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1.
Food Chem ; 366: 130576, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34348222

RESUMO

Cinnamon oil is obtained by steam distillation from cinnamon leaves and is usually considered highly cost-effective compared to bark oil, however, which results in tons of waste cinnamon leaves (WCL) discarded annually. By using MS/MS molecular networking (MN) assisted profiling, six main chemical diversities including flavonols and flavones, phenolic acids, lactones, terpenoids, phenylpropanoids and flavanols were rapid revealed from WCL aqueous extract. 101 compounds were tentatively identified by assigning their MS/MS fragments within typical pathways under ESI-MS/MS dissociation. The featured phenolic acids, terpenoids and their glycosides in cinnamon species were recognized as the main constituents of WCL. The hydrophilic lactones, lignans and flavanols were reported for the first time in cinnamon leaves. Furthermore, ABTS and FRAP assays integrated with MN analysis were conducted to uncover an antioxidant fraction, from which 40 potential antioxidant compounds were rapidly annotated. This fundamental information will help expand the utilization of WCL from cinnamon oil industry.


Assuntos
Antioxidantes , Cinnamomum zeylanicum , Cromatografia Líquida , Extratos Vegetais , Espectrometria de Massas em Tandem
2.
J Bone Joint Surg Am ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34793368

RESUMO

BACKGROUND: Newborn hip screening aims to prevent the late diagnosis of and subsequent surgical procedures for developmental dysplasia of the hip (DDH). Weather may affect how parents swaddle their babies in early life, but weather has never been formally regarded as a risk factor in hip screening. This study investigates the association between the incidence of surgically treated DDH and the outdoor temperature. METHODS: Surgical procedures for late-diagnosed DDH were investigated in 12 birth-year cohorts (1999 to 2010) using the Taiwan National Health Insurance Research Database. The number of children who underwent a DDH-related surgical procedure between 6 months and 5 years of age per total live births was evaluated as an outcome of hip screening. Trend and regression analyses were used to determine the association between the incidence of surgically treated DDH and birth year, birth month, and the temperature during the birth month and first 3 months of life. RESULTS: The mean incidence of surgically treated DDH was 0.48 per 1,000 live births (1,296 surgically treated patients per 2,712,002 live births). The incidence of surgically treated DDH among babies born in winter months (0.70 per 1,000) was significantly higher than that among babies born in summer months (0.32 per 1,000), and it was significantly correlated with mean temperature in the first 3 months of life (r2 = 0.91; p < 0.0001) and birth month (r2 = 0.68; p < 0.001). Multivariable regression revealed that external temperature in the first 3 months of life was the most significant factor (ß = -0.034 [95% confidence interval, -0.042 to -0.022]; p < 0.001) for the incidence of surgically treated DDH (adjusted r2 = 0.485). The trend of seasonal differences remained the same throughout the study years following implementation of the hip-screening policy. CONCLUSIONS: As the incidence of surgically treated DDH is the ultimate outcome of newborn hip screening, cold weather should be regarded as a risk factor and should be incorporated into future screening programs. Weather patterns of different geographical areas should be studied to determine if children born in the winter are at an increased risk for requiring a surgical procedure for DDH, and newborn hip-screening programs should be revised accordingly. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

3.
Phytomedicine ; : 153777, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34815154

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is a severe diabetic complication that is the principal cause of end-stage kidney disease worldwide. Huang-Lian-Jie-Du Decoction (HLJDD) is widely used to treat diabetes clinically. However, the nephroprotective effects and potential mechanism of action of HLJDD against DN have not yet been fully elucidated. PURPOSE: This study aimed to investigate the potential roles of HLJDD in DN and elucidate its mechanisms in db/db mice. METHODS: An integrated strategy of network pharmacology, pharmacodynamics, molecular biology, and metabolomics was used to reveal the mechanisms of HLJDD in the treatment of DN. First, network pharmacology was utilized to predict the possible pathways for DN using the absorbed ingredients of HLJDD in rat plasma in silico. Then, combined with histopathological examination, biochemical evaluation immunohistochemistry/immunofluorescence assay, western blot analysis, and UPLC-Q-Orbitrap HRMS/MS-based metabolomics approach were applied to evaluate the efficacy of HLJDD against DN and its underlying mechanisms in vivo. RESULTS: In silico, network pharmacology indicated that the AGEs/RAGE pathway was the most prominent pathway for HLJDD against DN. In vivo, HLJDD exerted protective effects against DN by ameliorating glycolipid metabolic disorders and kidney injury. Furthermore, we verified that HLJDD protected against DN by regulating the AGEs/RAGE/Akt/Nrf2 pathway for the first time. In addition, 22 potential biomarkers were identified in urine, including phenylalanine metabolism, tryptophan metabolism, glucose metabolism, and sphingolipid metabolism. CONCLUSION: These findings suggest that HLJDD ameliorates DN by regulating the AGEs/RAGE/Akt/Nrf2 pathway and metabolic profiling.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34639662

