Search

Background: Accumulating evidence suggests a pivotal role of vitamin B2 in the pathogenesis and progression of prostate cancer (PCa). Vitamin B2 intake has been postulated to modulate the screening rate for PCa by altering the concentration of prostate-specific antigen(PSA). However, the relationship between vitamin B2 and PSA remains indeterminate. Hence, we conducted a comprehensive evaluation of the association between vitamin B2 intake and PSA levels, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database., Methods: From a pool of 20,371 participants in the NHANES survey conducted between 2003 and 2010, a cohort of 2,323 participants was selected for the present study. The male participants were classified into four distinct groups based on their levels of vitamin B2 intake. We employed a multiple linear regression model and a non-parametric regression method to investigate the relationship between vitamin B2 and PSA levels., Results: The study cohort comprised of 2,323 participants with a mean age of 54.95 years (± 11.73). Our findings revealed a statistically significant inverse correlation between vitamin B2 intake (mg) and PSA levels, with a reduction of 0.13 ng/ml PSA concentration for every unit increase in vitamin B2 intake. Furthermore, we employed a fully adjusted model to construct a smooth curve to explore the possible linear relationship between vitamin B2 intake and PSA concentration., Conclusions: Our study in American men has unveiled a notable inverse association between vitamin B2 intake and PSA levels, potentially posing a challenge for the identification of asymptomatic prostate cancer. Specifically, our findings suggest that individuals with higher vitamin B2 intake may be at a greater risk of being diagnosed with advanced prostate cancer in the future, possibly indicating a detection bias. These results may offer a novel explanation for the observed positive correlation between vitamin B2 intake and prostate cancer., (© 2024. The Author(s).)

Background: Experimental results indicate that riboflavin is involved in tumorigenesis. Data regarding the relationship between riboflavin and colorectal cancer (CRC) are limited, and findings vary between observational studies., Design: This was a case-control retrospective study., Objective: This study aimed to evaluate the associations between serum riboflavin level and sporadic CRC risk., Methods: In total, 389 participants were enrolled in this study - including 83 CRC patients without family history and 306 healthy controls - between January 2020 and March 2021 at the Department of Colorectal Surgery and Endoscope Center at Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Age, sex, body mass index, history of polyps, disease conditions (e.g., diabetes), medications, and eight other vitamins were used as confounding factors. Adjusted smoothing spline plots, subgroup analysis, and multivariate logistic regression analysis were conducted to estimate the relative risk between serum riboflavin levels and sporadic CRC risk. After fully adjusting for the confounding factors, an increased risk of colorectal cancer was suggested for individuals with higher levels of serum riboflavin (OR = 1.08 (1.01, 1.15), p = 0.03) in a dose-response relationship., Conclusions: Our results support the hypothesis that higher levels of riboflavin may play a role in facilitating colorectal carcinogenesis. The finding of high levels of circulating riboflavin in patients with CRC warrants further investigation., Competing Interests: Conflict of interest statement The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aerobic organisms need antioxidant defense systems to deal with free radicals which either are produced during aerobic respiration or may have an external origin. Oxidative stress, which is resulted from an imbalance between the production of free radicals and the ability of antioxidant defense mechanism to deactivate them, is involved in the development of many chronic diseases such as cancer, diabetes, CVD and some neurodegenerative diseases. Reinforcing the antioxidant potential of the body has been considered as a strategy that could prevent and manage such conditions. In the previous review article published by British Journal of Nutrition, in 2014, for the first time, we concluded that riboflavin could alleviate oxidative stress. Although riboflavin can serve as a prooxidant when exposed to ultraviolet irradiation, the literature is replete with studies that support its antioxidant properties. Furthermore, recent evidence suggests that riboflavin may have a therapeutic potential in many conditions in which oxidative stress is involved, although the therapeutic efficacy of riboflavin as an antioxidant requires further study under conditions of wellness and clinical disease.

Objective: Migraine is a common disease worldwide and migraine prevention is primarily currently based on pharmaceuticals. The mechanism of Vitamin B2 may positively contribute to migraine. This systematic review and meta-analysis aimed to evaluate the impact of Vitamin B2 supplementation on the days, duration, frequency, and pain score of the migraine attack., Methods: : The PRISMA guideline was used for the studying process. Five electronic databases, PubMed, Embase, Cochrane, CINAHL, and CEPS were searched from 1990 to March 2019. The search terms were Vitamin B2, migraine, and prophylactic. A meta-analysis was performed using Comprehensive Meta-Analysis (CMA) version., Results: : Nine articles were included in systemic review and finally meta-analysis. Eight randomized controlled trials and one controlled clinical trial with 673 subjects were analyzed using meta-analysis. Vitamin B2 supplementation significantly decreased migraine days ( p  = .005, I 2   = 89%), duration ( p  = .003, I 2   = 0), frequency ( p  = .001, I 2   = 65%), and pain score ( p  = .015, I 2   = 84%)., Conclusions: A pooled analysis of available randomized controlled clinical trials demonstrated that Vitamin B2 400 mg/day for three months supplementation had significant effect on days, duration, frequency, and pain score of migraine attacks.

Fibrosing chronic graft-versus-host disease (cGVHD) is a debilitating complication of allogeneic stem cell transplantation (alloSCT). A driver of fibrosis is the kynurenine (Kyn) pathway, and Kyn metabolism patterns and cytokines may influence cGVHD severity and manifestation (fibrosing versus gastrointestinal [GI] cGVHD). Using a liquid chromatography-tandem mass spectrometry approach on sera obtained from 425 patients with allografts, we identified high CXCL9, high indoleamine-2,3-dioxygenase (IDO) activity, and an activated Kyn pathway as common characteristics in all cGVHD subtypes. Specific Kyn metabolism patterns could be identified for non-severe cGVHD, severe GI cGVHD, and fibrosing cGVHD, respectively. Specifically, fibrosing cGVHD was associated with a distinct pathway shift toward anthranilic and kynurenic acid, correlating with reduced activity of the vitamin-B2-dependent kynurenine monooxygenase, low vitamin B6, and increased interleukin-18. The Kyn metabolite signature is a candidate biomarker for severe fibrosing cGVHD and provides a rationale for translational trials on prophylactic vitamin B2/B6 supplementation for cGVHD prevention., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

A great deal of research was being done in studying of the age-related characteristics of carbohydrate metabolism and the provision of vitamins B1, B2 among the population of the Subarctic (SR) and Arctic (AR) regions, differing in the extreme natural and climatic-geographic living conditions. The surveyed population was divided into five age groups: 16-21, 22-35, 36-45, 46-60 and 61-74 years old. The parameters of carbohydrate metabolism (glucose, lactate, pyruvate) were determined in the blood serum, the content of thiamine (thiamin diphosphate effect) and riboflavin - in hemolysates, and the values of the lactate/pyruvate ratio (Lac/Pyr) were calculated. Statistical data processing was performed by nonparametric methods. An increase in glucose levels was found in persons of older age groups. Age-related fluctuations of metabolites of carbohydrate metabolism were manifested by a lower content of lactate and the value of the Lac/Pyr ratio in persons aged 16-21 years. Regardless of the age and region of the survey, there were revealed high lactate concentrations, Lac/Pyr values and reduced pyruvate levels, as well as low glucose levels in group aged 16-21 year in AR. For vitamins B1, B2, no pronounced age-related changes were observed, while the content of riboflavin was higher in persons of SR. Moderate hypovitaminosis of thiamin was detected in 13-20,1% and 6,1-22,7% of cases in SR and AR, pronounced - 8,3-11,6% and 4,6-23,5%, respectively, vitamin B2 deficiency was noted in 19,4-23,9% of persons in the AR and in 33,8-42,9% of persons in the AR. Vitamins in both regions at different age periods contributed to the formation of levels of indicators of carbohydrate metabolism: glucose and pyruvate in SR, lactate in AR., Competing Interests: The authors declare no conflict of interest.

