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1.
Development ; 150(4)2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36691900

RESUMO

Intestinal homeostasis depends on interactions between the intestinal epithelium, the immune system and the microbiota. Because of these complicated connections, there are many problems that need to be solved. Current research has indicated that genes targeted by Wnt signaling are responsible for controlling intestinal stem cell fate and for modulating intestinal homeostasis. Our data show that loss of frizzled 7 (Fzd7), an important element in Wnt signaling, interrupts the differentiation of mouse intestinal stem cells into absorptive progenitors instead of secretory progenitors (precursors of goblet and Paneth cells). The alteration in canonical Wnt and Notch signaling pathways interrupts epithelial homeostasis, resulting in a decrease in physical protection in the intestine. Several phenotypes in our Fzd7-deleted model were similar to the features of enterocolitis, such as shortened intestines, decreased numbers of goblet cells and Paneth cells, and severe inflammation. Additionally, loss of Fzd7 exacerbated the defects in a chemical-induced colitis model and could initiate tumorigenesis. These findings may provide important information for the discovery of efficient therapeutic methods to treat enterocolitis and related cancers in the intestines.


Assuntos
Enterocolite , Celulas de Paneth , Animais , Camundongos , Diferenciação Celular , Enterocolite/metabolismo , Células Caliciformes/metabolismo , Homeostase , Mucosa Intestinal/metabolismo , Intestinos , Via de Sinalização Wnt
2.
Vet Res ; 53(1): 3, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35012652

RESUMO

Trueperella pyogenes (T. pyogenes) is an opportunistic pathogen associated with a variety of diseases in many domestic animals. Therapeutic treatment options for T. pyogenes infections are becoming limited due to antimicrobial resistance, in which efflux pumps play an important role. This study aims to evaluate the inhibitory activity of luteolin, a natural flavonoid, on the MsrA efflux pump and investigate its mechanism. The results of antimicrobial susceptibility testing indicated that the susceptibility of msrA-positive T. pyogenes isolates to six macrolides increased after luteolin treatment, while the susceptibility of msrA-negative isolates showed no change after luteolin treatment. It is suspected that luteolin may increase the susceptibility of T. pyogenes isolates by inhibiting MsrA activity. After 1/2 MIC luteolin treatment for 36 h, the transcription level of the msrA gene and the expression level of the MsrA protein decreased by 55.0-97.7% and 36.5-71.5%, respectively. The results of an affinity test showed that the equilibrium dissociation constant (KD) of luteolin and MsrA was 6.462 × 10-5 M, and hydrogen bonding was predominant in the interaction of luteolin and MsrA. Luteolin may inhibit the ATPase activity of the MsrA protein, resulting in its lack of an energy source. The current study illustrates the effect of luteolin on MsrA in T. pyogenes isolates and provides insight into the development of luteolin as an innovative agent in combating infections caused by antimicrobial-resistant bacteria.


Assuntos
Actinomycetaceae , Farmacorresistência Bacteriana , Luteolina , Macrolídeos , Actinomycetaceae/efeitos dos fármacos , Animais , Animais Domésticos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Luteolina/farmacologia , Macrolídeos/farmacologia , Testes de Sensibilidade Microbiana/veterinária
3.
Int J Mol Sci ; 23(15)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35955509

RESUMO

TatD960 and TatD825 are DNases that contribute to biofilm formation and virulence in Trueperella pyogenes (T. pyogenes). Luteolin is a natural flavonoid commonly found in plants that exhibits antimicrobial capacity. Our study aims to investigate the effects of luteolin on TatD DNases as a natural inhibitor. In this research, the expression of tatD genes and TatD proteins in T. pyogenes treated with luteolin was detected, and then the effect of luteolin on the hydrolysis of DNA by TatD DNases was analyzed using agarose gel electrophoresis. Moreover, the interactions between luteolin and TatD DNases were tested using surface plasmon resonance (SPR) assays and molecular docking analysis. After 1/2 MIC luteolin treatment, the transcription of tatD genes and expression of TatD proteins appeared to be reduced in 80-90% of T. pyogenes (n = 20). The gel assay revealed that luteolin can inhibit the activity of TatD DNases. The SPR assay showed that the KD values of luteolin to TatD960 and TatD825 were 6.268 × 10-6 M and 5.654 × 10-6 M, respectively. We found through molecular docking that hydrogen bonding is predominant in the interaction of luteolin and TatD DNases. Our data indicate that luteolin inhibited the ability of TatD DNases by decreasing their binding to DNA. The current study provides an insight into the development of luteolin as a DNase inhibitor in preventing biofilm formation and virulence in T. pyogenes.


