RESUMO
Strobilanthes sarcorrhiza (CTS) is a medicinal plant with various pharmacological effects such as tonifying kidney and anti-inflammatory. However, the chemical composition and difference of its four parts (leaves, stems, rhizomes, and root tubers) have been rarely reported. In this study, ultrafast flow liquid chromatography coupled with quadrupole-time-of-flight MS was applied to analyze the chemical profile of CTS and identify 55 compounds, including terpenoids, phenylethanol glycosides, fatty acid derivatives, chain glycosides, flavonoid glycosides, and others. Among these compounds, 34 compounds were first identified in CTS. They were mainly terpenoids, phenylethanol glycosides, fatty acid derivatives, and so forth. Multivariate statistical analysis, such as principal component analysis and orthogonal partial least squares-discriminant analysis were also used to evaluate the difference in chemical compounds from the four parts of CTS. The results showed that phenylethanol glycosides were the main compounds of the underground parts, while terpenoids were the main compounds of the aboveground parts. This study revealed the chemical diversity and similarity of CTS and suggested that the rhizomes could be used as an alternative medicinal part to improve the resource utilization of CTS.
Assuntos
Espectrometria de Massas , Análise Multivariada , Espectrometria de Massas/métodos , Cromatografia Líquida/métodos , Extratos Vegetais/química , Terpenos/análise , Terpenos/química , Glicosídeos/análise , Glicosídeos/química , Cromatografia Líquida de Alta Pressão/métodosRESUMO
Methicillin-resistant Staphylococcus aureus (MRSA) is a highly infectious pathogen that poses a serious threat to human life and health. This study aimed to provide a scientific basis for the rational clinical use of antimicrobial drugs for treating MRSA infections and inform the development of preventive and control measures by analyzing the clinical distribution and resistance characteristics of MRSA in a hospital in Hebei China. To accomplish this, bacterial identification and drug sensitivity experiments were performed with 1858 Staphylococcus aureus (S. aureus) strains collected from a hospital from January 2018 to December 2022 using a phoenixTM-100 bacterial identification drug sensitivity analyzer. The experimental data were analyzed using WHONET 5.6 software, and the MRSA strains detected were analyzed for their clinical distribution and drug resistance. Of the 1858 S. aureus strains isolated, 429 were MRSA. Sputum samples had the highest MRSA detection rates (52.45%). Critical care medicine had the highest rate of MRSA (12.59%), followed by dermatology (9.79%). MRSA resistance to tetracycline increased by 13.9% over 5 years; resistance to quinupristin/dalfopristin also increased but remained low (1.9%). Resistance decreased to gentamicin, rifampicin, ciprofloxacin, and cotrimoxazole, though most significantly to erythromycin and clindamycin, exceeding 77% and 83%, respectively. No strains were resistant to vancomycin, teicoplanin, or linezolid, and drug resistance was most prevalent in patients ≥ 60 years old. This study will aid in improving the diagnosis and treatment of MRSA infections.
RESUMO
OBJECTIVE: To evaluate the effect of intensive oropharyngeal functional training on swallowing in patients with dysphagia after radiotherapy for nasopharyngeal carcinoma. METHODS: Fourteen patients with nasopharyngeal carcinomas and dysphagia after radiotherapy received intensive oropharyngeal training for two weeks. The Functional Oral Intake Scale (FOIS) and videofluoroscopic swallowing studies (VFSS) were used to evaluate swallowing function before and after intensive oropharyngeal training. Spatiotemporal parameters of the VFSS were analyzed using a digital image analysis system. RESULTS: After training, the FOIS, Rosenbek penetration-aspiration score, DIGEST, normalized residue ratio scale, and spatiotemporal parameters of VFSS were significantly improved (P < 0.05). CONCLUSIONS: This study indicated that intensive oropharyngeal training improves swallowing function after radiotherapy in patients with nasopharyngeal carcinoma.
