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1.
Cytokine ; 181: 156669, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38875750

RESUMO

OBJECTIVES: Alveolar echinococcosis (AE) represents one of the deadliest helminthic infections, characterized by an insidious onset and high lethality. METHODS: This study utilized the Gene Expression Omnibus (GEO) database, applied Weighted Correlation Network Analysis (WGCNA) and Differential Expression Analysis (DEA), and employed the Matthews Correlation Coefficient (MCC) to identify CCL17 and CCL19 as key genes in AE. Immunohistochemistry and immunofluorescence co-localization techniques were used to examine the expression of CCL17 and CCL19 in liver tissue lesions of AE patients. Additionally, a mouse model of multilocular echinococcus larvae infection was developed to study the temporal expression patterns of these genes, along with liver fibrosis and inflammatory responses. RESULTS: The in vitro model simulating echinococcal larva infection mirrored the hepatic microenvironment post-infection with multilocular echinococcal tapeworms. Quantitative RT-PCR analysis showed that liver fibrosis occurred in AE patients, with proximal activation and increased expression of CCL17 and CCL19 over time post-infection. Notably, expression peaked during the late stages of infection. Similarly, F4/80, a macrophage marker, exhibited corresponding trends in expression. Upon stimulation of normal hepatocytes by vesicular larvae in cellular experiments, there was a significant increase in CCL17 and CCL19 expression at 12 h post-infection, mirroring the upregulation observed with F4/80. CONCLUSION: CCL17 and CCL19 facilitate macrophage aggregation via the chemokine pathway and their increased expression correlates with the progression of infection, suggesting their potential as biomarkers for AE progression.


Assuntos
Biomarcadores , Quimiocina CCL17 , Quimiocina CCL19 , Progressão da Doença , Animais , Humanos , Camundongos , Biomarcadores/metabolismo , Quimiocina CCL19/metabolismo , Quimiocina CCL17/metabolismo , Quimiocina CCL17/genética , Equinococose/metabolismo , Cirrose Hepática/parasitologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Modelos Animais de Doenças , Fígado/parasitologia , Fígado/metabolismo , Fígado/patologia , Equinococose Hepática/metabolismo , Equinococose Hepática/parasitologia , Feminino , Masculino , Hepatócitos/metabolismo , Hepatócitos/parasitologia
2.
Angew Chem Int Ed Engl ; 62(13): e202217833, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36720709

RESUMO

Zinc (Zn) metal anode suffers from uncontrollable Zn dendrites and parasitic side reactions at the interface, which restrict the practical application of aqueous rechargeable zinc batteries (ARZBs). Herein, an amphoteric cellulose-based double-network is introduced as hydrogel electrolyte to overcome these obstacles. On one hand, the amphoteric groups build anion/cation transport channels to regulate electro-deposition behavior on Zn (002) crystal plane enabled by homogenizing Zn2+ ions flux. On the other hand, the strong bonding between negatively charged carboxyl groups and Zn2+ ions promote the desolvation process of [Zn(H2 O)6 ]2+ to eliminate side reactions. Based on the above two functions, the hydrogel electrolyte enables an ultra-stable cycling with a cumulative capacity of 7 Ah cm-2 at 20 mA cm-2 /20 mAh cm-2 for Zn||Zn cell. This work provides significant concepts for developing hydrogel electrolytes to realize stable anode for high-performance ARZBs.

