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A subset of children with autism spectrum disorder appear to show an improvement in their behavioural symptoms during the course of a fever, a sign of systemic inflammation1,2. Here we elucidate the molecular and neural mechanisms that underlie the beneficial effects of inflammation on social behaviour deficits in mice. We compared an environmental model of neurodevelopmental disorders in which mice were exposed to maternal immune activation (MIA) during embryogenesis3,4 with mouse models that are genetically deficient for contactin-associated protein-like 2 (Cntnap2)5, fragile X mental retardation-1 (Fmr1)6 or Sh3 and multiple ankyrin repeat domains 3 (Shank3)7. We establish that the social behaviour deficits in offspring exposed to MIA can be temporarily rescued by the inflammatory response elicited by the administration of lipopolysaccharide (LPS). This behavioural rescue was accompanied by a reduction in neuronal activity in the primary somatosensory cortex dysgranular zone (S1DZ), the hyperactivity of which was previously implicated in the manifestation of behavioural phenotypes associated with offspring exposed to MIA8. By contrast, we did not observe an LPS-induced rescue of social deficits in the monogenic models. We demonstrate that the differences in responsiveness to the LPS treatment between the MIA and the monogenic models emerge from differences in the levels of cytokine production. LPS treatment in monogenic mutant mice did not induce amounts of interleukin-17a (IL-17a) comparable to those induced in MIA offspring; bypassing this difference by directly delivering IL-17a into S1DZ was sufficient to promote sociability in monogenic mutant mice as well as in MIA offspring. Conversely, abrogating the expression of IL-17 receptor subunit a (IL-17Ra) in the neurons of the S1DZ eliminated the ability of LPS to reverse the sociability phenotypes in MIA offspring. Our data support a neuroimmune mechanism that underlies neurodevelopmental disorders in which the production of IL-17a during inflammation can ameliorate the expression of social behaviour deficits by directly affecting neuronal activity in the central nervous system.
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Interleucina-17/imunologia , Transtornos do Neurodesenvolvimento/imunologia , Animais , Comportamento Animal , Modelos Animais de Doenças , Feminino , Proteína do X Frágil da Deficiência Intelectual , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Comportamento SocialRESUMO
All life on Earth is unified by its use of a shared set of component chemical compounds and reactions, providing a detailed model for universal biochemistry. However, this notion of universality is specific to known biochemistry and does not allow quantitative predictions about examples not yet observed. Here, we introduce a more generalizable concept of biochemical universality that is more akin to the kind of universality found in physics. Using annotated genomic datasets including an ensemble of 11,955 metagenomes, 1,282 archaea, 11,759 bacteria, and 200 eukaryotic taxa, we show how enzyme functions form universality classes with common scaling behavior in their relative abundances across the datasets. We verify that these scaling laws are not explained by the presence of compounds, reactions, and enzyme functions shared across known examples of life. We demonstrate how these scaling laws can be used as a tool for inferring properties of ancient life by comparing their predictions with a consensus model for the last universal common ancestor (LUCA). We also illustrate how network analyses shed light on the functional principles underlying the observed scaling behaviors. Together, our results establish the existence of a new kind of biochemical universality, independent of the details of life on Earth's component chemistry, with implications for guiding our search for missing biochemical diversity on Earth or for biochemistries that might deviate from the exact chemical makeup of life as we know it, such as at the origins of life, in alien environments, or in the design of synthetic life.
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Fenômenos Bioquímicos , Enzimas/metabolismo , Planeta Terra , Origem da Vida , Biologia SintéticaRESUMO
Trophoblasts, the principal cellular component of the placenta, play an important role in nutrient and gas exchange. Previous studies have indicated that maternal immune activation (MIA) leads to an elevation in IL-17A cytokine levels in maternal serum, subsequently influencing fetal brain development during pregnancy. In this study, we aimed to elucidate the impact of the IL-17A cytokine on placental function. First, we treated JAR and JEG-3, which is a placenta cell line, with IL-17A in a concentration-dependent or time-dependent manner and observed cell morphology and viability. It was confirmed that treatment with IL-17A or a double-stranded RNA mimic (PolyI:C) had no effect on the morphology or cell viability. IL-17A treatment increased the expression of IL-17R at the mRNA and protein levels, and Poly(I:C) increased the levels of IFNγ and TNFα. Additionally, PPARγ, known as a metabolism regulator, was increased by IL-17A treatment. Also, we observed that the expression of Glut1 and Glut3 was increased by IL-17A treatment. To confirm this, we examined the expression of transporters in the placental tissue of the MIA rodent model, and we observed that mRNA expression of glut1 and glut3 was significantly increased. However, the expression of Gltu1 and Glut3 was observed to be significantly inhibited in the brains of MIA-induced offspring. This study suggests that IL-17A increases signaling through IL-17R in the placenta and fetal brain tissue; however, there is a mechanism for regulating the expression of glucose transporters by increased IL-17A in the placenta.
