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Virulence Dec 2021To resolve the growing problem of drug resistance in the treatment of bacterial and fungal pathogens, specific cellular targets and pathways can be used as targets for... (Review)
Review
To resolve the growing problem of drug resistance in the treatment of bacterial and fungal pathogens, specific cellular targets and pathways can be used as targets for new antimicrobial agents. Endogenous riboflavin biosynthesis is a conserved pathway that exists in most bacteria and fungi. In this review, the roles of endogenous and exogenous riboflavin in infectious disease as well as several antibacterial agents, which act as analogues of the riboflavin biosynthesis pathway, are summarized. In addition, the effects of exogenous riboflavin on immune cells, cytokines, and heat shock proteins are described. Moreover, the immune response of endogenous riboflavin metabolites in infectious diseases, recognized by MHC-related protein-1, and then presented to mucosal associated invariant T cells, is highlighted. This information will provide a strategy to identify novel drug targets as well as highlight the possible clinical use of riboflavin.
Topics: Anti-Infective Agents; Cytokines; Heat-Shock Proteins; Riboflavin
PubMed: 34490839
DOI: 10.1080/21505594.2021.1963909 -
Frontiers in Immunology 2020Mucosal associated invariant T (MAIT) cells are striking in their abundance and their strict conservation across 150 million years of mammalian evolution, implying they... (Review)
Review
Mucosal associated invariant T (MAIT) cells are striking in their abundance and their strict conservation across 150 million years of mammalian evolution, implying they must fulfill critical immunological function(s). MAIT cells are defined by their expression of a semi-invariant αβ TCR which recognizes biosynthetic derivatives of riboflavin synthesis presented on MR1. Initial studies focused on their role in detecting predominantly intracellular bacterial and mycobacterial infections. However, it is now recognized that there are several modes of MAIT cell activation and these are related to activation of distinct transcriptional programmes, each associated with distinct functional roles. In this minireview, we summarize current knowledge from human and animal studies of MAIT cell activation induced (1) in an MR1-TCR dependent manner in the context of inflammatory danger signals and associated with antibacterial host defense; (2) in an MR1-TCR independent manner by the cytokines interleukin(IL)-12/-15/-18 and type I interferon, which is associated with antiviral responses; and (3) a recently-described TCR-dependent "tissue repair" programme which is associated with accelerated wound healing in the context of commensal microbiota. Because of this capability for diverse functional responses in diverse immunological contexts, these intriguing cells now appear to be multifunctional effectors central to the interface of innate and adaptive immunity.
Topics: Animals; Bacterial Infections; Histocompatibility Antigens Class I; Humans; Interferon Type I; Lymphocyte Activation; Minor Histocompatibility Antigens; Mucosal-Associated Invariant T Cells; Receptors, Antigen, T-Cell, alpha-beta; Riboflavin; Virus Diseases
PubMed: 32536923
DOI: 10.3389/fimmu.2020.01014 -
Nutrients Jul 2021Riboflavin, a water-soluble member of the B-vitamin family, plays a vital role in producing energy in mitochondria and reducing inflammation and oxidative stress.... (Review)
Review
Riboflavin, a water-soluble member of the B-vitamin family, plays a vital role in producing energy in mitochondria and reducing inflammation and oxidative stress. Migraine pathogenesis includes neuroinflammation, oxidative stress, and mitochondrial dysfunction. Therefore, riboflavin is increasingly being recognized for its preventive effects on migraines. However, there is no concrete evidence supporting its use because the link between riboflavin and migraines and the underlying mechanisms remains obscure. This review explored the current experimental and clinical evidence of conditions involved in migraine pathogenesis and discussed the role of riboflavin in inhibiting these conditions. Experimental research has demonstrated elevated levels of various oxidative stress markers and pro-inflammatory cytokines in migraines, and riboflavin's role in reducing these marker levels. Furthermore, clinical research in migraineurs showed increased marker levels and observed riboflavin's effectiveness in reducing migraines. These findings suggest that inflammation and oxidative stress are associated with migraine pathogenesis, and riboflavin may have neuroprotective effects through its clinically useful anti-inflammatory and anti-oxidative stress properties. Riboflavin's safety and efficacy suggests its usefulness in migraine prophylaxis; however, insufficient evidence necessitates further study.
Topics: Animals; Humans; Inflammation; Migraine Disorders; Mitochondria; Neuroprotective Agents; Oxidative Stress; Riboflavin; Vitamins
PubMed: 34444772
DOI: 10.3390/nu13082612 -
Biochemistry Feb 2022The G-quadruplex is a noncanonical fold of DNA commonly found at telomeres and within gene promoter regions of the genome. These guanine-rich sequences are highly...
