Objective
Alzheimer's disease (AD) is the most common degenerative neurological disorder with limited therapeutic options. Therefore, it is particularly important to explore the potential biomarkers ...implicated in the occurrence and progression of AD prior to clinical testing.
Methods
We selected 119 unique blood metabolites from 3 metabolome genome‐wide association studies (GWASs) with 147,827 European participants. Summary data about AD were obtained from a GWAS meta‐analysis with 63,926 European individuals from the International Genomics of Alzheimer's Project. MR analyses were performed to assess the associations of blood metabolites with AD, and a phenome‐wide MR analysis was further applied to ascertain the potential on‐target side effects of metabolite interventions.
Results
Four metabolites were identified as causal mediators for AD, including epiandrosterone sulfate (odds ratio OR per SD increase: 0.60; 95% confidence interval CI: 0.51–0.71; p = 6.14 × 10−9), 5alpha‐androstan‐3beta‐17beta‐diol disulfate (OR per SD increase: 0.69; 95% CI: 0.57–0.84; p = 1.98 × 10−4), sphingomyelin (OR per SD increase: 2.53; 95% CI: 1.78–3.59; p = 2.10 × 10−7), and glutamine (OR per SD increase: 0.83; 95% CI: 0.77–0.89; p = 2.09 × 10−6). Phenome‐wide MR analysis showed that epiandrosterone sulfate, 5alpha‐androstan‐3beta‐17beta‐diol disulfate and sphingomyelin mediated the risk of multiple diseases, and glutamine had beneficial effects on the risk of 4 diseases.
Interpretation
Genetically predicted increased epiandrosterone sulfate, 5alpha‐androstan‐3beta‐17beta‐diol disulfate, and glutamine might be associated with a decreased risk of AD, while sphingomyelin was associated with an increased risk. Side‐effect profiles were characterized to help inform drug target prioritization, and glutamine might be a promising target for the prevention and treatment of AD with no predicted detrimental side effects. ANN NEUROL 2022;92:756–767
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(1) Background: Dietary fiber intake may provide beneficial effects on the components of metabolic syndrome (MetS); however, observational studies reported inconsistent results for the relationship ...between dietary fiber intake and MetS risk. We conducted a meta-analysis to quantify previous observational studies and a narrative review to summarize mechanisms involved in the potential relationship. (2) Methods: The literature was searched on PubMed and Web of Science until 28 November 2017. A random-effects model was used to calculate the summary risk estimates. Eleven cross-sectional studies and three cohort studies were included in the meta-analysis. Results from the original studies were reported as odds ratios (ORs) or relative ratios (RRs) of the MetS associated with different levels of dietary fiber intake, and the ORs/RRs comparing the highest with lowest categories of the intake were pooled. (3) Results: For the cross-sectional studies, the pooled OR was 0.70 (95% confidence interval (CI): 0.61-0.82) with evidence of high heterogeneity (
² = 74.4%,
< 0.001) and publication bias (
for Egger's test < 0.001). After removing four studies, results remained significant (OR = 0.67, 95% CI: 0.58-0.78) and the heterogeneity was largely reduced (
² = 32.4%,
= 0.181). For the cohort studies, the pooled RR was 0.86 (95% CI: 0.70-1.06). (4) Conclusion: Although the meta-analysis suggests an inverse association between dietary fiber intake and risk of MetS, and the association was supported by a wide range of mechanism studies, the findings are limited by insufficient cohort data. More prospective studies are needed to further verify the association between dietary fiber intake and the risk of MetS.
While cognitive impairment after stroke is common, cognitive trends before stroke are poorly understood, especially among the Chinese population who have a relatively high stroke burden. We aimed to ...model the trajectories of cognitive function before and after new-onset stroke among Chinese.
A total of 13,311 Chinese participants aged ≥ 45 years and without a history of stroke were assessed at baseline between June 2011 and March 2012 and in at least one cognitive test between 2013 (wave 2) and 2018 (wave 4). Cognitive function was assessed using a global cognition score, which included episodic memory, visuospatial abilities, and a 10-item Telephone Interview of Cognitive Status (TICS-10) test to reflect calculation, attention, and orientation abilities.
