Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 60
Filtrar
1.
BMC Genomics ; 25(1): 698, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014331

RESUMO

BACKGROUND: Inner Mongolia cashmere goat (IMCG), renowned for its superior cashmere quality, is a Chinese indigenous goat breed that has been developed through natural and artificial selection over a long period. However, recently, the genetic resources of IMCGs have been significantly threatened by the introduction of cosmopolitan goat breeds and the absence of adequate breed protection systems. RESULTS: In order to assess the conservation effectiveness of IMCGs and efficiently preserve and utilize the purebred germplasm resources, this study analyzed the genetic diversity, kinship, family structure, and inbreeding of IMCGs utilizing resequencing data from 225 randomly selected individuals analyzed using the Plink (v.1.90), GCTA (v.1.94.1), and R (v.4.2.1) software. A total of 12,700,178 high-quality SNPs were selected through quality control from 34,248,064 SNP sites obtained from 225 individuals. The average minor allele frequency (MAF), polymorphic information content (PIC), and Shannon information index (SHI) were 0.253, 0.284, and 0.530, respectively. The average observed heterozygosity (Ho) and the average expected heterozygosity (He) were 0.355 and 0.351, respectively. The analysis of the identity by state distance matrix and genomic relationship matrix has shown that most individuals' genetic distance and genetic relationship are far away, and the inbreeding coefficient is low. The family structure analysis identified 10 families among the 23 rams. A total of 14,109 runs of homozygosity (ROH) were identified in the 225 individuals, with an average ROH length of 1014.547 kb. The average inbreeding coefficient, calculated from ROH, was 0.026 for the overall population and 0.027 specifically among the 23 rams, indicating a low level of inbreeding within the conserved population. CONCLUSIONS: The IMCGs exhibited moderate polymorphism and a low level of kinship with inbreeding occurring among a limited number of individuals. Simultaneously, it is necessary to prevent the loss of bloodline to guarantee the perpetuation of the IMCGs' germplasm resources.


Assuntos
Variação Genética , Cabras , Polimorfismo de Nucleotídeo Único , Animais , Cabras/genética , Sequenciamento Completo do Genoma , Frequência do Gene , Endogamia , China
2.
Pestic Biochem Physiol ; 202: 105950, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879305

RESUMO

Hypoaconitine (HA), a major secondary metabolite of aconite (a plant-derived rodenticide), is a highly toxic di-ester alkaloidal constituent. The toxicity of HA is intense with a low LD50. However, studies on its toxicity mechanism have mainly focused on cardiotoxicity, with few reports on the mechanism of hepatotoxicity. In this study, we combined metabolomics and network toxicology to investigate the effects of HA on the liver and analyzed the mechanisms by which it causes hepatotoxicity. The results of metabolomics studies indicated diethylphosphate, sphingosine-1-phosphate, glycerophosphorylcholine, 2,8-quinolinediol, guanidinosuccinic acid, and D-proline as differential metabolites after HA exposure. These metabolites are involved in eight metabolic pathways including arginine and proline metabolism, ether lipid metabolism, ß-alanine metabolism, sphingolipid metabolism, glutathione metabolism, and glycerophospholipid metabolism. Network toxicology analysis of HA may affect the HIF-1 signaling pathway, IL-17 signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, and so on by regulating the targets of ALB, HSP90AA1, MMP9, CASP3, and so on. Integrating the results of metabolomics and network toxicology, it was concluded that HA may induce hepatotoxicity by triggering physiological processes such as oxidative stress, inflammatory response, and inducing apoptosis in hepatocytes.


Assuntos
Aconitina , Fígado , Metabolômica , Animais , Camundongos , Masculino , Aconitina/análogos & derivados , Aconitina/toxicidade , Fígado/metabolismo , Fígado/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Transdução de Sinais/efeitos dos fármacos
3.
Phytochem Anal ; 35(6): 1399-1417, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38837823

