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1.
Nutrients ; 16(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38999827

RESUMO

A very low calorie ketogenic diet (VLCKD) impacts host metabolism in people marked by an excess of visceral adiposity, and it affects the microbiota composition in terms of taxa presence and relative abundances. As a matter of fact, there is little available literature dealing with microbiota differences in obese patients marked by altered intestinal permeability. With the aim of inspecting consortium members and their related metabolic pathways, we inspected the microbial community profile, together with the set of volatile organic compounds (VOCs) from untargeted fecal and urine metabolomics, in a cohort made of obese patients, stratified based on both normal and altered intestinal permeability, before and after VLCKD administration. Based on the taxa relative abundances, we predicted microbiota-derived metabolic pathways whose variations were explained in light of our cohort symptom picture. A totally different number of statistically significant pathways marked samples with altered permeability, reflecting an important shift in microbiota taxa. A combined analysis of taxa, metabolic pathways, and metabolomic compounds delineates a set of markers that is useful in describing obesity dysfunctions and comorbidities.


Assuntos
Dieta Cetogênica , Microbioma Gastrointestinal , Metabolômica , Obesidade , Permeabilidade , Humanos , Dieta Cetogênica/métodos , Obesidade/dietoterapia , Obesidade/metabolismo , Microbioma Gastrointestinal/fisiologia , Feminino , Masculino , Adulto , Metabolômica/métodos , Pessoa de Meia-Idade , Redes e Vias Metabólicas , Fezes/microbiologia , Fezes/química , Mucosa Intestinal/metabolismo , Compostos Orgânicos Voláteis/análise , Restrição Calórica/métodos , Função da Barreira Intestinal , Multiômica
2.
Nat Commun ; 15(1): 5764, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982061

RESUMO

Machine learning (ML) systems can model quantitative structure-property relationships (QSPR) using existing experimental data and make property predictions for new molecules. With the advent of modalities such as targeted protein degraders (TPD), the applicability of QSPR models is questioned and ML usage in TPD-centric projects remains limited. Herein, ML models are developed and evaluated for TPDs' property predictions, including passive permeability, metabolic clearance, cytochrome P450 inhibition, plasma protein binding, and lipophilicity. Interestingly, performance on TPDs is comparable to that of other modalities. Predictions for glues and heterobifunctionals often yield lower and higher errors, respectively. For permeability, CYP3A4 inhibition, and human and rat microsomal clearance, misclassification errors into high and low risk categories are lower than 4% for glues and 15% for heterobifunctionals. For all modalities, misclassification errors range from 0.8% to 8.1%. Investigated transfer learning strategies improve predictions for heterobifunctionals. This is the first comprehensive evaluation of ML for the prediction of absorption, distribution, metabolism, and excretion (ADME) and physicochemical properties of TPD molecules, including heterobifunctional and molecular glue sub-modalities. Taken together, our investigations show that ML-based QSPR models are applicable to TPDs and support ML usage for TPDs' design, to potentially accelerate drug discovery.


Assuntos
Aprendizado de Máquina , Humanos , Ratos , Animais , Relação Quantitativa Estrutura-Atividade , Proteólise , Citocromo P-450 CYP3A/metabolismo , Citocromo P-450 CYP3A/química , Ligação Proteica , Permeabilidade
3.
Sci Rep ; 14(1): 15844, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982309

RESUMO

Predicting the blood-brain barrier (BBB) permeability of small-molecule compounds using a novel artificial intelligence platform is necessary for drug discovery. Machine learning and a large language model on artificial intelligence (AI) tools improve the accuracy and shorten the time for new drug development. The primary goal of this research is to develop artificial intelligence (AI) computing models and novel deep learning architectures capable of predicting whether molecules can permeate the human blood-brain barrier (BBB). The in silico (computational) and in vitro (experimental) results were validated by the Natural Products Research Laboratories (NPRL) at China Medical University Hospital (CMUH). The transformer-based MegaMolBART was used as the simplified molecular input line entry system (SMILES) encoder with an XGBoost classifier as an in silico method to check if a molecule could cross through the BBB. We used Morgan or Circular fingerprints to apply the Morgan algorithm to a set of atomic invariants as a baseline encoder also with an XGBoost classifier to compare the results. BBB permeability was assessed in vitro using three-dimensional (3D) human BBB spheroids (human brain microvascular endothelial cells, brain vascular pericytes, and astrocytes). Using multiple BBB databases, the results of the final in silico transformer and XGBoost model achieved an area under the receiver operating characteristic curve of 0.88 on the held-out test dataset. Temozolomide (TMZ) and 21 randomly selected BBB permeable compounds (Pred scores = 1, indicating BBB-permeable) from the NPRL penetrated human BBB spheroid cells. No evidence suggests that ferulic acid or five BBB-impermeable compounds (Pred scores < 1.29423E-05, which designate compounds that pass through the human BBB) can pass through the spheroid cells of the BBB. Our validation of in vitro experiments indicated that the in silico prediction of small-molecule permeation in the BBB model is accurate. Transformer-based models like MegaMolBART, leveraging the SMILES representations of molecules, show great promise for applications in new drug discovery. These models have the potential to accelerate the development of novel targeted treatments for disorders of the central nervous system.


