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1.
PNAS Nexus ; 3(1): pgae020, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38274121

RESUMO

Signaling molecules in cellular responses to foreign stimuli are described as static up- or down-concentration changes during signal transduction. This is because analytical methods for transducing molecules are much slower than the signaling events. In this study, we develop a dynamic cell model and reveal the temporal regulation of signal transduction events in response to reactive oxygen species (ROS). The model contained a set of 10 batches of redox-modified cells that mimic the temporal ROS accumulation events. Validating this dynamic cell model, we discover that cells survive early ROS attacks by activating the Nrf2/polysulfide/p62/CDK1 pathway. Nearly all signaling molecules exhibit time-dependent V-shape or inverse V-shape activation/feedback regulation dynamics in response to ROS accumulation. The results show that the dynamic cell model approach is invaluable for revealing complex signal intensity- and time-dependent cell signaling events.

2.
Water Res ; 250: 121047, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38154343

RESUMO

Despite extensive research into the presence and behavior of microplastics (MPs) in the environment, limited attention has been given to the investigation of the characteristics of dissolved organic matter (DOM) that leaches from MPs (MPs-DOM). Herein, two frequently encountered plastic particles in aquatic environments, specifically polyethylene terephthalate (PET)- and polyethylene (PE)-MPs, were subjected to leaching in the aquatic settings for seven days, both in the absence of light and under UV irradiation. Measurements of dissolved organic carbon (DOC) indicated that UV exposure enhanced the liberation of DOM from PET-MPs, while PE-MPs did not exhibit such leaching. After UV treatment for seven days, the DOM released from PET-MPs increased by 25 times, while that from PE-MPs remained almost unchanged. Then, the molecular diversity and the evolving formation of DOM originating from different MPs were comprehensively analyzed with fluorescence excitation-emission matrix (EEM) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Specifically, both PET- and PE-DOM exhibited three fluorescence signatures, with the predominant C1 (tryptophan-like) component showing a decline in PET-DOM and a rise in PE-DOM during aging. The FT-ICR-MS analysis unveiled that PET-DOM grew more recalcitrant under UV exposure, while PE-DOM became increasingly labile. In brief, UV irradiation influences MPs-DOM release and transformation differently, depending on the plastic composition. This highlights the significance of exploring MPs-DOM transformation in securing environmental safety.


Assuntos
Microplásticos , Água , Matéria Orgânica Dissolvida , Plásticos , Espectrometria de Massas
3.
Nat Commun ; 14(1): 7168, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37935672

RESUMO

Van der Waals (vdW) ferroelectrics have attracted significant attention for their potential in next-generation nano-electronics. Two-dimensional (2D) group-IV monochalcogenides have emerged as a promising candidate due to their strong room temperature in-plane polarization down to a monolayer limit. However, their polarization is strongly coupled with the lattice strain and stacking orders, which impact their electronic properties. Here, we utilize four-dimensional scanning transmission electron microscopy (4D-STEM) to simultaneously probe the in-plane strain and out-of-plane stacking in vdW SnSe. Specifically, we observe large lattice strain up to 4% with a gradient across ~50 nm to compensate lattice mismatch at domain walls, mitigating defects initiation. Additionally, we discover the unusual ferroelectric-to-antiferroelectric domain walls stabilized by vdW force and may lead to anisotropic nonlinear optical responses. Our findings provide a comprehensive understanding of in-plane and out-of-plane structures affecting domain properties in vdW SnSe, laying the foundation for domain wall engineering in vdW ferroelectrics.

