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1.
Int J Mol Sci ; 20(22)2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31731809

RESUMO

Gout Party is a Chinese medicine prescription composed of Aconiti Lateralis Radix Praeparaia, Aconiti Radix Cocta, Cremastrae Pseudobulbus Pleiones Pseudobulbus, Smilacis Glabrae Rhizoma, Rehmanniae Radix, and Glycyrrhizae Radix et Rhizoma, which can relieve joint pain caused by gouty arthritis (GA) and rheumatoid, and has a therapeutic effect on acute gouty arthritis (AGA). However, little information is available on the molecular biological basis and therapeutic mechanism of Gout Party for the treatment of AGA. AGA model was established by injecting sodium urate, and colchicine served as a positive control drug. We established a metabolomic method based on ultra-high-performance liquid chromatography-tandem quadrupole/time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) to analyze the plasma samples of model group rats and blank group rats. Multiple statistical analyses, including principal component analysis (PCA) and partial least square discrimination analysis (PLS-DA), were used to examine metabolite profile changes in plasma samples. Finally, we identified 2-ketobutyric acid, 3-hexenedioic acid, but-2-enoic acid, and so on; 22 endogenous metabolites associated with AGA. After successful molding, we found that 2-ketobutyric acid, 3-hexenedioic acid, but-2-enoic acid, argininic acid, galactonic acid, lactic acid, equol 4'-O-glucuronide, deoxycholic acid glycine conjugate, glycocholic acid, sphinganine 1-phosphate, LPE (0:0/20:3), LPE (0:0/16:0), LPC (15:0) decreased significantly (p < 0.05 or p < 0.01), alanine, erythrulose, 3-dehydrocarnitine, m-methylhippuric acid, 3-hydroxyoctanoic acid, p-cresol sulfate, estriol 3-sulfate 16-glucuronide, 10-hydroxy-9-(phosphonooxy)octadecenoate, docosahexaenoic acid increased significantly (p < 0.05 or p < 0.01). After Gout Party treatment, 14 biomarkers had a tendency to normal conditions. These above biomarkers were mainly involved in fatty acid metabolism, bile acid metabolism, amino acid metabolism, and energy metabolism pathways. These results suggested that Gout Party exerted therapeutic effects of treating AGA by improving energy metabolism disorder and amino acid metabolism dysfunction, and attenuating fatty acid metabolism abnormal and inflammation. The results of this experiment provided a reference for revealing the metabolic mechanism produced by Gout Party in the treatment of AGA, but the subsequent studies need to be further improved and supported by relevant cell experiments and clinical experiments.

2.
Sci Rep ; 9(1): 15219, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645643

RESUMO

In order to investigate the modification of the surface structure of FePS3 via Ga+ ion irradiation, we study the effect of thickness and Raman spectrum of multilayer FePS3 irradiated for 0 µs, 30 µs, and 40 µs, respectively. The results demonstrate that the intensity ratio of characteristic Raman peaks are obviously related to the thickness of FePS3. After Ga+ ion irradiation, the FePS3 sample gradually became thinner and the Eu peak and Eg(v11) peak in the Raman spectrum disappeared and the peak intensity ratio of A1g(v2) with respect to A1g(v1) weakened. This trend becomes more apparent while increasing irradiation time. The phenomenon is attributed to the damage of bipyramid structure of [P2S6]4- units and the cleavage of the P-P bands and the P-S bands during Ga+ ion irradiation. The results are of great significance for improving the two-dimensional characteristics of FePS3 by Ga+ ion beam, including structural and optical properties, which pave the way of surface engineering to improve the performance of various two-dimensional layered materials via ion beam irradiation.

3.
Free Radic Res ; 53(11-12): 1073-1083, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31631710

RESUMO

Of all the aerobic respiration by-products, cytotoxic superoxide derived from mitochondrial-leaked electrons, is the only one known to be disposed of intracellularly. Is this fate the only destiny for mitochondrial-leaked electrons? When Cynomolgus monkeys were injected intravenously with reactive oxygen species (ROS) indicators, the connective tissues of dura mater, facial fascia, pericardium, linea alba, dorsa fascia and other body parts, emitted specific and intense fluorescent signals. Moreover, the fluorescent signals along the linea alba of SD rats, did not result from the local presence of ROS but from the interaction of ROS indicators with electrons flowing through this tissue. Furthermore, the electrons travelling along the linea alba of mice were revealed to originate from mitochondria. These data suggest that mitochondrial-leaked electrons may be transported extracellularly to a hitherto undescribed system of connective tissues, which is pervasively networked, electrically conductive and metabolically related.