Assuntos
Transtornos de Deglutição , Neoplasias Nasofaríngeas , Humanos , Transtornos de Deglutição/etiologia , Carcinoma Nasofaríngeo/radioterapia , Deglutição , Neoplasias Nasofaríngeas/complicações , Neoplasias Nasofaríngeas/radioterapiaRESUMO
Triple-negative breast cancer (TNBC) remains the most challenging breast cancer subtype to treat because there are no targeted therapies. Currently, chemotherapy is the only clinical option for TNBC despite development of resistance. New therapeutic agents with unique mechanisms of action are urgently needed; therefore, this study investigated the potential anti-TNBC effects of budlein A methylacrylate (BAM), a natural sesquiterpene lactone isolated from plants of the Helianthus genus. We discovered that BAM selectively suppressed and induced apoptosis TNBC cell growth versus other breast cancer or normal mammary epithelial cells. Mechanistically, BAM co-inhibited inhibitor of nuclear factor κBα (IκBα) kinase subunit ß (IKKß) and exportin-1 (XPO-1; chromosome region maintenance 1, CRM1), which are two dysregulated onco-related proteins in TNBC cells, by covalently modifying key functional cysteine residues (Cys179 of IKKß, Cys528 of XPO-1). Dual inhibition led to the stabilization and nuclear retention of IκBα, impairment of NF-κB transcriptional activity, and consequent induction of TNBC cell apoptosis. In conclusion, this study provides evidence that co-inhibition of IKKß and XPO-1 by BAM was effective against TNBC, demonstrating it as a representative new generation inhibitor with potential for TNBC treatment.
Assuntos
Antineoplásicos/uso terapêutico , Quinase I-kappa B/antagonistas & inibidores , Carioferinas/antagonistas & inibidores , Lactonas/uso terapêutico , Metacrilatos/uso terapêutico , Sesquiterpenos/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Quinase I-kappa B/genética , Carioferinas/genética , Lactonas/farmacologia , Metacrilatos/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/metabolismo , RNA Interferente Pequeno/genética , Sesquiterpenos/farmacologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
The analysis of Forsythia suspensa was performed on Waters Symmetry C18 column( 4. 6 mm×250 mm,5 µm) and mobile phase was methanol( A)-0. 1% formic acid aqueous solution( B) with the elution gradient. Column temperature was maintained at 30â,and the flow rate was 1. 0 m L·min-1 with detection wavelength 265 nm. The HPLC-PDA fingerprint of F. suspensa was optimized.Chemical constituents in F. suspensa were analyzed by UFLC-Q-TOF-MS in positive and negative ion mode. The quality of 48 batches of F. suspensa from different habitats,processing methods and specifications was evaluated by similarity evaluation and cluster analysis.The 18 common peaks were confirmed. The similarity of F. suspensa from different habitats was more than 0. 98,and 56 chemical constituents were identified. Different processing methods had great influence on the quality of F. suspensa. Compared with boiled and direct drying,the quality of F. suspensa processed by sun-drying was obviously decreased. The similarity was about 0. 58. Different specifications of F. suspensa also had obvious distinction,and the similarity was about 0. 78. The effective components of grown F. suspensa,such as forsythoside A and phillyrin,were significantly reduced. The results of cluster analysis were basically consistent with the results of similarity evaluation. The establishment of fingerprint and the recognition of chemical pattern of F. suspensa can provide a more comprehensive reference for the quality control of herbs.
