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1.
Biomed Chromatogr ; : e4914, 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32515056

RESUMO

Dingkun Dan (DKD), a famous traditional Chinese medicine prescription since Qing Dynasty (1739), has been widely used in the treatment of irregular menstruation, leucorrhea abnormality and postpartum gynecological disease. It is comprised by 30 various types of herbal and animal orient medicine, which results in the complexity of its chemical compositions. In this study, an integrative method was established to rapidly characterize the chemical components of DKD by using UPLC-Q-TOF/MSE combined with the UNIFITM software. As a result, a total of 234 compounds were identified including 47 triterpenoid saponins, 55 flavonoids, 38 alkaloids and others. Among them, 170 compounds were characterized initially and 61 compounds were unambiguously identified by using standards. Under the same analysis conditions, 43 prototypical components, which were tentatively assigned as triterpenoid saponins, flavonoids, alkaloids, terpenoids, phenylpropanoids and others, have been absorbed in rat by serum pharmacochemistry analysis. DKD has exerted the diverse pharmacological activities through the combined effect of these various components. This study was the first systematic study of chemical components in vitro originating from 30 medicinal materials and prototypes in vivo of DKD, which could provide a scientific evidence for explaining its therapeutic effect.

2.
J Am Chem Soc ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32321243

RESUMO

Single-molecule conductance of a B-N substituted phenanthrene derivative and its isoelectronic C═C counterpart was investigated by the scanning tunneling microscopy break junction (STM-BJ) technique. The incorporation of the B-N motif results in a better single-molecule conductivity than the C═C analogue. Furthermore, the Lewis acid-base reaction between F- and the B atom of the B-N motif leads to a decrease of the conductance of the BN derivative, which can be understood due to the shifting of the energy positions of the LUMO, as revealed by quantum transport calculations, even though the HOMO-LUMO gap decreases in the B-F Lewis acid-base. These findings provide insights for modulating electron transport properties by isoelectronic structure design. The B-N isoelectronic substituted structure could be a feasible way to design single-molecule devices such as switches and chemical sensors.

3.
J Pharm Pharmacol ; 72(7): 969-978, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32246778

RESUMO

OBJECTIVES: To screen the cytotoxic activity of six secondary metabolites isolated from soil fungus Aspergillus niger. Importantly, to investigate the mechanism that pyoluteorin induced human triple-negative breast cancer MDA-MB-231 cells apoptosis in vitro. METHODS: The cell viability assay was tested with CTG assay. Cell cycle, apoptosis and intracellular reactive oxygen species (ROS) production assay were tested with flow cytometry. Additionally, intracellular ROS production assay and mitochondrial membrane potential assay were determined with laser scanning confocal microscopy. The expression of apoptosis-related proteins was determined with Western blot. KEY FINDINGS: Pyoluteorin displayed significantly selective cytotoxicity against human triple-negative breast cancer MDA-MB-231 cells (IC50  = 0.97 µm) with low toxicity against human breast epithelial cell MCF-10A. It was found that pyoluteorin could arrest MDA-MB-231 cells cycle at G2 /M phase and induce cell apoptosis. Further experiments demonstrated that the apoptosis-inducing effect of pyoluteorin was related to reduction of mitochondrial membrane potential, accumulation of ROS and change of apoptosis-related protein expressions. CONCLUSION: Our studies revealed that pyoluteorin had potent proliferation inhibition against MDA-MB-231 cells through arresting cell cycle at G2 /M phase and inducing caspase-3-dependent apoptosis by mitochondrial pathway, implying that pyoluteorin may be a potential lead compound for drug discovery of human triple-negative breast cancer.

