (P <0.05) . Conclusion The 1, 4-BQ can induce PINK1/Parkin-mediated mitophagy and ROS plays a significant role in 1, 4-BQ-induced mitophagy.
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[Objective]To investigate the characteristics of immunophenotypes in hepatocellular carcinoma(HCC) before liver transplantation.[Methods]The immunophenotypes of T-,B- cells,monocytes,dendritic cells(DC)and NK-cells in peripheral blood from 6 HCC patient who were ready to have liver transplantation and 6 healthy volunteers were analyzed by multicolor flow cytometry.[Results]In the patients,the proportions of CD4+PD-1+T cells,Treg cell (CD4+CD25+CD39+T cells),CD19+B cells,Plasmablasts(CD27highCD38highIgD-IgM-),classical monocytes(CD14high CD16-)and mature NK-cells(CD3-CD56high)were all higher than those in the healthy controls(all P<0.05).However, marginal zone B cell(CD27+IgD+),Non-switched B cells(CD27+CD38dimIgM+),intermediate monocytes(CD14high CD16+)and immature NK-cells(CD3-CD56+)were lower than those in the healthy controls(all P<0.05). And there wasn't any obvious difference in quantity being observed among other cell types.[Conclusion]There was difference in the immunophenotypes of immune cells in peripheral blood between HCC patients before liver transplantation and healthy people.And this finding exerts important effects on monitoring the immune status of the patients after liver transplantation and guiding the administrations of immunosuppressors.
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3D printing technology can be used in prosthodontics to obtain detailed structures. The technique offers a possible supersession for the most conventional restorations technologies. Contemporary aesthetic restorations encounter difficulties in the consistency between the analysis and design stages and the clinical implementation stage. 3D printing transfers aesthetic designs to customize the finial restoration fabrication, which could be an appropriate optimization to the aformentioned problem. Meanwhile, 3D printing technology can be employed to manufacture target restoration space guide (TRS guide), which is a blueprint for the aesthetic ceramic restorations and presents a general functional and aesthetic situation of patients. The guidance provided by TRS guide ensures precision and minimal invasive operation in aesthetic restorations. These new digital technologies have revolutionized aesthetic rehabilitation. This paper introduces the application of 3D printing in aesthetic oral rehabilitation.
Subject(s)
Humans , Ceramics , Esthetics, Dental , Printing, Three-Dimensional , ProsthodonticsABSTRACT
Objective To explore the influence of Mac-1 deficiency on tumor growth of melanoma. Methods The population of Mac-1 gene knock-out ( Mac-1 -/ -) mice was expanded. B16-F10 cells were subcutaneously injected into the C57BL/6J mice (control group) and Mac-1 -/ -mice (experiment group), respectively. Subsequently,the survival rate, tumor volume and body weight were recorded. The proliferation and infiltration of macrophages were detected by immunohistochemistry. Results The survival rate of Mac-1 -/ - mice was significantly improved compared with the C57BL/6J mice (P ﹤0. 001). The tumor volume and body weight were remarkably decreased in the Mac-1 -/ - mice compared with the control group (P﹤0. 001). Meanwhile, the tumor cell proliferation index was decreased in the Mac-1 -/ - mice compared with the control group (P﹤0. 01). Furthermore, the infiltration of macrophages in the tumor tissues was also decreased in Mac-1 -/ - tumor mice compared with control group. Conclusions Mac-1 gene deletion can significantly suppress melanoma growth.
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Objective To explore the influence of Mac-1 deficiency on tumor growth of melanoma. Methods The population of Mac-1 gene knock-out ( Mac-1 -/ -) mice was expanded. B16-F10 cells were subcutaneously injected into the C57BL/6J mice (control group) and Mac-1 -/ -mice (experiment group), respectively. Subsequently,the survival rate, tumor volume and body weight were recorded. The proliferation and infiltration of macrophages were detected by immunohistochemistry. Results The survival rate of Mac-1 -/ - mice was significantly improved compared with the C57BL/6J mice (P ﹤0. 001). The tumor volume and body weight were remarkably decreased in the Mac-1 -/ - mice compared with the control group (P﹤0. 001). Meanwhile, the tumor cell proliferation index was decreased in the Mac-1 -/ - mice compared with the control group (P﹤0. 01). Furthermore, the infiltration of macrophages in the tumor tissues was also decreased in Mac-1 -/ - tumor mice compared with control group. Conclusions Mac-1 gene deletion can significantly suppress melanoma growth.