Assuntos
Desoxirribonucleases , Luteolina , Desoxirribonucleases/metabolismo , Luteolina/farmacologia , Simulação de Acoplamento Molecular , Virulência , Fatores de Virulência/genética
4.
J Sep Sci ; 44(1): 6-16, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32926765

RESUMO

As a liquid-liquid partition chromatography, counter-current chromatography has advantages in large sample loading capacity without irreversible adsorption, which has been widely applied in separation and purification fields. The main factors, including partition coefficient, two-phase solvent systems, apparatus, and operating parameters greatly affect the separation process of counter-current chromatography. To promote the applications of counter-current chromatography, it is essential to develop theoretical research to master the principles of counter-current chromatographic separations so as to achieve predictions before laborious trials. In this article, recent progress about separation prediction methods are reviewed from a point of the steady and unsteady state of the mass transfer process of counter-current chromatography and its mass transfer characteristics, and then it is divided into three aspects: prediction of partition coefficient, modeling the thermodynamic process of counter-current chromatography, and modeling the dynamic process of counter-current chromatography.

5.
Int J Mol Sci ; 22(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34769168

RESUMO

Thoracic aortic aneurysm (TAA) formation is a multifactorial process that results in diverse clinical manifestations and drug responses. Identifying the critical factors and their functions in Marfan syndrome (MFS) pathogenesis is important for exploring personalized medicine for MFS. Methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) polymorphisms have been correlated with TAA severity in MFS patients. However, the detailed relationship between the folate-methionine cycle and MFS pathogenesis remains unclear. Fbn1C1039G/+ mice were reported to be a disease model of MFS. To study the role of the folate-methionine cycle in MFS, Fbn1C1039G/+ mice were treated orally with methionine or vitamin B mixture (VITB), including vitamins B6, B9, and B12, for 20 weeks. VITB reduced the heart rate and circumference of the ascending aorta in Fbn1C1039G/+ mice. Our data showed that the Mtr and Smad4 genes were suppressed in Fbn1C1039G/+ mice, while VITB treatment restored the expression of these genes to normal levels. Additionally, VITB restored canonical transforming-growth factor ß (TGF-ß) signaling and promoted Loxl1-mediated collagen maturation in aortic media. This study provides a potential method to attenuate the pathogenesis of MFS that may have a synergistic effect with drug treatments for MFS patients.


Assuntos
Ácido Fólico/farmacologia , Síndrome de Marfan , Mutação de Sentido Incorreto , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Animais , Modelos Animais de Doenças , Fibrilina-1/genética , Fibrilina-1/metabolismo , Humanos , Síndrome de Marfan/tratamento farmacológico , Síndrome de Marfan/enzimologia , Síndrome de Marfan/genética , Camundongos , Camundongos Transgênicos , Transdução de Sinais/genética , Fator de Crescimento Transformador beta/genética
6.
Pak J Pharm Sci ; 33(4): 1511-1517, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33583781

RESUMO

The extraction procedure and antioxidant activity were investigated for total proanthocyanidins extracts from Abutilon theophrasti Medic. leaves collected in August, September and October. The maximum extraction yield was achieved with 90% ethanol, 80°C of heating reflux temperature, 149.94 min of extraction time and 60(ml/g) of the ratio of solvent and material, which were optimized by Box-Behnken Design of response surface method. Spectrophotometric study displayed that total proanthocyanidins content was (0.44±0.02)% (0.52±0.01)% and (0.59±0.01)% for August, September and October samples, respectively. The proanthocyanidins extracts exhibited much stronger antioxidant activity to scavenge ABTS and DPPH free radicals, and reduce ferric power than the control synthetic antioxidant BHT. The present findings suggest that the proanthocyanidins extract from Abutilon theophrasti Medic. leaves was a very interesting candidate for the research and development of natural and healthy antioxidant for the pharmaceutical and food industries.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Malvaceae/química , Folhas de Planta/química , Proantocianidinas/química , Proantocianidinas/farmacologia , Etanol/química , Flavonoides/química , Flavonoides/farmacologia , Radicais Livres/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Solventes/química
7.
Biomed Chromatogr ; 33(4): e4474, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30577068