Assuntos
Medicamentos de Ervas Chinesas/química , Forsythia/química , Cromatografia Líquida de Alta Pressão , Controle de QualidadeRESUMO
The currently utilized ligand fishing for bioactive molecular screening from complex matrixes cannot perform imaging screening. Here, we developed a new solid-phase ligand fishing coupled with an in situ imaging protocol for the specific enrichment and identification of heat shock protein 90 (Hsp 90) inhibitors from Tripterygium wilfordii, utilizing a multiple-layer and microkernel-based mesoporous nanostructure composed of a protective silica coating CdTe quantum dot (QD) core and a mesoporous silica shell, i.e., microkernel-based mesoporous (SiO2-CdTe-SiO2)@SiO2 fluorescent nanoparticles (MMFNPs) as extracting carries and fluorescent probes. The prepared MMFNPs showed a highly uniform spherical morphology, retention of fluorescence emission, and great chemical stability. The fished ligands by Hsp 90α-MMFNPs were evaluated via the preliminary bioactivity based on real-time cellular morphology imaging by confocal laser scanning microscopy (CLSM) and then identified by mass spectrometry (MS). Celastrol was successfully isolated as an Hsp 90 inhibitor, and two other specific components screened by Hsp 90α-MMFNPs, i.e., demecolcine and wilforine, were preliminarily identified as potential Hsp 90 inhibitors through the verification of strong affinity to Hsp 90 and antitumor bioactivity. The approach based on the MMFNPs provides a strong platform for imaging screening and discovery of plant-derived biologically active molecules with high efficiency and selectivity.
Assuntos
Compostos de Cádmio/química , Corantes Fluorescentes/química , Nanopartículas/química , Imagem Óptica , Dióxido de Silício/química , Telúrio/química , Tripterygium/química , Compostos de Cádmio/síntese química , Compostos de Cádmio/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/farmacologia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Células MCF-7 , Tamanho da Partícula , Porosidade , Dióxido de Silício/síntese química , Dióxido de Silício/farmacologia , Relação Estrutura-Atividade , Propriedades de Superfície , Telúrio/farmacologiaRESUMO
BACKGROUND/AIMS: Peperomin E (PepE), a natural secolignan isolated from the whole plant of Peperomia dindygulensis, has been reported by ourselves and others to display potent anti-cancer effects in many types cancer cells, especially gastric cancer. However, the effects of PepE on the metastasis of poorly-differentiated gastric cancer cells and the underlying molecular mechanisms have not been well elucidated. METHODS: We evaluated PepE effects on gastric cancer cell invasion and migration in vitro via wound healing and transwell assays and those on growth and metastasis in vivo using an orthotopic xenograft NOD-SCID mouse model. DNA methyltransferase (DNMT) activity was determined using a colorimetric DNMT activity/inhibition assay kit. PepE binding kinetics to DNMTs were determined using the bio-layer interferometry binding assay. Gene and protein levels of DNMTs, AMPKα-Sp1 signaling molecules, and metastatic-suppressor genes in PepE-treated gastric cancer cells were determined using quantitative reverse transcription-PCR arrays and western blotting. The effect of PepE on Sp1 binding to the DNMT promoter was determined by electrophoretic mobility-shift assay. Global DNA methylation levels were determined using liquid chromatography coupled with electrospray ionization tandem mass spectrometry. The methylation status of silenced metastatic-suppressor genes (MSGs) in gastric cancer cells was investigated by methylation-specific PCR. RESULTS: PepE can dose-dependently suppress invasion and migration of poorly-differentiated gastric cancer cells in vitro and in vivo with low toxicity against normal cells. Mechanistically, PepE not only covalently binds to the catalytic domain of DNMT1 and inhibits its activity (IC50 value 3.61 µM) but also down-regulates DNMT1, 3a, and 3b mRNA and protein expression in in gastric cancer cells, by disruption of the physical interaction of Sp1 with the DNMT1, 3a, and 3b promoter and mediation of the AMPKα-Sp1 signaling pathway. The dual inhibition activity of PepE toward DNMTs renders a relative global DNA hypomethylation, which induces MSG promoter hypomethylation (e.g., E-cadherin and TIMP3) and enhances their expression in gastric cancer cells. CONCLUSION: Collectively, our data indicated that PepE may represent a promising therapeutic lead compound for intervention in gastric cancer metastasis and may also exhibit potential as a DNA methylation inhibitor for use in epigenetic cancer therapy.
