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1.
Nature ; 560(7720): 582-588, 2018 08.
Article in English | MEDLINE | ID: mdl-30158607

ABSTRACT

The Newtonian gravitational constant, G, is one of the most fundamental constants of nature, but we still do not have an accurate value for it. Despite two centuries of experimental effort, the value of G remains the least precisely known of the fundamental constants. A discrepancy of up to 0.05 per cent in recent determinations of G suggests that there may be undiscovered systematic errors in the various existing methods. One way to resolve this issue is to measure G using a number of methods that are unlikely to involve the same systematic effects. Here we report two independent determinations of G using torsion pendulum experiments with the time-of-swing method and the angular-acceleration-feedback method. We obtain G values of 6.674184 × 10-11 and 6.674484 × 10-11 cubic metres per kilogram per second squared, with relative standard uncertainties of 11.64 and 11.61 parts per million, respectively. These values have the smallest uncertainties reported until now, and both agree with the latest recommended value within two standard deviations.

2.
Appl Opt ; 60(26): 8016-8021, 2021 Sep 10.
Article in English | MEDLINE | ID: mdl-34613062

ABSTRACT

A novel, to the best of our knowledge, method is proposed in this study to permit the controllable resolution of a micro-angle measurement by using a Michelson interferometer. The resolution of the proposed system can be adjusted by changing the distances between a pair of parallel mirrors. Through experiments, it was observed that as the distance was changed from 0 to 6 mm, the corresponding resolution was significantly altered from 22.88 to 14.02 µrad. Compared with other small angle measurement methods, the proposed method can realize the conversion of multiple measurement resolutions more easily and conveniently.

3.
Phys Rev Lett ; 124(5): 051301, 2020 Feb 07.
Article in English | MEDLINE | ID: mdl-32083933

ABSTRACT

We improve the test of the gravitational inverse-square law at the submillimeter range by suppressing the vibration of the electrostatic shielding membrane to reduce the disturbance coupled from the residual surface potential. The result shows that, at a 95% confidence level, the gravitational inverse-square law holds (|α|≤1) down to a length scale λ=48 µm. This work establishes the strongest bound on the magnitude α of the Yukawa violation in the range of 40-350 µm, and improves the previous bounds by up to a factor of 3 at the length scale λ≈70 µm. Furthermore, the constraints on the power-law potentials are improved by about a factor of 2 for k=4 and 5.

4.
Phys Rev Lett ; 121(26): 261101, 2018 Dec 28.
Article in English | MEDLINE | ID: mdl-30636147

ABSTRACT

Here we present a new test of the equivalence principle designed to search for the possible violation of gravitational parity using test bodies with different chiralities. The test bodies are a pair of left- and right-handed quartz crystals, whose gravitational acceleration difference is measured by a rotating torsion pendulum. The result shows that the acceleration difference towards Earth Δa_{left-right}=[-1.7±4.1(stat)±4.4(syst)]×10^{-15} m s^{-2} (1-σ statistical uncertainty), correspondingly the Eötvös parameter η=[-1.2±2.8(stat)±3.0(syst)]×10^{-13}. This is the first reported experimental test of the equivalence principle for chiral masses and opens a new way to the search for the possible parity-violating gravitation.

5.
Phys Rev Lett ; 116(13): 131101, 2016 Apr 01.
Article in English | MEDLINE | ID: mdl-27081964

ABSTRACT

By using a torsion pendulum and a rotating eightfold symmetric attractor with dual modulation of both the interested signal and the gravitational calibration signal, a new test of the gravitational inverse-square law at separations down to 295 µm is presented. A dual-compensation design by adding masses on both the pendulum and the attractor was adopted to realize a null experiment. The experimental result shows that, at a 95% confidence level, the gravitational inverse-square law holds (|α|≤1) down to a length scale λ=59 µm. This work establishes the strongest bound on the magnitude α of Yukawa-type deviations from Newtonian gravity in the range of 70-300 µm, and improves the previous bounds by up to a factor of 2 at the length scale λ≈160 µm.

