Photodynamic therapy(PDT)has been established as one of the most promising novel cancer therapies with fewer side-effects and enhanced efficacy compared to the currently available conventional treatments.However,its a...Photodynamic therapy(PDT)has been established as one of the most promising novel cancer therapies with fewer side-effects and enhanced efficacy compared to the currently available conventional treatments.However,its application has been hindered by the limitations that photosensitizers(PS)have.The combination of PS with metallic nanoparticles like platinum nanoparticles(PtNPs),can help to overcome these intrinsic drawbacks.In this work,the combination of PtNPs and the natural photosensitizer riboflavin(RF)is proposed.PtNPs are synthesized using RF(Pt@RF)as reducing and stabilizing agent in a one-step method,obtaining nanoparticles with mesoporous structure for UV triggered PDT.In view of possible future UV irradiation treatments,the degradation products of RF,ribitol(RB)and lumichrome(LC),this last being a photosensitizing byproduct,are also employed for the synthesis of porous PtNPs,obtaining Pt@LC and Pt@RB.When administered in vitro to lung cancer cells,all the samples elicit a strong decrease of cell viability and a decrease of intracellular ATP levels.The antitumoral effect of both Pt@RF and Pt@LC is triggered by UV-A irradiation.This antitumoral activity is caused by the induction of oxidative stress,shown in our study by the decrease in intracellular glutathione and increased expression of antioxidant enzymes.展开更多
AIM:To investigate the relationship between blood riboflavin levels and riboflavin transporter 2(RFT2) gene expression in gastric carcinoma(GC) development.METHODS:High-performance liquid chromatography was used to de...AIM:To investigate the relationship between blood riboflavin levels and riboflavin transporter 2(RFT2) gene expression in gastric carcinoma(GC) development.METHODS:High-performance liquid chromatography was used to detect blood riboflavin levels in patients with GC.Real-time fluorogenic quantitative polymerase chain reaction and immunohistochemistry were used to analyze the expression of RFT2 mRNA and protein in samples from 60 GC patients consisting of both tumor and normal tissue.RESULTS:A significant decrease in the RFT2 mRNA levels was detected in GC samples compared with those in the normal mucous membrane(0.398 ± 0.149 vs 1.479 ± 0.587;P = 0.040).Tumors exhibited low RFT2 protein expression(75%,16.7%,8.3% and 0% for no RFT2 staining,weak staining,medium staining and strong staining,respectively),which was significantly lower than that in the normal mucous membrane(10%,16.7%,26.7% and 46.7% for no RFT2 staining,weak staining,medium staining and strong staining,respectively;P < 0.05).Tumors with low RFT2 expression were significantly associated with tumor stage and histological grade.Moreover,a significantly decrease in Uyghur patients was observed compared with Han patients.However,other parameters-gender,tumor location and lymph node metastasis-showed no significant relationship with RFT2 expression.Blood riboflavin levels were reverse correlated with development of GC(1.2000 ± 0.97 569 ng/mL in high tumor stage patients vs 2.5980 ± 1.31 129 ng/mL in low tumor stage patients;P < 0.05).A positive correlation of plasma riboflavin levels with defective expression of RFT2 protein was found in GC patients(2 = 2.619;P = 0.019).CONCLUSION:Defective expression of RFT2 is associated with the development of GC and this may represent a mechanism underlying the decreased plasma riboflavin levels in GC.展开更多
Fragment containing the whole riboflavin(rib)operons of B.cereus ATCC14579 was detected from GenBank and annotated.The rib operon of ATCC14579 was cloned with Pn,its native promoter,or with P43,the vegetative growth p...Fragment containing the whole riboflavin(rib)operons of B.cereus ATCC14579 was detected from GenBank and annotated.The rib operon of ATCC14579 was cloned with Pn,its native promoter,or with P43,the vegetative growth promoter,into the plasmid.Expression analysis showed that heterologous rib operon was operative in B.subtilis.Integrative plasmid with P43-rib fragment was integrated into the chromosome of B.subtilis RH33,yielding transformant B.subtilis PY.With optimized medium components,4.3 g·L -1 of riboflavin was achieved in batch culture of B.subtilis PY,which was 27%enhancement compared to the host strain.Real-time reverse transcription polymerase chain reaction(RT-PCR)analysis indicated that the transcriptional level of ribA maintained 2.8-fold higher with the expression of herterologous rib operon.Furthermore,the stability of B.subtilis PY was increased form 45%to 87%.The high transcriptional level of rib gene and higher stability of B.subtilis PY could explain the increased riboflavin production.展开更多
In this work, lemon and onion biomasses commonly found in street markets are for the first time used to develop a facile, fast and low-cost one-step microwave-assisted carbonization method for synthesis of highly fluo...In this work, lemon and onion biomasses commonly found in street markets are for the first time used to develop a facile, fast and low-cost one-step microwave-assisted carbonization method for synthesis of highly fluorescent carbon dots (CDs). The structure and optical properties of CDs were investigated by TEM, XRD, XRF, UV-Vis, FTIR, and fluorescence spectroscopy. CDs displayed satisfactory optical pro-prieties, a high quantum yield of 23.6%, and excellent water solubility, and the particle size was 4.23-8.22 nm with an average diameter of 6.15 nm. An efficient fluorescent resonance energy transfer (FRET) between the CDs and riboflavin was achieved with CDs acting as donor and riboflavin as acceptor. A linear relationship between FRET and the riboflavin concentration from 0.10 to 3.0 μg/mL was observed, allowing the development of an accurate and fast analytical method to determine this vitamin in multivitamin/mineral supplements. Despite the potential interferences in these supplements, CDs were selective for riboflavin under optimized conditions. A paired t-test at a 95% confidence level indicated no statistically significant difference between the proposed and the reference methods. Recovery test presented values ranged from 96.0% to 101.4%. The limit of detection and relative standard deviation were estimated at 1.0 ng/mL and <2.6% (n = 3), respectively. CDs were successfully synthesized in a domestic microwave oven (1450 W, 6 min), presenting satisfactory parameters when compared with results of other studies reported in the literature, suggesting that the proposed method is a potentially useful method for the synthesis of CDs and determination of riboflavin.展开更多