4.
ACS Appl Mater Interfaces ; 15(17): 21219-21227, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37083295

RESUMO

The extreme device-to-device variation of switching performance is one of the major obstacles preventing the applications of metal-oxide-based memristors in large-scale memory storage and resistive neural networks. Recent experimental works have reported that embedding metal nano-islands (NIs) in metal oxides can effectively improve the uniformity of the memristors, but the underlying role of the NIs is not fully understood. Here, to address this specific problem, we develop a physical model to understand the origin of the variability and how the embedded NIs can improve the performance and uniformity of memristors. We find that due to the dimension confinement effect, embedding metal NIs can modulate the electric field distribution and lead to a more deterministic formation of the conductive filament (CF) from their vicinity, in contrast to the random growth of CFs without embedded NIs. This deterministic CF formation, via vacancy nucleation, further reduces the forming, reset, and set voltages and enhances the uniformity of the operation voltages and current ON/OFF ratios. We further demonstrate that modifying the shapes of the metal NIs can modulate the field strengths/distributions around the NIs and that choosing the NI metal composition and shape that chemically facilitate vacancy formations can further optimize the CF morphology, reduce the operation voltages, and improve the switching performance. Our work thus provides a fundamental understanding of how embedded metal NIs improve the resistive switching performance in oxide-based memristors and could potentially guide the selection of embedded NIs to realize a more uniform memristor that also operates at a higher efficiency than present materials.

5.
ACS Appl Mater Interfaces ; 15(5): 6647-6656, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36696100

RESUMO

Aqueous zinc metal batteries show great promise in large-scale energy storage. However, the decomposition of water molecules leads to severe side reactions, resulting in the limited lifespan of Zn batteries. Here, the tetrahydrofuran (THF) additive was introduced into the zinc sulfate (ZnSO4) electrolyte to reduce water activity by modulating the solvation structure of the Zn hydration layer. The THF molecule can play as a proton acceptor to form hydrogen bonds with water molecules, which can prevent water-induced undesired reactions. Thus, in an optimal 2 M ZnSO4/THF (5% by volume) electrolyte, the hydrogen evolution reaction and byproduct precipitation can be suppressed, which greatly improves the cycling stability and Coulombic efficiency of reversible Zn plating/stripping. The Zn symmetrical cells exhibit ultralong working cycles with a wide range of current density and capacity. The THF additive also enables a high Coulombic efficiency in the Zn||Cu cell with an average value of 99.59% over 400 cycles and a high reversible capacity with a capacity retention of 97.56% after 250 cycles in the Zn||MnO2 full cells. This work offers an effective strategy with high scalability and low cost for the protection of the Zn metal electrodes in aqueous rechargeable batteries.

6.
ACS Chem Neurosci ; 14(1): 159-169, 2023 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-36516359

RESUMO

Ischemic stroke is a major cause of mortality with complicated pathophysiological mechanisms, and hematoxylin and eosin (HE) staining is a histochemical diagnosis technique heavily relying on subjective observation. In this study, we developed a noninvasive assay using Raman spectroscopy for in vitro diagnosis and visualization of cerebral ischemia/reperfusion injury and protective effects of ferulic acid. By establishing a middle cerebral artery occlusion (MCAO) model in Sprague-Dawley male rats, we found effective interventions by ferulic acid using the neurological function score and HE staining. Raman spectra of neuronal and neuroglial cells exhibited significant intensity changes of protein, nucleotide, lipid, and carbohydrate at 780, 814, 1002, 1012, 1176, 1224, 1402, 1520, 1586, 1614, and 1752 cm-1. Cluster vector analysis highlighted the alterations at 1002, 1080, 1298, 1430, 1478, 1508, 1586, and 1676 cm-1. To evaluate the levels of neuron injury and intervention performance, a random forest model was developed on Raman spectral data and achieved satisfactory accuracy (0.9846), sensitivity (0.9679-0.9932), and specificity (0.9945-0.9989), ranking peaks around 1002 cm-1 as key fingerprint for classification. Spectral phenylalanine-to-tryptophan ratio was the biomarker to visualize neuronal injury and intervention performance of ferulic acid with a resolution of 1 µm. Our results unravel the biochemical changes in neuronal cells with cerebral ischemia/reperfusion injury and ferulic acid treatment, and prove Raman spectroscopy coupled with machine learning as a power tool to classify neuron viability and evaluate the intervention performance in pharmacological research.


