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Metastasis is an important contributor to increased mortality rates in non-small cell lung cancer (NSCLC). The TGF-ß signalling pathway plays a crucial role in facilitating tumour metastasis through epithelial-mesenchymal transition (EMT). Glycolysis, a key metabolic process, is strongly correlated with NSCLC metastasis. Pirfenidone (PFD) has been shown to safely and effectively inhibit TGF-ß1 in patients with lung diseases. Furthermore, TGF-ß1 and glycolysis demonstrate an interdependent relationship within the tumour microenvironment. Our previous study demonstrated that PFD effectively inhibited glycolysis in NSCLC cells, prompting further investigation into its potential antitumour effects in this context. Therefore, the present study aims to investigate the potential antitumour effect of PFD in NSCLC and explore the relationship among TGF-ß1, glycolysis and EMT through further experimentation. The antitumour effects of PFD were evaluated using five different NSCLC cell lines and a xenograft tumour model. Notably, PFD demonstrated a significant antitumour effect specifically in highly glycolytic H1299 cells. To elucidate the underlying mechanism, we compared the efficacy of PFD after pretreatment with either TGF-ß1 or a TGF-ß receptor inhibitor (LY2109761). The energy metabolomics analysis of tumour tissue demonstrated that PFD, a chemosensitizing agent, reduced lactate and ATP production, thereby inhibiting glycolysis and exerting synergistic antineoplastic effects. Additionally, PFD combined with cisplatin targeted TGF-ß1 to inhibit glycolysis during EMT and enhanced the chemosensitization of A549 and H1299 cells. The magnitude of the anticancer effect exhibited by PFD was intricately linked to its metabolic properties.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Piridonas , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares/patologia , Reprogramação Metabólica , Fator de Crescimento Transformador beta1/metabolismo , Microambiente Tumoral , AnimaisRESUMO
BACKGROUND: The biological functions of ferulic acid (FA) have garnered significant interest but its limited solubility and stability have led to low bioavailability. Hydroxypropyl-ß-cyclodextrin (HP-ß-CD), with its distinctive hollow structure, offers the potential for encapsulating hydrophobic molecules. The formation of an inclusion complex between FA and HP-ß-CD may therefore be a viable approach to address the inherent limitations of FA. To investigate the underlying mechanism of the FA/HP-ß-CD inclusion complex formation, a combination of spectral analyses and computer simulation was employed. RESULTS: The disappearance of the characteristic peaks of FA in Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) confirmed the formation of an inclusion complex between FA and HP-ß-CD. Thermogravimetry-derivative thermogravimetry (TG-DTG) studies demonstrated that the thermal stability of FA was enhanced due to the encapsulation of FA within HP-ß-CD. Molecular dynamics simulation also provided evidence that FA successfully penetrated the HP-ß-CD cavity, primarily driven by van der Waals interactions. The formation of the complex resulted in more compact HP-ß-CD structures. The bioavailability of FA was also strengthened through the formation of inclusion complexes with HP-ß-CD. CONCLUSIONS: The findings of this study have contributed to a deeper understanding of the interactions between FA and HP-ß-CD, potentially advancing a delivery system for FA and enhancing the bioavailability of insoluble active components. © 2024 Society of Chemical Industry.
