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1.
Mater Today Bio ; 12: 100157, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34825161

RESUMO

Drug-induced liver injury (DILI) is a challenging clinical problem with respect to both diagnosis and management. As a newly emerging biomarker of liver injury, miR122 shows great potential in early and sensitive in situ detection of DILI. Glycyrrhetinic acid (GA) possesses desirable therapeutic effect on DILI, but its certain dose-dependent side effects after long-term and/or high-dose administration limit its clinical application. In this study, in order to improve the precise diagnosis and effective treatment of DILI, GA loaded all-in-one theranostic nanoplatform was designed by assembling of upconversion nanoparticles and gold nanocages. As a proof of concept, we demonstrated the applicability of this single-wavelength laser-triggered theranostic nanoplatform for the spatiotemporally controllable in situ imaging of DILI and miR122-controlled on-demand drug release in vitro and in vivo. This novel nanoplatform opens a promising avenue for the clinical diagnosis and treatment of DILI.

2.
Phytomedicine ; 93: 153518, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34735910

RESUMO

BACKGROUND: The hepatotoxicity of Chinese herbal medicine (CHM) is an important reason for its restrictive application. Psoraleae Fructus (PF), a commonly used CHM for treatment of osteoporosis and vitiligo etc., has caused serious concern due to the frequent occurrence of liver injury incidents. To date, its hepatotoxic equivalent markers (HEMs) and potential mechanisms are still unclear. PURPOSE: To discover and validate the HEMs of PF and further explore the potential mechanisms of hepatotoxicity. METHODS: Multi-parametric cellular imaging was performed by high content screening, and multi-component quantitative profiling was conducted by ultra-high performance liquid chromatography coupled with triple-quadrupole mass spectrometry. The correlations between hepatotoxic features and component contents were modeled by chemometrics including partial least square regression, back propagation-artificial neural network, and hierarchical cluster analysis. Then the candidate HEMs of PF were screened out and subjected to hepatotoxic equivalence assessment in primary hepatocytes, zebrafish, and mice, and the hepatotoxic mechanisms of PF were investigated. RESULTS: The chemical combination of psoralen and isopsoralen was discovered as the HEMs of PF through pre-screening and verifying process. PF was demonstrated to induce oxidative stress, mitochondrial dysfunction and cellular apoptosis. CONCLUSIONS: This study not only provides a rational strategy for screening HEMs from CHMs like PF, but also contributes to understanding the underlying mechanisms of PF hepatotoxicity.


Assuntos
Medicamentos de Ervas Chinesas , Animais , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/toxicidade , Frutas , Fígado , Camundongos , Peixe-Zebra
3.
Artigo em Inglês | MEDLINE | ID: mdl-34503922

RESUMO

BACKGROUND: To explore the development of central nervous system (CNS) symptoms and clinical application in predicting the clinical outcomes of SARS-COV-2 patients. METHODS: A retrospective cohort study was performed on the hospitalized patients with SARS-COV-2 recruited from four hospitals in Hubei Province, China from 18 January to 10 March 2020. The patients with CNS symptoms were determined. Data regarding clinical symptoms and laboratory tests were collected from medical records. RESULTS: Of 1268 patients studied, 162 (12.8%) had CNS symptoms, manifested as unconsciousness (71, 5.6%), coma (69, 5.4%), dysphoria (50, 3.9%), somnolence (34, 2.7%) and convulsion (3, 0.2%), which were observed at median of 14 (interquartile range 9-18) days after symptom onset and significantly associated with older age (OR = 5.71, 95% confidence interval [CI] 2.78-11.73), male (OR = 1.73, 95% CI 1.22-2.47) and preexisting hypertension (OR = 1.78, 95% CI 1.23-2.57). The presence of CNS symptoms could be predicted by abnormal laboratory tests across various clinical stages, including by lymphocyte counts of <0.93 × 109/L, LDH≥435 U/L and IL-6≥28.83 pg/L at 0-10 days post disease; by lymphocyte count<0.86 × 109/L, IL-2R ≥ 949 U/L, LDH≥382 U/L and WBC≥8.06 × 109/L at 11-20 days post disease. More patients with CNS symptoms developed fatal outcome compared with patients without CNS symptoms (HR = 33.96, 95% CI 20.87-55.16). CONCLUSION: Neurological symptoms of COVID-19 were related to increased odds of developing poor prognosis and even fatal infection.

