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Calcium-containing biochar ï¼ES-BCï¼ was prepared by pyrolyzing eggshell and kitchen wastesï¼ and the ES-BC composite was used to remove phosphate ï¼marked as ES-BC/Pï¼. Based on the high affinity of phosphate and carbonate to leadï¼ the ES-BC/P was then used to remove lead from the water. The results showed thatï¼ in the appropriate dosageï¼ ES-BC/P could remove lead efficiently at different initial concentrations ï¼1-100 mg·L-1ï¼ï¼ and the removal efficiency could reach to 99%. Meanwhileï¼ the release of phosphorus could be ignored after the reaction. As ES-BC/P was alkalineï¼ and the lead-containing solution was weakly acidicï¼ the addition of ES-BC/P could adjust the pH of the system automatically. The reaction kinetics and isotherm experiments showed that the lead removal by ES-BC/P was mainly monolayer chemisorption with a maximum adsorption capacity of 493.12 mg·g-1 ï¼318 Kï¼. The characterization results showed that lead was mainly removed through the ion exchanges of Pb2+ in the solution with Ca2+ in ES-BC/P. Thenï¼ the Pb2+ combined with CO32- and PO42- to form many precipitatesï¼ including Pb5ï¼PO4ï¼3OHï¼ Pb10ï¼PO4ï¼6ï¼OHï¼2ï¼ PbCO3ï¼ and Pb3ï¼CO3ï¼2ï¼OHï¼2. In summaryï¼ the ES-BC/P material could achieve the efficient removal of lead from the waterï¼ thereby realizing the resource utilization of the wastes.
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Two previously undescribed cholestanol saponins, parpetiosides F - G (1-2), and six known analogs (3-8) were isolated from the rhizomes of Paris fargesii var. petiolata. Their structures were elucidated by extensive spectroscopic data analysis and chemical methods. Compound 1 was a rare 6/6/6/5/5 fused-rings cholestanol saponin with disaccharide moiety linked at C-26 of aglycone which was hardly seen in genus Paris. All of these compounds were discovered in this plant for the first time. In addition, the cytotoxicities of saponins (1-8) against three human cancer cell lines (U87, HepG2 and SGC-7901) were evaluated by CCK-8 method, and saponins 5-8 displayed certain cytotoxicities. The strong interactions between saponins 5-8 and SCUBE3, an oncogene for glioma cells, were displayed by molecular docking.
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Antineoplásicos Fitogênicos , Colestanol , Simulação de Acoplamento Molecular , Rizoma , Saponinas , Rizoma/química , Humanos , Saponinas/isolamento & purificação , Saponinas/farmacologia , Saponinas/química , Estrutura Molecular , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Colestanol/farmacologia , Colestanol/química , Colestanol/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Melanthiaceae/química , China , Liliaceae/químicaRESUMO
The traditional Chinese medicine bufalin, extracted from toad's skin, has been demonstrated to exert anticancer activities in various kinds of human cancers. The mechanisms of action lie in its capacity to induce apoptosis, or termed type I programmed cell death (PCD). However, type II PCD, or autophagy, participates in cancer proliferation, progression, and relapse, as well. Recent studies on autophagy seem to be controversial because of the dual roles of autophagy in cancer survival and death. In good agreement with previous studies, we found that 100 nM bufalin induced extensive HepG2 cell apoptosis. However, we also noticed bufalin triggered autophagy and enhanced Beclin-1 expression, LC3-I to LC3-II conversion, as well as decreased p62 expression and mTOR signaling activation in HepG2 cells. Blockage of autophagy by selective inhibitor 3-MA decreased apoptotic ratio in bufalin-treated HepG2 cells, suggesting a proapoptotic role of bufalin-induced autophagy. Furthermore, we investigated the underlying mechanisms of bufalin-induced autophagy. Bufalin treatment dose-dependently promoted AMPK phosphorylation while AMPK inhibition by compound C significantly attenuated bufalin-induced autophagy. Taken together, we report for the first time that bufalin induces HepG2 cells PCD, especially for autophagy, and the mechanism of action is, at least in part, AMPK-mTOR dependent.