The G-quadruplex is a noncanonical fold of DNA commonly found at telomeres and within gene promoter regions of the genome. These guanine-rich sequences are highly susceptible to damages such as base oxidation and depurination, leading to abasic sites. In the present work, we address whether a vacancy, such as an abasic site, in a G-quadruplex serves as a specific ligand recognition site. When the G-tetrad is all guanines, the vacant (abasic) site is recognized and bound by free guanine nucleobase. However, we aim to understand whether the preference for a specific ligand recognition changes with the presence of a guanine oxidation product 8-oxo-7,8-dihydroguanine (OG) adjacent to the vacancy in the tetrad. Using molecular dynamics simulation, circular dichroism, and nuclear magnetic resonance, we examined the ability for riboflavin to stabilize abasic site-containing G-quadruplex structures. Through structural and free energy binding analysis, we observe riboflavin's ability to stabilize an abasic site-containing G-quadruplex only in the presence of an adjacent OG-modified base. Further, when compared to simulation with the vacancy filled by free guanine, we observe that the free guanine nucleobase is pushed outside of the tetrad by OG to interact with other parts of the structure, including loop residues. These results support the preference of riboflavin over free guanine to fill an OG-adjacent G-quadruplex abasic vacancy.
Topics: Circular Dichroism; DNA; G-Quadruplexes; Guanine; Humans; Magnetic Resonance Spectroscopy; Molecular Dynamics Simulation; Oxidation-Reduction; Promoter Regions, Genetic; Riboflavin; Telomere
PubMed: 35104101
DOI: 10.1021/acs.biochem.1c00598 -
BMC Public Health May 2023Kidney stone disease (KSD) is a common condition that affects 10% population in the United States (US). The relationship between thiamine and riboflavin intake and KSD...
BACKGROUND
Kidney stone disease (KSD) is a common condition that affects 10% population in the United States (US). The relationship between thiamine and riboflavin intake and KSD has not been well-studied. We aimed to investigate the prevalence of KSD and the association between dietary thiamine and riboflavin intake with KSD in the US population.
METHODS
This large-scale, cross-sectional study included subjects from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. KSD and dietary intake were collected from questionnaires and 24-hour recall interviews. Logistic regression and sensitivity analyses were performed to investigate the association.
RESULTS
This study included 26,786 adult participants with a mean age of 50.12 ± 17.61 years old. The prevalence of KSD was 9.62%. After adjusting for all potential covariates, we found that higher riboflavin intake was negatively related to KSD compared with dietary intake of riboflavin < 2 mg/day in the fully-adjusted model (OR = 0.541, 95% CI = 0.368 to 0.795, P = 0.002). After stratifying by gender and age, we found that the impact of riboflavin on KSD still existed in all age subgroups (P < 0.05) but only in males (P = 0.001). No such associations were found between dietary intake of thiamine and KSD in any of the subgroups.
CONCLUSIONS
Our study suggested that a high intake of riboflavin is independently inversely associated with kidney stones, especially in male population. No association was found between dietary intake of thiamine and KSD. Further studies are needed to confirm our results and explore the causal relationships.
Topics: Adult; Humans; Male; United States; Middle Aged; Aged; Thiamine; Cross-Sectional Studies; Nutrition Surveys; Riboflavin; Kidney Calculi; Eating
PubMed: 37237348
DOI: 10.1186/s12889-023-15817-2 -
Cells Sep 2023Riboflavin, a water-soluble vitamin B2, possesses unique biological and physicochemical properties. Its photosensitizing properties make it suitable for various... (Review)
Review
Riboflavin, a water-soluble vitamin B2, possesses unique biological and physicochemical properties. Its photosensitizing properties make it suitable for various biological applications, such as pathogen inactivation and photodynamic therapy. However, the effectiveness of riboflavin as a photosensitizer is hindered by its degradation upon exposure to light. The review aims to highlight the significance of riboflavin and its derivatives as potential photosensitizers for use in photodynamic therapy. Additionally, a concise overview of photodynamic therapy and utilization of blue light in dermatology is provided, as well as the photochemistry and photobiophysics of riboflavin and its derivatives. Particular emphasis is given to the latest findings on the use of acetylated 3-methyltetraacetyl-riboflavin derivative (3MeTARF) in photodynamic therapy.
