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Severe acute pancreatitis (SAP) is an inflammatory disease of the pancreas with a high mortality rate. Macrophages play a crucial role in the pathogenesis of pancreatitis. Tectoridin (Tec) is a highly active isoflavone with anti-inflammatory pharmacological activity. However, the role of Tec in the SAP process is not known. The purpose of this study was to investigate the therapeutic effect and potential mechanism of Tec on SAP. To establish SAP mice by intraperitoneal injection of caerulein and Lipopolysaccharide (LPS), the role of Tec in the course of SAP was investigated based on histopathology, biochemical indicators of amylase and lipase and inflammatory factors. The relationship between Tec and macrophage polarization was verified by immunofluorescence, real-time quantitative PCR and Western blot analysis. We then further predicted the possible targets and signal pathways of action of Tec by network pharmacology and molecular docking, and validated them by in vivo and in vitro. In this study, we demonstrated that Tec significantly reduced pancreatic injury in SAP mice, and decreased serum levels of amylase and lipase. The immunofluorescence and Western blot analysis showed that Tec promoted macrophage M2 polarization. Network pharmacology and molecular docking predicted that Tec may target ERK2 for the treatment of SAP, and in vivo and in vitro experiments proved that Tec inhibited the ERK MAPK signal pathway. In summary, Tec can target ERK2, promote macrophage M2 polarization and attenuate pancreatic injury, Tec may be a potential drug for the treatment of SAP.
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Isoflavonas , Pancreatite , Camundongos , Animais , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Pancreatite/metabolismo , Ceruletídeo/efeitos adversos , Doença Aguda , Simulação de Acoplamento Molecular , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Macrófagos/metabolismo , Amilases , LipaseRESUMO
Inflammation and oxidative stress (OS) are the major pathogenic characteristics of acute kidney injury (AKI). Studies have shown that Schisandrin (Sch) could regulate inflammatory disease. However, the function and mechanism of Sch in AKI progression are still unknown. Here, we investigated Sch's potential effects and mechanism on mice's renal damage and macrophages induced by lipopolysaccharide (LPS). Sch decreased LPS-induced inflammatory factor production while increasing the activity of related antioxidant enzymes in macrophages and mouse kidney tissues. Hematoxylin and eosin staining revealed that Sch may have the ability to profoundly inhibit inflammatory cell invasion and tissue damage caused by LPS in renal tissue. Furthermore, Western blot and immunohistochemical studies showed that Sch exerted its effects mainly through up-regulation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 and inhibition of Toll-like receptor 4âmitogen-activated protein kinases/nuclear factor-kappa B pathways. Collectively, this study illustrates that Sch suppresses LPS-stimulated AKI by descending inflammation and OS, illuminating prospective AKI treatment options.
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Qiangli Dingxuan (QLDX) tablet is a widely recognized traditional Chinese medicine formula that has been extensively used in China for decades to treat vertigo, tinnitus, and dizziness owing to its outstanding therapeutic outcomes. However, the complexity of the chemical components in this tablet makes it challenging to separate and identify these components. This study presented an effective and sensitive strategy for the rapid separation and simultaneous structural identification of QLDX tablet components using ultra-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry and the UNIFI platform. Based on retention times, accurate masses, fragment ions, related literature, and authentic standards, 119 compounds were identified or tentatively characterized; these included 9 iridoids, 12 lignans, 21 phenylpropanoids, 27 flavonoids, 7 phthalides, and 43 others. Among them, 36 were confirmed using reference standards. The representative compounds with various chemical structures were studied by analyzing their fragmentation patterns and characteristic ions. In conclusion, this study established a rapid approach for characterizing the chemical constituents in QLDX tablet. The proposed approach provides a basis for qualitative analysis and quality control in the manufacturing process and is beneficial for advancing investigations into the efficacy and mechanism of action of this tablet.
