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Pruni Semen, the dried ripe seed of Prunus humilis, P. japonica, or P. pedunculata as recorded in the Chinese Pharmacopoeia, has been widely used in pharmaceutical and food industries. The adulteration of the marketed product with morphologically similar plants of the same genus has led to variable product quality and clinical effectiveness. This study systematically investigated the phylogenetic relationships, morphological traits, and chemical profiles of 37 Pruni Semen samples from planting bases, markets, and fields. DNA barcoding could successfully distinguish the genuine and counterfeit Pruni Semen, and the results indicated that there was almost no authentic Pruni Semen available in the market. The samples were divided into "big seed" (P. pedunculata and P. salicina seeds) and "small seed" (P. humilis, P. japonica, P. tomentosa, and P. avium seeds) categories based on morphology results. The notable discrepancy in the chemical characteristics of "big seed" and "small seed" was that "small seeds" were rich in flavonoids and low in amygdalin, whereas "big seeds" were the opposite. Furthermore, principal component analysis and clustered heatmap analysis verified the distinguishing features of "big seed" and "small seed" based on morphological and chemical characteristics. This study suggested that a combination of DNA barcoding and morphological and chemical characteristics can aid in the identification and quality evaluation of authentic and adulterated Pruni Semen. These findings may help standardize Pruni Semen available in the market and protect the rights and interests of customers.
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Código de Barras de DNA Taxonômico , Filogenia , Prunus , Sementes , Sementes/química , Prunus/química , Prunus/classificação , Prunus/genética , Amigdalina , Flavonoides/análise , Contaminação de Medicamentos , China , Compostos FitoquímicosRESUMO
BACKGROUND: The immune checkpoint inhibitor (ICI) anti-PD-L1 monoclonal antibody can inhibit the progress of hepatocellular carcinoma (HCC). Epithelial-mesenchymal transformation (EMT) can promote tumor migration and the formation of immune-suppression microenvironment, which affects the therapeutic effect of ICI. Yin-yang-1 (YY1) is an important transcription factor regulating proliferation, migration and EMT of tumor cells. This work proposed a drug-development strategy that combined the regulation of YY1-mediated tumor progression with ICIs for the treatment of HCC. METHODS: We first studied the proteins that regulated YY1 expression by using pull-down, co-immunoprecipitation, and duo-link assay. The active compound regulating YY1 content was screened by virtual screening and cell-function assay. Isorhamnetin (ISO) and anti-PD-L1 antibody dual-functional mesoporous silica nanoparticles (HMSN-ISO@ProA-PD-L1 Ab) were prepared as an antitumor drug to play a synergistic anti-tumor role. RESULTS: YY1 can specifically bind with the deubiquitination enzyme USP7. USP7 can prevent YY1 from ubiquitin-dependent degradation and stabilize YY1 expression, which can promote the proliferation, migration and EMT of HCC cells. Isorhamnetin (ISO) were screened out, which can target USP7 and promote YY1 ubiquitin-dependent degradation. The cell experiments revealed that the HMSN-ISO@ProA-PD-L1 Ab nanoparticles can specifically target tumor cells and play a role in the controlled release of ISO. HMSN-ISO@ProA-PD-L1 Ab nanoparticles inhibited the growth of Hepa1-6 transplanted tumors and the effect was better than that of PD-L1 Ab treatment group and ISO treatment group. HMSN-ISO@ProA-PD-L1 Ab nanoparticles also exerted a promising effect on reducing MDSC content in the tumor microenvironment and promoting T-cell infiltration in tumors. CONCLUSIONS: The isorhamnetin and anti-PD-L1 antibody dual-functional nanoparticles can improve tumor immune microenvironment and inhibit YY1-mediated tumor progression. This study demonstrated the possibility of HCC treatment strategies based on inhibiting USP7-mediated YY1 deubiquitination combined with anti-PD-L1 monoclonal Ab.