4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(4): 662-670, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34323047

RESUMO

Objective: To analyze the prevalence of diabetes mellitus among middle-aged and older rural adults of Xinxiang county, Henan Province and its correlation with dietary patterns. Methods: The study was done based on the data collected from a cross-sectional survey of Xinxiang County, which was part of the Prospective Cohort Study on the Common Chronic Non-Communicable Diseases in Rural areas of Henan Province. Randomized cluster sampling was used to select adult respondents (≥18 years old) from among the residents of 17 villages in Xinxiang county. The respondents completed questionnaires, and underwent physical examinations and laboratory tests between April, 2017 and June, 2017. A total of 7604 individuals aged between 45 and 79 were included in our study. Dietary patterns were established through factor analysis and the dietary pattern factor scores were divided into quartiles (Q1-Q4). The relationship between dietary patterns and diabetes mellitus was analyzed with multivariate logistic regression model. Results: Out of the total of 7604 middle-aged and older rural adults in Xinxiang County, Henan Province, 1604 had diabetes mellitus, suggesting a 21.1% prevalence of diabetes mellitus. Factor analysis was used to establish four dietary patterns, namely animal-based diet, vegetable-egg diet, mixed diet and traditional diet. Subjects of these four dietary patterns displayed different demographic characteristics. There were no statistical difference in anthropometricor clinical indicators between the quartile with the lowest dietary pattern factor score (Q1) and the quartile with the highest dietary pattern factor score (Q4) for subjects with animal-based diet ( P>0.05). Compared with those in the Q1 quartile of vegetable-egg diet, subjects in the Q4 quartile of vegetable-egg diet showed lower levels of high-density lipoprotein cholesterol (HDL-C), along with different distribution of fasting blood glucose (FBG), showing statistically significant difference ( P<0.05). In comparison to subjects in Q1 quartile of mixed diet, those in Q4 quartile showed lower levels of systolic blood pressure (SBP), the difference being statistically significant ( P<0.05). In the traditional diet group, subjects in the Q4 quartile had lower waist circumference (WC), but higher levels of HDL-C than those of subjects in Q1 quartile. In addition, the distribution of glycated-hemoglobin (HbA1c) and FBG were different, the difference being statistically significant ( P<0.05). The results of multivariate logistic regression analysis demonstrated that traditional diet could be a protective factor of diabetes mellitus (odds ratio [ OR]=0.810, 95% CI: 0.690-0.952, P trend<0.05) after adjusting for multiple confounding factors. Conclusion: The prevalence of diabetes in middle-aged and older rural residents is relatively high in Xinxiang County, Henan Province, and there may be a protective relationship between traditional diet and diabetes mellitus.


Assuntos
Diabetes Mellitus , População Rural , Adolescente , Adulto , Idoso , Animais , China/epidemiologia , Estudos Transversais , Diabetes Mellitus/epidemiologia , Dieta , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
5.
World Allergy Organ J ; 14(6): 100552, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34178240

RESUMO

Background: A higher compliance with clinical guidelines helps improve treatment outcomes. But the clinical practice of otolaryngologists is not always consistent with guidelines. Objective: To describe otolaryngologists' compliance with guidelines about allergic rhinitis (AR) management and identify factors responsible for the discordance between clinical practice and guideline recommendations in China. Methods: A cross-sectional nationwide survey was designed and conducted via an online platform. Recruitment was done by emailing otolaryngologists registered in the Chinese Society of Otorhinolaryngology-Head and Neck Surgery or by inviting otolaryngologists to scan a Quick Respond (QR) code that linked to the questionnaire at various academic meetings. Results: A total of 2142 otolaryngologists were eligible and completed the survey. Of them, 64.7% had over 10 years work experience and 97.4% had a bachelor's degree or higher. About 18.3% of the participants strictly copied the guideline in clinical practice, while 73.7% used the guideline that had been adjusted according to their clinical experience. Otolaryngologists were most concerned about the efficacy, safety, and minimum age of AR medications, and least concerned about patient preferences. Regarding the use of intranasal steroids (INS), leukotriene receptor antagonists (LTRA), and H1-antihistamines, 86.8%, 55.7% and 51.2% of otolaryngologists complied with the guideline recommendations, respectively. Educational background was a factor affecting the compliance with guidelines and acceptance of INS. Conclusion: A vast majority of Chinese otolaryngologists complied with the current Chinese AR guidelines. A difference still existed between the otolaryngologists' real-world and guideline-recommended management. The otolaryngologists should pay more attention to patient preferences. A higher education could improve otolaryngologists' adherence to the guidelines.