4.
J Pharm Biomed Anal ; 184: 113197, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32120187

RESUMO

Untargeted mass spectrometry analysis is one of the most challenging and meaningful steps in the rapid structural elucidation of the highly complex and diverse constituents of traditional Chinese medicine. Specifically, it is a laborious and time-consuming way to identify unknown compounds. Herein, a workflow was proposed to expedite the annotations of the chemical structures in Pheretima aspergillum (E. Perrier) (Di-Long, DL). First, ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOFMS) was performed to obtain the untargeted mass spectral data. Then, the spectral data were uploaded to the Global Natural Products Social Molecular Networking (GNPS) platform to create a network and extract the Mass2Motifs (co-occurring fragments and neutral losses) using unsupervised substructure annotation topic modeling (MS2LDA). Finally, a structural analysis was performed using the proposed workflow of MS2LDA in combination with mass spectral molecular networking and in silico fragmentation prediction. As a result, a total of 124 compounds from DL were effectively characterized, of which 89 (7 furan sulfonic acids, 57 phospholipids and 25 carboxamides) were identified as potentially new compounds from DL. The results presented in this article significantly improve the understanding of the chemical composition of DL and provide a solid scientific basis for the future study of the quality control, underlying pharmacology and mechanism of DL. Moreover, the proposed workflow was used for the first time to accelerate the annotations of unknown molecules from TCM. Furthermore, this workflow will increase the efficiency of characterizing the 'unknown knowns' and elucidation of the 'unknown unknowns' from TCM, which are crucial steps of discovering the natural product drugs in TCM.

5.
Acta Pharmacol Sin ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32203078

RESUMO

Gastrodin (GAS) is the main bioactive component of Tianma, a traditional Chinese medicine widely used to treat neurological disorders as well as cardio- and cerebrovascular diseases. In the present study, the protective effects of GAS on H9c2 cells against ischemia-reperfusion (IR)-like injury were found to be related to decreasing of oxidative stress. Furthermore, GAS could protect H9c2 cells against oxidative injury induced by H2O2. Pretreatment of GAS at 20, 50, and 100 µM for 4 h significantly ameliorated the decrease in cell viability and increase in apoptosis of H9c2 cells treated with 400 µM H2O2 for 3 h. Furthermore, we showed that H2O2 treatment induced fragmentation of mitochondria and significant reduction in networks, footprint, and tubular length of mitochondria; H2O2 treatment strongly inhibited mitochondrial respiration; H2O2 treatment induced a decrease in the expression of mitochondrial fusion factors Mfn2 and Opa1, and increase in the expression of mitochondrial fission factor Fis1. All these alterations in H2O2-treated H9c2 cells could be ameliorated by GAS pretreatment. Moreover, we revealed that GAS pretreatment enhanced the nuclear translocation of Nrf2 under H2O2 treatment. Knockdown of Nrf2 expression abolished the protective effects of GAS on H2O2-treated H9c2 cells. Our results suggest that GAS may protect H9c2 cardiomycytes against oxidative injury via increasing the nuclear translocation of Nrf2, regulating mitochondrial dynamics, and maintaining the structure and functions of mitochondria.

6.
Fitoterapia ; 142: 104530, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32114035

RESUMO

A new azo compound, penoxalin (1), a new isochroman carboxylic acid, penisochroman B (3), two new natural products, penisochroman A (2) and 2,6-dihydroxy-4-[(2R)-2-hydroxyheptyl] benzoic acid (4), together with four known compounds (5-8) were isolated from wetland soil fungus Penicillium oxalicum GY1. All structures were elucidated by extensive NMR spectroscopic evidences together with mass spectrometry. The absolute configuration of penoxalin (1) was determined by calculated ECD spectrum, while the absolute configuration of new natural product penisochroman A (2) was established for the first time by single crystal X-ray diffraction. In addition, all compounds were evaluated for their cytotoxic activity in vitro. 2, 6-Dihydroxy-4-[(2R)-2-hydroxyheptyl] benzoic acid (4) displayed significant cytotoxicity against human esophageal carcinoma cells OE19 with an IC50 value of 5.50 µM.