Assuntos
Barreira Hematoencefálica , Aprendizado de Máquina , Permeabilidade , Barreira Hematoencefálica/metabolismo , Humanos , Células Endoteliais/metabolismo , Simulação por Computador , Descoberta de Drogas/métodos
4.
AAPS J ; 26(4): 76, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38955873

RESUMO

The selection of skin is crucial for the in vitro permeation test (IVPT). The purpose of this study was to investigate the influence of different freezing-thawing processes on the barrier function of skin and the transdermal permeability of granisetron and lidocaine. Rat and hairless mouse skins were thawed at three different conditions after being frozen at -20℃ for 9 days: thawed at 4℃, room temperature (RT), and 32℃. There were no significant differences in the steady-state fluxes of drugs between fresh and thawed samples, but compared with fresh skin there were significant differences in lag time for the permeation of granisetron in rat skins thawed at RT and 32℃. Histological research and scanning electron microscopy images showed no obvious structural damage on frozen/thawed skin, while immunohistochemical staining and enzyme-linked immunosorbent assay for the tight junction (TJ) protein Cldn-1 showed significantly impaired epidermal barrier. It was concluded that the freezing-thawing process increases the diffusion rate of hydrophilic drugs partly due to the functional degradation of TJs. It's recommended that hairless, inbred strains and identical animal donors should be used, and the selected thawing method of skin should be validated prior to IVPT, especially for hydrophilic drugs.


Assuntos
Congelamento , Camundongos Pelados , Permeabilidade , Absorção Cutânea , Pele , Animais , Pele/metabolismo , Camundongos , Absorção Cutânea/efeitos dos fármacos , Ratos , Masculino , Administração Cutânea , Lidocaína/administração & dosagem , Lidocaína/farmacocinética , Ratos Sprague-Dawley
5.
Chem Biol Drug Des ; 104(1): e14576, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38969623

RESUMO

Intestinal absorption of compounds is significant in drug research and development. To evaluate this efficiently, a method combining mathematical modeling and molecular simulation was proposed, from the perspective of molecular structure. Based on the quantitative structure-property relationship study, the model between molecular structure and their apparent permeability coefficients was successfully constructed and verified, predicting intestinal absorption of drugs and interpreting decisive structural factors, such as AlogP98, Hydrogen bond donor and Ellipsoidal volume. The molecules with strong lipophilicity, less hydrogen bond donors and receptors, and small molecular volume are more easily absorbed. Then, the molecular dynamics simulation and molecular docking were utilized to study the mechanism of differences in intestinal absorption of drugs and investigate the role of molecular structure. Results indicated that molecules with strong lipophilicity and small volume interacted with the membrane at a lower energy and were easier to penetrate the membrane. Likewise, they had weaker interaction with P-glycoprotein and were easier to escape from it and harder to export from the body. More in, less out, is the main reason these molecules absorb well.


Assuntos
Ligação de Hidrogênio , Absorção Intestinal , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Relação Quantitativa Estrutura-Atividade , Humanos , Estrutura Molecular , Preparações Farmacêuticas/metabolismo , Preparações Farmacêuticas/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/química , Interações Hidrofóbicas e Hidrofílicas , Permeabilidade
6.
Arch Dermatol Res ; 316(7): 476, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023797

RESUMO

Increased intestinal permeability and gut dysbiosis are important factors in the pathophysiology of psoriasis and its associated conditions. Claudin-3 is a protein that is found in tight junctions and may be used to assess the integrity of the gut barrier. The aim of this study was to investigate serum concentration of Claudin- 3 (CLDN3) in patients with psoriasis. Exploring its possible relations with patients' demographic, clinical and laboratory findings was another objective. Fifty psoriatic patients and thirty-five age- and sex-matched healthy volunteers served as the study's control group in this case-control, hospital-based research. The amount of serum CLDN3 was determined by means of an enzyme-linked immunosorbent test (ELISA). Concentration of serum CLDN3 was found to be significantly higher in patients with psoriasis. (p = 0.002). There was no statistically significant correlation between CLDN3 and patient's clinical & laboratory variables. We demonstrated that gut permeability is dysfunctional in patients with psoriasis as indicated by reduction of serum CLDN3. Further investigations are needed to determine whether modulation of gut barrier may represent a new therapeutic approach for psoriasis.


