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1.
Anesthesiology ; 141(1): 100-115, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38537025

RESUMO

BACKGROUND: Although it has been established that elevated blood pressure and its variability worsen outcomes in spontaneous intracerebral hemorrhage, antihypertensives use during the acute phase still lacks robust evidence. A blood pressure-lowering regimen using remifentanil and dexmedetomidine might be a reasonable therapeutic option given their analgesic and antisympathetic effects. The objective of this superiority trial was to validate the efficacy and safety of this blood pressure-lowering strategy that uses remifentanil and dexmedetomidine in patients with acute intracerebral hemorrhage. METHODS: In this multicenter, prospective, single-blinded, superiority randomized controlled trial, patients with intracerebral hemorrhage and systolic blood pressure (SBP) 150 mmHg or greater were randomly allocated to the intervention group (a preset protocol with a standard guideline management using remifentanil and dexmedetomidine) or the control group (standard guideline-based management) to receive blood pressure-lowering treatment. The primary outcome was the SBP control rate (less than 140 mmHg) at 1 h posttreatment initiation. Secondary outcomes included blood pressure variability, neurologic function, and clinical outcomes. RESULTS: A total of 338 patients were allocated to the intervention (n = 167) or control group (n = 171). The SBP control rate at 1 h posttreatment initiation in the intervention group was higher than that in controls (101 of 161, 62.7% vs. 66 of 166, 39.8%; difference, 23.2%; 95% CI, 12.4 to 34.1%; P < 0.001). Analysis of secondary outcomes indicated that patients in the intervention group could effectively reduce agitation while achieving lighter sedation, but no improvement in clinical outcomes was observed. Regarding safety, the incidence of bradycardia and respiratory depression was higher in the intervention group. CONCLUSIONS: Among intracerebral hemorrhage patients with a SBP 150 mmHg or greater, a preset protocol using a remifentanil and dexmedetomidine-based standard guideline management significantly increased the SBP control rate at 1 h posttreatment compared with the standard guideline-based management.


Assuntos
Anti-Hipertensivos , Pressão Sanguínea , Hemorragia Cerebral , Dexmedetomidina , Remifentanil , Humanos , Dexmedetomidina/uso terapêutico , Dexmedetomidina/administração & dosagem , Remifentanil/administração & dosagem , Remifentanil/uso terapêutico , Masculino , Feminino , Estudos Prospectivos , Hemorragia Cerebral/tratamento farmacológico , Idoso , Pessoa de Meia-Idade , Método Simples-Cego , Pressão Sanguínea/efeitos dos fármacos , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Resultado do Tratamento , Hipnóticos e Sedativos/uso terapêutico
2.
Mediators Inflamm ; 2023: 6051946, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36687218

RESUMO

Based on the multiomics analysis, this study is aimed at investigating the underlying mechanism of didymin against acute liver injury (ALI). The mice were administrated with didymin for 2 weeks, followed by injection with lipopolysaccharide (LPS) plus D-galactosamine (D-Gal) to induce ALI. The pathological examination revealed that didymin significantly ameliorated LPS/D-Gal-induced hepatic damage. Also, it markedly reduced proinflammatory cytokines release by inhibiting the TLR4/NF-κB pathway activation, alleviating inflammatory injury. A transcriptome analysis proved 2680 differently expressed genes (DEGs) between the model and didymin groups and suggested that the PI3K/Akt and metabolic pathways might be the most relevant targets. Meanwhile, the metabolome analysis revealed 67 differently expressed metabolites (DEMs) between the didymin and model groups that were mainly clustered into the glycerophospholipid metabolism, which was consistent with the transcriptome study. Importantly, a comprehensive analysis of both the omics indicated a strong correlation between the DEGs and DEMs, and an in-depth study demonstrated that didymin alleviated metabolic disorder and hepatocyte injury likely by inhibiting the glycerophospholipid metabolism pathway through the regulation of PLA2G4B, LPCAT3, and CEPT1 expression. In conclusion, this study demonstrates that didymin can ameliorate LPS/D-Gal-induced ALI by inhibiting the glycerophospholipid metabolism and PI3K/Akt and TLR4/NF-κB pathways.


Assuntos
NF-kappa B , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Lipopolissacarídeos/farmacologia , Transcriptoma , Receptor 4 Toll-Like/metabolismo , Fígado/metabolismo , Metaboloma , Glicerofosfolipídeos/metabolismo , Glicerofosfolipídeos/farmacologia , 1-Acilglicerofosfocolina O-Aciltransferase/genética , 1-Acilglicerofosfocolina O-Aciltransferase/metabolismo , 1-Acilglicerofosfocolina O-Aciltransferase/farmacologia , Fosfolipases A2 do Grupo IV/genética , Fosfolipases A2 do Grupo IV/metabolismo , Fosfolipases A2 do Grupo IV/farmacologia
3.
J Chem Inf Model ; 62(10): 2499-2509, 2022 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-35452230

RESUMO

The protein-ligand scoring function plays an important role in computer-aided drug discovery and is heavily used in virtual screening and lead optimization. In this study, we developed a new empirical protein-ligand scoring function with amino acid-specific interaction components for hydrogen bond, van der Waals, and electrostatic interactions. In addition, hydrophobic, π-stacking, π-cation, and metal-ligand interactions are also included in the new scoring function. To better evaluate the performance of the AA-Score, we generated several new test sets for evaluation of scoring, ranking, and docking performances, respectively. Extensive tests show that AA-Score performs well on scoring, docking, and ranking as compared to other widely used traditional scoring functions. The performance improvement of AA-Score benefits from the decomposition of individual interaction into amino acid-specific types. To facilitate applications, we developed an easy-to-use tool to analyze protein-ligand interaction fingerprint and predict binding affinity using the AA-Score. The source code and associated running examples can be found at https://github.com/xundrug/AA-Score-Tool.


Assuntos
Aminoácidos , Proteínas , Aminoácidos/metabolismo , Ligação de Hidrogênio , Ligantes , Simulação de Acoplamento Molecular , Ligação Proteica , Proteínas/química
4.
J Chem Inf Model ; 61(7): 3159-3165, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34251213

RESUMO

pKa is an important property in the lead optimization process since the charge state of a molecule in physiologic pH plays a critical role in its biological activity, solubility, membrane permeability, metabolism, and toxicity. Accurate and fast estimation of small molecule pKa is vital during the drug discovery process. We present MolGpKa, a web server for pKa prediction using a graph-convolutional neural network model. The model works by learning pKa related chemical patterns automatically and building reliable predictors with learned features. ACD/pKa data for 1.6 million compounds from the ChEMBL database was used for model training. We found that the performance of the model is better than machine learning models built with human-engineered fingerprints. Detailed analysis shows that the substitution effect on pKa is well learned by the model. MolGpKa is a handy tool for the rapid estimation of pKa during the ligand design process. The MolGpKa server is freely available to researchers and can be accessed at https://xundrug.cn/molgpka.


Assuntos
Descoberta de Drogas , Redes Neurais de Computação , Computadores , Humanos , Ligantes , Aprendizado de Máquina
5.
Phys Chem Chem Phys ; 23(40): 23173-23183, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34618881

RESUMO

MXenes represent an emerging family of two-dimensional materials of transition metal carbides/carbonitrides terminated with functional groups like -O, -OH, and -F on the chemically active surface of MX slabs. As a member of the family, Nb2CTx exhibits superior lithium storage capacity over most of the other MXenes as anode materials in lithium-ion batteries (LIBs). However, an in-depth understanding of the charge storage mechanism is still lacking so far. Here, through combining complementary experiments and density functional theory calculations, we provide insights into the (de)lithiation process. Specifically, Nb2CTx with dominant -O functional groups stores charge as a result of changes in the oxidation states of both transition metals Nb and O, which is supported by Bader charge analysis showing a significant change in the oxidation states of Nb and O upon lithiation. As monitored by ex situ X-ray diffraction, the interlayer spacing of Nb2CTx changes slightly upon lithium ion (de)intercalation, corresponding to a volume change of only 2.3% with a near zero-strain feature. By coupling with a LiFePO4/C cathode, the full cell presents superior rate capability and cycling stability as well. The insights into the charge storage mechanism of Nb2CTx in this work provide useful guidance for the rational design of MXene-based anode materials for high-performance LIBs.

6.
Biomed Chromatogr ; 32(2)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28801971

RESUMO

The aim of this study was to elucidate the pharmacokinetics of olerciamide A in rats after oral and intravenous administration of Portulaca oleracea L. extract by a simple and rapid ultra high-performance liquid chromatography method with bergapten as internal standard. The pharmacokinetic results indicated that olerciamide A was rapidly distributed with a time to peak concentration of 30 min after oral administration and presented a low oral absolute bioavailability of 4.57%. The metabolism of olerciamide A in rats was also investigated using ultra-high-performance liquid chromatography electrospray coupled with quadrupole-time of flight mass spectrometry to elucidate the reason for the low absolute bioavailability of olerciamide A and seven metabolites of oleraciamide A were found in rat plasma and urine.


Assuntos
Alcaloides , Cromatografia Líquida de Alta Pressão/métodos , Morfinanos , Portulaca/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Alcaloides/sangue , Alcaloides/metabolismo , Alcaloides/farmacocinética , Alcaloides/urina , Animais , Glucuronídeos/metabolismo , Glutationa/metabolismo , Limite de Detecção , Modelos Lineares , Masculino , Morfinanos/sangue , Morfinanos/metabolismo , Morfinanos/farmacocinética , Morfinanos/urina , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Sulfatos/metabolismo
7.
Molecules ; 23(11)2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30366473

RESUMO

The One Strain Many Compounds (OSMAC) method was applied to explore the chemical diversities of secondary metabolites produced by Neosartorya fischeri NRRL 181. Four pyripyropenes 1⁻4, eight steroids 5⁻11, and four prenylated indole alkaloids 12⁻15, were obtained from the fungus cultured in petri dishes containing potato dextrose agar (PDA). 1,7,11-trideacetylpyripyropene A (1) and 1,11-dideacetyl pyripyropene A (2) were obtained and spectroscopically characterized (1D, 2D NMR, and HR-ESI-MS) from a natural source for the first time. It offered a sustainable source of these two compounds, which were usually used as starting materials in preparing pyripyropene derivatives. In addition, as compared with all the other naturally occurring pyripyropenes, 1 and 2 possessed unique acetylation patterns that did not follow the established late-step biosynthetic rules of pyripyropenes. The natural occurrence of 1 and 2 in the fungus implied that the timing and order of hydroxylation and acetylation in the late-step biosynthetic pathway of pyripyropenes remained to be revealed. The isolation and identification of 1⁻15 indicated that the OSMAC method could remarkably alter the metabolic profile and enrich the chemical diversities of fungal metabolites. Compounds 1⁻4 exhibited no obvious cytotoxicity against the triple-negative breast cancer cell line MDA-MB-231 as compared with taxol.


Assuntos
Neosartorya/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Alcaloides Indólicos/química , Espectroscopia de Ressonância Magnética , Paclitaxel/farmacologia , Piridinas/química , Sesquiterpenos/química
8.
Biomed Chromatogr ; 30(2): 111-6, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26031900

RESUMO

Previous research in our laboratory found that the absolute bioavailability of vitexin-2''-O-rhamnoside (VR) was quite low at 4.89%. A rapid and sensitive UHPLC method using hesperidin as an internal standard was therefore developed and validated to investigate the reasons for this by determining VR in rat plasma after administering intravenously, intraportally (5 mg/kg), intraduodenally and intragastrically (40 mg/kg) to the rat model of the hepatic, gastric and intestinal first-pass effects. As only a high intestinal first-pass effect of VR was found, that is, there existed a low bioavailability of VR (2.40%), inhibitors of P-glycoprotein (P-gp) and cytochrome P450 3A (CYP3A), including verapamil, cyclosporin A and midazolam, and absorption enhancers, including bile salts and borneol, combined with VR, were instilled into duodenum to evaluate the effects on bioavailability of VR. The results demonstrated that area under the concentration-time curve (AUC) values of VR slightly increased after administration of verapamil, cyclosporin A and midazolam, indicating that CYP3A and P-gp do not play an important role in the first-pass effect in the intestine. AUC values of VR significantly increased after administering bile salts or borneol, indicating that the low bioavailability of VR was mainly related to its poor absorption in the intestine.


Assuntos
Apigenina/sangue , Apigenina/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Animais , Apigenina/administração & dosagem , Área Sob a Curva , Disponibilidade Biológica , Duodeno/irrigação sanguínea , Duodeno/metabolismo , Mucosa Gástrica/metabolismo , Fígado/irrigação sanguínea , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Sensibilidade e Especificidade , Estômago/irrigação sanguínea
9.
Chem Biodivers ; 12(8): 1222-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26265574

RESUMO

Two new triterpenoids, 30-hydroxylup-20(29)-ene 3ß-caffeate (1) and 24-nor-friedelan-6α,10-dihydroxy-1,2-dioxo-4,7-dien-29-oic acid (2), together with eight known compounds 3-10, were isolated from the roots of Celastrus stylosus. The structures of these compounds were elucidated on the basis of spectroscopic analyses. To the best of our knowledge, this represents the first study on the chemical constituents of C. stylosus. The antiproliferative activities of the triterpenoids against six human cancer cell lines (PANC-1, A549, PC-3, HepG2, SGC-7901, and HCCLM3) were evaluated. Compounds 3, 4, and 10 exhibited comparable activities against PC-3 and HCCLM3 cell lines as the positive control taxol.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Celastrus/química , Triterpenos/química , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Triterpenos/isolamento & purificação
10.
J Oleo Sci ; 73(5): 695-708, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38692892

RESUMO

This study was to investigate the effects of Smilax China L. saponins (SCS) on non-alcoholic fatty liver disease (NAFLD). Rats were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD, followed by SCS treatment for 8 weeks. The effect of SCS on liver injury was observed by H&E staining and the regulative mechanism of SCS on lipid formation was exposed by detecting Oil red O, insulin resistance (IR), and fatty acids synthesis (FAS). Furthermore, transcriptomics and metabolomics were performed to analyze the potential targets. The experimental results indicated that SCS exerted a positive curative effect in alleviating HFD-induced overweight, hepatic injury, steatosis, and lipid formation and accumulation in rats, and the preliminary mechanism studies showed that SCS could alleviate IR, inhibit FAS expression, and reduce Acetyl-CoA levels. Besides, the integrative analysis of transcriptomics and metabolomics exposed the targets of SCS to regulate lipid production likely being the sphingolipid metabolism and glycerophospholipid metabolism pathways. This study demonstrates that SCS significantly ameliorates lipid metabolic disturbance in rats with NAFLD by relieving insulin resistance, inhibiting the FAS enzymes, and regulating the sphingolipid and glycerophospholipid metabolism pathways.


Assuntos
Dieta Hiperlipídica , Resistência à Insulina , Metabolismo dos Lipídeos , Metabolômica , Hepatopatia Gordurosa não Alcoólica , Saponinas , Smilax , Transcriptoma , Animais , Smilax/química , Saponinas/farmacologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Masculino , Metabolômica/métodos , Dieta Hiperlipídica/efeitos adversos , Transcriptoma/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Esfingolipídeos/metabolismo , Glicerofosfolipídeos/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Modelos Animais de Doenças
11.
Front Chem ; 12: 1402502, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39036657

RESUMO

Biomass and its derivatives have broad applications in the fields of bio-catalysis, energy storage, environmental remediation. The structure and components of biomass, which are vital parameters affecting corresponding performances of derived products, need to be fully understood for further regulating the biomass and its derivatives. Herein, tobacco is taken as an example of biomass to introduce the typical characterization techniques in unraveling the structural information, chemical components, and properties of biomass and its derivatives. Firstly, the structural information, chemical components and application for biomass are summarized. Then the characterization techniques together with the resultant structural information and chemical components are introduced. Finally, to promote a wide and deep study in this field, the perspectives and challenges concerning structure and composition charaterization in biomass and its derivatives are put forward.

12.
Heliyon ; 10(13): e33920, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39055830

RESUMO

Tobacco, a widely cultivated crop, has been extensively utilized by humans for an extended period. However, the tobacco industry generates a significant amount of organic waste, and the effective utilization of this tobacco waste has been limited. Currently, most tobacco waste is either recycled as reconstituted tobacco sheets or disposed of in landfills. However, tobacco possesses far more potential value than just these applications. This article provides an overview of the diverse uses of tobacco waste in agriculture, medicine, chemical engineering, and energy sectors. In the realm of agriculture, tobacco waste finds primary application as fertilizers and pesticides. In medical applications, the bioactive compounds present in tobacco are fully harnessed, resulting in the production of phenols, solanesol, polysaccharides, proteins, and even alkaloids. These bioactive compounds exhibit beneficial effects on human health. Additionally, the applications of tobacco waste in chemical engineering and energy sectors are centered around the utilization of lignocellulosic compounds and certain fuels. Chemical platform compounds derived from tobacco waste, as well as selected fuel sources, play a significant role in these areas. The rational utilization of tobacco waste represents a promising prospect, particularly in the present era when sustainable development is widely advocated. Moreover, this approach holds significant importance for enhancing energy utilization.

