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Experimental and Therapeutic Medicine Aug 2024Excessive alcohol consumption is considered to be a major risk factor of alcohol-induced osteonecrosis of the femoral head (AONFH). The gut microbiota (GM) has been...
Excessive alcohol consumption is considered to be a major risk factor of alcohol-induced osteonecrosis of the femoral head (AONFH). The gut microbiota (GM) has been reported to aid in the regulation of human physiology and its composition can be altered by alcohol consumption. The aim of the present study was to improve the understanding of the GM and its metabolites in patients with AONFH. Metabolomic sequencing and 16S rDNA analysis of fecal samples were performed using liquid chromatography-mass spectrometry to characterize the GM of patients with AONFH and healthy normal controls (NCs). Metagenomic sequencing of fecal samples was performed to identify whether GM changes on the species level were associated with the expression of gut bacteria genes or their associated functions in patients with AONFH. The abundance of 58 genera was found to differ between the NC group and the AONFH group. Specifically, , , and were significantly more abundant in the AONFH group compared with those in the NC group. Metagenomic sequencing demonstrated that the majority of the bacterial species that exhibited significantly different abundance in patients with AONFH belonged to the genus . Fecal metabolomic analysis demonstrated that several metabolites were present at significantly different concentrations in the AONFH group compared with those in the NC group. These metabolites were products of vitamin B6 metabolism, retinol metabolism, pentose and glucuronate interconversions and glycerophospholipid metabolism. In addition, these changes in metabolite levels were observed to be associated with the altered abundance of specific bacterial species, such as , and . According to the results of the present study, a comprehensive landscape of the GM and metabolites in patients with AONFH was revealed, suggesting the existence of interplay between the gut microbiome and metabolome in AONFH pathogenesis.
PubMed: 38873043
DOI: 10.3892/etm.2024.12599 -
The Journal of Nutrition, Health & Aging Jun 2024To investigate the associations between circulating vitamins A, D, E, B6, B9, B12 and longitudinal changes in retinal nerve fiber layer (RNFL) thickness.
OBJECTIVE
To investigate the associations between circulating vitamins A, D, E, B6, B9, B12 and longitudinal changes in retinal nerve fiber layer (RNFL) thickness.
METHODS
The Alienor study, a prospective population-based cohort (Bordeaux, France), includes 963 individuals aged 73 years or older at baseline. The present study included 646 participants with complete RNFL measurement and vitamins. Study period is from 2009 to 2020. Peripapillary RNFL thickness was measured using spectral domain optical coherence tomography (SD-OCT). Plasma vitamins A, D and E and, serum vitamins B6, B9 and B12 were measured from blood sample. We performed linear mixed models, adjusted for age, gender, axial length, family history of glaucoma, and alcohol consumption to evaluated associations between vitamins and RNFL thickness changes over time.
RESULTS
Individuals having higher concentrations of vitamin E, D and B9 had a slower RNFL thinning during the 10-years of follow-up. Indeed, a 1-standard deviation (SD) increase of vitamin E (10.8 μmol/L), D (17.6 nmol/L) and B9 (11 μmol/L) were associated with slower RNFL thinning by 0.14 μm/year (95% confidence interval (CI), 0.03-0.25, p = 0.01), 0.14 μm/year (95% CI, 0.02-0.27, p = 0.02) and 0.11 μm/year (95% CI: 0.007-0.21, p = 0.04), respectively. No significant associations were observed for vitamins A, B6 and B12 with RNFL thinning.
CONCLUSIONS
Higher levels of vitamins E, D and B9 were associated with a slower RNFL thickness on SD-OCT over time, suggesting that those vitamins may contribute to the neuroprotection of the retina.
PubMed: 38861880
DOI: 10.1016/j.jnha.2024.100286 -
ELife Jun 2024Vitamin B6 deficiency has been linked to cognitive impairment in human brain disorders for decades. Still, the molecular mechanisms linking vitamin B6 to these...
Vitamin B6 deficiency has been linked to cognitive impairment in human brain disorders for decades. Still, the molecular mechanisms linking vitamin B6 to these pathologies remain poorly understood, and whether vitamin B6 supplementation improves cognition is unclear as well. Pyridoxal 5'-phosphate phosphatase (PDXP), an enzyme that controls levels of pyridoxal 5'-phosphate (PLP), the co-enzymatically active form of vitamin B6, may represent an alternative therapeutic entry point into vitamin B6-associated pathologies. However, pharmacological PDXP inhibitors to test this concept are lacking. We now identify a PDXP and age-dependent decline of PLP levels in the murine hippocampus that provides a rationale for the development of PDXP inhibitors. Using a combination of small-molecule screening, protein crystallography, and biolayer interferometry, we discover, visualize, and analyze 7,8-dihydroxyflavone (7,8-DHF) as a direct and potent PDXP inhibitor. 7,8-DHF binds and reversibly inhibits PDXP with low micromolar affinity and sub-micromolar potency. In mouse hippocampal neurons, 7,8-DHF increases PLP in a PDXP-dependent manner. These findings validate PDXP as a druggable target. Of note, 7,8-DHF is a well-studied molecule in brain disorder models, although its mechanism of action is actively debated. Our discovery of 7,8-DHF as a PDXP inhibitor offers novel mechanistic insights into the controversy surrounding 7,8-DHF-mediated effects in the brain.
