BACKGROUND Itraconazole is a broad-spectrum triazole antifungal inhibiting fungal growth by inhibiting ergosterol synthesis and exhibits a nonlinear pharmacokinetic profile.Erratic absorption pattern with wide fluctua...BACKGROUND Itraconazole is a broad-spectrum triazole antifungal inhibiting fungal growth by inhibiting ergosterol synthesis and exhibits a nonlinear pharmacokinetic profile.Erratic absorption pattern with wide fluctuations in blood levels causes inconsistent and unpredictable clinical behaviour of this drug despite its low minimum inhibitory concentration(MIC)as compared to other antifungal agents.AIM To compare the oral bioavailability and bioequivalence of Fixtral SB(supra bioavailable itraconazole)with reference product R2(supra bioavailable 2×50 mg itraconazole).METHODS The study population consisted of 54 healthy volunteers,aged between 18-45 years and randomized to receive a single oral dose of either test[T;Fixtral SB(supra bioavailable itraconazole)100 mg]or reference product(R1;Sporanox 100 mg×2 capsules and R2;Lozanoc capsules 50 mg×2 capsules).Blood samples were taken pre-dose and post-dose up to 96 h.The study evaluated bioequivalence by comparing the oral bioavailability of the test product with reference product R2.The pharmacodynamic characteristics of the drug were evaluated by comparing the test product with reference product R1.Pharmacokinetics(PK)-PD comparative analysis[area under the concentration-time curve(AUC)/minimum inhibitory concentration(MIC)>25]was performed for conventional itraconazole 100 mg and supra bioavailable itraconazole 50 mg.Adverse events(AEs)assessments were performed in each study period and post-study evaluation.RESULTS Statistical analysis of primary PK variables revealed bioequivalence,with confidence intervals being completely inside the acceptance criteria of 80%-125%.The peak concentration levels of itraconazole were achieved at 10 h(T)and 8.5 h(R2),respectively.Pharmacodynamic parameter assessment showed that AUC/MIC for R1 are comparable to Fixtral SB 100mg for MIC levels up to 16mcg/mL(P>0.05 and observed P=0.3196).Six AEs were observed that were mild to moderate in severity and resolved.No severe AE was reported.CONCLUSION Test product itraconazole Capsule 100 mg is bioequivalent with the reference product(R2)at 100 mg dose(2 capsules of Lozanoc®50 mg)under fed conditions.Pharmacodynamics activity in terms of AUC/MIC is comparable between the test product at 100 mg dose and marketed itraconazole 200 mg.Fixtral SB is expected to have therapeutically similar efficacy at half the equivalent dose.Tested formulations were found to be safe and well tolerated.展开更多
Although low testosterone levels in men have been associated with high risk for cardiovascular disease, little is known about the association between male sex hormones and subclinical coronary disease in men with appa...Although low testosterone levels in men have been associated with high risk for cardiovascular disease, little is known about the association between male sex hormones and subclinical coronary disease in men with apparently low cardiometabolic risk. This study was performed to investigate the association between male sex hormones and subclinical coronary artery calcification measured as coronary calcium score in non-obese Korean men. We examined the relationship of total testosterone, sex hormone-binding globulin, bioavai lable testosterone and free testosterone with coronary calcium score in 291 non-obese Korean men （mean age： 52.8--- 9.3 years） not having a history of cardiovascular disease. Using multiple linear regression, we evaluated associations between log （sex hormone） levels and log （coronary calcium score） after adjusting for confounding variables in 105 men with some degree of coronary calcification defined as coronary calcium score ~〉 1. In multiple linear regression analysis, bioavailable testosterone was inversely associated with coronary calcium score （P=0.046） after adjusting for age, body mass index, smoking status, alcohol consumption, regular exercise, mean blood pressure, resting heart rate, C-reactive protein, fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein （HDL） cholesterol, hypertension medication and hyperlipidernia medication, whereas total testosterone, sex hormone-binding globulin and free testosterone were not （P=0.674, P=O. 121 and P=O. 102, respectively）. Our findings indicate that bioavailable testosterone is inversely associated with the degree of subclinical coronary artery calcification in non-obese men.展开更多
Various forms of phosphorus (P) could become bioavailable such as from desorption, dissolution and enzymatic hydrolysis. Potential bioavailable P estimation is critical to minimize eutrophication in freshwater systems...Various forms of phosphorus (P) could become bioavailable such as from desorption, dissolution and enzymatic hydrolysis. Potential bioavailable P estimation is critical to minimize eutrophication in freshwater systems. Thus, this study was conducted to predict potential bioavailable P in the water columns and sediments and their relations with enzymatic hydrolysis, and estimate impacts of land use and anthropogenic activities on P bioavailability, P transport and water quality in the Bronx River, New York, USA. In sediment samples collected in 2006, total P (TP), total inor-ganic P (IP), total organic P (OP) and bioavailable P (BAP) were in highest concentrations in sites located at Bronx River Valley upstream in Westchester (site 2), Troublesome Brook (TB, site 4), Sprain Brook (SB, site 7b) and Bronx River estuary near Sound View Park (site 14) respectively. Also, phosphodiesterase and native phosphatases (PDEase and NPase) hydrolyzed distinguishingly high amounts of OP or enzymatically hydrolysable P (EHP) in samples from sites 4, 7b, 10 (New York Botanical Garden) and 14. Microbial P was in negative values (caused by different bacteria and microorganisms could not be paralyzed by chloroform), and the most negative concentrations were appeared at sties 4 and 14. Spatial comparisons among different locations showed distinguished characteristics in tributaries and estuary. In sediments collected in 2007, TP, BAP and IP were in highest concentrations at sites 7-SB, 11-Bronx Zoo, 12-East Tremont Ave Bridge where fresh and saline water meets, 13-estuary facing Hunts Point Waste Water Treatment Plant (HP WWTP) and 14-estuary along Sound View Park. Besides, PDEase-P highest concentrations ap-peared at sties 7, 13 and 11, NPase-P concentrations were highest at 7 and 11. Microbial P was highest at sties 11 and 14. Spatial variations showed that higher P content and more intense enzymatic hydrolysis in silty clay finer sediments at site 7, 11 and 13. Temporal variations between the two years’ data showed land use and other anthropogenic factors’ impacts on P transport in river and deposit in sediments. Analysis of the river water samples showed that average soluble reactive P (SRP, 67 μg.l-1) in 2006 and SRP (68μg.l-1) in 2007 both were greater than background P concentration in most natural water (42 μg.l-1).展开更多
[Objectives] The research was conducted to study characteristics of bioavailable levels pollution of heavy metals in the surface soil of the lead-zinc mine in Changhua.[Methods] A total of 56 surface samples were coll...[Objectives] The research was conducted to study characteristics of bioavailable levels pollution of heavy metals in the surface soil of the lead-zinc mine in Changhua.[Methods] A total of 56 surface samples were collected from the 3 study zones （peripheral zone, reclamation zone and tailing zone） located at the lead-zine mine in Changhua. Based on total and bioavailable heavy metals （Pb, Zn, Cu and Cd） in soils, the correlation of total content with bioavailable content was analyzed, and their pollution characteristics were assessed by methods of single factor pollution index, Nemerow pollution index, geological accumulation index and potential ecological risk index.[Results] （i） The surface soils were polluted by Pb, Zn, Cu, Cd in different degrees, and the overall trend of the contents of the 4 heavy metals was in order of Cd 〉 Pb 〉 Zn 〉 Cu. The average excess multiple of heavy metals of total and bioavailable content in soils were in the order of peripheral zone 〉 tailing zone 〉 reclaimed zone, and their pollution degrees were tailing zone 〉 peripheral zone 〉 reclaimed zone. （ii） In general, the total and bioavailable contents of Pb, Zn, Cu, Cd showed a significant correlation, but were not correlated in each study zone. （iii） Pollution degrees of the study zones were in the order of tailing zone 〉 peripheral zone 〉 reclamation zone. The pollutions of heavy metals Pb and Cd were more serious, especially Cd reached high levels of pollution degree, and the pollution degrees of Zn, Cu were lighter. Contributors of ecological risk were mainly Cd, Pb and Cu, and the contribution of Cd achieved more than 90 %, making it the main source of pollution.[Conclusions] The results not only revealed the pollution status of heavy metals in the surface soil of the abandoned coal mine, but also could provide scientific guidance for reasonable utilization and ecological recovery of the land.展开更多
