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PloS One 2023Monkeypox virus has recently emerged from endemic foci in Africa and, since October 20, 2022, more than 73,000 human infections have been reported by the CDC from over...
BACKGROUND
Monkeypox virus has recently emerged from endemic foci in Africa and, since October 20, 2022, more than 73,000 human infections have been reported by the CDC from over 100 countries that historically have not reported monkeypox cases. The detection of virus in skin lesions, blood, semen, and saliva of infected patients with monkeypox infections raises the potential for disease transmission via routes that have not been previously documented, including by blood and plasma transfusions. Methods for protecting the blood supply against the threats of newly emerging disease agents exist and include Pathogen Reduction Technologies (PRT) which utilize photochemical treatment processes to inactivate pathogens in blood while preserving the integrity of plasma and cellular components. Such methods have been employed broadly for over 15 years, but effectiveness of these methods under routine use conditions against monkeypox virus has not been reported.
STUDY DESIGN AND METHODS
Monkeypox virus (strain USA_2003) was used to inoculate plasma and whole blood units that were then treated with riboflavin and UV light (Mirasol Pathogen Reduction Technology System, Terumo BCT, Lakewood, CO). The infectious titers of monkeypox virus in the samples before and after riboflavin + UV treatment were determined by plaque assay on Vero cells.
RESULTS
The levels of spiked virus present in whole blood and plasma samples exceeded 103 infectious particles per dose, corresponding to greater than 105 DNA copies per mL. Treatment of whole blood and plasma units under standard operating procedures for the Mirasol PRT System resulted in complete inactivation of infectivity to the limits of detection. This is equivalent to a reduction of ≥ 2.86 +/- 0.73 log10 pfu/mL of infectivity in whole blood and ≥ 3.47 +/-0.19 log10 pfu/mL of infectivity in plasma under standard operating conditions for those products.
CONCLUSION
Based on this data and corresponding studies on infectivity in patients with monkeypox infections, use of Mirasol PRT would be expected to significantly reduce the risk of transfusion transmission of monkeypox.
Topics: Animals; Humans; Blood Platelets; Chlorocebus aethiops; Mpox (monkeypox); Monkeypox virus; Riboflavin; Ultraviolet Rays; Vero Cells; Viremia
PubMed: 36662705
DOI: 10.1371/journal.pone.0278862 -
Genes Jul 2023Riboflavin transporter 1 (RFVT1) deficiency is an ultrarare metabolic disorder due to autosomal dominant pathogenic variants in . The RFVT1 protein is mainly expressed...
Riboflavin transporter 1 (RFVT1) deficiency is an ultrarare metabolic disorder due to autosomal dominant pathogenic variants in . The RFVT1 protein is mainly expressed in the placenta and intestine. To our knowledge, only five cases of RFVT1 deficiency from three families have been reported so far. While newborns and infants with variants mainly showed a multiple acyl-CoA dehydrogenase deficiency-like presentation, individuals identified in adulthood were usually clinically asymptomatic. We report two patients with novel heterozygous variants. Patient 1 presented at the age of 62 with mild hyperammonemia following gastroenteritis. An acylcarnitine analysis in dried blood spots was abnormal with a multiple acyl-CoA dehydrogenase deficiency-like pattern, and genetic analysis confirmed a heterozygous variant, c.68C > A, p. Ser23Tyr. Patient 2 presented with recurrent seizures and hypsarrhythmia at the age of 7 months. Metabolic investigations yielded unremarkable results. However, whole exome sequencing revealed a heterozygous start loss variant, c.3G > A, p. Met1Ile in These two cases expand the clinical spectrum of riboflavin transporter 1 deficiency and demonstrate that symptomatic presentation in adulthood is possible.
Topics: Female; Humans; Infant; Infant, Newborn; Pregnancy; Heterozygote; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Receptors, G-Protein-Coupled; Riboflavin; Membrane Transport Proteins
PubMed: 37510312
DOI: 10.3390/genes14071408 -
Nutrients Oct 2023Micronutrient deficiencies are a well-established fact in obesity. However, few studies exist on the relationship between micronutrient intake and mental health. In this...
Micronutrient deficiencies are a well-established fact in obesity. However, few studies exist on the relationship between micronutrient intake and mental health. In this study, we investigated the associations between daily intakes of vitamins and minerals and scoring items that measure mental health in people living with central obesity. One hundred males and females with central obesity and metabolic abnormalities were included in the study. Demographic, clinical, anthropometric, and biochemical data were collected. Mental health statuses were assessed with validated questionnaires, and daily micronutrient intakes were assessed with food diaries and Nutritionist Pro software v7.9. The mental component score (MCS-12) positively correlated with vitamin A (Rho = 0.249, = 0.038), vitamin C (Rho = 0.293, = 0.014), riboflavin (Rho = 0.264, = 0.026), and folate (Rho = 0.238, = 0.046). Rosenberg Self-Esteem Scale (RSES) correlated with sodium (Rho = 0.269, = 0.026), and the Center for Epidemiologic Studies Depression Scale Revised (CESD-R) correlated with chromium (Rho = 0.313, = 0.009). In the regression analysis, after potential confounders were adjusted for, only riboflavin was positively associated with the MCS-12 log (beta ± SD = 0.047 ± 0.023, = 0.044). Our study provides evidence of the link between dietary riboflavin and mental health in people with obesity, and it highlights the importance of monitoring both nutritional status and mental health when managing obesity.