Rhodococcus erythropolis USTB-03 is a promising bacterial strain for the biodesulfurization of dibenzothiophene （DBT） via a sulfurspecific pathway in which DBT is converted to 2-hydroxybiphenyl （2HBP） as an end pr...Rhodococcus erythropolis USTB-03 is a promising bacterial strain for the biodesulfurization of dibenzothiophene （DBT） via a sulfurspecific pathway in which DBT is converted to 2-hydroxybiphenyl （2HBP） as an end product. The effects of nicotinamide and riboflavin on the sulfur specific activity （SA） of DBT biodesulfurization by R. erythropolis USTB-03 were investigated. Both nicotinamide and riboflavin were found to enhance the expression of SA, which was not previously reported. When R. erythropolis USTB-03 was grown on a medium containing nicotinamide of 10.0 mmol or riboflavin of 50.0 μmol, SA was raised from 68.0 or so to more than 130 mmol 2HBP/（kg dry cells.h）. When R. erythropolis USTB-03 was grown in the presence of both nicotinamide of 5.0 mmol and riboflavin of 25.0 μmol, SA was further increased to 159.0 mmol 2HBP/（kg dry cells.h）. It is suggested that the biological synthesis of reduced form of flavin mononucleotide （FMNH2）, an essential coenzyme for the activities of biodesulfurization enzyme Dsz C and A, might be enhanced by nicotinamide and riboflavin, which was responsible for the increased SA of R. erythropolis USTB-03.展开更多
AIM: To report the 3mo outcomes of collagen crosslinking(CXL) with a hypo-osmolar riboflavin in thin corneas with the thinnest thickness less than 400 μm without epithelium.METHODS: Eight eyes in 6 patients with age ...AIM: To report the 3mo outcomes of collagen crosslinking(CXL) with a hypo-osmolar riboflavin in thin corneas with the thinnest thickness less than 400 μm without epithelium.METHODS: Eight eyes in 6 patients with age 26.2±4.8y were included in the study. All patients underwent CXL using a hypo-osmolar riboflavin solution after its de-epithelization. Best corrected visual acuity, manifest refraction, the thinnest corneal thickness, and endothelial cell density were evaluated before and 3mo after the procedure.RESULTS: The mean thinnest thickness of the cornea was 408.5 ±29.0 μm before treatment and reduced to369.8 ±24.8 μm after the removal of epithelium. With the application of the hypo-osmolar riboflavin solution, the thickness increased to 445.0 ±26.5 μm before CXL and recover to 412.5 ±22.7 μm at 3mo after treatment, P =0.659). Before surgery, the mean K-value of the apex of the keratoconus corneas was 57.6 ±4.0 diopters, and slightly decreased(54.7±4.9 diopters) after surgery(P =0.085). Mean best-corrected visual acuity was 0.55 ±0.23 logarithm of the minimal angle of resolution, and increased to 0.53±0.26 logarithm after surgery(P =0.879).The endothelial cell density was 2706.4 ±201.6 cells/mm2 before treatment, and slightly decreased( 2641. 2 ±218.2 cells/mm2) at last fellow up(P =0.002).CONCLUSION: Corneal collagen cross-linking with a hypo-osmolar riboflavin in thin corneas seems to be a promising treatment. Further study should be done to evaluate the safety and efficiency of CXL in thin corneas for the long-term.展开更多
SDF-1/CXCR4 has been recognized as one of the most relevant chemokine signaling pathways to cancer metastasis,and siRNA targeting CXCR4 may provide potential improvements to treat those highly metastatic cancers,espec...SDF-1/CXCR4 has been recognized as one of the most relevant chemokine signaling pathways to cancer metastasis,and siRNA targeting CXCR4 may provide potential improvements to treat those highly metastatic cancers,especially when combined with chemotherapy.In the present study,we constructed riboflavin-modified lipo-polyplexes to co-deliver CXCR4 siRNA and doxorubicin for cancer therapy.Doxorubicin was covalently conjugated to polyethyleneimine(PEI)with acid-cleavable hydrazine bond,and the obtained acid-sensitive conjugate was efficiently condensed with siRNA to form polyplexes,which were further coated with riboflavin-tailed lipid-membrane to prepare the lipo-polyplexes conveniently.Utilizing the fact that tumor cells overexpress riboflavin receptors,the riboflavin modification effectively enhanced uptake of lipo-polyplexes by tumor cells in a receptor-mediated manner.The riboflavin-modified lipo-polyplexes co-delivering CXCR4 siRNA and doxorubicin effectively decreased viability and invasiveness of tumor cells in vitro,and inhibited primary tumor growth and tumor metastasis in vivo.展开更多
AIM：To report the clinical results of iontophoresis-assisted epithelium-on corneal crosslinking（I-CXL） using 0.1% riboflavin in distilled water for progressive keratoconus. METHODS：In this prospective clinical stu...AIM：To report the clinical results of iontophoresis-assisted epithelium-on corneal crosslinking（I-CXL） using 0.1% riboflavin in distilled water for progressive keratoconus. METHODS：In this prospective clinical study, we examined 94 eyes of 75 patients with progressive keratoconus who were treated with I-CXL using 0.1% riboflavin in distilled water. Best correct visual acuity（BCVA）, Scheimpflug tomography, corneal topography, anterior segment optical coherence tomography, intraocular pressure, and endothelial cell density were evaluated at baseline and 1, 3, 6, 12, and 24 mo after I-CXL.RESULTS：After 24 mo I-CXL, compared to the level at baseline, BCVA significantly improved 0.14±0.07（P=0.010）; mean keratometry signifi cantly decreased 0.72±1.97（P=0.021）; maximum keratometry significantly reduced 2.30±5.01（P=0.014）; central keratoconus index significantly reduced 0.04±0.08（P=0.007）. The demarcation line was visible in 83.1% of eyes at 1mo after treatment, with a depth of 298.95±51.97 μm, and gradually indistinguishable. One eye had repeat treatment. Intraocular pressure and endothelial cell density did not change significantly.CONCLUSION：I-CXL using 0.1% riboflavin halts keratoconus progression within 24 mo, resulting in a significant improvement in visual and topographic parameters. Moreover, the depth of the demarcation line is similar to that previously reported in standard epithelium-off CXL procedures.展开更多
A spectrofluorimetric method for the determining riboflavin (VB2) based on its enhancement on the fluorescence of hemoglobin-catalyzed enzymatic reaction was proposed. The proposed method consisted of two reactions. O...A spectrofluorimetric method for the determining riboflavin (VB2) based on its enhancement on the fluorescence of hemoglobin-catalyzed enzymatic reaction was proposed. The proposed method consisted of two reactions. One was the photochemical reaction of VB2, the other was a hemoglobin-catalyzed enzymatic reaction. The optimal experimental conditions for the determinations were established. The linear range of the method was 5.0×10?9?1.0×10?7 mol/L of VB2. The detection limit was calculated to be 3.65×10?9 mol/L. The relative standard deviation of this method was 2.3%at 7.0×10?2 mol/L for 11 determinations.展开更多
