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1.
Int J Mol Sci ; 25(5)2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38474201

RESUMO

In recent years, the potent influence of tocotrienol (T3) on diminishing blood glucose and lipid concentrations in both Mus musculus (rats) and Homo sapiens (humans) has been established. However, the comprehensive exploration of tocotrienol's hypolipidemic impact and the corresponding mechanisms in aquatic species remains inadequate. In this study, we established a zebrafish model of a type 2 diabetes mellitus (T2DM) model through high-fat diet administration to zebrafish. In the T2DM zebrafish, the thickness of ocular vascular walls significantly increased compared to the control group, which was mitigated after treatment with T3. Additionally, our findings demonstrate the regulatory effect of T3 on lipid metabolism, leading to the reduced synthesis and storage of adipose tissue in zebrafish. We validated the expression patterns of genes relevant to these processes using RT-qPCR. In the T2DM model, there was an almost two-fold upregulation in pparγ and cyp7a1 mRNA levels, coupled with a significant downregulation in cpt1a mRNA (p < 0.01) compared to the control group. The ELISA revealed that the protein expression levels of Pparγ and Rxrα exhibited a two-fold elevation in the T2DM group relative to the control. In the T3-treated group, Pparγ and Rxrα protein expression levels consistently exhibited a two-fold decrease compared to the model group. Lipid metabolomics showed that T3 could affect the metabolic pathways of zebrafish lipid regulation, including lipid synthesis and decomposition. We provided experimental evidence that T3 could mitigate lipid accumulation in our zebrafish T2DM model. Elucidating the lipid-lowering effects of T3 could help to minimize the detrimental impacts of overfeeding in aquaculture.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperlipidemias , Tocotrienóis , Humanos , Camundongos , Ratos , Animais , Tocotrienóis/metabolismo , Peixe-Zebra/metabolismo , Dieta Hiperlipídica , Hiperlipidemias/metabolismo , Óleo de Farelo de Arroz , Diabetes Mellitus Tipo 2/metabolismo , PPAR gama/metabolismo , RNA Mensageiro/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo
2.
Poult Sci ; 103(3): 103435, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38232620

RESUMO

Excessive corticosterone (CORT) exposure could cause hepatic cholesterol accumulation in chickens and maternal betaine supplementation could decrease hepatic cholesterol deposition through epigenetic modifications in offspring chickens. Nevertheless, it remains uncertain whether providing betaine to laying hens could protect CORT-induced hepatic cholesterol accumulation via epigenetic mechanisms. This study aimed to examine the effects of dietary betaine on plasma and hepatic cholesterol contents, expression of cholesterol metabolic genes, as well as DNA methylation on their promoters in the liver of laying hens exposed to CORT. A total of 72 laying hens at 130 d of age were randomly divided into 3 groups: control (CON), CORT, and CORT+betaine (CORT+BET) groups. The experiment lasted for 35 d. Chickens in CON and CORT groups were fed a basal diet, whereas the CORT+BET group chickens were fed the basal diet supplemented with 0.1% betaine for 35 d. On d 28 of the experiment, chickens in CORT and CORT+BET groups received daily subcutaneous injections of CORT (4.0 mg/kg body weight), whereas the CON group chickens were injected with an equal volume of solvent for 7 d. The results showed that CORT administration led to a significant increase (P < 0.05) in the contents of cholesterol in plasma and liver, associated with activation (P < 0.05) of sterol regulatory element binding transcription factor 2 (SREBP2), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), lecithin-cholesterol acyltransferase (LCAT) and low-density lipoprotein receptor (LDLR) genes expression, and inhibition of cholesterol-7-alpha hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1) genes expression in the liver compared to the CON. In contrast, CORT-induced up-regulation of HMGCR mRNA and protein abundances and downregulation of CYP7A1 mRNA and protein abundances were completely normalized (P < 0.05) by betaine supplementation. Besides, CORT injection led to significant hypomethylation (P < 0.05) on HMGCR promoter and hypermethylation (P < 0.05) on CYP7A1 promoter. Moreover, dietary betaine rescued (P < 0.05) CORT-induced changes in methylation status of HMGCR and CYP7A1 genes promoters. These results indicate that dietary betaine addition protects laying hens from CORT-induced hepatic cholesterol accumulation via epigenetic modulation of HMGCR and CYP7A1 genes.


Assuntos
Betaína , Oxirredutases , Animais , Feminino , Betaína/farmacologia , Corticosterona , Galinhas/genética , Fígado , Suplementos Nutricionais , Colesterol , Epigênese Genética , RNA Mensageiro
3.
J Exp Bot ; 74(21): 6551-6562, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37584205

RESUMO

In vitro pollen germination is considered the most efficient method to assess pollen viability. The pollen germination frequency and pollen tube length, which are key indicators of pollen viability, should be accurately measured during in vitro culture. In this study, a Mask R-CNN model trained using microscopic images of tree peony (Paeonia suffruticosa) pollen has been proposed to rapidly detect the pollen germination rate and pollen tube length. To reduce the workload during image acquisition, images of synthesized crossed pollen tubes were added to the training dataset, significantly improving the model accuracy in recognizing crossed pollen tubes. At an Intersection over Union threshold of 50%, a mean average precision of 0.949 was achieved. The performance of the model was verified using 120 testing images. The R2 value of the linear regression model using detected pollen germination frequency against the ground truth was 0.909 and that using average pollen tube length was 0.958. Further, the model was successfully applied to two other plant species, indicating a good generalizability and potential to be applied widely.


