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1.
Zhongguo Zhong Yao Za Zhi ; 46(23): 6163-6177, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34951243

RESUMO

This study aimed to qualitatively analyze the chemical components in Xiaoer Chiqiao Qingre Granules(XRCQ) by UHPLC-LTQ-Orbitrap-MS/MS and identify its material basis. The absorbed components in plasma were combined for exploring the potential action mechanism by integrated network pharmacology. ACQUITY UPLC HSS T3(2.1 mm×100 mm, 1.8 µm) column and mobile phase system of 0.1% formic acid solution(A)-acetonitrile(B) were used for gradient elution, followed by high resolution liquid chromatography-mass spectrometry in both positive and negative ion scanning modes. According to the precise relative molecular mass and MS/MS fragment ions, a total of 124 chemical components were identified in XRCQ by the comparison with references and literature reports, among which 29 compounds were completely confirmed by comparison with reference substances. Then, the main absorbed components of XRCQ in plasma were also analyzed and clarified by UHPLC-LTQ-Orbitrap-MS/MS. BATMAN-TCM and SwissTargetPrediction were used for target prediction of absorbed components in plasma. Following the plotting of association network with Cytoscape 3.8.2, the core targets were subjected to GO and KEGG pathway enrichment analysis and a component-target-pathway network was constructed. A total of eight main targets of XRCQ against fever in children were obtained together with eight absorbed components in plasma, including glycyrhydinic acid, hesperidin, emodin, reticuline, daidzein, magnolignan C, magnolignan A, and magnolaldehyde D. It was inferred that XRCQ might improve alimentary system abnormality, inflammatory response, oxidative stress, and endocrine disorder through tumor necrosis factor, PI3 K-AKT, and other signaling pathways. The present study comprehensively expounded the chemical profiles of XRCQ and the main absorbed components in plasma and predicted the potential mechanism of XRCQ based on integrated network pharmacology, which has provided certain theoretical reference for the clinical application of XRCQ.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Criança , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Humanos
2.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(5): 813-818, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34622598

RESUMO

Objective: To segment images through an unsupervised method as an alternative to manual labeling. Methods: A total of 100 whole slide image (WSI) data of HE stained and Pap stained slides were selected as the research and test objects, including 70 breast slides, 20 lung slides and 10 thyroid slides. In order to ensure the diversity of data, the breast slides included those of normal tissue, inflammation and tumor, the lung slides were mainly neoplasms in the lower lobe, including those of inflammation and tumor, and the thyroid slides were of cells, all benign, obtained through fine needle aspiration. The maximum total magnification (original magnification) of each image was 400 times, and the file format was NDPI. Each WSI was manually labeled, and the labeled area of each WSI was more than 10 fields of vision. The labeled information was to be used for validity verification. An unsupervised image segmentation technique based on superpixel and fully convolution neural network algorithms was constructed and used to segment any region of interest (ROI) of unlabeled WSI. In comparison with the region adjacency graph merging method, the segmentation effect of the two methods was assessed with the under segmentation error, the boundary recall and the mean Intersection-over-Union, and the efficiency of the two methods was also compared. In the comparison of execution efficiency, the test process included the preprocessing time of superpixel, and excluded the time of loading the deep learning engine. Results: Unsupervised automatic segmentation was implemented for any ROI region of WSI according to the texture and color. The results of the breast slides, lung slides and thyroid slides showed slight differences, and multiple tests yielded stable results. However, the performance of this method in differentiating inflammation and tumor was average. The under-segmentation error, the boundary recall and the mean Intersection-over-Union were 19.10%, 82.06% and 45.06%, respectively. The under segmentation error, the boundary recall and the mean Intersection-over-Union for the region adjacency graph merging method were 21.52%, 78.39% and 44.81%, respectively. The average time consumption of the whole process was 0.27 s in GPU mode and 1.30 s in CPU mode. The average time consumption of the region adjacency graph merging method was 10.5 s in CPU mode because the method of region adjacency graph merging was not realized in the GPU mode. Conclusion: This method produced ideal pixel level labeling results through simple human-computer interaction, which could effectively reduce the cost of digital pathology slide data labeling. Compared with the region adjacency graph merging method, this method had better performance in processing image texture and had faster processing speed.


