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1.
Biogerontology ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582786

RESUMO

Aging entails the progressive decline in the body's self-regulation and functionality over time. Notably, obesity and aging exhibit parallel phenotypes, with obesity further accelerating the aging process across multiple dimensions and diminishing lifespan. In this study, we explored the impact of trans fatty acid (TFA) consumption on the overall health and lifespan of male Drosophila melanogaster under an isocaloric high-sugar and high-fat diet. Our results indicate that TFA intake results in a shortened lifespan, elevated body weight, and increased triglyceride levels in flies fed a high-sugar and high-fat diet with equivalent caloric intake. Additionally, TFA exposure induces oxidative stress, locomotor deficits, and damage to the intestinal barrier in flies. Collectively, chronic TFA consumption expedites the aging process and reduces the lifespan of male Drosophila melanogaster. These results contribute supplementary evidence regarding the adverse health effects associated with TFAs.

2.
Foods ; 13(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38611298

RESUMO

In this study, we investigated the body characteristics, carotenoid composition, and nutritional quality of Eriocheir sinensis with different hepatopancreas redness (a*). We distributed the crabs into two groups based on the hepatopancreas a* values and compared their body characteristics, chroma, carotenoid composition, and protein, lipid, total sugar, amino acid, and fatty acid content via paired t-test. The results revealed that the relationships between hepatopancreas a* values and crab quality are sex specific. In female crabs, the differences in nutritional characteristics were evident mainly in the hepatopancreases and ovaries. In the redder hepatopancreases, the content of zeaxanthin and ß-carotene increased, and the levels of C22:6n3 and C20:5n3 decreased (p < 0.05). In the ovaries, the content of astaxanthin, canthaxanthin, ß-carotene, umami, and sweet amino acids were lower in the redder hepatopancreas crabs (p < 0.05). In male crabs, there were positive relationships between hepatopancreas a* and amino acid and fatty acid content. The content of leucine, arginine, and total umami amino acids in muscles and of unsaturated fatty acids and n-6 polyunsaturated fatty acids in hepatopancreases and testicles increased with increasing hepatopancreas a* values (p < 0.05). Therefore, the redder the hepatopancreas, the higher the nutritional quality of male crabs.

3.
Mar Drugs ; 22(3)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38535465

RESUMO

To improve the survivability of probiotics, Lactobacillus plantarum was microencapsulated using pufferfish skin gelatin (PSG)-based wall materials by spray-drying. This work investigated the protective effect of three different pH-dependent proteins (sodium caseinate (SC), soy protein isolate (SPI), and whey protein isolate (WPI)) combined with PSG on L. plantarum. The experimental results of spray-drying with an inlet temperature of 120 °C and an outlet temperature of 80 °C, storage at 4 °C for 6 months, simulated digestion, and turbidity indicated that PSG/SC had better stability and encapsulation effects and was more suitable to encapsulate L. plantarum than PSG/SPI and PSG/WPI. The optimum preparation conditions for L. plantarum microcapsules were a PSG/SC mass ratio of 2:1, an SC concentration of 20 g/L, and a cell concentration of 10 g/L. The encapsulation efficiency of the obtained microcapsules was 95.0%, and the survival rate was 94.2% in simulated gastric fluid for 2 h and 98.0% in simulated intestinal fluid for 2 h. Amino acid composition analysis exhibited that the imino acid and aspartic acid contents of PSG were 27.98 and 26.16 g/100 g protein, respectively, which was much higher than commercial bovine gelatin. This characteristic was favorable to the high encapsulation efficiency and stability of microcapsules. In vitro release experiments showed that the PSG/SC microcapsules did not disintegrate in simulated gastric fluid for 2 h but could completely release in simulated intestinal fluid for 2 h, which can maintain the high survivability of L. plantarum in simulated digestion. In general, this study demonstrated that microcapsules using PSG/SC as wall materials can effectively improve the survivability of probiotics and have great potential for application in probiotic products.