RESUMO

The objective of this study was to investigate the prevalence of regular physical activity (RPA) among middle-aged and older adults in urban communities in Jinan, China, and to identify the factors related to RPA. A cross-sectional survey was conducted among middle-aged and elderly urban residents. A total of 1406 participants were included in the final data analysis. The results of the four models consistently showed that the relevant factors of RPA were educational level, previously diagnosed hypertension (PDH) and depression. In terms of educational level, compared with illiteracy, from the first model to the fourth model, the odds ratios (ORs) and 95% confidence intervals (CIs) of senior middle school were 2.072 (1.418, 3.026), 2.072 (1.418, 3.026), 1.905 (1.289, 2.816) and 1.926 (1.302, 2.848), respectively, and the ORs and 95% CIs of college or above were 2.364 (1.462, 3.823), 2.364 (1.462, 3.823), 2.001 (1.208, 3.312) and 2.054 (1.239, 3.405). In terms of PDH, compared with those with PDH, from the first model to the fourth model, ORs and 95% CIs of non-PDH were 1.259 (1.003, 1.580), 1.259 (1.003, 1.580), 1.263 (1.006, 1.585) and 1.261 (1.004, 1.584), respectively. For depression, compared with those without depression, also from the first model to the fourth model, ORs and 95% CIs of depression were 0.702 (0.517, 0.951), 0.702 (0.517, 0.951), 0.722 (0.532, 0.981) and 0.719 (0.529, 0.977), respectively. In conclusion, the results of this study showed that participation in RPA among middle-aged and older adults in Jinan urban communities was significantly associated with education level, PDH and depression.


Assuntos
Exercício Físico , Idoso , China/epidemiologia , Estudos Transversais , Escolaridade , Humanos , Pessoa de Meia-Idade , Prevalência
5.
Artigo em Inglês | MEDLINE | ID: mdl-34682435

RESUMO

Cerebellar transcranial direct current stimulation (cerebellar tDCS) is a promising therapy for cerebellar ataxias and has attracted increasing attention from researchers and clinicians. A timely systematic review focusing on randomized sham-controlled trials and repeated measures studies is warranted. This study was to systematically review existing evidence regarding effects of anodal cerebellar tDCS on movements in patients with cerebellar ataxias. The searched databases included Web of Science, MEDLINE, PsycINFO, CINAHL, EMBASE, Cochrane Library, and EBSCOhost. Methodological quality of the selected studies was assessed using the Physiotherapy Evidence Database scale. Five studies with 86 patients were identified. Among these, four studies showed positive effects of anodal cerebellar tDCS. Specifically, anodal cerebellar tDCS decreased disease severity and improved finger dexterity and quality of life in patients, but showed incongruent effects on gait control and balance, which may be due to heterogeneity of research participants and choices of measures. The protocols of anodal cerebellar tDCS that improved movements in patients commonly placed the anode over the whole cerebellum and provided ten 2-mA 20-min stimulation sessions. The results may show preliminary evidence that anodal cerebellar tDCS is beneficial to reducing disease severity and improving finger dexterity and quality of life in patients, which lays the groundwork for future studies further examining responses in the cerebello-thalamo-cortical pathway. An increase in sample size, the use of homogeneous patient groups, exploration of the optimal stimulation protocol, and investigation of detailed neural mechanisms are clearly needed in future studies.