RESUMO

BACKGROUND: Radix Aconiti Lateralis (Fuzi), a mono-herbal preparation of Aconitum herbs in the genus Aconitum, is commonly used in traditional Chinese medicine (TCM) to treat critical illnesses. The curative effect of Fuzi is remarkable. However, the toxic effects of Fuzi are still a key clinical focus, and the substances inducing nephrotoxicity are still unclear. Therefore, this study proposes a research model combining "in vitro and in vivo component mining-virtual multi-target screening-active component prediction-literature verification" to screen potential nephrotoxic substances rapidly. METHOD: The UHPLC-Q-Exactive-Orbitrap MS analysis method was used for the correlation analysis of Fuzi's in vitro-in vivo chemical substance groups. On this basis, the key targets of nephrotoxicity were screened by combining online disease databases and a protein-protein interaction (PPI) network. The computer screening technique was used to verify the binding mode and affinity of Fuzi's components with nephrotoxic targets. Finally, the potential material basis of Fuzi-induced nephrotoxicity was screened. RESULTS: Eighty-one Fuzi components were identified. Among them, 35 components were absorbed into the blood. Based on the network biology method, 21 important chemical components and three potential key targets were screened. Computer virtual screening revealed that mesaconine, benzoylaconine, aconitine, deoxyaconitine, hypaconitine, benzoylhypaconine, benzoylmesaconine, and hypaconitine may be potential nephrotoxic substances of Fuzi. CONCLUSIONS: Fuzi may interact with multiple components and targets in the process of inducing nephrotoxicity. In the future, experiments can be designed to explore further. This study provides a reference for screening Fuzi nephrotoxic components and has certain significance for the safe use of Fuzi.


Assuntos
Aconitum , Medicamentos de Ervas Chinesas , Rim , Espectrometria de Massas , Aconitum/química , Rim/efeitos dos fármacos , Animais , Medicamentos de Ervas Chinesas/toxicidade , Medicamentos de Ervas Chinesas/química , Espectrometria de Massas/métodos , Cromatografia Líquida de Alta Pressão/métodos , Aconitina/análogos & derivados , Aconitina/toxicidade , Mapas de Interação de Proteínas/efeitos dos fármacos , Simulação de Acoplamento Molecular , Diterpenos
4.
Molecules ; 29(12)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38930800

RESUMO

Cangjie Temple was built to commemorate Cangjie, the legendary inventor of Chinese characters. It stands as one of the few remaining temples in China dedicated to the invention and creation of writing. In this study, the material properties of wooden paintings from the Cangjie temple were characterized using Polarized Light Microscopy (PLM), Scanning Electron Microscopy coupled with Energy Dispersive X-ray Spectroscopy (SEM-EDS), Micro-confocal Raman Spectroscopy, X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Pyrolysis-Gas Chromatography-Mass Spectrometry (Py-GC/MS). It was confirmed that the pigments of the paintings included cinnabar, lapis lazuli, lead white, Paris green, and carbon black. The proteinaceous glue was used as an adhesive in the pigment samples, with tung oil likely being utilized as a primer for the wooden structures before painting. This study not only provides valuable data support for the conservation and restoration of the architectural features of Cangjie Temple but also provides useful reference for the maintenance and inheritance of similar ancient buildings.

5.
Eur J Vasc Endovasc Surg ; 57(3): 434-441, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30087010

RESUMO

OBJECTIVES: Acute aortic dissection (AAD) is a severe clinical emergency with a high mortality, and is easily misdiagnosed in its early stage. This study aimed at discovering serum metabolomic markers with the potential to diagnose AAD and distinguish between two subtypes of AAD. METHODS: Thirty-five patients with AAD, including 20 with Stanford type A and 15 with Stanford type B were enrolled in this study, together with 20 healthy controls. All patients with AAD were admitted within 72 h of onset. Serum metabolomics profiles were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and the data were analysed by principal component analysis and partial least squares discriminant analysis. RESULTS: A total of 17 metabolites differing between the control and AAD groups were finally screened and identified as lysophosphatidylcholines (LPC) and sphingolipids including sphinganine, phytosphingosine, sphingomyelin, and ceramide. Compared with those in the healthy control group, LPC levels were significantly lower in both the Stanford type A and type B AAD groups. Interestingly, sphingolipids, including sphinganine, phytosphingosine, and ceramide, were remarkably reduced in the Stanford type A AAD group, but not in the Stanford type B AAD group. Subgroup analysis showed that the changes in LPC and sphingolipid levels were unrelated to hypertension or gender. CONCLUSIONS: The present results indicate that LPCs and sphingolipids are significantly altered in patients with AAD, and several sphingolipids, such as sphinganine, phytosphingosine, and ceramide, were dramatically decreased in patients with Stanford type A AAD. A combination of these two families of metabolites could serve as a potential biomarker for the diagnosis of AAD and distinguishing between Stanford type A and Stanford type B.


