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Background: Riboflavin transporter deficiency (RTD) is an inborn error of riboflavin transport causing progressive neurological symptoms if left untreated. While infants with symptomatic RTD rapidly deteriorate, presentation later in childhood or in adulthood is more gradual. Symptoms overlap with more common diseases, carrying a risk of misdiagnosis, and given the relatively recent discovery of the genetic basis of RTD in 2010 it is likely that older patients have not been tested. Treatment with oral riboflavin (vitamin B2) halts disease progression and can be lifesaving. We hypothesized that patients may have been left unrecognized at the time of presentation and therefore we performed a datamining study to detect undiagnosed RTD patients in a tertiary referral hospital. Methods: A systematic search in Electronic Health Records (EHR) of all patients visiting the Amsterdam University Medical Centers between January 2004 and July 2021 was performed by a medical data text-mining tool. Pseudonymized patient records, matching pre-defined search terms (hearing loss or auditory neuropathy spectrum disorders combined with key clinical symptoms or riboflavin) were screened and included if no definitive alternative diagnosis for symptoms indicating possible RTD was found. Included patients were offered genetic testing. We documented total number of patients with possible RTD, number of patients that underwent genetic testing for RTD and results of genetic testing. Results: EHR of 2.288.901 patients were automatically screened. Thirteen patients with possible RTD were identified and offered genetic testing. Seven patients chose not to participate. Genetic testing was performed in 6 patients and was negative. The datamining did detect all previously known RTD patients in the hospital. Conclusions: By screening a large cohort of patients of all ages in a tertiary referral hospital in a period spanning 17 years, no new RTD patients were found. Although not all suspected patients underwent genetic testing, our findings suggest that the prevalence of RTD is low and the chance of having missed this diagnosis in a tertiary referral hospital is limited. [ABSTRACT FROM AUTHOR]

Riboflavin (vitamin B2) has been proposed as a biomarker for breast cancer resistance protein (BCRP) activity. In recent studies in mice, cynomolgus monkeys, and humans, BCRP‐inhibiting drugs increased the plasma concentration of riboflavin. We showed recently that ticagrelor inhibits BCRP and raises the plasma concentrations of the BCRP substrate rosuvastatin in healthy volunteers. In the same drug–drug interaction study, we now investigated whether ticagrelor affects the plasma concentrations of riboflavin. Intake of 90 mg ticagrelor increased the ratio between the peak plasma riboflavin concentration and the fasting riboflavin concentration before ticagrelor administration by 1.20‐fold (90% confidence interval, 1.10–1.32; P = 0.006) compared to placebo. In vitro, riboflavin was transported by BCRP and multidrug‐resistance‐associated protein 4 (MRP4) but no clear transport was observed by MRP2, MRP3, or the P‐glycoprotein. Moreover, ticagrelor inhibited the transport of riboflavin in BCRP‐ and MRP4‐expressing membrane vesicles with unbound 50% inhibitory concentrations of 0.020 and 1.1 μM, respectively. Based on vesicle and tissue protein expression data, the small intestinal MRP4‐mediated efflux clearance of riboflavin (1.2–1.4 nL/min/mg) was estimated to be similar to that mediated by BCRP (0.23–1.3 nL/min/mg). As MRP4 is expressed in the basolateral membrane of enterocytes, it may facilitate the absorption of riboflavin and impair the utility of riboflavin as a biomarker of intestinal BCRP. To conclude, ticagrelor modestly raises the plasma concentration of riboflavin probably by inhibiting intestinal BCRP. Inhibition of intestinal MRP4 may have reduced the absorption of riboflavin and limited the effect of ticagrelor on riboflavin levels. [ABSTRACT FROM AUTHOR]

The photoATRP of methyl acrylate (MA) is investigated using riboflavin (RF) and CuBr2/Me6TREN as a dual catalyst system under green LED irradiation (λ ≈ 525 nm). Both RF and CuBr2/Me6TREN enhanced oxygen tolerance, enabling effective ATRP in the presence of residual oxygen. High molar mass polymers (up to Mn ≈ 129 000 g·mol−1) with low dispersity (Đ ≤ 1.16) are prepared, and chain‐end fidelity is confirmed through successful chain extension. The molecular masses of the obtained polymer increased linearly with conversion and showed high initiation efficiency. Mechanistic studies by laser flash photolysis reveal that the predominant activator generation mechanism is reductive quenching of RF by Me6TREN (83%, under [CuBr2]/[Me6TREN] = 1/3 condition), supported by polymerization kinetics and thermodynamic calculations. [ABSTRACT FROM AUTHOR]

Objective: This letter to the editor presents suggestions for the therapeutic use of riboflavin in perinatal brain lesions caused by oxygen deprivation.Methods: Clinical and preclinical studies using riboflavin conjugated with other components for the treatment of cerebral oxygen deprivation were included in the discussion.Results: Oxygen deprivation is predisposed by anoxia, hypoxia, or ischemia and causes severe early central damage, including sensorimotor impairment. At the moment, these lesions lack effective and affordable therapies. We present studies demonstrating the neuroprotective effects of riboflavin–containing drugs to treat children affected by hypoxic perinatal injuries.Discussion: This article suggests conducting preclinical studies to elucidate the potential isolated effects of riboflavin on the pathogenesis of perinatal brain injury caused by oxygen deprivation, by presenting routes for future clinical strategies for the prevention or treatment of perinatal encephalopathies. [ABSTRACT FROM AUTHOR]

The study focuses on the green synthesis of Ag@Ag2O nanostructures using Padina algae extract and functionalizing them with L-tryptophan to enhance their properties as a colorimetric sensor for simultaneous detection of ultra-trace levels of thiamin and riboflavin. The nanostructures are characterized using techniques like XRD, FESEM, FTIR, TEM, AFM, and DLS to understand their morphology, structure, and interactions with target molecules. FESEM analysis revealed the hierarchical flower-like Ag@Ag2O nanostructures. The TEM image shows the formation of core-shell nanostructures. Also, DLS analysis and surface zeta potential spectra illustrated the aggregated nature of fabricated nanocomposites in the presence of vitamins. The study is the first to report simultaneous determination of thiamin and riboflavin using a colorimetric sensor based on Ag@Ag2O-L-Try nanocomposites using partial leas square (PLS). The dynamic range of thiamin and riboflavin was achieved in 0.1 mol L−1 acetate buffer pH 4 and the ratio Ag@Ag2O: L-try 1:1. The Ag@Ag2O-L-Try sensor exhibited two linear ranges of 0.1- 1.0 and 3-350 µMol L− 1 for riboflavin and a linear range 3.0–60 µMol L− 1 for thiamin. Also, low detection limit of 1.92 µMol L− 1 and 0.048 µMol L− 1 was obtained for riboflavin and thiamin, respectively. The results indicated that the success of the method depends on the selective and sensitive colorimetric assay of the sensor along with the simultaneous determination by the PLS algorithm. Hence, the proposed technique can be used for the accurate and precise determination of vitamins in different pharmaceutical syrup and tablet samples. [ABSTRACT FROM AUTHOR]

Objectives: This pilot ex vivo study and first clinical experience in Italy evaluate the impact of using pre-implantation crosslinking on all-femtosecond laser-cut corneal allogenic intracorneal ring segments (AFXL CAIRSs). Methods: Six human donor eye-bank corneas were used for this preclinical ex vivo human study. Three donor (D) corneas were used for AFXL CAIRSs. First, they were prepared with an IntraLase™ femtosecond laser (Johnson & Johnson, New Brunswick, NJ, USA). The allogenic tissue rings were crosslinked before implantation with Riboflavin–UV-A accelerated crosslinking protocol (ACXL) with a 0.1% HPMC Riboflavin isotonic solution (Vibex Rapid, Glaukos-Avedro, Burlington, MA, USA) and a new KXL UV-A emitter (Glaukos-Avedro, USA). Three corneas were used as recipients (Rs) of the AFXL CAIRSs. After completing the ex vivo phase, IRB approval and signing a specific informed consent, the first two Italian patients were treated. A single ACXL CAIRS was implanted in a 51-year-old male with 53.53 D K steep, 363 μm minimum corneal thickness (MCT) and a double ACXL CAIRS was implanted in a 46-year-old male patient with 58.30 D K steep, 443 μm MCT. The longest follow-up was at three months. Results: Crosslinking of the segments enhanced tissue stiffness and grip, facilitating manipulation and CAIRS insertion into the recipient tunnels, and the yellowish color of the crosslinked segments improved visibility. The segment's thickness and volume remained unaltered during the follow-up. Both patients improved UDVA and BSCVA. K steep and High-Order Aberrations (HOAs) were reduced and MCT increased. Conclusions: Pre-implantation ACXL facilitated CAIRS insertion preserving dimensions and volume during the follow-up, rendering this important step a promising candidate in method standardization. Functional data and MCT improved significantly without adverse events. [ABSTRACT FROM AUTHOR]