Scope: Hyperoxaluria is a major cause of kidney stone disease. Around half of the oxalate in mammals is supplied from the diet and the other half is endogenously synthesized from glyoxylate. Reduction of hepatic glycolate oxidase (GO) activity is one approach to reduce endogenous production of oxalate. However, there are currently few effective dietary approaches to reduce hepatic GO activity., Methods and Results: In the present study, it is investigated whether restriction of dietary vitamin B2 (VB2) can reduce hepatic GO activity and oxalate excretion in mice with hyperoxaluria induce by hydroxyproline (Hyp) or obesity. It is found that VB2 restriction significantly reduces hepatic GO activity in both the Hyp- and obesity-induced model of hyperoxaluria in mice. However, VB2 restriction reduces urinary oxalate excretion only in the Hyp-treated mice and not the obese mice. This difference could be due to the contribution of endogenous oxalate production that manifests as increased hepatic GO activity in Hyp-treated mice but not obese mice., Conclusion: Together these results suggest that VB2 restriction could be a new dietary approach to improve hyperoxaluria when endogenous production of oxalate is increased., (© 2021 Wiley-VCH GmbH.)

Purpose: The present study investigated whether the pulmonary intersegmental planes could be identified with the intravenous injection of vitamin B 2 using a fluorescent camera and whether this method can be used instead of the inflation-deflation technique or the intravenous indocyanine green (ICG) method., Methods: In experiment 1, the vitamin B 2 was intravenously injected to visualize the pulmonary intersegmental plane and perform segmentectomy, and the visualized pulmonary intersegmental line was then compared to the inflation-deflation line in six pigs. In experiment 2, using six pigs, the fluorescent area and duration of fluorescence were compared after the intravenous injection of vitamin B 2 and ICG in the same animals., Results: In all animals in experiment 1, it was possible to clearly detect yellow-green fluorescence in the lung, in segments other than the one intended for resection, for at least 60 min. Moreover, the line visualized with vitamin B 2 fluorescence matched the inflation-deflation line in all animals. In experiment 2, the area of vitamin B 2 fluorescence corresponded to the area of ICG fluorescence in each animal., Conclusions: The visualization of fluorescence after the intravenous injection of vitamin B 2 using a fluorescent camera was a simple, safe, and accurate method for detecting intersegmental planes in a pig model. This method can be an alternative to the inflation-deflation technique and the intravenous ICG method.

The main causes of food spoilage come from the process of oxidation and the contamination by microorganisms. For the purpose of increasing food shelf-life the industries employ different techniques, being the addition of preservatives, one of the most used. The aim of this contribution was to investigate the potential antioxidant properties of tyrosol (4-hydroxyphenethyl alcohol, 4-OH) and tyrosol derived isomers (2-hydroxyphenethyl alcohol, 2-OH and 3-hydroxyphenethyl alcohol, 3-OH) against reactive oxygen species (ROS) and the antimicrobial effect on Staphylococcus aureus and Escherichia coli. Furthermore, the type of antioxidant effect of substrates and commercial antioxidants mixtures was studied. Upon visible-light, the substrates interacted with the vitamin B2 and different ROS were generated. All the compounds deactivated O 2 ( 1 Δ g ) and O 2 ●- , whereas only 2-OH and 3-OH inhibited H 2 O 2 and HO ● . The substrates exhibited a synergistic antioxidant effect when combined with commercial antioxidants. 2-OH showed antimicrobial activity against strains tested., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: We evaluated the efficacy of riboflavin in pediatric migraineurs., Methods: A retrospective observational study was performed on 42 patients (aged six to 18 years) with migraine who were evaluated from January to December 2019 at Dell Children's Medical Center in Austin, Texas. Weight-based dosing of riboflavin was recommended for migraine prevention. Descriptive statistics were used to study the population demographics. Nonparametric tests were used for inferential statistics to study the effect of riboflavin on headache frequency, intensity, and duration., Results: Patients treated with riboflavin had a significant reduction in headache days per month (frequency) at the first follow-up visit at 2 to 4 months (T1) (11.07 ± 10.52 days) compared with the baseline T0 (21.90 ± 9.85 days); P < 0.001 in regard to the primary outcome in 42 patients (mean age, 13.38 ± 3.38). Mean headache intensity decreased from 8.85 (±6.41; T0) to 2.30 (±2.51; T1); P < 0.001 on a 0 to 10 scale. The headache duration also reduced significantly from 18.23 ± 17.07 hours (T0) to 10.18 ± 10.49 hours (T1); P = 0.001. There was a positive correlation between riboflavin efficacy and reduced use of acute medications (r s  = 0.304; P = 0.05). Riboflavin was useful in reducing the frequency and intensity in two patients with new daily persistent headache., Conclusions: Patients treated with riboflavin had a reduction in headache frequency, use of acute medications, and days of school missed. Riboflavin prophylaxis also reduced migraine intensity and duration. Riboflavin is recommended as a safe, inexpensive, and effective nutraceutical in the treatment of pediatric migraine., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Mucositis is a common side-effect of chemotherapy treatment, inducing alterations in the composition of the gut microbiota. Redox active compounds, such as vitamins B2 and C, have been shown to reduce inflammation and enhance the growth of anaerobic bacteria in the gut. We therefore aimed to (1) validate the ability of these compounds to promote bacterial cell growth in vitro, and (2) determine their prophylactic efficacy in a rat model of methotrexate (MTX)-induced mucositis. Bacterial growth curves were performed to assess the growth kinetics of bacteria exposed to Vitamins C and B2 (0.5 mM). Male wistar rats (150-200 g) received vitamins B2 (12 mg/day) and C (50 mg/day) via daily oral gavage (from day -1 to day 10). MTX (45 mg/Kg) was administrated via I.V. injection (N = 4-8/group) on day 0. Body weight, water/food consumption and diarrhea were assessed daily. Blood and faecal samples were collected longitudinally to assess citrulline levels (mucositis biomarker) and gut microbiota composition. Vitamins C/B2 enhanced the in vitro growth of anaerobic bacteria Blautia coccoides and Roseburia intestinalis . Contrarily to vitamin B2, in vivo administration of Vitamin C significantly attenuated clinical symptoms of mucositis. Despite their influence on the composition of the gut microbiota, both vitamins did not modulate the course of MTX-induced mucositis, as accessed by plasma citrulline. Vitamins B2 and C enhanced anaerobic bacterial growth in vitro, however their ability to mitigate MTX-induced mucositis was limited.

Objectives: For small pulmonary nodules that are unidentifiable by palpation or in endoscopic surgeries wherein palpation is not feasible, visualizing their location is necessary when performing pulmonary sublobar resection procedures, such as wedge resection or segmentectomy. We invented a new transbronchial lung-marking technique using the photodynamic diagnosis endoscope system and vitamin B2 and examined its feasibility and safety via porcine studies., Methods: We established the marking procedure in pigs and examined the marking clarity and size, fluorescence intensity and duration and possible complications. In another study, sublobar resection for virtual target lesions was performed in pigs based on the fluorescent markings. The procedure duration, marking visibility, surgical margin from the lesions and technique-related complications were assessed., Results: All 36 markings in 6 pigs were identifiable and were widely distributed over the right lung. The median diameter and fluorescence intensity at 60 min after marking were 6.0 (5.5-6.7) mm and 137.5 (122-168), respectively. All 18 markings for the 6 virtual target lesions (3 markings for each target) were clearly identified, and all target lesions were found in the resected specimens. The median duration per marking was 244 (194-255) seconds. The shortest median surgical margin from a target lesion was 11.5 (9.3-13.5) mm. No procedure-related complications were observed., Conclusions: This novel transbronchial fluorescent lung-marking technique was useful and safe in sublobar resections for small non-palpable pulmonary lesions., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Candida albicans is a major cause of fungal infections, both superficial and invasive. The economic costs as well as consequences for patient welfare are substantial. Only a few treatment options are available due to the high resemblance between fungal targets and host molecules, as both are eukaryotes. Riboflavin is a yellow pigment, also termed vitamin B 2 Unlike animals, fungi can synthesize this essential component themselves, thereby leading us to appreciate that targeting riboflavin production is a promising novel strategy against fungal infections. Here, we report that the GTP cyclohydrolase encoded by C. albicans RIB1 ) is essential and rate-limiting for production of riboflavin in the fungal pathogen. We confirm the high potential of CaRIB1 ) is essential and rate-limiting for production of riboflavin in the fungal pathogen. We confirm the high potential of Ca Rib1 as an antifungal drug target, as its deletion completely impairs in vivo in model systems. Furthermore, the stimulating effect of iron deprivation and PKA activation on riboflavin production seems to involve C. albicans in model systems. Furthermore, the stimulating effect of iron deprivation and PKA activation on riboflavin production seems to involve Ca Sef1. Gathering insights in the synthesis mechanism of riboflavin in pathogenic fungi, like Ca Sef1. Gathering insights in the synthesis mechanism of riboflavin in pathogenic fungi, like C. albicans is an important fungal pathogen causing common superficial infections as well as invasive diseases with an extremely high morbidity and mortality. Antifungal therapies are limited in efficiency and availability. In this research, we describe the regulation of riboflavin production in IMPORTANCE Since riboflavin biosynthesis is essential to this organism, we can appreciate that targeting it would be a promising new strategy to combat these fungal infections. We provide evidence that one particular enzyme in the production process, Candida albicans is an important fungal pathogen causing common superficial infections as well as invasive diseases with an extremely high morbidity and mortality. Antifungal therapies are limited in efficiency and availability. In this research, we describe the regulation of riboflavin production in C. albicans Since riboflavin biosynthesis is essential to this organism, we can appreciate that targeting it would be a promising new strategy to combat these fungal infections. We provide evidence that one particular enzyme in the production process, Ca Rib1, would be most promising as an antifungal drug target, as it plays a central role in regulation and proves to be essential in a mouse model of systemic infection., (Copyright © 2020 Demuyser et al.)

