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Folding thermodynamics, quantitatively described using parameters such as ΔGfold°, ΔHfold°, and ΔSfold°, is essential for characterizing the stability and functionality of noncanonical nucleic acid structures but remains difficult to measure at the molecular level. Leveraging the programmability of dynamic deoxyribonucleic acid (DNA) chemistry, we introduce a DNA-based molecular tool capable of performing a free energy shift assay (FESA) that directly characterizes the thermodynamics of noncanonical DNA structures in their native environments. FESA operates by the rational design of a reference DNA probe that is energetically equivalent to a target noncanonical nucleic acid structure in a series of toehold-exchange reactions, yet is structurally incapable of folding. As a result, a free energy shift (ΔΔGrxn°) is observed when plotting the reaction yield against the free energy of each toehold-exchange. We mathematically demonstrated that ΔGfold°, ΔHfold°, and ΔSfold° of the analyte can be calculated based on ΔΔGrxn°. After validating FESA using six DNA hairpins by comparing the measured ΔGfold°, ΔHfold°, and ΔSfold° values against predictions made by NUPACK software, we adapted FESA to characterize noncanonical nucleic acid structures, encompassing DNA triplexes, G-quadruplexes, and aptamers. This adaptation enabled the successful characterization of the folding thermodynamics for these complex structures under various experimental conditions. The successful development of FESA marks a paradigm shift and a technical advancement in characterizing the thermodynamics of noncanonical DNA structures through molecular tools. It also opens new avenues for probing fundamental chemical and biophysical questions through the lens of molecular engineering and dynamic DNA chemistry.
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DNA , Conformação de Ácido Nucleico , Termodinâmica , DNA/químicaRESUMO
INTRODUCTION: Given the clinical association between thyroid dysfunction and iron deficiency anemia (IDA), as well as their shared association with iron status, this study aimed to investigate the causal relationship between iron status and thyroid dysfunction, while also examining the risk of IDA in relation to thyroid dysfunction. METHODS: A two-sample mendelian randomization (MR) study was conducted to identify the causal relationship of iron status on thyroid dysfunction, as well as thyroid dysfunction on IDA. Large-scale European population-based genome-wide association study databases were utilized (Genetics of Iron Status consortium, ThyroidOmics consortium, FinnGen consortium, and UK Biobank). Inverse variance-weighted (IVW) was used as the main analysis. In addition, we used weighted median and MR-Egger to enhance the robustness. Sensitivity analysis was conducted to evaluate the robustness of MR results. RESULTS: The IVW estimates did not reveal any significant causal relationship between serum iron status markers and thyroid dysfunction. However, a significant causal relationship was observed between hypothyroidism and IDA (odds ratio [OR] = 1.101, 95% confidence interval [CI] = 1.048-1.157, p < 0.001). Repeated analyses also demonstrated a similar trend (OR = 1.023, 95% CI = 1.011-1.035, p < 0.001). Sensitivity analysis supported that the MR estimates were robust. CONCLUSION: In our MR study, an upregulation of the hypothyroidism-associated gene was found to be significantly associated with an elevated risk of IDA in the European population. These findings may offer novel therapeutic insights for clinicians managing patients with hypothyroidism, IDA, or their comorbidities.
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Food withdrawal is usually used for accurate feed metabolizable energy (ME) assessment in poultry, but its effects on intestinal structure and the absorption of nutrients are unclear. In this study, broilers were fed ad libitum (CT) or withdrew food for 12 (FH12), 24 (FH24), 36 (FH36), or 48 hours (FH48). We showed that food withdrawal increased the energy assimilation when compared with the CT. Food withdrawal improved the digestibility of ether extract and the level of lipid substances and fatty acid-derived ß-hydroxybutyrate in serum. Compared to the CT, food withdrawal did not influence the digestibility of starch. Due to 12 hours or longer food withdrawal duration increased glutamate oxidation and uric acid excretion, the analyzed digestibility of crude protein was underestimated, although the upregulated amino acid transporter genes. In addition, histological analysis showed that short-term food withdrawal (12 hours) increased intestinal villus height, crypt depth, and proliferative cell, whereas prolonged food withdrawal (more than 24 hours) impaired villus structure due to the decreased cell proliferation. Moreover, proteomics analysis revealed upregulated pathways in birds withdrawn food for 36 hours involved in nutrient absorption and amino acid oxidation. In conclusion, food withdrawal changes nutrient absorption and utilization, especially for amino acid and ether extract, and results in increased ME. Both glutamate oxidation and fatty acid incomplete oxidation are involved in energy supply after refeeding. In contrast to short-term food withdrawal, prolonged food withdrawal impairs the intestinal structure and villus renewal. Our findings deserve attention from nutritionists who are analyzing food digestibility.