3.
Small ; 18(45): e2202235, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36089663

RESUMO

Cardiac microphysiological systems are accurate in vitro platforms that reveal the biological mechanisms underlying cardiopathy, accelerating pharmaceutical research in this field. Current cardiac microphysiological devices and organs-on-chips consist of several layers prepared with complex, multi-step processes. Incorporating inorganic photonic crystals may cause long-term biocompatibility issues. Herein, micropatterned hydrogels with anisotropic structural colors are prepared by locking shear-oriented tunicate cellulose nanocrystals (TCNCs) in hydrogel networks through in situ polymerization, allowing the visualization and monitoring of cardiomyocytes. The anisotropic hydrogels are composed of highly ordered TCNCs with bright interference color and micro-grooved methacrylated gelatin with excellent biocompatibility. The microgroove patterns induce cardiomyocyte alignment and the autonomous beating of cardiomyocytes causes the hydrogels to deform, dynamically shifting the interference color. These micropatterned hydrogels could noninvasively monitor real-time changes of cardiomyocytes under pharmaceutical treatment and electrical stimulation through wavelength shifts in the transmittance spectra. This system provides a new way to detect the beat rate of cardiac tissue and it may contribute to high throughput develop.


Assuntos
Hidrogéis , Nanopartículas , Hidrogéis/química , Miócitos Cardíacos , Celulose/química , Gelatina
4.
Anal Biochem ; 655: 114842, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-35934072

RESUMO

In this study, a novel, simple and reliable high-performance liquid chromatography with tandem mass spetrometry method (HPLC-MS/MS) was developed for the determination of hydronidone and its metabolites M3 and M4 in human plasma and urine so as to study the clinical pharmacokinetics of hydronidone. By effectively inhibiting the proliferation of hepatic stellate cells (HSC), hydronidone can reduce collagen synthesis and curbs the process of liver fibrosis, and is currently in the stage of clinical research for anti-liver fibrosis. Hydronidone and its metabolites M3, M4 were extracted from human plasma by protein precipitation, and the urine samples were directly diluted with acetonitrile and analyzed by HPLC-MS/MS. The quantification ranges in plasma were 1.00-1000 ng/mL, 2.00-2000 ng/mL and 4.00-4000 ng/mL, respectively and in urine were 10.0-2000 ng/L, 100-25000 ng/L and 300-75000 ng/L, respectively. Coefficients of variation of less than 15% between intraday and interday accuracy and precision values were observed for hydronidone, M3 and M4. The S/N (signal-to-noise ratio) of the analyte in each Low limit of quantification sample in the analytical batch was greater than 5, indicating good sensitivity. The recovery rates were above 50% for all analytes. The parameters such as linearity, selectivity, lower precision, accuracy, recovery, stability and matrix effects were validated by the methodology and met the requirements specified by the FDA and the European Medicines Agency. The method has been successfully applied to the pharmacokinetics of hydronidone and its metabolites M3 and M4 in healthy Chinese volunteers.


Assuntos
Espectrometria de Massas em Tandem , China , Cromatografia Líquida de Alta Pressão/métodos , Fibrose , Humanos , Piridonas , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
5.
Macromol Rapid Commun ; 42(3): e2000497, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33205538

RESUMO

Functional polymer, especially the one based on renewable and sustainable materials, has attracted increasing attention to satisfy the growing demand for the design of stimuli-responsive devices. Methylcellulose (MC) is a water-soluble derivative of cellulose, which has been widely used in many fields for its biocompatibility and biological inertness. In this work, MC is labeled by tetraphenylethylene (TPE) via azide-alkyne click reaction to obtain a fluorescent cellulose-based derivative of MC-TPE. The degree of substitution of MC-TPE is determined to be 0.074, which can be self-assembled into micelles in water with the size of 42 ± 6 nm. MC-TPE shows thermoresponsivity and thermoreversibility in size, transmittance, and fluorescence, enabling it to work as a fluorescent thermosensor. Moreover, MC-TPE exhibits nontoxicity and biocompatibility, allowing its application in MCF-7 cell imaging. Therefore, this newly functional natural polymer shows promising potentials in the fields of sensing and bioimaging.


