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Renewable energy electrolysis of water to produce hydrogen is an effective measure to break the energy dilemma. However, achieving activity and stability at a high current density is still a key problem in water electrolyzers. Transition metal phosphides (TMPs), with high activity and relative inexpensiveness, have become excellent candidates for the production of highly pure green hydrogen for industrial applications. In this mini-review, multilevel regulation strategies including nanoscale control, surface composition and interface structure design of high-performance TMPs for hydrogen evolution are systematically summarized. On this basis, in order to achieve large-scale hydrogen production in industry, the hydrogen evolution performance and stability of TMPs at a high current density are also discussed. Peculiarly, the practical application and requirements in proton exchange membrane (PEM) or anion exchange membrane (AEM) electrolyzers can guide the advanced design of regulatory strategies of TMPs for green hydrogen production from renewable energy. Finally, the challenges and prospects in the future development trend of TMPs for efficient and industrial water electrolysis are given.
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Depression is a common psychiatric comorbidity in patients with epilepsy, especially those with temporal lobe epilepsy (TLE). The aim of this study was to assess changes in high mobility group box protein 1 (HMGB1) expression in epileptic patients with and without comorbid depression. Sixty patients with drug-resistant TLE who underwent anterior temporal lobectomy were enrolled. Anterior hippocampal samples were collected after surgery and analyzed by immunofluorescence (n = 7/group). We also evaluated the expression of HMGB1 in TLE patients with hippocampal sclerosis and measured the level of plasma HMGB1 by enzyme-linked immunosorbent assay. The results showed that 28.3% of the patients (17/60) had comorbid depression. HMGB1 was ubiquitously expressed in all subregions of the anterior hippocampus. The ratio of HMGB1-immunoreactive neurons and astrocytes was significantly increased in both TLE patients with hippocampal sclerosis and TLE patients with comorbid depression compared to patients with TLE only. The ratio of cytoplasmic to nuclear HMGB1-positive neurons in the hippocampus was higher in depressed patients with TLE than in nondepressed patients, which suggested that more HMGB1 translocated from the nucleus to the cytoplasm in the depressed group. There was no significant difference in the plasma level of HMGB1 among patients with TLE alone, TLE with hippocampal sclerosis, and TLE with comorbid depression. The results of the study revealed that the translocation of HMGB1 from the nucleus to the cytoplasm in hippocampal neurons may play a previously unrecognized role in the initiation and amplification of epilepsy and comorbid depression. The direct targeting of neural HMGB1 is a promising approach for anti-inflammatory therapy.
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Epilepsia do Lobo Temporal , Epilepsia , Proteína HMGB1 , Humanos , Esclerose/metabolismo , Esclerose/patologia , Proteína HMGB1/metabolismo , Epilepsia do Lobo Temporal/cirurgia , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Epilepsia/cirurgia , Epilepsia/metabolismo , Gliose/patologia , Citoplasma/metabolismoRESUMO
Background: Circular ribonucleic acids (circRNAs) play a key role in the development of different types of cancer. Ferroptosis is a type of programmed cell death that contributes to cancer progression. However, the role of circRNAs in lung adenocarcinoma (LUAD) ferroptosis remains unclear. Methods: The gene expression levels of circRNA P4HB (circP4HB), microRNA-1184 (miR-1184) and Solute carrier family 7 member 11 (Slc7a11), also known as Xct were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Ferroptosis of established LUAD cells was induced by erastin. Cell viability was examined via Cell Counting Kit 8 assays. Ferroptosis was evaluated by malondialdehyde (MDA), Prostaglandin-endoperoxide Synthase 2 (Ptgs2), lipid reactive oxygen species (lipid ROS), and JC-1 detection. The mechanism of circP4HB/miR-1184/SLC7A11 was investigated by luciferase reporter assays, RNA immunoprecipitation, RNA pull-down, and western blot assays. A functional for circP4HB in vivo was determined using xenograft nude mice models. Results: CircP4HB expression levels were increased in LUAD. It triggered glutathione (GSH) synthesis and, therefore protected LUAD cells from ferroptosis induced by erastin. CircP4HB may function as a competing endogenous RNA by modulating miR-1184 to regulate SLC7A11. CircP4HB inhibited ferroptosis by regulating miR-1184/ SLC7A11-mediated GSH synthesis. In vivo, overexpression of circP4HB promoted tumor growth and inhibited ferroptosis. Conclusions: The circRNA, circP4HB acts as a novel ferroptosis suppressor in LUAD. Furthermore, circP4HB protects LUAD from ferroptosis via modulation of the miR-1184/SLC7A11 axis. Our findings identified circP4HB as a novel biomarker in LUAD and warrants further investigation in the early diagnosis and treatment of LUAD.