4.
Clin Chim Acta ; 497: 95-103, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31325445

RESUMO

BACKGROUND: Coronary heart disease (CHD) is the leading cause of death worldwide, and its pathogenesis has attracted much attention. Metabolomics serves as an important tool for diagnosing diseases and exploring their pathogenesis in recent years. In this study, CHD patients were studied by comparing them with normal subjects to elucidate biomarkers that are linearly correlated with the severity of coronary stenosis. METHODS: An ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to analyze the urine metabolites of CHD patients and normal subjects. A total of 131 subjects included 27 patients who presented with 50-69% coronary stenosis, 22 with 70-89% stenosis, 29 with 90-99% stenosis, 24 with 100% stenosis, and 29 normal subjects. RESULTS: A total of 14 potential biomarkers associated with CHD were identified, and among them 4 biomarkers were linearly correlated with the severity of coronary stenosis in CHD patients. The metabolic pathways involved were amino acid metabolism, fatty acid metabolism, energy metabolism, and other pathways. CONCLUSION: This study identified the biomarkers and metabolic pathways that may be involved in the occurrence and development of CHD, laying a theoretical foundation for better diagnosis and treatment of CHD in the future.


Assuntos
Doença das Coronárias/metabolismo , Doença das Coronárias/urina , Estenose Coronária/metabolismo , Estenose Coronária/urina , Metabolômica , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Doença das Coronárias/diagnóstico , Estenose Coronária/diagnóstico , Feminino , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores de Tempo
5.
Drug Deliv ; 26(1): 641-649, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31237148

RESUMO

This study is performed to elucidate the role of long non-coding RNA myocardial infarction associated transcript (lncRNA MIAT) in vulnerable plaque formation in rats with atherosclerosis (AS) through the regulation of the PI3K/Akt signaling pathway. The mice model of AS was established, and the successful modeled AS mice were treated with overexpressed MIAT and silenced MIAT. The levels of blood lipids, atherosclerotic plaques (AP) formation, the lipid content, collagen content, apoptosis of aortic cells, angiogenesis as well as the expression of inflammatory factors, such as tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were determined through a series of experiments. MIAT was found to be upregulated in AS. Additionally, MIAT up-regulated the levels of blood lipids, promoted AP formation, increased the lipid content and decreased the collagen content of AP, promoted the apoptosis of aortic cells in AS mice by activating the PI3K/Akt signaling pathway. Meanwhile, MIAT was determined to promote angiogenesis as well as the expression of inflammatory factors (IL-1ß, IL-6, and TNF-α) in AS mice through the activation of the PI3K/Akt signaling pathway. Furthermore, MIAT activated the PI3K/Akt signaling pathway to participate in AS progression. Our study suggests that upregulation of MIAT can aggravate AS injury in AS mice via the activation of the PI3K/Akt signaling pathway, which could provide a novel target for the treatment of AS.


Assuntos
Aterosclerose/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , RNA Longo não Codificante/genética , Transdução de Sinais/genética , Regulação para Cima/genética , Animais , Apoptose/genética , Modelos Animais de Doenças , Interleucina-1beta/genética , Interleucina-6/genética , Masculino , Camundongos , Infarto do Miocárdio/genética , Ratos , Fator de Necrose Tumoral alfa/genética
6.
Clin Chim Acta ; 495: 365-373, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31059703