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PURPOSE OF REVIEW: Plant-based diets are associated with a lower risk of hypertension, diabetes, cardiovascular disease, and mortality. Using the most recent evidence, we critically appraised the role of plant-based diets in primary and secondary prevention of chronic kidney disease (CKD) with a focus on key nutritional factors (dietary acid load, phosphorus, potassium, sodium, and fiber). RECENT FINDINGS: In healthy individuals, observational studies found that greater intake of plant protein and higher adherence to plant-based diets (overall, healthful, and provegetarian) was associated with a lower risk of CKD. In those with CKD, plant-based diets were associated with a lower risk of mortality, improved kidney function, and favorable metabolic profiles (fibroblast growth factor-23, uremic toxins, insulin sensitivity, inflammatory biomarkers). Only few studies reported nutrient content of plant-based diets. These studies found that plant-based diets had lower dietary acid load, lower or no significant difference in phosphorus and sodium, and higher potassium and fiber. One study reported that vegetarian diets were associated with severe vitamin D deficiency compared to nonvegetarian diets. SUMMARY: Plant-based diets provide several benefits for prevention and management of CKD, with little risk for individuals with CKD. Incorporation of vitamin D rich foods in plant-based diets may be helpful.
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RATIONALE & OBJECTIVE: Studies have shown that generally healthy individuals who consume diets rich in plant foods have a lower risk of incident chronic kidney disease (CKD) and cardiovascular disease. This study investigated the prospective associations of plant-based diets with the risk of CKD progression and all-cause mortality in individuals with CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 2,539 participants with CKD recruited between 2003-2008 into the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURE: Responses on the Diet History Questionnaire were used to calculate scores for the overall plant-based diet index, healthy plant-based diet index, and unhealthy plant-based diet index. OUTCOME: (1) CKD progression defined as≥50% estimated glomerular filtration rate decline from baseline or kidney replacement therapy (dialysis, transplant) and (2) all-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards models to compute hazard ratios and 95% confidence intervals adjusting for lifestyle, socioeconomic, and clinical covariates. RESULTS: There were 977 CKD progression events and 836 deaths during a median follow-up period of 7 and 12 years, respectively. Participants with the highest versus lowest adherence to overall plant-based diets and healthy plant-based diets had 26% (HR, 0.74 [95% CI, 0.62-0.88], P trend<0.001) and 21% (HR, 0.79 [95% CI, 0.66-0.95], P trend=0.03) lower risks of all-cause mortality, respectively. Each 10-point higher score of unhealthy plant-based diets was modestly associated with a higher risk of CKD progression (HR, 1.14 [95% CI, 1.03-1.25) and all-cause mortality (HR, 1.11 [95% CI, 1.00-1.23). LIMITATIONS: Self-reported diet may be subject to measurement error. CONCLUSIONS: Adherence to an overall plant-based diet and a healthy plant-based diet is associated with a reduced risk of all-cause mortality among individuals with CKD. An unhealthy plant-based was associated with an elevated risk of CKD progression and all-cause mortality. PLAIN-LANGUAGE SUMMARY: Plant-based diets are healthful dietary patterns that have been linked to a lower risk of chronic diseases. However, the impact of plant-based diets on clinical outcomes in patients with chronic kidney disease (CKD) is not well established. In 2,539 individuals with CKD, we examined the associations of adherence to 3 different types of plant-based diets with the risks of CKD progression and all-cause mortality. We found that following an overall plant-based diet and a healthy plant-based diet was associated with a lower risk of all-cause mortality. By contrast, following an unhealthy plant-based diet was associated with a higher risk of CKD progression and all-cause mortality. These results suggest that the quality of plant-based diets may be important for CKD management.
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Dieta Baseada em Plantas , Mortalidade , Insuficiência Renal Crônica , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Coortes , Progressão da Doença , Cooperação do Paciente , Estudos Prospectivos , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/dietoterapia , Fatores de RiscoRESUMO
BACKGROUND: Over the past 4 years, aesthetic surgery, notably liposuction, has substantially increased. Tumescent liposuction, a popular technique, has two variants-true tumescent liposuction (TTL) and semi-tumescent liposuction. While TTL reduces risks, it has limitations. There is no literature reported on semi-tumescent liposuction under deep sedation using the propofol-ketamine protocol, which is proposed as a potentially safe alternative. METHODS: The retrospective analysis covered 8 years and included 3094 patients performed for tumescent liposuction under deep sedation, utilizing the propofol-ketamine protocol. The evaluation of patient safety involved an examination of potential adverse events with a specific focus on respiratory issues related to sedation, including instances of mask ventilation. RESULTS: Among the 3094 cases, no fatalities were recorded. Noteworthy events included 43 mask ventilation instances, primarily occurring in the initial 10 min. Twelve cases experienced surgery cancellation due to various factors, including respiratory issues. Three patients were transferred to upper-level hospitals, while another three required blood transfusions. Vigilant management prevented significant complications, and other adverse events like venous thromboembolism (VTE), fat embolism, severe lidocaine toxicity, and so on were not observed. CONCLUSIONS: The analysis of 3094 tumescent liposuction cases highlighted the overall safety profile of the propofol-ketamine protocol under deep sedation. The scarcity of severe complications underscores its viability. The study emphasizes the significance of thorough preoperative assessments, careful patient selection, and awareness of potential complications. Prompt interventions, particularly in addressing sedation-related respiratory issues, further contribute to positive outcomes for patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Sedação Profunda , Ketamina , Lipectomia , Propofol , Humanos , Ketamina/efeitos adversos , Ketamina/administração & dosagem , Estudos Retrospectivos , Propofol/efeitos adversos , Propofol/administração & dosagem , Lipectomia/métodos , Lipectomia/efeitos adversos , Feminino , Sedação Profunda/efeitos adversos , Sedação Profunda/métodos , Adulto , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Medição de Risco , Segurança do Paciente , Estudos de Coortes , IdosoRESUMO
