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1.
Biomed Pharmacother ; 153: 113409, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076534

RESUMO

Ulcerative colitis is an idiopathic disease that is widely incident worldwide. Canagliflozin, antidiabetic agent, exhibited significant anti-inflammatory effects in a variety of animal models. Additionally, hyaluronic acid is considered one of the key players in the tissue regeneration process. It has been proven to modulate inflammation and cellular migration, which are the main phases of wound healing. The combination of hyaluronic acid with chitosan in microsphere fabrication was anticipated to reveal a synergistic muco-adhesiveness potential with additional advantage of the chitosan penetration enhancing effect. The current study aimed to explore the potential of canagliflozin-loaded chitosan-hyaluronic acid microspheres intrarectal administration to mitigate acetic acid-induced colitis in rats. Colon tissues were examined for macroscopic and microscopic pathological changes. ELISA and qRT-PCR techniques were applied for the detection of cytokines involved in the AMPK/NF-κB/NLRP3 axis. Intrarectal administration of this formula alleviated colitis severity, which was reflected by the reduced DAI, MES, colonic weight/length ratio and histopathological scoring values. Interestingly, canagliflozin-loaded chitosan-hyaluronic acid microspheres significantly enhanced AMPK phosphorylation and depressed NF-κB and NLRP3 expression leading to a subsequent reduction in caspase-1 cleavage and the inhibition of several inflammatory cytokines, including IL-1ß, and IL-18. Overall, the current study revealed that the protective effects of the formula against acetic acid-induced colitis are primarily mediated via augmenting AMPK phosphorylation and its consequences of NF-κB inactivation. Since canagliflozin is not associated with hypoglycemic effects, clinical application of canagliflozin-loaded chitosan-hyaluronic acid microspheres represent a novel therapeutic option for the treatment of patients with ulcerative colitis.


Assuntos
Quitosana , Colite Ulcerativa , Colite , Proteínas Quinases Ativadas por AMP/metabolismo , Ácido Acético/farmacologia , Animais , Canagliflozina/farmacologia , Canagliflozina/uso terapêutico , Quitosana/farmacologia , Colite/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo , Citocinas/metabolismo , Ácido Hialurônico/metabolismo , Microesferas , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Transdução de Sinais
2.
Methods Mol Biol ; 2574: 233-250, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36087205

RESUMO

CD4+ T cells play a vital role in the immune response, and their function requires T cell receptor (TCR) recognition of peptide epitopes presented in complex with MHC class II (MHCII) molecules. Consequently, rapidly identifying peptides that bind MHCII is critical to understanding and treating infectious disease, cancer, autoimmunity, allergy, and transplant rejection. Computational methods provide a fast, ultrahigh-throughput approach to predict MHCII-binding peptides but lack the accuracy of experimental methods. In contrast, experimental methods offer accurate, quantitative results at the expense of speed. To address the gap between these two approaches, we developed a high-throughput, semiquantitative experimental screening strategy termed microsphere-assisted peptide screening (MAPS). Here, we use the Zika virus envelope protein as an example to demonstrate the rapid identification of MHCII-binding peptides from a single pathogenic protein using MAPS. This process involves several key steps including peptide library design, peptide exchange into MHCII, peptide-MHCII loading onto microspheres, flow cytometry screening, and data analysis to identify peptides that bind to one or more MHCII alleles.


Assuntos
Infecção por Zika virus , Zika virus , Apresentação de Antígeno , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Microesferas , Biblioteca de Peptídeos , Peptídeos/química , Zika virus/metabolismo
3.
Sci Rep ; 12(1): 15363, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36100635

