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1.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3949-3959, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472272

RESUMO

Qishen Yiqi Dripping Pills(QSYQ) are used clinically to treat various myocardial ischemic diseases, such as angina pectoris, myocardial infarction, and heart failure; however, the molecular mechanism of QSYQ remains unclear, and the scientific connotation of traditional Chinese medicine(TCM) compatibility has not been systematically explained. The present study attempted to screen the critical pathway of QSYQ in the treatment of myocardial ischemia by network pharmacology and verify the therapeutic efficacy with the oxygen-glucose deprivation(OGD) model, in order to reveal the molecular mechanism of QSYQ based on the critical pathway. The key targets of QSYQ were determined by active ingredient identification and target prediction, and underwent pathway enrichment analysis and functional annotation with David database to reveal the biological role and the critical pathway of QSYQ. Cell counting Kit-8(CCK-8), lactate dehydrogenase(LDH), and Western blot tests were launched on high-content active ingredients with OGD cell model to reveal the molecular mechanism of QSYQ based on the critical pathway. The results of network pharmacology indicated that QSYQ, containing 18 active ingredients and 82 key targets, could protect cardiomyocytes by regulating biological functions, such as nitric oxide biosynthesis, apoptosis, inflammation, and angiogenesis, through TNF signaling pathway, HIF-1 signaling pathway, PI3 K-Akt signaling pathway, etc. HIF-1 signaling pathway was the critical pathway. As revealed by CCK-8 and LDH tests, astragaloside Ⅳ, salvianic acid A, and ginsenoside Rg_1 in QSYQ could enhance cell viability and reduce LDH in the cell supernatant in a concentration-dependent manner(P<0.05). As demonstrated by the Western blot test, astragaloside Ⅳ significantly down-regulated the protein expression of serine/threonine-protein kinase(Akt1) and hypoxia-inducible factor 1α(HIF-1α) in the HIF-1 signaling pathway, and up-regulated the protein expression of vascular endothelial growth factor A(VEGFA). Salvianic acid A significantly down-regulated the protein expression of upstream phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3 CA) and downstream HIF-1α of Akt1. Ginsenoside Rg_1 significantly down-regulated the expression of HIF-1α protein and up-regulated the expression of VEGFA. The therapeutic efficacy of QSYQ on myocardial ischemia was achieved by multiple targets and multiple pathways, with the HIF-1 signaling pathway serving as the critical one. The active ingredients of QSYQ could protect cardiomyocytes synergistically by regulating the targets in the HIF-1 signaling pathway to inhibit its expression.


Assuntos
Medicamentos de Ervas Chinesas , Isquemia Miocárdica , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/genética , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular
2.
Am J Physiol Lung Cell Mol Physiol ; 321(3): L533-L544, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34231388

RESUMO

Store-operated calcium entry (SOCE) is involved in the pathogenesis of airway inflammation and remodeling in asthma. Store-operated calcium entry-associated regulatory factor (SARAF) can downregulate SOCE. We sought to investigate the role of SARAF in the regulation of airway inflammation and remodeling in asthma mice models, as well as in the functional regulation of human airway smooth muscle cells (hASMCs). Balb/c mice were sensitized and challenged with ovalbumin to establish the asthma mice models. Mice were transfected with lentivirus, which expressed the SARAF gene + GFP (green fluorescence protein) or the negative control gene + GFP. Airway resistance was measured with the animal pulmonary function system. Airway inflammation and remodeling were evaluated via histological staining. In vitro cultured hASMCs were transfected with scrambled small interfering RNA (siRNA) or SARAF-specific siRNA, respectively. The proliferation, migration rate, hypertrophy, and SOCE activity of hASMCs were examined with Cell Counting Kit-8, wound healing test, bright field imaging, and Ca2+ fluorescence imaging, respectively. SARAF expression was measured by quantitative real-time PCR. Asthma mice models showed decreased SARAF mRNA expression in the lungs. SARAF overexpression attenuated airway inflammation, resistance, and also remodeling. Downregulation of SARAF expression with siRNA promoted the proliferation, migration, hypertrophy, and SOCE activity in hASMCs. SARAF plays a protective role against airway inflammation and remodeling in asthma mice models by blunting SOCE; SARAF may also be a functional regulating factor of hASMCs.


