Riboflavin Research Articles

Metabolomics reveals the potential metabolic mechanism of infliximab against DSS-induced acute and chronic ulcerative colitis.

Inflammatory bowel disease (IBD) is often accompanied by metabolic imbalance, and infliximab (IFX) can alleviate IBD symptoms, but its metabolic mechanisms remain unclear. To investigate the relationship between IBD, metabolism, and IFX, an acute and chronic ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) was established. Plasma samples were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by multivariate statistical analysis. The results showed that IFX could alleviate colonic shortening and reduce colonic pathological damage in acute and chronic mouse colitis, improve acute and chronic UC, and ameliorate metabolic disturbances. Among the 104 elevated metabolites and 170 decreased metabolites, these metabolites mainly belonged to amino acids, glucose, and purines. The changes in these metabolites were mainly associated with drug metabolism-other enzymes, riboflavin metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phosphonate and phosphinate metabolism, and phenylalanine metabolism. In summary, this study provides a valuable approach to explore the metabolic mechanisms of IFX in treating acute and chronic UC from a metabolomics perspective.

Genomic Characterization of Lactiplantibacillus plantarum Strains: Potential Probiotics from Ethiopian Traditional Fermented Cottage Cheese

Background: Lactiplantibacillus plantarum is a species found in a wide range of ecological niches, including vegetables and dairy products, and it may occur naturally in the human gastrointestinal tract. The precise mechanisms underlying the beneficial properties of these microbes to their host remain obscure. Although Lactic acid bacteria are generally regarded as safe, there are rare cases of the emergence of infections and antibiotic resistance by certain probiotics. Objective: An in silico whole genome sequence analysis of putative probiotic bacteria was set up to identify strains, predict desirable functional properties, and identify potentially detrimental antibiotic resistance and virulence genes. Methods: We characterized the genomes of three L. plantarum strains (54B, 54C, and 55A) isolated from Ethiopian traditional cottage cheese. Whole-genome sequencing was performed using Illumina MiSeq sequencing. The completeness and quality of the genome of L. plantarum strains were assessed through CheckM. Results: Analyses results showed that L. plantarum 54B and 54C are closely related but different strains. The genomes studied did not harbor resistance and virulence factors. They had five classes of carbohydrate-active enzymes with several important functions. Cyclic lactone autoinducer, terpenes, Type III polyketide synthases, ribosomally synthesized and post-translationally modified peptides-like gene clusters, sactipeptides, and all genes required for riboflavin biosynthesis were identified, evidencing their promising probiotic properties. Six bacteriocin-like structures encoding genes were found in the genome of L. plantarum 55A. Conclusions: The lack of resistome and virulome and their previous functional capabilities suggest the potential applicability of these strains in food industries as bio-preservatives and in the prevention and/or treatment of infectious diseases. The results also provide insights into the probiotic potential and safety of these three strains and indicate avenues for further mechanistic studies using these isolates.

Development of a xylose-inducible and glucose-insensitive expression system for Parageobacillus thermoglucosidasius

Inducible expression systems are pivotal for governing gene expression in strain engineering and synthetic biotechnological applications. Therefore, a critical need persists for the development of versatile and efficient inducible expression mechanisms. In this study, the xylose-responsive promoter xylA5p and its transcriptional regulator XylR were identified in Parageobacillus thermoglucosidasius DSM 2542. By combining promoter xylA5p with its regulator XylR, fine-tuning the expression strength of XylR, and reducing the glucose catabolite repression on xylose uptake, we successfully devised a xylose-inducible and glucose-insensitive expression system, denoted as IExyl*. This system exhibited diverse promoter strengths upon induction with xylose at varying concentrations and remained unhindered in the presence of glucose. Moreover, we showed the applicability of IExyl* in P. thermoglucosidasius by redirecting metabolic flux towards riboflavin biosynthesis, culminating in a 2.8-fold increase in riboflavin production compared to that of the starting strain. This glucose-insensitive and xylose-responsive expression system provides valuable tools for designing optimized biosynthetic pathways for high-value products and facilitates future synthetic biology investigations in Parageobacillus.Key points• A xylose-inducible and glucose-insensitive expression system IExyl* was developed.• IExyl* was applied to enhance the riboflavin production in P. thermoglucosidasius• A tool for metabolic engineering and synthetic biology research in Parageobacillus strains.