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Two terpenes, 3-keto-tirucalla-8,24-dien-21-oic acid(KTDA) and 2-methoxy-5-acetoxy-furanogermacr-1(10)-en-6-one(FSA), are isolated from Olibanum and Myrrha respectively, which are characterized by high yield and easy crystallization during the preparation. The present study explored the regulatory targets and anti-inflammatory mechanism of KTDA and FSA based on network pharmacology and cell viability assay. First, the drug-likeness of KTDA and FSA was predicted by Swiss ADME. The target prediction of active components was carried out by Swiss Target Prediction and Pharmmapper. TTD, Drug Bank, and Gene Cards were searched for inflammation-related target genes of KTDA and FSA. Protein-protein interaction(PPI) analysis was performed on the inflammatory targets of KTDA and FSA by STRING, and Cytoscape was used to conduct topological analysis of the interaction results and construct the PPI network. GO function and KEGG pathway enrichment analyses of inflammatory targets of KTDA and FSA were carried out by DAVID, and a " component-target-pathway" network was constructed. Finally, lipopolysaccharide(LPS)-induced RAW264. 7 cells were treated with KTDA and FSA at different concentrations, and nitric oxide(NO) concentration and protein and m RNA expression levels were detected. The results showed that both KTDA and FSA showed good drug-likeness. A total of 157 and 142 inflammation-related targets of KTDA and FSA were screened out. PPI network analysis showed that MAPK1, AKT1, MAPK8, PIK3 CA,PIK3 R1, EGFR, etc. might be the key proteins for the anti-inflammatory effect. PI3 K/AKT and MAPK signaling pathways were obtained by KEGG and GO-BP enrichment. Cell experiment results showed that KTDA and FSA could exert anti-inflammatory effects by inhibiting NO production, reducing the phosphorylation levels of JNK, p38, and AKT proteins, and down-regulating the m RNA expression of interleukin(IL)-1ß and IL-6. Meanwhile, FSA could also inhibit ERK phosphorylation. The results indicated that KTDA and FSA had significant anti-inflammatory activity, which provided a scientific basis and important support for the further research,development, and utilization of Olibanum and Myrrha.
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Formigas , Medicamentos de Ervas Chinesas , Franquincenso , Animais , Medicamentos de Ervas Chinesas/farmacologia , Lipopolissacarídeos , Simulação de Acoplamento Molecular , Farmacologia em RedeRESUMO
In this paper, network pharmacology method and molecular docking technique were used to investigate the target genes of Olibanum and Myrrha compatibility and the possible mechanism of action in the treatment of rheumatoid arthritis(RA). Our team obtained the main active components of Olibanum-Myrrha based on literatures study, relevant traditional Chinese medicine systematic pharmacological databases and literature retrieval, and made target prediction of the active components through SwissTargetPrediction database. At the same time, RA-related targets were collected through DrugBank, GeneCards and Therapeutic Target Database(TDD) databases; and VENNY 2.1 was use to collect intersection targets to map common targets of drug and disease of Venn diagram online. The team used STRING database to construct PPI protein interaction network diagram, and screen out core targets according to the size of the interaction, and Cytoscape 3.6.0 software was used to construct network models of "traditional Chinese medicine-component-target" "traditional Chinese medicine-component-target-disease" and core target interaction network model. The intersection target was analyzed by using DAVID 6.8 online database for GO function analysis and KEGG pathway enrichment analysis, and Pathon was used to visualization. AutoDock Vina and Pymol were used to connect the core active components with the core targets. Sixteen active components of Olibanum-Myrrha pairs were found and collected in the laboratory, and 320 relevant potential targets, 468 RA-related targets and 62 intersection targets were obtained through the Venn diagram. It mainly acted on multiple targets, such as IL6, TNF, IL1 B and MAPK1, involving TNF signaling pathway and Toll-like receptor signaling pathway in RA treatment. Finally, in this study, possible targets and signaling pathways of Olibanum-Myrrha compatibility therapy for RA were discussed, and molecular docking between core targets and core active components was conducted, which could provide scientific basis for the study on the mechanism of Olibanum-Myrrha compatibility.