Assuntos
Remodelação das Vias Aéreas/imunologia , Asma/imunologia , Proteínas de Ligação ao Cálcio/imunologia , Regulação da Expressão Gênica/imunologia , Pulmão/imunologia , Proteínas de Membrana/imunologia , Miócitos de Músculo Liso/imunologia , Remodelação das Vias Aéreas/efeitos dos fármacos , Remodelação das Vias Aéreas/genética , Resistência das Vias Respiratórias/efeitos dos fármacos , Resistência das Vias Respiratórias/genética , Resistência das Vias Respiratórias/imunologia , Animais , Asma/induzido quimicamente , Asma/genética , Proteínas de Ligação ao Cálcio/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/imunologia , Pulmão/patologia , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Miócitos de Músculo Liso/patologia
3.
Inorg Chem ; 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34075743

RESUMO

Polyoxometalate-based organic-inorganic hybrid compounds (POIHCs) have been greatly developed due to their wide application prospects, but the pursuit of their directed synthesis via molecular design still remains a challenge. Herein, we demonstrate that the coordination modes of the Keggin-type [ZnW12O40]6- anion can be tuned, which leads to different semiconductor characteristics. Using the same building block, ligand, and metal ion (ZnW12, phen, Cu2+), we synthesized three new POIHCs with different bonding patterns by means of different coordination modes of ZnW12. The three POIHCs (H2phen){ZnW12O40[Cu(phen)2]2}·3H2O (1), {ZnW12O40[Cu(phen)(H2O)2]2[Cu(phen)(H2O)]}n·3H2O (2), and (Me4N)2{ZnW12O40[Cu(phen)(H2O)]2}n·5H2O (3) (phen = 1,10-phenanthroline) have been structurally characterized by single-crystal X-ray diffraction. Compound 1 appears as a zero-dimensional coordination complex cluster, while compounds 2 and 3 are both 1D chain structures with different Cu2+ bridge linkages. Although these three POIHCs possess the same chemical components, their semiconductor properties are different, which is demonstrated by measurements of transient photocurrent and band gap (Eg) values. Furthermore, we carried out comparative experiments on the photoconductivity performance of compounds 1-3 and their photocatalytic reduction from O2 to H2O2, indicating the significant influence of the energy level matching on the photocatalytic activity.

4.
J Ethnopharmacol ; 268: 113673, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33301921

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Jatropha curcas L. (Euphorbiaceae), as a drought resistant shrub mainly cultivated in tropical and subtropical areas worldwide, is widely used as traditional medicine to cure arthritis, dysentery, abscess and pneumonia in Asian, African and South American folklores. The methanolic extracts of the roots have been revealed the anti-inflammatory activity in vivo and vitro. AIM OF STUDY: This research aimed to provide promising anti-inflammatory candidates from the roots of J. curcas. In addition, RNA-Seq was conducted to give targeted genes involved in the anti-inflammatory action. MATERIALS AND METHODS: The diterpenoids were isolated from the CH2Cl2 fraction of the methanolic extract from the roots of J. curcas by column chromatography (CC): silica gel, Sephadex LH-20, ODS, semi-preparative reversed-phase high-performance liquid chromatography (HPLC). The structures were identified based on HR-ESI-MS and 1D, 2D-NMR spectroscopic analysis. Their anti-inflammatory effects were tested on lipopolysaccharide (LPS, 500 ng/mL)-stimulated murine RAW264.7 macrophages. Furthermore, we conducted transcriptome-wide RNA sequencing to profile gene expression alterations in LPS-induced RAW264.7 cells upon treatment with jatrocurcasenone I (4) and analyzed the underlying genes targeted by this compound. RESULTS: Six diterpenoids were obtained from J. curcas, and four of them were identified to be new lathyrane diterpenoids: jatrocurcasenones F-I (1-4). Compounds 3 and 4 exhibited potent inhibitory activities against LPS-induced nitric oxide (NO) production in RAW264.7 cells with IC50 values of 11.28 µM and 7.71 µM, respectively. Western blotting analysis showed that the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were suppressed with the supplementation of 3 and 4. The results of RNA-seq showed that 4 (20 µM) exhibited regulation on the 587 differentially expressed genes (DEGs) induced by LPS (500 ng/mL). Transcriptome-wide RNA sequencing indicated that the protective activity of 4 supplementation was most likely driven by modulating expression levels of IL-1α, IL-1ß, IL-1f6, IL-6, IL-1rn, IL-27, Ccl2, Ccl5, Ccl7, Ccl9, Ccl22, Cxcl10, Tnfsf12, Tnfsf15, Lta, Trim25, Bcl2a1a, Dusp1, Dusp2, Ptgs2, Edn1 and Nr4a1. CONCLUSIONS: This study offered four new lathyrane diterpenoids, of them, jatrocurcasenone I (4) showed significant anti-inflammatory activity. RNA-Seq suggested that jatrocurcasenone I (4) could be a candidate drug for the prevention inflammation-mediated diseases by modulating 24 candidate DEGs.