The bioavailability of selenium(Se)from ground beef has been previously found in this laboratory to be greater than that of selenite or selenate when fed to female Fischer 344 rats(B. Shi,J.E.Spallholz,J Am Coil Nutr,...The bioavailability of selenium(Se)from ground beef has been previously found in this laboratory to be greater than that of selenite or selenate when fed to female Fischer 344 rats(B. Shi,J.E.Spallholz,J Am Coil Nutr,13:95￣101,1994).In the present study we examined the bioavailability of Se from various commercial portions of beef,the liver,striploin,round, shoulder and brisket.All beef was cooked, freeze-dried,finely powdered and mixed with the other dietary ingredients.The experimental diets were fed to the weanling Fischer 344 rats which had been subjected to dietary depletion of Se for 6 weeks.The bioavailability of Se from the beef diets was compared with that of Se as se lenite or L-seienomethionine(SeMet)added to torula-yeast diets.Each experimental diet contained 0'10mg Se/kg.After 8 weeks of dietary Se repletion,relative activity of liver glutathione peroxidase (EC 1.11.1.9;GSHPx) from the different dietary groups colllpared with that of control animals(100%)was(%):selenite 91,SeMet 122 (P<0.05),liver 108, striploin 105,round 106, shoulder 106,brisket 103.Se recovery in liver was generally highest from SeMet>beef muscle=beef liver>selenite.Muscle tissue deposition of Se was highest from SeMet>beef muscle>selenite=beef liver.In addition, the feeal excretion of Se was lowest from the SeMet dietary group and highest from the selenite dietary group.The experimetal results suggest that all cuts of beef appear to be highly bioavailable sources of dietary Se when compared with selenite or L-SeMet.展开更多
Inflammatory bowel disease(IBD)is a nonspecific inflammatory disease of the intestine that includes Crohn’s disease and ulcerative colitis.Because IBD is difficult to heal and easily relapses,it could worsen patient ...Inflammatory bowel disease(IBD)is a nonspecific inflammatory disease of the intestine that includes Crohn’s disease and ulcerative colitis.Because IBD is difficult to heal and easily relapses,it could worsen patient quality of life and increase economic burdens.Curcumin(CUR)is a bioactive component derived from the rhizome of turmeric(Curcuma longa).Many basic and clinical studies have shown that CUR can efficiently treat IBD by decreasing the activity of proinflammatory cytokines by communicating with transcription factors and signaling molecules.However,due to the limitations of being almost insoluble in aqueous solutions and having low oral bioavailability,it is important to select appropriate pharmaceutical preparations.展开更多
Experiments on Phosphorus （P） fraction characteristics in sediment resuspension were performed under adequate hydrodynamic conditions. It is found that the concentration of Suspended Particulate Matter （SPM） in th...Experiments on Phosphorus （P） fraction characteristics in sediment resuspension were performed under adequate hydrodynamic conditions. It is found that the concentration of Suspended Particulate Matter （SPM） in the eddy current region exhibits the ＂Matthew effect＂. Velocity is an impact factor of the Equilibrium Phosphate Concentration （EPC）, which is related to other hydraulic conditions. Overall bioavailable dissolved P in the SPM causes migration to overlying water and sediment, eventually being converted into a chemical speciation of P. Conditions of resuspension promote A1-P of SPM that migrated to the sediment and water. Concentrations of A1-P in SPM are reduced. P is released from SPM to water bodies, mainly through conversion into particulate P and dissolved total P. Meanwhile, exchange between SPM and sediments occur mainly through Ca-P migration. A1-P and BD-P possess similar geochemical characteristics or source. Ca-P and A1-P exhibit a negative correlation between migration and conversion.展开更多
Hyperuricemia,a metabolic disorder related to uric acid metabolism dysregulation,has become a common metabolic disease worldwide,due to changes in lifestyle and dietary structure.In recent years,owing to their high ac...Hyperuricemia,a metabolic disorder related to uric acid metabolism dysregulation,has become a common metabolic disease worldwide,due to changes in lifestyle and dietary structure.In recent years,owing to their high activity and few adverse effects,food-derived active peptides used as functional foods against hyperuricemia have attracted increasing attention.This article aims to focus on the challenge associated with peptide-specific preparation methods development,functional components identification,action mechanism(s)clarification,and bioavailability improvement.The current review proposed recent advances in producing the food-derived peptides with high anti-hyperuricemia activity by protein source screening and matched enzymatic hydrolysis condition adjusting,increased the knowledge about strategies to search antihyperuricemia peptides with definite structure,and emphasized the necessity of combining computer-aided approaches and activity evaluations.In addition,novel action mechanism mediated by gut microbiota was discussed,providing different insights from classical mechanism.Moreover,considering that little attention was paid previously on the structure-activity relationships of anti-hyperuricemia peptides,we collected the sequences from published studies and make a preliminary summary about the structure-activity relationships,which in turn provided guides for enzymatic hydrolysis optimization and bioavailability improvement.Hopefully,this article could promote the development,application and commercialization of food-derived anti-hyperuricemia peptides in the future.展开更多
Background Our previous studies demonstrated that divalent organic iron(Fe)proteinate sources with higher complexation or chelation strengths as expressed by the greater quotient of formation(Qf)values displayed highe...Background Our previous studies demonstrated that divalent organic iron(Fe)proteinate sources with higher complexation or chelation strengths as expressed by the greater quotient of formation(Qf)values displayed higher Fe bioavailabilities for broilers.Sodium iron ethylenediaminetetraacetate(NaFeEDTA)is a trivalent organic Fe source with the strongest chelating ligand EDTA.However,the bioavailability of Fe when administered as NaFeEDTA in broilers and other agricultural animals remains untested.Herein,the chemical characteristics of 12 NaFeEDTA products were determined.Of these,one feed grade NaFeEDTA(Qf=2.07×10^(8)),one food grade NaFeEDTA(Qf=3.31×10^(8)),and one Fe proteinate with an extremely strong chelation strength(Fe-Prot ES,Qf value=8,590)were selected.Their bioavailabilities relative to Fe sulfate(FeSO_(4)·7H_(2)O)for broilers fed with a conventional corn-soybean meal diet were evaluated during d 1 to 21 by investigating the effects of the above Fe sources and added Fe levels on the growth performance,hematological indices,Fe contents,activities and gene expressions of Fe-containing enzymes in various tissues of broilers.Results NaFeEDTA sources varied greatly in their chemical characteristics.Plasma Fe concentration(PI),transferrin saturation(TS),liver Fe content,succinate dehydrogenase(SDH)activities in liver,heart,and kidney,catalase(CAT)activity in liver,and SDH mRNA expressions in liver and kidney increased linearly(P<0.05)with increasing levels of Fe supplementation.However,differences among Fe sources were detected(P<0.05)only for PI,liver Fe content,CAT activity in liver,SDH activities in heart and kidney,and SDH mRNA expressions in liver and kidney.Based on slope ratios from multiple linear regressions of the above indices on daily dietary analyzed Fe intake,the average bioavailabilities of Fe-Prot ES,feed grade NaFeEDTA,and food grade NaFeEDTA relative to the inorganic FeSO_(4)·7H_(2)O(100%)for broilers were 139%,155%,and 166%,respectively.Conclusions The bioavailabilities of organic Fe sources relative to FeSO_(4)·7H_(2)O were closely related to their Qf values,and NaFeEDTA sources with higher Qf values showed higher Fe bioavailabilities for broilers fed with a conventional corn-soybean meal diet.展开更多
Boswellic acids is a general term for a series of pentacyclic triterpenoid compounds that are isolated from the oleogin resin of the Boswellia genus and serve as the main active ingredient.It exhibits a wide range of ...Boswellic acids is a general term for a series of pentacyclic triterpenoid compounds that are isolated from the oleogin resin of the Boswellia genus and serve as the main active ingredient.It exhibits a wide range of biological activities,such as anti-inflammatory,anti-cancer,antibacterial,antiviral,hepatoprotective,neuroprotective,anti-diabetic,and anti-thrombotic properties.As a result,it has gained significant recognition among practitioners of traditional Chinese and Indian medicine.These biological effects may be associated with multiple molecular targets and signal transduction pathways.However,the poor pharmacokinetic properties of the substance lead to lower bioavailability,which affects its effectiveness.To address this issue,scientists have proposed a number of strategies,such as solid dispersions,phytosome®technologies,and novel drug delivery systems.This article aims to provide a comprehensive overview for boswellic acids on the phytochemistry,molecular mechanisms,potential therapeutic applications,and strategies to improve bioavailability.展开更多