Assuntos
Isquemia Encefálica , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Infarto da Artéria Cerebral Média/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/complicações , Aprendizado de Máquina , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico
7.
Water Res ; 224: 119042, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36103778

RESUMO

Sulfidation of silver nanoparticles (AgNPs) to generate silver sulfide nanoparticles (Ag2S-NPs) significantly influences their fate and toxicity in natural environments. However, the correlational research in this field was limited by the lack of methods for speciation analysis of Ag2S-NPs. To address this challenge, a novel protocol for the selective Ag2S-NP extraction from real waters was developed using protein corona-induced extraction coupled to Fenton oxidation of AgNPs with Fe3+/H2O2 reagents. The ability of various concentrations of Fe3+/H2O2 to selectively dissociate AgNPs into ions was first evaluated. Then, selective separation and preconcentration of the remaining Ag2S-NPs was established by optimizing the parameters that may affect the protein corona-induced extraction efficiency, followed by quantification with inductively coupled plasma mass spectrometry (ICP-MS), enabling an ultrahigh enrichment factor of 10,000 and extremely low detection limit (LOD) of 1.8 ng/L. The presence of humic acid (HA), inorganic salts and particles at the environmentally relevant levels had limited effects on Ag2S-NP extraction. As demonstrated by transmission electron microscopy (TEM) analysis and single particle ICP-MS (spICP-MS), the sizes, shapes, and compositions of Ag2S-NPs extracted with the proposed method remain in intact. Good recoveries of 83.7-105% were achieved for the Ag2S-NPs spiked in four natural waters at the level of 97.8 ng/L. Due to the high yields and applicability to Ag2S-NPs at environmentally relevant concentrations, this proposed method is particularly suitable to track the generation and transformation of Ag2S-NPs in various scenarios.


Assuntos
Nanopartículas Metálicas , Coroa de Proteína , Substâncias Húmicas/análise , Peróxido de Hidrogênio , Nanopartículas Metálicas/química , Sais , Prata/análise , Sulfetos
8.
ACS Appl Mater Interfaces ; 14(27): 30658-30671, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35759337

RESUMO

Lithium (Li) dendrite growth in Li batteries is a long-standing problem, which causes critical safety concerns and severely limits the advancement of rechargeable Li batteries. Replacing a conventional liquid electrolyte with a solid electrolyte of high mechanical strength and rigidity has become a potential approach to inhibiting the Li dendrite growth. However, there still lacks an accurate understanding of the role of the mechanical properties of the metal electrode and the solid electrolyte in the Li dendrite growth. In this work, we develop a phase-field model coupled with the elastoplastic deformation to investigate the Li dendrite growth and its inhibition in the cell. Different mechanical properties, including the elastic modulus and the initial yield strength of both the metal electrode and the solid electrolyte, are explored to understand their independent roles in the inhibition of Li dendrite growth. High-throughput phase-field simulations are performed to establish a database of relationships between the aforementioned mechanical properties and the Li dendrite morphology, based on which a compressed-sensing machine learning model is trained to derive interpretable analytical correlations between the key material parameters and the dendrite morphology, as described by the dendrite length and area ratio. It is revealed that the Li dendrite can be effectively inhibited by electrolytes of high elastic moduli and initial yield strengths. Meanwhile, the role of the yield strength of the Li metal is also critical when the yield strength of the electrolyte becomes low. This work provides a fundamental understanding of the dendrite inhibition by mechanical suppression and demonstrates a computational data-driven methodology to potentially guide the electrode and electrolyte material selection for better inhibition of the dendrite growth.

9.
J Org Chem ; 87(2): 1249-1261, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-35015524

RESUMO

This study shows that various di- and tri-substituted alkenes with high chemoselectivity were obtained in good to high yields by coupling N-tosylhydrazones (NTHs) with benzylic phosphates as electrophilic partners. The obtained new catalytic system consisted of PdCl2(CH3CN)2/dppp, LiOtBu as a base, and cyclopentyl methyl ether as a green solvent. In addition, we performed a gram-scale transformation using NTH derivatives and benzylic phosphates having a C sp2-Cl bond. The latter was used as a starting point for further postfunctionalization of the key intermediates.