Assuntos
Aneurisma Aórtico/sangue , Aneurisma Aórtico/diagnóstico , Dissecção Aórtica/sangue , Dissecção Aórtica/diagnóstico , Lisofosfatidilcolinas/sangue , Metabolômica/métodos , Esfingolipídeos/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Cromatografia Líquida , Diagnóstico Diferencial , Análise Discriminante , Feminino , Humanos , Análise dos Mínimos Quadrados , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Análise de Componente Principal
6.
Analyst ; 144(5): 1696-1703, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30657480

RESUMO

In this paper, we introduced a new strategy for converting aggregation-induced emission (AIE) to fluorescence emission in solution into the rational design of new fluorescent probes. Two fluorescent probes based on this strategy, namely, PDAM-Lyso and PDAM-Me, have been synthesized and tested both in vitro and in vivo. The fluorophores of the two probes are both phenothiazine molecules, which link to the diaminomaleonitrile (DAMN) moiety through imine bonds. In the presence of imine bonds, the probes emit red fluorescence in an aqueous solution caused by the AIE effect. As the imine bonds are selectively cut-off by HClO, the DAMN moiety gets removed, inducing blue fluorescence of the reaction product. In this way, the selectivity of the DAMN-based probes toward HClO against metal ions and other reactive oxygen species (ROS) was successfully improved. The imaging of endogenous and exogenous HClO with these two probes reveals that lysosome-targeting probes are of great advantage in the detection of natively generated HClO. Furthermore, the imaging of endogenous HClO in zebrafish suggests that PDAM-Lyso is capable of monitoring the generation of HClO in vivo, illustrating that this strategy is of great significance in designing new probes.


Assuntos
Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Nitrilas/química , Fenotiazinas/química , Animais , Fenômenos Químicos , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Ácido Hipocloroso/química , Limite de Detecção , Lisossomos/metabolismo , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Nitrilas/síntese química , Nitrilas/toxicidade , Fenotiazinas/síntese química , Fenotiazinas/toxicidade , Células RAW 264.7 , Peixe-Zebra
7.
Biol Pharm Bull ; 41(8): 1243-1250, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30068874

RESUMO

Celastrol is well known for its anti-cancer effects, yet its specific mechanisms against colon cancer are still not fully elucidated. In this study, cytotoxic effect of celastrol against HCT116 colon cancer cells was investigated based on cell viability assay and flow cytometry assay, and the possible mechanism was explored using a strategy combining metabolic profiling and targeted metabolite analysis based on ultra performance liquid chromatography (UPLC)/MS. Celastrol was found to inhibit the growth of colon cancer cells and induce apoptosis. Metabolomics analysis revealed characteristic changes in metabolic profiles of the colon cancer cells, revealing altered levels of amino acids, carnitine, and lipid markers. Most interestingly, with the assistance of targeted metabolite analysis, tryptophan (Trp) level was significantly increased whereas kynurenine (Kyn) level was decreased in colon cancer cells after celastrol treatment, together with markedly declined Kyn/Trp ratios. Western blot analysis revealed that expression of indoleamine 2,3-dioxygenase (IDO), the enzyme catalyzing Trp to generate Kyn, was dramatically inhibited in colon cancer cells after celastrol treatment, with a dose-dependent manner. These results suggest that suppression of IDO expression and tryptophan catabolism may be part of the mechanisms of celastrol in its cytotoxic effect against HCT116 colon cancer cells. This study provided scientific basis for further development of celastrol on treating colon cancer.


Assuntos
Antineoplásicos/farmacologia , Neoplasias do Colo/metabolismo , Triterpenos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células HCT116 , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Cinurenina/metabolismo , Metabolômica , Triterpenos Pentacíclicos , Triptofano/metabolismo
8.
BMC Complement Altern Med ; 18(1): 288, 2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30355303

RESUMO

BACKGROUND: Iridoid glycosides (IGs), including monotropein (MON) and deacetyl asperulosidic acid (DA) as the main ingredients, are the major chemical components in Morinda officinalis How. (MO) root, possessing various pharmacological properties including anti-osteoporosis, anti-inflammation and anti-rheumatism activities.The aim of the present study was to further elucidate the pharmacological actions of MO by investigating the pharmacokinetics and tissue distribution of IGs in MO. METHODS: An ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) method was developed and validated for simultaneous determination of MON and DA levels in plasma and various tissues of Wistar rats. MON, DA and acetaminophen (ACE) as the internal standard (IS) were extracted from rat plasma and tissue samples by direct deproteinization with methanol. The rats were administered orally at 1650 mg/kg MO and 25, 50 and 100 mg/kg MO iridoid glycosides (MOIGs) or intravenously at MOIG 25 mg/kg for pharmacokinetic study of MON and DA. In addition, 100 mg/kg MOIG was administered orally for tissue distribution study of MON and DA. Non-compartmental pharmacokinetic profiles were constructed. Tissue distributions were calculated according to the validated methods. RESULTS: Significant differences in the pharmacokinetic parameters were observed in male and female rats. The AUC0-t, Cmax and bioavailability of MON and DA in female rats were higher than those in male rats. MON and DA mainly distributed in the intestine and stomach after oral administration, and noteworthily high concentrations of MON and DA were detected in the rat hypothalamus. CONCLUSION: The results of the present study may shed new lights on the biological behavior of MOIGs in vivo, help explain their pharmacological actions, and provide experimental clues for rational clinical use of these IGs extracted from the MO root.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Glicosídeos/farmacocinética , Iridoides/farmacocinética , Morinda/química , Administração Oral , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Feminino , Glicosídeos/administração & dosagem , Glicosídeos/química , Glicosídeos Iridoides/administração & dosagem , Glicosídeos Iridoides/química , Glicosídeos Iridoides/farmacocinética , Iridoides/administração & dosagem , Iridoides/química , Masculino , Estrutura Molecular , Raízes de Plantas/química , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem , Distribuição Tecidual
9.
Biol Pharm Bull ; 40(6): 936-940, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28321036