Alterations of the microbiota-gut-brain axis has been associated with intestinal and neuronal inflammation in Parkinson's disease (PD). The aim of this work was to study some mechanisms associated with the neuroprotective effect of a combination (MIX) of lactic acid bacteria (LAB) composed by Lactiplantibacillus plantarum CRL2130 (riboflavin overproducing strain), Streptococcus thermophilus CRL808 (folate producer strain), and CRL807 (immunomodulatory strain) in cell cultures and in a chronic model of parkinsonism induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in aged mice, and under levodopa-benserazide treatment. In vitro, N2a differentiated neurons were exposed to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) and treated with intracellular bacterial extracts or with conditioned media from BV-2 cells exposed to the bacterial extracts. In vivo, motor skills, tyrosine hydrolase (TH) in brain and cytokine concentrations in serum and in brain were evaluated. The study of the faecal microbiota and the histology of the small intestine was also performed. The results showed that the neuroprotective effect associated with LAB MIX administration did not interfere with levodopa-benserazide treatment. This effect could be associated with the antioxidant and immunomodulatory potential of the LAB selected in the MIX, and was associated with the significant improvement in the motor tests and a higher number of TH + cells in the brain. In addition, LAB MIX administration was associated with modulation of the immune response. LAB administration decreased intestinal damage with an increase in the villus length /crypt depth ratio. Finally, the administration of the LAB MIX in combination with levodopa-benserazide treatment was able to partially revert the intestinal dysbiosis observed in the model, showing greater similarity to the profiles of healthy controls, and highlighting the increase in the Lactobacillaceae family. Different mechanisms of action would be related to the protective effect of the selected LAB combination which has the potential to be evaluated as an adjuvant for conventional PD therapies. [ABSTRACT FROM AUTHOR]

Riboflavin-5-phosphate (riboflavin) is the most commonly used photosensitizer in corneal crosslinking (CXL); while its efficient delivery into the stroma through the corneal epithelial barrier is challenging. In this paper, we presented novel responsive porous microneedles with ocular microinjection capability to deliver riboflavin controllably inside the cornea to facilitate CXL. The microneedle patch was composed of Poly (N-isopropyl acrylamide) (PNIPAM), graphene oxide (GO), and riboflavin-loaded gelatin. After penetrating the cornea by the stiff and porous gelatin needle tip, the photothermal-responsive characteristic of the PNIPAM/GO hydrogel middle layer could realize the contraction of the gel under the stimulation of near-infrared light, which subsequently could control the release of riboflavin from the backing layer into the cornea stromal site both in vitro and in vivo. Based on the microneedles system, we have demonstrated that this microinjection technique exhibited superior riboflavin delivery capacity and treatment efficacy to the conventional epithelial-on protocol in a rabbit keratoconus model, with benefits including minimal invasiveness and precise administering. Thus, we believe the responsive porous microneedles with riboflavin ocular microinjection capability are promising for clinical corneal crosslinking without epithelial debridement. [ABSTRACT FROM AUTHOR]

The impact of vitamin B2 (riboflavin) intake on cognitive performance among older adults in the United States (US) remains inadequately understood. This study aimed to explore the association between vitamin B2 intake and cognitive performance among non-institutionalized elderly people in the US. Weighted logistic regression was used to evaluate the association between vitamin B2 intake and cognitive performance. Vitamin B2 intake was determined from the mean of two 24-hour dietary recall interviews. Three cognitive ability assessment tests, namely the Immediate Recall Test (IRT), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST), were performed. Participants included all older adults over 60 who underwent cognitive scoring, with cut-offs defined based on the lowest quartile (25th percentile) for each test (the cut-offs for the three scores were 15.625, 12, and 33, respectively). Sensitivity analysis, including dose-response curves, subgroup analyses, interaction effects, per 1 standard deviation (SD), recommended dietary allowance (RDA), and residual energy model analysis, were performed to solidify the solid association between vitamin B2 and cognitive performance. A total of 2893 individuals aged over 60 were included, with a mean age of 69 (7) years, and 46% were men. There was a significant association between vitamin B2 intake and all three cognitive scores (IRT, Odds Ratio = 0.77, 95% confidence interval: [0.65,0.92]; AFT, 0.75, [0.64,0.88]; DSST, 0.72, [0.59,0.88]). Moreover, vitamin B2 intake above the RDA reduced the risk of low cognitive performance (IRT, 0.66, [0.46,0.93]; AFT, 0.83, [0.62,1.11]; DSST, 0.65, [0.45,0.92]) compared to intake below the RDA. Dose-response curves indicated that higher vitamin B2 intake was negatively associated with the risk of low cognitive performance. Physical activity may modify the association between vitamin B2 and cognitive performance. Vitamin B2 intake was positively associated with cognitive performance among older adults. Adequate vitamin B2 intake could help protect cognitive function. [ABSTRACT FROM AUTHOR]

Simple Summary: Growth traits are important economic traits of broilers. We found the key metabolites that may be related to the body weight of Wumeng black-bone chicken by comparing their serum metabolomics between the high- and low-weight groups. Metabolites with high levels in serum such as riboflavin and 2-isopropylmalic acid may be beneficial to growth performance, and the enrichment of inflammation-related metabolites may be related to low body weight of chickens. Our results can provide a certain reference for the analysis of metabolic mechanism of body-weight formation of chickens. Growth performance is an important economic trait of broilers but the related serum metabolomics remains unclear. In this study, we utilized non-targeted metabolomics using ultra-high-performance liquid phase tandem mass spectrometry (UHPLC-MS/MS) to establish metabolite profiling in the serum of Chinese Wumeng black-bone chickens. The biomarker metabolites in serum associated with growth performance of chickens were identified by comparing the serum metabolome differences between chickens that significantly differed in their weights at 160 days of age when fed identical diets. A total of 766 metabolites were identified including 13 differential metabolite classes such as lipids and lipid-like molecules, organic acids and their derivatives, and organoheterocyclic compounds. The results of difference analysis using a partial least squares discriminant analysis (PLS-DA) model indicated that the low-body-weight group could be differentiated based on inflammatory markers including prostaglandin a2, kynurenic acid and fatty acid esters of hydroxy fatty acids (FAHFA), and inflammation-related metabolic pathways including tryptophan and arachidonic acid metabolism. In contrast, the sera of high-body-weight chickens were enriched for riboflavin and 2-isopropylmalic acid and for metabolic pathways including riboflavin metabolism, acetyl group transfer into mitochondria, and the tricarboxylic acid (TCA) cycle. These results provide new insights into the practical application of improving the growth performance of local chickens. [ABSTRACT FROM AUTHOR]

Many cell culture experiments are performed under light to evaluate the photodynamic or photosensitizing efficacy of various agents. In this study, the modulation of photosensitizing responses and phototoxicity under cell culture conditions by different medium components was investigated. The significant levels of reactive oxygen species (ROS) generated from DMEM, RPMI 1640, and MEM were observed under the irradiation of fluorescent light (FL) and white and blue LEDs, indicating that these media have their own photosensitizing properties; DMEM showed the most potent property. Phenol red-free DMEM (Pf-D) exhibited a stronger photosensitizing property than normal DMEM by 1.31 and 1.25 times under FL and blue LEDs, respectively; phenol red and riboflavin-free DMEM (PRbf-D) did not show any photosensitizing properties. The inhibitory effect on light transmission was more pronounced in DMEM than in RPMI, and the interference effect on green LED light was greatest at 57.8 and 27.4%, respectively; the effect disappeared in Pf-D. The media containing riboflavin induced strong phototoxicity in HaCaT keratinocytes by generating H2O2 under light irradiation, which was quenched by sodium pyruvate in the media. The presence of serum in the media was also reduced the phototoxicity; H2O2 levels in the media decreased serum content dependently. The phototoxicity of erythrosine B and protoporphyrin IX under FL was more sensitively pronounced in PRbf-D than in DMEM. The present results indicate that several medium components, including riboflavin, phenol red, sodium pyruvate, and serum, could modulate photosensitizing responses in a cell culture system by inducing photosensitizing activation and by interfering with irradiation efficacy and ROS generation. [ABSTRACT FROM AUTHOR]