Assuntos
Algoritmos , Aprendizado de Máquina não Supervisionado , Mama , Humanos , Redes Neurais de Computação
3.
Zhongguo Zhong Yao Za Zhi ; 46(18): 4774-4781, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34581088

RESUMO

Indolealkylamines(IAAs) are the main hydrophilic substances in toad skin, mainly including free N-methyl-5-hydroxytryptamine, bufotenine, bufotenidine, dehydrobufotenine, and binding bufothionine. In this study, the LPS-activated neutrophils were used to investigate the structure-activity relationship and anti-inflammatory mechanism of the above-mentioned five monomers from the toad skin in vitro. The neutrophils were divided into the control group, model group(1 µg·mL~(-1) LPS), positive drug group(100 µg·mL~(-1) indometacin), as well as the low-(50 µg·mL~(-1)), medium-(100 µg·mL~(-1)) and high-dose(200 µg·mL~(-1)) free N-methyl-5-hydroxytryptamine, bufotenine, bufotenidine, dehydrobufotenine, and binding bufothionine groups. The levels of IL-6, TNF-α and IL-1ß in the neutrophil supernatant of each group was measured by enzyme-linked immunosorbent assay(ELISA) after LPS stimulation, followed by the detection of apoptosis in each group after Annexin V/PI staining. The protein expression levels of caspase-3, Bax, Bcl-2, beclin1, LC3-I, and LC3-Ⅱ were assayed by Western blot. The results showed that IAAs reduced the excessive secretion of inflammatory cytokines caused by LPS compared with the model group. Besides, the activity of each free IAAs(N-methyl-5-hydroxytryptamine, bufotenine, bufotenidine and dehydrobufotenine), especially bufotenine, was stronger than that of the binding bufothionine. As revealed by Annexin V/PI staining, LPS delayed the early apoptosis of neutrophils compared with the control group, while bufotenine promoted the apoptosis of neutrophils in a dose-dependent manner, which might be related to the elevated expression of apoptosis-related protein Bax/Bcl-2. In addition, LPS activated the autophagy pathways in neutrophils. This study confirmed the efficacy of IAAs in reducing the secretion of inflammatory cytokines in neutrophils induced by LPS for the first time. For instance, bufotenine exerts the anti-inflammatory effect possibly by inducing the apoptosis of neutrophils.


Assuntos
Lipopolissacarídeos , Neutrófilos , Animais , Anti-Inflamatórios/farmacologia , Apoptose , Bufonidae , Lipopolissacarídeos/toxicidade , Pele
4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(4): 693-697, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34323051

RESUMO

Objective: To study the different methods of artificial intelligence (AI)-assisted Ki-67 scoring of clinical invasive ductal carcinoma (IDC) of the breast and to compare the results. Methods: A total of 100 diagnosed IDC cases were collected, including slides of HE staining and immunohistochemical Ki-67 staining and diagnosis results. The slides were scanned and turned into whole slide image (WSI), which were then scored with AI. There were two AI scoring methods. One was fully automatic counting by AI, which used the scoring system of Ki-67 automatic diagnosis to do counting with the whole image of WSI. The second method was semi-automatic AI counting, which required manual selection of areas for counting, and then relied on an intelligent microscope to conduct automatic counting. The diagnostic results of pathologists were taken as the results of pure manual counting. Then the Ki-67 scores obtained by manual counting, semi-automatic AI counting and automatic AI counting were pairwise compared. The Ki-67 scores obtained from the manual counting (pathological diagnosis results), semi-automatic AI and automatic AI counts were pair-wise compared and classified according to three levels of difference: difference ≤10%, difference of >10%-<30% and difference ≥30%. Intra-class correlation coefficient ( ICC) was used to evaluate the correlation. Results: The automatic AI counting of Ki-67 takes 5-8 minutes per case, the semi-automatic AI counting takes 2-3 minutes per case, and the manual counting takes 1-3 minutes per case. When results of the two AI counting methods were compared, the difference in Ki-67 scores was all within 10% (100% of the total), and the ICC index being 0.992. The difference between manual counting and semi-automatic AI was less than 10% in 60 cases (60% of the total), between 10% and 30% in 37 cases (37% of the total), and more than 30% in only 3 cases (3% of the total), ICC index being 0.724. When comparing automatic AI with manual counting, 78 cases (78% of the total) had a difference of ≤10%, 17 cases (17% of the total) had a difference of between 10% and 30%, and 5 cases (5%) had a difference of ≥30%, the ICC index being 0.720. The ICC values showed that there was little difference between the results of the two AI counting methods, indicating good repeatability, but the repeatability between AI counting and manual counting was not particularly ideal. Conclusion: AI automatic counting has the advantage of requiring less manpower, for the pathologist is involved only for the verification of the diagnosis results at the end. However, the semi-automatic method is better suited to the diagnostic habits of pathologists and has a shorter turn-over time compared with that of the fully automatic AI counting method. Furthermore, in spite of its higher repeatability, AI counting, cannot serve as a full substitute for pathologists, but should instead be viewed as a powerful auxiliary tool.