Riboflavin (vitamin B2) is essential for monogastric animals. It is mainly produced by recombinant microorganisms (Candida famata, Bacillus subtilis and Ashbya gossypii). The availability of genetically modified organism (GMO)-free riboflavin, obligatory in European organic agriculture, is a major issue. Besides, requirements for organic livestock might differ from conventional production because other genotypes and feed formulations are used. The effects of a fermentation suspension with a high native content of riboflavin produced with unmodified A. gossypii by fermentation were investigated at graded dosages as an alternative to conventional (GMO-based) riboflavin in slow-growing broilers on performance traits and health and welfare indicators. In 2 runs with 800 animals each, Ranger Gold™ broilers were fed with 4 dietary treatments. For starter diets (day 1 to 18), treatments included a basal diet (1) without any riboflavin supplementation (negative control, N-C), (2) with conventional riboflavin supplementation (Cuxavit B2 80% riboflavin) at 9.6 mg/kg (positive control, P-C), (3) with riboflavin supplementation from the alternative source at 3.5 mg/kg (A-low) and (4) with riboflavin supplementation from the alternative source at 9.6 mg/kg (A-high). For the finisher diet (day 29 until slaughtering), P-C and A-high were supplemented with 8.0 mg/kg and A-low with 3.5 mg/kg. Diets were formulated according to organic regulations. Animals were kept in floor pens with 20 chickens per pen. Weekly, BW, feed and water consumption were recorded. Every second week, animal-based health and welfare indicators (feather score and footpad dermatitis) were scored. Slaughter traits were assessed for five males and females per pen at 62/63 days of age. Final body weight of A-high differed from N-C and A-low, but not from P-C. From week 2 until six years of age, A-high had a higher daily weight gain when compared to all other groups. With 74.4%, dressing percentage was higher in A-high compared with all other groups (73.3%). Breast percentage of A-low was lower than that of both control groups but did not differ from A-high. The highest frequency of liver scores indicating fatty liver syndrome was found in P-C, followed by N-C and A-low. Feather scores did not respond to treatment; the highest frequency of mild footpad dermatitis was observed in A-high, however at a low prevalence. In conclusion, the tested fermentation suspension with a high native content of riboflavin derived from fermentation of A. gossypii can be used at levels of commercial recommendations as alternative to riboflavin produced from GMO in broiler feeding. Further studies must verify whether riboflavin can be reduced without inducing riboflavin deficiency in slow-growing broilers.

Microbes in the human gut play a role in the production of bioactive compounds, including some vitamins. Although several studies attempted to identify definitive markers for certain vitamin deficiencies, the role of gut microbiota in these deficiencies is unclear. To investigate the role of gut microbiota in deficiencies of four vitamins, B 2 , B 6 , folate, and B 12 , we conducted a comprehensive analysis of metabolites in mice treated and untreated with antibiotics. We identified glycolate (GA) as a novel marker of vitamin B 2 (VB2) deficiency, and show that gut microbiota sense dietary VB2 deficiency and accumulate GA in response. The plasma GA concentration responded to reduced VB2 supply from both the gut microbiota and the diet. These results suggest that GA is a novel marker that can be used to assess whether or not the net supply of VB2 from dietary sources and gut microbiota is sufficient. We also found that gut microbiota can provide short-term compensation for host VB2 deficiency when dietary VB2 is withheld., Competing Interests: The authors declare no conflict of interest.

Riboflavin (RF) is a water-soluble member of the B-vitamin family. Sufficient dietary and supplemental RF intake appears to have a protective effect on various medical conditions such as sepsis, ischemia etc., while it also contributes to the reduction in the risk of some forms of cancer in humans. These biological effects of RF have been widely studied for their anti-oxidant, anti-aging, anti-inflammatory, anti-nociceptive and anti-cancer properties. Moreover, the combination of RF and other compounds or drugs can have a wide variety of effects and protective properties, and diminish the toxic effect of drugs in several treatments. Research has been done in order to review the latest findings about the link between RF and different clinical aberrations. Since further studies have been published in this field, it is appropriate to consider a re-evaluation of the importance of RF in terms of its beneficial properties.

Mouth ulcer is associated with inflammation and high risk of bacterial infection, which aggravates the patient's condition. Currently, there is no effective treatment for mouth ulcer. Herein, we report that vitamin-modified iron oxide nanoparticles improve the healing of mouth ulcer through anti-inflammation and antibacterial activities. We discovered that vitamin B 2 (VB 2 ) modified iron oxide nanoparticles performed enhanced peroxidase-like, catalase-like, and superoxide dismutase (SOD)-like activities, acting as typical iron oxide nanozymes (IONzymes) with triad activities. In particular, VB 2 modification significantly improved the SOD-like activity, thus providing a reactive oxygen species (ROS)-scavenging ability. Cellular antioxidant experiments showed that vitamin B 2 modified IONzymes (VB 2 -IONzymes) protect human oral keratinocytes (HOK) and BALB/3T3 cells from hydrogen peroxide (H 2 O 2 ), and these cells have high biocompatibility to eukaryotic cells. In addition, VB 2 -IONzymes exerted an antibacterial activity against Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. Importantly, VB 2 -IONzymes accelerated the recovery of mouth ulcer and reduced the local secretion of inflammatory factors in mouse ulcer model via ROS scavenging and antibacterial activity. Taken together, our work demonstrates that vitamin B 2 modification endows iron oxide nanoparticles with enhanced enzyme-like activities and VB 2 -IONzymes may be a promising reagent in the treatment of mouth ulcer because of their intrinsic anti-inflammation and antibacterial capabilities.

Light is an energy source and key environmental factor for plants. Out of the different light wavelengths, blue-light is one of the most relevant spectral regions because of its relation to anthocyanins biosynthesis. Among the compounds present in grapes, anthocyanins determine their main organoleptic and healthy properties; while a minimum concentration of ammonium and amino acids is necessary for a desirable development of the alcoholic fermentation. Moreover, amino acids are precursors of several volatile compounds synthetized during the fermentation. The aim of this study was to assess the influence of riboflavin (vitamin B2) applications, at harvest and one week later,to grapevine leaves in combination with post-harvest blue-light irradiation on Tempranillo (Vitis vinifera L.) grape anthocyanins and amino acidscomposition. The combination of blue-light irradiation and two riboflavin doses as well as theseindividual factors affected both grape anthocyanins and amino acidsconcentrations. After one week of storage, anthocyanins concentration diminished when clusters were irradiated with blue-light; while for amino acids content, the trend to increase or decrease is dependent on the riboflavin dose applied in vines and the storage time., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Chronic inflammation can lead to tumour initiation and progression. Vitamin B complex has the ability to regulate the immune response and, therefore, inflammation but many of the mechanistic and molecular processes involved in this regulation are still not fully understood. This study sought to determine some of these processes by studying the effects of vitamin B2 (riboflavin) B6 (pyridoxine) and B9 (folic acid) on un-differentiated pro-monocytic lymphoma cells in regard to their ability to alter the proliferation, migration, apoptosis, cytokines and expression levels of programmed death ligand 1. We show that vitamin B2, B6 and B9, on pro-monocytic lymphoma cells exerted an anti-tumorigenic effect. This data could form the basis for future studies in using vitamin B supplementation to reduce cancer cell growth in vivo.