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Carcinoma Hepatocelular , Neuropatia Hereditária Motora e Sensorial , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Microambiente Tumoral , Peptidase 7 Específica de Ubiquitina , Ubiquitinas/farmacologia , Linhagem Celular Tumoral , Fator de Transcrição YY1/metabolismoRESUMO
BACKGROUND: Sepsis is one of the major threats to human health with high mortality. Simiao Yong'an decoction (SMYAD) has the efficacy of anti-inflammation, improving coagulation and microcirculation, which is applicable for the clinical assistance treatment of sepsis. Yet, its material basis and relevant mechanisms are still vague. PURPOSE: Explore the quality markers (Q-markers), biomarkers and potential mechanisms of SMYAD combined with imipenem/cilastatin sodium for anti-sepsis. METHODS: Linear-Trap-LC/MSn was employed to profile the compounds in the extract and medicated serum of SMYAD. Then, the components and targets obtained from databases were applied to network pharmacology. Q-markers' range was narrowed via the affinity of three times docking and determined as per its screening criteria. Also, the content of them was detected by HPLC. Next, cecal ligation and puncture (CLP) model was reproduced to observe the effect of SMYAD united antibiotic by survival rate, histopathology score, ELISA, western blot and qPCR. Finally, metabolomics based upon GC-MS was exerted to discover the differential endogenous metabolites, metabolic pathway and joint pathway of SMYAD combined with antibiotic for sepsis. RESULTS: The 25 serum migrant ingredients derived from 113 chemical compounds of SMYAD were identified for the first time, and 6 components were determined as the Q-markers of SMYAD. The enrichment analysis indicated that the potential mechanism was mainly associated with the IL-17 signaling pathway, complement-coagulation cascades signaling pathway and VEGF signaling pathway. Then, SMYAD united antibiotic declined the mortality of septic rats, restored cytokine levels, ameliorated histopathological lesions and decreased the mRNA and protein expression of target proteins in a dose-dependent way. Furthermore, 8 differential metabolites were regarded as latent biomarkers related to the antiseptic effect of SMYAD united antibiotic, which were mainly involved in the Citrate cycle (TCA cycle) metabolic pathway. CONCLUSIONS: Different skeletons of compounds, including iridoids, phenylpropanoids, organic acids, triterpenes and others, were the main compositions of SMYAD. Among them, 6 components were determined as the Q-markers, which provided a basis for the construction of quality standards for this ancient classic formula. The combination therapy of SMYAD and antibiotic obviously ameliorated inflammatory reaction, coagulation dysfunction and microcirculation abnormalities for sepsis by inhibiting IL-17 signaling pathway, complement-coagulation cascades signaling pathway and VEGF signaling pathway.
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Medicamentos de Ervas Chinesas , Sepse , Humanos , Ratos , Animais , Medicamentos de Ervas Chinesas/farmacologia , Interleucina-17 , Antibacterianos/farmacologia , Fator A de Crescimento do Endotélio Vascular , Sepse/tratamento farmacológico , Controle de QualidadeRESUMO
Objective: To elucidate the mechanism of Spatholobi Caulis (SC) in treating osteoporosis (OP) integrated zebrafish model and bioinformatics. Methods: Skeleton staining coupled with image quantification was performed to evaluate the effects of SC on skeleton mineralization area (SSA) and total optical density (TOD). Zebrafish locomotor activity was monitored using the EthoVision XT. Bioactive compounds of SC and their corresponding protein targets were acquired from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Potential therapeutic targets for OP were summarized through retrieving 5 databases, and then, the overlapping genes between SC and OP were acquired. The core genes were selected by CytoHubba. Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) functional analysis of the intersection target genes were carried out by R software. Finally, the molecular docking simulation was manipulated between the ingredients and the hub genes. Results: Compared with the model group, SC significantly increased the SSA and TOD at 10 mg/mL and improved the locomotor activity in a dose-dependent manner (p < 0.001). 33 components of SC were associated with 72 OP-related genes including 10 core genes (MAPK1, VEGFA, MMP9, AKT1, AR, IL6, CALM3, TP53, EGFR, and CAT). Advanced Glycation End Product (AGE) Receptor for AGE (RAGE) signaling pathway was screened out as the principal pathway of SC in anti-OP. The bioactive components (Aloe-emodin, Emodin, Formononetin, Licochalcone A, Luteolin, and Lopac-I-3766) have excellent affinity to core genes (MAPK1, VEGFA, MMP9, AKT1, and IL6). Conclusion: SC had the hierarchical network characteristics of "multicomponents/multitargets/multifunctions/multipathways" in reversing OP, but AGE-RAGE signaling pathway may be the main regulatory mechanism.
