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Plant Biotechnology Journal Aug 2022Riboflavin is the precursor of essential cofactors for diverse metabolic processes. Unlike animals, plants can de novo produce riboflavin through an ancestrally...
Riboflavin is the precursor of essential cofactors for diverse metabolic processes. Unlike animals, plants can de novo produce riboflavin through an ancestrally conserved pathway, like bacteria and fungi. However, the mechanism by which riboflavin regulates seed development is poorly understood. Here, we report a novel maize (Zea mays L.) opaque mutant o18, which displays an increase in lysine accumulation, but impaired endosperm filling and embryo development. O18 encodes a rate-limiting bifunctional enzyme ZmRIBA1, targeted to plastid where to initiate riboflavin biosynthesis. Loss of function of O18 specifically disrupts respiratory complexes I and II, but also decreases SDH1 flavinylation, and in turn shifts the mitochondrial tricarboxylic acid (TCA) cycle to glycolysis. The deprivation of cellular energy leads to cell-cycle arrest at G1 and S phases in both mitosis and endoreduplication during endosperm development. The unexpected up-regulation of cell-cycle genes in o18 correlates with the increase of H3K4me3 levels, revealing a possible H3K4me-mediated epigenetic back-up mechanism for cell-cycle progression under unfavourable circumstances. Overexpression of O18 increases riboflavin production and confers osmotic tolerance. Altogether, our results substantiate a key role of riboflavin in coordinating cellular energy and cell cycle to modulate maize endosperm development.
Topics: Cell Cycle; Endosperm; Gene Expression Regulation, Plant; Plant Proteins; Riboflavin; Seeds; Zea mays
PubMed: 35426230
DOI: 10.1111/pbi.13826 -
Transfusion Nov 2020Pathogen reduction technology has become an accepted method for limiting transfusion-transmitted infections (TTIs). Riboflavin and ultraviolet light (RUV) treatment of...
BACKGROUND
Pathogen reduction technology has become an accepted method for limiting transfusion-transmitted infections (TTIs). Riboflavin and ultraviolet light (RUV) treatment of platelets (PLTs) is an optional means of pathogen inactivation owing to its safety, effectiveness, and ease of use. However, the literature on effects of ultraviolet (UV) light spectra and doses on pathogen reduction is still contradictory.
METHODS
We tested the effectiveness of killing Escherichia coli following RUV exposure with one broad-spectrum and two narrow-spectrum light sources centered at 311 and 365 nm and at successively higher doses by limited dilution survival assays. After comparing the effectiveness of E coli and phage inactivation (n = 6) and the changes in PLT count and metabolism caused by RUV treatment with optimized UV light at increasing doses, we confirmed our results by using four model virus systems that represent common TTIs, as well as PLT function and activation assays at an optimized light dose.
RESULTS
The narrow-spectrum UV, centered at 311 nm, optimally reduced the E coli titer with a light dose ≥8.11 J/mL, resulting in the same trend of E coli and phage reduction at different light doses. At 8.11 J/mL, 311-nm narrow-spectrum UV had a good inactivation effect on E coli and phages, eliminating many viruses, and resulted in acceptable PLT quality after RUV treatment and during storage for 4 days.
CONCLUSIONS
Our data suggest restricting exposure to narrow-spectrum UV centered at 311 nm can increase E coli elimination and potentially optimize virus titer reduction without significantly compromising PLT quality.
Topics: Blood Platelets; Blood Preservation; Disinfection; Escherichia coli; Humans; Microbial Viability; Riboflavin; Ultraviolet Rays
PubMed: 32866308
DOI: 10.1111/trf.16053 -
Aging Cell Nov 2022Riboflavin is an essential cofactor in many enzymatic processes and in the production of flavin adenine dinucleotide (FAD). Here, we report that the partial depletion of...
Riboflavin is an essential cofactor in many enzymatic processes and in the production of flavin adenine dinucleotide (FAD). Here, we report that the partial depletion of riboflavin through knockdown of the C. elegans riboflavin transporter 1 (rft-1) promotes metabolic health by reducing intracellular flavin concentrations. Knockdown of rft-1 significantly increases lifespan in a manner dependent upon AMP-activated protein kinase (AMPK)/aak-2, the mitochondrial unfolded protein response, and FOXO/daf-16. Riboflavin depletion promotes altered energetic and redox states and increases adiposity, independent of lifespan genetic dependencies. Riboflavin-depleted animals also exhibit the activation of caloric restriction reporters without any reduction in caloric intake. Our findings indicate that riboflavin depletion activates an integrated hormetic response that promotes lifespan and healthspan in C. elegans.