Transcriptome analysis of tilapia streptococcus agalactiae in response to baicalin.

Streptococcus agalactiae (S. agalactiae) is a highly pathogenic bacterial pathogen in aquatic animals. Our previous study has demonstrated the significant inhibitory effect of baicalin on β-hemolytic/cytolytic activity, which is a key virulence factor of S. agalactiae. In this study, we aimed to elucidate the mechanism underlying baicalin's inhibition of S. agalactiae β-hemolytic/cytolytic activity by transcriptomic analysis. Bacteria were exposed to 39.06µg/mL baicalin for 6h, and their β-hemolytic/cytolytic activities were assessed using blood plates. Then, the differentially expressed genes (DEGs) were identified and characterized by RNA sequencing (RNA-Seq), and further confirmed using the qRT-PCR. A total of 10 DEGs with 7 significantly up-regulated and 3 significantly down-regulated, were found to be affected significantly under baicalin treatment. These DEGs were associated with 5 biological processes, 5 cellular components, and 3 molecular functions. They were primarily enriched in 3 pathways: lacD and lacC in galactose metabolism, lrgA and lrgB in the two-component system, and ribH/rib4 in riboflavin metabolism. These suggested that baicalin might inhibit the conversion of pyruvate to acetyl-CoA and malonyl-CoA, which are crucial precursors for β-hemolysin/cytolysin synthesis, and result in the accumulation of pyruvate, suppress the expressions of pyruvate cell membrane channel protein genes lrgA and lrgB. Baicalin could compensatory up-regulate the expressions of tryptophan/tyrosine ABC transporter family genes, ABC.X4.A, ABC.X4.P, and ABC.X4.S by inhibiting the expression of cyl A/B in cyl operons. Moreover, it hinders the conversion of D-glucose 1-phosphate to the dTDP-L-rhamnose pathway and leads to a deficiency of L-rhamnose, an important precursor for β-hemolysin/cytolysin synthesis.

Differences in Gut Microbiota and Metabolites between Wrestlers with Varying Pre-Competition Weight Control Effect.

This study intended to analyze the effects of body weight control by the diet, training adaptation, gut microbiota metabolites of wrestlers in the week leading up to competition. According to the weight difference of wrestlers from the target weight one week prior to the competition, those whose weight control effectiveness is less than 2 kg were classified as the CW group, while more than 2 kg were classified as the CnW group. The body weight, body composition and diet of wrestlers were recorded; urine samples were taken for standard urine testing, and stool samples were collected for the analysis of gut microbiota and metabolites. The data showed that the relative values of carbohydrate and fat energy in the CnW group were significantly higher than those of the CW group, but the relative values of protein energy was significantly lower. The white blood cells, occult blood, and protein appeared in urine in the CnW group. The microbiota with higher abundance values in the CnW group were positively correlated with the relative value of carbohydrate energy, while the abundance value of Streptococcus was negatively correlated; and the functional prediction of differential bacteria was related to riboflavin and selencompound metabolism. The differential metabolites of CW/CnW group were functionally enriched in the processes of lipid and amino acid metabolism. Overall, the extent of weight control in wrestlers was correlated with sensible dietary patterns, adaptability to training load, and distinct gut microbiota and metabolites.

