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Alzheimer's & Dementia : the Journal of... Oct 2023The objective was to analyze associations between dietary intake of multiple nutrients and altered cognitive function and/or decline. (Observational Study)
Observational Study
INTRODUCTION
The objective was to analyze associations between dietary intake of multiple nutrients and altered cognitive function and/or decline.
METHODS
Observational analyses of participants (n = 6334) in two randomized trials of nutritional supplements for age-related macular degeneration: Age-Related Eye Disease Study (AREDS) and AREDS2.
RESULTS
In AREDS, for 4 of 38 nutrients examined, higher intake quintiles were significantly associated with decreased risk of cognitive impairment on the Modified Mini-Mental State test (<80): β-carotene, copper, docosahexaenoic acid, and insoluble fiber. In AREDS2, for 13 of 44 nutrients, higher intake quintiles were associated with decreased risk on the Telephone Interview Cognitive Status-Modified (<30). Rate of cognitive decline over up to 10 years was not significantly different with higher intake of any nutrient.
DISCUSSION
Higher dietary intake of multiple nutrients, including specific vitamins, minerals, carotenoids, fatty acids, and fiber, was associated with lower risk of cognitive impairment but not slower decline in cognitive function.
Topics: Humans; Lutein; Zeaxanthins; Vitamins; Dietary Supplements; Macular Degeneration; Eating; Cognition
PubMed: 36939084
DOI: 10.1002/alz.13033 -
Journal of the American Chemical Society Aug 2023Alkene difunctionalizations enable the synthesis of structurally elaborated products from simple and ubiquitous starting materials in a single chemical step....
Alkene difunctionalizations enable the synthesis of structurally elaborated products from simple and ubiquitous starting materials in a single chemical step. Carbohydroxylations of olefins represent a family of reactivity that furnish structurally complex alcohols. While examples of this type of three-component coupling have been reported, catalytic asymmetric examples remain elusive. Here, we report an enzyme-catalyzed asymmetric carbohydroxylation of alkenes catalyzed by flavin-dependent "ene"-reductases to produce enantioenriched tertiary alcohols. Seven rounds of protein engineering reshape the enzyme's active site to increase activity and enantioselectivity. Mechanistic studies suggest that C-O bond formation occurs via a 5-endo-trig cyclization with the pendant ketone to afford an α-oxy radical which is oxidized and hydrolyzed to form the product. This work demonstrates photoenzymatic reactions involving "ene"-reductases can terminate radicals via mechanisms other than hydrogen atom transfer, expanding their utility in chemical synthesis.
Topics: Alkenes; Catalysis; Hydrogen; Oxidoreductases; Alcohols
PubMed: 37498747
DOI: 10.1021/jacs.3c06618 -
International Journal of Molecular... Aug 2023The catalytic epoxidation of small alkenes and allylic alcohols includes a wide range of valuable chemical applications, with many works describing vanadium complexes as... (Review)
Review
The catalytic epoxidation of small alkenes and allylic alcohols includes a wide range of valuable chemical applications, with many works describing vanadium complexes as suitable catalysts towards sustainable process chemistry. But, given the complexity of these mechanisms, it is not always easy to sort out efficient examples for streamlining sustainable processes and tuning product optimization. In this review, we provide an update on major works of tunable vanadium-catalyzed epoxidations, with a focus on sustainable optimization routes. After presenting the current mechanistic view on vanadium catalysts for small alkenes and allylic alcohols' epoxidation, we argue the key challenges in green process development by highlighting the value of updated kinetic and mechanistic studies, along with essential computational studies.