In this study, we investigated how geniposide (a bioactive ingredient of gardenia fruit) acts on lipopolysaccharide (LPS)-stimulated macrophages. Griess reagent assay, Fluo-4 calcium assay, dihydrorhodamine 123 assay, multiplex cytokine assay, quantitative RT-PCR, and flow cytometry assay were used for this study. Data showed that geniposide at concentrations of 10, 25, and 50 µM reduced significantly the levels of nitric oxide, intracellular Ca2+, and hydrogen peroxide in LPS-activated RAW 264.7. Multiplex cytokine assay showed that geniposide at concentrations of 10, 25, and 50 µM meaningfully suppressed levels of IL-6, G-CSF, MCP-1, and MIP-1α in RAW 264.7 provoked by LPS; additionally, geniposide at concentrations of 25 and 50 µM meaningfully suppressed the levels of TNF-α, IP-10, GM-CSF, and MIP-1ß. Flow cytometry assay showed that geniposide reduces significantly the level of activated P38 MAPK in RAW 264.7 provoked by LPS. Geniposide meaningfully suppressed LPS-induced transcription of inflammatory target genes, such as Chop, Jak2, Fas, c-Jun, c-Fos, Stat3, Nos2, Ptgs2, Gadd34, Asc, Xbp1, Nlrp3, and Par-2. Taken together, geniposide exerts alleviative effects in LPS-stimulated macrophages via the calcium pathway.
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Cálcio , Iridoides , Lipopolissacarídeos , Humanos , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Cálcio/metabolismo , Macrófagos/metabolismo , Citocinas/metabolismo , Óxido Nítrico/metabolismo , NF-kappa B/metabolismo , Inflamação/metabolismoRESUMO
Algal blooms contribute to water quality degradation, unpleasant odors, taste issues, and the presence of harmful substances in artificially constructed weirs. Mitigating these adverse effects through effective algal bloom management requires identifying the contributing factors and predicting algal concentrations. This study focused on the upstream region of the Seungchon Weir in Korea, which is characterized by elevated levels of total nitrogen and phosphorus due to a significant influx of water from a sewage treatment plant. We employed four distinct machine learning models to predict chlorophyll-a (Chl-a) concentrations and identified the influential variables linked to local algal bloom events. The gradient boosting model enabled an in-depth exploration of the intricate relationships between algal occurrence and water quality parameters, enabling accurate identification of the causal factors. The models identified the discharge flow rate (D-Flow) and water temperature as the primary determinants of Chl-a levels, with feature importance values of 0.236 and 0.212, respectively. Enhanced model precision was achieved by utilizing daily average D-Flow values, with model accuracy and significance of the D-Flow amplifying as the temporal span of daily averaging increased. Elevated Chl-a concentrations correlated with diminished D-Flow and temperature, highlighting the pivotal role of D-Flow in regulating Chl-a concentration. This trend can be attributed to the constrained discharge of the Seungchon Weir during winter. Calculating the requisite D-Flow to maintain a desirable Chl-a concentration of up to 20 mg/m3 across varying temperatures revealed an escalating demand for D-Flow with rising temperatures. Specific D-Flow ranges, corresponding to each season and temperature condition, were identified as particularly influential on Chl-a concentration. Thus, optimizing Chl-a reduction can be achieved by strategically increasing D-Flow within these specified ranges for each season and temperature variation. This study highlights the importance of maintaining sufficient D-Flow levels to mitigate algal proliferation within river systems featuring weirs.
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Monitoramento Ambiental , Rios , Temperatura , Clorofila A , Clorofila/análise , Qualidade da Água , Eutrofização , Nitrogênio/análise , Fósforo/análise , ChinaRESUMO
Peripheral nerve injuries have common clinical problems that are often accompanied by sensory and motor dysfunction and failure of axonal regeneration. Although various therapeutic approaches have been attempted, full functional recovery and axonal regeneration are rarely achieved in patients. In this study, we investigated the effects of recombinant adeno-associated virus (AAV) of mesencephalic astrocyte-derived neurotrophic factor (AAV-MANF) or placental growth factor (AAV-PlGF) transduced into mesenchymal stem cells (hMSC-MANF and hMSC-PlGF), which were then transplanted using human decellularized nerves (HDN) into sciatic nerve injury model. Our results showed that both AAV-MANF and AAV-PlGF were expressed in MSCs transplanted into the injury site. Behavioral measurements performed 2, 4, 6, 8, and 12 weeks after injury indicated that MANF facilitated the rapid and improved recovery of sensory and motor functions than PlGF. In addition, immunohistochemical analysis was used to quantitatively analyze the myelination of neurofilaments, Schwann cells, and regrowth axons. Both hMSC-MANF and hMSC-PlGF increased axon numbers and immunoreactive areas of axons and Schwann cells compared with the hMSC-GFP group. However, hMSC-MANF significantly improved the thickness of axons and Schwann cells compared with hMSC-PlGF. G-ratio analysis also showed a marked increase in axon myelination in axons thicker than 2.0 µm treated with MANF than that treated with PlGF. Our study suggests that transplantation of hMSC transduced with AAV-MANF has a potential to provide a novel and efficient strategy for promoting functional recovery and axonal regeneration in peripheral nerve injury.