Topics: Male; Female; Humans; Nutritional Status; Obesity, Abdominal; Mental Health; Vitamins; Obesity; Riboflavin; Vitamin A; Micronutrients
PubMed: 37892539
DOI: 10.3390/nu15204464 -
Scientific Reports Oct 2023Biomaterial engineering approaches involve using a combination of miscellaneous bioactive molecules which may promote cell proliferation and, thus, form a scaffold with...
Biomaterial engineering approaches involve using a combination of miscellaneous bioactive molecules which may promote cell proliferation and, thus, form a scaffold with the environment that favors the regeneration process. Chitosan, a naturally occurring biodegradable polymer, possess some essential features, i.e., biodegradability, biocompatibility, and in the solid phase good porosity, which may contribute to promote cell adhesion. Moreover, doping of the materials with other biocompounds will create a unique and multifunctional scaffold that will be useful in regenerative medicine. This study is focused on the manufacturing and characterization of composite materials based on chitosan, hydroxyapatite, and riboflavin. The resulting films were fabricated by the casting/solvent evaporation method. Morphological and spectroscopy analyses of the films revealed a porous structure and an interconnection between chitosan and apatite. The composite material showed an inhibitory effect on Staphylococcus aureus and exhibited higher antioxidant activity compared to pure chitosan. In vitro studies on riboflavin showed increased cell proliferation and migration of fibroblasts and osteosarcoma cells, thus demonstrating their potential for bone tissue engineering applications.
Topics: Biocompatible Materials; Chitosan; Durapatite; Tissue Scaffolds; Tissue Engineering; Bone Regeneration; Porosity; Riboflavin
PubMed: 37813934
DOI: 10.1038/s41598-023-44225-0 -
Frontiers in Immunology 2023Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells, which mediate host immunity to microbial infection by recognizing metabolite...
INTRODUCTION
Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells, which mediate host immunity to microbial infection by recognizing metabolite antigens derived from microbial riboflavin synthesis presented by the MHC-I-related protein 1 (MR1). Namely, the potent MAIT cell antigens, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) and 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU), form via the condensation of the riboflavin precursor 5-amino-6-D-ribitylaminouracil (5-A-RU) with the reactive carbonyl species (RCS) methylglyoxal (MG) and glyoxal (G), respectively. Although MAIT cells are abundant in humans, they are rare in mice, and increasing their abundance using expansion protocols with antigen and adjuvant has been shown to facilitate their study in mouse models of infection and disease.
METHODS
Here, we outline three methods to increase the abundance of MAIT cells in C57BL/6 mice using a combination of inflammatory stimuli, 5-A-RU and MG.
RESULTS
Our data demonstrate that the administration of synthetic 5-A-RU in combination with one of three different inflammatory stimuli is sufficient to increase the frequency and absolute numbers of MAIT cells in C57BL/6 mice. The resultant boosted MAIT cells are functional and can provide protection against a lethal infection of .
CONCLUSION
These results provide alternative methods for expanding MAIT cells with high doses of commercially available 5-A-RU (± MG) in the presence of various danger signals.
Topics: Humans; Animals; Mice; Mice, Inbred C57BL; Mucosal-Associated Invariant T Cells; Adjuvants, Immunologic; Pyruvaldehyde; Riboflavin
PubMed: 37720229
DOI: 10.3389/fimmu.2023.1109759 -
Microbial Cell Factories May 2023Previously, we isolated a riboflavin-overproducing Ashbya gossypii mutant (MT strain) and discovered some mutations in genes encoding flavoproteins. Here, we analyzed...
BACKGROUND
Previously, we isolated a riboflavin-overproducing Ashbya gossypii mutant (MT strain) and discovered some mutations in genes encoding flavoproteins. Here, we analyzed the riboflavin production in the MT strain, in view of flavoproteins, which are localized in the mitochondria.
