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1.
Zhongguo Zhong Yao Za Zhi ; 46(12): 3133-3143, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467705

RESUMO

To study the effect of mineral Chloriti Lapis on pulmonary metabolites and metabolic pathways in lung tissues of rats with acute exacerbation of chronic obstructive pulmonary disease(AECOPD). The AECOPD rat model of phlegm heat syndrome was replicated by the method of smoking combined with Klebsiella pneumoniae infection. Except for using UPLC-Q-TOF-MS analysis, SPSS 18.0, SIMCA 13.0 and other software were also used for statistical analysis. Through literature search and online database comparison, the differential metabolites were identified, and the possible metabolic pathways were analyzed. After 15 days of administration, PLS-DA analysis was carried out on lung tissue samples of rats in each group. The results showed that the metabolic profiles of lung tissues of rats in each group could be well separated, which indicated that Chloriti Lapis and aminophylline had significant intervention effect on the lung metabolic profile of rats with AECOPD. Moreover, the metabolic profile of Chloriti Lapis group was closer to that of control group, and the intervention effect was better than that of aminophylline group. As a result, 15 potential differential metabolites were identified: phytosphingosine, sphinganine, tetradecanoylcarnitine, L-palmitoylcarnitine, elaidic carnitine, lysoPC[18∶2(9Z,12Z)], lysoPC(16∶0), lysoPC[18∶1(9Z)], lysoPC(18∶0), stearic acid, lysoPC(15∶0), arachidonic acid, docosapentaenoic acid, linoleic acid and palmitic acid. Among them, Chloriti Lapis could significantly improve the levels of 10 differential metabolites of phytosphingosine, tetradecanoylcarnitine, L-palmitoylcarnitine, elaidic carnitine, lysoPC[18∶2(9Z,12Z)], lysoPC(16∶0), lysoPC[18∶1(9Z)], stearic acid, lysoPC(15∶0), and palmitic acid(P<0.05). The intervention effect of Chloriti Lapis group was better than that of aminophylline group. Analysis of metabolic pathways showed that there were 8 possible metabolic pathways that could be affected, and three of the most important metabolic pathways(pathway impact>0.1) were involved: linoleic acid metabolism, arachidonic acid metabolism, and sphingolipid metabolism. Chloriti Lapis had obvious intervention effects on lung tissue-related metabolites and metabolic pathways in rats with AECOPD, and the effect was better than that of aminophyllinne.


Assuntos
Medicina Tradicional Chinesa , Doença Pulmonar Obstrutiva Crônica , Animais , Pulmão , Metabolômica , Minerais , Ratos
2.
Zhongguo Zhong Yao Za Zhi ; 46(14): 3694-3704, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34402294

RESUMO

The effects of Chloriti Lapis on metal elements in plasma and lung tissue of acute exacerbation of chronic obstructive pulmonary disease( AECOPD) rats were studied. The rat AECOPD model with phlegm heat syndrome was established by smoking combined with Klebsiella pneumoniae infection. After the rats were treated by Chloriti Lapis,the contents of metal elements in plasma and lung tissue were determined by inductively coupled plasma-optical emission spectroscopy( ICP-OES) and inductively coupled plasma mass spectrometry( ICP-MS). The changes in the contents of metal elements were analyzed by SPSS 18. 0. Further,the correlations of differential metal elements( including Cu/Zn ratio) with differential metabolites in plasma,lung tissue and urine of AECOPD rats treated with Chloriti Lapis were analyzed. The results showed that Chloriti Lapis significantly up-regulated the contents of Fe,Al,Mn,Cu,Zn,Sn( P<0. 05),V,Co( P< 0. 01) and Cu/Zn ratio( P< 0. 05),and significantly down-regulated the contents of Ti( P< 0. 05)and Pb( P<0. 05) in the model rat plasma. It significantly increased the content of Be( P<0. 05) and decreased the contents of Mg,Ti and Al( P<0. 01) in model rat lung tissue. The element profiles of normal group,model group and Chloriti Lapis group can be well separated. Chloriti Lapis group and other groups were clustered into two categories. The taurine in plasma and phytosphingosine in lung tissue had the strongest correlations with differential metal elements. The Fe,Al,Mg,Be,Ti,V,Mn,Cu,Zn,Sn,and Co in Chloriti Lapis may directly or indirectly participate in the intervention of AECOPD rats. This group of metal elements may be the material basis of Chloriti Lapis acting on AECOPD rats,and reduce the Cu/Zn value in vivo. It was further confirmed that Chloriti Lapis could interfere with the metabolic pathways of taurine and hypotaurine in plasma and urine as well as the sphingolipid metabolism pathway in lung tissue of AECOPD rats. In addition,this study confirmed that long-term smoking can cause high-concentration Cd accumulation in the lung and damage the lung tissue.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Oligoelementos , Animais , Pulmão , Medicina Tradicional Chinesa , Minerais , Ratos , Análise Espectral , Oligoelementos/análise
3.
Zhongguo Zhong Yao Za Zhi ; 46(9): 2142-2148, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34047114