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Artrite Reumatoide , Medicamentos de Ervas Chinesas , Franquincenso , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Humanos , Medicina Tradicional Chinesa , Simulação de Acoplamento MolecularRESUMO
Two terpenes, 3-keto-tirucalla-8,24-dien-21-oic acid(KTDA) and 2-methoxy-5-acetoxy-furanogermacr-1(10)-en-6-one(FSA), are isolated from Olibanum and Myrrha respectively, which are characterized by high yield and easy crystallization during the preparation. The present study explored the regulatory targets and anti-inflammatory mechanism of KTDA and FSA based on network pharmacology and cell viability assay. First, the drug-likeness of KTDA and FSA was predicted by Swiss ADME. The target prediction of active components was carried out by Swiss Target Prediction and Pharmmapper. TTD, Drug Bank, and Gene Cards were searched for inflammation-related target genes of KTDA and FSA. Protein-protein interaction(PPI) analysis was performed on the inflammatory targets of KTDA and FSA by STRING, and Cytoscape was used to conduct topological analysis of the interaction results and construct the PPI network. GO function and KEGG pathway enrichment analyses of inflammatory targets of KTDA and FSA were carried out by DAVID, and a " component-target-pathway" network was constructed. Finally, lipopolysaccharide(LPS)-induced RAW264. 7 cells were treated with KTDA and FSA at different concentrations, and nitric oxide(NO) concentration and protein and m RNA expression levels were detected. The results showed that both KTDA and FSA showed good drug-likeness. A total of 157 and 142 inflammation-related targets of KTDA and FSA were screened out. PPI network analysis showed that MAPK1, AKT1, MAPK8, PIK3 CA,PIK3 R1, EGFR, etc. might be the key proteins for the anti-inflammatory effect. PI3 K/AKT and MAPK signaling pathways were obtained by KEGG and GO-BP enrichment. Cell experiment results showed that KTDA and FSA could exert anti-inflammatory effects by inhibiting NO production, reducing the phosphorylation levels of JNK, p38, and AKT proteins, and down-regulating the m RNA expression of interleukin(IL)-1β and IL-6. Meanwhile, FSA could also inhibit ERK phosphorylation. The results indicated that KTDA and FSA had significant anti-inflammatory activity, which provided a scientific basis and important support for the further research,development, and utilization of Olibanum and Myrrha.
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Animais , Formigas , Medicamentos de Ervas Chinesas/farmacologia , Franquincenso , Lipopolissacarídeos , Simulação de Acoplamento Molecular , Farmacologia em RedeRESUMO
In this paper, network pharmacology method and molecular docking technique were used to investigate the target genes of Olibanum and Myrrha compatibility and the possible mechanism of action in the treatment of rheumatoid arthritis(RA). Our team obtained the main active components of Olibanum-Myrrha based on literatures study, relevant traditional Chinese medicine systematic pharmacological databases and literature retrieval, and made target prediction of the active components through SwissTargetPrediction database. At the same time, RA-related targets were collected through DrugBank, GeneCards and Therapeutic Target Database(TDD) databases; and VENNY 2.1 was use to collect intersection targets to map common targets of drug and disease of Venn diagram online. The team used STRING database to construct PPI protein interaction network diagram, and screen out core targets according to the size of the interaction, and Cytoscape 3.6.0 software was used to construct network models of "traditional Chinese medicine-component-target" "traditional Chinese medicine-component-target-disease" and core target interaction network model. The intersection target was analyzed by using DAVID 6.8 online database for GO function analysis and KEGG pathway enrichment analysis, and Pathon was used to visualization. AutoDock Vina and Pymol were used to connect the core active components with the core targets. Sixteen active components of Olibanum-Myrrha pairs were found and collected in the laboratory, and 320 relevant potential targets, 468 RA-related targets and 62 intersection targets were obtained through the Venn diagram. It mainly acted on multiple targets, such as IL6, TNF, IL1 B and MAPK1, involving TNF signaling pathway and Toll-like receptor signaling pathway in RA treatment. Finally, in this study, possible targets and signaling pathways of Olibanum-Myrrha compatibility therapy for RA were discussed, and molecular docking between core targets and core active components was conducted, which could provide scientific basis for the study on the mechanism of Olibanum-Myrrha compatibility.
