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Find video protocols related to scientific articles indexed in Pubmed.
[Extraction and purification technologies of total flavonoids from Aconitum tanguticum].
Zhong Yao Cai
PUBLISHED: 10-28-2014
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To optimize the extraction and purification technologies of total flavonoids from Aconitum tanguticum whole plant.
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[Effect of arbuscular mycorrhizae on growth, heavy metal uptake and accumulation of Zenia insignis Chun seedlings].
Huan Jing Ke Xue
PUBLISHED: 10-24-2014
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To solve the trace metal pollution of a Pd/Zn mine in Hunan province, a greenhouse pot experiment was conducted to investigate the effect of two arbuscular mycorrhizal fungi, Glomus mosseae (Gm) and Glomus intraradices (Gi), on the growth, heavy metal uptake and accumulation of Zenia insignis Chun, the pioneer plant there. The results showed that symbiotic associations were successfully established between the two isolates and Z. insignis in heavy metal contaminated soil. AM fungi improved P absorption, biomass and changed heavy metal uptake and distribution of Z. insignis. AM fungi-inoculated plants had significantly lower Fe, Cu, Zn, Pd concentrations and higher Fe, Cu, Zn, Pd accumulation than non-inoculated plants. However, Gm and Gi showed different mycorrhizal effects on the distribution of heavy metal in hosts, depending on the species of heavy metal. Gi-inoculated Z. insignis showed significantly lower TF values of Fe, Zn, Pd than Gm and non-inoculated plants, while both strains had no effect on TF value of Cu, which indicated that Gi enhanced trace metal accumulation in root system, playing a filtering/sequestering role in the presence of trace metals. The overall results demonstrated that AM fungi had positive effect on Z. insignis in enhancing the ability to adapt the heavy metal contaminated soil and played potential role in the revegetation of heavy metal contaminated soil. But in practical application, the combination of AM, hosts and heavy metal should be considered.
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Anti-inflammatory Diterpenoids from the Root Bark of Acanthopanax gracilistylus.
J. Nat. Prod.
PUBLISHED: 10-23-2014
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Five new ent-pimarane (1-3, 7, and 8) and three new ent-kaurane diterpenoids (4-6) and a new oleanane triterpene acid (9), together with 22 known compounds, were isolated from the root bark of the medicinal herb Acanthopanax gracilistylus. The structures of 1-9 were established based on the interpretation of high-resolution MS and 1D- and 2D-NMR data. The absolute configurations of 7 and 11 were determined by single-crystal X-ray diffraction and electronic circular dichroism analysis. Compounds 7 and 8 represent rare naturally occurring structures based on the devinyl ent-pimarane skeleton. Compounds 3, 10, 14, 16, and 17 exhibited potent inhibitory effects on the release of interleukin-1? (IL-1?), interleukin-8 (IL-8), and tumor necrosis factor (TNF-?) in lipopolysaccharide-stimulated peripheral blood mononuclear cells.
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[Feasibility study of QAMS for quantitative analysis of multiple structural types of ingredients in Zhizi Jinhua pill].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-07-2014
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To study the technical feasibility of QAMS to determine different structural types of ingredients in Zhizi Jinhua pill, a Chinese patent medicine.
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[Effect of bear bile powder on STAT3 pathway in hepatocellular carcinoma xenograft].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 09-17-2014
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To observe the effect of bear bile powder (BBP) on the STAT3 pathway and its downstream target genes of nude mice hepatocellular carcinoma (HCC) xenograft, and to explore its mechanism for treating HCC.
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[A system review of randomized controlled trials on treating chronic stable angina by rhodiola].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 09-17-2014
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To systematically assess the efficacy and safety of Rhodiola in treating chronic stable angina pectoris.
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Tolerance of the Nanocellulose-Producing Bacterium Gluconacetobacter xylinus to Lignocellulose-Derived Acids and Aldehydes.
J. Agric. Food Chem.
PUBLISHED: 09-16-2014
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Lignocellulosic biomass serves as a potential alternative feedstock for production of bacterial nanocellulose (BNC), a high-value-added product of bacteria such as Gluconacetobacter xylinus. The tolerance of G. xylinus to lignocellulose-derived inhibitors (formic acid, acetic acid, levulinic acid, furfural, and 5-hydroxymethylfurfural) was investigated. Whereas 100 mM formic acid completely suppressed the metabolism of G. xylinus, 250 mM of either acetic acid or levulinic acid still allowed glucose metabolism and BNC production to occur. Complete suppression of glucose utilization and BNC production was observed after inclusion of 20 and 30 mM furfural and 5-hydroxymethylfurfural, respectively. The bacterium oxidized furfural and 5-hydroxymethylfurfural to furoic acid and 5-hydroxymethyl-2-furoic acid, respectively. The highest yields observed were 88% for furoic acid/furfural and 76% for 5-hydroxymethyl-2-furoic acid/5-hydroxymethylfurfural. These results are the first demonstration of the capability of G. xylinus to tolerate lignocellulose-derived inhibitors and to convert furan aldehydes.
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Characterization of the Grp94/OS-9 Chaperone-Lectin Complex.
J. Mol. Biol.
PUBLISHED: 09-03-2014
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Grp94 is a macromolecular chaperone belonging to the hsp90 family and is the most abundant glycoprotein in the endoplasmic reticulum (ER) of mammals. In addition to its essential role in protein folding, Grp94 was proposed to participate in the ER-associated degradation quality control pathway by interacting with the lectin OS-9, a sensor for terminally misfolded proteins. To understand how OS-9 interacts with ER chaperone proteins, we mapped its interaction with Grp94. Glycosylation of the full-length Grp94 protein was essential for OS-9 binding, although deletion of the Grp94 N-terminal domain relieved this requirement suggesting that the effect was allosteric rather than direct. Although yeast OS-9 is composed of a well-established N-terminal mannose recognition homology lectin domain and a C-terminal dimerization domain, we find that the C-terminal domain of OS-9 in higher eukaryotes contains "mammalian-specific insets" that are specifically recognized by the middle and C-terminal domains of Grp94. Additionally, the Grp94 binding domain in OS-9 was found to be intrinsically disordered. The biochemical analysis of the interacting regions provides insight into the manner by which the two associate and it additionally hints at a plausible biological role for the Grp94/OS-9 complex.
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[Isolation and characterization of two bacteria with heavy metal resistance and phosphate solubilizing capability].
Huan Jing Ke Xue
PUBLISHED: 08-28-2014
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Two phosphate solubilizing bacteria (T PSB1 and T PSB 2) with high heavy metal resistance were isolated from soil of a lead-zinc mine in Huayuan of Hunan Province, China. These two bacteria were identified as Stenotrophomonas maltophilia and Burkholderia gladioli by 16S rRNA sequencing analysis, respectively. In the media containing insoluble inorganic calcium phosphate, the soluble phosphate amounts reached respectively 402.9 mg x L(-1) and 589.9 mg x L(-1) with the bacteria T PSB1 and T PSB2 after two weeks' growth. Moreover, the two bacteria developed solubilizing halos on the plates supplemented with the organic phosphate compounds, and the resulting soluble phosphate amounts in the broth media were respectively 2.97 mg x L(-1) and 4.69 mg x L(-1). In addition, these two bacteria showed the resistance to up to 2000 mg x L(-1) Zn2+, and their phosphate solubilizing amounts reached respectively 114.8 mg x L(-1) and 125.1 mg x L(-1). Similarly, their heavy metal resistance and phosphate solubilizing ability were also found in the Cr and Pb broth media with the concentration of 1000 mg x L(-1). In the Pb media, the soluble phosphate amounts reached respectively 57.9 mg x L(-1) and 71.7 mg x L(-1), and the soluble P amounts in the Cr media were 60.1 mg x L(-1) and 98.4 mg x L(-1) at the concentration of 1000 mg x L(-1).
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[Roles of TRPV1 receptor in electroacupuncture regulating the jejunal motility of mice: an experimental study].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 08-21-2014
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To observe the intestinal movement of transient receptor potential vanilloid 1 or vanilloid receptor 1 (TRPV1) knockout mice after stimulated by electroacupuncture (EA), and to primarily explore the roles of TRPV1 receptor in the jejunal motility regulated by acupuncture.
