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Research on the comprehensive utilization of sour jujube and its beneficial properties to human health has attracted extensive attention. This study aims to conduct a bibliometric analysis of the bioactive profile of sour jujube and future trends in applications. The research advancements within this field from 2000 to 2023 were addressed using the Web of Science database and VOSviewer. Among the 322 results, the most frequent keywords of bioactivity are flavonoids, antioxidants, saponins, insomnia, polyphenols, terpenoids and anti-inflammatory; the most studied parts of sour jujube are seeds, fruits and leaves; the published articles with high citations mainly focus on identification, biological effects and different parts distribution of bioactive compounds. The bioactivity of various parts of sour jujube was reviewed considering their application potential. The seeds, rich in flavonoids, saponins and alkaloids, exhibit strong effects on central nervous system diseases and have been well-developed in pharmacology, healthcare products and functional foods. The pulp has antioxidant properties and is used to develop added-value foods (e.g., juice, vinegar, wine). The leaves can be used to make tea and flowers are good sources of honey; their extracts are rich sources of flavonoids and saponins, which show promising medicinal effects. The branches, roots and bark have healing properties in traditional folk medicine. Overall, this study provides a reference for future applications of sour jujube in food and medicine fields.
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This study was conducted to investigate the effects of tea polyphenols (TP) and probiotics (PB) on the production performance, biochemical indices, and gut health of laying hens. A total of 400 Hy-line Brown layers (45 weeks old) were randomly assigned to 8 diet groups for 8-week feeding trial. Compared with the control basal diet (CT), dietary high dosage of TP and PB (HTP-PB) increased egg mass (P < 0.05). Supplementation with HTP-PB improved the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the malonic dialdehyde (MDA) content (P < 0.05) without affecting the contents of immunoglobulins in the serum. The combination of HTP and PB supplementation promoted the secretion of estradiol (E2) and progesterone (PROG) compared with treatment with TP or PB alone (P < 0.05). The combined use of HTP and PB induced higher jejunal villus height (VH) than the CT group (P < 0.05). Dietary TP and PB could optimize the functional network of intestinal microflora and the interactions between the intestinal microflora and the host. Therefore, the combined use of the high dosage of TP and PB affected laying performance, improved antioxidant capacity, and promoted intestinal health, which may be associated with regulation of the intestinal microbiota.
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Suplementos Nutricionais , Probióticos , Animais , Feminino , Ração Animal/análise , Galinhas , Dieta/veterinária , Suplementos Nutricionais/análise , Polifenóis/farmacologia , Probióticos/farmacologia , Chá/químicaRESUMO
Previous research has established a strong link between attention and visual mental imagery, but it's remained uncertain whether attention networks influence individual differences in the vividness of visual mental imagery. In our study, we examined 140 participants, assessing the vividness of imagery using the Vividness of Visual Imagery Questionnaire in both eyes-open and eyes-closed conditions. We employed the Attention Network Test, coupled with EEG recording, to characterize three attention sub-networks: alerting, orienting, and executive control. To pinpoint the specific attentional networks associated with the vividness of visual mental imagery, we utilized latent profile analysis to categorize participants into distinct subgroups. Additionally, we constructed a regression mixture model to explore how attention networks predict different latent categories of visual imagery vividness. Our findings revealed that the efficiency of the alerting network, as indicated by the N1 component, demonstrated a positive correlation with the vividness of visual imagery. This electrophysiological evidence underscores the role of the alerting network in shaping individual differences in the vividness of visual mental imagery.