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Bufanolídeos/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/química , Proteínas Reguladoras de Apoptose/metabolismo , Proteína Beclina-1 , Western Blotting , Bufanolídeos/química , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/ultraestrutura , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/ultraestrutura , Proteínas de Membrana/metabolismo , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Proteínas Associadas aos Microtúbulos/metabolismo , Estrutura Molecular , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: The dried bark of Ailanthus altissima (Mill.) Swingle is widely used in traditional Chinese medicine for the treatment of ulcerative colitis. The objective of this study was to explore the therapeutic basis of the dried bark of Ailanthus altissima (Mill.) Swingle for the treatment of ulcerative colitis based on Virtual Screening-Molecular Docking-Activity Evaluation technology. METHODS: By searching the Traditional Chinese Medicine Systems Pharmacology TCMSP Database and Analysis Platform, 89 compounds were obtained from the chemical components of the dried bark of Ailanthus altissima (Mill.) Swingle. Then, after preliminarily screening the compounds based on Lipinski's rule of five and other relevant conditions, the AutoDock Vina molecular docking software was used to evaluate the affinity of the compounds to ulcerative colitis-related target proteins and their binding modes through use of the scoring function to identify the best candidate compounds. Further verification of the compound's properties was achieved through in vitro experiments. RESULTS: Twenty-two compounds obtained from the secondary screening were molecularly docked with ulcerative colitis-related target proteins (IL-1R, TLR, EGFR, TGFR, and Wnt) using AutoDock Vina. The free energies of the highest scoring compounds binding to the active cavity of human IL-1R, TLR, EGFR, TGFR, and Wnt proteins were - 8.7, - 8.0, - 9.2, - 7.7, and - 8.5 kcal/mol, respectively. The potential compounds, dehydrocrebanine, ailanthone, and kaempferol, were obtained through scoring function and docking mode analysis. Furthermore, the potential compound ailanthone (1, 3, and 10 µM) was found to have no significant effect on cell proliferation, though at 10 µM it reduced the level of pro-inflammatory factors caused by lipopolysaccharide. CONCLUSION: Among the active components of the dried bark of Ailanthus altissima (Mill.) Swingle, ailanthone plays a major role in its anti-inflammatory properties. The present study shows that ailanthone has advantages in cell proliferation and in inhibiting of inflammation, but further animal research is needed to confirm its pharmaceutical potential.
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Ailanthus , Colite Ulcerativa , Humanos , Animais , Ailanthus/química , Simulação de Acoplamento Molecular , Colite Ulcerativa/tratamento farmacológico , Casca de Planta/química , Receptores ErbBRESUMO
Genistein, a major phytoestrogen of soy, is considered a potential drug for the prevention and treatment of post-menopausal osteoporosis. Mounting evidence suggested a positive correlation between genistein consumption and bone health both in vivo and in vitro. Earlier studies have revealed that genistein acted as a natural estrogen analogue which activated estrogen receptor and exerted anti-osteoporotic effect. However, it remains unclear whether PTH, the most crucial hormone that regulates mineral homeostasis, participates in the process of genistein-mediated bone protection. In the present study, we compared the therapeutic effects between genistein and nilestriol and investigated whether PTH and its specific receptor PTHR1 altered in response to genistein-containing diet in the animal model of ovariectomy. Our results showed that genistein administration significantly improved femoral mechanical properties and alleviates femoral turnover. Genistein at all doses (4.5 mg/kg, 9.0 mg/kg and 18.0 mg/kg per day, respectively) exerted improved bending strength and b-ALP limiting effects than nilestriol in the present study. However, genistein administration did not exert superior effects on bone protection than nilestriol. We also observed circulating PTH restoration in ovariectomized rats receiving genistein at the dose of 18 mg/kg per day. Meanwhile, PTHR1 abnormalities were attenuated in the presence of genistein as confirmed by RT-PCR, Western blot and immunohistochemistry. These findings strongly support the idea that besides serving as an estrogen, genistein could interact with PTH/PTHR1, causing a superior mineral restoring effect than nilestriol on certain circumstance. In conclusion, our study reported for the first time that the anti-osteoporotic effect of genistein is partly PTH/PTHR1-dependent. Genistein might be a potential option in the prevention and treatment of post-menopausal osteoporosis with good tolerance, more clinical benefits and few undesirable side effects.
