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1.
Cell Death Dis ; 12(11): 1037, 2021 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-34718338

RESUMO

Bone metastasis is one of the most serious complications in lung cancer patients. MicroRNAs (miRNAs) play important roles in tumour development, progression and metastasis. A previous study showed that miR-106a is highly expressed in the tissues of lung adenocarcinoma with bone metastasis, but its mechanism remains unclear. In this study, we showed that miR-106a expression is dramatically increased in lung cancer patients with bone metastasis (BM) by immunohistochemical analysis. MiR-106a promoted A549 and SPC-A1 cell proliferation, migration and invasion in vitro. The results of bioluminescence imaging (BLI), micro-CT and X-ray demonstrated that miR-106a promoted bone metastasis of lung adenocarcinoma in vivo. Mechanistic investigations revealed that miR-106a upregulation promoted metastasis by targeting tumour protein 53-induced nuclear protein 1 (TP53INP1)-mediated metastatic progression, including cell migration, autophagy-dependent death and epithelial-mesenchymal transition (EMT). Notably, autophagy partially attenuated the effects of miR-106a on promoting bone metastasis in lung adenocarcinoma. These findings demonstrated that restoring the expression of TP53INP1 by silencing miR-106a may be a novel therapeutic strategy for bone metastatic in lung adenocarcinoma.

3.
Sci Rep ; 11(1): 17728, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489489

RESUMO

This study aimed to construct a widely accepted prognostic nomogram in Chinese high-grade osteosarcoma (HOS) patients aged ≤ 30 years to provide insight into predicting 5-year overall survival (OS). Data from 503 consecutive HOS patients at our centre between 12/2012 and 05/2019 were retrospectively collected. Eighty-four clinical features and routine laboratory haematological and biochemical testing indicators of each patient at the time of diagnosis were collected. A prognostic nomogram model for predicting OS was constructed based on the Cox proportional hazards model. The performance was assessed by the concordance index (C-index), receiver operating characteristic curve and calibration curve. The utility was evaluated by decision curve analysis. The 5-year OS was 52.1% and 2.6% for the nonmetastatic and metastatic patients, respectively. The nomogram included nine important variables based on a multivariate analysis: tumour stage, surgical type, metastasis, preoperative neoadjuvant chemotherapy cycle, postoperative metastasis time, mean corpuscular volume, tumour-specific growth factor, gamma-glutamyl transferase and creatinine. The calibration curve showed that the nomogram was able to predict 5-year OS accurately. The C-index of the nomogram for OS prediction was 0.795 (range, 0.703-0.887). Moreover, the decision curve analysis curve also demonstrated the clinical benefit of this model. The nomogram provides an individualized risk estimate of the 5-year OS in patients with HOS aged ≤ 30 years in a Chinese population-based cohort.


Assuntos
Neoplasias Ósseas/mortalidade , Nomogramas , Osteossarcoma/mortalidade , Adolescente , Adulto , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , China , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Osteossarcoma/patologia , Prognóstico , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida , Adulto Jovem
5.
Cell Death Discov ; 7(1): 210, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381023

RESUMO

Distant metastasis is the main cause of death for cancer patients. Recently, the newly discovered programmed cell death includes necroptosis, pyroptosis, and ferroptosis, which possesses an important role in the process of tumor metastasis. At the same time, it is widely reported that non-coding RNA precisely regulates programmed death and tumor metastasis. In the present review, we summarize the function and role of necroptosis, pyrolysis, and ferroptosis involving in cancer metastasis, as well as the regulatory factors, including non-coding RNAs, of necroptosis, pyroptosis, and ferroptosis in the process of tumor metastasis.

6.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3410-3421, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396762