RESULTS
In the MT strain, mitochondrial membrane potential was decreased compared with that in the wild type (WT) strain, resulting in increased reactive oxygen species. Additionally, diphenyleneiodonium (DPI), a universal flavoprotein inhibitor, inhibited riboflavin production in the WT and MT strains at 50 µM, indicating that some flavoproteins may be involved in riboflavin production. The specific activities of NADH and succinate dehydrogenases were significantly reduced in the MT strain, but those of glutathione reductase and acetohydroxyacid synthase were increased by 4.9- and 25-fold, respectively. By contrast, the expression of AgGLR1 gene encoding glutathione reductase was increased by 32-fold in the MT strain. However, that of AgILV2 gene encoding the catalytic subunit of acetohydroxyacid synthase was increased by only 2.1-fold. These results suggest that in the MT strain, acetohydroxyacid synthase, which catalyzes the first reaction of branched-chain amino acid biosynthesis, is vital for riboflavin production. The addition of valine, which is a feedback inhibitor of acetohydroxyacid synthase, to a minimal medium inhibited the growth of the MT strain and its riboflavin production. In addition, the addition of branched-chain amino acids enhanced the growth and riboflavin production in the MT strain.
CONCLUSION
The significance of branched-chain amino acids for riboflavin production in A. gossypii is reported and this study opens a novel approach for the effective production of riboflavin in A. gossypii.
Topics: Riboflavin; Acetolactate Synthase; Eremothecium; Flavoproteins; Mutation; Mitochondrial Proteins; Mitochondria; Reactive Oxygen Species; Amino Acids, Branched-Chain
PubMed: 37217979
DOI: 10.1186/s12934-023-02114-1 -
Proceedings of the National Academy of... Sep 2022Microbes can provide a more sustainable and energy-efficient method of food and nutrient production compared to plant and animal sources, but energy-intensive carbon...
Microbes can provide a more sustainable and energy-efficient method of food and nutrient production compared to plant and animal sources, but energy-intensive carbon (e.g., sugars) and nitrogen (e.g., ammonia) inputs are required. Gas-fixing microorganisms that can grow on H from renewable water splitting and gaseous CO and N offer a renewable path to overcoming these limitations but confront challenges owing to the scarcity of genetic engineering in such organisms. Here, we demonstrate that the hydrogen-oxidizing carbon- and nitrogen-fixing microorganism grown on a CO/N/H gas mixture can overproduce the vitamin riboflavin (vitamin B). We identify plasmids and promoters for use in this bacterium and employ a constitutive promoter to overexpress riboflavin pathway enzymes. Riboflavin production is quantified at 15 times that of the wild-type organism. We demonstrate that riboflavin overproduction is maintained when the bacterium is grown under hybrid inorganic-biological conditions, in which H from water splitting, along with CO and N, is fed to the bacterium, establishing the viability of the approach to sustainably produce food and nutrients.
Topics: Carbon Dioxide; Nitrogen; Riboflavin; Water; Xanthobacter
PubMed: 36067303
DOI: 10.1073/pnas.2210538119 -
Experimental Eye Research Jun 2022Corneal collagen cross-linking (CXL) is a treatment that is widely applied to halt the progression of ectatic diseases such as keratoconus by creating biomechanical...
Corneal collagen cross-linking (CXL) is a treatment that is widely applied to halt the progression of ectatic diseases such as keratoconus by creating biomechanical strength in the cornea. Most of the studies assessed the effect of the CXL on the cornea without any differentiation of its effect between periphery and the center of the untreated control cornea especially after the 7 days of CXL application. We investigate the ultrastructural changes in the architecture of the center and periphery of rat corneas, 7 days after standard CXL application. Five Wistar rats (10 corneas) were used in the present study. The left eye corneas (5 mm area) were de-epithelialized and irradiated with standard CXL application using riboflavin and Ultraviolet-A (UVA) (3 mW/cm for 30 min). The right eye corneas were used as a control. The sclera-cornea button was removed and processed for electron microscopy. Digital images were captured with a bottom mounted Quemesa camera and analyzed using the iTEM software. The ultrastructure of epithelium, hemi-desmosomes, Bowman's layer and stroma were organized in both untreated control and CXL rat cornea in both untreated control and CXL rat cornea. Within the same CXL cornea, both the collagen fibril (CF) diameter and interfibrillar spacing at the center were significantly smaller compared to the peripheral diameter and spacing of the cornea. When comparing the untreated control and CXL cornea, the central interfibrillar spacing of the CXL cornea was significantly smaller than the central spacing the untreated control cornea. In the CXL cornea the peripheral spacing was significantly higher compared to the peripheral interfibrillar spacing of the untreated control cornea. Within the CXL cornea, the proteoglycans (PGs) area and density of the periphery was significantly higher compared to the area and density of the center of the cornea. It suggests that CXL was more effective at the periphery of the cornea. This could be due to the higher amount of leucine rich PG lumican and higher diffusion of oxygen and riboflavin at the periphery cornea.