6.
Phytomedicine ; 85: 153542, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33799225

RESUMO

BACKGROUND: Paridis Rhizoma (PR) is a famous traditional herbal medicine. Apart from two officially recorded species, viz. Paris polyphylla Smith var. yunnanensis (Franch.) Hand. - Mazz. (PPY) and P. polyphylla Smith var. chinensis (Franch.) Hara (PPC), there are still many other species used as folk medicine. It is necessary to understand the metabolic differences among Paris species. PURPOSE: To establish a strategy that can discover species-specific steroidal saponin markers to distinguish closely-related Paris herbs for quality and safety control. METHODS: A new strategy of molecular-networking-guided discovery of species-specific markers was proposed. Firstly, the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was applied to obtain the MS and MS/MS data of all samples. Then, molecular networking (MN) was created using MS/MS data to prescreen the steroidal saponins for subsequent analysis. Next, the principal component analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA) models were established to discover potential markers. Finally, the verification, identification and distribution of chemical markers were performed. RESULTS: A total of 126 steroidal saponins were screened out from five species using MN. Five species were classified successfully by OPLS-DA model, and 18 species-specific markers were discovered combining the variable importance in the projection (VIP) value, P value (one-way ANOVA) and their relative abundance. These markers could predict the species of Paris herbs correctly. CONCLUSION: These results revealed that this new strategy could be an efficient way for chemical discrimination of medicinal herbs with close genetic relationship.


Assuntos
Melanthiaceae/classificação , Plantas Medicinais/classificação , Saponinas/análise , Cromatografia Líquida de Alta Pressão , Análise Discriminante , Análise dos Mínimos Quadrados , Melanthiaceae/química , Plantas Medicinais/química , Rizoma/química , Saponinas/química , Especificidade da Espécie , Espectrometria de Massas em Tandem
7.
Curr Med Sci ; 41(2): 318-322, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33877548

RESUMO

Serology tests for viral antibodies provide an important tool to support nucleic acid testing for diagnosis of the novel coronavirus disease 2019 (COVID-19) and is useful for documenting previous exposures to SARS-CoV-2, the etiological agent of COVID-19. The sensitivities of the chemiluminescent SARS-CoV-2 IgG/IgM immunoassay were assessed by using serum samples collected from 728 patients testing positive for SARS-CoV-2 RNA. The specificity was evaluated on a panel of 60 serum samples from non-COVID-19 patients with high levels of rheumatoid factor, antinuclear antibody, or antibodies against Epstein-Barr virus (EBV), cytomegalovirus (CMV), mycoplasma pneumonia, human respiratory syncytial virus (RSV), adenovirus, influenza A or influenza B. The imprecision and interference were assessed by adopting the Clinical and Laboratory Standards Institute (CLSI) EP15-A2 and EP7-A2, respectively. Sensitivities between 1 and 65 days after onset of symptoms were 94.4% and 78.7%, for IgG and IgM test, respectively. The sensitivity increased with the time after symptom onset, and rose to the top on the 22nd to 28th days. The total imprecision (CVs) was less than 6.0% for IgG and less than 6.5% for IgM. Limited cross-reactions with antibodies against EBV, CMV, mycoplasma pneumonia, human RSV, adenovirus, influenza A or influenza B were found. These data suggested the chemiluminescent SARS-CoV-2 IgG and IgM, assay with reliable utility and sensitivity, could be used for rapid screening and retrospective surveillance of COVID-19.


Assuntos
Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19/métodos , COVID-19/sangue , SARS-CoV-2/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/patologia , COVID-19/virologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Medições Luminescentes/métodos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Estudos Retrospectivos , SARS-CoV-2/patogenicidade , Adulto Jovem
8.
J Colloid Interface Sci ; 597: 29-38, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33862445

RESUMO

Hydrogen (H2) molecules are easy to leak during production, storage, transportation and usage. Because of their flammability and explosive nature, quick and reliable dectection of H2 molecule is of great significance. Herein, an excellent H2 gas sensor has been realized based on Pd nanocrystal sensitized two-dimensional (2D) porous TiO2 (Pd/TiO2). The formation of 2D porous TiO2 with the removal of graphene oxide template has been monitored by an in-situ transmission electron microscope. It is found that the size of the GO template can be almost completely replicated by 2D TiO2. The Pd/TiO2 sensor exhibited an instantaneous response and a satisfactory low detection limit for H2 detection. These excellent gas-sensing performances (good selectivity, unique linearity response and high stability) can be attributed to the unique 2D porous structure and the synergistic effect between oxidized Pd and TiO2, including the unique adsorption properties of O2 or/and H2 on Pd/TiO2, the reaction between PdO and H2 gas, and the regulated depletion layer arising from p-type PdO to n-type TiO2. This work demonstrates a rational design and synthesis of highly efficient H2 sensitive materials for energy and manufacturing security.