Topics: Alkenes; Vanadium; Epoxy Compounds; Stereoisomerism; Propanols; Catalysis; Alcohols
PubMed: 37569673
DOI: 10.3390/ijms241512299 -
Journal of Agricultural and Food... Sep 2023Lycopene is a common carotenoid found mainly in ripe red fruits and vegetables that is widely used in the food industry due to its characteristic color and health... (Review)
Review
Lycopene is a common carotenoid found mainly in ripe red fruits and vegetables that is widely used in the food industry due to its characteristic color and health benefits. Microbial synthesis of lycopene is gradually replacing the traditional methods of plant extraction and chemical synthesis as a more economical and productive manufacturing strategy. The biosynthesis of lycopene is a typical multienzyme cascade reaction, and it is important to understand the characteristics of each key enzyme involved and how they are regulated. In this paper, the catalytic characteristics of the key enzymes involved in the lycopene biosynthesis pathway and related studies are first discussed in detail. Then, the strategies applied to the key enzymes of lycopene synthesis, including fusion proteins, enzyme screening, combinatorial engineering, CRISPR/Cas9-based gene editing, DNA assembly, and scaffolding technologies are purposefully illustrated and compared in terms of both traditional and emerging multienzyme regulatory strategies. Finally, future developments and regulatory options for multienzyme synthesis of lycopene and similar secondary metabolites are also discussed.
Topics: Carotenoids; Catalysis; Fruit; Lycopene
PubMed: 37609695
DOI: 10.1021/acs.jafc.3c03942 -
Nature Apr 2024The development of bimolecular homolytic substitution (S2) catalysis has expanded cross-coupling chemistries by enabling the selective combination of any primary radical...
The development of bimolecular homolytic substitution (S2) catalysis has expanded cross-coupling chemistries by enabling the selective combination of any primary radical with any secondary or tertiary radical through a radical sorting mechanism. Biomimetic S2 catalysis can be used to merge common feedstock chemicals-such as alcohols, acids and halides-in various permutations for the construction of a single C(sp)-C(sp) bond. The ability to sort these two distinct radicals across commercially available alkenes in a three-component manner would enable the simultaneous construction of two C(sp)-C(sp) bonds, greatly accelerating access to complex molecules and drug-like chemical space. However, the simultaneous in situ formation of electrophilic and primary nucleophilic radicals in the presence of unactivated alkenes is problematic, typically leading to statistical radical recombination, hydrogen atom transfer, disproportionation and other deleterious pathways. Here we report the use of bimolecular homolytic substitution catalysis to sort an electrophilic radical and a nucleophilic radical across an unactivated alkene. This reaction involves the in situ formation of three distinct radical species, which are then differentiated by size and electronics, allowing for regioselective formation of the desired dialkylated products. This work accelerates access to pharmaceutically relevant C(sp)-rich molecules and defines a distinct mechanistic approach for alkene dialkylation.
Topics: Acids; Alcohols; Alkenes; Biomimetics; Catalysis; Hydrogen; Pharmaceutical Preparations
PubMed: 38350601
DOI: 10.1038/s41586-024-07165-x -
Nature Chemical Biology Feb 2024The anthraquinone-fused enediynes (AFEs) combine an anthraquinone moiety and a ten-membered enediyne core capable of generating a cytotoxic diradical species. AFE...
The anthraquinone-fused enediynes (AFEs) combine an anthraquinone moiety and a ten-membered enediyne core capable of generating a cytotoxic diradical species. AFE cyclization is triggered by opening the F-ring epoxide, which is also the site of the most structural diversity. Previous studies of tiancimycin A, a heavily modified AFE, have revealed a cryptic aldehyde blocking installation of the epoxide, and no unassigned oxidases could be predicted within the tnm biosynthetic gene cluster. Here we identify two consecutively acting cofactorless oxygenases derived from methyltransferase and α/β-hydrolase protein folds, TnmJ and TnmK2, respectively, that are responsible for F-ring tailoring in tiancimycin biosynthesis by comparative genomics. Further biochemical and structural characterizations reveal that the electron-rich AFE anthraquinone moiety assists in catalyzing deformylation, epoxidation and oxidative ring cleavage without exogenous cofactors. These enzymes therefore fill important knowledge gaps for the biosynthesis of this class of molecules and the underappreciated family of cofactorless oxygenases.