Assuntos
Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Mediadores da Inflamação/antagonistas & inibidores , Jatropha , Raízes de Plantas , Animais , Anti-Inflamatórios/isolamento & purificação , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Mediadores da Inflamação/metabolismo , Camundongos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Células RAW 264.7
5.
Steroids ; 166: 108776, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33338476

RESUMO

4ß-Hydroxywithanolide E, which can be obtained in large amounts from the Physalis genus, possessed anti-proliferative effects on a variety of human cancer cell lines. For discussing its anti-tumor structure-activity relationship, a series of 4ß-hydroxywithanolide E derivatives (1-17) were synthesized and evaluated for their antitumor activity in vitro towards acute promyelocytic leukemia NB4 cell line by the Alarma blue assay. Cytotoxicity data revealed that the enone structure and C-4 hydroxyl substituents of ring A, together with the side chain (C-20-C-28) play an important effect on the cytotoxicity.

6.
Phytother Res ; 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33350549

RESUMO

In China, the fruits of Physalis alkekengi L. var. franchetii, which are conventionally utilized as edible berry, have attracted wide attention due to its significant biological activities. In the present study, phytochemical studies on the fruits of Physalis plants afforded six compounds, including two new withanolides (1-2) and four known agnologues (3-6). The inhibitory effects of these compounds on the formation of nitric oxide (NO) stimulated by lipopolysaccharide (LPS) in RAW264.7 macrophages were evaluated. Physapubescin M (1), with IC50 value of 1.58 µM, was selected for further study. The protein expression of COX-2 and iNOS, and LPS-induced production of cytokines (IL-6, IL-1ß and TNF-α) were reduced by physapubescin M (1) in a dose-dependent way. In addition, transcriptomic analyses were conducted to profile gene expression alterations in LPS-induced RAW264.7 cells upon treatment of physapubescin M (1) and the potential antiinflammatory mechanism of withnolides was mentioned. These results provide broad view to the underlying antiinflammatory mechanism of withnolides, and give a theoretical basis for the utilization of the fruits of P. alkekengi L. var. franchetii.

7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(4): 573-577, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32691570

RESUMO

Objective: To evaluate the clinical value of prognostic nutritional index (PNI) in assessing the prognosis of small cell lung cancer (SCLC) patients. Methods: The clinical data of SCLC patients who were initial diagnosed by pathology and conformed to the conditions of this study from January 2017 to January 2018 were retrospectively collected. The PNI values were calculated and divided into high PNI and low PNI groups according to the median value. The potential prognostic factors for SCLC patients were analyzed. Results: One hundred and five patients were divided into high-PNI and low-PNI groups according to the PNI median (48.68). The median survival time was 25.1 months and 14.2 months respectively. The one-year survival rates were 82.5% and 65.3% respectively and the two-year survival rates were 49.7% and 28.4% respectively, the differences were all statistically significant ( P<0.05). Univariate analysis showed that gender, ECOG PS score, clinical stage and PNI were correlated with overall survival (OS) ( P<0.05). Multivariate analysis showed that PNI (odds ratio ( OR)=0.331,95% confidence interval: 0.189-0.580) and gender ( OR=1.897,95% confidence interval: 1.051-3.423) were independent prognostic factors for SCLC patients. Conclusion: Low PNI patients generally symbolize poor prognosis, PNI calculation is simple and easy to obtain, worthy of clinical promotion.