RESUMO

As an adjuvant drug, alprostadil lipid microsphere injection (Lipo-PGE1) is one of the best-selling drugs in China in recent years. However, the off-label use of Lipo-PGE1 is very common. This study aimed to investigate the use of Lipo-PGE1 and evaluate the clinical effects and economic benefits after administrative intervention on inappropriate use of Lipo-PGE1 in neurosurgical patients in a Chinese tertiary hospital. Administrative interventions were implemented from January to December 2018 by reducing the procurement volume of Lipo-PGE1, judging the rationality of medical records, and establishing reward and punishment mechanisms. Administrative interventions significantly decreased prescription rate (49.98% vs 22.49%), utilization (22,311 DDDs vs 8334 DDDs), drug use density (43.52 DDDs/TID vs 15.84 DDDs/TID), total expenditure (3.58 million RMB vs 1.30 million RMB), and average expenditure (2025.04 RMB vs 1466.49 RMB) of Lipo-PGE1. To our delight, these intervention effects were maintained or even better in the 1-year post-intervention period. Moreover, in the intervention and post-intervention phases, the Lipo-PGE1 use for no indications as well as inappropriate drug dose, frequency, menstruum type, combination, and contraindication were markedly reduced. Besides, the mean costs (P < 0.001), and mean duration (P < 0.001) of Lipo-PGE1 were also obviously decreased. The administrative intervention obviously reduced the off-label use of Lipo-PGE1. However, there still remains a number of inappropriate uses of Lipo-PGE1. To further improve the rational use of Lipo-PGE1, combination of administrative intervention and real-time clinical pharmacists intervention should be implemented.


Assuntos
Alprostadil , Uso Off-Label , Alprostadil/uso terapêutico , China , Humanos , Microesferas , Farmacêuticos
4.
ACS Appl Mater Interfaces ; 14(36): 40711-40723, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36063108

RESUMO

Clinically, intra-articular administration can hardly achieve the truly targeted therapy, and the drugs are usually insufficient to show local and long-term therapeutic effects because of their rapid clearance. Herein, inspired by the phenomenon that bees track the scent of flowers to collect nectar, we developed cartilage-targeting hydrogel microspheres with reactive oxygen species (ROS)-responsive ability via combining the microfluidic method and photopolymerization processes to integrate cartilage-targeting peptides and ROS-responsive nanoparticles in the hydrogel matrix. The hydrogel microspheres with cartilage-targeting properties promoted better retention in the joint cavity and enhanced cellular uptake of the nanoparticles. Moreover, the ROS-responsive nanoparticles could react with osteoarthritis (OA)-induced intracellular ROS, resulting in the depolymerization of nanoparticles, which could not only eliminate excess ROS and reduce inflammation but also promote the release of dexamethasone (Dex) and kartogenin (KGN) in situ, realizing effective OA therapy. It was demonstrated that this hydrogel microsphere showed favorable ROS-responsive ability and enhanced chondrogenic differentiation as well as the downregulation of pro-inflammatory factors in vitro. Additionally, the hydrogel microspheres, similar to bees, could target and effectively repair cartilage in the OA model. Thus, the injectable hydrogel microspheres exerted an excellent potential to repair OA and may also provide an effective avenue for inflammatory bowel disease therapy.


Assuntos
Cartilagem Articular , Osteoartrite , Animais , Cartilagem , Hidrogéis/química , Microesferas , Osteoartrite/tratamento farmacológico , Espécies Reativas de Oxigênio/farmacologia
5.
In Vivo ; 36(5): 2052-2060, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36099118

RESUMO

BACKGROUND/AIM: BAT-90 is an innovative active implantable device designed for the irradiation of unresectable tumors (e.g., liver cancer) or surgical tumor beds, based on the combination of Yttrium-90 beta-emitting microspheres and a tissue adhesive hydrogel, currently used in cardio-vascular surgery. The rationale behind BAT-90 is to localize the Yttrium-90 activity on the administration site, while minimizing its body dispersion. MATERIALS AND METHODS: The effective induction of necrosis in the target injection area was tested in a pig liver model, whereas the safety of BAT-90 was assessed and demonstrated in biocompatibility tests for acute systemic toxicity, intracutaneous reactivity, delayed hypersensitivity and subcutaneous implantation. RESULTS: BAT-90 administration induced necrosis into the target site, while the safety experiments in the treated animals highlighted results very similar to the controls. CONCLUSION: BAT-90 could be considered as a safe and innovative treatment option for inoperable solid tumors of the liver.