RESUMO

Inflammatory bowel disease (IBD) is a refractory illness with remarkably increasing incidence rate all over the world. However, no desirable treatment scheme is available. Therefore, research and development of new drugs for treating IBD are urgently needed. Histone deacetylase 6 (HDAC6) is considered to be a pro-inflammatory factor, thus the inhibitors specifically-targeting HDAC6 may find their way in IBD treatment. In this study, we evaluated the anti-inflammatory activity of a novel potent and selective HDAC6 inhibitor, LTB2, in dextran sulfate sodium (DSS)-induced colitis mouse model. It was found that LTB2 treatment significantly alleviated DSS-induced colitis in mice, as evidenced by body weight, colon length, histological examination, and the disease activity index (DAI) scores of rectal bleeding and diarrhea. More importantly, it showed a better protective effect on the DSS-induced colitis mice than the commonly used mesalazine in the clinic. Our results demonstrated that selective HDAC6 inhibitors may have a good prospect for IBD treatment.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/tratamento farmacológico , Desacetilase 6 de Histona/antagonistas & inibidores , Animais , Colite/induzido quimicamente , Colite/patologia , Colo/efeitos dos fármacos , Colo/patologia , Sulfato de Dextrana , Masculino , Camundongos Endogâmicos C57BL
10.
Biochim Biophys Acta ; 1851(1): 19-29, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24796972

RESUMO

Bile acid synthesis is the major pathway for catabolism of cholesterol. Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme in the bile acid biosynthetic pathway in the liver and plays an important role in regulating lipid, glucose and energy metabolism. Transgenic mice overexpressing CYP7A1 (CYP7A1-tg mice) were resistant to high-fat diet (HFD)-induced obesity, fatty liver, and diabetes. However the mechanism of resistance to HFD-induced obesity of CYP7A1-tg mice has not been determined. In this study, metabolomic and lipidomic profiles of CYP7A1-tg mice were analyzed to explore the metabolic alterations in CYP7A1-tg mice that govern the protection against obesity and insulin resistance by using ultra-performance liquid chromatography-coupled with electrospray ionization quadrupole time-of-flight mass spectrometry combined with multivariate analyses. Lipidomics analysis identified seven lipid markers including lysophosphatidylcholines, phosphatidylcholines, sphingomyelins and ceramides that were significantly decreased in serum of HFD-fed CYP7A1-tg mice. Metabolomics analysis identified 13 metabolites in bile acid synthesis including taurochenodeoxycholic acid, taurodeoxycholic acid, tauroursodeoxycholic acid, taurocholic acid, and tauro-ß-muricholic acid (T-ß-MCA) that differed between CYP7A1-tg and wild-type mice. Notably, T-ß-MCA, an antagonist of the farnesoid X receptor (FXR) was significantly increased in intestine of CYP7A1-tg mice. This study suggests that reducing 12α-hydroxylated bile acids and increasing intestinal T-ß-MCA may reduce high fat diet-induced increase of phospholipids, sphingomyelins and ceramides, and ameliorate diabetes and obesity. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics.