Assuntos
Neoplasias Pulmonares , Estado Nutricional , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/diagnóstico , Avaliação Nutricional , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Análise de Sobrevida
8.
Zhongguo Zhong Yao Za Zhi ; 45(8): 1772-1778, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32489060

RESUMO

Wogonin is a main effective component of Scutellaria baicalensis, with a significant anti-cancer activity. Recently, extensive studies focused on anti-cancer pharmacological effects of wogonin, but there were still a few studies on its molecular mechanism. Therefore, the molecular targets of its anti-cancer activity were still unclear. In this study, network pharmacology was applied to investigate the potential targets and molecular pathway of wogonin in inhibiting the growth of colorectal cancer. It indicated that Wnt/ß-catenin was a key pathway of wogonin on colorectal cancer. Then, pharmacology and molecular mechanism studies were performed according to network pharmacological results. Pharmacological results revealed that wogonin inhibited significantly the proliferation of SW480(P<0.001), with a concentration-dependent regularity in the range of 12.5-50 µmol·L~(-1). Additionally, wogonin could induce G_1 phase blocking of SW480 cells. Western blot was used to investigate the effect of wogonin on four characteristic proteins of Wnt/ß-catenin pathway. CTNNB1(ß-catenin), BIRC5(survivin) and GSK3 B were down-regulated significantly, while the expression level of BAX was up-regulated(P<0.05). In conclusion, wogonin could inhibit the proliferation of SW480 cells through Wnt/ß-catenin pathway. The feature protein CTNNB1(ß-catenin), BIRC5(survivin), GSK3 B and BAX were identified as the potential targets. This study illuminated the anti-cancer molecular mechanism and drug targets of wogonin, which provided a theoretical basis for anti-colon cancer drug discovery and clinical application.


Assuntos
Neoplasias Colorretais , Quinase 3 da Glicogênio Sintase , Linhagem Celular Tumoral , Proliferação de Células , Flavanonas , Humanos , Via de Sinalização Wnt , beta Catenina
9.
BMC Endocr Disord ; 19(1): 124, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729977

RESUMO

BACKGROUND: To investigate the risk factors of cervical lymph node (LN) metastasis in papillary thyroid microcarcinoma (PTMC) patients. METHODS: We retrospectively analyzed the clinicopathologic data of all patients who received standard lobectomy for PTMC at our institution between October 2017 and January 2019. Central LNs were dissected in all patients. Lateral LNs were dissected if metastasis to the lateral LNs was suggested based on pre-op fine-needle aspiration biopsy. The relationship between variables available prior to surgery and cervical LN metastasis was examined using multivariate regression. RESULTS: Post-op pathologic examination revealed cervical LN metastasis in 79 (29.5%) patients. Seventy subjects had metastasis only to central LNs, and 4 (1.5%) patients had metastasis only to lateral LNs. Five patients had metastasis to both central and lateral LNs. In comparison to patients without cervical LN metastasis, those with LN metastasis were significantly younger (40.63 ± 13.07 vs. 44.52 ± 12.23 years; P = 0.021) and had significantly larger tumor diameter on pathology (6.7 ± 2.2 vs. 5.9 ± 2.4 mm; P = 0.010). Multivariate regression analysis identified the following independent risks for cervical LN metastasis: male sex (OR 2.362, 95%CI 1.261~4.425; P = 0.007), age (OR 0.977, 95%CI 0.956~0.999; P = 0.042) and ultrasound tumor diameter at > 5 mm (OR 3.172, 95%CI 1.389~7.240; P = 0.006). CONCLUSION: Cervical LN metastasis occurs in a non-insignificant proportion of PTMC patients. Independent risks included male sex, younger age and larger tumor diameter on ultrasound.