Assuntos
Lactobacillus plantarum , Probióticos , Tetraodontiformes , Animais , Bovinos , Gelatina , Cápsulas , Cetonas
4.
J Med Chem ; 67(7): 5924-5934, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38507820

RESUMO

Real-time detection of cellular senescence remains a clinical challenge. Here, we aimed to develop a positron emission tomography (PET) imaging probe targeting senescence-associated ß-galactosidase (SA-ß-Gal), the most widely used biomarker of cellular senescence, and investigate its performance for real-time in vivo quantitative detection of cellular senescence. A stable PET imaging agent [68Ga]Ga-BGal was obtained with a high labeling yield (90.0 ± 4.3%) and a radiochemical purity (>95%). [68Ga]Ga-BGal displayed high sensitivity and specificity for ß-Gal both in vitro and in vivo. The reaction and uptake of the probe correlated with the ß-Gal concentration and reaction time. In PET imaging, high ß-Gal-expressing CT26.CL25 tumors and doxorubicin-treated HeLa tumors showed high signals from [68Ga]Ga-BGal, while a low signal was observed in CT26.WT and untreated HeLa tumors. In summary, we showcased successful PET imaging of senescence in preclinical models using probe [68Ga]Ga-BGal. This finding holds the potential for translating senescence imaging into clinical applications.


Assuntos
Radioisótopos de Gálio , Tomografia por Emissão de Pósitrons , Humanos , Tomografia por Emissão de Pósitrons/métodos , Células HeLa , Doxorrubicina , Linhagem Celular Tumoral
6.
Ann Nucl Med ; 38(4): 288-295, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38252229

RESUMO

OBJECTIVE: Most reported research has primarily investigated wild-type transthyretin cardiac amyloidosis (ATTRwt-CA). However, the application of bone scintigraphy for hereditary transthyretin cardiac amyloidosis (ATTRv-CA) has not been systematically investigated. Therefore, in this study, we aimed to evaluate the diagnostic value of 99mTc-PYP scintigraphy in ATTRv-CA. METHODS: Fifty-four patients were enrolled in a highly suspected cardiac amyloidosis cohort. Transthyretin (TTR) gene characteristics were summarized in the ATTRv-CA group. In 99mTc-PYP scintigraphy, the diagnostic efficiency of the visual score (VGS) and heart-to-contralateral chest (H/CL) ratio were evaluated. Furthermore, the interobserver consistency among the diagnosticians was investigated. RESULTS: Twenty-eight patients were diagnosed with ATTRv-CA with eight genotypes. The Ala97Ser genotype accounts for 46% (n = 13) with a mean age of disease onset, definite diagnosis, and interval of 61.6 ± 1.9, 66.5 ± 1.3, and 4.0 (3.0, 6.2) years, respectively. Their VGS is Grade 3, and their H/CL ratio is higher than that of the non-Ala97Ser group, but no statistical significance exists (mean H/CL: 1.95 ± 0.06 vs. 1.87 ± 0.02, p = 0.844). Additionally, ATTRv-CA patients showed VGS ≥ 2, and mean H/CL ratio of 2.09 ± 0.06. The sensitivity and specificity of VGS were 100% and 65%, respectively. And the interobserver consistency analysis of VGS showed the intraclass correlation coefficient is 0.522. The best cutoff value of H/CL ratio was 1.51 (AUC = 0.996), and the diagnostic consistency of H/CL (bias: 0.018) was high. CONCLUSIONS: Ala97Ser is the most common genotype in ATTRv-CA in our cohort, with characteristics of later onset and rapid progression, but delayed diagnosis and extensive 99mTc-PYP uptake. Overall, ATTRv-CA patients showed moderate-to-extensive myocardial 99mTc-PYP uptake. Additionally, VGS carries subjectivity, low specialty and interobserver consistency. But H/CL exhibit high diagnostic efficacy and interobserver consistency. The H/CL ratio is more useful than VGS.