Topics: Animals; Mice; Humans; Enzyme Inhibitors; Phosphoric Monoester Hydrolases; Hippocampus; Neurons; Pyridoxal Phosphate; Flavones; Mice, Inbred C57BL
PubMed: 38856179
DOI: 10.7554/eLife.93094 -
Frontiers in Nutrition 2024Currently, there is limited and inconsistent evidence regarding the risk association between daily dietary intake, antioxidants, minerals, and vitamins with Childhood...
BACKGROUND
Currently, there is limited and inconsistent evidence regarding the risk association between daily dietary intake, antioxidants, minerals, and vitamins with Childhood Asthma (CA). Therefore, this study employs Mendelian Randomization (MR) methodology to systematically investigate the causal relationships between daily dietary intake, serum antioxidants, serum minerals, and the circulating levels of serum vitamins with
METHODS
This study selected factors related to daily dietary intake, including carbohydrates, proteins, fats, and sugars, as well as serum antioxidant levels (lycopene, uric acid, and β-carotene), minerals (calcium, copper, selenium, zinc, iron, phosphorus, and magnesium), and vitamins (vitamin A, vitamin B6, folate, vitamin B12, vitamin C, vitamin D, and vitamin E), using them as Instrumental Variables (IVs). Genetic data related to CA were obtained from the FinnGen and GWAS Catalog databases, with the primary analytical methods being Inverse Variance Weighting (IVW) and sensitivity analysis.
RESULTS
Following MR analysis, it is observed that sugar intake (OR: 0.71, 95% CI: 0.55-0.91, P: 0.01) is inversely correlated with the risk of CA, while the intake of serum circulating magnesium levels (OR: 1.63, 95% CI: 1.06-2.53, P: 0.03), fats (OR: 1.44, 95% CI: 1.06-1.95, P: 0.02), and serum vitamin D levels (OR: 1.14, 95% CI: 1.04-1.25, P: 0.02) are positively associated with an increased risk of
CONCLUSION
This study identified a causal relationship between the daily dietary intake of sugars and fats, as well as the magnesium and vitamin D levels in serum, and the occurrence of However, further in-depth research is warranted to elucidate the specific mechanisms underlying these associations.
PubMed: 38846540
DOI: 10.3389/fnut.2024.1401881 -
BMC Musculoskeletal Disorders Jun 2024Although various anti-inflammatory medicines are widely recommended for osteoarthritis (OA) treatment, no significantly clinical effect has been observed. This study...
BACKGROUND
Although various anti-inflammatory medicines are widely recommended for osteoarthritis (OA) treatment, no significantly clinical effect has been observed. This study aims to examine the effects of vitamin B6, a component that has been reported to be capable of alleviating inflammation and cell death in various diseases, on cartilage degeneration in OA.
METHODS
Collagen-induced arthritis (CIA) mice model were established and the severity of OA in cartilage was determined using the Osteoarthritis Research Society International (OARSI) scoring system. The mRNA and protein levels of indicators associated with extracellular matrix (ECM) metabolism, apoptosis and inflammation were detected. The effect of vitamin B6 (VB6) on the mice were assessed using HE staining and masson staining. The apoptosis rate of cells was assessed using TdT-mediated dUTP nick end labeling.
RESULTS
Our results showed a trend of improved OARSI score in mice treated with VB6, which remarkably inhibited the hyaline cartilage thickness, chondrocyte disordering, and knees hypertrophy. Moreover, the VB6 supplementation reduced the protein expression of pro-apoptosis indicators, including Bax and cleaved caspase-3 and raised the expression level of anti-apoptosis marker Bcl-2. Importantly, VB6 improved ECM metabolism in both in vivo and in vitro experiments.
CONCLUSIONS
This study demonstrated that VB6 alleviates OA through regulating ECM metabolism, inflammation and apoptosis in chondrocytes and CIA mice. The findings in this study provide a theoretical basis for targeted therapy of OA, and further lay the theoretical foundation for studies of mechanisms of VB6 in treating OA.
Topics: Animals; Apoptosis; Mice; Vitamin B 6; Osteoarthritis; Arthritis, Experimental; Inflammation; Male; Chondrocytes; Mice, Inbred DBA; Anti-Inflammatory Agents; Extracellular Matrix; Cartilage, Articular
PubMed: 38844896
DOI: 10.1186/s12891-024-07530-x -
Clinical Drug Investigation Jun 2024Musculoskeletal disorders are an important cause of work absence. Clinical practice guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs) for grade I-II... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Musculoskeletal disorders are an important cause of work absence. Clinical practice guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs) for grade I-II cervical sprains. The combination of thiamine + pyridoxine + cyanocobalamin vitamins has been used, alone and in combination with NSAIDs, for pain and inflammation in musculoskeletal disorders.
