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BACKGROUND: Exploring the association between Childhood Emotional Support (CES) and the mechanisms of aging is pivotal for understanding its potential to lessen the incidence of age-related pathologies and promote a milieu for healthy aging. METHODS: Utilizing data from the UK Biobank comprising nearly 160,000 individuals, comprehensive analyses were conducted to explore associations between CES levels and age-related diseases, biological age and aging hallmarks. Cox proportional hazards regression models were used to investigate the relationship between CES and the risk of hospitalization for age-related diseases. Linear regression models were employed to explore the associations between CES and the frailty index (FI), Klemera-Doubal method (KDM) biological age acceleration, homeostatic dysregulation (HD), C-reactive protein (CRP), white blood cell (WBC) count, and telomere length. RESULTS: The analyses revealed a significant association between higher CES levels and a decreased risk of hospitalization for age-related diseases in later life. After adjustments for covariates, the hazard ratio for age-related diseases was 0.87 (95 % confidence interval, 0.83-0.91, p < 0.001) in those with the highest CES level compared to those with the lowest CES level. Participants with the highest CES level exhibited lower FI scores (coefficient = -0.033, p < 0.001), reduced CRP level (coefficient = -0.097, p < 0.05) and lower WBC counts (coefficient = -0.034, p < 0.05). Stratified analyses based on genetic susceptibility further elucidated the protective role of CES against age-related diseases. CONCLUSION: These findings underscore the potential of early interventions targeting CES to promote healthy aging and alleviating the burden of age-related diseases.
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BACKGROUND: Maternal smoking during pregnancy (MSDP) is significantly linked to the short- or long-term health of offspring. However, little research has examined whether MSDP affect the aging rate of offspring. METHODS: This study used questionnaires to determine out whether the participants' mothers smoked when they were pregnant. For evaluating aging rate, we used the following several outcome measures: telomere length, frailty index, cognitive function, homeostatic dysregulation score, KDM-age, age-related hospitalization rate, premature death, and life expectancy. RESULT: After adjusting for covariates, we found that the offspring of the MSDP group had significantly shorter telomere length in adulthood by 0.8 % (ß = -0.008,95%CI:-0.009 to -0.006) compared with non-MSDP group. Compared to the non-MSDP group, participants in MSDP group showed higher levels of homeostatic dysregulation (ß = 0.015,95%CI: 0.007-0.024) and were frailer (ß = 0.008,95%CI:0.007-0.009). The KDM age increased by 0.100 due to MSDP (ß = 0.100,95 % CI:0.018-0.181), and the age acceleration of KDM algorithm also increases significantly (ß = 0.101, 95%CI:0.020-0.183). Additionally, we found that the risk of aging-related hospitalizations was significantly higher than the non-MSDP group by 10.4 %(HR = 1.104,95%CI:1.066-1.144). Moreover, MSDP group had a 12.2 % increased risk of all-cause premature mortality (HR = 1.122,95%CI:1.064-1.182) and a significant risk of lung cancer-specific premature mortality increased by 55.4 %(HR = 1.554,95%CI:1.346-1.793). In addition, participants in the MSDP group had significantly decreased cognitive function and shorter life expectancies than those in non-MSDP group. CONCLUSION: Our findings indicated a significant association between MSPD and accelerated aging, elevated hospitalization rates, increased premature mortality rates, and reduced life expectancies in offspring.
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BACKGROUND: Although previous research has indicated a correlation between smoking and the mortality rate in patients with lung cancer, the impact of early life factors on this relationship remains unclear and requires further investigation. This study aimed to investigate the hypothesis that breastfeeding reduces the risk of lung cancer-related death. METHODS: The authors conducted a prospective cohort study involving 501 859 participants recruited from the United Kingdom Biobank to explore the potential association between breastfeeding and the risk of lung cancer mortality using a Cox proportional hazards model. Subsequently, the polygenic risk score for lung cancer was calculated to detect interactions between genes and the environment. RESULTS: Over a median follow-up duration of 11.8 years, encompassing a total of 501 859 participants, breastfeeding was found to reduce the risk of lung cancer-related death and the impact of maternal smoking on lung cancer mortality in adult offspring. This association remained consistent after stratification. Furthermore, the influence of maternal smoking and breastfeeding on the risk of lung cancer mortality was significant at a high genetic risk level. CONCLUSION: Breastfeeding can reduce the risk of lung cancer-related death and the impact of maternal smoking on lung cancer mortality in adult offspring. This correlation has the potential to reduce the probability of lung-cancer-related deaths in subsequent generations.
