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1.
Ecotoxicol Environ Saf ; 277: 116378, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38663191

RESUMO

Pesticide residues and microplastics (MPs) in agricultural soils are two major concerns for soil health and food safety. The degradation of chlorpyrifos (CPF), an organophosphorus pesticide, releases phosphates. This process may be affected by the presence of MPs in the soil. The combination of CPF and MPs presence in the soil may thus produce interaction effects that alter the soil phosphorus (P) balance. This study explores the degradation pathways of CPF (6 mg kg-1, 12 mg kg-1 of CPF addition) in soils with different levels of polylactic acid MPs (PLA-MPs) (0.0 %, 0.1 %, 0.5 %, 1.0 % w/w), and analyzes soil P fractions and phosphatase enzyme activities to investigate soil P bioavailability under different treatments. Results show that the degradation of CPF fits to a first-order decay model, with half-lives (DT50) ranging from 11.0 to 14.8 d depending on PLA-MPs treatment. The concentration of its metabolite 3, 5, 6-trichloropyridine 2-phenol (TCP) reached a peak of 0.93-1.67 mg kg-1 within 7-14 days. Similarly, the degradation of CPF led to a significant transient increase in P bioavailability within 3-7 days (p < 0.05), with a peak range of 22.55-26.01 mg kg-1 for Olsen-P content and a peak range of 4.63-6.76 % for the proportions of available P fractions (H2O-P+NaHCO3-P+NaOH-P), before returning to prior levels (Olsen-P: 11.28-19.52 mg kg-1; available soil P fractions: 4.15-5.61 %). CPF degradation (6 mg kg-1) was significantly inhibited in soil with 1.0 % PLA-MPs addition. The effects of MPs and CPF on soil P fractions occur at different time frames, implying that their modes of action and interactions with soil microbes differ.

2.
Food Chem ; 451: 139271, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38663245

RESUMO

Lightly milled rice is a healthier choice compared to refined white rice. In this study, the effects of variety, cooking equipment and pretreatment method on the quality of six varieties of lightly milled rice from China after cooking was investigated through physics, chemistry and instrumental analysis method. Nanjing-No.5055 has the best eating quality, Xiadao-No.1 has higher appearance score, and Fengliangyouxiang-No.1 has the lowest glycemic index. Compared with microwave oven and electric cooker, steamer has a more significant positive impact on component retention, eating quality and sensory quality, but the former has lower cooking time and higher glycemic index. Soaking can effectively improve the water absorption rate, thus reducing hardness. Cleaning affects component retention but is beneficial for sensory quality. The most obvious variation in organizational structure can be observed in the steamer and soaking processes. These findings could serve as a valuable reference for the processing of lightly milled rice.