RESUMO

BACKGROUND: As a recognized risk factor for cardiovascular disease (CVD), hyperlipidemia (HLP) has developed into a high incidence disease that seriously threatens human health. Finding a new target for effective treatment of HLP will be a powerful way to reduce the incidence of CVD. The purpose of this study was to find potential biomarkers in urine of HLP patients and analyze their metabolic pathways to study the pathogenesis of HLP. METHODS: An UPLC-Q-TOF/MS technology was used to detect the metabolites in urine of 60 HLP patients and 60 normal controls. Based on PLS-DA pattern recognition, potential biomarkers related to HLP were screened out. RESULTS: 22 potential biomarkers related to HLP were identified, which involved amino acid metabolism, fatty acid metabolism, nucleotide metabolism, steroid hormone metabolism and intestinal flora metabolism, and their possible pathogenesis was found to be related to inflammatory reaction and oxidative stress. CONCLUSION: The non-targeted metabolomic method based on UPLC-Q-TOF/MS technology can effectively identify potential biomarkers in the urine of HLP patients and explore the possible pathogenesis. Our research will lay a foundation for finding new targets for the treatment of HLP and provide a basis for clinical research on the treatment of HLP.


Assuntos
Biomarcadores/urina , Hiperlipidemias/diagnóstico , Metabolômica/métodos , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Humanos , Hiperlipidemias/urina , Inflamação/urina , Espectrometria de Massas , Redes e Vias Metabólicas , Estresse Oxidativo , Coleta de Urina
7.
J Ethnopharmacol ; 240: 111911, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31034953

RESUMO

ETHNOPHARMACOLOGICAL EVIDENCE: The Dan-Lou tablet (DLT), a well-known Chinese prescription, has definitive clinical efficacy in the treatment of precordial discomfort and pain caused by coronary heart disease (CHD). However, the pharmacological mechanism of DLT in the treatment of CHD has not been clearly elucidated and needs to be further explored. AIM OF THE STUDY: We aimed to identify relevant biological pathways by assessing changes in biomarkers in response to DLT intervention in CHD to reveal the potential biological mechanism of DLT treatment for CHD. MATERIALS AND METHODS: The major chemical components in DLT were qualitatively analyzed using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), and a model of CHD in rats was subsequently established with a high-fat diet and left anterior coronary artery ligation (LADCA) followed by DLT intervention. Next, the metabolic profile of rat serum samples was analyzed using nontargeted metabolomics, wherein changes in the metabolites in serum samples before and after DLT administration were measured by PLS-DA, and two pathways of DLT treatment for CHD were predicted. Finally, predicted metabolomic pathways were verified by detecting and analyzing tissues from the rat model, revealing the mechanism of DLT in the treatment of CHD. RESULTS: Forty-five major chemical components were identified by the chemical characterization of DLT. In terms of metabolism, 17 biomarkers of CHD in rats were identified. Among these biomarkers, linoleic acid, γ-linolenic acid and lysophosphatidylcholines (LPCs) were found to play an important role in energy metabolism and glycerophospholipid metabolism. Protein analysis revealed that EGFR phosphorylation was inhibited in CHD rats after DLT treatment, which lowered the expression of TNF-α, IL-6 and MMP9, decreased the expression levels of ox-LDL and MDA, and increased the expression of SOD. CONCLUSION: The mechanism of DLT in the treatment of CHD involves inhibiting the expression of EGFR and the activation of the MAPK signaling pathway by regulating glycerophospholipid metabolism (LPCs) and energy metabolism (linoleic acid and γ-linolenic acid). Therefore, inflammation-related (TNF-α, IL-6, MMP9) and oxidative stress-related (ox-LDL, MDA, SOD) indicators are affected, leading to the regulation of the oxidative stress state and anti-inflammatory effects.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Doença das Coronárias/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Biomarcadores/metabolismo , Doença das Coronárias/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Metabolômica , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar
8.
Food Chem ; 289: 419-425, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30955632

RESUMO

Surface plasmon resonance (SPR) analysis of the main components of liquorice was performed and a novel strong mineralocorticoid receptor (MR) agonist, namely liquiritinapioside (LA), whose the binding constant was 1.093 × 10-5 M, was reported. As a supplement, LA has been further demonstrated to have a strong MR binding capacity through competitive binding experiments (the enrichment factor of LA was 10.22%). This study also validated the activity of LA on H9c2 cells. The expression of collagen I and the results of Masson staining were used to determine the ability of this substance to cause H9c2 cell fibrosis. Moreover, western blotting was used to verify the mechanism of compound-induced myocardial fibrosis. Overall, the attained results showed that LA could induce the activation of the TGF-ß1/p38 MAPK signalling pathway through the MR to induce H9c2 cell fibrosis.