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Aleitamento Materno , Neoplasias Pulmonares , Fumar , Humanos , Estudos Prospectivos , Feminino , Neoplasias Pulmonares/mortalidade , Aleitamento Materno/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Adulto , Fumar/efeitos adversos , Reino Unido/epidemiologia , Modelos de Riscos Proporcionais , Filhos Adultos , Fatores de Risco , Idoso , GravidezRESUMO
OBJECTIVE: This study aims to prospectively examine the association between temperatures and the occurrence of type 2 diabetes (T2D). METHODS: We used the CPH models to analyze 103,215 non-diabetic participants in the UK Biobank cohort who answered questions about workplace temperature, to evaluate the survival relationship, and the interaction effects of working environmental temperature and T2D-related genetic risk scores (GRS) on the occurrence of T2D. The occurrence of T2D was assessed by hospital inpatient records. The weighted T2D-related GRS were calculated. RESULTS: During 1,355,200.6 person-years follow-up, a total of 2436 participants were documented as having diagnosed T2D. After adjustment, compared to the comfortable group, the participants working in non-comfortable environmental temperature had greater risk of T2D (HR: 1.27, 95 %CI: 1.04 to 1.55, for cold; HR: 1.32, 95 %CI: 1.17 to 1.48 for hot; HR: 1.51, 95 %CI: 1.38 to 1.65 for alternate). Similarly, individuals exposed to different levels of genetic risk scores in alternating hot and cold work environments had a higher risk of developing type 2 diabetes. CONCLUSIONS: This study found working in single non-comfortable environmental temperatures was associated with greater risk of T2D occurrence, and exposure to alternating environmental temperatures had the highest risk of range and severity.
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Bancos de Espécimes Biológicos , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Masculino , Feminino , Reino Unido/epidemiologia , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Adulto , Temperatura , Temperatura Baixa/efeitos adversos , Predisposição Genética para Doença , Biobanco do Reino UnidoRESUMO
BACKGROUND: Cellular communication among different types of vascular cells is indispensable for maintaining vascular homeostasis and preventing atherosclerosis. However, the biological mechanism involved in cellular communication among these cells and whether this biological mechanism can be used to treat atherosclerosis remain unknown. We hypothesized that endothelial autophagy mediates the cellular communication in vascular tissue through exosome-mediated delivery of atherosclerosis-related genes. METHODS: Rapamycin and adeno-associated virus carrying Atg7 short hairpin RNA under the Tie (TEK receptor tyrosine kinase) promoter were used to activate and inhibit vascular endothelial autophagy in high-fat diet-fed ApoE-/- mice, respectively. miRNA microarray, in vivo and in vitro experiments, and human vascular tissue were used to explore the effects of endothelial autophagy on endothelial function and atherosclerosis and its molecular mechanisms. Quantitative polymerase chain reaction and miRNA sequencing were performed to determine changes in miRNA expression in exosomes. Immunofluorescence and exosome coculture experiments were conducted to examine the role of endothelial autophagy in regulating the communication between endothelial cells and smooth muscle cells (SMCs) via exosomal miRNA. RESULTS: Endothelial autophagy was inhibited in thoracic aortas of high-fat diet-fed ApoE-/- mice. Furthermore, rapamycin alleviated high-fat diet-induced atherosclerotic burden and endothelial dysfunction, while endothelial-specific Atg7 depletion aggravated the atherosclerotic burden. miRNA microarray, in vivo and in vitro experiments, and human vascular tissue analysis revealed that miR-204-5p was significantly increased in endothelial cells after high-fat diet exposure, which directly targeted Bcl2 to regulate endothelial cell apoptosis. Importantly, endothelial autophagy activation decreased excess miR-204-5p by loading miR-204-5p into multivesicular bodies and secreting it through exosomes. Moreover, exosomal miR-204-5p can effectively transport to SMCs, alleviating SMC calcification by regulating target proteins such as RUNX2 (runt-related transcription factor 2). CONCLUSIONS: Our study revealed the exosomal pathway by which endothelial autophagy protects atherosclerosis: endothelial autophagy activation transfers miR-204-5p from endothelial cells to SMCs via exosomes, both preventing endothelial apoptosis and alleviating SMC calcification. REGISTRATION: URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR2200064155.