Background: Bioenhancers augment the bioavailability of co-administered molecules without showing any significant effect on their own. Piperine, an alkaloid from Piper nigrum, is an established natural bioenhancer. Ni...Background: Bioenhancers augment the bioavailability of co-administered molecules without showing any significant effect on their own. Piperine, an alkaloid from Piper nigrum, is an established natural bioenhancer. Nicotinamide mononucleotide (NMN), an antiaging supplement, is the precursor of coenzyme nicotinamide adenine dinucleotide (NAD) that plays an important role in intracellular redox reactions. Objective: The study compared the serum concentrations of NAD in normal healthy participants, supplemented with NMN 500 mg and NMN 500 mg + 5 mg BioPerine® (95% piperine). Methods: In a randomized, open-label, crossover study, NMN (500 mg) was compared to NMN + BioPerine® (500 mg + 5 mg) in 6 healthy adults, aged 18 - 45 years. The participants received a single oral dose of NMN or NMN + BioPerine® capsules with 240 mL water, and blood samples were collected over 8hr. After a 4-day washout period, the same procedures were repeated as per the crossover design. Total NAD (NADtotal), including oxidized NAD (the oxidized) and its reduced form NADH, was measured in human serum samples. Results: The maximum concentration (Cmax) of NAD in serum was higher with NMN + BioPerine® (282 pmol/mL) compared to NMN (246 pmol/mL) alone. In the presence of BioPerine®, the NAD concentrations reached 257 pmol/mL during the first 2 hr, whereas a comparable serum concentration (246 pmol/mL) was attained only after 6 hr in NMN alone. The AUC0-8hr was 1738 pmol/mL/hr in NMN compared to 2004 pmol/mL/hr in NMN+ BioPerine®. The time to reach peak concentration (t1/2) was similar (6hr) in both groups. No clinically relevant adverse events (AE) were observed, and safety parameters remained within normal ranges in all the participants with both formulations. Conclusion: These results reveal that BioPerine® can effectively increase the NAD concentrations in the serum following NMN supplementation in healthy volunteers. The present study was registered prospectively with the Clinical Trials Registry-India (CTRI/2023/11/059982).展开更多
Particulate matter (PM10) deposited as road dust is considered an important source of contamination from atmosphere. However, there are limited studies on the toxicity of road dust as such on different organisms. This...Particulate matter (PM10) deposited as road dust is considered an important source of contamination from atmosphere. However, there are limited studies on the toxicity of road dust as such on different organisms. This study evaluates the toxicity of road dust using different extraction scenarios on Daphnia magna and Artemia salina as aquatic organisms and also on Prosopis cineraria and Vachellia tortilis as local plant species. Chemical analysis of different extracts shows considerable amount of trace metals, however the trace metals in the dust extract associated with suspended sediment were not absorbed by the receptors. On the other hand, the concentration of trace metals in the artificial mixture was found bioavailable and absorbed causing a high percentage of mortality. In the plant assay, significant difference was obtained in the germination percentage between the control and three different extraction exposures in both plant species. The mean root length of P. cineraria and V. tortilis were higher in 20% and 50% extracts than the control probably due to the availability of nutrients from the dust extract. Interestingly however, the seedling vigor index was the opposite with higher index in the control and lower in dust extracts that contain heavy metals.展开更多
In recent years, metabolic syndrome has been a growing health concern across the world. The role of nutraceuticals and functional foods in this area has a significant place due to the adverse effects of contemporary m...In recent years, metabolic syndrome has been a growing health concern across the world. The role of nutraceuticals and functional foods in this area has a significant place due to the adverse effects of contemporary modes of treatment. CurCousin<sup>®</sup> is a nutritional ingredient containing bioactive Calebin A, (analog of Curcumin) with self-affirmed GRAS status. CurCousin<sup>®</sup> has been a clinically studied dietary supplement ingredient with a positive impact on body weight, lipid levels and metabolic health. Bioenhancers play an important role in increasing the bioavailability of the active in turn enhancing efficacy as well as reducing the dosage required to achieve the therapeutic effect. This study investigated the possible pharmacokinetic interaction between CurCousin<sup>®</sup> at two different doses (2.25 and 4.5 mg/kg) in the presence and absence of BioPerine<sup>®</sup> (0.27 mg/kg), a natural bioenhancer in Sprague-Dawley rats. The results revealed that the addition of BioPerine<sup>®</sup> into CurCousin<sup>®</sup> (2.25 mg/kg) half the dose when administered enhances the bioavailability and was equipotent to CurCousin<sup>®</sup> (4.5 mg/kg) double the dose without BioPerine<sup>®</sup>. Thus, leading to future clinical studies to evaluate its improved pharmacological efficacy as well as reduced therapeutic dosage.展开更多
The review provides an overview of the approaches, applications, and methods for ester prodrugs. Ester prodrugs are pharmacologically inactive compounds in their original form but become active drugs on biotransformat...The review provides an overview of the approaches, applications, and methods for ester prodrugs. Ester prodrugs are pharmacologically inactive compounds in their original form but become active drugs on biotransformation within the body, which offers advantages concerning the solubility, stability, and targeted delivery of the active drug. Several approaches of ester prodrugs have been reviewed in this review, including simple ester prodrugs, amino acid ester prodrugs, sugar ester prodrugs, lipid ester prodrugs, and polymeric ester prodrugs. This review incorporates in vitro and in vivo methods as well as the characterization of physical and chemical properties for ester prodrugs, cell culture systems, enzymatic assays, and animal models—all of these having a very important bearing on the evaluation of stability, bioavailability, and efficacy for ester prodrugs. While the benefits of using ester prodrugs are significant, there are also disadvantages like instability, poor or variable enzymatic hydrolysis, and toxicity from released promoieties or by-products. This review discusses solutions to the various limitations that include enhancing stability with ionizable promoieties and using physiologically-based pharmacokinetic modeling. The review also highlights the application of ester prodrugs in neurological disorders, such as Parkinson’s disease, and the ongoing efforts to address the critical limitations in treatment efficacy. Future prodrug strategies are poised to advance significantly by harnessing diverse transport mechanisms across the blood-brain barrier and integrating nanotechnology.展开更多
Curcumin is a widely studied natural compound which has shown tremendous in vitro therapeutic poten- tial. Despite that, the clinical efficacy of the native curcumin is weak due to its low bioavailability and high met...Curcumin is a widely studied natural compound which has shown tremendous in vitro therapeutic poten- tial. Despite that, the clinical efficacy of the native curcumin is weak due to its low bioavailability and high metabolism in the gastrointestinal tract. During the last decade, researchers have come up with dif- ferent formulations with a focus on improving the bioavailability of curcumin. As a result, a significant number of bioavailable curcumin-based formulations were introduced with the varying range of enhanced bioavailability. The purpose of this review is to collate the published clinical studies of cur- cumin products with.improved bioavailability over conventional （unformulated） curcumin. Based on the literature search, 11 curcumin formulations with available human bioavailability and pharmacokinet- ics data were included in this review. Further, the data on clinical study design, analytical method, phar- macokinetic parameters and other relevant details of each formulation were extracted. Based on a review of these studies, it is evident that better bioavailability of formulated curcumin products is mostly attrib- uted to improved solubility, stability, and possibly low first-pass metabolism. The review hopes to provide a quick reference guide for anyone looking information on these bioavailable curcumin formulations. Based on the published reports, NovaSol （185）, CurcuWin （136） and LongVida （100） exhibited over 100-fold higher bioavailability relative to reference unformulated curcumin. Suggested mechanisms accounting for improved bioavailability of the formulations and details on the bioanalysis methods are also discussed.展开更多