Assuntos
Neoplasias da Mama , Inteligência Artificial , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Antígeno Ki-67 , Microscopia , Reprodutibilidade dos Testes
5.
Diving Hyperb Med ; 51(2): 134-139, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34157727

RESUMO

INTRODUCTION: Exposure to very high oxygen partial pressure may cause central nervous system oxygen toxicity (CNS-OT). The role of necroptosis in the pathogenesis of CNS-OT is still unclear. METHODS: In experiment one, male C57BL/6 mice in the oxygen toxicity (OT) group (n = 5) and necrostatin-1 (Nec-1; a necroptosis inhibitor) (1.5 mg·kg-1, intraperitoneal) group (n = 5) were exposed to pure oxygen at 600 kPa, and the latency to tonic-clonic seizure was recorded. In experiment two, mice were divided into three groups: control group (n = 11), OT group (n = 12) and Nec-1 group (n = 12). Nec-1 was intraperitoneally administered 30 min before oxygen exposure. Mice in the OT group and Nec-1 group were exposed to pure oxygen at 400 kPa for 30 min, and then sacrificed; the brain was harvested for the assessment of inflammation, oxidative stress and necroptosis. RESULTS: Experiment one. Nec-1 pre-treatment significantly prolonged the latency to seizure (245 [SD 18] seconds in the OT group versus 336 (34) seconds in the Nec-1 group). Experiment two. Nec-1 pre-treatment markedly reduced inflammatory cytokines and inhibited cerebral necroptosis, but failed to significantly suppress cerebral oxidative stress. CONCLUSIONS: These findings indicate necroptosis is involved in the pathogenesis of CNS-OT, and inhibition of necroptosis may prolong seizure latency, but the specific mechanisms should be investigated further.


Assuntos
Oxigênio , Convulsões , Animais , Apoptose , Imidazóis , Indóis , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pressão Parcial , Convulsões/induzido quimicamente
6.
Undersea Hyperb Med ; 48(1): 13-23, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33648029

RESUMO

Neuropathic pain (NPP) refers to the pain caused by primary or secondary injury or dysfunction of the peripheral or central nervous system, and usually requires multidisciplinary treatment. However, most pharmacological and non-pharmacological interventions can only temporarily and/or moderately improve pain-related symptoms, and they often produce unbearable adverse reactions or cause drug resistance. Hyperbaric oxygen (HBO2) therapy has been widely used in the clinical treatment of some diseases due to its advantages of safety, few side effects, no resistance, and non-invasiveness. In recent years, increasing numbers of basic and clinical studies have been conducted to investigate the efficacy and mechanism of HBO2 in the treatment of NPP, and great progress has been made in this field. In this paper, we briefly introduce the pathogenesis of NPP and therapeutic effects of HBO2 and summarize the mechanisms underlying the effects of HBO2 in treating NPP, which may provide reference for the clinical treatment of pain with HBO2.


Assuntos
Oxigenação Hiperbárica/tendências , Neuralgia/terapia , Animais , Apoptose/fisiologia , Pressão Atmosférica , Modelos Animais de Doenças , Neurônios GABAérgicos/fisiologia , Humanos , Oxigenação Hiperbárica/métodos , Camundongos , Transtornos de Enxaqueca/terapia , Neuralgia/etiologia , Neurite (Inflamação)/complicações , Óxido Nítrico/fisiologia , Estresse Oxidativo/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Ratos , Receptores Opioides/fisiologia
7.
J Ethnopharmacol ; 272: 113917, 2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-33609729