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Humanos , Artrite Reumatoide/genética , Medicamentos de Ervas Chinesas , Franquincenso , Medicina Tradicional Chinesa , Simulação de Acoplamento MolecularRESUMO
Lung adenocarcinoma accounts for half of all lung cancer cases in most countries. Mounting evidence has demonstrated that microRNAs play important roles in cancer progression, and some of them can be identified as potential biomarkers. This study aimed to explore the role of miR-550a-5p, a lung adenocarcinoma-associated mature microRNA screened out from the TCGA database via R-studio and Perl, with abundant expression in samples and with 5-year survival prognosis difference, as well as having not been studied in lung cancer yet. Potential target genes were predicted by the online database. Gene ontology enrichment, pathway enrichment, protein-protein interaction network, and hub genes-microRNA network were constructed by FunRich, STRING database, and Cytoscape. Then, LIMD1, a known tumor suppressor gene reported by multiple articles, was found to have a negative correlation with miR-550a-5p. The expression of miR-550a-5p was up-regulated in tumor samples and tumor-associated cell lines. Its high expression was also correlated with tumor size. Cell line A549 treated with miR-550a-5p overexpression promoted tumor proliferation, while H1299 treated with miR-550a-5p knockdown showed the opposite result. Mechanically, miR-550a-5p negatively regulated LIMD1 by directly binding to its 3'-UTR validated by dual luciferase assay. In summary, a new potential prognostic and therapeutic biomarker, miR-550a-5p, has been identified by bioinformatics analysis and experimental validation in vitro and in vivo, which promotes lung adenocarcinoma by silencing a known suppressor oncogene LIMD1.
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AIM: The present study aims to investigate the antihypertensive effect and the underlying mechanism of GAO-ZI-YAO, one of the traditional Chinese medicines, in elderly spontaneous hypertensive rats (SHR). METHODS: 12-month-old male SHRs were randomly divided into five groups on the basis of treatment with different doses of GAO-ZI-YAO or angiotensin II receptor-1 blocker (ARB, Irbesartan) for four weeks. Systolic blood pressure (SBP), and serum levels of nitric oxide (NO), endothelin-1 (ET-1), angiotensin II (Ang II), vascular endothelial growth factor (VEGF), interleukin (IL)-1ß, IL-2, IL-6, and tumor necrotic factor (TNF)-α were measured. The pathological changes of ventricular muscle and thoracic aorta were observed by hematoxylin-eosin staining (H&E). RESULTS: GAO-ZI-YAO treatment reduced SBP in a dose-dependent manner accompanied by the inhibition of the development of cardiovascular remodeling. Although GAO-ZI-YAO treatment markedly increased serum levels of NO and suppressed serum levels of Ang II, this medicine did not affect the serum levels of ET-1 and VEGF. In addition, GAO-ZI-YAO also inhibited inflammatory response parameters (inflammatory cell infiltration in cardiac tissues and serum levels of IL-1ß, IL-2, IL-6, and TNF-α) in a dose-dependent manner. CONCLUSION: GAO-ZI-YAO exerts antihypertensive and anti-cardiovascular-remodeling effects in elderly SHR, which may be through regulation of NO, Ang II production, and inflammation.