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BACKGROUND: Multiflorin A (MA) is a potential active ingredient of traditional herbal laxative, Pruni semen, with unusual purgative activity and an unclear mechanism, and inhibiting intestinal glucose absorption is a promising mechanism of novel laxatives. However, this mechanism still lacks support and a description of basic research. PURPOSE: This study aimed to determine the main contribution of MA to the purgative activity of Pruni semen and elucidate the effect intensity, characteristics, site, and mechanism of MA in mice, and determine the novel mechanism of traditional herbal laxatives from the perspective of intestinal glucose absorption. METHODS: We induced diarrhoea in mice by administering Pruni semen and MA, and the defecation behaviour, glucose tolerance, and intestinal metabolism were analysed. The effects of MA and its metabolite on peristalsis of the intestinal smooth muscle were evaluated using an intestinal motility assay in vitro. Intestinal tight junction proteins, aquaporins, and glucose transporters expression were analysed using immunofluorescence; gut microbiota and faecal metabolites were analysed using 16S rRNA and liquid chromatography-mass spectrometry. RESULTS: MA administration (20 mg/kg) induced watery diarrhoea in over half of the experimental mice. The activity of MA in lowering peak postprandial glucose levels was synchronous with purgative action, with the acetyl group being the active moiety. MA was metabolised primarily in the small intestine, where it decreased sodium-glucose cotransporter-1, occludin, and claudin1 expression, then inhibited glucose absorption, resulting in a hyperosmotic environment. MA also increased the aquaporin3 expression to promote water secretion. Unabsorbed glucose reshapes the gut microbiota and their metabolism in the large intestine and the increasing gas and organic acid promoted defecation. After recovery, the intestinal permeability and glucose absorption function returned, and the abundance of probiotics such as Bifidobacterium increased. CONCLUSION: The purgative mechanism of MA involves inhibiting glucose absorption, altering permeability and water channels to promote water secretion in the small intestine, and regulating gut microbiota metabolism in the large intestine. This study is the first systematic experimental study on the purgative effect of MA. Our findings provide new insight into the study of novel purgative mechanisms.
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Catárticos , Glucose , Camundongos , Animais , Catárticos/farmacologia , Glucose/farmacologia , Laxantes/farmacologia , RNA Ribossômico 16S , Permeabilidade , Diarreia , Água , Absorção IntestinalRESUMO
To clarify the impact of human activities on the natural environment, as well as the current ecological risks to the environment surrounding Zhushan Bay in Taihu Lake, the characteristics of deposited organic materials, including elements and 16 polycyclic aromatic hydrocarbons (∑16PAHs), in a sediment core from Taihu Lake were determined. The nitrogen (N), carbon (C), hydrogen (H), and sulfur (S) contents ranged from 0.08 to 0.3%, 0.83 to 3.6%, 0.63 to 1.12%, and 0.02 to 0.24%, respectively. The most abundant element in the core was C followed by H, S, and N, while elemental C and the C/H ratio displayed a decreasing trend with depth. The ∑16PAH concentration was in the range of 1807.48-4674.83 ng g-1, showing a downward trend with depth, with some fluctuations. Three-ring PAHs dominated in surface sediment, while 5-ring PAHs dominated at a depth of 55-93 cm. Six-ring PAHs appeared in the 1830s and gradually increased over time before slowly decreasing from 2005 onward due to the establishment of environmental protection measures. The ratio of PAH monomers indicated that PAHs in samples from a depth of 0 to 55 cm were mainly derived from the combustion of liquid fossil fuels, while the PAHs in the deeper samples mainly originated from petroleum. The results of a principal component analysis (PCA) showed that the PAHs in the sediment core of Taihu Lake were mainly derived from the combustion of fossil fuels, such as diesel, petroleum, gasoline, and coal. The contributions of biomass combustion, liquid fossil fuel combustion, coal combustion, and unknown source were 8.99%, 52.68%, 1.65%, and 36.68%, respectively. The results of a toxicity analysis indicated that most of the PAH monomers had little impact on the ecology, and the annual increase of a small number of monomers might have toxic effects on the biological community, resulting in a serious ecological risks, that requires the imposition of control measures.