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Impact of estimated HDL particle size via the ratio of HDL-C and apoprotein A-I on short-term prognosis of diabetic patients with stable coronary artery disease.
J Geriatr Cardiol
PUBLISHED: 07-05-2014
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Revascularization and statin therapy are routinely used in the management of stable coronary artery disease. However, it is unclear whether the estimated high-density lipoprotein (HDL) particle size (eHDL-S), the ratio of HDL cholesterol (HDL-C) to apoprotein A-I (apoA-I), is associated with the clinical outcomes of diabetic patients with stable coronary artery disease (CAD).
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IFN regulatory factor 10 is a negative regulator of the IFN responses in fish.
J. Immunol.
PUBLISHED: 06-23-2014
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IFN regulatory factor (IRF) 10 belongs to the IRF family and exists exclusively in birds and fish. Most IRFs have been identified as critical regulators in the IFN responses in both fish and mammals; however, the role of IRF10 is unclear. In this study, we identified IRF10 in zebrafish (Danio rerio) and found that it serves as a negative regulator to balance the innate antiviral immune responses. Zebrafish IRF10 (DrIRF10) was induced by intracellular polyinosinic:polycytidylic acid in ZF4 (zebrafish embryo fibroblast-like) cells. DrIRF10 inhibited the activation of zebrafish IFN1 (DrIFN1) and DrIFN3 promoters in epithelioma papulosum cyprinid cells in the presence or absence of polyinosinic:polycytidylic acid stimulation through direct interaction with the IFN promoters, and this inhibition was also shown to block IFN signaling. Overexpression of DrIRF10 was able to abolish the induction of DrIFN1 and DrIFN3 mediated by the retinoic acid-inducible gene I-like receptors. In addition, functional domain analysis of DrIRF10 showed that either the DNA binding domain or the IRF association domain is sufficient for its inhibitory activity for IFN signaling. Lastly, overexpression of DrIRF10 decreased the transcription level of several IFN-stimulated genes, resulting in the susceptibility of host cells to spring viremia of carp virus infection. Collectively, these data suggest that DrIRF10 inhibits the expression of DrIFN1 and DrIFN3 to avoid an excessive immune response, a unique regulation mechanism of the IFN responses in lower vertebrates.
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Treatment of benign prostatic hyperplasia with Croton membranaceus in an experimental animal model.
J Ethnopharmacol
PUBLISHED: 05-10-2014
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Croton membranaceus leaf extracts are used in the Bahamas to aromatize tobacco. In Nigeria it is used to improve digestion and in Ghana, the root extract is used for the treatment of benign prostatic hyperplasia (BPH). Despite claims of efficacy no data exists to support this. The aim of this study was to determine if Croton membranaceus aqueous root extract (CMARE) could attenuate the development of BPH in an animal model.
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Construction of a novel secretion expression system guided by native signal peptide of PhoD in Zymomonas mobilis.
Biosci. Biotechnol. Biochem.
PUBLISHED: 05-09-2014
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In the current study, three native signal peptides (SPs) from PhoC, PhoD, and ZMO0331were investigated and compared to construct novel secretion expression systems in Zymomonas mobilis. The secretion expression of target protein, ?-amylase from Bacillus amyloliquefaciens (BAA), guided by PhoD's SP resulted in more hydrolysis of starch than that by the other two SPs. Extracellular and intracellular ?-amylase activities of the strain containing PhoD's SP were also higher than the other two strains containing PhoC or ZMO0331's SP. In addition, the evidence by alcohol dehydrogenase activity assay further confirmed that the starch hydrolysis was resulted from the secretion expression of BAA rather than the breakage of cells. Our results indicated that the SP of PhoD is able to serve as a promising candidate to assist secretion expression of heterogeneous genes in Z. mobilis. This will contribute to development of engineered Z. mobilis strains converting starch into ethanol.
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Yiqi formula enhances the antitumor effects of erlotinib for treatment of triple-negative breast cancer xenografts.
Evid Based Complement Alternat Med
PUBLISHED: 05-07-2014
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Yiqi formula (YF), a traditional herbal prescription, has long been used to treat triple-negative breast cancer (TNBC) patients. The present study aims to investigate the effects and the related mechanism of YF for treatment of TNBC xenografts. MDA-MB-231 (human TNBC) cells were subcutaneously injected into the second mammary fat pad of 40 female nude mice, which were divided into four groups: control, erlotinib (an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor), YF, and combination (YF plus erlotinib). All treatments were administered orally for 30 days. Inhibition rate of tumor weight by erlotinib, YF, and the combination was 26.47%, 17.24%, and 39.15%, respectively. Western blotting showed that YF, erlotinib, and the combination downregulated p-EGFR (P < 0.01) and p-Akt1 (pT308) (P < 0.05) and upregulated PTEN compared with control, and the combination was more efficacious than erlotinib alone (P < 0.05). Similar results were detected by immunohistochemistry. Real-time quantitative PCR showed that YF, erlotinib, and the combination increased PTEN mRNA (P < 0.05, P < 0.01) compared with control, and the combination was more efficacious than erlotinib alone (P < 0.05). In conclusion, YF can regulate the main components of the PI3K/Akt pathway in TNBC xenografts. When YF was used in combination with erlotinib, it enhanced the antitumor effects of erlotinib on TNBC xenografts. These findings suggest that YF is suitable to use for the treatment of TNBC patients.
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Effects of aromatic compounds on the production of bacterial nanocellulose by Gluconacetobacter xylinus.
Microb. Cell Fact.
PUBLISHED: 04-21-2014
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Bacterial cellulose (BC) is a polymeric nanostructured fibrillar network produced by certain microorganisms, principally Gluconacetobacter xylinus. BC has a great potential of application in many fields. Lignocellulosic biomass has been investigated as a cost-effective feedstock for BC production through pretreatment and hydrolysis. It is well known that detoxification of lignocellulosic hydrolysates may be required to achieve efficient production of BC. Recent results suggest that phenolic compounds contribute to the inhibition of G. xylinus. However, very little is known about the effect on G. xylinus of specific lignocellulose-derived inhibitors. In this study, the inhibitory effects of four phenolic model compounds (coniferyl aldehyde, ferulic acid, vanillin and 4-hydroxybenzoic acid) on the growth of G. xylinus, the pH of the culture medium, and the production of BC were investigated in detail. The stability of the phenolics in the bacterial cultures was investigated and the main bioconversion products were identified and quantified.
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Distinctive expression and cellular distribution of dopamine receptors in the pancreatic islets of rats.
Cell Tissue Res.
PUBLISHED: 04-10-2014
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Activation of the dopamine (DA) D2 receptor inhibits glucose-stimulated insulin secretion in isolated rodent islets in vitro; however, no information is available regarding the cellular localization of DA receptors (DRs, including D1-D5 receptors) in pancreatic islets in situ. We investigate the protein expression and cellular localization of five types of DRs in pancreatic islets by means of Western blotting and double-labeling immunofluorescence in both normal control and alloxan-induced type 1 diabetes model (T1DM) rats. In control rats, D1 immunoreactivity (-IR) was distributed in the core of the islet and co-localized with insulin-IR, D2-IR was peripherally distributed and found only in somatostatin-immunoreactive cells and D5-IR was co-localized with glucagon-IR and pancreatic polypeptide-IR. No IR for either the D3 or D4 receptor was observed in rat islets. The protein level of the D1 receptor was reduced in T1DM rats (D1/D-glyceraldehyde-3-phosphate dehydrogenase [GAPDH], 0.63?±?0.05 in control rats compared with 0.16?±?0.03 in T1DM rats, n?=?8, P?
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Increased vulnerability with aging to MPTP: the mechanisms underlying mitochondrial dynamics.
Neurol. Res.
