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Animal : An International Journal of... Jan 2022Data from breeder hens and chicks are particularly critical for the development of vitamin B2 recommendations for organic poultry. To test safe thresholds of...
Data from breeder hens and chicks are particularly critical for the development of vitamin B2 recommendations for organic poultry. To test safe thresholds of supplementation, 100 breeder hens (Hubbard JA 57 K) and ten cockerels were allocated to ten housing groups, with each receiving supplementation of either 4.0 (treatment CON) or 2.5 mg (treatment RED) riboflavin per kg feed. After 15 weeks of experimental feeding, 256 eggs were incubated. From the hatched chicks (Hubbard S757), 192 were allocated to four treatments based on their parents' treatment (CON- or RED-) and on their own supplementation of either 4.0 (-CON) or 2.5 mg (-RED) riboflavin per kg feed. Two groups of each combination (CON-CON, CON-RED, RED-CON, RED-RED), each with 24 chicks of both sexes, were fattened for nine weeks and slaughtered. Analysis of total riboflavin (sum of native concentrations and supplements) in the parent's feeds revealed an average, over the 15 weeks, of 7.8 and 5.8 mg per kg feed for CON and RED, respectively. Body weight, plumage integrity, gait appearance, footpad, claw and keel bone integrity, lesion scores, laying performance, and egg mass were found to be of similarly high levels for all hens without any treatment effects. Performance traits of the hens in both treatments reached the specifications of the producer for this genotype. Yolk and albumen riboflavin concentrations were not affected although yolk colour in the RED treatment group became darker. Fertility was not affected, and hatchability was 100 per cent. Total riboflavin concentrations in the broiler diets were on average, over 9 weeks, 8.2 and 6.1 mg/kg for CON and RED, respectively. In chicks, RED treatment of their parents led to significant depressions of feed intake and growth. The RED treatment of the chicks themselves also impaired growth. Growth rates of the CON-CON treatment were in line with the specifications of the producer for this genotype. Plumage scores, footpad integrity and walking appearance of the broilers, and dressing percentage of the carcasses were not affected by treatment. The RED treatment of chicks caused lower spleen and heart weights, while pancreas and liver weights, and liver riboflavin concentrations were not affected. In conclusion, supplementation of 4.0 mg/kg to organic diets did not evoke any health or performance problems for breeder hens or broiler chicks, while a supplementation level of 2.5 mg per kg feed led to reduced weight gains, although without any other riboflavin deficiency symptoms.
Topics: Animal Feed; Animals; Chickens; Diet; Dietary Supplements; Female; Fertility; Male; Riboflavin
PubMed: 34999564
DOI: 10.1016/j.animal.2021.100433 -
International Journal of Molecular... Dec 2022is a dangerous hospital pathogen primarily due to its ability to form biofilms on different abiotic and biotic surfaces. The present study investigated the effect of...
is a dangerous hospital pathogen primarily due to its ability to form biofilms on different abiotic and biotic surfaces. The present study investigated the effect of riboflavin- and chlorophyllin-based antimicrobial photodynamic therapy, performed with near-ultraviolet or blue light on the viability of bacterial cells in biofilms and their structural stability, also determining the extent of photoinduced generation of intracellular reactive oxygen species as well as the ability of to form biofilms after the treatment. The efficacy of antimicrobial photodynamic therapy was compared with that of light alone and the role of the photosensitizer type on the photosensitization mechanism was demonstrated. We found that the antibacterial effect of riboflavin-based antimicrobial photodynamic therapy depends on the ability of photoactivated riboflavin to generate intracellular reactive oxygen species but does not depend on the concentration of riboflavin and pre-incubation time before irradiation. Moreover, our results suggest a clear interconnection between the inactivation efficiency of chlorophyllin-based antimicrobial photodynamic therapy and the sensitivity of biofilms to used light. In summary, all the analyzed results suggest that riboflavin-based antimicrobial photodynamic therapy and chlorophyllin-based antimicrobial photodynamic therapy have the potential to be applied as an antibacterial treatment against biofilms or as a preventive measure against biofilm formation.