Assuntos
Ataxia Cerebelar , Estimulação Transcraniana por Corrente Contínua , Ataxia Cerebelar/terapia , Cerebelo , Eletrodos , Dedos , Humanos , Destreza Motora , Qualidade de Vida
6.
Biochem Pharmacol ; 194: 114798, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34678227

RESUMO

Drug affinity responsive target stability (DARTS) is a novel target discovery approach and is particularly adept at screening small molecule (SM) targets without requiring any structural modifications. The DARTS method is capable of revealing drug-target interactions from cells or tissues by tracking changes in the stability of proteins acting as receptors of bioactive SMs. Due to its simple operation and high efficiency, the DARTS method has been applied to uncover the drug-action mechanism. This review summarized analytical principles, protocols, validation approaches, applications, and challenges involved in the DARTS method. Due to the innate advantages of the DARTS method, it is expected to be a powerful tool to accelerate SM target discovery, especially for bioactive natural products with unknown mechanisms.

7.
J Agric Food Chem ; 69(37): 10943-10951, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34514791

RESUMO

Carbonyl compounds play a critical role in the pathogenesis of diabetic nephropathy (DN). Pueraria lobata (PL), also known as "Kudzu", is a widely consumed functional food or nutraceutical and has shown promise in the prevention of diabetes and complications such as DN. To explore the beneficial effects and the underlying mechanisms of PL against DN, a new strategy for in-depth metabolic profiling of carbonyl compounds in DN mice plasma by chemical derivatization combined with UPLC-Q-Orbitrap high-resolution mass spectrometry (HRMS)/MS analysis was developed for the first time. Pharmacological evaluation revealed that PL extracts containing a total of 73 identified compounds could ameliorate kidney injury and regulate abnormal glycolipid metabolism. In metabolomics analysis, 19 carbonyl compounds with significant differences were identified between DN mice and normal mice. Moreover, 12 metabolites had a tendency to return to normal levels after PL treatment. Overall, PL exerts beneficial effects on DN by regulating abnormal glycolipid metabolism and carbonyl stress, and endogenous carbonyl compounds might serve as potential biomarkers for DN.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Pueraria , Animais , Nefropatias Diabéticas/tratamento farmacológico , Rim , Espectrometria de Massas , Metabolômica , Camundongos
8.
J Behav Addict ; 10(3): 731-746, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34529588

RESUMO

Background and aims: The present longitudinal study examined the changes in problematic internet use (problematic smartphone use, problematic social media use, and problematic gaming) and changes in COVID-19-related psychological distress (fear of COVID-19 and worry concerning COVID-19) across three time-points (before the COVID-19 outbreak, during the initial stages of the COVID-19 outbreak, and during the COVID-19 outbreak recovery period). Methods: A total of 504 Chinese schoolchildren completed measures concerning problematic internet use and psychological distress across three time-points. Latent class analysis (LCA) was used to classify participants into three groups of problematic internet use comprising Group 1 (lowest level), Group 2 (moderate level), and Group 3 (highest level). Results: Statistical analyses showed that as problematic use of internet-related activities declined among Group 3 participants across the three time points, participants in Group 1 and Group 2 had increased problematic use of internet-related activities. Although there was no between-group difference in relation to worrying concerning COVID-19 infection, Groups 2 and 3 had significantly higher levels of fear of COVID-19 than Group 1 during the COVID-19 recovery period. Regression analysis showed that change in problematic internet use predicted fear of COVID-19 during the recovery period. Conclusion: The varied levels of problematic internet use among schoolchildren reflect different changing trends of additive behaviors during COVID-19 outbreak and recovery periods.


Assuntos
COVID-19 , Angústia Psicológica , Criança , China/epidemiologia , Surtos de Doenças , Humanos , Internet , Transtorno de Adição à Internet , Análise de Classes Latentes , Estudos Longitudinais , SARS-CoV-2
9.
Zhongguo Zhong Yao Za Zhi ; 46(14): 3614-3624, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34402285

