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Food & Function Jun 2024Currently, sleep disorders (SD) in the elderly are gaining prominence globally and are becoming a significant public health concern. Methyl donor nutrients (MDNs), such...
Currently, sleep disorders (SD) in the elderly are gaining prominence globally and are becoming a significant public health concern. Methyl donor nutrients (MDNs), such as vitamin B, vitamin B, folate, and choline, have been reported to have the potential to improve sleep disorders. Moreover, MDNs help to maintain gut flora homeostasis, and are closely associated with the development of SD. Nevertheless, there has been a lack of comprehensive human studies examining the association between MDNs intake and SD. In our study, we comprehensively evaluated the association between MDNs intake and SD in the elderly and used 16S rRNA gene sequencing to explore the underlying mechanism. We found that the SD group ( = 91) had a lower methyl-donor nutritional quality index (MNQI) and a trend toward lower intake compared to the control group ( = 147). Based on the intestinal microbiome, the beta diversity of the intestinal flora was higher in the high methyl-donor nutritional quality (HQ) group compared to the low methyl-donor nutritional quality (LQ) group, and it was lower in the SD group compared to the control group. This suggests that MDNs may regulate sleep by modulating the abundance distribution of the microbiota. Subsequently, we performed correlation analyses between the relative abundance of the microbiota, MDNs intake, and the Pittsburgh Sleep Quality Index (PSQI), identifying five genera with potential regulatory roles. The KEGG pathway analysis indicated that energy metabolism and one-carbon metabolism might be the pathways through which MDNs modulate sleep. This study offers dietary guidance strategies for managing SD in the elderly and provides insights for targeted microbiota intervention.
Topics: Humans; Gastrointestinal Microbiome; Aged; Female; Male; Sleep Wake Disorders; Bacteria; Vitamin B 6; Vitamin B 12; Folic Acid; Choline; RNA, Ribosomal, 16S; Nutrients; Middle Aged; Diet; Aged, 80 and over
PubMed: 38832472
DOI: 10.1039/d4fo01303d -
Physical Chemistry Chemical Physics :... Jun 2024The transsulfuration pathway plays a key role in mammals for maintaining the balance between cysteine and homocysteine, whose concentrations are critical in several...
The transsulfuration pathway plays a key role in mammals for maintaining the balance between cysteine and homocysteine, whose concentrations are critical in several biochemical processes. Human cystathionine β-synthase is a heme-containing, pyridoxal 5'-phosphate (PLP)-dependent enzyme found in this pathway. The heme group does not participate directly in catalysis, but has a regulatory function, whereby CO or NO binding inhibits the PLP-dependent reactions. In this study, we explore the detailed structural changes responsible for inhibition using quantum chemical calculations to validate the experimentally observed bonding patterns associated with heme CO and NO binding and molecular dynamics simulations to explore the medium-range structural changes triggered by gas binding and propagating to the PLP active site, which is more than 20 Å distant from the heme group. Our results support a previously proposed mechanical signaling model, whereby the cysteine decoordination associated with gas ligand binding leads to breaking of a hydrogen bond with an arginine residue on a neighbouring helix. In turn, this leads to a shift in position of the helix, and hence also of the PLP cofactor, ultimately disrupting a key hydrogen bond that stabilizes the PLP in its catalytically active form.
Topics: Cystathionine beta-Synthase; Molecular Dynamics Simulation; Humans; Pyridoxal Phosphate; Gases; Nitric Oxide; Hydrogen Bonding; Carbon Monoxide; Heme; Catalytic Domain; Quantum Theory; Cysteine
PubMed: 38832404
DOI: 10.1039/d4cp01321b -
Cell Death & Disease Jun 2024Vitamin B6 is a water-soluble vitamin which possesses antioxidant properties. Its catalytically active form, pyridoxal 5'-phosphate (PLP), is a crucial cofactor for DNA...