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Poluentes Ambientais , Petróleo , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Humanos , Poluentes Ambientais/análise , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Sedimentos Geológicos/análise , China , Combustíveis Fósseis/análise , Petróleo/análise , Carvão Mineral/análise , Medição de Risco , Hidrocarbonetos Policíclicos Aromáticos/análise , Lagos/análiseRESUMO
Leonurus japonicus Houtt. (Motherwort) is the fresh or dried aerial part of Leonurus japonicus Houtt. (Labiaceae), which is widely used in clinical practice and daily life, used to treat gynecological diseases. However, the differences between different parts, single index component in Pharmacopoeias and the less stability of active ingredients affect its clinical efficacy. This study aimed to find the multi-active compounds between different parts of Motherwort to ensure its clinical efficacy, which related to stability and had pharmacokinetic behavior. Firstly, HPLC-Q-TOF-MS/MS was used to analyze the components in vitro and in vivo, as well as multivariate statistical analysis and network pharmacology analysis was conducted to find the significant different components related to activity. Secondly, the content determination methods were established to study the stability of effective components during storage in order to establish the content limit for quality control of Motherwort. Thirdly, UFLC-MS/MS was used to analyze the pharmacokinetic behavior of active components in Motherwort. The results showed that a total of 131 chemical constituents were identified in vitro and 21 prototype absorption compounds and 72 metabolites were found in vivo. Meantime, multivariate statistical analysis and network pharmacology analysis was combined to find that leonurine, stachydrine and trigonelline were activity-related substance, which could be used as active components related to pharmacodynamics in different parts. Then the stability variation trend and content limit of three alkaloids were found, which could be used for the quality control of Motherwort. Furthermore, the results showed that three alkaloids had pharmacokinetic behavior in vivo. 3 alkaloids were screened, which could be used as active components most closely related to pharmacodynamics among different parts. The stable stage, assay tolerance and pharmacokinetic characteristics were studied by the active substances, which could provide a basis for quality control and clinical medication of Motherwort.
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Medicamentos de Ervas Chinesas , Leonurus , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Leonurus/química , Controle de Qualidade , Espectrometria de Massas em TandemRESUMO
Osteoporosis is a degenerative disease that endangers human health. At present, chemical drugs used for osteoporosis have serious side effects. Therefore, it is valuable to search herbs with high safety and good curative effect in antiosteoporosis. Erzhi formula (EZF), an ancient classic compound, has been reported to have a beneficial effect in antiosteoporosis, but its mechanism is unclear. In this paper, the active compounds of EZF were found in Systems Pharmacology Database, and gene targets related to osteoporosis were obtained in GeneCards. The GO functional and KEGG pathway enrichment analysis were performed by Metascape. The network of "components-targets-signal pathway" was constructed by Cytoscape. Next, molecular docking between the active components and hub genes related to the PI3K-Akt signaling pathway was conducted by Autodock. In the verification experiment, the zebrafish induced by prednisolone (PNSL) was used to reproduce glucocorticoid-induced osteoporosis (GIOP) model, and then the reversal effects of EZF were systematically evaluated according to the behavior, skull staining area, bone mineralization area (BMA), average optical density (AOD), and cumulative optical density (COD). Finally, it was shown that 24 components in EZF could regulate 39 common gene targets to exert antiosteoporosis effect. Besides, the main regulatory mechanisms of EZF were 4 signaling pathways: PI3K-Akt, JAK-STAT, AGE-RAGE, and cancer pathway. In PI3K-Akt signaling pathway, wedelolactone, dimethyl wedelolactone, specnuezhenide, ursolic acid, acacetin, beta-sitosterol, apigenin, and kaempferol can bind tightly with EGF, IL-2, and IL-4 genes. Compared with the model group, the moving distance, swimming speed, and cumulative swimming time of zebrafish in EZF group were significantly increased (P < 0.05). Meanwhile, the BMA and COD of zebrafish were significantly improved after the intervention of EZF (P < 0.05). In summary, the 24 components of EZF exert their antiosteoporosis effects by regulating 39 related gene targets, among which the PI3K signaling pathway is crucial. EZF can promote bone formation and reversed GIOP through "multicomponent/multitarget/multipathway" and the medium dose of EZF may be the most suitable concentration for the treatment of GIOP in zebrafish model.