RESUMO

The volatile oil of Curcumae Rhizoma has many active components,which are the key to the quality of Curcumae Rhizoma. Exploring the difference between volatile oil of different kinds of Curcumae Rhizoma facilitates the quality control and rational application of resources. In this study,GC-MS was applied to realize online qualitative and semi-quantitative analysis of the chemical composition spectrum of volatile oil from Curcuma wenyujin( CW),C. phaeocaulis( CP),and C. kwangsiensis( CK). Forty components were identified and their fingerprints were compared and evaluated. Hierarchical cluster analysis( HCA),principal component analysis( PCA),and orthogonal partial least squares discrimination analysis( OPLS-DA) were adopted to analyze the overall and outlier data. The results showed that the whole data could be divided into three kinds according to each analysis mode,and the volatile components of Curcumae Rhizoma vary greatly among species. PCA explored the difference between outliers and the mean value of the group and found that some volatile oils from CW may be greatly affected by the origin. By OPLS-DA,the samples from Zhejiang were able to gather,but those from Guizhou remained isolated,indicating the influence of growing environment on Curcumae Rhizoma metabolites. Based on VIP results combined with the heat map,characteristic volatile oil components of Curcumae Rhizoma from different varieties were screened out: curdione and linalool for CW; 2-undecanone for CP; humulene,γ-selinene,and zederone for CK. The GCMS method established in this study describes Curcumae Rhizoma samples comprehensively and accurately,and the characteristic components screened based on chemometrics can be used to distinguish Curcumae Rhizoma from different varieties and give them unique pharmacodynamic significance,which is fast,convenient,stable,and reliable and supports the rational application of Curcu-mae Rhizoma resources. It is found that the region of origin has great influence on CW,which is worthy of further study.


Assuntos
Óleos Voláteis , Curcuma , Cromatografia Gasosa-Espectrometria de Massas , Análise de Componente Principal , Rizoma
10.
Food Funct ; 12(17): 7607-7618, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34236368

RESUMO

Diabetic nephropathy (DN) is a microvascular complication that is becoming a worldwide public health concern. The aim of this study was to assess the effects of dietary soy isoflavone intervention on renal function and metabolic syndrome markers in DN patients. Seven databases including Medline, the Cochrane Central Register of Controlled Trials, Science Direct, Web of Science, Embase, China National Knowledge Infrastructure, and WanFang were searched for controlled trials that assessed the effects of soy isoflavone treatment in DN patients. Finally, a total of 141 patients from 7 randomized controlled trials were included. The meta-analysis showed that dietary soy isoflavones significantly decreased 24-hour urine protein, C-reactive protein (CRP), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose (FBG) in DN patients. The standard mean difference was -2.58 (95% CI: -3.94, -1.22; P = 0.0002) for 24-hour urine protein, -0.67 (95% CI: -0.94, -0.41; P < 0.00001) for BUN, -6.16 (95% CI: -9.02, -3.31; P < 0.0001) for CRP, -0.58 (95% CI: -0.83, -0.33; P < 0.00001) for TC, -0.41 (95% CI: -0.66, -0.16; P < 0.00001) for TG, -0.68 (95% CI: -0.94, -0.42; P < 0.00001) for LDL-C, and -0.39 (95% CI: -0.68, -0.10; P = 0.008) for FBG. Therefore, soy isoflavones may ameliorate DN by significantly decreasing 24-hour urine protein, BUN, CRP, TC, TG, LDL-C, and FBG.