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Aterosclerose , Autofagia , Comunicação Celular , Modelos Animais de Doenças , Exossomos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , MicroRNAs , Miócitos de Músculo Liso , MicroRNAs/metabolismo , MicroRNAs/genética , Exossomos/metabolismo , Exossomos/genética , Animais , Aterosclerose/patologia , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Humanos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Masculino , Camundongos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Proteína 7 Relacionada à Autofagia/metabolismo , Proteína 7 Relacionada à Autofagia/genética , Células Cultivadas , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Placa Aterosclerótica , Doenças da Aorta/patologia , Doenças da Aorta/genética , Doenças da Aorta/prevenção & controle , Doenças da Aorta/metabolismo , Técnicas de Cocultura , Transdução de Sinais , Aorta Torácica/metabolismo , Aorta Torácica/patologia , Dieta HiperlipídicaRESUMO
BACKGROUND: This study aims to investigate potential interactions between maternal smoking around birth (MSAB) and type 2 diabetes (T2D) pathway-specific genetic risks in relation to the development of T2D in offspring. Additionally, it seeks to determine whether and how nutritional factors during different life stages may modify the association between MSAB and risk of T2D. METHODS: This study included 460,234 participants aged 40 to 69 years, who were initially free of T2D from the UK Biobank. MSAB and breastfeeding were collected by questionnaire. The Alternative health eating index(AHEI) and dietary inflammation index(DII) were calculated. The polygenic risk scores(PRS) of T2D and pathway-specific were established, including ß-cell function, proinsulin, obesity, lipodystrophy, liver function and glycated haemoglobin(HbA1c). Cox proportion hazards models were performed to evaluate the gene/diet-MSAB interaction on T2D. The relative excess risk due to additive interaction (RERI) were calculated. RESULTS: During a median follow-up period of 12.7 years, we identified 27,342 cases of incident T2D. After adjustment for potential confounders, participants exposed to MSAB had an increased risk of T2D (HR=1.11, 95%CI:1.08-1.14), and this association remained significant among the participants with breastfeeding (HR= HR=1.10, 95%CI: 1.06-1.14). Moreover, among the participants in the highest quartile of AHEI or in the lowest quartile of DII, the association between MSAB and the increased risk of T2D become non-significant (HR=0.94, 95%CI: 0.79-1.13 for AHEI; HR=1.09, 95%CI:0.99-1.20 for DII). Additionally, the association between MSAB and risk of T2D became non-significant among the participants with lower genetic risk of lipodystrophy (HR=1.06, 95%CI:0.99-1.14), and exposed to MSAB with a higher genetic risk for ß-cell dysfunction or lipodystrophy additively elevated the risk of T2D(RERI=0.18, 95%CI:0.06-0.30 for ß-cell function; RERI=0.16, 95%CI:0.04-0.28 for lipodystrophy). CONCLUSIONS: This study indicates that maintaining a high dietary quality or lower dietary inflammation in diet may reduce the risk of T2D associated with MSAB, and the combination of higher genetic risk of ß-cell dysfunction or lipodystrophy and MSAB significantly elevate the risk of T2D in offspring.
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Diabetes Mellitus Tipo 2 , Lipodistrofia , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Estudos Prospectivos , Biobanco do Reino Unido , Bancos de Espécimes Biológicos , Fatores de Risco , Inflamação/complicações , Fumar , Lipodistrofia/complicaçõesRESUMO
BACKGROUND: Knowledge regarding the health impacts of daily eating frequency (DEF) and nighttime fasting duration (NFD) on mortality is very limited. OBJECTIVE: This study aimed to examine whether DEF and NFD are associated with CVD and all-cause mortality. METHODS: This was a prospective cohort study of a nationally representative sample from the United States, including 30,464 adults who participated in the National Health and Nutrition Examination Survey 2003-2014. Using 24-h dietary recall, DEF was assessed by the number of eating episodes, and NFD was calculated by the first and last eating time across a day. Death information was obtained from the National Death Index up to 2019. Weighted Cox proportional hazards regression models were used to assess survival relationships of DEF and NFD with mortality. RESULTS: During 307,686 person-years of follow-up, 4560 deaths occurred, including 1824 CVD cases. After adjustment for confounders, compared to DEF at 4-6 times, participants whose DEF was less than 3 times had greater CVD [hazard-ratio (HR) = 1.33, 95% confidence-interval (CI): 1.06-1.67] and all-cause (HR = 1.16, 95% CI: 1.01-1.33) mortality risks. Furthermore, compared to NFD of 10 to 11 h, participants whose NFD was shorter than 10 h had HRs of 1.30 (95% CI: 1.08-1.55) for CVD mortality and 1.23 (95% CI: 1.08-1.39) for all-cause mortality. NFD longer than 14 h was also related to CVD mortality (HR = 1.37, 95% CI: 1.12-1.67) and all-cause mortality (HR = 1.36, 95% CI: 1.19-1.54). Similar results for the association of NFD and DEF with heart-specific and stroke-specific mortality were observed. CONCLUSION: This study found that DEF less than 3 times and NFD shorter than 10 h or longer than 14 h were independently associated with greater cardiovascular and all-cause mortality.