6.
Phys Rev Lett ; 108(8): 081101, 2012 Feb 24.
Article in English | MEDLINE | ID: mdl-22463510

ABSTRACT

We report a new test of the gravitational inverse square law at millimeter ranges by using a dual-modulation torsion pendulum. An I-shaped symmetric pendulum and I-shaped symmetric attractors were adopted to realize a null experimental design. The non-Newtonian force between two macroscopic tungsten plates is measured at separations ranging down to 0.4 mm, and the validity of the null experimental design was checked by non-null Newtonian gravity measurements. We find no deviations from the Newtonian inverse square law with 95% confidence level, and this work establishes the most stringent constraints on non-Newtonian interaction in the ranges from 0.7 to 5.0 mm, and a factor of 8 improvement is achieved at the length scale of several millimeters.

7.
Zhong Xi Yi Jie He Xue Bao ; 10(5): 561-8, 2012 May.
Article in Zh | MEDLINE | ID: mdl-22587979

ABSTRACT

OBJECTIVE: To investigate the mechanism of Fuzheng Huayu recipe (FZHY), a compound traditional Chinese herbal medicine, against liver fibrosis related to transforming growth factor-ß1 (TGF-ß1)/Smads signaling transduction. METHODS: The research consisted of in vitro and in vivo experiments. In the in vivo experiment, 37 male Wistar rats were divided into 3 groups: 5 rats in normal group, 18 and 14 rats respectively in model and FZHY groups. Liver fibrosis was induced in rats of the model group and the FZHY group by intraperitoneal injection of dimethylnitrosamine with a dose of 10µg/kg body weight for 4 weeks. Rats in the FZHY group were administered with FZHY for 4 weeks after liver fibrosis was induced. After the treatment of FZHY, hydroxyproline (Hyp) content in rat liver tissue was assayed by Jamall's method and protein expressions of TGF-ß1, TGF-ß1 receptor I (TßR-I), Smad2, Smad3 and phosphorylated-Smad2/3 were analyzed by Western blotting. In the in vitro experiment, hepatic stellate cells (HSCs) were isolated from normal rats by in situ pronase/collagenase perfusion followed by density gradient centrifugation. On the 4th day of cell culture, HSCs were stimulated by 2.5 ng/mL TGF-ß1 for 24 h, then incubated with the medium containing 10% FZHY-medicated serum or 10µmol/L SB-431542 (a potent and specific inhibitor of TGF-ß1 receptor I kinase) for 24 h. And the HSCs without TGF-ß1 stimulating were used as control group. Protein expressions and location of α-smooth muscle actin (α-SMA) and Smad3 in HSCs were assayed by immunofluorescent staining, and the image was analyzed by Image-Pro Plus 6.1 System. RESULTS: In the in vivo experiment, liver Hyp content in the FZHY group was reduced significantly compared with the model group. FZHY also down-regulated the protein expressions of TGF-ß1, TßR-I and p-Smad2/3 in fibrotic liver tissue. In the in vitro experiment, FZHY-medicated serum incubated with TGF-ß1-stimulated HSCs significantly down-regulated the protein expression of α-SMA. It also inhibited Smad3 nuclear translocation in TGF-ß1-stimulated HSCs. CONCLUSION: The mechanism of FZHY against liver fibrosis is related to the regulation of TGF-ß1 signaling transduction pathway by inhibition of TGF-ß1 and TßR-I expressions and Smads activation in fibrotic liver tissue and HSCs.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Liver Cirrhosis, Experimental/drug therapy , Liver Cirrhosis, Experimental/metabolism , Phytotherapy , Signal Transduction , Animals , Male , Rats , Rats, Wistar , Smad Proteins/metabolism , Transforming Growth Factor beta1/metabolism
8.
Hepatobiliary Pancreat Dis Int ; 10(5): 502-8, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21947724