Assuntos
Neoplasias Hepáticas , Radioisótopos de Ítrio , Animais , Neoplasias Hepáticas/radioterapia , Microesferas , Necrose , Suínos , Radioisótopos de Ítrio/efeitos adversos
6.
Int J Mol Sci ; 23(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36077387

RESUMO

Carbohydrate antigen 199 (CA199) is a serum biomarker which has certain value and significance in the diagnosis, prognosis, treatment, and postoperative monitoring of cancer. In this study, a lateral flow immunoassay based on europium (III) polystyrene time-resolved fluorescence microspheres (TRFM-based LFIA), integrated with a portable fluorescence reader, has been successfully establish for rapid and quantitative analysis of CA199 in human serum. Briefly, time-resolved fluorescence microspheres (TRFMs) were conjugated with antibody I (Ab1) against CA199 as detection probes, and antibody II (Ab2) was coated as capture element, and a "TRFMs-Ab1-CA199-Ab2" sandwich format would form when CA199 was detected by the TRFM-based LFIA. Under the optimal parameters, the detection limit of the TRFM-based LFIA for visible quantitation with the help of an ultraviolet light was 4.125 U/mL, which was four times lower than that of LFIA based on gold nanoparticles. Additionally, the fluorescence ratio is well linearly correlated with the CA199 concentration (0.00-66.0 U/mL) and logarithmic concentration (66.0-264.0 U/mL) for quantitative detection. Serum samples from 10 healthy people and 10 liver cancer patients were tested to confirm the performances of the point-of-care application of the TRFM-based LFIA, 20.0 U/mL of CA199 in human serum was defined as the threshold for distinguishing healthy people from liver cancer patients with an accuracy of about 60%. The establishment of TRFM-based LFIA will provide a sensitive, convenient, and efficient technical support for rapid screening of CA199 in cancer diagnosis and prognosis.


Assuntos
Neoplasias Hepáticas , Nanopartículas Metálicas , Biomarcadores Tumorais , Ouro , Humanos , Imunoensaio , Limite de Detecção , Microesferas
7.
Int J Mol Sci ; 23(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36077392

RESUMO

Biomass fly ash (BFA) from a biomass cogeneration plant was encapsulated into calcium alginate microspheres (ALG/Ca) and characterized. An FTIR analysis indicated that BFA loading weakened molecular interactions between ALG/Ca constituents (mainly hydrogen bonding and electrostatic interactions), thus changing the crosslinking density. SEM and AFM analyses revealed a wrinkled and rough surface with elongated and distorted granules. The in vitro release of BFA's main components (K, Ca, and Mg) was controlled by diffusion through the gel-like matrix, but the kinetics and released amounts differed significantly. The smaller released amounts and slower release rates of Ca and Mg compared to K resulted from the differences in the solubility of their minerals as well as from the interactions of divalent cations with alginate chains. The physicochemical properties of the novel microsphere formulation reveal significant potential for the prolonged delivery of nutrients to crops in a safe manner.


Assuntos
Alginatos , Cinza de Carvão , Alginatos/química , Biomassa , Microesferas , Solo/química
8.
Molecules ; 27(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36080447

RESUMO

Curcumin's role in the treatment of ulcerative colitis (UC) has been proven by numerous studies, but its preventive administration, with the aim of reducing the remission episodes that are characteristic of this disease, must be further investigated. This study investigates the effects of a novel curcumin-loaded polymeric microparticulate oral-drug-delivery system for colon targeting (Col-CUR-MPs) in an experimental model of UC. Male Wistar rats (n = 40) were divided into five groups (n = 8), which were treated daily by oral gavage for seven days with a 2% aqueous solution of carboxymethylcellulose sodium salt (CMCNa) (healthy and disease control), free curcumin powder (reference), Col-CUR-MPs (test) and prednisolone (reference) prior to UC induction by the intrarectal administration of acetic acid (AA), followed by animal sacrification and blood and colonic samples' collection on the eighth day. Col-CUR-MPs exhibited an important preventive effect in the severity degree of oxidative stress that resulted following AA intrarectal administration, which was proved by the highest catalase (CAT) and total antioxidant capacity (TAC) levels and the lowest nitrites/nitrates (NOx), total oxidative status (TOS) and oxidative stress index (OSI) levels. Biochemical parameter analysis was supported by histopathological assessment, confirming the significant anti-inflammatory and antioxidant effects of this novel colon-specific delivery system in AA-induced rat models of UC. Thus, this study offers encouraging perspectives regarding the preventive administration of curcumin in the form of a drug delivery system for colon targeting.