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Traumatismos dos Nervos Periféricos , Neuropatia Ciática , Humanos , Feminino , Traumatismos dos Nervos Periféricos/metabolismo , Recuperação de Função Fisiológica/fisiologia , Astrócitos/metabolismo , Regeneração Nervosa/fisiologia , Fator de Crescimento Placentário/metabolismo , Neuropatia Ciática/metabolismo , Axônios/metabolismo , Fatores de Crescimento Neural/metabolismo , Células de Schwann/metabolismo , Nervo Isquiático/metabolismoRESUMO
BACKGROUND: NT-proBNP is an important predictor of mortality but is inversely related to estimated glomerular filtration rate (eGFR). Whether the prognostic value of NT-proBNP is similar at different levels of kidney function is unknown. AIMS: We evaluated the association of NT-proBNP with eGFR and its implications for all-cause and cardiovascular mortality risk in the general population. METHODS: We included adults without prior cardiovascular disease from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004. We used linear regression to characterize the cross-sectional associations of NT-proBNP with eGFR. We used Cox regression to assess the prospective associations of NT-proBNP with mortality across categories of eGFR. RESULTS: Among 11,456 participants (mean age 43 years, 48% female, 71% White, 11% Black), there was an inverse association between NT-proBNP and eGFR, which was stronger in those with more impaired kidney function. Per 15-unit decrease in eGFR, NT-proBNP was 4.3-fold higher for eGFR<30; 1.7-fold higher for eGFR 30 to 60, 1.4-fold higher for eGFR 61 to 90, 1.1-fold higher for eGFR 91 to 120 mL/min/1.73 m2. Over a median 17.6 years of follow-up, 2,275 deaths (622 cardiovascular) occurred. Higher NT-proBNP was associated with higher all-cause (HR per doubling of NT-proBNP: 1.20, 95% CI: 1.16-1.25) and cardiovascular mortality (HR: 1.34, 95% CI 1.25-1.44). Associations were similar across eGFR categories (P-interaction >.10). Adults with NT-proBNP≥450 pg/mL and eGFR<60 mL/min/1.73m2 had 3.4-fold higher all-cause mortality and 5.5-fold higher cardiovascular mortality risk, compared to those with NT-proBNP<125 pg/mL and eGFR>90 mL/min/1.73m2. CONCLUSION: Despite its strong inverse association with eGFR, NT-proBNP has robust associations with mortality across the full range of kidney function in the general US adult population.
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Doenças Cardiovasculares , Peptídeo Natriurético Encefálico , Humanos , Adulto , Feminino , Masculino , Taxa de Filtração Glomerular , Inquéritos Nutricionais , Biomarcadores , Estudos Transversais , Prognóstico , Fragmentos de PeptídeosRESUMO
RATIONALE & OBJECTIVE: Ultraprocessed foods are widely consumed in the United States and are associated with cardiovascular disease (CVD), mortality, and kidney function decline in the general population. We investigated associations between ultraprocessed food intake and chronic kidney disease (CKD) progression, all-cause mortality, and incident CVD in adults with chronic kidney disease (CKD). STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Chronic Renal Insufficiency Cohort Study participants who completed baseline dietary questionnaires. EXPOSURE: Ultraprocessed food intake (in servings per day) classified according to the NOVA system. OUTCOMES: CKD progression (≥50% decrease in estimated glomerular filtration rate [eGFR] or initiation of kidney replacement therapy), all-cause mortality, and incident CVD (myocardial infarction, congestive heart failure, or stroke). ANALYTICAL APPROACH: Cox proportional hazards models adjusted for demographic, lifestyle, and health covariates. RESULTS: There were 1,047 CKD progression events observed during a median follow-up of 7 years. Greater ultraprocessed food intake was associated with higher risk of CKD progression (tertile 3 vs tertile 1, HR, 1.22; 95% CI, 1.04-1.42; P=0.01 for trend). The association differed by baseline kidney function, such that greater intake was associated with higher risk among people with CKD stages 1/2 (eGFR≥60mL/min/1.73m2; tertile 3 vs tertile 1, HR, 2.61; 95% CI, 1.32-5.18) but not stages 3a-5 (eGFR<60mL/min/1.73m2; P=0.003 for interaction). There were 1,104 deaths observed during a median follow-up of 14 years. Greater ultraprocessed food intake was associated with higher risk of mortality (tertile 3 vs tertile 1, HR, 1.21; 95% CI, 1.04-1.40; P=0.004 for trend). LIMITATIONS: Self-reported diet. CONCLUSIONS: Greater ultraprocessed food intake may be associated with CKD progression in earlier stages of CKD and is associated with higher risk of all-cause mortality in adults with CKD. PLAIN LANGUAGE SUMMARY: Ultraprocessed foods are industrial formulations produced using ingredients and processes that are not commonly used in culinary preparations and contain few, if any, intact unprocessed foods. Ultraprocessed foods are widely consumed in the United States, and high intakes of such foods have been linked to cardiovascular disease, kidney disease, and mortality in the general population. In this study, we found that greater intake of ultraprocessed foods was associated with higher risk of kidney disease progression and mortality in adults with chronic kidney disease. Our findings suggest that patients with kidney disease may benefit from greater consumption of fresh, whole, and homemade or hand-prepared foods and fewer highly processed foods.