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Doenças Cardiovasculares , Carrubicina/análogos & derivados , Adulto , Humanos , Estados Unidos/epidemiologia , Inquéritos Nutricionais , Estudos Prospectivos , Comportamento Alimentar , JejumRESUMO
BACKGROUND: Type 2 diabetes (T2D) is the most common type of diabetes. However, research on the relationship between blue light exposure and diabetes development is limited. OBJECTIVE: The present study aimed to investigate the relationship between blue light exposure and T2D incidence and whether it is affected by sleep duration, physical activity, outdoor activity time, and genetic susceptibility. METHODS: A total of 471,686 participants without diabetes were recruited from the UK Biobank cohort. T2D incidence was assessed using hospital inpatient records. Blue light exposure was calculated based on the time spent watching TV, using a computer, and playing computer games, which was determined using an online questionnaire. Cox proportional hazards regression models were used to assess the survival relationship between blue light exposure and T2D, as well as the potential modification effects. RESULT: A total of 18,738 cases of T2D were documented during the median follow-up of 13.04 years. After adjusting for potential confounders, the participants with heavy blue light exposure had a greater risk of T2D compared to those with mild blue light exposure (hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.12-1.23). A significant association between blue light exposure and T2D risk was observed among the participants with heavy physical activity (HR = 1.39, 95%CI: 1.25-1.55), healthy sleep habits (HR = 1.23, 95%CI: 1.10-1.36), higher outdoor activity time (HR = 1.14, 95%CI: 1.07-1.22), or high genetic susceptibility (HR = 1.24, 95%CI: 1.14-1.35). However, this association became non-significant among the participants with low genetic susceptibility (HR = 1.05, 95%CI: 0.97-1.15). CONCLUSION: The present study showed that blue light exposure is associated with a greater risk of T2D independent of classical T2D risk factors.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Estudos Prospectivos , Fatores de Risco , Incidência , Bancos de Espécimes Biológicos , Luz Azul , Biobanco do Reino Unido , Predisposição Genética para DoençaRESUMO
AIMS: This study aims to examine the association between the rest-activity rhythm (RAR) and the incidence of type 2 diabetes (T2D). MATERIALS AND METHODS: In total, 97 503 participants without diabetes in the UK Biobank cohort were recruited. Wearable accelerometry was used to monitor circadian behaviour. The parameters of RAR including inter-daily stability, intra-daily variability, relative amplitude (RA), most active continuous 10 h period (M10), and least active continuous 5 h period (L5) were calculated to evaluate the robustness and regularity of the RAR. The weighted polygenic risk score for T2D (T2D-PRS) was calculated. Cox proportion hazards models were used to evaluate the survival relationship and the joint and interaction effects of RAR parameters and T2D-PRS on the occurrence of T2D. RESULTS: During 692 257 person-years follow-ups, a total of 2434 participants were documented. After adjustment for potential confounders, compared with participants in the highest quartile of RA and M10, the participants in the lowest quartile had a greater risk of T2D (HRRA = 2.06, 95% CI: 1.76-2.41; HRM10 = 1.33, 95% CI: 1.19-1.49). Meanwhile, the highest quartile of L5 was related to a higher risk of T2D (HR = 1.78, 95% CI: 1.55-2.24). The joint analysis showed that the high T2D-PRS with the lowest quartile of RA and M10, or highest quartile of L5 jointly increased the risk of T2D (HRRA = 4.46, 95% CI: 3.36-6.42; HRM10 = 3.15, 95% CI: 2.29-4.32; HRL5 = 3.09, 95% CI: 2.40-3.99). No modification effects of T2D-PRS on the association between the RAR parameters and risk of T2D were observed (p > .05). CONCLUSION: The unbalanced RAR are associated with a greater risk of T2D, which are independent of known risk factors of T2D.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Estudos Prospectivos , Predisposição Genética para Doença , Bancos de Espécimes Biológicos , Fatores de Risco , Reino Unido/epidemiologiaRESUMO
Emerging evidence suggests that in addition to metabolic, genetic and environmental factors, circadian rhythm also plays a role in non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the association of 24 h behavior rhythm (activity-rest and feeding-fasting rhythm) with NAFLD. A total of 4502 adult participants with overweight/obesity from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were included in the current study. The behavior rhythm indices were calculated and divided into quintiles for logistic regression models. Compared to those in the lowest quintile, participants in the highest quintile of relative amplitude (RA) had a lower risk of NAFLD (OR = 0.71, 95% CI, 0.55-0.91); participants in the highest quintile of the average activity of the least active continuous 5 h period (L5) were associated with a higher risk of NAFLD (OR = 1.35, 95% CI, 1.07-1.71). Additionally, participants in the highest quintile of fasting duration and feeding rhythm score were associated with a lower risk of NAFLD relative to those in the lowest quintile (OR = 0.76, 95% CI, 0.59-0.98 for fasting duration, OR = 0.74, 95% CI, 0.58-0.95 for feeding rhythm score). The associations were stronger among participants with obesity. No significant associations were found in the relationship of other behavior rhythm indices with NAFLD. This study indicated a significant association of 24 h behavior rhythm with NAFLD among American adults with overweight/obesity.
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Hepatopatia Gordurosa não Alcoólica , Sobrepeso , Adulto , Humanos , Sobrepeso/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Inquéritos Nutricionais , Obesidade/complicações , Ritmo CircadianoRESUMO
Hyperuricemia (HUA) is associated with a wide range of diseases and increases the public health burden on society as a whole. In addition to genetic variation, diet plays a crucial role in the prevention and treatment of HUA as an important modifiable behavior. The purpose of this study is to investigate whether food groups and consumption time are associated with HUA. A total of 41,230 participants from the National Health and Nutrition Examination Survey between 2005 and 2018 were included in the study. All meals, including breakfast, lunch, and dinner, were obtained according to their corresponding Food Patterns Equivalents Database dietary data. The binary logistic regression model was used to analyze the relationship between food groups, food consumption time and HUA. We found that the intake of fruit (mixed in various forms) (OR = 0.942, 95% CI: 0.909-0.976) or freshly squeezed juices (OR = 0.915, 95% CI: 0.859-0.975), milk (OR = 0.839, 95% CI: 0.808-0.872), and eggs (OR = 0.881, 95% CI: 0.839-0.924), poultry (OR = 1.055, 95% CI: 1.033-1.077) and seafood high in n-3 fatty acids (OR = 1.068, 95% CI: 0.1.018-1.120) at dinner, eating refined grains at breakfast (OR = 0.954, 95% CI: 0.924-0.985) and dinner (OR = 0.962, 95% CI: 0.944-0.980), eating whole grains (OR = 0.908, 95% CI: 0.845-0.976) at lunch, consuming alcoholic beverages or foods at breakfast (OR = 0.748, 95% CI: 0.564-0.990)/lunch (OR = 1.118, 95% CI: 1.008-1.240)/dinner (OR = 1.127, 95% CI: 1.073-1.185) were associated with HUA. Eating particular meals at particular times of the day was related to a lower risk of HUA.