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OBJECTIVE: The primary purpose of this study is to structure the available evidence relating to physical exercise programs and their impact on patients' cardiovascular system during the convalescence for breast cancer. METHODS: We searched six English databases and four Chinese databases from inception to May 19, 2021. Two reviewers independently screened literature, extracted data. They assessed the risk of bias according to the eligibility criteria, and the Cochrane Collaboration RevMan 5.3.0 version software and STATA 15.0 software were used for this meta-analysis. This study has been registered in the International Prospective Register of Systematic Reviews (CRD42021226319). RESULTS: In total, 3483 articles were screened and data from 11 randomized controlled trials (RCTs) involving 666 breast cancer patients were used in this meta-analysis. The results showed that exercise could decrease systolic blood pressure (SBP) (P = 0.006), diastolic blood pressure (DBP) (P = 0.0003), triglycerides (TG) levels (P < 0.00001), body mass index (BMI) (P = 0.009). Results also showed that exercise could significantly increase peak oxygen uptake (VO2peak) (P = 0.009), maximal oxygen consumption (VO2max) (P = 0.01), and High-density leptin cholesterol (HDL-C) levels (P < 0.0001). However, compared with the control group, there was no significant changes of mean arterial pressure (MAP), peak heart rate (HRpeak), and peak respiratory exchange ratio (PERpeak) (P > 0.05). CONCLUSIONS: Physical exercise could improve the cardiovascular system function associated with decreased the levels of SBP, DBP, TG, and increased the levels of VO2peak, VO2max, and HDL-C in breast cancer patients. These findings reveal that exercise may be a promising means for cardiovascular nursing.
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Neoplasias da Mama , Doenças Cardiovasculares , Sistema Cardiovascular , Neoplasias da Mama/terapia , Doenças Cardiovasculares/terapia , Exercício Físico , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Chemical constituents from aerial parts of Glycyrrhiza uralensis were analyzed and identified using ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS). The chromatographic column of Waters Acquity UPLC BEH-C_(18)(2.1 mm×100 mm, 1.7 µm) was adopted, with acetonitrile-water(0.5% formic acid) as mobile phase at a flow rate of 0.2 mL·min~(-1). Data was collected in positive and negative modes of electrospray ionization(ESI). A total of 55 compounds, including 42 flavonoids, 9 stilbenes, 2 coumarins, 1 lignin and 1 phenolic acid, which were characterized in the aerial parts of G. uralensis based on accurate molecular mass information of molecular and product ions provided by UPLC-Q-Exactive Orbitrap-MS based on comparison with standard substances and references. It is an effective and accurate method to provide chemical information of constituents in aerial parts of G. uralensis, and can provide a reference for further study on pharmacodynamic material basis and resources development and utilization.