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Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/análise , Comprimidos , ÍonsRESUMO
BACKGROUND: Systemic inflammatory response syndrome (SIRS) is an uncontrolled systemic inflammatory response. Proanthocyanidins (PC) is a general term of polyphenol compounds widely existed in blueberry fruits and can treat inflammation-related diseases. This study aimed to explore the regulatory effect of PC on lipopolysaccharide (LPS)-induced systemic inflammation and its potential mechanism, providing effective strategies for the further development of PC. METHODS: Here, RAW264.7 macrophages were stimulated with LPS to establish an inflammation model in vitro, while endotoxin shock mouse models were constructed by LPS in vivo. The function of PC was investigated by MTT, ELISA kits, H&E staining, immunohistochemistry, and Western blot analysis. RESULTS: Functionally, PC could demonstrate the potential to mitigate mortality in mice with endotoxin shock, as well as attenuated the levels of inflammatory cytokines (IL-6, TNF-α) and biochemical indicators (AST, ALT, CRE and BUN). Moreover, it had a significant protective effect on lung and kidney tissues damage. Mechanistically, PC exerted anti-inflammatory effects by inhibiting the activation of the NF-κB/NLRP3 signaling pathway. CONCLUSION: PC might have the potential ability of anti-inflammatory effects via modulation of the NF-κB/NLRP3 signaling pathway.
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Anti-Inflamatórios , Mirtilos Azuis (Planta) , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proantocianidinas , Transdução de Sinais , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proantocianidinas/farmacologia , Camundongos , Transdução de Sinais/efeitos dos fármacos , NF-kappa B/metabolismo , Mirtilos Azuis (Planta)/química , Células RAW 264.7 , Anti-Inflamatórios/farmacologia , Masculino , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/farmacologia , Choque Séptico/tratamento farmacológico , Choque Séptico/metabolismo , Choque Séptico/induzido quimicamenteRESUMO
An intelligent colorimetric sensing platform integrated with in situ immunomagnetic separation function was developed for ultrasensitive detection of Escherichia coli O157: H7 (E. coli O157: H7) in food. Captured antibody modified magnetic nanoparticles (cMNPs) and detection antibody/horseradish peroxidase (HRP) co-functionalized AuNPs (dHAuNPs) were firstly synthesized for targeted enrichment and colorimetric assay of E. coli O157: H7, in which remarkable signal amplification was realized by loading large amounts of HRP on the surface of AuNPs. Coupling with the optical collimation attachments and embedded magnetic separation module, a highly integrated optical device was constructed, by which in situ magnetic separation and high-quality imaging of 96-well microplates containing E. coli O157: H7 was achieved with a smartphone. The concentration of E. coli O157: H7 could be achieved in one-step by performing digital image colorimetric analysis of the obtained image with a custom-designed app. This biosensor possesses high sensitivity (1.63 CFU/mL), short detecting time (3 h), and good anti-interference performance even in real-sample testing. Overall, the developed method is expected to be a novel field detection platform for foodborne pathogens in water and food as well as for the diagnosis of infections due to its portability, ease of operation, and high feasibility.