Assuntos
Metilcelulose , Estilbenos , Corantes Fluorescentes , Polímeros
6.
Molecules ; 26(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071835

RESUMO

Water-soluble cellulose ethers are widely used as stabilizers, thickeners, and viscosity modifiers in many industries. Understanding rheological behavior of the polymers is of great significance to the effective control of their applications. In this work, a series of cyanoethylcellulose (CEC) samples with different molecular weights were prepared with cellulose and acrylonitrile in NaOH/urea aqueous solution under the homogeneous reaction. The rheological properties of water-soluble CECs as a function of concentration and molecular weight were investigated using shear viscosity and dynamic rheological measurements. Viscoelastic behaviors have been successfully described by the Carreau model, the Ostwald-de-Waele equation, and the Cox-Merz rule. The entanglement concentrations were determined to be 0.6, 0.85, and 1.5 wt% for CEC-11, CEC-7, and CEC-3, respectively. All of the solutions exhibited viscous behavior rather than a clear sol-gel transition in all tested concentrations. The heterogeneous nature of CEC in an aqueous solution was determined from the Cox-Merz rule due to the coexistence of single chain complexes and aggregates. In addition, the CEC aqueous solutions showed good thermal and time stability, and the transition with temperature was reversible.

7.
Electrophoresis ; 41(9): 729-734, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31975426

RESUMO

CE is a promising technique for the analysis of glycosylated proteins, especially at the intact level. In the present study, the utility of CE for the separation of protein glycoforms is developed by using methyl chitosan as capillary coating. Methyl chitosan, in contrast to the polymers commonly used for coating, bears different types of amine groups, allowing for tunable charge states for various applications. The addition of methyl chitosan in background electrolyte can modulate the EOF and improve the separation performance. The methyl chitosan-coated capillary provided good separation of acidic or basic glycosylated proteins. Five ribonuclease B glycoforms were resolved by CE in less than 18 min, and the profile was essentially in agreement with that obtained by MALDI-TOF MS. The recombinant human erythropoietin glycoforms were well separated within 9 min. The developed method shows a great potential in protein glycoform analysis.


Assuntos
Quitosana/química , Eletroforese Capilar/métodos , Glicoproteínas/análise , Glicosilação , Humanos , Concentração de Íons de Hidrogênio , Proteínas Recombinantes/análise
8.
Biomacromolecules ; 17(9): 2839-48, 2016 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-27519472

RESUMO

Polysaccharide-based injectable hydrogels have several advantages in the context of biomedical use. However, the main obstruction associated with the utilization of these hydrogels in clinical application is their poor mechanical properties. Herein, we describe in situ gelling of nanocomposite hydrogels based on quaternized cellulose (QC) and rigid rod-like cationic cellulose nanocrystals (CCNCs), which can overcome this challenge. In all cases, gelation immediately occurred with an increase of temperature, and the CCNCs were evenly distributed throughout the hydrogels. The nanocomposite hydrogels exhibited increasing orders-of-magnitude in the mechanical strength, high extension in degradation and the sustained release time, because of the strong interaction between CCNCs and QC chains mediated by the cross-linking agent (ß-glycerophosphate, ß-GP). The results of the in vitro toxicity and in vivo biocompatibility tests revealed that the hydrogels did not show obvious cytotoxicity and inflammatory reaction to cells and tissue. Moreover, DOX-encapsulated hydrogels were injected beside the tumors of mice bearing liver cancer xenografts to assess the potential utility as localized and sustained drug delivery depot systems for anticancer therapy. The results suggested that the QC/CCNC/ß-GP nanocomposite hydrogels had great potential for application in subcutaneous and sustained delivery of anticancer drug to increase therapeutic efficacy and improve patient compliance.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Cátions/química , Celulose/química , Hidrogéis/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/administração & dosagem , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Preparações de Ação Retardada , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Feminino , Glicerofosfatos/química , Humanos , Hidrogéis/química , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Engenharia Tecidual , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Arch Virol ; 161(6): 1437-45, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26935915