PUBLISHED: 03-14-2014
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The risk and vulnerability of Parkinson disease (PD) are especially high in the elderly. However, the underlying causes are unknown. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice are useful tools to some extent for investigating PD-related problems due to their PD-like symptoms. The study is aimed to determine whether and what mitochondrial-events during aging are related with the increased vulnerability of the elderly to MPTP.
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Bear bile powder (???) induces apoptosis of human hepatocellular carcinoma cells via mitochondrion-dependent pathway.
Chin J Integr Med
PUBLISHED: 03-06-2014
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To evaluate the effect of Bear Bile Powder(, BBP) on the growth and apoptosis of HepG2 human hepatocellular carcinoma cells, and investigate the possible molecular mechanisms mediating its anti-cancer activity.
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Ethanol extract of Cirsium japonicum attenuates hepatic lipid accumulation via AMPK activation in human HepG2 cells.
Exp Ther Med
PUBLISHED: 03-03-2014
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One of the most common causes of chronic liver disease, nonalcoholic fatty liver disease (NAFLD), is strongly associated with obesity and dysregulated insulin action in the liver. However, there are no pharmacological agents currently established for the treatment of NAFLD. A flowering plant in the Asteraceae family, Cirsium japonicum (CJ), exhibits a variety of pharmacological and antioxidative properties that promote hepatoprotection. In the present study, CJ ethanol extract was shown to reduce hepatic triglyceride (TG) and cholesterol accumulation. CJ significantly increased AMP-activated protein kinase (AMPK) phosphorylation in HepG2 hepatocytes and downregulated the level of the target genes, acetyl-CoA carboxylase and fatty acid synthase. In addition, CJ upregulated the expression of carnitine palmitoyltransferase-1, which is involved in fatty acid oxidation. The results of the present study indicated that the positive effects of CJ extract on high-fat diet-induced hepatic TG accumulation were mediated via the AMPK signaling pathway, indicating a potential target for the preventative treatment of NAFLD.
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Significance of red cell distribution width measurement for the patients with isolated coronary artery ectasia.
J Transl Med
PUBLISHED: 03-03-2014
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Red cell distribution width (RDW) has been recognized as a novel marker for several cardiovascular diseases. The aim of this study was to evaluate the association between RDW levels and the presence of isolated coronary artery ectasia (CAE).
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High glucose induces sumoylation of Smad4 via SUMO2/3 in mesangial cells.
Biomed Res Int
PUBLISHED: 02-27-2014
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Recent studies have shown that sumoylation is a posttranslational modification involved in regulation of the transforming growth factor-? (TGF-?) signaling pathway, which plays a critical role in renal fibrosis in diabetic nephropathy (DN). However, the role of sumoylation in the regulation of TGF-? signaling in DN is still unclear. In the present study, we investigated the expression of SUMO (SUMO1 and SUMO2/3) and Smad4 and the interaction between SUMO and Smad4 in cultured rat mesangial cells induced by high glucose. We found that SUMO1 and SUMO2/3 expression was significantly increased in the high glucose groups compared to the normal group (P < 0.05). Smad4 and fibronectin (FN) levels were also increased in the high glucose groups in a dose-dependent manner. Coimmunoprecipitation and confocal laser scanning revealed that Smad4 interacted and colocalized with SUMO2/3, but not with SUMO1 in mesangial cells. Sumoylation (SUMO2/3) of Smad4 under high glucose condition was strongly enhanced compared to normal control (P < 0.05). These results suggest that high glucose may activate TGF- ?/Smad signaling through sumoylation of Samd4 by SUMO2/3 in mesangial cells.
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New triterpenic acids from Uncaria rhynchophylla: chemistry, NO-inhibitory activity, and tandem mass spectrometric analysis.
Fitoterapia
PUBLISHED: 02-20-2014
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Five new oleanane and ursane type triterpenes, namely uncarinic acids F-J (1-5), together with six known triterpenic acids (6-11) were isolated from the stems and hooks of Uncaria rhynchophylla. Structure elucidation of 1-5 was based on the integrated analyses of high-resolution MS data, 1D ((1)H NMR, (13)C NMR, DEPT) and 2D (HSQC, HMBC, ROESY) NMR spectra. Compounds 4, 10, and 11 exhibited weak inhibitory effects on LPS-induced NO production in RAW264.7 cells (with IC50 1.48, 7.01, and 1.89 ?M, respectively) with dexamethasone (IC50 0.04 ?M) and quercetin (IC50 0.86 ?M) as the positive controls. 19-OH substituted oleanane triterpenic acids (1, 2, 5, 8) were prone to eliminate CH2O3, whereas those ursane-type encompassing 19-OH (3, 6, 7, 9, 4) were featured by preferred cleavage of H2O while performing the negative collision-induced MS/MS fragmentation on an LTQ/Orbitrap mass spectrometer.
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The proteasome inhibitor, MG132, attenuates diabetic nephropathy by inhibiting SnoN degradation in vivo and in vitro.
Biomed Res Int
PUBLISHED: 02-16-2014
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Transforming growth factor-? (TGF-?) has been shown to be involved in diabetic nephropathy (DN). The SnoN protein can regulate TGF-? signaling through interaction with Smad proteins. Recent studies have shown that SnoN is mainly degraded by the ubiquitin-proteasome pathway. However, the role of SnoN in the regulation of TGF- ?/Smad signaling in DN is still unclear. In this study, diabetic rats were randomly divided into a diabetic control group (DC group) and a proteasome inhibitor (MG132) diabetes therapy group (DT group). Kidney damage parameters and the expression of SnoN, Smurf2, and TGF-? were observed. Simultaneously, we cultured rat glomerular mesangial cells (GMCs) stimulated with high glucose, and SnoN and Arkadia expression were measured. Results demonstrated that 24-hour urine protein, ACR, BUN, and the expression of Smurf2 and TGF- ? were significantly increased (P < 0.05), whereas SnoN was significantly decreased in the DC group (P < 0.05). However, these changes diminished after treatment with MG132. SnoN expression in GMCs decreased significantly (P < 0.05), but Arkadia expression gradually increased due to high glucose stimulation (P < 0.05), which could be almost completely reversed by MG132 (P < 0.05). The present results support the hypothesis that MG132 may alleviate kidney damage by inhibiting SnoN degradation and TGF-? activation, suggesting that the ubiquitin-proteasome pathway may become a new therapeutic target for DN.
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Glycosylated hemoglobin A1c as a marker predicting the severity of coronary artery disease and early outcome in patients with stable angina.
Lipids Health Dis
PUBLISHED: 02-16-2014
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Glycosylated hemoglobin A1C (HbA1c) has been widely recognized as a marker for predicting the severity of diabetes mellitus (DM) and several cardiovascular diseases. However, whether HbA1c could predict the severity and clinical outcomes in patients with stable coronary artery disease (CAD) remains largely unknown. We determine relationship of HbA1c with severity and outcome in patients with stable CAD.
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Impact of admission triglyceride for early outcome in diabetic patients with stable coronary artery disease.
Lipids Health Dis
PUBLISHED: 02-12-2014
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The role of triglyceride (TG) in predicting the outcomes in diabetic patients with coronary artery disease (CAD) has not been well investigated.
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An Update to Returning Genetic Research Results to Individuals: Perspectives of the Industry Pharmacogenomics Working Group.
Bioethics
PUBLISHED: 01-30-2014
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The ease with which genotyping technologies generate tremendous amounts of data on research participants has been well chronicled, a feat that continues to become both faster and cheaper to perform. In parallel to these advances come additional ethical considerations and debates, one of which centers on providing individual research results and incidental findings back to research participants taking part in genetic research efforts. In 2006 the Industry Pharmacogenomics Working Group (I-PWG) offered some 'Points-to-Consider' on this topic within the context of the drug development process from those who are affiliated to pharmaceutical companies. Today many of these points remain applicable to the discussion but will be expanded upon in this updated viewpoint from the I-PWG. The exploratory nature of pharmacogenomic work in the pharmaceutical industry is discussed to provide context for why these results typically are not best suited for return. Operational challenges unique to this industry which cause barriers to returning this information are also explained.
