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Nutrients May 2024Phenylketonuria is an inherited metabolic disorder that leads to neurobehavioral dysfunction. The main treatment is a low-phenylalanine diet and/or the cofactor... (Comparative Study)
Comparative Study
Phenylketonuria is an inherited metabolic disorder that leads to neurobehavioral dysfunction. The main treatment is a low-phenylalanine diet and/or the cofactor tetrahydrobiopterin. Regular outpatient follow-up care and measurement of the phenylalanine levels in the blood are required. We aimed to analyze the economic burden of phenylketonuria on families and the state. The patients with phenylketonuria were divided into three groups according to their treatment: a low-phenylalanine diet group ( = 50), a tetrahydrobiopterin group ( = 44), and a group taking tetrahydrobiopterin together with the diet ( = 25). A comparative cost analysis was carried out. The annual economic burden to the state was calculated to average EUR 18,801 ± 15,345 and was lowest in the diet group, then in the tetrahydrobiopterin group, and highest in the tetrahydrobiopterin + diet group ( < 0.001). Out-of-pocket costs amounted to EUR 1531 ± 1173 per year, and indirect losses averaged EUR 2125 ± 1930 per year for all families. The economic loss was significantly lower in the families taking tetrahydrobiopterin than in the other groups ( = 0.001). The combined use of medical nutrition and BH4 treatments has been shown to increase the economic burden on the state. Reimbursing low-protein products and increasing the number of patients eligible for financial allowances may reduce the economic burden on families.
Topics: Phenylketonurias; Humans; Biopterins; Male; Female; Phenylalanine; Child; Turkey; Child, Preschool; Cost of Illness; Adolescent; Costs and Cost Analysis; Adult; Infant; Young Adult; Health Expenditures; Health Care Costs
PubMed: 38794682
DOI: 10.3390/nu16101444 -
Sensors (Basel, Switzerland) May 2024The origin of agricultural products is crucial to their quality and safety. This study explored the differences in chemical composition and structure of rice from...
The origin of agricultural products is crucial to their quality and safety. This study explored the differences in chemical composition and structure of rice from different origins using fluorescence detection technology. These differences are mainly affected by climate, environment, geology and other factors. By identifying the fluorescence characteristic absorption peaks of the same rice seed varieties from different origins, and comparing them with known or standard samples, this study aims to authenticate rice, protect brands, and achieve traceability. The study selected the same variety of rice seed planted in different regions of Jilin Province in the same year as samples. Fluorescence spectroscopy was used to collect spectral data, which was preprocessed by normalization, smoothing, and wavelet transformation to remove noise, scattering, and burrs. The processed spectral data was used as input for the long short-term memory (LSTM) model. The study focused on the processing and analysis of rice spectra based on NZ-WT-processed data. To simplify the model, uninformative variable elimination (UVE) and successive projections algorithm (SPA) were used to screen the best wavelengths. These wavelengths were used as input for the support vector machine (SVM) prediction model to achieve efficient and accurate predictions. Within the fluorescence spectral range of 475-525 nm and 665-690 nm, absorption peaks of nicotinamide adenine dinucleotide (NADPH), riboflavin (B2), starch, and protein were observed. The origin tracing prediction model established using SVM exhibited stable performance with a classification accuracy of up to 99.5%.The experiment demonstrated that fluorescence spectroscopy technology has high discrimination accuracy in tracing the origin of rice, providing a new method for rapid identification of rice origin.
Topics: Oryza; Spectrometry, Fluorescence; Support Vector Machine; Algorithms; Riboflavin; NADP; Starch; Seeds
PubMed: 38793849
DOI: 10.3390/s24102994 -
International Journal of Molecular... May 2024ferredoxin:NADP oxidoreductase (FNR) is a thioredoxin reductase-type FNR whose redox properties and reactivity with nonphysiological electron acceptors have been...
ferredoxin:NADP oxidoreductase (FNR) is a thioredoxin reductase-type FNR whose redox properties and reactivity with nonphysiological electron acceptors have been scarcely characterized. On the basis of redox reactions with 3-acetylpyridine adenine dinucleotide phosphate, the two-electron reduction midpoint potential of the flavin adenine dinucleotide (FAD) cofactor was estimated to be -0.240 V. Photoreduction using 5-deazaflavin mononucleotide (5-deazaFMN) as a photosensitizer revealed that the difference in the redox potentials between the first and second single-electron transfer steps was 0.024 V. We examined the mechanisms of the reduction of several different groups of non-physiological electron acceptors catalyzed by FNR. The reactivity of quinones and aromatic -oxides toward FNR increased when increasing their single-electron reduction midpoint redox potentials. The reactivity of nitroaromatic compounds was lower due to their lower electron self-exchange rate, but it exhibited the same trend. A mixed single- and two-electron reduction reaction was characteristic of quinones, whereas reactions involving nitroaromatics proceeded exclusively via the one-electron reduction reaction. The oxidation of FADH to FAD is the rate-limiting step during the oxidation of fully reduced FAD. The calculated electron transfer distances in the reaction with nitroaromatics were close to those of other FNRs including the plant-type enzymes, thus demonstrating their similar active site accessibility to low-molecular-weight oxidants despite the fundamental differences in their structures.