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2-Hidroxipropil-beta-Ciclodextrina , Disponibilidade Biológica , Simulação por Computador , Ácidos Cumáricos , Solubilidade , Ácidos Cumáricos/química , 2-Hidroxipropil-beta-Ciclodextrina/química , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X , Simulação de Dinâmica Molecular , Interações Hidrofóbicas e Hidrofílicas , TermogravimetriaRESUMO
Exposure to coal-burning arsenic leads to an increased risk of cancer, multi-systems damage and chronic diseases, with DNA methylation one potential mechanism of arsenic toxicity. There are few studies on genome-wide methylation in the coal-burning arsenic poisoning population. Illumina 850 K methylation beadchip is the most suitable technology for DNA methylation of epigenome-wide association analysis. This study used 850 K to detect changes in Genome-wide DNA methylation in whole blood samples of 12 patients with coal-burning arsenic poisoning ( Arsenic poisoning group) and four healthy control participants (Healthy control group). There is clearly abnormal genome-wide DNA methylation in coal-burning arsenic poisoning, with 647 significantly different methylation positions, 524 different methylation regions and 335 significantly different methylation genes in arsenic poisoning patients compared with healthy controls. Further functional analysis of Gene ontology (GO) and Kyoto encyclopedia of genes (KEGG) found 592 GO items and 131 KEGG pathways between patients of coal-burning arsenic poisoning and healthy control. Then, analysis of gene degree and combined-score identified NAPRT1, NT5C3B, NEDD4L, SLC22A3 and RAB11B as target genes. Further validation by qRT-PCR indicates that mRNA expression of five genes changes significantly in the arsenic poisoning group (n = 72) compared to the healthy control group (n = 72). These results showed the genome-wide methylation pattern and highlighted five critical genes within the coal-burning arsenic poisoning population that involve Nicotinate and nicotinamide metabolism, Choline metabolism in cancer, and Ubiquitin mediated proteolysis. Next, the methylation profile of coal burning arsenic poisoning will be further excavation and the mechanism of coal burning arsenic poisoning will be further explored from five genes related pathways and functions.
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Intoxicação por Arsênico , Arsênio , Humanos , Metilação de DNA/genética , Intoxicação por Arsênico/genética , Carvão Mineral , DNARESUMO
Chronic exposure to high-dose inorganic arsenic through groundwater, air, or food remains a major environmental public health issue worldwide. Apoptosis, a method of cell death, has recently become a hot topic of research in biology and medicine. Previous studies have demonstrated that extracellular signal-regulated kinase (ERK) is related to arsenic-induced apoptosis. However, the reports are contradictory, and the knowledge of the above-mentioned mechanisms and their mutual regulation remains limited. In this study, the associations between the TGF-ß1/ERK signaling pathway and arsenic-induced cell apoptosis were confirmed using the HaCaT cell model. The relative expressions of the indicators of the TGF-ß1/ERK signaling pathway, apoptosis-related genes (cytochrome C, caspase-3, caspase-9, cleaved caspase-3, cleaved caspase-9, and Bax), the mitochondrial membrane potential, and the total apoptosis rate were significantly increased (P < .05), while the expression of the antiapoptosis gene Bcl-2 was significantly decreased (P < .05) in cells of the group exposed to arsenic. Moreover, the results demonstrated that the ERK inhibitor (PD98059) and TGF-ß1 inhibitor (LY364947) could inhibit the activation of the ERK signaling pathway, thereby reducing the mitochondrial membrane potential, the total apoptosis rate, and the expression of pro-apoptosis-related genes in the cells, while the expression of the antiapoptosis gene Bcl-2 was significantly increased (P < .05). By contrast, the recombinant human TGF-ß1 could promote apoptosis of the HaCaT cells by increasing the activation of the ERK signaling pathway (P < .05). These results indicate that inorganic arsenic promotes the apoptosis of human immortal keratinocytes through the TGF-ß1/ERK signaling pathway.
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Arsênio , MAP Quinases Reguladas por Sinal Extracelular , Apoptose , Arsênio/metabolismo , Arsênio/toxicidade , Caspase 3/metabolismo , Caspase 9/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Queratinócitos/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Emerging evidence suggests that long non-coding RNAs (lncRNAs) are critical regulators of diverse biological processes, including adipogenesis. Despite being considered an ideal animal model for studying adipogenesis, little is known about the roles of lncRNAs in the regulation of rabbit preadipocyte differentiation. In the present study, visceral preadipocytes isolated from newborn rabbits were cultured in vitro and induced for differentiation, and global lncRNA expression profiles of adipocytes collected at days 0, 3, and 9 of differentiation were analyzed by RNA-seq. A total of 2066 lncRNAs were identified from nine RNA-seq libraries. Compared to protein-coding transcripts, lncRNA transcripts exhibited characteristics of a longer length and lower expression level. Furthermore, 486 and 357 differentially expressed (DE) lncRNAs were identified when comparing day 3 vs. day 0 and day 9 vs. day 3, respectively. Target genes of DE lncRNAs were predicted by the cis-regulating approach. Prediction of functions revealed that DE lncRNAs when comparing day 3 vs. day 0 were involved in gene ontology (GO) terms of developmental growth, growth, developmental cell growth, and stem cell proliferation, and involved in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of PI3K-Akt signaling pathway, fatty acid biosynthesis, and the insulin signaling pathway. The DE lncRNAs when comparing day 9 vs. day 3 were involved in GO terms that associated with epigenetic modification and were involved in the KEGG pathway of cAMP signaling pathway. This study provides further insight into the regulatory function of lncRNAs in rabbit visceral adipose and facilitates a better understanding of different stages of preadipocyte differentiation.