Assuntos
Benzodioxóis/farmacologia , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/química , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Benzodioxóis/química , Benzodioxóis/uso terapêutico , Sítios de Ligação , Movimento Celular/efeitos dos fármacos , DNA (Citosina-5-)-Metiltransferases/antagonistas & inibidores , DNA (Citosina-5-)-Metiltransferases/genética , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Simulação de Dinâmica Molecular , Regiões Promotoras Genéticas , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição Sp1/química , Fator de Transcrição Sp1/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Inibidor Tecidual de Metaloproteinase-3/genética , Inibidor Tecidual de Metaloproteinase-3/metabolismoRESUMO
Peperomin E (PepE), a naturally occurring secolignan isolated from Peperomia dindygulensis, has drawn much attention recently owing to its anticancer and DNA methyltransferase 1 (DNMT1) inhibitory activity. Here, a simple and sensitive ultra-fast liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of PepE in rat plasma for the first time. Samples were prepared by simple protein precipitation. Separation was performed on an XBridge™ C18 column using a mobile phase of acetonitrile and 0.1% (v/v) aqueous formic acid. PepE and the internal standard arctigenin were detected in a positive-ion mode using multiple reaction monitoring of the transitions at m/z 413.2 â 261.0 and 373.2 â 137.2, respectively. The calibration curve for PepE was linear over the range of concentrations of 1.46-6000 ng/mL, with a lower limit of quantitation of 1.46 ng/mL. Both intra- and interday precisions were within 11.05%, and the accuracy ranged from -11.5 to 5.51%. The extraction recovery and matrix effect were within acceptable limits. Stability tests showed that PepE remained stable throughout the analytical procedure. The validated method was then used to analyze the pharmacokinetics of PepE administered to rats orally (12.5 and 25 mg/kg) or intravenously (6.25 and 12.5 mg/kg).
Assuntos
Benzodioxóis/sangue , Cromatografia Líquida de Alta Pressão/métodos , DNA (Citosina-5-)-Metiltransferases/antagonistas & inibidores , Inibidores Enzimáticos/sangue , Espectrometria de Massas em Tandem/métodos , Administração Oral , Animais , Benzodioxóis/administração & dosagem , Benzodioxóis/análise , DNA (Citosina-5-)-Metiltransferase 1 , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/análise , Limite de Detecção , Masculino , Peperomia/química , Ratos , Ratos Sprague-DawleyRESUMO
Advanced lung cancer has poor prognosis owing to its low sensitivity to current chemotherapy agents. Therefore, discovery of new therapeutic agents is urgently needed. In this study, we investigated the antitumor effects of peperomin E, a secolignan isolated from Peperomia dindygulensis, a frequently used Chinese folk medicine for lung cancer treatment. The results indicate that peperomin E has antiproliferative effects, promoting apoptosis and cell cycle arrest in non-small-cell lung cancer (NSCLC) cell lines in a dose-dependent manner, while showing lower toxicity against normal human lung epidermal cells. Peperomin E inhibited tumor growth in A549 xenograft BALB/c nude mice without significant secondary adverse effects, indicating that it may be safely used to treat NSCLC. Furthermore, the mechanisms underlying the anticancer effects of peperomin E have been investigated. Using an in silico target fishing method, we observed that peperomin E directly interacts with the active domain of DNA methyltransferase 1 (DNMT1), potentially affecting its genome methylation activity. Subsequent experiments verified that peperomin E decreased DNMT1 activity and expression, thereby decreasing global methylation and reactivating the epigenetically silenced tumor suppressor genes including RASSF1A, APC, RUNX3, and p16INK4, which in turn activates their mediated pro-apoptotic and cell cycle regulatory signaling pathways in lung cancer cells. The observations herein report for the first time that peperomin E is a potential chemotherapeutic agent for NSCLC. The anticancer effects of peperomin E may be partly attributable to its ability to demethylate and reactivate methylation-silenced tumor suppressor genes through direct inhibition of the activity and expression of DNMT1.
