RESUMO
The imaginal disc growth factor (IDGF), belonging to the glycoside hydrolase 18 family, plays an important role in various physiological processes in insects. However, the detail physiological function of IDGF is still unclear. In this study, transcriptome analysis was performed on the fatbody isolated from staged control and BmIDGF mutant silkworm larvae. Transcriptional profiling revealed that the absence of BmIDGF significantly affected differentially expressed genes involved in tyrosine and purine metabolism, as well as multiple energy metabolism pathways, including glycolysis, galactose, starch, and sucrose metabolism. The interruption of BmIDGF caused similar and specific gene expression changes to male and female fatbody. Furthermore, a genome-scale metabolic network integrating metabolomic and transcriptomic datasets revealed 11 pathways significantly altered at the transcriptional and metabolic levels, including amino acid, carbohydrate, uric acid metabolism pathways, insect hormone biosynthesis, and ABC transporters. In conclusion, this multiomics analysis suggests that IDGF is involved in gene-metabolism interactions, revealing its unique role in melanin synthesis and energy metabolism. This study provides new insights into the physiological function of IDGF in insects.
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Bombyx , Masculino , Animais , Feminino , Bombyx/metabolismo , Melaninas/metabolismo , Discos Imaginais/metabolismo , Perfilação da Expressão Gênica , Metabolismo Energético , Peptídeos e Proteínas de Sinalização Intercelular/metabolismoRESUMO
The widespread use of pesticides hampers the immune system of non-target organisms, however, there is a lack of common biomarkers to detect such effects. Myeloid differentiation primary response factor 88 (MyD88) is a crucial junction protein in the Toll-like receptor signaling pathway, which plays an important role in the inflammatory response. In this study, we investigated MyD88 as a potential biomarker for pesticide-induced stress. Phylogenetic analysis revealed that MyD88 was a conserved protein in the evolution of vertebrates and invertebrates. MyD88s usually have death domain (DD) and Toll/interleukin-1 receptor (TIR) domain. Bombyx mori (B. mori) is an important economic insect that is sensitive to toxic substances. We found microbial pesticides enhanced the expression level of MyD88 in B. mori. Transcriptome analysis demonstrated that MyD88 expression level was increased in the fatbody after dinotefuran exposure, a third-generation neonicotinoid pesticide. Moreover, the expression of MyD88 was upregulated in fatbody and midgut by imidacloprid, a first-generation neonicotinoid pesticide. Additionally, insect growth regulator (IGR) pesticides, such as methoprene and fenoxycarb, could induce MyD88 expression in the fatbody of B. mori. These results indicated that MyD88 is a potential biomarker for pesticide-induced stress in B. mori. This study provides novel insights into screening common biomarkers for multiple pesticide stresses and important implications for the development of more sustainable pest management strategies.
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Bombyx , Praguicidas , Animais , Praguicidas/farmacologia , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/farmacologia , Filogenia , Biomarcadores , Neonicotinoides/toxicidade , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismoRESUMO
BACKGROUND: Few studies have reported on the use of intravoxel incoherent motion (IVIM) for renal tumors. PURPOSE: To investigate the value of IVIM for distinguishing renal tumors. MATERIAL AND METHODS: Thirty-one patients with clear cell renal cell carcinomas (CCRCCs), 13 patients with renal angiomyolipomas with minimal fat (RAMFs), eight patients with chromophobe renal cell carcinomas (ChRCCs), and ten patients with papillary renal cell carcinomas (PRCCs) were examined. The tissue diffusivity (D), pseudodiffusivity (D*), and perfusion fraction (f) were calculated. RESULTS: The D and f values were highest for CCRCCs, lowest for PRCCs, and intermediate for ChRCCs and RAMFs ( P < 0.05). The D values of CCRCCs differed significantly from those of ChRCCs and PRCCs ( P < 0.05). The D* values were highest for RAMFs, lowest for ChRCCs, and intermediate for CCRCCs and PRCCs ( P < 0.05). Statistically significant differences were observed between the D* values of CCRCCs and RAMFs ( P < 0.05). The D* values of the CCRCCs differed significantly from the D* values of the ChRCCs ( P < 0.05). Using the D and f values of 1.10 and 0.41, respectively, as the threshold values for differentiating CCRCCs from RAMFs, ChRCCs, and PRCCs, the best results had sensitivities of 81.0% and 66.8% and specificities of 85.7% and 81.0%, respectively. Using the D* value of 0.038 as the threshold value for differentiating RAMFs from CCRCCs, ChRCCs, and PRCCs, the best result obtained had a sensitivity of 90.5% and specificity of 76.2%. CONCLUSION: IVIM may provide information for differentiating renal tumor types.