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Doenças Cardiovasculares , Insuficiência Renal Crônica , Adulto , Humanos , Estados Unidos/epidemiologia , Estudos de Coortes , Estudos Prospectivos , Fatores de Risco , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/complicações , Taxa de Filtração Glomerular , Rim , Progressão da DoençaRESUMO
BACKGROUND: Within healthy dietary patterns, manipulation of the proportion of macronutrient can reduce CVD risk. However, the biological pathways underlying healthy diet-disease associations are poorly understood. Using an untargeted, large-scale proteomic profiling, we aimed to (1) identify proteins mediating the association between healthy dietary patterns varying in the proportion of macronutrient and lipoproteins, and (2) validate the associations between diet-related proteins and lipoproteins in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: In 140 adults from the OmniHeart trial, a randomized, cross-over, controlled feeding study with 3 intervention periods (carbohydrate-rich; protein-rich; unsaturated fat-rich dietary patterns), 4,958 proteins were quantified at the end of each diet intervention period using an aptamer assay (SomaLogic). We assessed differences in log2-transformed proteins in 3 between-diet comparisons using paired t-tests, examined the associations between diet-related proteins and lipoproteins using linear regression, and identified proteins mediating these associations using a causal mediation analysis. Levels of diet-related proteins and lipoprotein associations were validated in the ARIC study (n = 11,201) using multivariable linear regression models, adjusting for important confounders. RESULTS: Three between-diet comparisons identified 497 significantly different proteins (protein-rich vs. carbohydrate-rich = 18; unsaturated fat-rich vs. carbohydrate-rich = 335; protein-rich vs. unsaturated fat-rich dietary patterns = 398). Of these, 9 proteins [apolipoprotein M, afamin, collagen alpha-3(VI) chain, chitinase-3-like protein 1, inhibin beta A chain, palmitoleoyl-protein carboxylesterase NOTUM, cathelicidin antimicrobial peptide, guanylate-binding protein 2, COP9 signalosome complex subunit 7b] were positively associated with lipoproteins [high-density lipoprotein (HDL)-cholesterol (C) = 2; triglyceride = 5; non-HDL-C = 3; total cholesterol to HDL-C ratio = 1]. Another protein, sodium-coupled monocarboxylate transporter 1, was inversely associated with HDL-C and positively associated with total cholesterol to HDL-C ratio. The proportion of the association between diet and lipoproteins mediated by these 10 proteins ranged from 21 to 98%. All of the associations between diet-related proteins and lipoproteins were significant in the ARIC study, except for afamin. CONCLUSIONS: We identified proteins that mediate the association between healthy dietary patterns varying in macronutrients and lipoproteins in a randomized feeding study and an observational study. TRIAL REGISTRATION: NCT00051350 at clinicaltrials.gov.
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BACKGROUND: Molecular mechanisms underlying the benefits of healthy dietary patterns are poorly understood. Identifying protein biomarkers of dietary patterns can contribute to characterizing biological pathways influenced by food intake. OBJECTIVES: This study aimed to identify protein biomarkers associated with four indexes of healthy dietary patterns: Healthy Eating Index-2015 (HEI-2015); Alternative Healthy Eating Index-2010 (AHEI-2010); DASH diet; and alternate Mediterranean Diet (aMED). METHODS: Analyses were conducted on 10,490 Black and White men and women aged 49-73 y from the ARIC study at visit 3 (1993-1995). Dietary intake data were collected using a food frequency questionnaire, and plasma proteins were quantified using an aptamer-based proteomics assay. Multivariable linear regression models were used to examine the association between 4955 proteins and dietary patterns. We performed pathway overrepresentation analysis for diet-related proteins. An independent study population from the Framingham Heart Study was used for replication analyses. RESULTS: In the multivariable-adjusted models, 282 out of 4955 proteins (5.7%) were significantly associated with at least one dietary pattern (HEI-2015: 137; AHEI-2010: 72; DASH: 254; aMED: 35; P value < 0.05/4955 = 1.01 × 10-5). There were 148 proteins that were associated with only one dietary pattern (HEI-2015: 22; AHEI-2010: 5; DASH: 121; aMED: 0), and 20 proteins were associated with all four dietary patterns. Five unique biological pathways were significantly enriched by diet-related proteins. Seven out of 20 proteins associated with all dietary patterns in the ARIC study were available for replication analyses, and 6 out of these 7 proteins were consistent in direction and significantly associated with at least 1 dietary pattern in the Framingham Heart Study (HEI-2015: 2; AHEI-2010: 4; DASH: 6; aMED: 4; P value < 0.05/7 = 7.14 × 10-3). CONCLUSIONS: A large-scale proteomic analysis identified plasma protein biomarkers that are representative of healthy dietary patterns among middle-aged and older US adult population. These protein biomarkers may be useful objective indicators of healthy dietary patterns.