Assuntos
Glycyrrhiza/efeitos adversos , Glycyrrhiza/química , Mineralocorticoides , Receptores de Mineralocorticoides/agonistas , Animais , Linhagem Celular , China , Colágeno Tipo I/metabolismo , Fibrose , Flavanonas/efeitos adversos , Flavanonas/análise , Flavanonas/metabolismo , Glucosídeos/efeitos adversos , Glucosídeos/análise , Glucosídeos/metabolismo , Glycyrrhiza/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Miocárdio/patologia , Extratos Vegetais/química , Receptores de Mineralocorticoides/metabolismo , Transdução de Sinais/efeitos dos fármacos , Terpenos , Fator de Crescimento Transformador beta1/metabolismo
9.
Microb Drug Resist ; 25(7): 975-984, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30942653

RESUMO

It is becoming increasingly recognized that the environment plays an important role both in the emergence and in dissemination of antibiotic-resistant bacteria (ARB), Mechanisms and factors facilitating this development are, however, not yet well understood. The high detection rate of CTX-M genes in environmental sources provides an opportunity to explore this issue. In this study, 88 CTX-M-producing Escherichia coli were isolated from 30 pig feces samples from 30 pig farms and 201 environmental samples. CTX-M-producing E. coli was detected with the following frequencies in the different types of samples: pig feces, 73%; river water, 64%; river sediment, 52%; wastewater, 31%; drinking water, 23%; outlet sediment, 21%; soil, 17%; and vegetables, 4.4%. Dissemination of CTX-M-producing E. coli to different environmental matrices was evaluated by analyzing the genetic relatedness of isolates from different environmental sources, and putative transmission routes through bird feces, pig feces, drinking water, river sediment, river water, and wastewater were hypothesized. Dissemination through these routes is likely facilitated by anthropogenic activities and environmental factors. Wild birds as potential vectors for dissemination of CTX-M-producing E. coli have the capacity to spread ARB across long distances. Regional dissemination between different environmental matrices of CTX-M-producing E. coli increases the exposure risk of humans and animals in the area.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Infecções por Escherichia coli/genética , Escherichia coli/genética , beta-Lactamases/genética , Animais , China , Meio Ambiente , Microbiologia Ambiental , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Fazendas , Fezes/microbiologia , Humanos , Testes de Sensibilidade Microbiana/métodos , População Rural
10.
Artigo em Inglês | MEDLINE | ID: mdl-30925277

RESUMO

Purines and pyrimidines, the important components of DNA and RNA, are closely related to metabolic syndrome and disorder, such as renal disease, gout and diabetic nephropathy etc. Given the importance of the biological significance of purines and pyrimidines, it is necessary to further develop a rapid and sensitive method for practical detection of a large-scale analyses. In this study, based on 96-well solid phase extraction plates-ultra performance liquid chromatography-triple quadrupole mass spectrometry (SPE-UPLC-QqQ-MS/MS), a novel approach for simultaneous determination of 23 purines and pyrimidines in biological samples was developed. First, plasma samples were pretreated by SPE using 96-well plates, which lead to an automated, simplified and rapid sample preparation process. In the methodology development, a large-scale test was performed to evaluate the stability and reliability of the approach. Finally, the levels of purines and pyrimidines in the biological samples were analyzed by this strategy. Experimental results showed that lowest limit of quantification (LLOQ) range from 6.678 × 10-2 µg/mL to 4.275 × 10-6 µg/mL; intra- and inter-day precision are <15% for all analytes. The stability and maximal capability of a single analytical batch could be extended to at least 431 injections (about 70 h). Analysis time of a single run was controlled in 10 min. Under the optimized conditions, wide linear ranges and good correlation coefficients (R2 > 0.99) were acquired. The successful development of this method provides a feasible protocol for a large-scale metabolomics study and it also lays the foundation of quantitative analysis in endogenous analytes.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Metabolômica/métodos , Purinas/metabolismo , Pirimidinas/metabolismo , Espectrometria de Massas em Tandem/métodos , Adulto , Animais , Ensaios de Triagem em Larga Escala , Humanos , Limite de Detecção , Modelos Lineares , Masculino , Purinas/sangue , Pirimidinas/sangue , Ratos , Ratos Wistar , Reprodutibilidade dos Testes
11.
J Proteome Res ; 18(5): 1994-2003, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-30907085