11.
Eur Radiol ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215941

RESUMO

OBJECTIVES: The amount and distribution of intratumoural collagen fibre vary among different thymic tumours, which can be clearly detected with T2- and diffusion-weighted MR images. To explore the incidences of collagen fibre patterns (CFPs) among thymomas, thymic carcinomas and lymphomas on imaging, and to evaluate the efficacy and reproducibility of CFPs in differential diagnosis of thymic tumours. MATERIALS AND METHODS: Three hundred and ninety-eight patients with pathologically diagnosed thymoma, thymic carcinoma and lymphoma who underwent T2- and diffusion-weighted MR imaging were retrospectively enrolled. CFPs were classified into four categories: septum sign, patchy pattern, mixed pattern and no septum sign. The incidences of CFPs were compared among different thymic tumours, and the efficacy and reproducibility in differentiating the defined tumour types were analysed. RESULTS: There were significant differences in CFPs among thymomas, thymic squamous cell carcinomas (TSCCs), other thymic carcinomas and neuroendocrine tumours (OTC&NTs) and thymic lymphomas. Septum signs were found in 209 (86%) thymomas, which differed between thymomas and any other thymic neoplasms (all p < 0.005). The patchy, mixed patterns and no septum sign were mainly seen in TSCCs (80.3%), OTC&NTs (78.9%) and thymic lymphomas (56.9%), respectively. The consistency of different CFP evaluation between two readers was either good or excellent. CFPs achieved high efficacy in identifying the thymic tumours. CONCLUSION: The CFPs based on T2- and diffusion-weighted MR imaging were of great value in the differential diagnosis of thymic tumours. KEY POINTS: • Significant differences are found in intratumoural collagen fibre patterns among thymomas, thymic squamous cell carcinomas, other thymic carcinomas and neuroendocrine tumours and thymic lymphomas. • The septum sign, patchy pattern, mixed pattern and no septum sign are mainly seen in thymomas (86%), thymic squamous cell carcinomas (80.3%), other thymic carcinomas and neuroendocrine tumours (79%) and thymic lymphomas (57%), respectively. • The collagen fibre patterns have high efficacy and reproducibility in differentiating thymomas, thymic squamous cell carcinomas and thymic lymphomas.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34052562

RESUMO

Huang-Lian-Jie-Du Decoction (HLJDD), a well-known traditional Chinese formulation, has been proved to exert neuroprotective effects, however, the bioactive components in HLJDD still remain to be elucidated. In the present study, a rapid and effective method involving live cell biospecific extraction and HPLC-Q-Orbitrap HRMS/MS was utilized to rapidly screen and identify the neuroprotective compounds from the HLJDD crude extract directly. Firstly, sixteen principal components in HLJDD crude extract were identified by HPLC-Q-Orbitrap HRMS/MS analysis. After co-incubation with PC12 cells, which have been validated as the key target cells for neurodegenerative diseases, seven compounds of them were demonstrated to exhibit binding affinity to the target cells. Furthermore, three representative compounds named baicalin, wogonoside, and berberine were subsequently verified to exert cytoprotective effects on PC12 cells injured by hydrogen peroxide via inhibiting oxidative stress and cell apoptosis, indicating that these screened compounds may possess a potential for the treatment of neurodegenerative diseases and were responsible, in part at least, for the neuroprotective beneficial effects of HLJDD. Taken together, our study provides evidence that live cell biospecific extraction coupled with LC-HRMS/MS technique is an efficient method for rapid screening potential bioactive components in traditional Chinese medicines.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Técnicas Citológicas/métodos , Medicamentos de Ervas Chinesas , Fármacos Neuroprotetores , Animais , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/farmacologia , Fármacos Neuroprotetores/análise , Fármacos Neuroprotetores/farmacologia , Células PC12 , Ratos , Espectrometria de Massas em Tandem
13.
Food Chem Toxicol ; 153: 112244, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33930484

RESUMO

Methylglyoxal (MGO), a cytotoxic byproduct of glycolysis in biological systems, can induce endothelial cells dysfunction, implicated in diabetic vascular complications. Pterostilbene (PTS), a naturally occurring resveratrol derivative, is involved in various pharmacological activities. This study aimed to explore the effects of PTS on MGO induced cytotoxicity in human umbilical vein endothelial cells (HUVECs) and the underlying mechanisms for the first time. In the current study, it has been demonstrated that PTS could enhance the level of glyoxalase 1 (GLO-1) and elevate glutathione (GSH) content to active the glyoxalase system, resulting in elimination of the toxic MGO as well as advanced glycation end products (AGEs) in HUVECs. Meanwhile, PTS could also suppress oxidative stress and thus exert cytoprotective effects by elevating Nrf2 nuclear translocation and the corresponding down-stream antioxidant enzymes in MGO induced HUVECs. In addition, PTS could alleviate MGO induced apoptosis in HUVECs via inhibition of oxidative stress and associated downstream mitochondria-dependent signaling apoptotic cascades, as characterized by preventing caspases family activation. Taken together, these findings suggest that PTS could protect against MGO induced endothelial cell cytotoxicity by regulating glyoxalase, oxidative stress and apoptosis, suggesting that PTS could be beneficial in the treatment of diabetic vascular complications.