3.
Pulm Pharmacol Ther ; : 102299, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38663512

RESUMO

INTRODUCTION: Use of propellants with high global warming potential (such as HFA-134a) for pressurised metered-dose inhalers (pMDIs) is being phased down. Switching to dry-powder inhalers may not be clinically feasible for all patients; an alternative is reformulation using propellants with low global warming potential. The combination of beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB) is available for asthma or chronic obstructive pulmonary disease via pMDI using HFA-134a as propellant. This is being reformulated using the low global warming potential propellant HFA-152a. This manuscript reports three studies comparing BDP/FF/GB pharmacokinetics delivered via pMDI using HFA-152a vs HFA-134a. METHODS: The studies were four-way crossover, single-dose, randomised, double-blind, in healthy volunteers. In Studies 1 and 2, subjects inhaled four puffs of BDP/FF/GB (Study 1: 100/6/12.5 µg [medium-strength BDP]; Study 2: 200/6/12.5 µg [high-strength]), ingesting activated charcoal in two of the periods (once per propellant). In Study 3, subjects inhaled medium- and high-strength BDP/FF/GB using a spacer. All three studies compared HFA-152a vs HFA-134a in terms of lung availability and total systemic exposure of beclometasone-17-monopropionate (B17MP; active metabolite of BDP), BDP, formoterol and GB. Bioequivalence was concluded if the 90% confidence intervals (CIs) of the ratios between formulations of the geometric mean maximum plasma concentration (Cmax) and area under the plasma concentration-time curve between time zero and the last quantifiable timepoint (AUC0-t) for the analytes were between 80-125%. RESULTS: In Studies 1 and 2, systemic exposure bioequivalence (i.e., comparisons without charcoal block) was demonstrated, except for GB Cmax in Study 2 (upper 90% CI 125.11%). For lung availability (i.e., comparisons with charcoal block), B17MP and formoterol demonstrated bioequivalence in both studies, as did BDP in Study 2; in Study 1, BDP upper CIs were 126.96% for Cmax and 127.34% for AUC0-t). In Study 1, GB AUC0-t lower CI was 74.54%; in Study 2 upper limits were 135.64% for Cmax and 129.12% for AUC0-t. In Study 3, the bioequivalence criteria were met for BDP, B17MP and formoterol with both BDP/FF/GB strengths, and were met for GB AUC0-t, although not for Cmax. Both formulations were similarly well tolerated in all three studies. CONCLUSIONS: Overall, while formal bioequivalence cannot be concluded for all analytes, these data suggest therapeutic equivalence of the new formulation with the existing BDP/FF/GB pMDI formulation, therefore supporting reformulation using a propellant with low global warming potential.

4.
Sci Total Environ ; : 172637, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38663604

RESUMO

The interaction between pharmaceuticals and personal care products (PPCPs) with dissolved organic matter (DOM) can alter their bioavailability and toxicity. Nevertheless, little is known about how pH and DOM work together to affect the availability of PPCPs. This study investigated the impact of pH and DOM on the availability of seven PPCPs, namely Carbamazepine, Estrone, Bisphenol A, Testosterone Propionate, Triclocarban, 4-tert-Octylphenol and 4-n-Nonylphenol, using negligible depletion solid-phase microextraction (nd-SPME). The uptake kinetics of PPCPs by the nd-SPME fibers increased proportionally with DOM concentrations, likely due to enhanced diffusive conductivity in the unstirred water layer. At neutral pH, the partitioning coefficients of PPCPs for Humic Acid (log KDOC 3.87-5.25) were marginally higher than those for Fulvic Acid (log KDOC 3.64-5.11). Also, the log KDOC values correlated linearly with the log DOW (pH 7.0) values of PPCPs, indicating a predominant role for hydrophobic interactions in the binding of DOM and PPCPs. Additionally, specific interactions like hydrogen bonding, π-π, and electrostatic interactions occur for certain compounds, influenced by the polarity and spatial conformation of the compounds. For these ionizable PPCPs, the log DDOC values exhibit a strong dependence on pH due to the dual influence of pH on both DOM and PPCPs. The log DDOC values rose from pH 1.0 to 3.0, peaked at pH 5.0 to 9.0, and then (sharply) declined from 11.0 to 13.0. The reasons are that in strong acidic circumstances, the coiled and compressed shape of DOM inhibits the hydrophobic interaction, whereas in strong alkaline conditions, significant electrostatic repulsion reduces the sorption. This study reveals that the effects of DOM on the bioavailability of PPCPs are dependent on both pH and the specific compound involved.