RESUMO

This study aims to investigate metabolic activities of psoralidin in human liver microsomes( HLM) and intestinal microsomes( HIM),and to identify cytochrome P450 enzymes( CYPs) and UDP-glucuronosyl transferases( UGTs) involved in psoralidin metabolism as well as species differences in the in vitro metabolism of psoralen. First,after incubation serial of psoralidin solutions with nicotinamide adenine dinucleotide phosphate( NADPH) or uridine 5'-diphosphate-glucuronic acid( UDPGA)-supplemented HLM or HIM,two oxidic products( M1 and M2) and two conjugated glucuronides( G1 and G2) were produced in HLM-mediated incubation system,while only M1 and G1 were detected in HIM-supplemented system. The CLintfor M1 in HLM and HIM were 104. 3,and57. 6 µL·min~(-1)·mg~(-1),respectively,while those for G1 were 543. 3,and 75. 9 µL·min~(-1)·mg~(-1),respectively. Furthermore,reaction phenotyping was performed to identify the main contributors to psoralidin metabolism after incubation of psoralidin with NADPH-supplemented twelve CYP isozymes( or UDPGA-supplemented twelve UGT enzymes),respectively. The results showed that CYP1 A1( 39. 5 µL·min~(-1)·mg~(-1)),CYP2 C8( 88. 0 µL·min~(-1)·mg~(-1)),CYP2 C19( 166. 7 µL·min~(-1)·mg~(-1)),and CYP2 D6( 9. 1 µL·min~(-1)·mg~(-1)) were identified as the main CYP isoforms for M1,whereas CYP2 C19( 42. 0 µL·min~(-1)·mg~(-1)) participated more in producing M2. In addition,UGT1 A1( 1 184. 4 µL·min~(-1)·mg~(-1)),UGT1 A7( 922. 8 µL·min~(-1)·mg~(-1)),UGT1 A8( 133. 0 µL·min~(-1)·mg~(-1)),UGT1 A9( 348. 6 µL·min~(-1)·mg~(-1)) and UGT2 B7( 118. 7 µL·min~(-1)·mg~(-1)) played important roles in the generation of G1,while UGT1 A9( 111. 3 µL·min~(-1)·mg~(-1)) was regarded as the key UGT isozyme for G2. Moreover,different concentrations of psoralidin were incubated with monkey liver microsomes( MkLM),rat liver microsomes( RLM),mice liver microsomes( MLM),dog liver microsomes( DLM) and mini-pig liver microsomes( MpLM),respectively. The obtained CLintwere used to evaluate the species differences.Phase Ⅰ metabolism and glucuronidation of psoralidinby liver microsomes showed significant species differences. In general,psoralidin underwent efficient hepatic and intestinal metabolisms. CYP1 A1,CYP2 C8,CYP2 C19,CYP2 D6 and UGT1 A1,UGT1 A7,UGT1 A8,UGT1 A9,UGT2 B7 were identified as the main contributors responsible for phase Ⅰ metabolism and glucuronidation,respectively. Rat and mini-pig were considered as the appropriate model animals to investigate phase Ⅰ metabolism and glucuronidation,respectively.


Assuntos
Glucuronosiltransferase , Microssomos Hepáticos , Animais , Benzofuranos , Cumarínicos , Cães , Glucuronídeos , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Cinética , Camundongos , Microssomos Hepáticos/metabolismo , Fenótipo , Ratos , Especificidade da Espécie , Suínos , Porco Miniatura/metabolismo
7.
Front Immunol ; 12: 679839, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276668

RESUMO

Background: It is highly desirable to develop new strategies based on secretomics to more accurately selection of embryos with the highest developmental potential for transfer. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been reported to promote embryo development and pregnancy establishment. However, the predictive value of GM-CSF in single blastocyst selection remains unclear. This study is to determine the concentration of GM-CSF in human single-blastocyst conditioned medium (SBCM) and to evaluate its association with embryo quality and pregnancy outcome. Methods: The patients with ≤38 years of age receiving the first cycle of assisted reproductive therapy were included in this study. The patients who had <4 top-quality embryos formed by the fertilized two pronuclear zygotes on day 3 were excluded. A total of 126 SBCM samples (SBCMs) were included, of which blastocysts from 77 SBCMs were later transferred in subsequent frozen-thawed embryo transfer. The concentrations of GM-CSF were detected by single-molecule array (SIMOA) and analyzed for their possible association with embryo quality and pregnancy outcomes. The top-quality embryo (TQ), positive HCG (HP), clinical pregnancy (CP), and ongoing pregnancy (OP) rates were determined and compared between groups divided based on GM-CSF concentrations. Results: The detection rate of GM-CSF was found to be 50% in all SBCMs. There were significant differences in TQ rate, HP rate, CP rate and OP rate among high concentration group, medium concentration group and low concentration group. Both GM-CSF alone or GM-CSF combined with the morphological score (MS) had a greater AUC of ROC curve than that of MS alone to predict the pregnancy outcome, and GM-CSF combined with MS had the highest AUC. Conclusions: The concentration of GM-CSF in SBCM was detected at fg/ml levels, which was associated with embryo quality and pregnancy outcome. Collectively, GM-CSF may be used as a biomarker for prediction of pregnancy outcome and selection of embryos with high developmental potential for transfer in assisted reproductive technology (ART).