The ABCG2 membrane transporter affects bioavailability and milk secretion of xenobiotics and natural compounds, including vitamins such as riboflavin. We aimed to characterize the in vitro and in vivo interaction of ABCG2 with lumichrome, the main photodegradation product of riboflavin, which has proven in vitro anti-cancer activity and a therapeutical role in antibacterial photodynamic therapy as an efficient photosensitizer. Using MDCK-II polarized cells overexpressing murine Abcg2 and human ABCG2 we found that lumichrome was efficiently transported by both variants. After lumichrome administration to wild-type and Abcg2-/- mice, plasma AUC20–120 min was 1.8-fold higher in Abcg2-/- mice compared with wild-type mice. The liver and testis from Abcg2-/- mice showed significantly higher lumichrome levels compared with wild-type, whereas lumichrome accumulation in small intestine content of wild-type mice was 2.7-fold higher than in Abcg2-/- counterparts. Finally, a 4.1-fold-higher lumichrome accumulation in milk of wild-type versus Abcg2-/- mice was found. Globally, our results show that ABCG2 plays a crucial role in plasma levels, tissue distribution and milk secretion of lumichrome potentially conditioning its biological activity. [ABSTRACT FROM AUTHOR]

Manihot esculenta Crantz (cassava) is an important food crop in developing nations, with its tubers and leaves being a source of ascorbic acid, thiamin, riboflavin, and niacin (vitamins) and calcium, iron, potassium, and zinc (minerals). Malnutrition prevalence in some Kenyan Counties that relied on cassava‐based diets has partly been attributed to processing methods and/or nutrient bioaccessibility. The study area Kilifi County grows Kibandameno and Tajirika cassava varieties and is on record for high prevalence of undernutrition. The levels of vitamins and minerals, and their bioaccessibility in raw, boiled, and deep‐fried tubers, and pounded then boiled leaves of Kibandameno and Tajirika cassava varieties were studied. Digestion was done using static gastrointestinal digestion prior to the determination of vitamins (by HPLC) and minerals (by AAS and AES). Bioaccessibility of both vitamins and minerals was significantly higher (P < 0.001) in boiled followed by deep‐fried and lowest in raw tubers. Bioaccessibility ranged between 27% (Fe)–85% (vitamin C) in boiled, 20% (Fe)–79% (vitamin B1) in deep‐fried, and 15% (Fe)–(72% (K) in raw tubers. Bioaccessibility in processed leaves was significantly higher (P < 0.001) than in raw. This ranged between 11% (Fe)–81% (vitamin B1) in processed and between 8% (Fe)–67% (K) in raw leaves. Processing therefore significantly reduced levels of ascorbic acid, thiamin, riboflavin, niacin, calcium, iron, potassium, and zinc in raw tubers and leaves of Kibandameno and Tajirika Manihot esculenta Crantz varieties. Their bioaccessibility however significantly increased, being higher in tubers than in leaves. [ABSTRACT FROM AUTHOR]

Riboflavin is a common marker of microbial corrosion and can act as an electron shuttle in the solvated state to enhance electron transfer efficiency. In this paper, an in‐situ label‐free fiber‐optic biosensor modified by Ti3C2‐MXene@Square Gold nanoparticles (SGNps) composites and riboflavin kinase is developed, which behaved with high sensitivity for measuring riboflavin. The sensing interface of the sensor is constructed by stepwise assembly of SGNps and riboflavin kinase using Ti3C2‐MXene nanosheets as the supporting substrate. Riboflavin kinase catalyzed the phosphorylation of riboflavin to form flavin mononucleotides in the presence of adenine nucleoside triphosphate and Mg2+. Experimental results showed that the sensitivity of riboflavin measurement is 5.61 nm µm−1 and the limit of detection (LOD) is 115 nmol L−1 (nm) in the concentration range of 0–2.656 µm. In situ label‐free monitoring of riboflavin in Shewanella, the sensitivity of the sensor in bacterial fragmentation fluid is 53.90 nm/OD within the optical density (OD) of 0–0.175, and the LOD is OD = 0.017. The above results verified the feasibility of the sensor for in situ monitoring of riboflavin in microbial corrosive environments, with ultra‐low detection limit and good selectivity, which undoubtedly provided great research value for the application of optical fiber sensors in microbial corrosion monitoring. [ABSTRACT FROM AUTHOR]

The aim of this longitudinal case series was to describe long‐term functional outcome in a group of individuals with riboflavin transporter deficiency (RTD) treated with high‐dose oral riboflavin. Data were collected between 2012 to 2022. Eleven individuals with RTD were assessed at 12‐month intervals for monitoring of disease progression. Patients had commenced high‐dose oral riboflavin from the time of genetic diagnosis. Individuals for whom riboflavin supplementation was initiated early after disease onset had better outcomes compared to those in whom diagnosis was delayed. Despite ongoing riboflavin supplementation, the Charcot–Marie–Tooth disease Pediatric Scale (CMTPedS) total score and the subitems of balance and the 6‐Minute Walk Test distance as well as respiratory function worsened, while grip strength improved. There was evidence of improvement in hearing loss and optic atrophy limited to the first 12 months of treatment. While treatment with riboflavin slowed disease progression, patients were left with residual disability. To track disease progression and response to riboflavin supplementation over time, we recommend using the RTD Pediatric Scale and provide a list of clinical measures for regular surveillance of children with RTD. [ABSTRACT FROM AUTHOR]

ABSTRACT Milk, owing to its nutritional value, is a staple commodity in daily life. Ensuring its integrity and authenticity is paramount for researchers and the food industry. To evaluate spoilage and adulteration of milk, we proposed a robust and reliable optical method to guarantee milk quality by utilizing riboflavin as an internal biomarker. By precisely controlling the content of Eu3+, Tb3+, and Gd3+ ions, a two‐dimensional ratiometric luminescence lanthanide coordination polymer (Ln‐CP) with adjustable emission centers was synthesized for the detection of riboflavin (RF), leveraging a Förster resonance energy transfer (FRET) and photoinduced electron transfer (PET) process. This method demonstrates high sensitivity and selectivity towards RF and has been successfully applied to the detection of RF in both milk and calf serum. [ABSTRACT FROM AUTHOR]

Background and Aim: Increased oxidative stress within the airways is associated to epithelial damage and amplification of inflammatory responses that in turn contribute to Chronic Obstructive Pulmonary Disease (COPD) progression. This study was aimed to identify whether a new formulation of N-acetylcisteine (NAC), carnitine, curcumin and B2 vitamin could counteract oxidative stress and downstream pro-inflammatory events promoted by cigarette smoke extract (CSE) exposure in primary bronchial epithelial cells (PBEC), both submerged/ undifferentiated (S-PBEC) and cultured at the air-liquid interface (ALI-PBEC). Methods: PBEC were exposed to CSE with/without the new formulation or NAC alone and ROS production, IL-8 and IL-6 gene expression and protein release were evaluated. Results: CSE increased ROS, IL-8 and IL-6 gene expression and protein release and the new formulation counteracted these effects. NAC alone was not effective on IL-8 and IL-6 release. The effects of a similar nutraceutical formulation were evaluated in COPD patients treated for six months. The results showed that the treatment reduced the concentration of IL-8 in nasal wash and improved quality of life. Conclusion: The tested formulation, exerting antioxidant and anti-inflammatory effects, can preserve airway epithelial homeostasis and improve clinical symptoms in COPD. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop and validate methods for the determination of vitamins B2, B9, E and A in serum using liquid chromatography with mass spectrometry (MS) detection. Vitamin analysis was performed using an ultra performance liquid chromatography combined with tandem MS. The compounds were separated on a BEH C18 RP column (2.1 × 100 mm, 1.7 μm) using a gradient elution with an analysis time of 10 min. Sample preparation included protein precipitation with ethanol. The concentration range in human serum was as follows: riboflavin 5–1000 nmol/L, folic acid 2.5–250 nmol/L, α-tocopherol 0.5–100 μmol/L and all-trans-retinol 25–2500 nmol/L. Accuracy and precision were validated according to Food and Drug Administration guidelines, with coefficients of variation ranging from 3.1–11.7% and recoveries from 94.4–107.5%. Routine monitoring of the complex range of vitamins in bariatric medicine is still not common. This is despite the fact that patients are at risk for glitch deficits, especially of a neurological nature. An analytical method that allows for the complex measurement of both water-soluble and fat-soluble vitamins is important and necessary for the clinical monitoring of bariatric patients. The method we have described could benefit both clinical practice and nutritional research. [ABSTRACT FROM AUTHOR]