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Comportamento Alimentar , Hiperuricemia , Hiperuricemia/epidemiologia , Humanos , Refeições , Inquéritos Nutricionais , Dieta , FrutasRESUMO
In this study, monoamine oxidase B (MAOB) was activated under pathological conditions, and was the novel source of cardiovascular reactive oxygen species (ROS). ROS-induced endothelial dysfunction results in sustained and chronic vascular inflammation, which is central to atherosclerotic diseases. However, whether MAOB regulates endothelial oxidative stress and its related mechanism and whether gut microbiota mediates the anti-atherosclerosis effect of MAOB inhibitor remains unclear. In our study, MAOB expressions were elevated in high-fat diet (HFD) fed mice aortas, but only in vascular endothelial cells (not in smooth muscle cells). MAOB small interfering RNA significantly attenuated the palmitic-acid (PA)-induced endothelial oxidative stress and dysfunction. Furthermore, RNA-sequencing data revealed that MAOB knockdown decreased the levels of proinflammatory and apoptotic gene induced by PA. Microarray analysis and qPCR assay showed that miR-3620-5p was significantly decreased under the HFD condition. The dual-luciferase reporter, Western blot and qPCR assay confirmed that miR-3620-5p directly regulated MAOB by binding to its mRNA 3'UTR. Moreover, inhibition of MAOB by selegiline significantly ameliorated endothelial dysfunction and reduced atherosclerotic burden in HFD-fed ApoE-/- mice. Finally, 16S rRNA sequencing showed that selegiline significantly altered the community compositional structure of gut microbiota. Specifically, selegiline treatment enriched the abundance of Faecalibaculum and Akkermansia, decreased the abundance of unclassified_f__Lachnospiraceae, Desulfovibrio, and Blautia, and these genera were significantly correlated with the serum biochemical indices. Taken together, our findings showed that MAOB controlled endothelial oxidative stress homeostasis, and revealed the anti-atherosclerotic effect of selegiline by ameliorating endothelial dysfunction and modulating the composition and function of gut microbiota.
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Aterosclerose , Microbioma Gastrointestinal , MicroRNAs , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Células Endoteliais/metabolismo , Monoaminoxidase/metabolismo , RNA Ribossômico 16S/genética , Selegilina/metabolismo , Selegilina/farmacologia , Aterosclerose/tratamento farmacológico , Aterosclerose/etiologia , Aterosclerose/prevenção & controle , Inflamação/metabolismo , MicroRNAs/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Certain monoamine oxidase (MAO) inhibitors exhibit beneficial effects, such as reducing adiposity and metabolic disorders; however, their effects on hepatic lipid metabolism have not been revealed. This study aimed to investigate the effects of a selective MAO-B inhibitor, selegiline, on dyslipidemia and hepatic steatosis in mice induced by a high-fat diet (HFD). Administration of selegiline (0.6 mg/kg body weight) by intraperitoneal injection was found to reduce HFD-induced body weight gain and increases in liver and adiposity coefficients, blood lipids and fatty acid levels. Furthermore, selegiline dramatically reduced the total triglyceride (TG) and cholesterol (TC) levels and lipid accumulation in the livers of HFD-fed mice and palmitic acid (PA)-treated AML-12 hepatocytes. In vivo and in vitro results indicated that selegiline protects against HFD- and PA-induced hepatic inflammation by reducing the expression of proinflammatory cytokines, namely IL-6, TNF-α, IL-1ß, and IL-1α. Additionally, selegiline exhibited antioxidative effects on HFD and PA exposure in mouse liver and AML-12 cells by decreasing the levels of reactive oxygen species (ROS) and malonaldehyde (MDA) and increasing superoxide dismutase (SOD) activity. Further study showed that selegiline administration mitigated the expression of Srebf-1, Fasn, and Acaca and downregulated the expression of Cpt-1 and Pparα in HFD-fed mouse livers and PA-treated AML-12 cells. In conclusion, our findings suggest that selegiline exerts protective effects against HFD-induced dyslipidemia and hepatic steatosis, which may be related to an improved inflammatory response, oxidative stress, and hepatic lipid metabolism.