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Imaginação , Individualidade , Humanos , Imaginação/fisiologia , Imagens, Psicoterapia , Função Executiva , EletroencefalografiaRESUMO
Chronic heart failure (CHF) is a key part of cardiovascular continuum. Under the guidance of the theory of vessel-collateral doctrine, the present study proposes therapeutic benefits of Qili Qiangxin (QLQX) capsules, an innovative Chinese medicine, on chronic heart failure. The studies show that multiple targets of the drug on CHF, including enhancing myocardial systole, promoting urine excretion, inhibiting excessive activation of the neuroendocrine system, preventing ventricular remodeling by inhibiting inflammatory response, myocardial fibrosis, apoptosis and autophagy, enhancing myocardial energy metabolism, promoting angiogenesis, and improving endothelial function. Investigation on the effects and mechanism of the drug is beneficial to the treatment of chronic heart failure (CHF) through multiple targets and/or signaling pathways. Meanwhile, it provides new insights to further understand other refractory diseases in the cardiovascular continuum, and it also has an important theoretical and practical significance in enhancing prevention and therapeutic effect of traditional Chinese medicine for these diseases.
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BACKGROUND: Allergic rhinitis (AR) is a prevalent allergic disease, which seriously affects the sufferers' life quality and increases the socioeconomic burden. Guominkang (GMK), a well-known prescription for AR treatment, showed satisfactory effects; while its anti-allergic components remain to be disclosed. AlGaN/GaN HEMT biochip is more sensitive and cost-effective than other binding equipments, indicating its great potential for screening of active ingredients from herbal medicines. METHODS: AR mouse models were first established to test the anti-allergic effect of GMK and discover the ingredients absorbed into blood by ultra-high performance liquid chromatography-mass spectra (UHPLC-MS). Then, novel Syk/Lyn/Fyn-functionalized high electron mobility transistor (HEMT) biochips with high sensitivity and specificity were constructed and applied to screen the active components. Finally, the results from HEMT biochips screening were validated via in silico (molecular docking and molecular dynamics simulation), in vitro (RBL-2H3 cells), and in vivo (PCA mice model) assays. RESULTS: GMK showed a potent therapeutic effect on AR mice, and fifteen components were identified from the medicated plasma. Furthermore, hamaudol was firstly found to selectively inhibit the Syk and Lyn, and emodin was to selectively inhibit Lyn, which were further confirmed by isothermal titration calorimetry, molecular docking, and molecular dynamics simulation analyses. Suppression of the activation of FcεRI-MAPK signals might be the possible mechanism of the anti-allergic effect of hamaudol. CONCLUSIONS: The targets of emodin and hamaudol were discovered by HEMT biochips for the first time. This study provided a novel and effective strategy to discover active components in a complex herbal formula by using AlGaN/GaN HEMT biochips.
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Antialérgicos , Emodina , Rinite Alérgica , Camundongos , Animais , Antialérgicos/farmacologia , Simulação de Acoplamento Molecular , Emodina/farmacologia , Rinite Alérgica/tratamento farmacológico , Modelos Animais de DoençasRESUMO
Objective: The paper aimed to explore the effect of probiotic supplementation on nutrient intake, Ghrelin, and adiponectin concentrations in diabetic hemodialysis patients. Methods: A total of 86 patients with diabetic nephropathy who received hemodialysis treatment in the Department of Nephrology of the First People's Hospital of Shanghai from May 2019 to March 2021 were selected as the research subjects, including 52 male patients and 34 female patients, with an average age of 56.57 ± 4.28. According to the research protocol, the patients were divided into the control group (n = 30) and the observation group (n = 56). In the control group, dietary soybean milk was used as a placebo. In the observation group, capsules containing probiotics Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium were taken with soybean milk. All patients signed an informed consent form before being included in the study. The results of the experimental biochemical analysis and the archived data counted the general data of the patients. Plasma adiponectin concentrations were measured with a commercially available human enzyme immunoassay kit. Ghrelin concentrations were estimated by specific commercial methods. Correlation software was used to calculate patient nutritional intake data. Serum creatinine, insulin resistance, fasting blood glucose, and levels of oxidative stress and inflammatory factors were measured using appropriate biochemical assays. Results: There was no difference in baseline characteristics between the two groups (P > .05). Before treatment, there was no difference in serum adiponectin concentration between the two groups (P > .05). After treatment, the serum adiponectin concentration in the observation group was lower than in the control group (P < .05). Before treatment, there was no difference in serum ghrelin levels between the two groups (P > .05). After treatment, serum ghrelin levels in the observation group were higher than in the control group (P < .05). Before treatment, there was no difference in nutrient intake between the two groups (P > .05). After treatment, the nutrient intake in the observation group was higher than in the control group (P < .05). Serum creatinine, fasting blood glucose, urine protein/creatinine ratio, and HOMA-IR in the observation group were lower than in the control group (P < .05). The serum levels of malondialdehyde, C-reactive protein, and TNF-α in the observation group were lower than those in the control group (P < .05), and the levels of glutathione in the observation group were higher than those in the control group (P < .05). Conclusion: Supplementation of probiotics in DN dialysis patients can increase serum ghrelin concentration, increase nutrient intake through appetite regulation, and reduce adiponectin level, which is beneficial to blood sugar control, insulin resistance, and renal function.