Assuntos
Neuropatias Amiloides Familiares , Cardiomiopatias , Humanos , Pirofosfato de Tecnécio Tc 99m , Pré-Albumina/genética , Coração , Neuropatias Amiloides Familiares/diagnóstico por imagem , Neuropatias Amiloides Familiares/genética , Cintilografia , Cardiomiopatias/diagnóstico por imagem
7.
Artigo em Inglês | MEDLINE | ID: mdl-38198696

RESUMO

Weight regain subsequent to weight reduction resulting from dietary interventions represents a prevalent phenomenon recognized as "Yo-yo dieting." However, the impact of prolonged Yo-yo dieting on health, especially in relation to the aging process, remains poorly understood. This study aimed to investigate the influence of Yo-yo dieting on the aging process in male Drosophila melanogaster that have been exposed to a high-calorie (HC) diet. Fruit flies were fed with either a consistent HC diet or an alternating regimen of HC and low-calorie diets every 3 days (referred to as "Yo-yo dieting") for a total of 24 days. Biochemical assays were utilized to quantify levels of oxidative stress and activities of the mitochondrial respiratory chain complexes. The frozen section staining method was employed to assess the presence of lipid droplets, reactive oxygen species, cellular viability, and mitochondrial abundance in tissues. Additionally, we examined the expression of key regulators involved in mitochondrial dynamics and biogenic signaling pathways. Yo-yo dieting resulted in an extension of the fruit flies' lifespan, concomitant with reduced body weight, decreased body protein content, and lower triglyceride levels compared to continuous a HC diet feeding. Furthermore, Yo-yo dieting ameliorated impairments in motility and intestinal barrier function. Importantly, it improved mitochondrial function and upregulated the expression of essential mitochondrial fusion proteins, namely mitofusin 1 and mitofusin 2, optic atrophy 1, and peroxisome proliferator-activated receptor-γ coactivator-1α. Therefore, the practice of Yo-yo dieting extends the lifespan of fruit flies by modulating mitochondrial dynamics and the associated biogenic signaling pathways.


Assuntos
Envelhecimento , Drosophila melanogaster , Animais , Masculino , Drosophila melanogaster/metabolismo , Estresse Oxidativo , Mitocôndrias/metabolismo , Restrição Calórica
8.
Scand J Gastroenterol ; 59(4): 469-479, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38131633

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with dyslipidemia, and the connection between dyslipidemia and remnant cholesterol (RC), a component of triglyceride-rich lipoproteins, remains enigmatic. METHODS: In this cross-sectional study, our primary aim was to investigate the role of RC in the progression of NAFLD and to provide robust evidence of RC's involvement in the pathogenesis of NAFLD. We enrolled 2800 NAFLD patients from the National Health and Nutrition Examination Survey (NHANES). Logistic regression was employed to examine the relationship between serum RC levels and liver stiffness, while receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic capability of RC. RESULTS: RC exhibited an independent correlation with the extent of liver stiffness, with odds ratios (OR) of 1.02 for liver steatosis (p = 0.014) and 1.02 for liver fibrosis (p = 0.014). To predict NAFLD, the optimal RC thresholds were 17.25 mg/dL for males and 15.25 mg/dL for females in the case of liver steatosis. For advanced liver fibrosis, the best thresholds were 17.25 mg/dL for males and 16.25 mg/dL for females. CONCLUSIONS: RC demonstrated a positive correlation with the degree of liver stiffness and exhibited superior diagnostic efficacy for liver steatosis and fibrosis compared to other cholesterol indicators.


Elevated serum remnant cholesterol (RC) levels may serve as a potential indicator of metabolic diseases, including nonalcoholic fatty liver disease (NAFLD). The connection between serum RC and NAFLD has been previously undervalued. In our investigation, we examined 2800 NAFLD patients from the National Health and Nutrition Examination Survey (NHANES). Our cross-sectional study has revealed a more distinct relationship between RC and the degree of liver stiffness, especially concerning liver steatosis when compared to other cholesterol indicators. Recognizing RC's significant role in metabolic disorders may lead to innovative approaches for diagnosing and treating NAFLD patients.