Assuntos
Biomarcadores , Claudina-3 , Permeabilidade , Psoríase , Pele , Humanos , Psoríase/sangue , Psoríase/diagnóstico , Masculino , Feminino , Biomarcadores/sangue , Adulto , Claudina-3/sangue , Estudos de Casos e Controles , Pessoa de Meia-Idade , Pele/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Adulto Jovem , Junções Íntimas/metabolismo , Disbiose/diagnóstico
7.
Helicobacter ; 29(3): e13100, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873839

RESUMO

BACKGROUND: The formation of gallstones is often accompanied by chronic inflammation, and the mechanisms underlying inflammation and stone formation are not fully understood. Our aim is to utilize single-cell transcriptomics, bulk transcriptomics, and microbiome data to explore key pathogenic bacteria that may contribute to chronic inflammation and gallstone formation, as well as their associated mechanisms. METHODS: scRNA-seq data from a gallstone mouse model were extracted from the Gene Expression Omnibus (GEO) database and analyzed using the FindCluster() package for cell clustering analysis. Bulk transcriptomics data from patients with gallstone were also extracted from the GEO database, and intergroup functional differences were assessed using GO and KEGG enrichment analysis. Additionally, 16S rRNA sequencing was performed on gallbladder mucosal samples from asymptomatic patients with gallstone (n = 6) and liver transplant donor gallbladder mucosal samples (n = 6) to identify key bacteria associated with stone formation and chronic inflammation. Animal models were constructed to investigate the mechanisms by which these key pathogenic bacterial genera promote gallstone formation. RESULTS: Analysis of scRNA-seq data from the gallstone mouse model (GSE179524) revealed seven distinct cell clusters, with a significant increase in neutrophil numbers in the gallstone group. Analysis of bulk transcriptomics data from patients with gallstone (GSE202479) identified chronic inflammation in the gallbladder, potentially associated with dysbiosis of the gallbladder microbiota. 16S rRNA sequencing identified Helicobacter pylori as a key bacterium associated with gallbladder chronic inflammation and stone formation. CONCLUSIONS: Dysbiosis of the gallbladder mucosal microbiota is implicated in gallstone disease and leads to chronic inflammation. This study identified H. pylori as a potential key mucosal resident bacterium contributing to gallstone formation and discovered its key pathogenic factor CagA, which causes damage to the gallbladder mucosal barrier. These findings provide important clues for the prevention and treatment of gallstones.


Assuntos
Antígenos de Bactérias , Proteínas de Bactérias , Células Epiteliais , Vesícula Biliar , Cálculos Biliares , Helicobacter pylori , Animais , Cálculos Biliares/microbiologia , Cálculos Biliares/patologia , Células Epiteliais/microbiologia , Camundongos , Humanos , Vesícula Biliar/microbiologia , Vesícula Biliar/patologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Antígenos de Bactérias/genética , Antígenos de Bactérias/metabolismo , Helicobacter pylori/genética , Helicobacter pylori/patogenicidade , Helicobacter pylori/fisiologia , RNA Ribossômico 16S/genética , Modelos Animais de Doenças , Permeabilidade , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Feminino , Masculino , Camundongos Endogâmicos C57BL
8.
Int J Biol Macromol ; 272(Pt 1): 132817, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38834126

RESUMO

Multifunctional smart biopolymeric films were fabricated using rose petal anthocyanin (RPA) and carrageenan (CAR) doped with rose petal-derived carbon dots (RP-CDs). Response surface-optimized RPA showed the highest total anthocyanins and radical scavenging ability. Produced RP-CD exhibited UV absorption and high fluorescence with antibacterial/antioxidant abilities. Enrichment with 2 % RP-CD and 5 % RPA in the CAR matrix results in improved physicochemical, i.e., water contact angle, water vapor permeability, and UV-blocking properties of the fabricated material. Results showed that nanocomposite films scavenged radicals better than the neat CAR films. Zeta potential, FTIR, SEM, and XPS suggested improved compatibility/stability and enhanced elemental configuration of RP-CDs/RPA additives in the CAR polymer matrix. Perishable food packaging (minced pork and shrimp) demonstrated that nanocomposite films work efficiently and non-destructively and are promising tools for monitoring real-time freshness through interpretable visual changes from red to yellow. The CAR/RP-CDs/RPA-based nanocomposite indicator films are expected to be applied as various smart packaging materials. These films possess the ability to promptly detect changes in quality, preserve the quality, and prolong the shelf life of packaged foods.