ABSTRACT

BACKGROUND: Enzymes involved in drug and xenobiotic metabolism have been considered to exist in two groups: phase I and phase II enzymes. Cytochrome P450 isoenzymes (CYPs) are the most important phase I enzymes in the metabolism of xenobiotics. The products of phase I metabolism are then acted upon by phase II enzymes, including glutathione S-transferases (GSTs). Herbs that inhibit CYPs such as CYP3A4 or that induce GSTs may have the potential to protect against chemical carcinogenesis since the mutagenic effects of carcinogens are often mediated through an excess of CYP-generated reactive intermediates. This study was designed to investigate the effects of salvianolic acid B (Sal B), a pure compound extracted from Radix Salviae Miltiorrhizae, a Chinese herb, on cell proliferation and CYP1A2 and CYP3A4 mRNA expression in the presence or absence of rifampicin, a potent inducer of CYPs and GST protein expression in HepG2 cells. METHODS: HepG2 cells were incubated with different concentrations of Sal B. Cell proliferation was determined by SYTOX-Green nucleic acid staining. CYP3A4 and CYP1A2 mRNA expression was assayed by real-time PCR. GST protein expression was analyzed by Western blotting. RESULTS: Low concentrations of Sal B (0-20 µmol/L) had no significant effects on cell proliferation, while higher concentrations (100-250 µmol/L) significantly inhibited proliferation in a concentration-dependent manner. Ten µmol/L Sal B, but not 1 µmol/L, down-regulated CYP3A4 and CYP1A2 mRNA expression after 24 hours of incubation, whereas both 1 and 10 µmol/L Sal B down-regulated CYP3A4 mRNA expression after 96 hours of incubation; moreover, 1 and 10 µmol/L Sal B inhibited CYP3A4 mRNA expression induced by rifampicin. Both 1 µmol/L and 10 µmol/L Sal B increased GST expression. CONCLUSION: Sal B inhibits CYP3A4 and CYP1A2 mRNA expression and induces GST expression in HepG2 cells.


Subject(s)
Benzofurans/pharmacology , Cytochrome P-450 CYP1A2/genetics , Cytochrome P-450 CYP3A/genetics , Liver Neoplasms/genetics , Blotting, Western , Cell Proliferation/drug effects , Cytochrome P-450 CYP1A2/biosynthesis , Cytochrome P-450 CYP3A/biosynthesis , Dose-Response Relationship, Drug , Enzyme Induction , Enzyme Repression , Gene Expression Regulation, Neoplastic/drug effects , Glutathione Transferase/biosynthesis , Hep G2 Cells , Humans , Liver Neoplasms/enzymology , Liver Neoplasms/pathology , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Rifampin/pharmacology , Time Factors
9.
Zhong Xi Yi Jie He Xue Bao ; 9(2): 201-8, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21288457

ABSTRACT

OBJECTIVE: To observe the effects of vitamin E (Vit E) on mercuric chloride (HgCl2)-induced renal interstitial fibrosis (RIF) in rats and discuss its antioxidative mechanism. METHODS: A total of 32 Sprague-Dawley rats were randomly assigned to three groups: normal group, model group and Vit E group. RIF was induced by oral administration of HgCl(2) at a dose of 8 mg/kg body weight once a day for 9 weeks. Rats in Vit E group were administered with Vit E capsule at 100 mg/kg body weight, and rats in normal and model groups were treated with normal saline. At the end of the 9th week, rats were sacrificed and renal hydroxyproline (Hyp)'s trichrome and periodic acid-silver methenamine (PASM) staining. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and contents of glutathione (GSH) and malondialdehyde (MDA) in kidney tissue were tested with commercial kits. The expressions of nuclear factor-κB (NF-κB), inhibitor-κB (IκB), phospho-IκB (p-IκB) and tumor necrosis factor-α (TNF-α) were determined by Western blot. The expression of α-smooth muscle actin (α-SMA) was assayed by Western blot and immunofluorescent staining. RESULTS: Renal Hyp content, HE, Masson's trichrome and PASM staining results and α-SMA expression confirmed development of HgCl2-induced RIF in rats. Oxidative stress markers GSH, GSH-Px and MDA confirmed oxidative stress in RIF rats. Compared with model rats, rats in Vit E group had lower kidney Hyp content (P<0.01). GSH and MDA contents decreased significantly in Vit E group compared with model group (P<0.01). The expressions of NF-κB and IκB had no significant difference among all groups (P>0.05). In Vit E group, the expressions of p-IκB and TNF-α decreased significantly compared with model group (P<0.01). The expression of α-SMA in Vit E group was also decreased significantly compared with model group (P<0.01). CONCLUSION: Vit E has a protective effect on experimental RIF induced by HgCl(2) in rats and it is related to inhibition of lipid peroxidation, which involves blocking of NF-κB signaling pathway and the activation of cells producing extracellular matrix.