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Adipócitos/metabolismo , Adipogenia , Gordura Intra-Abdominal/citologia , RNA Longo não Codificante/genética , Adipócitos/citologia , Animais , Células Cultivadas , Insulina/genética , Insulina/metabolismo , Gordura Intra-Abdominal/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo , Coelhos , Transdução de Sinais , TranscriptomaRESUMO
BACKGROUND: MicroRNAs (miRNAs) regulate adipose tissue development, which are closely related to subcutaneous and intramuscular fat deposition and adipocyte differentiation. As an important economic and agricultural animal, rabbits have low adipose tissue deposition and are an ideal model to study adipose regulation. However, the miRNAs related to fat deposition during the growth and development of rabbits are poorly defined. METHODS: In this study, miRNA-sequencing and bioinformatics analyses were used to profile the miRNAs in rabbit perirenal adipose tissue at 35, 85 and 120 days post-birth. Differentially expressed (DE) miRNAs between different stages were identified by DEseq in R. Target genes of DE miRNAs were predicted by TargetScan and miRanda. To explore the functions of identified miRNAs, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. RESULTS: Approximately 1.6 GB of data was obtained by miRNA-seq. A total of 987 miRNAs (780 known and 207 newly predicted) and 174 DE miRNAs were identified. The miRNAs ranged from 18 nt to 26 nt. GO enrichment and KEGG pathway analyses revealed that the target genes of the DE miRNAs were mainly involved in zinc ion binding, regulation of cell growth, MAPK signaling pathway, and other adipose hypertrophy-related pathways. Six DE miRNAs were randomly selected, and their expression profiles were validated by q-PCR. CONCLUSIONS: This is the first report of the miRNA profiles of adipose tissue during different growth stages of rabbits. Our data provide a theoretical reference for subsequent studies on rabbit genetics, breeding and the regulatory mechanisms of adipose development.
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Tecido Adiposo/metabolismo , MicroRNAs/metabolismo , Tecido Adiposo/crescimento & desenvolvimento , Animais , Biologia Computacional , Metabolismo dos Lipídeos/fisiologia , RNA-Seq , CoelhosRESUMO
BACKGROUND: The rabbit is widely used as an important experimental model for biomedical research, and shows low adipose tissue deposition during growth. Long non-coding RNAs (lncRNAs) are associated with adipose growth, but little is known about the function of lncRNAs in the rabbit adipose tissue. METHODS: Deep RNA-sequencing and comprehensive bioinformatics analyses were used to characterize the lncRNAs of rabbit visceral adipose tissue (VAT) at 35, 85 and 120 days after birth. Differentially expressed (DE) lncRNAs were identified at the three growth stages by DESeq. The cis and trans prediction ways predicted the target genes of the DE lncRNAs. To explore the function of lncRNAs, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on the candidate genes. RESULTS: A total of 991,157,544 clean reads were generated after RNA-Seq of the three growth stages, of which, 30,353 and 107 differentially expressed (DE) lncRNAs were identified. Compared to the protein-coding transcripts, the rabbit lncRNAs shared some characteristics such as shorter length and fewer exons. Cis and trans target gene prediction revealed, 43 and 64 DE lncRNAs respectively, corresponding to 72 and 20 protein-coding genes. GO enrichment and KEGG pathway analyses revealed that the candidate DE lncRNA target genes were involved in oxidative phosphorylation, glyoxylate and dicarboxylate metabolism, and other adipose growth-related pathways. Six DE lncRNAs were randomly selected and validated by q-PCR. CONCLUSIONS: This study is the first to profile the potentially functional lncRNAs in the adipose tissue growth in rabbits, and contributes to our understanding of mammalian adipogenesis.
