作者: Martínez, Wilfrido ; Castillo, Ivan ; Bonilla, Myrna ; Fernández, Nora ; Torres, Nimbe ; Petlacalco, Beatriz ; Aliphat, Mario ; Morales, Alfredo ; Meneses, María E. ; Sánchez-Tapia, Mónica ; Tovar, Armando R. ; Hernández-Acosta, Julieta ; Sánchez, Miguel ; Coutiño-Hernández, Diana ; Martínez-Carrera, Daniel ; Pérez-Herrera, Aleyda ; Bautista-Montero, Zoha

Oxidative stress is a key factor of comorbidities in obesity. A Mexican genotype of the medicinal mushroom Ganoderma lucidum ( Gl ) contains bioactive compounds showing antioxidant, hypocholesterolemic, anti-inflammatory, anticancer, and prebiotic properties. We assessed the effect of standardized Gl -1 and Gl -2 extracts (1%) consumed by obese C57BL/6 mice fed with a high-fat and sugar diet (HFSD), on weight increase, serum parameters, liver lipid accumulation, and the expression of antioxidant genes (glutathione peroxidase 1, catalase [CAT], superoxide dismutase [SOD] 1, SOD2) and proteins (CAT, SOD2, nuclear factor erythroid 2-related factor 2) in the liver. Fifty-six male C57BL/6 mice were randomized into seven groups involving the control and treatments during 17 weeks, as well as using metformin (Met, 250 mg/kg/day) as a reference drug. Serum lipids and glucose levels decreased in mice groups consuming Gl extracts and metformin, in comparison with the HFSD group, as follows: total cholesterol (−11.8% to −35.7%), triglycerides (−8.3% to −24.8%), low-density lipoprotein cholesterol (−19.6% to −51.6%), and glucose (−3.1% to −25.7%). Gl -1 and Gl -2 extracts showed antioxidant properties and prevented lipid accumulation in the liver. The expression of antioxidant genes and proteins was significantly higher ( P < .001) in the mice groups consuming Gl extracts, as compared to the HFSD group. This evidence showed that Gl -1 and Gl -2 extracts prevented oxidative stress in the in vivo model of obesity induced by an HFSD.

2025-01-01·Journal of prosthodontics : official journal of the American College of Prosthodontists

Evaluation of one versus two glaze firings on the color stability and mechanical properties of an extrinsically characterized monolithic CAD‐CAM lithium disilicate glass ceramic

Article

作者: Loíky Sampaio de Souza, Matheus ; Whitehurst Ary Leitão, Andrea ; Kelma Palacio Gomes Magalhães, Aghata ; Matthes de Freitas Pontes, Karina ; Barros Moreira, Gabriela ; Fernandes Peixoto, Raniel ; Pontes, Cássio

Abstract:

Purpose:

To evaluate the effects of 1 versus 2 glaze firings on the color and mechanical properties of an extrinsically characterized lithium disilicate ceramic after thermal cycling, brushing, or both.

Materials and Methods:

Eighty specimens were divided into 2 groups: 1 glaze firing (GL1) and 2 glaze firings (GL2). Each group was subdivided into 4 groups (n = 10), according to the experimental conditions: thermal‐cycling, brushing, thermal‐cycling + brushing, and immersion in distilled water (control). Color variation, surface roughness, and Vickers microhardness were analyzed before each designated experiment and after the simulated periods of 2.5, 5, and 10 years. Three‐way mixed ANOVA was used for all outcomes, followed by 1‐way ANOVA, repeated measures 1‐way ANOVA, Bonferroni post hoc test, and t‐test to check for statistical differences (α = 0.05).

Results:

Thermal cycling generated greater color changes in the GL1 group at 2.5 and 5 years (p < 0.001; p = 0.013). Brushing generated color changes in GL1 at 5 years (p = 0.003) and in GL2 at 10 years (p = 0.017). Regarding surface roughness, the GL1 group suffered alterations in thermal cycling + brushing at 5 years. In the control group, the GL1 group exhibited higher roughness values than GL2 (p < 0.05). Most of the groups experienced an increase in microhardness at 2.5 years (p < 0.05). In the GL1 group, thermal‐cycling increased the microhardness at 5 years (p = 0.006); at 5 and 10 years, the GL1 group had a higher microhardness than the GL2 in thermal‐cycling + brushing (p < 0.05).

Conclusion:

Ceramics with 1 glaze firing showed greater color, roughness, and microhardness changes compared to those submitted to 2 firings.

2024-09-01·Advanced Science

DHPS‐Mediated Hypusination Regulates METTL3 Self‐m6A‐Methylation Modification to Promote Melanoma Proliferation and the Development of Novel Inhibitors

Article

作者: Yang, Yue‐hui ; Guo, Jing‐si ; Li, Xin‐yang ; Zhang, Ji‐fang ; Liu, Kai‐li ; Ma, Jian ; Meng, Fan‐hao ; Li, Long‐tian ; Zhao, Xi‐he ; Jian, Ling‐yan ; Qin, Yu‐xi

Abstract:

Discovering new treatments for melanoma will benefit human health. The mechanism by which deoxyhypusine synthase (DHPS) promotes melanoma development remains elucidated. Multi‐omics studies have revealed that DHPS regulates m6A modification and maintains mRNA stability in melanoma cells. Mechanistically, DHPS activates the hypusination of eukaryotic translation initiation factor 5A (eIF5A) to assist METTL3 localizing on its mRNA for m6A modification, then promoting METTL3 expression. Structure‐based design, synthesis, and activity screening yielded the hit compound GL‐1 as a DHPS inhibitor. Notably, GL‐1 directly inhibits DHPS binding to eIF5A, whereas GC‐7 cannot. Based on the clarification of the mode of action of GL‐1 on DHPS, it is found that GL‐1 can promote the accumulation of intracellular Cu2+ to induce apoptosis, and antibody microarray analysis shows that GL‐1 inhibits the expression of several cytokines. GL‐1 shows promising antitumor activity with good bioavailability in a xenograft tumor model. These findings clarify the molecular mechanisms by which DHPS regulates melanoma proliferation and demonstrate the potential of GL‐1 for clinical melanoma therapy.

100 项与 GL-1 相关的药物交易

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