RESUMO

Coronary heart disease (CHD) threatens human health. The discovery and assessment of potential biometabolic markers for different syndrome types of CHD may contribute to decipher pathophysiological mechanisms and identify new targets for diagnosis and treatment. On the basis of UPLC-Q-TOF/MS metabolomics technology, urine samples of 1072 participants from nine centers, including normal control, phlegm and blood stasis (PBS) syndrome and Qi and Yin deficiency (QYD) syndrome, and other syndromes of CHD, were conducted to find biomarkers. Among them, the discovery set ( n = 125) and the test set ( n = 337) were used to identify and validate biomarkers, and the validation set ( n = 610) was used for the application and evaluation of the support vector machine (SVM) prediction model. We discovered 15 CHD-PBS syndrome biomarkers and 12 CHD-QYD syndrome biomarkers, and the receiver-operator characteristic (ROC) area-under-the-curve (AUC) values of them were 0.963 and 0.990. The established SVM model has a good diagnostic ability and can well distinguish the two syndromes of CHD with a high predicted accuracy >98.0%. The discovery of biomarkers and metabolic pathways in different syndrome types of CHD provides a basis for the diagnosis and evaluation of CHD, thereby improving the accurate diagnosis and precise treatment level of Chinese medicine.

12.
Nanoscale ; 11(12): 5441-5449, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30855048

RESUMO

Stable and reliable electrical properties of interconnects and interfaces between flexible/stretchable and rigid materials/components are essential for the practical applications of flexible electronic devices and systems; traditional metal thin films and hard solder interconnects and interfaces can no longer meet these requirements. As an emerging soft conductive material, liquid metal has the advantages of high stretchability, flexibility, etc. over other soldering materials, and it has been used in interconnects and interfaces for some flexible electronics. In this study, we report a detailed investigation on the reliability and stability of liquid metal-based interconnects/interfaces under various mechanical deformations, including extension, bending, torsion, high frequency vibration and high temperature operation; we also compared the results with those of interconnects and interfaces using silver paste, the most commonly used solder for flexible electronics. The results show that liquid metal interconnects and interfaces maintain high conductivity under severe elongation up to 95% and 130%, upon bending with a curvature radius as low as ∼1.5 mm, and upon twisting up to 360°; meanwhile, interconnects and interfaces with silver paste filler lose electrical conductivity at elongations of 0.6% and 60%, respectively. Liquid metal interconnects and interfaces show superior performance to silver paste interconnects and interfaces because liquid metal can be re-shaped to make good contact with objects, while the silver paste becomes solid and rigid once dried and thus loses contact with other objects under deformation.

13.
Phytomedicine ; 54: 365-370, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30217547

RESUMO

BACKGROUND: Considering that the quality control indicators in Chinese medicine (CM) are disconnected from safety and effectiveness, Prof. Chang-xiao Liu et al. has proposed a concept regarding the quality marker (Q-marker) of CM to promote the healthy development of the CM industry and improve the CM quality control method. PURPOSE: In this study, we proposed a strategy to discover and verify the toxicity Q-marker of CM based on network toxicology. METHODS: First, traditional biochemical pathology indicators and sensitive biomarkers were used to predict the toxicity of CM. Next, the chemical composition of toxic CMs and their metabolites were rapidly identified by multidimensional detection techniques. Subsequently, the interaction network between "toxicity - toxic chemical composition - toxic target - effect pathway" was built through network toxicology, and the potential toxicity Q-marker of CM was initially screened. Finally, the chemical properties of toxicity Q-markers were verified by traceability and testability. RESULTS: Based on the predicted results of network toxicology, the toxic compounds of CM were preliminarily identified, and the toxic mechanism was comprehensively interpreted. In the context of definite biological properties and chemical properties, the toxicity Q-marker was finally confirmed. CONCLUSION: This extensive review provides a study method for the toxicity Q-marker of CM, which helps to systemically and thoroughly reveal the internal toxicity mechanism of CM. The in-depth study of the toxicity Q-marker provides the material basis and technical support for the safety evaluation of CM.