Topics: Acinetobacter baumannii; Reactive Oxygen Species; Anti-Infective Agents; Anti-Bacterial Agents; Photochemotherapy; Biofilms; Riboflavin
PubMed: 36614160
DOI: 10.3390/ijms24010722 -
Advanced Science (Weinheim,... Mar 2023Photodynamic therapy (PDT) is a light triggered therapy by producing reactive oxygen species (ROS), but traditional PDT may suffer from the real-time illumination that...
Photodynamic therapy (PDT) is a light triggered therapy by producing reactive oxygen species (ROS), but traditional PDT may suffer from the real-time illumination that reduces the compliance of treatment and cause phototoxicity. A supramolecular photoactive G-quartet based material is reported, which is self-assembled from guanosine (G) and 4-formylphenylboronic acid/1,8-diaminooctane, with incorporation of riboflavin as a photocatalyst to the G4 nanowire, for post-irradiation photodynamic antibacterial therapy. The G4-materials, which exhibit hydrogel-like properties, provide a scaffold for loading riboflavin, and the reductant guanosine for the riboflavin for phototriggered production of the therapeutic H O . The photocatalytic activity shows great tolerance against room temperature storage and heating/cooling treatments. The riboflavin-loaded G4 hydrogels, after photo-irradiation, are capable of killing gram-positive bacteria (e.g., Staphylococcus aureus), gram-negative bacteria (e.g., Escherichia coli), and multidrug resistant bacteria (methicillin-resistant Staphylococcus aureus) with sterilization ratio over 99.999%. The post-irradiated hydrogels also exhibit great antibacterial activity in the infected wound of the rats, revealing the potential of this novel concept in the light therapy.
Topics: Rats; Animals; Methicillin-Resistant Staphylococcus aureus; Photochemotherapy; Escherichia coli; Riboflavin; Anti-Bacterial Agents; Wound Infection; Hydrogels
PubMed: 36709479
DOI: 10.1002/advs.202206851 -
Microbiology Spectrum Feb 2023Oropharyngeal candidiasis (OPC), which has a high incidence in immunocompromised and denture stomatitis patients, is commonly caused by Candida albicans infection and in...
Oropharyngeal candidiasis (OPC), which has a high incidence in immunocompromised and denture stomatitis patients, is commonly caused by Candida albicans infection and in some cases develops into disseminated candidiasis throughout the throat and esophagus, resulting in high mortality. New drugs are needed to combat OPC because of the limited treatment options currently available and increasing resistance to existing drugs. Here, we confirmed that riboflavin (RF), a cofactor of flavin adenine mononucleotide and flavin adenine dinucleotide, has broad-spectrum anti- activity. The formation of C. albicans hyphae and biofilm was inhibited by RF. Mechanistically, RF disrupted membrane and cell wall integrity, as well as promoting reactive oxygen species and pyruvate accumulation. Furthermore, RF targeted multiple essential pathways via functional disruption of thiamine and RF metabolic pathways, central carbon metabolism, and ribosome metabolism. Similar to the results , the inhibitory effect of RF on C. albicans hyphae was confirmed in a mouse model of OPC. Moreover, after 5 consecutive days of intraperitoneal injection, RF exhibited therapeutic efficacy, as demonstrated by phenotype investigation, the fungal burden, and histopathological analysis. These findings revealed that RF exerts a multifaceted anti- effect and has potential benefits in the treatment of OPC. species are common pathogens in fungal infections, causing mucosal infection and invasive infection in immunodeficient patients. Given the limited classes of drugs and resistance to these drugs, new antifungal agents need to be developed. Drug repurposing is a potential method for antifungal drug development. This study demonstrated that riboflavin (RF) exhibited broad-spectrum anti- activity. RF affected multiple targets involving the membrane and cell wall integrity, the accumulation of reactive oxygen species and pyruvate, and the altered metabolic pathways in C. albicans. Moreover, RF exhibited efficacy in the treatment of C. albicans in an oropharyngeal candidiasis mouse model. Taken together, the antifungal activity and the promising clinical application of RF were highlighted.