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Diabetes Mellitus , Resistência à Insulina , Probióticos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adiponectina , Glicemia/metabolismo , Grelina , Creatinina , Biomarcadores , China , Probióticos/uso terapêutico , Diálise Renal , Ingestão de AlimentosRESUMO
α-Tocopherol, as an oil-soluble vitamin with strong antioxidant activity. It is the most naturally abundant and biologically active form of vitamin E in humans. In this study, a novel emulsifier (PG20-VES) was synthesized by attaching hydrophilic twenty-polyglycerol (PG20) to hydrophobic vitamin E succinate (VES). This emulsifier was shown to have a relatively low critical micelle concentration (CMC = 3.2 µg/mL). The antioxidant activities and emulsification properties of PG20-VES were compared with those of a widely used commercial emulsifier: D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS). PG20-VES exhibited a lower interfacial tension, stronger emulsifying capacity and similar antioxidant property to TPGS. An in vitro digestion study showed that lipid droplets coated by PG20-VES were digested under simulated small intestine conditions. This study showed that PG20-VES is an efficient antioxidant emulsifier, which may have applications in the formulation of bioactive delivery systems in the food, supplement, and pharmaceutical industries.
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Antioxidantes , alfa-Tocoferol , Humanos , Antioxidantes/química , alfa-Tocoferol/química , Emulsões , Vitamina E/química , Polímeros , Polietilenoglicóis/química , Emulsificantes/químicaRESUMO
INTRODUCTION: As a folk herbal medicine, Trillium tschonoskii has been used for thousands of years. However, due to the complexity of the chemical constituents of this herb, few investigations have acquired a comprehensive understanding of its quality markers. OBJECTIVE: This study was conducted to characterise the chemical composition of T. tschonoskii and identify its potential quality markers. MATERIAL AND METHODS: A systematic analytical method based on ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) was used to characterise the constituents of T. tschonoskii. Multivariate statistical analysis was performed to investigate the chemical differences between different tissues, as well as the relationship between chemical compositions and habitats. The potential quality markers were predicted via network pharmacology and molecular docking, then confirmed by cellular assays. RESULTS: A total of 77 compounds were co-isolated and identified, and among them, 26 were discovered from the genus Trillium for the first time. Ten batches of roots/rhizomes were explicitly clustered into five groups according to the climate types of the habitats, and the clusters of the fruits and roots/rhizomes from the same plants were independent due to the significant difference in chemical composition. Diosgenin had a good docking affinity with the relevant targets within the IL-17 pathway and cytokine pathway and could significantly inhibit TNF-α expression in hypoxic brain microvascular endothelial cells (BMECs). CONCLUSION: This is the first study to establish the chemical composition profile of T. tschonoskii by UHPLC-MS systematically, and diosgenin was confirmed to be a potential quality marker of T. tschonoskii for the treatment of headaches.