Assuntos
Carcinoma Papilar/secundário , Linfonodos/patologia , Procedimentos Cirúrgicos Operatórios/métodos , Câncer Papilífero da Tireoide/secundário , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Carcinoma Papilar/cirurgia , Feminino , Seguimentos , Humanos , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/secundário , Neoplasias da Glândula Tireoide/cirurgia , Adulto Jovem
10.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3637-3644, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602935

RESUMO

The biopharmaceutics classification system( BCS) is a scientific framework or method for classifying drugs based on drug solubility and permeability,which can be used to provide drug bioavailability-absorption correlation analysis. Based on the characteristics of multi-component and multi-target of traditional Chinese medicine( TCM) as well as the concept,method and technology of BCS,the research group proposed biopharmaceutics classification system of Chinese materia medica( CMMBCS) and carried out research and data accumulation of classical prescriptions. Based on the previous research results,further development ideas under the CMMBCS concept and framework were further proposed in this study. In the course of research,the influence of the intermediate links of the complex interactions of the multi-component environment was omitted,and the component absorption studies on the main clinical effects of prescription ingredients were directly concerned,or the components and data were reversely extracted from the aspects of metabolism,pharmacodynamic pathways and absorption principles. Studies were conducted from two aspects( single component and compound prescription) to comprehensively evaluate the absorption properties of TCM compound. In the research path,the different ways in which Chinese medicine could exert its efficacy were fully considered,and CMMBCS classification and establishment rules were clarified mainly by focusing on the absorption pathway into the blood. Specifically,the network pharmacology and molecular docking technology were used to screen the compound index components of TCM; the absorption rules were studied by the physiologically based pharmacokinetic models and the absorption parameters of CMMBCS were calculated by reverse reasoning. Then the CMMBCS classification of TCM prescription was corrected by studying the efficacy or absorption pathway. In this paper,the theoretical framework and research methodology of CMMBCS were systematically improved based on the establishment of CMMBCS basic theory,the supplementary of drug-oriented research ideas and the application of modern mature Chinese medicine methodology.


Assuntos
Biofarmácia/classificação , Medicamentos de Ervas Chinesas/classificação , Materia Medica/classificação , Simulação de Acoplamento Molecular
11.
Zhongguo Zhong Yao Za Zhi ; 44(5): 948-953, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30989854

RESUMO

Longshengzhi capsule consisting of 12 herbs is widely used in clinically treating cerebral ischemia during recovery period.In this study,in order to investigate the consistency of different batches of Longshengzhi capsules,a high performance liquid chromatography coupled to triple quadrupole mass spectrometry method(HPLC-QQQ/MS) was developed for the determination of 19 representative components in Longshengzhi Capsules within 9 min. Methodology validation indicated this method was simple,rapid,accurate,highly sensitive and reproducible,and it could be used for the content determination of components in Longshengzhi Capsules. The consistency analysis results showed that paeoniflorin and calycosin-7-glucoside in Longshengzhi Capsules had the highest content; RSD value of total content of 19 compounds was 5. 2% and the RSD value of main compounds such as astragaloside and calycosin-7-glucoside was all less than 15%,reflecting good consistency among different batches. This study has provided a scientific method and basis for the quality control and consistency evaluation of Longshengzhi Capsules.


Assuntos
Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/normas , Cápsulas , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Reprodutibilidade dos Testes
12.
Oxid Med Cell Longev ; 2019: 9817576, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30805086

RESUMO

The mitochondrial protein mitoNEET is a type of iron-sulfur protein localized to the outer membrane of mitochondria and is involved in a variety of human pathologies including cystic fibrosis, diabetes, muscle atrophy, and neurodegeneration. In the current study, we found that isoliquiritigenin (ISL), one of the components of the root of Glycyrrhiza glabra L., could decrease the expression of mitoNEET in A375 melanoma cells. We also demonstrated that mitoNEET could regulate the content of reactive oxygen species (ROS), by showing that the ISL-mediated increase in the cellular ROS content could be mitigated by the mitoNEET overexpression. We also confirmed the important role of ROS in ISL-treated A375 cells. The increased apoptosis rate and the decreased mitochondrial membrane potential were mitigated by the overexpression of mitoNEET in A375 cells. These findings indicated that ISL could decrease the expression of mitoNEET, which regulated ROS content and subsequently induced mitochondrial dysfunction and apoptosis in A375 cells. Our findings also highlight mitoNEET as a promising mitochondrial target for cancer therapy.