Vitamin B2 is an essential water-soluble vitamin. For most prokaryotes, a bifunctional enzyme called FAD synthase catalyzes the successive conversion of riboflavin to FMN and FAD. In this study, the plasmid pNEW-AZ containing six key genes for the riboflavin synthesis was transformed into strain R2 with the deleted FMN riboswitch, yielding strain R5. The R5 strain could produce 540.23 ± 5.40 mg/L riboflavin, which was 10.61 % higher than the R4 strain containing plasmids pET-AE and pAC-Z harboring six key genes. To further enhance the production of riboflavin, homology matching and molecular docking were performed to identify key amino acid residues of FAD synthase. Nine point mutation sites were identified. By comparing riboflavin kinase activity, mutations of T203D and N210D, which respectively decreased by 29.90 % and 89.32 % compared to wild-type FAD synthase, were selected for CRISPR/Cas9 gene editing of the genome, generating engineered strains R203 and R210. pNEW-AZ was transformed into R203, generating R6. R6 produced 657.38 ± 47.48 mg/L riboflavin, a 21.69 % increase compared to R5. This study contributes to the high production of riboflavin in recombinant E. coli BL21. [ABSTRACT FROM AUTHOR]

Riboflavin, an essential vitamin for humans, is extensively used in various industries, with its global demand being met through fermentative processes. Hyphopichia wangnamkhiaoensis is a novel dimorphic yeast species capable of producing riboflavin. However, the nutritional factors affecting riboflavin production in this yeast species remain unknown. Therefore, we conducted a kinetic study on the effects of various nutritional factors—carbon and energy sources, nitrogen sources, vitamins, and amino acids—on batch riboflavin production by H. wangnamkhiaoensis. Batch experiments were performed in a bubble column bioreactor to evaluate cell growth, substrate consumption, and riboflavin production. The highest riboflavin production was obtained when the yeast growth medium was supplemented with glucose, ammonium sulfate, biotin, and glycine. Using these chemical components, along with the mineral salts from Castañeda-Agullo's culture medium, we formulated a novel, low-cost, and effective culture medium (the RGE medium) for riboflavin production by H. wangnamkhiaoensis. This medium resulted in the highest levels of riboflavin production and volumetric productivity, reaching 16.68 mg/L and 0.713 mg/L·h, respectively, within 21 h of incubation. These findings suggest that H. wangnamkhiaoensis, with its shorter incubation time, could improve the efficiency and cost-effectiveness of industrial riboflavin production, paving the way for more sustainable production methods. [ABSTRACT FROM AUTHOR]

Honey is one of the oldest natural compounds that come from ancient times to nowadays with health benefits. It has been used for the treatment of several diseases, but its role in oral health faces real skepticism due to the high concentration of carbohydrates in its composition. Many studies over the years have confirmed several pharmacological activities such as antioxidant, antibacterial, antihistaminic, etc. It is composed of different chemical compounds like carbohydrates, proteins, amino acids, vitamins, minerals, organic acids, phenolic compounds, and volatile substances. Honey contains many enzymes such as invertase, catalase, glucose oxidase, and acid phosphorylase, as well as traces of vitamins B2, B4, B5, B6, B11, and vitamin C, minerals such as calcium, iron, zinc, potassium, magnesium. A promising challenge is the use of honey as a targeting product obtained from green synthesis, with high-efficiency thanks to nanotechnology. This study aims to investigate the potential benefits of honey in oral health, leveraging its diverse biological activity like antimicrobial, and antioxidant effects. Additionally, our scope was to provide scientific evidence supporting the use of honey in dentistry, emphasizing its broader health benefits and novel applications in oral health care. [ABSTRACT FROM AUTHOR]

Summary: A few Capsicum (pepper) species produce yellow‐colored floral nectar, but the chemical identity and biological function of the yellow pigment are unknown.A combination of analytical biochemistry techniques was used to identify the pigment that gives Capsicum baccatum and Capsicum pubescens nectars their yellow color. Microbial growth assays, visual modeling, and honey bee preference tests for artificial nectars containing riboflavin were used to assess potential biological roles for the nectar pigment.High concentrations of riboflavin (vitamin B2) give the nectars their intense yellow color. Nectars containing riboflavin generate reactive oxygen species when exposed to light and reduce microbial growth. Visual modeling also indicates that the yellow color is highly conspicuous to bees within the context of the flower. Lastly, field experiments demonstrate that honey bees prefer artificial nectars containing riboflavin.Some Capsicum nectars contain a yellow‐colored vitamin that appears to play roles in (1) limiting microbial growth, (2) the visual attraction of bees, and (3) as a reward to nectar‐feeding flower visitors (potential pollinators), which is especially interesting since riboflavin is an essential nutrient for brood rearing in insects. These results cumulatively suggest that the riboflavin found in some Capsicum nectars has several functions. [ABSTRACT FROM AUTHOR]

Background: Nutri Crackle rusk, developed using an innovative pigmented variety of black rice flour, possesses a rich nutritional profile with essential amino acids, dietary fibers, and antioxidants, offering unique health benefits beyond traditional rice varieties. Establishing healthy eating habits during childhood cancer treatment is crucial for long-term well-being. Mindful consumption, incorporating Nutri Crackle rusk instead of empty-calorie snacks, can significantly improve the quality of life of childhood cancer survivors during their survivorship period. Materials and Methods: The novel Nutri Crackle rusk using black rice flour was developed under proper hygienic conditions. Semi-trained panel and consumer panel members evaluated the organoleptic properties of the developed product. Nutrient components of the formulated Nutri Crackle rusk were examined through an organoleptic assessment. Results: The nutrient composition of the formulated Nutri Crackle rusk was analyzed using a standard procedure. Sensory evaluation indicated positive feedback, with an overall acceptability score of 8.01. Nutrient analysis revealed a well-rounded profile, emphasizing energy provision (464.285 kcal), (11.97 g protein), (11.29 g fiber), and essential micronutrients (zinc, iron, and vitamins B1 and B2). Nutri Crackle rusk is a favorable and potentially beneficial snack for this vulnerable group. Conclusion: The study signifies that the novel healthy Nutri Crackle rusk is rich in fiber, zinc, iron, protein, vitamin B1, and vitamin B2. Intake of the developed Nutri Crackle rusk could be a healthy alternative for pediatric cancer patients and cancer survivors. [ABSTRACT FROM AUTHOR]

Development of multi-, extensively-, and pandrug-resistant (MDR, XDR, and PDR) strains of Pseudomonas aeruginosa remains a major problem in medical care. The present study evaluated the effect of antimicrobial photodynamic therapy (aPDT) as a monotherapy and in combination with colistin against P. aeruginosa isolates. Two P. aeruginosa isolates recovered from patients with respiratory tract infections were examined in this study. Minimum inhibitory concentration (MIC) of colistin was determined by the colistin broth disk elution (CBDE) and the reference broth microdilution (rBMD) methods. aPDT was performed using the photosensitizer (Ps) riboflavin at several concentrations and a light-emitting diode (LED) emitting blue light for different irradiation times with or without colistin at 1/2 × MIC concentration. Both PA1 and PA2 isolates were identified as colistin-resistant P. aeruginosa with a MIC ≥4 μg/mL by the CBDE and MICs of 512 μg/mL and 256 μg/mL, respectively, by the rBMD. In aPDT, neither riboflavin nor LED light alone had antibacterial effects. The values of colony forming units per milliliter (CFU/mL) in both isolates were significantly reduced by LED + Ps treatments in a time-dependent manner (LED irradiation time) and dose-dependent manner (Ps concentration). In comparison with control, treatment with Ps (50 μM) + LED (120 s) and Ps (100 μM) + LED (120 s) resulted in 0.27 log 10 CFU/mL and 0.43 log 10 CFU/mL reductions in PA1, and 0.28 log 10 CFU/mL and 0.34 log 10 CFU/mL reductions in PA2, respectively, (P < 0.01). The best results were obtained after the combination of aPDT followed by colistin, which increased bacterial reduction, resulting in a 0.41−0.7 log 10 CFU/mL reduction for PA1 and 0.35−0.83 log 10 CFU/mL reduction for PA2 (P = 0.001). This study suggests the potential implications of aPDT in combination with antibiotics, such as colistin for treatment of difficult-to-treat P. aeruginosa infections. [ABSTRACT FROM AUTHOR]