Assuntos
Dislipidemias , Hepatopatia Gordurosa não Alcoólica , Masculino , Feminino , Humanos , Inquéritos Nutricionais , Estudos Transversais , Cirrose Hepática , Dislipidemias/complicações
9.
Molecules ; 28(20)2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37894601

RESUMO

As a substance present in organisms, nitrite is a metabolite of nitric oxide and can also be ingested. Nitrate is the metabolite of nitrite. Therefore, it is necessary to measure it quickly, easily and accurately to evaluate the health status of humans. Although there have been several reviews on analytical methods for non-biological samples, there have been no reviews focused on both sample preparation and analytical methods for biological samples. First, rapid and accurate nitrite measurement has significant effects on human health. Second, the detection of nitrite in biological samples is problematic due to its very low concentration and matrix interferences. Therefore, the pretreatment plus measuring methods for nitrite and nitrate obtained from biological samples since 2010 are summarized in the present review, and their prospects for the future are proposed. The treatment methods include liquid-liquid microextraction, various derivatization reactions, liquid-liquid extraction, protein precipitation, solid phase extraction, and cloud point extraction. Analytical methods include spectroscopic methods, paper-based analytical devices, ion chromatography, liquid chromatography, gas chromatography-mass spectrometry, electrochemical methods, liquid chromatography-mass spectrometry and capillary electrophoresis. Derivatization reagents with rapid quantitative reactions and advanced extraction methods with high enrichment efficiency are also included. Nitrate and nitrate should be determined at the same time by the same analytical method. In addition, much exploration has been performed on formulating fast testing through microfluidic technology. In this review, the newest developments in nitrite and nitrate processing are a focus in addition to novel techniques employed in such analyses.


Assuntos
Nitratos , Nitritos , Humanos , Nitratos/análise , Nitritos/química , Cromatografia Gasosa-Espectrometria de Massas , Cromatografia Líquida , Espectrometria de Massas
10.
Biochem Biophys Rep ; 35: 101545, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37731666

RESUMO

Nonalcoholic steatohepatitis (NASH) represents an inflammatory subtype of nonalcoholic fatty liver disease (NAFLD). The activation of the NOD-like receptor protein 3 (NLRP3) inflammasome triggers pyroptosis, thus propelling the progression from simple steatosis to NASH. Silibinin, a hepatoprotective compound derived from milk thistle, exerts diverse hepatoprotective effects. However, the direct impact of silibinin on NLRP3 inflammasome activation and its ability to mitigate pyroptosis remain uncertain. To address this, we utilized an in vitro model of NASH, employing HepG2 cells treated with deoxycholic acid (DCA) and free fatty acids. Subsequently, we treated these model cells with silibinin for 24 h. Our findings demonstrated that, although there were no significant changes in cellular lipid content, silibinin effectively ameliorated hepatocyte injuries. Silibinin treatment inhibited the activation of the NLRP3 inflammasome and suppressed DCA-induced pyroptosis. Additionally, molecular docking analysis revealed that silibinin exhibited a binding affinity to components of the NLRP3 inflammasome similar to that of MCC950, a selective NLRP3 inhibitor. These results suggest that silibinin may alleviate inflammation in DCA-exposed HepG2 cells by mitigating pyroptosis, possibly through its binding affinity and inhibition of the NLRP3 inflammasome. Overall, our study indicates that silibinin holds promise as a therapeutic agent for NASH by modulating pyroptosis and inhibiting NLRP3 inflammasome activation.

11.
Pharmaceutics ; 15(7)2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37514165

RESUMO

OBJECTIVE: Hydroxypropyl-ß-cyclodextrin (HP-ß-CD)/menthyl acetate (MA) microcapsules were developed to overcome the volatile and unstable defects of MA and improve the ease of use and storage. METHODS: MA microcapsules were prepared via spray drying using HP-ß-CD as the wall material. The embedding rate of MA microcapsules was determined through gas chromatography. The embedding characteristics were studied using phase solubility and nuclear magnetic resonance (NMR). The stability was characterized via differential scanning calorimetry (DSC) and the release and retention rates of MA microcapsules at different temperatures. RESULTS: The embedding rate of HP-ß-CD /MA microcapsules was 96.3%. The Gibbs free energy change, enthalpy change and entropy change of the embedding reaction between HP-ß-CD and MA were all less than zero, indicating that the embedding process was a spontaneous exothermic reaction. NMR spectra showed that MA entered the cavity of HP-ß-CD through the large opening end and interacted with the inner wall of the small opening end. DSC and the release and retention rates of MA microcapsules at different temperatures showed that the stability of MA was significantly enhanced after being embedded in HP-ß-CD. CONCLUSION: The HP-ß-CD/MA microcapsules are able to significantly improve the stability of MA and reduce the volatilization of MA.