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Diosgenina , Medicamentos de Ervas Chinesas , Trillium , Trillium/química , Cromatografia Líquida de Alta Pressão , Farmacologia em Rede , Células Endoteliais , Simulação de Acoplamento Molecular , Espectrometria de MassasRESUMO
Guominkang (GMK), a Chinese medicine formula, has been used to treat allergic diseases in clinical settings for many years. To evaluate the antiallergic effect and molecular mechanism of action of GMK extract, RBL-2H3 cell models and passive cutaneous anaphylaxis (PCA) mouse models were established. High performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) analyses were performed to characterize the chemical composition of GMK. A total of 94 compounds were identified or tentatively identified from GMK. Three of them, emodin, ursolic acid, and hamaudol, were identified for the first time as potential active compounds in GMK, since they inhibited the degranulation of mast cells. The anti-allergic effect of hamaudol was the first to be discovered. GMK could markedly mitigate the shade of Evans Blue extravasation and ear incrassation in PCA mouse models. Additionally, GMK significantly inhibited the degranulation of mast cells, suppressed mast cell degranulation by reducing Ca2+ influx and the levels of TNF-α, IL-4, and histamine, and markedly inhibited the phosphorylation of Lyn, Syk, PLCγ1, IκBα, and NF-κB p65. Molecular docking results indicated that hamaudol and emodin had strong interaction with FcÉRI and NF-κB related proteins, while ursolic acid only interacted with NF-κB associated proteins. These results suggest GMK suppresses the activation of MCs both in vivo and in vitro. The underlying mechanism of its anti-allergic activity is associated with the inhibition of FcÉRI and NF-κB activation.
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Antialérgicos , Emodina , Camundongos , Animais , Antialérgicos/farmacologia , Antialérgicos/uso terapêutico , Imunoglobulina E , NF-kappa B/genética , NF-kappa B/metabolismo , Anafilaxia Cutânea Passiva , Mastócitos/metabolismo , Emodina/metabolismo , Simulação de Acoplamento Molecular , Ácido UrsólicoRESUMO
Background: Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare disease characterized by hyperphosphatemia and ectopic calcification, predominantly at periarticular locations. This study was performed to characterize the clinical profile of tumoral calcinosis and to identify gene mutations associated with HFTC and elucidated its pathogenic role. Methods: The three subjects (two male and one female) were aged 30, 25 and 15 years, respectively. The clinical features, histopathological findings, and outcomes of three subjects with HFTC were retrospectively reviewed. The three subjects were analyzed for FGF23, GALNT3 and KL mutations. Function of mutant gene was analyzed by western blotting and wheat germ agglutinin affinity chromatography. Results: All subjects had hyperphosphatemia and elevated calcium-phosphorus product. Calcinosis positions included the left shoulder, left index finger, and right hip. Bone and joint damage were present in two cases and multiple foci influenced body growth in one case. The histopathological features were firm, rubbery masses comprising multiple nodules of calcified material bordered by the proliferation of mononuclear or multinuclear macrophages, osteoclastic-like giant cells, fibroblasts, and chronic inflammatory cells. The novel mutation c.484A>G (p.N162D) in exon 3 of FGF23 was identified in one subject and his family members. Measurement of circulating FGF23 in the subject confirmed low intact FGF23 and increased C-terminal fragment. In vitro experiments showed that the mutant FGF23 proteins had defective O-glycosylation and impaired protein proteolysis protection. Conclusion: We identified a novel FGF23 missense mutation, and confirmed its damaging role in FGF23 protein O-glycosylation. Our findings expand the current spectrum of FGF23 variations that influence phosphorus metabolism.