Methionine is an essential amino acid for mammals and it is limiting for monogastric animals. It can be oxidized easily by UV light. This could influence the bioaccessibility and bioavailability of methionine. In this work, the photosensitized degradation of peptide-bound methionine in the presence of riboflavin was investigated in a model system. Capillary electrophoresis was employed to analyze the time course of the degradation. The products were identified by liquid chromatography coupled to mass spectrometry (LC–MS/MS). Benzoyl methionine was degraded by 50% during UV irradiation in the presence of riboflavin after 5.0 min with 10 mol% riboflavin and 6.4 min with 3 mol% riboflavin. Homocysteine (16–20 mol%) and β-aspartic semialdehyde (ca. 30 mol%) were found as major degradation products next to methionine sulfoxide (ca. 25 mol%). A smaller molar ratio of riboflavin led to a higher formation of aspartic semialdehyde. The formation of homocysteine was paralleled by the formation of formaldehyde. Furthermore, the experiment was transferred to small peptides, which showed the analogous degradation products of peptide-bound methionine. [ABSTRACT FROM AUTHOR]

Brain oxygen deprivation causes morphological damage involved in the formation of serious pathological conditions such as stroke and cerebral palsy. Therapeutic methods for post-hypoxia/anoxia injuries are limited and still have deficiencies in terms of safety and efficacy. Recently, clinical studies of stroke have reported the use of drugs containing riboflavin for post-injury clinical rehabilitation, however, the effects of vitamin B2 on exposure to cerebral oxygen deprivation are not completely elucidated. This review aimed to investigate the potential antioxidant, anti-inflammatory and neuroprotective effects of riboflavin in cerebral hypoxia/anoxia. After a systematic search, 21 articles were selected, 8 preclinical and 12 clinical studies, and 1 translational study. Most preclinical studies used B2 alone in models of hypoxia in rodents, with doses of 1–20 mg/kg (in vivo) and 0.5–5 µM (in vitro). Together, these works suggested greater regulation of lipid peroxidation and apoptosis and an increase in neurotrophins, locomotion, and cognition after treatment. In contrast, several human studies have administered riboflavin (5 mg) in combination with other Krebs cycle metabolites, except one study, which used only B2 (20 mg). A reduction in lactic acidosis and recovery of sensorimotor functions was observed in children after treatment with B2, while adults and the elderly showed a reduction in infarct volume and cognitive rehabilitation. Based on findings from preclinical and clinical studies, we conclude that the use of riboflavin alone or in combination acts beneficially in correcting the underlying brain damage caused by hypoxia/anoxia and its inflammatory, oxidative, and behavioral impairments. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Chinese Institute of Food Science & Technology is the property of Journal of Chinese Institute of Food Science & Technology Periodical Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Mucosal-associated invariant T (MAIT) cells are unconventional T cells that recognize microbial riboflavin pathway metabolites presented by evolutionarily conserved MR1 molecules. We explored the human MAIT cell compartment across organ donor–matched blood, barrier, and lymphoid tissues. MAIT cell population size was donor dependent with distinct tissue compartmentalization patterns and adaptations: Intestinal CD103+ resident MAIT cells presented an immunoregulatory CD39highCD27low profile, whereas MAIT cells expressing NCAM1/CD56 dominated in the liver and exhibited enhanced effector capacity with elevated response magnitude and polyfunctionality. Both intestinal CD39high and hepatic CD56+ adaptations accumulated with donor age. CD56+ MAIT cells displayed limited T cell receptor–repertoire breadth, elevated MR1 binding, and a transcriptional profile skewed toward innate activation pathways. Furthermore, CD56 was dynamically up-regulated to a persistent steady-state equilibrium after exposure to antigen or IL-7. In summary, we demonstrate functional heterogeneity and tissue site adaptation in resident MAIT cells across human barrier tissues with distinct regulatory and effector signatures. Editor's summary: Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells that recognize microbial riboflavin pathway–derived metabolites. Our understanding of MAIT cell functions in tissue homeostasis and antimicrobial responses has primarily relied on studies of mice and human peripheral blood. Using paired samples from adult human blood and mucosal and lymphoid tissues, Kammann et al. performed a cross-tissue characterization of human MAIT cells. Tissue-specific adaptations included a population of intestinal CD39hi MAIT cells with an immunoregulatory phenotype and liver-enriched CD56+ MAIT cells bearing enhanced effector capacity and innate-like features. Together, these findings highlight the phenotypic and functional specialization of human MAIT cells within specific tissue sites. —Claire Olingy [ABSTRACT FROM AUTHOR]

Manidipine (MP) is widely used for reducing high blood pressure. Calslot® (CALS) tablets, which are the original MP medicines, and their generic medicines have been used for patients in clinical situations. The authors hypothesized that the photodegradability of MP drug substance in CALS tablets might be enhanced when the tablets were photo-exposed after the change of the dosage form by the presence of riboflavin (RF), which is utilized as a coloring agent and a well-known photosensitizer. The present study clarified that RF enhanced the photodegradation of MP when the powders and the suspensions of CALS tablets were ultraviolet light (UV) irradiated. The addition of RF to the suspension of MP standard substances also promoted MP photodegradation along with the increase of the generation rate of its main photoproduct, benzophenone. Finally, the authors performed the photostabilization of MP suspensions based on the addition of quercetin (QU), which is one of polyphenols and has both the antioxidative potency and the UV filtering potency. It is summarized that QU has a protective potency for MP's own photodegradation, and it partially suppresses the photocatalytic effect of RF. Further studies focused on the photochemical behaviors of utilized additives for medicines are needed for their safe use. [ABSTRACT FROM AUTHOR]

Copyright of Science & Technology of Food Industry is the property of Science & Technology of Food Industry Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

As reported by the FAO, in 2022, approximately 735 million people experienced undernourishment, underscoring the critical need for effective strategies to address micronutrient deficiencies. Among these strategies, the mass fortification of staple foods, particularly rice—a dietary staple for half of the global population—has emerged as one of the most effective approaches. Conventional milling processes diminish the nutritional content of rice, necessitating the development of fortification methods to enhance its nutrient profile. This study investigates advanced fortification techniques to improve the nutritional value of rice, focusing on vitamins B1, B2, and B6, with guidelines from the US Institute of Medicine's Dietary Reference Intakes. The results indicate that implementing ultrasonic treatments and optimal soaking conditions (60 °C for 60 min) significantly enhances the absorption of these vitamins. Effective parameters included a concentration of 1500 ppm for vitamin B1 and higher levels for vitamins B2 and B6, with a rice-to-vitamin solution ratio of 1:4. These conditions yielded an absorbed vitamin B1 content of 1050 mg/kg, bringing the fortified rice closer to meeting recommended intake levels. Given the global average daily consumption of 100 g of rice per person, this research demonstrates the feasibility of fortifying rice to address nutrient deficiencies effectively and contribute to improved dietary health worldwide. Further enhancement of vitamin B2 and B6 levels remains essential for optimal fortification, highlighting the potential of fortified rice as a sustainable solution for improving global nutrition. [ABSTRACT FROM AUTHOR]

Abstract Background Riboflavin transporter deficiency (RTD) is an inborn error of riboflavin transport causing progressive neurological symptoms if left untreated. While infants with symptomatic RTD rapidly deteriorate, presentation later in childhood or in adulthood is more gradual. Symptoms overlap with more common diseases, carrying a risk of misdiagnosis, and given the relatively recent discovery of the genetic basis of RTD in 2010 it is likely that older patients have not been tested. Treatment with oral riboflavin (vitamin B2) halts disease progression and can be lifesaving. We hypothesized that patients may have been left unrecognized at the time of presentation and therefore we performed a datamining study to detect undiagnosed RTD patients in a tertiary referral hospital. Methods A systematic search in Electronic Health Records (EHR) of all patients visiting the Amsterdam University Medical Centers between January 2004 and July 2021 was performed by a medical data text-mining tool. Pseudonymized patient records, matching pre-defined search terms (hearing loss or auditory neuropathy spectrum disorders combined with key clinical symptoms or riboflavin) were screened and included if no definitive alternative diagnosis for symptoms indicating possible RTD was found. Included patients were offered genetic testing. We documented total number of patients with possible RTD, number of patients that underwent genetic testing for RTD and results of genetic testing. Results EHR of 2.288.901 patients were automatically screened. Thirteen patients with possible RTD were identified and offered genetic testing. Seven patients chose not to participate. Genetic testing was performed in 6 patients and was negative. The datamining did detect all previously known RTD patients in the hospital. Conclusions By screening a large cohort of patients of all ages in a tertiary referral hospital in a period spanning 17 years, no new RTD patients were found. Although not all suspected patients underwent genetic testing, our findings suggest that the prevalence of RTD is low and the chance of having missed this diagnosis in a tertiary referral hospital is limited.