Topics: Humans; Photosensitizing Agents; Riboflavin; Photochemotherapy; Skin Neoplasms; Vitamins
PubMed: 37759526
DOI: 10.3390/cells12182304 -
The American Journal of Clinical... Dec 2022
Topics: Adult; Humans; Riboflavin Deficiency; Vitamin B 6; Riboflavin; Pyridoxine; Genotype; Vitamins; Methylenetetrahydrofolate Reductase (NADPH2)
PubMed: 36264295
DOI: 10.1093/ajcn/nqac269 -
PLoS Pathogens Mar 2024The emergence of resistance against antimalarials and insecticides poses a significant threat to malaria elimination strategies. It is crucial to explore potential risk... (Review)
Review
The emergence of resistance against antimalarials and insecticides poses a significant threat to malaria elimination strategies. It is crucial to explore potential risk factors for malaria to identify new targets and alternative therapies. Malnutrition is a well-established risk factor for malaria. Deficiencies of micronutrients such as vitamin A, zinc, iron, folic acid, and phenotypic measures of malnutrition, such as stunting and wasting, have been studied extensively in the context of malaria. Vitamin B2, also known as riboflavin, is a micronutrient involved in maintaining cellular homeostasis. Riboflavin deficiency has been shown to have an inverse correlation with malarial parasitaemia. This article reviews the role of riboflavin in maintaining redox homeostasis and probes how riboflavin deficiency could alter malaria pathogenesis by disrupting the balance between oxidants and antioxidants. Though riboflavin analogues have been explored as antimalarials, new in vivo and patient-based research is required to target riboflavin-associated pathways for antimalarial therapy.
Topics: Humans; Riboflavin Deficiency; Antimalarials; Malaria; Folic Acid; Micronutrients; Riboflavin
PubMed: 38427625
DOI: 10.1371/journal.ppat.1011991 -
Microbial Cell Factories Feb 2020Riboflavin (RF) and its active forms, the cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), have been extensively used in the food, feed and... (Review)
Review
Riboflavin (RF) and its active forms, the cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), have been extensively used in the food, feed and pharmaceutical industries. Modern commercial production of riboflavin is based on microbial fermentation, but the established genetically engineered production strains are facing new challenges due to safety concerns in the food and feed additives industry. High yields of flavin mononucleotide and flavin adenine dinucleotide have been obtained using whole-cell biocatalysis processes. However, the necessity of adding expensive precursors results in high production costs. Consequently, developing microbial cell factories that are capable of efficiently producing flavin nucleotides at low cost is an increasingly attractive approach. The biotechnological processes for the production of RF and its cognate cofactors are reviewed in this article.
Topics: Bacteria; Bacterial Proteins; Fermentation; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Fungal Proteins; Fungi; Industrial Microbiology; Secondary Metabolism
PubMed: 32054466
DOI: 10.1186/s12934-020-01302-7 -
International Journal of Molecular... May 2020As an essential vitamin, the role of riboflavin in human diet and health is increasingly being highlighted. Insufficient dietary intake of riboflavin is often reported... (Review)
Review
As an essential vitamin, the role of riboflavin in human diet and health is increasingly being highlighted. Insufficient dietary intake of riboflavin is often reported in nutritional surveys and population studies, even in non-developing countries with abundant sources of riboflavin-rich dietary products. A latent subclinical riboflavin deficiency can result in a significant clinical phenotype when combined with inborn genetic disturbances or environmental and physiological factors like infections, exercise, diet, aging and pregnancy. Riboflavin, and more importantly its derivatives, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), play a crucial role in essential cellular processes including mitochondrial energy metabolism, stress responses, vitamin and cofactor biogenesis, where they function as cofactors to ensure the catalytic activity and folding/stability of flavoenzymes. Numerous inborn errors of flavin metabolism and flavoenzyme function have been described, and supplementation with riboflavin has in many cases been shown to be lifesaving or to mitigate symptoms. This review discusses the environmental, physiological and genetic factors that affect cellular riboflavin status. We describe the crucial role of riboflavin for general human health, and the clear benefits of riboflavin treatment in patients with inborn errors of metabolism.
Topics: Acyl-CoA Dehydrogenases; Aging; Animals; Diet; Electron Transport; Energy Metabolism; Fatty Acids; Female; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Folic Acid; Genetic Variation; Homocysteine; Humans; Immune System; Metabolism, Inborn Errors; Mitochondria; Mutation; Phenotype; Pregnancy; Protein Folding; Riboflavin; Riboflavin Deficiency
PubMed: 32481712
DOI: 10.3390/ijms21113847