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1.
Molecules ; 27(24)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36558017

RESUMO

Yeasts from the Candida parapsilosis complex are clinically relevant due to their high virulence and pathogenicity potential, such as adherence to epithelial cells and emission of filamentous structures, as well as their low susceptibility to antifungals. D-limonene, a natural compound, emerges as a promising alternative with previously described antibacterial, antiparasitic, and antifungal activity; however, its mechanisms of action and antivirulence activity against C. parapsilosis complex species have not been elucidated. Therefore, in the present study, we aimed to evaluate the antifungal and antivirulence action, as well as the mechanism of action of D-limonene against isolates from this complex. D-limonene exhibited relevant antifungal activity against C. parapsilosis complex yeasts, as well as excellent antivirulence activity by inhibiting yeast morphogenesis and adherence to the human epithelium. Furthermore, the apoptotic mechanism induced by this compound, which is not induced by oxidative stress, represents an important target for the development of new antifungal drugs.


Assuntos
Antifúngicos , Candida parapsilosis , Humanos , Antifúngicos/farmacologia , Virulência , Limoneno/farmacologia , Fatores de Virulência , Testes de Sensibilidade Microbiana , Saccharomyces cerevisiae
2.
Life Sci ; 309: 121044, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36208657

RESUMO

The present study attempted to scrutinize the protective effect of the methanolic extract of P. chaba stem bark against paracetamol-induced hepatotoxicity in Sprague-Dawley rats, along with the gas chromatography-mass spectrometry (GC-MS) analysis to identify phytochemicals, which were further docked in the catalytic site of CYP2E1 and the MD simulation for system that plays a major role in the bio-activation of toxic substances that produce reactive metabolites, leading to hepatotoxicity. P. chaba stem methanol extract (250 and 500 mg/kg) were treated orally with the negative control and the negative control silymarin (50 mg/kg) groups. Phytochemical profiling was conducted using GC-MS. In in-silico studies, PyRx software was used for docking analysis and the stability of the binding mode in the target active sites was evaluated through a set of standard MD-simulation protocols using the Charmm 27 force field and Swiss PARAM. Co-administration of P. chaba at both doses with APAP significantly reduced the APAP-augmented liver marker enzymes ALT, AST, ALP, and LDH, along with serum albumin, globulin, hepatic enzymes, histopathological architecture, lipid profiles, total protein, and total bilirubin, and elevated the levels of MDA. The GC-MS analysis indicated that P. chaba extract is enriched in fatty acid methyl esters (46.23 %) and alkaloids (10.91 %) and piperine is represented as a main phytochemical. Among all the identified phytochemicals, piperine (-8.0 kcal/mol) was found to be more interacting and stable with the binding site of CYP2E1. Therefore, all of our findings may conclude that the P. chaba stem extract and its main compound, piperine, are able to neutralize APAP-induced hepatic damage.


Assuntos
Alcaloides , Doença Hepática Induzida por Substâncias e Drogas , Piper , Silimarina , Ratos , Animais , Acetaminofen/toxicidade , Ratos Sprague-Dawley , Citocromo P-450 CYP2E1 , Cromatografia Gasosa-Espectrometria de Massas , Doença Hepática Induzida por Substâncias e Drogas/patologia , Metanol/farmacologia , Casca de Planta , Extratos Vegetais/uso terapêutico , Fígado , Alcaloides/farmacologia , Silimarina/farmacologia , Bilirrubina , Lipídeos/farmacologia , Ácidos Graxos , Albumina Sérica , Ésteres/farmacologia
3.
Materials (Basel) ; 15(15)2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35955276

RESUMO

This study aimed to evaluate the influence of thermomechanical cycling (TMC) and type of abutment on the misfit and compressive strength of the implant−abutment interface. Forty 3.75-mm external hexagon implants with 25° angled abutments were divided into four groups (N = 10). Group A: overcast plus TMC; Group B: overcast without TMC; Group C: completely cast plus TMC; Group D: completely cast without TMC. Abutments were fixed to the implants with 32-Ncm torque, and groups A and C specimens were cyclically loaded at 80 N with 2 Hz for 1 million cycles. The misfit on the implant−abutment interface was evaluated by optical microscope (100×) and the compressive strength test was performed in a universal test machine. For statistical analysis, a two-way ANOVA and post hoc Tukey test were used. There was no difference in misfit presented by all the abutments in the absence of TMC (p > 0.05). When TMC was performed, the completely cast abutments showed greater misfit than overcast ones (p = 0.001). Regarding compressive strength, irrespective of TMC performed, the overcast abutments showed higher compressive strength values than completely cast abutments (p = 0.003). Moreover, disregarding the type of abutment used, the absence of TMC provided higher compressive strength values (p < 0.001). It was concluded that thermomechanical cyclic loading aggravated the misfit, especially in completely cast abutments, regardless of material or fabrication technique, and reduced the compressive strength of the two types of abutments tested.

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