Assuntos
Benzodioxóis/farmacologia , DNA (Citosina-5-)-Metiltransferases/antagonistas & inibidores , Inativação Gênica , Genes Supressores de Tumor , Neoplasias Pulmonares/genética , Ativação Transcricional/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Benzodioxóis/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , DNA (Citosina-5-)-Metiltransferases/química , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA , Modelos Animais de Doenças , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Modelos Moleculares , Conformação Molecular , Ligação Proteica , Relação Estrutura-AtividadeRESUMO
2,5-Dihydroxymethyl-3,6-dimethylpyrazine (liguzinediol) has been recently discovered as a potential agent for treatment of heart failure with low safety risk. In the present study, four main metabolites of liguzinediol were synthesized and their positive inotropic activities were evaluated. Synthetic compounds were identical with the isolated metabolites of liguzinediol. Pharmacological examinations showed that the four major metabolites were not observed positive inotropic activity, and revealed that the positive inotropic activity of liguzinediol was essentially attributed to the parent agent.
Assuntos
Cardiotônicos/síntese química , Pirazinas/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Masculino , Contração Muscular/efeitos dos fármacos , Pirazinas/síntese química , Pirazinas/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
To observe the effects of Atractylodis Macrocephale Rhizoma processed by different methods (sulfur-fumigation, different temperatures baking and microwave sterilization) on salivary amylase and D-xylose excretion rate in spleen deficiency rats. The rats were divided into blank control group, rhubarb-induced spleen deficiency model control group, and Atractylodis Macrocephale Rhizoma experimental groups processed with different methods. Amylase colorimetric method was used to determine the activities of salivary amylase and D-xylose excretion rate was measured with O-benzylamine method. Then the correlation of salivary amylase activity and D-xylose excretion rate in urinary was analyzed. As compared with blank control group, Atractylodis Macrocephale Rhizoma baked at 100,110 â can increase the unit content of rat salivary amylase and D-xylose excretion rate, with a significant difference (P<0.05). As compared with the model group, Atractylodis Macrocephale Rhizoma baked at 70 â and Atractylodis Macrocephale Rhizoma with microwave treatment had stronger effects than the others, with statistically significant differences (P<0.01). Atractylodis Macrocephale Rhizoma could improve D-xylose absorption function and salivary amylase activity in spleen deficiency rats. In addition, D-xylose excretion rate in urine was positively correlated with salivary amylase activity. Atractylodis Macrocephale Rhizoma processed with different temperatures baking and microwave sterilization had little impact on salivary amylase activity and D-xylose excretion rate in urine of spleen deficiency rats, while sulfur fumigation had great effects on the above two indexes.
Assuntos
Amilases/análise , Atractylodes/química , Medicamentos de Ervas Chinesas/farmacologia , Saliva/enzimologia , Xilose/análise , Animais , Ratos , Rizoma/químicaRESUMO
The potent positive inotropic effect, together with the relatively low safety risk of liguzinediol (LZDO), relative to currently available inotropic drugs, has prompted us to intensively research and develop LZDO as a potent positive inotropic agent. In this study, to obtain LZDO alternatives for oral chronic administration, a series of long-chain fatty carboxylic mono- and dual-esters of LZDO were synthesized, and preliminarily evaluated for physicochemical properties and bioconversion. Enhanced lipophilic properties and decreased solubility of the prodrugs were observed as the side chain length increased. All esters showed conspicuous chemical stability in phosphate buffer (pH 7.4). Moreover, the enzymatic hydrolysis of esters in human plasma and human liver microsomes confirmed that the majority of esters were converted to LZDO, with release profiles that varied due to the size and structure of the side chain. In vivo pharmacokinetic studies following oral administration of monopivaloyl (M5), monodecyl (M10) and monododecyl (M12) esters demonstrated the evidently extended half-lives relative to LZDO dosed alone. In particular the monopivaloyl ester M5 exhibited an optimal pharmacokinetic profile with appropriate physiochemical characteristics.