12.
J Nutr ; 153(7): 1903-1914, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37269906

RESUMO

BACKGROUND: Hepatic cholesterol accumulation is a significant risk factor in the progression of nonalcoholic fatty liver disease (NAFLD) to steatohepatitis. However, the precise mechanism by which stigmasterol (STG) mitigates this process remains unclear. OBJECTIVES: This study aimed to investigate the potential mechanism underlying the protective effect of STG in mice with NAFLD progressing to steatohepatitis while being fed a high-fat and high-cholesterol (HFHC) diet. METHODS: Male C57BL/6 mice were fed an HFHC diet for 16 wk to establish the NAFLD model. Subsequently, the mice received STG or a vehicle via oral gavage while continuing the HFHC diet for an additional 10 wk. The study evaluated hepatic lipid deposition and inflammation as well as the expression of key rate-limiting enzymes involved in the bile acid (BA) synthesis pathways. BAs in the colonic contents were quantified using ultra-performance liquid chromatography-tandem mass spectrometry. RESULTS: Compared with the vehicle control group, STG significantly reduced hepatic cholesterol accumulation (P < 0.01) and suppressed the gene expression of NLRP3 inflammasome and interleukin-18 (P < 0.05) in the livers of HFHC diet-fed mice. The total fecal BA content in the STG group was nearly double that of the vehicle control group. Additionally, the administration of STG increased the concentrations of representative hydrophilic BAs in the colonic contents (P < 0.05) along with the upregulation of gene and protein expression of CYP7B1 (P < 0.01). Furthermore, STG enhanced the α-diversity of the gut microbiota and partially reversed the alterations in the relative abundance of the gut microbiota induced by the HFHC diet. CONCLUSIONS: STG mitigates steatohepatitis by enhancing the alternative pathway for BA synthesis.


Assuntos
Hipercolesterolemia , Hepatopatia Gordurosa não Alcoólica , Camundongos , Masculino , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estigmasterol/metabolismo , Estigmasterol/farmacologia , Colesterol na Dieta/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Colesterol/metabolismo , Hipercolesterolemia/complicações , Ácidos e Sais Biliares/metabolismo
13.
Nutr Res ; 116: 1-11, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37320946

RESUMO

The relationship between anthocyanin intake and obesity-related inflammatory markers remains unclear in existing research. To investigate this, we hypothesized that anthocyanin supplementation could reduce plasma concentrations of inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), vascular cell adhesion molecule-1, and other cytokines in obesity. We conducted a systematic search of PubMed, Web of Science, Scopus, SinoMed, and other related literature and identified 16 randomized controlled trials that met our inclusion criteria. Our findings showed that anthocyanin intake was significantly associated with a reduction in vascular cell adhesion molecule-1 mean plasma concentrations (-53.56 ng/mL; 95% confidence interval [CI], -82.10 to -25.03). We also observed a modest decrease in CRP (-0.27 ng/mL; 95% CI, -0.58 to 0.05), TNF-α (-0.20 ng/mL; 95% CI, -0.54 to 0.15), and IL-6 (-0.53 ng/mL; 95% CI, -1.16 to 0.10) mean plasma concentrations. Subgroup analysis revealed that anthocyanin intake tended to decrease CRP and IL-6 concentrations in overweight or dyslipidemic individuals. Additionally, the intervention duration subgroup analysis showed that anthocyanin supplementation had a stronger effect on plasma IL-6 and TNF-α in participants after 8 to 12 weeks of intervention. In conclusion, our meta-analysis indicated that anthocyanin supplementation can effectively reduce obesity-related inflammatory markers associated with chronic low-grade inflammation.