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Objective To investigate the status of syphilis and HCV infection and the influencing factors among community drug addicts in Jiaxing City.Methods HCV and syphilis were detected among community drug addicts in Jiaxing City from 2014-2015 and a questionnaire survey were conducted.Influencing factors of syphilis and HCV was analyzed in this study.Results A total of 449 drug users including 356 males (79.29％) and 93 females (20.71％) were investigated,with the age ranged from 16 to 47 and averaged 27.50 ± 12.28.A total of 370 of them take addictive drugs (82.41％),including 42 of them take more than 2 kinds of drugs.15 cases of Syphihs (double positive) were found,and the positive rate was 3.34％.There were significant difference among community drug addicts with different education level (P ＜0.05).The positive rate of HCV among males were lower than that of females (P ＜ 0.05),and the positive rate of HCV among heroin addicts were higher than other drug addicts (P ＜ 0.05).The positive rate of HCV of injection drug users were higher than oral drug addicts(OR =17.341,95％ CI:8.387-35.857,P ＜ 0.01).There was associations among condom use with double positive syphilis and HCV (OR =0.210,95％ CI:0.064-0.689,P ＜0.01;OR =0.131,95％ CI:0.063 -0.273,P ＜ 0.01),respectively.Conclusion Community drug addics are mainly young adults,drug injection and not using condom may increase the risks of TP and HCV infection.
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Phyllanthus Urinaria L. (PUL) is a traditional Chinese medicine used to treat hepatic and renal disorders. However, the mechanism of its hepatoprotective action is not fully understood. In the present study, blood biochemical indexes and liver histopathological changes were used to estimate the extent of hepatic injury. GC/MS and LC/MS-based untargeted metabolomics were used in combination to characterize the potential biomarkers associated with the protective activity of PUL against CCl-induced liver injury in rats. PUL treatment could reverse the increase in ALT, AST and ALP induced by CCl and attenuate the pathological changes in rat liver. Significant changes in liver metabolic profiling were observed in PUL-treated group compared with liver injury model group. Seventeen biomarkers related to the hepatoprotective effects of PUL against CCl-induced liver injury were screened out using nonparametric test and Pearson's correlation analysis (OPLS-DA). The results suggested that the potential hepatoprotective effects of PUL in attenuating CCl-induced hepatotoxicity could be partially attributed to regulating L-carnitine, taurocholic acid, and amino acids metabolism, which may become promising targets for treatment of liver toxicity. In conclusion, this study provides new insights into the mechanism of the hepatoprotection of Phyllanthus Urinaria.
Subject(s)
Animals , Humans , Male , Rats , Amino Acids , Metabolism , Carbon Tetrachloride , Chemical and Drug Induced Liver Injury , Metabolism , Drugs, Chinese Herbal , Gas Chromatography-Mass Spectrometry , Liver , Metabolism , Metabolomics , Phyllanthus , Chemistry , Rats, Sprague-Dawley , Taurocholic Acid , MetabolismABSTRACT
The purpose of this study was to isolate and purify polysaccharide from Gynura divaricata and analyze its monosaccharide composition. A water-soluble crude polysaccharide was obtained by hot water extraction, ethanol precipitation and deproteinization after degreasing. The crude polysaccharide then purified with DEAE-Sepharose Fast Flow column chromatography and dialysis. The monosaccharide composition and structure were analyzed by HPLC, UV spectrophotometer and 1H-NMR. The results showed that the purity and molecular weight of GDPS-2 and GDPS-3 were 87.3%, 2.03 x 10(4) Da and 90.9%, 4.29 x 10(4) Da, respectively. The UV spectrophotometer and 1H-NMR data suggested that glycosidic bond of GDPS-2 and GDPS-3 were a type. Both GDPs-2 and GDPs-3 were homogeneous polysaccharides, and GDPs-2 was mainly composed of glucuronic acid and xylose at a molar ratio of 1.1:0.63. GDPs-3 was mainly composed of rhamnose, glucuronic acid, galactose, xylose and galacturonic acid at a molar ratio of 0.32:6.0:0.21:1.75:4.3.