RESUMO

Metallomics is a frontier interdisciplinary subject at its vigorous development stage. Its goal is to systematically study the content, distribution, chemical species, structural characteristics and functions of metal elements in biological system. It is also a comprehensive discipline to study the existing state and function of free or complex metal elements in life. Metallomics is an ideal tool to study the biological behavior of inorganic elements, which can be used to solve many problems in the research of mineral Chinese medicine(MCM). It provides a strong theoretical basis and technical support for the research of MCM. Its theory and methods provide re-ference and enlightenment for the in-depth study of MCM, and also provide new ideas and open up new ways for the research of MCM. The application of metallomics theory and methods in the research of MCM is of great significance to reveal the material basis and mec-hanism of MCM, promote the process of basic research on MCM, fully exploit and utilize medicinal mineral resources and carry forward the traditional MCM treasure in China. In this paper, we introduced the concept, academic development, research content and research methods of metallomics, and discussed the application prospects of metallomics in the analysis of inorganic element composition characteristics and quality control, material basis and mechanism of MCM, so as to provide reference for further researches on MCM.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , China , Minerais , Controle de Qualidade
4.
J Nat Prod ; 83(11): 3471-3475, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33180498

RESUMO

Penisarins A (1) and B (2), sesquiterpene coumarins with an unusual tricyclic sesquiterpene system, were isolated from endophytic Penicillium sp. KMU18029. Their structures were elucidated on the basis of spectroscopic methods, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compound 2 showed significant cytotoxicities against two human cancer cell lines, HL-60 and SMMC-7721, with IC50 values of 3.6 ± 0.2 and 3.7 ± 0.2 µM, respectively.

5.
Zhongguo Zhong Yao Za Zhi ; 42(15): 2989-2994, 2017 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-29139268

RESUMO

Models were established in mice with warfarin sodium method, and their bleeding time and hemostasis time were measured by tail cutting method and slide method respectively. Rats were administered for 15 consecutive days to measure their recalcification time, plasma viscosity, platelet adhesion rate, platelet aggregation rate and other blood indexes. As compared with the blank group, the bleeding time was prolonged in model groupn(P<0.05). As compared with the model group, the results showed that the positive vitamin K, the leaching type water decoction and the sediment type decoction could significantly shorten the bleeding time (P<0.01); positive vitamin K significantly (P<0.01) shortened clotting time, and the leaching type water decoction, the sediment type water decoction and the sediment type powder could also shorten the clotting time (P<0.05). As compared with blank group, low dose, medium dose of leaching type water decoction, medium dose of powder, high dose of sediment type decoction and low dose of drug residues could reduce plasma viscosity (P<0.05), and high dose of leaching powder and low dose of water decoction could significantly reduce (P<0.01) plasma viscosity. As compared with blank group, Limonitum leaching type decoction high dose group could significantly reduce the platelet adhesion rate (P<0.05), while sediment type water decoction could significantly increase the platelet adhesion rate (P<0.05); the high dose of leaching type water decoction, high dose of drug residues, low dose of leaching type powder and low dose of drug residues could decrease the platelet aggregation rate (P<0.05), while high dose of leaching type water decoction and high dose of the powder could increase the platelet aggregation rate (P<0.05). Analysis of mineral compositions was conducted by polarized light microscopy and X-ray diffraction (XRD). The results of the both methods showed that Limonitum mineral compositions contained goethite, quartz, and kaolinite, and sedimentary type also contained illite and albite. Sediment type of Limonitum showed better hemostatic effect, which may be related to the high content of goethite and illite.