Vitamin B6 is a water-soluble vitamin which possesses antioxidant properties. Its catalytically active form, pyridoxal 5'-phosphate (PLP), is a crucial cofactor for DNA and amino acid metabolism. The inverse correlation between vitamin B6 and cancer risk has been observed in several studies, although dietary vitamin B6 intake sometimes failed to confirm this association. However, the molecular link between vitamin B6 and cancer remains elusive. Previous work has shown that vitamin B6 deficiency causes chromosome aberrations (CABs) in Drosophila and human cells, suggesting that genome instability may correlate the lack of this vitamin to cancer. Here we provide evidence in support of this hypothesis. Firstly, we show that PLP deficiency, induced by the PLP antagonists 4-deoxypyridoxine (4DP) or ginkgotoxin (GT), promoted tumorigenesis in eye larval discs transforming benign Ras tumors into aggressive forms. In contrast, PLP supplementation reduced the development of tumors. We also show that low PLP levels, induced by 4DP or by silencing the sgll gene involved in PLP biosynthesis, worsened the tumor phenotype in another Drosophila cancer model generated by concomitantly activating Ras and downregulating Discs-large (Dlg) gene. Moreover, we found that Ras eye discs from larvae reared on 4DP displayed CABs, reactive oxygen species (ROS) and low catalytic activity of serine hydroxymethyltransferase (SHMT), a PLP-dependent enzyme involved in thymidylate (dTMP) biosynthesis, in turn required for DNA replication and repair. Feeding Ras 4DP-fed larvae with PLP or ascorbic acid (AA) plus dTMP, rescued both CABs and tumors. The same effect was produced by overexpressing catalase in Ras Dlg 4DP-fed larvae, thus allowing to establish a relationship between PLP deficiency, CABs, and cancer. Overall, our data provide the first in vivo demonstration that PLP deficiency can impact on cancer by increasing genome instability, which is in turn mediated by ROS and reduced dTMP levels.
Topics: Animals; Vitamin B 6 Deficiency; Drosophila Proteins; Vitamin B 6; Drosophila melanogaster; Drosophila; Pyridoxal Phosphate; Reactive Oxygen Species; Carcinogenesis; ras Proteins; Neoplasms; Larva; Humans
PubMed: 38830901
DOI: 10.1038/s41419-024-06787-3 -
Marine Life Science & Technology May 2024Mutualistic interactions between marine phototrophs and associated bacteria are an important strategy for their successful survival in the ocean, but little is known...
UNLABELLED
Mutualistic interactions between marine phototrophs and associated bacteria are an important strategy for their successful survival in the ocean, but little is known about their metabolic relationships. Here, bacterial communities in the algal sphere (AS) and bulk solution (BS) of nine marine red algal cultures were analyzed, and and were identified significantly more abundantly in AS than in BS. The metabolic features of RMAR6-6 (isolated and genome-sequenced), MAG 12 (obtained by metagenomic sequencing), and a marine red alga, CCMP1328 (from GenBank), were analyzed bioinformatically. RMAR6-6 has the genetic capability to fix nitrogen and produce B vitamins (B1, B2, B5, B6, B9, and B12), bacterioferritin, dimethylsulfoniopropionate (DMSP), and phenylacetate that may enhance algal growth, whereas MAG 12 may have a limited metabolic capability, not producing vitamins B9 and B12, DMSP, phenylacetate, and siderophores, but with the ability to produce bacitracin, possibly modulating algal microbiome. . CCMP1328 lacks the genetic capability to fix nitrogen and produce vitamin B12, DMSP, phenylacetate, and siderophore. It was shown that the nitrogen-fixing ability of RMAR6-6 promoted the growth of . , and DMSP reduced the oxidative stress of . . The metabolic interactions between strain RMAR6-6 and . CCMP1328 were also investigated by the transcriptomic analyses of their monoculture and co-culture. Taken together, potential metabolic relationships between and . were proposed. This study provides a better understanding of the metabolic relationships between marine algae and algae-associated bacteria for successful growth.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s42995-024-00227-z.
PubMed: 38827136
DOI: 10.1007/s42995-024-00227-z -
The British Journal of Nutrition Jun 2024The effect of single dietary fiber (DF) on lowering uric acid (UA) level has been reported in the literature. However, the potential protective mechanism of dietary...
