-
Journal of the Dermatology Nurses'... 2023The use of indoor UV tanning devices (also known as "indoor tanning") has declined in recent years. Less is known about use of dihydroxyacetone-containing products used...
The use of indoor UV tanning devices (also known as "indoor tanning") has declined in recent years. Less is known about use of dihydroxyacetone-containing products used for tanning (also known as "sunless tanning"). We analyzed data from the 2015 National Health Interview Survey. Analysis was limited to non-Hispanic White women ages 18-49 years. We estimated the proportion of women reporting spray tanning, self-applied lotion tanning, and indoor tanning and used weighted multivariable logistic regression models to examine the relationships between socio-demographic characteristics, skin cancer risk factors, and other cancer risk factors with sunless and indoor tanning. Overall, 17.7% of women reported sunless tanning. Lotion tanning was more common (15.3%) than spray tanning (6.8%), while 12.0% of women engaged in indoor tanning. Among sunless tanners, 23.7% also engaged in indoor tanning. Younger age, ever having a skin exam, skin reactions to the sun, binge drinking, and being at a healthy weight were associated with sunless tanning. While sunless tanning may be less harmful for skin cancer risk than indoor tanning, the frequency with which the two behaviors co-occur suggests that efforts to address societal pressures for women to alter their skin color may have important public health benefits.
PubMed: 38463180
DOI: 10.1097/jdn.0000000000000736 -
Angewandte Chemie (International Ed. in... Oct 2021The microbiome has a fundamental impact on the human host's physiology through the production of highly reactive compounds that can lead to disease development. One...
The microbiome has a fundamental impact on the human host's physiology through the production of highly reactive compounds that can lead to disease development. One class of such compounds are carbonyl-containing metabolites, which are involved in diverse biochemical processes. Mass spectrometry is the method of choice for analysis of metabolites but carbonyls are analytically challenging. Herein, we have developed a new chemical biology tool using chemoselective modification to overcome analytical limitations. Two isotopic probes allow for the simultaneous and semi-quantitative analysis at the femtomole level as well as qualitative analysis at attomole quantities that allows for detection of more than 200 metabolites in human fecal, urine and plasma samples. This comprehensive mass spectrometric analysis enhances the scope of metabolomics-driven biomarker discovery. We anticipate that our chemical biology tool will be of general use in metabolomics analysis to obtain a better understanding of microbial interactions with the human host and disease development.
Topics: Acetaldehyde; Acetamides; Acetone; Aldehydes; Butanones; Carbon; Carbon Isotopes; Dihydroxyacetone; Feces; Gastrointestinal Microbiome; Humans; Indicators and Reagents; Limit of Detection; Metabolomics; Urine
PubMed: 34339587
DOI: 10.1002/anie.202107101 -
PloS One 2024Glycerol dehydrogenase (GDH) catalyzes glycerol oxidation to dihydroxyacetone in a NAD+-dependent manner. As an initiator of the oxidative pathway of glycerol...
Glycerol dehydrogenase (GDH) catalyzes glycerol oxidation to dihydroxyacetone in a NAD+-dependent manner. As an initiator of the oxidative pathway of glycerol metabolism, a variety of functional and structural studies of GDH have been conducted previously. Structural studies revealed intriguing features of GDH, like the flexible β-hairpin and its significance. Another commonly reported structural feature is the enzyme's octameric oligomerization, though its structural details and functional significance remained unclear. Here, with a newly reported GDH structure, complexed with both NAD+ and glycerol, we analyzed the octamerization of GDH. Structural analyses revealed that octamerization reduces the structural dynamics of the N-domain, which contributes to more consistently maintaining a distance required for catalysis between the cofactor and substrate. This suggests that octamerization may play a key role in increasing the likelihood of the enzyme reaction by maintaining the ligands in an appropriate configuration for catalysis. These findings expand our understanding of the structure of GDH and its relation to the enzyme's activity.
Topics: NAD; Glycerol; Sugar Alcohol Dehydrogenases; Oxidation-Reduction; Glutamate Dehydrogenase
PubMed: 38483875
DOI: 10.1371/journal.pone.0300541 -
PLoS Pathogens Feb 2024The bacterial determinants that facilitate Mycobacterium tuberculosis (Mtb) adaptation to the human host environment are poorly characterized. We have sought to decipher...