RESUMO

H9N2 influenza viruses have been circulating in China since 1994, but a systematic investigation of H9N2 in Shanghai has not previously been undertaken. Here, using 14 viruses we isolated from poultry and pigs in Shanghai during 2002 and 2006-2014, together with the commercial vaccine A/chicken/Shanghai/F/1998 (Ck/SH/F/98), we analyzed the evolution of H9N2 influenza viruses in Shanghai and showed that all 14 isolates originated from Ck/SH/F/98 antigenically. We evaluated the immune protection efficiency of the vaccine. Our findings demonstrate that H9N2 viruses in Shanghai have undergone extensive reassortment. Various genotypes emerged in 2002, 2006 and 2007, while during 2009-2014 only one genotype was found. Four antigenic groups, A-D, could be identified among the 14 isolates and a variety of antigenically distinct H9N2-virus-derived avian influenza viruses (AIVs) circulated simultaneously in Shanghai during this period. Challenge experiments using vaccinated chickens indicated that the vaccine prevented shedding of antigenic group A and B viruses, but not those of the more recent groups C and D. Genetic analysis showed that compared to the vaccine strain, representative viruses of antigenic groups C and D possess greater numbers of amino acid substitutions in the hemagglutinin (HA) protein than viruses in antigenic groups A and B. Many of these substitutions are located in antigenic sites. Our results indicate that the persistence of H9N2 AIV in China might be due to incomplete vaccine protection and that the avian influenza vaccine should be regularly evaluated and updated to maintain optimal protection.


Assuntos
Antígenos Virais/genética , Evolução Molecular , Vírus da Influenza A Subtipo H9N2/genética , Vírus da Influenza A Subtipo H9N2/imunologia , Animais , Galinhas , China , Genótipo , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Vacinas contra Influenza/farmacologia , Influenza Aviária/prevenção & controle , Influenza Aviária/virologia , Influenza Humana/virologia , Infecções por Orthomyxoviridae/veterinária , Infecções por Orthomyxoviridae/virologia , Filogenia , Aves Domésticas , Doenças das Aves Domésticas/virologia , Suínos
10.
Angew Chem Int Ed Engl ; 55(43): 13504-13508, 2016 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-27676690

RESUMO

A facile method for the fabrication of inorganic hollow materials from cuprammonium cellulose composite filaments based on fast pyrolysis has been developed. Unlike Ostwald ripening, approaches based on the Kirkendall effect, and other template methods, this process yielded hollow materials within 100 s. The heterogeneous structure of the cellulose composite fibers and the gradient distribution of the metal oxides are the main reasons for the formation of the hollow structure. The diameter, wall thickness, and length of the hollow microfibers could be conveniently controlled. With their perfect morphology, these hollow structural materials have great potential for use in various fields.

11.
Virus Genes ; 51(1): 25-32, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25899857

RESUMO

Five H3N2 avian influenza viruses (AIVs) were isolated from live poultry markets (LPMs) and poultry slaughterhouses in Shanghai, China in 2013. All viruses were characterized by whole-genome sequencing with subsequent genetic comparison and phylogenetic analysis. The hemagglutinin cleavage site of all viruses indicated that the five strains were low-pathogenic AIVs. Phylogenetic analysis of all eight viral genes showed that the five H3N2 viruses clustered in the Eurasian lineage of influenza viruses. The eight genes showed evidence of reassortment events between these H3 subtype viruses and other subtype viruses, especially H5 and H7 subtypes, probably in pigeons, domestic ducks, and wild birds. These findings emphasized the importance of AIV surveillance in LPMs and poultry slaughterhouses for understanding the genesis and emergence of novel reassortants with pandemic potential.