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Angiomiolipoma/diagnóstico por imagem , Carcinoma Papilar/diagnóstico por imagem , Carcinoma de Células Renais/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Renais/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: The diversity of lichen fungal components and their photosynthetic partners reflects both ecological and evolutionary factors. In present study, molecular investigations of the internal transcribed spacer of the nuclear ribosomal DNA (ITS nrDNA) region were conducted to analyze the genetic diversity of Umbilicaria esculenta and U. muehlenbergii together with their associated green algae. RESULT: It was here demonstrated that the reproductive strategy is a principal reason for fungal selectivity to algae. U. muehlenbergii, which disperses via sexual spores, exhibits lower selectivity to its photosynthetic partners than U. esculenta, which has a vegetative reproductive strategy. The difference of genotypic diversity (both fungal and algal) between these two Umbilicaria species is low, although their nucleotide diversity can vary greatly. CONCLUSIONS: The present study illustrates that lichen-forming fungi with sexual reproductive strategies are less selective with respect to their photobionts; and reveals that both sexual and vegetative reproduction allow lichens to generate similar amounts of diversity to adapt to the environments. The current study will be helpful for elucidating how lichens with different reproductive strategies adapt to changing environments.
Assuntos
Ascomicetos/classificação , Ascomicetos/fisiologia , Clorófitas/classificação , Clorófitas/fisiologia , Variação Genética , Simbiose , Ascomicetos/genética , Clorófitas/genética , Clorófitas/crescimento & desenvolvimento , Análise por Conglomerados , DNA de Algas/química , DNA de Algas/genética , DNA Fúngico/química , DNA Fúngico/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Fungos , Genética Populacional , Haplótipos , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNARESUMO
Hyperlipidemia is a strong risk factor for numerous diseases. Resveratrol (Res) is a non-flavonoid polyphenol organic compound with multiple biological functions. However, the specific molecular mechanism and its role in hepatic lipid metabolism remain unclear. Therefore, the aim of the present study was to elucidate the mechanism underlying how Res improves hepatic lipid metabolism by decreasing microRNA-33 (miR-33) levels. First, blood miR-33 expression in participants with hyperlipidemia was detected by reverse transcription-quantitative PCR, and the results revealed significant upregulation of miR-33 expression in hyperlipidemia. Additionally, after transfection of HepG2 cells with miR-33 mimics or inhibitor, western blot analysis indicated downregulation and upregulation, respectively, of the mRNA and protein expression levels of sirtuin 6 (SIRT6). Luciferase reporter analysis provided further evidence for binding of miR-33 with the SIRT6 3'-untranslated region. Furthermore, the levels of peroxisome proliferator-activated receptor-γ (PPARγ), PPARγ-coactivator 1α and carnitine palmitoyl transferase 1 were increased, while the concentration levels of acetyl-CoA carboxylase, fatty acid synthase and sterol regulatory element-binding protein 1 were decreased when SIRT6 was overexpressed. Notably, Res improved the basic metabolic parameters of mice fed a high-fat diet by regulating the miR-33/SIRT6 signaling pathway. Thus, it was demonstrated that the dysregulation of miR-33 could lead to lipid metabolism disorders, while Res improved lipid metabolism by regulating the expression of miR-33 and its target gene, SIRT6. Thus, Res can be used to prevent or treat hyperlipidemia and associated diseases clinically by suppressing hepatic fatty acid synthesis and increasing fatty acid ß-oxidation.