Assuntos
Antocianinas , Carbono , Carragenina , Embalagem de Alimentos , Rosa , Embalagem de Alimentos/métodos , Antocianinas/química , Carragenina/química , Rosa/química , Carbono/química , Nanocompostos/química , Flores/química , Permeabilidade , Vapor , Antioxidantes/química , Pontos Quânticos/química , Antibacterianos/química , Antibacterianos/farmacologia
9.
Sci Rep ; 14(1): 13693, 2024 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-38871956

RESUMO

The present study utilized response surface methodology (RSM) to investigate the impact of varying concentrations of carboxymethyl cellulose (CMC: 0.75-1.75 wt%), Commiphora mukul polysaccharide (CMP: 0-1 wt%), and Chitosan Nanofiber (CHNF: 0-1 wt%) on the physical and antimicrobial characteristics of nanocomposite films based on CMC. The optimization process aimed to enhance ultimate tensile strength (UTS), strain at break (SAB), and antibacterial activity, while minimizing water vapor permeability (WVP), solubility, swelling, moisture content, opacity, and total color difference (ΔE). The results revealed that both CMP and CHNF had a positive influence on reducing moisture content, WVP, and increasing UTS. However, higher concentrations of CMP and CHNF had a divergent effect on SAB, ΔE, and swelling. The incorporation of CMP led to increased opacity and solubility, while the inclusion of CHNF resulted in decreased opacity and solubility. Notably, only CHNF addition significantly improved the antibacterial properties of the films. By applying the optimization procedure utilizing RSM, the formulation containing CMC (1.5 wt%), CMP (0.25 wt%), and CHNF (0.75 wt%) demonstrated superior physical, mechanical, and antibacterial properties in the biodegradable film matrix. These findings highlight the potential of utilizing these components to enhance the performance of CMC-based nanocomposite films.


Assuntos
Carboximetilcelulose Sódica , Quitosana , Nanocompostos , Nanofibras , Resistência à Tração , Quitosana/química , Carboximetilcelulose Sódica/química , Nanofibras/química , Nanocompostos/química , Antibacterianos/farmacologia , Antibacterianos/química , Gomas Vegetais/química , Polissacarídeos/química , Solubilidade , Commiphora/química , Permeabilidade , Vapor , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Testes de Sensibilidade Microbiana
10.
Clin Nutr ESPEN ; 62: 157-163, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38901937

RESUMO

AIMS: Patients with chronic obstructive pulmonary disease (COPD) frequently exhibit an inability to maintain postural balance. However, the contribution of increased intestinal permeability or leaky gut to the postural imbalance in COPD is not known. METHODS: We measured plasma zonulin, a marker of leaky gut, with relevance to postural balance in male controls (n = 70) and patients with mild (n = 67), moderate (n = 66), and severe (n = 58) COPD. We employed a short physical performance battery to evaluate postural balance in supine, tandem, and semi-tandem positions. We also measured handgrip strength (HGS), gait speed, plasma c-reactive proteins (CRP), and 8-isoprostanes as potential mechanistic connections between postural imbalance and leaky gut. RESULTS: COPD patients demonstrated higher plasma zonulin, CRP, and 8-isoprostanes levels and lower balance, HGS, and gait speed than controls (all p < 0.05). These findings were more robust in patients with moderate and severe than mild COPD. In addition, plasma zonulin exhibited significant potential in diagnosing poor balance, low HGS, and gait speed in COPD patients (all p < 0.05). We also found significant correlations of plasma zonulin with CRP and 8-isoprostanes, providing heightened inflammation and oxidative stress as mechanistic connections between leaky gut and postural imbalance. CONCLUSION: Plasma zonulin may be helpful in evaluating postural imbalance in COPD patients. Repairing intestinal leaks can be a therapeutic target to improve postural control in COPD.