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Qingxin Lianzi Yin Decoction (QXLZY), a Chinese classical formula, has been widely used in the treatment of various chronic kidney diseases over 1,000 years. However, the current studies on QXLZY were mostly focused on its clinical efficacy, lacking systematic material basis research on constituents. AIM OF THE STUDY: This work aims to elucidate and quantify the chemical constituents, clarify the blood-absorbed components and excretion pathways, predict major bioactive constituents and discover potential therapeutic targets. MATERIALS AND METHODS: UHPLC-LTQ-Orbitrap HRMS was employed to clarify the chemical constituents and metabolites of QXLZY. The extraction of diagnostic ion and neutral loss fragment was aimed for searching specific type of constituents. The plasma, urine, bile and feces samples of rats after oral administration of QXLZY were systematically studied. UHPLC-QQQ-MS/MS was employed to simultaneously detect different types of constitutes. Based on the analysis of ingredients in vivo, the bioactive constituents and potential therapeutic targets in the treatment of diabetic nephropathy (DN) was investigated by using network pharmacological analysis. RESULTS: Totally, 220 compounds were identified or tentatively characterized by UHPLC-LTQ-Orbitrap HRMS. Among them, 59 compounds were confirmed by reference standards. Meanwhile, 21 representative components were simultaneously determined within 15 min by UHPLC-QQQ-MS/MS. 123 components (74 prototypes as well as 49 metabolites) were identified or tentatively characterized. By using network pharmacological analysis, baicalein, liquiritigenin, succinic acid, formononetin, wogonin might be the major effective constituents in QXLZY during the treatment of DN. CONCLUSIONS: Flavonoids, saponins and organic acids were the major chemical ingredients of QXLZY. Flavonoids were the main components absorbed into blood, followed by organic acids. Phase II conjugation reaction was the major metabolic type. The pathways that QXLZY in the treatment of DN were probably related to glucose and lipid metabolism, oxidative stress and inflammation.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Ácidos/análise , Alcaloides/análise , Animais , Cromatografia Líquida de Alta Pressão , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/análise , Flavonoides/análise , Masculino , Metaboloma , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/análise , Mapas de Interação de Proteínas , Ratos Sprague-Dawley , Padrões de Referência , Reprodutibilidade dos Testes , Saponinas/análise , Espectrometria de Massas em Tandem
8.
World J Stem Cells ; 12(10): 1184-1195, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33178400

RESUMO

BACKGROUND: Liver organoids have recently been applied as models for liver disease and drug screening, especially when combined with liver-on-a-chip technologies. Compared to hepatocyte-like cells, primary hepatocytes have high functionality but cannot maintain their function when cultured in vitro. Mesenchymal stem cells (MSCs) enhance hepatocyte function and maintain hepatocyte metabolism when co-cultured with hepatocytes. MSCs can help induced pluripotent stem cells to generate an organoid structure via the MSC-based traction force triggered by extracellular matrix (ECM) proteins. In this study, primary hepatocytes were co-cultured with MSCs on a liver-derived ECM to generate liver organoids within a short duration. AIM: To create hepatocyte organoids by co-culturing primary hepatocytes with MSCs on a porcine liver extracellular matrix (PLECM) gel. METHODS: Perfusion and enzymatic hydrolysis were used to form the PLECM gel. Rat hepatocytes and human MSCs were mixed and plated on pre-solidified PLECM gel in a 48-well plate for 48 h to generate organoids. Generated organoids were evaluated through hematoxylin and eosin, periodic acid-Schiff, immuno-histological, and immunofluorescence staining, and quantitative PCR for alb, CYP450 gene markers, and urea cycle genes. Culture medium was collected to detect albumin (ALB) and urea production on days 2, 4, 6, 8, 14, and 20. RESULTS: The whole porcine liver was perfused and enzymatically hydrolyzed to form a PLECM gel. The structural components and basement membrane composition of the ECM, such as collagen type I, collagen type IV, fibronectin, and laminin, were demonstrated to be retained. Through interaction of human MSCs with the liver-derived ECM, primary hepatocytes and human MSCs assembled together into a 3D construction and generated primary hepatocyte organoids for 48 h. The mRNAs of the gene alb, the CYP450 gene markers cyp1a1, cyp1a2, and cyp3a2 as well as urea cycle genes arg-1, asl, ass-1, cps-1, nags were highly expressed in hepatocyte organoids. Long-term survival of the primary hepatocyte organoids, as well as stable functionality, was demonstrated via ALB and urea production in vitro. CONCLUSION: Our new method of creating primary hepatocyte organoids by co-culturing hepatocytes with MSCs on liver-derived ECM hydrogels could be used to develop models for liver disease and for drug screening.