5.
AAPS PharmSciTech ; 25(5): 91, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664316

RESUMO

Addressing poor solubility and permeability issues associated with synthetic drugs and naturally occurring active compounds is crucial for improving bioavailability. This review explores the potential of phospholipid complex formulation technology to overcome these challenges. Phospholipids, as endogenous molecules, offer a viable solution, with drugs complexed with phospholipids demonstrating a similar absorption mechanism. The non-toxic and biodegradable nature of the phospholipid complex positions it as an ideal candidate for drug delivery. This article provides a comprehensive exploration of the mechanisms underlying phospholipid complexes. Special emphasis is placed on the solvent evaporation method, with meticulous scrutiny of formulation aspects such as the phospholipid ratio to the drug and solvent. Characterization techniques are employed to understand structural and functional attributes. Highlighting the adaptability of the phospholipid complex, the review discusses the loading of various nanoformulations and emulsion systems. These strategies aim to enhance drug delivery and efficacy in various malignancies, including breast, liver, lung, cervical, and pancreatic cancers. The broader application of the drug phospholipid complex is showcased, emphasizing its adaptability in diverse oncological settings. The review not only explores the mechanisms and formulation aspects of phospholipid complexes but also provides an overview of key clinical studies and patents. These insights contribute to the intellectual and translational advancements in drug phospholipid complexes.


Assuntos
Antineoplásicos , Sistemas de Liberação de Medicamentos , Neoplasias , Fosfolipídeos , Fosfolipídeos/química , Humanos , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Solubilidade , Animais , Química Farmacêutica/métodos , Disponibilidade Biológica , Emulsões/química , Portadores de Fármacos/química , Composição de Medicamentos/métodos
6.
Food Sci Biotechnol ; 33(7): 1707-1714, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38623436

RESUMO

Attempts to improve low absorption and rapid metabolic conversion of curcumin were made by developing curcumin-loaded bilayer nanoliposomes coated with chitosan and alginate for intestinal-specific drug delivery. A curcumin-loaded nano-liposome was prepared with optimized formulations with phosphatidylcholine, curcumin, chitosan, and alginate. The particle size of the optimized formulation was approximately 400 nm, and the encapsulation efficiency was more than 99%. In the in vitro release study, curcumin release from the curcumin-loaded nanoliposome with double layers of chitosan/alginate (CNL-CH/AL) was suppressed in the simulated gastric fluid (SGF, pH 1.2) and enhanced in the simulated intestinal fluid (SIF, pH 6.8). In the in vivo pharmacokinetic study in rats, the CNL-CH/AL-treated group showed a prolonged absorption pattern of curcumin and the area under the plasma concentration-time curve from 0 to 24 h (AUC0-24) was improved 109-fold compared to the control group treated with a curcumin solution without a nanocarrier.

7.
Cureus ; 16(3): e56373, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38633979

RESUMO

Bariatric surgery is a commonly performed procedure for patients who have failed to achieve weight loss through medical and lifestyle interventions. However, the altered gastrointestinal anatomy resulting from the surgery can significantly impact the bioavailability of antidepressants in patients with generalized anxiety disorder, potentially leading to uncontrolled anxiety symptoms. This case report describes a patient with generalized anxiety disorder who underwent Roux-en-Y gastric bypass surgery and subsequently experienced increased anxiety symptoms due to poor antidepressant bioavailability. The patient's medication was adjusted to a sublingual formulation, resulting in improved anxiety control and reduced side effects. Healthcare providers should be aware of the potential impact of bariatric surgery on medication absorption and closely monitor patients with generalized anxiety disorder for potential psychiatric medication-related complications postoperatively. The use of alternative routes of administration, such as sublingual medication, may be beneficial in improving drug bioavailability and managing anxiety symptoms. Creating awareness in primary care offices about poor drug absorption and using alternatives such as the sublingual route of administration to achieve optimal systemic delivery requires a multifaceted approach involving education and training for healthcare providers as well as patient education to ensure they are informed and engaged in their own care. By implementing these strategies, primary care providers can improve patient outcomes and prevent unnecessary referrals to specialists.