Assuntos
Biomarcadores , Proteína C-Reativa , Haptoglobinas , Equilíbrio Postural , Doença Pulmonar Obstrutiva Crônica , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/sangue , Idoso , Pessoa de Meia-Idade , Proteína C-Reativa/metabolismo , Biomarcadores/sangue , Força da Mão , Precursores de Proteínas/sangue , Toxina da Cólera/sangue , Estudos de Casos e Controles , Permeabilidade , Dinoprosta/análogos & derivados
11.
Pharm Res ; 41(6): 1201-1216, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38834905

RESUMO

BACKGROUND: Some glucoside drugs can be transported via intestinal glucose transporters (IGTs), and the presence of carbohydrate excipients in pharmaceutical formulations may influence the absorption of them. This study, using gastrodin as probe drug, aimed to explore the effects of fructose, lactose, and arabic gum on intestinal drug absorption mediated by the glucose transport pathway. METHODS: The influence of fructose, lactose, and arabic gum on gastrodin absorption was assessed via pharmacokinetic experiments and single-pass intestinal perfusion. The expression of sodium-dependent glucose transporter 1 (SGLT1) and sodium-independent glucose transporter 2 (GLUT2) was quantified via RT‒qPCR and western blotting. Alterations in rat intestinal permeability were evaluated through H&E staining, RT‒qPCR, and immunohistochemistry. RESULTS: Fructose reduced the area under the curve (AUC) and peak concentration (Cmax) of gastrodin by 42.7% and 63.71%, respectively (P < 0.05), and decreased the effective permeability coefficient (Peff) in the duodenum and jejunum by 58.1% and 49.2%, respectively (P < 0.05). SGLT1 and GLUT2 expression and intestinal permeability remained unchanged. Lactose enhanced the AUC and Cmax of gastrodin by 31.5% and 65.8%, respectively (P < 0.05), and increased the Peff in the duodenum and jejunum by 33.7% and 26.1%, respectively (P < 0.05). SGLT1 and GLUT2 levels did not significantly differ, intestinal permeability increased. Arabic gum had no notable effect on pharmacokinetic parameters, SGLT1 or GLUT2 expression, or intestinal permeability. CONCLUSION: Fructose, lactose, and arabic gum differentially affect intestinal drug absorption through the glucose transport pathway. Fructose competitively inhibited drug absorption, while lactose may enhance absorption by increasing intestinal permeability. Arabic gum had no significant influence.


Assuntos
Álcoois Benzílicos , Excipientes , Frutose , Transportador de Glucose Tipo 2 , Glucose , Glucosídeos , Goma Arábica , Absorção Intestinal , Lactose , Ratos Sprague-Dawley , Transportador 1 de Glucose-Sódio , Animais , Absorção Intestinal/efeitos dos fármacos , Glucosídeos/farmacologia , Glucosídeos/administração & dosagem , Glucosídeos/farmacocinética , Transportador 1 de Glucose-Sódio/metabolismo , Transportador 1 de Glucose-Sódio/genética , Masculino , Transportador de Glucose Tipo 2/metabolismo , Transportador de Glucose Tipo 2/genética , Ratos , Excipientes/química , Excipientes/farmacologia , Glucose/metabolismo , Lactose/química , Álcoois Benzílicos/farmacologia , Álcoois Benzílicos/farmacocinética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Transporte Biológico/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos
12.
Expert Opin Drug Metab Toxicol ; 20(6): 439-458, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38850058

RESUMO

INTRODUCTION: Recent years have witnessed remarkable progress in the development of cell-based in vitro models aimed at predicting drug permeability, particularly focusing on replicating the barrier properties of the blood-brain barrier (BBB), intestinal epithelium, and lung epithelium. AREA COVERED: This review provides an overview of 2D in vitro platforms, including monocultures and co-culture systems, highlighting their respective advantages and limitations. Additionally, it discusses tools and techniques utilized to overcome these limitations, paving the way for more accurate predictions of drug permeability. Furthermore, this review delves into emerging technologies, particularly microphysiological systems (MPS), encompassing static platforms such as organoids and dynamic platforms like microfluidic devices. Literature searches were performed using PubMed and Google Scholar. We focus on key terms such as in vitro permeability models, MPS, organoids, intestine, BBB, and lungs. EXPERT OPINION: The potential of these MPS to mimic physiological conditions more closely offers promising avenues for drug permeability assessment. However, transitioning these advanced models from bench to industry requires rigorous validation against regulatory standards. Thus, there is a pressing need to validate MPS to industry and regulatory agency standards to exploit their potential in drug permeability prediction fully. This review underscores the importance of such validation processes to facilitate the translation of these innovative technologies into routine pharmaceutical practice.