Objective To estimate the association between three B-vitamin intakes and sociodemographic factors among adults in China.Methods We derived our data from the China Health and Nutrition Survey(CHNS) among 12,241 indivi...Objective To estimate the association between three B-vitamin intakes and sociodemographic factors among adults in China.Methods We derived our data from the China Health and Nutrition Survey(CHNS) among 12,241 individuals aged 18–64 years. Log binomial regression was used to estimate adjusted prevalence ratios for factors associated with the inadequate intake of B-vitamins.Results Females with low incomes and living in the north had a higher prevalence of inadequate riboflavin intake than those with high incomes and living in the south. Both males and females living in a village had a higher prevalence of inadequate riboflavin intake than adults living in a city. Adults with low income, low education, and living in the north or in a village had a higher prevalence of inadequate niacin intake than adults with a high income, high education, and living in the south or in a city.Conclusion We found that income, region, and area of residence were associated with riboflavin intake. Education, income, region, and area of residence were associated with niacin intake. Welltailored strategies and policies are needed to improve nutritional status in China.展开更多
Riboflavin(RF,vitamin B2)is an essential vitamin and has been considered as a promising natural photosensitizer for photodynamic therapy(PDT).However,further exploration of RF in antitumor application was limited by i...Riboflavin(RF,vitamin B2)is an essential vitamin and has been considered as a promising natural photosensitizer for photodynamic therapy(PDT).However,further exploration of RF in antitumor application was limited by its poor cellular uptake.In this study,using cell-penetrating peptides Arg8,(Cha-Arg)3 and small molecule triphenylphosphine(TPP)as delivery compounds,three RF conjugates were prepared to increase the accumulation of RF in cells,termed as Arg8-RF,(Cha-Arg)3-RF and TPP-RF,respectively.Compared with TPP-RF and Arg8-RF,(Cha-Arg)3-RF exhibited better cell internalization and stronger cytotoxicity against HeLa cells upon exposure to blue light.Further researches proved that(Cha-Arg)3-RF generated reactive oxygen species(ROS)under irradiation,which could indiscriminately destroy endogenous proteins and mitochondria,ultimately inducing cell death.This work provides a new approach to explore RF as a natural photosensitizer for antitumor photodynamic therapy.展开更多
After deregulating the purine and riboflavin synthesis in the Gram-positive bacterium Bacillus subtilis,it is critical to amplify riboflavin operon with appropriate dosage in the host strain for remarkable increase of...After deregulating the purine and riboflavin synthesis in the Gram-positive bacterium Bacillus subtilis,it is critical to amplify riboflavin operon with appropriate dosage in the host strain for remarkable increase of riboflavin production.Bacillus subtilis RH13, a riboflavin-producing strain, was selected as host strain in the construction of engineering strains by protoplast fusion. The integrative plasmid pRB63 and autonomous plasmid pRB49, pRB62 containing riboflavin operon of B.subtilis 24 were constructed and transformed into the host strain respectively. Increasing one operon copy in B.subtilis RH13 results in about 0.4 g/L improvement in riboflavin yield and the appropriate number of operon copies was about 7—8. Amplifying more riboflavin operons is of no use for further improvement of yield of riboflavin. Furthermore, excessive operon dosage results in metabolic unbalance and is fatal to the host cells producing riboflavin.展开更多
Efficient,cost‐effective electrocatalysts for an oxygen reduction reaction(ORR)are currently required for fuel cells.In the present work,riboflavin was used as a cheap,nontoxic carbon and nitrogen precursor to prepar...Efficient,cost‐effective electrocatalysts for an oxygen reduction reaction(ORR)are currently required for fuel cells.In the present work,riboflavin was used as a cheap,nontoxic carbon and nitrogen precursor to prepare Fe-N-C catalysts via one‐step pyrolysis in the presence of anhydrous iron chloride.Raman spectroscopy indicated that the catalyst containing nitrogen created a great quantity of defects in the carbon structures,while nitrogen adsorption‐desorption isotherms showed that the catalyst was mesoporous.Transmission electron microscopy demonstrated that the Fe-N-C catalyst was composed of very thin,curved and porous graphene layers together with some Fe2O3nanoparticles,and X‐ray diffraction patterns confirmed that the carbon in the catalyst was highly graphitized.X‐ray photoelectron spectroscopy indicated that the active sites for the ORR were primarily composed of graphitic nitrogen,although Fe sites also played an important role.The ORR activity of the Fe-N-C catalyst reached a maximum of4.16mA cm-2,and its chronoamperometric response was found to decrease by only3%after operating for3h at0.66V(vs RHE)in an O2‐saturated0.1mol L-1KOH solution.In contrast,a commercial40wt%Pt/C catalyst with a loading of0.2mgPt cm-2exhibited an activity of4.46mA cm-2and a40%loss of response.The electrochemical performance of this new Fe-N-C catalyst was therefore comparable to that of the Pt/C catalyst while showing significantly better stability.展开更多
The influence of irradiation on biosyntheses of ascorbic acid and riboflavin in germinating chickpea seeds at ambient (25-35℃) conditions, was investigated. The rate of syntheses of these vitamins significantly incre...The influence of irradiation on biosyntheses of ascorbic acid and riboflavin in germinating chickpea seeds at ambient (25-35℃) conditions, was investigated. The rate of syntheses of these vitamins significantly increased with increasing germination time upto 120 h depending upon the treatment (P【0.05). Maximum amounts of ascorbic acid, 22.32 and 16.84 mg/100g, were found in the 0.10 kGy sample after 120 h of germination in tap and distilled water respectively. However, a radiation dose of 0.15 kGy resulted in the development of maximum values of riboflavin, 11.40 and 11.38 μ g/g, on germination in tap and distilled water respectively. A significant linear relation (r = 0-954 to 0.997) was observed between the biosyntheses of these vitamins and the germination time upto 120 h of irradiated and unirradiated chickpea seed (P【0.05).展开更多