RESUMO

The current study focused on the extraction technology, components analysis, in vitro antioxidant and antibacterial activities of total flavonoids and fatty acids from Tribulus terrestris L. fruits. The extraction process of total flavonoids and fatty acids was optimized by the response surface method, and the compositions were identified from the two extracts by HPLC-DAD-ESI-MS- and GC-MS, respectively. In addition, the antioxidant and antibacterial activities were evaluated by assay of ABTS, DPPH radical scavenging activity, ferric reducing antioxidant power and minimal inhibitory concentration. The yields of total flavonoids and fatty acids were 0.46 and 9.76% under the optimized conditions. Moreover, nine and eight compositions were identified from the two extracts based on the related references, respectively. In addition, total flavonoids and fatty acids extracts both exhibited certain antioxidant and antibacterial activities. The present findings suggest that total flavonoids extracted from T. terrestris L. fruits comprised a more interesting candidate than fatty acids for the research and development of natural and healthy antioxidants and antibacterial agents for the pharmaceutical and food industries.


Assuntos
Antibacterianos/análise , Antioxidantes/análise , Ácidos Graxos/análise , Flavonoides/análise , Extratos Vegetais/análise , Tribulus/química , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Bactérias/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Ácidos Graxos/química , Ácidos Graxos/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Frutas/química , Cromatografia Gasosa-Espectrometria de Massas , Modelos Estatísticos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Espectrometria de Massas por Ionização por Electrospray
8.
Mediators Inflamm ; 2018: 3508506, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29725269

RESUMO

The flavonoid fraction was extracted from the leaves of Abutilon theophrasti Medic., which are usually used as a traditional Chinese herbal medicine for the treatment of inflammation and joint pain. The current study focused on the extraction process, component analysis, and in vitro antioxidant, antibacterial, and anti-inflammatory activities of the flavonoid fraction as a part of ongoing research on bioactive substances from natural plant sources. This study evaluated the antioxidant activities via assays of DPPH radical scavenging capacity, ABTS radical scavenging capacity, and reducing power and investigated inhibitory activities against Escherichia coli, Salmonella, Staphylococcus aureus, and Streptococcus. Moreover, the inflammatory activity of the flavonoid fraction was estimated by measurement of the content of tumor necrosis factor alpha, interleukin-1-beta, interleukin-6, interleukin-10, nitric oxide, and cyclooxygenase-2 and the gene expression levels of several inflammation markers, such as inducible nitric oxide synthase and cyclooxygenase-2, in RAW 264.7 macrophages after LPS treatment. In addition, the underlying anti-inflammatory mechanisms, that is, the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, were also revealed from the gene and protein expression levels. Taken together, these results suggested that the flavonoid fraction might exert in vitro antioxidant, antibacterial, and anti-inflammatory effects on LPS-stimulated RAW 264.7 macrophages and will be potentially useful as an adjuvant treatment for oxidative stress and bacterial and inflammatory diseases.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Interleucina-6/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Células RAW 264.7 , Salmonella/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Streptococcus/efeitos dos fármacos , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-38900614

RESUMO

In this article, the state estimation problem is studied for Markovian jump neural networks (MJNNs) within a digital network framework. The wireless communication channel with limited bandwidth is characterized by a constrained bit rate, and the occurrence of bit flips during wireless transmission is mathematically modeled. A transmission mechanism, which includes coding-decoding under bit-rate constraints and considers probabilistic bit flips, is introduced, providing a thorough characterization of the digital transmission process. A mode-dependent remote estimator is designed, which is capable of effectively capturing the internal state of the neural network. Furthermore, a sufficient condition is proposed to ensure the estimation error to remain bounded under challenging network conditions. Within this theoretical framework, the relationship between the neural network's estimation performance and the bit rate is explored. Finally, a simulation example is provided to validate the theoretical findings.