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Tecido Adiposo/crescimento & desenvolvimento , Desenvolvimento Embrionário/genética , Genoma/genética , RNA Longo não Codificante/genética , Adipogenia/genética , Tecido Adiposo/metabolismo , Animais , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/genética , Sequenciamento de Nucleotídeos em Larga Escala , RNA Mensageiro/genética , Coelhos , Análise de Sequência de RNARESUMO
The antioxidant effects of the triterpenoid-rich extracts from Euryale ferox shell (ES) have been confirmed in vitro. This study examined whether the triterpenoid-rich extract from ES eases human hyperglycemia and diabetes caused by metabolic disorders. Normal and streptozocin (STZ)-induced diabetic mice were used as controls for the four groups that received the triterpenoid-rich extracts of ES suspended in distilled water orally at doses of 200, 300, 400, 500±2 mg/L. Body weight, blood glucose and pancreatic tissue morphology were observed after 4 weeks. The expression of protein tyrosine phosphatase-1B (PTP1B) and insulin receptor substrate (IRS-1) proteins, which are related to the regulation of glucose metabolism in vivo, were also investigated. Compared with the model group (LD50 900±2 mg/L), it was found that the triterpenoid-rich extracts of ES could regulate glucose metabolism (P<0.01) and cause body weight to return to normal levels (P<0.05). Islet morphology recovered well, the expression of the negative regulation protein PTP1B gene was reduced and insulin receptor IRS-1 protein expression was increased. These data prove that the triterpenoid-rich extracts from ES have a therapeutic effect on diabetes by insulin resistance.
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Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Nymphaeaceae , Fitoterapia , Extratos Vegetais/farmacologia , Triterpenos/farmacologia , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Proteínas Substratos do Receptor de Insulina/fisiologia , Masculino , Camundongos , Proteína Tirosina Fosfatase não Receptora Tipo 1/fisiologia , EstreptozocinaRESUMO
High-sucrose (HS) consumption leads to metabolic disorders and increases susceptibility to colitis. Postbiotics hold great potentials in combating metabolic diseases and offer advantages in safety and processability, compared with living probiotics. We developed innovative oat-based postbiotics and extensively explored how they could benefit in rats with long-term high-sucrose consumption. The postbiotics fermented with Lactiplantibacillus plantarum (OF-1) and OF-5, the one fermented with the optimal selection of five probiotics (i.e., L. plantarum, Limosilactobacillus reuteri, Lacticaseibacillus rhamnosus, Lactobacillus acidophilus, and Bifidobacterium lactis) alleviated HS induced liver injury, impaired fatty acid metabolism and inflammation through activating AMPK/SREBP-1c pathways. Moreover, oat-based postbiotics restored detrimental effects of HS on fatty acid profiles in liver, as evidenced by the increases in polyunsaturated fatty acids and decreases in saturated fatty acids, with OF-5 showing most pronounced effects. Furthermore, oat-based postbiotics prevented HS exacerbated susceptibility to dextran sodium sulfate caused colitis and reconstructed epithelial tight junction proteins in colons. Oat-based postbiotics, in particular OF-5 notably remodeled gut microbiota composition, e.g., enriching the relative abundances of Akkermansia, Bifidobacterium, Alloprevotella and Prevotella, which may play an important role in the liver-colon axis responsible for improvements of liver functions and reduction of colitis susceptibility. The heat-inactivated probiotics protected against HS-induced liver and colon damage, but such effects were less pronounced compared with oat-based postbiotics. Our findings emphasize the great value of oat-based postbiotics as nutritional therapeutics to combat unhealthy diet induced metabolic dysfunctions.