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BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) showed great value in treating nonalcoholic fatty liver disease (NAFLD). We aimed to compare the effectiveness of long-acting and short-acting GLP-1RAs on improving body weight and related metabolic parameters in patients with type 2 diabetes (T2DM) as a reference for the treatment of NAFLD with T2DM. METHODS: We searched eligible randomized controlled trials (RCTs) in PubMed, Embase, Cochrane and web of science database until August 2023. The risk of bias of included RCTs were assessed by the Risk Assessment of Cochrane Review items. We mainly drew forest plots to compare the effects of long and short acting GLP-1 RAs using RevMan 5.4. RESULTS: Twelve RCTs involving 2751 patients were included in our meta-analysis. Compared with short-acting GLP-1 RAs, the long-acting group was better in body weight (Pâ <â .00001, MDâ =â -0.65, 95% confidence interval [CI] [-0.90, -0.40], I2 = 20%), and the same results in glycosylated hemoglobin (HbA1c) (Pâ <â .00001, MDâ =â -0.43, 95% CI [-0.54, -0.33], I2 = 55%) and fasting plasma glucose (FPG) (Pâ <â .00001, MDâ =â -0.77, 95% CI [-1.01, -0.52], I2 =70%). For the lipid parameters, long-acting drugs lowered cholesterol (TC) (Pâ =â .02, SMDâ =â -0.19, 95% CI [-0.35, -0.03], I2 =57%) and low-density lipoprotein (LDL) (Pâ =â .02, SMDâ =â -0.17, 95% CI [-0.33, -0.02], I2 =51%) more significantly compared with short-acting drugs. But treatment differences were not significant in triglycerides (TG) (Pâ =â .40, SMDâ =â -0.05, 95% CI [-0.15, -0.06], I2 = 0%), and high-density lipoprotein (HDL) (Pâ =â .85, SMDâ =â -0.01, 95% CI [-0.11, -0.09], I2 = 0%). CONCLUSION: Long-acting GLP-1RAs may be more promise than short-acting GLP-1RAs in improving weight and related metabolic parameters.
Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon , Peso CorporalRESUMO
As a third-generation neonicotinoid insecticide, dinotefuran is extensively used in agriculture, and its residue in the environment has potential effects on nontarget organisms. However, the toxic effects of dinotefuran exposure on nontarget organism remain largely unknown. This study explored the toxic effects of sublethal dose of dinotefuran on Bombyx mori. Dinotefuran upregulated reactive oxygen species (ROS) and malondialdehyde (MDA) levels in the midgut and fat body of B. mori. Transcriptional analysis revealed that the expression levels of many autophagy and apoptosis-associated genes were significantly altered after dinotefuran exposure, consistent with ultrastructural changes. Moreover, the expression levels of autophagy-related proteins (ATG8-PE and ATG6) and apoptosis-related proteins (BmDredd and BmICE) were increased, whereas the expression level of an autophagic key protein (sequestosome 1) was decreased in the dinotefuran-exposed group. These results indicate that dinotefuran exposure leads to oxidative stress, autophagy, and apoptosis in B. mori. In addition, its effect on the fat body was apparently greater than that on the midgut. In contrast, pretreatment with an autophagy inhibitor effectively downregulated the expression levels of ATG6 and BmDredd, but induced the expression of sequestosome 1, suggesting that dinotefuran-induced autophagy may promote apoptosis. This study reveals that ROS generation regulates the impact of dinotefuran on the crosstalk between autophagy and apoptosis, laying the foundation for studying cell death processes such as autophagy and apoptosis induced by pesticides. Furthermore, this study provides a comprehensive insight into the toxicity of dinotefuran on silkworm and contributes to the ecological risk assessment of dinotefuran in nontarget organisms.
Assuntos
Bombyx , Animais , Bombyx/genética , Bombyx/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Apoptose , Estresse Oxidativo , Neonicotinoides/metabolismo , AutofagiaRESUMO
Dinotefuran, a third-generation neonicotinoid insecticide, is widely utilized in agriculture for pest control; however, its environmental consequences and risks to non-target organisms remain largely unknown. Bombyx mori is an economically important insect and a good toxic detector for environmental assessments. In this study, ultrastructure analysis showed that dinotefuran exposure caused an increase in autophagic vesicles in the silk gland. Dinotefuran exposure triggered elevated levels of oxidative stress in silk glands. Reactive oxygen species, oxidized glutathione disulfide, glutathione peroxidase, the activities of UDP glucuronosyl-transferase and carboxylesterase were induced in the middle silk gland, while malondialdehyde, reactive oxygen species, superoxide dismutase ï¼ oxidized glutathione disulfide were increased in the posterior silk gland. Global transcription patterns revealed the physiological responses were induced by dinotefuran. Dinotefuran exposure substantially induced the expression levels of many genes involved in the mTOR and PI3K - Akt signaling pathways in the middle silk gland, whereas many differentially expressed genes involved in fatty acid and pyrimidine metabolism were found in the posterior silk gland. Additionally, functional, ultrastructural, and transcriptomic analysis indicate that dinotefuran exposure induced an increase of autophagy in the silk gland. This study illuminates the toxicity effects of dinotefuran exposure on silkworms and provides new insights into the underlying molecular toxicity mechanisms of dinotefuran to nontarget organisms.