AIM: To evaluate the enrichment of riboflavin in the corneal stroma after intracameral injection to research the barrier ability of the corneal endothelium to riboflavin in vivo.METHODS: The right eyes of 30 New Zeala...AIM: To evaluate the enrichment of riboflavin in the corneal stroma after intracameral injection to research the barrier ability of the corneal endothelium to riboflavin in vivo.METHODS: The right eyes of 30 New Zealand white rabbits were divided into three groups. Different concentrations riboflavin-balanced salt solutions(BSS)were injected into the anterior chamber(10 with 0.5%, 10 with 1%, and 10 with 2%). Eight corneal buttons of 8.5mm in diameter from each group were dissected at 30 min after injection and the riboflavin concentrations in the corneal stroma were determined using high-performance liquid chromatography(HPLC) after removing the epithelium and endothelium. The other two rabbits in every group were observed for 24 h and sacrificed. As a comparison, the riboflavin concentrations from 16 corneal stromal samples were determined using HPLC after instillation of 0.1% riboflavin-BSS solution for30 min on the corneal surface(8 without epithelium and 8with intact epithelium).RESULTS: The mean riboflavin concentrations were11.19, 18.97, 25.08, 20.18, and 1.13 μg/g for 0.5%, 1%, 2%,de-epithelialzed samples, and the transepithelial groups,respectively. The color change of the corneal stroma and the HPLC results showed that enrichment with riboflavin similar to classical de-epithelialized corneal collagen crosslinking(CXL) could be achieved by intracameral 1%riboflavin-BSS solution after 30min; the effect appeared to be continuous for at least 30 min.CONCLUSION: Riboflavin can effectively penetrate the corneal stroma through the endothelium after an intracameral injection in vivo, so it could be an enhancing method that could improve the corneal riboflavin concentration in transepithelial CXL.展开更多
Riboflavin has been suggested to act with folate to lower homocysteine (Hcy). However, these interactions may differ among the several known forms of folate. Therefore, we examined the effects of riboflavin interactio...Riboflavin has been suggested to act with folate to lower homocysteine (Hcy). However, these interactions may differ among the several known forms of folate. Therefore, we examined the effects of riboflavin interactions with 5-methyltetrahydrofolate (5-MTHF) and tetrahydrofolate (THF) on changes in Hcy and folate derivative levels, under conditions with and without methionine addition. Rat hepatocytes were cultured for 48 hours in medium with or without 2.64 μM riboflavin addition, under the following conditions: 1) without the addition of either methionine or folate;2) with addition of 2 μM folate derivatives [(A): 5-MTHF, (B): THF];3) with addition of both 5 mM methionine and 2 μM folate derivatives [(A): 5-MTHF, (B): THF]. The supernatants were collected at 0, 24, and 48 hours for Hcy and folate derivative measurements. The Hcy lowering effect of 5-MTHF, as well as inhibition of 5-MTHF reduction and THF elevation, appeared to be enhanced by riboflavin addition. THF addition did not lower the Hcy level, regardless of the presence of riboflavin and/or methionine, while THF and 5,10-methenyl THF levels were maintained. Further examination is needed to elucidate the interactive effects of riboflavin and folate derivatives on Hcy and folate metabolism.展开更多
A high performance liquid chromatographic assay has been developed for the simultaneous determination of five water soluble vitamins:thimine, riboflavin, niacin, pyridoxine and folic acid in cereal products and fresh ...A high performance liquid chromatographic assay has been developed for the simultaneous determination of five water soluble vitamins:thimine, riboflavin, niacin, pyridoxine and folic acid in cereal products and fresh vegetables. Food samples were hydrolyzed in 0.4 mol/L HCl, autoclaved at 120℃ 15 psi for 20 minutes, using a μ-Bondapak column (3.9×300mm, Waters Co.), a mobile phase of methanol-water (30:70) (0.005 mol/L heptanesulfonic acid) and a flow rate of 1.0 ml/min gave the most satisfactory separation of the five water soluble vitamins. A double channel deteetion was used: four vitamins (B_5, folic acid, B_2, B_1) were detected hy UV spectrophotometry (254 nm) first, pyridoxine (B_6) was detected by fluoromelry (EX 290nm, EM 395 nm) afterwards. Detection limits were 2, 5, 5, 2and 5ng, linear ranges were 5-10ng, 5-50ng, 5-40ng, 5-50ng and 10-50ng for B_1, B_2, B_5, B_6 and folic acid respectively. Recoveries were 92-100%(B_5), 51-52% (folio acid), 103—105% (B_2), 99—100% (B_6) and 91.3—102% (B_1) respectively. In comparison with a reference method and checking with food composition tables, very satisfactory results were obtained by this method.展开更多
The effects of riboflavin deficiency and simultaneously nitrosodimethylamine (NDMA) given by gastric intubation on the hepatic glutathione (GSH) content were examined in rats. On different days of the experiment, hepa...The effects of riboflavin deficiency and simultaneously nitrosodimethylamine (NDMA) given by gastric intubation on the hepatic glutathione (GSH) content were examined in rats. On different days of the experiment, hepatic GSH content of the riboflavin deficient rats decreased to 55-61% of the control rats. When NDMA was given 6 mg kg by gastric intubation to riboflavin deficient rats, hepatic GSH content decreased markedly to 39-43% of the control rats. After supplying riboflavin, hepatie GSH content of the deficient rats recovered to the level of the control rats. These results suggest that alterations of rat hepatic GSH content during riboflavin deficiency may imply as one of the promoting effects of riboflavin deficiency on the carcinogenesis of nitrosamines.展开更多
Dear Sir,UVA/riboflavin cross-linking （CXL） has been used clinically applied for the treatment of keratoconus and corneal edema via enhancement of corneal stiffness The safety of the corneal endothelium is of prime...Dear Sir,UVA/riboflavin cross-linking （CXL） has been used clinically applied for the treatment of keratoconus and corneal edema via enhancement of corneal stiffness The safety of the corneal endothelium is of prime importance during CXL treatment. In clinical practice, a corneal thickness （CT） of 400um has traditionally been regarded as the minimum treatable thickness, thereby avoiding damage to the corneal endothelium Although CXL has been applied to thinner corneas, using a hypoosmotic solution onto cornea and inducing edema . CXL safety still needs further evaluation because of lower relative concentration of collagen in the hydrated stroma . This study aims to evaluate the changes of corneal endothelial density （ECD） in cases where the CT is 〈400 um before iatrogenic corneal swelling and CXL treatment.展开更多
基金funded by the Horizon Europe Project"PERSEUS"(No.101099423)financed by the Ministry of Universities under application 33.50.460A.752by the European Union NextGenerationEU/PRTR through a contract Margarita Salas from Universidade de Vigo.