Topics: Animals; Mice; Candida albicans; Antifungal Agents; Reactive Oxygen Species; Candidiasis, Oral; Candidiasis; Candida; Ribosomes; Riboflavin; Microbial Sensitivity Tests
PubMed: 36625571
DOI: 10.1128/spectrum.03801-22 -
Scientific Reports Mar 2022The synthesis of polymeric nanoparticles (NPs) with efficient drug loading content and targeting moieties is an attractive field and remains a challenge in drug delivery...
The synthesis of polymeric nanoparticles (NPs) with efficient drug loading content and targeting moieties is an attractive field and remains a challenge in drug delivery systems. Atomistic investigations can provide an in-depth understanding of delivery devices and reduce the number of expensive experiments. In this paper, we studied the self-assembly of poly (lactic-co-glycolic acid)-b-poly (ethylene glycol) with different molecular weights and surface compositions. The innovation of this molecular study is the loading of an antitumor drug (docetaxel) on a targeting ligand (riboflavin). According to this work, a novel, biocompatible and targeted system for cancer treatment has been developed. The obtained results revealed a correlation between polymer molecular weight and the stability of particles. In this line, samples including 20 and 10 w/w% moiety NPs formed from polymers with 3 and 4.5 kDa backbone sizes, respectively, are the stable models with the highest drug loading and entrapment efficiencies. Next, we evaluated NP morphology and found that NPs have a core/shell structure consisting of a hydrophobic core with a shell of poly (ethylene glycol) and riboflavin. Interestingly, morphology assessments confirmed that the targeting moiety located on the surface can improve drug delivery to receptors and cancerous cells. The developed models provided significant insight into the structure and morphology of NPs before the synthesis and further analysis of NPs in biological environments. However, in the best cases of this system, Dynamic Light Scattering (DLS) tests were also taken and the results were consistent with the results obtained from All Atom and Coarse Grained simulations.
Topics: Docetaxel; Drug Carriers; Drug Delivery Systems; Nanoparticles; Pharmaceutical Preparations; Polyethylene Glycols; Polymers; Riboflavin
PubMed: 35332259
DOI: 10.1038/s41598-022-09164-2 -
Microbial Cell Factories Aug 2022Riboflavin is a precursor of FMN and FAD which act as coenzymes of numerous enzymes. Riboflavin is an important biotechnological commodity with annual market sales...
BACKGROUND
Riboflavin is a precursor of FMN and FAD which act as coenzymes of numerous enzymes. Riboflavin is an important biotechnological commodity with annual market sales exceeding nine billion US dollars. It is used primarily as a component of feed premixes, a food colorant, a component of multivitamin mixtures and medicines. Currently, industrial riboflavin production uses the bacterium, Bacillus subtilis, and the filamentous fungus, Ashbya gossypii, and utilizes glucose and/or oils as carbon substrates.
RESULTS
We studied riboflavin biosynthesis in the flavinogenic yeast Candida famata that is a genetically stable riboflavin overproducer. Here it was found that the wild type C. famata is characterized by robust growth on lactose and cheese whey and the engineered strains also overproduce riboflavin on whey. The riboflavin synthesis on whey was close to that obtained on glucose. To further enhance riboflavin production on whey, the gene of the transcription activator SEF1 was expressed under control of the lactose-induced promoter of the native β-galactosidase gene LAC4. These transformants produced elevated amounts of riboflavin on lactose and especially on whey. The strain with additional overexpression of gene RIB6 involved in conversion of ribulose-5-phosphate to riboflavin precursor had the highest titer of accumulated riboflavin in flasks during cultivation on whey. Activation of riboflavin synthesis was also obtained after overexpression of the GND1 gene that is involved in the synthesis of the riboflavin precursor ribulose-5-phosphate. The best engineered strains accumulated 2.5 g of riboflavin/L on whey supplemented only with (NH)SO during batch cultivation in bioreactor with high yield (more than 300 mg/g dry cell weight). The use of concentrated whey inhibited growth of wild-type and engineered strains of C. famata, so the mutants tolerant to concentrated whey were isolated.
