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Scientific Reports Feb 2024Tight junctions (TJs) are important factors constituting the physical barriers of the skin, and their suppression has been described in various conditions, such as aged...
Tight junctions (TJs) are important factors constituting the physical barriers of the skin, and their suppression has been described in various conditions, such as aged skin and atopic dermatitis lesions. However, the methods for improving skin TJ function remain insufficient. Therefore, to obtain compounds that can improve TJ function, we developed a novel high-throughput screening system termed live-cell immunostaining to evaluate cell surface-localized claudin-1 (CLDN1) with high selectivity using normal human epidermal keratinocytes (NHEKs). Heparinoid and phospho-pyridoxal (p-Pyr), a metabolite of pyridoxine, were identified as hit compounds. In addition, heparinoid was strongly suggested to increase CLDN1 expression by inhibiting epidermal growth factor receptor signaling. By contrast, p-Pyr did not enhance CLDN1 expression, but it accelerated the translocation of CLDN1 to the cell surface. Finally, we confirmed that heparinoid and p-Pyr improved barrier function in NHEKs in a transepithelial electrical resistance assay. In conclusion, heparinoid and p-Pyr could potentially ameliorate skin conditions by improving TJ function.
Topics: Humans; Aged; Claudin-1; Tight Junctions; Heparinoids; High-Throughput Screening Assays; Keratinocytes; Claudin-4
PubMed: 38332234
DOI: 10.1038/s41598-024-53649-1 -
Journal of Medicine and Life Oct 2023Pyridoxal-5-phosphate (PLP) is the bioactive derivative of vitamin B6, functioning as a coenzyme in over 150 metabolic pathways. Insufficient PLP levels could be... (Randomized Controlled Trial)
Randomized Controlled Trial
Pyridoxal-5-phosphate (PLP) is the bioactive derivative of vitamin B6, functioning as a coenzyme in over 150 metabolic pathways. Insufficient PLP levels could be associated with the onset and progression of diabetes. This study aimed to assess the effects of pyridoxine adjuvant treatment on blood glucose levels in patients with type 2 diabetes mellitus (T2DM). This interventional, randomized, open-label study was conducted in the Mesan Governorate, with participants from the Mesan Center for Diabetes and Endocrinology as the study population. This study included patients newly diagnosed with T2DM. Patients were randomized into three groups: Group 1, the control group, treated with non-pharmacological therapy (lifestyle modification) (n=20); Group 2, treated with Metformin 500 mg/day in addition to non-pharmacological therapy (lifestyle modification) (n=20). Group 3 was treated with Metformin 500 mg/day plus vitamin B6 300 mg/day in addition to non-pharmacological therapy (lifestyle modification) (n=68). The findings revealed a considerably favorable impact of pyridoxine adjuvant treatment with Metformin on blood glucose levels and other study variables. Compared to the patients in the control group G1, the reductions in fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) were statistically significant in groups G2 and G3 after a 4-week treatment period. Similar results were observed for fasting serum insulin and homeostasis model assessment of insulin resistance (HOMA-IR) levels, with a significant decrease in groups G2 and G3 (p<0.05). Furthermore, the reductions in indoleamine 2,3-dioxygenase levels were also significantly higher in groups G2 and G3 at the end of the 4-week treatment period (-14.48% -21.16%) (p<0.05). Adding pyridoxine adjuvant therapy to Metformin treatment could effectively improve the blood glucose levels of patients with T2DM.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Blood Glucose; Pyridoxine; Metformin; Insulin
PubMed: 38313181
DOI: 10.25122/jml-2023-0178 -
Chemical & Pharmaceutical Bulletin Feb 2024Ionic liquid (IL) technology was used to enhance the stability of L-ascorbic acid (AA). Pyridoxine was selected as the counter cation for anionic AA in IL. After AA was...
Ionic liquid (IL) technology was used to enhance the stability of L-ascorbic acid (AA). Pyridoxine was selected as the counter cation for anionic AA in IL. After AA was dissolved in water at 40 °C, its ratio decreased to 3.2% after 7 d. In contrast, the IL formulation showed negligible degradation, with almost no loss of AA even after 28 d. These results suggest that the use of IL enhances the stability of AA.