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Association of fibrinogen with severity of stable coronary artery disease in patients with type 2 diabetic mellitus.
Dis. Markers
PUBLISHED: 01-26-2014
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Some studies have suggested a relation of plasma fibrinogen to the severity of coronary artery disease (CAD). However, whether plasma fibrinogen can predict the presence and severity of CAD in patients with diabetes mellitus has not been determined.
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Molecular regulation of macrophages in unleashing cancer-related inflammation.
Oncoimmunology
PUBLISHED: 01-10-2014
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It is unclear how tumor-associated macrophages (TAMs) contribute to the initiation of oncogenesis and how they are regulated at the molecular level. By using a lineage-specific deletion strategy, we found that heat shock protein 90kDa ? (Grp94), member 1 (HSP90B1), a master chaperone for Toll-like receptors and integrins also known as GP96, critically endows TAMs with the ability to promote genotoxic stress and colitis-associated colon cancer.
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Epigallocatechin-3-gallate attenuates impairment of learning and memory in chronic unpredictable mild stress-treated rats by restoring hippocampal autophagic flux.
PLoS ONE
PUBLISHED: 01-01-2014
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Epigallocatechin gallate (EGCG) is a major polyphenol in green tea with beneficial effects on the impairment in learning and memory. Autophagy is a cellular process that protects neurons from stressful conditions. The present study was designed to investigate whether EGCG can rescue chronic unpredictable mild stress (CUMS)-induced cognitive impairment in rats and whether its protective effect involves improvement of autophagic flux. As expected, our results showed that CUMS significantly impaired memory performance and inhibited autophagic flux as indicated by elevated LC3-II and p62 protein levels. At the same time, we observed an increased neuronal loss and activated mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6k) signaling in the CA1 regions. Interestingly, chronic treatment with EGCG (25 mg/kg, i.p.) significantly improved those behavioral alterations, attenuated histopathological abnormalities in hippocampal CA1 regions, reduced amyloid beta1-42 (A?1-42) levels, and restored autophagic flux. However, blocking autophagic flux with chloroquine, an inhibitor of autophagic flux, reversed these effects of EGCG. Taken together, these findings suggest that the impaired autophagy in CA1 regions of CUMS rats may contribute to learning and memory impairment. Therefore, we conclude that EGCG attenuation of CUMS-induced learning and memory impairment may be through rescuing autophagic flux.
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Genotypic diversity analysis of Mycobacterium tuberculosis strains collected from Beijing in 2009, using spoligotyping and VNTR typing.
PLoS ONE
PUBLISHED: 01-01-2014
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Tuberculosis (TB) is a serious problem in China. While there have been some studies on the nationwide genotyping of Mycobacterium tuberculosis (M. tuberculosis), there has been little detailed research in Beijing, the capital of China, which has a huge population. Here, M. tuberculosis clinical strains collected in Beijing during 2009 were genotyped by classical methods.
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Relation of leukocytes and its subsets counts with the severity of stable coronary artery disease in patients with diabetic mellitus.
PLoS ONE
PUBLISHED: 01-01-2014
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Both coronary artery disease (CAD) and diabetes mellitus (DM) are associated with inflammation. However, whether and which leukocytes can predict the presence and extent of CAD in patients with DM has not been investigated. The aim of the present study was to examine the association of leukocyte and its subsets counts with the severity of CAD in patients with DM.
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Upregulation of ?1-adrenoceptors is involved in the formation of gastric dysmotility in the 6-hydroxydopamine rat model of Parkinson's disease.
Transl Res
PUBLISHED: 01-01-2014
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Gastrointestinal dysmotility is one of the nonmotor symptoms of Parkinson's disease (PD). Gastroparesis and upregulated ?-adrenoceptors (?-ARs) have been reported in rats with bilateral microinjection of 6-hydroxydopamine (6-OHDA) in the substantia nigra, but the underlying mechanism is unclear. The aim of the current study is to investigate the role of ?-ARs in gastroparesis in 6-OHDA rats. Gastric motility was studied through strain gauge measurement. Immunofluorescence, real-time reverse transcription-polymerase chain reaction and Western blotting were performed to examine the expression of ?-ARs. Norepinephrine (NE) inhibited gastric motility in a dose-dependent fashion in both control and 6-OHDA rats, but much stronger adrenergic reactivity was observed in the 6-OHDA rats. The inhibition of gastric motility by NE in both control and 6-OHDA rats was not affected by tetrodotoxin, a neural sodium channel blocker. Blocking ?1-AR or ?2-AR did not affect the inhibition of strip contraction by NE in control rats, but ?1-AR blockage obviously enhanced the half maximal inhibitory concentration value of NE in 6-OHDA rats. Selective inhibition of ?3-AR blocked the effect of NE significantly in both control and 6-OHDA rats. The protein expression of ?1-AR, but not ?2-AR and ?3-AR in gastric muscularis externa was increased significantly in 6-OHDA rats. In conclusion, ?3-AR involves the regulation of gastric motility in control rats, whereas the upregulation of ?1-AR is responsible for enhanced NE reactivity in 6-OHDA rats and therefore is involved in the formation of gastroparesis. The effect of both ?1-AR and ?3-AR on gastric motility is independent of the enteric nervous system.
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[Determination of eight ginsenosides in renshenshouwu capsules by HPLC-DAD].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 12-31-2013
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To establish an HPLC-DAD method for simultaneous determination of eight ginsenosides in Renshenshouwu capsules.
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[Preliminary screening of activity fraction of Alchornea trewioides suppresses expression of subgenomic hepatitis C virus RNA in vitro].
Zhong Yao Cai
PUBLISHED: 12-31-2013
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To screen activity fraction of Alchornea trewioides which suppresses expression of subgenomic Hepatitis C Virus (HCV) RNA in vitro.
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[Chronic combined effects of fluoride and arsenite on the Runx2 and downstream related factors of bone metabolism in rats].
Zhonghua Yu Fang Yi Xue Za Zhi
PUBLISHED: 12-20-2013
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To observe the chronic combined effects of sodium fluoride and sodium arsenite on the Runx2 and downstream related factors of bone metabolism in SD rats.
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Research on the relationship between fibrinogen level and subtypes of the TOAST criteria in the acute ischemic stroke.
BMC Neurol
PUBLISHED: 12-09-2013
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Cerebral infarction caused by different reasons seems differ in fibrinogen levels, so the current work intends to explore the relationship between the fibrinogen level and subtypes of the TOAST criteria in the acute stage of ischemic stroke.
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Immune chaperone gp96 drives the contributions of macrophages to inflammatory colon tumorigenesis.
Cancer Res.
PUBLISHED: 12-09-2013
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Macrophages are important drivers in the development of inflammation-associated colon cancers, but the mechanistic underpinnings for their contributions are not fully understood. Further, Toll-like receptors (TLR) have been implicated in colon cancer, but their relevant cellular sites of action are obscure. In this study, we show that the endoplasmic reticulum chaperone gp96 is essential in tumor-associated macrophages (TAM) to license their contributions to inflammatory colon tumorigenesis. Mice where gp96 was genetically deleted in a macrophage-specific manner exhibited reduced colitis and inflammation-associated colon tumorigenesis. Attenuation of colon cancer in these mice correlated strikingly with reduced mutation rates of ?-catenin, increased efficiency of the DNA repair machinery and reduced expression of pro-inflammatory cytokines, including IL-17 and IL-23 in the tumor microenvironment. The genotoxic nature of TAM-associated inflammation was evident by increased expression of genes in the DNA repair pathway. Our work deepens understanding of how TAM promote oncogenesis by altering the molecular oncogenic program within epithelial cells, and it identifies gp96 as a lynchpin chaperone needed in TAM to license their function and impact on expression of critical inflammatory cytokines in colon tumorigenesis. -
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Kinetics of Myosin light chain kinase activation of smooth muscle Myosin in an in vitro model system.