Assuntos
Ácidos e Sais Biliares/metabolismo , Diabetes Mellitus/metabolismo , Metabolismo dos Lipídeos/fisiologia , Metaboloma/genética , Obesidade/metabolismo , Animais , Ácidos e Sais Biliares/genética , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Diabetes Mellitus/genética , Dieta Hiperlipídica/métodos , Feminino , Glucose/genética , Glucose/metabolismo , Homeostase , Resistência à Insulina , Mucosa Intestinal/metabolismo , Fígado/metabolismo , Masculino , Metabolômica/métodos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Obesidade/genética , Ratos , Transdução de Sinais , Ácido Taurocólico/análogos & derivados , Ácido Taurocólico/genética , Ácido Taurocólico/metabolismo
11.
J Sep Sci ; 38(9): 1466-75, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25678068

RESUMO

Rhizoma Smilacis Glabrae (RSG) is a well-known herbal medicine with the homology of medicine and food. In this study, simultaneous chemical fingerprint and quantitative analysis of the bioactive flavonoid components of RSG were developed using accelerated solvent extraction and high-performance liquid chromatography coupled with ion trap tandem mass spectrometry. The operational parameters of accelerated solvent extraction including extraction solvent, extraction temperature, static extraction time, solid-to-liquid ratio, and extraction cycles were optimized. Hierarchical cluster analysis, similarity analysis, and principal component analysis were performed to evaluate the similarity and variation of the samples collected from several provinces in China. Subsequently, high-performance liquid chromatography fingerprints were established for the discrimination of 16 batches of RSG samples, and the major six flavonoids, namely, toxifolin, neoastilbin, astilbin, neoisoastilbin, isoastilbin, and engeletin were then quantitatively determined. The calibration curves for all the six analytes showed good linearity (r(2) > 0.999), and the limits of detection and quantification were less than 0.10 and 0.27 µg·mL(-1) , respectively. Therefore, the proposed extraction and determination methods were proved to be robust and reliable for the quality control of RSG.


Assuntos
Fracionamento Químico , Medicamentos de Ervas Chinesas/análise , Flavonoides/análise , Rizoma/química , Cromatografia Líquida de Alta Pressão , Solventes/química , Estereoisomerismo , Espectrometria de Massas em Tandem
12.
Biochim Biophys Acta ; 1830(3): 2779-89, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23142250

RESUMO

BACKGROUND: Celastrol, a quinine methide triterpene extracted from a Chinese medicine (Trypterygium wilfordii Hook F.), has the potential to become an anticancer drug with promising prospects. Cell culture metabolomics has been a powerful method to study metabolic profiles in cell line after drug treatment, which can be used for discovery of drug targets and investigation of drug effects. METHODS: We analyzed the metabolic modifications induced by celastrol treatment in human cervical cancer cells, using an ion-trap gas chromatography-mass spectrometry based metabolomics combined with multivariate statistical analysis, which allows simultaneous screening of multiple characteristic metabolic pathways related to celastrol treatment. Three representative apoptosis-inducing cytotoxic agents, namely cisplatin, doxorubicin hydrochloride and paclitaxel, were selected as positive control drugs to validate reasonableness and accuracy of our metabolomic investigation on celastrol. RESULTS: Anti-proliferation and apoptotic effects of celastrol were demonstrated by CCK-8 assay, Annexin-V/PI staining method, mitochondrial membrane potential (deltapsim) assay and caspase-3 assay. Several significant metabolites involved in energy, amino acid and nucleic acid metabolism in HeLa cells induced by celastrol and positive drugs were reported. Our method is proved to be effective and robust to provide new evidence of pharmacological mechanism of celastrol. CONCLUSIONS: The metabolic alterations induced by drug treatment showed the impaired physiological activity of HeLa cells, which also indicated anti-proliferative and apoptotic effects of celastrol and these positive drugs. GENERAL SIGNIFICANCE: GC/MS-based metabolomic approach applied to cell culture could give valuable information on the systemic effects of celastrol in vitro and help us to further study its anticancer mechanism.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Metaboloma/efeitos dos fármacos , Triterpenos/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo , Análise de Variância , Anexina A5 , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Doxorrubicina/farmacologia , Ativação Enzimática/efeitos dos fármacos , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Células HeLa , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Paclitaxel/farmacologia , Triterpenos Pentacíclicos , Neoplasias do Colo do Útero/patologia
13.
Am J Physiol Gastrointest Liver Physiol ; 307(5): G564-73, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-25035112

