Cobalt ion-enhanced chemiluminescence of boron-nitrogen co-doped carbon dots for sensitive detection of cobalt ions and vitamin B12.

Epidemiologic studies suggest that patients with Parkinson disease (PD) may have lower levels of vitamin B12 compared with healthy controls, and it was proposed that patients with PD could benefit from vitamin B12 supplementation. Functional studies have shown that B12 could modify LRRK2 activity and may directly interact with alpha-synuclein. The aim of this study was to investigate the role of common and rare variants in genes related to B12 metabolism and assess the potential causal relationships between B12 levels and PD risk, age at onset, and motor/cognitive progression. We investigated the association between common and rare variants in genes involved in vitamin B12 metabolism. Rare variants (minor allele frequency <0.01) were analyzed using the optimal sequence kernel association test in 4,815 patients with PD and 65,607 controls from 2 independent cohorts. We constructed pathway-specific polygenic risk scores (PRSs) for genes essential to B12 metabolism and for genes identified in previous genome-wide association studies (GWASs) on B12 metabolism. Mendelian randomization and genetic correlation analyses were applied to explore the relationship between vitamin B12 levels and PD risk, age at onset, and disease progression. Our analysis showed no associations between common variants of genes crucial in B12 metabolism and PD. Pathway PRSs identified nominal association between B12-related genes and PD (odds ratio [OR] = 1.061, 95% CI 1.004-1.121, p = 0.038), which did not survive Bonferroni correction. In the rare-variant analysis, we identified a significant association between variants with high Combined Annotation Dependent Depletion scores in the CUBN gene (p = 6.07E-05; Pfdr = 0.005) in the Accelerating Medicines Partnership-PD cohort, driven by the benign variant p.G3114S (OR = 3.3; p = 3.56E-05); however, this was not validated in the meta-analysis. We did not identify a potentially causal relationship between vitamin B12 levels and the risk, age at onset, or progression of PD. In addition, no genetic correlation was observed between vitamin B12 and PD risk or age-at-onset GWASs. Overall, our analyses indicate lack of genetic link between B12 levels or metabolism and PD.

Shared metabolic pathways in epilepsy and plant immunity: From evolution to diet.

Gestational diabetes mellitus (GDM) is a prevalent complication, affecting approximately 14% of pregnancies worldwide, and is associated with an elevated risk of both maternal and infant complications. It also exerts long-term adverse effects on offspring health, including metabolic, cardiovascular, and neurodevelopmental disorders, thereby compromising maternal and infant well-being. During pregnancy, an imbalance between folic acid and vitamin B12 has been linked to an increased risk of GDM and unfavorable metabolic outcomes in offspring, underscoring the potential clinical value of maintaining their balance and implementing early interventions. This review summarizes the role of folic acid and vitamin B12 in gestational diabetes and offspring development, aiming to bridge the gap between mechanistic insights and clinical evidence. It highlights the potential for reverse causality in linking vitamin B12-folic acid imbalance to GDM risk and underscores the need to integrate novel metabolic and epigenetic concepts into future intervention trials.

Association of lifestyle and metabolic factors with clinical performance in multiple sclerosis: A cross-sectional study.

A 3-year-old boy presented with dark-colored urine for 4months. His history was negative for infections, but he was taking oral methylcobalamin treatment for a persistent deficiency. His parents were first-degree cousins, and a female cousin had proteinuria of unknown etiology. A physical examination and laboratory examination revealed no abnormalities except for non-orthostatic nephritic proteinuria and low levels of vitamin B12. Albumin was the main protein in the urine. Kidney biopsy showed nonspecific changes. Genetic analysis identified a homozygous pathogenic AMN mutation, confirming Imerslund-Grâsbeck syndrome (IGS). Angiotensin-converting enzyme inhibitor was prescribed but discontinued due to stable protein levels. After 4years, kidney function remained stable. Imerslund-Grâsbeck syndrome is a rare autosomal recessive disorder that affects vitamin B12 and protein, particularly albumin absorption. While typically presenting with megaloblastic anemia, AMN mutations show variable phenotypes. Proteinuria is resistant to ACE inhibitors, and currently, there is no specific treatment.

Additive effect of free-choice olfactory training combined with pharmacotherapy: A retrospective analysis of post-viral olfactory dysfunction.

Molecular imprinting based electrochemical sensor for determination of vitamin B12 using holotranscobalamin as biomarker

Intravenous Hydroxocobalamin for Cyanide Poisoning From Smoke Inhalation: A Comprehensive Scoping Review.

Characterization of the effect of Levilactobacillus brevis CGMCC 1.5954 combined with Lactiplantibacillus plantarum subsp. plantarum CGMCC 1.5953 on the red bean sprouts GABA-enriched fermented milks.

Salts of vitamin B6 with aliphatic dicarboxylic acids. Experimental and theoretical research

Changes in composition and flavor of non-centrifugal sugar after traditional Pan and vacuum evaporation processes.

Heat therapy attenuates hepatic lipid accumulation via CSAD-driven metabolic reprogramming of fatty acid oxidation.