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Anti-Hipertensivos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Hipertensão/tratamento farmacológico , Medicina Tradicional Chinesa , Angiotensina II/sangue , Angiotensina II/fisiologia , Animais , Anti-Inflamatórios/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Citocinas/sangue , Medicamentos de Ervas Chinesas/farmacologia , Endotelina-1/sangue , Endotelina-1/fisiologia , Irbesartana/uso terapêutico , Masculino , Óxido Nítrico/sangue , Óxido Nítrico/fisiologia , Ratos , Ratos Endogâmicos SHR , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/fisiologiaRESUMO
Cyclin E is a key factor for S phase entry, and deregulation of Cyclin E results in developmental defects and tumors. Therefore, proper cycling of Cyclin E is crucial for normal growth. Here we found that transcription factors Apontic (Apt) and E2f1 cooperate to induce cyclin E in Drosophila. Functional binding motifs of Apt and E2f1 are clustered in the first intron of Drosophila cyclin E and directly contribute to the cyclin E transcription. Knockout of apt and e2f1 together abolished Cyclin E expression. Furthermore, Apt up-regulates Retinoblastoma family protein 1 (Rbf1) for proper chromatin compaction, which is known to repress cyclin E. Notably, Apt-dependent up-regulation of Cyclin E and Rbf1 is evolutionarily conserved in mammalian cells. Our findings reveal a unique mechanism underlying the induction and subsequent decline of Cyclin E expression.
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Frankincense and myrrha (FM), commonly used as a classical herbal pair, have a wide range of clinical applications and definite anti-inflammatory activity. However, anti-neuroinflammation effects and mechanisms are not clear. In this study, we adopted a lipopolysaccharide (LPS)-induced microglial (BV2) cell model and a network pharmacology method to reveal the anti-neuroinflammatory effects and mechanisms of boswellic acid (BA) and myrrha sesquiterpenes (MS) with different proportions of compatibility. The data showed that the different ratios of BA and MS had different degrees of inhibition of interleukin-1ß (IL-1ß), IL-6, and inducible nitric oxide synthase (iNOS) mRNA expression, down-regulated the phosphor-nuclear factor kappa B/nuclear factor kappa B (p-NF-Ò¡B)/(NF-Ò¡B), phosphorylated protein kinase b/protein kinase b (p-AKT/AKT), and Toll-like receptor 4 (TLR4) protein expression levels, and increased phospho-PI3 kinase (p-PI3K) protein expression levels. When the ratios of BA and MS were 10:1, 5:1, and 20:1, better effective efficacy was exhibited. According to the correlation analysis between the effect index and bioactive substances, it was suggested that 2-methoxy-5-acetoxy -fruranogermacr-1(10)-en-6-one (Compound 1), 3α-acetyloxylanosta-8,24-dien-21-oic acid (Compound 2), 11-keto-boswellic acid (Compound 3), and 3-acetyl-11-keto-ß -boswellic acid (Compound 4) made important contributions to the treatment of neuroinflammation. Furthermore, based on the network pharmacological analysis, it was found that these four active compounds acted on 31 targets related to neuroinflammation and were involved in 32 signaling pathways which mainly related to the immune system, cardiovascular system, and nervous system, suggesting that BA and MS could be used to treat neuroinflammation.
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Commiphora/química , Inflamação/tratamento farmacológico , Microglia/patologia , Fármacos Neuroprotetores/uso terapêutico , Sesquiterpenos/uso terapêutico , Triterpenos/uso terapêutico , Animais , Linhagem Celular , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Ontologia Genética , Inflamação/patologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos , Camundongos , Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sesquiterpenos/farmacologia , Receptor 4 Toll-Like/metabolismo , Triterpenos/farmacologiaRESUMO
The hydrogen evolution reaction activity of carbon-supported Pt catalyst is highly dependent on Pt-C interfaces. Herein, we focus on the relationships between Pt activity and N/O-functionalized hollow carbon sphere (HCS) substrate in acidic media. The electrochemical dissolution of Pt counter electrode is performed to prepare Pt nanoparticles in low loading. The N groups are beneficial for homogeneously sized Pt nanoparticles, whereas the O groups lead to aggregated nanoparticles. Moreover, the proper electronegativity of the N groups may enable capturing of protons to create proton-rich Pt-C interfaces and transfer them onto the Pt sites. The O groups may also capture protons by hydrogen bonding, but the subsequent release of protons is more difficult due to a stronger electronegativity and result in an inferior Pt activity. Consequently, the N-doped HCS with a low Pt loading (1.7 µg cm-2 and 0.05 wt %) possesses a higher intrinsic activity compared with Pt on O-doped HCS. Moreover, it outperforms the commercial 20% Pt/C with a stable operation for 12 h. This work may provide suggestions for constructing the advantageous Pt-C interfaces by proper functional groups for high catalytic efficiencies.