OBJECTIVE
The objective of this study was to demonstrate the analgesic synergy of dexketoprofen, and the combination of vitamins thiamine + pyridoxine + cyanocobalamin in a fixed-dose combination (FDC) for the treatment of acute pain caused by grade I-II cervical sprains.
METHODS
We conducted a multicentre, prospective, randomized, double-blind, phase IIIb clinical study comparing two treatment groups: (1) dexketoprofen 25 mg/vitamin B (thiamine 100 mg, pyridoxine 50 mg and cyanocobalamin 0.50 mg) in an FDC (two or more active ingredients combined in a single dosage form) versus (2) dexketoprofen 25 mg monotherapy (single drug to treat a particular disease), one capsule or tablet orally, every 8 h for 7 days. Final mean, average change, and percentage change in pain perception (measured using a visual analogue scale [VAS]) were compared with baseline between groups. A p value < 0.05 was considered statistically significant. Analyses were conducted using SPSS software, v.29.0.
RESULTS
A statistically significant reduction in pain intensity was observed from the third day of treatment with the FDC compared with monotherapy (- 3.1 ± - 1.5 and - 2.6 ± - 1.1 cm, respectively) measured using the VAS (p = 0.011). Regarding the degree of disability, using the Northwick Park Neck Pain Questionnaire (NPQ), statistical difference was observed for the final measurement (7.5%, interquartile range [IQR] 2.5, 10.5; vs. 7.9%, IQR 5.0, 13.8; p = 0.028). A lower proportion of adverse events was reported when using the FDC.
CONCLUSIONS
The FDC of dexketoprofen/thiamine + pyridoxine + cyanocobalamin vitamins demonstrated superior efficacy and a better safety profile compared with dexketoprofen monotherapy for pain treatment in patients with grade I-II cervical sprains.
CLINICAL TRIALS REGISTRATION
NCT05001555, registered 29 July 2021 ( https://clinicaltrials.gov/study/NCT05001555 ).
Topics: Humans; Double-Blind Method; Thiamine; Ketoprofen; Female; Adult; Pyridoxine; Male; Anti-Inflammatory Agents, Non-Steroidal; Vitamin B 12; Middle Aged; Tromethamine; Drug Combinations; Prospective Studies; Vitamin B Complex; Pain Measurement; Young Adult
PubMed: 38842764
DOI: 10.1007/s40261-024-01370-2 -
Frontiers in Endocrinology 2024Previous observational studies have identified a correlation between elevated plasma homocysteine (Hcy) levels and polycystic ovary syndrome (PCOS). This study aimed to...
OBJECTIVE
Previous observational studies have identified a correlation between elevated plasma homocysteine (Hcy) levels and polycystic ovary syndrome (PCOS). This study aimed to determine whether a causal relationship exists between Hcy and PCOS at the genetic level.
METHODS
A two-sample Mendelian Randomization (TSMR) study was implemented to assess the genetic impact of plasma levels of Hcy, folate, vitamin B12, and vitamin B6 on PCOS in individuals of European ancestry. Independent single nucleotide polymorphisms (SNPs) associated with Hcy (n=12), folate (n=2), vitamin B12 (n=10), and vitamin B6 (n=1) at genome-wide significance levels (<5×10) were selected as instrumental variables (IVs). Data concerning PCOS were obtained from the Apollo database. The primary method of causal estimation was inverse variance weighting (IVW), complemented by sensitivity analyses to validate the results.
RESULTS
The study found no genetic evidence to suggest a causal association between plasma levels of Hcy, folate, vitamin B12, vitamin B6, and PCOS. The effect sizes, determined through random-effect IVW, were as follows: Hcy per standard deviation increase, OR = 1.117, 95%CI: (0.842, 1.483), = 0.442; folate per standard deviation increase, OR = 1.008, CI: (0.546, 1.860), = 0.981; vitamin B12 per standard deviation increase, OR = 0.978, CI: (0.808, 1.185), = 0.823; and vitamin B6 per standard deviation increase, OR = 0.967, CI: (0.925, 1.012), = 0.145. The fixed-effect IVW results for each nutrient exposure and PCOS were consistent with the random-effect IVW findings, with additional sensitivity analyses reinforcing these outcomes.
CONCLUSION
Our findings indicate no causal link between Hcy, folate, vitamin B12, vitamin B6 levels, and PCOS.
Topics: Humans; Polycystic Ovary Syndrome; Female; Mendelian Randomization Analysis; Homocysteine; Polymorphism, Single Nucleotide; Vitamin B Complex; Folic Acid; Vitamin B 12; Genome-Wide Association Study; Vitamin B 6; Adult
PubMed: 38841299
DOI: 10.3389/fendo.2024.1393847 -
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 -
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