Assuntos
Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Lactoilglutationa Liase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Aldeído Pirúvico/toxicidade , Estilbenos/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Lactoilglutationa Liase/genética , Espécies Reativas de Oxigênio
14.
J Asian Nat Prod Res ; 23(6): 527-535, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33844615

RESUMO

A new neolignan compound, tonkinensisin A (1), and two phenylpropanoid compounds, tonkinensisin B (2) and tonkinensisin C (3), were isolated from the resin of Styrax tonkinensis (Pierre) Craib ex Hartw. The structures of these compounds were determined by spectroscopic analysis, and the relative configurations of compounds 1 and 3 were determined by J-based configuration analysis (JBCA) method. All compounds were assayed for cytotoxic activities against five tumor cell lines (HepG-2, A549, Hela, MCF-7, and PC-3) by CCK-8 test in vitro.[Formula: see text].


Assuntos
Medicamentos de Ervas Chinesas , Lignanas , Linhagem Celular Tumoral , Humanos , Lignanas/farmacologia , Estrutura Molecular , Resinas Vegetais , Styrax
15.
Drug Des Devel Ther ; 15: 705-720, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33658761

RESUMO

Purpose: This study aimed to reveal Danggui Buxue Decoction (DBD) candidate targets and mechanisms in the treatment of metastatic colon cancer (MCC), using network pharmacology-based analyses and experimental validation. Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) database query and text mining were used to screen active compounds in DBD, and the Swiss target prediction platform was applied to predict compound-related target proteins. Targets likely associated with MCC were determined using GeneCards and OMIM databases. Targets common to DBD and MCC were obtained from the Venn platform; subsequently, Cytoscape was used to construct drug-compound-target-disease and protein-protein interaction networks. The hub gene was determined by R, while GO and KEGG enrichment analyses were performed on common targets to elucidate biological processes and signaling pathways involved in DBD against MCC. Finally, the metastatic colon cancer mouse model was used to detect the levels of expression of protein Bax, Bcl2, Caspase3, and Cleaved caspase3 by Western blot. Results: A total of 28 active compounds and 61 common targets were predicted. The main compounds were quercetin, hederagenin, jaranol, methylnissolin, formononetin, calycosin, kaempferol, 3.9-di-O-methylnissolin, 24-propylcholesterol, and 7-O-methylisomucronulatol, present in Astragalus membranaceus (Huangqi, HQ). In addition, beta-sitosterol, ferulic acid, and stigmasterol, present in Angelica sinensis (Danggui, DG), were detected. JUN, PTSG2, EGFR, ESR1and, CASP3 genes were the top 5 hub genes in the PPI network. GO and KEGG enrichment analyses indicated that apoptosis played a major role in the biological processes and signaling pathways involved. Moreover, the in vivo experiment revealed that DBD inhibited MCC by up-regulating the expression of Bax, Caspase3, and Cleaved caspase3, and by down-regulating the expression of Bcl2. Conclusion: This study revealed candidate DBD targets and mechanisms in the treatment of MCC, using network pharmacology-based analyses and experimental validation. The present findings provide a reference for tumor treatment during the perioperative period.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Animais , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células Tumorais Cultivadas
16.
Toxicology ; 456: 152750, 2021 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-33737140

RESUMO

Paraquat, an herbicide used extensively worldwide, can cause severe toxicity in humans and animals, leading to irreversible, lethal lung fibrosis. The potential of CO-releasing molecules (CORMs), substances that release CO (Carbon monoxide) within animal tissues, for treating paraquat-induced ROS generation and inflammation is investigated here. Our results show that the fast CO releaser CORM-3 (4-20 µM) acts as a potential scavenger of free radicals and decreases fibrosis progression by inhibiting paraquat-induced overexpression of connective tissue growth factor and angiotensin II in MRC-5 cells. The slow CO releaser CORM-A1 (5 mg/kg) clearly decreased expression of the lung profibrogenic cytokines COX-2, TNF-α, and α-SMA and serum hydroxyproline, resulting in a lower mortality rate in paraquat-treated mice. Mice treated with higher-dose CORM-A1 (10 mg/kg) had relatively intact lung lobes and fewer fibrotic patches by gross observation, with less collagen deposition, mesangial matrix accumulation, and pulmonary fibrosis resulting from the mitigation of TGF-ß overexpression. In conclusion, our data demonstrate for the first time that CORM-A1 alleviated the development of the fibrotic process and improved survival rate in mice exposed to PQ, would be an attractive therapeutic approach to attenuate the progression of pulmonary fibrosis following PQ exposure.