9.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(1): 58-63, 2021 Feb 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33723938

RESUMO

OBJECTIVES: This study aimed to investigate the association between periodontal indexes and biomarkers in gingival crevicular fluid (GCF) and preterm birth (PTB) in pregnancy, as well as to assess the clinical value of these indexes as predictors of PTB. METHODS: A nested case-control study was conducted. A total of 300 systematically healthy pregnant women were selected within 36 weeks of gestation and grouped according to the enrolled weeks. Periodontal indexes, including probing depth (PD), bleeding index (BI), gingival index (GI), and five biomarkers in GCF, including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and 8-hydroxy-2-deoxyguanosine (8-OHdG) were measured at the enrolled date. The detailed birth outcome was recorded. RESULTS: Only women at 24-28 weeks of gestation per PTB case (four full-term births) were selected as controls subjects, PTB displayed significantly greater GI, BI, and 8-OHdG (P<0.05). Logistic regression analysis revealed that BI and 8-OHdG were the dependent risk factors of PTB (OR=5.90, P=0.034; OR=1.18, P=0.045, respectively). The areas under the receiver operating characteristic curve (ROC) of BI and 8-OHdG were 0.80 and 0.69, and that of the combined detection was 0.82, which was larger than the individual detection, although the differences were not significant (P>0.05). CONCLUSIONS: Increased BI and 8-OHdG at 24-28 weeks of gestation are risk factors for PTB. Their combined detection may have some value in the prediction of PTB, but further studies with a larger sample size are needed to explore it and thus provide experiment evidence for establishing an early warning system for PTB in pregnant women with periodontal disease.


Assuntos
Líquido do Sulco Gengival , Nascimento Prematuro , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Índice Periodontal , Gravidez
10.
Clin Infect Dis ; 72(4): 626-633, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33048116

RESUMO

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) experience a wide clinical spectrum, with over 2% developing fatal outcome. The prognostic factors for fatal outcome remain sparsely investigated. METHODS: A retrospective cohort study was performed in a cohort of patients with confirmed COVID-19 in one designated hospital in Wuhan, China, from 17 January-5 March 2020. The laboratory parameters and a panel of cytokines were consecutively evaluated until patients' discharge or death. The laboratory features that could be used to predict fatal outcome were identified. RESULTS: Consecutively collected data on 55 laboratory parameters and cytokines from 642 patients with COVID-19 were profiled along the entire disease course, based on which 3 clinical stages (acute stage, days 1-9; critical stage, days 10-15; and convalescence stage, day 15 to observation end) were determined. Laboratory findings based on 75 deceased and 357 discharged patients revealed that, at the acute stage, fatality could be predicted by older age and abnormal lactate dehydrogenase (LDH), urea, lymphocyte count, and procalcitonin (PCT) level. At the critical stage, the fatal outcome could be predicted by age and abnormal PCT, LDH, cholinesterase, lymphocyte count, and monocyte percentage. Interleukin 6 (IL-6) was remarkably elevated, with fatal cases having a more robust production than discharged cases across the whole observation period. LDH, PCT, lymphocytes, and IL-6 were considered highly important prognostic factors for COVID-19-related death. CONCLUSIONS: The identification of predictors that were routinely tested might allow early identification of patients at high risk of death for early aggressive intervention.