Assuntos
Alcenos , Paládio , Catálise , Fosfatos
10.
Pharmaceuticals (Basel) ; 14(8)2021 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-34451876

RESUMO

This review concerns the synthesis and biological activities of pyrazino[1,2-a]indoles and pyrazino[1,2-a]indol-1-ones reported since 1997 and the discovery of biological activity of pyrazinoindole derivatives. In the first part, we first presented the synthetic routes that have been reported from a methodological point of view to access the pyrazinoindole unit according to cyclization reactions using or not using metal catalysts. Then, syntheses and neuropsychiatric, auto-immune, anti-infectious and anti-cancer properties of pyrazinoindoles were detailed. In the second part, we first reported the main accesses to pyrazinoindol-1-one substrates according to Michael reactions, metal-catalyzed and metal-free cyclization reactions. The syntheses and anti-cancer, anti-infectious, anti-allergenic and neuropsychiatric properties of pyrazinoindolones were next described and discussed.

11.
Org Biomol Chem ; 19(24): 5358-5367, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34047324

RESUMO

A new methodology to synthesize sulfonyl-N-phenylaniline derivatives via the trapping of bromo-sulfone derivatives generated from N-tosylhydrazones (NTHs) with amines is described. The reaction proved successful for a wide range of NTHs and amines and tolerated various functional groups on either coupling partner (35 examples). The mechanism was studied, and we showed that the sulfone formation does not follow a radical pathway.

12.
Chem Commun (Camb) ; 57(18): 2289-2292, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33533382

RESUMO

Herein, a novel pathway to prepare a porous structured DNA hybrid hydrogel has been described, using a transiently existing Pickering emulsion that is continuously generated during the reaction. The as-prepared highly porous gel features significantly improved capability for trace amounts of PAH removal.


Assuntos
Materiais Biocompatíveis/química , DNA/química , Hidrogéis/química , Nanotubos de Carbono/química , Hidrocarbonetos Policíclicos Aromáticos/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação , Adsorção , Emulsões/química , Hidrocarbonetos Policíclicos Aromáticos/química , Porosidade , Poluentes Químicos da Água/química , Purificação da Água/métodos
13.
J Org Chem ; 84(21): 13807-13823, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31571478

RESUMO

A new strategy for the construction of 3-phenyl-1H-pyrrolo-imidazo[1,2-a]pyridine backbone is described. The reaction starts from the coupling between N-tosylhydrazones and 2-chloro-3-nitroimidazo[1,2-a]pyridines leading to the formation of 3-nitro-2-(arylvinyl)imidazo[1,2-a]pyridine derivatives. Optimization of Cadogan-reductive conditions allowed the conversion of the obtained nitro derivative to a new scaffold of the type 3-aryl-1H-pyrrolo-imidazo[1,2-a]pyridine. This method provides rapid access to new libraries in the context of diversity-oriented synthesis, which intends to generate small molecules with a large structure diversity in an efficient manner. Screening of the biological activity of the newly generated compounds leads to the identification of a new promising compound 5cc, which exhibits good antiproliferative activity in the submicromolar range against a human colon cancer cell line.

14.
Eur Phys J E Soft Matter ; 42(9): 118, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31493015

RESUMO

This report presents the results of high-pressure and broadband dielectric spectroscopy studies in polyvinylidene difluoride (PVDF) and barium strontium titanate (BST) microparticles composites (BST/PVDF). It shows that the Arrhenius behaviour for the temperature-related dynamics under atmospheric pressure is coupled to Super-Arrhenius/Super-Barus isothermal pressure changes of the primary relaxation time. Following these results, an explanation of the unique behaviour of the BST/PVDF composite is proposed. Subsequently, it is shown that when approaching the GPa domain the negative electric capacitance phenomenon occurs.