Assuntos
Apoptose/efeitos dos fármacos , Chalconas/farmacologia , Melanoma/metabolismo , Melanoma/patologia , Mitocôndrias/patologia , Proteínas Mitocondriais/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo
13.
Nanoscale ; 10(43): 20189-20195, 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30378626

RESUMO

Introducing nanoscale heterostructure interfaces into material matrix is an effective strategy to optimize the thermoelectric performance by energy-dependent carrier filtering effect. In this study, highly (00l)-oriented Bi2Te3/Te heterostructure thin films have been fabricated on single-crystal MgO substrates using a facile magnetron co-sputtering method. Bi2Te3/Te heterostructure thin films with Te contents of 63.8 at% show an optimized thermoelectric performance, which possess a Seebeck coefficient of -157.7 µV K-1 and an electrical conductivity of 9.72 × 104 S m-1, leading to a high power factor approaching 25 µW cm-1 K-2. The partially decoupled behavior of the Seebeck coefficient and electrical conductivity is contributed to Bi2Te3/Te heterostructure interfaces, which causes interfacial barrier filtering and scattering effects; thus, a high level of the Seebeck coefficient is obtained. Meanwhile, carrier transport in a-b plane can benefit from the highly preferred orientation, which guarantees a remarkably high electrical conductivity. We anticipate that our strategy may guide the way for preparing high-performance thermoelectric materials by microstructure design and regulation.

14.
Front Pharmacol ; 9: 956, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30233366

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting toxicity of many anti-neoplastic agents, especially paclitaxel, and oxaliplatin. Up to 62% of patients receiving paclitaxel regimens turn out to develop CIPN. Unfortunately, there are so few agents proved effective for prevention or management of CIPN. The reason for the current situation is that the mechanisms of CIPN are still not explicit. Traditional Chinese Medicine (TCM) has unique advantages for dealing with complex diseases. Wen-Luo-Tong (WLT) is a TCM ointment for topical application. It has been applied for prevention and management of CIPN clinically for more than 10 years. Previous animal experiments and clinical studies had manifested the availability of WLT. However, due to the unclear mechanisms of WLT, further transformation has been restricted. To investigate the therapeutic mechanisms of WLT, a metabolomic method on the basis of UPLC- MS was developed in this study. Multivariate analysis techniques, such as principal component analysis (PCA) and partial least squares discriminate analysis (PLS-DA), were applied to observe the disturbance in the metabolic state of the paclitaxel-induced peripheral neuropathy (PIPN) rat model, as well as the recovering tendency of WLT treatment. A total of 19 significant variations associated with PIPN were identified as biomarkers. Results of pathway analysis indicated that the metabolic disturbance of pathways of linoleic acid (LA) metabolism and glycerophospholipid metabolism. WLT attenuated mechanical allodynia and rebalanced the metabolic disturbances of PIPN by primarily regulating LA and glycerophospholipid metabolism pathway. Further molecular docking analysis showed some ingredients of WLT, such as hydroxysafflor yellow A (HSYA), icariin, epimedin B and 4-dihydroxybenzoic acid (DHBA), had high affinity to plenty of proteins within these two pathways.

15.
Zhongguo Zhong Yao Za Zhi ; 43(13): 2796-2805, 2018 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-30111034

RESUMO

To explore the drug-induced constituents in vivo of Polygonum multiflorum extract (PM). This study was the first to study the drug-induced constituents in target organ liver. Agilent MassHunter qualitative analysis software and Metabolite ID software were applied for the analysis of retention time, exact relative molecular mass, primary and secondary mass spectrum information based on ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and targeted-MS/MS. By comparison with literature and standards, a total of 5 prototypes and 6 metabolites were identified or tentatively elucidated from the liver samples. In addition, the drug-induced constituents in plasma and PM were also analyzed in this study and 8 prototypes and 19 metabolites were detected from the plasma samples, while 30 compounds were detected from the extract of PM. Emodin oxidative acetylation metabolites, hydroxyl methylation metabolites, carboxylation glucuronidation metabolites and ketone glucuronidation metabolites in this study were first reported. Through the comparative analysis between the in vivo and in vitro constituents of PM, the study preliminarily revealed the drug-induced constituents (prototypes and metabolites) in liver and clarified the transfer process and transmutation rules of constituents in PM, blood and liver, which would further deepen our understanding on constituents of PM in vivo.