Assuntos
Colite Ulcerativa , Curcumina , Ácido Acético/metabolismo , Animais , Antioxidantes/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo/metabolismo , Masculino , Microesferas , Estresse Oxidativo , Ratos , Ratos Wistar
9.
Cell Death Dis ; 13(9): 779, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085138

RESUMO

Duchenne muscular dystrophy (DMD) is a genetic disease caused by a mutation in the X-linked Dytrophin gene preventing the expression of the functional protein. Exon skipping therapy using antisense oligonucleotides (AONs) is a promising therapeutic strategy for DMD. While benefits of AON therapy have been demonstrated, some challenges remain before this strategy can be applied more comprehensively to DMD patients. These include instability of AONs due to low nuclease resistance and poor tissue uptake. Delivery systems have been examined to improve the availability and stability of oligonucleotide drugs, including polymeric carriers. Previously, we showed the potential of a hydrogel-based polymeric carrier in the form of injectable PEG-fibrinogen (PF) microspheres for delivery of chemically modified 2'-O-methyl phosphorothioate (2OMePs) AONs. The PF microspheres proved to be cytocompatible and provided sustained release of the AONs for several weeks, causing increased cellular uptake in mdx dystrophic mouse cells. Here, we further investigated this delivery strategy by examining in vivo efficacy of this approach. The 2OMePS/PEI polyplexes loaded in PF microspheres were delivered by intramuscular (IM) or intra-femoral (IF) injections. We examined the carrier biodegradation profiles, AON uptake efficiency, dystrophin restoration, and muscle histopathology. Both administration routes enhanced dystrophin restoration and improved the histopathology of the mdx mice muscles. The IF administration of the microspheres improved the efficacy of the 2OMePS AONs over the IM administration. This was demonstrated by a higher exon skipping percentage and a smaller percentage of centered nucleus fibers (CNF) found in H&E-stained muscles. The restoration of dystrophin expression found for both IM and IF treatments revealed a reduced dystrophic phenotype of the treated muscles. The study concludes that injectable PF microspheres can be used as a carrier system to improve the overall therapeutic outcomes of exon skipping-based therapy for treating DMD.


Assuntos
Distrofina , Oligonucleotídeos Antissenso , Animais , Distrofina/genética , Éxons/genética , Hidrogéis , Injeções Intra-Arteriais , Camundongos , Camundongos Endogâmicos mdx , Microesferas , Oligonucleotídeos Antissenso/farmacologia , Polímeros
10.
Opt Lett ; 47(17): 4560-4563, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048704

RESUMO

We propose a novel, to the best of our knowledge, sensor for nanovibration detection based on a microsphere. The sensor consists of a stretched single-mode fiber and a 2 µm microsphere. The light from the optical fiber passes through the microsphere, forming a photonic nanojet (PNJ) phenomenon at the front of the microsphere. The evanescent field in the PNJ enhances the light reflected from the measured object to the single-mode fiber-microsphere probe (SMFMP). Results showed that the system can detect arbitrary nanovibration waveforms in real time with an SMFMP detection resolution of 1 nm. The voltage signal received and the vibration amplitude showed a good linear relationship within the range of 0-100 nm, with a sensitivity of 0.7 mV/nm and a linearity of more than 99%. The sensor is expected to have potential applications in the field of cell nanovibration detection.