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Fêmur/efeitos dos fármacos , Genisteína/farmacologia , Hormônio Paratireóideo/metabolismo , Fitoestrógenos/farmacologia , Substâncias Protetoras/farmacologia , Receptor Tipo 1 de Hormônio Paratireóideo/metabolismo , Fosfatase Alcalina/sangue , Animais , Densidade Óssea/efeitos dos fármacos , Creatinina/sangue , Creatinina/urina , Modelos Animais de Doenças , Estriol/análogos & derivados , Estriol/química , Estriol/farmacologia , Feminino , Fêmur/fisiologia , Genisteína/química , Genisteína/uso terapêutico , Humanos , Rim/metabolismo , Rim/patologia , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/patologia , Osteoporose Pós-Menopausa/prevenção & controle , Ovariectomia , Hormônio Paratireóideo/sangue , Hormônio Paratireóideo/urina , Fitoestrógenos/química , Fitoestrógenos/uso terapêutico , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , Quinestrol/análogos & derivados , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Hormônio Paratireóideo/genética , Resistência à TraçãoRESUMO
OBJECTIVE: To study the HPLC fingerprint of toad skin and provide a reliable method for quality control and identification. METHODS: It used HPLC for detection and computer aided similarity evaluation system for processing and analysing HPLC fingerprint. RESULTS: The common pattern of HPLC fingerprint of toad skin was astablished, 29 peaks were identified as the characteristic fingerprints, in which 9 peaks corresponded to 9 bufogenins. (2) Each samples' similarity of relative retention time was all above 0.99, but the similarity of relative peak areas was low. CONCLUSION: (1) The method is accurate and with good reproducibility. The fingerprints can be used for the identification and quality control of toad skin. (2) The toad skin from different regions are stable in composition, but the contents of the components are different.
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Bufanolídeos/química , Bufonidae , Cromatografia Líquida de Alta Pressão/métodos , Materia Medica/química , Pele/química , Animais , Antineoplásicos/química , Controle de Qualidade , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To analysis liposoluble constituents of Holotrichia diomphalia by GC-MS and measure their anti-inflammatory and analgesic activities. METHODS: The composition of liposoluble constituents were determined by GC-MS. The dimethylbenzene-induced mice inflammatory models were established. The pain models were obtained by hot plate and acetic acid in mice. RESULTS: Twenty-two components were identified from the petroleum ether extract of Holotrichia diomphalia. The major components were oleic acid, palmitic acid and palmitoleic acid. The petroleum ether extract was able to significantly inhibit the mice ear edema induced by dimethyl-benzene. The pain in mice caused by acetic acid and hot plate were evidently suppressed by the petroleum ether extract. CONCLUSION: The petroleum ether extract of Holotrichia diomphalia has obvious anti-inflammation and analgesic effects.
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Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Besouros , Ácidos Graxos/análise , Materia Medica/farmacologia , Analgésicos/química , Analgésicos/isolamento & purificação , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Comportamento Animal/efeitos dos fármacos , Besouros/química , Edema/induzido quimicamente , Edema/prevenção & controle , Ácidos Graxos/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Temperatura Alta , Masculino , Materia Medica/química , Materia Medica/isolamento & purificação , Camundongos , Camundongos Endogâmicos ICR , Dor/prevenção & controle , Medição da Dor/efeitos dos fármacos , SolubilidadeRESUMO
Ilex rotunda Thunb (IR) is a traditional Chinese medicine used for the clinical treatment of gastric ulcers and duodenal ulcers; however, the effect of IR on ulcerative colitis (UC) and its underlying mechanism remains unclear. This study investigated the therapeutic effect of IR on UC mice induced by dextran sulfate sodium (DSS) as well as the potential underlying mechanism. The main components of IR were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Then we established a model of UC mice by administering 2.0% DSS for 7 days followed by 2 weeks of tap water for three cycles and administered IR. On day 56, the disease activity index (DAI), colon length, pathological changes, and inflammatory response of the colon tissue of mice were assessed. The oxidative stress and apoptosis of colon tissue were detected, and the integrity of the intestinal mucosal barrier was evaluated to assess the effect of IR. Furthermore, the relationship between oncostatin M (OSM) and its receptor (OSMR) in addition to the IR treatment of UC were evaluated using a mouse model and Caco2 cell model. The results showed that IR significantly alleviated the symptoms of UC including rescuing the shortened colon length; reducing DAI scores, serum myeloperoxidase and lipopolysaccharide levels, pathological damage, inflammatory cell infiltration and mRNA levels of interleukin one beta, tumor necrosis factor alpha, and interleukin six in colon tissue; alleviating oxidative stress and apoptosis by decreasing kelch-like ECH-associated protein 1 expression and increasing nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase-1 protein expression; and promoting the regeneration of epithelial cells. IR also promoted the restoration of the intestinal mucosal barrier and modulated the OSM/OSMR pathway to alleviate UC. It was found that IR exerted therapeutic effects on UC by restoring the intestinal mucosal barrier and regulating the OSM/OSMR pathway.