文摘Photodynamic therapy(PDT)has been established as one of the most promising novel cancer therapies with fewer side-effects and enhanced efficacy compared to the currently available conventional treatments.However,its application has been hindered by the limitations that photosensitizers(PS)have.The combination of PS with metallic nanoparticles like platinum nanoparticles(PtNPs),can help to overcome these intrinsic drawbacks.In this work,the combination of PtNPs and the natural photosensitizer riboflavin(RF)is proposed.PtNPs are synthesized using RF(Pt@RF)as reducing and stabilizing agent in a one-step method,obtaining nanoparticles with mesoporous structure for UV triggered PDT.In view of possible future UV irradiation treatments,the degradation products of RF,ribitol(RB)and lumichrome(LC),this last being a photosensitizing byproduct,are also employed for the synthesis of porous PtNPs,obtaining Pt@LC and Pt@RB.When administered in vitro to lung cancer cells,all the samples elicit a strong decrease of cell viability and a decrease of intracellular ATP levels.The antitumoral effect of both Pt@RF and Pt@LC is triggered by UV-A irradiation.This antitumoral activity is caused by the induction of oxidative stress,shown in our study by the decrease in intracellular glutathione and increased expression of antioxidant enzymes.
基金Supported by The National Natural Science Foundation of China,No.81160459
文摘AIM:To investigate the relationship between blood riboflavin levels and riboflavin transporter 2(RFT2) gene expression in gastric carcinoma(GC) development.METHODS:High-performance liquid chromatography was used to detect blood riboflavin levels in patients with GC.Real-time fluorogenic quantitative polymerase chain reaction and immunohistochemistry were used to analyze the expression of RFT2 mRNA and protein in samples from 60 GC patients consisting of both tumor and normal tissue.RESULTS:A significant decrease in the RFT2 mRNA levels was detected in GC samples compared with those in the normal mucous membrane(0.398 ± 0.149 vs 1.479 ± 0.587;P = 0.040).Tumors exhibited low RFT2 protein expression(75%,16.7%,8.3% and 0% for no RFT2 staining,weak staining,medium staining and strong staining,respectively),which was significantly lower than that in the normal mucous membrane(10%,16.7%,26.7% and 46.7% for no RFT2 staining,weak staining,medium staining and strong staining,respectively;P < 0.05).Tumors with low RFT2 expression were significantly associated with tumor stage and histological grade.Moreover,a significantly decrease in Uyghur patients was observed compared with Han patients.However,other parameters-gender,tumor location and lymph node metastasis-showed no significant relationship with RFT2 expression.Blood riboflavin levels were reverse correlated with development of GC(1.2000 ± 0.97 569 ng/mL in high tumor stage patients vs 2.5980 ± 1.31 129 ng/mL in low tumor stage patients;P < 0.05).A positive correlation of plasma riboflavin levels with defective expression of RFT2 protein was found in GC patients(2 = 2.619;P = 0.019).CONCLUSION:Defective expression of RFT2 is associated with the development of GC and this may represent a mechanism underlying the decreased plasma riboflavin levels in GC.
基金Supported by the National Natural Science Foundation of China（20536040） the State Key Development Program for Basic Research of China（2007CB707802） the Development Project of Science and Technology of Tianjin（05YFGZGX04500）
文摘Fragment containing the whole riboflavin(rib)operons of B.cereus ATCC14579 was detected from GenBank and annotated.The rib operon of ATCC14579 was cloned with Pn,its native promoter,or with P43,the vegetative growth promoter,into the plasmid.Expression analysis showed that heterologous rib operon was operative in B.subtilis.Integrative plasmid with P43-rib fragment was integrated into the chromosome of B.subtilis RH33,yielding transformant B.subtilis PY.With optimized medium components,4.3 g·L -1 of riboflavin was achieved in batch culture of B.subtilis PY,which was 27%enhancement compared to the host strain.Real-time reverse transcription polymerase chain reaction(RT-PCR)analysis indicated that the transcriptional level of ribA maintained 2.8-fold higher with the expression of herterologous rib operon.Furthermore,the stability of B.subtilis PY was increased form 45%to 87%.The high transcriptional level of rib gene and higher stability of B.subtilis PY could explain the increased riboflavin production.
文摘In this work, lemon and onion biomasses commonly found in street markets are for the first time used to develop a facile, fast and low-cost one-step microwave-assisted carbonization method for synthesis of highly fluorescent carbon dots (CDs). The structure and optical properties of CDs were investigated by TEM, XRD, XRF, UV-Vis, FTIR, and fluorescence spectroscopy. CDs displayed satisfactory optical pro-prieties, a high quantum yield of 23.6%, and excellent water solubility, and the particle size was 4.23-8.22 nm with an average diameter of 6.15 nm. An efficient fluorescent resonance energy transfer (FRET) between the CDs and riboflavin was achieved with CDs acting as donor and riboflavin as acceptor. A linear relationship between FRET and the riboflavin concentration from 0.10 to 3.0 μg/mL was observed, allowing the development of an accurate and fast analytical method to determine this vitamin in multivitamin/mineral supplements. Despite the potential interferences in these supplements, CDs were selective for riboflavin under optimized conditions. A paired t-test at a 95% confidence level indicated no statistically significant difference between the proposed and the reference methods. Recovery test presented values ranged from 96.0% to 101.4%. The limit of detection and relative standard deviation were estimated at 1.0 ng/mL and <2.6% (n = 3), respectively. CDs were successfully synthesized in a domestic microwave oven (1450 W, 6 min), presenting satisfactory parameters when compared with results of other studies reported in the literature, suggesting that the proposed method is a potentially useful method for the synthesis of CDs and determination of riboflavin.