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Doença Hepática Crônica Induzida por Substâncias e Drogas , Colite , Microbioma Gastrointestinal , Probióticos , Ratos , Animais , Camundongos , Avena , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Colite/induzido quimicamente , Colite/terapia , Colite/metabolismo , Ácidos Graxos/metabolismo , Probióticos/farmacologia , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Colo/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Pueraria lobata (Willd.) Ohwi is a traditional medicinal and edible homologous plant rich in flavonoids, triterpenes, saponins, polysaccharides and other chemical components. At present, studies have shown that Pueraria lobata radix (PR) has the effect of lowering blood sugar, improving insulin sensitivity and inhibiting obesity. However, the specific mechanism of PR inhibits obesity is still unclear, and there are few researches on the anti-obesity effect of PR through the combination of network pharmacology and experiment. AIM OF THE STUDY: Pharmacology, molecular docking technology and experimental verification through the network, revealing the PR the material basis of obesity and the potential mechanism. METHODS AND RESULTS: The present study used network pharmacology techniques to investigate the therapeutic effect and mechanism of action of PR. Through relevant databases, a total of 6 main chemical components and 257 potential targets were screened. Protein interaction analysis shows that AKT1, AKR1B1, PPARG, MMP9, TNF, TP53, BAD, and BCL2 are core targets. Enrichment analysis shows that the pathway of PR in preventing obesity involves the cancer signaling pathway and the PI3K-Akt signaling pathway, which may be the main pathways of action. Further molecular docking verification indicates that its core target exhibits good binding activity with 4 compounds: formononectin, purerin, 7,8,4 '- trihydroxide and daidzein. Using the ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) technology to detected and confirmed these main compounds. Cell experiment results revealed that puerarin inhibits cell proliferation and differentiation in a concentration dependent manner, significantly promoting cell apoptosis and affecting cell migration. Animal experiments have shown that puerarin reduces food intake and weight gain in mice. It was found that puerarin can upregulate HDL and downregulate TC, TG, and LDL blood biochemical indicators. Western blot results showed that puerarin significantly inhibited the expression of AKT1, AKR1B1, MMP9, TNF, TP53, BCL2, PPARG, and significantly increased the expression of BAD protein at both cellular and animal levels. CONCLUSION: The present study established a method for measuring PR content and predicted its active ingredients and their mechanisms of action in the treatment of obesity, providing a theoretical basis for further research.
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Rapid and accurate identification of lactic acid bacteria (LAB) species would greatly improve the screening rate for functional LAB. Although many conventional and molecular methods have proven efficient and reliable, LAB identification using these methods has generally been slow and tedious. Single-cell Raman spectroscopy (SCRS) provides the phenotypic profile of a single cell and can be performed by Raman spectroscopy (which directly detects vibrations of chemical bonds through inelastic scattering by a laser light) using an individual live cell. Recently, owing to its affordability, non-invasiveness, and label-free features, the Ramanome has emerged as a potential technique for fast bacterial detection. Here, we established a reference Ramanome database consisting of SCRS data from 1,650 cells from nine LAB species/subspecies and conducted further analysis using machine learning approaches, which have high efficiency and accuracy. We chose the ensemble meta-classifier (EMC), which is suitable for solving multi-classification problems, to perform in-depth mining and analysis of the Ramanome data. To optimize the accuracy and efficiency of the machine learning algorithm, we compared nine classifiers: LDA, SVM, RF, XGBoost, KNN, PLS-DA, CNN, LSTM, and EMC. EMC achieved the highest average prediction accuracy of 97.3% for recognizing LAB at the species/subspecies level. In summary, Ramanomes, with the integration of EMC, have promising potential for fast LAB species/subspecies identification in laboratories and may thus be further developed and sharpened for the direct identification and prediction of LAB species from fermented food.
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A hundred million tons of young apples are thinned and discarded in the orchard per year, aiming to increase the yield and quality of apples. We fermented thinned young apples using a potential probiotic fungus, Eurotium cristatum, which notably disrupted the microstructure of raw samples, as characterized by the scanning electron microscope. Fermentation substantially altered the metabolite profiles of samples, which are predicted to alleviate colitis via regulating inflammatory response and response to lipopolysaccharide by using network pharmacology analysis. In vivo, oral gavage of water extracts of E. cristatum fermented young apples (E.YAP) effectively alleviated DSS-induced colitis, restored the histopathology damage, reduced the levels of inflammatory cytokines, and promoted colonic expressions of tight junction proteins. Moreover, E.YAP ameliorated gut dysbacteriosis by increasing abundances of Lactobacillus,Blautia, Muribaculaceae, and Prevotellaceae_UCG-001 while inhibiting Turicibacter, Alistipes, and Desulfovibrio. Importantly, E.YAP increased colonic bile acids, such as CA, TCA, DCA, TUDCA, and LCA, thereby alleviating colitis via PXR/NF-κB signaling. Furthermore, a synbiotic combination with Limosilactobacillus reuteri WX-94, a probiotic strain isolated from feces of healthy individuals with anti-inflammatory properties, augmented anticolitis capacities of E.YAP. Our findings demonstrate that E.YAP could be a novel, potent, food-based anti-inflammatory prebiotic for relieving inflammatory injuries.