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Studies have found associations between cardio-metabolic disorders and socioeconomic status (SES) in developed areas. However, little epidemiological data are available on residents of less developed areas in North China. A cross-sectional study that consisted of 2,650 adults randomly selected from local residents was conducted on a developing province, Hebei. SES was assessed in terms of education, personal income per year, and occupation. The association between SES and metabolic syndrome (MetS) was determined by multivariate logistic regression. The weighted prevalence of MetS was 26.8% among residents of Hebei province. The lower prevalence of MetS and abdominal obesity was associated with increase in SES groups. After adjustments regarding age, sex, body mass index, living area, smoking, salt intake, and family history of diabetes, odds ratio (OR) for elevated blood pressure (BP) of individuals with higher SES level was 0.71 [95% confidence interval (CI): 0.542-0.921] compared with those with lower SES level. Cardio-metabolic risk factors were commonly identified among residents of Hebei province in north China and were associated with SES conditions. This study indicated that from a public health perspective, more attention should be paid to screening of cardio-metabolic disorders in less developed areas.
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INTRODUCTION: MI is defined by the presence of myocardial necrosis, which is caused by acute and persistent ischemia and hypoxia of the coronary artery. In recent years, its incidence rate has been on the rise in China. METHODS: GSE34198, GSE97320 and GSE141512 datasets were download for DEG analysis. KEGG pathway analysis, GO analysis, GSEA and PPI network construction were performed. Later, target genes of candidate miRNAs were predicted. Next, echocardiography was conducted to detect the effects of miR-29 on left ventricular structure and cardiac function in vivo, and H&E staining was adopted to study the effects of miR-29 on angiogenesis and fibrosis in vivo. Furthermore, Western blotting was employed to investigate the effects of miR-29 inhibition on the expressions of proteins related to the PI3K\mTOR\ HIF-1α\VEGF pathway. RESULTS: There were 162 DEGs involved in MI. GO analysis revealed that inflammatory responses, negative regulation of apoptosis and innate immune response were the main enriched biological processes. KEGG analysis manifested that DEGs were mainly enriched in the PI3K/Akt signaling pathway, and GSEA demonstrated that they were mainly enriched in the PI3K/Akt/mTOR, HIF and VEGF pathways. Moreover, target gene prediction showed that miR-29 was lowly expressed in MI. According to Masson's trichrome staining, miR-29 inhibition promoted angiogenesis, reduced fibrosis, and increased the protein expressions of p-PI3K, p-mTOR, HIF-1α, and VEGF. CONCLUSIONS: MiR-29 may play an important role in the growth and development of MI. After inhibition of miR-29, the PI3K/mTOR/HIF-1α/VEGF pathway is activated to alleviate MI.
Assuntos
MicroRNAs , Infarto do Miocárdio , Transdução de Sinais , Apoptose/genética , Fibrose , Humanos , MicroRNAs/metabolismo , Infarto do Miocárdio/metabolismo , Neovascularização Patológica/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Dinotefuran is a third-generation neonicotinoid pesticide and is increasingly used in agricultural production, which has adverse effects on nontarget organisms. However, the research on the impact of dinotefuran on nontarget organisms is still limited. Here the toxic effects of dinotefuran on an important economic species and a model lepidopteran insect, Bombyx mori, were investigated. Exposure to different doses of dinotefuran caused physiological disorders or death. Cytochrome P450, glutathione S-transferase, carboxylesterase, and UDP glycosyl-transferase activities were induced in the fat body at early stages after dinotefuran exposure. By contrast, only glutathione S-transferase activity was increased in the midgut. To overcome the lack of sensitivity of the biological assays at the individual organism level, RNA sequencing was performed to measure differential expressions of mRNA from silkworm larvae after dinotefuran exposure. Differential gene expression profiling revealed that various detoxification enzyme genes were significantly increased after dinotefuran exposure, which was consistent with the upregulation of the detoxifying enzyme. The global transcriptional pattern showed that the physiological responses induced by dinotefuran toxicity involved multiple cellular processes, including energy metabolism, oxidative stress, detoxification, and other fundamental physiological processes. Many metabolism processes, such as carbon metabolism, fatty acid biosynthesis, pyruvate metabolism, and the citrate cycle, were partially repressed in the midgut or fat body. Furthermore, dinotefuran significantly activated the MAPK/CREB, CncC/Keap1, PI3K/Akt, and Toll/IMD pathways. The links between physiological, biochemical toxicity and comparative transcriptomic analysis facilitated the systematic understanding of the integrated biological toxicity of dinotefuran. This study provides a holistic view of the toxicity and detoxification metabolism of dinotefuran in silkworm and other organisms.