RESUMO

Fibrates, such as fenofibrate, are peroxisome proliferator-activated receptor-α (PPARα) agonists and have been used for several decades as hypolipidemic agents in the clinic. However, contradictory observations exist on the role of fibrates in host response to acute inflammation, with unclear mechanisms. The role of PPARα in colitis was assessed using fenofibrate and Ppara-null mice. Wild-type or Ppara-null mice were subjected to acute colitis under three distinct protocols, dextran sulfate sodium, trinitrobenzenesulfonic acid, and Salmonella Typhi. Serum and colon lipidomics were analyzed to characterize the metabolic profiles by ultra-performance liquid chromatography-coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Messenger RNAs of PPARα target genes and genes involved in inflammation were determined by qunatitative PCR analysis. Fenofibrate treatment exacerbated inflammation and tissue injury in acute colitis, and this was dependent on PPARα activation. Lipidomics analysis revealed that bioactive sphingolipids, including sphingomyelins (SM) and ceramides, were significantly increased in the colitis group compared with the control group; this was further potentiated following fenofibrate treatment. In the colon, fenofibrate did not reduce the markedly increased expression of mRNA encoding TNFα found in the acute colitis model, while it decreased hydrolysis and increased synthesis of SM, upregulated RIPK3-dependent necrosis, and elevated mitochondrial fatty acid ß-oxidation, which were possibly related to the exacerbated colitis.


Assuntos
Colite/metabolismo , Colo/efeitos dos fármacos , Fenofibrato/efeitos adversos , Hipolipemiantes/efeitos adversos , PPAR alfa/metabolismo , Animais , Ceramidas/sangue , Colo/metabolismo , Colo/patologia , Fenofibrato/toxicidade , Hipolipemiantes/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , PPAR alfa/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Esfingomielinas/sangue , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
14.
Mol Biol Rep ; 41(2): 879-87, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24390232

RESUMO

The X-ray repair cross-complementing group 1 (XRCC1) gene, one of over 20 genes that participate in the base excision repair pathway, is thought to account for differences in susceptibility to hepatocellular carcinoma. To assess the relationship between the XRCC1 Arg399Gln polymorphism and the risk of hepatocellular carcinoma (HCC), we performed a meta-analysis. All the relevant studies were extracted from PubMed, Embase, the Chinese biomedicine databases, the Chinese national knowledge infrastructure, and the Wanfang databases (prior to August 2012). The meta-analysis was performed using all eligible studies, which covered a total of 2,554 cases and 3,320 controls, to examine the association between XRCC1 Arg399Gln polymorphism and the risk of HCC. Our analysis suggested that the variant genotypes of the XRCC1 Arg399Gln gene were associated with a significantly increased risk of HCC in a co-dominant model (Arg/Gln vs. Arg/Arg, odd ratios [OR] 1.39, 95 % confidence interval [CI] 1.08-1.79; Gln/Gln vs. Arg/Arg, OR 1.26, 95 % CI 1.04-1.52) and a dominant model (Arg/Gln + Gln/Gln vs. Arg/Arg OR 1.36, 95 % CI 1.07-1.72), whereas no association was observed in the recessive model (Gln/Gln vs. Arg/Gln + Arg/Arg, OR 1.05, 95 % CI 0.91-1.21). The results of the subgroup analysis by ethnicity indicated that the XRCC1 Arg399Gln polymorphism was associated with increased risk of HCC in Asian populations using the co-dominant model (Arg/Gln vs. Arg/Arg, OR 1.41, 95 % CI 1.06-1.87) and the dominant model (Gln/Gln vs. Arg/Gln + Arg/Arg, OR 1.35, 95 % CI 1.03-1.76). Our analysis provides evidence that the XRCC1 Arg399Gln polymorphism may be associated with a higher risk of HCC, especially among Asian populations.


Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Ligação a DNA/genética , Neoplasias Hepáticas/genética , Povo Asiático , Carcinoma Hepatocelular/patologia , Etnicidade/genética , Predisposição Genética para Doença , Humanos , Neoplasias Hepáticas/patologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Proteína 1 Complementadora Cruzada de Reparo de Raio-X
15.
J Sep Sci ; 37(17): 2300-6, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24923482

RESUMO

Silymarin extracted from Silybum marianum (L.) Gaertn consists of a large number of flavonolignans, of which diastereoisomeric flavonolignans including silybin A and silybin B, and isosilybin A and isosilybin B are the main bioactive components, whose preparation from the crude extracts is still a difficult task. In this work, binary-column recycling preparative high-performance liquid chromatography systems without sample loop trapping, where two columns were switched alternately via one or two six-port switching valves, were established and successfully applied to the isolation and purification of the four diastereoisomeric flavonolignans from silymarin. The proposed system showed significant advantages over conventional preparative high-performance liquid chromatography with a single column in increasing efficiency and reducing the cost. To obtain the same amounts of products, the proposed system spends only one tenth of the time that the conventional system spends, and needs only one eleventh of the solvent that the conventional system consumes. Using the proposed system, the four diastereoisomers were successfully isolated from silymarin with purities over 98%.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/isolamento & purificação , Flavonolignanos/isolamento & purificação , Silybum marianum/química , Cromatografia Líquida de Alta Pressão/instrumentação , Medicamentos de Ervas Chinesas/química , Flavonolignanos/química , Estereoisomerismo
16.
Spectrochim Acta A Mol Biomol Spectrosc ; 325: 124986, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39217960