Assuntos
Bactérias , Colite , Eurotium , Fermentação , Malus , Camundongos Endogâmicos C57BL , Animais , Malus/química , Camundongos , Colite/microbiologia , Colite/metabolismo , Colite/induzido quimicamente , Humanos , Masculino , Eurotium/metabolismo , Eurotium/química , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/administração & dosagem , Probióticos/farmacologia , Frutas/química , Frutas/microbiologia , Colo/microbiologia , Colo/metabolismo , Colo/imunologiaRESUMO
Obesity and its related metabolic diseases bring great challenges to public health. In-depth understanding on the efficacy of weight-loss interventions is critical for long-term weight control. Our study demonstrated the comparable efficacy of exercise (EX), intermittent fasting (IF), or the change of daily diet from an unhealthy to a normal chow (DR) for weight reduction, but largely divergently affected metabolic status and transcriptome of subcutaneous fat, scapular brown fat, skeletal muscles and liver in high-fat-high-fructose diet (HFHF) induced obese mice. EX and IF reduced systematic inflammation, improved glucose and lipid metabolism in liver and muscle, and amino acid metabolism and thermogenesis in adipose tissues. EX exhibited broad regulatory effects on TCA cycle, carbon metabolism, thermogenesis, propanoate-, fatty acid and amino acid metabolism across multiple tissues. IF prominently affected genes involved in mitophagy and autophagy in adipose tissues and core genes involved in butanoate metabolism in liver. DR, however, failed to improve metabolic homeostasis and biological dysfunctions in obese mice. Notably, by exploring potential inter-organ communication, we identified an obesity-resistant-like gene profile that were strongly correlated with HFHF induced metabolic derangements and could predict the degree of weight regain induced by the follow-up HFHF diet. Among them, 12 genes (e.g., Gdf15, Tfrc, Cdv3, Map2k4, and Nqo1) were causally associated with human metabolic traits, i.e., BMI, body fat mass, HbA1C, fasting glucose, and cholesterol. Our findings provide critical groundwork for improved understanding of the impacts of weight-loss interventions on host metabolism. The identified genes predicting weight regain may be considered regulatory targets for improving long-term weight control.
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Jejum , Homeostase , Camundongos Endogâmicos C57BL , Obesidade , Transcriptoma , Aumento de Peso , Redução de Peso , Animais , Masculino , Obesidade/metabolismo , Obesidade/dietoterapia , Dieta Hiperlipídica/efeitos adversos , Condicionamento Físico Animal , Camundongos , Fígado/metabolismo , Músculo Esquelético/metabolismo , Termogênese , Metabolismo dos Lipídeos , Tecido Adiposo/metabolismo , Jejum IntermitenteRESUMO
Allium mongolicum Regel (AMR) is a traditional Mongolian food. Various drying methods play an important role in foodstuff flavor. However, the effect of different drying methods on AMR is limited. In this study, freeze drying (FD), vacuum drying (VD), and hot-air drying (HAD) were applied to dry fresh AMR to a moisture content of 8% (wet basis); headspace gas chromatography mass spectrometry was adopted to identify volatile compounds in AMR; and principal component analysis and fingerprint similarity analysis based on the Euclidean distance was used to distinguish the fresh and three dried treatments. In total, 113 peaks were detected and 102 volatile compounds were identified. Drying causes significant changes to the amounts of volatile compounds in AMR, and the drying method plays a key role in determining which volatile compounds appear. Compared to FD, VD and HAD were more appropriate for drying AMR because the volatile compounds after VD and HAD were closer to those of fresh AMR. These findings can provide a scientific basis to help to preserve future seasonal functional food and aid in Mongolian medicine production.