15.
Braz J Med Biol Res ; 52(6): e7628, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31116255

RESUMO

This study aimed to explore the influence of gut microbiota alterations induced by Linderae radix ethanol extract (LREE) on alcoholic liver disease (ALD) in rats and to study the anti-inflammatory effect of LREE on ALD through the lipopolysaccharide (LPS) toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway. ALD rat models were established by intragastric liquor [50% (v/v) ethanol] administration at 10 mL/kg body weight for 20 days. Rats were divided into six groups: normal group (no treatment), model group (ALD rats), Essentiale group (ALD rats fed with Essentiale, 137 mg/kg), and LREE high/moderate/low dose groups (ALD rats fed with 4, 2, or 1 g LREE/kg). NF-κB and LPS levels were evaluated. Liver pathological changes and intestinal ultrastructure were examined by hematoxylin and eosin staining and transmission electron microscopy. The gut microbiota composition was evaluated by 16S rDNA sequencing. Expression levels of TLR4 and CD68 in liver tissue, and occludin and claudin-1 in intestinal tissue were measured. LREE treatment significantly reduced NF-κB and LPS levels, improved liver pathological changes, and ameliorated intestinal ultrastructure injury. Meanwhile, LREE-fed groups showed a higher abundance of Firmicutes and a lower abundance of Bacteroidetes than the rats in the model group. Administration of LREE suppressed TLR4 overexpression and promoted the expression of occludin and claudin-1 in intestine tissue. Thus, LREE could partly ameliorate microflora dysbiosis, suppress the inflammatory response, and attenuate liver injury in ALD rats. The protective effect of LREE might be related to the LPS-TLR4-NF-κB pathway.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/prevenção & controle , Lindera/química , Hepatopatias Alcoólicas/prevenção & controle , Fígado/ultraestrutura , Extratos Vegetais/farmacologia , Animais , Citocinas/sangue , Modelos Animais de Doenças , Lipopolissacarídeos/sangue , Hepatopatias Alcoólicas/diagnóstico por imagem , Masculino , Raízes de Plantas/química , Proteínas Serina-Treonina Quinases/sangue , Ratos , Ratos Sprague-Dawley , Receptor 4 Toll-Like/sangue , Quinase Induzida por NF-kappaB
16.
J Org Chem ; 84(1): 228-238, 2019 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-30523682

RESUMO

A one-pot Barluenga coupling between N-tosylhydrazones and nitro-benzyl bromide, followed by deoxygenation of ortho-nitrostyrenes, and subsequent cyclization has been developed, providing a new way to synthesize various C2-arylindoles. This method exhibits a good substrate scope and functional group tolerance, and it allows an access to NH-free indoles, which can present a potential utility in medicinal chemistry applications.

17.
Braz. j. med. biol. res ; 52(6): e7628, 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1001534

RESUMO

This study aimed to explore the influence of gut microbiota alterations induced by Linderae radix ethanol extract (LREE) on alcoholic liver disease (ALD) in rats and to study the anti-inflammatory effect of LREE on ALD through the lipopolysaccharide (LPS) toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway. ALD rat models were established by intragastric liquor [50% (v/v) ethanol] administration at 10 mL/kg body weight for 20 days. Rats were divided into six groups: normal group (no treatment), model group (ALD rats), Essentiale group (ALD rats fed with Essentiale, 137 mg/kg), and LREE high/moderate/low dose groups (ALD rats fed with 4, 2, or 1 g LREE/kg). NF-κB and LPS levels were evaluated. Liver pathological changes and intestinal ultrastructure were examined by hematoxylin and eosin staining and transmission electron microscopy. The gut microbiota composition was evaluated by 16S rDNA sequencing. Expression levels of TLR4 and CD68 in liver tissue, and occludin and claudin-1 in intestinal tissue were measured. LREE treatment significantly reduced NF-κB and LPS levels, improved liver pathological changes, and ameliorated intestinal ultrastructure injury. Meanwhile, LREE-fed groups showed a higher abundance of Firmicutes and a lower abundance of Bacteroidetes than the rats in the model group. Administration of LREE suppressed TLR4 overexpression and promoted the expression of occludin and claudin-1 in intestine tissue. Thus, LREE could partly ameliorate microflora dysbiosis, suppress the inflammatory response, and attenuate liver injury in ALD rats. The protective effect of LREE might be related to the LPS-TLR4-NF-κB pathway.