8.
Cell Rep ; 43(4): 114101, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38613786

RESUMO

Syntaxin-1A (stx1a) repression causes a neurodevelopmental disorder phenotype, low latent inhibition (LI) behavior, by disrupting 5-hydroxytryptaminergic (5-HTergic) systems. Herein, we discovered that lysine acetyltransferase (KAT) 3B increases stx1a neuronal transcription and TTK21, a KAT3 activator, induces stx1a transcription and 5-HT release in vitro. Furthermore, glucose-derived CSP-TTK21 could restore decreased stx1a expression, 5-HTergic systems in the brain, and low LI in stx1a (+/-) mice by crossing the blood-brain barrier, whereas the KAT3 inhibitor suppresses stx1a expression, 5-HTergic systems, and LI behaviors in wild-type mice. Finally, in wild-type and stx1a (-/-) mice treated with IKK inhibitors and CSP-TTK21, respectively, we show that KAT3 activator-induced LI improvement is a direct consequence of KAT3B-stx1a pathway, not a side effect. In conclusion, KAT3B can positively regulate stx1a transcription in neurons, and increasing neuronal stx1a expression and 5-HTergic systems by a KAT3 activator consequently improves the low LI behavior in the stx1a ablation mouse model.


Assuntos
Modelos Animais de Doenças , Histona Acetiltransferases , Sintaxina 1 , Animais , Sintaxina 1/metabolismo , Sintaxina 1/genética , Camundongos , Histona Acetiltransferases/metabolismo , Histona Acetiltransferases/genética , Fenótipo , Neurônios/metabolismo , Serotonina/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout
9.
Int J Nanomedicine ; 19: 3611-3622, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660022

RESUMO

Background: Mangiferin (MA), a bioactive C-glucosyl xanthone with a wide range of interesting therapeutic properties, has recently attracted considerable attention. However, its application in biomedicine is limited by poor solubility and bioavailability. Carbon dots (CDs), novel nanomaterials, have immense promise as carriers for improving the biopharmaceutical properties of active components because of their outstanding characteristics. Methods: In this study, a novel water-soluble carbon dot (MC-CDs) was prepared for the first time from an aqueous extract of Moutan Cortex Carbonisata, and characterized by various spectroscopies, zeta potential and high-resolution transmission electron microscopy (HRTEM). The toxicity effect was investigated using the CCK-8 assay in vitro. In addition, the potential of MC-CDs as carriers for improving the pharmacokinetic parameters was evaluated in vivo. Results: The results indicated that MC-CDs with a uniform spherical particle size of 1-5 nm were successfully prepared, which significantly increased the solubility of MA in water. The MC-CDs exhibited low toxicity in HT-22 cells. Most importantly, the MC-CDs effectively affected the pharmacokinetic parameters of MA in normal rats. UPLC-MS analysis indicated that the area under the maximum blood concentration of MA from mangiferin-MC-CDs (MA-MC-CDs) was 1.6-fold higher than that from the MA suspension liquid (MA control) after oral administration at a dose of 20 mg/kg. Conclusion: Moutan Cortex-derived novel CDs exhibited superior performance in improving the solubility and bioavailability of MA. This study not only opens new possibilities for the future clinical application of MA but also provides evidence for the development of green biological carbon dots as a drug delivery system to improve the biopharmaceutical properties of insoluble drugs.


Assuntos
Disponibilidade Biológica , Carbono , Paeonia , Tamanho da Partícula , Ratos Sprague-Dawley , Solubilidade , Xantonas , Xantonas/farmacocinética , Xantonas/química , Xantonas/administração & dosagem , Animais , Carbono/química , Carbono/farmacocinética , Masculino , Ratos , Paeonia/química , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/administração & dosagem , Pontos Quânticos/química , Pontos Quânticos/toxicidade , Linhagem Celular , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Sobrevivência Celular/efeitos dos fármacos
10.
J Funct Biomater ; 15(4)2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38667568

RESUMO

As an essential nutrient, lutein (LUT) has the ability to aid in the prevention of eye diseases, cardiovascular diseases, and cancer. However, the application of LUT is largely restricted by its poor solubility and susceptibility to oxidative degradation. Thus, in this study, LUT-loaded nanogel (OVM-COS-LUT) was prepared by a self-assembly of ovomucin (OVM) and chitosan oligosaccharide (COS) to enhance the effective protection and bioavailability of LUT. The nanogel had excellent dispersion (PDI = 0.25) and an 89.96% LUT encapsulation rate. XRD crystal structure analysis confirmed that the encapsulated LUT maintained an amorphous morphology. In addition, the nanogel showed satisfactory stability with pH levels ranging from 2 to 9 and high ionic strengths (>100 mM). Even under long-term storage, the nanogel maintained an optimistic stabilization and protection capacity; its effective retention rates could reach 96.54%. In vitro, digestion simulation showed that the bioaccessibility and sustained release of OVM-COS-LUT nanogel was superior to that of free LUT. The nanogel provided significant antioxidant activity, and no significant harmful effects were detected in cytotoxicity analyses at higher concentrations. In summary, OVM-COS-LUT can be utilized as a potential safe oral and functional carrier for encapsulating LUT.

11.
J Trace Elem Med Biol ; 84: 127459, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38640745

RESUMO

Trace elements such as zinc, manganese, copper, or iron are essential for a wide range of physiological functions. It is therefore crucial to ensure an adequate supply of these elements to the body. Many previous investigations have dealt with the role of transport proteins, in particular their selectivity for, and competition between, different ions. Another so far less well investigated major factor influencing the absorption of trace elements seems to be the intestinal mucus layer. This gel-like substance covers the entire gastrointestinal tract and its physiochemical properties can be mainly assigned to the glycoproteins it contains, so-called mucins. Interaction with mucins has already been demonstrated for some metals. However, knowledge about the impact on the respective bioavailability and competition between those metals is still sketchy. This review therefore aims to summarize the findings and knowledge gaps about potential effects regarding the interaction between gastrointestinal mucins and the trace elements iron, zinc, manganese, and copper. Mucins play an indispensable role in the absorption of these trace elements in the neutral to slightly alkaline environment of the intestine, by keeping them in a soluble form that can be absorbed by enterocytes. Furthermore, the studies so far indicate that the competition between these trace elements for uptake already starts at the intestinal mucus layer, yet further research is required to completely understand this interaction.

12.
Eur J Pharm Sci ; 196: 106760, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38574899

RESUMO

To date, characterization of the first-pass effect of orally administered drugs consisting of local intestinal absorption and metabolism, portal vein transport and hepatobiliary processes remains challenging. Aim of this study was to explore the applicability of a porcine ex-vivo perfusion model to study oral absorption, gut-hepatobiliary metabolism and biliary excretion of midazolam. Slaughterhouse procured porcine en bloc organs (n = 4), were perfused via the aorta and portal vein. After 120 min of perfusion, midazolam, atenolol, antipyrine and FD4 were dosed via the duodenum and samples were taken from the systemic- and portal vein perfusate, intestinal faecal effluent and bile to determine drug and metabolite concentrations. Stable arterial and portal vein flow was obtained and viability of the perfused organs was confirmed. After intraduodenal administration, midazolam was rapidly detected in the portal vein together with 1-OH midazolam (EG-pv of 0.16±0.1) resulting from gut wall metabolism through oxidation. In the intestinal faecal effluent, 1-OH midazolam and 1-OH midazolam glucuronide (EG-intestine 0.051±0.03) was observed resulting from local gut glucuronidation. Biliary elimination of midazolam (0.04±0.01 %) and its glucuronide (0.01±0.01 %) only minimally contributed to the enterohepatic circulation. More extensive hepatic metabolism (FH 0.35±0.07) over intestinal metabolism (FG 0.78±0.11) was shown, resulting in oral bioavailability of 0.27±0.05. Ex vivo perfusion demonstrated to be a novel approach to characterize pre-systemic extraction of midazolam by measuring intestinal as well as hepatic extraction. The model can generate valuable insights into the absorption and metabolism of new drugs.

13.
Vet Res Commun ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630426

RESUMO

Feed and water components may interact with drugs and affect their dissolution and bioavailability. The impact of the vehicle of administration (feed and water) and the prandial condition of weaner piglets on amoxicillin´s oral bioavailability was evaluated. First, amoxicillin's in vitro dissolution and stability in purified, soft, and hard water, as well as release kinetics from feed in simulated gastric and intestinal media were assessed. Then, pharmacokinetic parameters and bioavailability were determined in fasted and fed pigs using soft water, hard water, or feed as vehicles of administration following a balanced incomplete block design. Amoxicillin showed similar dissolution profiles in soft and hard water, distinct from the dissolution profile obtained with purified water. Complete dissolution was only achieved in purified water, and merely reached 50% in soft or hard water. Once dissolved, antibiotic concentrations decreased by around 20% after 24 h in all solutions. Korsmeyer-Peppas model best described amoxicillin release from feed in simulated gastric and intestinal media. Feed considerably reduced antibiotic dissolution in both simulated media. In vivo, amoxicillin exhibited significantly higher bioavailability when delivered via water to fasted than to fed animals, while in-feed administration yielded the lowest values. All treatments showed a similar rate of drug absorption. In conclusion, we demonstrated that water and feed components, as well as feed present in gastrointestinal tract of piglets decrease amoxicillin´s oral bioavailability. Therefore, the use of oral amoxicillin as a broad-spectrum antibiotic to treat systemic infections in pigs should be thoroughly revised.

14.
Pharm Dev Technol ; : 1-16, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38607310

RESUMO

In this study, a new gastro-floating sustained-release tablet (GFT) with a combination of Etoricoxib (ET) and Famotidine (FM) was successfully developed. GFTs were prepared by using a combination of hydrophilic swellable natural/semi-synthetic polymers as a controlled-release layer. Through a 24 full factorial statistical experimental design, the effects of formulation factors on the release of GFTs were conducted. The ideal floating tablet (FT) comprised konjac-gum (150 mg), guar-gum (26.57 mg), xanthan-gum (54.17 mg), and HPMC-K15-M (69.25 mg). The ideal FT exhibited a high swelling index (SI) (297.7%) and rapid FLT (around 50 s) in 0.1 N HCl as well as controlled release of ET (22.43% in 1 h and 77.47% in 8 h) and FM (24.89% in 1 h and 93.82% in 8 h) with the absence of any drug-excipient interactions. The AUC0∼72 (ng h/mL) of ET and FM in the GFTs were approximately double-fold of the market, respectively. The relative bioavailability was (207.48 ± 12.02% and 208.51 ± 13.11%) compared with commercial tablets. The X-ray imaging showed a promising buoyancy ability for approximately 8 h. These findings revealed the successful preparation of the sustained-release floating tablet with improved dual drug delivery.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38629192

RESUMO

Nanocrystals refer to materials with at least one dimension smaller than 100 nm, composing of atoms arranged in single crystals or polycrystals. Nanocrystals have significant research value as they offer unique advantages over conventional pharmaceutical formulations, such as high bioavailability, enhanced targeting selectivity and controlled release ability and are therefore suitable for the delivery of a wide range of drugs such as insoluble drugs, antitumor drugs and genetic drugs with broad application prospects. In recent years, research on nanocrystals has been progressively refined and new products have been launched or entered the clinical phase of studies. However, issues such as safety and stability still stand that need to be addressed for further development of nanocrystal formulations, and significant gaps do exist in research in various fields in this pharmaceutical arena. This paper presents a systematic overview of the advanced development of nanocrystals, ranging from the preparation approaches of nanocrystals with which the bioavailability of poorly water-soluble drugs is improved, critical properties of nanocrystals and associated characterization techniques, the recent development of nanocrystals with different administration routes, the advantages and associated limitations of nanocrystal formulations, the mechanisms of physical instability, and the enhanced dissolution performance, to the future perspectives, with a final view to shed more light on the future development of nanocrystals as a means of optimizing the bioavailability of drug candidates. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.