9.
Zhongguo Zhong Yao Za Zhi ; 45(13): 3035-3044, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32726009

RESUMO

UHPLC-LTQ-Orbitrap-MS was developed for the identification of chemical constituents in Qingfei Paidu Decoction, which will clarify its material basis. ACQUITY UHPLC HSS T3 chromatography column(2.1 mm×100 mm, 1.8 µm) was used with 0.1% formic acid(B)-acetonitrile(A) as the mobile phase in gradient elution. The decoction was detected by high-resolution liquid chromatography-mass spectrometry equipped with an ESI ion source in positive and negative mode. Based on the accurate mass measurements, retention time, mass fragmentation patterns combined with comparison of reference and literature reports, a total of 87 major compounds including 43 flavonoids, 9 alkaloids, 4 triterpenoid saponins, 1 sesquiterpene, 2 coumarins, 10 phenolic acids and 18 other compounds were tentatively screened and characterized. UHPLC-LTQ-Orbitrap-MS was employed to comprehensively elucidate the chemical components in Qingfei Paidu Decoction, which basically covered 20 Chinese medicines except gypsum in Qingfei Paidu Decoction. These collective results provide a scientific basis for further research on the quality control standard of Qingfei Paidu Decoction.


Assuntos
Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Cumarínicos/análise , Flavonoides/análise , Espectrometria de Massas
10.
Zhongguo Zhong Yao Za Zhi ; 45(3): 596-601, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237518

RESUMO

Matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) is a novel technique for in-situ distribution of various substances in tissue without labeling. This technique is increasingly applied to the study of medicinal plants owing to its high spatial resolution and its potential of in-situ analysis in small molecules. In this study, the structural information and their fragmentation patterns of the midazole alkaloids(1,3-dibenzyl-4,5-dimethylimidazolium chloride and 1,3-dibenzyl-2,4,5-trimethylimi-dazolium chloride) and benzylglucosinolate in the medicinal plant Maca(Lepdium meyeni) root were analyzed by ultra-high-performance liquid phase combined with LTQ-Orbitrap mass spectrometry(UHPLC-HR-MS). The localization of these active ingredients in the cross-sections of Maca root was performed by MALDI-MSI. These results demonstrated that the two types of imidazole alkaloids had a similar distributed pattern. They were located more in the cortex and the periderm than those in the medulla of a lateral root, while the localization of benzylglucosinolate was concentrated in the center of the root rather than in the cortex and the periderm. The precise spatial distribution of various secondary metabolites in tissue provides an important scientific basis for the accumulation of medicinal plant active ingredients in tissues. In addition, this imaging method is a promising technique for the rapid evaluation and identification of the active ingredients of traditional Chinese medicine in plant tissues, as well as assisting the research on the processing of medicinal plants.


Assuntos
Lepidium/química , Compostos Fitoquímicos/análise , Raízes de Plantas/química , Cromatografia Líquida de Alta Pressão , Plantas Medicinais/química , Metabolismo Secundário , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
11.
Med Gas Res ; 10(1): 30-36, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32189667

RESUMO

Carbon monoxide (CO) has been the leading cause of poisoning mortality in many countries and hyperbaric oxygen (HBO) is a widely accepted treatment for CO poisoning. However, some patients with CO poisoning will still develop neurocognitive sequelae regardless of HBO therapy, which can persist since CO poisoning or be present days to weeks after a recovery from CO poisoning. HBO has been used in the prevention and treatment of neurocognitive sequelae after CO poisoning, and some mechanisms are also proposed for the potential neuroprotective effects of HBO on the neurocognitive impairment after CO poisoning, but there is still controversy on the effectiveness of HBO on neurocognitive sequelae after CO poisoning. In this paper, we briefly introduce the neurocognitive sequelae after CO poisoning, summarize the potential predictive factors of neurocognitive sequelae, and discuss the use of HBO in the treatment and prevention of neurocognitive sequelae after CO poisoning.


Assuntos
Intoxicação por Monóxido de Carbono/complicações , Intoxicação por Monóxido de Carbono/terapia , Oxigenação Hiperbárica/efeitos adversos , Transtornos Neurocognitivos/complicações , Humanos
12.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4932-4939, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872603