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Técnicas Biossensoriais , Colorimetria , Escherichia coli O157 , Microbiologia de Alimentos , Ouro , Peroxidase do Rábano Silvestre , Separação Imunomagnética , Nanopartículas Metálicas , Escherichia coli O157/isolamento & purificação , Colorimetria/métodos , Ouro/química , Peroxidase do Rábano Silvestre/química , Separação Imunomagnética/métodos , Técnicas Biossensoriais/métodos , Nanopartículas Metálicas/química , Contaminação de Alimentos/análise , Limite de Detecção , Smartphone , Anticorpos Imobilizados/imunologia , Anticorpos Imobilizados/química , Nanopartículas de Magnetita/químicaRESUMO
Microorganisms play a critical role in maintaining the delicate balance of ecosystem services. However, the assembly processes that shape microbial communities are vulnerable to a range of environmental stressors, such as climate change, eutrophication, and the use of herbicides. Despite the importance of these stressors, little is known about their cumulative impacts on microbial community assembly in aquatic ecosystems. To address this knowledge gap, we established 48 mesocosm experiments that simulated shallow lake ecosystems and subjected them to warming (including continuous warming (W) and heat waves (H)), glyphosate-based herbicides (G), and nutrient loading (E). Our study revealed that in the control group, both deterministic and stochastic processes codominated the assembly of microbial communities in water, whereas in sediment, the processes were primarily stochastic. Interestingly, the effects of multiple stress factors on assembly in these two habitats were completely opposite. Specifically, stressors promoted the dominance of stochastic processes in water but increased the importance of deterministic processes in sediment. Furthermore, warming amplified the effects of herbicides but exerted an opposite and stronger influence on assembly compared to nutrients, emphasizing the complexity of these mechanisms and the significance of considering multiple stressors. The interaction of some factors significantly affected assembly (p < 0.05), with the effects of WEG being most pronounced in water. Both water and sediment exhibited homogeneous assembly of microbial communities (mean NTI >0), but the phylogenetic clustering of microbial communities in water was more closely related (NTI >2). Our research revealed the response model of microbial community assembly in aquatic ecosystems to multiple environmental stresses, such as agricultural pollution, climate change, and eutrophication, and indicated that microbial community changes in sediment may be an important predictor of lake ecosystem development. This provides scientific evidence that better environmental management can reduce impacts on aquatic ecosystems under the threat of future warming.
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Herbicidas , Microbiota , Ecossistema , Filogenia , Eutrofização , ÁguaRESUMO
BACKGROUND: To present an approach that autonomously identifies and selects a self-selective optimal target for the purpose of enhancing learning efficiency to segment infected regions of the lung from chest computed tomography images. We designed a semi-supervised dual-branch framework for training, where the training set consisted of limited expert-annotated data and a large amount of coarsely annotated data that was automatically segmented based on Hu values, which were used to train both strong and weak branches. In addition, we employed the Lovasz scoring method to automatically switch the supervision target in the weak branch and select the optimal target as the supervision object for training. This method can use noisy labels for rapid localization during the early stages of training, and gradually use more accurate targets for supervised training as the training progresses. This approach can utilize a large number of samples that do not require manual annotation, and with the iterations of training, the supervised targets containing noise become closer and closer to the fine-annotated data, which significantly improves the accuracy of the final model. RESULTS: The proposed dual-branch deep learning network based on semi-supervision together with cost-effective samples achieved 83.56 ± 12.10 and 82.67 ± 8.04 on our internal and external test benchmarks measured by the mean Dice similarity coefficient (DSC). Through experimental comparison, the DSC value of the proposed algorithm was improved by 13.54% and 2.02% on the internal benchmark and 13.37% and 2.13% on the external benchmark compared with U-Net without extra sample assistance and the mean-teacher frontier algorithm, respectively. CONCLUSION: The cost-effective pseudolabeled samples assisted the training of DL models and achieved much better results compared with traditional DL models with manually labeled samples only. Furthermore, our method also achieved the best performance compared with other up-to-date dual branch structures.
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Projetos de Pesquisa , Tomografia Computadorizada por Raios X , Algoritmos , BenchmarkingRESUMO
ß-Lactones are common substructures in a variety of natural products and drugs, and they serve as versatile synthetic intermediates in the production of valuable chemical derivatives. Traditional ß-lactone synthesis relies on laborious multi-step synthetic methods that use toxic compounds, sophisticated catalysts, expensive, and/or reactive chemicals. Based on the in situ electrochemical formation of metal-based nanoclusters, this paper describes the development of a one-step, room temperature electrocatalytic method for the formation of stable ß-lactone from CO2 and dienes. This one-step "electrosynthesis" method results in the formation of a new class of ß-lactone with high selectivity (up to 100%) and activity (up to 80% yields with respect to the reacted diene) by regulating the applied potential and current density. This work paves the way for more sustainable and environmentally friendly reaction pathways based on the in situ formation of nanoclusters as organic electrosynthesis catalysts.