Assuntos
Barreira Hematoencefálica , Mucosa Intestinal , Modelos Biológicos , Permeabilidade , Humanos , Barreira Hematoencefálica/metabolismo , Animais , Preparações Farmacêuticas/metabolismo , Preparações Farmacêuticas/administração & dosagem , Mucosa Intestinal/metabolismo , Pulmão/metabolismo , Organoides/metabolismo , Técnicas de Cocultura
13.
J Hazard Mater ; 474: 134827, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38850953

RESUMO

In our work, a gravity-driven ceramic membrane bioreactor (GDCMBR) was developed to remove Mn2+ and NH3-N simultaneously through the birnessite water purification layer in-situ construction on the ceramic membrane due to chemical pre-oxidation (powdered activated carbon (PAC)-MnOx). Considering the trade-off of biofouling and water production, the daily intermittent short-term vertical aeration mode was involving to balance this contradiction with the excellent water purification and improved membrane permeability. And the GDCMBR permeability of operation flux was improved for 5-7 LHM with intermittent short-term vertical aeration. Furthermore, only ∼7 % irreversible membrane resistance (Rir) also confirmed the improved membrane permeability with intermittent short-term vertical aeration. And some manganese oxidizing bacteria (MnOB) and ammonia oxidizing bacteria (AOB) species at genus level were identified during long-term operation with the contact circulating flowing raw water, resulting in the better Mn2+ and NH3-N removal efficiency. Additionally, the nano-flower-like birnessite water purification layer was verified in ceramsite@PAC-MnOx coupled GDCMBR, which evolute into a porous flake-like structure with the increasing intermittent short-term aeration duration. Therefore, the sustainable and effective intermittent short-term aeration mode in ceramsite@PAC-MnOx coupled GDCMBR could improve the membrane permeability with the satisfactory groundwater purification efficiency, as well as providing an energy-efficient strategy for membrane technologies applications in water supply safety.


Assuntos
Amônia , Cerâmica , Manganês , Membranas Artificiais , Permeabilidade , Cerâmica/química , Manganês/química , Amônia/química , Amônia/metabolismo , Purificação da Água/métodos , Reatores Biológicos , Carvão Vegetal/química , Óxidos/química , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/química , Nitrogênio/química , Nitrogênio/metabolismo , Compostos de Manganês/química , Gravitação , Bactérias/metabolismo
14.
Nutrients ; 16(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38892712

RESUMO

While the exact pathogenesis of IBD remains unclear, genetic, environmental and nutritional factors as well as the composition of the gut microbiome play crucial roles. Food additives, which are increasingly consumed in the Western diet, are being investigated for their potential effects on IBD. These additives can affect gut health by altering the composition of the microbiota, immune responses, and intestinal permeability, contributing to autoimmune diseases and inflammation. Despite the growing number of studies on food additives and IBD, the specific effects of carrageenan have not yet been sufficiently researched. This review addresses this gap by critically analyzing recent studies on the effects of carrageenan on the gut microbiota, intestinal permeability, and inflammatory processes. We searched the MEDLINE and SCOPUS databases using the following terms: carrageenan, carrageenan and inflammatory bowel disease, carrageenan and cancer, food additives and microbiome, food additives and intestinal permeability, and food additives and autoimmune diseases. In animal studies, degraded carrageenan has been shown to trigger intestinal ulceration and inflammation, highlighting its potential risk for exacerbating IBD. It can affect the gut microbiota, reduce bacterial diversity, and increase intestinal permeability, contributing to "leaky gut" syndrome. Some studies suggest that carrageenan may inhibit the growth of cancer cells by influencing the progression of the cell cycle, but the anti-cancer effect is still unclear. Carrageenan may also increase glucose intolerance and insulin resistance. Further research is needed to determine whether carrageenan should be excluded from the diet of individuals with IBD.


Assuntos
Carragenina , Dieta , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Aditivos Alimentares/efeitos adversos , Permeabilidade
15.
Biol Pharm Bull ; 47(6): 1123-1127, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38839364

RESUMO

This study aimed to validate the In vitro Dissolution Absorption System 2 (IDAS2) containing a biological barrier of Caco-2 or Madin-Darby canine kidney (MDCK) cell monolayer through dose sensitivity studies. Metoprolol and propranolol were selected as Biopharmaceutics Classification System (BCS) Class I model drugs, and atenolol as a Class III model drug. The IDAS2 is comprised of a dissolution vessel (500 mL) and two permeation chambers (2 × 8.0 mL) mounted with Caco-2 or MDCK cell monolayer. One or two immediate-release tablet(s) of the model drug were added to the dissolution vessel, and the time profiles of dissolution and permeation were observed. Greater than 85% of metoprolol and propranolol (tested at two dosing concentrations) were dissolved by 15 min, and all drugs were fully dissolved by 30 min. All three drugs were more permeable across Caco-2 cells than MDCK cells with a linear increase in permeation across both cells at both dose concentrations. Thus, the dose sensitivity of the IDAS2 was demonstrated using both cell barriers. These results indicate a successful qualification of IDAS2 for the development/optimization of oral formulations and that MDCK cells can be utilized as a surrogate for Caco-2 cells.


