RESUMO
PURPOSE: This study examined the relationship between structural brain networks and long-term treatment outcomes in patients with panic disorder (PD) using machine learning methods. METHOD: The study involved 80 participants (53 PD patients and 27 healthy controls) and included clinical assessments and MRI scans at baseline and after two years (160 MRIs). Patients were categorized based on their response to two-year pharmacotherapy. Brain networks were analyzed using white matter tractography and network-based statistics. RESULTS: Results showed structural network changes in PD patients, particularly in the extended fear network, including frontal regions, thalamus, and cingulate gyrus. Longitudinal analysis revealed that increased connections to the amygdala, hippocampus, and insula were associated with better treatment response. Conversely, overconnectivity in the amygdala and insula at baseline was associated with poor response, and similar patterns were found in the insula and parieto-occipital cortex related to non-remission. This study found that SVM and CPM could effectively predict treatment outcomes based on network pattern changes in PD. CONCLUSIONS: These findings suggest that monitoring structural connectome changes in limbic and paralimbic regions is critical for understanding PD and tailoring treatment. The study highlights the potential of using personalized biomarkers to develop individualized treatment strategies for PD.
RESUMO
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.
RESUMO
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.
RESUMO
Circulating α1-acid glycoprotein (AGP) and C-reactive protein (CRP) are commonly measured to assess inflammation, but these biomarkers fail to reveal the complex molecular biology of inflammation. We mined the maternal plasma proteome to detect proteins that covary with AGP and CRP. In 435 gravida predominantly in <12-week gestation, we correlated the relative quantification of plasma proteins assessed via a multiplexed aptamer assay (SOMAScan®) with AGP and CRP, quantified by immunoassay. We defined a plasma inflammasome as protein correlates meeting a false discovery rate <0.05. We examined potential pathways using principal component analysis. A total of 147 and 879 of 6431 detected plasma proteins correlated with AGP and CRP, respectively, of which 61 overlapped with both biomarkers. Positive correlates included serum amyloid, complement, interferon-induced, and immunoregulatory proteins. Negative correlates were micronutrient and lipid transporters and pregnancy-related anabolic proteins. The principal components (PCs) of AGP were dominated by negatively correlated anabolic proteins associated with gestational homeostasis, angiogenesis, and neurogenesis. The PCs of CRP were more diverse in function, reflecting cell surface and adhesion, embryogenic, and intracellular and extra-hepatic tissue leakage proteins. The plasma proteome of AGP or CRP reveals wide proteomic variation associated with early gestational inflammation, suggesting mechanisms and pathways that merit future research.
Assuntos
Proteína C-Reativa , Inflamassomos , Humanos , Feminino , Gravidez , Adulto , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Inflamassomos/metabolismo , Bangladesh , População Rural , Orosomucoide/metabolismo , Biomarcadores/sangue , Inflamação/sangue , Proteoma/metabolismo , Proteoma/análise , Análise de Componente Principal , Proteínas Sanguíneas/metabolismoRESUMO
The development of premalignant colorectal polyps is significantly influenced by various lifestyle and modifiable risk factors. In our study, we used a large cohort of 9025 patients, who underwent screening colonoscopies at a university hospital, to assess the risk factors associated with the development of three different colorectal cancer precursor lesions: non-advanced adenomas (NAs), advanced adenomatous lesions (ADLs), and sessile serrated lesions (SSLs). Among the participants, 3641 had NAs, 836 had ADLs, and 533 had SSLs. We identified obesity, current smoking, and appendicular skeletal muscle mass as modifiable lifestyle risk factors that increase the development of NAs and ADLs (all P < 0.05). Furthermore, we found a positive correlation between the degree of obesity and an increased risk of developing NAs and ADLs (all P for trend < 0.001), while non-smoking was associated with a decreased risk (P for trend < 0.001 and 0.003, respectively). Smoking was the only modifiable risk factor for developing SSLs (adjusted odds ratio [aOR] 1.58; 95% confidence interval [CI] 1.20-2.07), and the risk was even higher in patients with metabolic syndrome (aOR 1.71; 95% CI 1.05-2.77). Addressing modifiable lifestyle factors such as smoking and obesity could play an important role in reducing the risk of both non-advanced and advanced adenomatous lesions. Smoking cessation is especially important as it is a significant modifiable risk factor for sessile serrated lesions.