Assuntos
COVID-19 , SARS-CoV-2 , Idoso , COVID-19/mortalidade , China/epidemiologia , Humanos , Laboratórios , Prognóstico , Estudos Retrospectivos
11.
Phytochem Anal ; 32(2): 153-164, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31916640

RESUMO

INTRODUCTION: Dispensing granule, an innovative product of traditional Chinese medicine decoction, is widely practiced in clinic. As a prerequisite to support the clinical medication, quality consistency between dispensing granule and traditional decoction need to be evaluated. Furthermore, a generally applicable strategy for consistency evaluation of dispensing granule is needed. OBJECTIVE: In this study, we aimed to propose an integrated quality-based strategy to assess consistency between dispensing granule and traditional decoction taking Coptidis Rhizoma (CR) as a case study. METHODOLOGY: For chemical consistency evaluation, efficacy-related Coptis alkaloids were quantified with high-performance liquid chromatography (HPLC). The "Mean ± 3SD" of analyte contents in traditional decoction was considered as the criterion of consistency. And, as auxiliary analysis, principal component analysis (PCA) was employed for data visualisation. For biological consistency evaluation, two one-side t-tests and 90% confidence intervals of the geometric mean ratio of antibacterial zone diameter and 50% inhibitory concentration (IC50 ) of α-glucosidase inhibition were calculated. The scope of 80.00% to 125.00% was taken as in vitro bioequivalence interval. It was considered internally consistent with traditional decoction when the chemical and biological indices of dispensing granule fulfilled the preset criteria simultaneously. RESULTS: Eight out of 20 batches of CR dispensing granule were demonstrated consistent with traditional decoction in chemistry and biological activities. CONCLUSIONS: A generally applicable strategy was recommended that integrates chemical and biological characteristics for consistency evaluation of dispensing granule.


Assuntos
Coptis , Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Medicina Tradicional Chinesa , Rizoma
13.
Autophagy ; 17(7): 1592-1613, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32432943

RESUMO

SCAP (SREBF chaperone) regulates SREBFs (sterol regulatory element binding transcription factors) processing and stability, and, thus, becomes an emerging drug target to treat dyslipidemia and fatty liver disease. However, the current known SCAP inhibitors, such as oxysterols, induce endoplasmic reticulum (ER) stress and NR1H3/LXRα (nuclear receptor subfamily 1 group H member 3)-SREBF1/SREBP-1 c-mediated hepatic steatosis, which severely limited the clinical application of this inhibitor. In this study, we identified a small molecule, lycorine, which binds to SCAP, which suppressed the SREBF pathway without inducing ER stress or activating NR1H3. Mechanistically, lycorine promotes SCAP lysosomal degradation in a macroautophagy/autophagy-independent pathway, a mechanism completely distinct from current SCAP inhibitors. Furthermore, we determined that SQSTM1 captured SCAP after its exit from the ER. The interaction of SCAP and SQSTM1 requires the WD40 domain of SCAP and the TB domain of SQSTM1. Interestingly, lycorine triggers the lysosome translocation of SCAP independent of autophagy. We termed this novel protein degradation pathway as the SQSTM1-mediated autophagy-independent lysosomal degradation (SMAILD) pathway. In vivo, lycorine ameliorates high-fat diet-induced hyperlipidemia, hepatic steatosis, and insulin resistance in mice. Our study demonstrated that the inhibition of SCAP through the SMAILD pathway could be employed as a useful therapeutic strategy for treating metabolic diseases.Abbreviation: 25-OHD: 25-hydroxyvitamin D; 3-MA: 3-methyladenine; ABCG5: ATP binding cassette subfamily G member 5; ABCG8: ATP binding cassette subfamily G member 8; ACACA: acetyl-CoA carboxylase alpha; AEBSF: 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride; AHI: anhydroicaritin; AKT/protein kinase B: AKT serine/threonine kinase; APOE: apolipoprotein E; ATF6: activating transcription factor 6; ATG: autophagy-related; BAT: brown adipose tissue; CD274/PD-L1: CD274 molecule; CETSA: cellular thermal shift assay; CMA: chaperone-mediated autophagy; COPII: cytoplasmic coat protein complex-II; CQ: chloroquine; DDIT3/CHOP: DNA damage inducible transcript 3; DNL: de novo lipogenesis; EE: energy expenditure; EGFR: epithelial growth factor receptor; eMI: endosomal microautophagy; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; FADS2: fatty acid desaturase 2; FASN: fatty acid synthase; GOT1/AST: glutamic-oxaloacetic transaminase 1; GPT/ALT: glutamic-pyruvate transaminase; HMGCR: 3-hydroxy-3-methylglutaryl-CoA reductase; HMGCS1: 3-hydroxy-3-methylglutaryl-CoA synthase 1; HSP90B1/GRP94: heat shock protein 90 beta family member 1; HSPA5/GRP78: heat hock protein family A (Hsp70) member 5; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; INSIG1: insulin induced gene 1; LAMP2A: lysosomal associated membrane protein 2A; LDLR: low density lipoprotein receptor; LyTACs: lysosome targeting chimeras; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MBTPS1: membrane bound transcription factor peptidase, site 1; MEF: mouse embryonic fibroblast; MST: microscale thermophoresis; MTOR: mechanistic target of rapamycin kinase; MVK: mevalonate kinase; PROTAC: proteolysis targeting chimera; RQ: respiratory quotient; SCAP: SREBF chaperone; SCD1: stearoyl-coenzemy A desaturase 1; SMAILD: sequestosome 1 mediated autophagy-independent lysosomal degradation; SQSTM1: sequestosome 1; SREBF: sterol regulatory element binding transcription factor; TNFRSF10B/DR5: TNF receptor superfamily member 10b; TRAF6: TNF receptor associated factor 6; UPR: unfolded protein response; WAT: white adipose tissue; XBP1: X-box binding protein 1.