Topics: Animals; Collagen; Cornea; Corneal Stroma; Cross-Linking Reagents; Keratoconus; Photosensitizing Agents; Rats; Rats, Wistar; Riboflavin; Ultraviolet Rays
PubMed: 35385757
DOI: 10.1016/j.exer.2022.109064 -
Frontiers in Cellular and Infection... 2022Some spp. are globally emerging opportunistic pathogens that can be dangerous to individuals with underlying medical conditions and for those who are immunocompromised....
Some spp. are globally emerging opportunistic pathogens that can be dangerous to individuals with underlying medical conditions and for those who are immunocompromised. Gram-negative spp. can form resilient sessile biofilms and are found not only in different confined terrestrial settings (e.g., hospitals) but are also frequently detected in spacecraft which is inhabited by astronauts that can have altered immunity. Therefore, spp. pose a serious health hazard in different environments, especially in its biofilm form. Conventional antimicrobials applied to disrupt, inactivate, or prevent biofilm formation have limited efficiency and applicability in different closed-loop systems. Therefore, new, effective, and safe biofilm control technologies are in high demand. The present work aimed to investigate antimicrobial photoinactivation (API) of sp. ESA1 monocultural biofilms mediated by non-toxic, natural photosensitizers such as riboflavin (RF) and chlorophyllin (Chl) with an emphasis of this technology as an example to be safely used in closed-loop systems such as spacecraft. The present study showed that Chl-based API had a bactericidal effect on sp. ESA1 biofilms at twice the lower irradiation doses than was needed when applying RF-based API. Long-term API based on RF and Chl using 450 nm low irradiance plate has also been studied in this work as a more practically applicable API method. The ability of sp. ESA1 biofilms to reduce alamarBlue™ and regrowth analysis have revealed that after the applied photoinactivation, bacteria can enter a viable but non-culturable state with no ability to resuscitate in some cases.
Topics: Humans; Photosensitizing Agents; Biofilms; Anti-Bacterial Agents; Anti-Infective Agents; Riboflavin
PubMed: 36262183
DOI: 10.3389/fcimb.2022.1006723 -
Journal of Crohn's & Colitis Jun 2020Crohn's disease [CD] is characterised by chronic intestinal inflammation and dysbiosis in the gut. Riboflavin [vitamin B2] has anti-inflammatory, antioxidant and... (Clinical Trial)
Clinical Trial
BACKGROUND AND AIMS
Crohn's disease [CD] is characterised by chronic intestinal inflammation and dysbiosis in the gut. Riboflavin [vitamin B2] has anti-inflammatory, antioxidant and microbiome-modulatory properties. Here, we analysed the effect of riboflavin on oxidative stress, markers of inflammation, clinical symptoms, and faecal microbiome in patients with CD.
METHODS
In this prospective clinical intervention study, patients received 100 mg riboflavin [DSM, Nutritional Products Ltd] daily for 3 weeks. Clinical disease activity [Harvey-Bradshaw Index: HBI], serum biomarkers of inflammation and redox status [plasma free thiols], and faecal microbiome taxonomical composition and functionality [fluorescent in situ hybridisation: FISH; and metagenomic shotgun sequencing: MGS], were analysed before and after riboflavin intervention.
RESULTS
In total, 70 patients with CD with varying disease activity were included. Riboflavin supplementation significantly decreased serum levels of inflammatory markers. In patients with low faecal calprotectin [FC] levels, IL-2 decreased, and in patients with high FC levels, C-reactive protein [CRP] was reduced and free thiols significantly increased after supplementation. Moreover, HBI was significantly decreased by riboflavin supplementation. Riboflavin supplementation led to decreased Enterobacteriaceae in patients with low FC levels as determined by FISH; however, MGS analysis showed no effects on diversity, taxonomy, or metabolic pathways of the faecal microbiome.
CONCLUSIONS
Three weeks of riboflavin supplementation resulted in a reduction in systemic oxidative stress, mixed anti-inflammatory effects, and a reduction in clinical symptoms [HBI]. FISH analysis showed decreased Enterobacteriaceae in patients with CD with low FC levels, though this was not observed in MGS analysis. Our data demonstrate that riboflavin supplementation has a number of anti-inflammatory and anti-oxidant effects in CD.
Topics: Adult; Biomarkers; Blood Sedimentation; C-Reactive Protein; Crohn Disease; Dietary Supplements; Enterobacteriaceae; Fatty Acids, Volatile; Feces; Female; Gastrointestinal Microbiome; Humans; Interleukin-2; Leukocyte L1 Antigen Complex; Male; Middle Aged; Oxidative Stress; Platelet Count; Prospective Studies; Quality of Life; Riboflavin; Severity of Illness Index; Sulfhydryl Compounds; Vitamin B Complex
PubMed: 31873717
DOI: 10.1093/ecco-jcc/jjz208