Topics: Oxidation-Reduction; Ferredoxin-NADP Reductase; Bacillus subtilis; Xenobiotics; Flavin-Adenine Dinucleotide; Bacterial Proteins; Potentiometry; Oxidants; Quinones; Electron Transport
PubMed: 38791410
DOI: 10.3390/ijms25105373 -
Fullerene C Conjugate with Folic Acid and Polyvinylpyrrolidone for Targeted Delivery to Tumor Cells.International Journal of Molecular... May 2024The use of targeted drug delivery systems, including those based on selective absorption by certain receptors on the surface of the target cell, can lead to a decrease...
The use of targeted drug delivery systems, including those based on selective absorption by certain receptors on the surface of the target cell, can lead to a decrease in the minimum effective dose and the accompanying toxicity of the drug, as well as an increase in therapeutic efficacy. A fullerene C conjugate (FA-PVP-C) with polyvinylpyrrolidone (PVP) as a biocompatible spacer and folic acid (FA) as a targeting ligand for tumor cells with increased expression of folate receptors (FR) was obtained. Using C NMR spectroscopy, FT-IR, UV-Vis spectrometry, fluorometry and thermal analysis, the formation of the conjugate was confirmed and the nature of the binding of its components was established. The average particle sizes of the conjugate in aqueous solutions and cell culture medium were determined using dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). The FA-PVP-C showed antiradical activity against DPPH, OH and O, but at the same time, it was shown to generate O. It was found that the conjugate in the studied concentration range (up to 200 μg/mL) is non-toxic in vitro and does not affect the cell cycle. To confirm the ability of the conjugate to selectively accumulate through folate-mediated endocytosis, its uptake into cells was analyzed by flow cytometry and confocal microscopy. It was shown that the conjugate is less absorbed by A549 cells with low FR expression than by HeLa, which has a high level of expression of this receptor.
Topics: Folic Acid; Humans; Povidone; Fullerenes; Drug Delivery Systems; Cell Line, Tumor; A549 Cells; HeLa Cells; Particle Size
PubMed: 38791388
DOI: 10.3390/ijms25105350 -
International Journal of Molecular... May 2024Previous studies have documented that FOLFOX and XELOX therapies negatively impact the metabolism of skeletal muscle and extra-muscle districts. This pilot study tested...
Previous studies have documented that FOLFOX and XELOX therapies negatively impact the metabolism of skeletal muscle and extra-muscle districts. This pilot study tested whether three-month FOLFOX or XELOX therapy produced changes in plasma amino acid levels (PAAL) (an estimation of whole-body amino acid metabolism) and in plasma levels of malondialdehyde (MDA), a marker of lipid hyper oxidation. Fourteen ambulatory, resected patients with colorectal cancer scheduled to receive FOLFOX (n = 9) or XELOX (n = 5) therapy, after overnight fasting, underwent peripheral venous blood sampling, to determine PAAL and MDA before, during, and at the end of three-month therapy. Fifteen healthy matched subjects (controls) only underwent measures of PAAL at baseline. The results showed changes in 87.5% of plasma essential amino acids (EAAs) and 38.4% of non-EAAs in patients treated with FOLFOX or XELOX. These changes in EAAs occurred in two opposite directions: EAAs decreased with FOLFOX and increased or did not decrease with XELOX (interactions: from = 0.034 to = 0.003). Baseline plasma MDA levels in both FOLFOX and XELOX patients were above the normal range of values, and increased, albeit not significantly, during therapy. In conclusion, three-month FOLFOX or XELOX therapy affected plasma EAAs differently but not the baseline MDA levels, which were already high.