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Aterosclerose , Dieta Mediterrânea , Masculino , Adulto , Pessoa de Meia-Idade , Humanos , Feminino , Idoso , Proteômica , Dieta , Estudos Longitudinais , Biomarcadores , Proteínas Sanguíneas , Aterosclerose/epidemiologiaRESUMO
BACKGROUND: Dairy consumption is related to chronic disease risk; however, the measurement of dairy consumption has largely relied upon self-report. Untargeted metabolomics allows for the identification of objective markers of dietary intake. OBJECTIVES: We aimed to identify associations between dietary dairy intake (total dairy, low-fat dairy, and high-fat dairy) and serum metabolites in 2 independent study populations of United States adults. METHODS: Dietary intake was assessed with food frequency questionnaires. Multivariable linear regression models were used to estimate cross-sectional associations between dietary intake of dairy and 360 serum metabolites analyzed in 2 subgroups of the Atherosclerosis Risk in Communities study (ARIC; n = 3776). Results from the 2 subgroups were meta-analyzed using fixed effects meta-analysis. Significant meta-analyzed associations in the ARIC study were then tested in the Bogalusa Heart Study (BHS; n = 785). RESULTS: In the ARIC study and BHS, the mean age was 54 and 48 years, 61% and 29% were Black, and the mean dairy intake was 1.7 and 1.3 servings/day, respectively. Twenty-nine significant associations between dietary intake of dairy and serum metabolites were identified in the ARIC study (total dairy, n = 14; low-fat dairy, n = 10; high-fat dairy, n = 5). Three associations were also significant in BHS: myristate (14:0) was associated with high-fat dairy, and pantothenate was associated with total dairy and low-fat dairy, but 23 of the 27 associations significant in the ARIC study and tested in BHS were not associated with dairy in BHS. CONCLUSIONS: We identified metabolomic associations with dietary intake of dairy, including 3 associations found in 2 independent cohort studies. These results suggest that myristate (14:0) and pantothenate (vitamin B5) are candidate biomarkers of dairy consumption.
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Aterosclerose , Miristatos , Adulto , Humanos , Estados Unidos/epidemiologia , Estudos Transversais , Estudos Longitudinais , Biomarcadores , Aterosclerose/epidemiologia , Laticínios/análise , Fatores de Risco , DietaRESUMO
INTRODUCTION: Changes in the DNA methylation of 5-HTTLPR are associated with the pathophysiology of panic disorder (PD). This study was conducted to investigate the association between stressful life events and the level of 5-HTTLPR methylation in patients with PD. We also examined whether these factors were associated with white matter alterations in psychological trauma-related regions. METHODS: The participants comprised 232 patients with PD and 93 healthy adults of Korean descent. DNA methylation levels of five cytosine-phosphate-guanine (CpG) sites in the 5-HTTLPR region were analyzed. Voxel-wise statistical analysis of diffusion tensor imaging data was performed within the trauma-related regions. RESULTS: PD patients showed significantly lower levels of the DNA methylation at 5-HTTLPR 5 CpG sites than healthy controls. In patients with PD, the DNA methylation levels at 5-HTTLPR 5 CpG sites showed significant negative association with the parental separation-related psychological distress, and positive correlations with the fractional anisotropy values of the superior longitudinal fasciculus (SLF) which might be related to trait anxiety. CONCLUSION: Early life stress was significantly associated with DNA methylation levels at 5-HTTLPR related to the decreased white matter integrity in the SLF region in PD. Decreased white matter connectivity in the SLF might be related to trait anxiety and is vital to the pathophysiology of PD.
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Experiências Adversas da Infância , Transtorno de Pânico , Substância Branca , Adulto , Humanos , Imagem de Tensor de Difusão , Metilação de DNA , Transtorno de Pânico/diagnóstico por imagem , Transtorno de Pânico/genética , Transtorno de Pânico/psicologia , República da Coreia , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Substância Branca/diagnóstico por imagemRESUMO
Maternal immune activation (MIA) contributes to behavioural abnormalities associated with neurodevelopmental disorders in both primate and rodent offspring. In humans, epidemiological studies suggest that exposure of fetuses to maternal inflammation increases the likelihood of developing autism spectrum disorder. In pregnant mice, interleukin-17a (IL-17a) produced by T helper 17 (TH17) cells (CD4+ T helper effector cells involved in multiple inflammatory conditions) induces behavioural and cortical abnormalities in the offspring exposed to MIA. However, it is unclear whether other maternal factors are required to promote MIA-associated phenotypes. Moreover, the underlying mechanisms by which MIA leads to T cell activation with increased IL-17a in the maternal circulation are not well understood. Here we show that MIA phenotypes in offspring require maternal intestinal bacteria that promote TH17 cell differentiation. Pregnant mice that had been colonized with mouse commensal segmented filamentous bacteria or human commensal bacteria that induce intestinal TH17 cells were more likely to produce offspring with MIA-associated abnormalities. We also show that small intestine dendritic cells from pregnant, but not from non-pregnant, females secrete IL-1ß, IL-23 and IL-6 and stimulate T cells to produce IL-17a upon exposure to MIA. Overall, our data suggest that defined gut commensal bacteria with a propensity to induce TH17 cells may increase the risk of neurodevelopmental disorders in the offspring of pregnant mothers undergoing immune system activation owing to infections or autoinflammatory syndromes.