Assuntos
Fibras Ópticas , Óptica e Fotônica , Microesferas , Fótons
11.
Anal Chim Acta ; 1228: 340336, 2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-36127009

RESUMO

A multiplex and DNA amplification-free sensor based on electrical resistance microsphere counter (ERMC) and DNA hybridization reaction has been developed for simultaneous detection of Listeria monocytogenes, Salmonella Typhimurium, and Staphylococcus aureus in egg samples. In this strategy, magnetic nanoparticles (MNPs) and polystyrene microspheres (PMs) were labeled with DNA probes, the PMs with different sizes (3 µm, 4 µm and 6 µm) were used as multiplex signal reporters due to the high resolution of ERMC. After magnetic separation, the number of unbound PM-probe was related to the concentration of pathogens, and their sizes were attributed to types of pathogens. The limit of detection of this sensor was 20 CFU/mL for Listeria monocytogenes, 89 CFU/mL for Salmonella, and 94 CFU/mL for Staphylococcus aureus, respectively. The DNA amplification-free, simplicity and low-cost of this assay make it a promising tool for the rapid screening of multiple pathogens in food samples.


Assuntos
Listeria monocytogenes , Poliestirenos , DNA/genética , Sondas de DNA , Impedância Elétrica , Listeria monocytogenes/genética , Microesferas , Salmonella typhimurium/genética , Staphylococcus aureus/genética
12.
Biosens Bioelectron ; 216: 114598, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36087400

RESUMO

Early and precise detection of tumors could lead to more effective treatments. Microfluidic technology holds great promise as an emerging tool for the early diagnosis of cancer. However, since the flow in microchannels is usually laminar, the mass transfer efficiency is low, resulting in low biosensing efficiency and sensitivity. In this paper, we employed immunofluorescence analysis in a microfluidic chip to develop a continuous, fast and efficient liquid biopsy chip. We disrupt the laminar flow and improve mass transfer efficiency by filling the chip with antibody-conjugated microbeads. Meanwhile, the microbeads increased the contact area of the immunoaffinity reaction, which greatly enhanced the binding of the antibody to the target protein, amplified the fluorescent signal, and significantly improved the sensitivity and efficiency of detection. This microfluidics-based liquid biopsy device required only a small volume of plasma sample (20-50 µL), realized a low limit of detection (LOD, 0.1 ng/mL), and can detect biomarkers within 55-75 min. We tested plasma from 15 breast cancer (BC) patients and 5 non-cancer controls to demonstrate its clinical application in breast cancer diagnosis, showing that the biomarkers carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) reflect the presence of BC, and the method can accurately distinguish cancer patients from non-cancer controls. Receiver operator characteristic (ROC) curves showed that the combined assessment of the two biomarkers provided extremely high sensitivity and specificity. This study provides a new strategy for rapid early diagnosis of cancer and other diseases.


Assuntos
Técnicas Biossensoriais , Neoplasias da Mama , Biomarcadores Tumorais , Técnicas Biossensoriais/métodos , Neoplasias da Mama/diagnóstico , Antígeno Carcinoembrionário , Detecção Precoce de Câncer , Feminino , Imunofluorescência , Humanos , Biópsia Líquida , Microfluídica/métodos , Microesferas
13.
J Chromatogr A ; 1681: 463461, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36108352

RESUMO

How to improve the performance of chromatographic media is very important in chromatography. Uniform agarose microspheres were successfully prepared using membrane emulsification method with a controllable particle size, followed by multi-step crosslinking and dextran-grafting, respectively. To obtain both fine pore structure and good pressure-resistant property, the effects of both dextran-grafting and crosslinking process were studied carefully and also, the preparation conditions were delicately adjusted. Inverse size-exclusion chromatography was used for determining the pore structure of these agarose microspheres. Uniform agarose microspheres with an average particle size of about 8 µm were obtained with regularly spherical, transparent and smooth appearance. By introducing a certain molecular weight of dextran or pentaerythritol glycidyl ether at different crosslinking steps, both the pressure-resistant and the chromatographic properties of microspheres were improved. Both the maximum flow velocity and the corresponding pressure drop increased with the decrease of the molecular weight of dextran, i.e., 99 cm/h and 3.22 MPa, respectively, using dextran T3 (3 kDa). The average pore size of agarose microspheres decreased from 6.04±0.56 nm to 2.50±0.12 nm with the increase of the molecular weight of dextran from dextran T3 (3 kDa) to dextran T100 (100 kDa), with a high resolution obtained for a certain molecular range of model proteins. Also, the pressure-resistant property was highly improved in multi-step crosslinking process, with a maximum flow velocity of 107 cm/h and a corresponding pressure drop of 3.62 MPa obtained after the whole crosslinking steps. The average pore size of agarose microspheres was 3.72±0.32, 3.90±0.21 and 3.60±0.27 nm for the introduction of pentaerythritol glycidyl ether as the crosslinking agent at different steps, respectively. These uniform dextran-grafted agarose microspheres have a finely controllable molecular range with a high resolution compared with traditional ones, which are beneficial for chromatographic selectivity. Therefore, they are very useful for high-resolution chromatography and have wide applications in downstream process.