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Doxorubicin (Dox) is a high-efficiency agent for cancer therapy. However, it causes cardiotoxicity which limits its clinical application. Despite more efforts has been made to seek protective decisions, unfortunately, the poor prognosis suggests the need for new treatments. As a powerful mitochondrial antioxidant, melatonin (Mel) has been found to confer cardioprotection against various cardiovascular diseases. Currently, the mechanism through which Mel confers protection is not well understood. In this study, we established a Dox-induced cardiotoxicity model in H9c2 cardiomyocytes, zebrafish, and SD rats to explore the mechanism by which Mel alleviates Dox-induced cardiotoxicity. In vivo and in vitro experiments showed that Dox significantly decreased the viability of H9c2 cells, induced apoptosis, myocardial injury, and effectively up-regulated the expression of p-YAP but down-regulated the expression of YAP. Furthermore, we found that Dox significantly up-regulated the expression of ferroptosis-associated protein ACSL4 and down-regulated expression of GPX4. Interestingly, these effects of Dox were reversed following treatment with Mel, indicating that ferroptosis mediated the protective effects of Mel against Dox-induced cardiomyocyte injury. Furthermore, we used YAP-siRNA in vitro and verteporfin (Ver) in vivo to down-regulate the expression level of YAP. The results showed that YAP down-regulation abolished the protective effects of Mel including apoptosis, mitochondrial lipid peroxidation, and ferroptosis. Collectively, these results show that Mel regulates ferroptosis by modulating YAP expression to counteract Dox-induced cardiotoxicity.
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Doxorrubicina/toxicidade , Ferroptose/efeitos dos fármacos , Melatonina/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Sinalização YAP/metabolismo , Animais , Linhagem Celular , Regulação para Baixo , Embrião não Mamífero , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Peroxidação de Lipídeos , Masculino , Mitocôndrias/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Proteínas de Sinalização YAP/genética , Peixe-Zebra , Proteínas de Peixe-ZebraRESUMO
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by inflammation infiltration of the synovial tissues and the fibroblast-like synoviocytes. Tectoridin is a botanical active ingredient with anti-inflammatory properties. In this study, the anti-arthritic effects of tectoridin and its mechanism of action are examined in TNF-α-induced human fibroblast-like synovial cells (HFLSs cells) and complete Freund's adjuvant (CFA)-stimulated arthritic mice. Arthritis progression was evaluated via bodyweight, hind paw swelling, organ index, and synovial pathology. IL-1ß, IL-6 and other pro-inflammatory factors concentrations, and the expression of MAPK pathway proteins in HFLSs cells and arthritic mice were measured using ELISA and western blotting. Results showed that tectoridin significantly decreased the swelling of the paws and joints as well as the increased immune organ index within CFA-induced arthritic mice. Histopathological analysis showed that tectoridin alleviated the lesions of ankle joints and synovial tissues induced by CFA. Secretion of pro-inflammatory cytokines in TNF-α-induced HFLSs cells and CFA-stimulated arthritic mice were also abated by tectoridin. Similarly, the presence of tectoridin significantly inhibited the abnormal phosphorylation levels of ERK, JNK, and p38 in vivo and in vitro. All those results highlighted that tectoridin exhibits anti-arthritis effects by inhibiting MAPK-mediated inflammatory responses.
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Artrite Experimental , Artrite Reumatoide , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Citocinas/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/patologia , Adjuvante de Freund/efeitos adversos , Humanos , Isoflavonas , Camundongos , Fator de Necrose Tumoral alfa/efeitos adversosRESUMO
BACKGROUND: Tectoridin, widely extracted and separated from the rhizome of Iris tectorum Maxim, is extensively reported to have affluent bioactivity, but rarely reported to have anti-inflammatory effects. In this study, we aim to investigate the anti-inflammatory effects and the underlying mechanisms of tectoridin. METHODS: Here, RAW264.7 macrophages were stimulated with Lipopolysaccharide (LPS) for the inflammation model in vitro. Experimental animals received tectoridin and Dexamethasone (DEX) before LPS injection for endotoxic shock mouse model in vivo. The pro-inflammatory mediators and cytokines in the cell supernatant and serum were detected by ELISA kits. The tissue damages were assessed by biochemical indexes and H&E staining. Immunohistochemistry and Western blot were performed for the detection of proteins. RESULTS: Our data showed that tectoridin attenuated the LPS-up-regulated nitric oxide (NO), interleukin-6 (IL-6), and interleukin-18 (IL-18) from macrophages and tumor necrosis factor-α (TNF-α); (IL-6) and (IL-1ß) in the serum levels. Besides, our histopathological study showed that the damages caused by LPS in the lung, liver, and kidney tissues were decreased. Furthermore, our results demonstrated that tectoridin inhibited the activation of TLR4-NF-κB/NLRP3 signaling proved by immunohistochemistry assay and Western blot. CONCLUSION: Taken all together, tectoridin might have the potential ability of anti-inflammatory effects and the possible mechanism may be relevant to its inhibition of TLR4-NF-κB/NLRP3 signaling.