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Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Galinhas/metabolismo , Metabolismo Energético , Mucosa Intestinal , Animais , Mucosa Intestinal/anatomia & histologia , Mucosa Intestinal/crescimento & desenvolvimento , Mucosa Intestinal/metabolismo , MasculinoRESUMO
In this study, headspace solid-phase micro-extraction (HS-SPME) coupled with GC-MS was used to analyze the trend of volatile compounds in fresh and oxidative infant nutrition package. Among the volatile compounds, aldehydes and ketones, alcohols, lipids, cycloalkenes, alkanes, alkenes, aromatic hydrocarbons, oxygenated compound were identified. A total of 65 volatile compounds were detected in the fresh nutrition package, whereas 9 new volatile compounds were detected during the accelerated oxidation process, which was oxidized at 45 °C for 4 weeks. The main components of the rancid flavor formed and the relative content of volatile substances gradually changed during the accelerated oxidation process. The volatile substances hexanal, nonanal, and 2-pentylfuran substantially increased. Linalool, α-terpineol, d-limonene, and 1-methoxy-nonane presented an evidently downward trend. The relative content of the newly formed compound 3-hydroxy-2-methylpyran-4-one during the oxidation process was always large, its relative content initially increased, then decreased, and finally increased again. The formation of rancid flavor of the nutrient package was speculated to have been formed by the interaction of hexanal, nonanal, 2-pentylfuran, and 3-hydroxy-2-methylpyran-4-one.
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In this investigation, the improved electrochemical behavior in Si-doped Li-rich cathodes is studied with scanning transmission electron microscopy (STEM) and electron energy loss spectroscopy (EELS). Z-contrast images show a layered structure that develops a thin, spinel-like surface layer after the first charge cycle. Si-doping increases discharge capacity by â¼25% and appears to retard the surface phase transformation. Based on electron energy loss spectra, the surface layer in the doped material has an altered oxygen electronic environment, which supports the STEM findings. Furthermore, Si-doping changes the redox behavior during the activation cycle. Density functional theory calculations indicate that Si-doping can increase oxygen vacancy formation, and change the sequence of the redox couples by introducing more oxygen vacancies before or during the typical high voltage activation process. The results of this work indicate that the type of doping employed here is an effective strategy for controlling the complex charge compensation mechanisms in lithium-rich cathodes.
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OBJECTIVE: Vitamin D is an essential nutrient that regulates the activity of calcium and bone hormones throughout life; however, vitamin D levels in children, which is the most crucial period during human development, has not been established. METHODS: As the first descriptive study of serum vitamin D levels in children in Yunnan Province, we determined the serum vitamin D levels in children 0â4 years of age who underwent physical examinations at Kunming Children's Hospital, and the association between the serum vitamin D level and the calcium, phosphorus and alkaline levels. RESULTS: Vitamin D levels in children were highest in the summer months and lowest in the winter months. Vitamin D deficiency was more common in girls than boys. A social-economic effect was shown, as evidenced by the significantly higher serum vitamin D levels in children from the top five cities compared with the lower-ranked cities. Moreover, we also demonstrated a significant correlation between vitamin D and serum calcium levels. CONCLUSION: Our study suggested that sex and age affected the vitamin D levels of children, and a reasonable reference range in children 0-4 years of age in Yunnan Province was determined.