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Chronic arsenic exposure is a risk factor for human fatty liver disease, and the ERK signaling pathway plays an important role in the regulation of liver lipid metabolism. However, whether ERK plays a role in the progression of arsenic-induced liver lipid metabolism disorder and the specific mechanism remain unclear. Here, by constructing a rat model of liver lipid metabolism disorder induced by chronic arsenic exposure, we demonstrated that ERK might regulate arsenic-induced liver lipid metabolism disorders through the PPAR signaling pathway. Arsenic could upregulate the expression of PPARγ and CD36 in the rat liver, decrease the expression of PPARα and CPT-1 in the rat liver, increase the organ coefficient of the rat liver, decrease the content of TG in rat serum, and promote fat deposition in the rat liver. In the arsenic-induced rat model of hepatic lipid metabolism disorder, we found that the expression of p-ERK was increased. In order to further explore whether the ERK signaling pathway was involved in arsenic-induced liver lipid metabolism disorder, we exposed L-02 cells to different arsenic concentrations, and the results showed that arsenic significantly increased the expression of P-ERK in L-02 cells in a dose-dependent manner. We further treated L-02 cells with ERK inhibitors and found that the expression of TG, PPARα, and CPT-1 in L-02 cells increased, while the expression of P-ERK, PPARγ, and CD36 decreased. In conclusion, ERK may be involved in arsenic-induced liver lipid metabolism disorder by regulating the PPAR signaling pathway. These findings are expected to provide a new targeting strategy for arsenic-induced liver lipid metabolism disorder.
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Transtornos do Metabolismo dos Lipídeos , Metabolismo dos Lipídeos , Animais , Transtornos do Metabolismo dos Lipídeos/metabolismo , Fígado/metabolismo , PPAR alfa/metabolismo , Ratos , Transdução de SinaisRESUMO
Long-term arsenic (As) exposure can cause liver injury, hepatic cirrhosis, and cancer. Meanwhile, Dictyophora polysaccharides (DIP) have excellent antioxidation, anti-inflammation, and immune protection effects. There are currently few reports on the protection effects of DIP on As-induced hepatotoxicity and its pharmacological value. Therefore, this study was aimed at elucidating the protection of DIP on As-induced hepatotoxicity and exploring its preventive role in antifibrosis. In our study, the SD rat As poisoning model was established by the feeding method to explore the influence of As exposure on liver fibrosis. Then, DIP treatment was applied to the rats with As-induced liver fibrosis, and the changes of serum biochemical indexes and liver tissue pathology were observed. And the expression of fibrosis-related proteins TGF-ß1, CTGF, and α-SMA levels was then determined to explore the DIP intervention function. The results demonstrated that through reduced pathological changes of hepatic and increased serum AST, ALT, TP, ALB, and A/G levels, DIP ameliorated liver fibrosis induced by As as reflected. And the administration of DIP decreased the concentration of HA, LN, PCIII, CIV, TBIL, and DBIL. In addition, the synthesis of TGF-ß1 inhibited by DIP might regulate the expression of CTGF and decrease the proliferation of fibrinogen and fibroblasts, which reduced the synthesis of fibroblasts to transform into myofibroblasts. And a decrease of myofibroblasts downregulated the expression of α-SMA, which affected the synthesis and precipitation of ECM and alleviated the liver fibrosis caused by exposure to As. In conclusion, based on the pathological changes of liver tissue, serum biochemical indexes, and related protein expression, DIP can improve the As-induced liver fibrosis in rats and has strong medicinal value.
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Arsênio , Doença Hepática Induzida por Substâncias e Drogas , Animais , Arsênio/efeitos adversos , Tetracloreto de Carbono/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Polissacarídeos/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/metabolismoRESUMO
This study systematically analyzed and compared thechanges of physicochemical, functional and molecular structural characteristics between thick egg white (KEW) and thin egg white (NEW) during storage. Analysis of physicochemical properties showed that moisture content decreased significantly with the increase of pH during storage. KEW was gradually thinning, while NEW was closer to Newtonian fluid. Functional properties indicated that KEW thermal gel was gradually hard and brittle with the properties of NEW. KEW had better emulsifying property than NEW, and NEW had superior foaming ability. The α-helix and ß-sheet in the FT-IR spectrum showed a downward trend, revealing secondary structure changed from order to disorder. Enhancement of fluorescence intensity indicated the structural unfolding and exposure of tryptophan residues. SDS-PAGE proved that OVO might be related to the difference between KEW and NEW characteristics. This study provided new idea and reference value for egg storage and diversified utilization of egg white.