Topics: Animals; Caenorhabditis elegans; Longevity; Caenorhabditis elegans Proteins; Hormesis; Riboflavin; Forkhead Transcription Factors
PubMed: 36181246
DOI: 10.1111/acel.13718 -
Experimental Eye Research Dec 2021Avoiding damage of the endothelial cells, especially in thin corneas, remains a challenge in corneal collagen crosslinking (CXL). Knowledge of the riboflavin gradients...
Avoiding damage of the endothelial cells, especially in thin corneas, remains a challenge in corneal collagen crosslinking (CXL). Knowledge of the riboflavin gradients and the UV absorption characteristics after topical application of riboflavin in concentrations ranging from 0.1% to 0.5% could optimize the treatment. In this study, we present a model to calculate the UV-intensity depending on the corneal thickness. Ten groups of de-epithelialized porcine corneas were divided into 2 subgroups. Five groups received an imbibition of 10 min and the other five groups for 30 min. The applied riboflavin concentrations were 0.1%, 0.2%, 0.3%, 0.4% and 0.5% diluted in a 15% dextran solution for each subgroup. After the imbibition process, two-photon fluorescence microscopy was used to determine fluorescence intensity, which was compared to samples after saturation, yielding the absolute riboflavin concentration gradient of the cornea. The extinction coefficient of riboflavin solutions was measured using a spectrophotometer. Combining the obtained riboflavin concentrations and the extinction coefficients, a depth-dependent UV-intensity profile was calculated for each group. With increasing corneal depth, the riboflavin concentration decreased for all imbibition solutions and application times. The diffusion coefficients of 10 min imbibition time were higher than for 30 min. A higher RF concentration and a longer imbibition time resulted in higher UV-absorption and a lower UV-intensity in the depth of the cornea. Calculated UV-transmission was 6 percentage points lower compared to the measured transmission. By increasing the riboflavin concentration of the imbibition solution, a substantially higher UV-absorption inside the cornea is achieved. This offers a simple treatment option to control the depth of crosslinking e.g. in thin corneas, resulting in a lower risk of endothelial damage.
Topics: Absorption, Radiation; Administration, Ophthalmic; Animals; Corneal Pachymetry; Corneal Stroma; Cross-Linking Reagents; Microscopy, Fluorescence, Multiphoton; Ophthalmic Solutions; Photochemotherapy; Photosensitizing Agents; Riboflavin; Swine; Ultraviolet Rays
PubMed: 34793829
DOI: 10.1016/j.exer.2021.108842 -
The Journal of Nutritional Biochemistry Dec 2023Insufficient riboflavin intake has been associated with poor bone health. This study aimed to investigate the effect of riboflavin deficiency on bone health in vivo and...
Insufficient riboflavin intake has been associated with poor bone health. This study aimed to investigate the effect of riboflavin deficiency on bone health in vivo and in vitro. Riboflavin deficiency was successfully developed in rats and osteoblasts. The results indicated that bone mineral density, serum bone alkaline phosphatase, bone phosphorus, and bone calcium were significantly decreased while serum ionized calcium and osteocalcin were significantly increased in the riboflavin-deficient rats. Riboflavin deficiency also induced the reduction of Runx2, Osterix, and BMP-2/Smad1/5/9 cascade in the femur. These results were further verified in cellular experiments. Our findings demonstrated that alkaline phosphatase activities and calcified nodules were significantly decreased while intracellular osteocalcin and pro-collagen I c-terminal propeptide were significantly increased in the riboflavin-deficient osteoblasts. Additionally, the protein expression of Osterix, Runx2, and BMP-2/Smad1/5/9 cascade were significantly decreased while the protein expression of p-p38 MAPK were significantly increased in the riboflavin-deficient cells compared to the control cells. Blockage of p38 MAPK signaling pathway with SB203580 reversed these effects in riboflavin-deficient osteoblastic cells. Our data suggest that riboflavin deficiency causes osteoblast malfunction and retards bone matrix mineralization via p38 MAPK/BMP-2/Smad1/5/9 signaling pathway.