Assuntos
Bombyx , Animais , Bombyx/genética , Glutationa Transferase/metabolismo , Guanidinas , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Neonicotinoides/metabolismo , Neonicotinoides/toxicidade , Nitrocompostos , Fosfatidilinositol 3-Quinases/metabolismo , TranscriptomaRESUMO
Vertical Si nano-rings with a uniform thickness of about 100 nm have been fabricated by conventional optical photolithography with a low cost based on Poisson diffraction. Moreover, the roughness of the Si nano-rings can be effectively reduced by sacrificial oxidation. In order to increase the density of the nano-rings, coaxial twin Si nano-rings have been fabricated by the Poisson diffraction method combined with the spacer technique. The thickness of both the inner and outer Si nano-rings is about 60 nm, and the gap between the twin nano-rings is about 100 nm.
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BACKGROUND: The results of previous studies of the relationship between serum uric acid (SUA) and the risk of cardiovascular disease (CVD) have been inconsistent due to confounding factors caused by other known cardiovascular risk factors. OBJECTIVES: This study aimed to evaluate the relationship between SUA and incident CVD in middle-aged and elderly Chinese people, who were stratified according to body mass index (BMI). METHODS: This study recruited 5,721 participants of 40-75 years of age, who were free of CVD at baseline and who underwent follow-up from 2008 to 2017. Participants were categorized in SUA quintiles. Cox proportional hazard and Kaplan-Meier survival analysis were used to compare CVD incidence among the SUA groups. The correlations between SUA and CVD incidence in groups with differing BMI and waist circumference (WC) were also analyzed. A P value <0.05 was considered statistically significant. RESULTS: During a mean follow-up period of 7.6 years, CVD incidence increased with SUA (log-rank test p<0. 001). Compared with the first quintile, the adjusted hazard ratios (95% confidence interval (CI)) for the development of CVD were 1.08 (0.78-1.65), 1.17 (0.88-1.77), 1.47 (1.12-2.21), and 1.68 (1.28-2.44) for the second to fifth quintiles, respectively. This relationship was clearer in participants with normal BMI and WC. The adjusted hazard ratio for each 100 µmol/L increase in SUA was 1.13 (95% CI: 1.02-1.39) for CVD events. CONCLUSIONS: High SUA is an independent risk factor for CVD in middle-aged and elderly northern Chinese people. This effect is maintained even after stratification according to measures of leanness/obesity.
FUNDAMENTO: Os resultados de estudos anteriores sobre a relação entre ácido úrico sérico (AUS) e o risco de doença cardiovascular (DCV) até agora são inconsistentes devido aos fatores de confusão causados por outros fatores de risco cardiovascular conhecidos. OBJETIVOS: Este estudo tem o objetivo de avaliar a relação entre o AUS e as DCV incidentes em chineses de meia-idade e idosos, que foram estratificados de acordo com o índice de massa corporal (IMC). MÉTODOS: Recrutamos 5.721 participantes com idades entre 40 e 75 anos que não tinham diagnóstico de DCV na linha de base, e que foram monitorados de 2008 a 2017. Os participantes foram categorizados em quintis de AUS. A regressão de Cox e a análise de sobrevivência de Kaplan-Meier foram utilizadas para comparar a incidência de DCV entre os grupos de AUS. As correlações entre AUS e a incidência de DCV em grupos com IMC e circunferência de cintura (CC) variados também foram analisadas. Um P valor <0,05 foi considerado estatisticamente significativo. RESULTADOS: Durante um período médio de monitoramento de 7,6 anos, a incidência de DCV aumentou com o AUS (teste de Log-rank p<0,001). Em comparação com o primeiro quintil, as razões de risco padronizadas (intervalos de confiança de 95%) para p desenvolvimento de DCV foram 1,08 (0,781,65), 1,17 (0,881,77), 1,47 (1,122,21), e 1,68 (1,282,44) para o segundo, terceiro, quarto e quinto quintis, respectivamente. Essa relação ficou mais clara em participantes com IMC e CC normais. A razão de risco ajustada para cada aumento de 100 µmol/L de AUS foi de 1,13 (intervalo de confiança de 95%: 1,021,39) para eventos de DCV. CONCLUSÕES: O AUS alto é um fator de risco de DCV independente em pessoas de meia-idade e idosas do norte da China. Esse efeito é mantido mesmo depois da estratificação de acordo com medidas de magreza/obesidade.