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Survivin belongs to the family of genes known as inhibitors of apoptosis, and although it has been implicated in the prevention of cancer, its potential role in burn-induced cardiac injury is unknown. In this study, we investigated the effects of survivin blockade on burn-induced cardiac apoptosis. Using a standardized Sprague-Dawley rat model of third-degree burn injury over 40% of total body surface area, apoptosis was measured in vivo followed by in vitro assessment of burn serum-stimulated cardiomyocytes. Based on the Western blot analyses, real-time PCR, ELISA, and TUNEL, apoptosis and caspase activation both in vivo and in vitro were significantly increased after severe burn injury, while survivin expression was increased (up to 2.90-fold) during the early stage of burn injury and was almost completely abolished 8 h after the burn. Survivin-deficient cardiomyocytes, as well as hearts from rats treated with the survivin inhibitor YM155, exhibited increased caspase-3 protein and mRNA expression and apoptosis ratio at different times after the burn. Furthermore, inhibition of ERK, phosphoinositol 3-kinase contributed the burn serum-induced increase in apoptosis and caspase-3 protein expression, and decreased survivin expression, whereas burn serum-induced increase in apoptosis was attenuated by P38 mitogen-activated protein kinase inhibition. These data identify survivin as a critical anti-apoptotic regulator of cardiomyocytes after burn injury. ERK, P38 MAPK and PI3K were found to be upstream regulators of survivin.
Assuntos
Apoptose/fisiologia , Queimaduras/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Miócitos Cardíacos/metabolismo , Transdução de Sinais/fisiologia , Animais , Western Blotting , Queimaduras/patologia , Citocinas/sangue , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Survivina , Transfecção , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
In this study, the functional material SZVI-SA is successfully prepared to efficiently remove Cr(â ¥) from water. This composite, with micron zero-valent iron (ZVI) as its core, is sulfurized and loaded by sodium alginate (SA). Some parameters affecting the Cr(â ¥) removal are also tested, including the type and mass fraction of chelating agents as well as S/Fe. SEM-EDS, TEM, XRD, and XPS are used to characterize and analyze the material. The results show that 7% Fe3+ is most suitable as the chelating agent for sodium alginate, and a S/Fe ratio of 3.5 and drying temperature of 70â are the ideal formation conditions. The effect of SZVI-SA on the removal of Cr(â ¥) is in line with the secondary adsorption rate model, mainly affected by the availability of binding sites. The active ingredient was identified as FeS, and the specific surface area can reach 97.83 m2·g-1. Many pores, especially micropores, are present in this material and in addition to Cr(â ¥), SZVI-SA was found to effectively remove Cr(â ¢) and Fe(â ¢) from the test solution. Overall, the Cr(â ¥)-removal efficiency was 92%; the removal mechanism is mainly via redox reactions; and the main reducing active substances are Fe2+, S2-, and S22-. Following the reaction of Fe(â ¢) and Cr(â ¢), Fe(OH)3 and Cr(OH)3 are formed and Cr2O3 precipitation separation occurs.
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An analysis method was developed to determine the chemical speciation of Cu, Zn, Fe and Mn in radix scutellariae decoction using atomic absorption spectroscopy(AAS). The decoction can be divided into suspension and soluble species by 0.45 microm filter membrane and the soluble species can be separated into organism and inorganic species by LSA-10 macroporous resin. These elements in water-soluble test samples can be divided into alcohol-soluble and water-soluble by adopting n-octyl alcohol-water allocation system in man-made gastric acidity. Then, the concentration of these elements was determined by AAS, which provided more chemical speciation information about these elements instead of the total amount of them only in radix scutellariae. Deteotion limit of Cu, Zn and Mn by using the method was all 0.01 microg x mL(-1) and was 0.02 microg x mL(-1) for Fe. The RSD was in the range of 1.5%-3.6% (n=11) and the recovery rate of soluble species and inorganic species were in range of 96.7%-105.0%. The method has been successfully applied to determine the chemical speciation of Cu, Zn, Fe and Mn in radix scutellariae, which was very important for overall study of radix scutellariae.