CONCLUSIONS
Our data show that the waste of dairy industry is a promising substrate for riboflavin production by C. famata. Possibilities for using the engineered strains of C. famata to produce high-value commodity (riboflavin) from whey are discussed.
Topics: Candida; Cheese; Flavin Mononucleotide; Glucose; Lactose; Phosphates; Riboflavin; Whey
PubMed: 35964025
DOI: 10.1186/s12934-022-01888-0 -
PloS One 2020Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has recently been identified as the causative agent for Coronavirus Disease 2019 (COVID-19). The ability of...
BACKGROUND
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has recently been identified as the causative agent for Coronavirus Disease 2019 (COVID-19). The ability of this agent to be transmitted by blood transfusion has not been documented, although viral RNA has been detected in serum. Exposure to treatment with riboflavin and ultraviolet light (R + UV) reduces blood-borne pathogens while maintaining blood product quality. Here, we report on the efficacy of R + UV in reducing SARS-CoV-2 infectivity when tested in human plasma and whole blood products.
STUDY DESIGN AND METHODS
SARS-CoV-2 (isolate USA-WA1/2020) was used to inoculate plasma and whole blood units that then underwent treatment with riboflavin and UV light (Mirasol Pathogen Reduction Technology System, Terumo BCT, Lakewood, CO). The infectious titers of SARS-CoV-2 in the samples before and after R + UV treatment were determined by plaque assay on Vero E6 cells. Each plasma pool (n = 9) underwent R + UV treatment performed in triplicate using individual units of plasma and then repeated using individual whole blood donations (n = 3).
RESULTS
Riboflavin and UV light reduced the infectious titer of SARS-CoV-2 below the limit of detection for plasma products at 60-100% of the recommended energy dose. At the UV light dose recommended by the manufacturer, the mean log reductions in the viral titers were ≥ 4.79 ± 0.15 Logs in plasma and 3.30 ± 0.26 in whole blood units.
CONCLUSION
Riboflavin and UV light effectively reduced the titer of SARS-CoV-2 to the limit of detection in human plasma and by 3.30 ± 0.26 on average in whole blood. Two clades of SARS-CoV-2 have been described and questions remain about whether exposure to one strain confers strong immunity to the other. Pathogen-reduced blood products may be a safer option for critically ill patients with COVID-19, particularly those in high-risk categories.
Topics: Betacoronavirus; Blood Chemical Analysis; Blood Transfusion; COVID-19; Coronavirus Infections; Humans; Immunization, Passive; Pandemics; Plasma; Pneumonia, Viral; RNA, Viral; Riboflavin; SARS-CoV-2; Ultraviolet Rays; Viral Load; COVID-19 Serotherapy
PubMed: 32470046
DOI: 10.1371/journal.pone.0233947 -
Blood Transfusion = Trasfusione Del... Sep 2022Combining pathogen reduction and automated separation of whole blood (WB), together with the use of improved additive solutions, may increase reproducibility and extend...
BACKGROUND
Combining pathogen reduction and automated separation of whole blood (WB), together with the use of improved additive solutions, may increase reproducibility and extend shelf-life of blood components.
MATERIALS AND METHODS
Forty WB units were collected from volunteer donors and randomised 1:1 into two groups: 1) pathogen reduction with riboflavin and ultraviolet light (PRT); or 2) no treatment (Control). After two hours (h) at room temperature, all units underwent fully automated separation into red blood cell concentrate (RBCC), plasma and leukopack components. RBCCs were leukoreduced and stored in phosphate-adenine-glucose-guanosine-saline-mannitol (PAGGSM) solution while plasma units were shock frozen within 8 h of collection and stored at ≤ -25°C. RBCCs were sampled on day 1 and weekly thereafter until day 42, while plasma was sampled on days 1 and 30. The main study objective was to assess the in vitro quality of separated RBCCs using biochemical and haematological parameters. Plasma protein content after one cycle of freeze-thaw was also analysed.