Assuntos
Doenças Cardiovasculares , Ácido Úrico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , China/epidemiologia , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: Few studies have explored the associations between ambient air pollution and blood lipid levels. This study aimed to fill this knowledge gap based on a routine health examination cohort in Shijiazhuang, China. METHODS: We included 7063 participants who took the routine health examination for 2-3 times at Hebei General Hospital from January 2016 to December 2018. Individual serum levels of cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured. Their three-month average exposure to air pollution prior to the routine health examinations was estimated using inverse distance weighted method. We used linear mixed-effects regression models to examine the associations between air pollution and levels of blood lipids while controlling for age, gender, body mass index (BMI), smoking, alcohol drinking, temperature, humidity, with a random effect for each individual. RESULTS: Particles with diameters ≤2.5 µm and ≤10 µm (PM2.5 and PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2) and ozone (O3) were all positively associated with TC, TG, and LDL-C and negatively associated with HDL-C, in single pollutant models. Each 10 µg/m3 increment of 3-month average PM2.5 was associated with 0.65% [95% confidence interval (CI): 0.03%-1.28%], 0.56% (95%CI: 0.33%-0.79%) and 0.63% (95%CI: 0.35%-0.91%) increment in TG, TC, and LDL-C, and 0.91% (95%CI: 0.68%-1.13%) decrease in HDL-C. In two-pollutant models, the effects of gaseous pollutants on blood lipids were weakened, while those of PMs were strengthened. Stronger associations were presented in the elderly (≥60 years) and overweight/obese (BMI ≥ 24) participants. CONCLUSIONS: Ambient air pollution had significantly adverse effects on blood lipid levels, especially in overweight/obese and elderly individuals. CAPSULE: Significant associations between increased air pollution and worse blood lipid levels were found, especially in overweight/obese and elderly individuals.
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Poluentes Atmosféricos , Poluição do Ar , Idoso , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Exposição Ambiental/análise , Humanos , Lipídeos , Estudos Longitudinais , Dióxido de Nitrogênio/efeitos adversos , Dióxido de Nitrogênio/análise , Material Particulado/análiseRESUMO
Aging has been attributed to oxidative stress and inflammatory response, in which NF-κB and Nrf2-ARE signaling pathways play significant roles. Senescence accelerated mouse prone 8 (SAMP8) is generally used an animal model for aging studies. Here, we investigated the NF-κB and Nrf2-ARE signaling pathways in SAMP8 brains at different ages and their responses to SS31 peptide treatment. Thirty six SAMP8 mice were separated into aging groups and SS31-treatment groups. The hippocampus from each mouse was dissected for RNA and protein extraction. Cytokines and ROS levels were measured using ELISA and standardised method. Gene expressions of NF-κB, Nrf2 and HO-1 were measured by RT-qPCR. Total protein amount of NF-κB and HO-1, as well as the concentrations of nuclear and cytoplasmic Nrf2 were measured using Western blots. Our data showed that aging could activate both NF-κB and Nrf2-ARE signaling pathways, which could be suppressed and activated by SS31 treatment respectively. Regression analysis revealed that NF-κB gene expression was the most important parameter predicting aging process and SS31 treatment effects in SAMP8. Our findings suggested that SS31 treatment may modulate the inflammatory and oxidative stress status of the aged brains and exert protective effects during brain aging.