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Calcinose , Hiperostose Cortical Congênita , Hiperfosfatemia , Calcinose/genética , Calcinose/patologia , Cálcio/metabolismo , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Glicosilação , Humanos , Hiperostose Cortical Congênita/genética , Hiperfosfatemia/complicações , Hiperfosfatemia/genética , Hiperfosfatemia/patologia , Masculino , Proteínas Mutantes/genética , Mutação , Fósforo , Estudos Retrospectivos , Aglutininas do Germe de Trigo/genética , Aglutininas do Germe de Trigo/metabolismoRESUMO
Mantle cell lymphoma (MCL) is a highly aggressive and heterogeneous B-cell lymphoma. Though Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has shown great efficacy as a single agent for MCL treatment, the real-world use of ibrutinib is still subject to limitations. Our previous study has shown the treatment with HSP90 inhibitor ganetespib can attack major targets of MCL, luckily complementary to ibrutinib's targets. In this study, transient ganetespib treatment sensitizes MCL cells to ibrutinib as manifested by the significant decrease of IC50 values, percentages of EdU (5-Ethynyl-2'-deoxyuridine) positive cells, and levels of p-AKT and NF-κB after combinational treatment. Additionally, pretreatment with ganetespib enhanced cell cycle arrest induced by ibrutinib at G0/G1 phase and significantly decreased levels of cell cycle promoting proteins CDK2, 4, and 6. Pretreatment with ganetespib also enhanced cell apoptosis induced by ibrutinib through the upregulation of cleaved-caspase 9 and downregulation of BCL-2 in MCL cells at the molecular level. The sequential administration of ganetespib and ibrutinib had similar effects on increasing DNA damage as the transient treatment with ganetespib as demonstrated by the improved percentage of γH2AX and 53BP1 foci. Furthermore, ganetespib significantly increased inhibition of tumor growth mediated by ibrutinib in vivo, confirmed by the changes of the expression levels of Ki-67 and BCL-2 through immunohistochemistry assays. This study indicates that HSP90 inhibitor ganetespib maybe ideal for the combinational use with BTK inhibitor ibrutinib to target major pathogenesis-associated signaling pathways for MCL treatment which may help identify new possibilities for clinical trials.
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ETHNOPHARMACOLOGICAL RELEVANCE: Persicaria orientalis (L.) Spach (syn. Polygonum orientale L.) is a potent medicinal herb widely used in many ethnic groups, such as the Han, Tibetan, Mongolian, Zhuang, Miao, Yao, Yi, Korean, Dong, Hani, Lisu, Naxi and She people in China. Aims of the review: This article aims to present the research progress on P. orientalis, which is helpful to understand the multi-purpose of Chinese herbal medicine (CHM) and prompt its medicinal value. MATERIALS AND METHODS: Information on P. orientalis was obtained from published materials, including monographs on medicinal plants, ancient and modern recorded classics, pharmacopoeias and electronic databases, such as Web of Science, Science Direct, Springer, AGRIS, Europe PMC, SCI Finder, PubMed, CNKI, Wanfang DATA, J-STAGE, classical treatises of modern pharmaceutical science and Flora Reipublicae Popularis Sinicae (FRPS). RESULTS: Clinical applications of traditional medicine of P. orientalis have therapeutic effects for dispelling rheumatism, promoting digestion, aiding diuresis and activating blood circulation. A total of 153 chemical constituents have been identified from P. orientalis, including flavonoids, carboxylic acids, phenolic acids, amino acids, hydrocarbons, chromones, lignans, volatile oils, amides and other components. Its active ingredients have a wide range of pharmacological effects, such as anti-oxidative, anti-aging, anti-inflammation, analgesia, anti-myocardial ischemia, anti-abortion, and anti-rheumatoid arthritis, as well as protective effects on cerebral ischemia and liver injury. By establishing stable detection methods, the quality standards of P. orientalis medicinal materials have been guaranteed, such as determination of the iconic components, harvesting periods and optimization of specific components extraction processes. CONCLUSIONS: P. orientalis has different pharmacological activities based on the diversity of chemical constituents. However, the existing reports mainly focus on the extracts, and these studies on its corresponding compounds are not clear enough. The information suggests that P. orientalis has good potential medicinal value, and more attention should be paid to further explore its bioactive components.