Riboflavin‐Catalyzed Photoinduced Atom Transfer Radical Polymerization

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

Untargeted metabolomic analysis reveals a time-course hepatic metabolism disorder induced by short-term 6PPD exposure in rats

The tire antioxidant 6PPD has garnered extensive attention due to its widespread presence in the environment and the harmful effects of its transformation products on aquatic organisms. 6PPD has been detected in airborne dust, and it can enter mammals through inhalation exposure. While the toxic effects of 6PPD exposure have been reported in mammals, its effects on hepatic metabolism still remain poorly understood. Here, we collected the serum and liver samples at 1, 6, and 72 h following a single oral exposure of 100 mg/kg body weight (bw) 6PPD, respectively. We also investigated changes in serum and hepatic physiological indicators and metabolites, correspondingly. Results indicated that single time oral exposure a high dose of 6PPD did not significantly affect the physiological indexes of rats within a short time frame. However, untargeted metabolomics analysis of the metabolites in the liver at 1, 6, and 72 h revealed that the number of differential expression metabolites gradually increased over time and the most affected substances were lipids and lipid-like molecules. Interestingly, the KEGG pathway enrichment analysis indicated that 6PPD disrupted the riboflavin metabolism, leading to a significant decrease in FMN levels at all time points. In addition, the hepatic glucose metabolism was significantly affected at 6 and 72 h after oral administration. Taken together, short-term exposure to 6PPD disturbed lipid and riboflavin metabolism and gradually affected glucose metabolism in the liver of rats. These findings revealed the impacts of 6PPD on the hepatic metabolism in animals, and also offered some important insights into its toxicology and health risk.

PCL/soy peptide nanofibers incorporated with riboflavin/HP-β-CD assemblies for improving fruit storage quality

In this study, we first successfully developed functionalized electrospun nanofibers (PCL/SP/ICs) loaded with Riboflavin (RF) for fruit preservation with inclusion complexes (RF/HP-β-CD, IC) formed by encapsulating RF with hydroxypropyl-β-cyclodextrin (HP-β-CD) as a core material and soy peptide-assisted polycaprolactones (PCL/SP) as an overwrap material. Compared to 1 wt% and 5 wt% IC, nanofibers implanted with 3 wt% IC had an acceptable water contact angle (87.40°), good thermal stability, and superior mechanical properties. Also, RF/HP-β-CD integration conferred antimicrobial and antioxidant capabilities to PCL/SP fiber membranes. High-performance liquid chromatography (HPLC) studies revealed that produced films of PCL/SP/ICs could continuously and controllably release RF (within 200 h), hence retarding grape degradation and decreasing mass loss rate and titratable acid content throughout an 8-day storage period. Based on these findings, electrospun nanofiber films may be useful for vitamin loading in active food packaging.

Whole-transcriptome analysis reveals the effect of retinoic acid on small intestinal mucosal injury in cage-stressed young laying ducks

Retinoic acid (RA) is an active derivative of vitamin A and is involved in a variety of physiological processes, including cell growth, antioxidant, and inflammation. However, the role of RA in intestinal oxidative stress injury in caged-stressed laying ducks is unknown. In this study, we analyzed the effect and underlying mechanism of RA supplementation on intestinal damage in cage-stressed young laying ducks. One hundred and sixty laying ducks were divided into 5 treatment groups, including a control group (CR) and 4 treatment groups exposed to different RA concentrations (2,500, 5,000, 7,500 and 10,000 IU/kg, TG1 to TG4). The experimental period comprised a 7-d prefeeding period and a 10-d experimental feeding period, for a total of 17 d. Phenotypic analysis revealed that compared with the control group, RA addition increased the intestinal villus height and the villus-to-crypt ratio; decreased the crypt depth (P < 0.01); decreased the serum diamine oxidase and D-lactate concentrations (P < 0.05); increased the serum antioxidant capacity and intestinal antioxidant gene expression levels (P < 0.05); and increased the expression levels of tight junction-related genes, with the greatest effect observed in TG2 group. Our further whole-transcriptome analysis of duodenum tissues from CR and TG2 ducks revealed 706 differentially expressed mRNAs (DEmRNAs), 357 differentially expressed lncRNAs (DElncRNAs), 14 differentially expressed circRNAs (DEcircRNAs), and 4 differentially expressed miRNAs (DEmiRNAs). These DEGs are involved in calcium signaling, NOD-like receptor signaling, pyruvate metabolism, Jak-STAT signaling, Wnt signaling, riboflavin metabolism, and the adherens junction and tight junction pathways. The results of omics and marker gene expression analysis suggested that RA treatment may play a role in endoplasmic reticulum stress (ERS) and apoptosis. In conclusion, the addition of RA to the diet improved intestinal injury by improving the redox homeostasis of intestinal cells associated with ERS, enhancing the intestinal tight junction structure and alleviating the apoptosis of intestinal epithelial cells; moreover, 5,000 IU/kg RA was determined to be the most appropriate concentration for supplementation.