Subject(s)
Kidney Diseases/metabolism , Kidney/metabolism , Vitamin E/pharmacology , Animals , Disease Models, Animal , Extracellular Matrix/metabolism , Fibrosis , Kidney/drug effects , Kidney Diseases/drug therapy , Kidney Diseases/pathology , Lipid Peroxidation , Male , Mercuric Chloride/toxicity , Rats , Rats, Sprague-Dawley , Signal Transduction
10.
BMC Cell Biol ; 11: 31, 2010 May 05.
Article in English | MEDLINE | ID: mdl-20441599

ABSTRACT

BACKGROUND: Salvianolic Acid B (Sal B) is a water-soluble component from Danshen (a traditional Chinese herb widely used for chronic renal diseases) with anti-oxidative and cell protective properties. Sal B also has potential protective effects on renal diseases. Tubular epithelial cells can undergo epithelial-to-mesenchymal transition (EMT), which plays an important role in the pathogenesis of renal interstitial fibrosis (RIF) and is mainly regulated by TGF-beta1/Smads pathway. The aims of the study are to investigate the effect of Sal B on tubular EMT in vivo and in vitro, and to elucidate its underlying mechanism against EMT related to TGF-beta1/Smads pathway. RESULTS: For in vivo experiments, RIF was induced in rats by oral administration of HgCl2 and prophylaxised with Sal B and vitamin E. The protein expression of E-cadherin was down-regulated, while the expression of alpha-SMA, TGF-beta1, TbetaR-I, p-Smad2/3 and the activity of matrix metalloproteinase-2 (MMP-2) were up-regulated in kidneys of model rats when compared with those of normal rats. In contrast, Sal B and vitamin E significantly attenuated the expression of alpha-SMA, TGF-beta1, TbetaR-I, p-Smad2/3, and MMP-2 activity, but increased E-cadherin expression. For in vitro experiments, HK-2 cells were incubated with TGF-beta1 to induce EMT, and the cells were co-cultured with 1 and 10 microM Sal B or SB-431542 (a specific inhibitor of TbetaR-I kinase). TGF-beta1 induced a typical EMT in HK-2 cells, while it was blocked by Sal B and SB-431542, as evidenced by blocking morphologic transformation, restoring E-cadherin and CK-18 expression, inhibiting alpha-SMA expression and F-actin reorganization, and down-regulating MMP-2/9 activities in TGF-beta1 mediated HK-2 cells. Furthermore, Sal B and SB-431542 profoundly down-regulated the expressions of TbetaR-I and p-Smad2/3 but prevented the decreased expression of Smad7 in TGF-beta1 stimulated HK-2 cells. CONCLUSIONS: Sal B can prevent tubular EMT in the fibrotic kidney induced by HgCl2 as well as HK-2 cells triggered by TGF-beta1, the mechanism of Sal B is closely related to the regulation of TGF-beta1/Smads pathway, manifested as the inhibition of TGF-beta1 expression, suppression of TbetaR-I expression and function, down-regulation of Smad2/3 phosphorylation, and restoration of the down-regulation of Smad7, as well as inhibition of MMP-2 activity.