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The traditional synthesis for bimetallic-based electrocatalysts is challengeable for fine composition and elemental distribution because of the uncontrollable growth speed of nanostructures utilizing metal salt precursors. Herein, a unique electrochemical corrosion engineering strategy is developed via electrochemically transforming metal solid substrates (iron foil and nickel foam) into a highly active Ni-Fe oxide film for oxygen evolution, rather than directly utilizing metal ion precursors. This synthesis involves electrochemical corrosion of a Fe foil in an aqueous electrolyte along with electrochemical passivation of Ni foam (NF). The released trace Fe ions gradually incorporate into passivated NF surfaces to construct Ni-Fe oxide film and crucially improve composition distribution in the catalyst film. As a result, the resulted film with an ultralow mass loading (0.22 mg cm-2) delivers large current densities of 500 mA cm-2 at overpotential of only 270 mV in 6.0 M KOH at 60 °C, outperforming many reported NiFe catalysts requiring much higher mass loadings. More interestingly, the as-prepared catalyst almost reaches the standard (500 mA cm-2 within the overpotential of 300 mV) in commercial water electrolysis with long-term stability for at least 10 h. This work may provide a unique synthesis strategy for nonprecious transition-metal catalysts for desirable water splitting and can be expanded to many other electrocatalysis systems.
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Hypolipidemic effects of the newly synthesized 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione-based fibrates were evaluated in Triton WR-1339 and high-fat diet (HFD)-induced hyperlipidemic mice. Preliminary screening of all the synthesized compounds was done by using an acute model (Triton WR-1339 model), in which compound 6 shown more significant antidyslipidemic activity than fenofibrate (FF). The compound 6 was also found to reduce serum triglyceride (TG), total cholesterol (TC) and low density lipoprotein cholesterin (LDL) in HFD-induced hyperlipidemic mice. Moreover, compound 6 displayed hepatoprotective effect, a significant amelioration in hepatic indices (AST and ALT) toxicity was observed and the histological examination showed that compound 6 inhibited the development of hepatic lipid accumulation and ameliorated the damage in hepatic tissue compared to model mice. Additional effects such as the potent antioxidant and anti-inflammatory action confirmed and reinforced the efficacy of compound 6 as a new agent of dual-effect hypolipidemic and hepatoprotective activities.
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Ácidos Fíbricos/química , Ácidos Fíbricos/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/química , Hipolipemiantes/uso terapêutico , Tionas/química , Tionas/uso terapêutico , Tiofenos/química , Tiofenos/uso terapêutico , Animais , Dieta Hiperlipídica/efeitos adversos , Ácidos Fíbricos/farmacologia , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Hipolipemiantes/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Tionas/farmacologia , Tiofenos/farmacologiaRESUMO
Oxidative stress has been regarded as the leading mechanism of the hepatotoxicity of clofibrate (CF). To achieve multifunctional novel hypolipidemic agents with hypolipidemia, antioxidant, and ameliorating liver injury, clofibric acid derivative hydroxytyrosol-clofibrate (CF-HT) was synthesized by molecular hybridization. CF-HT exhibited significant hypolipidemia, reducing serum triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 30%, 33%, and 29% in hyperlipidemic mice induced by Triton WR 1339. CF-HT also shown hepatoprotective effect, a significant decrease in hepatic indices toxicity was observed, i.e. aspartate and lactate transaminases (AST and ALT) activities, alkalines phosphatases (ALP), and total bilirubin (TBIL) levels. The liver weight and liver coefficient were also ameliorated. Serum superoxide dismutase (SOD) was significantly elevated, and serum catalase (CAT) and malondialdehyde (MDA) content were remarkably restored. The hepatic glutathione (GSH) content was obviously increased and hepatic oxidized glutathione (GSSG) content was reduced dramatically by CF-HT, as compared to the CF treated mice (pâ¯<â¯0.05). Moreover, the histopathological damage that hepatocyte hyperplasia and hypertrophy was also significantly ameliorated by treatment with CF-HT. Therefore, the results indicated that CF-HT exerted more potent hypolipidemic activity and definite hepatoprotective effect which may mainly be associated with its antioxidative property in mice.