Assuntos
Genoma Viral , Vírus da Influenza A Subtipo H3N2/classificação , Vírus da Influenza A Subtipo H3N2/genética , Influenza Aviária/virologia , RNA Viral/genética , Matadouros , Animais , China , Análise por Conglomerados , Variação Genética , Dados de Sequência Molecular , Filogenia , Aves Domésticas , Vírus Reordenados/classificação , Vírus Reordenados/genética , Análise de Sequência de DNA , Homologia de Sequência
12.
Arch Virol ; 159(10): 2777-85, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24818713

RESUMO

The complete genome sequence of a porcine epidemic diarrhea virus variant, strain SHQP/YM/2013, from China was determined and compared with those of other porcine epidemic diarrhea viruses. The full-length genome was 28,038 nucleotides (nt) in length without the poly (A) tail, and it was similar to that of other reported PEDV strains, with the characteristic gene order 5'-replicase (1a/1b) -S-ORF3-E-M-N-3'. Nucleotide sequence analysis based on individual virus genes indicated a close relationship between the S gene of SHQP/YM/2013 and those of the four Korean field strains from 2008-2009. Its ORF3 gene, however, fell into three groups. Recent prevalent Chinese PEDV field isolates were divided between group 1 and group 3, which suggests that the recent prevalent Chinese PEDV field isolates represent a new genotype that differs from the genotype that includes the vaccine strains. Based on phylogenetic analysis of the M gene, ORF3 gene and S gene, our study demonstrated that prevalent PEDV isolates in China may have originated from Korean strains. This report describes the complete genome sequence of SHQP/YM/2013, and the data will promote a better understanding of the molecular epidemiology and genetic diversity of PEDV field isolates in eastern China.


Assuntos
Genoma Viral/genética , Fases de Leitura Aberta/genética , Vírus da Diarreia Epidêmica Suína/genética , Proteínas Estruturais Virais/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , China , Infecções por Coronavirus/virologia , Fezes/virologia , Variação Genética , Dados de Sequência Molecular , RNA Viral/genética , Alinhamento de Sequência , Análise de Sequência de RNA , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico , Suínos/virologia , Doenças dos Suínos/virologia
13.
Arch Virol ; 159(11): 3029-41, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25085623

RESUMO

The first reported human case of H7N9 influenza virus infection in Shanghai prompted a survey of local avian strains of influenza virus, involving the analysis of a large number of samples taken from poultry, wild birds, horses, pigs, dogs and mice. Seven instances of H7N9 virus infection were identified by real-time RT-PCR (1.47 % of samples), all in chickens sold in live-poultry markets. H7N9 antibody was not detected in serum samples collected from local poultry farms since 2006. The two H7N9 virus strains in the live-poultry markets and one H9N2 virus strain in the same market were genetically characterized. Resequencing of two of the seven isolates confirmed that they closely resembled H7N9 virus strains characterized elsewhere. Various strains co-exist in the same market, presenting a continuing risk of strain re-assortment. The closure of live-poultry markets has been an effective short-term means of minimizing human exposure to H7N9 virus.


Assuntos
Doenças do Cão/virologia , Doenças dos Cavalos/virologia , Subtipo H7N9 do Vírus da Influenza A/genética , Influenza Aviária/virologia , Influenza Humana/epidemiologia , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/virologia , Animais , China/epidemiologia , Doenças do Cão/epidemiologia , Cães , Doenças dos Cavalos/epidemiologia , Cavalos , Humanos , Subtipo H7N9 do Vírus da Influenza A/classificação , Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Influenza Aviária/epidemiologia , Camundongos , Dados de Sequência Molecular , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/virologia , Filogenia , Aves Domésticas , Suínos , Doenças dos Suínos/epidemiologia
14.
Nanomicro Lett ; 16(1): 106, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38305845

RESUMO

Aqueous rechargeable Zn-metal batteries (ARZBs) are considered one of the most promising candidates for grid-scale energy storage. However, their widespread commercial application is largely plagued by three major challenges: The uncontrollable Zn dendrites, notorious parasitic side reactions, and sluggish Zn2+ ion transfer. To address these issues, we design a sustainable dual cross-linked cellulose hydrogel electrolyte, which has excellent mechanical strength to inhibit dendrite formation, high Zn2+ ions binding capacity to suppress side reaction, and abundant porous structure to facilitate Zn2+ ions migration. Consequently, the Zn||Zn cell with the hydrogel electrolyte can cycle stably for more than 400 h under a high current density of 10 mA cm-2. Moreover, the hydrogel electrolyte also enables the Zn||polyaniline cell to achieve high-rate and long-term cycling performance (> 2000 cycles at 2000 mA g-1). Remarkably, the hydrogel electrolyte is easily accessible and biodegradable, making the ARZBs attractive in terms of scalability and sustainability.