Subject(s)
Benzofurans/pharmacology , Cell Differentiation/drug effects , Drugs, Chinese Herbal/pharmacology , Epithelial Cells/cytology , Kidney/pathology , Mesoderm/cytology , Signal Transduction , Transforming Growth Factor beta1/metabolism , Actins/metabolism , Animals , Cell Line , Fibrosis/metabolism , Humans , Phosphorylation , Protein Serine-Threonine Kinases/metabolism , Rats , Receptor, Transforming Growth Factor-beta Type I , Receptors, Transforming Growth Factor beta/metabolism , Smad7 Protein/metabolism , Up-Regulation
11.
J Integr Med ; 18(6): 505-513, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32912827

ABSTRACT

OBJECTIVE: MicroRNAs (miRNAs) may be viable targets for treating renal interstitial fibrosis (RIF). Fuzheng Huayu recipe (FZHY), a traditional Chinese compound herbal medicine, is often used in China to treat fibrosis. This study sought to assess the mechanisms through which FZHY influences miRNAs to treat RIF. METHODS: RIF was induced in rats by mercury chloride and treated with FZHY. Hydroxyproline content, Masson's staining and type I collagen expression were used to evaluate renal collagen deposition. Renal miRNA profiles were evaluated using a miRNA microarray. Those miRNAs that were differentially expressed following FZHY treatment were identified and subjected to bioinformatic analyses. The miR-21 target gene phosphatase and tensin homolog (PTEN) expression and AKT phosphorylation in kidney tissues were assessed via Western blotting. In addition, HK-2 human proximal tubule epithelial cells were treated using angiotensin II (Ang-II) to induce epithelial-to-mesenchymal transition (EMT), followed by FZHY exposure. miR-21 and PTEN expressions were evaluated via quantitative reverse transcription-polymerase chain reaction (qRT-PCR), while E-cadherin and α-smooth muscle actin (α-SMA) expressions were assessed by immunofluorescent staining and qRT-PCR. Western blotting was used to assess PTEN and AKT phosphorylation. RESULTS: FZHY significantly decreased kidney collagen deposition, hydroxyproline content and type I collagen level. The miRNA microarray identified 20 miRNAs that were differentially expressed in response to FZHY treatment. Subsequent bioinformatic analyses found that miR-21 was the key fibrosis-related miRNA regulated by FZHY. FZHY also decreased PTEN expression and AKT phosphorylation in fibrotic kidneys. Results from in vitro tests also suggested that FZHY promoted E-cadherin upregulation and inhibited α-SMA expression in Ang-II-treated HK-2 cells, effectively reversing Ang-II-mediated EMT. We also determined that FZHY reduced miR-21 expression, increased PTEN expression and decreased AKT phosphorylation in these cells. CONCLUSION: miR-21 is the key fibrosis-related miRNA regulated by FZHY. The ability of FZHY to modulate miR-21/PTEN/AKT signaling may be a viable approach for treating RIF.


Subject(s)
Drugs, Chinese Herbal/pharmacology , MicroRNAs , Nephritis, Interstitial/drug therapy , PTEN Phosphohydrolase , Proto-Oncogene Proteins c-akt , Animals , China , Fibrosis , Kidney/drug effects , Kidney/pathology , Rats
12.
Zhonghua Yi Xue Za Zhi ; 89(3): 187-90, 2009 Jan 20.
Article in Zh | MEDLINE | ID: mdl-19537036

ABSTRACT

OBJECTIVE: To summarize the experience of internet-based online database of orthopedic failure surgery. METHODS: Based on the OrthoChina project, a sub-database for orthopedic failure surgery was established, open to the orthopedic surgeons for viewing, uploading, and sharing the experience. All cases were uploaded by the orthopedic surgeon users registering in the OrthoChina project from 25 August 2006 to 31 December 2007 were summarized. RESULTS: 102 failure surgery cases had been uploaded in the database, in which 87 were caused by internal instrumentation, 5 by external fixation, 7 by conservative treatment, and 3 by hip arthroplasty. Sixty-seven cases involved the poor performance of the orthopedic surgeons, 4 involved the patients related, and the causes of the other 31 cases remained unknown. Six failure cases occurred in class 1 hospitals, 76 cases in class 2 hospitals, and 20 in class 3 hospitals. CONCLUSION: Internet based online database for orthopedic failure surgery helps collect the failed orthopedic treatment from different surgeons and different hospitals. Sharing such experience helps the orthopedic surgeons avoid such therapeutic errors and improve their work. Qualified training and certification are necessary for the application of new techniques and implants.


