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Strategies to Increase the Production of Biosynthetic Riboflavin.
Zhao, G, Dong, F, Lao, X, Zheng, H
Molecular biotechnology. 2021;(10):909-918
Abstract
Riboflavin is widely regarded as an essential nutrient that is involved in biological oxidation in vivo. In addition to preventing and treating acyl-CoA dehydrogenase deficiency in patients with keratitis, stomatitis, and glossitis, riboflavin is also closely related to the treatment of radiation mucositis and cardiovascular disease. Chemical synthesis has been the dominant method for producing riboflavin for approximately 50 years. Nevertheless, due to the intricate synthesis process, relatively high cost, and high risk of pollution, alternative methods of chemical syntheses, such as the fermentation method, began to develop and eventually became the main methods for producing riboflavin. At present, there are three types of strains used in industrial riboflavin production: Ashbya gossypii, Candida famata, and Bacillus subtilis. Additionally, many recent studies have been conducted on Escherichia coli and Lactobacillus. Fermentation increases the yield of riboflavin using genetic engineering technology to modify and induce riboflavin production in the strain, as well as to regulate the metabolic flux of the purine pathway and pentose phosphate pathway (PP pathway), thereby optimizing the culture process. This article briefly introduces recent progress in the fermentation of riboflavin.
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Alteration of Flavin Cofactor Homeostasis in Human Neuromuscular Pathologies.
Tolomeo, M, Nisco, A, Barile, M
Methods in molecular biology (Clifton, N.J.). 2021;:275-295
Abstract
The aim of this short review chapter is to provide a brief summary of the relevance of riboflavin (Rf or vitamin B2) and its derived cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) for human neuromuscular bioenergetics.Therefore, as a completion of this book we would like to summarize what kind of human pathologies could derive from genetic disturbances of Rf transport, flavin cofactor synthesis and delivery to nascent apoflavoproteins, as well as by alteration of vitamin recycling during protein turnover.
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3.
Metabolic treatments of migraine.
Lisicki, M, Schoenen, J
Expert review of neurotherapeutics. 2020;(3):295-302
Abstract
Introduction: Most preventive migraine treatments modify the brain's excitation/inhibition balance and/or serotonin metabolism, which likely accounts for their unfavorable adverse effect profile. Novel biological therapies blocking CGRP transmission are effective and better tolerated, but they are expensive and may not influence brain dysfunctions upstream in the pathophysiological cascade of migraine, including premonitory and aura symptoms. Biochemical and clinical studies suggest that there may be another complimentary treatment strategy, the one that targets the underestimated metabolic facet of migraine pathophysiology.Areas covered: After a brief description of the metabolic abnormalities found in migraine patients, we will review and discuss published data on metabolic treatments of migraine. There is evidence that riboflavin and co-enzyme Q10 are effective for the prevention of migraine and quasi devoid of adverse effects. Response rates are close to those of topiramate, propranolol, and CGRP/CGRPrec mAbs. The evidence is weaker for thioctic acid. Dietary and pharmacological strategies inducing ketosis are novel promising approaches for which preliminary trials with favorable outcomes have been published.Expert opinion: Metabolic treatments of migraine constitute an effective, well-tolerated, inexpensive, and evidence-supported therapeutic option for migraine prophylaxis, and may be considered as first treatment line in many patients, including in children and adolescents.
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4.
Corneal refractive surgery combined with simultaneous corneal cross-linking: Indications, protocols and clinical outcomes-A review.
Ma, J, Wang, Y, Jhanji, V
Clinical & experimental ophthalmology. 2020;(1):78-88
Abstract
Corneal refractive surgery is one of the most common approaches for correction of refractive errors. Combined corneal refractive surgery and corneal cross-linking (CXL) has been proposed as a method to achieve better refractive stability and to prevent iatrogenic corneal ectasia. However, there are concerns regarding its indications, surgical safety, standardization of protocols and long-term effect on corneal tissue. This review article aims to discuss the current knowledge and recent updates on combination of CXL and refractive surgery.
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5.
Corneal Cross-Linking: The Science Beyond the Myths and Misconceptions.
Rubinfeld, RS, Caruso, C, Ostacolo, C
Cornea. 2019;(6):780-790
Abstract
PURPOSE There has been a recent explosion in the variety of techniques used to accomplish corneal cross-linking (CXL) for the treatment of ectatic corneal diseases. To understand the success or failure of various techniques, we review the physicochemical basis of corneal CXL and re-evaluate the current principles and long-standing conventional wisdom in the light of recent, compelling, and sometimes contradictory research. METHODS Two clinicians and a medicinal chemist developed a list of current key topics, controversies, and questions in the field of corneal CXL based on information from current literature, medical conferences, and discussions with international practitioners of CXL. RESULTS Standard corneal CXL with removal of the corneal epithelium is a safe and efficacious procedure for the treatment of corneal ectasias. However, the necessity of epithelium removal is painful for patients, involves risk and requires significant recovery time. Attempts to move to transepithelial corneal CXL have been hindered by the lack of a coherent understanding of the physicochemistry of corneal CXL. Misconceptions about the applicability of the Bunsen-Roscoe law of reciprocity and the Lambert-Beer law in CXL hamper the ability to predict the effect of ultraviolet A energy during CXL. Improved understanding of CXL may also expand the treatment group for corneal ectasia to those with thinner corneas. Finally, it is essential to understand the role of oxygen in successful CXL. CONCLUSIONS Improved understanding of the complex interactions of riboflavin, ultraviolet A energy and oxygen in corneal CXL may provide a successful route to transepithelial corneal CXL.