13.
J Adv Pharm Technol Res ; 14(1): 6-11, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36950465

RESUMO

Nitrogen mustards are important alkylating anticancer drugs used for neoplasms treatment. However, little research about the integration of luminophore into nitrogen mustard-based compounds for both imaging and therapeutic application was reported. In this study, we report a series of novel nitrogen mustard-containing 1-furyl-2-en-1-one and 1-thienyl-2-en-1-one derivatives as intramolecular charge transfer-based luminophore for research in both imaging subcellular localization and antiproliferation toward lung cancer cells. The target products were prepared by Knoevenagel condensation and characterized by nuclear magnetic resonance and high-resolution mass spectrometer. The absorption and fluorescence studies were carried out by ultraviolet-visible and fluorescence spectrophotometers, respectively. Cell morphology was observed under an inverted microscope. Cytotoxicity test was detected by MTT assay. Cellular localization was observed by a confocal laser scanning microscope. Colony formation ability was carried out by colony formation assay. Cell migration ability was detected by transwell migration assay. Differences between the two groups were analyzed by two-tailed Student's t-test. The difference with P < 0.05 (*) was considered statistically significant. The compounds were synthesized in high yield. The λmax and Stokes shift of these compounds reach up to 567 and 150 nm, respectively. These compounds exhibited good antiproliferative activity against lung cancer cells, with compound 3h exhibiting the best IC50 of 13.1 ± 2.7 µM. Furthermore, the selected compound 3h is located preferentially in lysosomes and a small amount in nuclei, effectively inhibiting cell colony formation and migration abilities toward A549 cells. These findings suggested that nitrogen mustard-based fluorophores might be a potential effective chemotherapeutic agent in lung cancer therapy.

14.
Int Immunopharmacol ; 118: 110082, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36989889

RESUMO

Sepsis-associated acute lung injury remains to be a major cause of morbidity and mortality worldwide, and there is a lack of effective therapeutic drugs. Curdione, an activeingredient of Curcuma zedoary, a traditional Chinese medicine (TCM), possesses a variety of pharmacological actions, such as anti-inflammatory, antioxidant and inhibition of platelet aggregation. However, whether curdione protects against sepsis-induced lung injury is still undetermined. In this study, we investigated the effects of curdione on sepsis-induced lung injury. Cecal ligation and puncture (CLP) surgery was performed in mice to establish a model of sepsis. Twenty-four hours after CLP, bronchoalveolar lavage fluid (BALF) and lung tissue samples were harvested for investigation. The protective effects of curdione on acute lung injury and potential mechanisms were explored by detecting pathological sections, exudative proteins, oxidative responses, inflammatory factors, platelet activation, neutrophil infiltration, and neutrophil extracellular trap (NET) formation in the lung and were further verified in vitro. We showed that treatment with curdione clearly relieved histopathological changes, reduced inflammatory cytokine elevation and total protein concentrations in BALF, and decreased oxidative stress responses in lung tissues. In addition, curdione inhibited platelet activation, further blocking the interaction between platelets and neutrophils. Finally, neutrophil infiltration and NET formation was also reduced in mice treated with curdione. In conclusion, curdione alleviates sepsis-induced lung injury by inhibiting platelet-mediated neutrophil recruitment, infiltration, and NET formation as well as its anti-inflammatory and antioxidant properties. Curdione has great therapeutic potential in sepsis.


Assuntos
Lesão Pulmonar Aguda , Armadilhas Extracelulares , Sepse , Camundongos , Animais , Armadilhas Extracelulares/metabolismo , Antioxidantes/farmacologia , Pulmão/patologia , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Sepse/complicações , Sepse/tratamento farmacológico , Infiltração de Neutrófilos , Camundongos Endogâmicos C57BL
15.
Drug Des Devel Ther ; 16: 1713-1729, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35698653