Assuntos
Animais , Masculino , Ratos , Extratos Vegetais/farmacologia , Lindera/química , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/prevenção & controle , Fígado/ultraestrutura , Hepatopatias Alcoólicas/prevenção & controle , Lipopolissacarídeos/sangue , Citocinas/sangue , Ratos Sprague-Dawley , Proteínas Serina-Treonina Quinases/sangue , Raízes de Plantas/química , Modelos Animais de Doenças , Receptor 4 Toll-Like/sangue , Hepatopatias Alcoólicas/diagnóstico por imagem
18.
PLoS One ; 13(8): e0203128, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30161257

RESUMO

Low serum cholinesterase (SCHE) activity has been associated with poor prognoses in a variety of conditions, including sepsis. However, such an association has not been well characterized since the Third International Consensus Definitions Task Force modified the definition of sepsis to "life-threatening organ dysfunction due to a dysregulated host response to infection" (known as sepsis-3) in 2016. In the current retrospective cohort study, we examined whether 30-day mortality in sepsis-3 patients is associated with SCHE activity. A total of 166 sepsis-3 patients receiving treatment at an emergency intensive care unit (EICU) were included. The 30-day death rate was 33.1% (55/166). SCHE activity upon EICU admission was lower in nonsurvivors (3.3 vs. 4.5 KU/L in survivors, p = 0.0002). Subjects with low SCHE activity (defined as <4 KU/L) had higher 30-day mortality rates than subjects with normal SCHE activity (45.5%, 40/88 vs. 19.2%, 15/78; p<0.001). A multivariate logistic regression analysis revealed an association between 30-day mortality and lower SCHE activity after adjustments for relevant factors, such as acute multiple organ dysfunction. The odds ratio (OR) for every unit decrease in SCHE activity was 2.11 (95% confidence interval (CI), 1.37-3.27; p = 0.0008). The area under the curve (AUC) of SCHE activity for predicting 30-day mortality was 0.67 (95% CI 0.59-0.74), and the AUC of lactate for predicting 30-day mortality was 0.64 (95% CI 0.57-0.70). Using a combination of SCHE and lactate, the AUC was 0.74 (95% CI 0.69-0.83). These data suggest that lower SCHE activity is an independent risk factor for 30-day mortality in sepsis-3 patients.


Assuntos
Colinesterases/sangue , Sepse/sangue , Sepse/mortalidade , Biomarcadores/sangue , Cuidados Críticos , Serviços Médicos de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sepse/enzimologia , Sepse/terapia , Fatores de Tempo
19.
Exp Ther Med ; 15(2): 2156-2164, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29434819

RESUMO

The present study investigated the mechanism underlying the anti-inflammatory effects of Tangshen formula (TS) in Sprague Dawley (SD) rats with diabetic nephropathy (DN). A rat model of DN was established by intraperitoneal injection of 1% (40 mg/kg) streptozotocin and administration of a high fat and glucose diet. Subsequently, SD rats were randomly divided into six groups (n=8): A DN group, a valsartan group, a high-dose TS group, a middle-dose TS group, a low-dose TS group and a control group with normal SD rats. Once rats received their allocated treatment for 12 weeks, body weight and kidney weight were recorded, and fasting blood glucose, ratio of urinary protein, ß2-MG and creatinine clearance rate were determined. Furthermore, hemodynamic indices, including plasma viscosity and whole blood reduction viscosity were detected. Immunohistochemistry was used to detect the infiltration of macrophages in the kidneys of rats. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to investigate the activation; mRNA and protein expression levels of monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibitory factor (MIF), nuclear factor-κB (NF-κB) and sirtuin-1 (SIRT1) in each group. In comparison with the DN group, each biochemical indicator of rats in the high-dose TS group was significantly decreased (P<0.05). Blood viscosity in each treatment group was significantly decreased when compared with the DN group (P<0.01). Hematoxylin and eosin staining indicated that the infiltration of macrophages was significantly decreased in the high-dose TS group when compared with the DN group (P<0.01). mRNA and protein expression levels of MCP-1 and MIF in the high-dose TS group were significantly decreased when compared with the DN group (P<0.05). In the treatment groups, SITR1 mRNA expression levels were significantly increased, whereas the mRNA expression levels of NF-κB were significantly decreased (P<0.01). Western blotting results indicated a significant decrease in the protein expression levels of acetylated NF-κB in the treatment groups when compared with the DN group (P<0.01) and the propensity of protein expression of the other inflammatory factors were consistent with the mRNA findings. The results of the high-dose TS group were similar to those of the valsartan group. The present study indicates that TS was able to activate SITR1, which lead to NF-κB deacetylation, thus reducing the release of inflammatory factors and decreasing the severity of diabetic nephropathy.