Assuntos
Dextranos , Cromatografia em Gel , Dextranos/química , Compostos de Epóxi , Microesferas , Tamanho da Partícula , Porosidade , Propilenoglicóis , Sefarose/química
14.
AAPS PharmSciTech ; 23(7): 258, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123513

RESUMO

In vitro-in vivo correlation (IVIVC) analysis reveals a relationship between in vitro release and in vivo pharmacokinetic response of the drug of interest. Sandostatin LAR Depot (SLD) for endocrine tumors and acromegaly is a sustained-release formulation of octreotide, a cyclic oligomer of 8 amino acids, which prolongs therapeutic efficacy and enhances medication compliance of octreotide. Since the efficacy of SLD is dependent on the pharmacokinetic characteristics of octreotide released from a biodegradable matrix polymer, poly(lactide-co-glycolide)-glucose, of SLD, the IVIVC of SLD is critical for predicting an in vivo behavior of the octreotide. In this study, in vitro release of octreotide from SLD was investigated using the release test media each containing 0.02% or 0.5% surfactant and having different pH values of 7.4 and 5.5. In vivo pharmacokinetic profiles of SLD were determined by LC-MS/MS analysis of the systemic blood concentration of octreotide after the SLD injection to rodents. In IVIVC analysis, the Weibull model was adopted as a drug release model for biodegradable microsphere formulation. The IVIVC analyses revealed the in vitro release test condition of SLD with the highest IVIV correlation coefficient. By applying the in vitro release data to the model derived from the IVIVC analysis, pharmacokinetic parameters of SLD could be predicted with the prediction error of ± 10 ~ 15%. IVIVC analysis and pharmacokinetic prediction model of SLD in our study can be an efficient tool for the development of long-acting pharmaceutical dosage forms.


Assuntos
Glucose , Octreotida , Aminoácidos , Cromatografia Líquida , Preparações de Ação Retardada/farmacocinética , Microesferas , Poliglactina 910 , Tensoativos , Espectrometria de Massas em Tandem
15.
Cell Death Dis ; 13(9): 782, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088391

RESUMO

This study aimed to at explore exploring the biological functions of dysregulated circRNA in Crohn's disease (CD) pathogenesis, with the overarching goal of and providing potential novel therapeutic targets. CircRNA microarray and quantitative real time-polymerase chain reaction (qRT-PCR) analyses were performed to investigate and verify the candidate dysregulated circRNA. The Next, clinical, in vivo, and in vitro studies were performed to investigate explore the biological function and mechanisms of the candidate circRNA in CD. The therapeutic effect of poly (lactic-co-glycolic acid)-microspheres (PLGA MSs)-carried oe-circGMCL1 in experimental colitis models of IL-10 knock-out mice was assessed. CircGMCL1 was identified as the candidate circRNA by microarray and qRT-PCR analyses. Results showed that circGMCL1 expression was negatively correlated with CD-associated inflammatory indices, suggesting that it is a CD-associated circRNA. Microarray and bioinformatics analyses identified miR-124-3p and Annexin 7 (ANXA7) as its downstream mechanisms. The in vitro studies revealed that circGMCL1 mediates its effects on autophagy and NLRP3 inflammasome-mediated pyroptosis in epithelial cells through the ceRNA network. Moreover, the in vivo studies identified the therapeutic effect of PLGA MSs-carried oe-circGMCL1 in experimental colitis models. This study suggests that circGMCL1 protects intestinal barrier function against Crohn's colitis through alleviating NLRP3 inflammasome-mediated epithelial pyroptosis by promoting autophagy through regulating ANXA7 via sponging miR-124-3p. Therefore, circGMCL1 can serve as a potential biological therapeutic target for Crohn's colitis.