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Lipopolissacarídeos , NF-kappa B , Animais , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Dexametasona/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-18 , Interleucina-6 , Isoflavonas , Lipopolissacarídeos/toxicidade , Camundongos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Óxido Nítrico/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfaRESUMO
Two new dinor-eudesmane sesquiterpenoids, named multistalin A (1), and multistalin B (2), together with three sesquiterpene glycosides (3-5), and a norlabdane-type diterpene (6) were isolated from the root extract of Chloranthus multistachys Pei. Their structures were elucidated on the basis of spectroscopic analysis including 1D, 2D NMR techniques and HR-ESI-MS. In addition, the cytotoxicity activities of the isolated compounds against selected cancer cells (Hela and A-549) were evaluated by MTT assay.
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Sesquiterpenos de Eudesmano , Sesquiterpenos , Células HeLa , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos de Eudesmano/química , Sesquiterpenos de Eudesmano/farmacologiaRESUMO
Atherosclerosis (AS) is a common chronic inflammatory disease of the arteries, which is closely related to dyslipidemia, inflammatory factors, and oxidative stress. Poria cocos polysaccharides (PCP) are one of the main active ingredients of Poria, which has significant pharmacological effects. In this study, the potential protective mechanism of PCP on AS was discussed in the ApoE-/- mice model induced by high-fat diet. These pathological changes were evaluated by H&E and oil red O staining. The levels of pro-inflammatory cytokines in aortic tissue were measured by enzyme-linked immunosorbent assay kit. These protein expressions were detected by Western blot and immunohistochemistry. The results showed that PCP inhibited the serum inflammatory mediators (tumor necrosis factor-α, interleukin-6, and nitric oxide) and lipids (low-density lipoprotein-cholesterol, triglyceride, and total cholesterol) increase. Moreover, PCP also reduced the concentration of malondialdehyde, increased the activity of superoxide dismutase, and improved the pathological changes of the aorta. Finally, PCP inhibited the activation of the TLR4/NF-κB pathway in the aorta and blocked the expression of matrix metalloproteinase 2 and intercellular adhesion molecule 1 proteins. In short, PCP intervenes in AS by reducing inflammatory factors and blood lipid levels.
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Apolipoproteínas E/metabolismo , Aterosclerose/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Inflamação/tratamento farmacológico , Wolfiporia/química , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Transdução de SinaisRESUMO
LAPONITE® sheets have been widely used for the preparation of tough nanocomposite hydrogels for enticing applications; however, their inferior dispersion in aqueous media resulting from electrostatic interactions between the nanosheets remarkably limits further improvements in the mechanical performances of the nanocomposite hydrogels. Here, we show a simple approach to dramatically accelerate the dispersion of LAPONITE® sheets in water, and in turn further improve the mechanical performances of the resulting nanocomposite hydrogels. Upon addition of poly(acrylic acid) (PAA), the electrostatic interactions between the LAPONITE® sheets were effectively reduced due to the adsorption of PAA onto the positively charged edges of the LAPONITE® sheets, thereby accelerating the dispersion of the LAPONITE® sheets in water. On this basis, a series of polyacrylamide (PAAm) hydrogels with a high content of LAPONITE® sheets was prepared, showing excellent tensile strength, stretchability, and anti-fatigue properties. This study will be beneficial for the preparation of LAPONITE®-based nanocomposite hydrogels bearing excellent mechanical properties for new applications.