10.
Neural Netw ; 162: 288-296, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36933514

RESUMO

This paper investigates the bounded synchronization of the discrete-time master-slave neural networks (MSNNs) with uncertainty. To deal with the unknown parameter in the MSNNs, a parameter adaptive law combined with the impulsive mechanism is proposed to improve the estimation efficiency. Meanwhile, the impulsive method also is applied to the controller design for saving the energy. In addition, a novel time-varying Lyapunov functional candidate is employed to depict the impulsive dynamical characteristic of the MSNNs, wherein a convex function related to the impulsive interval is used to obtain a sufficient condition for bounded synchronization of the MSNNs. Based on the above condition, the controller gain is calculated utilizing an unitary matrix. An algorithm is proposed to reduce the boundary of the synchronization error by optimizing its parameters. Finally, a numerical example is provided to illustrate the correctness and the superiority of the developed results.


Assuntos
Algoritmos , Redes Neurais de Computação , Incerteza , Fatores de Tempo
11.
Environ Pollut ; 336: 122442, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37634567

RESUMO

Long-term human smelting activities have resulted in substantial heavy metals (HMs) pollution of farmland soils around smelting sites, and the safety of farmland products is critical for human health. The current study focuses on HMs in farmland soils surrounding a single smelter, therefore the impact of smelting on a national scale needs to be investigated further. This study was based on 116 papers and 1143 sets of relevant data for meta-analysis, and a hierarchical mixed-effects model was used to quantify the changes of HMs concentrations in farmland soils affected by non-ferrous metal smelting on a national scale, as well as their relationships with relevant explanatory variables in China. Results showed that: (i) non-ferrous metal smelting substantially increased farmland soils HMs concentrations (323%), with each HM concentration increasing in the following order: Cd (2753%) > Pb (562%) > Hg (455%) > Zn (228%) > Cu (158%) > As (107%) > Ni (52%); (ii) the highest increase of HMs in vegetable fields (361%), but not significant in comparison to other farmland categories, and the increase of Pb, Zn, Cu and As concentrations were significantly different in different types of smelting areas; (iii) the increase of Hg was significantly higher in the northern region than in the southern region, and the opposite increase of Cu; (iv) the soil depth from 0 to 40 cm was significantly affected by smelting, and the increase of multiple HMs were significantly positively correlated with soil pH and negatively correlated with distance; (v) the other explanatory variables (farmland category and soil organic matter) were not significantly related to the effect of smelting. The results can provide some reference for protecting and restoring farmland soils around smelting areas.


Assuntos
Mercúrio , Metais Pesados , Poluentes do Solo , Humanos , Solo , Fazendas , Chumbo/análise , Poluentes do Solo/análise , Monitoramento Ambiental/métodos , Metais Pesados/análise , Mercúrio/análise , China
12.
J Sci Food Agric ; 91(8): 1517-22, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21445856

RESUMO

BACKGROUND: This study analysed the content of ascorbic acid, phenolic acids and flavonoids in aqueous and ethanol extracts of pepino (Solanum muricatum Ait.), and examined the protective effects of pepino aqueous extract (PAE) in a mouse model of diabetes. PAE at 1, 2 and 4% was supplied for 5 weeks. RESULTS: Aqueous and ethanol extracts had similar levels of total phenolic acids, but PAE had a higher content of ascorbic acid and total flavonoids than the ethanol extract. PAE treatments at 2% and 4% significantly lowered plasma glucose level (P < 0.05); however, only the 4% PAE significantly elevated plasma insulin level at week 5 (P < 0.05). PAE treatments significantly decreased the levels of malonyldialdehyde and reactive oxygen species in kidney (P < 0.05); however, only the 2% and 4% treatments significantly reduced oxidised glutathione formation, increased glutathione level, and retained renal glutathione peroxidase and catalase activities (P < 0.05). PAE treatments at 2% and 4% significantly lowered renal interleukin (IL)-6 and tumour necrosis factor-α levels (P < 0.05); however, only the 4% treatments significantly diminished renal IL-1ß and levels of monocyte chemoattractant protein-1 (P < 0.05). PAE treatments at 4% significantly decreased aldose reductase activity and sorbitol production in kidney (P < 0.05). CONCLUSION: These findings support the suggestion that pepino aqueous extract could attenuate the progression of diabetes via its antioxidative, anti-inflammatory and antiglycative effects.