Assuntos
Adenoma , Colonoscopia , Neoplasias Colorretais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Adenoma/epidemiologia , Adenoma/etiologia , Adenoma/patologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/diagnóstico , Idoso , Obesidade/complicações , Fumar/efeitos adversos , Detecção Precoce de Câncer , Pólipos do Colo/patologia , Pólipos do Colo/epidemiologia , Pólipos do Colo/diagnóstico , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/epidemiologiaRESUMO
BACKGROUND & AIMS: Plant-based diets are associated with a lower risk of chronic diseases. Large-scale proteomics can identify objective biomarkers of plant-based diets, and improve our understanding of the pathways that link plant-based diets to health outcomes. This study investigated the plasma proteome of four different plant-based diets [overall plant-based diet (PDI), provegetarian diet, healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI)] in the Atherosclerosis Risk in Communities (ARIC) Study and replicated the findings in the Framingham Heart Study (FHS) Offspring cohort. METHODS: ARIC Study participants at visit 3 (1993-1995) with completed food frequency questionnaire (FFQ) data and proteomics data were divided into internal discovery (n = 7690) and replication (n = 2543) data sets. Multivariable linear regression was used to examine associations between plant-based diet indices (PDIs) and 4955 individual proteins in the discovery sample. Then, proteins that were internally replicated in the ARIC Study were tested for external replication in FHS (n = 1358). Pathway overrepresentation analysis was conducted for diet-related proteins. C-statistics were used to predict if the proteins improved prediction of plant-based diet indices beyond participant characteristics. RESULTS: In ARIC discovery, a total of 837 diet-protein associations (PDI = 233; provegetarian = 182; hPDI = 406; uPDI = 16) were observed at false discovery rate (FDR) < 0.05. Of these, 453 diet-protein associations (PDI = 132; provegetarian = 104; hPDI = 208; uPDI = 9) were internally replicated. In FHS, 167/453 diet-protein associations were available for external replication, of which 8 proteins (PDI = 1; provegetarian = 0; hPDI = 8; uPDI = 0) replicated. Complement and coagulation cascades, cell adhesion molecules, and retinol metabolism were over-represented. C-C motif chemokine 25 for PDI and 8 proteins for hPDI modestly but significantly improved the prediction of these indices individually and collectively (P value for difference in C-statistics<0.05 for all tests). CONCLUSIONS: Using large-scale proteomics, we identified potential candidate biomarkers of plant-based diets, and pathways that may partially explain the associations between plant-based diets and chronic conditions.
Assuntos
Aterosclerose , Proteínas Sanguíneas , Dieta Baseada em Plantas , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aterosclerose/sangue , Aterosclerose/epidemiologia , Biomarcadores/sangue , Proteínas Sanguíneas/análise , Estudos de Coortes , Dieta Saudável/estatística & dados numéricos , Dieta Baseada em Plantas/estatística & dados numéricos , Estudos Prospectivos , Proteômica/métodos , Fatores de RiscoRESUMO
Med1 binds to a nuclear receptor and regulates transcription. Elevated Med1 protein expression promotes cancer growth in hormone-dependent breast and prostate cancers. Med1 protein expression was investigated by deubiquitinating enzymes (DUBs) overexpression in breast cancer cell lines. Various DNA constructs of SRT-DUBs were overexpressed in the MCF7 cell line, and Med1 protein expression was investigated by western blotting. The cell growth and in vitro invasion assay were performed in BRCA1-associated protein 1 (BAP1) wild type and mutant (C91A) overexpressed cells. Ubiquitination of the Med1 protein was observed, and Med1 protein expression and transcriptional activity were verified by various DUBs overexpressed. Although Med1 protein expression increased upon the overexpression of BAP1, it was not affected by the overexpression of BAP1 mutant (C91A). BAP1 was increased by the E2 treatment, which has an important effect on the breast cancer growth, and cell growth was decreased by BAP1 C91A overexpression. However, metastatic capacities were decreased by BAP1. In addition, the binding between the Med1 and the BAP1 protein was observed. These data suggested that BAP1 regulated Med1 protein expression in breast cancer cells and involved in cancer cell growth and metastasis by binding to Med1 protein.
RESUMO
As IoT technology advances, using machine learning to detect user activities emerges as a promising strategy for delivering a variety of smart services. It is essential to have access to high-quality data that also respects privacy concerns and data streams from ambient sensors in the surrounding environment meet this requirement. However, despite growing interest in research, there is a noticeable lack of datasets from ambient sensors designed for public spaces, as opposed to those for private settings. To bridge this gap, we design the DOO-RE dataset within an actual meeting room environment, equipped with three types of ambient sensors: those triggered by actuators, users, and the environment itself. This dataset is compiled from the activities of over twenty students throughout a period of four months. DOO-RE provides reliable and purpose-oriented activity data in a public setting, with activity labels verified by multiple annotators through a process of cross-validation to guarantee data integrity. DOO-RE categorizes nine different types of activities and facilitates the study of both single and group activities. We are optimistic that DOO-RE will play a significant role in advancing human activity recognition technologies, enhancing smart automation systems, and enabling the rapid setup of smart spaces through ambient sensors.