Integrating fecal metabolomics and gut microbiome to reveal the mechanism of Schisandra chinensis-Acorus tatarinowii Schott treatment in Alzheimer’s disease rats

BackgroundSchisandra chinensis (Turcz.) Baill (Schisandraceae) and Acorus tatarinowii Schott (Araceae Juss) (Sc-At) are two traditional Chinese medicinal herbs that are widely used in the treatment of neurological disorders such as insomnia. In our previous study, we found that Sc-At could improve the therapeutic efficacy of Alzheimer’s disease by affecting aromatase activity and estrogen levels, among other pathways. Material and methodsIn this study, first, the ameliorative effect of Sc-At on cognitive dysfunction in Alzheimer’s disease model rats was verified by Y-maze test together with Elisa assay. Second, fecal untargeted metabolomics analysis was performed using a UPLC-Q-TOF/MS-based metabolomics approach. 16S rDNA sequencing was utilized to screen the differential flora between groups, and linear discriminantan alysis effect size (LEfSe) was used to find the target flora. Finally, Spearman correlation analysis was combined to find the relationship between differential flora and differential metabolites in feces. Results(1) The results of Y-maze test and Elisa assay indicated that Sc-At could improve the cognitive dysfunction of AD model rats. (2) Metabolomics results showed that fecal metabolite levels were significantly different from those of rats in the blank group, and 18 potential biomarkers in feces were screened, mainly affecting linoleic acid metabolism, steroid hormone biosynthesis, sphingomyelin metabolism, riboflavin metabolism, etc. The 16S rDNA results showed that the abundance and diversity of intestinal flora in AD rats were destroyed, and the Sc-At treatment was able to reverse these changes. (3) Spearman’s correlation analysis showed a significant correlation between differential metabolites in feces and intestinal flora, further suggesting that Sc-At treats Alzheimer’s disease through the gut-brain axis. ConclusionsIn this study, we explored the mechanism of Sc-At in the treatment of Alzheimer’s disease by integrating fecal untargeted metabolomics and 16S rDNA gene sequencing, and the results showed that Sc-At exerts therapeutic effects on Alzheimer’s disease by improving the intestinal flora and related metabolic pathways.

Mechanism of Panax notoginseng saponins in improving cognitive impairment induced by chronic sleep deprivation based on the integrative analysis of serum metabolomics and network pharmacology

Panax notoginseng saponin (PNS) has a variety of biological activities, such as improvement of myocardial ischemia, improvement of learning and memory, hypolipidemia, and immunomodulation. However, its protective mechanism on the central nervous system (CNS) is not clear. The present study initially evaluated the possible mechanism of PNS to improve cognitive dysfunction due to chronic sleep deprivation (CSD). In the present study, we used a modified multi-platform aquatic environment sleep deprivation method to induce a cognitively impaired rat model, and explored the mechanism of action of PNS by integrating serum metabolomics and network pharmacology, which was further verified by molecular docking and experiments. The results showed that PNS significantly shortened the escape latency, increased the target quadrant time and the number of traversing platforms, and attenuated the inflammatory damage in the hippocampal Cornu Ammonis 1 (CA1) region in CSD rats. The non-targeted metabolomics results indicated that 35 biomarkers significantly altered following PNS therapy intervention, with metabolic pathways enriched for the effects of One carbon pool by folate, Riboflavin metabolism, Glycerophospholipid metabolism, Sphingolipid metabolism, Glycerolipid metabolism, Arachidonic acid metabolism, and Tryptophan metabolism. In addition, network pharmacology identified 234 potential targets for PNS intervention in CSD with cognitive impairment. Metabolite-response-enzyme-gene network was constructed by MetaScape and matched with the network pharmacology results to identify a total of five shared targets (LPL, GPAM, HSD11B1, HSD11B2, and SULT2A1) and two metabolic pathways (Sphingolipid metabolism and Steroid hormone biosynthesis). The results of molecular docking revealed that the five active ingredients had good binding ability with the five core targets. qPCR analysis confirmed the ability of PNS to modulate the above five targets. The combination of metabolomics and network analysis provides a scientific basis for promoting the clinical application of PNS in cognitive impairment.