Assuntos
Antocianinas , Interleucina-6 , Humanos , Antocianinas/farmacologia , Antocianinas/uso terapêutico , Fator de Necrose Tumoral alfa , Molécula 1 de Adesão de Célula Vascular , Ensaios Clínicos Controlados Aleatórios como Assunto , Obesidade/complicações , Obesidade/tratamento farmacológico , Proteína C-Reativa , Inflamação/tratamento farmacológico , Suplementos Nutricionais
14.
Curr Protein Pept Sci ; 24(9): 758-766, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37350006

RESUMO

AIMS: Identify novel tyrosinase inhibitory peptides from sea cucumber (Apostichopus japonicus) collagen using in silico methods and elucidate the molecular interaction mechanism. BACKGROUND: Tyrosinase is a key enzyme in the melanin biosynthesis pathway, to restrain melanin production and reduce the appearance of associated skin diseases, inhibition of tyrosinase activity is one of the most effective methods. OBJECTIVE: The collagen from Apostichopus japonicus, which consists of 3,700 amino acid residues, was obtained from the National Center for Biotechnology Information (NCBI) as the accession number of PIK45888. METHOD: Virtual hydrolyzed method was used, and the peptides generated were compared to the previously established BIOPEP-UWM database. In addition, peptides were examined for their solubility, toxicity, and tyrosinase-binding capacity. RESULT: A tripeptide CME with optimal potential inhibitory activity against tyrosinase was identified, and its inhibitory activity was validated by in vitro experiments. The IC50 value of CME was 0.348 ± 0.02 mM for monophenolase, which was inferior to the positive control peptide glutathione, while it had an IC50 value of 1.436 ± 0.07 mM for diphenolase, which was significantly better than glutathione, and the inhibition effect of CME on tyrosinase was competitive and reversible. CONCLUSION: In silico methods were efficient and useful in the identification of new peptides.

15.
Mol Nutr Food Res ; 67(14): e2200595, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37148502

RESUMO

SCOPE: Intermittent fasting (IF) has a protective role across a wide range of chronic disorders, including obesity, diabetes, and cardiovascular disease, but its protection against non-alcoholic steatohepatitis (NASH) is still lacking. This study seeks to investigate how IF alleviates NASH by regulating gut microbiota and bile acids (BAs) composition. METHODS AND RESULTS: Male C57BL/6 mice are fed a high-fat and high-cholesterol (HFHC) diet for 16 weeks to establish a NASH model. Mice then continued HFHC feeding and are treated with or without every other day fasting for 10 weeks. Hepatic pathology is assessed using hematoxylin-eosin staining. Gut microbiota of the cecum are profiled using 16S rDNA gene sequencing and the levels of BAs in serum, colon contents, and feces are measured using ultra-performance liquid chromatography-tandem mass spectrometry. Results indicate that IF significantly decreases murine body weight, insulin resistance, hepatic steatosis, ballooning, and lobular inflammation. IF reshapes the gut microbiota, reduces the accumulation of serum BAs, and increases total colonic and fecal BAs. Moreover, IF increases the expression of cholesterol 7α-hydroxylase 1 in liver, but decreases the expressions of both farnesoid-X-receptor and fibroblast growth factor 15 in the ileum. CONCLUSION: IF alleviates NASH by regulating bile acid metabolism and promoting fecal bile acid excretion.


Assuntos
Hipercolesterolemia , Hepatopatia Gordurosa não Alcoólica , Masculino , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ácidos e Sais Biliares/metabolismo , Jejum Intermitente , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Hipercolesterolemia/metabolismo , Colesterol/metabolismo
16.
J Nutr Biochem ; 117: 109347, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37031879

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most widespread chronic liver disorder globally. Unraveling the pathogenesis of simple fatty liver to nonalcoholic steatohepatitis (NASH) has important clinical significance for improving the prognosis of NAFLD. Here, we explored the role of a high-fat diet alone or combined with high cholesterol in causing NASH progression. Our results demonstrated that high dietary cholesterol intakes accelerate the progression of spontaneous NAFLD and induces liver inflammation in mice. An elevation of hydrophobic unconjugated bile acids cholic acid (CA), deoxycholic acid (DCA), muricholic acid and chenodeoxycholic acid, was observed in high-fat and high-cholesterol diet fed mice. Full-length sequencing of the 16S rDNA gene of gut microbiota revealed a significant increase in the abundance of Bacteroides, Clostridium, and Lactobacillus that possess bile salt hydrolase activity. Furthermore, the relative abundance of these bacterial species was positively correlated with content of unconjugated bile acids in liver. Moreover, the expression of genes related to bile acid reabsorption (organic anion-transporting polypeptides, Na+-taurocholic acid cotransporting polypeptide, apical sodium dependent bile acid transporter and organic solute transporter ß) was found to be increased in mice with a high-cholesterol diet. Lastly, we observed that hydrophobic bile acids CA and DCA induce an inflammatory response in free fatty acids-induced steatotic HepG2 cells. In conclusion, high dietary cholesterol promotes the development of NASH by altering gut microbiota composition and abundance and thereby influencing with bile acid metabolism.