14.
Microsc Res Tech ; 83(12): 1530-1543, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32734676

RESUMO

Prevention against the adulteration of traditional Chinese medicine in an accurate way has been long exploring. Vitex trifolia fruit (VTF), as a widely used analgesic in East Asia, has frequently been found to be adulterated with five adulterants, namely Vitex cannabifolia fruit (VCF) (Fam. Verbenaceae), Vitex negundo fruit (VNF) (Fam. Verbenaceae), Piper cubeba fruit (PCF) (Fam. Lauraceae), Euphorbia lathyris seed (ELS) (Fam. Euphorbiaceae), and Vaccinium bracteatum fruit (VBF) (Fam. Ericaceae). In this study, the methods of micromorphological identification, microscopic identification, and chemical analysis were combined to distinguish VTF from its five adulterants comprehensively. As a result, the micromorphological features in terms of fruit or seed epidermis were photographed by stereomicroscopy firstly. Secondly, the microscopic characteristics of various herb powders were captured under light microscopy. Thirdly, 33 nonvolatile components and 124 volatile components in VTF were identified by ultra-performance liquid chromatography coupled with Orbitrap mass spectrometry (UPLC-Orbitrap-MS) and comprehensive two-dimensional gas chromatography hyphenated with mass spectrometry (GC × GC-MS), respectively. Furthermore, betulinic acid, persicogenin, and the volatile 4-(2,2,6-trimethyl-bicyclo[4.1.0]hept-1-yl)-butan-2-one were screened out to be the specific markers of VTF distinctive from the adulterants. Collectively, VTF and its five adulterants were distinguished successfully by the comparison of micromorphological, microscopic characteristics, and chemical profiles.


Assuntos
Vitex , Frutas , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Massas , Medicina Tradicional Chinesa
15.
Nanoscale ; 12(28): 15325-15335, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32648877

RESUMO

Drug-induced liver injury (DILI) is increasingly recognized as one of the most challenging global health problems. Conventional in vitro detection methods not only lack specificity and sensitivity but also cannot achieve real-time, straightforward visualization of hepatotoxicity in vivo. Liver-specific miR122 has been observed to be a superior and sensitive biomarker for DILI diagnosis. Herein, a sensitive upconverting nanoprobe synthesized with upconversion nanoparticles (UCNPs) and gold nanorods (GNR) was designed to diagnose hepatotoxicity in vivo. After injection, the nanoprobes accumulated in the liver and were activated by miR122, and the signal amplification technology fully yielded luminescent amplification; hence, the detection sensitivity was improved. Because of the high tissue penetration capability of near-infrared light, this nanoprobe can achieve real-time in situ detection, thereby providing a novel technology for precise biological and medical analysis.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Nanopartículas , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Ouro , Humanos , Luminescência , Tecnologia
16.
J Mass Spectrom ; 55(9): e4528, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32559823