Assuntos
Cardiotônicos , Pró-Fármacos , Pirazinas , Administração Oral , Animais , Cardiotônicos/síntese química , Cardiotônicos/química , Cardiotônicos/farmacocinética , Cardiotônicos/farmacologia , Feminino , Humanos , Masculino , Microssomos Hepáticos/metabolismo , Plasma/metabolismo , Pró-Fármacos/síntese química , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Pró-Fármacos/farmacologia , Pirazinas/síntese química , Pirazinas/química , Pirazinas/farmacocinética , Pirazinas/farmacologia , RatosRESUMO
Liguzinediol (LZDO) ester prodrugs 3-5 were synthesized and evaluated in vitro and in vivo for their potential use in prolonging the half-life of the parent drug LZDO (1a) in vivo. Prodrugs 3-5 were found to display a potent positive inotropic effect on the myocardium, without the risk of arrhythmia. Prodrugs 3-5 rapidly underwent enzymatic hydrolysis to release the parent compound LZDO in 1-3 h in rat liver microsomes and rat plasma. The half-life of the parent compound was prolonged after intragastric administration of prodrug 3, which was found to be a superior prodrug candidate for increasing myocardial contractility.
Assuntos
Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Pirazinas/química , Pirazinas/farmacocinética , Animais , Pressão Sanguínea/efeitos dos fármacos , Estabilidade de Medicamentos , Coração/efeitos dos fármacos , Masculino , Microssomos Hepáticos/metabolismo , Contração Miocárdica/efeitos dos fármacos , Miocárdio/metabolismo , Pró-Fármacos/metabolismo , Pirazinas/metabolismo , RatosRESUMO
OBJECTIVE: To explore the characteristics of time-based prospective memory (TBPM) and event-based prospective memory (EBPM) in patients with severe traumatic brain injury (TBI) during recovery stage. METHODS: A total of 20 patients with severe TBI were recruited along with another 20 age, gender and education-matched healthy volunteers. The Chinese version of Cambridge Prospective Memory Test was used to assess the TBPM and EBPM characteristics. The TBPM score, EBPM score, time monitoring frequency, cue finding frequency, and whether or not the participants choose to take notes were recorded and compared between patients and controls. RESULTS: The TBPM and EBPM scores (9.05 ± 3.59, 11.35 ± 2.25 respectively) of TBI patients were lower than that of controls (14.95 ± 2.09, 16.45 ± 1.54, respectively) (P < 0.05). Compared with the controls, time monitoring frequency of the patients[times] was less (1 (1, 2) vs 4 (3, 5.25) times) (P < 0.05); cue discovery frequency also less (2 (2, 3) vs 5 (4.25, 5) times). And there were fewer note-taking subjects in TBI group (P < 0.05). CONCLUSION: With deficits in both the time- and event-based prospective memory, the TBI patients have difficulty of finding time or event cue during interference and auxiliary memory strategy is rarely utilized to realize the prospective memory tasks.
Assuntos
Traumatismos Craniocerebrais/psicologia , Memória Episódica , Adulto , Estudos de Casos e Controles , Convalescença , Traumatismos Craniocerebrais/reabilitação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
To establish a fingerprint spectrum for Atractylodis Macrocephalae Rhizoma stir-fried with wheat bran based on UFLC/Q-TOF-MS, and make a principal component analysis (PCA) with Markview software, in order to compare the changes of components between raw and processed Atractylodis Macrocephalae Rhizoma with raw wheat bran as the blank. The results showed that the changed in components raw Atractylodis Macrocephalae Rhizoma and Atractylodis Macrocephalae Rhizoma stir-fried with wheat bran were apparently observed by PCA. Six compounds were identified to have significant changes in mass fraction before and after being stir-fried, namely atractylenolide-I, atractylenolide-II, atractylenolide-III, atractylentrid, atractylon and an unknown compound. Among them, atractylenolide-I and atractylenolide-II generated from dehydration and dehydrogenation of atractylenolide-III may be the material base of Atractylodis Macrocephalae Rhizoma stir-fried with wheat bran for strengthening spleen.