Topics: Rats; Animals; Bone Density; Core Binding Factor Alpha 1 Subunit; Osteocalcin; Signal Transduction; Riboflavin Deficiency; Alkaline Phosphatase; Calcium; Bone Morphogenetic Protein 2; Osteoblasts; p38 Mitogen-Activated Protein Kinases; Riboflavin; Cell Differentiation
PubMed: 37788723
DOI: 10.1016/j.jnutbio.2023.109453 -
Cells Oct 2019Collagen crosslinking provides the mechanical strength required for physiological maintenance of the extracellular matrix in most tissues in the human body, including... (Review)
Review
Collagen crosslinking provides the mechanical strength required for physiological maintenance of the extracellular matrix in most tissues in the human body, including the cornea. Aging and diabetes mellitus (DM) are processes that are both associated with increased collagen crosslinking that leads to increased corneal rigidity. By contrast, keratoconus (KC) is a corneal thinning disease associated with decreased mechanical stiffness leading to ectasia of the central cornea. Studies have suggested that crosslinking mediated by reactive advanced glycation end products during DM may protect the cornea from KC development. Parallel to this hypothesis, riboflavin-mediated photoreactive corneal crosslinking has been proposed as a therapeutic option to halt the progression of corneal thinning by inducing intra- and intermolecular crosslink formation within the collagen fibrils of the stroma, leading to stabilization of the disease. Here, we review the pathobiology of DM and KC in the context of corneal structure, the epidemiology behind the inverse correlation of DM and KC development, and the chemical mechanisms of lysyl oxidase-mediated crosslinking, advanced glycation end product-mediated crosslinking, and photoreactive riboflavin-mediated corneal crosslinking. The goal of this review is to define the biological and chemical pathways important in physiological and pathological processes related to collagen crosslinking in DM and KC.
Topics: Collagen; Diabetes Mellitus; Disease Progression; Glycation End Products, Advanced; Humans; Keratoconus; Protein-Lysine 6-Oxidase; Riboflavin
PubMed: 31614631
DOI: 10.3390/cells8101239 -
BMC Ophthalmology Jul 2023To describe visual and refractive outcomes of intrastromal corneal ring segments (ICRS) and toric implantable collamer lenses (TICL) implantation in cases of mild and...
PURPOSE
To describe visual and refractive outcomes of intrastromal corneal ring segments (ICRS) and toric implantable collamer lenses (TICL) implantation in cases of mild and moderate keratoconus.
METHODS
A prospective descriptive interventional case series. 40 eyes were allocated into two groups. First group (20 eyes) was treated with corneal collagen crosslinking (CXL) 1 month after ICRS implantation and the second group was treated using TICL after 1 year of CXL.
RESULTS
Both groups showed statistically significant improvement in spherical equivalent, cylindrical refraction, uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) over the follow-up period.
CONCLUSION
Both ICRS and TICL are effective in treatment of mid and moderate keratoconus with more predictable visual results with TICL.
Topics: Humans; Prosthesis Implantation; Photosensitizing Agents; Riboflavin; Keratoconus; Ultraviolet Rays; Refraction, Ocular; Lenses, Intraocular; Corneal Topography; Corneal Stroma; Cross-Linking Reagents
PubMed: 37460958
DOI: 10.1186/s12886-023-03040-x -
Journal of Applied Microbiology Feb 2022Effects of a proteasome inhibitor, MG-132, on the riboflavin production in Ashbya gossypii were investigated to elucidate the relationship of the riboflavin production...
AIMS
Effects of a proteasome inhibitor, MG-132, on the riboflavin production in Ashbya gossypii were investigated to elucidate the relationship of the riboflavin production with flavoprotein homeostasis.
METHODS AND RESULTS
The addition of MG-132 to the liquid medium reduced the specific riboflavin production by 79% in A. gossypii at 25 μM after 24 h. The addition of the inhibitor also caused the accumulation of reactive oxygen species and ubiquitinated proteins. These results indicated that MG-132 works in A. gossypii without any genetic engineering and reduces riboflavin production. In the presence of 25 μM MG-132, specific NADH dehydrogenase activity was increased by 1.4-fold compared to DMSO, but specific succinate dehydrogenase (SDH) activity was decreased to 52% compared to DMSO. Additionally, the amount of AgSdh1p (ACR052Wp) was also reduced. Specific riboflavin production was reduced to 22% when 20 mM malonate, a SDH inhibitor, was added to the culture medium. The riboflavin production in heterozygous AgSDH1 gene-disrupted mutant (AgSDH1 ) was reduced to 63% compared to that in wild type.
CONCLUSIONS
MG-132 suppresses the riboflavin production and SDH activity in A. gossypii. SDH is one of the flavoproteins involved in the riboflavin production in A. gossypii.