Assuntos
Medicamentos de Ervas Chinesas/química , Hemostáticos/farmacologia , Plumbaginaceae/química , Animais , Hemostasia , Camundongos , Minerais , Agregação Plaquetária , Ratos
6.
ACS Omega ; 2(3): 873-889, 2017 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30023617

RESUMO

Self-labeled inhibitors (SLIs) are promising for creating links, ranging from cancer therapy and metastatic pathways to mechanistic elucidation. In this study, a new category of "two-in-one" fluorescent xanthone inhibitors was developed for the systematic evaluation of anticancer activity and the selective imaging of cytoplasm in vitro. These xanthone inhibitors presented high fluorescent brightness, working over a wide pH range enabled by a "switchable reaction" of the heterocyclic backbone. The strength and nature of fluorescence were probed via spectroscopic methods and density functional theory calculations on the molecular level, respectively. Along with the potent anticancer activity, which was demonstrated using MTT and clonogenic assays with high fluorescent brightness in the cytoplasm, SLI 3fd could be established as a modeled self-monitoring drug in cancer therapy.

7.
Chem Commun (Camb) ; 52(9): 1923-5, 2016 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-26680998

RESUMO

Utilizing (R)-H3CIA as a chiral template, an unprecedented homochiral metal-organic framework (MOF) with zeotype GIS topology is obtained from achiral 1.4-DIB ligands and Zn(II) ions, which opens up a feasible approach to create zeolitic MOFs with homochirality.


Assuntos
Metais/química , Compostos Orgânicos/química , Zeolitas/química , Dicroísmo Circular , Ligantes , Espectroscopia de Prótons por Ressonância Magnética , Estereoisomerismo
8.
PLoS One ; 10(2): e0118286, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25706956

RESUMO

OBJECTIVES: Human airway epithelial cells are the principal target of human rhinovirus (HRV), a common cold pathogen that triggers the majority of asthma exacerbations. The objectives of this study were 1) to evaluate an in vitro air liquid interface cultured human airway epithelial cell model for HRV infection, and 2) to identify gene expression patterns associated with asthma intrinsically and/or after HRV infection using this model. METHODS: Air-liquid interface (ALI) human airway epithelial cell cultures were prepared from 6 asthmatic and 6 non-asthmatic donors. The effects of rhinovirus RV-A16 on ALI cultures were compared. Genome-wide gene expression changes in ALI cultures following HRV infection at 24 hours post exposure were further analyzed using RNA-seq technology. Cellular gene expression and cytokine/chemokine secretion were further evaluated by qPCR and a Luminex-based protein assay, respectively. MAIN RESULTS: ALI cultures were readily infected by HRV. RNA-seq analysis of HRV infected ALI cultures identified sets of genes associated with asthma specific viral responses. These genes are related to inflammatory pathways, epithelial structure and remodeling and cilium assembly and function, including those described previously (e.g. CCL5, CXCL10 and CX3CL1, MUC5AC, CDHR3), and novel ones that were identified for the first time in this study (e.g. CCRL1). CONCLUSIONS: ALI-cultured human airway epithelial cells challenged with HRV are a useful translational model for the study of HRV-induced responses in airway epithelial cells, given that gene expression profile using this model largely recapitulates some important patterns of gene responses in patients during clinical HRV infection. Furthermore, our data emphasize that both abnormal airway epithelial structure and inflammatory signaling are two important asthma signatures, which can be further exacerbated by HRV infection.