Biochemistry
PUBLISHED: 11-11-2013
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During activation of smooth muscle contraction, one myosin light chain kinase (MLCK) molecule rapidly phosphorylates many smooth muscle myosin (SMM) molecules, suggesting that muscle activation rates are influenced by the kinetics of MLCK-SMM interactions. To determine the rate-limiting step underlying activation of SMM by MLCK, we measured the kinetics of calcium-calmodulin (Ca(2+)CaM)-MLCK-mediated SMM phosphorylation and the corresponding initiation of SMM-based F-actin motility in an in vitro system with SMM attached to a coverslip surface. Fitting the time course of SMM phosphorylation to a kinetic model gave an initial phosphorylation rate, kp(o), of ?1.17 heads s(-1) MLCK(-1). Also, we measured the dwell time of single streptavidin-coated quantum dot-labeled MLCK molecules interacting with surface-attached SMM and phosphorylated SMM using total internal reflection fluorescence microscopy. From these data, the dissociation rate constant from phosphorylated SMM was 0.80 s(-1), which was similar to the kp(o) mentioned above and with rates measured in solution. This dissociation rate was essentially independent of the phosphorylation state of SMM. From calculations using our measured dissociation rates and Kd values, and estimates of SMM and MLCK concentrations in muscle, we predict that the dissociation of MLCK from phosphorylated SMM is rate-limiting and that the rate of the phosphorylation step is faster than this dissociation rate. Also, association with SMM (11-46 s(-1)) would be much faster than with pSMM (<0.1-0.2 s(-1)). This suggests that the probability of MLCK interacting with unphosphorylated versus phosphorylated SMM is 55-460 times greater. This would avoid sequestering MLCK to unproductive interactions with previously phosphorylated SMM, potentially leading to faster rates of phosphorylation in muscle.
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[Combined immunoprophylaxis induces changes in anti-hepatitis B surface protein titer in infants born to mothers with positivity for hepatitis B surface antigen].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 10-15-2013
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To conduct a prospective randomized controlled trial of infants born to hepatitis B virus (HBV) surface antigen (HBsAg)-positive mothers in order to investigate the dynamic changes in the titer of anti-HBV surface protein (HBS) induced by treatment with combined immunoprophylaxis (200 IU hepatitis B immunoglobulin (HBIG) and 5 or 10 mug yeast recombinant hepatitis B vaccine), to compare the protective effect of 5 and 10 mug hepatitis B vaccine, and to provide an immunization strategy, monitoring mode and booster immunization schedule for the high-risk group.
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Draft Genome Sequence of Bacillus subtilis Strain S1-4, Which Degrades Feathers Efficiently.
Genome Announc
PUBLISHED: 09-28-2013
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Bacillus subtilis strain S1-4, with the capacity to efficiently degrade feathers, was isolated from chicken feathers. Sequencing showed that the genome of strain S1-4 differs from that of other B. subtilis strains, with limited insertions and deletions. The genome encodes multiple extracellular proteases and keratinases.
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[Retrospective study on the treatment of ankylosing spondylitis with cervical spine fracture: 8 cases report].
Zhongguo Gu Shang
PUBLISHED: 09-11-2013
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To discuss surgical procedures and curative effect of ankylosing spondylitis with cervical spine fracture.
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Dual positive feedback regulation of protein degradation of an extra-cytoplasmic function ? factor for cell differentiation in Streptomyces coelicolor.
J. Biol. Chem.
PUBLISHED: 09-06-2013
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Here we report that in Streptomyces coelicolor, the protein stability of an ECF ? factor SigT, which is involved in the negative regulation of cell differentiation, was completely dependent on its cognate anti-? factor RstA. The degradation of RstA caused a ClpP/SsrA-dependent degradation of SigT during cell differentiation. This was consistent with the delayed morphological development or secondary metabolism in the ?clpP background after rstA deletion or sigT overexpression. Meanwhile, SigT negatively regulated clpP/ssrA expression by directly binding to the clpP promoter (clpPp). The SigT-clpPp interaction could be disrupted by secondary metabolites, giving rise to the stabilized SigT protein and retarded morphological development in a non-antibiotic-producing mutant. Thus a novel regulatory mechanism was revealed that the protein degradation of the ECF ? factor was initiated by the degradation of its anti-? factor, and was accelerated in a dual positive feedback manner, through regulation by secondary metabolites, to promote rapid and irreversible development of the secondary metabolism. This ingenious cooperation of intracellular components can ensure economical and exquisite control of the ECF ? factor protein level for the proper cell differentiation in Streptomyces.
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New perspectives of vesicular monoamine transporter 2 chemical characteristics in mammals and its constant expression in type 1 diabetes rat models.
Transl Res
PUBLISHED: 08-10-2013
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Vesicular monoamine transporter 2 (VMAT2) has been exploited as a biomarker of ?-cell mass in human islets. However, a current report suggested no immunoreactivity of VMAT2 in the ? cells of rat islets. To investigate the cellular localization of VMAT2 in islets further, the pancreatic tissues from monkeys and humans were compared with those of rats and mice. The study was performed using among-species comparisons and a type 1 diabetes model (T1DM) for rats by Western blotting, double-label immunofluorescence, and confocal laser scanning microscopy. We found that VMAT2-immunoreactivity (IR) was distributed peripherally in the islets of rodents, but was widely scattered throughout the islets of primates. Consistent with rodent islets, VMAT2-IR did not exist in insulin (INS)-IR cells but was abundantly present in glucagon (GLU)-IR and pancreatic polypeptide (PP)-IR cells in monkey and human islets. VMAT2-IR had no colocalization with INS-IR in any part of the rat pancreas (head, body, and tail). INS-IR cells were reduced dramatically in T1DM rat islets, but no significant alteration in the proportion of VMAT2-IR cells and GLU-IR cells was observed. Furthermore, a strong colocalization of VMAT2-IR with GLU-IR was distributed in the peripheral regions of diabetic islets. For the first time, the current study demonstrates the presence of VMAT2 in ? cells and PP cells but not in ? cells in the islets of monkeys and humans. This study provides convinced morphologic evidence that VMAT2 is not present in ? cells. There needs to be studies for new markers for ? cell mass.
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Series of dinuclear and tetranuclear lanthanide clusters encapsulated by salen-type and ?-diketionate ligands: single-molecule magnet and fluorescence properties.
Dalton Trans
PUBLISHED: 07-26-2013
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Three dinuclear [Ln2H2OL(1)2(acac)2]·solvent (1, Ln = Gd, solvent = 2CH2Cl2; 2, Ln = Tb, no solvent; 3, Ln = Er, solvent = (C2H5)2O), and two tetranuclear lanthanide clusters [Ln4(?3-OH)2L(2)2(acac)6]·2(solvent) (4, Ln = Tb, solvent = CH3OH; 5, Ln = Dy, solvent = CH3CN) were characterized in terms of structure, fluorescence and magnetism. The dinuclear lanthanide complexes were constructed by a rigid salen-type ligand H2L(1) = N,N-bis(salicylidene)-o-phenylenediamine and ?-diketonate (acac = acetylacetonate) ligands, while the tetranuclear clusters were formed from the flexible ligand H2L(2) = N,N-bis(salicylidene)-1,2-ethanediamine. Crystal structure analysis indicates that the rigid ligand favors the double-decker sandwich structure (Ln2L(1)2), in which the two lanthanide ions have different coordination numbers and geometry, while the more flexible ligand (H2L(2)) leads to planar tetranuclear clusters. The relationship between their respective magnetic anisotropy and ligand-field geometries and their fluorescence properties was investigated. The Dy and Tb-containing clusters exhibit typical visible fluorescence properties, and single-molecule magnet behavior is seen in complex 5.
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High glucose induces activation of NF-?B inflammatory signaling through I?B? sumoylation in rat mesangial cells.
Biochem. Biophys. Res. Commun.