RESUMO

Introduction: Origanum vulgare L. is a traditional Chinese herb, having a strong hepatoprotective effect. In our previous experiments, we have isolated an ingredient from this herb and identified it as didymin. This study aimed to investigate the effects and underlying mechanisms of didymin on liver injury and fibrosis, elucidating whether it was the pharmacodynamic material basis of Origanum vulgare L. Methods: Mice were injected with CCl4 for 10 weeks to induce liver fibrosis, followed by didymin treatment for 6 weeks. Then, biochemical analysis and histopathological examinations were conducted to evaluate the therapeutic effects of didymin in alleviating fibrosis. Next, the possible mechanisms of didymin were predicted by transcriptomics and then verified by the multiple relevant examinations. Results: The pharmacodynamic experiments indicated that didymin significantly attenuated CCl4-induced hepatic injury and fibrogenesis, as evidenced by the ameliorative pathological tissue, low transaminase activity, and decreased collagen accumulation. Interestingly, the transcriptome analysis predicted that the potential targets were likely to be endoplasmic reticulum stress (ERS), inflammation, apoptosis, and metabolic pathways. And the predictions were then verified by the following examinations: (1) didymin significantly inhibited ERS by regulating the ATF6, IRE1α, and PERK pathways; (2) didymin markedly alleviated hepatocyte apoptosis by restoring the expression of Bcl-2 and caspase families, as well as the mitochondrial dysfunction; (3) didymin significantly decreased the production of the pro-inflammatory cytokines (IL-1ß and IL-6); (4) didymin inhibited the glycerophospholipid metabolism pathway by decreasing the synthesis of phosphatidylethanolamines and phosphatidylcholines. Conclusion: Our findings demonstrate that didymin can ameliorate liver fibrosis, which is mainly attributed to the inhibition of ERS, inflammation, and glycerophospholipid metabolism.


Assuntos
Estresse do Retículo Endoplasmático , Flavonoides , Glicerofosfolipídeos , Glicosídeos , Cirrose Hepática , Animais , Apoptose , Tetracloreto de Carbono , Flavonoides/farmacologia , Glicerofosfolipídeos/metabolismo , Glicosídeos/farmacologia , Inflamação/tratamento farmacológico , Fígado , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Metabolômica , Camundongos , Transcriptoma
16.
Eur J Pharmacol ; 919: 174770, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35120860

RESUMO

This study aimed to investigate the protective mechanisms of helenalin on hepatic fibrosis. In brief, rats were intragastrically administrated with 50% CCl4 for 9 weeks to induce liver fibrosis, followed by treatment with various agents for 6 weeks. The effects of helenalin on hepatic injury were assessed by pathological examinations. The potential targets were predicted by the "Drug-Disease" bioinformatic analysis and then verified by multiple experiments. Moreover, the underlying mechanism was investigated by transcriptomics and metabolomics as a whole. The results showed that helenalin significantly alleviated hepatocyte necrosis and hepatic injury, as proved by the pathological examinations. Also, helenalin markedly attenuated hepatocyte apoptosis by regulating the expression of caspase-3 and Bcl-2 families. Besides, helenalin could significantly reduce collagen accumulation, as evidenced by the decreased contents of collagen, hyaluronic acid and laminin. Moreover, helenalin significantly down-regulated the phosphorylation of PI3K, Akt, FAK, mTOR and P70S6K, and PTEN protein expression, suggesting that helenalin inhibited the PI3K/Akt signaling cascade. Meanwhile, helenalin inhibited the NF-κB signaling pathway by reducing the phosphorylation of IκBα, NF-κB p65 and IKKα/ß, alleviating inflammation response. Interestingly, the analysis of transcriptomics and metabolomics indicated that helenalin inhibited the glycerophospholipid metabolism pathway by down-regulating the target genes (CHKA, ETNPPL, LYPLA1, PCYT2, PLD4 and PNPLA6), ultimately ameliorating hepatocyte damage. In conclusion, helenalin ameliorates hepatic fibrosis by regulating the PI3K/Akt and NF-κB signaling pathways and the glycerophospholipid metabolism pathway.


Assuntos
Antioxidantes/farmacologia , Asteraceae , Medicamentos de Ervas Chinesas/farmacologia , Cirrose Hepática/tratamento farmacológico , Sesquiterpenos de Guaiano/farmacologia , Animais , Antioxidantes/química , Antioxidantes/uso terapêutico , Tetracloreto de Carbono , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , Cirrose Hepática/patologia , Masculino , Metabolômica , Ratos , Ratos Sprague-Dawley , Sesquiterpenos de Guaiano/química , Sesquiterpenos de Guaiano/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Transcriptoma
17.
Chem Commun (Camb) ; 58(19): 3198-3201, 2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35174832

RESUMO

Based on STM imaging and DFT calculations, we show the real-space experimental evidence of the interconversion between G-quartets and G-triads on the Au(111) surface, and further reveal the relative stabilities of these two elementary motifs, which helps to increase the fundamental understanding of the relationship between G-triplex and G-quadruplex DNA structures.