Assuntos
Boranos/uso terapêutico , Monóxido de Carbono , Carbonatos/uso terapêutico , Herbicidas/toxicidade , Doenças Pulmonares Intersticiais/induzido quimicamente , Paraquat/toxicidade , Fibrose Pulmonar/induzido quimicamente , Animais , Boranos/farmacologia , Monóxido de Carbono/metabolismo , Carbonatos/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Distribuição Aleatória
17.
Ther Drug Monit ; 43(2): 292-297, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32947555

RESUMO

BACKGROUND: With the outbreak of COVID-19, it has become very important to improve biosafety measures taken by medical staff. Fewer pretreatment steps correspond to lower chances of infection. The authors established a direct injection technique to analyze levetiracetam (LEV) concentrations in human serum and studied its application in therapeutic drug monitoring. METHODS: Serum samples were prepared by hollow fiber centrifugal ultrafiltration and the filtrate was directly injected into a ultra-high performance liquid chromatography apparatus (Waters UPLC BEH C18 column: 50 × 2.1 mm, 1.7 µm) for analysis. The mobile phase consisted of acetonitrile and water (8:92) at a flow rate of 1.0 mL/min. The column temperature was maintained at 30°C. The detected wavelength was 210 nm. RESULTS: A linear relationship was obtained for LEV from 0.625 to 80 mcg/mL (r2 = 0.999). The limit of detection for the analysis of LEV was 0.125 mcg/mL. The analysis time was shortened to 4 minutes. The recovery rate of LEV based on the current method was 96.6%-100.1%, whereas the absolute recovery rate was 93.2%-96.8%. The relative SD of intraday and interday precision was <7.3%. Stability was achieved at room temperature for 24 hours after 3 freeze-thaw cycles and at -80°C for 21 days. The method was successfully applied to determine LEV concentrations in the serum of 19 patients. CONCLUSIONS: The present method is simple, accurate, and sensitive, and can improve biosafety with the direct injection technique. It is suitable for the analysis of LEV concentrations in therapeutic drug monitoring.


Assuntos
Coleta de Amostras Sanguíneas/métodos , COVID-19/epidemiologia , Monitoramento de Medicamentos/métodos , Levetiracetam/sangue , Cromatografia Líquida de Alta Pressão , Humanos , Reprodutibilidade dos Testes , SARS-CoV-2 , Fatores de Tempo
18.
J Pharm Biomed Anal ; 193: 113636, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33221574

RESUMO

The screening of marker compound is of great significance to the quality control of traditional Chinese medicine (TCM). One approach which combines fingerprint and biological evaluation has developed rapidly. Multi-wavelength fusion fingerprints and antioxidant activity screening are integrated in this study to evaluate the quality of NAODESHENG. Characteristic multiwavelength fusion fingerprints of 14 batches of samples were generated at five different wavelengths and evaluated by quantitative fingerprinting with ultra-performance liquid chromatography (UPLC). In the quantitative fingerprinting method, 21 components in NAODESHENG were qualitatively and quantitatively analyzed by external standard method. The antioxidant activities of these 21 components was determined by pre-column antioxidant activity test. Multivariate statistical methods such as hierarchical clustering analysis and principal component analysis(PCA) was used to reduce the dimensions and variables from a large number of original data to screening marker compound with bioactivity. Based on the above results, it is suggested that 3'-Methoxy Puerarin and 11 other components should be used as the quality marker of NAODESHENG. This study demonstrates the feasibility of multi-wavelength fusion fingerprinting combined with antioxidant activity analysis, which associates quality control with bioactivity, providing a reliable and efficient method for quantitative assessment of TCM quality consistency.