Purpose: Several epidemiological studies have assessed the ability of vitamin B 2 to prevent colorectal cancer (CRC), but the results are controversial results. We conducted a dose-response meta-analysis to investigate the association between vitamin B 2 and CRC risk., Methods: We searched the PubMed and EMBASE database until January 3, 2018 to identify relevant studies. The pooled relative risks (RRs) with the corresponding 95% confidence intervals (CIs) were calculated using a random-effects model or fixed-effects model. The dose-response relationship was assessed by restricted cubic splines., Results: A total of 14 studies reporting vitamin B 2 intake and two studies reporting blood vitamin B 2 concentration, comprising 14,934 cases and 1593 cases, respectively, were included in the meta-analysis. Vitamin B 2 intake was inversely associated with CRC risk (RR = 0.87; 95% CI 0.81-0.93). Similar results were found for total vitamin B 2 intake from diet and supplements (RR = 0.86; 95% CI 0.78-0.94) and dietary vitamin B 2 intake (RR = 0.89, 95% CI 0.82-0.98) in subgroup analyses. The dose-response model indicated a non-linear trend, and CRC risk was reduced by 10% when vitamin B 2 intake increased to 5 mg/day. In addition, high blood concentrations of vitamin B 2 could also reduce the CRC risk (RR = 0.74; 95% CI 0.59-0.92)., Conclusions: This dose-response analysis indicates that vitamin B 2 intake is inversely associated with CRC risk. The inverse association may also exist between blood vitamin B 2 concentration and CRC risk. These results suggest the importance of vitamin B 2 intake in the prevention of CRC.

Great success has been achieved in recent years in the development of synthetic or assembled nanobiomaterials. Among these, biomolecule-based nanoarchitectures with special optical property are of particular interest. Here, we demonstrate that vitamin B 2 nanocrystals assembled as nanorods can be obtained with precise control. Excitingly, such one-dimensional nanostructures not only exhibit intrinsic optical waveguiding properties but also the ability to sensitize oxygen to produce reactive oxygen species. With these properties, we applied the obtained vitamin B 2 nanorods under remotely localized light illumination into single tumour cells in vitro for anticancer photodynamic therapy. Further, vitamin B 2 nanorods were explored for in vivo photodynamic therapy by using a tumour model. With such bionanostructures, new features and functions of vitamin B 2 and its derivatives have been developed., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Vitamin B2 (riboflavin) is an essential constituent of the coenzymes flavin mononucleotide and flavin adenine dinucleotide and is critical for human metabolism and energy production. Liquid chromatography separation, then tandem mass spectrometry detection (LC-MS/MS) is a highly specific technique that enables quick analysis. An isotope dilution method for determination of riboflavin in human plasma using LC-MS/MS has been developed and validated in this study. In this method, 100 μL of plasma were added of 75 μL of an internal standard and treated with 125 μL of 0.1 M zinc sulfate. The analysis was performed using an Agilent 6460C tandem mass spectrometer system operated in the positive-ion mode. Chromatography separation performance was obtained with an Agilent 1290 UHPLC equipped with a Poroshell 120 SB-Aq column (100 mm × 2.1 mm × 2.7 μm) at a flow rate of 350 μL·min -1 . Riboflavin was measured within an instrument run time of 2.5 min. Riboflavin content was found to follow a linear trend in the 0.5 to 50.0 ng·mL -1 range and dilution was validated for samples that exceed the last point of the calibration curve until two times. The intra-day relative standard deviation (RSD) was less than 10% and inter-day RSD was less than 11%. The average of recovery was 90.5-99.5%. A sensitive and selective method has been developed and validated successfully for quantitative analysis of riboflavin in human plasma with a simple sample extraction method and short execution time. The method is reliable and can be applied in clinical diagnosis of deficiency and supplementation monitored of this vitamin., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Insufficiency or deficiency of some micronutrients may be additional modifying factors that influence the pathogenesis of the disease and the effectiveness of standard pharmacotherapy. The aim of the study - to evaluate the level of magnesium and vitamin B 2 in blood serum of patients with bronchial asthma and obesity in order to develop methods for individual correction of deficiency. Material and methods . The study included 51 children aged 12-17 years. The first group included 23 patients (12 girls and 11 boys) with asthma with comorbidities (obesity), and the second group consisted of 28 children (10 girls and 18 boys) with obesity. The concentration of magnesium in blood serum was determined by a colorimetric method without deproteinization, and vitamin B 2 - by an immunological microbiological method. Results and discussion . When analyzing the concentration of magnesium in blood serum of the examined children, it was found that in patients with bronchial asthma and obesity, a reduced content of this mineral was observed in 15 (65.2%) patients. The average magnesium concentration was 0.66±0.02 mmol/l at a rate of 0.7-1.2 mmol/l. A statistically significant decrease in the magnesium level in children suffering from asthma and obesity was noted, compared with the level in children with obesity (0.66 [0.57; 0.73] vs 0.71 [0.67; 0.73] mmol/l, р<0.05). Low serum magnesium levels in obese patients were detected more rarely (р<0.05) - only in 6 (21.4%) children, mostly in patients with grade III obesity. The remaining 22 (78.6%) children had magnesium level within the normal range. Patients with low serum magnesium levels showed increased irritability, sleep disturbance, loss of memory and concentration. Vitamin B2 levels in all examined children were within the normal range (137-370 ng/ml). Conclusion . The results indicate a decrease in the concentration of magnesium and normal levels of vitamin B 2 in serum in patients with bronchial asthma and obesity. Low serum magnesium levels were observed in children with low bronchial asthma control. To increase the effectiveness of therapy and control the symptoms of bronchial asthma, especially when combined with obesity, correction of the accompanying magnesium deficiency is necessary., Competing Interests: The authors declare no overt and potential conflict of interest related to the publication of this article., (Copyright© GEOTAR-Media Publishing Group.)

A bioelectrochemical system (BES) allows direct electricity production from wastes, but its low-power density, which is mainly associated with its poor anodic performance, limits its practical applications. Here, the anodic performance of a BES can be significantly improved by electrodepositing vitamin B 2 (VB 2 ) onto a graphene [reduced graphene oxide (rGO)]-modified glassy carbon electrode (VB 2 /rGO/GC) with Geobacter sulfurreducens as the model microorganisms. The VB 2 /rGO/GC electrode results in 200% higher electrochemical activity than a bare GC anode. Additionally, in microbial electrolysis cells, the current density of this composite electrode peaks at ∼210 μA cm -2 after 118 h and is maintained for 113 h. An electrochemical analysis coupled with molecular simulations reveals that using VB 2 as a linker between the electrochemically active protein of this model strain and the rGO surface accelerates the electron transfer, which further improves the bioelectricity generation and favors the long-term stability of the BES. The VB 2 bound with a flexible ribityl group as the organic molecular bridge efficiently mediates energy conversion in microbial metabolism and artificial electronics. This work provides a straightforward and effective route to significantly enhance the bioenergy generation in a BES.