Assuntos
Biomarcadores , Blastocisto/metabolismo , Meios de Cultivo Condicionados/metabolismo , Implantação do Embrião , Fator Estimulador de Colônias de Granulócitos e Macrófagos/biossíntese , Embrião de Mamíferos , Feminino , Humanos , Gravidez , Resultado da Gravidez , Curva ROC , Técnicas de Reprodução Assistida
8.
Microb Biotechnol ; 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34165875

RESUMO

Trichophyton rubrum is responsible for the majority of dermatophytosis. Current systemic and topical antifungals against dermatophytosis are often tedious and sometimes unsatisfactory. Antimicrobial photodynamic therapy (aPDT) is a non-invasive alternative suitable for the treatment of superficial fungal infections. This work investigated the photodynamic inactivation efficacy and effects of aloe-emodin (AE), a natural photosensitizer (PS) against T. rubrum microconidia in vitro, and evaluated the treatment effects of AE-mediated aPDT for T. rubrum-caused tinea corporis in vivo and tinea unguium ex vivo. The photodynamic antimicrobial efficacy of AE on T. rubrum microconidia was evaluated by MTT assay. The inhibition effect of AE-mediated aPDT on growth of T. rubrum was studied. Intracellular location of AE, damage induced by AE-mediated aPDT on cellular structure and surface of microconidia and generation of intracellular ROS were investigated by microscopy and flow cytometry. The therapeutic effects of AE-mediated aPDT against dermatophytosis were assessed in T. rubrum-caused tinea corporis guinea pig model and tinea unguium ex vivo model. AE-mediated aPDT effectively inactivated T. rubrum microconidia in a light energy dose-dependent manner and exhibited strong inhibitory effect on growth of T. rubrum. Microscope images indicated that AE is mainly targeted to the organelles and caused damage to the cytoplasm of microconidia after irradiation through generation of abundant intracellular ROS. AE-mediated aPDT demonstrated effective therapeutic effects for T. rubrum-caused tinea corporis on guinea pig model and tinea unguium in ex vivo model. The results obtained suggest that AE is a potential PS for the photodynamic treatment of dermatophytosis caused by T. rubrum, but its permeability in skin and nails needs to be improved.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34058528

RESUMO

Xian-Ling-Gu-Bao capsule (XLGB) has been proven to prevent and treat osteoporosis. However, as a long-term oral formula, XLGB's effects on the metabolic capacity, structure and function of gut microbiota have yet to be elucidated in ovariectomized (OVX) rats. Our objectives were to evaluate the capacity of gut microbiota for metabolizing XLGB ingredients and to assess the effect of this prescription on gut microbiota. Herein, an integrated analysis that combined ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and ultrahigh-performance liquid chromatography tandem triple quadrupole mass spectrometry (UPLC-TQD-MS) was conducted to determine the metabolic capacity of gut microbiota. The effects of XLGB on gut microbiota were explored by metagenomic sequencing in OVX rats. Fecal samples from each group were collected after intragastric administration for three months. In total, 64 biotransformation products were fully characterized with rat gut microbiota from the OVX group and the XLGB group. The deglycosylation reaction was the main biotransformation pathway in core structures in the group that was incubated with XLGB. Compared with the OVX group, different biotransformation products and pathways of the XLGB group after incubation for 2 h and 8 h were described. After three months of feeding with XLGB, the domesticated gut microbiota was conducive to the production of active absorbed components via deglycosylation, such as icaritin, psoralen and isopsoralen. Comparisons of the gut microbiota of the OVX and XLGB groups showed differences in the relative abundances of the two dominant bacterial divisions, namely, Firmicutes and Bacteroidetes. The proportion of Firmicutes was significantly lower and that of Bacteroidetes was significantly higher in the XLGB group. This result demonstrated that XLGB could provide a basis for the treatment of osteoporosis by regulating lipid and bile acid metabolism. In addition, the increase in Lactobacillus, Bacteroides and Prevotella could be an important factor that led to easier production of active absorbed aglycones in the XLGB group. Our observation provided further evidence of the importance of gut microbiota in the metabolism and potential activity of XLGB.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Ovariectomia , Animais , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
10.
Artigo em Inglês | MEDLINE | ID: mdl-33992976