SIGNIFICANCE AND IMPACT OF THE STUDY
This study shows that MG-132 has a negative influence on the riboflavin production and SDH activity in A. gossypii and leads to the elucidation of the connection of the riboflavin production with flavoproteins.
Topics: Genetic Engineering; Leupeptins; Proteasome Inhibitors; Riboflavin; Saccharomycetales
PubMed: 34496097
DOI: 10.1111/jam.15296 -
Poultry Science Mar 2020An experiment was conducted to investigate the effects of dietary riboflavin levels on reproductive performance, riboflavin status, and antioxidant status of laying duck... (Review)
Review
An experiment was conducted to investigate the effects of dietary riboflavin levels on reproductive performance, riboflavin status, and antioxidant status of laying duck breeders, to estimate the requirement of this vitamin for duck breeders. Different levels crystalline riboflavin (0, 2.5, 5, 10, and 15 mg/kg) were supplemented to a corn-soybean-corn gluten meal basal diet to produce 5 dietary treatments with different analyzed total riboflavin levels (1.48, 3.20, 6.30, 11.71, and 16.83 mg/kg). A total of 80 White Pekin duck breeders aged 40 wk were allotted to 5 dietary treatments of 16 birds each (8 replicates per treatment and 2 breeders per replicate), and all birds were raised individually for 9 wk. At the end of the experiment, reproductive performance, tissue riboflavin concentrations, and antioxidant status of White Pekin duck breeders were measured. The results showed that body weight, egg weight, egg production, and egg fertility were not affected by dietary riboflavin levels. However, among all of the laying duck breeders, the birds fed the basal diet without riboflavin supplementation had the lowest egg hatchability, plasma riboflavin, egg yolk riboflavin, and egg albumen riboflavin (P < 0.001). In addition, the duck breeders fed the basal diet without riboflavin supplementation showed the lowest antioxidant capacity indicated by greatest plasma malondialdehyde (MDA) content and lowest reduced glutathione content, total superoxide dismutase (T-SOD) activities, and total antioxidant capacity in both plasma (P < 0.001) and egg yolk (P < 0.001). These results revealed that dietary riboflavin supplementation improved the reproductive performance and antioxidant status of the duck breeders. According to the broken-line model, the riboflavin requirements (based on dietary total riboflavin) of laying duck breeders in terms of the egg hatchability, plasma riboflavin, egg yolk riboflavin, egg albumen riboflavin, plasma T-SOD activity, and plasma MDA content were 3.19, 7.42, 3.88, 7.44, 6.45, and 8.84 mg/kg, respectively.
Topics: Animal Feed; Animals; Antioxidants; Diet; Dietary Supplements; Dose-Response Relationship, Drug; Ducks; Female; Random Allocation; Reproduction; Riboflavin; Vitamins
PubMed: 32111323
DOI: 10.1016/j.psj.2019.11.014 -
International Ophthalmology Jan 2022Riboflavin/UV-A corneal cross-linking (CXL) for treating keratoconus and iatrogenic corneal ectasia has been well-established as first treatment option to stabilize... (Review)
Review
BACKGROUND
Riboflavin/UV-A corneal cross-linking (CXL) for treating keratoconus and iatrogenic corneal ectasia has been well-established as first treatment option to stabilize corneal tissue biomechanical instability. Although the plethora of clinical studies has been published into the field, there is no systematic review assessing the type and frequency of adverse events after CXL.
METHODS
A systemic literature review on clinical safety and adverse events after CXL in patients with keratoconus and corneal ectasia was performed using PubMed. A literature search was performed for relevant peer-reviewed publications. The main outcome measures extracted from the articles were adverse events, endothelial cell density, corrected distance visual acuity and maximum simulated keratometry.
RESULTS
The most frequent adverse events after CXL were corneal haze and corneal edema, which were mild and transient. The severe adverse events were infrequent (cumulative incidence: < 1.3%) after CXL. The clinical benefits of CXL highly outweighed the risks for the treatment of keratoconus and corneal ectasia.
CONCLUSIONS
The severe adverse events with permanent sequelae are infrequent after CXL and all are associated with corneal de-epithelialization, such as infectious keratitis and corneal scarring.
Topics: Collagen; Corneal Topography; Cross-Linking Reagents; Humans; Keratoconus; Photochemotherapy; Photosensitizing Agents; Riboflavin; Ultraviolet Rays
PubMed: 34448966
DOI: 10.1007/s10792-021-02019-1