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1.
bioRxiv ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36778350

RESUMO

Chronic exposure of the lung to irritants such as allergen is a primary cause of asthma characterized by exaggerated airway constriction, also called hyperreactivity, which can be life-threatening. Aside from immune cells, vagal sensory neurons are important for airway hyperreactivity 1-4 . However, the identity and signature of the downstream nodes of this adaptive circuit remains poorly understood. Here we show that a single population of Dbh + neurons in the nucleus of the solitary tract (nTS) of the brainstem, and downstream neurons in the nucleus ambiguous (NA), are both necessary and sufficient for chronic allergen-induced airway hyperreactivity. We found that repeated exposures of mice to inhaled allergen activates nTS neurons in a mast cell-, interleukin 4 (IL-4)-and vagal nerve-dependent manner. