Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 36
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Food Funct ; 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35776077

RESUMO

The death of dopaminergic neurons is a dominant factor during the occurrence and development of Parkinson's disease (PD). Previous studies demonstrated that ferroptosis is implicated in the death of dopaminergic neurons. Besides, polyphenols have been proven to be effective in preventing the death of dopaminergic neurons. This work aims to explore the neuroprotective effect and mechanism of thonningianin A (Th A), a polyphenolic compound in natural plant foods, against 6-hydroxydopamine (6-OHDA)-induced ferroptosis in dopaminergic cells. The results of molecular docking and other binding assays collectively demonstrated that Th A can strongly target the Kelch domain of Keap1. Th A treatment significantly facilitated the nuclear factor erythroid 2-like 2 (Nrf2) nuclear translocation and subsequently increased the heme oxygenase-1 (HO-1) protein level through inhibiting the protein-protein interaction (PPI) of Keap1 and Nrf2. Compared with the nomifensine (Nomi) treatment, Th A had a more potent protective effect on 6-OHDA-induced ferroptosis during PD pathology in zebrafish, which was associated with assuaging the reduction of the total swimming distance, glutathione (GSH) depletion, iron accumulation, lipid peroxidation, and aggregation of α-synuclein (α-syn). Furthermore, Th A also exhibited a strong protective effect against 6-OHDA-induced ferroptosis in vitro in the human neuroblastoma cell line SH-SY5Y. Th A degraded Keap1 protein through activating Atg7-dependent autophagy. Additionally, Th A treatment facilitated the degradation of Keap1 protein by promoting the interaction between p62/SQSTM1 (sequestosome 1, hereafter referred to as p62) and Keap1. Taken together, our findings indicated that Th A protects dopaminergic cells against 6-OHDA-induced ferroptosis through activating the Nrf2-based cytoprotective system, thus enabling a potential application of Keap1-Nrf2 PPI inhibitors in the restraint of ferroptosis and treatment of PD.

2.
Water Res ; 221: 118734, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35714469

RESUMO

Possibility of human exposure to microplastics (MPs) in water environment has been escalating, and subsequent challenges of MPs to biostability and biosafety in drinking water deserve more attention, especially in stagnant water. The present study explored the integrated impacts of MPs and chlorine on disinfection kinetics, microbial growth, and microbial community formation in drinking water, by setting MPs or microplastic-biofilm (MP-BM) under different disinfection conditions. The following were the primary conclusions: (1) The presence of MP and MP-BM led to the deterioration of water indices (especially turbidity) when chlorine was less than 1 mg/L. (2) MP/MP-BM accelerated the decay of disinfectants and MP-BM consumed more rapidly. Meanwhile, chlorine contributed to the level of BRP, ranging from 4.78 × 105 CFU/mL to 1.42 × 107 CFU/mL. (3) MP/MP-BM and chlorine integrally shaped microbial communities in water samples and biofilm samples. Microbial dissimilarity between isolated and hybrid MP-BM indicated manners of microbial field or non-contact communication. Microbial abundance and OPs were effectively controlled when chlorine was over 1 mg/L. (4) According to time-lag differential equations simulation, impulsive chlorination contributed to controlling microbial risks and DBPs induced by MP/MP-BM and water stagnation.

3.
Front Nutr ; 9: 865257, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571927

RESUMO

Atractylodes macrocephala rhizome (called Bái-zhú in China) has a long history as a functional food and herbal medicine in East Asia, especially China. Sesquiterpenoids are one of the main active compounds of Atractylodes macrocephala rhizome. This study aimed to explore the unknown sesquiterpenoids of A. macrocephala rhizome using a molecular networking strategy. Two new nitrogen-containing sesquiterpenoids, atractylenolactam A (1) and atractylenolactam B (2), and 2 new sesquiterpene lactones, 8-methoxy-atractylenolide V (6) and 15-acetoxyl atractylenolide III (7), along with 12 known analogs (3-5 and 8-16) were discovered and isolated. All the structures were assigned based on detailed spectroscopic analyses. The absolute configurations of 1, 2, 6, and 7 were established by time-dependent density functional theory ECD (TDDFT-ECD) calculations. All these compounds had different degrees of concentration-dependent activating effects on nuclear-factor-E2-related factor-2 (Nrf2).

4.
Chemosphere ; 291(Pt 1): 132794, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34742765

RESUMO

Recently, the microplastics, as well as the compound pollution of heavy metals and antibiotics, in the aqueous environment have attracted increasing attention, but studies on the behavior of heavy metals on aged microplastics in antibiotics-heavy metals coexisting system are limited. Herein, to explore the impact of antibiotics on the adsorption of heavy metals by aged microplastics, the adsorption behavior of Cu(II) and Cr(VI) on aged polystyrene (PS) and polyvinyl chloride (PVC) were investigated. The results presented that ciprofloxacin (CIP) had negative and positive impacts on the adsorption of Cu(II) and Cr(VI) by aged microplastics, respectively. Moreover, the existence of CIP seemed to have no evident effect on the type of adsorption isotherm model and kinetic model in most adsorption systems of Cu(II). The negative impact of CIP on adsorption of Cu(II) may result from the competition adsorption and high steric hindrance effect, while non-specific interactions between neutral antibiotic-heavy metal complexes and the hydrophobic surface of aged microplastics as well as CIP as bridges influenced positively on adsorption of Cr(VI) on aged microplastics. This work was concerned with the interaction between binary pollutants and aging microplastics to clarify the risks of microplastics in the aqueous environment.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Adsorção , Antibacterianos , Cromo , Microplásticos , Plásticos , Poluentes Químicos da Água/análise
5.
J Affect Disord ; 296: 660-666, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34565588

RESUMO

OBJECTIVES: Male lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) is common and may increase the risk of depressive symptoms. This study aimed to investigate the associated factors of LUTS/BPH and its association with depressive symptoms in middle-aged and older Chinese men. METHODS: This study used data from the 2015 China Health and Retirement Longitudinal Study (CHARLS). A total number of 8,586 men aged ≥45 years were included in this study. Participants answered positively to whether they have ever been diagnosed with a prostate illness (excluding prostatic cancer) were defined as LUTS/BPH individuals. Depressive symptoms were assessed using the 10-item Center for Epidemiological Studies Depression Scale (CESD-10). Multivariate logistic analyses were applied to explore the associated factors of LUTS/BPH, association between LUTS/BPH and depressive symptoms, and risk factors of depressive symptoms according to LUTS/BPH status. RESULTS: The weighted overall prevalence of LUTS/BPH was 13.1% in Chinese men aged ≥45 years. The prevalence of depressive symptoms was 29.1% in LUTS/BPH individuals and 22.9% in non-LUTS/BPH individuals. Depressive symptoms and LUTS/BPH shared some same risk factors, which were education, living regions, annual household consumption, sleep duration and multimorbidity. The results from logistic models showed that education, sleep duration and multimorbidity were significantly and independently associated with depression of LUTS/BPH individuals (P<0.001). CONCLUSIONS: Prevalence of depressive symptoms in LUTS/BPH population was higher than in non-LUTS/BPH population. Education, sleep duration and multimorbidity were associated with the onset of depressive symptoms in LUTS/BPH individuals (P<0.001).


Assuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Idoso , China/epidemiologia , Depressão/epidemiologia , Humanos , Estudos Longitudinais , Sintomas do Trato Urinário Inferior/epidemiologia , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/epidemiologia , Aposentadoria
6.
ACS Appl Mater Interfaces ; 13(45): 53850-53858, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34738780

RESUMO

Designing electrode materials with excellent comprehensive properties was of top priority in promoting development of flow electrode capacitive deionization (FCDI). To date, most FCDI studies involved the application and modification of carbon-based materials, which suffered the contradiction between rheological behavior and electrochemical performance. In this study, a Na+ superionic conductor (NASICON) sodium vanadium fluorophosphate@reduced graphene oxide (NVOPF@rGO) was synthesized and applied as a flow electrode in FCDI. Benefiting from the confinement effect of the three-dimensional (3D) reduced graphene oxide (rGO) network, thin and uniform NVOPF nanosheets formed and provided abundant active sites for adsorbing Na+. Moreover, the interconnected rGO network formed a 3D conductive network for Na+ and electron transport. Compared with an activated carbon (AC)-AC system (AC was used as an anode and a cathode), a NVOPF@rGO-AC system (NVOPF@rGO was used as a cathode and AC was used as an anode) exhibited preferable dispersibility and stability of electrode dispersion, lower internal resistance, higher desalination rate, and lower energy consumption. Besides, the average salt adsorption rate (ASAR) reached 5.32 µg·cm-2·min-1 by adjusting the concentration of the electrode (4.73 wt %), the flow rate of the electrode (25 mL·min-1), and the operation voltage (1.6 V). This study demonstrated the potential of faradic flow electrodes for promoting the development and application of FCDI.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34487502

RESUMO

Filter pruning is a significant feature selection technique to shrink the existing feature fusion schemes (especially on convolution calculation and model size), which helps to develop more efficient feature fusion models while maintaining state-of-the-art performance. In addition, it reduces the storage and computation requirements of deep neural networks (DNNs) and accelerates the inference process dramatically. Existing methods mainly rely on manual constraints such as normalization to select the filters. A typical pipeline comprises two stages: first pruning the original neural network and then fine-tuning the pruned model. However, choosing a manual criterion can be somehow tricky and stochastic. Moreover, directly regularizing and modifying filters in the pipeline suffer from being sensitive to the choice of hyperparameters, thus making the pruning procedure less robust. To address these challenges, we propose to handle the filter pruning issue through one stage: using an attention-based architecture that adaptively fuses the filter selection with filter learning in a unified network. Specifically, we present a pruning method named adding before pruning (ABP) to make the model focus on the filters of higher significance by training instead of man-made criteria such as norm, rank, etc. First, we add an auxiliary attention layer into the original model and set the significance scores in this layer to be binary. Furthermore, to propagate the gradients in the auxiliary attention layer, we design a specific gradient estimator and prove its effectiveness for convergence in the graph flow through mathematical derivation. In the end, to relieve the dependence on the complicated prior knowledge for designing the thresholding criterion, we simultaneously prune and train the filters to automatically eliminate network redundancy with recoverability. Extensive experimental results on the two typical image classification benchmarks, CIFAR-10 and ILSVRC-2012, illustrate that the proposed approach performs favorably against previous state-of-the-art filter pruning algorithms.

8.
J Hazard Mater ; 420: 126662, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34329077

RESUMO

Microplastics (MPs) are emerging pollutants as vectors for microbial colonization, but their role as nutrients sources for microbial communities has rarely been reported. This study explored the impact of six types of MPs on assimilable organic carbon (AOC) and microbial communities over eight weeks. The following were the primary conclusions: (1) MPs contributed to AOC increment and subsequently increased bacterial regrowth potential. The maximum AOC reached 722.03 µg/L. The increase in AOC formation corresponded to AOC NOX, except in PVC samples where AOC P17 primarily increased. (2) The MPs accelerated bacterial growth and changed the bacterial distribution between the biofilm and water phases. A high MP surface-area-to-volume ratio or low MPs density contributed to bacterial accumulation and biofilm formation around the plastisphere, thereby decreasing the relative microbial proportion in the water phase. (3) High-throughput sequencing and scanning electron microscope revealed that different MPs shaped various microbial communities temporally and spatially. (4) Biofilm formatting and formatted models were established and simulated to explain the kinetic interaction between the AOC and bacteria inhabiting the plastisphere. Finally, the challenges that plastic-deprived AOC represent in terms of anti-bacterial measures and chemical safety are discussed.


Assuntos
Carbono , Microbiota , Microplásticos , Nutrientes , Plásticos , Água
9.
Adv Mater ; 33(29): e2006836, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34096113

RESUMO

Macromolecular films are crucial functional materials widely used in the fields of mechanics, electronics, optoelectronics, and biology, due to their superior properties of chemical stability, small density, high flexibility, and solution-processing ability. Their electronic and mechanical properties, however, are typically much lower than those of crystalline materials, as the macromolecular films have no long-range structural ordering. The state-of-the-art for producing highly ordered macromolecular films is still facing a great challenge due to the complex interactions between adjacent macromolecules. Here, the growth of textured macromolecular films on a designed graphene/high-index copper (Cu) surface is demonstrated. This successful growth is driven by a patterned potential that originates from the different amounts of charge transfer between the graphene and Cu surfaces with, alternately, terraces and step edges. The textured films exhibit a remarkable improvement in remnant ferroelectric polarization and fracture strength. It is also demonstrated that this growth mechanism is universal for different macromolecules. As meter-scale graphene/high-index Cu substrates have recently become available, the results open a new regime for the production and applications of highly ordered macromolecular films with obvious merits of high production and low cost.

10.
J Ethnopharmacol ; 270: 113775, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33406386

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Veronica ciliata Fisch. existed in various Tibetan medicine prescriptions, which was recorded to treat liver diseases in the Tibetan medicine roll of Chinese materia medica. HYPOTHESIS/PURPOSE: The current study aimed to examine the effect of active constituents from V.ciliata relieving oxidative stress-mediated liver injury and clarify the underlying mechanism. MATERIALS AND METHODS: tert-Butyl hydroperoxide (BHP) induced liver injury in mice model was established to evaluate the hepatoprotective effect of ethyl acetate extract of V. ciliata (EAFVC). Serum and liver indicators, as well as the histopathological change of liver were examined. Next, the constituents of EAFVC were separated and characterized by high-speed countercurrent chromatography (HSCCC) and Ultra performance liquid chromatography-mass spectrometer (UPLC-MS), respectively. Based on the above, the antioxidant activity of EAFVC and two fractions was evaluated using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2, 2'-azino-bis (3-ethylbenzothiazoli- ne-6-sulfonic acid) (ABTS) free radical scavenging assays. The hepatoprotective activity of EAFVC and its fractions/compounds attenuating ethanol-induced hepatocyte damage in BRL-3A cells was evaluated using the MTT method. The effect of the fraction and compounds with the strongest protective activity on ethanol-induced cytotoxicity, reactive oxygen species (ROS) accumulation, and glutathione (GSH) depletion was investigated. mRNA expression of nuclear factor-E2-related factor 2 (Nrf2) and nuclear factor of κB (NF-κB), as well as their downstream target genes, was determined by RT-qPCR. Finally, the potential mechanism of fraction 1 and luteolin on the AMPK/p62/Nrf2 signal pathway was studied using western blotting. RESULTS: Firstly, EAFVC could relieve liver impairment induced by t-BHP in mice. Next, fraction 1 enriched with polyphenolic compounds and luteolin derived from EAFVC were screened to yield the highest hepatoprotective activity against ethanol-induced hepatocyte damage. Further study demonstrated that fraction 1 and luteolin relieved BRL-3A cells damage by decreasing the aspartate aminotransferase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) activities, ROS accumulation, as well as the depletion of GSH. Also, we determined that fraction 1 and luteolin suppressed inflammation and apoptosis of BRL-3A cells. The mechanistic studies indicated that fraction 1 could attenuate oxidative stress, inflammation, and apoptosis by activating AMPK phosphorylation, which promotes autophagy associated protein expression (LC3-B, Beclin1 and p62) as well as promote phosphorylation of p62 -dependent autophagic degradation of Keap1, to induce Nrf2 dissociation from Keap1 and translocate to nuclear. Nrf2 in the nuclear activate cytoprotective related genes to exert hepatoprotective function. Finally, we found that luteolin activated the protein expression of p-AMPK, p-p62, p62, Nrf2, and its downstream target genes. CONCLUSIONS: This study clarified that fraction 1 enriched phenolic compounds could attenuate ethanol-induced liver injury in BRL-3A cells via activating AMPK/p62/Nrf2 pathway. Luteolin could serve as the major bioactive component in the therapeutic effect of fraction 1. These active constituents in V. ciliata could be used as the potential drugs targeted activation of AMPK or p62 for relieving oxidative stress-mediated liver disorders.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Proteína Sequestossoma-1/metabolismo , Veronica/química , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular , Doença Hepática Induzida por Substâncias e Drogas/patologia , Etanol/toxicidade , Inflamação/tratamento farmacológico , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Luteolina/farmacologia , Masculino , Camundongos Endogâmicos ICR , Simulação de Acoplamento Molecular , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , terc-Butil Hidroperóxido/toxicidade
11.
J Ethnopharmacol ; 266: 113432, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33011367

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Veronica ciliata Fisch. is a traditional medical herb that present in more than 100 types of Tibetan medicine prescriptions, most of which are used for liver disease therapy. Iridoid glycosides have been identified as the major active components of V.ciliata with a variety of biological activities. AIMS OF THE STUDY: The aim of this study is to explore the protective effect and potential mechanism of n-Butanol extract (BE) and iridoid glycosides (IG) from V.ciliata against ɑ-naphthyl isothiocyanate (ANIT)-induced hepatotoxicity and cholestasis in mice. MATERIALS AND METHODS: Mice were intragastrically (i.g.) given BE and IG at different dose or positive control ursodeoxycholic acid (UCDA) once a day for 14 consecutive days, and were treated with ANIT to cause liver injury on day 12th. Serum levels of hepatic injury markers and cholestasis indicators, liver index and liver histopathology were measured to evaluate the effect of BE and IG on liver injury caused by ANIT. The protein levels of tumor necrosis factor-α (TNF-α), nuclear factor kappa B(NF-κB), interleukin-6 (IL-6), Na+/taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2), and the levels of oxidative stress indicators in liver tissue were investigated to reveal the underlying protective mechanisms of BE and IG against ANIT-induced hepatotoxicity and cholestasis. RESULTS: The n-Butanol extract (BE) and iridoid glycosides (IG) isolated from V.ciliata significantly decreased serum level of cholestatic liver injury markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total bile acid (TBA), total bilirubin (TBIL), and direct bilirubin (DBIL) in ANIT-treated mice. Histopathology of the liver tissue showed that pathological damages were relieved upon BE and IG treatment. Meanwhile, the results indicated BE and IG notably restored relative liver weights, inhibited oxidative stress induced by ANIT through increasing hepatic level of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and decreasing hepatic content of malondialdehyde (MDA). Western blot revealed that BE and IG inhibited the expression of pro-inflammatory factors TGF-α, IL-6 and NF-κB. Furthermore, the decreased protein expression of bile acid transporters NTCP, BSEP, MRP2 were upregulated by BE and IG in a dose-dependent manner. CONCLUSION: The results have demonstrated that BE and IG exhibited a dose-dependently protective effect against ANIT-induced liver injury with acute intrahepatic cholestasis in mice, which might be related to the regulation of oxidative stress, inflammatory response and bile acid transport. In addition, these findings pointed out that iridoid glycosides as main active components of V.ciliata play a critical role in hepatoprotective effect of V.ciliata.


Assuntos
Colestase/tratamento farmacológico , Glicosídeos Iridoides/farmacologia , Extratos Vegetais/farmacologia , Veronica/química , 1-Butanol/química , 1-Naftilisotiocianato , Animais , Ácidos e Sais Biliares/metabolismo , Transporte Biológico/efeitos dos fármacos , Colestase/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Glicosídeos Iridoides/administração & dosagem , Glicosídeos Iridoides/isolamento & purificação , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Medicina Tradicional Tibetana , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem
12.
J Ethnopharmacol ; 266: 113454, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33065254

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Adhatoda vasica Nees., which existed in a large; number of Tibetan medicine prescriptions for hepatopathy, used as an adjuvant to treat liver diseases. HYPOTHESIS/PURPOSE: Oxidative stress is the key player in the development and progression of liver pathogenesis. In recent years, research is increasingly being focused on exploitation of the active components from medicinal plants to combat the liver oxidative injury. In our study, we aimed to screen the active principles from A. vasica and clarify whether they could relieve oxidative damage induced by tert-Butyl hydroperoxide (t-BHP) and its potential mechanism via activating AMPK/p62/Nrf2 pathway. MATERIALS AND METHODS: Ultra performance liquid chromatography (UPLC) was adopted for analysis of chemical composition in the extracts. Furthermore, the antioxidant activity of the fractions was evaluated using DPPH, ABTS and reducing power assay. Along with this, the compounds in this fraction with highest antioxidant activity were analyzed using UPLC-MS. Based on this, the condition for extracting flavonoids of this subfraction was optimized via response surface method. CCK-8 assay was used to detect cell viability. Detection kits were used to measure the activity changes of AST, ALT, LDH and CAT as well as MDA and GSH levels induced by t-BHP. Detection of reactive oxygen species (ROS) production was used DCFH-DA probe. DAPI staining and flow cytometry was used to detect cell apoptosis. In terms of the mechanistic studies, the expression of proteins involved in AMPK/p62/Nrf2 pathway was measured using western blotting. RESULTS: Eventually, 70% ethanol extract from leaf of A. vasica was chosen due to its highest active components compared with other extracts. Further, ethyl acetate fraction derived from 70% ethanol extract in A. vasica (AVEA) possess highest ability for scavenging DPPH and ABTS free radicals as well as strongest reducing power than other fractions. Chemical composition analysis showed that AVEA contained 17 compounds, including 1 quinazoline alkaloid, 12 flavonoid-C-glycosides and 4 flavonoid-O-glycosides. In addition, the conditions (ratio of solid-liquid 1:14, the concentration of ethanol 73%, and the temperature 65 °C) were selected to enrich the flavonoids in AVEA. Furthermore, AVEA could attenuate t-BHP induced hepatocyte damage via increasing the cell viability, restoring abnormal the activities of AST, ALT, LDH and CAT as well as the levels of MDA and GSH. ROS fluorescence intensity was reduced by AVEA. Meanwhile, it could inhibit the cell apoptosis of BRL 3 A cells, as evidenced by restoration of cell morphology and decreasing the number of apoptotic cells. Further mechanistic studies indicated AVEA could promote p-AMPK expression to further induce autophagy adaptor-p62 protein expression, which could autophagic degradation of Keap1, leading to Nrf2 release and translocation into nucleus to induce antioxidant genes (HO-1, NQO-1, GCLC and GCLM) expression. CONCLUSION: In our study, AVEA was first to screen as the active fraction in A. vasica with alkaloids and abundant flavones. Moreover, the fraction potentiates its beneficial aspect by displaying the protective role on relieving t-BHP induced oxidative stress and activating AMPK/p62/Nrf2 pathway. AVEA helps maintain the redox homeostasis of hepatic cells and could be considered as an effective candidate against oxidative stress related liver disorders.


Assuntos
Justicia, Planta/química , Hepatopatias/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Células Cultivadas , Fator 2 Relacionado a NF-E2/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Ratos , Ratos Endogâmicos BUF , Espécies Reativas de Oxigênio/metabolismo , terc-Butil Hidroperóxido
13.
J Ethnopharmacol ; 268: 113617, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33307053

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Penthorum chinense Pursh is used for promoting diuresis and alleviating "heat"-associated disorders, which were considered to be related to diabetic in Traditional Chinese Medicine (TCM). AIMS OF THIS STUDY: Here, we aimed to evaluate the ability and underlying mechanism of the ethyl acetate fraction of Penthorum chinense Pursh stems (PSE) to inhibit vascular inflammation in high glucose (HG)-induced human umbilical vein endothelial cells (HUVEC cells). MATERIALS AND METHODS: HUVEC cells were pre-treated with PSE following HG treatment. The cell viability, mitochondrial membrane potential (MMP), lactate dehydrogenase (LDH) levels, reactive oxygen species (ROS) generation were analyzed. Inflammatory, and antioxidant,-related proteins were analyzed using western blotting. Molecular docking and drug affinity targeting experiments (DARTS) were utilized to analyze and verify the binding of the Keap1 protein and polyphenols of PSE. RESULTS: HG can significantly increase the activity of lactic dehydrogenase (LDH), destroy the mitochondrial membrane potential (MMP), and promote the generation of reactive oxygen species (ROS), while PSE treatment reversed these changes. Mechanistically, PSE inhibited NF-κB and inflammatory cytokines activation induced by HG through activating the expression of Nrf2 and its downstream antioxidant proteins Heme oxygenase-1 (HO-1), NAD (P)H Quinone Dehydrogenase 1 (NQO1), Glutamate cysteine ligase catalytic subunit (GCLC), Glutamate-cysteine ligase modifier (GCLM). Further study indicated that PSE activated Nrf2 antioxidant pathway mainly by the binding of primary polyphenols from PSE and the Keap1 protein. CONCLUSION: Taken together, the present data highlight the health benefits of polyphenols from Penthorum chinense Pursh. regarding diabetes, proving it to be an important source of health care products. Besides, binding of the Keap1 protein may be an effective strategy to activate Nrf2 antioxidant pathway and prevent diabetes.


Assuntos
Medicamentos de Ervas Chinesas/metabolismo , Glucose/toxicidade , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Polifenóis/metabolismo , Saxifragaceae , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/uso terapêutico , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/prevenção & controle , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Polifenóis/isolamento & purificação , Polifenóis/uso terapêutico
14.
Oxid Med Cell Longev ; 2020: 1208726, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33144913

RESUMO

Idesia polycarpa Maxim. var. vestita Diels (I. polycarpa) is well known as an edible oil plant which contains abundant linoleic acid and polyphenols. The objective of this study was to maximize the by-product of defatted fruit of I. polycarpa. We found that the fraction D of ethyl acetate extract (EF-D) contained more polyphenols, which contribute to its strong antioxidant activity by antioxidant assays (DPPH, ABTS, and FRAP). Meanwhile, EF-D showed a significant lipid-lowering effect on oleic acid- (OA-) induced hepatic steatosis in HepG2 cells through enhancing antioxidant activity, reducing liver damage, and regulating lipid metabolism, antioxidant, and inflammation-related gene expression. The SOD and T-AOC levels significantly increased, but the levels of MDA, AST, and ALT decreased obviously when treated with EF-D. In general, EF-D improved the antioxidant enzyme activities and decreased the hepatic injury activities. Besides, treatment with EF-D for NAFLD influenced lipid metabolism and inflammation by activating PPARα which was associated with the increased expression of CPT1 and decreased expression of SCD, NF-κB, and IL-1. Moreover, EF-D improved the oxidative stress system through activation of the Nrf2 antioxidant signal pathways and upregulated its target genes of HO-1, NQO1, and GSTA2. The results highlighted the EF-D from the defatted fruit of I. polycarpa regarding lipid-lowering, proving it to be a potential drug resource of natural products for treating the nonalcoholic fatty liver disease (NAFLD).


Assuntos
Antioxidantes/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Salicaceae/química , Acetatos/química , Biomarcadores/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Flavonoides/análise , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Mediadores da Inflamação/metabolismo , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Hepatopatia Gordurosa não Alcoólica/genética , Ácido Oleico , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Fenóis/análise , Extratos Vegetais/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Triglicerídeos/metabolismo
15.
Mol Neurobiol ; 57(11): 4628-4641, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32770451

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disorder primarily caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SNpc). However, the manner of death of dopaminergic neurons remains indistinct. Ferroptosis is a form of cell death involving in the iron-dependent accumulation of glutathione depletion and lipid peroxide. Besides, previous studies indicated that ferroptosis might be involved in the death of dopaminergic neurons. In this study, we aim to explore the protective effect of the p62-Keap1-Nrf2 pathway against 6-hydroxydopamine (6-OHDA)-induced ferroptosis in dopaminergic cells. Firstly, our results demonstrated that 6-OHDA-induced ferroptosis could be observed in vivo zebrafish and in vitro human dopaminergic cell line (SH-SY5Y cells) model. Moreover, ferroptosis induced by 6-OHDA mitigates in SH-SY5Y cells upon ferrostatin-1 (Fer, an inhibitor of ferroptosis) treatment via upregulating the protein expression of glutathione peroxidase 4 (GPX4). Then, we found that high p62/SQSTM1 (p62) expression could protect SH-SY5Y cells against ferroptosis through promoting Nrf2 nuclear transfer and upregulating the expression of the antioxidant protein heme oxygenase-1 (HO-1). Ultimately, high p62 expression activates the Nrf2/HO-1 signaling pathway through binding to Kelch-like ECH-associated protein 1 (Keap1). Collectively, the activation of the p62-Keap1-Nrf2 pathway prevents 6-OHDA-induced ferroptosis in SH-SY5Y cells, targeting this pathway in combination with a pharmacological inhibitor of ferroptosis can be a potential approach for PD therapy.


Assuntos
Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Ferroptose , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Neuroproteção , Proteína Sequestossoma-1/metabolismo , Transdução de Sinais , Animais , Linhagem Celular , Cicloexilaminas/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Modelos Biológicos , Neuroproteção/efeitos dos fármacos , Oxidopamina , Fenilenodiaminas/farmacologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Ligação Proteica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra
16.
Environ Pollut ; 265(Pt B): 114864, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32505960

RESUMO

Microplastics (MPs) pollution has become a global environmental concern. MPs alone and in combination with pollutants can potentially cause significant harm to organisms and human beings. Weathering of MPs under various environmental stresses increases the uncertainty of their environmental fates. Compared with field surveys, laboratory simulation experiments are appropriate to simplify the research procedures and investigate the mechanisms. In this review, the effects of abrasion, solar radiation, chemical and thermal oxidation, microbial adhesion and colonization, and other environmental factors on the MPs and the relative laboratory simulation methods were summarized and discussed. Photo-oxidation and abrasion are the most appliable methods due to easy operation and adjustable weathering degree. Furthermore, the structural and components changes in weathering process and the applied characterization methods were generalized. In addition, one of important environmental behaviors, adsorption of the weathered MPs towards two typical pollutants was analyzed. Finally, three priorities for research were proposed. This paper conducts systematic summarized of the MPs weathering process and provides a reference for future studies to accurately determine the environmental risks of weathering MPs.


Assuntos
Poluição Ambiental , Microplásticos , Poluentes Químicos da Água/análise , Adsorção , Monitoramento Ambiental , Humanos , Plásticos , Tempo (Meteorologia)
17.
Environ Pollut ; 264: 114748, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32416428

RESUMO

Deoxynivalenol (DON) is an unavoidable cereal crops contaminants and environmental pollutants, which seriously threated the health of human and animal. DON has been reported to exert significant toxicity effects on spermatogenesis, but the underlying mechanisms remain largely inconclusive. The blood-testis barrier (BTB) provides a specialized biochemical microenvironment for maintaining spermatogenesis. Thus, we hypothesized that DON could impair BTB and lead to spermatogenesis disorder. To confirm this hypothesis, sixty male mice were intragastrically administered with 0, 1.2, 2.4 and 4.8 mg/kg body weight DON for 28 days, and several important observations were obtained in present study. First, we found that DON induced spermatogenesis disorder, reflected by the declines of sperm concentration and quality, sperm ultrastructural damage as well as seminiferous tubular damage. Then, we proved that DON induced BTB disruption as well as decreased the expressions of BTB junction proteins, including Occludin, Connexin 43 and N-cadherin. Finally, the present study showed that DON induced inflammation and inhibited T biosynthesis in testis of mice. These results revealed that DON induced spermatogenesis disorder by BTB disruption associated with testosterone deficiency and inflammation in mice, which shed a new light on the potential mechanisms of reproductive toxicity induced by DON.