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Antioxidantes/farmacologia , Clofibrato/farmacologia , Hepatócitos/efeitos dos fármacos , Hipolipemiantes/farmacologia , Álcool Feniletílico/análogos & derivados , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Peso Corporal/efeitos dos fármacos , Clofibrato/administração & dosagem , Clofibrato/química , Relação Dose-Resposta a Droga , Hepatócitos/metabolismo , Hipolipemiantes/administração & dosagem , Hipolipemiantes/química , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estrutura Molecular , Tamanho do Órgão/efeitos dos fármacos , Álcool Feniletílico/administração & dosagem , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia , Polietilenoglicóis/farmacologia , Relação Estrutura-AtividadeRESUMO
Hydroxytyrosol (HT) is a natural polyphenol antioxidant that exists in olive oil. In the study of multifunctional hypolipidemic of nicotinic derivatives, we found that hydroxytyrosol nicotinate (HT-N) incorporation of niacin with HT displayed ?-glucosidase inhibitory activities in vitro, such as yeast ?-glucosidase (IC50?=?117.72??M) and rat intestinal ?-glucosidases maltase (IC50?=?31.86??M) and sucrase (IC50?=?22.99??M), and had a good control of postprandial blood glucose (PBG). HT-N shown significantly hypoglycemic action by 16.9% and protection of pancreatic tissue in type 2 diabetic mellitus (T2DM) mouse model. HT-N also shown a potent antioxidant activity and property of anti-glycation in vitro, which were benefit for ameliorating diabetic complications. Moreover, HT-N exhibited much significant hypolipidemia, lowering plasma triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 34.6%, 45.8% and 32.1% respectively, in hyperlipidemic mice induced by Triton WR 1339. The results indicated that HT-N has hypolipidemic, hypoglycemic and antioxidant actions. All these properties could be conducive to amelioration of oxidative stress, hyperlipidemia, and diabetes that HT-N may serve as a multifunctional potential therapeutic strategy in diabetic patients with hyperlipidemia.
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Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Niacina/farmacologia , Álcool Feniletílico/análogos & derivados , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/farmacologia , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Hipolipemiantes/administração & dosagem , Hipolipemiantes/química , Concentração Inibidora 50 , Lipídeos/sangue , Masculino , Camundongos , Niacina/administração & dosagem , Niacina/química , Estresse Oxidativo/efeitos dos fármacos , Álcool Feniletílico/administração & dosagem , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia , RatosRESUMO
The surface composite and morphology of binary metal sulfides are the key for efficient overall water splitting. However, tuning the morphology and surface composition of binary metal sulfides in a facile way is still a challenge. Herein, binary Fe-Ni sulfides supported on nickel foam (FeNi-S/NF) with different morphology and composition ratio of Fe/Ni have been synthesized through a facile one-step electrodeposition assisted by liquidcrystaltemplate (LCT). The binary FeNi-S has improved activity and conductivity compared to single metal sulfides. LCT-assisted porous FeNi-S film composed of uniform nanospheres is obviously different from planar film electrodeposited in water solution. LCT-assisted FeNi-S nanospheres are covered by many interwoven nanosheets, implying more exposed active sites for water splitting. Furthermore, the different Fe/Ni ratios of FeNi-S/NF samples have been systematically studied to explore the influence of Fe-incorporation on intrinsic activity of FeNi-S/NF. And the sample with Fe/Ni ratio (3/1) demonstrates the best activity and excellent stability for overall water electrolysis. Therefore, our work provides a facile and controllable access to binary metal sulfides with excellent performances for overall water splitting.