PUBLISHED: 07-11-2013
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The posttranslational modification of proteins by small ubiquitin-like modifiers (SUMOs) has emerged as an important regulatory mechanism for the alteration of protein activity, stability, and cellular localization. The latest research demonstrates that sumoylation is extensively involved in the regulation of the nuclear factor ?B (NF-?B) pathway, which plays a critical role in the regulation of inflammation and contributes to fibrosis in diabetic nephropathy (DN). However, the role of sumoylation in the regulation of NF-?B signaling in DN is still unclear. In the present study, we cultured rat glomerular mesangial cells (GMCs) stimulated by high glucose and divided GMCs into six groups: normal glucose group (5.6mmol/L), high glucose groups (10, 20, and 30mmol/L), mannitol group (i.e., osmotic control group), and MG132 intervention group (30mmol/L glucose with MG132, a proteasome inhibitor). The expression of SUMO1, SUMO2/3, I?B?, NF-?Bp65, and monocyte chemotactic protein 1 (MCP-1) was measured by Western blot, reverse-transcription polymerase chain reaction, and indirect immunofluorescence laser scanning confocal microscopy. The interaction between SUMO1, SUMO2/3, and I?B? was observed by co-immunoprecipitation. The results showed that the expression of SUMO1 and SUMO2/3 was dose- and time-dependently enhanced by high glucose (p<0.05). However, the expression of I?B? sumoylation in high glucose was significantly decreased compared with the normal glucose group (p<0.05). The expression of I?B? was dose- and time-dependently decreased, and NF-?Bp65 and MCP-1 were increased under high glucose conditions, which could be mostly reversed by adding MG132 (p<0.05). The present results support the hypothesis that high glucose may activate NF-?B inflammatory signaling through I?B? sumoylation and ubiquitination.
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Accelerated tumor growth mediated by sublytic levels of antibody-induced complement activation is associated with activation of the PI3K/AKT survival pathway.
Clin. Cancer Res.
PUBLISHED: 07-05-2013
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We addressed the possibility that low levels of tumor cell-bound antibodies targeting gangliosides might accelerate tumor growth.
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Comparison of methods for detoxification of spruce hydrolysate for bacterial cellulose production.
Microb. Cell Fact.
PUBLISHED: 06-18-2013
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Bacterial cellulose (BC) is a nanostructured material with unique properties and wide applicability. In order to decrease the production cost of bacterial cellulose, lignocellulose-based media have considerable potential as alternative cost-effective feedstocks. However, pretreatment and enzymatic hydrolysis of lignocellulose to sugars also generate fermentation inhibitors. Detoxification of lignocellulosic hydrolysates is needed to achieve efficient production of BC. In this investigation, different methods for detoxification of spruce hydrolysate prior to production of BC were compared with respect to effects on potential inhibitors and fermentable sugars, sugar consumption, BC yield, and cell viability. The objectives were to identify efficient detoxification methods and to achieve a better understanding of the role played by different inhibitors in lignocellulosic hydrolysates.
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The effect of donor-recipient gender mismatch on short- and long-term graft survival in kidney transplantation: a systematic review and meta-analysis.
Clin Transplant
PUBLISHED: 06-10-2013
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There is no limitation of gender matching in renal transplantation. This study was intended to evaluate its effect on short- and long-term graft survival.
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Arsenic may be involved in fluoride-induced bone toxicity through PTH/PKA/AP1 signaling pathway.
Environ. Toxicol. Pharmacol.
PUBLISHED: 06-06-2013
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Chronic exposure to combined fluoride and arsenic continues to be a major public health problem worldwide, affecting thousands of people. In recent years, more and more researchers began to focus on the interaction between the fluorine and the arsenic. In this study, the selected investigation site was located in China. The study group was selected from people living in fluoride-arsenic polluted areas due to burning coal. The total number of participants was 196; including the fluoride-arsenic anomaly group (130) and the fluoride-arsenic normal group (63). By observing the changes in gene and protein expression of PTH/PKA/AP1 signaling pathway, the results show that fluoride can increase the expression levels of PTH, PKA, and AP1, but arsenic can only affect the expression of AP1; fluoride and arsenic have an interaction on the expression of AP1. Further study found that fluoride and arsenic can affect the mRNA expression level of c-fos gene (AP1 family members), and have an interaction on the expression of c-fos, but not c-jun. The results indicate that PTH/PKA/AP1 signaling pathway may play an important role in bone toxicity of fluoride. Arsenic can affect the expression of c-fos, thereby affecting the expression of transcription factor AP1, indirectly involved in fluoride-induced bone toxicity.
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Phenanthrenes, 9,10-dihydrophenanthrenes, bibenzyls with their derivatives, and malate or tartrate benzyl ester glucosides from tubers of Cremastra appendiculata.
Phytochemistry
PUBLISHED: 06-03-2013
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Eleven previously unknown compounds and 23 known compounds, including 20 phenanthrene or 9,10-dihydrophenanthrene derivatives, five bibenzyls, seven malate or tartrate benzyl ester glucosides, adenosine and gastrodin were isolated from tubers of Cremastra appendiculata. Among the obtained compounds, two are the first isolated dimers with one phenanthrene or bibenzyl unit connected to C-3 of 2,3,4,5-tetrahydro-phenanthro[2,1-b]furan moiety. In addition, 33 of these compounds were evaluated in vitro for their cytotoxic activity against two cancer cell lines. Among the compounds examined, one compound showed moderate cytotoxic activity, while five showed weak cytotoxic activity against the A549 cell line.
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A simple and reproducible method for directed evolution: combination of random mutation with dITP and DNA fragmentation with endonuclease V.
Mol. Biotechnol.
PUBLISHED: 05-28-2013
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An alternative method to combine mutagenesis PCR with dITP and fragmentation by endonuclease V for directed evolution was developed. In comparison to the routine protocol for directed evolution, dITP was used as mutation reagent in the mutagenesis PCR. Subsequently, the incorporated dITP in the PCR products could represent as being the target of endonuclease V. Finally, the mutated dsDNA was fragmented by endonuclease V and then shuffled via assembly and reamplification as is usually done. In this study, the gene encoding kanamycin resistance has been used as reporter to verify the novel method for directed evolution. However, the mutation frequency could be easily adjusted by the amount of dITP used in the mutagenesis PCR reaction. Besides, this protocol yielded the mutation types with an obvious bias to transition substitutions as the normal error-prone PCR did. Conclusively, this novel method for directed evolution has been demonstrated to be efficient, reproducible, and easy to handle in actual practice. Using this protocol, we have successfully constructed a random mutation library for the gene encoding a serine alkaline protease.
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?7 helix region of ?I domain is crucial for integrin binding to endoplasmic reticulum chaperone gp96: a potential therapeutic target for cancer metastasis.
J. Biol. Chem.
PUBLISHED: 05-13-2013
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Integrins play important roles in regulating a diverse array of cellular functions crucial to the initiation, progression, and metastasis of tumors. Previous studies have shown that a majority of integrins are folded by the endoplasmic reticulum chaperone gp96. Here, we demonstrate that the dimerization of integrin ?L and ?2 is highly dependent on gp96. The ?I domain (AID), a ligand binding domain shared by seven integrin ?-subunits, is a critical region for integrin binding to gp96. Deletion of AID significantly reduced the interaction between integrin ?L and gp96. Overexpression of AID intracellularly decreased surface expression of gp96 clients (integrins and Toll-like receptors) and cancer cell invasion. The ?7 helix region is crucial for AID binding to gp96. A cell-permeable ?7 helix peptide competitively inhibited the interaction between gp96 and integrins and blocked cell invasion. Thus, targeting the binding site of ?7 helix of AID on gp96 is potentially a new strategy for treatment of cancer metastasis.
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Role of caveolin-1 and caveolae signaling in endotoxemia and sepsis.
Life Sci.
PUBLISHED: 05-09-2013
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Caveolae, plasma membrane invaginations of 60-80nm in diameter, are a subset of lipid rafts enriched in cholesterol and sphingolipids. Caveolae are expressed in various tissues and cell types, such as endothelial cells, macrophages, neutrophils and adipocytes. The functions of caveolae are diverse and include endocytosis, transcytosis, potocytosis, calcium signaling, and regulation of various signaling events. Although growing evidence has increased our understanding of caveolae function, the role of caveolae in sepsis is still a controversial issue. In this review, we present a number of studies addressing caveolae and sepsis and describe the signaling pathways involved, including the LPS-eNOS-TLR4-NF?B, MKK3/p38 MAPK, cPLA2/p38 MAPK, STAT3/NF?B and IL-1?-IL-1R1 pathways. Different studies using endotoxemia and bacteremia animal models have provided distinct conclusions about the function of caveolae, and we discuss these inconsistencies. Taken together, the current data suggest that the function of caveolae in sepsis, which involves a number of signaling pathways, is complex and warrants further studies.
