Electrochemical sensing of vitamin B6 (pyridoxine) by adapted carbon paste electrode.

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.

B-vitamins and one-carbon metabolism during pregnancy: health impacts and challenges.

Folate, vitamin B12, vitamin B6 and riboflavin interact by functioning as cofactors within one-carbon metabolism (OCM), a network of interrelated cellular pathways essential for numerous biological processes, including the biosynthesis of DNA, amino acid interconversions and methylation reactions. The pathways of OCM are influenced by endocrine signals and genetic polymorphisms and are particularly responsive to relevant B-vitamin intakes. Physiological changes in healthy pregnancy, leading to a steady decline in B-vitamin status, add another layer of complexity to the regulation of OCM. Although significant advances have been made to improve our understanding of these pregnancy-related changes, no specific reference ranges yet exist for B-vitamin biomarkers in pregnancy to support normal fetal growth without depleting maternal stores. The lack of pregnancy-related criteria for adequacy of B-vitamin status is in turn a major limitation in identifying pregnant women most at risk of B-vitamin deficiency. Another challenge is that the evidence is very limited to provide a basis for establishing pregnancy-specific dietary recommendations for B-vitamins to support successful pregnancy outcomes. In terms of preventing adverse outcomes, periconceptional folic acid supplementation has a proven role, established more than 30 years ago, in protecting against neural tube defect-affected pregnancies and this has been the major focus of public health policy worldwide. This review evaluates the emerging evidence for the less well recognised role of B-vitamins in preventing hypertensive disorders in pregnancy and the intergenerational effects of B-vitamins on offspring neurodevelopment and cognitive performance during childhood. We also consider the underlying biological mechanisms.

Factors influencing survival in sphingosine phosphate lyase insufficiency syndrome: a retrospective cross-sectional natural history study of 76 patients.

BACKGROUND: Sphingosine-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. RESULTS: Overall 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. CONCLUSION: Our 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.

Does Vitamin B6 Act as an Exercise Mimetic in Skeletal Muscle?

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.

Metal complexes containing vitamin B6-based scaffold as potential DNA/BSA-binding agents inducing apoptosis in hepatocarcinoma (HepG2) cells.

A ligand (HL) was synthesized from the pyridoxal hydrochloride (vitamin B6 form) and 1-(2-Aminoethyl)piperidine in one single step. The metal complexes [Zn(L)(Bpy)]NO3 (1), [Cu(L)(Bpy)]NO3 (2), and [Co(L)(Bpy)]NO3 (3) were prepared by tethering HL and 2,2'-bipyridine. The synthesized HL and metal complexes 1-3 were thoroughly characterized using spectroscopic techniques such as 1H NMR, 13C NMR, FTIR, EI-MS, molar conductance, and magnetic moment, in addition to CHN elemental analysis. The geometry of complexes was square pyramidal around the metal ions {Zn(II), Cu(II), and Co(II)}. The interaction of ligand and metal complexes with DNA and BSA macromolecules was accomplished by UV-Vis absorption and fluorescence spectroscopy in vitro. The hyperchromism in band at 303-325 with no shift supports the groove binding with some partial intercalation in grooves. Similarly, in BSA-binding studies, complex 2 shows greater binding potential in the hydrophobic core probably near the Trp-212 in the subdomain IIA. Furthermore, complex 2 shows excellent cytotoxicity on HepG2 cancer cells with IC50 = 25.0 ± 0.45 µM. The detailed analysis by cell-cycle studies shows cell arrest at the G2/M phase. The type of cell death was authenticated by an annexin V-FTIC dual staining experiment that reveals maximum death by apoptosis together with non-specific necrosis.

Dietary vitamin B6 supplementation alleviates heat stress-induced intestinal barrier impairment by regulating the gut microbiota and metabolites in broilers.