The effect of single dietary fiber (DF) on lowering uric acid (UA) level has been reported in the literature. However, the potential protective mechanism of dietary fibre against potassium oxybate-induced hyperuricaemia (HUA), as modelled by prophylactic administration, remains unclear.The data demonstrates that DF significantly decreased serum and cerebral tissue UA concentrations, inhibited xanthine oxidase (XOD) expression and activity in the liver, and reduced levels of creatinine (Cr) and urea nitrogen (BUN) in the serum. Additionally, it mitigated the deposition of amyloid-β (Aβ) in cerebral tissue. Correlation analysis showed that DF modulated the TLR4/NF-κB signaling pathway, attenuating oxidative stress and inflammatory responses in HUA mice. Additionally, DF helps to maintain the composition of the gut microbiota, reducing harmful and enriching beneficial and populations.The results of the faecal metabolomics analysis indicate that DF facilitates the regulation of metabolic pathways involved in oxidative stress and inflammation. These pathways include pyrimidine metabolism, tryptophan metabolism, nucleotide metabolism, and vitamin B6 metabolism. Additionally, the study found that DF has a preventive effect on anxiety-like behaviour induced by HUA. In summary, DF shows promise in mitigating HUA and cognitive deficits, primarily by modulating gut microbiota and metabolites.
PubMed: 38826102
DOI: 10.1017/S0007114524001211 -
Nature Metabolism Jun 2024Oxygen is critical for all metazoan organisms on the earth and impacts various biological processes in physiological and pathological conditions. While oxygen-sensing...
Oxygen is critical for all metazoan organisms on the earth and impacts various biological processes in physiological and pathological conditions. While oxygen-sensing systems inducing acute hypoxic responses, including the hypoxia-inducible factor pathway, have been identified, those operating in prolonged hypoxia remain to be elucidated. Here we show that pyridoxine 5'-phosphate oxidase (PNPO), which catalyses bioactivation of vitamin B6, serves as an oxygen sensor and regulates lysosomal activity in macrophages. Decreased PNPO activity under prolonged hypoxia reduced an active form of vitamin B6, pyridoxal 5'-phosphate (PLP), and inhibited lysosomal acidification, which in macrophages led to iron dysregulation, TET2 protein loss and delayed resolution of the inflammatory response. Among PLP-dependent metabolism, supersulfide synthesis was suppressed in prolonged hypoxia, resulting in the lysosomal inhibition and consequent proinflammatory phenotypes of macrophages. The PNPO-PLP axis creates a distinct layer of oxygen sensing that gradually shuts down PLP-dependent metabolism in response to prolonged oxygen deprivation.
Topics: Lysosomes; Macrophages; Animals; Mice; Pyridoxal Phosphate; Hypoxia; Cell Hypoxia; Vitamin B 6; Oxygen; Inflammation
PubMed: 38822028
DOI: 10.1038/s42255-024-01053-4 -
Anticancer Research Jun 2024Breast cancer remains a global health challenge, prompting a search for preventive strategies beyond conventional approaches. This review explores the potential of... (Review)
Review
Breast cancer remains a global health challenge, prompting a search for preventive strategies beyond conventional approaches. This review explores the potential of specific micronutrients, including antioxidants, vitamins, and probiotics, in breast cancer prevention. Through an extensive literature search encompassing PubMed up to March 2024, 14 micronutrients emerged with promising roles in breast cancer prevention. These include five vitamins: folate, vitamin D, vitamin B6, beta carotene, and vitamin C and nine other micronutrients: curcumin, piperine, epigallocatechin-3-gallate, quercetin, sulforaphane, indole-3-carbinol, lactobacillus, n-3 polyunsaturated fatty acids and lycopene. Understanding the efficacy of these micronutrients could pave the way for personalized preventive interventions, offering new avenues for reducing breast cancer incidence and improving public health outcomes.
Topics: Humans; Breast Neoplasms; Probiotics; Antioxidants; Female; Vitamins; Micronutrients
PubMed: 38821606
DOI: 10.21873/anticanres.17036 -
Frontiers in Pediatrics 2024The association between vitamins and eczema has garnered attention, yet few studies have evaluated the effects of co-exposure to multiple vitamins on this condition....
AIM
The association between vitamins and eczema has garnered attention, yet few studies have evaluated the effects of co-exposure to multiple vitamins on this condition. This study aims to assess the association of vitamin mixtures with eczema in children.