Abstract Riboflavin (vitamin B2) is an essential B-vitamin crucial for the metabolism, development, and overall well-being of porcine species. As pig production intensifies, understanding the micronutrient needs of swine, particularly riboflavin, becomes increasingly vital. Riboflavin acts as a precursor for coenzymes involved in key redox reactions essential for energy production, growth, and immune regulation. Ariboflavinosis can disrupt metabolic functions, leading to impaired growth, reproductive issues, decreased feed efficiency, compromised immune function, ocular problems, and liver dysfunction. To ensure optimal growth and health, pig diets are consistently supplemented with riboflavin-enriched supplements. This review explores the diverse functions of riboflavin in swine metabolism, focusing on biochemical basics, metabolic pathways, riboflavin uptake and distribution, consequences of deficiency, and benefits of adequate intake. It emphasizes the need for optimized riboflavin supplementation strategies tailored to different production stages and environmental conditions. According to recommendations from four major breeding companies, the dietary riboflavin levels for swine are advised to range between 7.5 and 15 mg/kg for piglets, 3.5 to 8.0 mg/kg for finishing gilts and barrows, 4 to 10 mg/kg for gestating sows, and 5 to 10 mg/kg for lactating sows. Advances in precision nutrition, microbial production of riboflavin, and the development of functional feed additives are potential innovations to enhance swine health, growth performance, and sustainability. Comprehensive studies on the long-term effects of subclinical riboflavin deficiency and the broader health and welfare implications of supplementation are also needed. Addressing knowledge gaps and embracing future trends and innovations will be key to optimizing riboflavin supplementation and advancing the swine industry.

Abstract The impact of vitamin B2 (riboflavin) intake on cognitive performance among older adults in the United States (US) remains inadequately understood. This study aimed to explore the association between vitamin B2 intake and cognitive performance among non-institutionalized elderly people in the US. Weighted logistic regression was used to evaluate the association between vitamin B2 intake and cognitive performance. Vitamin B2 intake was determined from the mean of two 24-hour dietary recall interviews. Three cognitive ability assessment tests, namely the Immediate Recall Test (IRT), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST), were performed. Participants included all older adults over 60 who underwent cognitive scoring, with cut-offs defined based on the lowest quartile (25th percentile) for each test (the cut-offs for the three scores were 15.625, 12, and 33, respectively). Sensitivity analysis, including dose-response curves, subgroup analyses, interaction effects, per 1 standard deviation (SD), recommended dietary allowance (RDA), and residual energy model analysis, were performed to solidify the solid association between vitamin B2 and cognitive performance. A total of 2893 individuals aged over 60 were included, with a mean age of 69 (7) years, and 46% were men. There was a significant association between vitamin B2 intake and all three cognitive scores (IRT, Odds Ratio = 0.77, 95% confidence interval: [0.65,0.92]; AFT, 0.75, [0.64,0.88]; DSST, 0.72, [0.59,0.88]). Moreover, vitamin B2 intake above the RDA reduced the risk of low cognitive performance (IRT, 0.66, [0.46,0.93]; AFT, 0.83, [0.62,1.11]; DSST, 0.65, [0.45,0.92]) compared to intake below the RDA. Dose-response curves indicated that higher vitamin B2 intake was negatively associated with the risk of low cognitive performance. Physical activity may modify the association between vitamin B2 and cognitive performance. Vitamin B2 intake was positively associated with cognitive performance among older adults. Adequate vitamin B2 intake could help protect cognitive function.

Abstract Riboflavin transporter deficiency (RTD) is a genetic disorder of reduced riboflavin (vitamin B2) uptake that causes progressive, multifocal neurological dysfunction. Most patients present in early childhood; if patients present later in life, symptoms usually develop more gradually. We report three previously healthy young adults, who developed rapidly progressive neurological symptoms after decreasing dietary intake of meat and dairy. After a diagnostic odyssey, the diagnosis of a riboflavin transporter deficiency was made. Treatment with high dose oral riboflavin (20–40 mg/kg/day) partially reversed symptoms. This case series highlights that reduced riboflavin intake as a result of dietary changes can unmask RTD at a later age. We emphasize the importance of early recognition of this progressive and potentially lethal disease and show that timely treatment with high dose riboflavin is highly effective.

Alcoholic liver disease (ALD) is a disease with high incidence, limited therapies, and poor prognosis. The present study aims to investigate the effect of riboflavin on ALD and explore its potential therapeutic mechanisms. C57BL/6 mice were divided into the control, alcohol, and alcohol+ riboflavin groups. 16S rRNA-seq and RNA-seq analysis were utilized to analyze the polymorphism of intestinal microbiota and the transcriptome heterogeneity respectively. KEGG and GO enrichment analysis were performed. CIBERSORTx was applied to evaluate the immune cell infiltration level. Publicly available transcriptome data of ALD was enrolled and combined with the RNA-seq data to identify the immune subtypes of ALD. Pathological and histology analysis demonstrated that riboflavin reversed the progression of ALD. 16S rRNA-seq results showed that riboflavin could regulate alcohol-induced intestinal microbiota alteration. Intestinal microbiota polymorphism analysis indicated that VLIDP may contribute to the progression of ALD. Based on the VLIDP pathway, two subtypes were identified. Immune microenvironment analysis indicated that the upregulated inflammatory factors may be important regulators of ALD. In conclusion, intestinal microbiota homeostasis was associated with the protective effect of riboflavin against ALD, which was likely mediated by modulating inflammatory cell infiltration. Riboflavin emerges as a promising therapeutic candidate for the management of ALD. Riboflavin attenuates alcoholic liver disease progression, regulates alcohol-induced changes in intestinal microbiota, and affects inflammatory cell infiltration suggesting that riboflavin may be a potentially effective agent for treating ALD [ABSTRACT FROM AUTHOR]

Simple Summary: Pigeons are one of the oldest domesticated birds in the world, and humans have been raising pigeons for thousands of years. Pigeon meat is edible and rich in protein, polyunsaturated fatty acids, minerals, and vitamins. As a late-maturing bird, pigeons need to be fed by their parents to obtain nutrients. Therefore, the dietary nutritional level of pigeon breeders is vital for production and reproduction. However, there is currently no explicit nutritional requirement for pigeon riboflavin internationally. This study aimed to investigate the effects of dietary riboflavin levels on the reproductive performance of pigeon breeders and the growth performance and carcass traits of offspring squabs to estimate the riboflavin requirement of pigeon breeders. The natural riboflavin content in the basic diet of corn–peas–soybean–wheat–sorghum–corn gluten is 1.20 mg/kg. Different doses of riboflavin (0, 2.5, 5, 10, and 15 mg/kg) were supplemented with the basal diet to produce five dietary treatments with total riboflavin levels of 1.20, 3.70, 6.20, 10.20, and 16.20 mg/kg. A total of 120 pairs of White King pigeons, aged 60 wks, were randomly allocated into five treatment groups, each consisting of 24 pairs. Each pair was individually raised for 8 wks. After the experiment, an assessment was conducted to evaluate the reproductive performance of the pigeon breeders, as well as the growth and carcass traits of offspring squabs at 28 days of age. The results showed that the dietary riboflavin levels had no significant effect on body weight, feed intake, egg weight, egg production, and egg fertility (p > 0.05). However, pigeons fed a diet without riboflavin had the lowest egg hatchability, egg yolk color, carcass trait, and riboflavin status, while exhibiting higher liver weight and liver index (p < 0.05). Moreover, the indices above showed increased or decreased linearly as the level of riboflavin was increased in the diet. Based on the broken-line regression model, pigeon breeders were determined to require a dietary riboflavin content of 11.4, 13.6, 13.4, 6.60, 4.28, 4.47, 4.67, 6.69, and 6.82 mg/kg to optimize hatchability, eviscerated weight, half-eviscerated weight, breast muscle weight, breast muscle percentage, liver weight, liver index, egg yolk riboflavin, and squab plasma riboflavin, respectively. In conclusion, the optimal supplemental dosage of riboflavin in the diets of pigeon breeders is 13.6 mg/kg. [ABSTRACT FROM AUTHOR]

