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BackgroundSphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) is a recently recognized inborn error of metabolism associated with steroid-resistant nephrotic syndrome as well as adrenal insufficiency and immunological, neurological, and skin manifestations. SPLIS is caused by inactivating mutations in SGPL1, encoding the pyridoxal 5'phosphate-dependent enzyme sphingosine-1-phosphate lyase, which catalyzes the final step of sphingolipid metabolism. Some SPLIS patients have undergone kidney transplantation, and others have been treated with vitamin B6 supplementation. In addition, targeted therapies including gene therapy are in preclinical development. In anticipation of clinical trials, it will be essential to characterize the full spectrum and natural history of SPLIS. We performed a retrospective analysis of 76 patients in whom the diagnosis of SPLIS was established in a proband with at least one suggestive finding and biallelic SGPL1 variants identified by molecular genetic testing. The main objective of the study was to identify factors influencing survival in SPLIS subjects.ResultsOverall survival at last report was 50%. Major influences on survival included: (1) age and organ involvement at first presentation; (2) receiving a kidney transplant, and (3) SGPL1 genotype. Among 48 SPLIS patients with nephropathy who had not received a kidney transplant, two clinical subgroups were distinguished. Of children diagnosed with SPLIS nephropathy before age one (n = 30), less than 30% were alive 2 years after diagnosis, and 17% were living at last report. Among those diagnosed at or after age one (n = 18), ~ 70% were alive 2 years after diagnosis, and 72% were living at time of last report. SPLIS patients homozygous for the SPL R222Q variant survived longer compared to patients with other genotypes. Kidney transplantation significantly extended survival outcomes.ConclusionOur results demonstrate that SPLIS is a phenotypically heterogeneous condition. We find that patients diagnosed with SPLIS nephropathy in the first year of life and patients presenting with prenatal findings represent two high-risk subgroups, whereas patients harboring the R222Q SGPL1 variant fare better than the rest. Time to progression from onset of proteinuria to end stage kidney disease varies from less than one month to five years, and kidney transplantation may be lifesaving.

Vitamin B6 is frequently utilized as a therapeutic agent for nausea and vomiting of pregnancy (NVP). Research indicates that excessive intake of vitamin B6 can have implications on neurological function, underscoring the importance of cautious consideration when administering vitamin B6 treatment during early pregnancy. This systematic review investigates the effects of high doses of vitamin B6 on pregnant women experiencing NVP. We searched the PubMed® MEDLINE® database for articles using the following terms: “pregnancy” or “nausea and vomiting during pregnancy” and “vitamin B6.” Women with nausea and vomiting symptoms during pregnancy use more than the tolerable amount of vitamin B6. A total of 136 articles were identified from the PubMed® MEDLINE® database. The etiology and treatment of NVP are briefly outlined, followed by a summary and analysis of 19 relevant literature sources. Among these sources, 12 reports detailed the adverse effects of excessive vitamin B6 intake in women; 164/1226 individuals experienced neurological symptoms such as burning, tingling, paresthesia, ataxia, or perioral numbness. Additionally, out of 245 women, four experienced miscarriages and one had an intrauterine demise. The overconsumption of vitamin B6 has the potential to impact nerve function, particularly during the critical first trimester of embryonic development. It might result in adverse outcomes such as miscarriage, intrauterine fetal demise, and congenital abnormalities. [ABSTRACT FROM AUTHOR]

Pyridoxal 5′‐phosphate (PLP), the catalytically active form of vitamin B6, acts as a cofactor in many metabolic processes. In humans, PLP is produced in the reactions catalysed by pyridox(am)ine 5′‐phosphate oxidase (PNPO) and pyridoxal kinase (PDXK). Both PNPO and PDXK are involved in cancer progression of many tumours. The silencing of PNPO and PDXK encoding genes determines a strong reduction in tumour size and neoplastic cell invasiveness in models of acute myeloid leukaemia (in the case of PDXK) and ovarian and breast cancer (in the case of PNPO). In the present work, we demonstrate that pyridoxilidenerhodanine 5′‐phosphate (PLP‐R), a PLP analogue that has been tested by other authors on malignant cell lines reporting a reduction in proliferation, inhibits PNPO in vitro following a mixed competitive and allosteric mechanism. We also show that the unphosphorylated precursor of this inhibitor (PL‐R), which has more favourable pharmacokinetic properties according to our predictions, is phosphorylated by PDXK and therefore transformed into PLP‐R. On this ground, we propose the prototype of a novel prodrug‐drug system as a useful starting point for the development of new, potential, antineoplastic agents. [ABSTRACT FROM AUTHOR]

Background: A nutritional supplement based on medicinal plants (saffron and ashwagandha), tryptophan, and vitamin B6 could contribute to alleviating/improving mood and associated disorders. The aim of this study was to evaluate the potential benefits of this combination supplement. During the study period, participants underwent a period of forced home confinement due to the COVID‐19 pandemic, which represented an unexpected impact factor. Methods: This open‐label prospective trial enrolled a cohort of female employees who reported mild to moderate anxiety. The primary objective was to evaluate changes in the level of anxiety using the adapted Hamilton Anxiety Rating Scale (HARS) after 12 weeks of regular supplementation with Safromotive (two tablets daily, for 12 weeks). The secondary objectives were to evaluate health‐related quality of life (HRQoL) and tolerability. Results: In total, 46 women with a mean age of 45.0 (6.5) years were included. A statistically significant improvement in HARS was observed, with a 7.5‐unit decrease from baseline to 12 weeks (p < 0.0001) and from 4 to 12 weeks of supplement intake (p = 0.0058). However, no significant changes were found during the lockdown period (between weeks 8 and 12 of the study). No relationship was found between women's sociodemographic characteristics and the HARS total score. A significant reduction in the HRQoL questionnaire score of 1.2 units was observed between baselines and 12 weeks of treatment (p = 0.0273). At the end of the study, 78.6% of the women reported consistency the supplement intake during the study course. Conclusion: This nutritional supplement composed of saffron, ashwagandha, tryptophan, and vitamin B6 appears to improve anxiety and HRQoL, but confinement could have impacted the evolution of the outcome. [ABSTRACT FROM AUTHOR]

Background: Phenotypic age (PhenoAge), a widely used marker of biological aging, has been shown to be a robust predictor of all-cause mortality and morbidity in different populations. Existing studies on biological aging have primarily focused on individual domains, resulting in a lack of a comprehensive understanding of the multi-systemic dysregulation that occurs in aging. Methods: PhenoAge was evaluated based on a linear combination of chronological age (CA) and 9 clinical biomarkers in 952 multi-ethnic Asian women of reproductive age. Phenotypic age acceleration (PhenoAgeAccel), an aging biomarker, represents PhenoAge after adjusting for CA. This study conducts an in-depth association analysis of PhenoAgeAccel with clinical, nutritional, lipidomic, gut microbiome, and genetic factors. Results: Higher adiposity, glycaemia, plasma saturated fatty acids, kynurenine pathway metabolites, GlycA, riboflavin, nicotinamide, and insulin-like growth factor binding proteins were positively associated with PhenoAgeAccel. Conversely, a healthier diet and higher levels of pyridoxal phosphate, all-trans retinol, betaine, tryptophan, glutamine, histidine, apolipoprotein B, and insulin-like growth factors were inversely associated with PhenoAgeAccel. Lipidomic analysis found 132 lipid species linked to PhenoAgeAccel, with PC(O-36:0) showing the strongest positive association and CE(24:5) demonstrating the strongest inverse association. A genome-wide association study identified rs9864994 as the top genetic variant (P = 5.69E-07) from the ZDHHC19 gene. Gut microbiome analysis revealed that Erysipelotrichaceae UCG-003 and Bacteroides vulgatus were inversely associated with PhenoAgeAccel. Integrative network analysis of aging-related factors underscored the intricate links among clinical, nutritional and lipidomic variables, such as positive associations between kynurenine pathway metabolites, amino acids, adiposity, and insulin resistance. Furthermore, potential mediation effects of blood biomarkers related to inflammation, immune response, and nutritional and energy metabolism were observed in the associations of diet, adiposity, genetic variants, and gut microbial species with PhenoAgeAccel. Conclusions: Our findings provide a comprehensive analysis of aging-related factors across multiple platforms, delineating their complex interconnections. This study is the first to report novel signatures in lipidomics, gut microbiome and blood biomarkers specifically associated with PhenoAgeAccel. These insights are invaluable in understanding the molecular and metabolic mechanisms underlying biological aging and shed light on potential interventions to mitigate accelerated biological aging by targeting modifiable factors. [ABSTRACT FROM AUTHOR]