Assuntos
Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fitoterapia , Polifenóis/uso terapêutico , Solanum/química , Aldeído Redutase/metabolismo , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Glicemia/metabolismo , Catalase/metabolismo , Quimiocina CCL2/metabolismo , Diabetes Mellitus Experimental/metabolismo , Frutas , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Hipoglicemiantes/farmacologia , Insulina/sangue , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Polifenóis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sorbitol/metabolismo
13.
Front Microbiol ; 12: 758465, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867886

RESUMO

TatD DNases are conserved proteins in a variety of organisms and are considered potential virulence factors in Plasmodium falciparum and Streptococcus pneumoniae. However, the function of TatD DNases has not yet been determined in Trueperella pyogenes, which causes various infections in animals and leads to economic losses. In this study, we describe the roles of TatD DNases in T. pyogenes (TpTatDs). A bioinformatics analysis was performed to investigate the sequence characteristics of TpTatDs, and then the ability of recombinant TatD proteins to hydrolyze DNA was determined in the presence of divalent cations. Moreover, we constructed tatD-deficient mutants. The biofilms formed by the wild-type and mutant strains were observed under a microscope. The mortality and bacterial load in the spleen of mice infected with the wild-type strain and tatD-deficient mutants were determined to obtain insights into the role of TatDs in the virulence of T. pyogenes. Two TatD DNases were identified in T. pyogenes. They were Mg2+-dependent DNases and exhibited DNA endonuclease activity. Compared with those formed by the parental strain, biofilms formed by mutants showed a significantly reduced thickness and biomass. Moreover, mutants produced a lower bacterial load in the spleen of mice and compromised virulence. Our data indicated that TatD DNases in T. pyogenes are involved in biofilm formation and required for virulence during infections.

14.
Eur J Nutr ; 49(7): 429-34, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20229096

RESUMO

PURPOSE: The association of dietary advanced glycation endproducts (AGEs) intake with the oxidative and inflammatory status in type 2 diabetic patients was examined. METHODS: Seventy-four healthy controls, 50 low AGEs intake and 68 high AGEs intake type 2 diabetic patients were requested to complete a 7-day dietary record. Blood levels of several oxidative and inflammatory biomarkers were determined. RESULTS: Diabetic patients with high AGEs intake had significantly elevated plasma levels of AGEs, HbA1c, low-density lipoprotein (LDL), LDL-cholesterol and glycated LDL than low AGEs intake patients and controls (P < 0.05). These high AGEs intake patients also had significantly increased plasma levels of 8-isoprostane, interleukin (IL)-1α, tumor necrosis factor-α, monocyte chemoattractant protein (MCP)-1 and lower superoxide dismutase (SOD) activity than low AGEs intake patients (P < 0.05). Correlation coefficients of dietary AGEs versus plasma AGEs, HbA1c, 8-isoprostane, IL-1α and MCP-1 were >0.6; but the correlation coefficient of dietary AGEs versus plasma SOD activity was <-0.6. CONCLUSION: Increasing dietary AGEs intake might enrich circulating AGE level and contribute to oxidative and inflammatory progression under diabetic condition. The circulating 8-isoprostane, IL-1α and MCP-1 levels and SOD activity might be appropriate biomarkers used to evaluate dietary AGEs-associated oxidative and inflammatory stress.


Assuntos
Quimiocina CCL2/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Interleucina-1alfa/metabolismo , Lipoproteínas LDL/sangue , Adulto , Idoso , Biomarcadores , Estudos de Casos e Controles , Quimiocina CCL2/sangue , LDL-Colesterol/sangue , Dinoprosta/análogos & derivados , Dinoprosta/sangue , Dinoprosta/metabolismo , Feminino , Produtos Finais de Glicação Avançada/sangue , Humanos , Inflamação/metabolismo , Interleucina-1alfa/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo
15.
IEEE Trans Neural Netw Learn Syst ; 31(11): 4980-4989, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32584771

RESUMO

This article addresses the problem of the average stochastic finite-time synchronization (ASFTS) for a set of coupled neural networks (NNs) with energy-bounded noises. Due to the channel capacity constraint, the impulsive approach is introduced so as to cut down the communication times among the leader NNs and the follower NNs. Then, a nonfragile controller is designed to improve the robustness of the controller with randomly occurred uncertainty. The sufficient conditions that guarantee the ASFTS of the coupled NNs and the leader NNs are achieved. The boundary of the synchronization error is also obtained by constructing the monotonic increasing functions. Finally, the controller gains are given based on the derived conditions, and their effectiveness is illustrated by a numerical example.