RESUMO
Resilient individuals are less likely to develop psychiatric disorders despite extreme psychological distress. This study investigated the multimodal structural neural correlates of dispositional resilience among healthy individuals. Participants included 92 healthy individuals. The Korean version of the Connor-Davidson Resilience Scale and other psychological measures were used. Gray matter volumes (GMVs), cortical thickness, local gyrification index (LGI), and white matter (WM) microstructures were analyzed using voxel-based morphometry, FreeSurfer, and tract-based spatial statistics, respectively. Higher resilient individuals showed significantly higher GMVs in the inferior frontal gyrus (IFG), increased LGI in the insula, and lower fractional anisotropy values in the superior longitudinal fasciculus II (SLF II). These resilience's neural correlates were associated with good quality of life in physical functioning or general health and low levels of depression. Therefore, the GMVs in the IFG, LGI in the insula, and WM microstructures in the SLF II can be associated with resilience that contributes to emotional regulation, empathy, and social cognition.
Assuntos
Substância Cinzenta , Resiliência Psicológica , Substância Branca , Humanos , Masculino , Feminino , Adulto , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/fisiologia , Substância Cinzenta/anatomia & histologia , Substância Branca/diagnóstico por imagem , Substância Branca/fisiologia , Adulto Jovem , Imageamento por Ressonância Magnética , Voluntários Saudáveis , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Qualidade de VidaRESUMO
In this study, the effects of 3,5,7,3',4'-pentamethoxyflavone (KP1), a major bioactive ingredient isolated from the Kaempferia parviflora rhizomes, on a neurite outgrowth in Neuro2a cells and its mechanism have been investigated. KP1 increased concentration-dependently the percentage of neurite-bearing cells. KP1 showed a remarkable capability to elicit neurite outgrowth in Neuro2a cells, as evidenced by morphological alterations and immunostaining using anti-class III ß-tubulin and anti-NeuN antibodies. KP1 also displayed a higher neurogenic activity than retinoic acid (RA), a promoter of neurite outgrowth in Neuro2a cells. KP1 treatment caused significant elevation in phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK) and glycogen synthase kinase-3ß (GSK-3ß). However, KP1-triggered neurite outgrowth was markedly inhibited by treatment with the ERK inhibitor U0126, whereas p38 MAPK inhibitor SB203580 and GSK-3ß inhibitor SB216763 did not influence KP1-induced neurite outgrowth. These results demonstrate that KP1 elicits neurite outgrowth and triggers cell differentiation of Neuro2a cells through ERK signal pathway.
Assuntos
Sistema de Sinalização das MAP Quinases , Crescimento Neuronal , Animais , Crescimento Neuronal/efeitos dos fármacos , Camundongos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Neuritos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Flavonoides/farmacologia , Flavonas/farmacologia , Flavonas/química , Linhagem Celular Tumoral , Glicogênio Sintase Quinase 3 beta/metabolismo , Linhagem CelularRESUMO
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.
Assuntos
Monitoramento Ambiental , Rios , Temperatura , Clorofila A , Clorofila/análise , Qualidade da Água , Eutrofização , Nitrogênio/análise , Fósforo/análise , ChinaRESUMO
Rationale & Objective: While urine excretion of nitrogen estimates the total protein intake, biomarkers of specific dietary protein sources have been sparsely studied. Using untargeted metabolomics, this study aimed to identify serum metabolomic markers of 6 protein-rich foods and to examine whether dietary protein-related metabolites are associated with incident chronic kidney disease (CKD). Study Design: Prospective cohort study. Setting & Participants: A total of 3,726 participants from the Atherosclerosis Risk in Communities study without CKD at baseline. Exposures: Dietary intake of 6 protein-rich foods (fish, nuts, legumes, red and processed meat, eggs, and poultry), serum metabolites. Outcomes: Incident CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2 with ≥25% estimated glomerular filtration rate decline relative to visit 1, hospitalization or death related to CKD, or end-stage kidney disease). Analytical Approach: Multivariable linear regression models estimated cross-sectional associations between protein-rich foods and serum metabolites. C statistics assessed the ability of the metabolites to improve the discrimination of highest versus lower 3 quartiles of intake of protein-rich foods beyond covariates (demographics, clinical factors, health behaviors, and the intake of nonprotein food groups). Cox regression models identified prospective associations between protein-related metabolites and incident CKD. Results: Thirty significant associations were identified between protein-rich foods and serum metabolites (fish, n = 8; nuts, n = 5; legumes, n = 0; red and processed meat, n = 5; eggs, n = 3; and poultry, n = 9). Metabolites collectively and significantly improved the discrimination of high intake of protein-rich foods compared with covariates alone (difference in C statistics = 0.033, 0.051, 0.003, 0.024, and 0.025 for fish, nuts, red and processed meat, eggs, and poultry-related metabolites, respectively; P < 1.00 × 10-16 for all). Dietary intake of fish was positively associated with 1-docosahexaenoylglycerophosphocholine (22:6n3), which was inversely associated with incident CKD (HR, 0.82; 95% CI, 0.75-0.89; P = 7.81 × 10-6). Limitations: Residual confounding and sample-storage duration. Conclusions: We identified candidate biomarkers of fish, nuts, red and processed meat, eggs, and poultry. A fish-related metabolite, 1-docosahexaenoylglycerophosphocholine (22:6n3), was associated with a lower risk of CKD.