Heat stress (HS) brings great challenges to the poultry industry. Vitamin B6 (VB6) is an essential micro-nutrient for animals to maintain normal physiological functions and possesses antioxidant and anti-inflammatory properties. This study aimed to explore the effect of VB6 on alleviating HS-induced intestinal barrier impairment in broilers. A total of 250 broilers (609.76 ± 0.34 g) were randomly allocated to 5 groups with 5 replicate cages of 10 birds each. The broilers in thermoneutral (TN) group were raised in thermoneutral conditions (23 ± 1°C) and fed with a basal diet. The birds in other four groups were housed under cycle high temperature (34 ± 1°C for 8 h/d) from d 21 to 35 and fed with the basal diet (HS group) or basal diet supplemented with 6, 12, or 24 mg/kg VB6 (HB-6, HB-12, HB-24 groups). The results showed that HS reduced the growth performance, increased ileum inflammatory cytokines levels, and impaired the gut barrier function (P < 0.05). Compared to the HS group, final body weight, average daily gain, and average daily feed intake, and the feed conversion ratio were improved by VB6 supplementation. The diamine oxidase, interleukin (IL)-1ß, tumor necrosis factor-α, IL-18, IL-10, and interferon-γ levels were reduced by VB6 supplementation (P < 0.05). Moreover, VB6 supplementation linearly or quadratically enhanced villus height and villus height-to-crypt depth ratio of duodenum and jejunum, and decreased crypt depth of duodenum and ileum. The mRNA expression of Occlaudin, ZO1, Mucin2, Mucin4, E-cadhein, and ß-catenin were increased by VB6 treatment (P < 0.05). Furthermore, dietary VB6 altered the diversity and community of gut microbiota (P < 0.05). A total of 83 differential metabolites associated with the amelioration of VB6 were identified, which were primarily enriched in glycerophospholipid metabolism, caffeine metabolism, and glutathione metabolism pathway. Collectively, VB6 may improve the growth performance and intestinal barrier function of heat-stressed broilers by regulating the ileal microbiota and metabolic homeostasis.

Uracil phosphoribosyltransferase is required to establish a functional cytochrome b6f complex.

Arabidopsis uracil phosphoribosyltransferase (UPP) is an essential enzyme and plants lacking this enzyme are strongly compromised in chloroplast function. Our analysis of UPP amiRNA mutants has confirmed that this vital function is crucial to establish a fully functional photosynthesis as the RIESKE iron sulfur protein (PetC) is almost absent, leading to a block in photosynthetic electron transport. Interestingly, this function appears to be unrelated to nucleotide homeostasis since nucleotide levels were not altered in the studied mutants. Transcriptomics and proteomic analysis showed that protein homeostasis but not gene expression is most likely responsible for this observation and high light provoked an upregulation of protease levels, including thylakoid filamentation temperature-sensitive 1, 5 (FtsH), caseinolytic protease proteolytic subunit 1 (ClpP1), and processing peptidases, as well as components of the chloroplast protein import machinery in UPP amiRNA lines. Strongly reduced PetC amounts were not only detected by immunoblot from mature plants but in addition in a de-etiolation experiment with young seedlings and are causing reduced high light-induced non-photochemical quenching Φ(NPQ) but increased unregulated energy dissipation Φ(NO). This impaired photosynthesis results in an inability to induce flavonoid biosynthesis. In addition, the levels of the osmoprotectants raffinose, proline, and fumarate were found to be reduced. In sum, our work suggests that UPP assists in stabilization PetC during import, processing or targeting to the thylakoid membrane, or protects it against proteolytic degradation.

Optimization of Vitamin B1, B2, and B6 Absorption in Nang Tay Dum Floating Rice Grains.

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.

The Z isomer of pyridoxilidenerhodanine 5'-phosphate is an efficient inhibitor of human pyridoxine 5'-phosphate oxidase, a crucial enzyme in vitamin B6 salvage pathway and a potential chemotherapeutic target.

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.

Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo.

Extracellular hydrolysis of the phosphate esters of B vitamins (B1, B2, and B6) is crucial for their cellular uptake and metabolism. Although a few zinc-dependent enzymes have been implicated in these processes, their exact mechanisms of action remain largely unknown. This study investigated the potential involvement of phosphate group hydrolyzing enzymes in the hydrolysis of B vitamin phosphate esters. We evaluated enzyme activity in membrane lysates prepared from cells transiently transfected with these enzymes or those endogenously expressing them. Specifically, we investigated how zinc deficiency affects the rate of hydrolysis of B vitamin phosphate esters in cellular lysates. Assessment of the activities of zinc-dependent ectoenzymes in the lysates prepared from cells cultured in zinc-deficient conditions and in the serum of rats fed zinc-deficient diets revealed that zinc deficiency reduced the extracellular hydrolysis activity of B vitamin phosphate esters. Furthermore, our findings explain the similarities between several symptoms of B vitamin and zinc deficiencies. Collectively, this study provides novel insights into the diverse symptoms of zinc deficiency and could guide the development of appropriate clinical strategies.