文摘Rhodococcus erythropolis USTB-03 is a promising bacterial strain for the biodesulfurization of dibenzothiophene （DBT） via a sulfurspecific pathway in which DBT is converted to 2-hydroxybiphenyl （2HBP） as an end product. The effects of nicotinamide and riboflavin on the sulfur specific activity （SA） of DBT biodesulfurization by R. erythropolis USTB-03 were investigated. Both nicotinamide and riboflavin were found to enhance the expression of SA, which was not previously reported. When R. erythropolis USTB-03 was grown on a medium containing nicotinamide of 10.0 mmol or riboflavin of 50.0 μmol, SA was raised from 68.0 or so to more than 130 mmol 2HBP/（kg dry cells.h）. When R. erythropolis USTB-03 was grown in the presence of both nicotinamide of 5.0 mmol and riboflavin of 25.0 μmol, SA was further increased to 159.0 mmol 2HBP/（kg dry cells.h）. It is suggested that the biological synthesis of reduced form of flavin mononucleotide （FMNH2）, an essential coenzyme for the activities of biodesulfurization enzyme Dsz C and A, might be enhanced by nicotinamide and riboflavin, which was responsible for the increased SA of R. erythropolis USTB-03.
文摘AIM: To report the 3mo outcomes of collagen crosslinking(CXL) with a hypo-osmolar riboflavin in thin corneas with the thinnest thickness less than 400 μm without epithelium.METHODS: Eight eyes in 6 patients with age 26.2±4.8y were included in the study. All patients underwent CXL using a hypo-osmolar riboflavin solution after its de-epithelization. Best corrected visual acuity, manifest refraction, the thinnest corneal thickness, and endothelial cell density were evaluated before and 3mo after the procedure.RESULTS: The mean thinnest thickness of the cornea was 408.5 ±29.0 μm before treatment and reduced to369.8 ±24.8 μm after the removal of epithelium. With the application of the hypo-osmolar riboflavin solution, the thickness increased to 445.0 ±26.5 μm before CXL and recover to 412.5 ±22.7 μm at 3mo after treatment, P =0.659). Before surgery, the mean K-value of the apex of the keratoconus corneas was 57.6 ±4.0 diopters, and slightly decreased(54.7±4.9 diopters) after surgery(P =0.085). Mean best-corrected visual acuity was 0.55 ±0.23 logarithm of the minimal angle of resolution, and increased to 0.53±0.26 logarithm after surgery(P =0.879).The endothelial cell density was 2706.4 ±201.6 cells/mm2 before treatment, and slightly decreased( 2641. 2 ±218.2 cells/mm2) at last fellow up(P =0.002).CONCLUSION: Corneal collagen cross-linking with a hypo-osmolar riboflavin in thin corneas seems to be a promising treatment. Further study should be done to evaluate the safety and efficiency of CXL in thin corneas for the long-term.
基金The National Nature Science Foundation of China(Grant No.81973258 and 81673365)State Key Laboratory of Advanced Pharmaceutical Formulation with High Technology in Yangtze River Pharmaceutical Group.
文摘SDF-1/CXCR4 has been recognized as one of the most relevant chemokine signaling pathways to cancer metastasis,and siRNA targeting CXCR4 may provide potential improvements to treat those highly metastatic cancers,especially when combined with chemotherapy.In the present study,we constructed riboflavin-modified lipo-polyplexes to co-deliver CXCR4 siRNA and doxorubicin for cancer therapy.Doxorubicin was covalently conjugated to polyethyleneimine(PEI)with acid-cleavable hydrazine bond,and the obtained acid-sensitive conjugate was efficiently condensed with siRNA to form polyplexes,which were further coated with riboflavin-tailed lipid-membrane to prepare the lipo-polyplexes conveniently.Utilizing the fact that tumor cells overexpress riboflavin receptors,the riboflavin modification effectively enhanced uptake of lipo-polyplexes by tumor cells in a receptor-mediated manner.The riboflavin-modified lipo-polyplexes co-delivering CXCR4 siRNA and doxorubicin effectively decreased viability and invasiveness of tumor cells in vitro,and inhibited primary tumor growth and tumor metastasis in vivo.
基金Supported by Beijing Municipal Science and Technology Commission(No.Z151100004015217)
文摘AIM：To report the clinical results of iontophoresis-assisted epithelium-on corneal crosslinking（I-CXL） using 0.1% riboflavin in distilled water for progressive keratoconus. METHODS：In this prospective clinical study, we examined 94 eyes of 75 patients with progressive keratoconus who were treated with I-CXL using 0.1% riboflavin in distilled water. Best correct visual acuity（BCVA）, Scheimpflug tomography, corneal topography, anterior segment optical coherence tomography, intraocular pressure, and endothelial cell density were evaluated at baseline and 1, 3, 6, 12, and 24 mo after I-CXL.RESULTS：After 24 mo I-CXL, compared to the level at baseline, BCVA significantly improved 0.14±0.07（P=0.010）; mean keratometry signifi cantly decreased 0.72±1.97（P=0.021）; maximum keratometry significantly reduced 2.30±5.01（P=0.014）; central keratoconus index significantly reduced 0.04±0.08（P=0.007）. The demarcation line was visible in 83.1% of eyes at 1mo after treatment, with a depth of 298.95±51.97 μm, and gradually indistinguishable. One eye had repeat treatment. Intraocular pressure and endothelial cell density did not change significantly.CONCLUSION：I-CXL using 0.1% riboflavin halts keratoconus progression within 24 mo, resulting in a significant improvement in visual and topographic parameters. Moreover, the depth of the demarcation line is similar to that previously reported in standard epithelium-off CXL procedures.