METHODS
This cross-sectional study analyzed data from 2,244 children aged 6-17 years from the National Health and Nutrition Examination Surveys. Eczema served as the primary outcome. Six serum vitamins, namely, vitamins A, B, B, C, D, and E, were the main variables. Weighted multivariate logistic regression was adopted to analyze the association between each serum vitamin and eczema. Odds ratios (OR) with a 95% confidence interval (CI) were calculated. Bayesian kernel machine regression (BKMR) analysis and the quantile g-computation (qgcomp) model were used to evaluate the association of co-exposure to multiple vitamins with eczema.
RESULTS
In total, 10.83% of children ( = 243) developed eczema. After adjusting for confounding factors, we observed that compared with the reference group (vitamin B with second quartile), the OR for eczema was 0.604 (95% CI: 0.373-0.978, = 0.041) for the first quartile of vitamin B. Both BKMR analysis and the qgcomp model consistently showed that co-exposure to the six vitamins was positively correlated with the risk of eczema, with vitamin B contributing most to the overall effect. In BKMR analyses, we observed an interaction between vitamins B and B concerning eczema risk.
CONCLUSION
Co-exposure to vitamins A, C, B, B, D, and E was found to be associated with an increased risk of eczema in children, with vitamin B as the greatest positive contributor driving the overall effect.
PubMed: 38813547
DOI: 10.3389/fped.2024.1328592 -
Scientific Reports May 2024The effect of high-dose pyridoxine (PN) on activity of 5-fluorouracil (FUra) and folinic acid (FA)-containing regimens was studied in 50 patients including 14 with...
The effect of high-dose pyridoxine (PN) on activity of 5-fluorouracil (FUra) and folinic acid (FA)-containing regimens was studied in 50 patients including 14 with digestive tract, and 36 with breast carcinomas (BC) in advanced stages with poor prognostic characteristics. Patients with colorectal, and pancreas adenocarcinoma received oxaliplatin, irinotecan, FUra, FA (Folfirinox), and patients with squamous cell carcinoma of the esophagus had paclitaxel, carboplatin, FUra, FA (TCbF). Patients with BC received AVCF (doxorubicin, vinorelbine, cyclophosphamide, FUra, FA) followed by TCbF or TCbF only, and patients who overexpressed HER2 received TCbF plus trastuzumab and pertuzumab. PN (1000-3000 mg/day iv) preceded each administration of FUra and FA. 47 patients (94%) responded, including 16 (32%) with CR. Median tumor reduction was 93%. Median event-free survival (EFS) was 37.7 months. The 25 patients with tumor shrinkage ≥ 91% had EFS of 52% from 42 months onwards. Unexpected toxicity did not occur. PN enhances potency of chemotherapy regimens comprising FUra and FA.
Topics: Humans; Fluorouracil; Leucovorin; Pyridoxine; Female; Middle Aged; Aged; Male; Antineoplastic Combined Chemotherapy Protocols; Adult; Breast Neoplasms; Neoplasm Staging; Treatment Outcome
PubMed: 38802419
DOI: 10.1038/s41598-024-62860-z -
Microorganisms May 2024Pyridoxine, also known as vitamin B, is an essential cofactor in numerous cellular processes. Its importance in various applications has led to a growing interest in...
Pyridoxine, also known as vitamin B, is an essential cofactor in numerous cellular processes. Its importance in various applications has led to a growing interest in optimizing its production through microbial biosynthesis. However, an imbalance in the net production of NADH disrupts intracellular cofactor levels, thereby limiting the efficient synthesis of pyridoxine. In our study, we focused on multiple cofactor engineering strategies, including the enzyme design involved in NAD-dependent enzymes and NAD regeneration through the introduction of heterologous NADH oxidase (Nox) coupled with the reduction in NADH production during glycolysis. Finally, the engineered achieved a pyridoxine titer of 676 mg/L in a shake flask within 48 h by enhancing the driving force. Overall, the multiple cofactor engineering strategies utilized in this study serve as a reference for enhancing the efficient biosynthesis of other target products.
PubMed: 38792763
DOI: 10.3390/microorganisms12050933