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Fígado Gorduroso , Hipercolesterolemia , Leucemia Mieloide Aguda , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Selegilina/farmacologia , Selegilina/uso terapêutico , Selegilina/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/metabolismo , Fígado , Metabolismo dos Lipídeos , Obesidade/metabolismo , Hipercolesterolemia/metabolismo , Leucemia Mieloide Aguda/metabolismo , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismoRESUMO
Polystyrene nano-plastics (PS-NPs) can be accumulated in the food chain and can penetrate biological barriers to affect multiple physiological functions. However, the adverse effects of nano-plastics on mammals and the underlying mechanism still remain unknown. To fill the gaps, our study administrated low-dose PS-NPs (50 and 100 µg/L) for 24 consecutive weeks in rats. Behavioral and morphological evaluations were performed to assess the neurobehavoirs. A combined analysis of multiple omics was used to evaluate the dysfunctions of the gut-microbe-brain axis. After dihydrochalcone(NHDC) treatment in the PS-NPs rat model, the inflammation response and apoptosis process were assessed and proteomics was used to explore the underlying mechanism. Our results indicated that long-term exposure to low-dose PS-NPs could induce abnormal neurobehaviors and amygdaloid nucleus impairment, and stimulate inflammatory responses and apoptosis. Metagenomics results revealed that four microbial phyla including Proteobacteria, Firmicutes, Defferibacteres, and Bacteroidetes changed significantly compared to the control. Targeted metabolomics analysis in the feces showed alteration of 122 metabolites induced by the PS-NPs exposure, among which the content of dihydrocaffeic acid was significantly associated with the different microbial genera and pivotal differential metabolites in the amygdaloid nucleus. And NHDC treatment significantly alleviated PS-NP-induced neuroinflammation and apoptosis and the cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/phosphorylated cAMP-response element binding protein(p-CREB)/plasma membrane calcium-transporting ATPase 2(Atp2b2) signaling pathway was identified in the proteomics. In conclusion, long-term exposure to low-dose PS-NPs has adverse effects on emotion through the dysregulation of the gut-brain axis, and dihydrocaffeic acid can alleviate these effects via the cAMP/PKA/p-CREB/Atp2b2 signaling pathway.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Microbiota , Nanopartículas , Poluentes Químicos da Água , Ratos , Animais , Microplásticos/metabolismo , Poliestirenos/metabolismo , Poluentes Químicos da Água/metabolismo , Encéfalo/metabolismo , Nanopartículas/química , Mamíferos/metabolismoRESUMO
BACKGROUND: Studies about the prognostic role of gut microbiota-derived metabolites including phenylacetyl glutamine (PAGln), indoxyl sulfate (IS), lithocholic acid (LCA), deoxycholic acid (DCA), trimethylamine (TMA), trimethylamine N-oxide (TMAO), and its precursor trimethyllysine (TML) are limited in patients with ST-segment elevation myocardial infarction (STEMI). OBJECTIVES: To examine the relationship between plasma metabolite levels and major adverse cardiovascular events (MACEs), including nonfatal MI, nonfatal stroke, all-cause mortality, and heart failure in patients with STEMI. METHODS: We enrolled 1004 patients with STEMI undergoing percutaneous coronary intervention (PCI). Plasma levels of these metabolites were determined by targeted liquid chromatography/mass spectrometry. The associations of metabolite levels with MACEs were assessed with the Cox regression model and quantile g-computation. RESULTS: During a median follow-up of 360 d, 102 patients experienced MACEs. Higher plasma PAGln (hazard ratio [HR], 3.17 [95% CI: 2.05, 4.89]; P < 0.001), IS (2.67 [1.68, 4.24], P < 0.001), DCA (2.36 [1.40, 4.00], P = 0.001), TML (2.66 [1.77,3.99], P < 0.001), and TMAO (2.61 [1.70, 4.00], P < 0.001) levels were significantly associated with MACEs independent of traditional risk factors. According to quantile g-computation, the joint effect of all these metabolites was 1.86 (95% CI: 1.46, 2.27). PAGln, IS and TML had the greatest proportional positive contributions to the mixture effect. Additionally, plasma PAGln and TML combined with coronary angiography scores including the Synergy between PCI with Taxus and cardiac surgery (SYNTAX) score (area under the curve [AUC]: 0.792 vs. 0.673), Gensini score (0.794 vs. 0.647) and Balloon pump-assisted Coronary Intervention Study (BCIS-1) jeopardy score (0.774 vs. 0.573) showed better prediction performance for MACEs. CONCLUSIONS: Higher plasma PAGln, IS, DCA, TML, and TMAO levels are independently associated with MACEs suggesting that these metabolites may be useful markers for prognosis in patients with STEMI.