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Clara de Ovo , Clara de Ovo/análise , Eletroforese em Gel de Poliacrilamida , Estrutura Molecular , Estrutura Secundária de Proteína , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Greenly synthesized silver nanoparticles (AgNPs) on different cellulosic materials show tremendous potential for colorful, biocidal, and reasonably strong products by replacing the traditional chemical-based synthesis protocols. This study reports on a novel in situ synthesis protocol for synthesizing green and sustainable AgNPs over cellulosic kraft paper substrates using a bio-based stabilizing agent (Cephalotaxus harringtonia fruit extract). The protocol could play a significant role in packaging industries. The aqueous extracts of Cephalotaxus harringtonia fruits have been used to synthesize the metallic silver. The deposited AgNPs values were investigated through XRF (X-ray fluorescence) analysis. The number of deposited nanoparticles (NPs) was 268 ± 7, 805 ± 14, and 1,045 ± 16 PPM, respectively for 0.5, 1.5, and 2.5 mm silver precursors. The developed products were tested with SEM (scanning electron microscopy), SEM-mediated elemental mapping, EDX (energy disruptive X-ray), FTIR (Fourier transform infrared spectroscopy), and XRD (X-Ray diffraction). XRD analysis further confirmed the presence of peaks for elemental AgNP on the deposited papers. Colorimetric values were measured to confirm the colorful appearances of the developed metallic silvers. Mechanical properties were tested in terms of the tensile index and bursting index. Moreover, the statistical analysis of coefficient of variations (R2) and a post-hoc ANOVA test that adopted the Newman-Keul methodology also confirm the significance of developed nanoparticles in the papers. The shielding capacity against UV light was also investigated; all the AgNPs-treated products provided values higher than 40, demonstrating the strong UV resistance capability of the kraft paper material. Overall, the study confirms a successful development of green AgNPs on paper materials.
RESUMO
The effect of different glycosylation degrees on molecular structure and foaming property of egg white protein (EWP) was investigated using ball milling-assisted glycosylation. The results showed the foaming ability (FA) and foam stability (FS) of EWP improved when the degree of glycosylation was increased. In particular, FA of ball milling-assisted glycosylation of EWP enhanced by 39.9% and 28.8%, and the FS increased by 28.7% and 24.0% compared with EWP and ball milling egg white protein (BE) at 150 min of reaction. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) analysis could reflect the grafting degree of EWP and glucose molecules from the side. When EWP was fully grafted with glucose, endogenous fluorescence and free sulfhydryl groups indicated that tertiary structure of EWP was depolymerized, and Fourier transform infrared spectroscopy showed the secondary structure tended to change from order to disorder. The results of this study indicated that ball milling-assisted glycosylation modification was a practical method to improve the foaming property of EWP. PRACTICAL APPLICATION: EWP has great FA and FS, making it indispensable in the baking industry. In this study, ball milling-assisted glycosylation was used to improve the foaming property of EWP, and the molecular structure of EWP with different degrees of glycosylation was fully resolved. The results demonstrated that ball milling, as a physical pretreatment, can fully unfold the structure of EWP. When sugar molecules were fully grafted, the particle size of EWP reduced, solubility increased, and the stability of system improved, thus enhancing the foaming property of EWP. The results can provide theoretical basis for improving the foaming property of EWP and provide a reference value for its industrial application.
Assuntos
Proteínas do Ovo , Glucose , Proteínas do Ovo/química , Glicosilação , Tamanho da Partícula , SolubilidadeRESUMO
As a typical colloidal solution system, egg white (EW) will naturally thin during storage. This paper discussed mechanism of EW thinning and protein depolymerization from the perspective of "protein composition and molecular structure". The results of rheology showed that viscoelasticity of EW declined substantially. Analysis of EW protein in gel system demonstrated that arrangement of EW thermal gel gradually tightened with dissociation of skeleton protein during storage. Molecular characteristics of EW protein in solution showed that particle size and free sulfhydryl content decreased. The increase of disulfide bonds enhanced intermolecular electrostatic force and hindered molecular aggregation, which improved solubility of molecules and reduced surface hydrophobicity. Quantitative proteomic analysis indicated the reduced abundance of ß-ovomucin (OVO) might be the direct cause of EW thinning. Notably, some proteins extensively involved in the aggregation of proteins during later storage. The results can provide scientific basis for depolymerization and aggregation of EW during storage.