Integration of bile proteomics and metabolomics analyses reveals novel insights into different types of gallstones in a high-altitude area

BackgroundTo explore the pathogenesis of different subtypes of gallstones in high-altitude populations from a molecular perspective.MethodsWe collected bile samples from 20 cholesterol gallstone disease (CGD) patients and 20 pigment gallstone disease (PGD) patients. Proteomics analysis was performed by LC/MS DIA, while metabolomics analysis was performed by UPLC- Q-TOF/MS.ResultsWe identified 154 up-regulated and 196 down-regulated differentially expressed proteins, which were significantly enriched in neurodegenerative diseases, energy metabolism, amino acid metabolism etc. In metabolomics analysis, 20 up-regulated and 63 down-regulated differentially expressed metabolites were identified, and they were significantly enriched in vitamin B6 metabolism. Three pathways of integrated proteomics and metabolomics were significantly enriched: porphyrin and chlorophyll metabolism, riboflavin metabolism and aminoacyl-tRNA biosynthesis. Remarkably, 7 differentially expressed proteins and metabolites showed excellent predictive performance and were selected as potential biomarkers.ConclusionThe findings of our metabolomics and proteomics analyses help to elucidate the underlying mechanisms of gallstone formation in high-altitude populations.

Creative synthesis of pH-dependent nanoporous pectic acid grafted with acrylamide and acrylic acid copolymer as an ultrasensitive and selective riboflavin electrochemical sensor in real samples

In current research, an innovative pectic acid was grafted with poly (acrylamide-co-acrylic acid) [PA-g-poly (AAm-co-AA)] nanoporous membrane using a free radical-mediated grafting copolymerization process. The optimized parameters for the grafting copolymerization reaction such as initiator concentration, monomer concentrations, polymerization reaction time, and temperature were studied. Additionally, the solid content, graft percentage, and conversion were calculated. The unique polymeric membrane was characterized using Fourier-transform infrared spectroscopy (FT-IR), thermal gravimetry (TG), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) supported by energy dispersive X-ray spectroscopy (EDX). The formulated novel PA-g-poly (AAm-co-AA) had a nanoporous structure with a diameter of 113 nm. pH-dependent swelling and biodegradation measurements were also studied. The electrochemical characterizations of PA-g-poly (AAm-co-AA) were conducted through cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Furthermore, the screen-printed electrode (SPE) was modified with pure PA and the new generation of its grafted polymeric nanoparticles to detect and quantify the concentration of riboflavin (RF) in real samples using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques. The modified electrode showed two linear concentration ranges from 0.01 - 2 nM and 2 – 90 nM with low detection limits (LODs) of 0.004 and 0.97 nM, respectively, demonstrating high sensitivity. Besides, the fabricated sensor exhibited more selectivity, simplicity, great reproducibility, repeatability, and good stability. Finally, the PA-g-poly (AAm-co-AA)-modified SPE based sensor was effectively used in real sample analysis of egg yolk, milk, and vitamin B2 drugs with good recovery rates.

Non-Targeted Metabolomics of Serum Reveals Biomarkers Associated with Body Weight in Wumeng Black-Bone Chickens.