Assuntos
Biomarcadores/análise , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa/normas , Humanos , Medicina Tradicional Chinesa/efeitos adversos , Controle de Qualidade
14.
Toxicol Res (Camb) ; 8(6): 850-861, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32110379

RESUMO

Triptolide (TP) is one of the important active components in Tripterygium wilfordii Hook. F., which shows strong anti-inflammatory and immunomodulatory effects. However, a large number of literature studies have reported that TP is the main component causing nephrotoxicity, and the mechanism of nephrotoxicity has not yet been revealed. Therefore, it is of great practical significance to clarify the toxicity mechanism of TP. This study integrated network pharmacology and targeted metabolomics to reveal the nephrotoxicity mechanism of TP. Firstly, network pharmacology screening of 61 action targets related to TP induced nephrotoxicity, with 39 direct targets and 22 indirect targets, was performed. Subsequently, based on a large-scale protein-protein interaction (PPI) and molecular docking validation, the core targets were identified. Based on the above targets and enrichment analysis, the purine metabolism, Toll-like receptor signaling pathway and NF-κB signaling pathway were found play a pivotal role in TP-induced nephrotoxicity. Literature investigation showed that purine and pyrimidine metabolism pathways were closely related to kidney diseases. Therefore, by using the quantitative method of determining endogenous purine and pyrimidine previously established in the laboratory, a targeted metabolomic analysis of TP was carried out. Finally, six nephrotoxicity biomarkers, dihydroorotate, thymidine, 2-deoxyinosine, uric acid, adenosine and xanthine, were found. Combining the above results, the mechanisms underlying the nephrotoxicity of TP were speculated to be due to the over-consumption of xanthine and uric acid, which would result in enormous ROS being released in response to oxidative stress in the body. Furthermore, activation of the Toll-like receptor signalling pathway can promotes the phosphorylation of the downstream protein NF-κB and causes an inflammatory response that ultimately leads to nephrotoxicity.

15.
Toxicol Res (Camb) ; 7(6): 1153-1163, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30510685

RESUMO

Both Strychnos nux-vomica Linn. (SNV) and Tripterygium wilfordii Hook F (TwHF) have received extensive attention due to their excellent clinical efficacies. However, clinical applications of SNV and TwHF have been limited by their narrow therapeutic windows and severe kidney toxicities. In this paper, based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS), endogenous metabolites after administration of SNV and TwHF extracts were detected, and biomarkers were screened successfully. Additionally, the levels of Cr and BUN in serum and pathological findings of kidneys were detected and observed. Finally, both biochemical and pathological tests of the SNV group and TwHF group indicated that kidney damage had occurred. After comparison with the normal saline group, 15 nephrotoxic biomarkers were selected from the SNV group, and 17 nephrotoxic biomarkers were selected from the TwHF group. The experimental results showed that there are some differences in the mechanisms of nephrotoxicity induced by SNV and TwHF, which are significant for revealing the mechanisms of renal injury of different medicines.

16.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1100-1101: 106-112, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30308417

RESUMO

Tongmai Yangxin Pill (TMYX) is a traditional Chinese medicine for the treatment of angina and arrhythmia. Although its clinical application is extensive, and the curative effect is significant, little information is available on the molecular biological basis and therapeutic mechanism of TMYX for the treatment of stable angina. In this study, we analyzed serum samples of clinical patients collected from seven different clinical units in China after oral administration of TMYX using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS). Multiple statistical analysis including principal component analysis (PCA) and partial least square discrimination analysis (PLS-DA), were used to examine metabolite profile changes in serum samples. After TMYX treatment, 10 biomarkers were reversed to the normal conditions. The above biomarkers were mainly involved in energy metabolism, amino acid metabolism, oxidative stress and inflammation. These results suggested that TMYX exerted therapeutic effects by improving myocardial energy supply disorder and amino acid dysfunction, and attenuating oxidative stress and inflammation. The present study, as the first multicenter clinical study which reveals the molecular biological basis and therapeutic mechanism of TMYX on stable angina, can provide objective indicators for efficacy evaluation of TMYX on stable angina. And it also lays a foundation for the use of TMYX clinically.