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Medicamentos de Ervas Chinesas/farmacologia , Polygonum/química , Animais , Medicamentos de Ervas Chinesas/química , Etnofarmacologia , Humanos , Medicina Tradicional Chinesa/métodos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologiaRESUMO
Dihydrochalcones are a subclass of flavonoids. There has been growing interest in dihydrochalcones for their health benefits and potential to modulate flavor, but their comprehensive profile in diverse plant species is lacking. Star fruit is a tropical fruit rich in dihydrochalcones. In this study, a systematic annotation using UHPLC/Q-Orbitrap-MS and molecular networking was established to rapidly identify dihydrochalcones in 12 star fruit cultivars. A total of 53 dihydrochalcones were characterized within a short retention time including one novel compound (phloretin-3'-C-(2-O-trans-p-coumaroyl)-ß-d-fucopyranoside) and 23 compounds identified from the Averrhoa genus for the first time. 3-Hydroxyphloretin was the most abundant dihydrochalcone in star fruit. All the identified dihydrochalcones had a higher abundance in leaves compared to fruits. This is the first report that systematically investigates dihydrochalcones in star fruit of multiple cultivars, and the results could provide a useful reference for the future development and utilization of plant genetic resources.
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Averrhoa/química , Chalconas/química , Cromatografia Líquida de Alta Pressão/métodos , Frutas/química , Espectrometria de Massas/métodos , Extratos Vegetais/química , Estrutura MolecularRESUMO
OBJECTIVE: As a noninvasive and nonpharmacological therapeutic approach, superficial acupuncture (SA) is a special method of acupuncture. In this study, using nonlinear dynamics and multivariate statistics, we studied the electroencephalography (EEG) of primary insomnia under SA intervention to investigate how brain regions change. METHOD: This study included 30 adults with primary insomnia. They underwent superficial acupuncture at the Shangen acupoint. The EEG signals were collected for 10 minutes at each state, including the resting state, the intervention state, and the postintervention state. The data were conducted using nonlinear dynamics (including approximate entropy (ApEn) and correlation dimension (CD)) and multivariate statistics. RESULT: The repeated-measures ANOVA results showed that both ApEn and CD values were not significantly different at the three states (p > 0.05). The paired t-test results showed that the ApEn values of electrodes O2 (the right occipital lobe) at the postintervention state have decreased, compared with the resting state (p < 0.05), and no difference was detected in CD (p > 0.05). The cluster analysis results of ApEn showed that patients' EEG has changed from the right prefrontal lobe (electrode Fp2) to the right posterior temporal lobe (electrode T6) and finally to the right occipital lobe (electrode O2), before, during, and after the SA intervention. In addition, the factor analysis results of CD revealed that patients' EEG of all brain regions except for the occipital lobes has changed to the frontal lobes and anterior temporal and frontal lobes from pre- to postintervention. CONCLUSION: SA activated the corresponding brain regions and reduced the complexity of the brain involved. It is feasible to use nonlinear dynamics analysis and multivariate statistics to examine the effects of SA on the human brain.
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Sparassis crispa is a kind of edible fungus widely grows in the north temperate zone, which shows various medicinal properties. Due to the complexity of chemical constitutes of this species, few investigations have acquired a comprehensive configuration for the chemical profile of it. In this study, a strategy based on ultra-high performance liquid chromatography (UPLC) combined with Orbitrap mass spectrometer (MS) was established for rapidly characterizing various chemical components in S. crispa. Through the summarized MS/MS fragmentation patterns of reference compounds and systematic identification strategy, a total of 110 components attributed to six categories were identified for the first time. Moreover, allergic rhinitis (AR) is a worldwide inflammatory disease seriously affecting human health, and the development of drugs to treat AR has been a topic of interest. It has been reported that the extracts of S. crispa showed obvious inhibitory effects on degranulation of mast cell- and allergen-induced IgE and proinflammatory mediators, but the active components and specific mechanism were still not clear. Src family kinases (SFKs) participate in the initial stage of allergy occurrence, which are considered the targets of AR treatment. Herein, on the basis of that self-built chemical database, virtual screening was applied to predict the potential SFKs inhibitors in S. crispa, using known crystal structures of Hck, Lyn, Fyn, and Syk as receptors, followed by the anti-inflammatory activity evaluation for screened hits by intracellular calcium mobilization assay. As results, sparoside A was directly confirmed to have strong anti-inflammatory activity with an IC50 value of 5.06 ± 0.60 µM. This study provides a useful elucidation for the chemical composition of S. crispa, and demonstrated its potential inhibitory effects on AR, which could promote the research and development of effective agents from natural resources.