Assuntos
Atractylodes/química , Cromatografia Líquida/métodos , Fibras na Dieta , Lactonas/análise , Espectrometria de Massas , Análise de Componente Principal , Sesquiterpenos/análiseRESUMO
The function of the p53 protein is impaired by the overexpression of its negative regulator murine double minute 2 protein (MDM2) and homologous protein MDMX. Disruption of the p53-MDM2/MDMX interaction to restore the transcriptional function of p53 is considered a promising strategy for cancer therapy. To design dual MDM2/MDMX inhibitors, the binding modes of MDM2 or MDMX with their inhibitors are elucidated. Several hot-spot residues of MDM2 or MDMX are identified by molecular dynamics simulations, alanine scanning and MM-GBSA calculations. Then, focusing on the interaction with hot-spot residues, two series of derivatives bearing 1,3-diketone and α-aminoketone scaffolds are designed and synthesized. Among these compounds, C16 is identified as the most potent compound with low micromolar binding affinities with MDM2 and MDMX. C16 also displays moderate antiproliferative activities against MDM2-overexpressing and MDMX-overexpressing cells, with IC50 values of 0.68 µM in HCT116 cells and 0.54 µM in SH-SY5Y cells. Furthermore, C16 inhibits cell migration and invasion, reactivates the function of p53, arrests the cell cycle and induces cellular apoptosis in HCT116 and SH-SY5Y cells. Collectively, C16 can be developed as a dual MDM2 and MDMX inhibitor for cancer therapy.
Assuntos
Antineoplásicos , Neuroblastoma , Camundongos , Animais , Humanos , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Proteínas de Ciclo Celular/metabolismo , Antidepressivos , Ligação ProteicaRESUMO
Radiation therapy is considered the most effective non-surgical treatment for brain tumors. However, there are no available treatments for radiation-induced brain injury. Bisdemethoxycurcumin (BDMC) is a demethoxy derivative of curcumin that has anti-proliferative, anti-inflammatory, and anti-oxidant properties. To determine whether BDMC has the potential to treat radiation-induced brain injury, in this study, we established a rat model of radiation-induced brain injury by administering a single 30-Gy vertical dose of irradiation to the whole brain, followed by intraperitoneal injection of 500 µL of a 100 mg/kg BDMC solution every day for 5 successive weeks. Our results showed that BDMC increased the body weight of rats with radiation-induced brain injury, improved learning and memory, attenuated brain edema, inhibited astrocyte activation, and reduced oxidative stress. These findings suggest that BDMC protects against radiation-induced brain injury.
RESUMO
Objective: More than half of post-stroke patients develop dysphagia, which manifests as delayed swallowing and is associated with a high risk of aspiration. In this study, we aimed to investigate the immediate effect of neuromuscular electrical stimulation (NMES) on swallowing initiation in post-stroke patients using videofluoroscopic swallowing study (VFSS) data. Materials and methods: This randomized, self-controlled crossover study included 35 patients with post-stroke dysphagia. All selected patients received real and sham NMES while swallowing 5 ml of thin liquid. Participants completed the conditions in random order, with a 10-min interval between conditions. The primary evaluation indicators included the Modified Barium Swallow Impairment Profile-6 (MBSImp-6) and Penetration-Aspiration Scale (PAS). Secondary indicators included oral transit time (OTT), pharyngeal transit time (PTT), and laryngeal closure duration (LCD). Results: Modified Barium Swallow Impairment Profile-6 (P = 0.008) and PAS (P < 0.001) scores were significantly lower in the Real-NMES condition than in the Sham-NMES condition. OTT (P < 0.001) was also significantly shorter during Real-NMES than during Sham-NMES. However, LCD (P = 0.225) and PTT (P = 0.161) did not significantly differ between the two conditions. Conclusion: Neuromuscular electrical stimulation may represent a supplementary approach for promoting early feeding training in patients with post-stroke dysphagia. Clinical trial registration: [https://clinicaltrials.gov/], identifier [ChiCTR2100052464].