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Microbioma Gastrointestinal , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Prognóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Resultado do TratamentoRESUMO
Few studies examined the association of energy, macronutrients and food consumption at dinner v. breakfast with hypercholesterolaemia. A total of 27 911 participants from the National Health and Nutrition Examination Survey (2003-2016) were included in the cross-sectional study. Energy, macronutrients and food consumption at breakfast, dinner and the difference at dinner v. breakfast (Δratio) were calculated. Multiple logistic regression models and substitution effects of foods at dinner with breakfast were also performed. After adjustment for potential covariates, compared with the lowest quintile, participants in the highest quintile of Δratio in terms of energy had a higher risk of prevalent hypercholesterolaemia (ORΔratio of energy 1·16, 95 % CI (1·01, 1·33)) mainly due to Δratio of low-quality carbohydrates and plant protein (ORΔratio of low-quality carbohydrates 1·19; 95 % CI (1·05, 1·35)); ORΔratio of plant protein 1·13; 95 % CI (1·01, 1·28)). ΔAdded sugars and Δnuts were associated with hypercholesterolaemia (ORΔadded sugars 1·01; 95 % CI (1·00, 1·02)); ORΔnuts 1·08; 95 % CI (1·01, 1·16)). Furthermore, the substitution of added sugars, nuts and processed meat at dinner with breakfast could reduce the OR of hypercholesterolaemia. This study indicated that among US adults, overconsumption of energy, macronutrients including low-quality carbohydrates and plant protein at dinner than breakfast was significantly associated with a higher risk of prevalent hypercholesterolaemia. The replacing of added sugar, nuts and processed meat at dinner with breakfast reduced the risk of prevalent hypercholesterolaemia. This study emphasised the importance of meal timing in the prevention of hypercholesterolaemia.
Assuntos
Dieta , Hipercolesterolemia , Humanos , Adulto , Inquéritos Nutricionais , Hipercolesterolemia/epidemiologia , Estudos Transversais , Refeições , Desjejum , Nutrientes , Carboidratos , Açúcares , Ingestão de Energia , Comportamento AlimentarRESUMO
CONTEXT: The hyperglycemia condition disrupts metabolism of nitrate/nitrite and nitric oxide, and dietary nitrate intake can restore nitric oxide homeostasis. OBJECTIVE: This study aims to examine whether urinary nitrate is associated with diabetes complications and long-term survival among people with hyperglycemia. METHODS: A total of 6208 people with hyperglycemia who participated in the National Health and Nutrition Examination Survey from 2005 to 2014 were enrolled. Diabetes complications included congestive heart failure, coronary heart disease, angina, stroke, myocardial infarction, diabetic retinopathy, and nephropathy. Mortality was obtained from the National Death Index until 2015. Urinary nitrate was measured by ion chromatography coupled with electrospray tandem mass spectrometry, which was log-transformed and categorized into tertiles. Logistic regression models and Cox proportional hazards models were respectively performed to assess the association of urinary nitrate with the risk of diabetes complications and disease-specific mortalities. RESULTS: After adjustment for potential confounders, including urinary perchlorate and thiocyanate, compared with the participants in the lowest tertile of nitrate, the participants in the highest tertile had lower risks of congestive heart failure (odds ratio [OR] 0.41; 95% CI, 0.27-0.60) and diabetic nephropathy (OR 0.50; 95% CI, 0.41-0.62). Meanwhile, during a total follow-up period of 41 463 person-years, the participants in the highest tertile had lower mortality risk of all-cause (hazard ratio [HR] 0.78; 95% CI, 0.62-0.97), cardiovascular disease (CVD) (HR 0.56; 95% CI, 0.37-0.84), and diabetes (HR 0.47; 95% CI, 0.24-0.90), which showed dose-dependent linear relationships (P for nonlinearity > 0.05). Moreover, no association between nitrate and cancer mortality was observed (HR 1.13; 95% CI, 0.71-1.80). CONCLUSION: Higher urinary nitrate is associated with lower risk of congestive heart failure and diabetic nephropathy, and lower risk of all-cause, CVD, and diabetes mortalities. These findings indicate that inorganic nitrate supplementation can be considered as a supplementary treatment for people with hyperglycemia.
Assuntos
Doenças Cardiovasculares , Complicações do Diabetes , Diabetes Mellitus , Nefropatias Diabéticas , Insuficiência Cardíaca , Hiperglicemia , Humanos , Adulto , Nitratos , Nefropatias Diabéticas/etiologia , Inquéritos Nutricionais , Óxido Nítrico , Fatores de Risco , Diabetes Mellitus/epidemiologiaRESUMO
Introduction: People with sleep disorders are under disrupted biological rhythms. Whether changing the timing of specific food consumption contributes to decreasing cardiovascular and all-cause risk is unknown. Methods: A total of 8,005 participants with sleep disorders were selected from the U.S. National Health and Nutrition Examination Survey (NHANES) from 2005 to 2014. Cox proportional hazards regression models were used to analyze the relationship between the consumption time of foods and cardiovascular disease (CVD) and all-cause death. Moreover, equivalent food substitution models were carried out to evaluate the alterations in the risk of CVD mortality for the changed food intake time. Results: After adjusting for multiple confounders, participants who consume red and orange vegetables, starchy vegetables, and fermented dairy in the morning (hazard ratio (HR) red and orange vegetables = 0.45, 95% CI: 0.26-0.81; HR starchy vegetables = 0.47, 95% CI: 0.25-0.88; HR fermented dairy = 0.57, 95% CI: 0.36-0.89) and milk and eggs in the evening contribute to reducing the likelihood of death from CVD (HR milk = 0.65, 95% CI: 0.43-0.96; HR eggs = 0.72, 95% CI: 0.53-0.98). Iso-calorically switching 0.1 serving of starchy vegetable and fermented dairy and milk intake from one period to another does significantly reduce the mortality risk of CVD. Conclusion: Higher intake of red and orange vegetables, starchy vegetables, and fermented dairy in the morning and milk and eggs in the evening confers a lower risk of CVD among individuals with sleep disorders.