Subject(s)
Asteraceae , Chemistry , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Chemistry , Magnetic Resonance Spectroscopy , Molecular Weight , Polysaccharides , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To explore the improvement of dendritic cells' (DCs) functions in chronic hepatitis B (CHB) patients by two different drugs plasma, i.e., Shen supplementing and detoxification (SSD) and Pi invigorating and detoxification (PID), thus comparing which method was more effective to activate DCs to improve T lymphocyte functions.</p><p><b>METHODS</b>Totally 30 CHB outpatients were recruited. They were assigned to the immune tolerant group and the immune clearance group, 15 in each group. Totally 60 mL peripheral blood was extracted to isolate and develop mature DCs. Chinese compound containing (Liuwei Ganlu Syrup for SSD) and (Sijun Ganlu Syrup for PID) plasma were added to promote the maturation of DCs on the 7th day. Besides, non-drug plasma was taken as the control. On the ninth day, HBV core 18-27 loaded core peptide and its own T lymphocyte were co-cultivated for 72 h. Then T lymphocytes were collected. The expression levels of CD3, CD28, CD4, and CD8, programmed death-1 (PD-1) were detected using flow cytometry.</p><p><b>RESULTS</b>Compared with non-drug plasma, the expression levels of CD3, CD4, and CD28 could be improved, and the expression levels of CD8 and PD-1 could be reduced by the two methods, showing statistical difference (P < 0.05). Besides, SSD containing plasma showed better effect in improving the molecular CD28 expression rate, and reducing the molecular PD-1 expression rate on the T cell surface, showing statistical difference when compared with that of PID containing plasma (P < 0.05).</p><p><b>CONCLUSIONS</b>In vitro intervention of DCs by SSD and PID containing plasmas combined co-cultivation of its own T lymphocytes could promote the activation of DCs to improve the function of T cells and the expression of T cell surface molecules. Besides, SSD showed more significant effect on infection immune of HBV patients in the tolerance stage.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Cells, Cultured , Dendritic Cells , Allergy and Immunology , Drugs, Chinese Herbal , Pharmacology , Hepatitis B, Chronic , Allergy and Immunology , T-Lymphocytes , Allergy and ImmunologyABSTRACT
<p><b>OBJECTIVE</b>To investigate infections of syphilis, neisseria gonorrhoeae, chlamydia trachomatis and the related risk factors in men who have sex with men (MSM) in Jiangsu province.</p><p><b>METHODS</b>A total of 400 MSM were enrolled by Snowball Sampling Method from August to October in 2010 and then 328 cases were surveyed by a questionnaire and collected serum sample 5 ml per person as well as rectal swab on the spot; all of the serum samples were tested for syphilis by ELISA and TRUST, and all of the rectal swabs were tested for neisseria gonorrhoeae or chlamydia trachomatis. The influencing factors of syphilis, neisseria gonorrhoeae, chlamydia trachomatis were analyzed by logistic regression analysis.</p><p><b>RESULTS</b>The 328 MSM were (32.46 ± 9.72) years old, 59.15% (194/328) were unmarried.75.00% (246/328) MSM had rectal sex with men in the past 3 months, and condom use rate for recent sex was 56.71% (186/328), while 53.05% (174/328) MSM didn't have sex with women in the last 3 months. The syphilis infection rate among MSM was 13.41% (44/328), the neisseria gonorrhoeae infection rate was 3.66% (12/328), and the chlamydia trachomatis rate was 11.59% (38/328). The number of sex partners was the key factor that influenced syphilis infections (OR = 4.213, 95%CI: 1.133 - 15.656).</p><p><b>CONCLUSION</b>The prevalence of syphilis and chlamydia trachomatis was high in MSM in Jiangsu, while risk behavior rate were high in the MSM and then should be intervened.</p>
Subject(s)
Adult , Humans , Male , Young Adult , China , Epidemiology , Chlamydia Infections , Epidemiology , Gonorrhea , Epidemiology , Homosexuality, Male , Risk Factors , Risk-Taking , Surveys and Questionnaires , Syphilis , EpidemiologyABSTRACT
<p><b>BACKGROUND</b>Insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) can activate hepatic stellate cells and increase extracellular matrix (ECM) in vitro. However, the effects of IGFBPrP1 in mice with hepatic fibrosis, and the mechanisms of these effects, are currently unknown. We aim to address these issues in this study.</p><p><b>METHODS</b>Intraperitoneal injection of thioacetamide (TAA) is a classic method for establishing a mouse model of hepatic fibrosis. Using this model, we administered anti-IGFBPrP1 antibody, again via intraperitoneal injection. The morphological changes of liver fibrosis were observed with both HE and Masson stainning. The immunohistochemical assays and Western blotting were used to measure changes in IGFBPrP1, α-smooth muscle actin (α-SMA) and ECM in liver tissues, and the expression of transforming growth factor-β1 (TGF-β1) and Smad3. Data were statistically analyzed using one-way analysis of variance (ANOVA), the SNK-q test for inter-group differences.</p><p><b>RESULTS</b>The Masson staining analysis showed that compared with normal control group, content of collagen fiber in TAA5w group was significantly increased (P < 0.01), and it was significantly decreased in TAA5w/aIGFBPrP1 group compared with in TAA5w group (P < 0.01). The expression of hepatic IGFBPrP1, α-SMA, TGF-β1, Smad3, collagen I and fibronectin (FN) was significantly up-regulated in the TAA5w group (P < 0.01). Anti-IGFBPrP1 treatment reversed these changes (P < 0.01).</p><p><b>CONCLUSIONS</b>IGFBPrP1 plays an important role in the development of hepatic fibrosis. Anti-IGFBPrP1 prevents fibrosis in mice by suppressing the activation of hepatic stellate cells, inhibiting the synthesis of major components of the ECM (namely, collagen I and FN). The mechanism for this suppression of fibrosis is associated with the TGF-β1/Smad3 signaling pathways.</p>