RESUMO

This study is aimed to establish a method for the determination of baicalin,baicalin and purpurin in the plasma of rats after oral administration of Pudilan Xiaoyan Oral Liquid( PDL) by using liquid chromatography-mass spectrometry( LC-MS),analyze the pharmacokinetics of three components in rats,and investigate the effects of PDL on drug-metabolizing enzymes in rat liver. C18 column was used for liquid chromatography separation,with acetonitrile-water( containing 0. 2% formic acid) as the mobile phase for gradient elution. The mass spectrometry was detected by electrospray ion source( ESI) under multi-reaction monitoring mode( MRM),as well as positive and negative ion alternating mode. Plasma sample collection was performed by using an automatic blood collection meter for small animals. The pharmacokinetic parameters were calculated by Win Nonlin software. The total protein concentration of rat liver microsomes and the total enzyme content of CYP450 were determined by BCA method and spectrophotometry respectively. The methodological study in terms of linear range,recovery rate,precision and sample stability,was used to confirm that the LC-MS analysis method established in this experiment was simple,exclusive,accurate and reliable,and can meet the requirement of determining the content of baicalin,oroxindin and corynoline in plasma after PDL administration in rats. The drug-time curve showed that baicalin and oroxindin had a bimodal phenomenon,and the pharmacokinetic parameters indicated that baicalin,oroxindin and corynoline in PDL had certain drug-like properties. After 7 consecutive days of PDL administration,the rat liver coefficient,total liver microparticle protein and CYP450 enzyme content were increased,but there was no significant difference,indicating that PDL was less likely to develop drug-drug interaction based on CYP enzyme. The results of this experiment can provide reference for the research on in vivo efficacy and drug interaction of PDL as well as on its clinical application.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Espectrometria de Massas em Tandem , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Fígado , Ratos , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray
13.
Endokrynol Pol ; 69(3): 259-263, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29952415

RESUMO

OBJECTIVE: This study aims to evaluate EZSCAN detection in pilots and the general population, and determine the significance of EZSCAN detection in the identification of a pilot's health. METHODS: A total of 87 cases of non-diabetic Air Force pilots (pilot group) and 49 cases from the general population without diabetes were collected. These two groups of subjects underwent EZSCAN detection, as well as the detection of blood glucose, lipid and uric acid levels. RESULTS: Subjects in the pilot group had the highest detection rate of no risk and the lowest detection rate of high risk, while the general population had the highest detection rate of high risk, followed by low risk. The difference in diabetic risk between these two groups were statistically significant (P < 0.01). Various indicators were compared according to different risk levels. In the no risk group, age, BMI and the triglyceride of pilots were lower than in the general population; and the difference was statistically significant (P < 0.05). In high risk group, BMI and blood uric acid of pilots were lower than in the general population; and the difference was statistically significant (P < 0.05). CONCLUSIONS: BMI and blood uric acid are positively correlated to diabetic risk. The EZSCAN detection system can be used for assessment of pilot's diabetic risk, and has certain significance in a pilot's health identification.


Assuntos
Diabetes Mellitus/epidemiologia , Programas de Rastreamento , Pilotos , Adulto , Idoso , Glicemia/análise , Diabetes Mellitus/prevenção & controle , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Ácido Úrico/sangue
15.
J Ethnopharmacol ; 206: 55-64, 2017 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-28461119

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive and deadly breast cancer subtype with limited treatment options. It is necessary to seek complementary strategies for TNBC management. Taraxacum mongolicum, commonly named as dandelion, is a herb medicine with anti-cancer activity and has been utilized to treat mammary abscess, hyperplasia of mammary glands from ancient time in China, but the scientific evidence and action mechanisms still need to be studied. AIM OF THE STUDY: This study was intended to investigate the therapeutic effect and molecular mechanisms of dandelion extract in TNBC cell line. METHODOLOGY: Dandelion extract was prepared and purified, and then its chemical composition was determined. Cell viability was evaluated by MTT assay. Analysis of cell apoptosis and cell cycle was assessed by flow cytometry. The expression levels of mRNA and proteins were determined by real-time PCR and Western blotting, respectively. Caspase inhibitor Z-VAD-FMK and CHOP siRNA were used to confirm the cell apoptosis induced by dandelion extract. RESULTS: Dandelion extract significantly decreased MDA-MB-231cell viability, triggered G2/M phase arrest and cell apoptosis. Concurrently, it caused a markedly increase of cleaved caspase-3 and PARP proteins. Caspase inhibitor Z-VAD-FMK abolished the apoptosis triggered by dandelion extract. The three ER stress-related signals were strongly induced after dandelion treatment, including increased mRNA expressions of ATF4, ATF6, XBP1s, GRP78 and CHOP genes, elevated protein levels of phosphorylated PERK, eIF-2α, IRE1, as well as the downstream molecules of CHOP and GRP78. MDA-MB-231 cells transfected with CHOP siRNA significantly reduced apoptosis induced by dandelion extract. The underlying mechanisms at least partially ascribe to the strong activation of PERK/p-eIF2α/ATF4/CHOP axis. CONCLUSION: ER stress related cell apoptosis accounted for the anti-cancer effect of dandelion extract, and these findings support dandelion extract might be a potential therapeutic approach to treat TNBC.