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Medicamentos de Ervas Chinesas , Glycyrrhiza uralensis , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Componentes Aéreos da PlantaRESUMO
AIM OF THE STUDY: The husks of Xanthoceras sorbifolia Bunge mainly used in north China as folk medicine were reported to have potential protective effect on cognitive impairment. However, the mechanism remains unclear. In order to fully understand the mechanism of the protection, a complementary study of the husks was conducted. MATERIALS AND METHODS: The urinary and fecal metabolomics were used to analyze the potential biomarkers by the liquid chromatography-tandem time of flight mass spectrometry, and the16S rDNA technology was applied to conduct the analysis of microbiota species in the fecal samples of the rats, which is a significant influencing factor for the development of cognitive impairment. RESULTS: In metabolomics study, ten potential metabolic biomarkers, which are hippuric acid, kynurenic acid, creatinine, phenylalanine, xanthurenic acid, phenylacetylglycine, succinyladenosine, cresol sulfate, tryptophan 2-C-mannoside and N4-Acetylcytidine in urine, along with two, including isoleucine and phenylalanine in feces, were preliminarily identified, involving multiple pathways such as tryptophan, purine, kynurenine, and phenylalanine metabolism. The perturbation of these metabolic pathways could be related with insulin resistance, oxidative stress, energy metabolism deficit and neuroinflammation, which were risk factors to cause cognitive impairment. In gut microbiota analysis, the relative abundance of c_Bacteroidia, c_Alphaproteobacteria, f_Prevotellaceae, f_Sphingomonadaceae, f_Burkholderiaceae, g_Prevotellaceae_NK3B31_group and p_Bacteroidetes was significantly changed in the rats with cognitive impairment. Spearman's analysis showed obvious correlation between the metabolites and the microbiota species. In the rats with pretreatment of the husks extract, metabolites maintained a relative normal level, and the husks extract could regulate the gut microbiota, especially f_Prevotellaceae and g_Prevotellaceae_NK3B31_group, indicating the effect of the husks on the metabolic pathways via GMs. Such amino acids as isoleucine and phenylalanine failed to show any significant correlation with the microbiota species, indicating that the husks exhibited the potential protective effect through gut microbiota and other pathways. CONCLUSIONS: The husks extract could improve the intestinal microenvironment, and the stability of intestinal microenvironment was associated with normality of tryptophan, purine, kynurenine and phenylalanine metabolic pathways etc, which probably had an effect on cognitive function. This complementary work suggested that gut microbiotas were potential targets of the husks to exert its effect on cognitive impairment.
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Transtornos Cognitivos/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sapindaceae/química , Animais , Biomarcadores/metabolismo , Cognição/efeitos dos fármacos , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/microbiologia , Modelos Animais de Doenças , Masculino , Metabolômica , Ratos , Ratos Sprague-DawleyRESUMO
Rationale: Malignant ascites caused by cancer cells results in poor prognosis and short average survival time. No effective treatment is currently available for malignant ascites. In this study, the effects of lentinan (LNT)-functionalized selenium nanoparticles (Selene) on malignant ascites were evaluated. Furthermore, the mechanism of Selene targeting mitochondria of tumor cells were also investigated. Methods: Selene were synthesized and characterized by TEM, AFM and particle size analysis. The OVCAR-3 and EAC cells induced ascites models were used to evaluate the effects of Selene on malignant ascites. Proteomic analysis, immunofluorescence, TEM and ICP-MS were used to determine the location of Selene in tumor cells. Mitochondrial membrane potential, ROS, ATP content, and caspase-1/3 activity were detected to evaluate the effect of Selene on mitochondrial function and cell apoptosis. Immunofluorescence, Co-IP, pull-down, duolink, Western blot, and FPLC were used to investigate the pathway of Selene targeting mitochondria. Results: Selene could effectively inhibit ascites induced by OVCAR-3 and EAC cells. Selene was mainly located in the mitochondria of tumor cells and induced apoptosis of tumor cells. The LNT in Selene was involved in caveolae-mediated endocytosis through the interaction between toll-like receptor-4 (TLR4) and caveolin 1 (CAV1). Furthermore, the Selene in the endocytic vesicles could enter the mitochondria via the mitochondrial membrane fusion pathway, which was mediated by TLR4/TNF receptor associated factor 3 (TRAF3)/mitofusin-1 (MFN1) protein complex. Conclusion: Selene is a candidate anticancer drug for the treatment of malignant ascites. And TLR4/TRAF3/MFN1 may be a specific nano-drug delivery pathway that could target the mitochondria.