15.
J Colloid Interface Sci ; 658: 1025-1034, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38161098

RESUMO

Rational design of hierarchical porous architecture with abundant pseudocapacitive sites is highly desirable for carbon electrode materials. However, the lengthy production process and high economic input limit its broader application. Herein, we successfully prepared N, O co-doped hierarchical porous carbon (NOHC) through hydrothermal carbonization (HTC) of chitin biomass with the assist of NH4Cl and subsequent carbonization with NaNH2. The optimal NOHC600 exhibits a remarkable hierarchical porous structure and an ultrahigh specific surface area (SSA) of 2555 m2 g-1. Furthermore, it showcases a significant content of N, O co-doping, thereby providing abundant defects and additional active sites for ion adsorption. The aforementioned characteristics ensure outstanding capacitance performance of NOHC600. In the three-electrode system, NOHC600 exhibits a remarkable specific capacitance of up to 455 F g-1 at a current density of 0.5 A g-1. The symmetric supercapacitors (SCs) based on NOHC600 achieve an impressive energy density of 30.4 Wh kg-1 at a power density of 180 W kg-1. Moreover, the all-solid-state NOHC600 microsupercapacitors (MSCs) demonstrate an exceptional areal capacitance of 78.2 mF cm-2 and an areal energy density of up to 10.8 µWh cm-2. Accordingly, this facile and scalable strategy shows a great potential for producing high-heteroatom-doped porous carbon materials from chitin biomass, which can be applied in practical energy-related applications.

16.
Carbohydr Polym ; 338: 122184, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38763707

RESUMO

Taking the perspective of cellulose molecular chain assembly via the "bottom-top" route, we delve into the influence of both the cellulose solution and the coagulation bath on the assembly process and structure of regenerated cellulose beads (RCBs). The results show that cellulose molecular weight, mass fraction, and the presence of surfactant have an impact on RCBs. Contrary to traditional views where the structures of material are determined by solvent-nonsolvent exchange rate, ion-cellulose binding capacity also affects RCBs. Overall, the influence of ions follows the Hofmeister sequence. Kosmotropes promote the assembly of cellulose chains and elementary fibers, leading to "salting out" effects, reduced pore size of RCBs, increased crystallinity, and enhanced mechanical properties. In contrast, chaotropes induce "salting in" effects, resulting in opposite outcomes. The average pore size of RCBs coagulated in NaSCN solution was approximately 15-folds larger than those prepared in sodium citrate solution. Anions have a greater impact than cations, and both "salting out" and "salting in" effects strengthen with concentration. Temperature variations primarily affect solvent and nonsolvent exchange speed during cellulose regeneration. These findings provide new insights into regulating RCBs, enabling tailored performance for different applications.