Assuntos
Antioxidantes , Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida
19.
J Pharm Biomed Anal ; 192: 113652, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33039912

RESUMO

Diabetic encephalopathy (DE) is a severe diabetic complication with cognitive dysfunction. Huang-Lian-Jie-Du Decoction (HLJDD), a famous traditional Chinese formula, is effective for the treatment of diabetes mellitus and Alzheimer's disease in clinical practices, however, the therapeutic effects and the underlying mechanisms of HLJDD on DE is unclear yet. With this purpose, behavior test, brain histological and biochemical analysis were estimated to assess the beneficial effects of HLJDD on DE. Plasma samples were collected for metabolomics analysis based on UPLC-Q-Orbitrap HRMS/MS and chemometric analysis. As a result, morris water maze test revealed that HLJDD could effectively improve the learning and memory abilities in db/db mice. Brain histological and biochemical analysis indicated that HLJDD could protect against neurodegeneration and oxidative stress in db/db mice. Meanwhile, a total of 21 potential biomarkers with significant differences were identified between Model group and Control group using untargeted metabolomics strategy. Among them, 11 metabolites showed a trend towards the normal levels after HLJDD intervention. These metabolites principally involved in glycerophospholipid metabolism, fatty acid ß-oxidation, linoleic acid metabolism, glucose metabolism and glutathione metabolism based on the metabolic pathway analysis, which were regulated in DE model mice after HLJDD intervention. Generally, the results demonstrated that HLJDD had beneficial effects on DE, which could be mediated via ameliorating the metabolic disorders.


Assuntos
Doença de Alzheimer , Diabetes Mellitus , Medicamentos de Ervas Chinesas , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Metabolômica , Camundongos , Camundongos Endogâmicos
20.
Pharmacol Res ; 163: 105232, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33027716

RESUMO

Patients with colorectal cancer treated with 5-fluorouracil (5-FU) and irinotecan (CPT-11) exhibit a risk for chemotherapy-induced colitis (CIC) that may lead to fatal consequences. Cryptotanshinone (CTS) is a natural compound extracted from the root of Salvia miltiorrhiza Bunge that shows potent antitumor activities. We previously reported CTS relieved 5-FU/ CPT-11 induced colitis in tumor-free mice. In this study, we studied the effect of CTS on 5-FU/ CPT-11 induced colitis in mice with colitis associated colon cancer (CAC). The effects of CTS on CIC were evaluated by disease activity index (DAI) and histological assessment via hematoxylin-and-eosin staining. Serum lipids and lipid-metabolic enzymes were detected by commercial kits. Fecal microbial diversity was detected by 16S ribosomal RNA gene sequencing. To find the role of fecal bacteria in CAC mice with 5-FU/ CPT-11 induced colitis, pseudo-germ-free mice were established by intragastric administration of mixed antibiotics. Except for decreasing tumor number (3 ± 1 vs 6 ± 1, p < 0.05), CTS significantly alleviated DAI (1.9 ± 0.6 vs 2.6 ± 0.5, p < 0.05) and regulated serum lipids in CAC mice with 5-FU/ CPT-11induced colitis. Compared with model group, CTS significantly increased serum triglycerides (TG) (1.13 ± 0.26 mM vs 0.79 ± 0.03 mM, p < 0.05), high density lipoprotein (HDL) (3.88 ± 0.1 mM vs 3.28 ± 0.05 mM, p < 0.001) and oxidized low-density lipoprotein (oxLDL) (288.12 ± 65.92 ng/mL vs 150.72 ± 42.13 ng/mL, p < 0.05) level but decreased serum adiponectin level (1177.47 ± 179.2 pg/mL vs 1523.43 ± 91.8 pg/mL, p < 0.05). Among fecal bacteria significantly correlated with lipid metabolism, CTS significantly decreased the abundance of g__norank_f__Muribaculaceae (21.15 % ± 5.7 % vs 41.84 ± 12.0 %, p < 0.01) but increased that of g_Lactobacillus (11.13 % ± 6.6 % vs 5.7 % ± 4.6 %, p < 0.05), g__Alistipes (3.66 % ± 0.7 % vs 1.47 % ± 1,0%, p < 0.01) and g__Odoribacter (1.31 % ± 0.7 % vs 0.30 % ± 0.2 %, p < 0.01). In addition, the development of CIC and abnormal lipid metabolism were significantly prevented in pseudo-germ-free mice. Therefore, we concluded CTS alleviated 5FU/CPT-11 induced colitis in CAC mice via regulating fecal flora associated lipid metabolism.

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