Assuntos
Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Extratos Vegetais/farmacologia , Taraxacum/química , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Fase G2/efeitos dos fármacos , Humanos , Espectrometria de Massas em Tandem
16.
Sci Rep ; 7(1): 1873, 2017 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-28500349

RESUMO

Lysine succinylation is a novel dynamic and evolutionarily conserved post-translational modification (PTM) that regulates various biological processes. 'Anji Baicha' is an albino tea variety that exhibits temperature-based variability of leaf colour and amino acid concentrations. However, the mechanism underlying albinism in 'Anji Baicha' has not been investigated at the level of succinylation. Here, we identify 3530 lysine succinylation sites mapped to 2132 proteins in 'Anji Baicha', representing the first extensive data on the lysine succinylome in the tea plant. Eleven conserved succinylation motifs were enriched among the identified succinylated peptides. The protein-protein interaction maps were visualized using Cytoscape software. Comparison across three typical developmental stages of 'Anji Baicha' revealed that proteins exhibiting differential succinylation levels were primarily involved in photosynthesis, carbon fixation, biosynthesis of amino acids and porphyrin and chlorophyll metabolism, suggesting that these succinylated proteins are involved in 'Anji Baicha' leaf colour variability. These results not only deepen our understanding of the mechanism underlying 'Anji Baicha' albinism and the regulatory role of succinylation in the tea plant but also provide new insight into molecular breeding for leaf colour variety.


Assuntos
Albinismo/metabolismo , Camellia sinensis/metabolismo , Proteoma , Proteômica , Motivos de Aminoácidos , Sequência de Aminoácidos , Camellia sinensis/genética , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Lisina/química , Anotação de Sequência Molecular , Fenótipo , Desenvolvimento Vegetal/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Processamento de Proteína Pós-Traducional , Proteômica/métodos
17.
Ying Yong Sheng Tai Xue Bao ; 28(7): 2327-2338, 2017 Jul 18.
Artigo em Chinês | MEDLINE | ID: mdl-29741067

RESUMO

The Daya Bay is a typical subtropical bay in Southern China, and chronically stressed by heavy metal pollution. The bioaccumulation of heavy metals in Daya Bay ecosystem is still unclear. In this study, heavy metals (Cr, Co, Ni, Cu, Zn, Ag, Cd, Pb) and stable isotopes (δ13C and δ15N) were analyzed in seawater, sediment, and organisms (planktons, benthos and nektons) sampled from Daya Bay in June and December of 2015, in order to illuminate the influences of heavy metals to Daya Bay ecosystem and the basic information of environmental monitoring and risk assessment. Results showed that the major source of matter in the organisms in Daya Bay was originated from the ocean, while the freshwater input was limited. The food chain of Daya Bay was short and the highest trophic level was 3.48. The nekton predators (e.g. fish) in Daya Bay were omnivorous, and preferred benthic feeding habit in the winter. The levels of heavy metals in environment and organisms generally did not exceed the criteria according to the National Agriculture Products and the National Water Quality of China, except Zn and Pb in seawater and Cd in two crustaceans (Oratosquilla oratoria and Oratosquilla interrupta). Cr, Co, Ni, Zn, Cd and Pb were found to be biominimized along the Daya Bay food web. Cu was biominimized in the summer, but this trend was not significant in the winter. There was no significant correlation between Ag concentration and trophic level in both seasons, in contrast, there was a potential biomagnification of Ag in crustacean. Overall, the levels of heavy metals in Daya Bay ecosystems were relatively low, and further attention should be paid to Zn, Ag, Cd and Pb.


Assuntos
Baías , Cadeia Alimentar , Metais Pesados , Poluentes Químicos da Água , Animais , China , Monitoramento Ambiental , Sedimentos Geológicos , Isótopos
18.
Front Plant Sci ; 8: 2104, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29312376

RESUMO

Tea leaf color is not only important from an aesthetics standpoint but is also related to tea quality. To investigate the molecular mechanisms that determine tea leaf color, we examined Camellia sinensis cv. 'Anjin Baicha' (an albino tea cultivar) by tandem mass tag isobaric labeling to generate a high-resolution proteome and acetyl-proteome atlas of three leaf developmental stages. We identified a total of 7,637 proteins and quantified 6,256; of these, 3,232 were classified as differentially accumulated proteins (DAPs). We also identified 3,161 lysine acetylation sites in 1,752 proteins and quantified 2,869 in 1,612 proteins. The acetylation levels at 468 sites were significantly altered across the three developmental stages during periodic albinism; the corresponding proteins were associated with a variety of biological processes. Interestingly, a large number of DAPs and acetylated proteins with increased/decreased acetylation were related to photosynthesis and secondary metabolite biosynthetic pathways, suggesting that the accumulation or acetylation level of these proteins regulates periodic albinism in 'Anjin Baicha.' Additionally, overlap between succinylome and acetylome among three 'Anjin Baicha' developmental stages were found. These data provide important insight into the mechanisms of leaf coloration in the tea plant. The mass spectrometry data have been deposited to Proteome X change via the PRIDE partner repository with the data set identifier PXD008134.