Topics: Oxygenases; Antineoplastic Agents; Anthraquinones; Enediynes; Epoxy Compounds
PubMed: 37945897
DOI: 10.1038/s41589-023-01476-2 -
Journal of Experimental & Clinical... Nov 2023Gastric-cancer is a heterogeneous type of neoplastic disease and it lacks appropriate therapeutic options. There is an urgent need for the development of innovative...
BACKGROUND
Gastric-cancer is a heterogeneous type of neoplastic disease and it lacks appropriate therapeutic options. There is an urgent need for the development of innovative pharmacological strategies, particularly in consideration of the potential stratified/personalized treatment of this tumor. All-Trans Retinoic-acid (ATRA) is one of the active metabolites of vitamin-A. This natural compound is the first example of clinically approved cyto-differentiating agent, being used in the treatment of acute promyelocytic leukemia. ATRA may have significant therapeutic potential also in the context of solid tumors, including gastric-cancer. The present study provides pre-clinical evidence supporting the use of ATRA in the treatment of gastric-cancer using high-throughput approaches.
METHODS
We evaluated the anti-proliferative action of ATRA in 27 gastric-cancer cell-lines and tissue-slice cultures from 13 gastric-cancer patients. We performed RNA-sequencing studies in 13 cell-lines exposed to ATRA. We used these and the gastric-cancer RNA-sequencing data of the TCGA/CCLE datasets to conduct multiple computational analyses.
RESULTS
Profiling of our large panel of gastric-cancer cell-lines for their quantitative response to the anti-proliferative effects of ATRA indicate that approximately half of the cell-lines are characterized by sensitivity to the retinoid. The constitutive transcriptomic profiles of these cell-lines permitted the construction of a model consisting of 42 genes, whose expression correlates with ATRA-sensitivity. The model predicts that 45% of the TCGA gastric-cancers are sensitive to ATRA. RNA-sequencing studies performed in retinoid-treated gastric-cancer cell-lines provide insights into the gene-networks underlying ATRA anti-tumor activity. In addition, our data demonstrate that ATRA exerts significant immune-modulatory effects, which seem to be largely controlled by IRF1 up-regulation. Finally, we provide evidence of a feed-back loop between IRF1 and DHRS3, another gene which is up-regulated by ATRA.
CONCLUSIONS
ATRA is endowed with significant therapeutic potential in the stratified/personalized treatment gastric-cancer. Our data represent the fundaments for the design of clinical trials focusing on the use of ATRA in the personalized treatment of this heterogeneous tumor. Our gene-expression model will permit the development of a predictive tool for the selection of ATRA-sensitive gastric-cancer patients. The immune-regulatory responses activated by ATRA suggest that the retinoid and immune-checkpoint inhibitors constitute rational combinations for the management of gastric-cancer.
Topics: Humans; Tretinoin; Retinoids; Stomach Neoplasms; Transcriptome; RNA; Antineoplastic Agents
PubMed: 37951921
DOI: 10.1186/s13046-023-02869-w -
Food & Function Sep 2023Evidence on the association between dietary nutrient-wide intake and cardiovascular disease (CVD) is inconclusive. Therefore, we systematically assessed the association...
A nutrient-wide association study for the risk of cardiovascular disease in the China Health and Nutrition Survey (CHNS) and the National Health and Nutrition Examination Survey (NHANES).
Evidence on the association between dietary nutrient-wide intake and cardiovascular disease (CVD) is inconclusive. Therefore, we systematically assessed the association between dietary intake of 29 nutrients and CVD risk using a nutrient-wide association study. Data were obtained from 7878 Chinese adults participating in the China Health and Nutrition Survey (CHNS) wave 2004-2015. We estimated the association of 29 nutrients with CVD risk. Significant findings were replicated in the National Health and Nutrition Examination Survey (NHANES). Four nutrients (selenium, vitamin A, carotenoids, and total protein) were significantly associated with CVD risk in the CHNS. The hazard ratio (HR) and 95% confidence interval (CI) for nutrient intake in the third tertile compared to the first tertile were 0.68 (0.51-0.90), 0.70 (0.54-0.91), 0.64 (0.50-0.83), and 0.54 (0.38-0.77), respectively. In the NHANES replication, selenium maintained a similar direction and strength of association, while the other nutrients were not replicated successfully. Our results provide support for a negative association between selenium intake and CVD risk, while the association of vitamin A, carotenoids and protein with CVD warrants further studies to confirm.