Background: The fungus Ashbya gossypii is an important industrial producer of the vitamin riboflavin. Using this microbe, riboflavin is manufactured in a two-stage process based on a rich medium with vegetable oil, yeast extract and different precursors: an initial growth and a subsequent riboflavin production phase. So far, our knowledge on the intracellular metabolic fluxes of the fungus in this complex process is limited, but appears highly relevant to better understand and rationally engineer the underlying metabolism. To quantify intracellular fluxes of growing and riboflavin producing A. gossypii, studies with different 13 C tracers were embedded into a framework of experimental design, isotopic labeling analysis by MS and NMR techniques, and model-based data processing. The studies included the use 13 C of yeast extract, a key component used in the process., Results: During growth, the TCA cycle was found highly active, whereas the cells exhibited a low flux through gluconeogenesis as well as pentose phosphate pathway. Yeast extract was the main carbon donor for anabolism,  while vegetable oil selectively contributed to the proteinogenic amino acids glutamate, aspartate, and alanine. During the subsequent riboflavin biosynthetic phase, the carbon flux through the TCA cycle remained high. Regarding riboflavin formation, most of the vitamin's carbon originated from rapeseed oil (81 ± 1%), however extracellular glycine and yeast extract also contributed with 9 ± 0% and 8 ± 0%, respectively. In addition, advanced yeast extract-based building blocks such as guanine and GTP were directly incorporated into the vitamin., Conclusion: Intracellular carbon fluxes for growth and riboflavin production on vegetable oil provide the first flux insight into a  fungus on complex industrial medium. The knowledge gained therefrom is valuable for further strain and process improvement. Yeast extract, while being the main carbon source during growth, contributes valuable building blocks to the synthesis of vitamin B 2 . This highlights the importance of careful selection of the right yeast extract for a process based on its unique composition.

This study was aimed to observe the effects of vitamin B 1 , vitamin B 2 , and niacin supplementation on hepatic gene expression profiles in mice exposed to acute hypoxia. Thirty mice were randomly divided into normal, acute hypoxia, and acute hypoxia plus vitamin B 1 , vitamin B 2 , and niacin supplementation groups and fed corresponding diets for 2 weeks and then exposed to a simulated altitude of 6000 m for 8 h. Hepatic gene expression profiles were analyzed using a microarray technique. Several biochemical markers were also assayed. The results showed that a total of 2476 genes were expressed differentially after acute hypoxia exposure (1508 upregulated genes and 968 downregulated genes). Compared with the acute hypoxia group, there were 1382 genes differentially expressed (626 upregulated genes and 756 downregulated genes) in the acute hypoxia plus vitamin B 1 , vitamin B 2 , and niacin supplementation group. Pathway analysis indicated that carbohydrate, lipid, and amino acid metabolism, as well as electron transfer chain, were improved to some extent after vitamin B 1 , vitamin B 2 , and niacin supplementation. Supportive results were obtained from biochemical assays. Our findings suggest that the supplementation of vitamin B 1 , vitamin B 2 , and niacin is beneficial in improving nutritional metabolism partly via gene expression under acute hypoxia condition.

B vitamins play an essential role in the biosynthesis of nucleotides, replication of DNA, supply of methyl-groups, growth and repair of cells, aberrancies of which have all been implicated in carcinogenesis. Although the potential role of vitamin B in relation to the risk of cancer, including breast, and colorectal cancer, has been investigated in several observational studies, the mechanism of action is still unclear. In this study, vitamin B2 exhibited efficient activation of LSD1 by occupying the active sites where FAD stands. Interestingly, vitamin B2 significantly downregulated expression of CD86, a sensitive surrogate biomarker of LSD1 inhibition, and showed marked activation of gastric cancer cell migration and invasion. Meanwhile, vitamin B2 induced activation of LSD1 may attenuate the proliferation inhibition, and anti-migration effects of apatinib in gastric cancer cells. These findings suggested that vitamin B supplementation may interfere with the efficacy of apatinib in patients with gastric cancer., (© 2018 Wiley Periodicals, Inc.)

The actinobacterium Microbacterium maritypicum splits riboflavin (vitamin B 2 ) into lumichrome and d-ribose. However, such degradation by other bacteria and the involvement of a two-component flavin-dependent monooxygenase (FMO) in the reaction remain unknown. Here we investigated the mechanism of riboflavin degradation by the riboflavin-assimilating alphaproteobacterium Devosia riboflavina (formerly Pseudomonas riboflavina ). We found that adding riboflavin to bacterial cultures induced riboflavin-degrading activity and a protein of the FMO family that had 67% amino acid identity with the predicted riboflavin hydrolase (RcaE) of M. maritypicum MF109. The D. riboflavina genome clustered genes encoding the predicted FMO, flavin reductase (FR), ribokinase, and flavokinase, and riboflavin induced their expression. This finding suggests that these genes constitute a mechanism for utilizing riboflavin as a carbon source. Recombinant FMO (rFMO) protein of D. riboflavina oxidized riboflavin in the presence of reduced flavin mononucleotide (FMN) provided by recombinant FR (rFR), oxidized FMN and NADH, and produced stoichiometric amounts of lumichrome and d-ribose. Further investigation of the enzymatic properties of D. riboflavina rFMO indicated that rFMO-rFR coupling accompanied O 2 consumption and the generation of enzyme-bound hydroperoxy-FMN, which are characteristic of two-component FMOs. These results suggest that D. riboflavina FMO is involved in hydroperoxy-FMN-dependent mechanisms to oxygenize riboflavin and a riboflavin monooxygenase is necessary for the initial step of riboflavin degradation. IMPORTANCE Whether bacteria utilize either a monooxygenase or a hydrolase for riboflavin degradation has remained obscure. The present study found that a novel riboflavin monooxygenase, not riboflavin hydrolase, facilitated this process in D. riboflavina The riboflavin monooxygenase gene was clustered with flavin reductase, flavokinase, and ribokinase genes, and riboflavin induced their expression and riboflavin-degrading activity. The gene cluster is uniquely distributed in Devosia species and actinobacteria, which have exploited an environmental niche by developing adaptive mechanisms for riboflavin utilization., (Copyright © 2018 American Society for Microbiology.)

A new method for the separation and analysis of vitamin B 2 and its fluorescent photolysis products was established based on pressurized capillary electrochromatography (pCEC) coupled with laser induced fluorescence (LIF) detection.The relationship between the photolysis reaction rate of vitamin B 2 and the ionic strength of aqueous solution or phosphate buffered solution was studied.The analysis was carried out by using a C18 capillary column.The mobile phase was acetonitrile-water with 0.1%(v/v) trifluoroacetic acid with gradient elution.The excitation wavelength was 488 nm and the emission wavelength was 520 nm.Vitamin B 2 and many fluorescent photolysis products were well separated.Based on the above, the influence of photo degradation rate of vitamin B 2 with ionic strength was studied.The apparent rate constant of photolysis was calculated by kinetic calculation.The results showed that the ionic strength had a significant effect on the photolysis of vitamin B 2 solution.The photolysis rate of vitamin B 2 was positively related to the ionic strength.This study provides a highly efficient method for the stability research of vitamin B 2 , which may serve as a good reference for the preservation and clinical use of it.

Background: The liver disease is one of the most important traditional public health problems in Egypt. Oxidative stress is attributed to such pathological condition that further contributes to the initiation and progression of liver injury. In the present study, we have investigated if the strong antioxidant power of Nicotinamide (NA), Vitamin B2 (VB2), and Vitamin C (VC) can ameliorate TAA-induced oxidative stress-mediated liver injury in the rats., Methods: Thirty-six albino rats were divided into six groups: Control group; TAA group (IP injection with TAA at a dosage of 200 mg/Kg three times a week for two months); TAA + NA group (rats administered with NA at a dosage of 200 mg/kg daily besides TAA as in the control); TAA + VB2 group (rats administered with vitamin B2 at a dosage of 30 mg/kg daily besides injection with TAA); TAA + VC group (rats administered with vitamin C at a dosage of 200 mg/kg daily along with injection of TAA). TAA + NA + VB + VC group (rats administered the with the three vitamins daily in TAA pre-injected at the respective doses described above)., Results: Treatment of rats with TAA led to a significant elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total bilirubin, cholesterol, triglycerides, low-density lipoprotein (LDL) and tumor necrosis factor-alpha (TNF-α) in the serum samples. Moreover, malondialdehyde (MDA), hydroxyproline and nitic oxide (NO) were also significantly increased in the TAA-treated rats, while reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were significantly compromised in the hepatic samples. Rats administered with NA, VB2, and VC as individually or in combination ameliorated the deleterious effects of TAA that was confirmed by histopathology. However, the combination of the three vitamins was found more effective as compared to each of the vitamins., Conclusion: Our work demonstrates that NA, VB2, and VC cross-talk with each other that act as a more potent biochemical chain of antioxidant defense against TAA-induced toxicities in vivo.