Assuntos
Antineoplásicos , Nanopartículas , Disponibilidade Biológica , Nanopartículas/química , Preparações Farmacêuticas/química , Solubilidade
16.
J Agric Food Chem ; 72(15): 8618-8631, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38569082

RESUMO

Daidzein (DAN) is an isoflavone, and it is often found in its natural form in soybean and food supplements. DAN has poor bioavailability owing to its extremely low water solubility and first-pass metabolism. Herein, we hypothesized that a bioactivatable natural amino acid-bearing carbamate prodrug strategy could increase the water solubility and metabolic stability of DAN. To test our hypothesis, nine amino acid prodrugs of DAN were designed and synthesized. Compared with DAN, the optimal prodrug (daidzein-4'-O-CO-N-isoleucine, D-4'-I) demonstrated enhanced water solubility and improved phase II metabolic stability and activation to DAN in plasma. In addition, unlike the passive transport of DAN, D-4'-I maintained high permeability via organic anion-transporting polypeptide 2B1 (OATP2B1)-mediated transport. Importantly, D-4'-I increased the oral bioavailability by 15.5-fold, reduced the gender difference, and extended the linear absorption capacity in the pharmacokinetics of DAN in rats. Furthermore, D-4'-I exhibited dose-dependent protection against liver injury. Thus, the natural amino acid-bearing carbamate prodrug strategy shows potential in increasing water solubility and improving phase II metabolic stability to enhance the oral bioavailability of DAN.


Assuntos
Isoflavonas , Pró-Fármacos , Ratos , Animais , Aminoácidos/química , Disponibilidade Biológica , Solubilidade , Pró-Fármacos/química , Carbamatos/química , Água , Administração Oral
17.
Curr Dev Nutr ; 8(4): 102129, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38559312

RESUMO

There is an urgent need for global food systems transformation to realize a future where planetary health reaches its full potential. Paramount to this vision is the ability of stakeholders across sectors to understand how foods and dietary patterns impact food systems inclusive of all domains of sustainability-environmental, nutrition/health, economic and social. This article is a synopsis of presentations by 3 food systems experts to share the latest science in a session entitled "How do you measure sustainability? Opportunities for consistent and holistic metrics to support food systems transformation" at the American Society for Nutrition's 2023 annual conference. As summarized here, global population data showing widespread malnutrition underscore the important role of dietary diversity through a balance of plant- and animal-source foods to achieve nutritionally adequate diets and reduce risk of noncommunicable diseases. Yet, recent international audits of countries, companies, and organizations and their sustainability targets largely demonstrate an underrepresentation of robust nutrition/health metrics to support public nutrition and health progress. Addressing limitations in diet-sustainability modeling systems provides a viable opportunity to accurately reflect the important contributions and trade-offs of diets across all domains of sustainability to ultimately support evidence-based decision making in advancing healthy food systems.

18.
Bull Environ Contam Toxicol ; 112(4): 57, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565676

RESUMO

Both livestock-manure and livestock-manure-derived biochar have been used to remediate heavy metal-contaminated soil. However, direct comparisons of the heavy metal stabilization efficiency of livestock-manure and EQC-manure-biochar (derived from an equal quantity of corresponding livestock-manure) are limited. In the present study, the effect of livestock-manures and EQC-manure-biochars on soil properties and heavy metal bioavailability and leachability were compared using two contrasting soils (Ferralsols and Fluvisols). The results showed that both the livestock-manures and EQC-manure-biochars significantly changed soil pH, available phosphorus, available potassium, alkaline nitrogen and organic matter content (p < 0.05), but the trends were variable. In Ferralsols, the DTPA-extractable Cd and Zn decreased by -0.38%~5.70% and - 3.79%~9.98% with livestock-manure application and by -7.99%~7.23% and - 5.67%~7.17% with EQC-manure-biochars application. In Fluvisols, the DTPA-extractable Cd and Zn decreased by 13.39%~17.41% and - 45.26%~14.24% with livestock-manure application and by 10.76%~16.90% and - 36.38%~16.37% with EQC-manure-biochar application. Furthermore, the change in TCLP-extractable Cd and Zn in both soils was similar to that of DTPA-extractable Cd and Zn. Notably, the Cd and Zn stabilization efficiency of the EQC-manure-biochars was no better than that of the corresponding livestock-manures. These results suggest that the use of livestock-manure-derived biochar is not cost-effective for the remediation of heavy metal-contaminated soil.