RESUMO

Huo-Tan-Chu-Shi Decoction (HTCSD), a traditional Chinese medicine (TCM) prescription within Guangdong Provincial TCM Hospital (the largest TCM hospital in China), is used for effective clinical treatment of coronary heart disease (CHD) caused by phlegm-dampness syndrome with high incidence in the hot and humid climate of Lingnan region. However, its chemical components responsible for the therapeutic effects remain unclear, which restricts its application and further development. Hence, a detailed workflow, combing with UHPLC-Q/TOF-MS, network pharmacology analysis and experimental verification, was proposed and applied to characterize the chemical profile and potential mechanism of HTCSD against CHD. As a result, a total of 130 components from all six composed herbal medicines were characterized in a rapid and sensitive manner through UHPLC-Q/TOF-MS, of which 33 compounds were unambiguously confirmed with reference standards. Consequently, based on the integrated pharmacology network of "herbs-chemicals-targets-pathways-therapeutic effects", four chemicals (magnoflorine, menisperine, 13-hydroxyberberine, luteolin) with four CHD related targets (SRC, MAPK1, EGFR and AKT1) were considered as the key components and targets of HTCSD in the treatment of CHD. Furthermore, the effect of HTCSD was confirmed in animal experiments by enhancing the phosphorylation of MAPK, and the published literature and molecular binding results suggested that magnoflorine and luteolin tended to be the critical compounds involved in the process. Taken together, the characterization of chemical profile combined with network pharmacology analysis and experimental verification not only provided an efficient insight into the overall chemical profile of HTCSD but also revealed the potential pharmacological components and mechanisms of HTCSD against CHD, which laid a necessary chemical and biological basis for the discovery of in vivo bioactive components and the further revelation of functionary mechanism.


Assuntos
Doença das Coronárias/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Compostos Heterocíclicos , Compostos Orgânicos , Animais , Cromatografia Líquida de Alta Pressão , Compostos Heterocíclicos/análise , Compostos Heterocíclicos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Compostos Orgânicos/análise , Compostos Orgânicos/farmacologia , Espectrometria de Massas em Tandem
11.
Phytomedicine ; 85: 153535, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33819766

RESUMO

BACKGROUND: Quality control exerted great importance on the clinical application of drugs for ensuring effectiveness and safety. Due to chemical complexity, diversity among different producing areas and harvest seasons, as well as unintentionally mixed with non-medicinal parts, the current quality standards of traditional Chinese medicine (TCM) still faced challenges in evaluating the overall chemical consistency. PURPOSE: We aimed to develop a new strategy to discover potential quality marker (Q-marker) of TCM by integrating plant metabolomics and network pharmacology, using Periplocae Cortex (GP, the dried root bark of Periploca sepium Bge.) as an example. METHODS: First, plant metabolomics analysis was performed by UPLC/Q-TOF MS in 89 batches of samples to discover chemical markers to distinguish medicinal parts (GP) and non-medicinal parts (the dried stem bark of Periploca sepium Bge. (JP)), harvest seasons and producing region of Periplocae Cortex. Second, network pharmacology was applied to explore the initial linkages among chemical constituents, targets and diseases. Last, potential Q-marker were selected by integrating analysis of plant metabolomics and network pharmacology, and the quantification method of Q-marker was developed by using UPLC-TQ-MS. RESULTS: The chemical profiling of GP and JP was investigated. Fifteen distinguishing features were designated as core chemical markers to distinguish GP and JP. Besides, the content of 4-methoxybenzaldehyde-2-O-ß-d-xylopyranosyl-(1→6)-ß-d-glucopyranoside could be used to identify Periplocae Cortex harvested in spring-autumn or summer. Meanwhile, a total of 15 components targeted rheumatoid arthritis were screened out based on network pharmacology. Taking absorbed constituents into consideration, 23 constituents were selected as potential Q-marker. A simultaneous quantification method (together with 11 semi-quantitative analysis) was developed and applied to the analysis of 20 batches of commercial Periplocae Cortex on the market. The PLS-DA model was successfully developed to distinguish GP and JP samples. In addition, the artificially mixed GP sample, which contained no less than 10% of the adulterant (JP), could also be correctly identified. CONCLUSION: Our results indicated that 9 ingredients could be considered as Q-marker of Periplocae Cortex. This study has also demonstrated that the plant metabolomics and network pharmacology could be used as an effective approach for discovering Q-marker of TCM to fulfill the evaluation of overall chemical consistency among samples from different producing areas, harvest seasons, and even those commercial crude drugs, which might be mixed with a small amount of non-medicinal parts.


Assuntos
Medicamentos de Ervas Chinesas/química , Metabolômica , Periploca/química , Controle de Qualidade , Animais , Biomarcadores , China , Cromatografia Líquida de Alta Pressão , Contaminação de Medicamentos , Espectrometria de Massas , Medicina Tradicional Chinesa/normas , Camundongos , Raízes de Plantas/química , Células RAW 264.7
12.
J Pharm Sci ; 110(5): 2285-2294, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33610566