Assuntos
Angina Estável/tratamento farmacológico , Biomarcadores/sangue , Medicamentos de Ervas Chinesas/farmacologia , Metaboloma/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Masculino , Metabolômica/métodos , Análise de Componente Principal , Curva ROC , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
17.
BMC Psychiatry ; 18(1): 337, 2018 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-30333002

RESUMO

BACKGROUND: The etiology of depression and its effective therapeutic treatment have not been clearly identified. Using behavioral phenotyping and resting-state functional magnetic resonance imaging (r-fMRI), we investigated the behavioral impact and cerebral alterations of chronic unpredictable mild stress (CUMS) in the rat. We also evaluated the efficacy of telmisartan therapy in this rodent model of depression. METHODS: Thirty-two rats were divided into 4 groups: a control group(C group), a stress group(S group), a stress + telmisartan(0.5 mg/kg)group (T-0.5 mg/kg group) and a stress + telmisartan(1 mg/kg) group (T-1 mg/kg group). A behavioral battery, including an open field test (OFT), a sucrose preference test (SPT), and an object recognition test (ORT), as well as r-fMRI were conducted after 4 weeks of CUMS and telmisartan therapy. The r-fMRI data were analyzed using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) approach. The group differences in the behavior and r-fMRI test results as well as the correlations between these 2 approaches were examined. RESULTS: CUMS reduced the number of rearings and the total moved distance in OFT, the sucrose preference in SPT, and novel object recognition ability in ORT. The telmisartan treatment (1 mg/kg) significantly improved B-A/B + A in the ORT and improved latency scores in the OFT and SPT. The S group exhibited a decreased ReHo in the motor cortex and pons, but increased ReHo in the thalamus, visual cortex, midbrain, cerebellum, hippocampus, hypothalamus, and olfactory cortex compared to the C group. Telmisartan (1 mg/kg)reversed or attenuated the stress-induced changes in the motor cortex, midbrain, thalamus, hippocampus, hypothalamus, visual cortex, and olfactory cortex. A negative correlation was found between OFT rearing and ReHo values in the thalamus. Two positive correlations were found between ORT B-A and the ReHo values in the olfactory cortexand pons. CONCLUSIONS: Telmisartan may be an effective complementary drug for individuals with depression who also exhibit memory impairments. Stress induced widespread regional alterations in the cerebrum in ReHo measures while telmissartan can reverse part of theses alterations. These data lend support for future research on the pathology of depression and provide a new insight into the effects of telmisartan on brain function in depression.


Assuntos
Encéfalo/diagnóstico por imagem , Depressão/diagnóstico por imagem , Comportamento Exploratório/fisiologia , Imagem por Ressonância Magnética/métodos , Estresse Psicológico/diagnóstico por imagem , Telmisartan/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Animais , Encéfalo/efeitos dos fármacos , Depressão/tratamento farmacológico , Depressão/psicologia , Avaliação Pré-Clínica de Medicamentos/métodos , Comportamento Exploratório/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , /fisiologia , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/psicologia , Telmisartan/farmacologia
18.
BMC Complement Altern Med ; 18(1): 245, 2018 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-30176849