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Deficiência de Vitamina D , Vitamina D , Cálcio , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/epidemiologia , VitaminasRESUMO
BACKGROUND: In recent years, increased attention has been focused on breast muscle yield and meat quality in poultry production. Supplementation with nicotinamide and butyrate sodium can improve the meat quality of broilers. However, the potential molecular mechanism is not clear yet. This study was designed to investigate the effects of supplementation with a combination of nicotinamide and butyrate sodium on breast muscle transcriptome of broilers under high stocking density. A total of 300 21-d-old Cobb broilers were randomly allocated into 3 groups based on stocking density: low stocking density control group (L; 14 birds/m2), high stocking density control group (H; 18 birds/m2), and high stocking density group provided with a combination of 50 mg/kg nicotinamide and 500 mg/kg butyrate sodium (COMB; 18 birds/m2), raised to 42 days of age. RESULTS: The H group significantly increased cooking losses, pH decline and activity of lactate dehydrogenase in breast muscle when compared with the L group. COMB showed a significant decrease in these indices by comparison with the H group (P < 0.05). The transcriptome results showed that key genes involved in glycolysis, proteolysis and immune stress were up-regulated whereas those relating to muscle development, cell adhesion, cell matrix and collagen were down-regulated in the H group as compared to the L group. In contrast, genes related to muscle development, hyaluronic acid, mitochondrial function, and redox pathways were up-regulated while those associated with inflammatory response, acid metabolism, lipid metabolism, and glycolysis pathway were down-regulated in the COMB group when compared with the H group. CONCLUSIONS: The combination of nicotinamide and butyrate sodium may improve muscle quality by enhancing mitochondrial function and antioxidant capacity, inhibiting inflammatory response and glycolysis, and promoting muscle development and hyaluronic acid synthesis.
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Proteínas Aviárias/genética , Ácido Butírico/administração & dosagem , Perfilação da Expressão Gênica/métodos , Niacinamida/administração & dosagem , Músculos Peitorais/crescimento & desenvolvimento , Produtos Avícolas/análise , Ração Animal , Animais , Ácido Butírico/farmacologia , Galinhas , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Glicólise , Concentração de Íons de Hidrogênio , Niacinamida/farmacologia , Músculos Peitorais/química , Músculos Peitorais/efeitos dos fármacos , Distribuição Aleatória , Análise de Sequência de RNARESUMO
To study why flaxseed supplementation causes adverse effects on the performance of poultry, we investigated the gut microbiota of Peking ducks after consumption of a flaxseed diet. A total of 792, 12-day-old white Peking ducks were divided into four groups. In the control group, birds were provided with a basal diet. In the three experimental groups, the birds were fed flaxseed containing diet (10% flaxseed and 90% basal diet) for 30, 20 and 10 d, respectively. On day 42, ceca were collected to evaluate the bacterial diversity of the gut microbiota using microbial 16S rDNA gene profiling; serums were obtained to determine the levels of inflammatory mediators. The flaxseed diet decreased the alpha diversity and shifted the predominant genera of the gut microbiota. Flaxseed-fed groups had higher abundances of Escherichia/Shigella (p < 0.1) and Campylobacter (p < 0.05) than the control group. The abundance of pro-inflammatory bacteria such as Veillonellaceae increased (p < 0.05) at first and then decreased (p < 0.05) with prolonged flaxseed supplementation. The levels of prostaglandin E2 and Leukotriene B4 in serum showed the same pattern as that of the pro-inflammatory bacteria. In conclusion, flaxseed diets are associated with inflammation by altering the cecal microbiota dynamics.