20.
Chin J Integr Med ; 22(12): 910-917, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26712211

RESUMO

OBJECTIVE: To explore the mechanism of the protective effects of Panax notoginseng saponins (PNS) on kidney in diabetic rats. METHODS: Diabetic rat model was obtained by intravenous injection of alloxan, and the rats were divided into model, PNS-100 mg/(kg day) and PNS-200 mg/(kg day) groups, 10 each. Another 10 rats injected with saline were served as control. Periodic acid-Schiff staining and immunological histological chemistry were used to observe histomorphology and tissue expression of bone morphogenetic protein-7 (BMP-7). Silent information regulator 1 (SIRT1) was silenced in rat mesangial cells by RNA interference. The mRNA expressions of SIRT-1, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor ß1 (TGF-ß1) and plasminogen activator inhibitor-1 (PAI-1) were analyzed by reverse transcription polymerase chain reaction. The protein expressions of SIRT1 and the acetylation of nuclear factor κB (NF-κB) P65 were determined by western blotting. The concentration of MCP-1, TGF-ß1 and malondialdehyde (MDA) in culture supernatant were detected by enzyme-linked immuno sorbent assay. The activity of superoxide dismutase (SOD) was detected by the classical method of nitrogen and blue four. RESULTS: In diabetic model rats, PNS could not only reduce blood glucose and lipid (P<0.01), but also increase protein level of BMP-7 and inhibit PAI-1 expression for suppressing fibrosis of the kidney. In rat mesangial cells, PNS could up-regulate the expression of SIRT1 (P<0.01) and in turn suppress the transcription of TGF-ß1 (P<0.05) and MCP-1 (P<0.05). PNS could also reverse the increased acetylation of NF-κB p65 by high glucose. In addition, redox regulation factor MDA was down-regulated (P<0.05) and SOD was up-regulated (P<0.01), which were both induced by SIRT1 up-regulation. CONCLUSIONS: PNS could protect kidney from diabetes with the possible mechanism of up-regulating SIRT1, therefore inhibiting inflammation through decreasing the induction of inflammatory cytokines and TGF-ß1, as well as activating antioxidant proteins.


Assuntos
Antioxidantes/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Rim/patologia , Panax notoginseng/química , Substâncias Protetoras/uso terapêutico , Saponinas/uso terapêutico , Sirtuína 1/genética , Regulação para Cima/efeitos dos fármacos , Acetilação/efeitos dos fármacos , Animais , Glicemia/metabolismo , Proteína Morfogenética Óssea 7/metabolismo , Quimiocina CCL2/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/fisiopatologia , Técnicas de Silenciamento de Genes , Imuno-Histoquímica , Rim/efeitos dos fármacos , Testes de Função Renal , Lipídeos/sangue , Masculino , Malondialdeído/metabolismo , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Saponinas/farmacologia , Superóxido Dismutase/metabolismo , Fator de Transcrição RelA/metabolismo , Transcrição Gênica/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo
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