The method to remove bioavailable amounts of heavy metals from a contaminated soil by using plants is defined as bioavailable contaminant stripping （BCS） and could safely be applied if the soil＇s long-term ability ...The method to remove bioavailable amounts of heavy metals from a contaminated soil by using plants is defined as bioavailable contaminant stripping （BCS） and could safely be applied if the soil＇s long-term ability to replenish the bioavuilable pool is known. The aim of this study was to evaluate the ability of three common plant species selected, Brassica juncea, Poa annua, and Helianthus annus, to remove bioavailable amounts of mercury （Hg） from a contaminated industrial soil containing 15.1 mg kg-1 Hg. Trials were carried out under greenhouse conditions using pots （mesocosms）. According to the precautionary principle, we modified the BCS remediation approach by adding a new step, in which mercury bioavailability was increased by the addition of a strong mobilizing agent, ammonium thiosulphate, （NH4）28203, to obtain an estimate of the likely long-term bioavailable Hg pool. The modified BCS remediation approach was called enhanced bioavailable contaminant stripping （EBCS）. After one growth cycle, nearly all the bioavailable mercury （95.7%） was removed and the metal remaining in the soil was considered inert since it was neither extractable by （NH4）2S2O3 nor taken up by plants during a second growth cycle. The results demonstrated that EBCS appeared promising since it removed the most dangerous metal forms while substantially shortening the cleanup time.展开更多
Taxifolin loaded zein-caseinate nanoparticles(TZP)were fabricated by the anti-solvent method and were used as an oral delivery vehicle to improve their bioavailability in the rat.The formulations of TZP were optimized...Taxifolin loaded zein-caseinate nanoparticles(TZP)were fabricated by the anti-solvent method and were used as an oral delivery vehicle to improve their bioavailability in the rat.The formulations of TZP were optimized.With mass ratio of 1:1:2 between taxifolin,zein and sodium caseinate,the particle size andζpotential of TZP were(168.74±0.35)nm and−(57.67±0.25)mV,while the encapsulation and loading efficiency of taxifolin were(85.83±0.89)%and(17.11±0.88)%,respectively.After freeze-drying,TZP exhibited excellent redispersibility in water without aggregation.Physicochemical characterization showed that taxifolin existed in amorphous form in TZP and its interaction with the protein was observed.After encapsulating in TZP,the excellent dispersion of taxifolin in water signifi cantly improve its diffusion velocity through a semipermeable membrane.After oral administration,taxifolin and its 5 metabolites were identifi ed in rat plasma by ultra high performance liquid chromatography(UPLC)with quadrupole time-of-flight mass spectrometry(UPLC-QTOF-MS).The dynamic variation of taxifolin and its metabolites in plasma were then quantifi ed by UPLC with a triple-quadrupole typemass spectroscopy(UPLC-QqQ-MS/MS).A pharmacokinetic study showed that the bioavailability of taxifolin increased from 0.35%to 0.52%through TZP fabrication.The plasma concentration of taxifolin glucuronide and methylated taxifolin glucuronide was much higher than taxifolin.Glucuronidation was the dominating metabolism pathway of taxifolin in vivo.展开更多
The brown seaweed,Sacchairna japonica,has been used in traditional Chinese medicine for over one thousand years.Oral administration of fucoidan or low molecular weight fucoidan(LMWF)from S.japonica could ameliorate ki...The brown seaweed,Sacchairna japonica,has been used in traditional Chinese medicine for over one thousand years.Oral administration of fucoidan or low molecular weight fucoidan(LMWF)from S.japonica could ameliorate kidney dysfunction in chronic kidney diseases and inhibit diabetic vascular complications.In many studies,LMWF was found to be more potent than fucoidan with high molecular weight.However,the pharmacokinetics of LMWF still remains unclear.The purpose of the research is to compare the pharmacokinetics of fucoidan with high molecular weight(136 kDa)with that low molecular weight(9.5 kDa)after oral administration to ICR mice.Since fucose is the main and representative monosaccharide of fucoidans,we evaluate the pharmacokinetics of fucoidan and LMWF by determining the fucose concentration in mice serum.Both fucoidan and LMWF were absorbed following oral administration.Fucoidan and LMWF were provided to mice by oral administration with 60 mg/kg and the maximum Concentration(C_(max))was found at 2.5 h(0.66±0.32 mg/L)for Fucoidan and 1.5 h(1.01±0.56 mg/L)for LMWF,respectively.It seems that LMWF had a higher area under the curve(AUC_(0–t))and was absorbed more quickly than fucoidan.The estimated bioavailability of LMWF was28.3%in the mice treated with a single dose of 30 mg/kg.In addition,LMWF was found widely spreaded into different tissues following oral administration and the highest concentration was found in kidney at 19.93±7.02μg/g.In this study,we first studied the pharmacokinetics of LMWF,in order to help to understand the function of LMWF.And our results shed light on the potential of development of drugs based on LMWF.展开更多
In a single sample plot,the total amount of heavy metals in the soil could not necessarily reflect the contents of their effective states.This must be considered when attempting to determine the degree of soil heavy-m...In a single sample plot,the total amount of heavy metals in the soil could not necessarily reflect the contents of their effective states.This must be considered when attempting to determine the degree of soil heavy-metal pollution in an area.In the present study,the soil around the molybdenum mining area in Huludao,China,was surveyed and sampled to evaluate soil heavy-metal pollution using the Nemerow multifactor pollution index method.The Tessier continuous extraction method was used to analyze the distribution of heavy-metal forms'and their content changes in the soil of this area.Thus,the bioactivity of heavy metals in the soil,the absorption of heavy metals by plants,and the distribution of heavy metals in plants were explored to provide data supporting the use of phytoremediation technology to treat the heavy-metal pollution in the molybdenum mining area and develop ecological restoration strategies for the area's wastelands.The pollution index results indicate that heavy-metal pollution in the soil around the tailings pond is severe,mainly due to Pb and Zn heavy metals.Heavy-metal pollution in the surrounding land is mainly due to Cd and Zn.Content analysis of the heavy-metal forms/states in soils shows that exchangeable forms,which are most effective and toxic to plants,of the following metals are highest in the following areas:Cd,Cu,and Zn in the mountains around the stope;Zn,Mo,and Cu in the cultivated land around the dump;and Cd,Zn,and Mo in the cultivated land around the tailings pond.The pollution index analysis provides a basic overview of soil heavy-metal pollution across the entire mining area.However,content analysis of heavy-metal forms/states better reflects the relationship between the availability of heavy metals in the soil and the effectiveness of plants.Thus,the latter analysis can help ensure that phytoremediation strategies are adequately targeted,science-based,and effective.展开更多
Iron deficiency anemia(IDA)is a major global health problem.Tegillarca granosa has been considered as an excellent source of iron given its high content of iron-binding protein,ferritin.The aim of the present study wa...Iron deficiency anemia(IDA)is a major global health problem.Tegillarca granosa has been considered as an excellent source of iron given its high content of iron-binding protein,ferritin.The aim of the present study was to determine the physicochemical properties,protein structures,and iron uptake of ferritin extracted from T.granosa,and to evaluate the potential impacts of chitosan glycosylation on these characteristics.Based on Box-Behnken design and response surface methodology,the optimal conditions for glycosylation included a ferritin/chitosan mass ratio of 4:1,a pH of 5.5,a reaction time of 10 min,and a reaction temperature of 50℃.Glycosylation caused decreased surface hydrophobicity and elevated water-holding capacity of ferritin due to the introduction of hydrophilic groups.Additionally,glycosylation improved antioxidant capacity of ferritin by 20.69%–189.66%,likely owing to the protons donated by saccharide moiety to terminate free radical chain reaction.The in vitro digestibility of ferritin was elevated by 22.56%–104.85%after glycosylation,which could be associated with lessβ-sheet content in secondary structure that made the glycosylated protein less resistant to enzymatic digestion.The results of the iron bioavailability in Caco-2 cells revealed that ferritin(78.85–231.77 ngmg^(−1))exhibited better iron bioavailability than FeSO4(51.48–114.37 ngmg^(−1))and the values were further elevated by glycosylation with chitosan(296.23–358.20 ngmg^(−1)),which may be related to the physicochemical properties of ferritin via glycosylation modification.These results provide a basis for the development of T.granosa derived ferritin and its glycosylated products,and can promote the utilization of aquatic resources.展开更多
文摘BACKGROUND Itraconazole is a broad-spectrum triazole antifungal inhibiting fungal growth by inhibiting ergosterol synthesis and exhibits a nonlinear pharmacokinetic profile.Erratic absorption pattern with wide fluctuations in blood levels causes inconsistent and unpredictable clinical behaviour of this drug despite its low minimum inhibitory concentration(MIC)as compared to other antifungal agents.AIM To compare the oral bioavailability and bioequivalence of Fixtral SB(supra bioavailable itraconazole)with reference product R2(supra bioavailable 2×50 mg itraconazole).METHODS The study population consisted of 54 healthy volunteers,aged between 18-45 years and randomized to receive a single oral dose of either test[T;Fixtral SB(supra bioavailable itraconazole)100 mg]or reference product(R1;Sporanox 100 mg×2 capsules and R2;Lozanoc capsules 50 mg×2 capsules).Blood samples were taken pre-dose and post-dose up to 96 h.The study evaluated bioequivalence by comparing the oral bioavailability of the test product with reference product R2.The pharmacodynamic characteristics of the drug were evaluated by comparing the test product with reference product R1.Pharmacokinetics(PK)-PD comparative analysis[area under the concentration-time curve(AUC)/minimum inhibitory concentration(MIC)>25]was performed for conventional itraconazole 100 mg and supra bioavailable itraconazole 50 mg.Adverse events(AEs)assessments were performed in each study period and post-study evaluation.RESULTS Statistical analysis of primary PK variables revealed bioequivalence,with confidence intervals being completely inside the acceptance criteria of 80%-125%.The peak concentration levels of itraconazole were achieved at 10 h(T)and 8.5 h(R2),respectively.Pharmacodynamic parameter assessment showed that AUC/MIC for R1 are comparable to Fixtral SB 100mg for MIC levels up to 16mcg/mL(P>0.05 and observed P=0.3196).Six AEs were observed that were mild to moderate in severity and resolved.No severe AE was reported.CONCLUSION Test product itraconazole Capsule 100 mg is bioequivalent with the reference product(R2)at 100 mg dose(2 capsules of Lozanoc®50 mg)under fed conditions.Pharmacodynamics activity in terms of AUC/MIC is comparable between the test product at 100 mg dose and marketed itraconazole 200 mg.Fixtral SB is expected to have therapeutically similar efficacy at half the equivalent dose.Tested formulations were found to be safe and well tolerated.
文摘Although low testosterone levels in men have been associated with high risk for cardiovascular disease, little is known about the association between male sex hormones and subclinical coronary disease in men with apparently low cardiometabolic risk. This study was performed to investigate the association between male sex hormones and subclinical coronary artery calcification measured as coronary calcium score in non-obese Korean men. We examined the relationship of total testosterone, sex hormone-binding globulin, bioavai lable testosterone and free testosterone with coronary calcium score in 291 non-obese Korean men （mean age： 52.8--- 9.3 years） not having a history of cardiovascular disease. Using multiple linear regression, we evaluated associations between log （sex hormone） levels and log （coronary calcium score） after adjusting for confounding variables in 105 men with some degree of coronary calcification defined as coronary calcium score ~〉 1. In multiple linear regression analysis, bioavailable testosterone was inversely associated with coronary calcium score （P=0.046） after adjusting for age, body mass index, smoking status, alcohol consumption, regular exercise, mean blood pressure, resting heart rate, C-reactive protein, fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein （HDL） cholesterol, hypertension medication and hyperlipidernia medication, whereas total testosterone, sex hormone-binding globulin and free testosterone were not （P=0.674, P=O. 121 and P=O. 102, respectively）. Our findings indicate that bioavailable testosterone is inversely associated with the degree of subclinical coronary artery calcification in non-obese men.
文摘Various forms of phosphorus (P) could become bioavailable such as from desorption, dissolution and enzymatic hydrolysis. Potential bioavailable P estimation is critical to minimize eutrophication in freshwater systems. Thus, this study was conducted to predict potential bioavailable P in the water columns and sediments and their relations with enzymatic hydrolysis, and estimate impacts of land use and anthropogenic activities on P bioavailability, P transport and water quality in the Bronx River, New York, USA. In sediment samples collected in 2006, total P (TP), total inor-ganic P (IP), total organic P (OP) and bioavailable P (BAP) were in highest concentrations in sites located at Bronx River Valley upstream in Westchester (site 2), Troublesome Brook (TB, site 4), Sprain Brook (SB, site 7b) and Bronx River estuary near Sound View Park (site 14) respectively. Also, phosphodiesterase and native phosphatases (PDEase and NPase) hydrolyzed distinguishingly high amounts of OP or enzymatically hydrolysable P (EHP) in samples from sites 4, 7b, 10 (New York Botanical Garden) and 14. Microbial P was in negative values (caused by different bacteria and microorganisms could not be paralyzed by chloroform), and the most negative concentrations were appeared at sties 4 and 14. Spatial comparisons among different locations showed distinguished characteristics in tributaries and estuary. In sediments collected in 2007, TP, BAP and IP were in highest concentrations at sites 7-SB, 11-Bronx Zoo, 12-East Tremont Ave Bridge where fresh and saline water meets, 13-estuary facing Hunts Point Waste Water Treatment Plant (HP WWTP) and 14-estuary along Sound View Park. Besides, PDEase-P highest concentrations ap-peared at sties 7, 13 and 11, NPase-P concentrations were highest at 7 and 11. Microbial P was highest at sties 11 and 14. Spatial variations showed that higher P content and more intense enzymatic hydrolysis in silty clay finer sediments at site 7, 11 and 13. Temporal variations between the two years’ data showed land use and other anthropogenic factors’ impacts on P transport in river and deposit in sediments. Analysis of the river water samples showed that average soluble reactive P (SRP, 67 μg.l-1) in 2006 and SRP (68μg.l-1) in 2007 both were greater than background P concentration in most natural water (42 μg.l-1).
基金Supported by the Natural Science Foundation of Hainan Province(411102)the Scientific Research Innovation Project for College Graduates of Hainan Normal University(Hsyx2015-33)the College Students Science and Technology Innovation Project in Hainan Province(cxcyxj2017016)
文摘[Objectives] The research was conducted to study characteristics of bioavailable levels pollution of heavy metals in the surface soil of the lead-zinc mine in Changhua.[Methods] A total of 56 surface samples were collected from the 3 study zones （peripheral zone, reclamation zone and tailing zone） located at the lead-zine mine in Changhua. Based on total and bioavailable heavy metals （Pb, Zn, Cu and Cd） in soils, the correlation of total content with bioavailable content was analyzed, and their pollution characteristics were assessed by methods of single factor pollution index, Nemerow pollution index, geological accumulation index and potential ecological risk index.[Results] （i） The surface soils were polluted by Pb, Zn, Cu, Cd in different degrees, and the overall trend of the contents of the 4 heavy metals was in order of Cd 〉 Pb 〉 Zn 〉 Cu. The average excess multiple of heavy metals of total and bioavailable content in soils were in the order of peripheral zone 〉 tailing zone 〉 reclaimed zone, and their pollution degrees were tailing zone 〉 peripheral zone 〉 reclaimed zone. （ii） In general, the total and bioavailable contents of Pb, Zn, Cu, Cd showed a significant correlation, but were not correlated in each study zone. （iii） Pollution degrees of the study zones were in the order of tailing zone 〉 peripheral zone 〉 reclamation zone. The pollutions of heavy metals Pb and Cd were more serious, especially Cd reached high levels of pollution degree, and the pollution degrees of Zn, Cu were lighter. Contributors of ecological risk were mainly Cd, Pb and Cu, and the contribution of Cd achieved more than 90 %, making it the main source of pollution.[Conclusions] The results not only revealed the pollution status of heavy metals in the surface soil of the abandoned coal mine, but also could provide scientific guidance for reasonable utilization and ecological recovery of the land.
文摘The bioavailability of selenium(Se)from ground beef has been previously found in this laboratory to be greater than that of selenite or selenate when fed to female Fischer 344 rats(B. Shi,J.E.Spallholz,J Am Coil Nutr,13:95￣101,1994).In the present study we examined the bioavailability of Se from various commercial portions of beef,the liver,striploin,round, shoulder and brisket.All beef was cooked, freeze-dried,finely powdered and mixed with the other dietary ingredients.The experimental diets were fed to the weanling Fischer 344 rats which had been subjected to dietary depletion of Se for 6 weeks.The bioavailability of Se from the beef diets was compared with that of Se as se lenite or L-seienomethionine(SeMet)added to torula-yeast diets.Each experimental diet contained 0'10mg Se/kg.After 8 weeks of dietary Se repletion,relative activity of liver glutathione peroxidase (EC 1.11.1.9;GSHPx) from the different dietary groups colllpared with that of control animals(100%)was(%):selenite 91,SeMet 122 (P<0.05),liver 108, striploin 105,round 106, shoulder 106,brisket 103.Se recovery in liver was generally highest from SeMet>beef muscle=beef liver>selenite.Muscle tissue deposition of Se was highest from SeMet>beef muscle>selenite=beef liver.In addition, the feeal excretion of Se was lowest from the SeMet dietary group and highest from the selenite dietary group.The experimetal results suggest that all cuts of beef appear to be highly bioavailable sources of dietary Se when compared with selenite or L-SeMet.
文摘Inflammatory bowel disease(IBD)is a nonspecific inflammatory disease of the intestine that includes Crohn’s disease and ulcerative colitis.Because IBD is difficult to heal and easily relapses,it could worsen patient quality of life and increase economic burdens.Curcumin(CUR)is a bioactive component derived from the rhizome of turmeric(Curcuma longa).Many basic and clinical studies have shown that CUR can efficiently treat IBD by decreasing the activity of proinflammatory cytokines by communicating with transcription factors and signaling molecules.However,due to the limitations of being almost insoluble in aqueous solutions and having low oral bioavailability,it is important to select appropriate pharmaceutical preparations.
基金supported by the National Basic Research Program of China (973 Program,Grant No.2008CB418203)the National Science and Technology Specific Project of China (Grant No.20080ZX07422-005)
文摘Experiments on Phosphorus （P） fraction characteristics in sediment resuspension were performed under adequate hydrodynamic conditions. It is found that the concentration of Suspended Particulate Matter （SPM） in the eddy current region exhibits the ＂Matthew effect＂. Velocity is an impact factor of the Equilibrium Phosphate Concentration （EPC）, which is related to other hydraulic conditions. Overall bioavailable dissolved P in the SPM causes migration to overlying water and sediment, eventually being converted into a chemical speciation of P. Conditions of resuspension promote A1-P of SPM that migrated to the sediment and water. Concentrations of A1-P in SPM are reduced. P is released from SPM to water bodies, mainly through conversion into particulate P and dissolved total P. Meanwhile, exchange between SPM and sediments occur mainly through Ca-P migration. A1-P and BD-P possess similar geochemical characteristics or source. Ca-P and A1-P exhibit a negative correlation between migration and conversion.
基金sponsored by the National Natural Science Foundation China(32270115)National Key R&D Program of China(2018YFD0901102)+1 种基金Fundamental Research Funds for the Provincial Universities of Zhejiang(SJLY2021015)K.C.Wong Magna Fund of Ningbo University。
文摘Hyperuricemia,a metabolic disorder related to uric acid metabolism dysregulation,has become a common metabolic disease worldwide,due to changes in lifestyle and dietary structure.In recent years,owing to their high activity and few adverse effects,food-derived active peptides used as functional foods against hyperuricemia have attracted increasing attention.This article aims to focus on the challenge associated with peptide-specific preparation methods development,functional components identification,action mechanism(s)clarification,and bioavailability improvement.The current review proposed recent advances in producing the food-derived peptides with high anti-hyperuricemia activity by protein source screening and matched enzymatic hydrolysis condition adjusting,increased the knowledge about strategies to search antihyperuricemia peptides with definite structure,and emphasized the necessity of combining computer-aided approaches and activity evaluations.In addition,novel action mechanism mediated by gut microbiota was discussed,providing different insights from classical mechanism.Moreover,considering that little attention was paid previously on the structure-activity relationships of anti-hyperuricemia peptides,we collected the sequences from published studies and make a preliminary summary about the structure-activity relationships,which in turn provided guides for enzymatic hydrolysis optimization and bioavailability improvement.Hopefully,this article could promote the development,application and commercialization of food-derived anti-hyperuricemia peptides in the future.
基金funded by Jiangsu Shuang Chuang Tuan Dui program (JSSCTD202147)Jiangsu Shuang Chuang Ren Cai program (JSSCRC2021541)+1 种基金Young Elite Scientists Sponsorship Program by CAST (2022QNRC001)the Initiation Funds of Yangzhou University for Distinguished Scientists
文摘Background Our previous studies demonstrated that divalent organic iron(Fe)proteinate sources with higher complexation or chelation strengths as expressed by the greater quotient of formation(Qf)values displayed higher Fe bioavailabilities for broilers.Sodium iron ethylenediaminetetraacetate(NaFeEDTA)is a trivalent organic Fe source with the strongest chelating ligand EDTA.However,the bioavailability of Fe when administered as NaFeEDTA in broilers and other agricultural animals remains untested.Herein,the chemical characteristics of 12 NaFeEDTA products were determined.Of these,one feed grade NaFeEDTA(Qf=2.07×10^(8)),one food grade NaFeEDTA(Qf=3.31×10^(8)),and one Fe proteinate with an extremely strong chelation strength(Fe-Prot ES,Qf value=8,590)were selected.Their bioavailabilities relative to Fe sulfate(FeSO_(4)·7H_(2)O)for broilers fed with a conventional corn-soybean meal diet were evaluated during d 1 to 21 by investigating the effects of the above Fe sources and added Fe levels on the growth performance,hematological indices,Fe contents,activities and gene expressions of Fe-containing enzymes in various tissues of broilers.Results NaFeEDTA sources varied greatly in their chemical characteristics.Plasma Fe concentration(PI),transferrin saturation(TS),liver Fe content,succinate dehydrogenase(SDH)activities in liver,heart,and kidney,catalase(CAT)activity in liver,and SDH mRNA expressions in liver and kidney increased linearly(P<0.05)with increasing levels of Fe supplementation.However,differences among Fe sources were detected(P<0.05)only for PI,liver Fe content,CAT activity in liver,SDH activities in heart and kidney,and SDH mRNA expressions in liver and kidney.Based on slope ratios from multiple linear regressions of the above indices on daily dietary analyzed Fe intake,the average bioavailabilities of Fe-Prot ES,feed grade NaFeEDTA,and food grade NaFeEDTA relative to the inorganic FeSO_(4)·7H_(2)O(100%)for broilers were 139%,155%,and 166%,respectively.Conclusions The bioavailabilities of organic Fe sources relative to FeSO_(4)·7H_(2)O were closely related to their Qf values,and NaFeEDTA sources with higher Qf values showed higher Fe bioavailabilities for broilers fed with a conventional corn-soybean meal diet.