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Ração Animal/efeitos adversos , Patos/microbiologia , Linho , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/induzido quimicamente , Animais , Bactérias/classificação , Bactérias/genética , Inflamação/veterináriaRESUMO
OBJECTIVE: To study the association between interleukin-8 (IL-8) rs4073 polymorphisms and susceptibility to sepsis in full-term neonates through a prospective study. METHODS: A total of 50 neonates who were diagnosed with sepsis based on positive blood culture from January to December 2017 were enrolled as the sepsis group. Fifty neonates who had clinical symptoms and negative blood culture were enrolled as the clinical sepsis group. Fifty neonates without infection were enrolled as the control group. Sequencing was used to detect the polymorphisms of IL-8 rs4073. The three groups were compared in terms of the frequencies of genotypes and alleles. A multivariate logistic regression analysis was used to investigate the association of IL-8 rs4073 genotypes with sepsis in full-term neonates. RESULTS: There were significant differences in the frequencies of genotypes and alleles at IL-8 rs4073 among the three groups (P<0.05). The logistic regression analysis showed that a low gestational age and TT genotype at IL-8 rs4073 were risk factors for the pathogenesis of sepsis in neonates (P<0.05). CONCLUSIONS: The full-term neonates with TT genotype at IL-8 rs4073 may be susceptible to sepsis.
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Interleucina-8/genética , Sepse Neonatal , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Recém-Nascido , Sepse Neonatal/genética , Polimorfismo de Nucleotídeo Único , Estudos ProspectivosRESUMO
BACKGROUND: Functional dyspepsia (FD) is considered a bio-psychosocial disorder. The role of psychosocial factors in FD pathogenesis remains unclear. METHODS: This study evaluated sleep quality and mood symptoms in patients with FD, assessing the associations of FD severity, disordered sleep, and psychological symptoms. One-hundred-and-fifteen adult patients with typical FD symptoms were enrolled alongside 61 healthy volunteers. Rome III criteria were used to evaluate FD symptoms; sleep disorder was assessed with the Pittsburgh Sleep Quality Index (PSQI), and Symptom Checklist-90-Revised (SCL-90R) was utilized to determine the status of depression, anxiety and other psychological symptoms. RESULTS: PSQI scores and nine symptomatic dimensions of SCL-90R were significantly higher in FD patients than in controls. Multiple logistic regression indicated that lower BMI, lower level of education, and sleep disturbance were independently associated with FD and FD subgroups. Hostility and phobic anxiety were independent risk factors for FD. Further analysis showed that hostility was an independent risk factor for both FD subgroups, and somatization and additional psychiatric symptoms for epigastric pain syndrome. CONCLUSIONS: We found that FD was associated with sleep disorder and psychopathological factors. These findings suggest that implementing sleeping and/or psychological therapies may help reduce FD symptoms.
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Dispepsia/psicologia , Transtornos do Sono-Vigília/etiologia , Estresse Psicológico/etiologia , Dor Abdominal/fisiopatologia , Dor Abdominal/psicologia , Adolescente , Adulto , Ansiedade/complicações , Ansiedade/psicologia , Depressão/complicações , Depressão/psicologia , Dispepsia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Sono , Transtornos do Sono-Vigília/psicologia , Estresse Psicológico/psicologia , Inquéritos e Questionários , Adulto JovemRESUMO
PURPOSE: There is compelling evidence that long-stranded non-coding RNAs (lncRNAs) play an important role in the progression of hepatocellular carcinoma (HCC). The aim of this study was to investigate the role of lncRNA XXYLT1 antisense-2 (XXYLT1-AS2) in HCC progression. METHODS: Real-time PCR was used to assess the levels of XXYLT1-AS2 in plasma from HCC and normal patients. Cell proliferation, apoptosis, migration, and invasion were monitored, and tumor xenografts were established to investigate the biological functions of XXYLT1-AS2 by gain-of-function and loss-of-function studies in vitro and in vivo, the expression of autophagy biomarkers and transcriptional factor EB (TFEB) was examined by immunoprecipitation, ubiquitination assays, and western blotting. Autophagy inhibitor, 3-methyladenine (3MA), and proteasome inhibitor, MG132, were used to verify the role of autophagy in HCC progression and the effect of XXYLT1-AS2 on TFEB ubiquitination, respectively. RESULTS: In this study, we identified that lncRNA XXYLT1-AS2 is highly expressed in HCC plasma and promotes tumor growth in vivo. In functional studies, it was found that silent expression of XXYLT1-AS2 inhibited HCC proliferation, migration, invasion, and activated autophagy of HCC cells, which were attenuated by autophagy inhibitor, 3MA. Mechanistically, XXYLT1-AS2 decreased the protein level of TFEB through promoting its degradation by ubiquitin proteasome pathway. CONCLUSION: XXYLT1-AS2 plays an oncogenic role in HCC progression through inhibition of autophagy via promoting the degradation of TFEB, and thus could be a novel target for HCC treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Humanos , Carcinoma Hepatocelular/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Hepáticas/patologia , Linhagem Celular Tumoral , Autofagia/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , MicroRNAs/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismoRESUMO
Alcoholic liver disease (ALD) encompasses liver damage caused by chronic, excessive alcohol consumption. It manifests initially as marked hepatocellular steatosis and can progress to steatohepatitis, liver fibrosis, and cirrhosis. With China's rapid economic growth, coupled with a complex social background and the influence of a deleterious wine culture, the number of patients with ALD in China has increased significantly; the disease has become a social and health problem that cannot be ignored. In this review, we briefly described the social factors affecting ALD in China and elaborated on differences between alcoholic and other liver diseases in terms of complications (e.g., cirrhosis, upper gastrointestinal bleeding, hepatic encephalopathy, hepatocellular carcinoma, addiction, and other extrahepatic diseases). We also emphasized that ALD was more dangerous and difficult to treat than other liver diseases due to its complications, and that precise and effective treatment measures were lacking. In addition, we considered new ideas and treatment methods that may be generated in the future.
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NonSMC condensin I complex subunit D2 (NCAPD2) is a newly identified oncogene; however, the specific biological function and molecular mechanism of NCAPD2 in liver cancer progression remain unknown. In the present study, the aberrant expression of NCAPD2 in liver cancer was investigated using public tumor databases, including TNMplot, The Cancer Genome Atlas and the International Cancer Genome Consortium based on bioinformatics analyses, and it was validated using a clinical cohort. It was revealed that NCAPD2 was significantly upregulated in liver cancer tissues compared with in control liver tissues, and NCAPD2 served as an independent prognostic factor and predicted poor prognosis in liver cancer. In addition, the expression of NCAPD2 was positively correlated with the percentage of Ki67+ cells. Finally, singlecell sequencing data, geneset enrichment analyses and in vitro investigations, including cell proliferation assay, Transwell assay, wound healing assay, cell cycle experiments, cell apoptosis assay and western blotting, were carried out in human liver cancer cell lines to assess the biological mechanisms of NCAPD2 in patients with liver cancer. The results revealed that the upregulation of NCAPD2 enhanced tumor cell proliferation, invasion and cell cycle progression at the G2/Mphase transition, and inhibited apoptosis in liver cancer cells. Furthermore, NCAPD2 overexpression was closely associated with the phosphatidylinositol 3kinase (PI3K)Aktmammalian target of rapamycin (mTOR)/cMyc signaling pathway and epithelialmesenchymal transition (EMT) progression in HepG2 and Huh7 cells. In addition, upregulated NCAPD2 was shown to have adverse effects on overall survival and diseasespecific survival in liver cancer. In conclusion, the overexpression of NCAPD2 was shown to lead to cell cycle progression at the G2/Mphase transition, activation of the PI3KAktmTOR/cMyc signaling pathway and EMT progression in human liver cancer cells.
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Proliferação de Células , Neoplasias Hepáticas , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Humanos , Serina-Treonina Quinases TOR/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Transdução de Sinais/genética , Fosfatidilinositol 3-Quinases/metabolismo , Masculino , Feminino , Proliferação de Células/genética , Carcinogênese/genética , Carcinogênese/patologia , Carcinogênese/metabolismo , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica , Progressão da Doença , Linhagem Celular Tumoral , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Transição Epitelial-Mesenquimal/genética , Apoptose/genética , Movimento Celular/genética , PrognósticoRESUMO
Immune rejection remains the major cause of corneal graft failure. Immunosuppressants (such as rapamycin; RAPA) adjunctive to antibiotics (such as levofloxacin hydrochloride; Lev) are a clinical mainstay after corneal grafts but suffer from poor ocular bioavailability associated with severe side effects. In this study, we fabricated a Lev@RAPA micelle loaded cationic peptide-based hydrogel (NapFFKK) as a dual-drug delivery system by integrating RAPA micelles with Lev into a cationic NapFFKK hydrogel to potentially reduced the risk of corneal graft rejection. The properties of the resulting hydrogels were characterized using transmission electronmicroscopy and rheometer. Lev@RAPA micelles loaded NapFFKK hydrogel provided sustained in vitro drug release without compromising their inherent pharmacological activities. Topical instillation of Lev@RAPA micelles loaded NapFFKK hydrogel resulted in the great ocular tolerance and extended precorneal retention over 60 min, thus significantly enhancing the ocular bioavailability of both Lev and RAPA. Overall, such dual-drug delivery system might be a promising formulation for the suppression of corneal graft failure.