RESUMO

Fully understanding the chemicals in an herbal medicine remains a challenging task. Molecular networking (MN) allows to organize tandem mass spectrometry (MS/MS) data in complex samples by mass spectral similarity, which yet suffers from low coverage and accuracy of compound annotation due to the size limitation of available databases and differentiation obstacle of similar chemical scaffolds. In this work, an enhanced MN-based strategy named diagnostic fragmentation-assisted molecular networking coupled with in silico dereplication (DFMN-ISD) was introduced to overcome these obstacles: the rule-based fragmentation patterns provide insights into similar chemical scaffolds, the generated in silico candidates based on metabolic reactions expand the available natural product databases, and the in silico annotation method facilitates the further dereplication of candidates by computing their fragmentation trees. As a case, this approach was applied to globally profile the steroidal alkaloids in Fritillariae bulbus, a commonly used antitussive and expectorant herbal medicine. Consequently, a total of 325 steroidal alkaloids were discovered, including 106 cis-D/E-cevanines, 142 trans-D/E-cevanines, 29 jervines, 23 veratramines, and 25 verazines. And 10 of them were confirmed by available reference standards. Approximately 70% of the putative steroidal alkaloids have never been reported in previous publications, demonstrating the benefit of DFMN-ISD approach for the comprehensive characterization of chemicals in a complex plant organism.


Assuntos
Alcaloides/química , Fritillaria/química , Fitosteróis/química , Plantas Medicinais/química , Espectrometria de Massas em Tandem/métodos , Alcaloides/análise , Simulação por Computador , Estrutura Molecular , Fitosteróis/análise
17.
Plant Mol Biol ; 103(6): 705-718, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32577984

RESUMO

Fritillariae Bulbus are the most commonly used antitussive and edible herbs in China. Based on UPLC-QTOF-MS and UPLC-QQQ-MS, the validated MRM-based non-targeted quantitative method was applied to determinate the contents of 48 Fritillaria alkaloids (FAs) in three Fritillaria species (F. thunbergii Miq., F. unibracteata and F. ussuriensis). The RNA-Seq results showed that gene transcript levels have different expression patterns in three Fritillaria species. Based on transcriptome data, the full-length cDNA sequences of squalene epoxidase gene were cloned and characterized. Natural evolution of squalene epoxidase genes resulted in four mutations (C236R, M489L, G510A and K517R) in three Fritillaria species. Molecular docking analysis showed that the 236 residue is located inside the pocket and the binding center while other three residues are located on the surface of the protein. Functional verification indicated the mutations of SQE (C236R) could effectively increase the activity of SQE and obtain higher yield of 2,3-oxidosqualene in recombinant yeast. And the mutations of SQE (M489L and G510A), which increased the hydrophobicity of the protein surface, could also enhance the activity of SQE. This study provides major insights into the metabolites differentiation of FAs biosynthesis, and a firm foundation for the quality control and metabolic engineering of Fritillariae bulbus.


Assuntos
Fritillaria/enzimologia , Esqualeno Mono-Oxigenase/metabolismo , Alcaloides/metabolismo , Cromatografia Líquida de Alta Pressão , DNA Complementar/genética , Simulação de Acoplamento Molecular , Mutação/genética , Filogenia , Alinhamento de Sequência , Esqualeno Mono-Oxigenase/genética
19.
J Sep Sci ; 43(9-10): 1755-1772, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32160388

RESUMO

Alkaloids are a widespread group of basic compounds in herbal medicines and have attracted great interest due to various pharmaceutical activities and desirable druggability. Their distinctive structures make chromatographic separation fairly difficult. Peak tailing, poor resolution, and inferior column-to-column reproducibility are common obstacles to overcome. In order to provide a valuable reference, the methodologies and/or strategies on liquid chromatographic separation of alkaloids in herbal medicines proposed from 2012 to 2019 are thoroughly summarized.


Assuntos
Alcaloides/isolamento & purificação , Medicamentos de Ervas Chinesas/química , Plantas Medicinais/química , Alcaloides/química , Cromatografia Líquida , Concentração de Íons de Hidrogênio
20.
Spectrochim Acta A Mol Biomol Spectrosc ; 231: 118110, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32007906

RESUMO

A morpholine-functionalized pyrrole-cyanine probe was synthesized via a simple condensation reaction in high yield. This probe exhibits high selectivity toward ClO- on fluorescence and UV-vis spectra in neat aqueous solution. The strong green emission of the probe solution was quenched and the yellow color faded immediately upon the addition of ClO-. The detection limit of the probe for ClO- was 0.165 µM. The mechanism of hypochlorite-induced CC breakage was supposed on the basis of EIS-MS, NMR, and density functional theory (DFT) calculation. Finally, the probe was utilized to image ClO- in lysosomes of living cells.


Assuntos
Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Lisossomos/química , Células HeLa , Humanos , Lisossomos/ultraestrutura , Microscopia Confocal , Modelos Moleculares , Imagem Óptica , Solubilidade , Espectrometria de Fluorescência , Água/química
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