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

Accelerated measurement technology quantifying packaging light protection performance for soymilk nutrient and chemical stability

An accelerated in situ (AIS) light exposure and measurement technology for prediction of retail light protection performance of soymilk packaging is reported. The ability of a packaging material to protect light sensitive marker solutions, either comprising riboflavin (RF) or chlorophyll-a (CHLA), from an intense light source was determined. The light-induced decay of the marker was tracked with in situ spectroscopy and modeled to quantify the light protection performance of each packaging material. For a set of packages, chemical analyses (RF, thiobarbituric acid reactive substances (TBARS), hexanal) of packaged soymilk under Simulated Retail (SR) storage conditions demonstrated excellent correlation to the light protection performance data of the same package set determined by AIS (R2 > 0.97). The use of AIS enables rapid quantification of soymilk packaging material light protection performance and the associated preservation of soymilk nutrient and sensory properties, thus it may be applied to improve the design of soymilk packaging materials for light protection performance and contribute towards the improvement of packaged soymilk product shelf life.

Electroanalysis of bromate at riboflavin impregnated Ketjen black porous electrode via an autocatalytic cycle with finite length diffusion

The emergence of elevated concentrations of bromate, classified as a 2B type carcinogen, in drinking water following the treatment of water supplies with ozonation and other oxidation methods has underscored the importance of developing methods for reliable and rapid screening of drinking water. In this work, we report the use of electro activated riboflavin (RF) impregnated Ketjen black (KB) modified screen-printed electrode (elRF@KB-SPE) for the determination of bromate. The sensing surfaces were subjected to morphological and structural characterization using scanning electron microscopy and Raman spectroscopy. These analyses confirmed the successful modification of the electrode with an extended elRF@KB porous coating. Based on cyclic voltammetry (CV) and electrochemical impedance spectroscopy measurements, the response of elRF@KB-SPE towards bromate can be described through a dual mechanism involving i) an autocatalytic chemical/electrochemical process that predominantly occurs in the finite length pores of KB, and ii) an RF-mediated electrocatalytic process. Notably, the data demonstrated that the advanced electrocatalytic properties of the otherwise electrocatalytically inactive absorbed RF molecules are endowed after a simple electro activation process (three CV scans). Amperometric measurements at −0.05 V vs. Ag/AgCl revealed a linear relationship between the current response and the concentration of bromates over the concentration range 0.50−18.0 μM, achieving a limit of detection (3σ/slope) of 0.04 μM. The interference effect of various electroactive species was investigated demonstrating that elRF@KB-SPE is highly selective to bromate. The analytical utility of the method was evaluated in spiked tap water samples. Recoveries were 91.2 − 106.4 %.

Effect of exercise intensity on growth performance, serum biochemistry parameters, liver antioxidant capacity, and intestinal health of common carp (Cyprinus carpio) in recirculating aquaculture system