Assuntos
Atenolol , Metoprolol , Propranolol , Solubilidade , Cães , Células CACO-2 , Humanos , Animais , Células Madin Darby de Rim Canino , Propranolol/farmacocinética , Metoprolol/farmacocinética , Metoprolol/administração & dosagem , Atenolol/farmacocinética , Atenolol/administração & dosagem , Relação Dose-Resposta a Droga , Biofarmácia/métodos , Permeabilidade , Absorção Intestinal
16.
Exp Dermatol ; 33(6): e15107, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38840418

RESUMO

The skin plays an essential role in preventing the entry of external environmental threats and the loss of internal substances, depending on the epidermal permeability barrier. Nuclear receptors (NRs), present in various tissues and organs including full-thickness skin, have been demonstrated to exert significant effects on the epidermal lipid barrier. Formation of the lipid lamellar membrane and the normal proliferation and differentiation of keratinocytes (KCs) are crucial for the development of the epidermal permeability barrier and is regulated by specific NRs such as PPAR, LXR, VDR, RAR/RXR, AHR, PXR and FXR. These receptors play a key role in regulating KC differentiation and the entire process of epidermal lipid synthesis, processing and secretion. Lipids derived from sebaceous glands are influenced by NRs as well and participate in regulation of the epidermal lipid barrier. Furthermore, intricate interplay exists between these receptors. Disturbance of barrier function leads to a range of diseases, including psoriasis, atopic dermatitis and acne. Targeting these NRs with agonists or antagonists modulate pathways involved in lipid synthesis and cell differentiation, suggesting potential therapeutic approaches for dermatosis associated with barrier damage. This review focuses on the regulatory role of NRs in the maintenance and processing of the epidermal lipid barrier through their effects on skin lipid synthesis and KC differentiation, providing novel insights for drug targets to facilitate precision medicine strategies.


Assuntos
Diferenciação Celular , Epiderme , Queratinócitos , Metabolismo dos Lipídeos , Receptores Citoplasmáticos e Nucleares , Humanos , Epiderme/metabolismo , Queratinócitos/metabolismo , Queratinócitos/fisiologia , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores Citoplasmáticos e Nucleares/fisiologia , Animais , Permeabilidade
17.
Wiad Lek ; 77(4): 732-738, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38865630

RESUMO

OBJECTIVE: Aim: To investigate the effectiveness of rifaximin and probiotics for the correction of intestinal permeability in patients with metabolic-associated fatty liver disease (MAFLD) in combination with type 2 diabetes mellitus. PATIENTS AND METHODS: Materials and Methods: The prospective interventional randomized investigation included 68 patients with MAFLD in combination with type 2 diabetes, who were examined and divided into the 2 groups of treatment. RESULTS: Results: The serum levels of interleukin (IL) - 6, IL-10 and zonulin, indicators of liver functional activity, liver attenuation coefficient between treatment group vs. control group after 2 weeks, 1 month, 3 and 6 months of therapy were significant differed. The serum levels of IL-6 and zonulin significantly decreasing and increasing of IL-10 in the treatment group after 2 weeks, 1, 3 and 6 months of combined therapy. When comparing of stool short-chain fatty acids concentration between treatment group vs. control group after 2 weeks, 1 month, 3 and 6 months of therapy the levels of acetic, butyric and propionic acids significantly differences and increase in their levels were established. CONCLUSION: Conclusions: The results of the study in dynamics during 6 months show that the additional appointment of rifaximin, multispecies probiotic and prebiotic to metformin in patients with MAFLD and type 2 diabetes led to the elimination of subclinical inflammation, modulation of the permeability of the intestinal barrier and lowering increased intestinal permeability, as well as to the lower serum activity of liver aminotransferases and decrease the stage of steatosis.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Permeabilidade , Probióticos , Rifaximina , Humanos , Rifaximina/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Probióticos/uso terapêutico , Probióticos/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Permeabilidade/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Haptoglobinas/metabolismo , Rifamicinas/uso terapêutico , Rifamicinas/administração & dosagem , Resultado do Tratamento , Adulto , Interleucina-6/sangue , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Precursores de Proteínas/sangue , Função da Barreira Intestinal
18.
J Environ Manage ; 362: 121352, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38833930