Introduction: Food security and waste management represent the main challenges that need to be addressed in the near future. The use of bioformulations and bioactive compounds obtained from agricultural wastes could represent some of the solutions for the management of soil-borne pathogens. Methods: In the present study, Aureobasidium pullulans strain AP1, tested in oil dispersion (OD) formulation prototype and bio-extracts [hot water extract (HWE) and warm water extract (WWE)] derived from spent mushroom substrate (SMS) of Agaricus bisporus , was tested as sustainable strategies to manage Rhizoctonia solani of lettuce. Results: By in vitro assays, AP1OD at 600 mg L−1 displayed an inhibition by 57% of pathogen mycelial growth, and the SMS extract WWE (40°C) showed a growth stimulation of lettuce seedling by 27%. By In vivo assays, AP1OD formulation used against R. solani reduced by 66.6% the soil-borne pathogen incidence on lettuce plants, and both bio-extracts significantly stimulated lettuce leaves and roots growth (>200%). AP1OD formulation and HWE treatments increased the lettuce genes expression levels (ggps and hppd pdx1) mainly imputed to plant antioxidant potential, vitamin E, and vitamin B6 biosynthesis. Discussion: The present study reported the potential of a new formulation and two bio-extracts, derived from an agricultural waste, to use against R. solani of lettuce, respectively, with antifungal and biostimulant properties. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a common cause of female reproductive problems, and vitamin intake may affect its incidence. Therefore, we further explored the association between multivitamin intake and endometriosis in a large population-based study. Methods: This study included 3351 participants from the National Health and Nutrition Examination Survey (NHANES) 1999–2006. The dietary intake of eight vitamins was calculated as the average of two 24-h recall interviews, and information on endometriosis was obtained through questionnaires that included gynecological history. Multiple logistic regression analysis was used to explore the relationship between multivitamin intake and endometriosis. Smoothed curve fitting analysis was employed to assess the dose–response relationship between vitamins and endometriosis. Finally, subgroup analysis and interaction tests were conducted to determine the association of covariates between vitamins and endometriosis. Results: In this large-scale cross-sectional study, multiple logistic regression analysis showed that the intake of vitamins A, B1, B2, B6, C and folate was negatively associated with the occurrence of endometriosis. The odds ratios associated with a per-SD increase were 0.836 (95%CI: 0.702, 0.997), 0.817 (95%CI: 0.702, 0.951), 0.860 (95%CI: 0.746, 0.991), 0.784 (95%CI: 0.669, 0.919), 0.845 (95%CI: 0.718, 0.994), and 0.772 (95%CI: 0.660, 0.903), respectively. Smoothed curve fitting analysis revealed that the intake of vitamins A, B1, B2, B6, C, and folate was negatively associated with the risk of endometriosis (P < 0.05). Vitamin E showed a saturating effect, with an optimal cutoff point at 13.18. Below this cutoff, the intake of vitamin E was negatively correlated with the risk of endometriosis (OR = 0.947, 95% CI: 0.906, 0.989), whereas above the cutoff, there was no significant correlation between vitamin E intake and the risk of endometriosis (OR = 1.001, 95% CI: 0.997, 1.005). Conclusions: The results of this study indicate a significant linear negative correlation between the intake of vitamins A, B1, B2, B6, C, and folate, and the risk of endometriosis, and reveal a threshold effect for vitamin E intake on the risk of endometriosis. These findings could inform clinical dietary interventions and may support the development of preventive strategies for endometriosis, potentially aiding in its reduction. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota can facilitate host growth under nutrient-constrained conditions. However, whether this effect is limited to certain bacterial species remains largely unclear, and the relevant underlying mechanisms remain to be thoroughly investigated. Results: We found that the microbiota was required for Bactrocera dorsalis larval growth under poor dietary conditions. Monoassociation experiments revealed that Enterobacteriaceae and some Lactobacilli promoted larval growth. Among the 27 bacterial strains tested, 14 significantly promoted larval development, and the Enterobacteriaceae cloacae isolate exhibited the most obvious promoting effect. A bacterial genome-wide association study (GWAS) revealed that the vitamin B6 synthesis pathway was critical for the promotion of E. cloacae growth. Deletion of pdxA, which is responsible for vitamin B6 biosynthesis, deprived the mutant strains of larval growth-promoting function, indicating that the 4-hydroxythreonine-4-phosphate dehydrogenase(pdxA) gene was crucial for promoting larval growth in E. cloacae. Importantly, supplementation of a poor diet with vitamin B6 successfully rescued the axenic larval growth phenotype of B. dorsalis. Conclusion: Our results suggest that gut microbes promote insect larval growth by providing vitamin B6 under nutrient scarcity conditions in B. dorsalis. Dswoh3a91svsnnT3oBX6dH Video Abstract [ABSTRACT FROM AUTHOR]

Clinical relevance: Investigating the role of dietary vitamin B6 intake in the risk and prognosis of diabetic retinopathy (DR) could facilitate the management of DR. Background: This study aimed to assess the association between dietary vitamin B6 intake and the risk of DR and further explore the association between vitamin B6 intake and mortality in patients with DR. Methods: This retrospective cohort study gained data from the National Health and Nutrition Examination Survey (NHANES) 2005–2006 and 2007–2008. The intake of dietary vitamin B6 was assessed by two 24-h dietary recall interviews. Mortality information in the National Death Index was recorded from the date of survey participation through 31 December 2019. Multivariate regression analyses were employed to assess the association between vitamin B6 intake and the risk of DR, and the association between vitamin B6 intake and the risk of mortality in patients with DR. Results: A total of 5559 subjects were included, of which 693 (12.47%) had DR. Among these patients with DR, 429 (61.90%) were survivors. Multivariate analyses showed that the intake of vitamin B6 was negatively associated with the risk of DR (odds ratio = 0.81, 95% confidence level: 0.69–0.95, p = 0.012), and patients with DR with an increased intake of vitamin B6 had a significantly decreased risk of all-cause death (hazard ratio = 0.81, 95% confidence level: 0.66–0.99, p = 0.041) or cardiovascular disease-related death (hazard ratio = 0.76, 95% confidence level: 0.58–0.98, p = 0.037). Conclusion: The intake of vitamin B6 was negatively associated with the risk of DR, and in patients with DR, a higher intake of vitamin B6 was associated with a lower risk of all-cause death and cardiovascular disease-related death, indicating the possible protective role of increased vitamin B6 intake. [ABSTRACT FROM AUTHOR]

Due to insufficient dietary intake and altered digestion and absorption of nutrients, patients after gastroesophageal cancer surgery are at risk of becoming malnourished and consequently develop micronutrient deficiencies. The aim of this study was to determine the prevalence of micronutrient deficiencies and anemia during follow-up after gastroesophageal cancer surgery. This single-center cross-sectional study included patients after resection for esophageal or gastric cancer visiting the outpatient clinic in 2016 and 2017. Only patients without signs of recurrent disease were included. All patients were guided by a dietician in the pre- and postoperative phase. Dietary supplements or enteral tube feeding was prescribed in case of inadequate dietary intake. Blood samples were examined for possible deficiencies or abnormalities in hemoglobin, prothrombin time, iron, ferritin, folic acid, calcium, zinc, vitamin A, vitamin B1, vitamin B6, vitamin B12, vitamin D and vitamin E. The percentage of patients with micronutrient deficiencies were scored. Of the 335 patients visiting the outpatient clinic, measurements were performed in 263 patients (221 after esophagectomy and 42 after gastrectomy), resulting in an inclusion rate of 79%. In the esophagectomy group, deficiencies in iron (36%), vitamin D (33%) and zinc (20%) were most prevalent. After gastric resection, deficiencies were most frequently observed in vitamin D (52%), iron (33%), zinc (28%) and ferritin (17%). Low levels of hemoglobin were found in 21% of patients after esophagectomy and 24% after gastrectomy. Despite active nutritional guidance, deficiencies in vitamin D, iron, zinc and ferritin, as well as low levels of hemoglobin, are frequently observed following gastroesophageal resection for cancer. These micronutrients should be periodically checked during follow-up and supplemented if needed. [ABSTRACT FROM AUTHOR]

Objectives: Because angiotensin (Ang) II is an essential vasoconstrictive peptide, we analyzed the impact of its post‐translational modification to pyruvamide–Ang II (Ang P) by pyridoxal‐5′‐phosphate (PLP) on blood pressure. PLP is a less expensive vitamin B6 derivative and, therefore, could be a cost‐effective drug against hypertension. Methods: Effect of Ang P on calcium ion entry into vascular smooth muscle cells (VSMCs) was analyzed. Binding affinity of Ang P to angiotensin II type 1 receptor (AT1R) was measured. Vasoconstrictive effect of Ang P was investigated using the bioassay of isolated perfused rat kidneys. Spontaneously hypertensive rats (SHR) were administered PLP. Additionally, Wistar Kyoto rats (WKY) received Ang II and PLP. Blood pressure was measured time‐dependently. Results: Ang II, incubated with PLP, was post‐translationally modified to Ang P. Calcium ion entry in VSMCs was significantly lower with Ang P compared to Ang II. Binding affinity of Ang P to AT1R was lower compared to Ang II. Perfusion pressure of isolated perfused rat kidneys increased less by Ang P than by Ang II. Blood pressure of SHR treated with PLP decreased significantly. Blood pressure of WKY rats treated with Ang II was increased to hypertensive values, whereas blood pressure of WKY rats cotreated with Ang II and PLP was not. Conclusion: PLP induces a post‐translational modification of Ang II decreasing blood pressure in rats. Assuming that increased PLP intake in the form of vitamin B6 might reduce blood pressure in hypertensive patients, PLP might be a cost‐effective drug against hypertension. [ABSTRACT FROM AUTHOR]