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Transplante de Córnea , Sistemas de Liberação de Medicamentos , Rejeição de Enxerto , Hidrogéis , Micelas , Nanopartículas , Rejeição de Enxerto/prevenção & controle , Hidrogéis/química , Animais , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Transplante de Córnea/métodos , Coelhos , Liberação Controlada de Fármacos , Sirolimo/administração & dosagem , Sirolimo/farmacocinética , Sirolimo/química , Levofloxacino/administração & dosagem , Levofloxacino/farmacocinética , Levofloxacino/química , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Imunossupressores/química , Disponibilidade Biológica , Masculino , Córnea/efeitos dos fármacos , Córnea/metabolismo , Portadores de Fármacos/químicaRESUMO
During the cold chain storage process, changes in metabolites and microorganisms are highly likely to lead to changes in meat quality. To elucidate the changes in the composition of metabolites and microbiota during cold chain storage of mutton, this study utilized untargeted metabolome and 5R 16S rRNA sequencing analyses to investigate the changes in the longissimus dorsi under different cold chain temperatures (4 °C and -20 °C). With the extension of cold chain storage time, the meat color darkened and the content of C18:2n-6, C20:3n-6, and C23:0 were significantly increased in mutton. In this study, nine metabolites, including 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine, alanylphenylala-nine, indole-3-acrylic acid and the others, were significantly altered during cold chain storage. The abundance of the dominant microorganisms, including Brachymonas, Aeromonas, Corynebacterium and Steroidobacter, was significantly altered. Furthermore, a high correlation was observed between the different metabolites and microorganisms. These findings provide an in-depth understanding of the effects of different cold chain storage temperatures and times on the quality of mutton.
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Temperatura Baixa , Armazenamento de Alimentos , Armazenamento de Alimentos/métodos , Animais , Carne/microbiologia , RNA Ribossômico 16S/genética , Bactérias/genética , Bactérias/classificação , Bactérias/metabolismo , Microbiologia de Alimentos , Microbiota , Metaboloma , RefrigeraçãoRESUMO
Background: Qinggan Huoxue recipe (QGHXR), a traditional Chinese medicinal formula, has a protective effect against liver fibrosis. However, the underlying mechanisms remain unclear. Objective: This study investigated the antifibrotic role of QGHXR and its underlying mechanisms. Methods: The composition of QGHXR was determined using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Female C57BL/6J mice were fed either a Lieber-DeCarli liquid diet or pair-fed control diet and intraperitoneally injected with CCl4 for 8 weeks (n = 8). In week 5, the mice were administered 100, 200, and 400 mg/kg QGHXR via oral gavage daily for 4 weeks. Results: UPLC-MS result showed that QGHXR contained 45 compounds including salvianolic acid A, scutellarin, baicalin, rutin, and chai saponin D. QGHXR alleviated pathological alterations in the liver. The alanine aminotransferase (ALT) level was reduced to 44.88 ± 4.39 U/L, aspartate aminotransferase (AST) to 76.25 ± 4.17 U/L, alkaline phosphatase (ALP) to 60.75 ± 5.41 U/L, and acetaldehyde to 38.54 ± 1.01 U/L compared with that of the control group (ALT 72.38 ± 5.19 U/L, AST 119.63 ± 9.82 U/L, and ALP 98.63 ± 6.71 U/L and acetaldehyde 64.86 ± 4.70 U/L). QGHXR inhibited lipid overproduction and fibrotic gene expression. The serum concentration of chemokine C-X-C ligand 16 (CXCL16) was reduced to 62.83 ± 6.80 pg/ml compared with that of the control group (130.91 ± 13.72 pg/mL). QGHXR downregulated CXCL16 mRNA and protein expressions. Pharmacological CXCL16 treatment reversed the QGHXR-induced protective effects in ethanol plus CCl4 fed mice. QGHXR reduced CXCL16 levels (91.97 ± 5.86 pg/ml) in LPS-stimulated RAW264.7 cells compared with that of the control group (148.68 ± 8.62 pg/ml) and inhibited toll-like receptor 4 and nuclear factor-kappa B phosphorylation. Conclusions: This study demonstrated that QGHXR mitigates experimental alcoholic liver fibrosis by CXCL16 inhibition, and may be considered a potential therapeutic agent for treating liver fibrosis.