Assuntos
Colite , Doença de Crohn , MicroRNAs , Animais , Autofagia/genética , Colite/genética , Doença de Crohn/genética , Inflamassomos/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/farmacologia , Microesferas , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , RNA Circular/genética
16.
Food Res Int ; 160: 111749, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36076471

RESUMO

Colon targeted delivery of quercetin by encapsulation has the potential to manage colonic diseases due to quercetin's pharmacological effects. To strengthen the functionalities of commonly used alginate microspheres for quercetin encapsulation, inulin was added as filling material and chitosan as coating material. Empty/quercetin-loaded alginate (AL-E/Q), alginate + inulin (ALIN-E/Q), alginate + inulin + chitosan (ALINCH-E/Q) microspheres were fabricated, with particle sizes ranging from 25.1 ± 1.8 to 79.4 ± 4.5 µm. All the formulated microspheres were negatively charged, and zeta potential was dependent mainly on chitosan coating and the pH of surrounding media. FTIR spectra of the microspheres suggested successful encapsulation of quercetin, formation of chitosan coating and potential hydrogen bonding between inulin and alginate. Scanning electron micrographs showed that inulin filling enhanced gel strength by filling up the pores in the alginate polymer network, and that loading of quercetin also helped to fill up the pores compared to empty microspheres. Combination of inulin as filling material and chitosan as coating material in quercetin loaded ALINCH-Q achieved superior performance compared to other formulations with encapsulation efficiency of 53.2 ± 1.2 %, and retention rate of the loaded quercetin up to 80.3 ± 4.4 % through in vitro gastrointestinal digestion, thus was chosen for colonic fermentation. Subjecting ALINCH-Q to colonic fermentation using pig fecal material as microbiota source showed that quercetin release was delayed but occurred within 3 h of fermentation and was completely metabolized by the microbiota by 24 h. Thus, ALINCH-Q microsphere showed potential in targeted delivery and release of quercetin to the colon.


Assuntos
Alginatos , Quitosana , Alginatos/metabolismo , Animais , Quitosana/metabolismo , Colo/metabolismo , Inulina/farmacologia , Microesferas , Quercetina/farmacologia , Suínos
17.
Carbohydr Polym ; 296: 119947, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36087995

RESUMO

Currently, microspheres with high adsorption capacity play a crucial role in dye adsorption and drug loading. In this study, 2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO)-oxidized cellulose nanofibrils (TOCN) could be used to form nanocellulose microspheres by the emulsion method. The prepared hydrangea-like nanocellulose microspheres presented a stable three-dimensional network porous structure and exhibited excellent adsorption properties. The TOCN microspheres had a high adsorption capacity for methylene blue (MB) and methyl orange (MO) with the optimal adsorption capacity of 412.1 mg g-1 and 286.5 mg g-1 under neutral conditions, respectively. The TOCN microspheres displayed excellent adsorption selectivity on MB/MO mixed dyes, which could be used to selectively adsorb MB. Besides, the encapsulation rate of the positively charged drug doxorubicin hydrochloride (DOX) was as high as 93 %, and the drug loading capacity was as high as 34.5 %. Overall, our prepared nanocellulose microspheres had great potential for application in dye adsorption and drug delivery systems.


Assuntos
Corantes , Hydrangea , Adsorção , Corantes/química , Emulsões , Azul de Metileno/química , Microesferas
18.
J Vasc Interv Radiol ; 33(9): 1097-1100, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36049842

RESUMO

The purpose of this study was to compare complications and the number of ghrelin-expressing cells (GECs) after bariatric arterial embolization (BAE) using soluble gelatin sponge particles (SGSs) or tris-acryl gelatin microspheres (MSs) in swine. Twelve swine underwent embolization of gastric fundal arteries with SGSs (n = 4) or MSs (n = 4) or underwent saline infusion (n = 4, control group). One week later, the number of gastric ulcers and the percentage of GECs were compared among the 3 groups. There were no ulcers in the SGS and control groups. Two swine in the MS group had 4 large ulcers (12-50 mm in size). The mean percentages of GECs were significantly lower in the SGS (2.7% ± 0.9%) and MS (2.5% ± 1.0%) groups compared with the control group (3.7% ± 1.3%; P = .038 and P = .016, respectively). SGSs may be safer than MSs for BAE while inducing a similar reduction of GECs in swine.