Objectives: Catechins are important components of human diet and have received special attention due to their antioxidant capacity. The purpose of this paper was to study the antioxidant action of (+)-catechin (CTQ) in the presence of vitamin B 2 (riboflavin) as light-absorbing agent. Furthermore, two model compounds, catechol (CTC) and resorcinol (RSC), were selected in order to elucidate the reactive target of the CTQ molecule. The influence of pH-medium was investigated., Methods: Stationary photolysis, polarographic detection of dissolved oxygen, reactive oxygen species (ROS)-scavengers, time-resolved near-IR phosphorescence detection, stationary, and time-resolved fluorescence and laser flash photolysis techniques were employed., Results: CTQ interacts with riboflavin under visible-light photoirradiation as well as with different ROS which are generated in this mechanism. Radical-scavenging activity increases with increasing of pH-medium., Discussion: pH-effect of the medium on radical-scavenging activity comes from the increased electron-donating ability of CTQ upon deprotonation. These results are very interesting due to the fact that the pH of the food products displays important variations. The [Formula: see text]-scavenging ability of CTQ, would be equal to the additive contribution of each reactive center, CTC, and RSC, present at the molecule of CTQ. However, CTQ would have a moderate ability to removal of [Formula: see text]-species at pH 7.

Efficient screening technologies aim to reduce both the time and the cost required for identifying rare mutants possessing a phenotype of interest in a mutagenized population. In this study, we combined a mild mutagenesis strategy with high-throughput screening based on microfluidic droplet technology to identify Lactococcus lactis variants secreting vitamin B 2 (riboflavin). Initially, we used a roseoflavin-resistant mutant of L. lactis strain MG1363, JC017, which secreted low levels of riboflavin. By using fluorescence-activated droplet sorting, several mutants that secreted riboflavin more efficiently than JC017 were readily isolated from the mutagenesis library. The screening was highly efficient, and candidates with as few as 1.6 mutations per million base pairs (Mbp) were isolated. The genetic characterization revealed that riboflavin production was triggered by mutations inhibiting purine biosynthesis, which is surprising since the purine nucleotide GTP is a riboflavin precursor. Purine starvation in the mutants induced overexpression of the riboflavin biosynthesis cluster ribABGH When the purine starvation was relieved by purine supplementation in the growth medium, the outcome was an immediate downregulation of the riboflavin biosynthesis cluster and a reduction in riboflavin production. Finally, by applying the new isolates in milk fermentation, the riboflavin content of milk (0.99 mg/liter) was improved to 2.81 mg/liter, compared with 0.66 mg/liter and 1.51 mg/liter by using the wild-type strain and the original roseoflavin-resistant mutant JC017, respectively. The results obtained demonstrate how powerful classical mutagenesis can be when combined with droplet-based microfluidic screening technology for obtaining microorganisms with useful attributes. IMPORTANCE The food industry prefers to use classical approaches, e.g., random mutagenesis followed by screening, to improve microorganisms used in food production, as the use of recombinant DNA technologies is still not widely accepted. Although modern automated screening platforms are widely accessible, screening remains as a bottleneck in strain development, especially when a mild mutagenesis approach is applied to reduce the chance of accumulating unintended mutations, which may cause unwanted phenotypic changes. Here, we incorporate a droplet-based high-throughput screening method into the strain development process and readily capture L. lactis variants with more efficient vitamin secretion from low-error-rate mutagenesis libraries. This study shows that useful mutants showing strong phenotypes but without extensive mutations can be identified with efficient screening technologies. It is therefore possible to avoid accumulating detrimental mutations while enriching beneficial ones through iterative mutagenesis screening. Due to the low mutation rates, the genetic determinants are also readily identified., (Copyright © 2017 Chen et al.)

Aim: The present study aimed to determine the levels of total cholesterol, triglycerides (TG), low-density lipoproteins (LDL), high-density lipoproteins (HDL), and vitamins B1 and B2 in intrahepatic cholestasis of pregnancy (ICP) patients, and to evaluate if these were involved in the pathophysiology of the disease., Methods: The prospective randomized study included 35 pregnant patients who were admitted to the Gynecology and Obstetrics Polyclinic, Faculty of Medicine at Dicle University and who were diagnosed with ICP (Group 1), and 40 healthy pregnant women who were admitted in the same period and who had no systemic diseases that might complicate the pregnancy during the pregnancy follow-up (Group 2). Serum lipid levels and vitamins B1 and B2 were determined and compared, and statistical comparisons of the groups were made., Results: There was no difference between the TG levels of the two groups (P=0.631). Total cholesterol, LDL, HDL, and vitamin B1 and B2 levels were higher in Group 1 than in Group 2 (P=0.001, P=0.001, P=0.001, P=0.001, and P=0.032, respectively)., Conclusions: Increased levels of vitamins B1 and B2 may indicate a need for increased energy metabolism at the fetus. So we believe that new studies are required, which will be supported by the placental analyses of the pyruvate and lactate levels in maternal blood at delivery and fetal cord blood in order to develop a better understanding on the fetal effects of energy metabolism.

[b]Introduction[/b]. Prolonged shortages of protein in the diet significantly alter the composition and content of polyunsaturated fatty acids (PUFA) in tissues and body fluids. One of nutritional factors which may reduce negative effects of protein malnutrition might be vitamin B[sub]2[/sub] due to its influence on lipids metabolism. [b]Objective. [/b]The aim of the study was to investigate the influence of low protein (LP) diet enriched with vitamin B[sub]2[/sub] on the content and composition of PUFA in the blood serum of rats treated with dosed physical exercise. [b]Materials and method. [/b]The experiment was carried out for 3 months on 72 growing male Wistar rats divided into 5 groups. Animals were fed ad libitum on a diet with an energy value of 350 kcal/100 g, in which 4.5% of the energy was provided by protein. In the control diet, 20% of the energy was provided by protein. Two groups were fed the diet enriched with vitamin B2. The two groups of tested animals were trained for 5 days a week. [b]Results.[/b] LP diet caused a decrease in α-linolenic acid (ALA) after 30 days, and a decrease in docosahexaenoic acid (DHA) after 60 days of experiment, compared with rats fed the control diet. After 60 and 90 days of the experiment, a significant decrease was noted in arachidonic acid (AA) in serum of trained rats, compared with sedentary rats fed the LP diet. Physical activity increased LA (mainly on day 30), EPA (on day 90) and reduced AA content (on day 90) in serum of rats fed the LP diet. B2 supplementation in the trained LP group did not change the EPA and AA dependence; however, there was a decrease in LA content in comparison to the non-supplemented trained group. [b]Conclusions. [/b] Results of this study suggest that all investigated factors (protein deficiency, physical exercise and supplementation of vitamin B2) have significant impact on PUFA composition of serum in rats.

Riboflavin (vitamin B 2 ) is an essential nutrient for humans and animals that must be obtained from the diet. To ensure an optimal supply, riboflavin is used on a large scale as additive in the food and feed industries. Here, we describe a historical overview of the industrial process of riboflavin production starting from its discovery and the need to produce the vitamin in bulk at prices that would allow for their use in human and animal nutrition. Riboflavin was produced industrially by chemical synthesis for many decades. At present, the development of economical and eco-efficient fermentation processes, which are mainly based on Bacillus subtilis and Ashbya gossypii strains, has replaced the synthetic process at industrial scale. A detailed account is given of the development of the riboflavin overproducer strains as well as future prospects for its improvement.

Riboflavin derivatives are essential cofactors for a myriad of flavoproteins. In bacteria, flavins importance extends beyond their role as intracellular protein cofactors, as secreted flavins are a key metabolite in a variety of physiological processes. Bacteria obtain riboflavin through the endogenous riboflavin biosynthetic pathway (RBP) or by the use of importer proteins. Bacteria frequently encode multiple paralogs of the RBP enzymes and as for other micronutrient supply pathways, biosynthesis and uptake functions largely coexist. It is proposed that bacteria shut down biosynthesis and would rather uptake riboflavin when the vitamin is environmentally available. Recently, the overlap of riboflavin provisioning elements has gained attention and the functions of duplicated paralogs of RBP enzymes started to be addressed. Results point towards the existence of a modular structure in the bacterial riboflavin supply pathways. Such structure uses subsets of RBP genes to supply riboflavin for specific functions. Given the importance of riboflavin in intra and extracellular bacterial physiology, this complex array of riboflavin provision pathways may have developed to contend with the various riboflavin requirements. In riboflavin-prototrophic bacteria, riboflavin transporters could represent a module for riboflavin provision for particular, yet unidentified processes, rather than substituting for the RBP as usually assumed.