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Anti-Inflamatórios não Esteroides/farmacologia , Espectrometria de Massas/métodos , Polyporales/química , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Quinases da Família src/antagonistas & inibidores , Alcaloides/análise , Alcaloides/química , Animais , Anti-Inflamatórios não Esteroides/química , Benzofuranos/análise , Benzofuranos/química , Linhagem Celular , Cromatografia Líquida/métodos , Simulação por Computador , Avaliação Pré-Clínica de Medicamentos , Humanos , Ratos , Rinite Alérgica/tratamento farmacológico , Sesquiterpenos/análise , Sesquiterpenos/química , Esteróis/análise , Esteróis/química , Espectrometria de Massas em TandemRESUMO
Qiliqiangxin capsule (QLQX) is a well-known traditional Chinese medicine that exhibits cardioprotective effects in heart failure patients. However, it remains unclear whether and by which mechanism QLQX attenuates oxidative stress-induced mitochondria-dependent myocardial apoptosis. In vivo, Sprague Dawley (SD) rats received left anterior descending coronary artery ligation for 4 weeks to establish a model of heart failure after acute myocardial infarction, and then were treated with QLQX for another 4 weeks. We evaluated cardiac function, oxidative stress injury, as well as the expressions of mitochondria-dependent apoptosis and its signaling factors. The results indicated that QLQX protected cardiac function and attenuated oxidative stress-induced myocardial apoptosis. Meanwhile, QLQX elevated the Bcl-2 expression, declined the expressions of Bax, cytochrome c, apoptotic protease activating factor-1 (Apaf-1), cleaved-caspase 9 and cleaved-caspase 3, and up-regulated the ratios of phospho-AKT/AKT and phospho-glycogen synthase kinase-3ß (GSK3ß)/GSK3ß. In vitro, H9c2 cardiomyocytes were pretreated with QLQX, then exposed to H2O2 for 24 h. QLQX promoted the proliferation of H9c2 cardiomyocytes induced by H2O2 and reversed oxidative stress damage. Moreover, QLQX inhibited the apoptosis rate and the pro-apoptosis protein expressions, but improved the Bcl-2 expression as well as the ratios of phospho-AKT/AKT and phospho-GSK3ß/GSK3ß. Meanwhile, it further ameliorated mitochondrion-related apoptosis by inhibiting the mitochondrial fission, mitochondrial permeability transition pore (MPTP) opening, and mitochondrial membrane potential (MMP) decline in H9c2 cardiomyocytes induced by H2O2. In addition, all the effects of QLQX on H2O2-induced mitochondria-dependent apoptosis could be blocked by the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002. We conclude that QLQX may ameliorate oxidative stress-induced mitochondria-dependent apoptosis in cardiomyocytes through PI3K/AKT/GSK3ß signaling pathway.