RESUMO

Near-infrared (NIR) fluorophores have promoted the development of materials for bioimaging, but traditional NIR dyes usually suffer from aggregation-caused quenching (ACQ), impeding their applications. Herein, we propose two difluoroboron ß-diketonate complexes TBO and TBS, consisting a donor-acceptor (D-A) structure with triphenylamine (TPA) moiety as an electron donors and difluoroboron as well as furan or thiophene building block as an electron acceptor. The theoretical calculation and optical data shows that both of them have intramolecular charge transfer (ICT) characteristics. Such ICT characteristics endow them with both solvatochromism and dual-state emission (DSE) properties. In the solvent CH2Cl2, the emission wavelength of TBO ranges from 550 nm to 750 nm, with a low fluorescence quantum yield (Φ = 7.0 %). However, in the less polar solvent hexane, the emission wavelength blue-shifts, with an increased Φ reaching up to 18 %. Moreover, TBO and TBS exhibit mechanochromic characteristics and rare multi-channel fluorescence emission phenomena at solid-state. Their solid-state samples can emit fluorescence in four spectral bands with maximum emission wavelengths at 300 nm, 400 nm, 600 nm, and 770 nm under excitation at 240 nm. These unique optical properties are expected to be utilized for detecting polarity of system and deformation. Moreover, according to the results of cell imaging and flow cytometry, TBO molecular were easily internalized into Hela cells and distributed in the cytoplasm with strong red fluorescence. Therefore, this research inspires more insight into development of NIR luminogens for biomedical imaging.

17.
J Ethnopharmacol ; 333: 118475, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38908496

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The pathophysiological mechanism of thromboinflammation involves the intricate interplay between the inflammatory responses and coagulation cascades. Rhubarb is frequently used in traditional Chinese medicine to treat thromboinflammatory diseases. The scorched rhubarb (prepared by stir-baking the dried raw rhubarb till it partly turns to charcoal) is believed to possess enhanced blood-cooling and stasis-removing functions compared to the raw rhubarb, thereby augmenting the therapeutic effects on thromboinflammation. AIM OF THE STUDY: This study aimed to explore the chemical and pharmacological foundations of the scorch processing of rhubarb in order to ensure and enhance the efficacy and safety of the scorched rhubarb for treating thromboinflammatory diseases. MATERIALS AND METHODS: The dried raw rhubarb pieces were subjected to stir-baking at 180 °C for 10∼80 min to obtain the rhubarbs with varying degrees of scorching. Typical ingredients present in rhubarb pieces and extracts were determined by high-performance liquid chromatography. The therapeutic effects of the raw and scorched rhubarb on thromboinflammation were evaluated using a rat model. Proteomics analysis was employed to screen potential biological pathways associated with thromboinflammation treatment by the raw and scorched rhubarb, which were further verified using a cell model. RESULTS: Morphological properties indicated that the rhubarb baked at 180 °C for 50 min in this research showed the optimal degree of scorching. Compared to the raw rhubarb, the properly scorched rhubarb exhibited lower levels of anthraquinone glucosides, higher levels of anthraquinone aglycones, superior anti-thromboinflammatory effects, and no purgative side effects. Proteomics analysis revealed that the complement and coagulation cascades pathway played a significant role in mediating the therapeutic effects of the raw and scorched rhubarb on thromboinflammation. Furthermore, it was found that anthraquinone aglycones were more effective than their glucoside counterparts in restoring the impaired vascular endothelial cells as well as regulating the complement and coagulation cascades pathway. CONCLUSIONS: Proper scorch processing may augment the therapeutic effects of rhubarb on thromboinflammation via relieving inflammation and oxidative stress, repairing vascular endothelial cells, restoring coagulation cascades and blood rheology, and regulating some other biological processes. This may be partly caused by the scorch-induced thermolysis of anthraquinone glucosides into their aglycone counterparts that seemed to perform better in regulating the complement and coagulation cascades pathway.