Subject(s)
Databases as Topic , Internet , Orthopedics , Humans , Treatment Failure
13.
Clin Res Hepatol Gastroenterol ; 43(5): 575-584, 2019 10.
Article in English | MEDLINE | ID: mdl-30857885

ABSTRACT

BACKGROUND: MicroRNA-101 (miR-101) is markedly downregulated in both hepatitis B virus-related liver cirrhosis and hepatocellular carcinoma (HCC). In this study, we aimed to investigate the effect and mechanism of miR-101 on hepatic stellate cell (HSC) activation and liver fibrosis. MATERIALS AND METHODS: HSC LX-2 was treated with TGF-ß1 and with or without miR-101 mimics. LX-2 vitality and proliferation, the expression of F-actin and mRNAs for α-SMA, collagen 1α1 (Col 1α1), and connective tissue growth factor 2 (CCN2) were measured. A 6-week intraperitoneal injection of carbon tetrachloride (CCl4) was used to induce experimental liver fibrosis in mice, which were treated using a miR-101 negative control or miR-101 agomir from the fourth week until the end of the experiment. Liver function, hepatic hydroxyproline, liver histopathology, collagen deposition, α-SMA, type I collagen (Col I) and the protein-expressions of p-PI3K, p-Akt and p-mTOR were measured. RESULTS: MiR-101 significantly suppressed the increased LX-2 vitality and high accumulation of extracellular matrix (ECM) induced by TGF-ß1. Exposure to CCl4 led to the impairment of liver function and disruption of normal hepatic parenchyma in mice, as well as obvious liver fibrosis indicated by elevated levels of hydroxyproline, α-SMA, and Col 1α1 in liver tissues. MiR-101 administration significantly improved liver function, relieved hepatic parenchyma damage, and reversed liver fibrosis by decreasing the accumulation of ECM components. Furthermore, miR-101 substantially downregulated the CCl4-increased p-PI3K, p-Akt, and p-mTOR in mouse liver. CONCLUSIONS: MiR-101 has antifibrotic effects in experimental liver fibrosis, and downregulating the PI3K/Akt/mTOR signaling pathway may be one of its antifibrotic mechanisms.


Subject(s)
Liver Cirrhosis/etiology , MicroRNAs/physiology , Phosphatidylinositol 3-Kinases/physiology , Proto-Oncogene Proteins c-akt/physiology , TOR Serine-Threonine Kinases/physiology , Animals , Down-Regulation , Hepatic Stellate Cells/physiology , Male , Mice , Mice, Inbred ICR , Signal Transduction
14.
Chin J Integr Med ; 23(8): 598-604, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28197934