Collagen crosslinking employing ultraviolet A rays and riboflavin (UVA/R) has emerged as a pivotal technique in clinical therapies, especially in ophthalmology since the 1990s. Despite its clinical adoption, the lack of clarity of the detailed mechanism and the imperative for a refined manufacturing process necessitates further investigation. This study advances the understanding of UVA/R crosslinked collagen, concentrating on identifying the primary crosslinking sites using seven synthetic peptides and exploring the pathways of riboflavin‐mediated crosslinking. The results demonstrate that tyrosine residues are key crosslinking sites, and riboflavin plays a dual role as both a catalyst and a competitive inhibitor in the crosslinking process. Furthermore, the UVA/R crosslinked collagen matrix exhibits a more harmonious balance between stability and degradability compared with chemically crosslinked collagen matrices, coupled with superior mechanical properties and augmented biocompatibility. In vivo experiments further validate its excellent biocompatibility, reduced tissue inflammation, and promotion of tissue regeneration. The research provides crucial insights into collagen crosslinking mechanisms, paving the way for the development of sophisticated collagen‐based biomaterials tailored for biomedical applications. [ABSTRACT FROM AUTHOR]

Garlic (Allium sativum L.) is one of the most esteemed plants due to its medicinal properties. Its health benefits for humans are attributed to its chemical compounds. Few studies characterize garlic genotypes cultivated in Romania concerning their chemical composition. In this context, this study aimed to determine the chemical compounds for 16 local garlic genotypes cultivated under the same climatic and technological conditions. The chemical characteristics studied were the total phenolic content (TPC), total flavonoid content (TFC), reducing sugar content, antioxidant activity (AO), vitamin C, and acidity level. Chemical composition varied significantly among genotypes: TPC ranged from 656.07 to 1317.32 µg GAE/g FW; TFC ranged from 427.08 to 1447.90 µg QE/g FW; vitamin C ranged from 3.24 to 5.37 mg/g FW; reducing sugar content ranged from 3.24 to 5.37 mg/g FW; and the acidity level for the control was 6 meq/100 g. Among the selected genotypes, differences were observed between 3.48 and 11.02 meq/100 g. Significant correlations were noted between different compounds, specifically between TPC and AO, as well as between TPC and acidity level. In conclusion, this study highlights significant variability in terms of chemical composition of local garlic genotypes, which indicates notable differences between them and suggests that the genotypes may have different potential in medicinal and nutritional uses due to their distinctive chemical compositions. [ABSTRACT FROM AUTHOR]

Insects and their gut bacteria form a tight and beneficial relationship, especially in utilization of host nutrients. The red turpentine beetle (RTB), a destructive and invasive pine pest, employs mutualistic microbes to facilitate its invasion success. However, the molecular mechanism underlying the utilization of nutrients remains unknown. In this study, we found that gut bacteria are crucial for the utilization of D-glucose, a main carbon source for RTB development. Downstream assays revealed that gut bacteria-induced gut hypoxia and the secretion of riboflavin are responsible for RTB development by regulating D-glucose transport via the activation of a hypoxia-induced transcription factor 1 (Hif-1α). Further functional investigations confirmed that Hif-1α mediates glucose transport by direct upregulation of two glucose transporters (ST10 and ST27), thereby promoting RTB development. Our findings reveal how gut bacteria regulate the development of RTB, and promote our understanding of the mutualistic relationship of animals and their gut bacteria. [ABSTRACT FROM AUTHOR]

Mucosal-associated invariant T (MAIT) cells are unconventional T cells that respond to riboflavin biosynthesis and cytokines through TCR-dependent and -independent pathways, respectively. MAIT cell activation plays an immunoprotective role against several pathogens, however the functional capacity of MAIT cells following direct infection or exposure to infectious agents remains poorly defined. We investigated the impact of Varicella Zoster Virus (VZV) on blood-derived MAIT cells and report virus-mediated impairment of activation, cytokine production, and altered transcription factor expression by VZV infected (antigen+) and VZV exposed (antigen-) MAIT cells in response to TCR-dependent and -independent stimulation. Furthermore, we reveal that suppression of VZV exposed (antigen-) MAIT cells is not mediated by a soluble factor from neighbouring VZV infected (antigen+) MAIT cells. Finally, we demonstrate that VZV impairs the cytolytic potential of MAIT cells in response to riboflavin synthesising bacteria. In summary, we report a virus-mediated immune-evasion strategy that disarms MAIT cell responses. Author summary: Mucosal-associated invariant T (MAIT) cells are a uniquely specialised and substantial innate-T cell population that can rapidly respond to diverse bacterial and fungal pathogens through T cell receptor dependent recognition of riboflavin synthesis derived metabolite antigens. Additionally, MAIT cells can be triggered by local pro-inflammatory cues such as cytokines; therefore extending their functionality to non-riboflavin pathogens such as viral infections. Despite the capacity of MAIT cells to play a protective role against several classes of pathogens, there remains a dearth of studies investigating direct pathogenic suppression of MAIT cell functionality. Here, we investigate a previously uncharacterised interplay between MAIT cells and the causative agent of varicella (chickenpox) and shingles (zoster): Varicella Zoster Virus (VZV). VZV successfully infects and establishes lifelong latency within the host; in part to their ability to effectively manipulate several innate and adaptive axes of the host immune response. In this study, we report that VZV profoundly impairs MAIT cell activation in response to both riboflavin synthesis and cytokine stimulation, therefore resulting in a downstream paralysis of several effector functions such as cytokine production and cytotoxic potential. This work highlights a previously uncharacterised strategy of viral pathogens to effectively target and restrict the MAIT cell effector response. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodsResultsConclusionTo comparatively evaluate the influence of different riboflavin formulations and soaking durations on the anterior segment optical coherence tomography (AS-OCT) findings following accelerated corneal crosslinking (ACXL) at 9 mW/cm2 for in progressive keratoconus.In this prospective study, consecutive patients with progressive keratoconus were randomized into 4 groups. Group 1: hydroxypropyl methylcellulose (HPMC)-based riboflavin for 10 min; Group 2: HPMC-based riboflavin for 20 min; Group 3: dextran-based riboflavin (0.1%) for 30 min. Riboflavin soaking was followed by ultraviolet-A irradiation at 9 mW/cm2 for 10 min in all three groups. Group 4 underwent conventional CXL (CCXL) using Dresden protocol. The AS-OCT features of the crosslinked cornea were evaluated at postoperative month 1 and correlated to the clinical outcomes at postoperative month 12.The study enrolled 26 eyes of 26 patients in each group. In groups 1 and 2, the AS-OCT findings were similar (p > .05) and the demarcation lines depth (DLD) were deep as obtained following CCXL. The DLD was significantly shallower in group 3 compared to the other groups (p < .01). There were no between-group differences in regards to the visual, refractive, keratometric, and tomographic outcomes at postoperative month 12. No significant endothelial cell loss or any other clinically significant adverse event was encountered in any patient’s eye at 12 months follow-up.Although structural variations were noted in the crosslinked cornea, DLDs observed following ACXL (9 mW/cm2) using HPMC-based solution for 10 or 20 min were similar to those observed following CCXL. Whereas, ACXL (9 mW/cm2) using dextran-based solution for 30 min resulted in the shallowest DLD. Despite these remodeling differences, the visual, refractive and tomographic outcomes of all groups were comparable at postoperative 1-year follow-up. Studies with a greater number of patients and longer follow-ups are required to establish any relation between AS-OCT characteristics of crosslinked cornea and ACXL efficacy. [ABSTRACT FROM AUTHOR]