Assuntos
Microbioma Gastrointestinal , Hipercolesterolemia , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Colesterol na Dieta/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Dieta Hiperlipídica/métodos , Microbioma Gastrointestinal/fisiologia , Fígado/metabolismo , Ácidos e Sais Biliares/metabolismo , Ácido Cólico , Hipercolesterolemia/metabolismo , Camundongos Endogâmicos C57BL
17.
Animal Model Exp Med ; 2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36942644

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in recent years, but the pathogenesis is not fully understood. Therefore, it is important to establish an effective animal model for studying NAFLD. METHODS: Adult zebrafish were fed a normal diet or a high-fat diet combined with egg yolk powder for 30 days. Body mass index (BMI) was measured to determine overall obesity. Serum lipids were measured using triglyceride (TG) and total cholesterol (TC) kits. Liver lipid deposition was detected by Oil Red O staining. Liver injury was assessed by measuring glutathione aminotransferase (AST) and glutamic acid aminotransferase (ALT) levels. Reactive oxygen species (ROS) and malondialdehyde (MDA) were used to evaluate oxidative damage. The level of inflammation was assessed by qRT-PCR for pro-inflammatory factors. H&E staining was used for pathological histology. Caspase-3 immunofluorescence measured apoptosis. Physiological disruption was assessed via RNA-seq analysis of genes at the transcriptional level and validated by qRT-PCR. RESULTS: The high-fat diet led to significant obesity in zebrafish, with elevated BMI, hepatic TC, and TG. Severe lipid deposition in the liver was observed by ORO and H&E staining, accompanied by massive steatosis and ballooning. Serum AST and ALT levels were elevated, and significant liver damage was observed. The antioxidant system in the body was severely imbalanced. Hepatocytes showed massive apoptosis. RNA-seq results indicated that several physiological processes, including endoplasmic reticulum stress, and glucolipid metabolism, were disrupted. CONCLUSION: Additional feeding of egg yolk powder to adult zebrafish for 30 consecutive days can mimic the pathology of human nonalcoholic fatty liver disease.

18.
Molecules ; 28(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36677742

RESUMO

Paraquat (PQ) and diquat (DQ) are quaternary ammonium herbicides which have been used worldwide for controlling the growth of weeds on land and in water. However, PQ and DQ are well known to be toxic. PQ is especially toxic to humans. Moreover, there is no specific antidote for PQ poisoning. The main treatment for PQ poisoning is hemoperfusion to reduce the PQ concentration in blood. Therefore, it is essential to be able to detect PQ and DQ concentrations in biological samples. This critical review summarizes the articles published from 2010 to 2022 and can help researchers to understand the development of the sample treatment and analytical methods for the determination of PQ and DQ in various types of biological samples. The sample preparation includes liquid-liquid extraction, solid-phase extraction based on different novel materials, microextration methods, and other methods. Analytical methods for quantifying PQ and DQ, such as different chromatography and spectroscopy methods, electrochemical methods, and immunological methods, are illustrated and compared. We focus on the latest advances in PQ and DQ treatment and the application of new technologies for these analyses. In our opinion, tandem mass spectrometry is a good choice for the determination of PQ and DQ, due to its high sensitivity, high selectivity, and high accuracy. As far as we are concerned, the best LOD of 4 pg/mL for PQ in serum can be obtained.