RESUMO
In this study, daphnetin and its major metabolites in the intestinal wall of rats were identified by liquid chromatography and quatrupole-time of flight mass spectrometry. Perfusion fluid of duodenum, jejunum, ileum and colon were collected separately for 2 hours from the rat intestine following perfusion with daphnetin. The metabolites of daphnetin in the perfusion fluid of different intestine segments were analyzed by the liquid chromatography and quatrupole-time of flight mass spectrometry. It is shown that the parent drug daphnetin and four metabolites were found in the perfusion fluid of duodenum, jejunum and ileum. However, no metabolites were found in the colon. Among the four metabolites, two daphnetin sulfates (m/z 257) were first discovered as the phase II metabolites of daphnetin in rats, which revealed a new way of daphnetin metabolism in rats.
Assuntos
Mucosa Intestinal/metabolismo , Perfusão , Umbeliferonas/metabolismo , Umbeliferonas/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão , Colo/metabolismo , Duodeno/metabolismo , Íleo/metabolismo , Jejuno/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
OBJECTIVE: To compare the difference of muscle dynamic characteristics for the ankle dorsiflexors and plantarflexors between stroke patients at the chronic stage and healthy controls so as to provide a new method of assessing the in vivo muscle function in patients with hemiplegia. METHODS: From May 2008 to May 2009, 26 stroke patients and 21 age-and gender-matched normal controls were recruited. All subjects were positioned on a scanner table and requested to perform the voluntary movement of ankle flexion-extension. The velocity encoded phase contrast magnetic resonance imaging (VE-PC MRI) provided the images of tibialis anterior muscle (TA), medial head of gastrocnemius muscle (MG) and soleus muscle (SOL) during a movement cycle. By measuring the calf muscle contraction velocity, the balance function was assessed by Berg balance scale (BBS). The correlation between scores of BBS and the mean maximum velocity were compared and analyzed. RESULTS: The peak velocity of TA (1 - 8 phase, 8.900 - 21.120 mm/s vs 12.99 - 34.50 mm/s), MG (12-19phase, 13.60 - 13.28 mm/s vs 25.85 - 18.38 mm/s) and SOL (12 - 16 phase, 18.63 - 33.62 mm/s vs 27.68 - 47.22 mm/s) was lower in the affected side than that in the controls during ankle extension (P < 0.05); During ankle dorsiflexion, the co-contraction index of SOL/TA (2 - 9 phase, 0.81 - 0.82 vs 0.27 - 0.44) and the co-contraction index of GM/TA (2 - 9 phase, 0.73 - 0.58 vs 0.10 - 0.11) was markedly higher in the affected side than the controls. The patient score of BBS was negatively correlated with the mean velocity of TA (r = -0.69, P = 0.001) and GM (r = -0.47, P = 0.01) in the affected side. There was correlation between TA (r = -0.60, P = 0.001) and GM (r = -0.49, P = 0.01) in the unaffected side. CONCLUSION: During the movement of active ankle flexion-extension, the velocities of TA, SOL and MG are lower in the affected side. The co-contraction index is markedly higher in the affected side during ankle dorsiflexion. This in turn leads to a decline of balance function in patients. VE-PC MRI can provide quantitative in vivo measurements of lower extremity muscle function in stroke patients.