The bacterial determinants that facilitate Mycobacterium tuberculosis (Mtb) adaptation to the human host environment are poorly characterized. We have sought to decipher the pressures facing the bacterium in vivo by assessing Mtb genes that are under positive selection in clinical isolates. One of the strongest targets of selection in the Mtb genome is lldD2, which encodes a quinone-dependent L-lactate dehydrogenase (LldD2) that catalyzes the oxidation of lactate to pyruvate. Lactate accumulation is a salient feature of the intracellular environment during infection and lldD2 is essential for Mtb growth in macrophages. We determined the extent of lldD2 variation across a set of global clinical isolates and defined how prevalent mutations modulate Mtb fitness. We show the stepwise nature of lldD2 evolution that occurs as a result of ongoing lldD2 selection in the background of ancestral lineage-defining mutations and demonstrate that the genetic evolution of lldD2 additively augments Mtb growth in lactate. Using quinone-dependent antibiotic susceptibility as a functional reporter, we also find that the evolved lldD2 mutations functionally increase the quinone-dependent activity of LldD2. Using 13C-lactate metabolic flux tracing, we find that lldD2 is necessary for robust incorporation of lactate into central carbon metabolism. In the absence of lldD2, label preferentially accumulates in dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P) and is associated with a discernible growth defect, providing experimental evidence for accrued lactate toxicity via the deleterious buildup of sugar phosphates. The evolved lldD2 variants increase lactate incorporation to pyruvate while altering triose phosphate flux, suggesting both an anaplerotic and detoxification benefit to lldD2 evolution. We further show that the mycobacterial cell is transcriptionally sensitive to the changes associated with altered lldD2 activity which affect the expression of genes involved in cell wall lipid metabolism and the ESX- 1 virulence system. Together, these data illustrate a multifunctional role of LldD2 that provides context for the selective advantage of lldD2 mutations in adapting to host stress.
Topics: Humans; Mycobacterium tuberculosis; L-Lactate Dehydrogenase; Lactic Acid; Pyruvates; Quinones; Phosphates
PubMed: 38422159
DOI: 10.1371/journal.ppat.1012050 -
Microbiome Feb 2022Establishing fecal microbiota transplantation (FMT) to prevent multifactorial diarrhea in calves is challenging because of the differences in farm management practices,...
BACKGROUND
Establishing fecal microbiota transplantation (FMT) to prevent multifactorial diarrhea in calves is challenging because of the differences in farm management practices, the lack of optimal donors, and recipient selection. In this study, the underlying factors of successful and unsuccessful FMT treatment cases are elucidated, and the potential markers for predicting successful FMT are identified using fecal metagenomics via 16S rRNA gene sequencing, fecal metabolomics via capillary electrophoresis time-of-flight mass spectrometry, and machine learning approaches.
RESULTS
Specifically, 20 FMT treatment cases, in which feces from healthy donors were intrarectally transferred into recipient diarrheal calves, were conducted with a success rate of 70%. Selenomonas was identified as a microorganism genus that showed significant donor-recipient compatibility in successful FMT treatments. A strong positive correlation between the microbiome and metabolome data, which is a prerequisite factor for FMT success, was confirmed by Procrustes analysis in successful FMT (r = 0.7439, P = 0.0001). Additionally, weighted gene correlation network analysis confirmed the positively or negatively correlated pairs of bacterial taxa (family Veillonellaceae) and metabolomic features (i.e., amino acids and short-chain fatty acids) responsible for FMT success. Further analysis aimed at establishing criteria for donor selection identified the genus Sporobacter as a potential biomarker in successful donor selection. Low levels of metabolites, such as glycerol 3-phosphate, dihydroxyacetone phosphate, and isoamylamine, in the donor or recipients prior to FMT, are predicted to facilitate FMT.
CONCLUSIONS
Overall, we provide the first substantial evidence of the factors related to FMT success or failure; these findings could improve the design of future microbial therapeutics for treating diarrhea in calves. Video abstract.
Topics: Animals; Cattle; Diarrhea; Fecal Microbiota Transplantation; Feces; RNA, Ribosomal, 16S; Treatment Outcome
PubMed: 35184756
DOI: 10.1186/s40168-021-01217-4 -
Proceedings of the National Academy of... May 2023Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) contains an active site Cys and is one of the most sensitive cellular enzymes to oxidative inactivation and redox...
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) contains an active site Cys and is one of the most sensitive cellular enzymes to oxidative inactivation and redox regulation. Here, we show that inactivation by hydrogen peroxide is strongly enhanced in the presence of carbon dioxide/bicarbonate. Inactivation of isolated mammalian GAPDH by HO increased with increasing bicarbonate concentration and was sevenfold faster in 25 mM (physiological) bicarbonate compared with bicarbonate-free buffer of the same pH. HO reacts reversibly with CO to form a more reactive oxidant, peroxymonocarbonate (HCO), which is most likely responsible for the enhanced inactivation. However, to account for the extent of enhancement, we propose that GAPDH must facilitate formation and/or targeting of HCO to promote its own inactivation. Inactivation of intracellular GAPDH was also strongly enhanced by bicarbonate: treatment of Jurkat cells with 20 µM HO in 25 mM bicarbonate buffer for 5 min caused almost complete GAPDH inactivation, but no loss of activity when bicarbonate was not present. HO-dependent GAPDH inhibition in bicarbonate buffer was observed even in the presence of reduced peroxiredoxin 2 and there was a significant increase in cellular glyceraldehyde-3-phosphate/dihydroxyacetone phosphate. Our results identify an unrecognized role for bicarbonate in enabling HO to influence inactivation of GAPDH and potentially reroute glucose metabolism from glycolysis to the pentose phosphate pathway and NAPDH production. They also demonstrate what could be wider interplay between CO and HO in redox biology and the potential for variations in CO metabolism to influence oxidative responses and redox signaling.
Topics: Humans; Animals; Hydrogen Peroxide; Carbon Dioxide; Bicarbonates; Glyceraldehyde-3-Phosphate Dehydrogenases; Peroxiredoxins; Oxidation-Reduction; Mammals
PubMed: 37098065
DOI: 10.1073/pnas.2221047120 -
Frontiers in Nutrition 2023Polydatin is a biologically active compound found in mulberries, grapes, and , and it has uric acid-lowering effects. However, its urate-lowering effects and the...
INTRODUCTION
Polydatin is a biologically active compound found in mulberries, grapes, and , and it has uric acid-lowering effects. However, its urate-lowering effects and the molecular mechanisms underlying its function require further study.
METHODS
In this study, a hyperuricemic rat model was established to assess the effects of polydatin on uric acid levels. The body weight, serum biochemical indicators, and histopathological parameters of the rats were evaluated. A UHPLC-Q-Exactive Orbitrap mass spectrometry-based metabolomics approach was applied to explore the potential mechanisms of action after polydatin treatment.
RESULTS
The results showed a trend of recovery in biochemical indicators after polydatin administration. In addition, polydatin could alleviate damage to the liver and kidneys. Untargeted metabolomics analysis revealed clear differences between hyperuricemic rats and the control group. Fourteen potential biomarkers were identified in the model group using principal component analysis and orthogonal partial least squares discriminant analysis. These differential metabolites are involved in amino acid, lipid, and energy metabolism. Of all the metabolites, the levels of L-phenylalanine, L-leucine, -butanoylcarnitine, and dihydroxyacetone phosphate decreased, and the levels of L-tyrosine, sphinganine, and phytosphingosine significantly increased in hyperuricemic rats. After the administration of polydatin, the 14 differential metabolites could be inverted to varying degrees by regulating the perturbed metabolic pathway.
CONCLUSION
This study has the potential to enhance our understanding of the mechanisms of hyperuricemia and demonstrate that polydatin is a promising potential adjuvant for lowering uric acid levels and alleviating hyperuricemia-related diseases.
PubMed: 37187876
DOI: 10.3389/fnut.2023.1117460 -
Brazilian Journal of Biology = Revista... 2021The most common form of psycho-social dysfunction is anxiety with depression being related closely without any age bar. They are present with combined state of sadness,...
The most common form of psycho-social dysfunction is anxiety with depression being related closely without any age bar. They are present with combined state of sadness, confusion, stress, fear etc. Glyoxalase system contains enzyme named glyoxalase 1 (GLO1).It is a metabolic pathway which detoxifies alpha-oxo-aldehydes, particularly methylglyoxal (MG). Methylglyoxal is mainly made by the breakdown of the glycolytic intermediates, glyceraldehyde-3-phosphates and dihydroxyacetone phosphate. Glyoxylase-1 expression is also related with anxiety behavior. A casual role or GLO-1 in anxiety behavior by using viral vectors for over expression in the anterior cingulate cortex was found and it was found that local GLO-1 over expression increased anxiety behavior. The present study deals with the molecular mechanism of protective activity of eugenol against anxiolytic disorder. A pre-clinical animal study was performed on 42 BALB/c mice. Animals were given stress through conventional restrain model. The mRNA expression of GLO-1 was analyzed by real time RT-PCR. Moreover, the GLO-1 protein expression was also examined by immunohistochemistry in whole brain and mean density was calculated. The mRNA and protein expressions were found to be increased in animals given anxiety as compared to the normal control. Whereas, the expressions were decreased in the animals treated with eugenol and its liposome-based nanocarriers in a dose dependent manner. However, the results were better in animals treated with nanocarriers as compared to the compound alone. It is concluded that the eugenol and its liposome-based nanocarriers exert anxiolytic activity by down-regulating GLO-1 protein expression in mice.
Topics: Animals; Anxiety; Eugenol; Lactoylglutathione Lyase; Liposomes; Mice; Mice, Inbred BALB C
PubMed: 34669914
DOI: 10.1590/1519-6984.251219 -
PLoS Pathogens Mar 2022We have identified GpsA, a predicted glycerol-3-phosphate dehydrogenase, as a virulence factor in the Lyme disease spirochete Borrelia (Borreliella) burgdorferi: GpsA is...
The glycerol-3-phosphate dehydrogenases GpsA and GlpD constitute the oxidoreductive metabolic linchpin for Lyme disease spirochete host infectivity and persistence in the tick.
We have identified GpsA, a predicted glycerol-3-phosphate dehydrogenase, as a virulence factor in the Lyme disease spirochete Borrelia (Borreliella) burgdorferi: GpsA is essential for murine infection and crucial for persistence of the spirochete in the tick. B. burgdorferi has a limited biosynthetic and metabolic capacity; the linchpin connecting central carbohydrate and lipid metabolism is at the interconversion of glycerol-3-phosphate and dihydroxyacetone phosphate, catalyzed by GpsA and another glycerol-3-phosphate dehydrogenase, GlpD. Using a broad metabolomics approach, we found that GpsA serves as a dominant regulator of NADH and glycerol-3-phosphate levels in vitro, metabolic intermediates that reflect the cellular redox potential and serve as a precursor for lipid and lipoprotein biosynthesis, respectively. Additionally, GpsA was required for survival under nutrient stress, regulated overall reductase activity and controlled B. burgdorferi morphology in vitro. Furthermore, during in vitro nutrient stress, both glycerol and N-acetylglucosamine were bactericidal to B. burgdorferi in a GlpD-dependent manner. This study is also the first to identify a suppressor mutation in B. burgdorferi: a glpD deletion restored the wild-type phenotype to the pleiotropic gpsA mutant, including murine infectivity by needle inoculation at high doses, survival under nutrient stress, morphological changes and the metabolic imbalance of NADH and glycerol-3-phosphate. These results illustrate how basic metabolic functions that are dispensable for in vitro growth can be essential for in vivo infectivity of B. burgdorferi and may serve as attractive therapeutic targets.
Topics: Animals; Bacterial Proteins; Borrelia burgdorferi; Borrelia burgdorferi Group; Glycerol; Glycerolphosphate Dehydrogenase; Lyme Disease; Mice; NAD; Oxidation-Reduction; Phosphates; Ticks
PubMed: 35255112
DOI: 10.1371/journal.ppat.1010385 -
IScience Dec 2022D-Tagatose is a promising low-calorie sugar-substituting sweetener in the food industry. Most ingested D-tagatose is fermented by intestinal microorganisms. Until now,...
D-Tagatose is a promising low-calorie sugar-substituting sweetener in the food industry. Most ingested D-tagatose is fermented by intestinal microorganisms. Until now, has been considered incapable of growing on D-tagatose. Here, we discovered a gene cluster involved in D-tagatose utilization in . The chromosome of the intestinal probiotic Nissle 1917 contains a six-gene cluster encoding the ABC transporter, D-tagatose kinase, D-tagatose-bisphosphate aldolase, and putative aldose 1-epimerase. The functionality of the gene cluster was experimentally validated. Based on single-gene deletions, D-tagatose dissimilation occurs via D-tagatose 6-phosphate to D-tagatose 1,6-bisphosphate to D-glyceraldehyde 3-phosphate plus dihydroxyacetone phosphate. Remarkably, this gene cluster was located in 93% of the completely sequenced genomes of the B2 phylogroup, which contains the majority of extraintestinal pathogenic and adherent-invasive strains prevalent in patients with inflammatory bowel disease. This highlights the importance of understanding the clinical significance of D-tagatose in microbiota alterations.
PubMed: 36479150
DOI: 10.1016/j.isci.2022.105655