During the 7-year follow-up, 610 (4.6%) participants experienced a first stroke. Both stroke and non-stroke groups showed declined cognitive function during follow-up. After adjustment for covariates, there was no significant difference in pre-stroke cognitive trajectories between stroke patients and stroke-free participants. The stroke group showed an acute decline in episodic memory (- 0.123 SD), visuospatial abilities (- 0.169 SD), and global cognition (- 0.135 SD) after stroke onset. In the years following stroke, the decline rate of the TICS-10 test was higher than the rate before stroke (- 0.045 SD/year).
Chinese stroke patients had not experienced steeper declines in cognition before stroke compared with stroke-free individuals. Incident stroke was associated with acute declines in global cognition, episodic memory, visuospatial abilities, and accelerated declines in calculation, attention, and orientation abilities.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Breast cancer is the most common cancer among women with limited treatment options. To identify promising drug targets for breast cancer, we conducted a systematical Mendelian randomization (MR) ...study to screen blood metabolome for potential causal mediators of breast cancer and further predict target-mediated side effects.
We selected 112 unique blood metabolites from 3 large-scale European ancestry-based genome-wide association studies (GWASs) with a total of 147,827 participants. Breast cancer data were obtained from a GWAS in the Breast Cancer Association Consortium (BCAC), involving 122,977 cases and 105,974 controls of European ancestry. We conducted MR analyses to systematically assess the associations of blood metabolites with breast cancer, and a phenome-wide MR analysis was further applied to ascertain the potential on-target side effects of metabolite interventions.
Two blood metabolites were identified as the potential causal mediators for breast cancer, including high-density lipoprotein cholesterol (HDL-C) (odds ratio OR, 1.09; 95% confidence interval CI, 1.06-1.12; P = 9.67 × 10
) and acetate (OR, 1.24; 95% CI, 1.13-1.37; P = 1.35 × 10
). In the phenome-wide MR analysis, lowering HDL-C might have deleterious effects on the risk of the circulatory system and foreign body injury, while lowering acetate had deleterious effects on mental disorders disease.
The present systematic MR analysis revealed that HDL-C and acetate may be the causal mediators in the risk of developing breast cancer. Side-effect profiles were characterized to help inform drug target prioritization for breast cancer prevention. HDL-C and acetate might be promising drug targets for preventing breast cancer, but they should be applied under weighting advantages and disadvantages.
Prospective studies linking dietary pattern and cognitive function in the elderly are limited in Asian populations.
We examined the associations between various healthful dietary patterns and risk of ...cognitive impairment in Chinese adults.
We used data from the Singapore Chinese Health Study of 16,948 men and women who were aged 45–74 y at baseline (1993–1998) and reinterviewed at the third follow-up visit (2014–2016), ∼20 y later. Diet quality at baseline was assessed according to the alternate Mediterranean diet (aMED), the Dietary Approaches to Stop Hypertension (DASH) diet, the alternative Healthy Eating Index (AHEI)-2010, overall plant-based diet index (PDI), and healthful plant-based diet index (hPDI). Cognitive function was evaluated using a Singapore-modified Mini-Mental State Examination during the third follow-up visit when subjects were aged 61–96 y. Multivariable logistic regression models were used to compute ORs and 95% CIs associated with the risk of cognitive impairment defined using education-specific cut-offs.
Cognitive impairment was present in 2443 (14.4%) participants. The OR (95% CI) for cognitive impairment comparing the highest with the lowest quartile of diet quality scores was 0.67 (0.59, 0.77) for aMED, 0.71 (0.62, 0.81) for DASH, 0.75 (0.66, 0.85) for AHEI-2010, 0.82 (0.71, 0.94) for PDI, and 0.78 (0.68, 0.90) for hPDI (all P values for trend <0.001). Each SD increment in different diet quality scores was associated with 7–16% lower risk of cognitive impairment.
These results provide evidence that adherence to healthy dietary patterns in midlife is associated with a lower risk of cognitive impairment in late life in Chinese adults.