文摘A spectrofluorimetric method for the determining riboflavin (VB2) based on its enhancement on the fluorescence of hemoglobin-catalyzed enzymatic reaction was proposed. The proposed method consisted of two reactions. One was the photochemical reaction of VB2, the other was a hemoglobin-catalyzed enzymatic reaction. The optimal experimental conditions for the determinations were established. The linear range of the method was 5.0×10?9?1.0×10?7 mol/L of VB2. The detection limit was calculated to be 3.65×10?9 mol/L. The relative standard deviation of this method was 2.3%at 7.0×10?2 mol/L for 11 determinations.
基金The National Institute for Nutrition and Health,China Center for Disease Control and Prevention,Carolina Population Center[P2C HD050924,T32 HD007168]the University of North Carolina at Chapel Hill,the NIH[R01-HD30880,DK056350,R24 HD050924,and R01-HD38700]+3 种基金the NIH Fogarty International Center[D43 TW009077,D43 TW007709]the China-Japan Friendship Hospitalthe Chinese Ministry of HealthBeijing Municipal Center for Disease Prevention and Control and Chinese Nutrition Society(CNS)Nutrition Research Foundation-DSM Research Fund[No.CNS2015075B].
文摘Objective To estimate the association between three B-vitamin intakes and sociodemographic factors among adults in China.Methods We derived our data from the China Health and Nutrition Survey(CHNS) among 12,241 individuals aged 18–64 years. Log binomial regression was used to estimate adjusted prevalence ratios for factors associated with the inadequate intake of B-vitamins.Results Females with low incomes and living in the north had a higher prevalence of inadequate riboflavin intake than those with high incomes and living in the south. Both males and females living in a village had a higher prevalence of inadequate riboflavin intake than adults living in a city. Adults with low income, low education, and living in the north or in a village had a higher prevalence of inadequate niacin intake than adults with a high income, high education, and living in the south or in a city.Conclusion We found that income, region, and area of residence were associated with riboflavin intake. Education, income, region, and area of residence were associated with niacin intake. Welltailored strategies and policies are needed to improve nutritional status in China.
基金supported by the National Natural Science Foundation of China(Nos.21977111 and 22007096)the National Key Research and Development Program of China(No.2021YFA0910000)+1 种基金the Natural Science Foundation of Guangdong Province(Nos.2019A1515012073 and 2018B030308001)the Shenzhen Science and Technology Innovation Commission(No.JCYJ20210324120200001).
文摘Riboflavin(RF,vitamin B2)is an essential vitamin and has been considered as a promising natural photosensitizer for photodynamic therapy(PDT).However,further exploration of RF in antitumor application was limited by its poor cellular uptake.In this study,using cell-penetrating peptides Arg8,(Cha-Arg)3 and small molecule triphenylphosphine(TPP)as delivery compounds,three RF conjugates were prepared to increase the accumulation of RF in cells,termed as Arg8-RF,(Cha-Arg)3-RF and TPP-RF,respectively.Compared with TPP-RF and Arg8-RF,(Cha-Arg)3-RF exhibited better cell internalization and stronger cytotoxicity against HeLa cells upon exposure to blue light.Further researches proved that(Cha-Arg)3-RF generated reactive oxygen species(ROS)under irradiation,which could indiscriminately destroy endogenous proteins and mitochondria,ultimately inducing cell death.This work provides a new approach to explore RF as a natural photosensitizer for antitumor photodynamic therapy.
文摘After deregulating the purine and riboflavin synthesis in the Gram-positive bacterium Bacillus subtilis,it is critical to amplify riboflavin operon with appropriate dosage in the host strain for remarkable increase of riboflavin production.Bacillus subtilis RH13, a riboflavin-producing strain, was selected as host strain in the construction of engineering strains by protoplast fusion. The integrative plasmid pRB63 and autonomous plasmid pRB49, pRB62 containing riboflavin operon of B.subtilis 24 were constructed and transformed into the host strain respectively. Increasing one operon copy in B.subtilis RH13 results in about 0.4 g/L improvement in riboflavin yield and the appropriate number of operon copies was about 7—8. Amplifying more riboflavin operons is of no use for further improvement of yield of riboflavin. Furthermore, excessive operon dosage results in metabolic unbalance and is fatal to the host cells producing riboflavin.
基金supported by Open Project from State Key Laboratory of Catalysis(N-14-1)Scientific Research Foundation for Returned Scholars,Ministry of Education of ChinaInternational Technology Collaboration of Chengdu Science and Technology Division~~
文摘Efficient,cost‐effective electrocatalysts for an oxygen reduction reaction(ORR)are currently required for fuel cells.In the present work,riboflavin was used as a cheap,nontoxic carbon and nitrogen precursor to prepare Fe-N-C catalysts via one‐step pyrolysis in the presence of anhydrous iron chloride.Raman spectroscopy indicated that the catalyst containing nitrogen created a great quantity of defects in the carbon structures,while nitrogen adsorption‐desorption isotherms showed that the catalyst was mesoporous.Transmission electron microscopy demonstrated that the Fe-N-C catalyst was composed of very thin,curved and porous graphene layers together with some Fe2O3nanoparticles,and X‐ray diffraction patterns confirmed that the carbon in the catalyst was highly graphitized.X‐ray photoelectron spectroscopy indicated that the active sites for the ORR were primarily composed of graphitic nitrogen,although Fe sites also played an important role.The ORR activity of the Fe-N-C catalyst reached a maximum of4.16mA cm-2,and its chronoamperometric response was found to decrease by only3%after operating for3h at0.66V(vs RHE)in an O2‐saturated0.1mol L-1KOH solution.In contrast,a commercial40wt%Pt/C catalyst with a loading of0.2mgPt cm-2exhibited an activity of4.46mA cm-2and a40%loss of response.The electrochemical performance of this new Fe-N-C catalyst was therefore comparable to that of the Pt/C catalyst while showing significantly better stability.