In this study, we aimed to identify associations between protein-rich foods (fish, nuts, legumes, red and processed meat, eggs, and poultry) and serum metabolites, which are small biological molecules involved in metabolism. Metabolites significantly associated with a protein-rich food individually and collectively improved the discrimination of the respective protein-rich food, suggesting that these metabolites should be prioritized in future diet biomarker research. We also studied associations between significant diet-related metabolites and incident kidney disease. One fish-related metabolite was associated with a lower kidney disease risk. This finding supports the recent nutritional guidelines recommending a Mediterranean diet, which includes fish as the main dietary protein source.
RESUMO
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 .
Assuntos
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
OBJECTIVE: Plant-based dietary patterns emphasize plant foods and minimize animal-derived foods. We investigated the association between plant-based dietary patterns and diabetes in a community-based U.S. sample of Black and White adults. RESEARCH DESIGN AND METHODS: We included middle-aged adults from the Atherosclerosis Risk in Communities (ARIC) study without diabetes at baseline who completed a food-frequency questionnaire (n = 11,965). We scored plant-based diet adherence according to three indices: overall, healthy, and unhealthy plant-based diet indices. Higher overall plant-based diet index (PDI) scores represent greater intakes of all plant foods and lower intakes of animal-derived foods. Higher healthy plant-based diet index (hPDI) scores represent greater healthy plant food intake and lower intakes of animal-derived and unhealthy plant foods. Higher unhealthy plant-based diet index (uPDI) scores represent greater unhealthy plant food intake and lower intakes of animal-derived and healthy plant foods. We used Cox regression to estimate hazard ratios (HRs) for incident diabetes (defined according to self-reported diagnosis, medication use, or elevated blood glucose) associated with each index. RESULTS: Over a median follow-up of 22 years, we identified 4,208 cases of diabetes among subjects. Higher PDI scores were associated with a lower risk of diabetes (quintile 5 vs. 1 HR 0.89 [95% CI 0.80, 0.98]; Ptrend = 0.01). hPDI scores were also inversely associated with diabetes risk (quintile 5 vs. 1 HR 0.85 [95% CI 0.77, 0.94]; Ptrend < 0.001). uPDI scores were not associated with diabetes risk. CONCLUSIONS: A dietary pattern that minimizes animal-derived foods and emphasizes plant foods may reduce diabetes risk.
Assuntos
Aterosclerose , Diabetes Mellitus , Adulto , Pessoa de Meia-Idade , Humanos , Dieta Vegetariana , Padrões Dietéticos , Dieta , Diabetes Mellitus/epidemiologia , Aterosclerose/epidemiologiaRESUMO
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.