Interfacial engineering of perovskite hydroxide embedded within reduced graphene oxide framework: A sensitive vitamin B2 detection and density functional theory insights

Certain human mutations in the mitochondrial aldehyde dehydrogenase 4A1 (ALDH4A1) lead to a severe, paediatric form of epilepsy and developmental abnormalities, yet the precise molecular mechanism leading to the clinical phenotypes remains unexplained. ALDH4A1 metabolizes glutamic-γ-semialdehyde (GSA). Mutations in ALDH4A1, which lead to inactive enzyme variants, cause GSA to accumulate and vitamin B6 inactivation. Patients with severe ALDH4A1 deficiency have paediatric epilepsy and are resistant to prescribed therapies. We develop knock-in cell culture and mouse models of the S352L variant to help characterize this human pathology. The knock-in models show that ALDH4A1 is necessary for clearing a non-canonical substrate, 4-hydroxynonenal (4-HNE), without becoming inactivated, like the main clearance mechanism of 4-HNE, ALDH2, and that ALDH4A1 deficiency alters transcriptional profiles in genes that regulate brain development, including LGI1 and FOXB1. Protein levels, including those in the proline metabolic pathway (e.g., spermine synthase), are also downregulated in both S352L iPSCs and the brains of S352L homozygous mice. This work identifies additional metabolic and transcriptional pathways regulated by ALDH4A1, and potential pathways that can be targeted to treat patients with ALDH4A1 deficiency.

Fungal dysbiosis is increasingly recognized as a critical factor in gut-related diseases, yet natural antifungal agents remain scarce. Lycopene is known to influence gut health, but its effects on fungi also remain unclear. This study investigated the impact of lycopene on the gut microbiota, particularly gut fungi. In vivo, lycopene significantly promoted the growth of beneficial species such as Lactobacillus johnsonii and altered microbial vitamin B6 metabolism. Metabolomics analysis further confirmed that lycopene enhanced vitamin B6 metabolism. In vitro fermentation using human gut microbiota confirmed similar effects. Then, inhibition of bacteria and fungi, along with the antagonism of vitamin B6, confirmed significant changes in the abundance of L. johnsonii and Trichocladium, mediated through vitamin B6 metabolism. Further monoculture experiments with Trichocladium demonstrated that vitamin B6, rather than lycopene itself, significantly reduced the abundance of Trichocladium. Structural equation modeling revealed lycopene's potential in modulating fungi within the gut ecosystem.

Over the past few decades, numerous studies have reported significant associations between nutrient intake, cognition, and later academic achievement in school-aged children. Most of these studies were conducted in Western countries, with a limited number in sub-Saharan Africa (SSA). This study provides a systematic review of research exploring the links between nutrients and cognition and/or academic performance in SSA and proposes appropriate cognitive and academic performance assessments for future research in this area. Systematic searches were conducted in the Web of Science, HINARI, ScienceDirect, PsycINFO, PubMed, and Google Scholar databases, as well as in the reference lists of relevant publications, from January to June 2023. Data were manually extracted from included publications by independent reviewers and registered in predefined sheets. A total of 31 publications were included in this review. Of these, 11 assessed the relationship between nutrients and cognition and/or academic performance, and 14 and 6 reported on cognitive and academic assessment tests, respectively. Fortification-based interventions were generally more effective than multimicronutrient (MMN) supplementation (MMNS). Additionally, micronutrients including iron, zinc, iodine, riboflavin, vitamin B6, folate, and vitamin B12 demonstrated positive associations with cognition, whereas evidence for vitamin A, vitamin D, and omega-3 fatty acids remains inconclusive. Noteworthy, most of the included studies focused on micronutrients, and there is a lack of research on the potential impacts of other types of nutrients, such as complex lipids. Furthermore, the Raven's Coloured Progressive Matrices (RCPM) and academic performance assessment using school marks have been repeatedly used, with acceptable validity for the RCPM. Cognitive and academic performance may be associated with specific micronutrients in school-aged children in SSA. The RCPM is a promising tool for assessing cognition in this population. Nevertheless, the findings remain inconclusive for MMNS and some nutrients, which further research may help elucidate. PROSPERO registration number: CRD42023392215.

Membrane protection against oxidative insults is achieved by the concerted action of glutathione peroxidase 4 (GPX4) and endogenous lipophilic antioxidants such as ubiquinone and vitamin E. More recently, ferroptosis suppressor protein 1 (FSP1) was identified as a critical ferroptosis inhibitor, acting via the regeneration of membrane-embedded antioxidants. Yet, regulators of FSP1 are largely uncharacterized, and their identification is essential for understanding the mechanisms buffering phospholipid peroxidation and ferroptosis. Here we report a focused CRISPR-Cas9 screen to uncover factors influencing FSP1 function, identifying riboflavin (vitamin B2) as a modulator of ferroptosis sensitivity. We demonstrate that riboflavin supports FSP1 stability and the recycling of lipid-soluble antioxidants, thereby mitigating phospholipid peroxidation. Furthermore, we show that the riboflavin antimetabolite roseoflavin markedly impairs FSP1 function and sensitizes cancer cells to ferroptosis. Our findings provide a rational strategy to modulate the FSP1-antioxidant recycling pathway and underscore the therapeutic potential of targeting riboflavin metabolism, with implications for understanding the interaction of nutrients, as well as their contributions to a cell's antioxidant capacity.

Advances in microbial fermentation of agro-industrial and food waste for sustainable vitamin B12 production

The human gut microbiome is important for host health, yet over 60% of gut species remain uncultured and inaccessible to experimental manipulation. Here, we analyze 11,115 human gut metagenomes from 39 countries, 13 noncommunicable diseases, and healthy individuals to understand the clinical relevance of the uncultured microbiome worldwide. We identify 317 species linked to distinct clinical states, noting an overrepresentation of uncultured bacteria in healthy subjects. The genus CAG-170 emerged as the strongest health-associated lineage across multiple diseases and geographies, standing as the most central taxon based on ecological networks of healthy populations. We find that CAG-170 is temporally stable, with its abundance and subspecies diversity negatively correlated with gut imbalance over time. Functional predictions show CAG-170 species have greater vitamin B12 biosynthesis capacity and cross-feeding potential, providing important biological insights into this elusive genus. Our findings shed light on the underexplored role of uncultured gut species in health and disease.