Assuntos
Bariatria , Embolização Terapêutica , Resinas Acrílicas , Animais , Gelatina , Microesferas , Suínos
19.
Lab Chip ; 22(18): 3545-3554, 2022 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-35989675

RESUMO

Conventional bioparticle extraction requires labor-intensive operation, and expensive and bulky centrifuges. Herein, we report a miniaturized centrifuge by cascading four paralleled inertial spiral channels with a two-stage serpentine channel, allowing for the efficient washing and acquisition of concentrated bioparticles from background fluids. First, the effects of channel size and flow rate on particle focusing dynamics and solution exchange performances are explored to enable the optimization and wide application of our device. Then, the integrated device is fabricated and tested experimentally. The results indicate that 10-20 µm particles can be washed from the original samples with increased concentrations and with recovery efficiencies of >93%. Finally, to verify its versatility, we use our miniaturized centrifuge to successfully change the culture medium for cultured MCF-7 breast cancer cells, extract A549 lung cancer cells from a calcein-AM staining solution, purify white blood cells (WBCs) from lysed whole blood, and extract target cells from an unbonded magnetic microbead background. Compared with conventional centrifuges, our device has the advantages of simple fabrication, easy operation, and small footprint. More importantly, it offers outstanding capability for extracting bioparticles from various background fluids, and avoids bioparticle damage that may be caused by high-speed centrifugation. Therefore, we envision that our miniaturized centrifuge could be a promising alternative to traditional centrifuges in many applications.


Assuntos
Técnicas Analíticas Microfluídicas , Microfluídica , Centrifugação , Humanos , Leucócitos , Células MCF-7 , Microesferas
20.
ACS Biomater Sci Eng ; 8(9): 3831-3841, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-35969206

RESUMO

Spheroidal cancer microtissues are highly advantageous for a wide range of biomedical applications, including high-throughput drug screening, multiplexed target validation, mechanistic investigation of tumor-extracellular matrix (ECM) interactions, among others. Current techniques for spheroidal tissue formation rely heavily on self-aggregation of single cancer cells and have substantial limitations in terms of cell-type-specific heterogeneities, uniformity, ease of production and handling, and most importantly, mimicking the complex native tumor microenvironmental conditions in simplistic models. These constraints can be overcome by using engineered tunable hydrogels that closely mimic the tumor ECM and elucidate pathologically relevant cell behavior, coupled with microfluidics-based high-throughput fabrication technologies to encapsulate cells and create cancer microtissues. In this study, we employ biosynthetic hybrid hydrogels composed of poly(ethylene glycol diacrylate) (PEGDA) covalently conjugated to natural protein (fibrinogen) (PEG-fibrinogen, PF) to create monodisperse microspheres encapsulating breast cancer cells for 3D culture and tumorigenic characterization. A previously developed droplet-based microfluidic system is used for rapid, facile, and reproducible fabrication of uniform cancer microspheres with either MCF7 or MDA-MB-231 (metastatic) breast cancer cells. Cancer cell-type-dependent variations in cell viability, metabolic activity, and 3D morphology, as well as microsphere stiffness, are quantified over time. Particularly, MCF7 cells grew as tight cellular clusters in the PF microspheres, characteristic of their epithelial morphology, while MDA-MB-231 cells displayed elongated and invasive morphology, characteristic of their mesenchymal and metastatic nature. Finally, the translational potential of the cancer microsphere platform toward high-throughput drug screening is also demonstrated. With high uniformity, scalability, and control over engineered microenvironments, the established cancer microsphere model can be potentially used for mechanistic studies, fabrication of modular cancer microtissues, and future drug-testing applications.


Assuntos
Neoplasias da Mama , Microfluídica , Neoplasias da Mama/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos , Detecção Precoce de Câncer , Feminino , Fibrinogênio , Humanos , Hidrogéis , Microesferas , Polietilenoglicóis , Microambiente Tumoral
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