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Metais Pesados/análise , Metais Pesados/química , Scutellaria baicalensis/química , Espectrofotometria Atômica/métodos , Cobre/análise , Cobre/química , Ferro/análise , Ferro/química , Cinética , Limite de Detecção , Manganês/análise , Manganês/química , Solventes/química , Zinco/análise , Zinco/químicaRESUMO
Although gastroenteritis and pelvic inflammatory disease (PID) occur in the gastrointestinal tract and pelvis, respectively, they display similar pathogeneses. The incidence of inflammation in these conditions is usually associated with dysbacteriosis, and, at times, they are caused by the same pathogenic bacteria, Escherichia coli and Streptococcus aureus. Feiyangchangweiyan capsule (FYC) is a traditional Chinese patent medicine that is widely used to treat bacterial dysentery and acute and chronic gastroenteritis. However, whether it has an effect on PID is unclear. The aim of this study was to investigate the anti-inflammatory effect of FYC and its main components, gallic acid (GA), ellagic acid (EA), and syringin (SY), on a pathogen-induced PID model and illustrate their potential mechanism of action. Female specific pathogen-free SD rats (n = 1110) were randomly divided into control, PID, FYC, GA, EA, SY, GA + EA, GA + SY, EA + SY, GA + EA + SY, and Fuke Qianjin capsule (FKC) positive groups. Histological examination and enzyme-linked immunosorbent assay (ELISA) were carried out as well as western blot analysis to detect the expression of NF-κB, BAX, BCL-2, and JNK. In this study, FYC and its main components dramatically suppressed the infiltration of inflammatory cells, reduced the production of IL-1ß, TNF-α, and MCP-1, and elevated the IL-10 level to varying degrees. We also found that FYC and its main components inhibited the expression of BAX induced by infection and increased the expression of Bcl-2. FYC, GA, EA, and SY could also block the activation of the NF-κB pathway. Finally, we found that the phosphorylation of JNK could be decreased by FYC, GA, and SY. FYC and its main components exhibit anti-inflammatory effect on a pathogen-induced PID model by regulating the NF-κB and apoptosis signaling pathways.
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Some of traditional Chinese medicine (TCM) contain arsenide, such as realgar. The total amount of arsenic in the TCM exceeds the limits according to related regulations. But the roles of arsenic in TCM or its side-effects depend on its species existing in those therapies, not on the total amount of arsenic. Therefore, in recent years, the analysis of arsenic in TCM focuses on the species of arsenic. The present paper combines the method of extracting chemical composition from bunge pricklyash seed and analyzing the contents and the speciation of arsenic of bunge pricklyash seed (BPS) in different habitat by atomic fluorescence spectrometry (AFS-3100). By using 0.45 microm filter membrane and mixed solvent, two different species of the decoction of BPS were extracted, named the suspended and the soluble, and by using ion-exchange resin, the soluble arsenic could be separated as As(III), As(V), MMA and DMA. The authors established the segregation analysis methods for those species. The results shows that BPS in different habitat all contain arsenic, mostly as the species of inorganic arsenic, and the contents of As(V) are higher than As(III). The lixiviating rate of arsenic is highest with the solvent of methanol-water (4/1), reaching 53.7%-62.3%. The recovery of the method was 96.0%-101.3% and the relative standard deviation was less than 2.66%. The results show that the sensitivity and reproducibility of this method were excellent, and provided theoretical basis for further development of BPS
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Arsênio/análise , Medicamentos de Ervas Chinesas/química , Sementes/química , Espectrometria de Fluorescência/métodos , Zanthoxylum/química , Reprodutibilidade dos TestesRESUMO
A method was developed for the investigation of the contents and the speciation of zinc in bunge pricklyash seed (BPS) in different habitats by atomic absorption spectrum (AAS). By using 0.45 microm filter membrane and chloroform, four different species of the decoction of BPS, named the suspended, the soluble, the inorganic and organic species, were obtained, and the segregation analysis methods for those species were developed. The octanol-water system was proposed to simulate the distribution of decocted zinc in the stomach and the intestine of the human body. The results showed that the decocted zinc was the main content of the total zinc, and the contents of zinc were different in different habitats, but the percentages of decocted zinc and the organism zinc were similar. The recovery for the method was 97.5%-104.0% and the relative standard deviation was less than 2.36%. The results showed that the sensitivity and reproducibility of this method were excellent.