Background: Epidemiological studies assessing the relationship between dietary vitamin B2 and the risk of breast cancer have produced inconsistent results. Thus, we conducted this meta-analysis of epidemiologic studies to evaluate this association., Methods: We searched English-language MEDLINE publications and conducted a manual search to screen eligible articles. A random-effect model was used to pool study-specific risk estimates. Egger's linear regression test was also used to detect publication bias in meta-analysis., Results: In our meta-analysis, ten studies comprising totally 12,268 breast cancer patients were available in the analyses. Pooled relative risk (RR) comparing the highest to the lowest vitamin B2 intake and breast cancer incidence was 0.85 [95% confidence interval (CI) = 0.76-0.95]. No significant heterogeneity existed across the studies (P = 0.086, I 2  = 40.7%). No publication bias was found. The results of dose-response analysis also showed that an increment of 1 mg/day was inversely related to the risk of breast cancer (RR = 0.94; 95% CI = 0.90-0.99)., Conclusions: Results from our meta-analysis indicated that dietary vitamin B2 intake is weakly related to the reduced risk of breast cancer. Additional research is also necessary to further explore this association.

Purpose: To examine the associations between the dietary intakes of certain B-vitamins from different food sources with the relevant plasma status indices in children., Methods: A representative subsample of 600 children aged 9-13 years from the Healthy Growth Study was selected. Dietary intakes of vitamins B 2 , B 12 , B 6 and folate derived from different food sources were estimated. Plasma levels of vitamin B 2 (or riboflavin), methylmalonic acid (MMA) and total homocysteine (tHcy) were also measured., Results: Plasma concentrations of vitamin B 2 below 3 μg/L were found in 22.8 % of the children. Children in the lower quartile of dietary vitamin B 2 intake were found to have the lowest plasma vitamin B 2 levels compared to children in the upper three quartiles (5.06 ± 7.63 vs. 6.48 ± 7.88, 6.34 ± 7.63 and 6.05 ± 4.94 μg/L respectively; P = 0.003). Regarding vitamin B 12 children in the lower quartile of dietary intake had higher mean plasma tHcy levels compared to children in the upper two quartiles, respectively (6.00 ± 1.79 vs. 5.41 ± 1.43 and 5.46 ± 1.64 μmol/L; P = 0.012). Positive linear associations were observed between plasma vitamin B 2 levels and dietary vitamin B 2 derived from milk and fruits (β = 0.133; P = 0.001 and β = 0.086; P = 0.037). Additionally, nonlinear associations were also observed between plasma vitamin B 2 levels and vitamin B 2 derived from red meat, as well as between tHcy levels and vitamins B 12 and B 6 derived from milk; vitamins B 12 , B 6 and folate derived from cereal products and folate derived from fruits., Conclusion: A considerably high prevalence of poor plasma vitamin B 2 status was observed in children. The intake of milk, fruits and cereals was associated with more favorable tHcy levels, while the intake of milk and fruits with more favorable plasma B2 levels. However, these findings need to be further confirmed from controlled dietary intervention studies examining the modulation of biomarkers of B-vitamins.

Riboflavin (vitamin B2) plays a role in various biochemical oxidation-reduction reactions. Flavin mononucleotide (FMN) and FAD, the biologically active forms, are made from riboflavin. Riboflavin transporters (RFVTs), RFVT1-3/Slc52a1-3, have been identified. However, the roles of human (h)RFVTs in FMN and FAD homeostasis have not yet been fully clarified. In this study, we assessed the contribution of each hRFVT to riboflavin, FMN and FAD uptake and efflux using in vitro studies. The transfection of hRFVTs increased cellular riboflavin concentrations. The uptake of riboflavin by human embryonic kidney cells transfected with hRFVTs was significantly increased, and the efflux was accelerated in a time-dependent manner. However, the uptake and efflux of FMN and FAD hardly changed. These results strongly suggest that riboflavin, rather than FMN or FAD, passes through plasma membranes via hRFVTs. Our findings could suggest that hRFVTs are involved in riboflavin homeostasis in the cells, and that FMN and FAD concentrations are regulated by riboflavin kinase and FAD synthase.

Background: Vitamins are chemical compounds whose derivatives are involved in vital metabolic pathways of all living organisms. The complete endogenous biosynthesis of vitamins can be performed by many bacteria, yeast and plants, but humans need to acquire most of these essential nutrients with food. In recent years, new types of action of the well-recognized vitamins or their more sophisticated relationships have been reported., Conclusion: In this review we present the current knowledge of factors that can influence the yield and regulation of vitamin B1, B2, B3 and B9 biosynthesis in plants which can be important for human nutrition. A summary of modern methods applied for vitamin analysis in biological materials is also provided. Contributions of selected vitamins to the homeostasis of the human organism, as well as their relations to the progress or prevention of some important diseases such as cancer, cardiovascular diseases, diabetes and Alzheimer's disease are discussed in the light of recent investigations. Better understanding of the mechanisms of vitamin uptake by human tissues and possible metabolic or genetic backgrounds of vitamin deficiencies can open new perspectives on the medical strategies and biotechnological processes of food fortification., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Riboflavin is a common cofactor, and its biosynthetic pathway is well characterized. However, its catabolic pathway, despite intriguing hints in a few distinct organisms, has never been established. This article describes the isolation of a Microbacterium maritypicum riboflavin catabolic strain, and the cloning of the riboflavin catabolic genes. RcaA, RcaB, RcaD, and RcaE were overexpressed and biochemically characterized as riboflavin kinase, riboflavin reductase, ribokinase, and riboflavin hydrolase, respectively. Based on these activities, a pathway for riboflavin catabolism is proposed., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

The benefits of dairy consumption seem to extend beyond its significant contribution to ensuring nutrient intake adequacy as indicated by the favourable associations with several health outcomes reported by different studies. The aims of the present study were to examine the associations of milk consumption with fitness, anthropometric and biochemical indices in children and further explore whether the observed associations are attributed to vitamins B₂ and B 12 derived from milk. A representative subsample of 600 children aged 9-13 years participating in the Healthy Growth Study was examined. Data were collected on children's dietary intake, using 24 h recalls, as well as on fitness, anthropometric and biochemical indices. Regression analyses were performed for investigating the research hypothesis, adjusting for potential confounders and for B-vitamin status indices (i.e., plasma riboflavin, methylmalonic acid and total homocysteine concentrations), dietary calcium intake and plasma zinc concentrations that could possibly act as effect modifiers. Milk consumption was positively associated with the number of stages performed in the endurance run test (ERT) (β = 0.10; p = 0.017) and negatively with body mass index (BMI) (β = -0.10; p = 0.014), after adjusting for several potential confounders and effect modifiers. Dietary intakes of vitamin B₂ and B 12 derived from milk were also positively associated with the number of ERT stages (β = 0.10; p = 0.015 and β = 0.10; p = 0.014 respectively). In conclusion, higher intake of milk as well as vitamin B₂ and B 12 derived from milk were independently associated with higher cardiorespiratory fitness in Greek preadolescents. The key roles of these B-vitamins in substrate oxidation, energy production, haemoglobin synthesis and erythropoiesis could provide a basis for interpreting these associations. However, further research is needed to confirm this potential interpretation., Competing Interests: E.v.d.H. and C.M.S.-P. are employees at FrieslandCampina. None of the other authors have any potential conflict of interest. Any opinions, findings, conclusions or recommendations expressed in the current study are those of the authors and do not necessarily reflect the views of FrieslandCampina.

