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Nature Communications Sep 2023Induction of hypothermia during hibernation/torpor enables certain mammals to survive under extreme environmental conditions. However, pharmacological induction of...
Induction of hypothermia during hibernation/torpor enables certain mammals to survive under extreme environmental conditions. However, pharmacological induction of hypothermia in most mammals remains a huge challenge. Here we show that a natural product P57 promptly induces hypothermia and decreases energy expenditure in mice. Mechanistically, P57 inhibits the kinase activity of pyridoxal kinase (PDXK), a key metabolic enzyme of vitamin B6 catalyzing phosphorylation of pyridoxal (PL), resulting in the accumulation of PL in hypothalamus to cause hypothermia. The hypothermia induced by P57 is significantly blunted in the mice with knockout of PDXK in the preoptic area (POA) of hypothalamus. We further found that P57 and PL have consistent effects on gene expression regulation in hypothalamus, and they may activate medial preoptic area (MPA) neurons in POA to induce hypothermia. Taken together, our findings demonstrate that P57 has a potential application in therapeutic hypothermia through regulation of vitamin B6 metabolism and PDXK serves as a previously unknown target of P57 in thermoregulation. In addition, P57 may serve as a chemical probe for exploring the neuron circuitry related to hypothermia state in mice.
Topics: Animals; Mice; Body Temperature Regulation; Hypothermia; Pyridoxal Kinase; Pyridoxine; Vitamin B 6; Biological Products
PubMed: 37752106
DOI: 10.1038/s41467-023-41435-y -
Frontiers in Immunology 2020Schistosomes are parasitic platyhelminths that currently infect >200 million people globally. The adult worms can live within the vasculature of their hosts for many...
Schistosomes are parasitic platyhelminths that currently infect >200 million people globally. The adult worms can live within the vasculature of their hosts for many years where they acquire all nutrients necessary for their survival and growth. In this work we focus on how parasites acquire and metabolize vitamin B6, whose active form is pyridoxal phosphate (PLP). We show here that live intravascular stage parasites (schistosomula and adult males and females) can cleave exogenous PLP to liberate pyridoxal. Of the three characterized nucleotide-metabolizing ectoenzymes expressed at the schistosome surface (SmAP, SmNPP5, and SmATPDase1), only SmAP hydrolyzes PLP. Heat-inactivated recombinant SmAP can no longer cleave PLP. Further, parasites whose SmAP gene has been suppressed by RNAi are significantly impaired in their ability to cleave PLP compared to controls. When schistosomes are incubated in murine plasma, they alter its metabolomic profile-the levels of both pyridoxal and phosphate increase over time, a finding consistent with the action of host-exposed SmAP acting on PLP. We hypothesize that SmAP-mediated dephosphorylation of PLP generates a pool of pyridoxal around the worms that can be conveniently taken in by the parasites to participate in essential, vitamin B6-driven metabolism. In addition, since host PLP-dependent enzymes play active roles in inflammatory processes, parasite-mediated cleavage of this metabolite may serve to limit parasite-damaging inflammation. In this work we also identified schistosome homologs of enzymes that are involved in intracellular vitamin B6 metabolism. These are pyridoxal kinase (SmPK) as well as pyridoxal phosphate phosphatase (SmPLP-Ph) and pyridox(am)ine 5'-phosphate oxidase (SmPNPO) and cDNAs encoding these three enzymes were cloned and sequenced. The three genes encoding these enzymes all display high relative expression in schistosomula and adult worms suggestive of robust vitamin B6 metabolism in the intravascular life stages.
Topics: Alkaline Phosphatase; Amino Acid Sequence; Animals; Female; Gene Expression Regulation, Developmental; Male; Mice; Phosphates; Phosphoric Monoester Hydrolases; Phosphorylation; Phylogeny; Pyridoxal; Pyridoxal Kinase; Pyridoxal Phosphate; Pyridoxaminephosphate Oxidase; RNA Interference; Recombinant Proteins; Schistosoma mansoni; Sequence Alignment; Vitamin B 6
PubMed: 33613557
DOI: 10.3389/fimmu.2020.622162 -
Current Oncology Reports Oct 2017The purpose of this mini review is to evaluate the literature on B vitamins and chemotherapy-induced peripheral neuropathy. (Review)
Review
PURPOSE OF REVIEW
The purpose of this mini review is to evaluate the literature on B vitamins and chemotherapy-induced peripheral neuropathy.
RECENT FINDINGS
One hundred and five journal articles were evaluated and nine manuscripts were included. There was one in vitro, one was an animal and seven were human studies. The in vitro study was a safety study on vitamin B and oxaliplatin which was not directly related to CIPN. The animal study evaluated vitamin B on paclitaxel administration with positive results. The human studies varied using a vitamin B complex, vitamin B only and vitamin B. Chemotherapy-induced peripheral neuropathy (CIPN) continues to plague patients and the medical fraternity. Currently, there are still no conclusive protective or treatment options. B vitamins have been found to play a role in CIPN prevention, but further studies are required to ascertain possible protection and treatment options.
Topics: Animals; Humans; Neoplasms; Niacinamide; Organoplatinum Compounds; Oxaliplatin; Peripheral Nervous System Diseases; Vitamin B 12; Vitamin B 6; Vitamin B Complex
PubMed: 28983799
DOI: 10.1007/s11912-017-0636-z -
Brain : a Journal of Neurology Sep 2022
Topics: Humans; Levodopa; Parkinson Disease; Pyridoxine; Vitamin B 6; Vitamins
PubMed: 35802009
DOI: 10.1093/brain/awac225 -
European Journal of Clinical Nutrition Nov 2023Patients with inflammatory bowel diseases (IBD) are at risk of micronutrient deficiencies, particularly during flares. Vitamin B6 is required for the proper development...
BACKGROUND
Patients with inflammatory bowel diseases (IBD) are at risk of micronutrient deficiencies, particularly during flares. Vitamin B6 is required for the proper development of brain, nerves, and many other parts of the body. However, limited studies are available to describe the prevalence, relevance and consequences of vitamin B6 deficiencies in IBD. We aim to estimate the prevalence of vitamin B6 deficiencies in Crohn's disease (CD) patients, to identify associated risk factors and to explore the alteration of intestinal microbiota related to vitamin B6 status.
METHODS
A total of 360 CD patients and 55 ulcerative colitis (UC) patients from Shanghai Tenth People's Hospital of Tongji University were included. Serum vitamin B6 concentrations were collected from the computerized laboratory data. The logistic regression was used for statistical analysis. Fecal-associated microbiota was also analyzed using 16S rRNA sequencing in another 20 CD patients (10 of vitamin B6 normal, 10 of vitamin B6 deficiency).
RESULTS
The prevalence of vitamin B6 abnormality was significantly higher in CD than in UC patients. Logistic regression analysis showed that small bowel lesion, ileocolonic lesion (L3), extraintestinal manifestations, ileal resection, and usage of immunosuppressor were independently associated with abnormal vitamin B6 in CD. Interestingly, the microbial structure presented significant differences between two CD groups. PICRUSt2 prediction revealed that some enzymes and metabolic pathways between the two groups were significantly different.
CONCLUSIONS
Collectively, our analysis showed that vitamin B6 reduction occurred frequently in patients with CD and affected the intestinal flora of patients.
Topics: Humans; Crohn Disease; Retrospective Studies; Vitamin B 6 Deficiency; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; China; Colitis, Ulcerative; Inflammatory Bowel Diseases; Vitamin B 6
PubMed: 37550534
DOI: 10.1038/s41430-023-01324-5 -
Brain : a Journal of Neurology Sep 2022
Topics: Humans; Levodopa; Parkinson Disease; Pyridoxine; Vitamin B 6; Vitamins
PubMed: 35802498
DOI: 10.1093/brain/awac248 -
Annual Review of Nutrition 2015Measures of B6 status are categorized as direct biomarkers and as functional biomarkers. Direct biomarkers measure B6 vitamers in plasma/serum, urine and erythrocytes,... (Review)
Review
Measures of B6 status are categorized as direct biomarkers and as functional biomarkers. Direct biomarkers measure B6 vitamers in plasma/serum, urine and erythrocytes, and among these plasma pyridoxal 5'-phosphate (PLP) is most commonly used. Functional biomarkers include erythrocyte transaminase activities and, more recently, plasma levels of metabolites involved in PLP-dependent reactions, such as the kynurenine pathway, one-carbon metabolism, transsulfuration (cystathionine), and glycine decarboxylation (serine and glycine). Vitamin B6 status is best assessed by using a combination of biomarkers because of the influence of potential confounders, such as inflammation, alkaline phosphatase activity, low serum albumin, renal function, and inorganic phosphate. Ratios between substrate-products pairs have recently been investigated as a strategy to attenuate such influence. These efforts have provided promising new markers such as the PAr index, the 3-hydroxykynurenine:xanthurenic acid ratio, and the oxoglutarate:glutamate ratio. Targeted metabolic profiling or untargeted metabolomics based on mass spectrometry allow the simultaneous quantification of a large number of metabolites, which are currently evaluated as functional biomarkers, using data reduction statistics.
Topics: Amino Acids; Biomarkers; Body Mass Index; Female; Health Status; Humans; Infant; Infant, Newborn; Inflammation; Kynurenine; Life Style; Male; Metabolome; Metabolomics; Nutritional Status; Pregnancy; Pyridoxal; Pyridoxal Phosphate; Pyridoxic Acid; Transaminases; Vitamin B 6; Vitamin B 6 Deficiency
PubMed: 25974692
DOI: 10.1146/annurev-nutr-071714-034330 -
International Journal of Molecular... Nov 2020Pathological neovascularization in the eye is a leading cause of blindness in all age groups from retinopathy of prematurity (ROP) in children to age-related macular...
Pathological neovascularization in the eye is a leading cause of blindness in all age groups from retinopathy of prematurity (ROP) in children to age-related macular degeneration (AMD) in the elderly. Inhibiting neovascularization via antivascular endothelial growth factor (VEGF) drugs has been used for the effective treatment. However, anti-VEGF therapies may cause development of chorioretinal atrophy as they affect a physiological amount of VEGF essential for retinal homeostasis. Furthermore, anti-VEGF therapies are still ineffective in some cases, especially in patients with AMD. Hypoxia-inducible factor (HIF) is a strong regulator of VEGF induction under hypoxic and other stress conditions. Our previous reports have indicated that HIF is associated with pathological retinal neovascularization in murine models of ROP and AMD, and HIF inhibition suppresses neovascularization by reducing an abnormal increase in VEGF expression. Along with this, we attempted to find novel effective HIF inhibitors from natural foods of our daily lives. Food ingredients were screened for prospective HIF inhibitors in ocular cell lines of 661W and ARPE-19, and a murine AMD model was utilized for examining suppressive effects of the ingredients on retinal neovascularization. As a result, rice bran and its component, vitamin B6 showed inhibitory effects on HIF activation and suppressed mRNA induction under a CoCl-induced pseudo-hypoxic condition. Dietary supplement of these significantly suppressed retinal neovascularization in the AMD model. These data suggest that rice bran could have promising therapeutic values in the management of pathological ocular neovascularization.
Topics: Aged; Animals; Cobalt; Disease Models, Animal; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Infant, Newborn; Macular Degeneration; Mice; Neovascularization, Pathologic; Oryza; Retina; Retinal Pigment Epithelium; Rice Bran Oil; Vascular Endothelial Growth Factor A; Vitamin B 6
PubMed: 33255657
DOI: 10.3390/ijms21238940 -
Nutrients May 2022The evidence regarding the intake of dietary folate, vitamin B6, and vitamin B12 in relation to mortality in the general population is limited. This study aimed to...
The evidence regarding the intake of dietary folate, vitamin B6, and vitamin B12 in relation to mortality in the general population is limited. This study aimed to examine the relationship between dietary intakes of folate, vitamin B6, and vitamin B12 in relation to all-cause and cause-specific mortality in a large U.S. cohort. This study included a total of 55,569 adults from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 1999-2014. Vital data were determined by linking with the National Death Index records through 31 December 2015. Cox proportional hazards models were used to investigate the relationships of all-cause and cause-specific mortality with dietary folate, vitamin B6, and vitamin B12 intake. Dietary intakes of folate and vitamin B6 were inversely associated with mortality from all-cause, cardiovascular disease, and cancer for men and with mortality from all-cause and cardiovascular disease for women. In men, the multivariable hazard ratios (95% confidence intervals) for the highest versus lowest quintiles of folate and vitamin B6 were 0.77 (0.71-0.85) and 0.79 (0.71-0.86) for all-cause mortality, 0.59 (0.48-0.72) and 0.69 (0.56-0.85) for CVD mortality, and 0.68 (0.56-0.84) and 0.73 (0.60-0.90) for cancer mortality, respectively. Among women, the multivariable hazard ratios (95% confidence intervals) for the highest versus lowest quintiles of folate and vitamin B6 were 0.86 (0.78-0.95) and 0.88 (0.80-0.97) for all-cause mortality and 0.53 (0.41-0.69) and 0.56 (0.44-0.73) for CVD mortality, respectively. No significant associations between dietary vitamin B12 and all-cause and cause-specific mortality were observed. In conclusion, higher dietary intakes of folate and vitamin B6 were significantly associated with lower all-cause and cardiovascular mortality. Our findings suggest that increasing the intake of folate and vitamin B6 may lower the mortality risk among U.S. adults.
Topics: Adult; Cardiovascular Diseases; Cause of Death; Female; Folic Acid; Humans; Male; Nutrition Surveys; Pyridoxine; Vitamin B 12; Vitamin B 6
PubMed: 35684053
DOI: 10.3390/nu14112253 -
European Journal of Nutrition Mar 2022Although overt vitamin B6 deficiency is rare, marginal vitamin B6 deficiency is frequent and occurs in a consistent proportion of the population. The marginal vitamin... (Review)
Review
Although overt vitamin B6 deficiency is rare, marginal vitamin B6 deficiency is frequent and occurs in a consistent proportion of the population. The marginal vitamin B6 deficiency appears to relate to an increased risk of inflammation-related diseases, such as cardiovascular diseases and cancers. Of all the cardiovascular diseases, heart failure is a complex clinical syndrome associated with a high mortality rate. So far, information regarding the cardioprotective mechanisms of vitamin B6 has been limited. Meanwhile, recent studies have revealed that vitamin B6 treatment increases cardiac levels of imidazole dipeptides (e.g., carnosine, anserine, and homocarnosine), histamine, and γ-aminobutyric acid (GABA) and suppresses P2X7 receptor-mediated NLRP3 inflammasome. These modulations may imply potential cardioprotective mechanisms of vitamin B6. These modulations may also be involved in the underlying mechanisms through which vitamin B6 suppresses oxidative stress and inflammation. This review provides an up-to-date evaluation of our current understanding of the cardioprotective mechanisms of vitamin B6.
Topics: Heart; Humans; Inflammasomes; Inflammation; Vitamin B 6; Vitamin B 6 Deficiency
PubMed: 34436643
DOI: 10.1007/s00394-021-02665-2