Assuntos
Herbicidas , Paraquat , Humanos , Diquat/análise , Herbicidas/análise , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem
19.
Artigo em Inglês | MEDLINE | ID: mdl-36626958

RESUMO

Ammonia and nano-TiO2 are commonly found pollutants in aquatic environments around the world. NH3 has been proved to be absorbed on nano-TiO2 surface, therefore, the biosafety and environmental effects of ammonia and co-occurring nano-TiO2 in aquatic environments has increased considerably in recent years. To explore the potential interactive effects and mechanisms of ammonia and nano-TiO2 on the intestinal immune system, three-month-old female zebrafish were exposed to total ammonia nitrogen (TAN; 0, 3, 30 mg/L) with or without nano-TiO2 (1 mg/L) for 60 d. The results showed that intestinal ammonia levels increased with the increase of TAN exposure concentration in the presence of nano-TiO2. Histopathological analysis demonstrated that both TAN and nano-TiO2 caused cell vacuolation, lymphocyte infiltration and goblet cells hyperplasia in the intestine mucosa. Our study also found that the contents and gene expression levels of lysozyme (lys) and ß-defensin (def-ß) in the intestine of zebrafish exposed to TAN alone or combined with nano-TiO2 were significantly reduced, suggesting a decline in the intestinal innate immunity of fish. A broad upregulation of TLRs-related genes indicated that TAN and nano-TiO2 could activate TLR4/5-mediated MyD88-dependent pathway, and eventually induce intestinal inflammation. It should be noted that TAN combined with nano-TiO2 had more significant inhibitory effects on the intestinal structure and innate immune responses than TAN alone. Current data suggested that ammonia and nano-TiO2 had a synergistic inhibitory effect on intestinal mucosal immunity, and their associated health risk to aquatic animals and the water ecosystem should not be underestimated.


Assuntos
Nanopartículas , Poluentes Químicos da Água , Animais , Feminino , Peixe-Zebra/metabolismo , Amônia/toxicidade , Ecossistema , Titânio/toxicidade , Titânio/química , Mucosa Intestinal/metabolismo , Nanopartículas/toxicidade , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismo
20.
Environ Int ; 171: 107660, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36470123

RESUMO

Gut microbiome can participate in arsenic metabolism. However, its efficacy in the host under arsenic stress is still controversial. To clarify their roles in fecal arsenic excretion, tissue arsenic accumulation, host physiological states and metabolism, in this study, ninety-six C57BL/6 male mice were randomly divided to four groups, groups A and B were given sterile water, and groups C and D were given the third generation of broad-spectrum antibiotic (ceftriaxone) to erase the background gut microbiome. Subsequently, groups B and D were subchronicly exposed to arsenic containing feed prepared by adding arsenical mixture (rice arsenic composition) into control feed. In group D, the fecal total arsenic (CtAs) decreased by 25.5 %, iAsIII composition increased by 46.9 %, unclarified As (uAs) composition decreased by 92.4 %, and the liver CtAs increased by 26.7 %; the fecal CtAs was positively correlated with microbial richness and some metabolites (organic acids, amino acids, carbohydrates, SCFAs, hydrophilic bile acids and their derivatives); and fecal DMA was positively correlated with microbial richness and some metabolites (ferulic acid, benzenepropanoic acid and pentanoic acid); network analysis showed that the numbers of modules, nodes, links were decreased and vulnerability was increased; some SCFAs and hydrophilic bile acid decreased, and hydrophobic bile acids increased (Ps < 0.05). In the tissue samples of group D, Il-18 and Ifn-γ gene expression increased and intestinal barrier-related genes Muc2, Occludin and Zo-1 expression decreased (Ps < 0.05); serum glutathione and urine malondialdehyde significantly increased (Ps < 0.05); urine metabolome significantly changed and the variation was correlated with six SCFAs-producing bacteria, and some SCFAs including isobutyric acid, valeric acid and heptanoic acid decreased (Ps < 0.05). Therefore, the normal gut microbiome increases fecal arsenic excretion and biotransformation, which can maintain a healthier microbiome and metabolic functions, and alleviate the metabolic disorder for their mammal host under arsenic exposure.


Assuntos
Arsênio , Microbioma Gastrointestinal , Masculino , Animais , Camundongos , Arsênio/toxicidade , Camundongos Endogâmicos C57BL , Metaboloma , Fezes/microbiologia , Mamíferos , Ácidos e Sais Biliares
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