Assuntos
Medicamentos de Ervas Chinesas , Fallopia multiflora , Animais , Cromatografia Líquida de Alta Pressão , Fígado , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
16.
Clin Rheumatol ; 37(11): 2999-3007, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29980876

RESUMO

To systematically evaluate the diagnostic accuracy of miRNAs as potential biomarkers for systemic lupus erythematosus (SLE). Studies were searched in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and China Biology Medicine (CBM) disc database, and languages were limited in English and Chinese. QUADAS-2 tool was applied to assess the quality of eligible studies. Random-effect model was applied to calculate pooled effects of miRNAs on diagnosing SLE. Subgroup analysis was used to explore the sources of heterogeneity. All data were calculated and analyzed by Meta-Disc 1.4 and RevMan 5.3 software. Six eligible studies were included in this meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio of miRNAs were 0.75(95% CI 0.71-0.79), 0.72(95% CI 0.66-0.78), and 8.79(95% CI 4.91-15.73), respectively. The pooled positive likelihood ratio was 2.71(95% CI 2.20-3.33) and negative likelihood ratio was 0.34(95% CI 0.24-0.48). The area under the curve was 0.787. The subgroup analysis showed that the number of healthy controls might be the sources of heterogeneity. MiRNAs in blood have moderate accuracy and influence on diagnosing SLE, and the exact diagnostic value should be confirmed by further studies.


Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , MicroRNAs/sangue , Biomarcadores/sangue , Humanos , Funções Verossimilhança , Lúpus Eritematoso Sistêmico/sangue , Sensibilidade e Especificidade
17.
Acta Pharmacol Sin ; 39(6): 961-974, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29345255

RESUMO

Both baicalin (BA) and jasminoidin (JA) are active ingredients in Chinese herb medicine Scutellaria baicalensis and Fructus gardeniae, respectively. They have been shown to exert additive neuroprotective action in ischemic stroke models. In this study we used transcriptome analysis to explore the pure therapeutic mechanisms of BA, JA and their combination (BJ) contributing to phenotype variation and reversal of pathological processes. Mice with middle cerebral artery obstruction were treated with BA, JA, their combination (BJ), or concha margaritifera (CM). Cerebral infarct volume was examined to determine the effect of these compounds on phenotype. Using the hippocampus microarray and ingenuity pathway analysis (IPA) software, we exacted the differentially expressed genes, networks, pathways, and functions in positive-phenotype groups (BA, JA and BJ) by comparing with the negative-phenotype group (CM). In the BA, JA, and BJ groups, a total of 7, 4, and 11 specific target molecules, 1, 1, and 4 networks, 51, 59, and 18 canonical pathways and 70, 53, and 64 biological functions, respectively, were identified. Pure therapeutic mechanisms of BA and JA were mainly overlapped in specific target molecules, functions and pathways, which were related to the nervous system, inflammation and immune response. The specific mechanisms of BA and JA were associated with apoptosis and cancer-related signaling and endocrine and hormone regulation, respectively. In the BJ group, novel target profiles distinct from mono-therapies were revealed, including 11 specific target molecules, 10 functions, and 10 pathways, the majority of which were related to a virus-mediated immune response. The pure additive effects between BA and JA were based on enhanced action in virus-mediated immune response. This pure mechanistic analysis may provide a clearer outline of the target profiles of multi-target compounds and combination therapies.


Assuntos
Flavonoides/farmacologia , Hipocampo/efeitos dos fármacos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Iridoides/farmacologia , Fármacos Neuroprotetores/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Redes Reguladoras de Genes/efeitos dos fármacos , Hipocampo/imunologia , Hipocampo/metabolismo , Hipocampo/patologia , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/genética , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Masculino , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Biologia de Sistemas/métodos , Transcriptoma/efeitos dos fármacos
18.
Acta Pharmacol Sin ; 39(3): 345-356, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29119967