18.
Artigo em Inglês | MEDLINE | ID: mdl-36342995

RESUMO

Distributed ray tracing algorithms are widely used when rendering massive scenes, where data utilization and load balancing are the keys to improving performance. One essential observation is that rays are temporally coherent, which indicates that temporal information can be used to improve computational efficiency. In this paper, we use temporal coherence to optimize the performance of distributed ray tracing. First, we propose a temporal coherence-based scheduling algorithm to guide the task/data assignment and scheduling. Then, we propose a virtual portal structure to predict the radiance of rays based on the previous frame, and send the rays with low radiance to a precomputed simplified model for further tracing, which can dramatically reduce the traversal complexity and the overhead of network data transmission. The approach was validated on scenes of sizes up to 355 GB. Our algorithm can achieve a speedup of up to 81% compared to previous algorithms, with a very small mean squared error.

19.
J Colloid Interface Sci ; 623: 9-20, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35561576

RESUMO

Visible light-driven photo-Fenton-like technology is a promising advanced oxidation process for water remediation, while the construction of effective synergetic system remains a great challenge. Herein, iron hydroxide oxide (α-FeOOH) with controllable oxygen vacancy defects were engineered on reduced graphene oxide (rGO) nanosheets (named as OVs-FeOOH/rGO) through an in-situ redox method for boosting visible light-driven photo-Fenton-like oxidation. By adjusting the pH environment to modulate the redox reaction kinetics between graphene oxide (GO) and ferrous salt precursors, the oxygen vacancy concentration in α-FeOOH could be precisely controlled. With optimized oxygen vacancy defects obtained at pH 5, the OVs-FeOOH/rGO displayed superior photo-Fenton-like performance for Rhodamine B degradation (99% within 40 mins, rate constant of 0.2278 mg-1 L min-1) with low H2O2 dosage (5 mM), standing out among the reported photo-Fenton-like catalysts. The catalyst also showed excellent reusability, general applicability, and tolerance ability of realistic environmental conditions, which demonstrates great potential for practical applications. The results reveal that moderate oxygen vacancy defects can not only strengthen absorption of visible light and organic pollutants, but also promote the charge transfer to simultaneously accelerate the photogenerated electron-hole separation and Fe(III)/Fe(II) Fenton cycle, leading to the remarkable photo-Fenton-like oxidation performance. This work sheds light on the controllable synthesis and mechanism of oxygen vacancy defects to develop efficient photo-Fenton-like catalysts for wastewater treatment.


Assuntos
Compostos Férricos , Peróxido de Hidrogênio , Catálise , Grafite , Hidróxidos , Ferro , Luz , Oxirredução , Oxigênio
20.
Front Pharmacol ; 13: 801982, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359829

RESUMO

This study aimed to investigate the effects and underlying mechanisms of tormentic acid (TA) on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. The rats were intragastrically administered with 50% CCl4 for 9 weeks to induce hepatic fibrosis, followed by various agents for 6 weeks. Transcriptomic analysis was carried out to predict the potential targets, and then multiple examinations were performed to verify the prediction. The results showed that TA significantly alleviated liver injury and fibrosis, as evidenced by the ameliorative pathological tissue, low transaminase activity, and decreased collagen accumulation. Besides, TA markedly reduced hepatocyte apoptosis by regulating the expression of caspase-3 and Bcl-2 families. The transcriptomic analysis revealed 2,173 differentially expressed genes (DEGs) between the TA and model groups, which could be enriched in the metabolic pathways and the PI3K/Akt and NF-κB signaling pathways. The metabolomics analysis showed that TA could regulate the glycerophospholipid metabolism pathway by regulating the synthesis of phosphatidylserines, phosphatidylethanolamines and phosphatidylcholines. Moreover, the integrative analysis of the transcriptomics and metabolomics data indicated that TA inhibited the glycerophospholipid metabolism pathway by inhibiting the expression of LPCAT4, PTDSS2, PLA2G2A and CEPT1. In addition, the relevant signaling pathways analysis confirmed that TA inhibited HSCs activation by blocking the PI3K/Akt/mTOR pathway and ameliorated inflammatory injury by inhibiting the NF-κB pathway. In conclusion, TA significantly alleviates liver fibrosis in vivo by inhibiting the glycerophospholipid metabolism pathway and the PI3K/Akt/mTOR and NF-κB signaling pathways.

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