Assuntos
Metais Pesados , Poluentes do Solo , Animais , Cádmio/química , Zinco , Esterco , Gado , Poluentes do Solo/análise , Metais Pesados/análise , Carvão Vegetal/química , Solo/química , Ácido Pentético
19.
Artigo em Inglês | MEDLINE | ID: mdl-38573580

RESUMO

Lead (Pb) is commonly found in urban soils and can transfer to vegetables. This entails a health risk for consumers of garden crops. The increasing demand of gardening on urban soil linked to the population increase and concentration in urban areas induces an increase in the risk, as people could be forced to cultivate contaminated soils. The aim of this study was to evaluate the performance of a cropping system that allows simultaneously (i) growing eatable vegetables that accumulate few Pb and (ii) cleaning up the soil with other plants by phytoextraction. The tests were carried out in an allotment garden (Nantes, France) where soils are moderately enriched by Pb from geogenic origin (178 mg.kg-1 of dry soil on average). Four vegetables known to accumulate slightly Pb (Solanum lycopersicum, Brassica oleracea cv. "Capitata," Solanum tuberosum, and Phaseolus vulgaris) were grown. The in situ ability of Brassica juncea L. to progressively absorb the phytoavailable Pb of the soil was assessed during four seasons. Analyses of the edible parts of the four vegetables confirmed that they can all be safely cultivated. The accumulation of Pb in B. juncea shoots was too low (ca. 1 mg.kg-1 of dry matter at best) for phytoextraction purposes. Our results confirm that it is possible to grow very low Pb-accumulating vegetables on soils moderately contaminated with Pb, although it was not possible to reduce phytoavailable Pb rapidly enough with B. juncea. This study identifies possible avenues of research to improve this cropping system by using appropriate vegetables that will allow food production to continue on moderately contaminated soil while cleaning it up.

20.
Int J Biol Macromol ; 266(Pt 2): 131284, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38569984

RESUMO

Low bioavailability of quercetin (Que) reduces its preclinical and clinical benefits. In order to improve Que bioavailability, a novel whey protein isolate (WPI)-zein nanogel was prepared by pH-driven self-assembly and heat-induced gelatinization. The results showed that hydrochloric acid can be substituted by both acetic acid and citric acid during the pH-driven process. After encapsulation, the bioavailability of Que in nanogels (composed of 70 % WPI) induced by different acidifiers increased to 19.89 % (citric acid), 21.65 % (hydrochloric acid) and 24.34 % (acetic acid), respectively. Comparatively, nanogels induced by acetic acid showed higher stability (pH and storage stability), re-dispersibility (75.62 %), Que bioavailability (24.34 %), and antioxidant capacity (36.78 % for DPPH scavenging rates). s improved performance of nanogels. In mechanism, acetic acid significantly balanced different intermolecular forces by weakening "acid-induced denaturation" effect. Moreover, the faster binding of Que and protein as well as higher protein molecular flexibility and randomness (higher ratio of random coil) was also observed in nanogels induced by acetic acid. All of these changes contributed to improve nanogels performances. Overall, WPI-zein nanogels induced by acetic acid might be a safe, efficiency and stable delivery system to improve the bioavailability of hydrophobic active ingredients.

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