ABSTRACT

OBJECTIVE: To investigate the mechanism of action of Fuzheng Huayu Formula (, FZHY) against renal interstitial fibrosis (RIF) relating to oxidative injury and nuclear factor-kappa B (NF-κB) activity. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into 3 groups: normal group, model group and FZHY treatment group. The RIF model was induced by oral administration of HgCl2 at a dose of 8 mg/kg body weight once a day for 9 weeks. Meanwhile, rats in FZHY treatment group orally took FZHY at a dose of 4.0 g/kg rat weight for 9 weeks. The content of hydroxyproline (Hyp) and collagen deposition in kidney were observed. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), the content of glutathione (GSH) and malondialdehyde (MDA) of kidney were tested. The expressions of inhibitor-κappa B (IκB), phospho-IκB (p-IκB), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-2 (MMP-2) and α-smooth muscle actin (α-SMA) were analyzed by Western blot. α-SMA expression was also observed by immunofluorescent staining. MMP-2 activity was measured by gelatin zymography. NF-κB activation was determined by electrophoretic mobility shift assay. RESULTS: Renal interstitial fibrosis was induced by HgCl2, demonstrated by remarkably increased Hyp contents and excessive collagen deposition in kidney (P<0.01). FZHY significantly inhibited renal interstitial collagen deposition and reduced Hyp content of the HgCl2-treated rats (P<0.01). GSH content decreased obviously, and MDA content increased signifificantly in HgCl2-treated rats compared with that of normal rats (P<0.01). FZHY significantly increased GSH content and decreased MDA content in the model rats (P<0.01). The expression α-SMA was increased in model rats compared with that of normal rats, FZHY signifificantly decreased its expression (P<0.01). The expressions of p-IκB and TNF-α and MMP-2, MMP-2 activity, and NF-κB activation were increased in model group compared with that in normal group (P<0.01), FZHY signifificantly decreased NF-κB activation, MMP-2 activity and p-IκB and TNF-α expressions (P<0.01). CONCLUSIONS: FZHY could protect kidney from oxidative injury intoxicated by HgCl2, and antagonized oxidative stress-stimulated NF-κB activity through inhibition of IκB phosphorylation in the interstitial fibrotic kidney, these effects importantly contributed to FZHY action mechanism against renal interstitial fifibrosis.


Subject(s)
Down-Regulation , Drugs, Chinese Herbal/therapeutic use , Kidney Diseases/drug therapy , NF-kappa B/metabolism , Oxidative Stress , Animals , Down-Regulation/drug effects , Fibrosis , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Kidney/drug effects , Kidney/pathology , Kidney Diseases/chemically induced , Male , Malondialdehyde/metabolism , Matrix Metalloproteinase 2/metabolism , Mercuric Chloride , Models, Biological , NF-KappaB Inhibitor alpha/metabolism , Oxidative Stress/drug effects , Phosphorylation/drug effects , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism , Tumor Necrosis Factor-alpha/metabolism
15.
Exp Biol Med (Maywood) ; 238(11): 1284-96, 2013 Nov 01.
Article in English | MEDLINE | ID: mdl-24006304

ABSTRACT

Salvianolic acid B (Sal B) is a major water soluble component extracted from Radix Salviae miltiorrhizae, a traditional Chinese herb widely used for treating cardiovascular and hepatic diseases. Sal B has been reported to inhibit transforming growth factor (TGF)-ß1-stimulated hepatic stellate cells (HSCs) activation and collagen type I expression. In this study, we further investigated the mechanisms of Sal B on liver fibrosis relating to TGF-ß/Smads signalling pathway, especially to TGF-ß1 receptors. Liver fibrosis model was induced by intraperitoneal injection of dimethylnitrosamine (DMN) for four weeks. Rats were randomly divided into three groups: normal, model, and Sal B groups. Rats in Sal B group were treated by oral administration of Sal B for four weeks from the first day of DMN exposure. Hydroxyproline (Hyp) content in liver tissue was assayed using Jamall's method and collagen deposition was visualized using Sirius red staining. HSCs were isolated from normal rats, and were cultured primarily in uncoated plastics. At day 4 after isolation, cells were stimulated with 2.5 ng/mL TGF-ß1, and treated with 1 and 10 µmol/L Sal B and 10 µmol/L SB-431542 (TßR-I inhibitor) for 24 h, respectively. Cell proliferation was examined with 5-ethynyl-2'-deoxyuridine assay. The expressions of alpha smooth muscle actin (α-SMA) and Smad3 were assayed by immunofluorescent stain and Western blotting. The expression of TßR-I was analysed by Western blotting and real-time polymerase chain reaction. The activity of TßR-I kinase was measured by ADP-Glo kinase assay. The results showed that Sal B could inhibit collagen deposition and reduce Hyp content significantly, and decrease expressions of TGF-ß1 and TßR-I in fibrotic liver in vivo. Also, Sal B decreased the expressions of α-SMA and TßR-I, inhibited Smad3 nuclear translocation and down-regulated TßR-I kinase activity in vitro. These findings suggested that Sal B could prevent HSCs activation through TGF-ß signalling pathway, i.e. inhibiting TGF-ß1 expression, activity of TßR-I kinase and Smads phosphorylation.