RESUMO

Isobavachalcone, a naturally occurring chalcone in Psoralea corylifolia, posses many biological properties including anticancer, antiplatelet, and antifungal. However, its glucuronidation, glucuronides excretion, and drug-drug interaction (DDI) involving in human cytochrome P450 (CYP), UDP-glucuronosyltransferase (UGT) enzymes, and efflux transporters (BCRP and MRPs) remains unclear so far. After incubation, three glucuronides were produced by HLM and HIM with total intrinsic clearance (CLint) of 236.71 and 323.40 µL/min/mg, respectively. Reaction phenotyping proved UGT1A1, 1A3, 1A7, 1A8, and 1A9 played important roles in glucuronidation with total CLint values of 62.69-143.00 µL/min/mg. Activity correlation analysis indicated UGT1A1 and UGT1A3 participated more in the glucuronidation. In addition, the glucuronidation showed marked species differences, and rabbits and dogs were probably appropriate model animals to investigate the in vivo glucuronidation. Furthermore, BCRP, MRP1, and MRP4 transporters were identified as the most important contributors to glucuronides excretion in HeLa1A1 cells based on gene silencing method. Moreover, isobavachalcone demonstrated broad-spectrum inhibitory effects against CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, UGT1A1, UGT1A9, UGT2B7 with IC50 values of 1.08-9.78 µM. Except CYP2B6 and CYP2D6, the calculated [I]/Ki values for other enzymes were all greater than 0.1, indicating the inhibition of systemic metabolism or elimination for these enzyme substrates seems likely. Taken together, we summarized metabolic fates of isobavachalcone including glucuronidation and efflux transport as well as inhibitory effects involving in human CYP and UGT enzymes.


Assuntos
Chalconas , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Chalconas/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Cães , Glucuronídeos , Glucuronosiltransferase/metabolismo , Humanos , Cinética , Microssomos Hepáticos/metabolismo , Proteínas de Neoplasias/metabolismo , Coelhos
13.
J Pharm Biomed Anal ; 197: 113950, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33609948

RESUMO

Gualou-Xiebai-Banxia decoction (GXB) is one of the famous classical traditional Chinese Medicine (TCM) formula for the treatment of chest stuffiness and pains syndrome in Chinese medicine, i.e., coronary heart disease (CHD) in modern medicine. Being compared with Gualou-Xiebai Baijiu-decoction which only consists of Trichosanthis Pericarpium (TP), Allii Macrostemonis Bulbus (AMB) and wine, GXB is composed of another one additional herbal medicine, Pinellinae Rhizoma Praeparatum (PRP), and is more suitable to treat severe atherosclerosis and dyslipidemia. However, the comprehensive chemical composition of GXB is still unclear, which has seriously hindered the discovery of its effective components for improving the clinical symptoms of CHD. The present study aimed to investigate the overall chemical profile of GXB qualitatively and quantitatively by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS), and further explore the chemical contribution of PRP to this formula combined with chemometric approach. First, a total of 151 components, including steroidal saponins, flavonoids, triterpenoids, nitrogenous and other types components, were detected and characterized by UPLC-Q/TOF-MS in GXB. Then, flavonoids and nitrogenous could be qualitatively observed enrichment in GXB compared to those in GXB-dePRP (GXB deducted PRP in the formula). Furthermore, 19 characteristic components were selected for quantitative comparison between GXB and GXB-dePRP by UPLC-MS/MS combined with chemometric method. These findings indicated that steroidal saponins were the most abundant components in GXB, while the introduction of PRP could not only enrich the structural types of chemical compounds in this formula, but also increase the abundance of active components from other composed herbal medicines, TP and AMB. Taken together, this study developed and validated sensitive and practical methods for qualitative and quantitative analysis of GXB, and clarified the chemical contribution of PRP to this formula. These results laid a solid chemical foundation for further in vivo disposal investigation to screen out the potential effective components as well as therapeutic mechanism research of GXB.


Assuntos
Doença das Coronárias , Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Humanos , Medicina Tradicional Chinesa , Espectrometria de Massas em Tandem
14.
J Sep Sci ; 44(5): 1036-1061, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33403778

RESUMO

Wendan decoction, a classical traditional Chinese medicine formula consisting of six herbal medicines, has been widely used in clinical treatments for thousands of years due to the expectorant effects. However, the chemical basis of Wendan decoction remains unclear, which hinders the elucidation of the scientific connotation and mechanism of its effective components. In this study, an ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry method was first developed for characterization of its chemical profile, and a total of 142 chemical components including flavonoids, triterpenoids, alkaloids, coumarins, pungent phytochemicals, and other types were detected, among which 41 components were definitively identified with authentic standards. Furthermore, 14 major representative components were simultaneously quantified by high-performance liquid chromatography with ultraviolet detector, indicating that the content levels of flavonoids were the most abundant in Wendan decoction. In summary, this study established sensitive and practical methods to systematically characterize chemical profile for the first time and simultaneous quantify representative components of Wendan decoction. These findings above would provide a solid chemical basis for disclosure of potential effective components by further in vivo disposal study, and promote therapeutic mechanism researches of Wendan decoction.