16.
Infect Drug Resist ; 13: 1697-1711, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606820

RESUMO

PURPOSE: This research aimed to investigate the antibacterial activity and potential mechanism of luteolin against T. pyogenes. MATERIALS AND METHODS: The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of luteolin against various T. pyogenes strains. The potential mechanism of action of luteolin was elucidated through testing and analysing the luteolin-induced alterations of T. pyogenes in several aspects, including cell wall, cell membrane, protein expression, nucleic acid content, topoisomerase activity and energy metabolism. RESULTS: The MIC values of luteolin against various T. pyogenes isolates and ATCC19411 were 78 µg/mL. The increased cell membrane permeability, destruction of cell wall integrity and TEM images after exposure to luteolin showed that the cell wall and membrane were damaged. The content of total protein and nucleic acid in T. pyogenes decreased significantly after treatment with luteolin (1/2 MIC) for 12, 24, and 36 h. Moreover, a hypochromic effect was observed in the absorption spectrum of luteolin when deoxyribonucleic acid (DNA) was added. In addition, after treatment with luteolin, a decrease in nicked or relaxed DNA content, which was catalysed by T. pyogenes-isolated DNA topoisomerase, was observed. In addition, the adenosine triphosphate (ATP) content in cells and the activity of succinate dehydrogenase (SDH) both decreased when T. pyogenes was exposed to different concentrations (1/4 MIC, 1/2 MIC, 1 MIC, 2 MIC) of luteolin for 1 h. CONCLUSION: Luteolin showed distinct antibacterial activity against T. pyogenes by multiple actions, which mainly include destroying the integrity of the cell wall and cell membrane, influencing the expression of proteins, inhibiting nucleic acid synthesis, and interfering with energy metabolism.

17.
Biomed Pharmacother ; 109: 1024-1031, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551352

RESUMO

Accompanied by the damages of epithelial and capillary endothelial cell, acute lung injury is diagnosed with the typical pathological symptoms in clinic, including diffusing of pulmonary interstitial, alveolar oedema and hypoxic respiratory insufficiency. Current study focused on the investigation the anti-inflammatory action and mechanisms of total flavonoids extract (TFE) from Abutilon theophrasti Medic. leaves on ALI mice induced by LPSs. Mice were administrated intragastrically with TFE at the concentrations of 0.25, 0.5, or 1.0 g/kg for 5 days, and on last day, nasal administration of LPSs for 6 h after 30 min for intragastric administration of TFE. Pretreatment with TFE not only reduced oxidative damage but also alleviated lung edema in ALI mice. Increased secretion of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6, caused by LPSs was reversed by TFE; on the contrary, the anti-inflammatory cytokine IL-10 was upregulated. The proteins expressions of pro-inflammatory mediators iNOS and COX-2 induced by LPSs, were down-regulated by TFE. Moreover, the activation of NF-κB and MAPK signalling pathways was inhibited by TFE in LPSs induced ALI mice. The results revealed that the anti-inflammatory mechanisms of TFE were via inhibition of NF-κB and MAPK activation. Combined, the results suggested that TFE might exert in vivo antioxidant and anti-inflammatory functions in LPSs stimulated mice, and will be potential in adjuvant treatment in oxidative stress and inflammation diseases.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Flavonoides/farmacologia , Malvaceae/química , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Folhas de Planta/química , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Camundongos
18.
Sci Rep ; 9(1): 13238, 2019 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519977

RESUMO

Renal diseases impose considerable health and economic burdens on health systems worldwide, and there is a lack of efficient methods for the prevention and treatment due to their complexity and heterogeneity. Kidneys are organs with a high demand for energy produced by mitochondria, in which Rrm2b has critical functions as reported. The Rrm2b kidney-specific knockout mice we generated exhibited age-dependent exacerbated features, including mitochondrial dysfunction and increased oxidative stress; additionally, resulted in severe disruption of mitochondria-related metabolism. Rrm2b is vital not only to supply dNTPs for DNA replication and repair, but also to maintain structural integrity and metabolic homeostasis in mitochondria. Thence, Rrm2b deletion might induce chronic kidney defects in mice. This model can facilitate exploration of novel mechanisms and targeted therapies in the kidney diseases and has important translational and clinical implications.