基金supported by the National Natural Science Foundation of China(82274313)Key R&D Program of Shaanxi Province(2023GHZD43).
文摘Boswellic acids is a general term for a series of pentacyclic triterpenoid compounds that are isolated from the oleogin resin of the Boswellia genus and serve as the main active ingredient.It exhibits a wide range of biological activities,such as anti-inflammatory,anti-cancer,antibacterial,antiviral,hepatoprotective,neuroprotective,anti-diabetic,and anti-thrombotic properties.As a result,it has gained significant recognition among practitioners of traditional Chinese and Indian medicine.These biological effects may be associated with multiple molecular targets and signal transduction pathways.However,the poor pharmacokinetic properties of the substance lead to lower bioavailability,which affects its effectiveness.To address this issue,scientists have proposed a number of strategies,such as solid dispersions,phytosome®technologies,and novel drug delivery systems.This article aims to provide a comprehensive overview for boswellic acids on the phytochemistry,molecular mechanisms,potential therapeutic applications,and strategies to improve bioavailability.
文摘Background: Bioenhancers augment the bioavailability of co-administered molecules without showing any significant effect on their own. Piperine, an alkaloid from Piper nigrum, is an established natural bioenhancer. Nicotinamide mononucleotide (NMN), an antiaging supplement, is the precursor of coenzyme nicotinamide adenine dinucleotide (NAD) that plays an important role in intracellular redox reactions. Objective: The study compared the serum concentrations of NAD in normal healthy participants, supplemented with NMN 500 mg and NMN 500 mg + 5 mg BioPerine® (95% piperine). Methods: In a randomized, open-label, crossover study, NMN (500 mg) was compared to NMN + BioPerine® (500 mg + 5 mg) in 6 healthy adults, aged 18 - 45 years. The participants received a single oral dose of NMN or NMN + BioPerine® capsules with 240 mL water, and blood samples were collected over 8hr. After a 4-day washout period, the same procedures were repeated as per the crossover design. Total NAD (NADtotal), including oxidized NAD (the oxidized) and its reduced form NADH, was measured in human serum samples. Results: The maximum concentration (Cmax) of NAD in serum was higher with NMN + BioPerine® (282 pmol/mL) compared to NMN (246 pmol/mL) alone. In the presence of BioPerine®, the NAD concentrations reached 257 pmol/mL during the first 2 hr, whereas a comparable serum concentration (246 pmol/mL) was attained only after 6 hr in NMN alone. The AUC0-8hr was 1738 pmol/mL/hr in NMN compared to 2004 pmol/mL/hr in NMN+ BioPerine®. The time to reach peak concentration (t1/2) was similar (6hr) in both groups. No clinically relevant adverse events (AE) were observed, and safety parameters remained within normal ranges in all the participants with both formulations. Conclusion: These results reveal that BioPerine® can effectively increase the NAD concentrations in the serum following NMN supplementation in healthy volunteers. The present study was registered prospectively with the Clinical Trials Registry-India (CTRI/2023/11/059982).
文摘Particulate matter (PM10) deposited as road dust is considered an important source of contamination from atmosphere. However, there are limited studies on the toxicity of road dust as such on different organisms. This study evaluates the toxicity of road dust using different extraction scenarios on Daphnia magna and Artemia salina as aquatic organisms and also on Prosopis cineraria and Vachellia tortilis as local plant species. Chemical analysis of different extracts shows considerable amount of trace metals, however the trace metals in the dust extract associated with suspended sediment were not absorbed by the receptors. On the other hand, the concentration of trace metals in the artificial mixture was found bioavailable and absorbed causing a high percentage of mortality. In the plant assay, significant difference was obtained in the germination percentage between the control and three different extraction exposures in both plant species. The mean root length of P. cineraria and V. tortilis were higher in 20% and 50% extracts than the control probably due to the availability of nutrients from the dust extract. Interestingly however, the seedling vigor index was the opposite with higher index in the control and lower in dust extracts that contain heavy metals.
文摘In recent years, metabolic syndrome has been a growing health concern across the world. The role of nutraceuticals and functional foods in this area has a significant place due to the adverse effects of contemporary modes of treatment. CurCousin<sup>®</sup> is a nutritional ingredient containing bioactive Calebin A, (analog of Curcumin) with self-affirmed GRAS status. CurCousin<sup>®</sup> has been a clinically studied dietary supplement ingredient with a positive impact on body weight, lipid levels and metabolic health. Bioenhancers play an important role in increasing the bioavailability of the active in turn enhancing efficacy as well as reducing the dosage required to achieve the therapeutic effect. This study investigated the possible pharmacokinetic interaction between CurCousin<sup>®</sup> at two different doses (2.25 and 4.5 mg/kg) in the presence and absence of BioPerine<sup>®</sup> (0.27 mg/kg), a natural bioenhancer in Sprague-Dawley rats. The results revealed that the addition of BioPerine<sup>®</sup> into CurCousin<sup>®</sup> (2.25 mg/kg) half the dose when administered enhances the bioavailability and was equipotent to CurCousin<sup>®</sup> (4.5 mg/kg) double the dose without BioPerine<sup>®</sup>. Thus, leading to future clinical studies to evaluate its improved pharmacological efficacy as well as reduced therapeutic dosage.
文摘The review provides an overview of the approaches, applications, and methods for ester prodrugs. Ester prodrugs are pharmacologically inactive compounds in their original form but become active drugs on biotransformation within the body, which offers advantages concerning the solubility, stability, and targeted delivery of the active drug. Several approaches of ester prodrugs have been reviewed in this review, including simple ester prodrugs, amino acid ester prodrugs, sugar ester prodrugs, lipid ester prodrugs, and polymeric ester prodrugs. This review incorporates in vitro and in vivo methods as well as the characterization of physical and chemical properties for ester prodrugs, cell culture systems, enzymatic assays, and animal models—all of these having a very important bearing on the evaluation of stability, bioavailability, and efficacy for ester prodrugs. While the benefits of using ester prodrugs are significant, there are also disadvantages like instability, poor or variable enzymatic hydrolysis, and toxicity from released promoieties or by-products. This review discusses solutions to the various limitations that include enhancing stability with ionizable promoieties and using physiologically-based pharmacokinetic modeling. The review also highlights the application of ester prodrugs in neurological disorders, such as Parkinson’s disease, and the ongoing efforts to address the critical limitations in treatment efficacy. Future prodrug strategies are poised to advance significantly by harnessing diverse transport mechanisms across the blood-brain barrier and integrating nanotechnology.
文摘Curcumin is a widely studied natural compound which has shown tremendous in vitro therapeutic poten- tial. Despite that, the clinical efficacy of the native curcumin is weak due to its low bioavailability and high metabolism in the gastrointestinal tract. During the last decade, researchers have come up with dif- ferent formulations with a focus on improving the bioavailability of curcumin. As a result, a significant number of bioavailable curcumin-based formulations were introduced with the varying range of enhanced bioavailability. The purpose of this review is to collate the published clinical studies of cur- cumin products with.improved bioavailability over conventional （unformulated） curcumin. Based on the literature search, 11 curcumin formulations with available human bioavailability and pharmacokinet- ics data were included in this review. Further, the data on clinical study design, analytical method, phar- macokinetic parameters and other relevant details of each formulation were extracted. Based on a review of these studies, it is evident that better bioavailability of formulated curcumin products is mostly attrib- uted to improved solubility, stability, and possibly low first-pass metabolism. The review hopes to provide a quick reference guide for anyone looking information on these bioavailable curcumin formulations. Based on the published reports, NovaSol （185）, CurcuWin （136） and LongVida （100） exhibited over 100-fold higher bioavailability relative to reference unformulated curcumin. Suggested mechanisms accounting for improved bioavailability of the formulations and details on the bioanalysis methods are also discussed.