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Background: Current studies on the protective effects of dietary spermidine (SPD) on cardiovascular disease (CVD) are mainly limited to animal studies, and the relationship between dietary SPD and CVD mortality remains inconclusive. Objective: This study aims to evaluate the association between dietary SPD intake and CVD and all-cause mortality. Methods: A total of 23,894 people enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2014 were recruited for this study. The dietary intake of SPD from 11 specific food origins and total SPD was categorized into tertiles or quartiles. Cox proportional hazard regression models were developed to evaluate the association of SPD intake with CVD and all-cause mortalities. Results: Among the 23,894 participants, 2,365 deaths, including 736 deaths due to CVD, were documented. After adjustment for potential confounders, compared with participants in the lowest quartile, participants in the highest quartile of total SPD had a significantly lower risk of CVD mortality (HR = 0.68, 95% CI: 0.51-0.91) and all-cause mortality (HR = 0.70, 95% CI: 0.60-0.82); participants in the highest tertiles or quartiles of vegetable-derived SPD, cereal-derived SPD, legume-derived SPD, nut-derived SPD, and cheese-derived SPD had a lower risk of CVD mortality (HR vegetable - derivedSPD = 0.68, 95% CI: 0.54-0.86; HR cereal - derivedSPD = 0.75, 95% CI: 0.57-0.97; HR legume - derivedSPD = 0.68, 95% CI: 0.52-0.88; HR nut - derivedSPD = 0.66, 95% CI: 0.53-0.80; HR cheese - derivedSPD = 0.68, 95% CI: 0.52-0.88) and all-cause mortality (HR vegetable - derivedSPD = 0.73, 95% CI: 0.64-0.84; HR cereal - derivedSPD = 0.80, 95% CI: 0.69-0.93; HR legume - derivedSPD = 0.70, 95% CI: 0.60-0.80;HR nut - derivedSPD = 0.72, 95% CI: 0.64-0.81; HR cheese - derivedSPD = 0.70, 95% CI: 0.61-0.81) than those in the lowest tertiles or quartiles. Moreover, subgroup analysis showed consistent associations among the people with hypertension and hyperlipidemia. Conclusion: Higher intake of dietary SPD is associated with decreased risk of CVD and all-cause mortality, and among specific food origin SPD, SPD derived from vegetables, cereals, legumes, nuts, and cheese was associated with reduced CVD and all-cause mortality.
Assuntos
Doenças Cardiovasculares , Dieta , Inquéritos Nutricionais , Estudos Prospectivos , Espermidina , VerdurasRESUMO
Dietary carbohydrate consumption was related to cognitive function. Whereas, there was no study investigate the association of dietary carbohydrate consumption with cognitive function modification by daily fasting duration. This study aims to examine the association between dietary carbohydrate consumption and cognitive function among participants with different daily fasting duration. In this cross-sectional study, 2485 adults aged over 60 years from the nationally representative data of the National Health and Nutrition Examination Survey (NHANES, 2011-2014) were enrolled. Percentage energy from carbohydrates was present in both quartiles and continuous forms. Daily fasting duration = 24 - (timing for dinner - breakfast). Cognitive function was assessed by the Consortium to Establish a Registry for Alzheimer's Disease Word List Learning (CERAD-WL), CERAD Word List Delayed Recall (CERAD-DR), Animal Fluency (AF), and Digit Symbol Substitution (DSST) Test. Multiple logistic regression and linear regression models were developed to examine the association of dietary carbohydrates with cognitive function among participants with different daily fasting duration. Restricted cubic spline models were also applied. Compared with the lowest quartile of percentage energy from carbohydrates, the highest quartile had higher ORs of poor cognitive performance among total participants [(ORCERAD-WL 1.84 95% CI 1.25-2.71); (ORCERAD-DR 1.45 95% CI 1.10-1.91)] and participants with daily fasting duration fewer than 16 h [(ORCERAD-WL 2.14 95% CI 1.29-3.55); (ORCERAD-DR 1.51 95% CI 1.05-2.17)] but not in participants with daily fasting duration of more than 16 h. Further, the negative associations between percentage energy from carbohydrates and CERAD-WL score were still significant in addition to participants whose daily fasting duration was more than 16 h. Additionally, dose-response associations were detected between dietary carbohydrates and cognitive decline, while "U" curves were observed among participants whose daily fasting duration was more than 16 h. This study indicated that dietary carbohydrates consumption was associated with poor cognitive performance, but not in participants whose daily fasting duration was more than 16 h among US older adults. The current analysis provides evidence that a longer daily fasting duration may improve the harmful effect of dietary carbohydrates on cognitive function.