Assuntos
Extratos Vegetais/análise , Rutaceae/química , Espectrofotometria Atômica/métodos , Zinco/análise , China , Sementes/químicaRESUMO
Thromboxane A2 (TXA2) acts on TXA2 receptors (TP) to regulate renal artery blood flow and subsequently contributes to the pathogenesis of renal ischemia. The present study was designed to examine if nuclear factor-kappaB (NF-κB) signaling pathway is involved in the downregulation of TP receptors in rat renal artery. Rat renal artery segments were organ cultured for 6 or 24 h. Downregulation of TP receptors was monitored using myograph (contractile function), real-time PCR (receptor mRNA), and immunohistochemistry (receptor protein). Specific inhibitors (MG-132 and BMS345541) for NF-κB signaling pathway were used to dissect the underlying molecular mechanisms involved. Compared to fresh (noncultured) segments, organ culture of the renal artery segments for 24 h induced a significant rightward shift of U46619 (TP receptor agonist) contractile response curves (pEC50: 6.89 ± 0.06 versus 6.48 ± 0.04, P < 0.001). This decreased contractile response to U46619 was paralleled with decreased TP receptor mRNA and protein expressions in the renal artery smooth muscle cells. Specific inhibitors (MG-132 and BMS345541) for NF-κB signaling pathway significantly abolished the decreased TP protein expression and receptor-mediated contractions. In conclusion, downregulation of TP receptors in the renal artery smooth muscle cells occurs mainly via the NF-κB signaling pathway.
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BACKGROUND: The seed oil of Zanthoxylum bungeanum Maxim (ZBSO) is considered to be rich source of fatty acids, mainly oleic and linoleic acids, and has been used for the treatment of burns in Chinese medicine. OBJECTIVE: We evaluated the healing efficacy of ZBSO and explored its possible mechanism on scalded rats. MATERIALS AND METHODS: Sprague-Dawley rat models with deep second-degree burns were set up, and ZBSO (500 and 1000 µl/wound) was topically applied twice daily for 7 days and then once daily until wound healing. The therapeutic effects of ZBSO were evaluated by observing wound closure time, decrustation time, wound-healing ratio, and pathological changes. Collagen type-III, matrix metalloproteinase-2 (MMP-2), MMP-9, phospho-nuclear factor-κB (p-NF-κB) p65, inhibitor of NF-κB subunit α p-IκBα, and inhibitor of NF-κB subunit α (IκBα) expression were determined using Western blotting. RESULTS: The ZBSO-treated group showed a higher wound-healing ratio and shorter decrustation and wound closure times than the untreated group. The topical application of ZBSO increased collagen synthesis as evidenced by an increase in hydroxyproline level and upregulated expression of collagen type-III on days 7, 14, and 21 posttreatment. A reduction in MMP-2 and MMP-9 expressions also confirmed the collagen formation efficacy of ZBSO. Furthermore, there was a significant increase in superoxide dismutase levels and a decrease in malondialdehyde levels in ZBSO-treated wounds. ZBSO also decreased tumor necrosis factor alpha, interleukin-1 (IL-1) ß, and IL-6 levels in serum, upregulated IκBα, and downregulated p-NF-κB p65 and p-IκBα expression in vivo, indicating the anti-inflammatory action of ZBSO. CONCLUSION: ZBSO has significant potential to treat burn wounds by accelerating collagen synthesis and the anti-inflammatory cascade of the healing process. SUMMARY: The seed oil of Zanthoxylum bungeanum Maxim (ZBSO) is rich of fatty acidsThe healing efficacy of ZBSO on experimentally scalded rats was evaluatedZBSO has significant potential to treat deep second-degree burn woundsZBSO could accelerate collagen synthesis and inhibit the inflammatory signaling. Abbreviations used: ECL: Enhanced chemiluminescence; ECM: Extracellular matrix; ELISA: Enzyme-linked immunosorbent assay; GC-MS: Gas chromatography-mass spectrometry; HRP: Horseradish peroxidase; HYP: Hydroxyproline; IκBα: Inhibitor of NF-κB subunit α; IL: Interleukin; MDA: Malondialdehyde; MMP: Matrix metalloproteinase-2; NF-κB: Nuclear factor-κB; SFE: Supercritical fluid extraction; SOD: Superoxide dismutase; SSD: Silver sulfadiazine; TCM: Traditional Chinese medicine; TNF: Tumor necrosis factor.