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Objective: To investigate the correlation between FGA gene polymorphisms and coronary artery lesion in Kawasaki disease. Methods: Two hundred and thirty four children with Kawasaki disease (KD group), 200 healthy children (normal group) and 208 children with non-KD fever (fever group) were enrolled. General clinical indicators, the concentration of serum MMPs, TIMP-1, FG-α,fibrinogen level, molecular function (FMPV/ODmax) and FGA Thr312Ala polymorphism were detected individually by testing peripheral venous blood after fasting in the morning. Results: There was no significant difference in average age among the three groups, which were 3.03 ± 1.22 years, 3.17 ± 1.30 years, and 3.21 ± 1.31 years, respectively. Compared with those in the fever group, the levels of white blood cell count (WBC), platelet count (PLT), procalcitonin (PCT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and fibrinogen (Fg) levels were significantly increased in the KD group. Red blood cell count (RBC) and hemoglobin (Hb) levels were significantly decreased (p < 0.05).The concentration of serum MMPs, TIMP-1, and FG-α in the KD and fever groups were significantly higher than those in the normal group (p < 0.05). The concentration of MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1, and FG-α in the KD group were significantly higher than those in the fever group (p < 0.05).The KD group was divided into two subgroups,55 patients with combined CAL and 179 patients without combined CAL. The plasma fibrinogen concentration in the combined CAL group was significantly higher than that in the non-combined CAL and normal groups (p < 0.01). There was no statistically significant difference in FMPV/ODmax among the three groups (p > 0.05). Compared with normal group, the FGA GG, GA, and AA genotype and G, A allele frequency of the FGA gene polymorphism in the KD group showed no significant difference (p > 0.05). In the KD group, the most common type in children with CAL was GA, while the most common type in children without CAL was GG. Conclusion: MMPs and FG-α were significantly upregulated in KD patients. The proportion of FGA genotype GA in children with CAL was significantly higher than that in children without CAL, suggesting that FGA gene polymorphisms affect coronary artery lesion in children with KD.
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Objectives: We previously revealed that scorpio and centipede (SC) improve the inflammatory response in asthma, whereas it is unclear whether ferroptosis is involved in this process. Materials and Methods: The asthmatic mouse model was established and lung tissues were collected for histopathological examination. The levels of tumor necrosis factor-α (TNF-α), interleukin- (IL-)1ß, Fe2+, malondialdehyde (MDA), glutathione peroxidase 4 (GPX4), ferritin heavy chain 1(FTH1), and reactive oxygen species (ROS) were assessed in asthmatic mice and mouse airway epithelial cells. Results: Our results showed that ferroptosis was induced in asthmatic mice, as evidenced by the reduction of FTH1 and GPX4 expression and the increase of MDA and Fe2+ levels (all P<0.05). Ferrostatin-1 repressed inflammation and ferroptosis of asthmatic mice. Additionally, SC significantly inhibited the levels of TNF-α, IL-1ß, MDA, and Fe2+, while enhancing FTH1 and GPX4 expression. However, SC plus erastin showed the reverse results. Moreover, ferroptosis remarkably increased in asthmatic airway epithelial cells, while SC suppressed ferroptosis of the cells (all P<0.05). Conclusion: SC ameliorated asthma by inhibiting the crosstalk between ferroptosis and inflammation in airway epithelial cells.