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Although a variety of biomimetic mineralized materials have been created in the lab, the vast majority of these manmade examples lack response to external stimuli. Here, mineralized supramolecular hydrogels with on-demand thermo-responsiveness that are formed by a simple, physical crosslinking between amorphous CaCO3 (ACC) nanoparticles and poly(acrylic acid) (PAA) are reported. Upon the addition of Na2 CO3 solution into a mixture composed of PAA and CaCl2 , amorphous ACC nanoparticles are formed in situ and simultaneously crosslinked by PAA chains, giving rise to the mineralized hydrogels. Interestingly, upon tuning the content of the formed ACC, hydrogels with different types of thermo-responsiveness can be easily obtained, and the transparencies of the resulting hydrogels are dramatically changed during the temperature-driven phase transitions. As an application, these thermo-responsive mineralized hydrogels are used to control the exposure of UV light, which is successfully applied to switch fluorescent signals in response to temperature.
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Hidrogéis/química , Temperatura , Resinas Acrílicas/química , Materiais Biomiméticos/química , Carbonato de Cálcio/química , Reagentes de Ligações Cruzadas/química , Substâncias Macromoleculares/química , Nanopartículas/químicaRESUMO
Pathogenesis of atherosclerosis is characterized by the proliferation and migration of vascular smooth muscle cells (VSMCs) and inflammatory lesions. The aim of this study is to elucidate the effect of atractylenolide I (AO-I) on smooth muscle cell inflammation, proliferation and migration induced by oxidized modified low density lipoprotein (Ox-LDL). Here, We found that atractylenolide I inhibited Ox-LDL-induced VSMCs proliferation and migration in a dose-dependent manner, and decreased the production of inflammatory cytokines and the expression of monocyte chemoattractant protein-1 (MCP-1) in VSMCs. The study also identified that AO-I prominently inhibited p38-MAPK and NF-κB activation. More importantly, the specific heme oxygenase-1 (HO-1) inhibitor zinc protoporphyrin (ZnPP) IX partially abolished the beneficial effects of atractylenolide I on Ox-LDL-induced VSMCs. Furthermore, atractylenolide I blocked the foam cell formation in macrophages induced by Ox-LDL. In summary, inhibitory roles of AO-I in VSMCs proliferation and migration, lipid peroxidation and subsequent inflammatory responses might contribute to the anti-atherosclerotic property of AO-I.
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Heme Oxigenase-1/genética , Lactonas/farmacologia , Lipoproteínas LDL/fisiologia , Miócitos de Músculo Liso/fisiologia , Sesquiterpenos/farmacologia , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/imunologia , Aterosclerose/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Feminino , Células Espumosas/efeitos dos fármacos , Células Espumosas/fisiologia , Heme Oxigenase-1/metabolismo , Masculino , Camundongos , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Ratos Sprague-DawleyRESUMO
The actual casting filling process can be deemed as the coupled flow of air, molten metal and solid-phase particles (such as slag) inside the cavity, which may cause air entrapment, slag inclusion and other casting defects, and affect the quality of casting. Through computation simulation of the casting filling process on the basis of smoothed particle hydrodynamics (SPH) method, it can not only precisely track the motion trajectories of air, molten metal and slag particles, but also precisely predict air entrapment, slag inclusion and other casting defects. This paper established a mathematical model of gas-liquid-solid three-phase flow for the SPH-based casting filling process. The model eliminated the instability of gas-liquid interface pressure by introducing the corrected gas-liquid two-phase momentum equation, and maintained a clear interface between air and molten metal by introducing the surface tension model. In addition, it introduced the motion model of rigid body to deal with the coupled flow process of slag, air and molten metal. The mathematical model established in this paper was used to calculate the bubble floating and the flowing process of the gas-liquid two-phase during mold filling through the bottom side of the injection cavity and of the gas-liquid-solid three-phase flow during mold filling for casting of plate (the plate was composite reinforced with nano SiC, and the viscosity of the composite melt was calculated from the viscosity formula of the composite melt). The calculated results were compared with the experimental results to verify the accuracy and validity of the mathematical model established.