Topics: Humans; Colorectal Neoplasms; Male; Female; Middle Aged; Amino Acids; Antineoplastic Combined Chemotherapy Protocols; Aged; Fluorouracil; Oxaloacetates; Leucovorin; Capecitabine; Malondialdehyde; Deoxycytidine; Organoplatinum Compounds; Pilot Projects; Oxidation-Reduction; Adult; Lipid Peroxidation; Lipid Metabolism
PubMed: 38791339
DOI: 10.3390/ijms25105300 -
International Journal of Molecular... May 2024The published data on the vitamin status of patients with phenylketonuria (PKU) is contradictory; therefore, this systematic review and meta-analysis evaluated the... (Meta-Analysis)
Meta-Analysis Review
The published data on the vitamin status of patients with phenylketonuria (PKU) is contradictory; therefore, this systematic review and meta-analysis evaluated the vitamin status of PKU patients. A comprehensive search of multiple databases (PubMed, Web of Sciences, Cochrane, and Scopus) was finished in March 2024. The included studies compared vitamin levels between individuals diagnosed with early-treated PKU and healthy controls while excluding pregnant and lactating women, untreated PKU or hyperphenylalaninemia cases, control groups receiving vitamin supplementation, PKU patients receiving tetrahydrobiopterin or pegvaliase, and conference abstracts. The risk of bias in the included studies was assessed by the Newcastle-Ottawa scale. The effect sizes were expressed as standardised mean differences. The calculation of effect sizes with 95% CI using fixed-effects models and random-effects models was performed. A -value < 0.05 was considered statistically significant. The study protocol was registered in the PROSPERO database (CRD42024519589). Out of the initially identified 11,086 articles, 24 met the criteria. The total number of participants comprised 770 individuals with PKU and 2387 healthy controls. The meta-analyses of cross-sectional and case-control studies were conducted for vitamin B12, D, A, E, B6 and folate levels. PKU patients demonstrated significantly higher folate levels (random-effects model, SMD: 1.378, 95% CI: 0.436, 2.320, = 0.004) and 1,25-dihydroxyvitamin D concentrations (random-effects model, SMD: 2.059, 95% CI: 0.250, 3.868, = 0.026) compared to the controls. There were no significant differences in vitamin A, E, B6, B12 or 25-dihydroxyvitamin D levels. The main limitations of the evidence include a limited number of studies and their heterogeneity and variability in patients' compliance. Our findings suggest that individuals with PKU under nutritional guidance can achieve a vitamin status comparable to that of healthy subjects. Our study provides valuable insights into the nutritional status of PKU patients, but further research is required to confirm these findings and explore additional factors influencing vitamin status in PKU.
Topics: Phenylketonurias; Humans; Vitamins; Vitamin D; Folic Acid; Vitamin B 12; Vitamin A
PubMed: 38791104
DOI: 10.3390/ijms25105065 -
Journal of Controlled Release :... Jul 2024Ovarian cancer (OC) is one of the most lethal cancers among women. Frequent recurrence in the peritoneum due to the presence of microscopic tumor residues justifies the...
Ovarian cancer (OC) is one of the most lethal cancers among women. Frequent recurrence in the peritoneum due to the presence of microscopic tumor residues justifies the development of new therapies. Indeed, our main objective is to develop a targeted photodynamic therapy (PDT) treatment of peritoneal carcinomatosis from OC to improve the life expectancy of cancer patients. Herein, we propose a targeted-PDT using a vectorized photosensitizer (PS) coupled with a newly folic acid analog (FAA), named PS, in order to target folate receptor alpha (FRα) overexpressed on peritoneal metastasis. This PS was the result of the coupling of pyropheophorbide-a (Pyro-a), as the PS, to a newly synthesized FAA via a polyethylene glycol (PEG) spacer. The selectivity and the PDT efficacy of PS was evaluated on two human OC cell lines overexpressing FRα compared to fibrosarcoma cells underexpressing FRα. Final PS, including the synthesis of a newly FAA and its conjugation to Pyro-a, was obtained after 10 synthesis steps, with an overall yield of 19%. Photophysical properties of PS in EtOH were performed and showed similarity with those of free Pyro-a, such as the fluorescence and singlet oxygen quantum yields (Φ = 0.39 and Φ = 0.53 for free Pyro-a, and Φ = 0.26 and Φ = 0.41 for PS). Any toxicity of PS was noticed. After light illumination, a dose-dependent effect on PS concentration and light dose was shown. Furthermore, a PDT efficacy of PS on OC cell secretome was detected inducing a decrease of a pro-inflammatory cytokine secretion (IL-6). This new PS has shown promising biological properties highlighting the selectivity of the therapy opening new perspectives in the treatment of a cancer in a therapeutic impasse.
Topics: Photochemotherapy; Humans; Ovarian Neoplasms; Female; Photosensitizing Agents; Folic Acid; Cell Line, Tumor; Chlorophyll; Interleukin-6; Cell Death; Folate Receptor 1; Inflammation; Cell Survival
PubMed: 38789088
DOI: 10.1016/j.jconrel.2024.05.033 -
Insects May 2024Pteridines are important cofactors for many biological functions of all living organisms, and they were first discovered as pigments of insects, mainly in butterfly... (Review)
Review
Pteridines are important cofactors for many biological functions of all living organisms, and they were first discovered as pigments of insects, mainly in butterfly wings and the eye and body colors of insects. Most of the information on their structures and biosynthesis has been obtained from studies with the model insects and the silkworm . This review discusses, and integrates into one metabolic pathway, the different branches which lead to the synthesis of the red pigments "drosopterins", the yellow pigments sepiapterin and sepialumazine, the orange pigment erythropterin and its related yellow metabolites (xanthopterin and 7-methyl-xanthopterin), the colorless compounds with violet fluorescence (isoxanthopterin and isoxantholumazine), and the branch leading to tetrahydrobiopterin, the essential cofactor for the synthesis of aromatic amino acids and biogenic amines.