RESUMO

BACKGROUND: Er-Xian decoction (EXD), a formula of Chinese medicine, is often used to treat menopausal syndrome in China. The aim of the present study was to explore the potential cardioprotective mechanism of EXD against myocardial injury in an ovariectomy-induced menopausal rat model. METHODS: We divided the female Wistar rats into ovariectomy group and sham operation group (SHAM group). The ovariectomized (OVX) rats received treatment of vehicle (OVX group), EXD (EXD group) or 17ß-estradiol (E2 group). After 12-week of treatment, the level of estradiol in serum was detected using an electrochemiluminescence immunoassay, and electrophysiologic changes in myocardial action potentials (AP) were evaluated using intracellular microelectrode technique. Changes in the histopathology of the left ventricle and the ultrastructure of the cardiomyocytes were observed by hematoxylin and eosin (HE) staining and transmission electronmicroscopy to assess myocardial injury. Microarrays were applied for the evaluation of gene expression profiles in ventricular muscle of the OVX and EXD rats. Further pathway analyses of the differential expression genes were carried out using the Kyoto Encyclopedia of Genes and Genomes (KEGG). And real-time quantitative RT-PCR (qRT-PCR) was used for verification of the key findings. RESULTS: The results from electrophysiological and histomorphological observations demonstrated that EXD had a substantial myocardial protective effect. The EXD-treated rats, in comparison with the OVX rats, demonstrated up-regulated expression of 28 genes yet down-regulated expression of 157 genes in the ventricular muscle. The qRT-PCR assay validated all selected differential expression genes. The KEGG pathway analysis showed that the down-regulated genes were relevant to cardiomyopathy and myocardial contractility. EXD could decrease the mRNA expressions of cardiac myosin (Myh7, Myl2) and integrin (Itgb5) in the ventricular myocardium. CONCLUSION: EXD had a protective effect against myocardial injury in OVX rats, and this cardioprotective effect may be associated with modulation of the expression of cardiac myosin or integrin at the mRNA level.


Assuntos
Cardiomiopatias , Cardiotônicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Coração/efeitos dos fármacos , Menopausa/metabolismo , Animais , Cardiomiopatias/genética , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Feminino , Miocárdio/química , Miocárdio/metabolismo , Miocárdio/patologia , Tamanho do Órgão/efeitos dos fármacos , Ovariectomia , Ratos , Ratos Wistar , Transcriptoma/efeitos dos fármacos , Útero/efeitos dos fármacos
19.
J Sep Sci ; 41(19): 3791-3805, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30074686

RESUMO

Bupleuri radix and liquorice are commonly used as a hepatoprotectants. Their main effective ingredients are triterpenoid saponins. It is known that the saponins in liquorice and Bupleuri radix not only promote the metabolism of sugar and lipids but also have anti-inflammatory functions and hepatoprotective effect. However, the complexity of these compounds results in difficulty in studying their pharmacodynamics and mechanism. In this study, glycosides were the main components that were identified and selected as the main research object. First, the mass spectrometry information of the main chemical components in liquorice and Bupleuri radix were collected from the literature. The characteristic fragments and neutral losses were summarized according to typical cleavage methods. Second, the samples were analysed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry, and characteristic fragment filters and neutral loss filters were successfully applied to screen 18 saponins from Bupleuri radix and 23 saponins and nine flavonoid glycosides from liquorice. Rapid classification and identification of the main components in Bupleuri radix and liquorice were finally achieved. This method promoted the development of chemical components in Bupleuri radix and liquorice, and provided a new way for screening, classifying, and identifying target components in complex samples of metabolomics and pharmacokinetics.


Assuntos
Bupleurum/química , Medicamentos de Ervas Chinesas/análise , Glicosídeos/análise , Glycyrrhiza/química , Extratos Vegetais/análise , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Fatores de Tempo
20.
Toxicol Res (Camb) ; 7(3): 529-537, 2018 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-30090603

RESUMO

Oxaliplatin is a third generation antitumor agent, which is often used in treating advanced colorectal cancer, but the use of oxaliplatin is limited by its side effects, especially peripheral nerve toxicity. Metabonomics techniques, as a holistic analytical technique, could provide basic information on the metabolic profile of biological fluids during drug administration. In this study, we used the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technique to analyze rat plasma samples collected seven days after oxaliplatin administration. The changes of metabolites in plasma samples were evaluated by principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), and 15 kinds of neurotoxicity-related biomarkers were screened. The metabolic pathways of interference involved amino acid biosynthesis and metabolism, glycerophospholipid metabolism, sphingolipid metabolism and so on. The biomarkers found in this study are significant for the study of neurotoxicity.

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