Assuntos
Aprendizado Profundo , Germinação , Pólen , Tubo Polínico
4.
Trials ; 22(1): 566, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34521466

RESUMO

BACKGROUND: Non-alcohol fatty liver disease (NAFLD) is the most common chronic liver disease in the world, with a high incidence and no effective treatment. At present, the targeted therapy of intestinal microbes for NAFLD is highly valued. Lycium barbarum polysaccharide (LBP), as the main active ingredient of Lycium barbarum, is considered to be a new type of prebiotic substance, which can improve NAFLD by regulating the gut microbiota. The purpose of this study is to evaluate the safety and efficacy of LBP supplementation in modulating gut microbiota for NAFLD patients. METHODS: This randomized, double-blind, placebo-control study will be conducted in the physical examination center of the Ningxia Hui Autonomous Region People's Hospital. A total of 50 patients with NAFLD confirmed by abdominal ultrasound, laboratory tests, and questionnaire surveys will be recruited and randomly assigned into the control group (maltodextrin placebo capsules) and the intervention group (LBP supplementation capsules) for 3 months. Neither patients, nor investigators, nor data collectors will know the contents in each capsule and the randomization list. The primary outcome measure is the level of ALT concentration relief after the intervention. Secondary outcomes include gut microbiota abundance and diversity, intestinal permeability, patient's characteristic demographic data and body composition, adverse effects, and compliance from patients. DISCUSSION: LBPs are potential prebiotics with the property of regulating host gut microbiota. Our previous studies have documented that LBP supplement can improve the liver damage and the gut microflora dysbiosis in NAFLD rats. This treatment would provide a more in-depth understanding of the effect of this LBP supplementation. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2000034740 . Registered on 17 July 2020.


Assuntos
Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Animais , Suplementos Nutricionais , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ratos
5.
Bioorg Chem ; 114: 105044, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34157554

RESUMO

Helicobacter pylori (H. pylori) infection is a common disease that can cause H. pylori-associated gastritis (HAG), peptic ulcers, and gastric cancer. As a traditional Chinese medicine, Polygonum capitatum (PC) manifests its unique advantages in the prevention and treatment of complex diseases and chronic diseases, due to its ability to clear heat, detoxify and relieve pain, promote blood circulation, and remove blood stasis. In order to explore the molecular mechanism of PC for HAG, the study collected the predicted targets of active compounds, conducted functional analysis by the STRING database, collected HAG differential expression genes, and conducted KEGG enrichment analysis on the intersection of predicted targets and differential expression genes of gastritis by Cluego. The results show that PC works mainly by affecting phosphorylation of IκBα, NF-κB p65, p38MAPK, and ERK1/2 and nuclear transposition of NF-κB p65 and p-p38MAPK, which has been proved by in vivo and in vitro experiments. These results suggest that PC may act on HAG with multiple targets and pathways, and play a key role in the process of HAG treatment.


Assuntos
Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Gastrite/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Polygonum/química , Animais , Linhagem Celular , Feminino , Gastrite/genética , Gastrite/microbiologia , Expressão Gênica/fisiologia , Infecções por Helicobacter/genética , Helicobacter pylori/efeitos dos fármacos , Humanos , Inflamação/tratamento farmacológico , Inflamação/microbiologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Farmacologia em Rede , Ratos Sprague-Dawley
6.
Int J Biol Macromol ; 183: 1379-1392, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33992651

RESUMO

Gut microbiota and intestinal permeability have been demonstrated to be the key players in the gut-liver cross talk in nonalcoholic fatty liver disease (NAFLD). Lycium barbarum polysaccharides (LBPs), which seem to be a potential prebiotic, and aerobic exercise (AE) have shown protective effects on NAFLD. However, their combined effects on intestinal microecology remain unclear. This study evaluated the effects of LBP, AE, and its combination (LBP + AE) on gut microbiota composition, intestinal barrier, and hepatic inflammation in NAFLD. LBP + AE showed high abundance and diversity of gut microbiota, restored the gut microbiota composition, increased some Bacteroidetes, short chain fatty acids, but decreased Proteobacteria and the ratio of Firmicutes/Bacteroidetes. Simultaneously, LBP, AE, and LBP + AE could restore the colonic and ileum tight junctions by increasing the expression of zonula occludens-1 and occludin. They also downregulated gut-derived lipopolysaccharides (LPSs), hepatic LPS-binding proteins, inflammatory factors, and related indicators of the LPS/TLR4/NF-κB signaling pathway for the liver. Our results implied that LBP could be considered a prebiotic agent, and LBP + AE might be a promising treatment for NAFLD because it could maintain gut microbiota balance, thereby restoring intestinal barrier and exerting hepatic benefits.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/terapia , Condicionamento Físico Animal/métodos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/microbiologia , Inflamação/terapia , Mucosa Intestinal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/imunologia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Prebióticos
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