RESULTS
The quality of RBCCs was largely comparable between the PRT and Control groups, except for a significantly higher degree of haemolysis and extracellular potassium levels in the PRT group after 35 days of storage. While potassium concentration was significantly higher in the PRT group at all timepoints, the degree of haemolysis exceeded the accepted European threshold (i.e., <0.8% of red cell mass in ≥ 90.0% of tested units) after day 35. Most plasma protein levels were significantly lower in the PRT than the Control group at both day 1 and day 30.
DISCUSSION
Pathogen reduction with riboflavin and ultraviolet light treatment of WB can be combined with fully automated separation to obtain RBCCs that may be stored for up to 35 days in PAGGSM solution with acceptable quality, comparable to that of RBCCs from untreated blood. The relative differences between factor concentrations in plasma from the PRT and the Control groups were similar during the 30-day storage.
Topics: Adenine; Blood Preservation; Blood Proteins; Erythrocytes; Glucose; Guanosine; Hemolysis; Humans; Mannitol; Phosphates; Potassium; Reproducibility of Results; Riboflavin; Ultraviolet Rays
PubMed: 35175188
DOI: 10.2450/2022.0278-21 -
Balkan Medical Journal Jul 2022To evaluate the clinical, pathological, and genetic features of patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD).
AIMS
To evaluate the clinical, pathological, and genetic features of patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD).
METHODS
Thirty-one patients with RR-MADD admitted to our hospital from January 2005 to November 2020 were enrolled, and their clinical data were collected. Pathological characteristics of the muscle tissue and possible pathogenic gene mutations were analyzed.
RESULTS
The most common clinical features in all patients were symmetrical proximal muscle weakness. Laboratory examination revealed elevated levels of creatine kinase, homocysteine, and uric acid, acylcarnitines, and organic acid. The muscle biopsy revealed typical pathological changes like lipid deposition. Genetic analysis identified ETFDH mutations in 29 patients, among which one had homozygotes, 19 had compound heterozygotes, 7 had heterozygous mutations, and 2 had heterozygous mutations of both ETFDH and ETFA. Two patients had no pathogenic gene mutations. All patients were treated with riboflavin, and their symptoms improved, which was consistent with the diagnosis of RR-MADD.
CONCLUSION
The clinical manifestations and genetic test results of patients with RR-MADD are heterogeneous. Therefore, a comprehensive analysis of clinical, pathological, and genetic testing is essential for the early diagnosis of RR-MADD.
Topics: Electron-Transferring Flavoproteins; Humans; Iron-Sulfur Proteins; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Oxidoreductases Acting on CH-NH Group Donors; Riboflavin
PubMed: 35734957
DOI: 10.4274/balkanmedj.galenos.2022.2022-1-127 -
Scientific Reports Apr 2022The development of effective pathogen reduction strategies is required due to the rise in antibiotic-resistant bacteria and zoonotic viral pandemics. Photodynamic...
The development of effective pathogen reduction strategies is required due to the rise in antibiotic-resistant bacteria and zoonotic viral pandemics. Photodynamic inactivation (PDI) of bacteria and viruses is a potent reduction strategy that bypasses typical resistance mechanisms. Naturally occurring riboflavin has been widely used in PDI applications due to efficient light-induced reactive oxygen species (ROS) release. By rational design of its core structure to alter (photo)physical properties, we obtained derivatives capable of outperforming riboflavin's visible light-induced PDI against E. coli and a SARS-CoV-2 surrogate, revealing functional group dependency for each pathogen. Bacterial PDI was influenced mainly by guanidino substitution, whereas viral PDI increased through bromination of the flavin. These observations were related to enhanced uptake and ROS-specific nucleic acid cleavage mechanisms. Trends in the derivatives' toxicity towards human fibroblast cells were also investigated to assess viable therapeutic derivatives and help guide further design of PDI agents to combat pathogenic organisms.
Topics: Bacteria; COVID-19; Escherichia coli; Humans; Light; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Riboflavin; SARS-CoV-2
PubMed: 35449377
DOI: 10.1038/s41598-022-10394-7