Topics: Ionic Liquids; Ascorbic Acid; Antioxidants
PubMed: 38281765
DOI: 10.1248/cpb.c23-00861 -
BMC Chemistry Jan 2024High performance liquid chromatography is one of the techniques of choice for the separation and quantitative determination of drugs in mixture form. Ipriflavone,...
Development of chromatographic methods to determine multivitamins formulation depending on their solubility and polarity: comparative study using three greenness assessment tools.
High performance liquid chromatography is one of the techniques of choice for the separation and quantitative determination of drugs in mixture form. Ipriflavone, ascorbic acid, pyridoxine, vitamin D3, and lysine are formulated together as an adjuvant combination in osteoporosis. In this work, we developed and validated two complementary high performance liquid chromatographic methods to determine the five compounds in their pharmaceutical dosage form. The first method (method A) was capable of determining ipriflavone, ascorbic acid, pyridoxine, and vitamin D3 in their bulk and combined pharmaceutical formulation. The method is based on Liquid Chromatographic separation with UV detection at 254 nm using Agilent Eclipse XDB-C18 column with a mobile phase consisting of 25 mM ammonium acetate buffer (pH 4.2): methanol in gradient mode. Due to the high polarity of lysine, it was difficult to achieve satisfactory retention on reversed phase columns. So, we separated it on a strong cation exchange column (Exsil 100 SCX) without derivatization with a mobile phase consisting of 10 mM sodium dihydrogen phosphate and 200 mM sodium chloride (pH 6) with UV detection at 210 nm (method B). Validation of the proposed methods was performed according to ICH guidelines Q2(R1). The proposed methods proved to be valid for selective analysis of the stated drugs in their bulk and combined pharmaceutical formulation. Greenness assessment of the developed methods was evaluated using three assessment tools: ESA, GAPI and the most recently developed tool AGREE, showing a satisfactory comprehensive guide of the greenness of the developed methods.
PubMed: 38281043
DOI: 10.1186/s13065-024-01118-1 -
Scientific Reports Jan 2024Limited studies are available on vitamin B6 status in domestic cats. To this end, we evaluated glutamate-oxaloacetate transaminase (GOT) activity in hemolysates with and...
Limited studies are available on vitamin B6 status in domestic cats. To this end, we evaluated glutamate-oxaloacetate transaminase (GOT) activity in hemolysates with and without pyridoxal 5'-phosphate addition in two feline populations: a cohort of 60 healthy, domestic (sexually intact and specific pathogen-free) cats maintained under strictly controlled conditions with appropriate diets housed at the Feline Nutrition and Pet Care Center, and a cohort of 57 cats randomly selected between December 2022 to January 2023 that visited the Veterinary Medicine Teaching Hospital to seek care under different circumstances. The GOT activity expressed as the ratio with and without pyridoxal 5'-phosphate addition (primary activation ratio; PAR) decreased significantly with age in the healthy cohort. The PAR values normalized to age established a cut-off for vitamin B6 deficiency in both cohorts, identifying 17 of 101 animals as vitamin B6 deficient. Using machine learning, a partition-based model (decision tree) was built to identify the most important factors that predicted vitamin B6 deficiency while using the resulting tree to make predictions for new observations. This analysis, performed with all 101 cats, revealed that the diagnosis of an infectious, chronic or acute condition (0.55) was the main contributor, followed by age (0.26), and body condition score (optimal-overweight; 0.19). Thus, our study supports that vitamin B6 supplementation may be indicated in junior to adult animals diagnosed with an infectious, chronic, or acute conditions or healthy cats with body weight ranging from optimal to overweight. In older cats, even if healthy, underweight to optimal cats appear to be at risk of vitamin B6 deficiency.
Topics: Animals; Cats; Hospitals, Teaching; Overweight; Phosphates; Pyridoxal Phosphate; Pyridoxine; Vitamin B 6; Vitamin B 6 Deficiency
PubMed: 38263201
DOI: 10.1038/s41598-024-52367-y -
Nutrients Jan 2024Marginal vitamin B6 (B6) deficiency is a widespread global concern. Inadequate B6 levels have been linked to an increased risk of age-related chronic diseases such as... (Review)
Review
Marginal vitamin B6 (B6) deficiency is a widespread global concern. Inadequate B6 levels have been linked to an increased risk of age-related chronic diseases such as cardiovascular diseases and cancers. In recent years, the growing concern over sarcopenia (the age-related loss of muscle mass and strength) and frailty (a decline in physiological resilience and increased vulnerability associated with aging) is particularly relevant due to the emergence of super-aged societies in developed countries. Notably, among the thirty-one studies included in this review, twenty-five showed a significant association of B6 status with sarcopenia, frailty, and all-cause mortality in adults ( < 0.05), while six showed no association. Emerging studies have suggested novel mechanisms underlying this association. These mechanisms involve P2X7 receptor-mediated NLRP3 inflammasome signaling, AMPK signaling, PD-L1 signaling, and satellite cell-mediated myogenesis. Furthermore, the modulation of PLP-dependent enzymes due to B6 deficiency is associated with impaired metabolic processes, affecting energy utilization, imidazole peptide production, and hydrogen sulfide production, as well as the kynurenine pathway, all of which play vital roles in skeletal muscle health and pathophysiology. This narrative review provides an up-to-date assessment of our current understanding of the potential role of nutritional B6 status in combating sarcopenia, frailty, and mortality.
Topics: Adult; Humans; Aged; Vitamin B 6; Sarcopenia; Frailty; Pyridoxine; Aging
PubMed: 38202006
DOI: 10.3390/nu16010177 -
ACS Omega Dec 2023Gold nanoparticles (AuNPs) were synthesized and stabilized using ecological strategies: the extracts of the leaves of the plants (GS) and (PA) reduced the metallic Au...
Gold nanoparticles (AuNPs) were synthesized and stabilized using ecological strategies: the extracts of the leaves of the plants (GS) and (PA) reduced the metallic Au ions to AuNPs. The AuNPs were analyzed as surface-enhanced Raman scattering (SERS) substrates for pyridoxine detection (vitamin B6). UV-vis spectroscopy was carried out to assess the stability of the AuNPs. As a result, absorption bands around 530 and 540 nm were obtained for AuNPs-PA and AuNPs-GS, respectively. Both cases associated it with localized surface plasmon resonance (LSPR). In the final stage of the synthesis, to stabilize the AuNPs, carboxymethyl cellulose (CMC) was added; however, LSPR bands do not exhibit bathochromic or hypsochromic shifts with the addition of CMC. Transmission electron microscopy (TEM) micrographs show relatively spherical morphologies; the particle diameters were detected around 7.7 and 12.7 nm for AuNPs-PA and AuNPs-GS, respectively. The nanomaterials were evaluated as SERS substrates on pyridoxine, revealing an intensification in the vibrational mode centered at 688 cm associated with the pyridinic ring. Complementarily, different density functional theory functionals were included to obtain molecular descriptors on the Au-cluster-pyridoxine interaction to study the SERS behavior.
PubMed: 38107913
DOI: 10.1021/acsomega.3c03813 -
Cureus Nov 2023Vitamin B6 is a water-soluble vitamin that is an important cofactor in various metabolic processes. Although rare, its consumption can sometimes result in toxicity,...
Vitamin B6 is a water-soluble vitamin that is an important cofactor in various metabolic processes. Although rare, its consumption can sometimes result in toxicity, which typically presents with peripheral neuropathy in the early stage. While vitamin B6 toxicity is most often associated with supplemental mega-doses of more than 50 mg/day, more recent studies have shown that toxicity can occur in cases of much smaller doses as well. We present a case of a 73-year-old male with a three-year history of progressive peripheral neuropathy who was found to have a serum vitamin B6 level of 259.9 nmol/L (reference range: 20-125 nmol/L) but only reported taking a daily multivitamin containing 6 mg of vitamin B6. This case of toxicity in the setting of a daily intake lower than the European Food Safety Administration's (EFSA) newly established Tolerable Upper Intake Level (UL) of 12 mg/day highlights the need for further research into the effects of relatively low-dose vitamin B6 supplementation.
PubMed: 38098895
DOI: 10.7759/cureus.48792 -
Frontiers in Cellular and Infection... 2023Although tremendous success has been achieved in the development and deployment of effective COVID-19 vaccines, developing effective therapeutics for the treatment of...
BACKGROUND
Although tremendous success has been achieved in the development and deployment of effective COVID-19 vaccines, developing effective therapeutics for the treatment of those who do come down with the disease has been with limited success. To repurpose existing drugs for COVID-19, we previously showed, qualitatively, that erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit SARS-COV-2-induced cytopathic effect (CPE) in Vero cells.
AIM
This study aimed to quantitatively explore the inhibition of SARS-CoV-2-induced CPE by erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin and to determine the effect of these drugs on SARS-CoV-2 papain-like protease and 3CL protease (M) enzymes.
METHODS
Neutral red (3-amino-7-dimethylamino-2-methyl-phenazine hydrochloride) cell viability assay was used to quantify CPE after infecting pre-treated Vero cells with clinical SARS-Cov-2 isolates. Furthermore, SensoLyte 520 SARS-CoV-2 papain-like protease and SensoLyte 520 SARS-CoV-2 M activity assay kits were used to evaluate the inhibitory activity of the drugs on the respective enzymes.
RESULTS
Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin dose-dependently inhibit SARS-CoV-2-induced CPE in Vero cells, with inhibitory concentration-50 (IC) values of 3.27 µM, 4.23 µM, 9.29 µM, 3.19 µM, and 84.31 µM, respectively. Furthermore, erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin dose-dependently inhibited SARS-CoV-2 papain-like protease with IC values of 0.94 µM, 0.88 µM, 1.14 µM, 1.07 µM, and 1.51 µM, respectively, and inhibited the main protease (M) with IC values of 1.35 µM, 1.25 µM, 7.36 µM, 1.15 µM, and 2.44 µM, respectively.
CONCLUSION
The IC for all the drugs, except ivermectin, was at the clinically achievable plasma concentration in humans, which supports a possible role for the drugs in the management of COVID-19. The lack of inhibition of CPE by ivermectin at clinical concentrations could be part of the explanation for its lack of effectiveness in clinical trials.
Topics: Animals; Chlorocebus aethiops; Humans; SARS-CoV-2; COVID-19; Papain; Ivermectin; Pyridoxine; Peptide Hydrolases; Vero Cells; COVID-19 Vaccines; Erythromycin; Folic Acid; Antiviral Agents; Protease Inhibitors
PubMed: 38089816
DOI: 10.3389/fcimb.2023.1273982 -
International Journal of Molecular... Nov 2023Many inherited metabolic disorders (IMDs), including disorders of amino acid, fatty acid, and carbohydrate metabolism, are treated with a dietary reduction or exclusion... (Review)
Review
Many inherited metabolic disorders (IMDs), including disorders of amino acid, fatty acid, and carbohydrate metabolism, are treated with a dietary reduction or exclusion of certain macronutrients, putting one at risk of a reduced intake of micronutrients. In this review, we aim to provide available evidence on the most common micronutrient deficits related to specific dietary approaches and on the management of their deficiency, in the meanwhile discussing the main critical points of each nutritional supplementation. The emerging concepts are that a great heterogeneity in clinical practice exists, as well as no univocal evidence on the most common micronutrient abnormalities. In phenylketonuria, for example, micronutrients are recommended to be supplemented through protein substitutes; however, not all formulas are equally supplemented and some of them are not added with micronutrients. Data on pyridoxine and riboflavin status in these patients are particularly scarce. In long-chain fatty acid oxidation disorders, no specific recommendations on micronutrient supplementation are available. Regarding carbohydrate metabolism disorders, the difficult-to-ascertain sugar content in supplementation formulas is still a matter of concern. A ketogenic diet may predispose one to both oligoelement deficits and their overload, and therefore deserves specific formulations. In conclusion, our overview points out the lack of unanimous approaches to micronutrient deficiencies, the need for specific formulations for IMDs, and the necessity of high-quality studies, particularly for some under-investigated deficits.
Topics: Humans; Diet; Dietary Supplements; Micronutrients; Trace Elements; Metabolic Diseases; Fatty Acids
PubMed: 38069347
DOI: 10.3390/ijms242317024