Assuntos
Asma/genética , Asma/virologia , Diferenciação Celular/genética , Células Epiteliais/virologia , Infecções por Picornaviridae/genética , Sistema Respiratório/virologia , Adolescente , Adulto , Células Cultivadas , Quimiocinas/genética , Criança , Feminino , Expressão Gênica/genética , Humanos , Inflamação/genética , Inflamação/virologia , Masculino , Pessoa de Meia-Idade , Infecções por Picornaviridae/virologia , Rhinovirus , Transdução de Sinais/genética
9.
Eur J Pharmacol ; 718(1-3): 290-8, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-24012780

RESUMO

Accumulating evidence indicates protective actions of mineralocorticoid antagonists (MR antagonists) on cardiovascular pathology, which includes blunting vascular inflammation and myocardial fibrosis. We examined the anti-inflammatory and anti-fibrotic potential of MR antagonists in rodent respiratory models. In an ovalbumin allergic and challenged Brown Norway rat model, the total cell count in nasal lavage was 29,348 ± 5451, which was blocked by spironolactone (0.3-60 mg/kg, p.o.) and eplerenone (0.3-30 mg/kg, p.o.). We also found that MR antagonists attenuated pulmonary inflammation in the Brown Norway rat. A series of experiments were conducted to determine the actions of MR blockade in acute/chronic lung injury models. (1) Ex vivo lung slice rat experiments found that eplerenone (0.01 and 10 µM) and spironolactone (10 µM) diminished lung hydroxyproline concentrations by 55 ± 5, 122 ± 9, and 83 ± 8%. (2) In in vivo studies, MR antagonists attenuated the increases in bronchioalveolar lavage (BAL) neutrophils and macrophages caused by lung bleomycin exposure. In separate studies, bleomycin (4.0 U/kg, i.t.) increased lung levels of hydroxyproline by approximately 155%, which was blocked by spironolactone (10-60 mg/kg, p.o.). In a rat Lipopolysaccharide (LPS) model, spironolactone inhibited acute increases in BAL cytokines with moderate effects on neutrophils. Finally, we found that chronic LPS exposure significantly increased end expiratory lung and decreased lung elastance in the mouse. These functional effects of chronic LPS were improved by MR antagonists. Our results demonstrate that MR antagonists have significant pharmacological actions in the respiratory system.


Assuntos
Bleomicina/efeitos adversos , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Pneumonia/tratamento farmacológico , Receptores de Mineralocorticoides/metabolismo , Animais , Modelos Animais de Doenças , Elasticidade/efeitos dos fármacos , Fibrose , Hidroxiprolina/metabolismo , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/metabolismo , Hipersensibilidade/patologia , Hipersensibilidade/fisiopatologia , Lipopolissacarídeos/efeitos adversos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Camundongos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Pneumonia/metabolismo , Pneumonia/patologia , Pneumonia/fisiopatologia , Ventilação Pulmonar/efeitos dos fármacos , Ratos
10.
Cancer Res ; 69(4): 1517-26, 2009 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-19208838

RESUMO

Inhibition of specific matrix metalloproteinases (MMP) is an attractive noncytotoxic approach to cancer therapy. MMP-14, a membrane-bound zinc endopeptidase, has been proposed to play a central role in tumor growth, invasion, and neovascularization. Besides cleaving matrix proteins, MMP-14 activates proMMP-2 leading to an amplification of pericellular proteolytic activity. To examine the contribution of MMP-14 to tumor growth and angiogenesis, we used DX-2400, a highly selective fully human MMP-14 inhibitory antibody discovered using phage display technology. DX-2400 blocked proMMP-2 processing on tumor and endothelial cells, inhibited angiogenesis, and slowed tumor progression and formation of metastatic lesions. The combination of potency, selectivity, and robust in vivo activity shows the potential of a selective MMP-14 inhibitor for the treatment of solid tumors.


Assuntos
Anticorpos Monoclonais , Antineoplásicos/uso terapêutico , Divisão Celular/efeitos dos fármacos , Inibidores Enzimáticos/uso terapêutico , Inibidores de Metaloproteinases de Matriz , Neovascularização Patológica/prevenção & controle , Animais , Anticorpos Monoclonais Humanizados , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Feminino , Genes Reporter , Humanos , Imuno-Histoquímica , Camundongos , Invasividade Neoplásica/patologia , Transfecção , Transplante Heterólogo , Veias Umbilicais/citologia , Veias Umbilicais/efeitos dos fármacos
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