Assuntos
Proteínas de Ciclo Celular/fisiologia , Túbulos Renais/patologia , Mitocôndrias/patologia , Estresse Oxidativo , Ribonucleotídeo Redutases/fisiologia , Animais , Replicação do DNA , Feminino , Túbulos Renais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo , Oxirredução
19.
Artigo em Inglês | MEDLINE | ID: mdl-28292553

RESUMO

Dietary fatty acid patterns have been linked to the prevalence of certain cancers, however in oral carcinoma is limited. Thus, we investigated the chemopreventive effects of various dietary n-6 and n-3 fatty acids in a 9,10-dimethyl-1,2-benz[a]-anthracene (DMBA)- and betel quid extract (BQE) -induced hamster oral cancer model. Thirty 6-week-old adult male hamsters were housed and divided into normal, low, and high dietary n-6 and n-3 fatty acid groups under DMBA + BQE treatment for 16 weeks. The right buccal pouch of all hamsters were evaluated by tumor number, volume, burden and selected inflammatory parameters. The results indicate that the low dietary n-6/n-3 fatty acid group exhibited a significantly lower tumor number, volume, and burden than those of the other groups. Furthermore, this group had significantly lower nuclear factor-κB, proliferating cell nuclear antigen, and cyclin D1 expression in the right buccal pouch tissue. In conclusion, the lower dietary n-6/n-3 fatty acid ratio exerted chemopreventive effects in the DMBA- and BQE-induced hamster oral cancer model.


Assuntos
9,10-Dimetil-1,2-benzantraceno/toxicidade , Anticarcinógenos/administração & dosagem , Areca/química , Ácidos Graxos Insaturados/administração & dosagem , Neoplasias Bucais/dietoterapia , Extratos Vegetais/toxicidade , Animais , Areca/toxicidade , Cricetinae , Ciclina D1/metabolismo , Relação Dose-Resposta a Droga , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-6/administração & dosagem , Ácidos Graxos Ômega-6/farmacologia , Ácidos Graxos Insaturados/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Masculino , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/metabolismo , NF-kappa B/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Zhongguo Gu Shang ; 31(10): 916-921, 2018 Oct 25.
Artigo em Zh | MEDLINE | ID: mdl-30373344

RESUMO

OBJECTIVE: To investigate the relationship between living habit and cervical instability in adolescent patients with neck pain. METHODS: Fifty-nine adolescent patients with neck pain(neck pain group) and seventeen healthy teenagers (control group) were recruited and divided into two groups, and clinical information, living habit were collected. In addition, all people were taken lateral, hyperextension and hyperflexion radiography to analyze relationship between living habit and cervical instability. RESULTS: There was no obvious difference in age, height, weight and body mass index between two groups. The neck pain group using cellphone time per day is longer than control group, while control group had more exercise time than neck pain group(P<0.01). The incidence of instability in neck pain group was significantly higher than that in control group(P<0.01). In hyperflexion, angular displacement(AD) of neck pain group in vertebral body between C3-C4, C4-C5 and C5-C6 was significantly higher than that of control group. In neck pain group, AD of hyperflexion was higher than that of hyperextension on C4-C5(P<0.01), and AD of hyperextension is higher than that of hyperflexion on C6-C7(P<0.05). In neck pain group, AD of hyperextension on C4-C5 was positively correlated with time of using cellphone every day(r=0.275, P=0.035). And AD of hyperflexion was significantly positive correlated with time of using cellphone(r=0.577, P<0.001), but was negatively correlated with exercise time(r=-0.279, P=0.032). The AD of hyperflexion on C5-C6 was negatively correlated with exercise time every day(r=-0.292, P=0.025), AD of hyperextension was negatively correlated with time of using computer every day(r=-0.262, P=0.045). CONCLUSIONS: Adolescent neck pain patients had more time to use cellphone than normal teens every day, and exercise time is less than healthy teenagers, and occurrence rate of cervical instability is higher on C3-C4, C4-C5, C5-C6 segment. The longer daily exercise time, the smaller C4-C5 and C5-C6 AD values; the longer cellphone usage every day, the greater C4-C5 AD values.


Assuntos
Instabilidade Articular , Cervicalgia , Adolescente , Vértebras Cervicais , Hábitos , Humanos , Radiografia
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