This study examined the impact of different exercise intensities on the growth performance, serum biochemistry, liver antioxidant capacity, and intestinal health of common carp (Cyprinus carpio). A total of 270 common carp with an initial weight of 63.91 ± 1.45 g were divided into three groups: a Sustained Exercise group [SE, 1 bl/s (body length per second), 24 h/day], an Intermittent Exercise group (IE, 1 bl/s, 8 h/day), and a Control group (CG, 3 cm/s) for a 90-days experiment. The results demonstrated that exercise substantially improved weight gain rates in common carp. Analysis of serum biochemical parameters revealed that increased exercise intensity significantly reduced levels of triglycerides (TG), total cholesterol (T-CHO), and glucose (GLU) (P < 0.05). Post-exercise evaluations also indicated significant reductions in immune-related markers, including lysozyme (LZM), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Regarding liver antioxidant enzyme activities, the levels of glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) were significantly higher in the IE group relative to the CG group (P < 0.05). Conversely, the total antioxidant capacity (T-AOC) was significantly lower in the SE group than in the CG group (P < 0.05). In terms of intestinal health, intermittent exercise significantly reduced the expression of pro-inflammatory cytokine genes and increased gut villus length. Additionally, an increase in exercise intensity significantly enhanced the activities of intestinal amylase and lipase. Analysis of the intestinal microbiota through 16S rRNA sequencing revealed that intermittent exercise fostered a more diverse microbial community. Specifically, with an increase in exercise intensity, the relative abundance of Fusobacteriota rose, while those of Firmicutes decreased. At the genus level, the abundances of Cetobacterium and Aeromonas increased, contrasting with declines in Muribaculaceae, Bacteroides, and Escherichia-Shigella. PICRUSt2 functional predictions suggest that exercise might modify the intestinal environment by increasing the prevalence of pathogenic bacterial communities, potentially leading to intestinal damage and adversely affecting the physiological state of the intestine. An observed increase in riboflavin metabolism in the SE group likely contributed to its markedly improved growth performance relative to other groups. In summary, sustained exercise at 1 bl/s improved growth and intestinal digestive enzyme activity in common carp. However, it also induced stress, potentially compromising physiological health, liver function, and immune strength, consequently elevating the risk of disease. These findings provide crucial insights for optimizing growth and physiological health in common carp and other fish species in recirculating aquaculture systems through exercise.

Nanogel-Carbon Dot Conjugates: A Synergistic Approach for Enhanced Cancer Treatment through Combination Therapy.

The present study reports the development of a novel nanoconjugate, NG-FACD, comprising a positively charged self-assembled nanogel (NG) derived from a peptide amphiphilic hydrogelator and a negatively charged folic acid-functionalized blue-emitting carbon dot (FACD), bound via electrostatic interactions. NG-FACD was developed to combine the advantages of the individual nanocarriers and overcome their drawbacks. The presence of folic acid enables NG-FACD to be successfully used in selective bioimaging and targeted combination therapy against folate receptor-positive (FR+) B16F10 over FR- cells. NG-FACD demonstrated improved riboflavin (RbF) and paclitaxel (PTX) loading compared to individual nanocarriers that made it ∼1.8- and 1.5-fold more cytotoxic toward FR+ B16F10 cells over RbF- and PTX-loaded individual nanocarriers. The concurrent presence of RbF and PTX on NG-FACD displayed ∼1.9-2.8-fold higher cytotoxicity than single drug-loaded individual nanocarriers and ∼3-4.5-fold higher cytotoxicity through RbF-mediated photodynamic therapy and PTX-induced chemotherapy in synergy compared to free drugs against FR+ B16F10 cells.

Riboflavin as a Coloring Agent of Tablets Affects the Photostability of Manidipine after the Change of Dosage Forms

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

Customized Corneal Cross-Linking with Microneedle-Mediated Riboflavin Delivery for Keratoconus Treatment.

In this study, a novel customized corneal cross-linking (CXL) treatment is explored that utilizes microneedles (MNs) for targeted riboflavin (RF) administration prior to the CXL procedure. Unlike the conventional "one-size-fits-all" approach, this protocol offers an option for more precise and efficacious treatment. To simulate a customized corneal crosslinking technique, four distinct microneedle (MN) molds designs, including circular, semi-circular, annular and butterfly shaped, are crafted for loading an optimized RF-hyaluronic acid solution and for the subsequent fabrication of MN arrays with varying morphologies. These MNs can gently puncture the corneal epithelium while preserving the integrity of the underlying stromal layer. Following the application of these microneedles, RF solution is replenished to enhance the RF content within the stroma through the punctures created by the MNs, resulting in exceptional customized corneal cross-linking effects that are comparable to the conventional epi-off CXL protocol. Additionally, it flattened the corneal curvature within the treated zone and facilitated rapid postoperative recovery of corneal tissue. These findings suggest that the integration of customized microneedle RF delivery with corneal crosslinking technology represents a potential novel treatment modality, holding promise for the tailored treatment of corneal pathologies, and offering a more precise and efficient alternative to traditional methods.