Topics: Humans; Nutrition Surveys; Cardiovascular Diseases; Selenium; Vitamin A; Nutrients; Carotenoids; China
PubMed: 37665296
DOI: 10.1039/d3fo01758c -
ELife Feb 2024β-Carotene oxygenase 1 (BCO1) catalyzes the cleavage of β-carotene to form vitamin A. Besides its role in vision, vitamin A regulates the expression of genes involved...
β-Carotene oxygenase 1 (BCO1) catalyzes the cleavage of β-carotene to form vitamin A. Besides its role in vision, vitamin A regulates the expression of genes involved in lipid metabolism and immune cell differentiation. BCO1 activity is associated with the reduction of plasma cholesterol in humans and mice, while dietary β-carotene reduces hepatic lipid secretion and delays atherosclerosis progression in various experimental models. Here we show that β-carotene also accelerates atherosclerosis resolution in two independent murine models, independently of changes in body weight gain or plasma lipid profile. Experiments in mice implicate vitamin A production in the effects of β-carotene on atherosclerosis resolution. To explore the direct implication of dietary β-carotene on regulatory T cells (Tregs) differentiation, we utilized anti-CD25 monoclonal antibody infusions. Our data show that β-carotene favors Treg expansion in the plaque, and that the partial inhibition of Tregs mitigates the effect of β-carotene on atherosclerosis resolution. Our data highlight the potential of β-carotene and BCO1 activity in the resolution of atherosclerotic cardiovascular disease.
Topics: Mice; Humans; Animals; beta Carotene; Vitamin A; Liver; Atherosclerosis; Lipids
PubMed: 38319073
DOI: 10.7554/eLife.87430 -
Nutrients Oct 2023We examined the associations of perinatal plasma carotenoids and E vitamers concentrations with glycemia, insulin resistance, and gestational and type 2 diabetes...
We examined the associations of perinatal plasma carotenoids and E vitamers concentrations with glycemia, insulin resistance, and gestational and type 2 diabetes mellitus during pregnancy and post-pregnancy in GUSTO women. Plasma carotenoid and E vitamer concentrations were measured at delivery, and principal component analysis was used to derive the patterns of their concentrations. Fasting and 2 h glucose levels and fasting insulin were measured at 26-28 weeks gestation and 4-6 years post-pregnancy, with the derivation of homeostatic model assessment for insulin resistance (HOMA-IR). In 678 women, two carotenoid patterns (CP1: α- and β-carotene and lutein; CP2: zeaxanthin, lycopene, and β-cryptoxanthin) and one E vitamer pattern (VE: γ-, δ-, and α-tocopherols) were derived. A higher CP1 score (1-SD) was associated with lower gestational fasting glucose (β (95%CI): -0.06 (-0.10, -0.02) mmol/L) and lower gestational (-0.17 (-0.82, 0.01) mmol/L, = 0.06) and post-pregnancy HOMA-IR (-0.11 (-0.15, -0.08) mmol/L). A higher VE score (1 SD) was associated with higher gestational and post-pregnancy fasting and 2 h glucose (gestational: 0.05 (0.01, 0.08) and 0.08 (0.01, 0.16); post-pregnancy: 0.19 (0.07, 0.31) and 0.24 (0.06, 0.42) mmol/L). Higher α- and β-carotene and lutein may be beneficial for gestational fasting glycemia, but higher vitamin E may increase gestational and post-pregnancy glycemia, although these findings require confirmation in cohorts with prospective longitudinal measurements of these vitamins.
Topics: Pregnancy; Humans; Female; Carotenoids; beta Carotene; Vitamin E; Lutein; Insulin Resistance; Diabetes Mellitus, Type 2; Prospective Studies; Glucose
PubMed: 37892496
DOI: 10.3390/nu15204421