RESUMO
MoO42-@aniline-pyrrole (MoO42-@polymer) spheres as precursors have been used to synthesize unique core-shell nanostructure consisting of molybdenum carbide and molybdenum phosphide composites encapsulated into uniformly dual N, P-doped carbon shells (Mo2C/MoP@NPC) through a facile two-step strategy. Firstly, porous core-shell N-doped Mo2C@C (Mo2C@NC) nanospheres have been synthesized with ultrafine Mo2C nanoparticles as core and ultrathin NC as shell by a annealing route. Secondly, Mo2C/MoP@NPC has been obtained maintaining intact spherical-like morphology through a phosphidation reaction in high temperature. The synergistic effect of Mo2C and MoP may reduce the strong MoH bonding energy of pure Mo2C and provide a fast hydrogen release process. In addition, the dual N, P-doped carbon matrix as shell can not only improve the electroconductivity of catalysts but also prevent the corrosion of Mo2C/MoP nanoparticles during the electrocatalytic process. When used as HER cathode in acids, the resulting Mo2C/MoP@NPC shows excellent catalytic activity and durability, which only needs an overpotential of 160â¯mV to drive 10â¯mAâ¯cm-2. Moreover, it also exhibits better HER performance in basic and neutral media with the need for overpotentials of only 169 and 228â¯mV to achieve 10â¯mAâ¯cm-2, respectively. This inorganic-organic combination of Mo-based catalysts may open up a new way for water-splitting to produce large-scale hydrogen.
RESUMO
Hedgehog (Hh) signaling pathway and Cyclin E are key players in cell proliferation and organ development. Hyperactivation of hh and cyclin E has been linked to several types of cancer. However, coordination of the expression of hh and cyclin E was not well understood. Here we show that an evolutionarily conserved transcription factor Apontic (Apt) directly activates hh and cyclin E through its binding site in the promoter regions of hh and cyclin E. This Apt-dependent proper expression of hh and cyclin E is required for cell proliferation and development of the Drosophila wing. Furthermore, Fibrinogen silencer-binding protein (FSBP), a mammalian homolog of Apt, also positively regulates Sonic hh (Shh), Desert hh (Dhh), Cyclin E1 (CCNE1) and Cyclin E2 (CCNE2) in cultured human cells, suggesting evolutionary conservation of the mechanism. Apt-mediated expression of hh and cyclin E can direct proliferation of Hh-expressing cells and simultaneous growth, patterning and differentiation of Hh-recipient cells. The discovery of the simultaneous expression of Hh and principal cell-cycle regulator Cyclin E by Apt implicates insight into the mechanism by which deregulated hh and cyclin E promotes tumor formation.
Assuntos
Padronização Corporal/genética , Ciclina E/genética , Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Proteínas Hedgehog/genética , Fatores de Transcrição/genética , Asas de Animais/metabolismo , Animais , Sequência de Bases , Sítios de Ligação , Evolução Biológica , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Sequência Conservada , Ciclina E/metabolismo , Ciclinas/genética , Ciclinas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Feminino , Proteínas Fetais/genética , Proteínas Fetais/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Células HEK293 , Proteínas Hedgehog/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Transdução de Sinais , Fatores de Transcrição/metabolismo , Asas de Animais/citologia , Asas de Animais/crescimento & desenvolvimentoRESUMO
Theoretical and compelling experimental evidence indicates that the interaction between an anion and an aromatic π system when the anion is directly above the ring face ("η(6)"-type anion-π), can be attractive. This may play an important role in the formation and recognition of biomolecular structures. We examined high-resolution structures of proteins and nucleic acids for the presence of "η(6)"-type anion-π. Though less frequent than its counterpart cation-π, "η(6)"-type anion-π is observed unambiguously, occurring in protein/nucleic acid loops and often involving conserved/coevolving sites in proteins, suggesting it plays an important role in macromolecular folding and function.