Assuntos
Antraquinonas , Coagulação Sanguínea , Glucosídeos , Ratos Sprague-Dawley , Rheum , Animais , Rheum/química , Antraquinonas/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Masculino , Glucosídeos/farmacologia , Glucosídeos/química , Ratos , Inflamação/tratamento farmacológico , Trombose/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Proteínas do Sistema Complemento/metabolismo , Modelos Animais de Doenças , Extratos Vegetais/farmacologia , Extratos Vegetais/química
18.
Materials (Basel) ; 17(9)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38730973

RESUMO

This study analyzes the pigments and binders used in the painted wooden structure of DaZhong Gate in the Confucius Temple in Qufu, Shandong Province, China. Five samples were collected from the building and analyzed using techniques such as polarized light microscopy (PLM), energy-dispersive X-ray spectroscopy (EDX), micro-Raman spectroscopy (m-RS), and Fourier-transform infrared spectroscopy (FT-IR). The findings reveal that the red, yellow, green, and blue pigments are identified as lead red, lead chromate yellow, emerald green, and ultramarine, respectively. The white pigment is determined to be a combination of chalk and lead white or anglesite. Considering the production period of the yellow and green pigments, it is inferred that architectural paintings underwent restoration or repainting during the late Qing Dynasty. The analysis of the binder in the pigment using pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) reveals that the binder employed is a protein-based glue. Additionally, the detected presence of Heat-bodied tung oil suggests a potential connection to traditional Chinese painting techniques on wooden surfaces. This discovery not only contributes to the historical research of the Confucius Temple but also provides crucial data for the conservation and restoration efforts of this culturally significant heritage site.

19.
ChemSusChem ; 17(10): e202301725, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38225682

RESUMO

Rechargeable aluminum battery (RAB) is expected to be a promising energy storage technique for grid-scale energy storage. However, the development of RABs is seriously plagued by the lack of suitable cathode materials. Herein, we report two p-type conjugated polymers of L-PBPz and C-PBPz with the same building blocks of diphenylphenazine but different linkage patterns of linear and crosslinked structures as the cathode materials for Al dual-ion batteries. Compared to the linear polymer skeleton in L-PBPz, the crosslinked structure endows C-PBPz with amorphous nature and low dihedral angles of the polymer chains, which severally contribute to the fast diffusion of AlCl4 - with large size and the electron transfer during the redox reaction of diphenylphenazine. As a result, C-PBPz delivers a much better rate performance than L-PBPz. The crosslinked structure also leads to a stable cyclability with over 80000 cycles for C-PBPz. Benefiting from the fast kinetics, meanwhile, the C-PBPz cathode could realize a high redox activity of 117 mAh g-1, corresponding to an areal capacity of 2.30 mAh cm-2, even under a high mass loading of 19.7 mg cm-2 and a low content of 10 wt% conductive agent. These results might boost the development of polymer cathodes for RABs.

20.
Vet Sci ; 11(7)2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39057993

RESUMO

The purpose of this study was to investigate the effects of non-genetic factors on the growth and development performance of Inner Mongolia white cashmere goats (Erlanghan type), such as birth weight (BW), weaning weight (WW), 6-month weight (6 WT), 12-month weight (12 WT), body height (BH), and body length (BL), and wool production performance, such as cashmere fineness (CF), cashmere thickness (CT), and cashmere yield (CY). The research objects were 4654 kids produced by 45 buck goats and 2269 doe goats in the Erlang Mountain Ranch of Beiping Textile Co., Ltd., Inner Mongolia, from 2020 to 2023. Based on the generalized linear model, ANOVA was used to analyze the effects of non-genetic factors, such as birth year (Y), birth month (M), sex (S), birth type (T), birth herd (H), assay flock (F), age at measurement (MA), and the age of doe goats at lambing (DLA), on growth and development traits and cashmere traits. The results show that the birth weight (BW), weaning weight (WW), 6-month weight (6 WT), 12-month weight (12 WT), body length (BL), body height (BH), chest depth (CD), chest width (CW), chest circumference (CC), cannon circumference (CNC), wool length (WL), and cashmere yield (CY) of buck goats were significantly higher than those of doe goats (p < 0.01), and the fineness of the cashmere produced by doe goats was significantly finer than that produced by buck goats (p < 0.01). The birth weight, weaning weight, and 6-month weight of single kids were significantly higher than those of multiple kids (p < 0.01), but the effect on the 12-month weight was not significant (p > 0.05). The age of doe goats at lambing had significant effects on birth weight, weaning weight, and 6-month weight (p < 0.01). Assay flock and age at measurement had significant effects on cashmere fineness, cashmere thickness, and cashmere yield (p < 0.01). This study will provide a basis for the scientific breeding and management of cashmere goats and lay a foundation for the setting of fixed effects in the genetic evaluation model of Inner Mongolia white cashmere goats (Erlangshan type).

SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa