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Photodiagnosis and Photodynamic Therapy Mar 2023Patients with erythropoietic protoporphyria (EPP) are hypersensitive to long wave ultraviolet (UVA) radiation and visible light and they experience severe skin pain by... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients with erythropoietic protoporphyria (EPP) are hypersensitive to long wave ultraviolet (UVA) radiation and visible light and they experience severe skin pain by light exposure. The patients have very limited treatment options. Sunless skin tanning with dihydroxyacetone (DHA) is now being investigated as a possible treatment modality of skin photosensitivity in EPP.
METHODS
We simulated the theoretical light protection factor provided by DHA application. In addition, we present 19 cases with EPP who were treated at our department with DHA weekly during spring and summer from 2018 to 2021 inclusive.
RESULTS
The protection factor against UVA and visible light was estimated to approximately two. Out of the 19 patients with EPP who were treated with DHA in 2018, 11 patients experienced a sustained good effect and continued to use the treatment on a weekly basis in the spring and summer of 2019, 2020, and 2021.
CONCLUSION AND PERSPECTIVES
Both the theoretical estimates and the uncontrolled study suggest that sunless tanning with DHA reduces photosensitivity in patients with EPP. Our hypothesis is that skin treated with DHA can tolerate twice the daylight dose compared to untreated skin before onset of skin symptoms. To validate this conclusion, we plan a randomized clinical trial to determine the effect of DHA application to reduce photosensitivity in patients with EPP under controlled clinical conditions. The study protocol for this trial is presented in the paper.
Topics: Humans; Protoporphyria, Erythropoietic; Dihydroxyacetone; Photochemotherapy; Photosensitizing Agents; Light; Photosensitivity Disorders
PubMed: 36690194
DOI: 10.1016/j.pdpdt.2023.103302 -
Theranostics 2023Despite growing evidence for mitochondria's involvement in cancer, the roles of specific metabolic components outside the respiratory complex have been little explored....
Despite growing evidence for mitochondria's involvement in cancer, the roles of specific metabolic components outside the respiratory complex have been little explored. We conducted metabolomic studies on mitochondrial DNA (mtDNA)-deficient (ρ0) cancer cells with lower proliferation rates to clarify the undefined roles of mitochondria in cancer growth. Despite extensive metabolic downregulation, ρ0 cells exhibited high glycerol-3-phosphate (G3P) level, due to low activity of mitochondrial glycerol-3-phosphate dehydrogenase (GPD2). Knockout (KO) of GPD2 resulted in cell growth suppression as well as inhibition of tumor progression Surprisingly, this was unrelated to the conventional bioenergetic function of GPD2. Instead, multi-omics results suggested major changes in ether lipid metabolism, for which GPD2 provides dihydroxyacetone phosphate (DHAP) in ether lipid biosynthesis. GPD2 KO cells exhibited significantly lower ether lipid level, and their slower growth was rescued by supplementation of a DHAP precursor or ether lipids. Mechanistically, ether lipid metabolism was associated with Akt pathway, and the downregulation of Akt/mTORC1 pathway due to GPD2 KO was rescued by DHAP supplementation. Overall, the GPD2-ether lipid-Akt axis is newly described for the control of cancer growth. DHAP supply, a non-bioenergetic process, may constitute an important role of mitochondria in cancer.
Topics: Energy Metabolism; Ethers; Glycerolphosphate Dehydrogenase; Mitochondria; Proto-Oncogene Proteins c-akt; Animals; Mice; Neoplasms; Humans
PubMed: 36632231
DOI: 10.7150/thno.75973 -
ACS Omega Dec 2022Sunless tanning has become incredibly prevalent due to the increasing fashionable demand and the awareness of photodamage risks. The brown pigments are induced by...
Sunless tanning has become incredibly prevalent due to the increasing fashionable demand and the awareness of photodamage risks. The brown pigments are induced by dihydroxyacetone (DHA) and amino groups in the stratum corneum (SC) of skin via the Maillard reaction. While most studies concerning sunless tanning reactions have focused on free amino acids (AAs), little information is available on the impact of the side chain of AAs or proteins on this important reaction in cosmetic chemistry. To explore the reactivity and color development kinetics of different types of amino groups, three basic free AAs (Arg, His, and Lys) and three Nα-protected AAs (Boc-Arg-OH, Boc-His-OH, and Boc-Lys-OH) were used to react with DHA using a simplified model system at different reaction times, pH, and temperatures. Full factorial experiments were employed to design and analyze the effects of these three factors. The browning intensity and color characteristics were quantitatively evaluated. The factorial experiments showed that temperature had the most significant influence on the browning intensity and played a dominant role in the interactions with the reaction time and pH. It was found, for the first time, that Arg and His reacted with DHA more rapidly than Boc-Arg-OH and Boc-His-OH, while Boc-Lys-OH developed a stronger color than Lys under the same conditions, suggesting that ε-NH of a lysine residue in peptides or proteins of SC may play a crucial role in the color development of DHA tanning. This study not only clearly illustrates the capability of the side chain of AAs to produce colored compounds but also provides a deeper understanding of DHA tanning.
PubMed: 36530253
DOI: 10.1021/acsomega.2c06124 -
Biomedicine & Pharmacotherapy =... Feb 2023Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are characterized by skin photosensitivity caused by accumulation of protoporphyrin IX. We aimed to... (Review)
Review
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are characterized by skin photosensitivity caused by accumulation of protoporphyrin IX. We aimed to review the clinical evidence of efficacy and safety of skin photosensitivity treatments in individuals with EPP or XLP. We systematically searched MEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov. A total of 40 studies with data on 18 treatment modalities were included. Comprehensive treatment safety data were obtained from the European Medicines Agency and the United States Food and Drug Administration. The studies used different outcome measures to evaluate the sensitivity without a generally accepted method to assess treatment effect on skin photosensitivity. Of the included studies, 13 were controlled trials. Gathered, the trials showed moderate positive effect of inorganic sunscreen application and subcutaneous implant of afamelanotide and no effect of organic sunscreen application, or oral treatment with beta-carotene, cysteine, N-acetylcysteine, vitamin C, or warfarin. Studies without control groups suggested treatment effect of foundation cream, dihydroxyacetone/lawsone cream, narrow-band ultraviolet B phototherapy, erythrocyte transfusion, extracorporeal erythrocyte photodynamic therapy, or oral treatment with zinc sulphate, terfenadine, cimetidine, or canthaxanthin, but the real effect is uncertain. Assessment of treatment effect on photosensitivity in patients with EPP or XLP carries a high risk of bias since experienced photosensitivity varies with both weather conditions, exposure pattern, and pigmentation. Controlled trials of promising treatment options are important although challenging in this small patient population.
Topics: United States; Humans; Protoporphyria, Erythropoietic; Sunscreening Agents; Photosensitivity Disorders; Genetic Diseases, X-Linked; Protoporphyrins
PubMed: 36525819
DOI: 10.1016/j.biopha.2022.114132 -
Frontiers in Microbiology 2022Glycerol is a readily available and low-cost simple polyol compound, which can be used as a carbon source for microorganisms to produce various value-added products....
Glycerol is a readily available and low-cost simple polyol compound, which can be used as a carbon source for microorganisms to produce various value-added products. Understanding the underlying regulatory mechanism in glycerol metabolism is critical for making better use of glycerol for diverse applications. In a few reported strains, the glycerol utilization gene cluster ( operon) was shown to be regulated by the IclR family transcriptional regulator GylR. However, the molecular regulatory mechanism mediated by GylR has not been fully elucidated. In this study, we first analyzed the available genomes in the NCBI Genome database, and found that the operon-like gene clusters are conserved in and several other genera of . By taking NRRL 3585 as a model system, we identified that GylR represses the expressions of operon and by directly binding to their promoter regions. Both glycerol-3-phosphate and dihydroxyacetone phosphate can induce the dissociation of GylR from its binding sequences. Furthermore, we identified a minimal essential operator site (a palindromic 18-bp sequence) of GylR-like regulators in . Our study for the first time reported the binding sequences and effector molecules of GylR-like proteins in . The molecular regulatory mechanism mediated by GylR presumably exists widely in . Our findings would facilitate the design of glycerol utilization pathways for producing valuable products. Moreover, our study provided new basic elements for the development of glycerol-inducible regulatory tools for synthetic biology research in the future.
PubMed: 36504789
DOI: 10.3389/fmicb.2022.1078293 -
Molecules (Basel, Switzerland) Nov 2022In this paper, evidence is provided that the model reaction of aqueous dihydroxyacetone (DHA) conversion is as sensitive to the TiO catalysts' basicity as to their...
In this paper, evidence is provided that the model reaction of aqueous dihydroxyacetone (DHA) conversion is as sensitive to the TiO catalysts' basicity as to their acidity. Two parallel pathways transformed DHA: while the pathway catalyzed by Lewis acid sites gave pyruvaldehyde (PA) and lactic acid (LA), the base-catalyzed route afforded fructose. This is demonstrated on a series of six commercial TiO samples and further confirmed by using two reference catalysts: niobic acid (NbOH), an acid catalyst, and a hydrotalcite (MgAlO), a basic catalyst. The original acid-base properties of the six commercial TiO with variable structure and texture were investigated first by conventional methods in gas phase (FTIR or microcalorimetry of pyridine, NH and CO adsorption). A linear relationship between the initial rates of DHA condensation into hexoses and the total basic sites densities is highlighted accounting for the water tolerance of the TiO basic sites whatever their strength. Rutile TiO samples were the most basic ones. Besides, only the strongest TiO Lewis acid sites were shown to be water tolerant and efficient for PA and LA formation.
Topics: Dihydroxyacetone; Water; Lewis Acids; Catalysis; Adsorption; Lactic Acid
PubMed: 36500265
DOI: 10.3390/molecules27238172 -
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 -
Dihydroxyacetone suppresses mTOR nutrient signaling and induces mitochondrial stress in liver cells.PloS One 2022Dihydroxyacetone (DHA) is the active ingredient in sunless tanning products and a combustion product from e-juices in electronic cigarettes (e-cigarettes). DHA is...
Dihydroxyacetone (DHA) is the active ingredient in sunless tanning products and a combustion product from e-juices in electronic cigarettes (e-cigarettes). DHA is rapidly absorbed in cells and tissues and incorporated into several metabolic pathways through its conversion to dihydroxyacetone phosphate (DHAP). Previous studies have shown DHA induces cell cycle arrest, reactive oxygen species, and mitochondrial dysfunction, though the extent of these effects is highly cell-type specific. Here, we investigate DHA exposure effects in the metabolically active, HepG3 (C3A) cell line. Metabolic and mitochondrial changes were evaluated by characterizing the effects of DHA in metabolic pathways and nutrient-sensing mechanisms through mTOR-specific signaling. We also examined cytotoxicity and investigated the cell death mechanism induced by DHA exposure in HepG3 cells. Millimolar doses of DHA were cytotoxic and suppressed glycolysis and oxidative phosphorylation pathways. Nutrient sensing through mTOR was altered at both short and long time points. Increased mitochondrial reactive oxygen species (ROS) and mitochondrial-specific injury induced cell cycle arrest and cell death through a non-classical apoptotic mechanism. Despite its carbohydrate nature, millimolar doses of DHA are toxic to liver cells and may pose a significant health risk when higher concentrations are absorbed through e-cigarettes or spray tanning.
Topics: Dihydroxyacetone; Electronic Nicotine Delivery Systems; Reactive Oxygen Species; Mitochondria; Liver
PubMed: 36472985
DOI: 10.1371/journal.pone.0278516 -
Communications Biology Nov 2022Bacteria and Eucarya utilize the non-oxidative pentose phosphate pathway to direct the ribose moieties of nucleosides to central carbon metabolism. Many archaea do not...
Bacteria and Eucarya utilize the non-oxidative pentose phosphate pathway to direct the ribose moieties of nucleosides to central carbon metabolism. Many archaea do not possess this pathway, and instead, Thermococcales utilize a pentose bisphosphate pathway involving ribose-1,5-bisphosphate (R15P) isomerase and ribulose-1,5-bisphosphate (RuBP) carboxylase/oxygenase (Rubisco). Intriguingly, multiple genomes from halophilic archaea seem only to harbor R15P isomerase, and do not harbor Rubisco. In this study, we identify a previously unrecognized nucleoside degradation pathway in halophilic archaea, composed of guanosine phosphorylase, ATP-dependent ribose-1-phosphate kinase, R15P isomerase, RuBP phosphatase, ribulose-1-phosphate aldolase, and glycolaldehyde reductase. The pathway converts the ribose moiety of guanosine to dihydroxyacetone phosphate and ethylene glycol. Although the metabolic route from guanosine to RuBP via R15P is similar to that of the pentose bisphosphate pathway in Thermococcales, the downstream route does not utilize Rubisco and is unique to halophilic archaea.
Topics: Ribulose-Bisphosphate Carboxylase; Ribose; Pentoses; Archaea; Guanosine; Phosphates
PubMed: 36434094
DOI: 10.1038/s42003-022-04247-2 -
Polymers Nov 2022Biomass rapid pyrolysis technology is easy to implement in continuous production and industrial application, and has become one of the leading technologies in the field...
Biomass rapid pyrolysis technology is easy to implement in continuous production and industrial application, and has become one of the leading technologies in the field of world renewable energy development. Agricultural and forestry waste is an important resource of renewable energy in China. In general, abandoned leaves in forest areas cause serious waste of resources. Its utilization may help to settle the problems of energy deficiency and environment pollution. In this study, Bunge leaves (A. Bunge) are used as the research object to study the pyrolysis and extract. The results showed that there are a lot of bioactive components in A. Bunge leaves extract, including acetamide, 5-hydroxymethylfurfural, R-limonene, d-mannose, and dihydroxyacetone. The active components of A. Bunge leaves supply scientific evidence for the exploration and exploitation of this plant. The pyrolysis products of A. Bunge leaves are rich in organic acids, aldehydes, and ketones, which means that A. Bunge leaves can be used as a crude material for the manufacturing of bio-oil or bio-fuel. The pyrolysis products include batilol, pregnenolone, benzoic acid, butyrolactone, and propanoic acid, which can be used in biological medicine, chemical crude materials, and industrial raw material reagents. Therefore, A. Bunge leaves can be used as a good crude material for bio-oil or biofuel production. Combining A. Bunge leaves and fast pyrolysis methods can effectively solve the problem of forestry and agricultural residues in the future.
PubMed: 36433130
DOI: 10.3390/polym14225003