7.
J Cardiovasc Pharmacol ; 75(4): 314-320, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32040035

RESUMO

BACKGROUND: The current light transmission aggregation method is a recognized conventional method for platelet function evaluation, but it is time-consuming and poor in parallelism and cannot simultaneously monitor multiple inducers at multiple levels. The microtiter plate method has been established because of the high-throughput characteristic, but it needs more practical applications. OBJECTIVES: To evaluate the microtiter plate method by using aspirin and clopidogrel in vivo and in vitro. METHODS: In vitro, the platelet aggregations inhibited by aspirin (0.3, 1, 3, 10, 30, 90 µM) and clopidogrel (1, 3, 10, 30, 100, 300 µM) were evaluated with the presence of arachidonic acid (AA) and adenosine diphosphate (ADP) agonists. Using the combination index (CI), the effect of the combination of aspirin and clopidogrel on platelet aggregation was evaluated. In vivo, New Zealand rabbits (n = 18) were randomly divided into 3 groups, aspirin group (5 mg/kg, intragastrical gavage [i.g.]), clopidogrel group (14 mg/kg at the first day, followed by 4 mg/kg, i.g.), and the combination of these two drugs, administered (i.g.) continuously for 7 days. Then, the blood was collected to measure platelet aggregation. RESULTS: Different concentrations of AA (12.5, 25, 50, 100 µM) and ADP (1.25, 2.5, 5, 10 µM) could promote platelet aggregation in concentration-dependent manner, and the most stable induction concentrations of AA and ADP were 50 and 5 µM. In vitro, with the above optimized detection system, aspirin and clopidogrel alone or in combination had concentration-dependent antiplatelet aggregation. The combination of aspirin and clopidogrel also showed synergistic inhibition effect within the concentration range studied. In vivo, aspirin and clopidogrel alone or in combination inhibited platelet aggregation induced by multiple concentrations of AA and ADP agonists, and the combined inhibition was more significant during the administration than aspirin or clopidogrel alone. CONCLUSIONS: The improved microtiter plate method combining the use of multiple levels of multiple agonists avoids the variation of the effective inducer concentrations due to individual different response of platelets to agonists. It may be a potential approach in the detection of platelet aggregation.

8.
Drug Resist Updat ; 49: 100681, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32014648

RESUMO

The presence of multidrug resistance (MDR) in malignant tumors is one of the primary causes of treatment failure in cancer chemotherapy. The overexpression of the ATP binding cassette (ABC) transporter, P-glycoprotein (P-gp), which significantly increases the efflux of certain anticancer drugs from tumor cells, produces MDR. Therefore, inhibition of P-gp may represent a viable therapeutic strategy to overcome cancer MDR. Over the past 4 decades, many compounds with P-gp inhibitory efficacy (referred to as first- and second-generation P-gp inhibitors) have been identified or synthesized. However, these compounds were not successful in clinical trials due to a lack of efficacy and/or untoward toxicity. Subsequently, third- and fourth-generation P-gp inhibitors were developed but dedicated clinical trials did not indicate a significant therapeutic effect. In recent years, an extraordinary array of highly potent, selective, and low-toxicity P-gp inhibitors have been reported. Herein, we provide a comprehensive review of the synthetic and natural products that have specific inhibitory activity on P-gp drug efflux as well as promising chemosensitizing efficacy in MDR cancer cells. The present review focuses primarily on the structural features, design strategies, and structure-activity relationships (SAR) of these compounds.

9.
Fitoterapia ; 142: 104516, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32081701

RESUMO

A new bilobalide isomer (1), together with two flavonol glycosides (2, 3), have been isolated and elucidated from the extract of Ginkgo biloba leaves. Significantly, 1 was a new sesquiterpene lactone with two lactone ring groups, both 2 and 3 were two flavonol glycosides with a same cis-coumaroylated fragment. Their chemical structures were elucidated by NMR and MS spectroscopic date and the absolute configuration of 1 was specific established by Cu-Kα X-ray crystallographic analyses. However, 1-3 showed no obvious anti-platelet aggregation activity.