RESUMO

Autophagy plays an important role in alleviating oxidative stress and stabilizing atherosclerotic plaques. However, the potential role of autophagy in endothelial vasodilation function has rarely been studied. This study aimed to investigate whether rhynchophylla total alkaloid (RTA) has a positive role in enhancing autophagy through decreasing oxidative stress, and improving endothelial vasodilation. In oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs), RTA (200 mg/L) significantly suppressed ox-LDL-induced oxidative stress through rescuing autophagy, and decreased cell apoptosis. In spontaneous hypertensive rats (SHR), administration of RTA (50 mg·kg-1·d-1, ip, for 6 weeks) improved endothelin-dependent vasodilation of thoracic aorta rings. Furthermore, RTA administration significantly increased the antioxidant capacity and alleviated oxidative stress through enhancing autophagy in SHR. In ox-LDL-treated HUVECs, we found that the promotion of autophagy by RTA resulted in activation of the AMP-activated protein kinase (AMPK) signaling pathway. Our results show that RTA treatment rescues the ox-LDL-induced autophagy impairment in HUVECs and improves endothelium-dependent vasodilation function in SHR.


Assuntos
Alcaloides/farmacologia , Autofagia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Uncaria/química , Vasodilatação/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Aorta/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Lipoproteínas LDL/metabolismo , Masculino , Ratos , Transdução de Sinais/efeitos dos fármacos
19.
Oncotarget ; 8(48): 83673-83683, 2017 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-29137373

RESUMO

This study aims to investigate the prognostic power of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) in gastric cancer (GC) and its potential role in cancer development and progression. Data mining results show that CEACAM6 is overexpressed in gastric cancer and is correlated with lymph node metastasis. Subsequently, immunohistochemical staining was performed to determine CEACAM6 protein levels in paraffin gastric tumor specimens. Real-time reverse-transcription-polymerase chain reaction (RT-PCR) was conducted to detect CEACAM6 mRNA levels in fresh GC samples. CEACAM6 protein and mRNA levels were significantly up regulated in GC compared with paired normal mucosa. The IHC staining intensity of CEACAM6 was positively correlated with tumor size, Lauren's classification, vascular invasion, lymph node metastasis, distant metastasis, and TNM stage. CEACAM6 expression was inversely correlated with the five-year survival rate of GC patients. Cox multivariate analysis results demonstrated that the overall survival was independently correlated with CEACAM6 expression. A significant association was observed between CEACAM6 and distant metastases. Network analysis of downstream gene signatures revealed several hub genes such as SRC and DNM1L etc. which may mediating tumor promoting functions of CEACAM6. Further data mining discovered that Tamoxifen etc. could be therapeutic alternatives for gastric patients with CEACAM6 overexpression. Collectively, CEACAM6 overexpression is a common characteristic of GC and is associated with poor 5 year survival rate in GC. Besides, potential molecular mechanisms and treatment options were also provided.

20.
Phys Chem Chem Phys ; 18(14): 9412-8, 2016 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-26979556

RESUMO

The charge trapping properties of the blend of polystyrene (PS) and a sterically hindered organic semiconductor SFDBAO (spiro[fluorene-9,7-dibenzo[c,h]acridin-5-one]) are investigated by electrostatic and Kelvin probe force microscopy (EFM and KPFM). EFM signals of trapped charge spots injected with controllable tip biases, which are recorded with different dissipation times t, the percent of SFDBAO in blends, and the scanning tip bias, have been measured. By the quantitative analysis, the excellent trapped charge density of PS/SFDBAO blend films for the holes (∼×10(-5) C m(-2)) is much higher than that of the SFDBAO film (∼×10(-6) C m(-2)) and the PS film (∼×10(-7) C m(-2)). However, the trapped charge density of electrons (∼×10(-7) C m(-2)) has the same order magnitude for SFDBAO, PS and the blend films. The results indicate that the blend of PS and SFDBAO enhances the high-density storage and retention abilities of the holes to a larger extent, but the endurance improvement of the electrons is not that obvious. By the KPFM measurement, we further verify the different diffusion rates of the trapped holes and electrons in the PS/SFDBAO blend films, and discuss the possible physical mechanism. The qualitative and quantitative determination of charge trapping properties in this work can be very useful for the characterization of PS/SFDBAO based charge trapping memory devices.

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