文摘The influence of irradiation on biosyntheses of ascorbic acid and riboflavin in germinating chickpea seeds at ambient (25-35℃) conditions, was investigated. The rate of syntheses of these vitamins significantly increased with increasing germination time upto 120 h depending upon the treatment (P【0.05). Maximum amounts of ascorbic acid, 22.32 and 16.84 mg/100g, were found in the 0.10 kGy sample after 120 h of germination in tap and distilled water respectively. However, a radiation dose of 0.15 kGy resulted in the development of maximum values of riboflavin, 11.40 and 11.38 μ g/g, on germination in tap and distilled water respectively. A significant linear relation (r = 0-954 to 0.997) was observed between the biosyntheses of these vitamins and the germination time upto 120 h of irradiated and unirradiated chickpea seed (P【0.05).
文摘AIM: To evaluate the enrichment of riboflavin in the corneal stroma after intracameral injection to research the barrier ability of the corneal endothelium to riboflavin in vivo.METHODS: The right eyes of 30 New Zealand white rabbits were divided into three groups. Different concentrations riboflavin-balanced salt solutions(BSS)were injected into the anterior chamber(10 with 0.5%, 10 with 1%, and 10 with 2%). Eight corneal buttons of 8.5mm in diameter from each group were dissected at 30 min after injection and the riboflavin concentrations in the corneal stroma were determined using high-performance liquid chromatography(HPLC) after removing the epithelium and endothelium. The other two rabbits in every group were observed for 24 h and sacrificed. As a comparison, the riboflavin concentrations from 16 corneal stromal samples were determined using HPLC after instillation of 0.1% riboflavin-BSS solution for30 min on the corneal surface(8 without epithelium and 8with intact epithelium).RESULTS: The mean riboflavin concentrations were11.19, 18.97, 25.08, 20.18, and 1.13 μg/g for 0.5%, 1%, 2%,de-epithelialzed samples, and the transepithelial groups,respectively. The color change of the corneal stroma and the HPLC results showed that enrichment with riboflavin similar to classical de-epithelialized corneal collagen crosslinking(CXL) could be achieved by intracameral 1%riboflavin-BSS solution after 30min; the effect appeared to be continuous for at least 30 min.CONCLUSION: Riboflavin can effectively penetrate the corneal stroma through the endothelium after an intracameral injection in vivo, so it could be an enhancing method that could improve the corneal riboflavin concentration in transepithelial CXL.
文摘Riboflavin has been suggested to act with folate to lower homocysteine (Hcy). However, these interactions may differ among the several known forms of folate. Therefore, we examined the effects of riboflavin interactions with 5-methyltetrahydrofolate (5-MTHF) and tetrahydrofolate (THF) on changes in Hcy and folate derivative levels, under conditions with and without methionine addition. Rat hepatocytes were cultured for 48 hours in medium with or without 2.64 μM riboflavin addition, under the following conditions: 1) without the addition of either methionine or folate;2) with addition of 2 μM folate derivatives [(A): 5-MTHF, (B): THF];3) with addition of both 5 mM methionine and 2 μM folate derivatives [(A): 5-MTHF, (B): THF]. The supernatants were collected at 0, 24, and 48 hours for Hcy and folate derivative measurements. The Hcy lowering effect of 5-MTHF, as well as inhibition of 5-MTHF reduction and THF elevation, appeared to be enhanced by riboflavin addition. THF addition did not lower the Hcy level, regardless of the presence of riboflavin and/or methionine, while THF and 5,10-methenyl THF levels were maintained. Further examination is needed to elucidate the interactive effects of riboflavin and folate derivatives on Hcy and folate metabolism.
文摘A high performance liquid chromatographic assay has been developed for the simultaneous determination of five water soluble vitamins:thimine, riboflavin, niacin, pyridoxine and folic acid in cereal products and fresh vegetables. Food samples were hydrolyzed in 0.4 mol/L HCl, autoclaved at 120℃ 15 psi for 20 minutes, using a μ-Bondapak column (3.9×300mm, Waters Co.), a mobile phase of methanol-water (30:70) (0.005 mol/L heptanesulfonic acid) and a flow rate of 1.0 ml/min gave the most satisfactory separation of the five water soluble vitamins. A double channel deteetion was used: four vitamins (B_5, folic acid, B_2, B_1) were detected hy UV spectrophotometry (254 nm) first, pyridoxine (B_6) was detected by fluoromelry (EX 290nm, EM 395 nm) afterwards. Detection limits were 2, 5, 5, 2and 5ng, linear ranges were 5-10ng, 5-50ng, 5-40ng, 5-50ng and 10-50ng for B_1, B_2, B_5, B_6 and folic acid respectively. Recoveries were 92-100%(B_5), 51-52% (folio acid), 103—105% (B_2), 99—100% (B_6) and 91.3—102% (B_1) respectively. In comparison with a reference method and checking with food composition tables, very satisfactory results were obtained by this method.
文摘The effects of riboflavin deficiency and simultaneously nitrosodimethylamine (NDMA) given by gastric intubation on the hepatic glutathione (GSH) content were examined in rats. On different days of the experiment, hepatic GSH content of the riboflavin deficient rats decreased to 55-61% of the control rats. When NDMA was given 6 mg kg by gastric intubation to riboflavin deficient rats, hepatic GSH content decreased markedly to 39-43% of the control rats. After supplying riboflavin, hepatie GSH content of the deficient rats recovered to the level of the control rats. These results suggest that alterations of rat hepatic GSH content during riboflavin deficiency may imply as one of the promoting effects of riboflavin deficiency on the carcinogenesis of nitrosamines.
文摘Dear Sir,UVA/riboflavin cross-linking （CXL） has been used clinically applied for the treatment of keratoconus and corneal edema via enhancement of corneal stiffness The safety of the corneal endothelium is of prime importance during CXL treatment. In clinical practice, a corneal thickness （CT） of 400um has traditionally been regarded as the minimum treatable thickness, thereby avoiding damage to the corneal endothelium Although CXL has been applied to thinner corneas, using a hypoosmotic solution onto cornea and inducing edema . CXL safety still needs further evaluation because of lower relative concentration of collagen in the hydrated stroma . This study aims to evaluate the changes of corneal endothelial density （ECD） in cases where the CT is 〈400 um before iatrogenic corneal swelling and CXL treatment.