10.
J Ethnopharmacol ; 254: 112687, 2020 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-32105748

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese medicine formula (CMF) has a long history of clinical use in the treatment of various diseases under the guidance of traditional Chinese medicine (TCM) theory. The application of CMF can be divided into three levels, crude extracts, homologous compounds mixture, and specific compounds. However, the modern scientific connotation of the CMF theory has not been clarified. AIM OF THE REVIEW: To critically evaluate the research strategy for the investigation of compound-based CMF (CCMF). MATERIALS AND METHODS: The related information was collected from the scientific databases, including CNKI, Elsevier, ScienceDirect, PubMed, SpringerLink, Web of Science, and Wiley Online. RESULTS: The research design including discovery, screening, optimization, pharmacodynamics models, and target research techniques including the targets for compatibility compounds were evaluated. Essentially it has been evaluated that the in vitro multicellular three-dimensional culture or organoid model has been proposed for the optimization model for compatibility research of CCMF. Based on these, the traditional compatibility theory of CMF, such as Monarch-Minister-Assistant-Guide (Jun-Chen-Zuo-Shi in Chinese), can probably be elucidated by the CCMF research. CONCLUSIONS: CCMF has the clear advantage of providing the exact composition and controllable quality of modern medicines, in addition to having the characteristics of multi-ingredients and multi-targets synergistic effects of TCM. However, CCMF is still associated with challenges which need to be addressed for its future use.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32081422

RESUMO

BACKGROUND AND OBJECTIVES: Formononetin has protective effect against ischemic stroke. It's unclear whether it can restore the nerve functions after stroke. METHODS: SD rats were subjected with middle cerebral artery occlusion (MCAO), and divided into sham, model and formononetin (30 mg/kg) groups. Neurobehavioral tests (modified Neurological Severity Score [mNSS] and rotarod) were performed before and at 1, 3, 7 and 14 days after MCAO. Then, the rats were sacrificed and the brain sections were processed for neuronal differentiation and synaptic plasticity. RESULTS: Compared with the sham group, the scores of mNSS were significantly increased, and the residence time on the rotating drum was significantly decreased in the MCAO rats. Compared with the model group, the scores of mNSS were significantly decreased, and the residence time on the rotating drum was increased in the formononetin (30 mg/kg) group. Formononetin significantly increased the number of neuronal dendritic spines and the expression of ß III-tubulin, GAP-43, NGF, BDNF, p-Trk A, p-Trk B, p-AKT and p-ERK 1/2. CONCLUSIONS: Formononetin recovered injured nerve functions after ischemic stroke. PI3K/AKT/ERK pathway might involve in the beneficial effect of formononetin on the neuronal differentiation and synaptic plasticity.

12.
Nat Prod Bioprospect ; 10(1): 13-21, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31786736

RESUMO

Eight new triterpenoids were isolated from Ainsliaea latifolia. The structures of these compounds were elucidated by interpretation of spectroscopic data, including HRESIMS and NMR data. Compounds 4-6 are identified as rare trinorcucurbitane or tetranorcucurbitane triterpenoids. The absolute configurations of compounds 1 and 2 were confirmed by Snatzke's method. All compounds were evaluated for their inhibition against cyclooxyenase-2 (COX-2), in which compound 4 showed significant inhibitory effect against COX-2 with IC50 value of 3.98 ± 0.32 µM, comparable to that of positive control NS-398 (IC50 4.14 ± 0.28 µM).

13.
Malar J ; 18(1): 429, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852503

RESUMO

BACKGROUND: Imported malaria has been an important challenge for China. Fatality rates from malaria increased in China, particularly in Henan Province, primarily due to malpractice and misdiagnoses in healthcare institutions, and the level of imported malaria. This study aims to investigate the relationship between the state of diagnosis and subsequent complications among imported malaria cases at healthcare institutions, based on malaria surveillance data in Henan Province from 2012 to 2017. METHODS: A retrospective descriptive analysis was performed using data from the Centre for Disease Control and Prevention, Zhengzhou City, the capital of Henan Province. A decision tree method was exploited to provide valuable insight into the correlation between imported malaria cases and healthcare institutions. RESULTS: From 2012 to 2017, there were 371 imported malaria cases, mostly in males aged between 20 and 50 years, including 319 Plasmodium falciparum cases. First visits of 32.3%, 19.9% and 15.9% malaria cases for treatment were to provincial, municipal and county healthcare institutions, respectively. The time interval between onset and initial diagnosis of 284 cases (76.5%) and the time interval between initial diagnosis and final diagnosis of 197 cases (53.1%) was no more than 72 h. An apparent trend was found that there were notably fewer patients misdiagnosed at first visit to healthcare institutions of a higher administrative level; 12.5% of cases were misdiagnosed in provincial healthcare institutions compared to 98.2% in private clinics, leading to fewer complications at healthcare institutions of higher administrative level due to correct initial diagnosis. In the tree model, the rank of healthcare facilities for initial diagnosis, and number of days between onset and initial diagnosis, made a major contribution to the classification of initial diagnosis, which subsequently became the most significant factor influencing complications developed in the second tree model. The classification accuracy were 82.2 and 74.1%, respectively for the tree models of initial diagnosis and complications developed. CONCLUSION: Inadequate seeking medical care by imported malaria patients, and insufficient capacity to diagnose malaria by healthcare institutions of lower administrative level were identified as major factors influencing complications of imported malaria cases in Henan Province. The lack of connection between uncommon imported malaria cases and superior medical resources was found to be the crucial challenge. A web-based system combined with WeChat to target imported malaria cases was proposed to cope with the challenge.