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CMK, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary
The photolyases PHR1 and PHR2 enable photorepair of fungal DNA lesions in the forms of UV‐induced cyclobutane pyrimidine dimer (CPD) and (6‐4)‐pyrimidine‐pyrimidone (6‐4PP) photoproducts, but ...their regulation remains mechanistically elusive. Here, we report that the white collar proteins WC1 and WC2 mutually interacting to form a light‐responsive transcription factor regulate photolyase expression required for fungal UV resistance in the insect‐pathogenic fungus Metharhizum robertsii. Conidial UVB resistance decreased by 54% in Δwc1 and 67% in Δwc2. Five‐hour exposure of UVB‐inactivated conidia to visible light resulted in photoreactivation rates of 30% and 9% for the Δwc1 and Δwc2 mutants, contrasting to 79%–82% for wild‐type and complemented strains. Importantly, abolished transcription of phr1 in Δwc‐2 and of phr2 in Δwc1 resulted in incapable photorepair of CDP and 6‐4PP DNA lesions in UVB‐impaired Δwc2 and Δwc1 cells respectively. Yeast two‐hybrid assays revealed interactions of either WC protein with both PHR1 and PHR2. Therefore, the essential roles for WC1 and WC2 in both photorepair of UVB‐induced DNA lesions and photoreactivation of UVB‐inactivated conidia rely upon their interactions with, and hence transcriptional activation of, PHR1 and PHR2. These findings uncover a novel WC‐cored pathway that mediates filamentous fungal response and adaptation to solar UV irradiation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Tryptophan can be catabolised to various metabolites through host kynurenine and microbial indole pathways. We aimed to examine relationships of host and microbial tryptophan metabolites with ...incident type 2 diabetes (T2D), host genetics, diet and gut microbiota.
We analysed associations between circulating levels of 11 tryptophan metabolites and incident T2D in 9180 participants of diverse racial/ethnic backgrounds from five cohorts. We examined host genome-wide variants, dietary intake and gut microbiome associated with these metabolites.
Tryptophan, four kynurenine-pathway metabolites (kynurenine, kynurenate, xanthurenate and quinolinate) and indolelactate were positively associated with T2D risk, while indolepropionate was inversely associated with T2D risk. We identified multiple host genetic variants, dietary factors, gut bacteria and their potential interplay associated with these T2D-relaetd metabolites. Intakes of fibre-rich foods, but not protein/tryptophan-rich foods, were the dietary factors most strongly associated with tryptophan metabolites. The fibre-indolepropionate association was partially explained by indolepropionate-associated gut bacteria, mostly fibre-using
. We identified a novel association between a host functional
variant (determining lactase persistence) and serum indolepropionate, which might be related to a host gene-diet interaction on gut
, a probiotic bacterium significantly associated with indolepropionate independent of other fibre-related bacteria. Higher milk intake was associated with higher levels of gut
and serum indolepropionate only among genetically lactase non-persistent individuals.
Higher milk intake among lactase non-persistent individuals, and higher fibre intake were associated with a favourable profile of circulating tryptophan metabolites for T2D, potentially through the host-microbial cross-talk shifting tryptophan metabolism toward gut microbial indolepropionate production.
Abstract
Context
The prevalence of type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs) is increasing in Asia and several countries are adopting preventive policies to reduce ...consumption of sugar-sweetened beverages (SSBs). However, evidence on the relation between SSB consumption and cardiometabolic health in Asian populations has not been summarized.
Objective
In this systematic review, the associations between consumption of SSBs and cardiometabolic outcomes, including obesity, T2DM, and CVD, are examined in Asian populations.
Data sources
The PubMed, Scopus, and Web of Science databases, and gray literature were searched up to October, 2020 to identify relevant articles.
Data extraction
Two investigators independently extracted data from included studies.
Data analysis
When sufficient studies were available, a random-effects meta-analysis was used to calculate the pooled estimates (expressed as risk ratio RR and 95% confidence interval CI). Heterogeneity was tested and quantified using the Cochrane Q test and I2 statistic, respectively.