17.
Int Immunopharmacol ; 126: 111233, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37979449

RESUMO

BACKGROUNDS: Tacrolimus (TAC) concentration in peripheral blood mononuclear cells (PBMCs) is regarded as a better predictor of its immunosuppressive effect than the TAC concentration in whole blood. However, whether the exposure of TAC in PBMCs or WB was altered in post-transplant recipients with renal impairment remains unclear. METHODS: We investigated the relationship of trough TAC concentration in WB and PBMCs with renal functions in post-transplant recipients. The pharmacokinetic profiles of TAC in PBMCs and WB in the two chronic kidney disease (CKD) rat models were examined using UPLC-MS/MS. Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to analyze the expression of proteins and mRNAs related to TAC metabolism and transport, respectively. In addition, the effects of uremic toxins on human PBMCs were investigated using whole-transcriptome sequencing (RNA sequencing [RNA-seq]). RESULTS: We observed a decrease in the trough TAC concentration in PBMCs in the recipients with estimated glomerular filtration rate (eGFR) < 90 mL/min, compared with those of recipients with eGFR > 90 mL/min, but there was no difference in blood based on TAC concentrations (C0Blood). In a 150-patient post-transplant cohort, no significant relationship was observed between PBMCs and WB concentrations of TAC, and the eGFR value was correlated with TAC C0PBMCs but not with TAC C0Blood. In two CKD rat models, the TAC pharmacokinetic profile in the PBMCs was significantly lower than that in the control group; however, the blood TAC pharmacokinetic profiles in the two groups were similar. Transcriptome results showed that co-incubation of human PBMCs with uremic toxins upregulated the expression of AHR, ABCB1, and ABCC2. Compared to control rats, plasma IS increased by 1.93- and 2.26-fold and the expression of AHR, P-gp, and MRP2 in PBMCs was higher in AD and 5/6 nephrectomy (NX) rats, without modifying the expression of other proteins related to TAC exposure. CONCLUSION: The pharmacokinetics of TAC in PBMCs changed with a decline in renal function. Uremic toxins accumulate during renal insufficiency, which activates AHR, upregulates the expression of P-gp and MRP2, and affects their intracellular concentrations. Our findings suggest that monitoring TAC concentrations in PBMCs is more important than monitoring WB concentrations in post-transplant recipients with renal impairment.


Assuntos
Insuficiência Renal Crônica , Insuficiência Renal , Humanos , Animais , Ratos , Tacrolimo/uso terapêutico , Imunossupressores , Transportadores de Cassetes de Ligação de ATP , Cromatografia Líquida , Leucócitos Mononucleares/metabolismo , Toxinas Urêmicas , Espectrometria de Massas em Tandem , Rim/metabolismo , Insuficiência Renal/metabolismo , Insuficiência Renal Crônica/metabolismo
18.
Gut Microbes ; 16(1): 2310277, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38332701

RESUMO

Up to 40% of transplant recipients treated long-term with tacrolimus (TAC) develop post-transplant diabetes mellitus (PTDM). TAC is an important risk factor for PTDM, but is also essential for immunosuppression after transplantation. Long-term TAC treatment alters the gut microbiome, but the mechanisms of TAC-induced gut microbiota in the pathogenesis of PTDM are poorly characterized. Here, we showed that vancomycin, an inhibitor of bacterial beta-glucuronidase (GUS), prevents TAC-induced glucose disorder and insulin resistance in mice. Metagenomics shows that GUS-producing bacteria are predominant and flourish in the TAC-induced hyperglycemia mouse model, with upregulation of intestinal GUS activity. Targeted metabolomics analysis revealed that in the presence of high GUS activity, the hydrolysis of bile acid (BAs)-glucuronic conjugates is increased and most BAs are overproduced in the serum and liver, which, in turn, activates the ileal farnesoid X receptor (FXR) and suppresses GLP-1 secretion by L-cells. The GUS inhibitor vancomycin significantly eliminated GUS-producing bacteria and inhibited bacterial GUS activity and BAs levels, thereby enhancing L-cell GLP-1 secretion and preventing hyperglycemia. Our results propose a novel clinical strategy for inhibiting the bacterial GUS enzyme to prevent hyperglycemia without requiring withdrawal of TAC treatment. This strategy exerted its effect through the ileal bile acid-FXR-GLP-1 pathway.