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Document authentication at molecular levels using desorption atmospheric pressure chemical ionization mass spectrometry imaging.
J Mass Spectrom
PUBLISHED: 05-08-2013
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Molecular images of documents were obtained by sequentially scanning the surface of the document using desorption atmospheric pressure chemical ionization mass spectrometry (DAPCI-MS), which was operated in either a gasless, solvent-free or methanol vapor-assisted mode. The decay process of the ink used for handwriting was monitored by following the signal intensities recorded by DAPCI-MS. Handwritings made using four types of inks on four kinds of paper surfaces were tested. By studying the dynamic decay of the inks, DAPCI-MS imaging differentiated a 10-min old from two 4 h old samples. Non-destructive forensic analysis of forged signatures either handwritten or computer-assisted was achieved according to the difference of the contour in DAPCI images, which was attributed to the strength personalized by different writers. Distinction of the order of writing/stamping on documents and detection of illegal printings were accomplished with a spatial resolution of about 140 µm. A Matlab® written program was developed to facilitate the visualization of the similarity between signature images obtained by DAPCI-MS. The experimental results show that DAPCI-MS imaging provides rich information at the molecular level and thus can be used for the reliable document analysis in forensic applications.
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Essential roles of grp94 in gut homeostasis via chaperoning canonical Wnt pathway.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-09-2013
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Increasing evidence points to a role for the protein quality control in the endoplasmic reticulum (ER) in maintaining intestinal homeostasis. However, the specific role for general ER chaperones in this process remains unknown. Herein, we report that a major ER heat shock protein grp94 interacts with MesD, a critical chaperone for the Wnt coreceptor low-density lipoprotein receptor-related protein 6 (LRP6). Without grp94, LRP6 fails to export from the ER to the cell surface, resulting in a profound loss of canonical Wnt signaling. The significance of this finding is demonstrated in vivo in that grp94 loss causes a rapid and profound compromise in intestinal homeostasis with gut-intrinsic defect in the proliferation of intestinal crypts, compromise of nuclear ?-catenin translocation, loss of crypt-villus structure, and impaired barrier function. Taken together, our work has uncovered the role of grp94 in chaperoning LRP6-MesD in coordinating intestinal homeostasis, placing canonical Wnt-signaling pathway under the direct regulation of the general protein quality control machinery in the ER.
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Percutaneous coronary intervention with anomalous origin of right coronary artery: case reports and literature review.
J Geriatr Cardiol
PUBLISHED: 04-03-2013
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Percutaneous coronary intervention (PCI) in an anomalous right coronary artery (RCA) can be technically difficult because selective cannulation of the vessel may not be easy. We thereby present two cases with unstable angina pectoris of anomalous originated RCA. The PCI were successfully performed in two patients with a special guiding wire manipulating skill which we called "gone with the flow" combined with balloon anchoring technology, providing excellent angiographic visualization and sound guide support for stent delivery throughout the procedure without severe cardiovascular adverse effects. Our primary data suggested that PCI for geriatric patients with an anomalous origin of RCA accompanied by severe atherosclerotic lesions might also be a safe, available, and feasible strategy.
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Positive feedback regulation of stgR expression for secondary metabolism in Streptomyces coelicolor.
J. Bacteriol.
PUBLISHED: 03-01-2013
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LysR-type transcriptional regulators (LTTRs) compose a large family and are responsible for various physiological functions in bacteria, while little is understood about their regulatory mechanism on secondary metabolism in Streptomyces. Here we reported that StgR, a typical LTTR in Streptomyces coelicolor, was a negative regulator of undecylprodigiosin (Red) and ?-actinorhodin (Act) production in the early developmental phase of secondary metabolism by suppressing the expression of two pathway-specific regulator genes, redD and actII-orf4, respectively. Meanwhile, stgR expression was downregulated during secondary metabolism to remove its repressive effects on antibiotic production. Moreover, stgR expression was positively autoregulated by direct binding of StgR to its own promoter (stgRp), and the binding site adjacent to translation start codon was determined by a DNase I footprinting assay. Furthermore, the StgR-stgRp interaction could be destroyed by the antibiotic ?-actinorhodin produced from S. coelicolor. Thus, our results suggested a positive feedback regulatory mechanism of stgR expression and antibiotic production for the rapid and irreversible development of secondary metabolism in Streptomyces.
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[Health survey of plant workers for an occupational exposure to ammonium perchlorate].
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi
PUBLISHED: 02-26-2013
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To understand the occupational hazards of ammonium perchlorate dust on operating workers and to provide the basis preventive measures for protecting the workers health.
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Electroacupuncture Stimulation at CV12 Inhibits Gastric Motility via TRPV1 Receptor.
Evid Based Complement Alternat Med
PUBLISHED: 02-25-2013
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Gastric dysmotility is one of the major pathophysiological factors in functional gastrointestinal disorders. Acupuncture, as one of the alternative approaches, is efficacious in the treatment of gastrointestinal motility disorders; however, the mechanism underlying its action is unclear. In the present study, we used both capsazepine, a TRPV1 antagonist, and TRPV1 knockout mice. Animals were divided into wild-type group (WT), capsazepine injection group (CZP, 0.5?mg/kg, i.p.), and TRPV1 knockout mice group (TRPV1(-/-)). Each of these three groups was divided into three subgroups, which were subjected to EA stimulation at acupoint Zhongwan (CV12) at a different intensity (1, 2, or 4?mA). We demonstrated that electroacupuncture at Zhongwan (CV12) markedly inhibited gastric motility at 2 and 4?mA in an intensity-dependent manner in wild-type mice. The inhibitory effect was also observed in capsazepine-injected and TRPV1(-/-) mice but was no longer intensity dependent, indicating that TRPV1 is partially involved in the electroacupuncture-mediated modulation of gastric motility.
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The design and features of apatite-coated chitosan microspheres as injectable scaffold for bone tissue engineering.
Biomed Mater
PUBLISHED: 02-22-2013
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In this paper we developed two types of chitosan-based microspheres with and without biomimetic apatite coatings and compared their potential as injectable scaffolds for bone regeneration. The microspheres were obtained by emulsion cross-linking (E0) and coacervate precipitation (C0), respectively. They were then biomimetically coated with apatite to become E1 and C1 microspheres. The physicochemical properties and biocompatibility of the microspheres were characterized. Both E0 and C0 microspheres presented favorable ranges of diameter, density and Rockwell hardness. However, there were differences in the degree of cross-linking, shape, morphology, degradation rate, swelling rate, pH value after PBS immersion and the biocompatibility between E0 and C0. The apatite coating was successfully prepared for both C0 and E0, which enhanced the attachment, proliferation and differentiation of MC3T3-E1 cells. In conclusion, our results suggest the feasibility of using chitosan microspheres as a potential injectable scaffold. Both the preparation method and the biomimetic apatite coating contribute to their biological properties.
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PI3K/mTOR inhibition can impair tumor invasion and metastasis in vivo despite a lack of antiproliferative action in vitro: implications for targeted therapy.
Breast Cancer Res. Treat.