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Medicamentos de Ervas Chinesas/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Mitocôndrias Cardíacas/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 9/metabolismo , Técnicas de Cultura de Células , Modelos Animais de Doenças , Ecocardiografia , Glicogênio Sintase Quinase 3 beta/metabolismo , Insuficiência Cardíaca/induzido quimicamente , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Masculino , Medicina Tradicional Chinesa , Mitocôndrias Cardíacas/metabolismo , Miócitos Cardíacos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/metabolismoRESUMO
OBJECTIVES: We aimed to confirm the clinical effectiveness of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) in patients with hepatocellular carcinoma after liver resection, and further identify the patients who could benefit most from PA-TACE. PATIENTS AND METHODS: Propensity score matching at a ratio of 1 : 2 was used between hepatectomy patients with and without receiving PA-TACE. Kaplan-Meier analysis was performed to compare overall survival and recurrence-free survival between two groups. Univariate COX regression and stratified analyses were performed to screen and identify survival predictors for PA-TACE patients. The identified predictive markers were validated in an external cohort. RESULTS: The propensity analysis matched 116 patients in PA-TACE group to 232 in the control group. Visible protective effect of PA-TACE was shown by survival curves in matched series (log-rank P=0.009 and 0.008), with hazard ratio of being 0.599 (95% confidence interval: 0.420-0.855) and 0.623 (95% confidence interval: 0.449-0.866), respectively, for overall survival and recurrence-free survival. The identified prognostic predictors for PA-TACE included TNM stage, tumor size and number, hepatitis B infection, spleen diameter, preoperative serum α-fetoprotein, alkaline phosphatase, γ-glutamyl transpeptidase and monocyte, and three risk signatures (aspartate aminotransferase-to-alanine aminotransferase ratio, neutrophil-to-lymphocyte ratio, and systemic immune-inflammation index). CONCLUSION: The treatment effectiveness of adjuvant transcatheter arterial chemoembolization for patients with hepatocellular carcinoma after surgery was validated in this study, and the best candidates for PA-TACE were identified as well, including patients with late-stage tumor, portal hypertension, and high preoperative serum levels of α-fetoprotein, alkaline phosphatase, γ-glutamyl transpeptidase, and monocytes.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Hepatectomia , Neoplasias Hepáticas/terapia , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Hepatite B Crônica/epidemiologia , Humanos , Hipertensão Portal/epidemiologia , Contagem de Leucócitos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Monócitos , Estadiamento de Neoplasias , Neutrófilos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Carga Tumoral , alfa-Fetoproteínas/metabolismo , gama-Glutamiltransferase/sangueRESUMO
TAS2R14 is of great potential as a therapeutic target against asthma, and the discovery of TAS2R14 agonists can be very valuable for treating this disease. Herein, we developed a strategy using virtual screening and affinity screening based on a fabricated biosensor combined with UPLC-MS analysis to screen TAS2R14 agonists from Platycodon grandiflorum. By ligand-based virtual screening, 16 best-fit candidates were yielded. A novel TAS2R14-functionalized high-electron-mobility transistor (HEMT) sensor was applied to detect and fish out the potential TAS2R14 agonists from P. grandiflorum extracts. Those components captured by the immobilized TAS2R14 were eluted and characterized on UPLC-QTOF MS. As a result, six potential TAS2R14 agonists were screened out and identified. Among them, platycodin L was confirmed to be a special agonist of TAS2R14 for the first time and had an EC50 of 15.03 ± 1.15 µM via intracellular calcium mobilization assay ( n = 6). The results indicated that the proposed strategy was efficient to discover TAS2R14 agonists from the herb directly.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Espectrometria de Massas/métodos , Extratos Vegetais/química , Platycodon/química , Receptores Acoplados a Proteínas G/agonistas , Avaliação Pré-Clínica de Medicamentos/instrumentação , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Receptores Acoplados a Proteínas G/metabolismoRESUMO
Bolbostemma paniculatum is a traditional Chinese medicine (TCM) showed various therapeutic effects. Owing to its complex chemical composition, few investigations have acquired a comprehensive cognition for the chemical profiles of this herb and explicated the differences between samples collected from different places. In this study, a strategy based on UPLC tandem LTQ-Orbitrap MSn was established for characterizing chemical components of B. paniculatum. Through a systematic identification strategy, a total of 60 components in B. paniculatum were rapidly separated in 30 min and identified. Then based on peak intensities of all the characterized components, principle component analysis (PCA) and hierarchical cluster analysis (HCA) were employed to classify 18 batches of B. paniculatum into four groups, which were highly consistent with the four climate types of their original places. And five compounds were finally screened out as chemical markers to discriminate the internal quality of B. paniculatum. As the first study to systematically characterize the chemical components of B. paniculatum by UPLC-MSn, the above results could offer essential data for its pharmacological research. And the current strategy could provide useful reference for future investigations on discovery of important chemical constituents in TCM, as well as establishment of quality control and evaluation method.