Assuntos
Diabetes Mellitus , Microbioma Gastrointestinal , Hiperglicemia , Camundongos , Animais , Tacrolimo/farmacologia , Tacrolimo/uso terapêutico , Vancomicina/farmacologia , Imunossupressores/uso terapêutico , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Bactérias/genética , Bactérias/metabolismo , Glucuronidase/metabolismo , Glucuronidase/farmacologia , Ácidos e Sais Biliares/farmacologia , Peptídeo 1 Semelhante ao Glucagon
19.
Int J Nurs Sci ; 11(1): 91-98, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38352296

RESUMO

Objective: This study aimed to investigate the level and influencing factors of nurses' antimicrobial stewardship (AMS) engagement in China based on the capability, opportunity, motivation, and behavior (COM-B) theory, providing valuable insights for developing effective strategies to improve nursing quality in AMS. Methods: This cross-sectional study was conducted in 17 tertiary hospitals in Hunan, China, from November 2021 to January 2022. A total of 4,514 nurses were selected. The Nurse AMS Engagement Questionnaire (NAEQ), developed using the COM-B theory, was used for evaluation. The questionnaire included capability (14 items), opportunity (7 items), motivation (6 items), and behavior (12 items) four dimensions, 39 items. Results: The total NAEQ score was 155.08 ± 27.12, indicating a moderate level. The score of the capability, opportunity, motivation, and behavior dimensions were 52.33 ± 13.48, 28.64 ± 5.76, 24.57 ± 4.57 and 49.53 ± 8.83, respectively. Significant differences in nurses' AMS engagement were based on professional titles, whether working as a part-time infection control nurse, whether knowing the AMS teams and the defined daily doses of antibiotics, department type, the deployment of clinical pharmacists, and frequency of antimicrobial training and physician-nurse joint rounds (P < 0.05). Nurses with junior titles had higher scores on the NAEQ than nurses with intermediate titles (P < 0.05). Nurses who worked as part-time infection control nurses, knew the AMS team, and the defined daily doses of antibiotics had higher NAEQ scores than those who didn't (P < 0.01). Nurses working in the ICU and infectious disease department had lower NAEQ scores than those in other departments, such as the ear, nose, and throat (ENT) department (P < 0.01). Nurses who had clinical pharmacists deployed in their department had higher NAEQ scores than those without or unclear deployment (P < 0.01). Furthermore, nurses who received more frequent antimicrobial training and participated in physician-nurse joint rounds had higher NAEQ scores (P < 0.01). Conclusion: Multiple strategies, including enhanced education and training and improved multidisciplinary communication and collaboration, are expected to improve nurse AMS engagement. It is important to give more attention to nurses with intermediate professional titles, less experience, and those working in specific departments.

20.
Food Chem ; 458: 140293, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38970959

RESUMO

The present study aimed to determine microbial community, short-chain fatty acids (SCFAs), and volatilome of Bulang pickled tea during fermentation. Sequencing of 16S rRNA and ITS revealed that Bualng pickled tea was dominated by Lactobacillus plantarum, unclassified Enterobacteriaceae, unclassified Debaryomyces, Candida metapsilosis, Cladosporium sphaerospermum, and unclassified Aspergillus. The overall contents of SCFAs increased, with acetic acid showing the highest content. A total of 398 differential volatile metabolites were detected using differential metabolomics analysis. Out of these different volatile compounds, ten key volatile compounds including (Z)-4-heptenal, 1-(2-thienyl)-ethanone, 5-methyl-(E)-2-hepten-4-one, 2-ethoxy-3-methylpyrazine, p-cresol, 2-methoxy-phenol, ethy-4-methylvalerate, 3-ethyl-phenol, p-menthene-8-thiol, and 2-s-butyl-3-methoxypyrazinewere were screened based on odor activity value (OAV). The Spearman correlation analysis showed a high correlation of SCFAs and volatile compounds with microorganisms, especially L. plantarum and C. sphaerospermum. This study provided a theoretical basis for elucidating the flavor quality formation mechanism of Bulang pickled tea.


Assuntos
Bactérias , Fermentação , Chá , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/metabolismo , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/análise , Bactérias/metabolismo , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Chá/química , Chá/microbiologia , Chá/metabolismo , Microbiota , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/análise , Camellia sinensis/metabolismo , Camellia sinensis/química , Camellia sinensis/microbiologia , Fungos/metabolismo , Fungos/classificação , Fungos/genética , Odorantes/análise
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