Results
Of the 17 studies included, 8 provided results about measures of adiposity (3 on weight change, 4 on body mass index (BMI), 2 on percent body fat, and 1 on abdominal obesity), 6 reported results about T2DM, and 3 reported on different CVD outcomes. High SSB consumption was significantly associated with greater weight gain and with a higher risk of selected CVD outcomes as compared with low consumption. In the meta-analysis, high SSB consumption was associated with greater T2DM risk before (RR, 1.51; 95%CI, 1.15–1.98 for highest vs lowest category; I2 = 76%) and after (RR, 1.38; 95%CI, 1.09–1.73; I2 = 56%) adjustment for BMI.
Conclusions
These findings suggest that high SSB consumption is directly associated with weight gain, risk of T2DM, and, possibly, selected CVD outcomes in Asian populations. Public health strategies to reduce SSB consumption in Asian countries are warranted.
Systematic Review Registration
PROSPERO registration no. CRD42019129456.Keywords: adiposity. cardiovascular disease, Asia, sugar-sweetened beverages, type 2 diabetes.
Obesity and related comorbidities are major health concerns among many US immigrant populations. Emerging evidence suggests a potential involvement of the gut microbiome. Here, we evaluated gut ...microbiome features and their associations with immigration, dietary intake, and obesity in 2640 individuals from a population-based study of US Hispanics/Latinos.
The fecal shotgun metagenomics data indicate that greater US exposure is associated with reduced ɑ-diversity, reduced functions of fiber degradation, and alterations in individual taxa, potentially related to a westernized diet. However, a majority of gut bacterial genera show paradoxical associations, being reduced with US exposure and increased with fiber intake, but increased with obesity. The observed paradoxical associations are not explained by host characteristics or variation in bacterial species but might be related to potential microbial co-occurrence, as seen by positive correlations among Roseburia, Prevotella, Dorea, and Coprococcus. In the conditional analysis with mutual adjustment, including all genera associated with both obesity and US exposure in the same model, the positive associations of Roseburia and Prevotella with obesity did not persist, suggesting that their positive associations with obesity might be due to their co-occurrence and correlations with obesity-related taxa, such as Dorea and Coprococcus.
Among US Hispanics/Latinos, US exposure is associated with unfavorable gut microbiome profiles for obesity risk, potentially related to westernized diet during acculturation. Microbial co-occurrence could be an important factor to consider in future studies relating individual gut microbiome taxa to environmental factors and host health and disease.
We demonstrate for the first time an interfacial polymerization method for the synthesis of high‐quality polyaniline‐modified graphene nanosheets (PANI/GNs), which represents a novel type of ...graphene/polymer heterostructure. The interfacial polymerization at a liquid–liquid interface allows PANI to grow uniformly on the surface of the GNs. An ultra‐high loading of Pt nanoparticles was then controllably deposited on the surface of the PANI/GNs to form a Pt/PANI/GNs hybrid. The obtained composites were characterized by scanning electron microscopy, transmission electron microscopy, energy‐dispersive spectrometry, X‐ray diffraction, X‐ray photoelectron spectroscopy, and thermogravimetric analysis. The Pt/PANI/GNs hybrid shows excellent electrocatalytic activity toward methanol oxidation and oxygen reduction. H2O2 and glucose were used as two representative analytes to demonstrate the sensing performance of a Pt/PANI/GNs‐modified electrode. It is found that this sensing element shows high sensitivity and a low detection limit for H2O2 and glucose. The results demonstrate that the Pt/PANI/GNs hybrid may be an attractive and advanced electrode material with potential applications in the construction of electrochemical sensors and biosensors.
Hybrids make sensors! High‐quality polyaniline‐modified graphene nanosheets (PANI/GNs) were prepared by using an interfacial polymerization method, then an ultra‐high loading of Pt nanoparticles (Pt NPs) was controllably deposited on the surface of PANI/GNs to form a Pt/PANI/GNs hybrid (see figure). The resultant hybrid shows high electrocatalytic activity toward the electrooxidation of methanol and reduction of oxygen.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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