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1.
Nat Prod Res ; : 1-7, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39222481

RESUMO

Excessive alcohol consumption is leading to increased rates of liver injury and disease. A new research strategy focuses on manipulating gut microbiota to lessen alcohol-induced harm. This study examined the hepatoprotective effects of extracts from Acanthus ilicifolius (EAI) on acute alcoholic liver injury by inhibiting the TLR4/NF-κB signalling pathway and modulating intestinal microbiota in mice. The results showed that EAI dose-dependently reduced alcohol-induced elevations of AST, ALT, and ALP levels. EAI showed significant inhibitory effects on the expressions of TLR4, NF-κB, and pNF-κB proteins. Furthermore, EAI caused a notable reduction in hepatic levels of IL-1ß, IL-6, and TNF-α. Supplementation with EAI could ameliorate alcohol-induced dysbiosis of intestinal bacteria. The levels of ALT, AST, and ALP levels were negatively correlated with Ligilactobacillus, Lactobacillus, and Alistipes, but positively correlated with Helicobacter and Bacteroides. Overall, EAI alleviated alcoholic liver injury in mice by inhibiting the TLR4/NF-κB signalling pathway and modulating intestinal bacteria.

2.
J Med Chem ; 67(17): 15438-15455, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39151117

RESUMO

Psoriasis, which severely affects the sufferer's life quality, is a chronic skin disease still lacking satisfactory medication. Recently, signal transducer and activator of transcription 3 (STAT3) was revealed playing an important role in the progression of psoriasis. In this paper, a total of 59 quinone derivatives with various scaffolds were designed, synthesized, and evaluated for antipsoriatic potential as STAT3 inhibitors. Among them, 15e was identified as the most potent antipsoriatic agent and could bind to STAT3; reduce both total and phosphorylated STAT3 levels, inhibit the nuclear translocation of STAT3; and, therefore, inhibit the transcription and expression of the propsoriatic factor IL-17A. In vivo experiments on mice showed that the topical application of 15e was effective in alleviating IMQ-induced psoriasis without noticeable side effects. In all, this research rendered 15e as a promising drug candidate for psoriasis.


Assuntos
Desenho de Fármacos , Psoríase , Fator de Transcrição STAT3 , Psoríase/tratamento farmacológico , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo , Animais , Humanos , Camundongos , Interleucina-17/metabolismo , Interleucina-17/antagonistas & inibidores , Quinonas/farmacologia , Quinonas/síntese química , Quinonas/uso terapêutico , Quinonas/química , Relação Estrutura-Atividade , Camundongos Endogâmicos BALB C
3.
Chemosphere ; 355: 141835, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38552799

RESUMO

This study provides insights regarding the selective metal leaching of brass in various tap water conditions, which benefits water utilities to predict the potential of metal released from brass water meters. The long-term time-dependent selective metal dissolution of brass with various ß phase fractions have not previously been investigated. In this study, a 201-d immersion experiment was carried out in low and high conductivity tap water (LCTW and HCTW, respectively). Three commercialized brass samples in different ß phase fractions (ß = 51%, ß = 43%, ß = 39%), named brass 51, brass 43, and brass 39, respectively, were used. The results showed that brass 51 had the most negative corrosion potential (-0.17 V) and the lowest polarization resistance (8.5 kΩ) compared to brass 43 and brass 39 (-0.04 V and 10.1-14.7 kΩ, respectively) in LCTW. This trend was verified by the 201-d immersion experiment in which brass 51 exhibited the highest zinc leaching rate (21-30 µg L-1 cm-2 d-1), followed by brass 43 and brass 39 (16-23 µg L-1 cm-2 d-1) in both waters. The leaching amounts of lead and copper were extremely low compared to zinc. In LCTW, the uniform corrosion (UC) mechanism dominated from day 1 to day 120. Afterwards, UC was replaced by the galvanic corrosion (GC) mechanism, with the selective leaching coefficient of Zn over Cu (SZn/Cu) increasing from 10 to 25 to 40-80. In HCTW, however, the SZn/Cu reached 300-1000, and the transition of UC to GC occurred earlier on day 30 due to the rapid formation of the ZnO layer on the brass surface that hindered the ion attack.


Assuntos
Cobre , Água , Chumbo , Zinco
4.
Yao Xue Xue Bao ; 51(7): 1077-82, 2016 07.
Artigo em Chinês | MEDLINE | ID: mdl-29897181

RESUMO

This study was designed to evaluate the anti-inflammatory effect of recombinant human kallistatin (Kal) on ulcerative colitis (UC) in the mouse model. Acute colitis was induced by administration of 4% dextran sodium suffate (DSS) to KM mice for 7 days. The mice were then randomized into 5 groups: model control, Kal 0.2 mg·kg(-1)·d(-1), 1.0 mg·kg(-1)·d(-1) and 2.0 mg·kg-1·d(-1) group, salazosulfapyridine (SASP) group. Ten age-matched normal KM mouse were administered with saline in the normal control. The weight, colon length, inflammation factor (MPO/SOD/MDA) and TNF-α/IL-10 levels among the five groups of mice were determined. The results showed that histological index score and MPO/MDA/TNF-α levels of high-dose Kal treatment group and SASP group were significantly lower compared with the model group (P < 0.01), but the weight, colon length, IL-10 level and SOD activity were significant higher than the model group (P < 0.01), approaching the normal group. These parameters showed that Kal can significantly relieve the UC state in a dose-dependent manner. This study demonstrates that Kal significantly remits UC in mice, and participates in the regulation of inflammatory cytokines TNF-α/IL-10 levels and has some antioxidant activity.


Assuntos
Colite Ulcerativa/terapia , Serpinas/farmacologia , Animais , Colite Ulcerativa/induzido quimicamente , Sulfato de Dextrana , Modelos Animais de Doenças , Humanos , Interleucina-10/metabolismo , Camundongos , Distribuição Aleatória , Proteínas Recombinantes/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
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