Assuntos
Medicamentos de Ervas Chinesas/análise , Plantas Medicinais/química , Composição de Medicamentos , Medicina Tradicional Chinesa
15.
Phytomedicine ; 82: 153443, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33429210

RESUMO

BACKGROUND: Qiliqiangxin Capsule (QLQX), a traditional Chinese medicine (TCM) prescription, is especially used for clinical treatment of chronic heart failure (CHF) in China. However, the holistic quality control of QLQX has not been well established due to lack of system research on the quality marker (Q-marker). PURPOSE: In this study, a new strategy of multi-dimensional "radar chart" mode was proposed to overcome the problem that traditional methods cannot evaluate the multiple properties of Q-markers comprehensively and visually, and the strategy was successfully applied to discover the Q-markers of QLQX. METHODS: First, nineteen prototypes that entered the in vivo systemic circulation were selected out as the candidate Q-markers based on our previous studies of chemical and in vivo metabolic profiles. Then, their contents in QLQX were quantitatively analyzed by UHPLC-MS/MS, and the bioactivities on the H9c2 cardiomyocytes cell model was evaluated. The network of in vivo component-target closely related to CHF was further constructed. Finally, a multi-dimensional "radar chart" mode was developed and corresponding Regression Area (RA) and Coefficient Variation (CV) were calculated after data standardization and integration visually based on the Q-marker related multiple characteristics (including the compatibility contribution of herbal medicines, the content, the bioactivity, the in vivo predicted bioavailability and the degree of network pharmacology of candidate components in the TCM prescription). RESULTS: By comparison of RA and CV of the chemicals in the "radar chart", seven compounds mainly from King and Minister herbs (songorin, calycosin-7-O-ß-D-glucopyranoside, astragaloside, tanshinone IIA, ginsenoside Re, hesperidin and alisol A) were screened out as the Q-markers of QLQX, showing the reasonable compatibility contribution and high content in QLQX, preferable pharmacological effect on CHF, as well as good bioavailable characteristics and high target hits in system pharmacology. CONCLUSION: The Q-marker discovery of QLQX in this study laid an important foundation for its quality control improvement, and the mode standardized the abstract definitions of Q-marker and realized the comprehensive assessment of multiple properties of Q-marker in TCM prescriptions, which has a reference value for revealing the Q-marker in the quality control researches of TCM prescriptions.


Assuntos
Medicamentos de Ervas Chinesas/análise , Insuficiência Cardíaca/tratamento farmacológico , Medicina Tradicional Chinesa , Biomarcadores/análise , Doença Crônica , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Controle de Qualidade , Espectrometria de Massas em Tandem
16.
J Ethnopharmacol ; 268: 113660, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33276058

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shuang-Huang-Lian preparation has captured wide attention since its clinical applications for the successful treatment of upper respiratory tract infection. However, its functional basis under actual therapeutic dose in vivo was still unrevealed. AIM OF THE STUDY: This study aimed to reveal the anti-flu substances and mechanism of Shuang-Huang-Lian water extract (SHL) on H1N1 infected mouse model by a strategy based on serum pharmaco-chemistry under actual therapeutic dose and network pharmacology. MATERIALS AND METHODS: H1N1 infected mouse model was employed for evaluation of the anti-flu effects of SHL. A simultaneous quantification method was developed by UPLC-TQ-XS MS coupled switch-ions mode and applied to characterize the pharmacokinetics of the multiple components of SHL under actual therapeutic dose. The potential active ingredients were screened out based on their pharmacokinetic parameters. And then, a compound mixture of these active candidates was re-evaluated for the anti-flu activity on H1N1 infected mouse model. Furthermore, the anti-flu mechanism of SHL was also predicted by network pharmacology coupled with the experimental result. RESULTS: SHL significantly increased the survival rate and prolonged survival days on H1N1 infected mice at a dosage of 20 g crude drug/kg/day by reversing the increased lung index, down-regulating the inflammatory cytokines (TNF-α, IL-1ß, IL-6) and inhibiting the release of IFN-ß in bronchoalveolar lavage fluids (BALF). Concomitantly, the pharmacokinetic parameters of fourteen quantified and twenty-one semi-quantified constituents of SHL were characterized. And then, five compounds (baicalin, sweroside, chlorogenic acid, forsythoside A and phillyrin), which displayed satisfactory pharmacokinetic features, were considered as potential active ingredients. Thus, a mixture of these five ingredients was administered to H1N1-infected mice at a dose of 4.24 mg/kg/day. As a result, the therapeutical effects of the mixture were similar to SHL in terms of survival rate, lung index and the release of cytokines (TNF-α, IL-1ß and IL-6) in BALF. Moreover, network pharmacology analysis indicated that the TNF-signal pathways might play a role in the anti-flu mechanism of SHL. CONCLUSIONS: A mixture of five compounds (baicalin, sweroside, chlorogenic acid, forsythoside A and phillyrin) were the anti-flu substances of SHL. The strategy based on serum pharmaco-chemistry under actual therapeutic dose provided a new sight on exploring in vivo effective substances of TCM.