Comparative transcriptomics uncovered distinct expression patterns of genes associated with cofactor and vitamin metabolism in the high-yielding mutant strain Saccharopolyspora erythraea HL3168 E3, as compared to the wild-type NRRL 2338. An in-depth analysis was conducted on the effects of nine vitamins, and it was determined that thiamine pyrophosphate (TPP), vitamin B2, vitamin B6, vitamin B9, vitamin B12, and hemin are key enhancers in erythromycin production in E3, increasing the erythromycin titer by 7.96–12.66%. Then, the Plackett-Burman design and the path of steepest ascent were applied to further optimize the vitamin combination for maximum production efficiency, enhancing the erythromycin titer in shake flasks by 39.2%. Otherwise, targeted metabolomics and metabolic flux analysis illuminated how vitamin supplementation modulates the central carbon metabolism with notable effects on the TCA cycle and methionine synthesis to augment the provision of energy and precursors essential for erythromycin synthesis. This work highlights the capacity for precise vitamin supplementation to refine metabolic pathways, thereby boosting erythromycin production, and provides valuable directions for application on an industrial scale. [ABSTRACT FROM AUTHOR]

Background: Diabetic retinopathy (DR) is a major microvascular complication of diabetes and a leading cause of blindness worldwide. The pathogenesis of DR involves complex interactions between metabolic disturbances, immune cells, and proteolytic enzymes such as cathepsins (CATs). Despite various studies, the precise roles of different CATs, metabolites, and vitamins in DR remain unclear. Method: In this study, we employed Mendelian Randomization (MR) to assess causal relationships using genetic instruments selected based on genome-wide association studies (GWAS). We employed two-sample and mediation MR to explore the causal effects between nine CATs, immune cells, metabolites, vitamins, and DR. Additionally, the study also incorporated data from the NHANES survey to explore the associated relationship between vitamins and DR. We utilized cross-sectional data from the NHANES to analyze the association between vitamin intake and diabetic retinopathy (DR), adjusting for potential confounders to strengthen the validity of our findings. Results: The MR analysis identified CAT H as a significant risk factor for both NPDR and PDR, with no evidence of reverse causality. Additionally, 62 immune cell traits were found to have causal relationships with NPDR and 49 with PDR. Enrichment analysis revealed that metabolic pathways such as sphingolipid metabolism are crucial in DR progression. Vitamins B6 and E were significantly associated with a reduced risk of PDR. Cross-sectional data indicated that vitamins B1, B2, B6, B12, and E progressively decreased with DR severity. Conclusion: This study is the first to identify CAT H as a key risk factor for DR, while vitamins B6 and E showed significant protective effects, particularly against PDR. These findings suggest that CAT H, along with vitamins B6 and E, could serve as therapeutic targets for DR. Further validation through larger, multicenter studies is recommended to enhance the accuracy and applicability of these findings. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a metabolic disorder. Discovering the metabolic products involved in the development of AD may help not only in the early detection and prevention of AD but also in understanding its pathogenesis and treatment. This study investigated the causal association between the latest large-scale plasma metabolites (1091 metabolites and 309 metabolite ratios) and AD. Through the application of Mendelian randomization analysis methods such as inverse-variance weighted (IVW), MR-Egger, and weighted median models, 66 metabolites and metabolite ratios were identified as potentially having a causal association with AD, with 13 showing significant causal associations. During the replication validation phase, six metabolites and metabolite ratios were confirmed for their roles in AD: N-lactoyl tyrosine, argininate, and the adenosine 5'-monophosphate to flavin adenine dinucleotide ratio were found to exhibit protective effects against AD. In contrast, ergothioneine, piperine, and 1,7-dimethyluric acid were identified as contributing to an increased risk of AD. Among them, argininate showed a significant effect against AD. Replication and sensitivity analyses confirmed the robustness of these findings. Metabolic pathway analysis linked "Vitamin B6 metabolism" to AD risk. No genetic correlations were found, but colocalization analysis indicated potential AD risk elevation through top SNPs in APOE and PSEN2 genes. This provides novel insights into AD's etiology from a metabolomic viewpoint, suggesting both protective and risk metabolites. [ABSTRACT FROM AUTHOR]

The article delves into the impact of pyridoxal-5-phosphate (PLP) on aspartate aminotransferase (AST) assays, leading to falsely elevated AST values in specimens deficient in vitamin B6. A patient with macro-AST exhibited significantly elevated AST values associated with immunoglobulins, which were removed by Protein G treatment, confirming the presence of macro-AST. The study recommends using non-PLP assays for accurate AST testing and further investigation to avoid unnecessary procedures when macro-AST is suspected. [Extracted from the article]

Kashin‐Beck disease (KBD) is a chronic degenerative, disabling disease of the bones and joints and its exact aetiology and pathogenesis remain uncertain. This study is to investigate the role of m6A modification in the pathogenesis of KBD. Combined analysis of m6A MeRIP‐Seq and RNA‐Seq were used to analyse human peripheral blood samples from three KBD patients and three normal controls (NC). Bioinformatic methods were used to analyse m6A‐modified differential genes and RT‐qPCR was performed to validate the mRNA expression of several KBD‐related genes. The results indicated that the total of 16,811 genes were modified by m6A in KBD group, of which 4882 genes were differential genes. A large number of differential genes were associated with regulation of transcription, signal transduction and protein binding. KEGG analysis showed that m6A‐enriched genes participated the pathways of Vitamin B6 metabolism, endocytosis and Rap 1 signalling pathway. There was a positive association between m6A abundance and levels of gene expression, that there were 6 hypermethylated and upregulated genes (hyper‐up), 23 hypomethylated and downregulated genes (hypo‐down) in KBD group compared with NC. In addition, the mRNA expression of levels of MMP8, IL32 and GPX1 were verified and the protein–protein interaction networks of these key factors were constructed. Our study showed that m6A modifications may play a vital role in modulating gene expression, which represents a new clue to reveal the pathogenesis of KBD. [ABSTRACT FROM AUTHOR]

A 10‐week feeding trial was conducted to investigate the dietary pyridoxine requirements of coho salmon (Oncorhynchus kisutch) post‐smolts with an initial mean body weight of 180.22 ± 0.41 g. Seven diets were prepared with gradient pyridoxine levels of 0.32, 1.25, 2.56, 4.08, 8.24, 16.02, and 32.32 mg/kg, respectively, and each diet was assigned to three replication groups of 10 fish. The results revealed that coho salmon fed the diet with pyridoxine supplementation gained more final body weight (FBW), specific growth rate (SGR), and better feed conversion ratio (FCR). FBW and SGR of the fish fed the diet with 8.24 mg/kg pyridoxine were significantly higher than those of the other groups (P < 0.05). An inverse trend was observed for FCR, which was the lowest in fish fed the diet with 8.24 mg/kg pyridoxine. The gradient pyridoxine levels did not yield any statistically (P > 0.05) significant impact on the whole‐body composition including moisture, ash, crude lipid, and crude protein. The hepatic pyridoxine concentration, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activities increased significantly with dietary pyridoxine levels increasing from 0.32 to 4.08 mg/kg (P < 0.05) and plateaued after that (P > 0.05). The coho salmon fed the diet with 8.24 mg/kg pyridoxine achieved the maximum superoxide dismutase and catalase, as well as the minimum total cholesterol, triglyceride, and malondialdehyde. Broken line analysis of SGR, FCR, AST, and ALT activities reflected the optimal dietary pyridoxine requirements for coho salmon post‐smolts from 3.92 to 7.08 mg/kg diet. [ABSTRACT FROM AUTHOR]