PubMed: 38786926
DOI: 10.3390/insects15050370 -
Ethiopian Journal of Health Sciences Jul 2023Neural tube defects (NTDs) occur as a result of incomplete closure of the neural tube by the embryonic age of 26 to 28 days. Addressing factors associated with NTDs...
BACKGROUND
Neural tube defects (NTDs) occur as a result of incomplete closure of the neural tube by the embryonic age of 26 to 28 days. Addressing factors associated with NTDs would help to identify and prioritize high-risk women, which in turn guides the preventive strategy. The study aimed to identify factors associated with NTDs among women who gave birth or had a second-trimester abortion at Adama Hospital Medical College, from January 1st to December 31st, 2019.
METHODS
Hospital based unmatched case-control study was conducted on 344 women. Data were analyzed with SPSS 20. Descriptive statistics were computed. Binary logistic regression analysis was performed to determine factors associations with NTDs.
RESULTS
The odds of having a fetus with NTDs were 2.19 times higher among women who are not in a marital relationship (AOR = 2.19; 95% CI: 1.13, 4.25). Women with a previous history of Abortion or stillbirth had 3 fold increased risk of having a fetus with NTDs (AOR = 3.05; 95% CI: 1.58, 5.88). Inadequate housing condition nearly doubles the odds of having a fetus with NTDs (AOR = 1.91; 95% CI: 1.20, 3.04). Folic acid or multivitamin supplementation early in pregnancy reduced the odds of having a fetus with NTDs by 43% (AOR = 0.57; 95% CI: 0.35, 0.91).
CONCLUSION
Being not in a marital relationship, previous history of abortion or stillbirth, and living in inadequate housing conditions were risk factors for NTDs, while multivitamins or folic acid supplementation was a protective factor.
Topics: Humans; Neural Tube Defects; Female; Ethiopia; Case-Control Studies; Pregnancy; Adult; Risk Factors; Young Adult; Abortion, Induced; Folic Acid; Stillbirth; Logistic Models; Prenatal Care; Adolescent
PubMed: 38784206
DOI: 10.4314/ejhs.v33i4.9 -
Biochemistry Jun 2024OxaD is a flavin-dependent monooxygenase (FMO) responsible for catalyzing the oxidation of an indole nitrogen atom, resulting in the formation of a nitrone. Nitrones...
OxaD is a flavin-dependent monooxygenase (FMO) responsible for catalyzing the oxidation of an indole nitrogen atom, resulting in the formation of a nitrone. Nitrones serve as versatile intermediates in complex syntheses, including challenging reactions like cycloadditions. Traditional organic synthesis methods often yield limited results and involve environmentally harmful chemicals. Therefore, the enzymatic synthesis of nitrone-containing compounds holds promise for more sustainable industrial processes. In this study, we explored the catalytic mechanism of OxaD using a combination of steady-state and rapid-reaction kinetics, site-directed mutagenesis, spectroscopy, and structural modeling. Our investigations showed that OxaD catalyzes two oxidations of the indole nitrogen of roquefortine C, ultimately yielding roquefortine L. The reductive-half reaction analysis indicated that OxaD rapidly undergoes reduction and follows a "cautious" flavin reduction mechanism by requiring substrate binding before reduction can take place. This characteristic places OxaD in class A of the FMO family, a classification supported by a structural model featuring a single Rossmann nucleotide binding domain and a glutathione reductase fold. Furthermore, our spectroscopic analysis unveiled both enzyme-substrate and enzyme-intermediate complexes. Our analysis of the oxidative-half reaction suggests that the flavin dehydration step is the slow step in the catalytic cycle. Finally, through mutagenesis of the conserved D63 residue, we demonstrated its role in flavin motion and product oxygenation. Based on our findings, we propose a catalytic mechanism for OxaD and provide insights into the active site architecture within class A FMOs.
Topics: Nitrogen Oxides; Oxidation-Reduction; Mixed Function Oxygenases; Kinetics; Mutagenesis, Site-Directed; Flavins; Models, Molecular; Bacterial Proteins; Oxygenases
PubMed: 38779817
DOI: 10.1021/acs.biochem.3c00656