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Microbioma Gastrointestinal/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Efeitos Tardios da Exposição Pré-Natal/microbiologia , Animais , Comportamento Animal , Células Dendríticas/imunologia , Feminino , Inflamação/imunologia , Inflamação/microbiologia , Interleucina-17/imunologia , Interleucina-1beta/imunologia , Interleucina-23/imunologia , Interleucina-6/imunologia , Intestino Delgado/citologia , Intestino Delgado/imunologia , Intestino Delgado/microbiologia , Masculino , Camundongos , Fenótipo , Gravidez , Simbiose , Células Th17/citologia , Células Th17/imunologiaRESUMO
Viral infection during pregnancy is correlated with increased frequency of neurodevelopmental disorders, and this is studied in mice prenatally subjected to maternal immune activation (MIA). We previously showed that maternal T helper 17 cells promote the development of cortical and behavioural abnormalities in MIA-affected offspring. Here we show that cortical abnormalities are preferentially localized to a region encompassing the dysgranular zone of the primary somatosensory cortex (S1DZ). Moreover, activation of pyramidal neurons in this cortical region was sufficient to induce MIA-associated behavioural phenotypes in wild-type animals, whereas reduction in neural activity rescued the behavioural abnormalities in MIA-affected offspring. Sociability and repetitive behavioural phenotypes could be selectively modulated according to the efferent targets of S1DZ. Our work identifies a cortical region primarily, if not exclusively, centred on the S1DZ as the major node of a neural network that mediates behavioural abnormalities observed in offspring exposed to maternal inflammation.
Assuntos
Comportamento Animal , Inflamação/fisiopatologia , Transtornos Mentais/etiologia , Complicações Infecciosas na Gravidez/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Células Th17 , Animais , Feminino , Masculino , Transtornos Mentais/psicologia , Camundongos , Mães , Fenótipo , Gravidez , Células Piramidais/patologia , Células Piramidais/fisiologia , Comportamento Social , Córtex Somatossensorial/anormalidades , Córtex Somatossensorial/patologia , Córtex Somatossensorial/fisiopatologia , Células Th17/fisiologiaRESUMO
Moutan Cortex, Paeonia suffruticosa root, has long been used as a medicine for the treatment of inflammatory diseases. The aim of this study was to evaluate the modulative properties of Moutan Cortex water extract (CP) on endoplasmic reticulum (ER) stress-related macrophage activation via the calcium-CHOP pathway. RAW 264.7 mouse macrophages were activated by lipopolysaccharide (LPS), and the levels of various inflammatory mediators from RAW 264.7 were evaluated. The multiplex cytokine assay was used to investigate both cytokines and growth factors, and RT-PCR was used to investigate the expressions of inflammation-related genes, such as CHOP. Data represent the levels of NO and cytosolic calcium in LPS-stimulated RAW 264.7 were significantly inhibited by CP as well as hydrogen peroxide (p < 0.05). Minutely, NO production in LPS-stimulated RAW 264.7 incubated with CP at concentrations of 25, 50, 100, and 200 µg/mL for 24 h was 97.32 ± 1.55%, 95.86 ± 2.26%, 94.64 ± 1.83%, and 92.69 ± 2.31% of the control value (LPS only), respectively (p < 0.05). Calcium release in LPS-stimulated RAW 264.7 incubated with CP at concentrations of 25, 50, 100, and 200 µg/mL for 18 h was 95.78 ± 1.64%, 95.41 ± 1.14%, 94.54 ± 2.76%, and 90.89 ± 3.34% of the control value, respectively (p < 0.05). Hydrogen peroxide production in LPS-stimulated RAW 264.7 incubated with CP at concentrations of 25, 50, 100, and 200 µg/mL for 24 h was 79.15 ± 7.16%, 63.83 ± 4.03%, 46.27 ± 4.38%, and 40.66 ± 4.03% of the control value, respectively (p < 0.05). It is interesting that the production of IL-6, TNF-α, G-CSF, MIP-1α, MIP-2, and M-CSF in LPS-stimulated RAW 264.7 were significantly inhibited by CP (p < 0.05), while the production of LIX, LIF, RANTES, and MIP-1ß showed a meaningful decrease. CP at concentrations of 25, 50, 100, and 200 µg/mL significantly reduced the transcription of Chop, Camk2α, NOS, STAT1, STAT3, Ptgs2, Jak2, c-Jun, Fas, c-Fos, TLR3, and TLR9 in LPS-stimulated RAW 264.7 (p < 0.05). CP at concentrations of 25, 50, and 100 µg/mL significantly reduced the phosphorylation of STAT3, p38 MAPK, and IκB-α in LPS-stimulated RAW 264.7 (p < 0.05). These results suggest that CP might modulate macrophage activation via LPS-induced calcium signaling and the ER stress-CHOP pathway.