Subject(s)
Benzofurans/pharmacology , Hepatic Stellate Cells/drug effects , Transforming Growth Factor beta1/metabolism , Animals , Benzofurans/chemistry , Cell Proliferation/drug effects , Collagen Type I/metabolism , Disease Models, Animal , Hydroxyproline/metabolism , Liver Cirrhosis/chemically induced , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Male , Phosphorylation , Rats , Rats, Sprague-Dawley , Rats, Wistar , Signal Transduction/drug effects , Smad Proteins/metabolism
16.
J Ethnopharmacol ; 127(3): 631-40, 2010 Feb 17.
Article in English | MEDLINE | ID: mdl-20015471

ABSTRACT

AIM: To investigate the mechanism of action of Fuzheng Huayu recipe (FZHY) and vitamin E (Vit E) against renal interstitial fibrosis related to transforming growth factor-beta1 (TGF-beta1) mediated tubular epithelial-to-mesenchymal transition. MATERIALS AND METHODS: Renal interstitial fibrosis was induced by administration of HgCl(2) at a dose of 8 mg/kg body weight once a day for 9 weeks. Rats were randomly divided into four groups: normal, model, FZHY, and Vit E group. Rats in the latter two groups were treated with the FZHY recipe and Vit E respectively. HK-2 cells were treated with TGF-beta1 for 24h, followed by incubation with either SB-431542 (a potent and specific inhibitor of TbetaR-I kinase) or FZHY drug-containing serum for another 24h. Hyp content in rat kidney tissue was assayed with Jamall's method and collagen deposition in kidney was visualized using Masson stain. Protein expression of TGF-beta1, TbetaR-I, Smad2, p-Smad2, Smad3, and p-Smad3 was analyzed by Western blotting. Protein expression and the location of Smad3 in kidney was assayed by immunohistochemistry, E-cadherin, cytokeratin 18 (CK-18), alpha-SMA and TGF-beta1 by immunofluorescent stain. RESULTS: FZHY and Vit E inhibited renal collagen deposition and reduced Hyp content significantly. They upregulated E-cadherin protein expression and down-regulated the protein expression of alpha-SMA, TGF-beta1, p-Smad2, p-Smad3, and TbetaR-I. Lastly, they inhibited the nuclear translocation of Smad3 in fibrotic kidney tissue. FZHY drug-containing serum significantly upregulated the expression of CK-18 and down-regulated the expression of alpha-SMA, TbetaR-I, p-Smad2/3 in TGF-beta1 stimulated HK-2 cells. CONCLUSION: The mechanism of action of FZHY and Vit E against renal interstitial fibrosis is related to the reversal of tubular EMT induced by TGF-beta1.


Subject(s)
Collagen/metabolism , Drugs, Chinese Herbal/pharmacology , Kidney/drug effects , Phytotherapy , Vitamin E/pharmacology , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Animals , Benzamides , Biological Transport/drug effects , Cadherins/genetics , Cadherins/metabolism , Dioxoles , Drugs, Chinese Herbal/therapeutic use , Epithelial Cells/drug effects , Fibrosis , Fungi , Humans , Hydroxyproline/metabolism , Keratin-18/metabolism , Kidney/metabolism , Kidney/pathology , Kidney Diseases/drug therapy , Male , Mesoderm/drug effects , Plants, Medicinal , Random Allocation , Rats , Rats, Sprague-Dawley , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/metabolism , Vitamin E/therapeutic use
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