Vitamin B2 serves as a cofactor to enhance one-carbon metabolism, maintain mucous membranes, and has been implicated in lowering colorectal cancer (CRC) risk. However, few prospective studies have examined the association between vitamin B2 intake and CRC. In this study, we estimated the associations between vitamin B2 intake and CRC risk using the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS) cohorts. Vitamin B2 intake was measured by a validated food frequency questionnaire every 4 years. Among 100,033 women in the NHS and 44,007 men in the HPFS we documented a total of 3,037 incident CRC cases (2,093 women and 944 men) during 24-26 years of follow-up until 2010. Intakes of total (from food and supplements), dietary (from food only), and supplemental vitamin B2 were inversely related to CRC risk in age-adjusted analysis in NHS. However, the association was attenuated and no longer statistically significant in multivariate analysis (p-trend ≥0.08). The pooled multivariate relative risks (95% confidence interval) comparing individuals in the extreme quintiles of intakes were 0.93 (0.81-1.06) for total vitamin B2, 0.89 (0.61-1.28) for dietary vitamin B2 and 0.94 (0.81-1.08) for supplemental vitamin B2. These associations of total vitamin B2 intake were similar for risk of CRC with varying lag-time periods (0-4, 4-8, 8-12 or 12-16 years), for risk of CRC subtypes by tumor location, and across strata of intake of folate or alcohol. Our prospective data do not support a beneficial role of vitamin B2 intake in lowering incidence of CRC., (© 2016 UICC.)

Phenylalanine ethyl ester (PAE)-alginate (Alg) conjugate (PAE-Alg, PEA) was synthesized and formation of an amide bond between PAE and Alg was confirmed by Fourier transformed-infrared and (1)H nuclear magnetic resonance spectroscopy. The degree of PAE substitution was 3.5-4.7 (PAE group per hundred sugar residues of Alg) which was determined by elemental analysis. The critical aggregation concentration values determined for PEA conjugates PEA1, PEA2, and PEA3 were 0.20, 0.12, and 0.10 mg/ml, respectively. The particle size of PEA nanoparticles (PEA-NPs) decreased from 425 nm to 226 nm with the increasing degree of PAE substitution. Vitamin B2 (VB2), as a model nutrient, was encapsulated into the nanoparticles. The drug-loading content increased with increasing degree of PAE substitution. The maximum VB2 loading capacity and loading efficiency of PEA3 nanoparticles were 3.53 ± 0.03% and 91.48 ± 0.80%, respectively. The in vitro release behavior of VB2 from the PEA-NPs showed a biphasic release profile with an initial burst release of about 40-50% of VB2 in the first 10 h followed by a steady and continuous release phase for the following 50 h in PBS, pH 7.4. The human colorectal carcinoma cell line was used to investigate the cytotoxicity of PEA-NPs. Our results showed that various concentrations of nanoparticles did not cause significant cytotoxicity against cell lines at normal concentrations., (© The Author(s) 2016.)

Sepsis, also known as systemic inflammatory response syndrome, is a life-threatening condition caused by a pathogenic agent and leading to multiple organ dysfunction syndrome. One of the factors responsible for the excessive intensification of the inflammatory response in the course of inflammation is high-mobility group protein B1 (HMGB1). HMG-1 is a nuclear protein which, after being released to the intercellular space, has a highly pro-inflammatory effect and acts as a late mediator of lethal damage. The purpose of this study was to examine whether the anti-inflammatory action of riboflavin is accompanied by inhibition of HMGB1 release during peritoneal inflammation and zymosan stimulation of macrophages. Peritonitis was induced in male BALB/c and C57BL/6J mice via intraperitoneal injection of zymosan (40 mg/kg). RAW 264.7 macrophages were activated with zymosan (250 µg/ml). Riboflavin (mice, 50 mg/kg; RAW 264.7, 25 µg/ml) was administered 30 min before zymosan, simultaneously with, or 2, 4, 6 h after zymosan. Additionally, mRNA expression of HMGB1 and its intracellular and serum levels were evaluated. The research showed that riboflavin significantly reduces both the expression and the release of HMGB1; however, the effect of riboflavin was time-dependent. The greatest efficacy was found when riboflavin was given 30 min prior to zymosan, and also 2 and 4 h (C57BL/6J; RAW 264.7) or 4 and 6 h (BALB/c) after zymosan. Research showed that riboflavin influences the level of HMGB1 released in the course of inflammation; however, further study is necessary to determine its mechanisms of action.

Riboflavin (vitamin B2) production has shifted from chemical synthesis to exclusive biotechnological synthesis in less than 15 years. The underlying extraordinary achievement in metabolic engineering and bioprocess engineering is reviewed in this article with regard to the two most important industrial producers Bacillus subtilis and Ashbya gossypii. The respective biosynthetic routes and modifications are discussed, and also the regulation of riboflavin synthesis. As the terminal biosynthesis of riboflavin starts from the two precursors, ribulose 5-phosphate and guanosine triphosphate (GTP), both strains have been optimized for an improved flux through the pentose phosphate pathway as well as the purine biosynthetic pathway. Specific targets for improvement of A. gossypii were the increase of the glycine pool and the increase of carbon flow through the glyoxylic shunt. In B. subtilis, research interest, amongst others, has focused on gluconeogenesis and overexpression of the rib operon. In addition, insight into large-scale production of vitamin B2 is given, as well as future prospects and possible developments.

An enzyme catalysing the essential dephosphorylation of the riboflavin precursor, 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione 5'-phosphate (6), was purified about 800-fold from a riboflavin-producing Bacillus subtilis strain, and was assigned as the translation product of the ycsE gene by mass spectrometry. YcsE is a member of the large haloacid dehalogenase (HAD) superfamily. The recombinant protein was expressed in Escherichia coli. It catalyses the hydrolysis of 6 (vmax , 12 μmol mg(-1)  min(-1) ; KM , 54 μm) and of FMN (vmax , 25 μmol mg(-1)  min(-1) ; KM , 135 μm). A ycsE deletion mutant of B. subtilis was not riboflavin dependent. Two additional proteins (YwtE, YitU) that catalyse the hydrolysis of 6 at appreciable rates were identified by screening 13 putative HAD superfamily members from B. subtilis. The evolutionary processes that have resulted in the handling of an essential step in the biosynthesis of an essential cofactor by a consortium of promiscuous enzymes require further analysis., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Vitamin C is an essential dietary nutrient that has a variety of biological functions. Recent studies have provided promising evidence for its additional health benefits, including anticancer activity. Vitamin B2, another essential dietary nutrient, often coexists with vitamin C in some fruits, vegetables, or dietary supplements. The objective of the present study is to determine whether the combination of vitamin C and B2 can achieve a synergistic anticancer activity. MDA-MB-231, MCF-7, and A549 cells were employed to evaluate the combinatory effects of vitamin C and B2. We found that the combination of vitamin C and B2 resulted in a synergistic cell death induction in all cell lines tested. Further mechanistic investigations revealed that vitamin B2 sensitized cancer cells to vitamin C through inhibition of Akt and Bad phosphorylation. Our findings identified vitamin B2 as a promising sensitizer for improving the efficacy of vitamin-C-based cancer chemoprevention and chemotherapy.

Riboflavin, also known as vitamin B2, is transported across the biological membrane into various organs by transport systems. Riboflavin transporter RFVT3 is expressed in the small intestine and has been suggested to localize in the apical membranes of the intestinal epithelial cells. In this study, we investigated the functional involvement of RFVT3 in riboflavin absorption using intestinal epithelial T84 cells and mouse small intestine. T84 cells expressed RFVT3 and conserved unidirectional riboflavin transport corresponding to intestinal absorption. Apical [(3)H]riboflavin uptake was pH-dependent in T84 cells. This uptake was not affected by Na(+) depletion at apical pH 6.0, although it was significantly decreased at apical pH 7.4. The [(3)H]riboflavin uptake from the apical side of T84 cells was prominently inhibited by the RFVT3 selective inhibitor methylene blue and significantly decreased by transfection of RFVT3-small-interfering RNA. In the gastrointestinal tract, RFVT3 was expressed in the jejunum and ileum. Mouse jejunal and ileal permeabilities of [(3)H]riboflavin were measured by the in situ closed-loop method and were significantly reduced by methylene blue. These results strongly suggest that RFVT3 would functionally be involved in riboflavin absorption in the apical membranes of intestinal epithelial cells.

The missing link: Studies on the biosynthesis of riboflavin have failed to characterise dephosphorylation of the intermediate 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione 5'-phosphate. We show that this reaction can be catalysed in Escherichia coli by YigB and YbjI and in plant chloroplasts by AtcpFHy1, which are members of the haloacid dehalogenase superfamily., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)