Assuntos
Lipopolissacarídeos , Paeonia , Animais , Camundongos , Cálcio/metabolismo , Sinalização do Cálcio , Citocinas/metabolismo , Peróxido de Hidrogênio/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Ativação de Macrófagos , Macrófagos/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Paeonia/metabolismo , Células RAW 264.7 , Estresse do Retículo EndoplasmáticoRESUMO
BACKGROUND: Prior studies have documented lower cardiovascular disease (CVD) risk among people with a higher adherence to a plant-based dietary pattern. Non-Hispanic black Americans are an understudied group with high burden of CVD, yet studies of plant-based diets have been limited in this population. METHODS AND FINDINGS: We conducted an analysis of prospectively collected data from a community-based cohort of African American adults (n = 3,635) in the Jackson Heart Study (JHS) aged 21-95 years, living in the Jackson, Mississippi, metropolitan area, US, who were followed from 2000 to 2018. Using self-reported dietary data, we assigned scores to participants' adherence to 3 plant-based dietary patterns: an overall plant-based diet index (PDI), a healthy PDI (hPDI), and an unhealthy PDI (uPDI). Cox proportional hazards models were used to estimate associations between plant-based diet scores and CVD incidence and all-cause mortality. Over a median follow-up of 13 and 15 years, there were 293 incident CVD cases and 597 deaths, respectively. After adjusting for sociodemographic characteristics (age, sex, and education) and health behaviors (smoking, alcohol intake, margarine intake, physical activity, and total energy intake), no significant association was observed between plant-based diets and incident CVD for overall PDI (hazard ratio [HR] 1.06, 95% CI 0.78-1.42, p-trend = 0.72), hPDI (HR 1.07, 95% CI 0.80-1.42, p-trend = 0.67), and uPDI (HR 0.95, 95% CI 0.71-1.28, p-trend = 0.76). Corresponding HRs (95% CIs) for all-cause mortality risk with overall PDI, hPDI, and uPDI were 0.96 (0.78-1.18), 0.94 (0.76-1.16), and 1.06 (0.86-1.30), respectively. Corresponding HRs (95% CIs) for incident coronary heart disease with overall PDI, hPDI, and uPDI were 1.09 (0.74-1.61), 1.11 (0.76-1.61), and 0.79 (0.52-1.18), respectively. For incident total stroke, HRs (95% CIs) for overall PDI, hPDI, and uPDI were 1.00 (0.66-1.52), 0.91 (0.61-1.36), and 1.26 (0.84-1.89) (p-trend for all tests > 0.05). Limitations of the study include use of self-reported dietary intake, residual confounding, potential for reverse causation, and that the study did not capture those who exclusively consume plant-derived foods. CONCLUSIONS: In this study of black Americans, we observed that, unlike in prior studies, greater adherence to a plant-based diet was not associated with CVD or all-cause mortality.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Doenças Cardiovasculares/epidemiologia , Dieta Vegetariana/estatística & dados numéricos , Mortalidade/etnologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mississippi/epidemiologia , Adulto JovemRESUMO
RATIONALE & OBJECTIVE: Ultraprocessed foods have become readily available in the global food supply in the past few decades. Several adverse health outcomes have been linked with higher consumption of ultraprocessed foods. However, the impact of ultraprocessed foods on chronic kidney disease (CKD) risk remains unknown. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 14,679 middle-aged adults without CKD at baseline in the Atherosclerosis Risk in Communities (ARIC) study. EXPOSURE: Ultraprocessed foods consumption (servings per day) calculated using dietary data collected via a food frequency questionnaire at visit 1 and visit 3. OUTCOME: Incident CKD defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 accompanied by ≥25% eGFR decline, CKD-related hospitalization or death, or kidney failure with kidney replacement therapy. ANALYTICAL APPROACH: Multivariable-adjusted Cox proportional hazards models were used to assess the association between ultraprocessed foods consumption and CKD. Restricted cubic splines were used to examine the shape of the association. RESULTS: During a median follow-up period of 24 years, there were 4,859 cases of incident CKD. The incidence rate for the highest quartile of ultraprocessed foods consumption was 16.5 (95% CI, 15.6-17.4) per 1,000 person-years and 14.7 (95% CI, 13.9-15.5) per 1,000 person-years for the lowest quartile of consumption. After adjusting for a range of confounders including lifestyle factors, demographic characteristics, and health behaviors, participants in the highest quartile of ultraprocessed foods consumption had a 24% higher risk (HR, 1.24 [95% CI, 1.15-1.35]) of developing CKD compared with those in the lowest quartile. There was an approximately linear relationship observed between ultraprocessed food intake and risk of CKD. By substituting 1 serving of ultraprocessed foods with minimally processed foods, there was a 6% lower risk of CKD observed (HR, 0.94 [95% CI, 0.93-0.96]; P < 0.001). LIMITATIONS: Self-reported data and residual confounding. CONCLUSIONS: Higher ultraprocessed foods consumption was independently associated with a higher risk of incident CKD in a general population.