Purpose: With dairy products and fish being major sources of iodine in Switzerland, the growing popularity of plant-based alternatives may impact iodine nutrition. This study aimed to assess the iodine content in plant-based dairy and fish alternatives available in the Swiss market and compare them with conventional products. Methods: In 2022, a market survey was conducted in Zurich, Switzerland, to identify the plant-based dairy and fish alternatives available and assess their iodine content. To evaluate the impact of plant-based alternatives on iodine consumption in Switzerland, we modeled dietary scenarios by substituting the intake of dairy and fish items with plant-based alternatives. In addition, we investigated fortification with calcium, vitamins B2, B12, and D. Results: Out of 477 identified products, only four milk-alternative products were iodine fortified (median iodine concentration: 22.5 μg/100 ml). The median iodine concentration in unfortified plant-based alternatives was negligible compared to conventional dairy and fish products (milk: 0.21 vs 9.5 μg/100 ml; yogurt 0.36 vs 6.1 μg/100 g; cheese: 0.10 vs 20 μg/100 g; fish 0.50 vs 44 μg/100 g). Three portions of dairy per day as recommended by the Swiss Food Pyramid provide 25% of the RDA for iodine (150 μg/day), whereas substituting those with unfortified alternatives provides only 0.7% of the RDA. Conclusion: Only four out of 477 plant-based alternative products are iodine fortified in the Swiss market. Thus, the risk for consumers to miss out on the ca. 25% of the RDA for iodine by consuming plant-based alternatives is high, placing them at a risk for inadequate iodine intake. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The present study was conducted to assess the individual or combined effects of feeding dietary fat (whole-cracked rapeseed), nitrate, and 3-nitrooxypropanol (3-NOP) on protein profile, mineral composition, B vitamins, and nitrate residues in milk from dairy cows. A total of 48 Danish Holstein cows used in an 8 × 8 incomplete Latin square design were fed 8 factorially arranged diets: (30 or 63 g crude fat/kg DM) × (0 or 10 g nitrate/kg DM) × (0 or 80 mg 3-NOP/kg DM) over 6 periods of 21 d each. In each period, milk samples were collected from individual cows during the third week by pooling milk obtained from 4 consecutive milkings and analyzed for protein profile, including protein modifications, mineral composition, riboflavin, cobalamin, and presence of nitrate residues. Fat supplementation led to an increase in the phosphorylation degree of α S1 -CN by 8.5% due to a decreased relative proportion of α S1 -CN 8P and an increased relative proportion of α S1 -CN 9P and further to a decrease in the relative proportion of α S2 -CN by 2.4%. Additionally, fat supplementation decreased the relative proportions of glycosylated and unglycosylated forms of κ-CN, consequently leading to a 3.6% decrease in total κ-CN. In skim milk, K, Ca, P, and Mg concentrations were altered by individual use of fat, nitrate, and 3-NOP. Feeding nitrate resulted in a 5.4% increase in riboflavin concentration in milk, whereas supplementing 3-NOP increased the cobalamin concentration in milk by 21.1%. The nitrate concentration in milk was increased upon feeding nitrate, but this increased concentration was well below the maximum permissible limit of nitrate in milk (<50 mg/L). Overall, no major changes were observed in milk protein, and mineral compositions by feeding fat, nitrate, and 3-NOP to dairy cows, but the increased riboflavin and cobalamin concentrations by nitrate and 3-NOP, respectively, could be of beneficial nutritional value for milk consumers. [ABSTRACT FROM AUTHOR]

Purpose: To assess the feasibility of theranostics to determine the riboflavin concentration in the cornea using clinically available ophthalmic formulations during epithelium-off (epi-off) and transepithelial (epi-on) corneal cross-linking procedures. Methods: Thirty-two eye bank human donor corneas were equally randomized in eight groups; groups 1 to 3 and groups 4 to 8 underwent epi-off and epi-on delivery of riboflavin respectively. Riboflavin ophthalmic solutions were applied onto the cornea according to the manufacturers' instructions. The amount of riboflavin into the cornea was estimated, at preset time intervals during imbibition time, using theranostic UV-A device (C4V CHROMO4VIS, Regensight srl, Italy) and expressed as riboflavin score (d.u.). Measurements of corneal riboflavin concentration (expressed as µg/cm3) were also performed by spectroscopy absorbance technique (AvaLight-DH-S-BAL, Avantes) for external validation of theranostic measurements. Results: At the end of imbibition time in epi-off delivery protocols, the average riboflavin score ranged from 0.77 ± 0.38 (the average corneal riboflavin concentration was 213 ± 190 µg/cm3) to 1.79 ± 0.07 (554 ± 103 µg/cm3). In epi-on delivery protocols, the average riboflavin score ranged from 0.17 ± 0.01 to 0.67 ± 0.19 (corneal riboflavin concentration ranged from 6 ± 5 µg/cm3 to 122 ± 39 µg/cm3) at the end of imbibition time. A statistically significant linear correlation (P ≤ 0.05) was found between the theranostic and spectrophotometry measurements in all groups. Conclusions: Real-time theranostic imaging provided an accurate strategy for assessing permeation of riboflavin into the human cornea during the imbibition phase of corneal cross-linking, regardless of delivery protocol. A large variability in corneal riboflavin concentration exists between clinically available ophthalmic formulations both in epi-off and epi-on delivery protocols. [ABSTRACT FROM AUTHOR]

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The monitoring of antioxidants is crucial to prevent damage caused by reactive oxygen species (ROS). In this study, we introduce an innovative electrochemical sensor tailored for detecting riboflavin (RF), a powerful antioxidant. The sensor was developed by modifying a gold electrode (AuE) with cobalt oxide (Co3O4) and reduced graphene oxide (rGO). The resulting nanocomposite‐modified electrode (AuE/Co3O4‐rGO) exhibited a substantial surface area of 0.41 cm2 in the redox probe, leading to an enhanced RF peak characterized by remarkably low charge transfer resistance (1.61 KΩ) and a high exchange current density (18.6 μA/cm2). Under optimized conditions, the sensor achieved a limit of detection (LOD) for RF at 1.30 μM, over a concentration range of 6.5–42.2 μM. These results highlight the sensor's potential applicability in real‐world scenarios, including the analysis of milk and pharmaceutical samples. A kinetics study revealed that the electrochemical reaction involving RF is adsorption‐controlled, emphasising the critical role of surface interactions. The modified electrode's interaction with RF significantly influences overall reaction kinetics. These findings were further supported by density functional theory (DFT) calculations and molecular simulations. Our nanocomposite‐modified electrode provides valuable insights into the atomistic interactions governing sensor performance, advancing the field of electrochemical sensing for antioxidants like riboflavin. [ABSTRACT FROM AUTHOR]

Introduction: Vaccination is the effective strategy for coronavirus disease 2019 (COVID‐19). However, few studies have investigated the association between severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) immunoglobulin (Ig)G and vitamin D. Methods: This study aimed to investigate the association between SARS‐CoV‐2 IgG and active vitamin D analogs in hemodialysis patients. Blood samples were collected four times: before vaccination and 30, 60, and 90 days after vaccination, BNT162b2 (Pfizer©). Results: A total of 418 patients were enrolled. The mean age was 71.1 ± 12 years. Almost two thirds of the patients were prescribed active vitamin D analogs. The distribution of SARS‐CoV‐2 IgG before vaccination was 235 (93–454) AU/mL. After multiple regression analyses, active vitamin D analog use was found to be associated with higher SARS‐CoV‐2 IgG levels from prevaccination to 90 days postvaccination. Conclusion: This study demonstrated an association between higher SARS‐CoV‐2 IgG and active vitamin D analog use in hemodialysis patients. Clinical trial registration: The study information was registered in the UMIN‐CTR (UMIN 000046906). [ABSTRACT FROM AUTHOR]

Bacterial synthesis of vitamin B2 generates a by‐product, 5‐(2‐oxopropylideneamino)‐d‐ribityl‐aminouracil (5‐OP‐RU), with potent immunological properties in mammals, but it is rapidly degraded in water. This natural product covalently bonds to the key immunological protein MR1 in the endoplasmic reticulum of antigen presenting cells (APCs), enabling MR1 refolding and trafficking to the cell surface, where it interacts with T cell receptors (TCRs) on mucosal associated invariant T lymphocytes (MAIT cells), activating their immunological and antimicrobial properties. Here, we strategically modify this natural product to understand the molecular basis of its recognition by MR1. This culminated in the discovery of new water‐stable compounds with extremely powerful and distinctive immunological functions. We report their capacity to bind MR1 inside APCs, triggering its expression on the cell surface (EC50 17 nM), and their potent activation (EC50 56 pM) or inhibition (IC50 80 nM) of interacting MAIT cells. We further derivatize compounds with diazirine‐alkyne, biotin, or fluorophore (Cy5 or AF647) labels for detecting, monitoring, and studying cellular MR1. Computer modeling casts new light on the molecular mechanism of activation, revealing that potent activators are first captured in a tyrosine‐ and serine‐lined cleft in MR1 via specific pi‐interactions and H‐bonds, before more tightly attaching via a covalent bond to Lys43 in MR1. This chemical study advances our molecular understanding of how bacterial metabolites are captured by MR1, influence cell surface expression of MR1, interact with T cells to induce immunity, and offers novel clues for developing new vaccine adjuvants, immunotherapeutics, and anticancer drugs. [ABSTRACT FROM AUTHOR]