基金Supported by the National Council of Research (CNR), Italy
文摘The method to remove bioavailable amounts of heavy metals from a contaminated soil by using plants is defined as bioavailable contaminant stripping （BCS） and could safely be applied if the soil＇s long-term ability to replenish the bioavuilable pool is known. The aim of this study was to evaluate the ability of three common plant species selected, Brassica juncea, Poa annua, and Helianthus annus, to remove bioavailable amounts of mercury （Hg） from a contaminated industrial soil containing 15.1 mg kg-1 Hg. Trials were carried out under greenhouse conditions using pots （mesocosms）. According to the precautionary principle, we modified the BCS remediation approach by adding a new step, in which mercury bioavailability was increased by the addition of a strong mobilizing agent, ammonium thiosulphate, （NH4）28203, to obtain an estimate of the likely long-term bioavailable Hg pool. The modified BCS remediation approach was called enhanced bioavailable contaminant stripping （EBCS）. After one growth cycle, nearly all the bioavailable mercury （95.7%） was removed and the metal remaining in the soil was considered inert since it was neither extractable by （NH4）2S2O3 nor taken up by plants during a second growth cycle. The results demonstrated that EBCS appeared promising since it removed the most dangerous metal forms while substantially shortening the cleanup time.
基金supported by the National Natural Science Foundation of China(32060541).
文摘Taxifolin loaded zein-caseinate nanoparticles(TZP)were fabricated by the anti-solvent method and were used as an oral delivery vehicle to improve their bioavailability in the rat.The formulations of TZP were optimized.With mass ratio of 1:1:2 between taxifolin,zein and sodium caseinate,the particle size andζpotential of TZP were(168.74±0.35)nm and−(57.67±0.25)mV,while the encapsulation and loading efficiency of taxifolin were(85.83±0.89)%and(17.11±0.88)%,respectively.After freeze-drying,TZP exhibited excellent redispersibility in water without aggregation.Physicochemical characterization showed that taxifolin existed in amorphous form in TZP and its interaction with the protein was observed.After encapsulating in TZP,the excellent dispersion of taxifolin in water signifi cantly improve its diffusion velocity through a semipermeable membrane.After oral administration,taxifolin and its 5 metabolites were identifi ed in rat plasma by ultra high performance liquid chromatography(UPLC)with quadrupole time-of-flight mass spectrometry(UPLC-QTOF-MS).The dynamic variation of taxifolin and its metabolites in plasma were then quantifi ed by UPLC with a triple-quadrupole typemass spectroscopy(UPLC-QqQ-MS/MS).A pharmacokinetic study showed that the bioavailability of taxifolin increased from 0.35%to 0.52%through TZP fabrication.The plasma concentration of taxifolin glucuronide and methylated taxifolin glucuronide was much higher than taxifolin.Glucuronidation was the dominating metabolism pathway of taxifolin in vivo.
基金Supported by the National Natural Science Foundation of China (Nos.42176137,81872906)the Nantong Science and Technology Project (No.MS12021037)+2 种基金the STS Program of Chinese Academy of Sciences (No.KFJ-STS-QYZD-195)the K.C.Wong Education FoundationCAS。
文摘The brown seaweed,Sacchairna japonica,has been used in traditional Chinese medicine for over one thousand years.Oral administration of fucoidan or low molecular weight fucoidan(LMWF)from S.japonica could ameliorate kidney dysfunction in chronic kidney diseases and inhibit diabetic vascular complications.In many studies,LMWF was found to be more potent than fucoidan with high molecular weight.However,the pharmacokinetics of LMWF still remains unclear.The purpose of the research is to compare the pharmacokinetics of fucoidan with high molecular weight(136 kDa)with that low molecular weight(9.5 kDa)after oral administration to ICR mice.Since fucose is the main and representative monosaccharide of fucoidans,we evaluate the pharmacokinetics of fucoidan and LMWF by determining the fucose concentration in mice serum.Both fucoidan and LMWF were absorbed following oral administration.Fucoidan and LMWF were provided to mice by oral administration with 60 mg/kg and the maximum Concentration(C_(max))was found at 2.5 h(0.66±0.32 mg/L)for Fucoidan and 1.5 h(1.01±0.56 mg/L)for LMWF,respectively.It seems that LMWF had a higher area under the curve(AUC_(0–t))and was absorbed more quickly than fucoidan.The estimated bioavailability of LMWF was28.3%in the mice treated with a single dose of 30 mg/kg.In addition,LMWF was found widely spreaded into different tissues following oral administration and the highest concentration was found in kidney at 19.93±7.02μg/g.In this study,we first studied the pharmacokinetics of LMWF,in order to help to understand the function of LMWF.And our results shed light on the potential of development of drugs based on LMWF.
基金financially supported by the National Natural Science Foundation of China (51504066).
文摘In a single sample plot,the total amount of heavy metals in the soil could not necessarily reflect the contents of their effective states.This must be considered when attempting to determine the degree of soil heavy-metal pollution in an area.In the present study,the soil around the molybdenum mining area in Huludao,China,was surveyed and sampled to evaluate soil heavy-metal pollution using the Nemerow multifactor pollution index method.The Tessier continuous extraction method was used to analyze the distribution of heavy-metal forms'and their content changes in the soil of this area.Thus,the bioactivity of heavy metals in the soil,the absorption of heavy metals by plants,and the distribution of heavy metals in plants were explored to provide data supporting the use of phytoremediation technology to treat the heavy-metal pollution in the molybdenum mining area and develop ecological restoration strategies for the area's wastelands.The pollution index results indicate that heavy-metal pollution in the soil around the tailings pond is severe,mainly due to Pb and Zn heavy metals.Heavy-metal pollution in the surrounding land is mainly due to Cd and Zn.Content analysis of the heavy-metal forms/states in soils shows that exchangeable forms,which are most effective and toxic to plants,of the following metals are highest in the following areas:Cd,Cu,and Zn in the mountains around the stope;Zn,Mo,and Cu in the cultivated land around the dump;and Cd,Zn,and Mo in the cultivated land around the tailings pond.The pollution index analysis provides a basic overview of soil heavy-metal pollution across the entire mining area.However,content analysis of heavy-metal forms/states better reflects the relationship between the availability of heavy metals in the soil and the effectiveness of plants.Thus,the latter analysis can help ensure that phytoremediation strategies are adequately targeted,science-based,and effective.
基金supported by the National Key R&D Program of China(No.2018YFD0901105).
文摘Iron deficiency anemia(IDA)is a major global health problem.Tegillarca granosa has been considered as an excellent source of iron given its high content of iron-binding protein,ferritin.The aim of the present study was to determine the physicochemical properties,protein structures,and iron uptake of ferritin extracted from T.granosa,and to evaluate the potential impacts of chitosan glycosylation on these characteristics.Based on Box-Behnken design and response surface methodology,the optimal conditions for glycosylation included a ferritin/chitosan mass ratio of 4:1,a pH of 5.5,a reaction time of 10 min,and a reaction temperature of 50℃.Glycosylation caused decreased surface hydrophobicity and elevated water-holding capacity of ferritin due to the introduction of hydrophilic groups.Additionally,glycosylation improved antioxidant capacity of ferritin by 20.69%–189.66%,likely owing to the protons donated by saccharide moiety to terminate free radical chain reaction.The in vitro digestibility of ferritin was elevated by 22.56%–104.85%after glycosylation,which could be associated with lessβ-sheet content in secondary structure that made the glycosylated protein less resistant to enzymatic digestion.The results of the iron bioavailability in Caco-2 cells revealed that ferritin(78.85–231.77 ngmg^(−1))exhibited better iron bioavailability than FeSO4(51.48–114.37 ngmg^(−1))and the values were further elevated by glycosylation with chitosan(296.23–358.20 ngmg^(−1)),which may be related to the physicochemical properties of ferritin via glycosylation modification.These results provide a basis for the development of T.granosa derived ferritin and its glycosylated products,and can promote the utilization of aquatic resources.