Assuntos
Descoberta de Drogas/métodos , Medicamentos de Ervas Chinesas/uso terapêutico , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Infecções por Orthomyxoviridae/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Mapas de Interação de Proteínas/efeitos dos fármacos , Animais , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Vírus da Influenza A Subtipo H1N1/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Mapas de Interação de Proteínas/fisiologia , Água/farmacologia
17.
J Ethnopharmacol ; 267: 113615, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33242624

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The dried rhizome of Cimicifuga heracleifolia Kom. (C. heracleifolia) is a popular traditional Chinese medicine, which has been extensively used in Asian countries for its anti-inflammatory, antipyretic and analgesic activities. However, further utilization and application of C. heracleifolia have been hampered due to a lack of full understanding of its active ingredients. AIM OF STUDY: The present study aims for clarification of the systematical chemical profile of C. heracleifolia and the immunomodulatory effect of its main bioavailable component. MATERIALS AND METHODS: Comprehensive chemical profile of C. heracleifolia was systematically analyzed by ultra-performance liquid chromatography hyphenated with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS). Xenobiotics after oral administration of C. heracleifolia extracts were investigated to hunt for bioavailable components. The immunomodulatory activity evaluation of cimigenoside was achieved on poly(I:C)-induced airway inflammation mouse and BEAS-2B cell models from aspects of neutrophil infiltration, lung inflammation by using microscope analysis, quantification of production and expression of inflammatory cytokine and chemokines by using ELISA and quantitative PCR. RESULTS: By UPLC-Q-TOF/MS analysis, 110 compounds (including 81 triterpenoids, 21 cinnamic acid derivatives, and 8 other structure types) were identified or tentatively characterized in ethanolic extract of C. heracleifolia. Based on the data of chemical profile, xenobiotics of C. heracleifolia were subsequently analyzed, and triterpene glycosides were detected as the major bioavailable ingredients. Oral administration of cimigenoside, a representative triterpene glycoside, could prevent neutrophils infiltration in the lung due to suppression of the production of CXCL2 and CXCL10, and the expression of P-selectin, VCAM1 in poly(I:C)-induced airway inflammation model mice. Moreover, cimigenoside also inhibited the productions of inflammatory cytokines and chemokines from human airway epithelial cell line (BEAS-2B cells) induced by poly(I:C). CONCLUSION: Triterpene glycosides were the main components of C. heracleifolia extract, and cimigenoside was considered as the effective component with immunomodulatory effect on the pulmonary immune system by oral administration.


Assuntos
Anti-Inflamatórios/farmacologia , Cimicifuga , Fatores Imunológicos/farmacologia , Pulmão/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pneumonia/prevenção & controle , Animais , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , Cimicifuga/química , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Fatores Imunológicos/isolamento & purificação , Mediadores da Inflamação/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Infiltração de Neutrófilos/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Pneumonia/induzido quimicamente , Pneumonia/imunologia , Pneumonia/metabolismo , Poli I-C , Ratos Sprague-Dawley , Transdução de Sinais
18.
J Safety Res ; 75: 262-274, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33334485