Assuntos
Cálcio , Iridoides , Lipopolissacarídeos , Humanos , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Cálcio/metabolismo , Macrófagos/metabolismo , Citocinas/metabolismo , Óxido Nítrico/metabolismo , NF-kappa B/metabolismo , Inflamação/metabolismoRESUMO
BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet score lowers blood pressure (BP). We examined interactions between genotype and the DASH diet score in relation to systolic BP. METHODS: We analyzed up to 9â 420â 585 single nucleotide polymorphisms in up to 127â 282 individuals of 6 population groups (91% of European population) from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (n=35â 660) and UK Biobank (n=91â 622) and performed European population-specific and cross-population meta-analyses. RESULTS: We identified 3 loci in European-specific analyses and an additional 4 loci in cross-population analyses at Pinteraction<5e-8. We observed a consistent interaction between rs117878928 at 15q25.1 (minor allele frequency, 0.03) and the DASH diet score (Pinteraction=4e-8; P for heterogeneity, 0.35) in European population, where the interaction effect size was 0.42±0.09 mmâ Hg (Pinteraction=9.4e-7) and 0.20±0.06 mmâ Hg (Pinteraction=0.001) in Cohorts for Heart and Aging Research in Genomic Epidemiology and the UK Biobank, respectively. The 1 Mb region surrounding rs117878928 was enriched with cis-expression quantitative trait loci (eQTL) variants (P=4e-273) and cis-DNA methylation quantitative trait loci variants (P=1e-300). Although the closest gene for rs117878928 is MTHFS, the highest narrow sense heritability accounted by single nucleotide polymorphisms potentially interacting with the DASH diet score in this locus was for gene ST20 at 15q25.1. CONCLUSIONS: We demonstrated gene-DASH diet score interaction effects on systolic BP in several loci. Studies with larger diverse populations are needed to validate our findings.
Assuntos
Abordagens Dietéticas para Conter a Hipertensão , Hipertensão , Humanos , Pressão Sanguínea/genética , Dieta , GenótipoRESUMO
BACKGROUND: Mounting evidence indicates that although some plant-based diets are healthful, others are not. Changes in the gut microbiome and microbiome-dependent metabolites, such as trimethylamine N-oxide (TMAO), may explain differential health effects of plant-based diets. However, human data are sparse on whether qualitatively distinct types of plant-based diets differentially affect gut microbiome diversity, composition, particularly at the species level, and/or metabolites. OBJECTIVES: We aimed to examine cross-sectional associations of different plant-based indices with adult gut microbiome diversity, composition, and the metabolite TMAO. METHODS: We studied 705 adults in the Baltimore Longitudinal Study of Aging with data for diet, fecal microbiome (shotgun metagenomic sequencing), and key covariates. We derived healthful plant-based diet index (hPDI) and unhealthful plant-based diet index (uPDI) using data from food frequency questionnaires. We examined plant-based diet indices with microbiome α-diversity (richness and evenness measures), ß-diversity (Bray-Curtis and UniFrac measures), composition (species level), and plasma TMAO. We used regression models to determine associations before and after adjustment for age, sex, education, physical activity, smoking status, body mass index, and total energy intake. RESULTS: The analytic sample (mean age, 71.0 years, SD = 12.8 years) comprised 55.6% female and 67.5% non-Hispanic White participants. hPDI was positively and uPDI negatively associated with microbiome α-diversity, driven by microbial evenness (Pielou P < 0.05). hPDI was also positively associated with relative abundance of 3 polysaccharide-degrading bacterial species (Faecalibacterium prausnitzii, Eubacterium eligens, and Bacteroides thetaiotaomicron) and inversely associated with 6 species (Blautia hydrogenotrophica, Doreasp CAG 317, Eisenbergiella massiliensis, Sellimonas intestinalis, Blautia wexlerae, and Alistipes shahii). Furthermore, hPDI was inversely associated with TMAO. Associations did not differ by age, sex, or race. CONCLUSIONS: Greater adherence to a healthful plant-based diet is associated with microbiome features that have been linked to positive health; adherence to an unhealthful plant-based diet has opposing or null associations with these features.
Assuntos
Microbioma Gastrointestinal , Metilaminas , Adulto , Idoso , Humanos , Envelhecimento , Baltimore , Estudos Transversais , Dieta , Dieta Baseada em Plantas , Dieta Vegetariana , Estudos Longitudinais , Masculino , Feminino , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
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
Subthreshold social anxiety (SSA) is a condition in which individuals experience social anxiety that does not reach the threshold required for a clinical diagnosis of a social anxiety disorder (SAD). Although SSA may not impair lives as severely as SAD, it can affect social functioning. However, only a few studies focused on structural neural correlates of SSA. We recruited 65 individuals with SSA and used the Leibowitz Social Anxiety Scale to assess their social and performance anxiety levels and other relevant measures of social anxiety. Voxel-wise whole-brain correlational analyses showed a positive association between the cortical thickness (CT) of the superior frontal gyrus (SFG) and social anxiety levels and a negative correlation between the CT of the fusiform gyrus (FG) and performance anxiety levels in individuals with SSA. Exploratory Pearson's correlation analyses showed significant positive correlations between the CT of the SFG and Generalized Anxiety Disorder-7 total scores and negative associations between the CT of the FG and Beck Anxiety Inventory total scores. Our study provides insight into the neural basis of SSA, particularly performance anxiety, by highlighting the association between CT in specific brain regions and SSA characteristics.