Background : Nematodes are the most abundant metazoans in marine sediments, many of which are bacterivores; however, how habitat bacteria affect physiological outcomes in marine nematodes remains largely unknown. Results: Here, we used a Litoditis marina inbred line to assess how native bacteria modulate host nematode physiology. We characterized seasonal dynamic bacterial compositions in L. marina habitats and examined the impacts of 448 habitat bacteria isolates on L. marina development, then focused on HQbiome with 73 native bacteria, of which we generated 72 whole genomes sequences. Unexpectedly, we found that the effects of marine native bacteria on the development of L. marina and its terrestrial relative Caenorhabditis elegans were significantly positively correlated. Next, we reconstructed bacterial metabolic networks and identified several bacterial metabolic pathways positively correlated with L. marina development (e.g., ubiquinol and heme b biosynthesis), while pyridoxal 5'-phosphate biosynthesis pathway was negatively associated. Through single metabolite supplementation, we verified CoQ10, heme b, acetyl-CoA, and acetaldehyde promoted L. marina development, while vitamin B6 attenuated growth. Notably, we found that only four development correlated metabolic pathways were shared between L. marina and C. elegans. Furthermore, we identified two bacterial metabolic pathways correlated with L. marina lifespan, while a distinct one in C. elegans. Strikingly, we found that glycerol supplementation significantly extended L. marina but not C. elegans longevity. Moreover, we comparatively demonstrated the distinct gut microbiota characteristics and their effects on L. marina and C. elegans physiology. Conclusions: Given that both bacteria and marine nematodes are dominant taxa in sedimentary ecosystems, the resource presented here will provide novel insights to identify mechanisms underpinning how habitat bacteria affect nematode biology in a more natural context. Our integrative approach will provide a microbe–nematodes framework for microbiome mediated effects on host animal fitness. [ABSTRACT FROM AUTHOR]

Lawesson’s reagent reacted with racemic diethyl malate to yield O-(1,2-bis(ethylcarboxylate)ethyl-1 4-methoxyphenyl dithiophosphonic acid. The acid formed pyridinium dithiophosphonate salts with 3-(hydroxymethyl)pyridine, pyridoxine, and (S)-(–)-nicotine. The salts revealed antifungal activity against Candida albicans. [ABSTRACT FROM AUTHOR]

Background Social isolation and loneliness are associated with increased risk of adverse health outcomes at older ages. This study evaluated whether isolation and loneliness are related to inadequate intake of micronutrients in the diet. Methods We tested associations between social isolation and loneliness and dietary micronutrient intake 2 years later in 3713 men and women (mean age 68.26, standard deviation 7.81 years) who completed two online 24-h dietary recalls. Associations of isolation and loneliness with intake of nine minerals and vitamins that fell below national recommendations were tested using logistic regressions, adjusting for age, gender, ethnicity, education, marital status, smoking and physical activity and total energy intake. Results The prevalence of low dietary intake varied markedly across micronutrients. Social isolation (1-point increase in a score ranging 0–5) was associated with increased odds (adjusted for covariates) of low intake of magnesium [odds ratio (OR) 1.153, 95% confidence interval (CI) 1.037–1.282, P  = .009], potassium (OR 1.201, 95% CI 1.087–1.327, P  < .001), vitamin B6 (OR 1.263, 95% CI 1.110–1.438, P  < .001), folate (OR 1.211, 95% CI 1.093–1.341, P  < .001) and vitamin C (OR 1.238, 95% CI 1.098–1.394, P  < .001). These associations remained unchanged when food insecurity and impaired activities of daily living were taken into account. By contrast, loneliness was not related to the inadequate intake of any micronutrient. Conclusions Low intake of micronutrients increases risk of age-related health problems. Attention to the dietary quality of older people with limited social contacts and little involvement in community activities might enhance health outcomes. [ABSTRACT FROM AUTHOR]

Objective To determine the causal relationship between trace elements and bipolar disorder (BD) by employing Mendelian randomization (MR) methods to eliminate confounding factors and reverse causation bias. Methods Utilizing publicly available summary-level genetic statistical data, we conducted a bidirectional two-sample MR analysis to assess the potential causal associations between 15 trace elements, including copper, calcium, carotene, folate, iron, magnesium, potassium, selenium, vitamin A, vitamin B12, vitamin B6, vitamin C, vitamin D, vitamin E, and zinc, and BD. The reliability of the associations was verified using Bayesian weighted MR, and sensitivity analyses were performed to evaluate the effects of heterogeneity and horizontal pleiotropy. Additionally, in the multivariable MR analysis, inverse variance weighting was employed as the primary method, incorporating potential confounding variables that may affect the outcomes to determine the independent causal effects of the relevant trace elements on BD. Results The causal impacts of carotene (OR=1.227, 95%Cl: 1.064-1.414) and vitamin B12 (OR=1.255, 95%Cl: 1.090-1.445) on BD were validated through the Bayesian weighted MR method, suggesting statistically significant correlations. Furthermore, these associations were unlikely to be influenced by heterogeneity and horizontal pleiotropy (P>0.05). In addition, the remaining 13 trace elements did not show significant causal associations with BD. In the subsequent multivariable MR analysis, after adjusting for potential confounding factors, the causal effect of vitamin B12 (OR =1.366, 95%Cl: 1.105-1.687) on BD remained statistically significant, even after Bonferroni correction. Conclusion This study indicates that specific trace elements, particularly carotene and vitamin B12, may play a modulatory role in the development of BD, providing new potential targets for the prevention and treatment strategies of BD. [ABSTRACT FROM AUTHOR]

Objectives: The United Nations recommends that women consume ≥5 food groups, also known as the minimum dietary diversity score for women (MDD‐W), for nutritional health. This is increasingly unattainable for populations in climate hot zones coping with food insecurity by prioritizing calories over dietary breadth. Breastfeeding mothers may be particularly vulnerable to adverse health impacts of low dietary diversity due to elevated nutritional requirements for lactation. We investigated how the protective effects of MDD‐W for folate adequacy varies by MDD‐W score and mother–infant life history characteristics. Methods: We conducted a secondary analysis of cross‐sectional data from breastfeeding mothers (n = 228) in northern Kenya, surveyed during the 2006 Horn‐of‐Africa drought. Logistic regression models for adequate dietary folate (and vitamins B12 and B6) and normal homocysteine (folate‐replete status) evaluated the effect of MDD‐W alone and in interaction with infant/maternal characteristics. Results: MDD‐W (as ordinal or dichotomous variable) was positively associated with adequate folate (and vitamin B12). Having male infant was inversely associated with adequate dietary folate. MDD‐W was generally unassociated with homocysteine. However, there was an interaction between MDD‐W and sex of the infant. Namely, MDD‐W ≥ 3 predicted increased probability of normal homocysteine among mothers with female infants but not male infants. Conclusions: Diets consisting of three or more food groups may protect adequate folate intake for many breastfeeding mothers. More research is needed to establish what level of dietary diversity would protect against hyperhomocysteinemia during breastfeeding and what factors promote or hinder the benefit of diversified diets on maternal folate nutrition. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a deadly brain cancer. The prognosis of GBM patients has marginally improved over the last three decades. The response of GBMs to initial treatment is inevitably followed by relapse. Thus, there is an urgent need to identify and develop new therapeutics to target this cancer and improve both patient outcomes and long-term survival. Metabolic reprogramming is considered one of the hallmarks of cancers. However, cell-based studies fail to accurately recapitulate the in vivo tumour microenvironment that influences metabolic signalling and rewiring. Against this backdrop, we conducted global, untargeted metabolomics analysis of the G7 and R24 GBM 2D monolayers and 3D spheroid cultures under identical cell culture conditions. Our studies revealed that the levels of multiple metabolites associated with the vitamin B6 pathway were significantly altered in 3D spheroids compared to the 2D monolayer cultures. Importantly, we show that pharmacological intervention with hydralazine, a small molecule that reduces vitamin B6 levels, resulted in the cell death of 3D GBM spheroid cultures. Thus, our study shows that inhibition of the vitamin B6 pathway is a novel therapeutic strategy for the development of targeted therapies in GBMs. [ABSTRACT FROM AUTHOR]

Glutamate dehydrogenase (GDH) participates in the energy metabolism of proteins and the synthesis of metabolites important for the organism. In this study, GDH enzyme was purified from the liver of rainbow trout (Oncorhynchus mykiss) by 2',5'‐ADP Sepharose 4B affinity chromatography in one step. As a result of this purification process, GDH enzyme was purified 171‐fold with 5.83 U/mg protein‐specific activity. The characterization experiments presented that the storage stability of the purified GDH enzyme was determined as −80°C; optimum temperature 40°C; it was determined that the optimum ionic strength was 100 mM phosphate buffer and the optimum pH was 8.00. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) and PAGE studies showed that the natural molar mass of the purified GDH enzyme was 346.74 kDa, and the molar mass of its subunits was 53.71 kDa. Km and Vmax values for substrates and coenzymes of GDH enzyme purified from rainbow trout liver were calculated, and the lowest Km value was found in NAD+ (1.86 mM) and the highest Vmax value in NH4+ (1.79 U/mL). The effects of some metal ions, vitamins, and solvents on the activity of the purified GDH enzyme were investigated and also IC50 values and inhibition types. The metal ion with the lowest IC50 value is Ag+ (8.65 ± 1.68 μM), and the vitamin is B6 (0.77 ± 0.04 mM). The binding affinities of inhibitors were investigated with molecular docking, based on the conformational state of GDH. [ABSTRACT FROM AUTHOR]

Context Previous research evaluating the effects in B-vitamins on the prevention and treatment of cardiovascular disease (CVD) has substantial limitations and lacks recently published large prospective studies; hence, conducting an updated meta-analysis is needed. Objective We investigated the association between vitamin B status and human CVD development in order to provide more specific advice about vitamin B intake for those at risk of CVD. Data Sources Relevant articles were identified by JSTOR, PubMed, and ProQuest databases. Data Extraction Key words used to identify the studies included the different combinations of B-vitamins, folate, folic acid, vitamin B6, vitamin B12, homocysteine, cardiovascular disease, stroke, coronary disease, myocardial infarction, and cerebrovascular and transient ischemic attack. The database search was supplemented by hand-searching of reference lists of selected articles. Data Analysis Pooled estimates were calculated from the mean differences using a random-effects model. Results Supplementation with folic acid was reported to have a clinical benefit of significantly reducing carotid intima-media thickness. Higher intakes of folic acid, vitamin B6, and vitamin B12 were generally associated with a lower risk of CVD in the general population, except in those without normal renal function and those with unstable angina or past non–ST-elevation myocardial infarction. Conclusion Vitamin B supplementation resulted in the greatest cardiovascular benefit in those with normal renal function and without unstable angina or non–ST-elevation myocardial infarction recently. Factors such as age, gender, and genetic polymorphisms contribute to varying effects. [ABSTRACT FROM AUTHOR]

Introduction: Sjogren's syndrome (SS) is an autoimmune chronic inflammatory disorder affecting women in their fourth to sixth decade, affecting gastrointestinal, and musculoskeletal systems. A 35-year-old female with SS with polymyositis (PM) presented with symptoms of weakness in all four limbs, difficulty in sitting, rising, swallowing solid foods, vomiting, and difficulty in climbing stairs. She was diagnosed with SS in 2018 and was treated with prednisolone, Vitamin D, calcium, pyridoxine, methylcobalamin, artificial tears, pilocarpine, and painkillers. However, a muscle biopsy was never done. Methods: The data were collected from the patient's file along with her consent when she came for follow-up. Results: A muscle biopsy was done at our center to confirm the diagnosis of PM. The patient was prescribed IV prednisolone and other symptomatic treatment until symptoms resolved and was discharged with oral drugs when they were manageable. Conclusion: The diagnosis of primary SS along with PM is a rare occurrence. Although it does not change the treatment plan much, its diagnosis is very important for managing any complications that may arise from it. Patients' noncompliance and loss of follow-up can create issues in the treatment. Such cases help in forming the guidelines for the future and restructuring the classification of autoimmune conditions. [ABSTRACT FROM AUTHOR]

Introduction: Pregnant women with a history of metabolic bariatric surgery (MBS) are at high risk of developing nutrient deficiencies, leading to greater challenges to reach nutritional requirements. This study compared nutrient status of women using specialized "weight loss surgery" multivitamin supplementation (WLS-MVS) to those using standard supplementation (sMVS) during pregnancy following MBS. Methods: Multicenter observational cohort study including 119 pregnant women at 41.0 (18.5–70.0) months after Roux-en-Y gastric bypass (RYGB, n = 80) or sleeve gastrectomy (SG, n = 39). Routine blood samples were analyzed every trimester (T1, T2, T3), and micronutrient serum levels were compared between WLS-MVS and sMVS users. Results: During pregnancy after RYGB, WLS-MVS users demonstrated higher serum concentrations of hemoglobin (7.4 [7.2, 7.5] vs. 7.0 [6.8, 7.3] mmol/L), ferritin (23.2 [15.0, 35.7] vs. 13.7 [8.4, 22.4] µg/L), and folic acid (31.4 [28.7, 34.2] vs. 25.4 [21.3, 29.4] nmol/L) and lower serum vitamin B6 levels (T1: 90.6 [82.0, 99.8] vs. 132.1 [114.6, 152.4] nmol/L) compared to sMVS users. Iron deficiencies and elevated serum vitamin B6 levels were less prevalent in the WLS-MVS group. During pregnancy after SG, WLS-MVS users showed higher serum vitamin D concentrations (89.7 [77.6, 101.8] vs. 65.4 [53.3, 77.4] nmol/L) and lower serum vitamin B1 concentrations (T2: 137.4 [124.2, 150.6] vs. 161.6 [149.0, 174.1] nmol/L, T3: 133.9 [120.1, 147.7] vs. 154.7 [141.9, 167.5] nmol/L) compared to sMVS users. Conclusion: Low maternal concentrations of micronutrients are highly prevalent during pregnancy after MBS. The use of specialized multivitamin supplementation generally resulted in higher serum levels during pregnancy compared to standard supplementation. Future research is needed to investigate how supplementation strategies can be optimized for this high-risk population. [ABSTRACT FROM AUTHOR]

The recent investigation targets to use adapted carbon paste (CP) with copper nanoparticles (CuNs) operating in a phosphate buffer (PBS) medium with a pH range of 5.0–8.0, to synthesize a novel, susceptible, and simple electrochemical sensor for the detection of one of the most important drugs, vitamin B6. Copper (Cu) is one of the most three common essential trace elements found in the bodies of both humans and animals, along with iron and zinc for all crucial physiological and biochemical functions. Its properties, which are assessed using a variety of methods including scanning electron microscopy (SEM), cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS), have also drawn a lot of attention recently. We considered the effects of pH, buffer, scan rate, interference, and calibration curve. The susceptible electrode's linear calibration curve encompassed concentration values between 8.88 and 1000.0 µM. The calculated limits of detection and quantification were 32.12 and 107.0 µM, respectively. Furthermore, this method was established in real human urine samples and drug validation which have been shown satisfactory results for vitamin B6 detection. [ABSTRACT FROM AUTHOR]

Marginal vitamin B6 (B6) deficiency is common in various segments worldwide. In a super-aged society, sarcopenia is a major concern and has gained significant research attention focused on healthy aging. To date, the primary interventions for sarcopenia have been physical exercise therapy. Recent evidence suggests that inadequate B6 status is associated with an increased risk of sarcopenia and mortality among older adults. Our previous study showed that B6 supplementation to a marginal B6-deficient diet up-regulated the expression of various exercise-induced genes in the skeletal muscle of rodents. Notably, a supplemental B6-to-B6-deficient diet stimulates satellite cell-mediated myogenesis in rodents, mirroring the effects of physical exercise. These findings suggest the potential role of B6 as an exercise-mimetic nutrient in skeletal muscle. To test this hypothesis, we reviewed relevant literature and compared the roles of B6 and exercise in muscles. Here, we provide several pieces of evidence supporting this hypothesis and discuss the potential mechanisms behind the similarities between the effects of B6 and exercise on muscle. This research, for the first time, provides insight into the exercise-mimetic roles of B6 in skeletal muscle. [ABSTRACT FROM AUTHOR]

Three novel polypyridyl‐Co(III)‐vitamin B6 complexes viz., [Co(CF3‐phtpy)(SBVB6)]Cl (Co1), [Co(anthracene‐tpy)(SBVB6)]Cl (Co2), [Co(NMe2‐phtpy)(SBVB6)]Cl (Co3), where 4’‐(4‐(trifluoromethyl)phenyl)‐2,2’:6’,2’’‐terpyridine=CF3‐phtpy, 4’‐(anthracen‐9‐yl)‐2,2’:6’,2’’‐terpyridine=anthracene‐tpy;, 4‐([2,2’:6’,2’’‐terpyridin]‐4’‐yl)‐N,N‐dimethylaniline=NMe2‐phtpy, (E)‐5‐(hydroxymethyl)‐4‐(((2‐hydroxyphenyl)imino)methyl)‐2‐methylpyridin‐3‐ol=H2SBVB6 were successfully developed for aPDT (antibacterial photodynamic therapy) applications. Co1–Co3 exhibited an intense absorption band at ca. 435–485 nm, which is attributed to ligand‐to‐metal charge transfer and was beneficial for antibacterial photodynamic therapy. The distorted octahedral geometry of the complexes with CoIIIN4O2 core was evident from the DFT study. The visible light absorption ability and good photo‐stability of Co1–Co3 made them good photosensitizers for aPDT. Co1–Co3 displayed significant antibacterial responses against gram‐positive (S. aureus) and gram‐negative (E. coli) bacteria upon light exposure (10 J cm−2, 400–700 nm) and showed MIC values between 0.01–0.005 μg mL−1. The aPDT activities of these complexes were due to their ability to damage bacterial cell membranes via ROS generation. Overall, this study shows the photo‐triggered ROS‐mediated bacteria‐killing potential of Co(III) complexes. [ABSTRACT FROM AUTHOR]

Endosymbionts provide essential nutrients for hosts, promoting growth, development, and reproduction. However, the molecular regulation of nutrient transport from endosymbiont to host is not well understood. Here, we used bioinformatic analysis, RNA-Sequencing, luciferase assays, RNA immunoprecipitation, and in situ hybridization to show that a bacteriocyte-distributed MRP4 gene (multidrug resistance-associated protein 4) is negatively regulated by a host (aphid)-specific microRNA (miR-3024). Targeted metabolomics, microbiome analysis, vitamin B6 (VB6) supplements, 3D modeling/molecular docking, in vitro binding assays (voltage clamp recording and microscale thermophoresis), and functional complementation of Escherichia coli were jointly used to show that the miR-3024/MRP4 axis controls endosymbiont (Serratia)-produced VB6 transport to the host. The supplementation of miR-3024 increased the mortality of aphids, but partial rescue was achieved by providing an external source of VB6. The use of miR-3024 as part of a sustainable aphid pest-control strategy was evaluated by safety assessments in nontarget organisms (pollinators, predators, and entomopathogenic fungi) using virus-induced gene silencing assays and the expression of miR-3024 in transgenic tobacco. The supplementation of miR-3024 suppresses MRP4 expression, restricting the number of membrane channels, inhibiting VB6 transport, and ultimately killing the host. Under aphids facing stress conditions, the endosymbiont titer is decreased, and the VB6 production is also down-regulated, while the aphid's autonomous inhibition of miR-3024 enhances the expression of MRP4 and then increases the VB6 transport which finally ensures the VB6 homeostasis. The results confirm that miR-3024 regulates nutrient transport in the endosymbiont-host system and is a suitable target for sustainable pest control. [ABSTRACT FROM AUTHOR]

In the fall agricultural season of 2021-2022, an experiment was conducted in two areas of Nineveh Governorate, the first experiment in Yarmgah and the second one in Badush, each experiment included two types of board bean Vicia faba L to study their response to antioxidants and ammonium phosphate diphosphate fertilizer. The experiment included two factors, the first factor varieties (Aquadlge and Luz de otono) with antioxidants with seven levels. without the addition of catechins and DAP fertilizer, spray and soak at a concentration of 250 mg. L -1 for each of AsA, B1, B6 with the addition of 20 kg DAP. Spray and soak at a concentration of 500 mg.L-1 for each of AsA, B1, B6 with the addition of 20 kg DAP.H-1 .spray and soak at a concentration of 250 mg.L-1 for each of AsA, B1, B6 with the addition of 40 kg DAP.H-1, spray and soak at a concentration of 500 mg.L-1 for each of AsA, B1, B6 with the addition of 40 kg DAP.H-1, spray and soak at a concentration of 250 mg.L-1 for each of AsA, B1, B6 with the addition of 60 kg DAP.H-1, and Spray and soak at a concentration of 500 mg.L-1 for each of AsA, B1, B6 with the addition of 60 kg DAP.H-1). The seeds were soaked in water with antioxidants for 6 hours before planting and sprayed with antioxidant until complete wetness took place 30 and 45 days of planting, and the results showed the superiority of the Aquadlge Variety over the Luz de otono variety morally at the Yarmgah and Badush experiment sites for all the studied qualities: the chlorophyll content, the number of pods in the plant, the number of seeds per pod, the number of seeds per plant, the weight of 100 seeds and the protein percentage. The seventh level of the fertilizer combination with antioxidants gave the highest value of all the studied qualities: the chlorophyll content, the number of pods in the plant, the number of seeds in the pod, the number of seeds in the plant, the weight of 100 seeds and the percentage of protein [ABSTRACT FROM AUTHOR]

Objective: To discuss the clinical phenotype and genotype characteristics of two pediatric patients with late-onset methylmalonic acidemia (MMA) cblC type, and to provide the basis for early clinical recognition of MMA. Methods: The clinical data of two pediatric patients with late-onset MMA cblC type were collected, including clinical phenotypes, biochemical detection results, blood and urine organic acid analyses, neuroimaging, electroencephalograms, genotypes and so on. The characteristics of the disease were analyzed in combination with the related literature review. Results: Both pediatric patients were female, with onset in adolescence. Patient 1 presented with psychiatric symptoms, while pediatric patient 2 presented with cognitive impairment. Both pediatric patients experienced weakness in both lower limbs and speech disorders. At initial diagnosis, the serum homocysteine (Hcy) levels were severely increased, the urine methylmalonic acid levels were increased, the brain magnetic resonance imaging results indicated brain atrophy, and the electroencephalogram results showed the increased slow wave activity in both cerebral hemispheres. The pediatric patient 2 exhibited epileptiform discharges in bilateral frontal and temporal regions. The genetic testing results showed the c.482G>A mutation in the MMACHC gene. Both two pediatric patients were treated with intramuscular injections of vitamin B12, along with oral folic acid, vitamin B6, levocarnitine, and betaine. The symptoms of two patierts were improved, the serum Hcy levels were decreased, and the urine methylmalonic acid levels returned to normal. Conclusion: The phenotype of late-onset MMA cblC type is diverse, primarily involving neuropsychiatric impairment, with the c. 482G>A mutation being the most common genotype. The increasing of serum Hcy levels and brain atrophy can serve as the biomarkers for the early recognition of late-onset cblC type pediatric patients. [ABSTRACT FROM AUTHOR]

Coenzyme management is important for homeostasis of the pool of active metabolic enzymes. The coenzyme pyridoxal 5′-phosphate (PLP) is involved in diverse enzyme reactions including amino acid and hormone metabolism. Regulatory proteins that contribute to PLP homeostasis remain to be explored in plants. Here, we demonstrate the importance of proteins annotated as PLP homeostasis proteins (PLPHPs) for controlling PLP in Arabidopsis (Arabidopsis thaliana). A systematic analysis indicates that while most organisms across kingdoms have a single PLPHP homolog, Angiosperms have two. PLPHPs from Arabidopsis bind PLP and exist as monomers, in contrast to reported PLP-dependent enzymes, which exist as multimers. Disrupting the function of both PLPHP homologs perturbs vitamin B6 (pyridoxine) content, inducing a PLP deficit accompanied by light hypersensitive root growth, unlike PLP biosynthesis mutants. Micrografting studies show that the PLP deficit can be relieved distally between shoots and roots. Chemical treatments probing PLP-dependent reactions, notably those for auxin and ethylene, provide evidence that PLPHPs function in the dynamic management of PLP. Assays in vitro show that Arabidopsis PLPHP can coordinate PLP transfer and withdrawal from other enzymes. This study thus expands our knowledge of vitamin B6 biology and highlights the importance of PLP coenzyme homeostasis in plants. Pyridoxal phosphate homeostasis proteins contribute to vitamin B6 (pyridoxine) homeostasis, likely acting as a rheostat in adaptive responses involving the coenzyme pyridoxal 5′-phosphate. [ABSTRACT FROM AUTHOR]

In various organisms, the coenzyme form of vitamin B6, pyridoxal phosphate (PLP), is synthesized from pyridoxine phosphate (PNP). Control of PNP levels is crucial for metabolic homeostasis because PNP has the potential to inhibit PLP-dependent enzymes and proteins. Although the only known pathway for PNP metabolism in Escherichia coli involves oxidation by PNP oxidase, we detected a strong PNP phosphatase activity in E. coli cell lysate. To identify the unknown PNP phosphatase(s), we performed a multicopy suppressor screening using the E. coli serA pdxH strain, which displays PNP-dependent conditional lethality. The results showed that overexpression of the yigL gene, encoding a putative sugar phosphatase, effectively alleviated the PNP toxicity. Biochemical analysis revealed that YigL has strong phosphatase activity against PNP. A yigL mutant exhibited decreased PNP phosphatase activity, elevated intracellular PNP concentrations, and increased PNP sensitivity, highlighting the important role of YigL in PNP homeostasis. YigL also shows reactivity with PLP. The phosphatase activity of PLP in E. coli cell lysate was significantly reduced by mutation of yigL and nearly abolished by additional mutation of ybhA, which encodes putative PLP phosphatase. These results underscore the important contribution of YigL, in combination with YbhA, as a primary enzyme in the dephosphorylation of both PNP and PLP in E. coli. [ABSTRACT FROM AUTHOR]

Vitamin B6 is an essential micronutrient for humans which is synthesized in plants via de novo pathway. Since this pathway involves only two enzymes, it can be easily exploited to develop biofortified crops. In the present study, we investigated the effect of overexpressing PDX2 gene from Arabidopsis under endosperm-specific promoter for enhancing B6 levels in wheat seeds. Calli of two elite wheat varieties, Faisalabad-2008 and Galaxy, were transformed with PDX2 construct in expression vector via Agrobacterium-mediated transformation with the efficiency of 2.11% and 1.09%, respectively. Among the ten transgenic lines evaluated, the highest gene expression observed was 22.49-fold leading to 6.49-fold increase in B6 accumulation in mature seeds determined via HPLC. Vitamin B6 accumulation did not alter the chlorophyll content. However, the soluble protein content significantly decreased in some transgenic lines as compared to control plants. Some Faisalabad-2008 transgenic lines exhibited significant increase while all Galaxy transgenic lines showed significant decrease in their carbohydrate content than control plants. Moreover, seed yield increased in some transgenic lines without posing any variation in other agro-economically important traits. Previously vitamin B6 accumulation has been reported to confer resistance to abiotic factors because of its antioxidant properties. However, the transgene expression and vitamin B6 accumulation in the seed did not confer salt resistance to the transgenic lines. The amount of proline increased in salt-stressed plants while chlorophyll, protein, carbohydrate, and relative water content decreased. Thus, overexpression of PDX2 under seed-specific promoter enhances accumulation of vitamin B6 without conferring any resistance to salt stress conditions. [ABSTRACT FROM AUTHOR]

Vitamin B1 (thiamine pyrophosphate (TPP)) and B6 (pyridoxal 5'- phosphate (PLP)) deficiencies pose significant health risks. The current measurement method employs High-Performance Liquid Chromatography (HPLC), though, Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS) is considered a more sensitive and selective analytical method. However, there is a lack of LC-MS/MS-based reference intervals. Moreover, none of the existing reference intervals are established in Danish populations. Therefore, the aim of this study was to establish a reference interval for whole blood concentrations of TPP and PLP in Danish blood donors using LC-MS/MS. Blood samples were collected from healthy Danish blood donors and analysed using the reagent kit, MassChrom® Vitamins B1 and B6 in whole blood (Chromsystems Instruments & Chemicals GmbH, Munich, Germany) for quantitative determination of both TPP and PLP concentration in whole blood, using LC-MS/MS. Reference intervals were determined with non-parametric methods as the 2.5th and 97.5th percentile and presented with 90% confidence intervals (CI). In total 120 blood donors were included. The concentrations of TTP or PLP were not statistically different between sexes just as age did not affect the concentrations, hence, combined reference intervals were employed. The resulting reference intervals are: TPP, nmol/L: 101.0 (90% CI: 96.4–108.5) − 189.0 (90% CI: 184.7–192.0) and PLP, nmol/L: 64.0 (90% CI: 60.9–66.7) − 211.8 (90% CI: 168.3–231.0). In conclusion, reference intervals for whole blood TTP and PLP in a healthy Danish population were established based on a LC-MS/MS method. Furthermore, the reference intervals were not affected by age or sex. [ABSTRACT FROM AUTHOR]

Calcium stress can negatively impact plant growth, prompting plants to respond by mitigating this effect. However, the specific mechanisms underlying this response remain unclear. In this study, we used non-targeted metabolomics and transcriptomics to investigate the response mechanisms of Zelkova schneideriana leaves under varying degrees of calcium stress. Results revealed that calcium stress led to wilt in young leaves. When calcium stress exceeds the tolerance threshold of the leaf, it results in wilting of mature leaves, rupture of chloroplasts in palisade tissue, and extensive wrinkling and breakage of leaf cells. Transcriptomic analysis indicated that calcium stress inhibited photosynthesis by suppressing the expression of genes related to photosynthetic system II and electron transport. Leaf cells activate phenylpropanoid biosynthesis, flavonoid biosynthesis, and Vitamin B6 metabolism to resist calcium stress. When calcium accumulation gradually surpassed the tolerance threshold of the cells, this results in failure of conventional anti-calcium stress mechanisms, leading to cell death. Furthermore, excessive calcium stress inhibits the expression of CNGC and anti-pathogen genes. The results of the metabolomics study showed that five key metabolites increased in response to calcium stress, which may play an important role in countering calcium stress. This study provides insights into the response of Z. schneideriana leaves to different levels of calcium stress, which could provide a theoretical basis for cultivating Z. schneideriana in karst areas and enhance our understanding of plant responses to calcium stress. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a typical inflammatory bowel disease (IBD), impairing the quality of life of patients. Dehydroevodiamine (DHE) is an active alkaloid isolated from Tetradium ruticarpum that exerts significant anti-inflammatory effects in gastrointestinal diseases. However, the effect and mechanisms of DHE on UC remain unclear. We performed a DSS-induced experimental UC rat model to reveal the efficacy and potential mechanisms of DHE on UC. HE and AB-PAS staining were used for the evaluation of pathologies, and 16S rRNA sequencing was used to detect changes in gut microbes. Metabolomics was used to detect changes in serum metabolites. Network pharmacology and transcriptomics were conducted to reveal the underlying mechanisms of DHE for UC. HuProt proteome microarrays, molecular docking, and SPR were used to reveal the targets of action of DHE. WB, RT-qPCR, and IHC were used to assess the action effects of DHE. DHE demonstrated significant alleviation of DSS-induced colitis symptoms in rats by suppressing inflammatory and oxidative stress responses, amending colonic barrier injury, and inhibiting apoptosis. In terms of gut microbial modulation, DHE decreased the abundance of Allobaculum, Clostridium, Escherichia, Enterococcus, and Barnesiella and increased the abundance of Lactobacillus, Bifidobacterium, and SMB5. Moreover, metabolomics suggested that the regulation of DHE in DSS-induced UC rats mainly involved aminoacyl-tRNA biosynthesis, vitamin B6 metabolism, phenylalanine, tyrosine, and so on. Mechanically, DHE alleviated UC in rats by targeting AKT1, thereby inhibiting the PI3K/AKT/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

This research implements a computer-aided formulation development algorithm based on a novel SeDeM-ODT expert system in establishing the design space for paediatric pyridoxine hydrochloride orodispersible tablets (ODTs) using Prosolv® ODTG2, Prosolv® EasyTab SP, and Ludiflash® systems. For each formulation ingredient, expert system-defined preformulation parameter values were experimentally determined according to standardized methods and then normalized to the theoretical radius range [0,10]. Expert diagrams were constructed and the quantitative performance of each ingredient was evaluated using parametric profile index (IPP), flowability (ff'), and compressibility (ffc) functions. The net direct compression capability was quantitatively expressed as the product of expert system reliability and IPP. Direct compression was conducted in an eccentric tablet press and properties were evaluated using weight, dimension, disintegration test, contact angle, tensile strength, x-ray diffraction, and Fourier-transform infrared spectroscopy. The ODTs dissolution profiles were fitted and compared using zero-order, first-order, Hixson-Crowell, and Hopfenberg models. Results of the expert diagram of pyridoxine hydrochloride indicated suboptimal normalized radii values in 8 out of 12 parameters, implying a compromised mechanical zone (ff'=3.61, ffc=2.11). By setting a target ffc for the optimized formulation mix at 5.0, the predicted proportions of the fillers to remedy the direct compression deficits of the drug were computed as 89.00%, 83.23%, and 76.62% for Prosolv® ODTG2 (ffc=5.36), Prosolv® EasyTab SP (ffc=5.58), and Ludiflash® (ffc=5.88), respectively. The produced ODTs were of acceptable target quality, hence the SeDeM-ODT system was considered a reliable formulation tool for establishing the design space of this particular drug-filler systems. [ABSTRACT FROM AUTHOR]

Microcephaly, epilepsy and diabetes syndrome 1 (MEDS1) is a rare autosomal recessive disorder caused by defects in the immediate early response 3 interacting protein 1 (IER3IP1) gene. Only nine cases have been described in the literature. MEDS1 manifests as microcephaly with simplified gyral pattern in combination with severe infantile epileptic encephalopathy and early-onset permanent diabetes. A simplified gyral pattern has been described in all cases reported to date. Diagnosis is made by demonstration of specific mutations in the IER3IP1 gene. In this study, we present an additional case of a patient with MEDS1 who was homozygous for the c.53C>T p.(Ala18Val) variant. This case, the first to be reported from Turkey, differs from other cases due to the absence of a typical simplified gyral pattern on early brain magnetic resonance imaging, the late onset of diabetes, and the presence of a new genetic variant. The triad of microcephaly, generalized seizures and permanent neonatal diabetes should prompt screening for mutations in IER3IP1. [ABSTRACT FROM AUTHOR]

Summary: Our study showed that B vitamins did not have significant effect on fracture incidence, bone mineral density, and bone turnover markers. However, the research data of B vitamins on bone mineral density and bone turnover markers are limited, and more clinical trials are needed to draw sufficient conclusions. Purpose: The objective of this study was to identify the efficacy of B vitamin (VB) (folate, B6, and B12) supplements on fracture incidence, bone mineral density (BMD), and bone turnover markers (BTMs). Methods: A comprehensive search was performed in PubMed, MEDLINE, EMBASE, Cochrane databases, and ClinicalTrials.gov up to September 4, 2023. The risk of bias was assessed according to Cochrane Handbook and the quality of evidence was assessed according to the GRADE system. We used trial sequential analysis (TSA) to assess risk of random errors and Stata 14 to conduct sensitivity and publication bias analyses. Results: Data from 14 RCTs with 34,700 patients were extracted and analyzed. The results showed that VBs did not significantly reduce the fracture incidence (RR, 1.06; 95% CI, 0.95 − 1.18; p = 0.33; I2 = 40%) and did not affect BMD in lumbar spine and femur neck. VBs had no significant effect on bone specific alkaline phase (a biomarker for bone formation), but could increase the serum carboxy-terminal peptide (a biomarker for bone resorption) (p = 0.009; I2 = 0%). The TSA showed the results of VBs on BMD and BTMs may not be enough to draw sufficient conclusions due to the small number of sample data included and needed to be demonstrated in more clinical trials. The inability of VBs to reduce fracture incidence has been verified by TSA as sufficient. Sensitivity analysis and publication bias assessment proved that our meta-analysis results were stable and reliable, with no significant publication bias. Conclusions: Available evidence from RCTs does not support VBs can effectively influence osteoporotic fracture risk, BMD, and BTMs. Trial registration: PROSPERO registration number: CRD42023427508. [ABSTRACT FROM AUTHOR]

Background: Burning mouth syndrome (BMS) is a chronic condition characterized by an intractable burning sensation in the oral cavity without visible mucosal lesions. Current treatment options are diverse but often limited by variable efficacy and patient tolerance. This study aimed to evaluate the efficacy of turmeric combined with vitamin B6 (pyridoxine HCl) in treating BMS. Methods: In this retrospective, single-arm study, 28 non-smoking female patients with BMS were treated with a daily regimen of turmeric and vitamin B6 for 60 days. The pain intensity was assessed using the visual analog scale (VAS) before treatment initiation (baseline VAS, BVAS) and after the treatment period (final VAS, FVAS). The Wilcoxon signed-rank test was utilized to analyze changes in the VAS scores. Results: The mean BVAS score was 5.61 (SD = 1.87), indicating moderate pain at baseline. Post-treatment, the mean FVAS score significantly decreased to 2.14 (SD = 1.35). The median delta in the VAS scores demonstrated a substantial reduction in pain intensity (median delta = 4.0; mean delta = 3.46; SD = 2.05). Statistical analyses revealed a significant reduction in the VAS scores (W = 0.0, p < 0.0001). Conclusions: The combination of turmeric and vitamin B6 was found to significantly reduce pain scores in patients with BMS, indicating this therapeutic approach may be a promising alternative for BMS management. Larger-scale clinical trials are warranted to further validate these findings. [ABSTRACT FROM AUTHOR]

As reported by the FAO, in 2022, approximately 735 million people experienced undernourishment, underscoring the critical need for effective strategies to address micronutrient deficiencies. Among these strategies, the mass fortification of staple foods, particularly rice—a dietary staple for half of the global population—has emerged as one of the most effective approaches. Conventional milling processes diminish the nutritional content of rice, necessitating the development of fortification methods to enhance its nutrient profile. This study investigates advanced fortification techniques to improve the nutritional value of rice, focusing on vitamins B1, B2, and B6, with guidelines from the US Institute of Medicine's Dietary Reference Intakes. The results indicate that implementing ultrasonic treatments and optimal soaking conditions (60 °C for 60 min) significantly enhances the absorption of these vitamins. Effective parameters included a concentration of 1500 ppm for vitamin B1 and higher levels for vitamins B2 and B6, with a rice-to-vitamin solution ratio of 1:4. These conditions yielded an absorbed vitamin B1 content of 1050 mg/kg, bringing the fortified rice closer to meeting recommended intake levels. Given the global average daily consumption of 100 g of rice per person, this research demonstrates the feasibility of fortifying rice to address nutrient deficiencies effectively and contribute to improved dietary health worldwide. Further enhancement of vitamin B2 and B6 levels remains essential for optimal fortification, highlighting the potential of fortified rice as a sustainable solution for improving global nutrition. [ABSTRACT FROM AUTHOR]

Abstract Background Pyridoxamine 5′-phosphate oxidase deficiency is a rare inborn error of vitamin B6 metabolism that presents with drug-resistant epileptic seizures. However, the condition is responsive to supplementation with the active vitamin B6 metabolite pyridoxal 5′-phosphate and, in some cases, pyridoxine. Case presentation In this case report, a 10-year-old Iranian male of Fars ethnicity came to a regional hospital in Tehran, Iran with a chief complaint of tic-like movement. He had a history of unintentional, repetitive, and stereotypic movements of both arms since the age of 4 years. The physical examination depicted facial dimorphism. During admission, the patient experienced habitual hypermotor seizures and generalized tonic–clonic seizures. Ictal electroencephalography demonstrated a generalized background attenuation and bursts of generalized, predominantly left-sided, biphasic spike-wave complexes. Whole-genome sequencing revealed a pyridoxamine 5′-phosphate oxidase deficiency as the underlying cause of the drug-resistant seizures, resulting in a low serum level of pyridoxal 5′-phosphate. The patient underwent pyridoxine supplementation therapy, which ultimately resolved his seizures. At 6 months, he was seizure free. Conclusion Physicians ought to be aware of manifestations of vitamin B6 deficiency such as mimicking tic and consider it in the differential for drug-resistant epilepsy.

Abstract Background The gut microbiota can facilitate host growth under nutrient-constrained conditions. However, whether this effect is limited to certain bacterial species remains largely unclear, and the relevant underlying mechanisms remain to be thoroughly investigated. Results We found that the microbiota was required for Bactrocera dorsalis larval growth under poor dietary conditions. Monoassociation experiments revealed that Enterobacteriaceae and some Lactobacilli promoted larval growth. Among the 27 bacterial strains tested, 14 significantly promoted larval development, and the Enterobacteriaceae cloacae isolate exhibited the most obvious promoting effect. A bacterial genome-wide association study (GWAS) revealed that the vitamin B6 synthesis pathway was critical for the promotion of E. cloacae growth. Deletion of pdxA, which is responsible for vitamin B6 biosynthesis, deprived the mutant strains of larval growth-promoting function, indicating that the 4-hydroxythreonine-4-phosphate dehydrogenase(pdxA) gene was crucial for promoting larval growth in E. cloacae. Importantly, supplementation of a poor diet with vitamin B6 successfully rescued the axenic larval growth phenotype of B. dorsalis. Conclusion Our results suggest that gut microbes promote insect larval growth by providing vitamin B6 under nutrient scarcity conditions in B. dorsalis. Video Abstract

The in-vitro drug release study of vitamin B6 encapsulated into sodium tripolyphosphate crosslinked chitosan-alginate (B6-TCA) nanoparticles aims to determine the effect of sodium tripolyphosphate on the encapsulation efficiency of vitamin B6 and effectiveness of the nanoparticles to release vitamin B6. The focus of this research is synthesizing and characterizing TCA nanoparticles to encapsulate vitamin B6 as an effective delivery system by studying the kinetics release of vitamin B6. The research resulted in the formation of coarse solid powder nanoparticles in yellowish-white color with a nanoparticle size of 22.55 nm. Sodium tripolyphosphate decreased the percentage of encapsulation efficiency in the B6-TCA nanoparticles as its concentration increased. However, the increasing sodium tripolyphosphate causes a slower release of vitamin B6 from nanoparticles. The encapsulation efficiency of vitamin B6 is 82.04%. The optimum composition of B6-TCA nanoparticles ratio is 2:1:1.5:2, where Korsmeyer-Peppas kinetics model suited its better with the Fickian diffusion mechanism of 0.989 and has the smallest reaction rate constant of 0.039 occurred within 6 h.

Abstract The recent investigation targets to use adapted carbon paste (CP) with copper nanoparticles (CuNs) operating in a phosphate buffer (PBS) medium with a pH range of 5.0–8.0, to synthesize a novel, susceptible, and simple electrochemical sensor for the detection of one of the most important drugs, vitamin B6. Copper (Cu) is one of the most three common essential trace elements found in the bodies of both humans and animals, along with iron and zinc for all crucial physiological and biochemical functions. Its properties, which are assessed using a variety of methods including scanning electron microscopy (SEM), cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS), have also drawn a lot of attention recently. We considered the effects of pH, buffer, scan rate, interference, and calibration curve. The susceptible electrode's linear calibration curve encompassed concentration values between 8.88 and 1000.0 µM. The calculated limits of detection and quantification were 32.12 and 107.0 µM, respectively. Furthermore, this method was established in real human urine samples and drug validation which have been shown satisfactory results for vitamin B6 detection.