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.

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.

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.

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.

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.

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.

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.

A case series of low-level laser therapy treatment in patients with peripheral facial palsy.

BACKGROUND: Peripheral Facial Palsy (PFP) is a facial paralysis with various etiologies, including idiopathic causes (Bell's palsy), infections, trauma, and genetic factors. Traditional treatments involve antiviral medications, corticosteroids, and physiotherapy. However, new therapies, such as Low-Level Laser Therapy (LLLT), are emerging with promising results. METHODS: This case series reports on two patients with PFP treated with LLLT combined with Vitamin B1, B6, and B12 supplementation. The first case involved a 52-year-old female with PFP due to a viral infection. The second case was a 33-year-old male who developed PFP following a traumatic brain injury. Both patients received LLLT sessions every two weeks, targeting 10 points along the facial nerve pathway from the facial notch across the face. The laser device used was the Theraphy EC (DMC, Sao Carlos, SP, Brazil), with each point receiving 4 Joules of energy applied perpendicular to the skin after cleaning the face with water and soap to remove lipids that could interfere. The administration of Vitamin B was done using NEUROBIONTA tablets (Vitamin B1 + Vitamin B6 + Vitamin B12; Procter & Gamble, Santiago, Chile) with one tablet taken daily for 30 days. RESULTS: After six to seven sessions, both patients showed significant improvement in facial muscle function and overall facial symmetry. In the first case, improvements were noted in muscle tonicity and facial movements, with the patient reporting reduced facial disfigurement. In the second case, notable recovery in facial mobility and symmetry was observed, with the patient experiencing decreased paresthesia and restored muscle functionality. CONCLUSION: These findings suggest that LLLT, combined with Vitamin B1, B6, and B12 supplementation, may effectively improve facial muscle function and symmetry in PFP patients. The non-invasive nature and ease of application make LLLT a viable option for PFP treatment. Further studies with larger sample sizes and standardized protocols are necessary to confirm these results and establish LLLT as a standard treatment for PFP.

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.

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.

The impact of vitamin E, vitamin B6, and niacin intake on cataract incidence based on NHANES 2005-2008 data.

Objective: This investigation aims to elucidate the correlations between dietary intakes of vitamin E, B6, and niacin and the incidence of cataracts, utilizing the comprehensive NHANES 2005-2008 dataset to affirm the prophylactic roles of these nutrients against cataract formation. Methods: Using data from the NHANES 2005-2008 cycles, this analysis concentrated on 7,247 subjects after exclusion based on incomplete dietary or cataract data. The identification of cataracts was determined through participants' self-reported ophthalmic surgical history. Nutritional intake was gauged using the automated multiple pass method, and the data were analyzed using logistic and quantile regression analyses to investigate the relationship between vitamin consumption and cataract prevalence. Results: Our analysis identified significant inverse associations between the intake of vitamins E, B6, and niacin and the risk of cataract development. Specifically, higher intakes of vitamin B6 (OR = 0.85, 95% CI = 0.76-0.96, p = 0.0073) and niacin (OR = 0.98, 95% CI = 0.97-1.00, p = 0.0067) in the top quartile were significantly associated with a reduced likelihood of cataract occurrence. Vitamin E intake showed a consistent reduction in cataract risk across different intake levels (OR = 0.96, 95% CI = 0.94-0.99, p = 0.0087), demonstrating a nonlinear inverse correlation. Conclusion: The outcomes indicate that elevated consumption of vitamin B6 and niacin, in conjunction with regular vitamin E intake, may have the potential to delay or prevent cataract genesis. These results suggest a novel nutritional strategy for cataract prevention and management, advocating that focused nutrient supplementation could be instrumental in preserving eye health and reducing the risk of cataracts. Further research is recommended to validate these findings and establish optimal dosages for maximum benefit.

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.

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.

Vitamin B6 inhibits activity of Helicobacter pylori adenylosuccinate synthetase and growth of reference and clinical, antibiotic-resistant H. pylori strains.

The current therapies against gastric pathogen Helicobacter pylori are ineffective in over 20% of patients. Enzymes belonging to the purine salvage pathway are considered as novel drug targets in this pathogen. Therefore, the main aim of the current study was to determine the antibacterial activity of pyridoxal 5'-phosphate (PLP), an active form of vitamin B6, against reference and clinical strains of H. pylori. Using a broad set of microbiological, physicochemical (UV absorption, LC-MS, X-ray analysis) and in silico experiments, we were able to prove that PLP inhibits adenylosuccinate synthetase (AdSS) from H. pylori by the competition with GTP (IC50eq ∼30 nM). This behaviour was attributed to formation of a Schiff base with a lysine residue (a covalent bond with Lys322 in the GTP binding site of AdSS) and was potentiated by the presence of vitamin C. This antibacterial activity of PLP gives hope for its future use against H. pylori.

Association between Vitamin E, Vitamin B6, and Vitamin B12 with coronary heart disease.

Conflicting evidence still exists regarding Vitamin B12's involvement in coronary heart disease (CHD). There is no precedent for previous studies to include both Vitamin B12, Vitamin B6, as well as Vitamin E in the consideration of CHD associating factors. Our data derived from the National Health and Nutrition Examination Survey (NHANES), which covers the period 2003-2020. 33,640 samples were included in this cross-sectional study. We used an unadjusted covariates and three adjusted covariates. The intake percentage of Vitamins E, B6, and B12 was categorized into continuous and categorical variables using multivariate logistic regression analysis and subgroup logistic regression. To estimate these trends, we applied the percentage categories of Vitamin E, B6, and B12 intake as continuous variables. We recorded Vitamin E, B6, B12, age, race, BMI, gender, household annual income, education level, hypertension status, diabetes status, smoking status, and drinking status for included samples. Multivariate regression analysis revealed that Vitamin E and B6 were negatively associated with CHD and exerted protective effects, while Vitamin B12 had little correlation with CHD. Based on the quartiles of Vitamin E and Vitamin B6 percentage, the strongest protective effect was observed in the third quartile (Q3). Analyses of subgroups showed the effects of Vitamin B6 and Vitamin E on CHD were more noticeable in women, the participant's BMI was in the 25-30 range, and participants who smoked. We identified the possible protective effect of Vitamin E and Vitamin B6 against CHD, especially in female, obese, and smoking populations, whereas income and education were also viewed as influencing factors that could be taken into account.

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.

Primary hyperoxaluria: Long-term outcomes of isolated kidney versus simultaneous liver/kidney transplant.

OBJECTIVES: To compare long-term transplant outcomes (organ rejection and retransplant) of simultaneous liver/kidney transplant (SLK) versus isolated kidney transplant (IK) for patients with primary hyperoxaluria (PH). METHODS: The Rare Kidney Stone Consortium PH registry was queried to identify patients with PH who underwent SLK or IK from 1999 to 2021. Patient characteristics and long-term transplant outcomes were abstracted and analyzed. Statistical comparisons were performed with Kaplan-Meier plots and Cox proportional hazards models. RESULTS: We identified 250 patients with PH, of whom 35 received care at Mayo Clinic and underwent SLK or IK. Patients who underwent SLK as their index transplant had lower odds of kidney rejection than did those who underwent IK (hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.08-0.99; p = .048). The immunoprotective effect of concomitant liver and kidney transplant appeared to enhance outcomes for patients with PH. Additionally, the odds of retransplant were significantly lower for patients who underwent SLK as their index transplant than for those who underwent IK (HR, 0.08; 95% CI, 0.02-0.42; p = .003). Of five patients who underwent IK and had maintained graft function for at least 5 years after transplant, three (60%) had documented vitamin B6 responsiveness. CONCLUSIONS: Patients with PH who underwent SLK had a lower risk of kidney rejection and retransplant than those who underwent IK. Accurate genetic assessment for vitamin B6 responsiveness may optimize IK allocation. Novel therapeutics, such as lumasiran, have been introduced as promising agents for the management of PH.

Vitamin B6 Cofactor Pyridoxal 5'-phosphate Conjugated Papain-Stabilized Fluorescent Gold Nanoclusters for Switch-on Detection of Zinc(II).

In this study, fluorescent gold nanoclusters (AuNCs) conjugated with pyridoxal-5-phosphate (PLP) were synthesized, characterized, and used for Zn2+ fluorescence turn-on sensing. PLP was conjugated over the surface of papain-stabilized fluorescent gold nanoclusters (pap-AuNCs; λex = 380 nm, λem = 670 nm) by forming imine linkage. Due to this modification, the red color emitting pap-AuNCs changed to orange color emitting nanoclusters PLP_pap-AuNCs. The nano-assembly PLP_pap-AuNCs detect Zn2+ selectively by showing a notable fluorescence enhancement at 477 nm. Zn2+ detection with PLP_pap-AuNCs was quick and easy, with an estimated detection limit of 0.14 µM. Further, paper strips and cotton buds coated with PLP_pap-AuNCs were developed for affordable on-site visual detection of Zn2+. Finally, the detection of Zn2+ in actual environmental water samples served as validation of the usefulness of PLP_pap-AuNCs.

Vitamin B6 and diabetes and its role in counteracting advanced glycation end products.

Naturally occurring forms of vitamin B6 include six interconvertible water-soluble compounds: pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM), and their respective monophosphorylated derivatives (PNP, PLP, and PMP). PLP is the catalytically active form which works as a cofactor in approximately 200 reactions that regulate the metabolism of glucose, lipids, amino acids, DNA, and neurotransmitters. Most of vitamers can counteract the formation of reactive oxygen species and the advanced glycation end-products (AGEs) which are toxic compounds that accumulate in diabetic patients due to prolonged hyperglycemia. Vitamin B6 levels have been inversely associate with diabetes, while vitamin B6 supplementation reduces diabetes onset and its vascular complications. The mechanisms at the basis of the relation between vitamin B6 and diabetes onset are still not completely clarified. In contrast more evidence indicates that vitamin B6 can protect from diabetes complications through its role as scavenger of AGEs. It has been demonstrated that in diabetes AGEs can destroy the functionality of macromolecules such as protein, lipids, and DNA, thus producing tissue damage that result in vascular diseases. AGEs can be in part also responsible for the increased cancer risk associated with diabetes. In this chapter the relationship between vitamin B6, diabetes and AGEs will be discussed by showing the acquired knowledge and questions that are still open.