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Medical Applications of Rose Bengal- and Riboflavin-Photosensitized Protein Crosslinking.
Redmond, RW, Kochevar, IE
Photochemistry and photobiology. 2019;(5):1097-1115
Abstract
This review summarizes research on many of the potential applications of photosensitized crosslinking of tissue proteins in surgery and current knowledge of the photochemical mechanisms underlying formation of the covalent protein-protein crosslinks involved. Initially developed to close wounds or reattach tissues, protein photocrosslinking has also been demonstrated to stiffen and strengthen tissues, decrease inflammatory responses and facilitate tissue bioengineering. These treatments appear to result largely from crosslinks within and between collagen molecules in tissue that typically form by an oxygen-dependent mechanism. Surgical applications discussed include sealing wounds in skin, cornea and bowel; reattaching severed nerves, blood vessels and tendons; strengthening cornea and vein; reducing capsular contracture after breast implants; and regenerating joint cartilage.
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7.
Corneal Cross-Linking for Pediatric Keratcoconus Review.
Perez-Straziota, C, Gaster, RN, Rabinowitz, YS
Cornea. 2018;(6):802-809
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Abstract
PURPOSE To comprehensively review the available published literature for cross-linking in the pediatric population. METHODS Review of the literature published in English in PubMed. RESULTS Two hundred ten publications were considered. One hundred fifteen were considered relevant to this review. CONCLUSIONS Studies of cross-linking in pediatric patients are sparse, with relatively short follow-up times, and mostly on small groups of patients. Treatment with cross-linking halts progression of keratoconus in the pediatric population, and early treatment seems to be cost-effective compared with later penetrating keratoplasty. Long-term effects and regression rates remain unclear, and further studies are needed in this population.
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Overlapping riboflavin supply pathways in bacteria.
García-Angulo, VA
Critical reviews in microbiology. 2017;(2):196-209
Abstract
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.
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Riboflavin, MTHFR genotype and blood pressure: A personalized approach to prevention and treatment of hypertension.
McNulty, H, Strain, JJ, Hughes, CF, Ward, M
Molecular aspects of medicine. 2017;:2-9
Abstract
Hypertension is the leading risk factor contributing to mortality worldwide, primarily from cardiovascular disease (CVD), while effective treatment of hypertension is proven to reduce CVD events. Along with the well recognized nutrition and lifestyle determinants, genetic factors are implicated in the development and progression of hypertension. In recent years genome-wide association studies have identified a region near the gene encoding the folate-metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR) among eight loci associated with blood pressure. Epidemiological studies, which provide a separate line of evidence to link this gene with blood pressure, show that the 677C→T polymorphism in MTHFR increases the risk of hypertension by 24-87% and CVD by up to 40%, albeit with a large geographical variation in the extent of excess disease risk suggestive of a gene-environment interaction. Emerging evidence indicates that the relevant environmental factor may be riboflavin, the MTHFR co-factor, via a novel and genotype-specific effect on blood pressure. Randomized trials conducted in hypertensive patients (with and without overt CVD) pre-screened for this polymorphism show that targeted riboflavin supplementation in homozygous individuals (MTHFR 677TT genotype) lowers systolic blood pressure by 6 to 13 mmHg, independently of the effect of antihypertensive drugs. The latest evidence, that the blood pressure phenotype associated with this polymorphism is modifiable by riboflavin, has important clinical and public health implications. For hypertensive patients, riboflavin supplementation can offer a non-drug treatment to effectively lower blood pressure in those identified with the MTHFR 677TT genotype. For sub-populations worldwide with this genotype, better riboflavin status may prevent or delay the development of high blood pressure. Thus riboflavin, targeted at those homozygous for a common polymorphism in MTHFR, may offer a personalized treatment or preventative strategy for hypertension. Further investigations of this novel gene-nutrient interaction in relation to blood pressure, hypertension and hypertension in pregnancy are required.
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Dietary vitamin B2 intake and breast cancer risk: a systematic review and meta-analysis.
Yu, L, Tan, Y, Zhu, L
Archives of gynecology and obstetrics. 2017;(3):721-729
Abstract
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.