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Envelhecimento/efeitos dos fármacos , Envelhecimento/patologia , Antioxidantes/farmacologia , Disfunção Cognitiva/patologia , NF-kappa B/genética , Oligopeptídeos/farmacologia , Envelhecimento/metabolismo , Envelhecimento/psicologia , Animais , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Masculino , Camundongos , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genéticaRESUMO
Resumo Fundamento Os resultados de estudos anteriores sobre a relação entre ácido úrico sérico (AUS) e o risco de doença cardiovascular (DCV) até agora são inconsistentes devido aos fatores de confusão causados por outros fatores de risco cardiovascular conhecidos. Objetivos Este estudo tem o objetivo de avaliar a relação entre o AUS e as DCV incidentes em chineses de meia-idade e idosos, que foram estratificados de acordo com o índice de massa corporal (IMC). Métodos Recrutamos 5.721 participantes com idades entre 40 e 75 anos que não tinham diagnóstico de DCV na linha de base, e que foram monitorados de 2008 a 2017. Os participantes foram categorizados em quintis de AUS. A regressão de Cox e a análise de sobrevivência de Kaplan-Meier foram utilizadas para comparar a incidência de DCV entre os grupos de AUS. As correlações entre AUS e a incidência de DCV em grupos com IMC e circunferência de cintura (CC) variados também foram analisadas. Um P valor <0,05 foi considerado estatisticamente significativo. Resultados Durante um período médio de monitoramento de 7,6 anos, a incidência de DCV aumentou com o AUS (teste de Log-rank p<0,001). Em comparação com o primeiro quintil, as razões de risco padronizadas (intervalos de confiança de 95%) para p desenvolvimento de DCV foram 1,08 (0,78-1,65), 1,17 (0,88-1,77), 1,47 (1,12-2,21), e 1,68 (1,28-2,44) para o segundo, terceiro, quarto e quinto quintis, respectivamente. Essa relação ficou mais clara em participantes com IMC e CC normais. A razão de risco ajustada para cada aumento de 100 μmol/L de AUS foi de 1,13 (intervalo de confiança de 95%: 1,02-1,39) para eventos de DCV. Conclusões O AUS alto é um fator de risco de DCV independente em pessoas de meia-idade e idosas do norte da China. Esse efeito é mantido mesmo depois da estratificação de acordo com medidas de magreza/obesidade.
Abstract Background The results of previous studies of the relationship between serum uric acid (SUA) and the risk of cardiovascular disease (CVD) have been inconsistent due to confounding factors caused by other known cardiovascular risk factors. Objectives This study aimed to evaluate the relationship between SUA and incident CVD in middle-aged and elderly Chinese people, who were stratified according to body mass index (BMI). Methods This study recruited 5,721 participants of 40-75 years of age, who were free of CVD at baseline and who underwent follow-up from 2008 to 2017. Participants were categorized in SUA quintiles. Cox proportional hazard and Kaplan-Meier survival analysis were used to compare CVD incidence among the SUA groups. The correlations between SUA and CVD incidence in groups with differing BMI and waist circumference (WC) were also analyzed. A P value <0.05 was considered statistically significant. Results During a mean follow-up period of 7.6 years, CVD incidence increased with SUA (log-rank test p<0. 001). Compared with the first quintile, the adjusted hazard ratios (95% confidence interval (CI)) for the development of CVD were 1.08 (0.78-1.65), 1.17 (0.88-1.77), 1.47 (1.12-2.21), and 1.68 (1.28-2.44) for the second to fifth quintiles, respectively. This relationship was clearer in participants with normal BMI and WC. The adjusted hazard ratio for each 100 μmol/L increase in SUA was 1.13 (95% CI: 1.02-1.39) for CVD events. Conclusions High SUA is an independent risk factor for CVD in middle-aged and elderly northern Chinese people. This effect is maintained even after stratification according to measures of leanness/obesity.
Assuntos
Humanos , Ácido Úrico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Fatores de Risco , Estudos de Coortes , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To explore the safety and efficacy of a therapeutic regimen for treating severe aplastic anemia (SAA) in its early stage. METHODS: Two groups of SAA patients were enrolled in the present study. One was a treatment group including 21 patients being treated with anti-CD(4), CD(8) monoclonal antibodies as well as cyclosporine A. Another was a control group including 20 patients being treated with anti-lymphocyte globulin and cyclosporine A. RESULTS: The response rates in the two groups were more or less some, being 76.2% for the treatment group and 65.0% for the control group (P > 0.05), but the blood routine examination results showed quicker recovery in the treatment group than in the control group (P < 0.05) and the incidences of side effects related to therapy such as fever were less in the treatment group than in the control group (P < 0.01). CONCLUSIONS: The combination of anti-CD(4), CD(8) monoclonal antibodies and cyclosporine A is safe and efficient in treating SAA.