RESUMO

The increased production of polystyrene waste has led to the need to find efficient ways to dispose of it. One possibility is the use of solid waste to produce filter media by the electrospinning technique. The aim of this work was to develop an ultra-fast electrospinning process applied to recycled polystyrene, with statistical evaluation of the influence of polymeric solution parameters (polymer concentration and percentage of DL-limonene) and process variables (flow rate, voltage, and type of support) on nanoparticle collection efficiency, air permeability, and fiber diameter. An extensive characterization of the materials and evaluation of the morphology of the fibers was also carried out. It was found that recycled expanded polystyrene could be used in electrospinning to produce polymeric membranes. The optimized condition that resulted in the highest nanoparticle collection efficiency was a polymer concentration of 13.5%, percentage of DL-limonene of 50%, voltage of 25 kV, and flow rate of 1.2 mL/h, resulting in values of 99.97 ± 0.01%, 2.6 ± 0.5 × 10-13 m2, 0.19 Pa-1, and 708 ± 176 nm for the collection efficiency of nanoparticles in the range from 6.38 to 232.9 nm, permeability, quality factor, and mean fiber diameter, respectively. All the parameters were found to influence collection efficiency and fiber diameter. The use of DL-limonene, a natural solvent, provided benefits including increased collection efficiency and decreased fiber size. In addition, the electrostatic filtration mechanism was evaluated using the presence of a copper grid as a support for the nanofibers. The findings demonstrated that an electrospinning time of only 5 min was sufficient to obtain filters with high collection efficiencies and low pressure drops, opening perspectives for the application of polystyrene waste in the development of materials with excellent characteristics for application in the area of atmospheric pollution mitigation.


Assuntos
Filtração , Nanopartículas , Poliestirenos , Poliestirenos/química , Nanopartículas/química , Filtração/métodos , Membranas Artificiais , Polímeros/química , Reciclagem , Permeabilidade
19.
Int J Mol Sci ; 25(11)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38892151

RESUMO

Astaxanthin (AST) is a natural compound derived from shellfish, microorganisms, and algae, with several healthy properties. For this reason, it is widely used in the diet of humans and animals, such as pigs, broilers, and fish, where its addition is related to its pigmenting properties. Moreover, AST's ability to reduce free radicals and protect cells from oxidative damage finds application during the weaning period, when piglets are exposed to several stressors. To better elucidate the mechanisms involved, here we generate ad hoc pig and rainbow trout in vitro platforms able to mimic the intestinal mucosa. The morphology is validated through histological and molecular analysis, while functional properties of the newly generated intestinal barriers, both in porcine and rainbow trout models, are demonstrated by measuring trans-epithelial electrical resistance and analyzing permeability with fluorescein isothiocyanate-dextran. Exposure to AST induced a significant upregulation of antioxidative stress markers and a reduction in the transcription of inflammation-related interleukins. Altogether, the present findings demonstrate AST's ability to interact with the molecular pathways controlling oxidative stress and inflammation both in the porcine and rainbow trout species and suggest AST's positive role in prevention and health.


Assuntos
Mucosa Intestinal , Oncorhynchus mykiss , Estresse Oxidativo , Xantofilas , Animais , Xantofilas/farmacologia , Oncorhynchus mykiss/metabolismo , Suínos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Intestinos/efeitos dos fármacos , Modelos Biológicos , Permeabilidade/efeitos dos fármacos
20.
Int J Mol Sci ; 25(11)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38892341

RESUMO

Anthocyanins are amazing plant-derived colorants with highly valuable properties; however, their chemical and color instability issues limit their wide application in different food industry-related products such as active and intelligent packaging. In a previous study, it was demonstrated that anthocyanins could be stabilized into green plasticizers namely deep eutectic solvents (DESs). In this work, the fabrication of edible films by integrating anthocyanins along with DESs into biocompatible chitosan (CHT)-based formulations enriched with polyvinyl alcohol (PVA) and PVA nanoparticles was investigated. CHT/PVA-DES films' physical properties were characterized by scanning electron microscopy, water vapor permeability, swelling index, moisture sorption isotherm, and thermogravimetry analysis. Innovative red-to-blue formulation films were achieved for CHT/PVA nanoparticles (for 5 min of sonication) at a molar ratio 1:1, and with 10% of ternary DES (TDES)-containing malvidin-3-glucoside (0.1%) where the physical properties of films were enhanced. After immersion in solutions at different pH values, films submitted to pHs 5-8 were revealed to be more color stable and resistant with time than at acidic pH values.


Assuntos
Antocianinas , Quitosana , Álcool de Polivinil , Solventes , Álcool de Polivinil/química , Antocianinas/química , Quitosana/química , Solventes/química , Biofilmes/efeitos dos fármacos , Nanopartículas/química , Embalagem de Alimentos/métodos , Concentração de Íons de Hidrogênio , Cor , Permeabilidade
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