RESUMO

INTRODUCTION: Connected automated vehicles (CAVs) technology has deeply integrated advanced technologies in various fields, providing an effective way to improve traffic safety. However, it would take time for vehicles on the road to vehicles from human-driven vehicles (HDVs) progress to CAVs. Moreover, the Cooperative Adaptive Cruise Control (CACC) vehicle would degrade into the Adaptive Cruise Control (ACC) vehicle due to communication failure. METHOD: First, the different car-following models are used to capture characteristics of different types of vehicles (e.g., HDVs, CACC, and ACC). Second, the stability of mixed traffic flow is analyzed under different penetration rates of CAVs. Then, multiple safety measures, such as standard deviation of vehicle speed (SD), time exposed rear-end crash risk (TER), time exposed time-to-collision (TET), and time-integrated time-to-collision (TIT) are used to evaluate the safety of mixed traffic flow on expressways. Finally, the sensitivity of traffic demand, the threshold of time-to-collision (TTC), and the parameters of car-following models are analyzed based on a numerical simulation. RESULTS: The results show that the ACC vehicle has no significant impact on the SD of mixed traffic flows, but it leads to the deterioration of TET and TIT, making the reduction proportion of TER slower. When the penetration rate exceeds 50%, the increase of CACC vehicles reduces traffic safety risks significantly. Furthermore, the increase in traffic demand and car-following parameters worsens traffic safety on expressways. CONCLUSIONS: This paper suggests that the CACC vehicles degenerate into ACC vehicles due to communication failure, and the safety risk of mixed traffic flow increases significantly. Practical Applications: The application of CAVs can improve the stability and safety of traffic flow.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Condução de Veículo/estatística & dados numéricos , Segurança/estatística & dados numéricos , China , Simulação por Computador
19.
Reprod Biomed Online ; 41(5): 807-817, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32843308

RESUMO

RESEARCH QUESTION: Is it possible to establish a visualized clinical model predicting good quality blastocyst (GQB) formation for patients in their first IVF/intracytoplasmic sperm injection (ICSI) cycle? DESIGN: A total of 4783 patients in their first IVF/ICSI cycle between January 2015 and December 2019 were retrospectively included and randomly divided into the training set (n = 3826) and the testing set (n = 957) in an 8:2 ratio. The least absolute shrinkage and selection operator (LASSO) regression was adopted to select the most critical predictors for GQB formation to construct a visualized nomogram model based on the data of patients in the training set. Receiver operating characteristic and calibration curves were used to evaluate the predictive accuracy and discriminative ability. The performance of the model was also validated on independent data from patients treated in the testing set. RESULTS: Maternal age, maternal serum anti-Müllerian hormone (MsAMH) concentration and the number of oocytes retrieved were highlighted as critical predictors of GQB development and were incorporated into the nomogram model. Based on the area under the curve (AUC) values, the predictive ability for ≥1, ≥3 and ≥5 GQB were 0.831, 0.734 and 0.748, respectively. The calibration curve also showed high concordance between the observed and predicted results. The AUC for predicting ≥1, ≥3 and ≥5 GQB in the testing set were 0.805, 0.695 and 0.707, respectively, which were similar to those for the training set. CONCLUSIONS: The visualized nomogram model provides great predictive value for GQB development in patients in their first IVF/ICSI cycle and can be used to improve clinical counselling.


Assuntos
Desenvolvimento Embrionário/fisiologia , Fertilização In Vitro , Modelos Teóricos , Injeções de Esperma Intracitoplásmicas , Adulto , Feminino , Humanos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
20.
BMC Pregnancy Childbirth ; 20(1): 460, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787803

RESUMO

BACKGROUND: Early rescue intracytoplasmic sperm injection (ICSI) has been used in clinic as appropriate currently. While the outcomes of children born after this method were not well assessed. The purpose of this study was to evaluate the effect of early rescue ICSI on women with primary infertility. METHODS: Fresh embryo transfer cycles after rescue (n = 214) and conventional (n = 546) ICSI were retrospectively evaluated from women with primary infertility who underwent their first assisted reproductive technology cycles at our center in 2012-2017. The conventional ICSI group was subdivided into ICSI-1 (semen suitable for in vitro fertilization, IVF) and ICSI-2 (poor semen quality) to minimize bias from differences in semen quality. Pregnancy, delivery and neonatal outcomes were compared between groups. RESULTS: There was a higher rate of polyspermy and a lower rate of top-quality embryos (TQE) on day 3 for oocytes subject to rescue ICSI compared with conventional ICSI. This reduced the total number of TQE and the number of TQE transferred in the rescue ICSI group. There was no significant difference between groups in clinical pregnancy, ongoing pregnancy, early miscarriage and live birth. For pregnant women, gestational age, route of delivery, risk of preterm birth and gestational diabetes mellitus were also comparable. Neonatal outcomes including sex ratio, birth weight, neonatal intensive care unit admission and birth defects were also similar after rescue and conventional ICSI. Moreover, no differences were observed with the different ICSI subgroups. CONCLUSIONS: For women with primary infertility who have a high risk of IVF fertilization failure (FF), rescue ICSI provides a safe and efficient alternative to minimize FF after initial IVF, but results in fewer TQE on day 3.


Assuntos
Infertilidade Feminina , Injeções de Esperma Intracitoplásmicas , Adulto , Transferência Embrionária , Feminino , Humanos , Gravidez , Resultado da Gravidez , Estudos Retrospectivos
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