PUBLISHED: 02-21-2013
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Oncogenic PI3K/mTOR activation is frequently observed in human cancers and activates cell motility via p27 phosphorylations at T157 and T198. Here we explored the potential for a novel PI3K/mTOR inhibitor to inhibit tumor invasion and metastasis. An MDA-MB-231 breast cancer line variant, MDA-MB-231-1833, with high metastatic bone tropism, was treated with a novel catalytic PI3K/mTOR inhibitor, PF-04691502, at nM doses that did not impair proliferation. Effects on tumor cell motility, invasion, p27 phosphorylation, localization, and bone metastatic outgrowth were assayed. MDA-MB-231-1833 showed increased PI3K/mTOR activation, high levels of cytoplasmic p27pT157pT198 and increased cell motility and invasion in vitro versus parental. PF-04691502 treatment, at a dose that did not affect proliferation, reduced total and cytoplasmic p27, decreased p27pT157pT198 and restored cell motility and invasion to levels seen in MDA-MB-231. p27 knockdown in MDA-MB-231-1833 phenocopied PI3K/mTOR inhibition, whilst overexpression of the phosphomimetic mutant p27T157DT198D caused resistance to the anti-invasive effects of PF-04691502. Pre-treatment of MDA-MB-231-1833 with PF-04691502 significantly impaired metastatic tumor formation in vivo, despite lack of antiproliferative effects in culture and little effect on primary orthotopic tumor growth. A further link between cytoplasmic p27 and metastasis was provided by a study of primary human breast cancers which showed cytoplasmic p27 is associated with increased lymph nodal metastasis and reduced survival. Novel PI3K/mTOR inhibitors may oppose tumor metastasis independent of their growth inhibitory effects, providing a rationale for clinical investigation of PI3K/mTOR inhibitors in settings to prevent micrometastasis. In primary human breast cancers, cytoplasmic p27 is associated with worse outcomes and increased nodal metastasis, and may prove useful as a marker of both PI3K/mTOR activation and PI3K/mTOR inhibitor efficacy.
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Production of bacterial cellulose and enzyme from waste fiber sludge.
Biotechnol Biofuels
PUBLISHED: 02-14-2013
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Bacterial cellulose (BC) is a highly crystalline and mechanically stable nanopolymer, which has excellent potential as a material in many novel applications, especially if it can be produced in large amounts from an inexpensive feedstock. Waste fiber sludge, a residue with little or no value, originates from pulp mills and lignocellulosic biorefineries. A high cellulose and low lignin content contributes to making the fiber sludge suitable for bioconversion, even without a thermochemical pretreatment step. In this study, the possibility to combine production of BC and hydrolytic enzymes from fiber sludge was investigated. The BC was characterized using field-emission scanning electron microscopy and X-ray diffraction analysis, and its mechanical properties were investigated.
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Elution-extrusion counter-current chromatography separation of two new benzyl ester glucosides and three other high-polarity compounds from the tubers of Pleione bulbocodioides.
Phytochem Anal
PUBLISHED: 01-29-2013
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The tubers of Pleione bulbocodioides (Franch.) Rolfe, with gastrodin and benzyl ester glucosides as main components, have been used in traditional Chinese medicine for the treatment of various cancers and bacterial infections. Up to now, their official quality control method is still inadequate, and the difficulty of obtaining these high-polarity compounds is one of the major reasons.
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A novel mechanism of formaldehyde neurotoxicity: inhibition of hydrogen sulfide generation by promoting overproduction of nitric oxide.
PLoS ONE
PUBLISHED: 01-24-2013
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Formaldehyde (FA) induces neurotoxicity by overproduction of intracellular reactive oxygen species (ROS). Increasing studies have shown that hydrogen sulfide (H(2)S), an endogenous gastransmitter, protects nerve cells against oxidative stress by its antioxidant effect. It has been shown that overproduction of nitric oxide (NO) inhibits the activity of cystathionine-beta-synthase (CBS), the predominant H(2)S-generating enzyme in the central nervous system.
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A review on indole alkaloids isolated from Uncaria rhynchophylla and their pharmacological studies.
Fitoterapia
PUBLISHED: 01-21-2013
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Uncaria rhynchophylla (Miq.) Jacks, Rubiaceae, is one of the original plants of the important Chinese crude drug, Gou-teng, mainly used for the treatment of convulsion, hypertension, epilepsy, eclampsia, and cerebral diseases. The pharmacological activities of this plant are related to the presence of active compounds predominantly indole alkaloids. In this article, we have reviewed some reports about the pharmacological activities of the main indole alkaloids isolated from U. rhynchophylla. This review paper will contribute to the studies on the chemistry, safety and quality control of medicinal preparations containing Uncaria species.
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Simultaneous determination of 24 constituents in Cortex Lycii using high-performance liquid chromatography-triple quadrupole mass spectrometry.
J Pharm Biomed Anal
PUBLISHED: 01-05-2013
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A fast high-performance liquid chromatography (HPLC) coupled with electrospray ionization (ESI) tandem mass spectrometry method was developed to determine 24 components including 11 phenolic compounds, 9 phenolic amides, and 4 cyclic peptides in Cortex Lycii. The analytes were quantified by a triple quadrupole instrument in multiple reaction monitoring (MRM) mode. The fragmentation patterns of phenolic amides and cyclic peptides using ESI and collision-induced dissociation (CID) techniques are reported. This assay method was validated with respect to linearity (r(2)>0.9920), precision, repeatability, and accuracy (recovery rate between 93.0 and 105.9% with RSD<4.4%). The analytical results of 28 batches of Cortex Lycii indicated that cyclic peptides and phenolic amides were not only the abundant constituents, but also the characteristic components for Cortex Lycii to distinguish from the adulterants. Principle component analysis (PCA) was used to discriminate samples from different geographical regions of China, and cyclic peptides were considered to be the chemical markers responsible for the classification. The systematic and integrated assessment of Cortex Lycii provides sufficient evidence for the establishment of the quality standard.
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Neolignanamides, lignanamides, and other phenolic compounds from the root bark of Lycium chinense.
J. Nat. Prod.
PUBLISHED: 01-02-2013
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Seven new neolignanamides (1-7), including two pairs of cis- and trans-isomers, and a new lignanamide (8) were isolated from the EtOAc-soluble fraction of an EtOH extract of the root bark of Lycium chinense, together with 22 known phenolic compounds (9-30), four of which were obtained from the genus Lycium for the first time. Compounds 5, 6, and 7 are unusual dimers having a rare connection mode between the two cinnamic acid amide units, while compounds 6, 7, and 8 are the first naturally occurring dimers derived from two dissimilar cinnamic acid amides. The cinnamic acid amides, neolignanamides, and lignanamides possess moderate radical-scavenging activity against the DPPH (2,2-diphenyl-1-picrylhydrazyl) and superoxide radicals.
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Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease.
PLoS ONE
PUBLISHED: 01-01-2013
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Galectin-3 protein is critical to the development of liver fibrosis because galectin-3 null mice have attenuated fibrosis after liver injury. Therefore, we examined the ability of novel complex carbohydrate galectin inhibitors to treat toxin-induced fibrosis and cirrhosis. Fibrosis was induced in rats by intraperitoneal injections with thioacetamide (TAA) and groups were treated with vehicle, GR-MD-02 (galactoarabino-rhamnogalaturonan) or GM-CT-01 (galactomannan). In initial experiments, 4 weeks of treatment with GR-MD-02 following completion of 8 weeks of TAA significantly reduced collagen content by almost 50% based on Sirius red staining. Rats were then exposed to more intense and longer TAA treatment, which included either GR-MD-02 or GM-CT-01 during weeks 8 through 11. TAA rats treated with vehicle developed extensive fibrosis and pathological stage 6 Ishak fibrosis, or cirrhosis. Treatment with either GR-MD-02 (90 mg/kg ip) or GM-CT-01 (180 mg/kg ip) given once weekly during weeks 8-11 led to marked reduction in fibrosis with reduction in portal and septal galectin-3 positive macrophages and reduction in portal pressure. Vehicle-treated animals had cirrhosis whereas in the treated animals the fibrosis stage was significantly reduced, with evidence of resolved or resolving cirrhosis and reduced portal inflammation and ballooning. In this model of toxin-induced liver fibrosis, treatment with two galectin protein inhibitors with different chemical compositions significantly reduced fibrosis, reversed cirrhosis, reduced galectin-3 expressing portal and septal macrophages, and reduced portal pressure. These findings suggest a potential role of these drugs in human liver fibrosis and cirrhosis.
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