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The chemical property of cinnamaldehyde is unstable in vivo, although early experiments have shown its obvious therapeutic effects on viral myocarditis (VMC). To overcome this problem, we used cinnamaldehyde as a leading compound to synthesize derivatives. Five derivatives of cinnamaldehyde were synthesized: 4-methylcinnamaldehyde (1), 4-chlorocinnamaldehyde (2), 4-methoxycinnamaldehyde (3), α-bromo-4-methylcinnamaldehyde (4), and α-bromo-4-chlorocinnamaldehyde (5). Neonatal rat cardiomyocytes and HeLa cells infected by coxsackievirus B3 (CVB3) were used to evaluate their antiviral and cytotoxic effects. In vivo BALB/c mice were infected with CVB3 for establishing VMC models. Among the derivatives, compound 4 and 5 inhibited the CVB3 in HeLa cells with the half-maximal inhibitory concentrations values of 11.38 ± 2.22 µM and 2.12 ± 0.37 µM, respectively. The 50% toxic concentrations of compound 4 and 5-treated cells were 39-fold and 87-fold higher than in the cinnamaldehyde group. Compound 4 and 5 effectively reduced the viral titers and cardiac pathological changes in a dose-dependent manner. In addition, compound 4 and 5 significantly inhibited the secretion, mRNA and protein expressions of inflammatory cytokines TNF-α, IL-1ß and IL-6 in CVB3-infected cardiomyocytes, indicating that brominated cinnamaldehyde not only improved the anti-vital activities for VMC, but also had potent anti-inflammatory effects in cardiomyocytes induced by CVB3.
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Paeonol and danshensu is the representative active ingredient of traditional Chinese medicinal herbs Cortex Moutan and Radix Salviae Milthiorrhizae, respectively. Paeonol and danshensu combination (PDSS) has putative cardioprotective effects in treating ischemic heart disease (IHD). However, the evidence for the protective effect is scarce and the pharmacological mechanisms of the combination remain unclear. The present study was designed to investigate the protective effect of PDSS on isoproterenol (ISO)-induced myocardial infarction in rats and to elucidate the potential mechanism. Assays of creatine kinase-MB, cardiac troponin I and T and histopathological analysis revealed PDSS significantly prevented myocardial injury induced by ISO. The ISO-induced profound elevation of oxidative stress was also suppressed by PDSS. TUNEL and caspase-3 activity assay showed that PDSS significantly inhibited apoptosis in myocardia. In exploring the underlying mechanisms of PDSS, we found PDSS enhanced the nuclear translocation of Nrf2 in myocardial injured rats. Furthermore, PDSS increased phosphorylated PI3K and Akt, which may in turn activate antioxidative and antiapoptotic signaling events in rat. These present findings demonstrated that PDSS exerts significant cardioprotective effects against ISO-induced myocardial infarction in rats. The protective effect is, at least partly, via activation of Nrf2/HO-1 signaling and involvement of the PI3K/Akt cell survival signaling pathway.