19.
Tumour Biol ; 2016 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-27722987

RESUMO

The pretreatment nutritional and immunological status play indispensable roles in predicting the outcome of patients with various types of malignancies. The aim of the study was to investigate whether preoperative prognostic nutritional index (PNI), which simply accounts for nutritional and immunological status, was associated with overall survival (OS) in patients with gallbladder carcinoma (GBC). The retrospective study included a total of 315 GBC patients after surgery between 2002 and 2012. PNI was calculated according to the following formula: 10× serum albumin (g/dl) +0.005× total lymphocyte count (per mm3). A receiver operating characteristic (ROC) curve for survival prediction was plotted to verify the optimal cutoff value for LMR, which was set at 46.14. According the value, patients were categorized into two different groups, namely high-PNI group (n = 133) and low-PNI group (n = 182). The univariate and multivariate Cox regression models were used to identify the independent prognostic factors. The results showed that low pretreatment PNI value was significantly associated with elderly age, partial surgery procedure, and advanced tumor status such as tumor stage, node stage, and tumor-node-metastasis stage (P < 0.05). The low-PNI group had a worse OS compare with the high-PNI group (P < 0.05). Via univariate and multivariate analyses, pretreatment PNI was identified as an independent prognostic factor for OS [HR: 0.613; 95%CI: 0.448-0.838; P < 0.001]. Subgroup analyses further revealed that PNI was significantly associated with postoperative OS independent of tumor node metastasis stage and surgical procedure. In conclusion, pretreatment PNI might serve as an effective predictor to evaluate prognosis of GBC patients after surgery. Based on the findings, PNI, characterized with accessibility, objectivity and noninvasiveness, should be included in the routine assessment of GBC.

20.
Onco Targets Ther ; 9: 5317-28, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27601923

RESUMO

BACKGROUND: Pretreatment nutritional and immunological statuses play an indispensable role in predicting the outcome of patients with various types of malignancies. The purpose of this study is to evaluate the predictive value of albumin/globulin ratio (AGR) in overall survival (OS) and recurrence in patients with hepatocellular carcinoma (HCC) following radical hepatic carcinectomy. PATIENTS AND METHODS: This retrospective study included a total of 172 patients with HCC with complete medical and follow-up information between 2002 and 2012. AGR was calculated according to the following formula: AGR = albumin/globulin. Receiver operating characteristic curve analysis was performed to determine the optimal cutoff value. The associations of AGR with clinicopathological characteristics and prognosis were assessed. Further multivariate analysis using Cox regression model and subgroup analysis was performed to evaluate the predictive value. RESULTS: Receiver operating characteristic curve determined 37.65, 31.99, and 1.48 as the optimal cutoff values of albumin, globulin, and AGR in terms of 5-year OS or death, respectively. On the basis of the cutoff value of AGR, all the patients were divided, respectively, into low-AGR (n=105) and high-AGR (n=67) groups. AGR was found to be significantly correlated with age, cancer embolus, international normalized ratio, and postoperative outcome (P<0.05). Hepatitis B virus infection (hazard ratio [HR]: 2.125; 95% confidence interval [CI]: 1.285-3.153), tumor node metastasis stage (HR: 1.656; 95% CI: 1.234-2.223), serum albumin (HR: 0.546; 95% CI: 0.347-0.857), and AGR (HR: 0.402; 95% CI: 0.233-0.691) were independent predictors of OS via univariate and multivariate survival analyses. However, alpha-fetoprotein (HR: 1.708; 95% CI: 1.027-2.838), tumor node metastasis stage (HR: 1.464; 95% CI: 1.078-1.989), and AGR (HR: 0.493; 95% CI: 0.293-0.828) functioned as independent risk variables for predicting recurrence. Moreover, AGR showed superior prognostic value for OS and recurrence in the subgroups with normal level of albumin or survival time beyond 6 months. CONCLUSION: Pretreatment AGR might serve as an effective biomarker to evaluate the prognosis of patients with a diagnosis of HCC. Based on the results, AGR, characterized with easy accessibility, objectivity, and noninvasiveness, should be included in the routine assessment of HCC.

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