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The objective of the following study was to investigate the effects of naturally oxidized corn oil on the antioxidant capacity and lipid metabolism of broilers. A total of 450, 1-day-old Arbor Acres male broilers were randomly divided into 5 treatments with 6 replicate cages and 15 birds/cage. The dietary treatment array consisted of ratios of naturally oxidized corn oil to non-oxidized corn oil from 0:100, 25:75, 50:50, 75:25, and 100:0, respectively. Serum, liver, and abdominal fat samples were taken at 42 d. The results showed that the liver organ index, liver catalase (CAT) activity, malondialdehyde (MDA) content, and the serum aspartate aminotransferase (AST) content had significant quadratic relationships with the ratio of naturally oxidized corn oil (P < 0.05). Inflammatory infiltrating cells appeared in the liver of the 50% and 75% oxidized corn oil group. The percentage of abdominal fat, and serum free fatty acids (FFA) content increased linearly with the increased proportion of oxidized corn oil (P < 0.05). The mRNA expression of NADH quinone oxidoreductase 1 (NQO-1), nuclear factor kappa B (NF-κB), toll-like receptor-4 (TLR-4), peroxisome proliferators activate receptor-α (PPARα), carnitine acyltransferase (CPT1), and acyl-coenzyme oxidase (ACO) of the liver increased linearly while oxidized corn oil increased in the diet (P < 0.05). Diets containing 100% oxidized corn oil significantly changed the mRNA expression of liver Caveolin compared with other treatment groups (P < 0.05). Taken together, this study demonstrated that naturally oxidized corn oil could change liver lipid metabolism and accelerate lipid deposition of broilers by upregulating PPARα.
Assuntos
Óleo de Milho , Proliferadores de Peroxissomos , Masculino , Animais , Óleo de Milho/metabolismo , Proliferadores de Peroxissomos/metabolismo , Proliferadores de Peroxissomos/farmacologia , Metabolismo dos Lipídeos , Galinhas/fisiologia , PPAR alfa/genética , PPAR alfa/metabolismo , PPAR alfa/farmacologia , Dieta/veterinária , Fígado/metabolismo , Antioxidantes/metabolismo , RNA Mensageiro/metabolismo , Suplementos Nutricionais/análise , Ração Animal/análise , Ensaios Clínicos Veterinários como AssuntoRESUMO
Objective: To investigate the effects of the training of aerobic function on clinical symptoms and quality of life in patients with medium and advanced lung cancer. Methods: The study objects were 84 patients with medium and advanced lung cancer who were treated in our hospital (July 2019-July 2021) and their materials were retrospectively reviewed. Depending on the different intervention modes, they were equally divided into control group (routine nursing intervention measures) and experiment group (training of aerobic function), with 42 cases in each group. The clinical symptoms and living quality were compared between the two groups. Results: After intervention, affective meaning, behavior/severity, cognitive/mood, and sensory scores in both groups were decreased, and the various indexes in the experiment group were lower compared with the control group (P < 0.05). After intervention, the patients' clinical symptoms, such as pain, inappetence, insomnia, and dyspnea in the two groups were improved, and the experiment group achieved eminently better improvement compared with the control group (P < 0.05). After intervention, the walking distances in 6 minute walk test (6MWT) in both groups were increased, and the experiment group achieved observably longer walking distance compared with the control group (P < 0.05). After intervention, the patients' pulmonary function indexes of forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), and FEV1/FVC% level in the two groups were all improved, and the experiment group had signally better indexes compared with the control group (P < 0.05). After intervention, the patients' scores of Quality of Life Questionnaire-Core Questionnaire (QLQ-C30) in both groups were decreased, and the experiment group achieved much lower score compared with the control group (P < 0.05). Conclusion: The training of aerobic function has obvious therapeutic effect on medium and advanced lung cancer. This training can mitigate the patients' cancer-related fatigue and clinical symptoms, improve their pulmonary function, and enhance their athletic ability and quality of life.