Assuntos
Acetofenonas/farmacologia , Apoptose/efeitos dos fármacos , Lactatos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Acetofenonas/administração & dosagem , Acetofenonas/química , Animais , Western Blotting , Cardiotônicos/química , Cardiotônicos/farmacologia , Creatina Quinase Forma MB/metabolismo , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Heme Oxigenase-1/metabolismo , Isoproterenol , Lactatos/administração & dosagem , Lactatos/química , Masculino , Microscopia Eletrônica de Transmissão , Estrutura Molecular , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Miocárdio/ultraestrutura , Fator 2 Relacionado a NF-E2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fitoterapia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Troponina I/metabolismo , Troponina T/metabolismoRESUMO
OBJECTIVE: To compare the clinical effects between hip anterior S-P approach combined with iliac bone flap transplantation with deep circumflex iliac artery and posterior K-L approach combined with quadratus femoris bone flap transplantation for the treatment of femoral neck fracture of Garden III-IV in young and middle-aged patients. METHODS: From January 2004 to January 2011,46 patients with femoral neck fractures were treated by two kinds of operation. Among them, 20 cases were treated with anterior S-P approach combined with iliac bone flap transplantation with deep circumflex iliac artery, included 12 males and 8 females with an average age of (32.1 ± 7.3) years old, involved 12 cases of Garden III and 8 cases of Garden IV. The other 26 cases were treated with posterior K-L approach combined with quadratus femoris bone flap transplantation, included 20 males and 6 females with an average age of (37.8 ± 6.9) years old, involved 16 cases of Garden III and 10 cases of Garden IV. The index of hospitalization (hospitalization time, total cost, operative time, intraoperative blood loss, postoperative complications), the quality index of operation (fracture reduction, position of internal fixation, fracture healing time, nonunion and femoral head necrosis) of two groups were observed and compared. Hip joint function were evaluated by Harris score. RESULTS: All patients were followed up from 28 to 41 months with an average of 36 months. The intraoperative blood loss of group S-P (92.3 ± 10.4) ml was less than that of group K-L (132.4 ± 11.2) ml, there was significant difference between two groups (P < 0.05). The operation time of group S-P (81.4 ± 9.2) min was more than that of group K-L (67.1 ± 4.5) min, the difference was statistically significant (P < 0.05). One case in group S-P and 9 cases in group K-L appeared postoperative complications, there was significant difference between two groups (P < 0.05). The fracture healing time of S-P group (83.5 ± 7.3) d was shorter than that of group K-L (103.2 ± 12.6) d, there was significant difference between two groups (P < 0.05). At 30 months after operation, there were significant difference in Harris scoring between two groups (P < 0.05). CONCLUSION: Anterior S-P approach combined with iliac bone flap transplantation with deep circumflex iliac artery for treatment of femoral neck fracture of Garden III-IV of young and middle-aged patients, it has characteristics in clear anatomic and easy to operate. As compared with K-L approach, S-P approach can better reserve residual blood supply of femoral neck. While combining with the iliac bone flap transplantation with deep circumflex iliac artery, it could better reconstruct the blood supply of femoral neck to promote fracture healing.
Assuntos
Fraturas do Colo Femoral/cirurgia , Retalhos Cirúrgicos/transplante , Adulto , Estudos de Casos e Controles , Feminino , Fraturas do Colo Femoral/fisiopatologia , Consolidação da Fratura , Humanos , Artéria Ilíaca , Masculino , Pessoa de Meia-IdadeRESUMO
AIM: To study the effects of 2, 3, 5, 4'-tetrahydroxystilbene-2-O-ß-d-glucoside (THSG) on proliferation of rat cardiac stem cells (CSCs) in vitro. MATERIALS AND METHODS: C-kit(+) cells were isolated from neonatal (1 day old) Sprague-Dawley rats by using flow cytometry. Optimal THSG treatment times and doses for growth of CSCs were analyzed. CSCs were treated with various THSG doses (0, 1, 10, and 100 µM) for 12h. RESULTS: Sorted c-kit(+) cells exhibited self-renewing and clonogenic capabilities. Cell Counting Kit (CCK-8) and Proliferating Cell Nuclear Antigen (PCNA) ELISA test positive cells were significantly increased in THSG-treated groups compared with untreated controls. The percentage of S-phase cells also increased after THSG treatment. Moreover, we show that some c-kit(+) cells spontaneously express vascular endothelial growth factor (VEGF), T-box transcription factor (Tbx5), hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2), hyperpolarization-activated cyclic nucleotide gated 4 (HCN4), alpha myosin heavy chain (αMHC), and beta myosin heavy chain (ßMHC) mRNA, and stem cell antigen 1 (Sca-1), cardiac troponin-I, GATA-4, Nkx2.5, and connexin 43 protein were also assessed in CSCs. However, their expression was significantly increased with THSG treatment when compared to untreated controls. CONCLUSION: THSG can increase proliferation of rat CSCs in vitro and thus, shows promise as a potential treatment strategy for stimulating endogenous stem cells to help repair the injured heart after myocardial infarction in patients.