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GTP Fosfo-Hidrolases/metabolismo , Lentinano/farmacologia , Mitocôndrias/efeitos dos fármacos , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Nanopartículas/química , Selênio/farmacologia , Fator 3 Associado a Receptor de TNF/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cavéolas/efeitos dos fármacos , Cavéolas/metabolismo , Linhagem Celular Tumoral , Endocitose/efeitos dos fármacos , Feminino , Humanos , Lentinano/química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Proteômica/métodos , Espécies Reativas de Oxigênio/metabolismo , Selênio/química , Transdução de Sinais/efeitos dos fármacosRESUMO
In the manuscript, water-soluble polysaccharides WPNI was extracted from notopterygium incisum roots and separated into two homogeneous fractions WPNI-A-a and WPNI-A-b. WPNI-A-a was an arabinogalactan (AG). WPNI-A-b belonged to HG type pectin. The structure of WPNI-A-b was analyzed by FT-IR, NMR, enzymatic hydrolysis (Endo-PG) and UPLC-FLD-MSn. WPNI-A-b was dominated by HG domain, covalently linked with AG and RG-II domains. Oligogalacturonides produced by Endo-PG from HG domain were non-, mono-, di- or tri-methyl esterified with degree of polymerization (DP) from 1 to 6. The distribution of methyl-ester groups was in a block-wise manner. The interaction of WPNI-A-b and its enzymatic hydrolysis products with galectin-1, galectin-3, galectin-7 and galectin-8 showed that AG domain exhibited stronger binding avidity to galectins than RG-II and HG domain, while oligogalacturonides showed no binding activities to galectins. The results would be useful for the application of the pectin from notopterygium incisum.
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Apiaceae/química , Galectinas/química , Pectinas , Raízes de Plantas/química , Pectinas/química , Pectinas/isolamento & purificaçãoRESUMO
Galectin-3 (Gal-3) can induce T-cell activation and apoptosis and plays a role in tumor immune tolerance. Here, we demonstrate that ginseng pectins selectively inhibit Gal-3-induced T-cell apoptosis, while not affecting T-cell activation. This finding stands in contrast to that from the use of modified citrus pectin (MCP) and potato galactan (P-galactan) that inhibit both. Whereas PKC/ERK and ROS/ERK pathways are involved in both T-cell activation and apoptosis, the Ras/PI3K/Akt pathway is unique to T-cell activation. Ginseng pectins selectively inhibit the ROS/ERK pathway. Using the Sarcomar-180 mouse model in which Gal-3 expression is increased, we found that ginseng pectins (but not MCP or P-galactan) significantly promote T-cell proliferation and IL-2 expression, and inhibit tumor growth by 45%. These in vivo data correlate well with selective effects of pectins on Gal-3-mediated T-cell apoptosis and activation. Our study suggests a novel approach for the development of polysaccharide-based agents that target Gal-3 function.
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Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Galactanos/farmacologia , Galectina 3/metabolismo , Panax/metabolismo , Pectinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Linfócitos T , Animais , Linhagem Celular Tumoral , Humanos , Interleucina-2/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
Sinomenine is a pure alkaloid with immunosuppressive effects that is extracted from the Chinese medicinal plant Sinomenium acutum. We studied the therapeutic effects of sinomenine on inflammatory bowel disease. In this study, we randomly divided mice into the following ten groups: Control group; DSS-induced colitis group; Salicylazosulfapyridine (SASP)-treated group; Chitosan-treated group; low-, medium-, and high-dose sinomenine-treated and sinomenine enteric-coated microspheres-treated groups. We recorded changes in colon length, disease activity index (DAI), and colon pathology, measured TLR4, MyD88, SIGIRR, NF-κB p65 protein levels and inflammatory serum cytokine levels. Except for the Control group, the weight of mice in each group decreased, the DAI of the DSS-induced colitis group was significantly higher than the other groups, and the DAIs of the sinomenine- and sinomenine enteric-coated microspheres-treated groups were significantly lower than that of the SASP-treated group. TLR4, MyD88, NF-κB p65 and proinflammatory cytokine expressions decreased dose dependently in the sinomenine and sinomenine enteric-coated microspheres-treated groups and were generally lower in the sinomenine enteric-coated microspheres groups. However, SIGIRR and anti-inflammatory IL-10 expressions exhibited the opposite pattern. Based on the superior therapeutic effect, sinomenine enteric-coated microspheres might regulate TLR/NF-κB signaling and would be beneficial for an effective and safe therapy of inflammatory bowel disease.