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The breakdown of the Stokes-Einstein relation (SER) in three model metallic liquids is investigated via molecular dynamics simulations. It is found that the breakdown of SER is closely correlated with the clustering behavior of well-packed atoms. When the SER breaks down, many cluster properties have almost the same value in these metallic liquids. At the breakdown temperature of SER, the temperature dependence of the number of clusters begins to deviate from a linear increase and the average number of well-packed atoms in the clusters reaches about 2, which indicates an increase in structure heterogeneity. Moreover, the size of the largest cluster shows a direct correlation with the SER. Therefore, our study provides a possible structural origin for the breakdown of SER in metallic liquids.
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AIM: This study was designed to develop sanguinarine-loaded solid lipid nanoparticles (SG-SLNs) and investigate its gastroprotective effect on ethanol-induced gastric mucosal lesions in mice. METHODS: SG-SLNs were prepared by high temperature melt-cool solidification method using glycerol monostearate as the lipid and a combination of lecithin with poloxamer 188 as the surfactants. Solid lipid nanoparticles (SLNs) were designed at varying lipid concentrations (5, 10, 15, and 20 mg/mL), surfactant mixture concentrations (6, 12, and 18 mg/mL), and drug contents (5, 10, 15, and 20 mg/mL) in "one factor at a time" fashion. Ethanol-induced gastric ulcer model was performed on Kunming mice to examine the anti-inflammatory activity of SG-SLNs and compare it with sanguinarine (SG). RESULTS: The high temperature melt-cool solidification method provided consistent production of SLNs with smaller size and high entrapment efficiency (EE%). The composition of optimal formulation was 10 mg/mL lipid concentration, 18 mg/mL surfactant mixture concentration, and 15 mg/mL drug amount. The mean particle size and EE% of optimized formulation were 238 ± 10.9 nm and 79 ± 2.8%, respectively. Additionally, SG-SLNs significantly decreased tumor necrosis factor-alpha and interleukin-6 levels in the serum and gastric tissue, and reduced the content of NO in serum, and strengthened the protection of mucosal membrane. Moreover, SG-SLNs treatment markedly inhibited ethanol-induced nuclear factor-kappa B (NF-κB) activation when compared with SG. CONCLUSIONS: SLNs could be potentially applied as a delivery system of SG. The protective effect of SG-SLNs is due to the suppression of NF-κB expression and subsequent pro-inflammatory cytokines release.
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Benzofenantridinas/farmacologia , Isoquinolinas/farmacologia , Lipídeos/química , Nanopartículas , Úlcera Gástrica/prevenção & controle , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/farmacologia , Benzofenantridinas/administração & dosagem , Química Farmacêutica/métodos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Etanol/toxicidade , Isoquinolinas/administração & dosagem , Lecitinas/química , Masculino , Camundongos , NF-kappa B/metabolismo , Tamanho da Partícula , Poloxâmero/química , Tensoativos/químicaRESUMO
The yam (Dioscorea opposita Thunb) is a well-known edible food and widely used as the traditional Chinese medicine. The present investigation was designed to evaluate the immunomodulatory activity of glycoprotein (DOT) from yam and explore its possible molecular mechanisms. Results showed that the DOT could improve the cell immunity, humoral immunity and phagocytic system function of the normal mice. The DOT could also increase the production of TNF-α, interleukin-6 and nitric oxide and enhance the pinocytosis function of macrophages. Furthermore, the DOT increased phosphor-p38, JNK, ERK1/2 and nuclear factor kappa B (NF-κB) p65 protein expression in peritoneal macrophages. Taken together, our data suggest that DOT could be used as a potential immunostimulant and exert its immunomodulatory activity via mitogen-activated protein kinases and NF-κB signal pathways. Copyright © 2017 John Wiley & Sons, Ltd.