Assuntos
Doenças Transmissíveis Importadas/prevenção & controle , Árvores de Decisões , Instalações de Saúde , Malária/prevenção & controle , Adolescente , Adulto , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Plasmodium/fisiologia , Estudos Retrospectivos , Adulto Jovem
14.
Zhongguo Zhong Yao Za Zhi ; 44(18): 3917-3923, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31872725

RESUMO

Dengzhan Shengmai Capsules( DZSMC),a well-known traditional Chinese medicine( TCM) formula,is comprised of the main drug of Erigeron breviscapus,and supplemented with Panax ginseng,Ophiopogon japonicus and Schisandra chinensis,with functions of supplementing Qi and nourishing Yin,promoting blood circulation and strengthening brain. DZSMC is the only Chinese patent drug with A-level evidence-based medicine in secondary prevention for stroke and ranks first among TCMs for neurological treatment. Modern studies indicate that the chemical constituents of DZSMC mainly include flavonoids,phenolic acids,lignans,saponins and so on. Pharmacological experimental studies have shown that DZSMC has such pharmacological effects as anti-oxidation,anti-inflammatory and anti-myocardial ischemia. DZSMC is mainly used in the convalescent care of ischemic cardiovascular and cerebrovascular diseases,and is often used in combination with various conventional therapeutic drugs to exert clinical efficacy through brain protection,neuroprotection,etc.,and improve clinical symptoms in patients. In this review,according to domestic and international related literature combined with research results obtained by our project,the research advances in the chemical constituents,pharmacological effects and clinical application of DZSMC have been systematically reviewed and summarized,providing reference and support for further study and secondary development of the formula.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Erigeron/química , Humanos , Medicina Tradicional Chinesa , Ophiopogon , Panax , Compostos Fitoquímicos/farmacologia , Fitoterapia , Schisandra
15.
Cell Commun Signal ; 17(1): 121, 2019 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511020

RESUMO

Pancreatic cancer (PC) is one of the most fatal diseases with a very high rate of metastasis and low rate of survival. Despite the advances in understanding this devastating disease, PC still accounts for 3% of all cancers and causes almost 7% of death of cancer patients. Recent studies have demonstrated that the transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) and its key negative regulator Kelch-like ECH-associated protein 1 (Keap1) are dysregulated in PC and the Keap1-Nrf2 pathway is an emerging target for PC prevention and therapy. Indeed, Nrf2 plays an either tumor-suppressive or promoting function in PC, which depends on the developmental stages of the disease and the cellular context. Several natural-product Nrf2 activators have been developed to prevent pancreatic carcinogenesis, while the Nrf2 inhibitors have been examined for their efficacy in inhibiting PC growth and metastasis and reversing chemoresistance. However, further preclinical and clinical studies for determining the effectiveness and safety of targeting the Keap1-Nrf2 pathway for PC prevention and therapy are warranted. In this review, we comprehensively discuss the dual roles of the Keap1-Nrf2 signaling pathway in PC as well as the current targeting strategies and known activators and inhibitors of Nrf2. We also propose new strategies that may be used to address the current issues and develop more specific and more effective Nrf2 activator/inhibitors for PC prevention and therapy.