Metabolic Stability and Metabolite Identification of CYP450 Probe Substrates in Ferret Hepatocytes.

BACKGROUND: Ferrets exhibit similar lung physiology to humans and display similar clinical signs following influenza infection, making them a valuable model for studying high susceptibility and infection patterns. However, the metabolic fate of several common human CYP450 probe substrates in ferrets is still unknown and has not been studied. OBJECTIVE: The purpose of this study was to investigate the metabolism of nine human CYP450 probe substrates in ferret hepatocytes and explore their metabolic rate differences between ferrets and other species. METHOD: Nine substrates were individually incubated in ferret hepatocytes for up to 120 min. At each time point, 30 µL mixtures were extracted for stability analysis using LC-MS/MS methods. After a 120-minute incubation period, 400 µL of the mixtures were extracted for metabolite identification using UHPLC-QExactive Plus. RESULTS: The metabolic clearance was determined as follows: diclofenac > taxol > chlorzoxazone > dextromethorphan > midazolam > omeprazole > bupropion > phenacetin > testosterone. Seven metabolites were identified from phenacetin. Deethylation was found to be the major pathway, and the major metabolite was matched with acetaminophen as probed with the CYP1A2 enzyme. Six metabolites were identified from diclofenac. Glucuronidation was the primary pathway, and a metabolite was found to match 4-OH-diclofenac as probed with the CYP2C9 enzyme. Twenty-two metabolites were identified from omeprazole. The major metabolic pathways included mono-oxygenation and sulfoxide to thioether conversion. No metabolite was found to match with the 5-OH-omeprazole as probed with the CYP2C19 enzyme. Twenty-two metabolites were identified from dextromethorphan. Demethylation was found to be the major metabolic pathway, and one demethylation metabolite was matched with dextrorphan as probed with CYP2D6. Fourteen metabolites were identified from midazolam. Mono-oxygenation was found to be the primary metabolic pathway, and one of the mono-oxygenation metabolites was matched with 1-OH-midazolam as probed with the CYP3A4 enzyme. Eight metabolites were identified from testosterone. Mono-oxygenation and glucuronidation were identified as the major metabolic pathways. One mono-oxygenation was matched with 6-ß-testosterone as probed with CYP3A4 enzyme. Six metabolites were identified from taxol. Hydrolysis and mono-oxygenation were the top two metabolic pathways. No metabolite was matched with 6-α-OH-taxol as probed with the CYP2C8 enzyme. Ten metabolites were identified from bupropion. Mono-oxygenation and hydrogenation were identified as the top two metabolic pathways. No mono-oxygenation metabolite was matched with hydroxy-bupropion as probed with the CYP2B6 enzyme. Nine metabolites were identified from chlorzoxazone. Monooxygenation and sulfation were the top two metabolic pathways. One mono-oxygenation metabolite was matched with 6-OH-chlorzoxazone as probed with the CYP2E1 enzyme. CONCLUSION: Nine human CYP probe substrates were clearly metabolized in ferret hepatocytes, demonstrating substrate-dependent metabolic rates in ferret hepatocytes and species-dependent metabolic rates in mouse, rat, dog, monkey, and human hepatocytes. Except for 6-a-5-OH-omeprazole, 6-α-OH-taxol, and hydroxy-bupropion, specific metabolites of other six probe substrates in ferret hepatocytes were detected and identified as probed with six human CYP enzymes, respectively.

Functional significance of CYP2B6 gene rare allelic variants identified in Japanese individuals.

Cytochrome P450 2B6 (CYP2B6) catalyzes the metabolism of many drugs, including efavirenz and propofol. Genetic polymorphisms in CYP2B6 alter its enzymatic activity and substantially affect its pharmacokinetics. High-frequency variants, such as CYP2B6*6, are associated with the risk of developing side effects due to reduced CYP2B6 activity. However, the impact of rare alterations on enzyme function remains unknown, and some of these variants may significantly decrease the CYP2B6 activity. Therefore, in this study, we evaluated in vitro the functional alterations in 29 missense variants of the CYP2B6 gene identified in 8,380 Japanese individuals. Wild-type CYP2B6 and 29 rare CYP2B6 variants were transiently expressed in mammalian cells. The expression levels of variant CYP2B6 proteins in the microsomal fractions extracted from 293FT cells were assessed using western blotting and reduced-carbon monoxide difference spectroscopy, and a specific peak at 450 nm was detected in the wild-type and 19 variants. Furthermore, kinetic parameters were determined by assaying the reactions with efavirenz and propofol and quantifying the metabolite concentrations. We found that 12 variants had significantly lower or abolished enzymatic activity with both the substrates. In silico three-dimensional docking and molecular-dynamics simulations suggested that these functional changes were due to conformational changes in essential regions, such as the heme-binding site and ligand channels involved in transporting substrates to the active site. These findings have implications for predicting the plasma concentrations of CYP2B6 substrates and controlling their side effects.

Role of pyridoxine and oxidative stress in asthenozoospermia.

Purpose: Infertility is a worldwide concern, and recent research indicates that vitamin B6 deficiency may play a role in male infertility, primarily by inducing hyperhomocysteinemia and oxidative stress. These processes can have a detrimental effect on semen quality, ultimately affecting male fertility. Here, we aim to evaluate the biochemical status of pyridoxine (vitamin B6) in relation to total glutathione and total antioxidant capacity. Materials and methods: A case control study samples were collected of asthenozoospermic (n = 63) and normospermic (n = 43) cases, with average men age 30.35 ± 7.03 years old. Semen plasma specimens representing both fertile and sub-fertile men visiting two different secondary care health institute in Irbid province, Jordan. All samples were assessed according to WHO guidelines (2021) and by using spectrophotometry to evaluate the semen plasma levels of vitamin B6, glutathione (GSH) and total antioxidant capacity (TAC). Results: Our main finding is there is significant positive correlations between the seminal plasma concentration of GSH (p < 0.0001) and TAC (p < 0.0073) are significantly correlated with vitamin B6 deficiency in asthenozoospermia group in comparison to normozoospermia cases. A significant decrease (p < 0.0001) the levels of vitamin B6 in men with asthenozoospermia compared to normozoospermic men (control) with an approximate 80 % percent reduction in the mean levels between groups. Conclusions: These findings suggest that pyridoxine deficiency may very well alter the GSH system, in so doing affecting the antioxidant defense mechanism against reactive oxygen species to sperm, impacting sperm development and maturation. leading to asthenozoospermia.

Vitamin B-6 Prevents Heart Failure with Preserved Ejection Fraction Through Downstream of Kinase 3 in a Mouse Model.

BACKGROUND: There is an urgent need to develop an efficient therapeutic strategy for heart failure with preserved ejection fraction (HFpEF), which is mediated by phenotypic changes in cardiac macrophages. We previously reported that vitamin B-6 inhibits macrophage-mediated inflammasome activation. OBJECTIVES: We sought to examine whether the prophylactic use of vitamin B-6 prevents HFpEF. METHODS: HFpEF model was elicited by a combination of high-fat diet and Nω-nitro-l-arginine methyl ester supplement in mice. Cardiac function was assessed using conventional echocardiography and Doppler imaging. Immunohistochemistry and immunoblotting were used to detect changes in the macrophage phenotype and myocardial remodeling-related molecules. RESULTS: Co-administration of vitamin B-6 with HFpEF mice mitigated HFpEF phenotypes, including diastolic dysfunction, cardiac macrophage phenotypic shifts, fibrosis, and hypertrophy. Echocardiographic improvements were observed, with the E/E' ratio decreasing from 42.0 to 21.6 and the E/A ratio improving from 2.13 to 1.17. The exercise capacity also increased from 295.3 to 657.7 min. However, these beneficial effects were negated in downstream of kinase (DOK) 3-deficient mice. Mechanistically, vitamin B-6 increased DOK3 protein concentrations and inhibited macrophage phenotypic changes, which were abrogated by an AMP-activated protein kinase inhibitor. CONCLUSIONS: Vitamin B-6 increases DOK3 signaling to lower risk of HFpEF by inhibiting phenotypic changes in cardiac macrophages.

Identification of YigL as a PLP/PNP phosphatase in Escherichia coli.

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.IMPORTANCEPyridoxine phosphate (PNP) metabolism is critical for both vitamin B6 homeostasis and cellular metabolism. In Escherichia coli, oxidation of PNP was the only known mechanism for controlling PNP levels. This study uncovered a novel phosphatase-mediated mechanism for PNP homeostasis. Multicopy suppressor screening, kinetic analysis of the enzyme, and knockout/overexpression studies identified YigL as a key PNP phosphatase that contributes to PNP homeostasis when facing elevated PNP concentrations in E. coli. This study also revealed a significant contribution of YigL, in combination with YbhA, to PLP metabolism, shedding light on the mechanisms of vitamin B6 regulation in bacteria.

Taurine, alpha lipoic acid and vitamin B6 ameliorate the reduced developmental competence of immature mouse oocytes exposed to methylglyoxal.

Advanced glycation end products (AGEs) are the final products of the Maillard reaction, formed through the interaction of carbohydrates and proteins. Reactive dicarbonyl compounds such as methylglyoxal (MGO) serve as precursors for AGEs formation. Elevated levels of MGO/AGEs are observed in conditions like obesity, polycystic ovarian syndrome (PCOS), and diabetes, negatively impacting oocyte development. Previous studies have shown that hydrogen sulfide, a gasotransmitter with anti-AGEs effects, is produced in a process influenced by vitamin B6. R-α-lipoic acid (ALA) inhibits protein glycation and AGEs formation while stimulating glutathione (GSH) production. Taurine mitigates oxidative stress and acts as an anti-glycation compound, preventing in vitro glycation and AGEs accumulation. This study aimed to explore the ameliorative effects of a micronutrient support (Taurine, ALA and B6: TAB) on mouse oocytes challenged with MGO. Our results indicate that MGO reduces oocyte developmental competence, while TAB supplementation improves maturation, fertilization, and blastocyst formation rates. TAB also restores cell lineage allocation, redox balance and mitigates mitochondrial dysfunction in MGO-challenged oocytes. Furthermore, cumulus cells express key enzymes in the transsulfuration pathway, and TAB enhances their mRNA expression. However, TAB does not rescue MGO-induced damage in denuded oocytes, emphasizing the supportive role of cumulus cells. Overall, these findings suggest that TAB interventions may have significant implications for addressing reproductive dysfunctions associated with elevated MGO/AGEs levels. This study highlights the potential of TAB supplementation in preserving the developmental competence of COCs exposed to MGO stress, providing insights into mitigating the impact of dicarbonyl stress on oocyte quality and reproductive outcomes.

Establishing reference intervals for thiamine pyrophosphate and pyridoxal 5'-phosphate in whole blood in a Danish cohort using liquid chromatography tandem-mass spectrometry (LC-ms/ms).

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.

Effect of protein binding on the pharmacokinetics of the six substrates in the Basel phenotyping cocktail in healthy subjects and patients with liver cirrhosis.

Phenotyping serves to estimate enzyme activities in healthy persons and patients in vivo. Low doses of enzyme-specific substrates are administered, and activities estimated using metabolic ratios (MR, calculated as AUCmetabolite/AUCparent). We administered the Basel phenotyping cocktail containing caffeine (CYP1A2 substrate), efavirenz (CYP2B6), flurbiprofen (CYP2C9), omeprazole (CYP2C19), metoprolol (CYP2D6) and midazolam (CYP3A) to 36 patients with liver cirrhosis and 12 control subjects and determined free and total plasma concentrations over 24 h. Aims were to assess whether MRs reflect CYP activities in patients with liver cirrhosis and whether MRs calculated with free plasma concentrations (MRfree) provide better estimates than with total concentrations (MRtotal). The correlation of MRtotal with MRfree was excellent (R2 >0.910) for substrates with low (<30 %, caffeine and metoprolol) and intermediate protein binding (≥30 and <99 %, midazolam and omeprazole) but weak (R2 <0.30) for substrates with high protein binding (≥99 %, efavirenz and flurbiprofen). The correlations between MRtotal and MRfree with CYP activities were good (R2 >0.820) for CYP1A2, CYP2C19 and CYP2D6. CYP3A4 activity was reflected better by midazolam elimination than by midazolam MRtotal or MRfree. The correlation between MRtotal and MRfree with CYP activity was not significant or weak for CYP2B6 and CYP2C9. In conclusion, MRs of substrates with an extensive protein binding (>99 %) show high inter-patient variabilities and do not accurately reflect CYP activity in patients with liver cirrhosis. Protein binding of the probe drugs has a high impact on the precision of CYP activity estimates and probe drugs with low or intermediate protein binding should be preferred.

Effects of an Acute Dose of Zinc Monomethionine Asparate and Magnesium Asparate (ZMA) on Subsequent Sleep and Next-Day Morning Performance (Countermovement Jumps, Repeated Sprints and Stroop Test).

The goal of the present study was to determine whether an acute dose of a zinc-containing nutritional supplement (ZMA) has any effects on sleep and morning performance in recreationally trained males. Nineteen males participated in a repeated-measures within-subjects study to assess objective and subjective measures of sleep, completed counter-movement jumps (CMJ) and repeated sprint morning performance (RSP). Three days of baseline food intake showed no major deficiencies of zinc, magnesium or vitamin B6 for all participants (11.9 ± 3.4, 395 ± 103 and 2.7 ± 0.9 mg.day-1, respectively). Sleep (22:30-06:30 h) was assessed via actimetry, and either a control (no tablets, NoPill), dextrose placebo (PLAC) or ZMA was ingested 30-60 min before retiring to bed for two nights. The participants undertook the three conditions (NoPill, PLAC or ZMA) administered in a counterbalanced order. The data were analyzed using general linear models with repeated measures. In healthy active males who consume diets of adequate micronutrients, sleep normally and maintain good sleep hygiene (time to bed and wake times), ZMA supplementation had no beneficial effect on RSP or performance in the Stroop test (p > 0.05) but did improve CMJ height (p < 0.001) compared to that of PLAC but not NoPill (p > 0.05). Supplementation of ZMA for two nights had no effect on sleep, RSP or cognitive function. The NoPill condition elucidated the effects of the intervention under investigation.

A critical review of electrochemical and optical Vitamin B6 sensing: evolution of biosensor platforms based on advanced nanosystems.

Vitamin B6 (VB6) is a member of the water-soluble B vitamins which have a vital performance in nervous system operating activities. VB6 is highly demanded to maintain excellent skin and immune systems in the human body. furthermore, VB6 is tremendously substantial in the functions of some enzymes that participate in the metabolism of proteins, amino acids, etc. The deficiency of VB6 will eventuate in anemic situations and may lead to permanent injuries in the brain. moreover, recent studies disclosed that adequate Vitamin B6 in the human body can decrease the intensity of illnesses such as diabetes, stress, etc., in patients with COVID-19 infections. Thus, the detection of VB6 from real samples is crucial to control the amount of this vitamin in biological fluids and to monitor the pharmaceutical dosage quality. Various analytical approaches have been employed for the VB6 detection in biological and pharmaceutical samples. Although biosensing and sensing approaches hold several obvious advantages such as simplicity, capability for miniaturization, quick response time, etc. from other analytical methods. Hence, through the last decades, designing and fabricating biosensors with sufficient sensitivity and selectivity have been investigated by many researchers in order to detect VB6. The purpose of this review is to illustrate the importance of diverse electrochemical and optical approaches for VB6 detection. Additionally, novel VB6 detection techniques based on electrochemical, optical, and conventional methods have been considerably discussed, and compared with each other. Furthermore, a comprehensive summary of the current limitations and future challenges in VB6 analysis are explained and also create a pathway for subsequent expansions and applications.

Vitamin B₆ is an essential compound for proper function of human body.Various nanomaterial-based methods such as conational approach, electrochemical biosensing and apta-sensing analyses for Vitamin B₆ detection has been developed.Different techniques for detecting of Vitamin B₆ have been comprehensively discussed.Various electrochemical sensors fabrication and its application in Vitamin B₆ detection with nanomaterials have been assessed.The article points out the recent progress limitations, and also the upcoming tasks in the successful sensor fabrication with the functionalized nanomaterials.