Assuntos
Barreira Hematotesticular , Espermatogênese , Animais , Humanos , Inflamação , Masculino , Camundongos , Testículo , Testosterona , Tricotecenos
18.
Mol Ecol ; 29(13): 2492-2510, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32163643

RESUMO

Understanding diversity patterns requires accounting for the roles of both historical and contemporary factors in the assembly of communities. Here, we compared diversity patterns of two moth assemblages sampled from Taihang and Yanshan mountains in Northern China and performed ancestral range reconstructions using the Multi-State Speciation and Extinction model, to track the origins of these patterns. Further, we estimated diversification rates of the two moth assemblages and explored the effects of contemporary ecological factors. From 7,788 specimens we identified 835 species belonging to 23 families, using both DNA barcode analysis and morphology. Moths in Yanshan mountains showed higher species diversity than in Taihang mountains. Ancestral range analysis indicated Yanshan as the origin, with significant historical dispersals from Yanshan to Taihang. Asymmetrical diversification, population expansion, along with frequent and considerable gene flow were detected between communities. Moreover, dispersal limitation or the joint effect of environment filtering and dispersal limitation were inferred as main driving forces shaping current diversity patterns. In summary, we demonstrate that a multiscale (community, population and species level) analysis incorporating both historical and contemporary factors can be useful in delineating factors contributing to community assembly and patterning in diversity.


Assuntos
Biodiversidade , Mariposas/classificação , Animais , China , Código de Barras de DNA Taxonômico , Fluxo Gênico , Filogenia
19.
Sci Total Environ ; 715: 136968, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32014782

RESUMO

Microplastic (MP) pollution is a significant environmental concern due to the persistence of MPs and their potential adverse effects on biota. Most scientific studies have examined the distribution, ingestion, fate, behavior, amount, and effect of MPs. However, few studies have described the development of methods for the removal and remediation of MPs. Therefore, in this review, we summarize the recent literature regarding the microbial-mediated degradation of MPs and discuss the associated degradation characteristics and mechanisms. Different types and combinations of microorganisms, such as bacteria, fungi, bacterial consortia, and biofilms, that can degrade different MPs are categorized. This article summarizes approximately 50 recent papers. Twelve and 6 papers reported that bacteria and fungi, respectively, can degrade MPs. Nine articles indicated that bacterial consortia have the ability to degrade MPs, and 6 articles found that biofilms can also utilize MPs. Furthermore, to evaluate their associated degradation effects, the corresponding structural changes (i.e., macro size, surface morphology, and functional groups) in MPs after microbial degradation are examined. In addition, MP biodegradation is affected by microbial characteristics and environmental factors; therefore, the environmental factors (i.e., temperature, pH and strain activity) influencing MP degradation and the associated degradation effects (i.e., weight loss, degradation rate, and molecular weight change) are generalized. Furthermore, the mechanisms associated with the microbial-mediated degradation of MPs are briefly discussed. Finally, prospects for the degradation of MPs using microbes and future research directions are envisioned. This review provides the first systematic summary of the microbial-mediated degradation of MPs and provides a reference for future studies investigating effective means of MP pollution control.


Assuntos
Microplásticos , Plásticos , Monitoramento Ambiental , Poluição Ambiental , Poluentes Químicos da Água
20.
J Ethnopharmacol ; 253: 112579, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31978521

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Veronica ciliata Fisch. is used in numerous of Tibetan medicine prescriptions because of its hepatoprotective effect. AIMS OF THIS STUDY: Here, we aimed to investigate the hepatoprotective effect and mechanism of phenolic fraction (PF) of V. ciliata Fisch. on liver injury induced by free radical. MATERIALS AND METHODS: BRL 3A cells were pre-treated with PF and luteolin (Lut) following tert-butyl hydroperoxide (t-BHP) treatment. The cell viability, lactate dehydrogenase (LDH) levels, reactive oxygen species (ROS) generation, apoptosis, cell cycle and autophagy were analyzed. Apoptotic, inflammatory, and autophagy,- related proteins were analyzed using Western blotting. The combination of molecular docking and drug affinity targeting experiments (DARTS) were first utilized to analysis the target protein of Lut. RESULTS: PF effectively suppressed t-BHP-induced apoptosis caused by mitochondrial dysfunction, which were associated with inhibiting ROS generation. Further investigation indicated that PF significantly suppressed apoptosis, inflammation, and autophagy by regulating the expression of related proteins. The results of molecular docking and drug affinity targeting experiments (DARTS) revealed that PI3K was the target protein of PF and Lut. Further studies have shown that PF relieved liver injury induced by t-BHP via suppressing phosphorylated expression of PI3K. CONCLUSION: Our results indicate that PF effectively protect against hepatotoxicity induced by t-BHP through inhibiting the abnormal activation of PI3K-Akt signaling pathway and highlight the health benefits of PF regarding oxidative stress, proving it to be an important source of bioactive compounds associated with Nonalcoholic fatty liver disease (NAFLD).


Assuntos
Hepatócitos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Fenóis/farmacologia , Veronica/química , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Radicais Livres/toxicidade , Hepatócitos/patologia , Simulação de Acoplamento Molecular , Estresse Oxidativo/efeitos dos fármacos , Fenóis/isolamento & purificação , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Endogâmicos BUF , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , terc-Butil Hidroperóxido/toxicidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...