16.
Phytomedicine ; 64: 153073, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31542661

RESUMO

BACKGROUND: Ginkgo biloba (Gb) extracts have been used as a traditional Chinese medicine. Gb contains flavonoids, which are considered to be its active ingredients and have been used in the treatment of a variety of diseases. However, few scientific research studies on the side effects of flavonoid in Gb have been reported. PURPOSE: The present study aimed to investigate the effect of bilobetin on the kidney of Sprague-Dawley (SD) rats. STUDY DESIGN AND RESULT: In this study, rats were injected with 50 mg/kg of bilobetin, a biflavone isolated from Gb, for 7 days and aristolochic acid was used as positive controls. The results showed that the body weight and urine output of the rats were dramatically decreased, and urinary protein increased after the intraperitoneal injection of bilobetin compared with the control group. Bilobetin treatment showed vacuolar degeneration in the renal tubular epithelium, glomerular atrophy by histostaining, and podocyte fusion by electron microscopy. This study further showed that bilobetin promoted the trafficking of aquaporin 2 (AQP-2) onto the plasma membrane to achieve the function of urine concentration by in vivo study in rats and in vitro study in IMCD-3 cells. The redistribution of AQP-2 is due to increased expression of cGMP in IMCD-3 cells, which in turn promoted the phosphorylation of AQP-2 at site Ser-256. The proteinuria caused by bilobetin may be attributed to podocyte cell cycle arrest at G2/M transition, which is may associated with AKT and MAPK signaling. CONCLUSIONS: The current study showed that bilobetin has some side effects on kidneys at a dose of 50 mg/kg in SD rats and provides insight into the potential detrimental effects of monomeric ingredients in Gb.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/patologia , Aquaporina 2/metabolismo , Flavonoides/efeitos adversos , Podócitos/efeitos dos fármacos , Lesão Renal Aguda/metabolismo , Animais , Aquaporina 2/genética , Pontos de Checagem do Ciclo Celular , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , GMP Cíclico/metabolismo , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/química , Flavonoides/administração & dosagem , Células HEK293 , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Glomérulos Renais/metabolismo , Masculino , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Podócitos/metabolismo , Podócitos/patologia , Proteinúria/induzido quimicamente , Ratos Sprague-Dawley
17.
ACS Omega ; 4(1): 2047-2052, 2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31459455

RESUMO

Five new guaiane dimers, xylopidimers A-E (1-5), were isolated and identified from the roots of Xylopia vielana. The structures of 1-5 were elucidated by spectroscopic analysis and further confirmed by single-crystal X-ray diffraction. On the basis of the results of single-crystal X-ray analysis, 1-5 showed different carbon skeletons. Among these compounds, the unique connecting patterns of 1 and 2 caused significant differences on their carbon skeletons, which have not been reported. Moreover, 3-5 were also three new guaiane dimers. Among these compounds, 4 exhibited potent inhibitory activity against the production of nitric oxide with an IC50 value of 4.59 µM in RAW264.7 cells stimulated by lipopolysaccharide.

18.
Chin J Nat Med ; 17(5): 321-330, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31171266

RESUMO

Traditional Chinese Medicine (TCM) is the treasure of Chinese Nation and gained the gradual acceptance of the international community. However, the methods and theories of TCM understanding of diseases are lack of appropriate modern scientific characterization systems. Moreover, traditional risk factors cannot promote to detection and prevent those patients with coronary artery disease (CAD) who have not developed acute myocardial infarction (MI) in time. To sum up, there is still no objective systematic evaluation system for the therapeutic mechanism of TCM in the prevention and cure of cardiovascular disease. Thus, new ideas and technologies are needed. The development of omics technology, especially metabolomics, can be used to predict the level of metabolites in vivo and diagnose the physiological state of the body in time to guide the corresponding intervention. In particular, metabolomics is also a very powerful tool to promote the modernization of TCM and the development of TCM in personalized medicine. This article summarized the application of metabolomics in the early diagnosis, the discovery of biomarkers and the treatment of TCM in CAD.


Assuntos
Doença das Coronárias/sangue , Doença das Coronárias/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Metabolômica , Biomarcadores/sangue , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Medicina Tradicional Chinesa/tendências , Metabolômica/instrumentação , Resultado do Tratamento
19.
Int J Radiat Oncol Biol Phys ; 105(1): 124-131, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31075310

RESUMO

PURPOSE: To evaluate the evolution of radiation-induced brain stem injury (BSI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiation therapy (IMRT) and to identify the critical dosimetric predictors of BSI. METHODS AND MATERIALS: A total of 6288 NPC patients treated with IMRT between 2009 and 2015 were retrospectively reviewed. Among these 6288 patients, 24 had radiation-induced BSI, which manifested as edematous lesions and contrast-enhanced lesions (CLs) on magnetic resonance imaging. Latency, symptoms, and evolution of BSI were assessed. Critical dosimetric predictors of BSI were identified using a penalized regression model with performance evaluated by receiver operating characteristic curve analysis. RESULTS: Median BSI latency was 14.5 months (range, 7.6-37.5 months), and 9 out of 24 patients (37.5%) were clinically symptomatic. Edematous lesions and CLs were both present in all patients. Necrosis was significantly more common in larger CLs (P = .007). After median follow-up of 12.5 months, 13 out of 24 patients (54.2%) had complete remission, and 5 out of 24 patients (20.8%) had partial remission. Remission was unaffected by whether or not symptomatic treatment was given. Maximum point dose (Dmax) was identified as the critical predictor of BSI (area under the receiver operating curve = 0.898), with the optimal cutoff equivalent dose in 2-Gy fractions (D2) being 67.4 Gy (sensitivity = 0.833, 20 out of 24; specificity = 0.835, 5234 out of 6264). Patients with Dmax ≥67.4 Gy (D2) were significantly more likely to develop BSI (odds ratio = 25.29; 95% CI, 8.63-74.14; P < .001) than those with Dmax <67.4 Gy (D2). CONCLUSIONS: In patients with NPC treated with IMRT, BSI generally tends to improve over time. Dmax = 67.4 Gy (D2) appears to be the dose constraint for brain stem, potentially providing clinicians with greater choice and flexibility when balancing the tumor target coverage and brain stem protection. Further studies are needed to validate our findings.


Assuntos
Tronco Encefálico/efeitos da radiação , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Lesões por Radiação/diagnóstico por imagem , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Tronco Encefálico/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Curva ROC , Radiometria , Dosagem Radioterapêutica , Estudos Retrospectivos
20.
J Exp Clin Cancer Res ; 38(1): 195, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088482

RESUMO

Triple negative breast cancer (TNBC), which is typically lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), represents the most aggressive and mortal subtype of breast cancer. Currently, only a few treatment options are available for TNBC due to the absence of molecular targets, which underscores the need for developing novel therapeutic and preventive approaches for this disease. Recent evidence from clinical trials and preclinical studies has demonstrated a pivotal role of signal transducer and activator of transcription 3 (STAT3) in the initiation, progression, metastasis, and immune evasion of TNBC. STAT3 is overexpressed and constitutively activated in TNBC cells and contributes to cell survival, proliferation, cell cycle progression, anti-apoptosis, migration, invasion, angiogenesis, chemoresistance, immunosuppression, and stem cells self-renewal and differentiation by regulating the expression of its downstream target genes. STAT3 small molecule inhibitors have been developed and shown excellent anticancer activities in in vitro and in vivo models of TNBC. This review discusses the recent advances in the understanding of STAT3, with a focus on STAT3's oncogenic role in TNBC. The current targeting strategies and representative small molecule inhibitors of STAT3 are highlighted. We also propose potential strategies that can be further examined for developing more specific and effective inhibitors for TNBC prevention and therapy.


Assuntos
Antineoplásicos/uso terapêutico , Terapia de Alvo Molecular , Fator de Transcrição STAT3/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/metabolismo , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/genética , Neovascularização Patológica/imunologia , Oncogenes , Neoplasias de Mama Triplo Negativas/etiologia , Evasão Tumoral/genética , Evasão Tumoral/imunologia
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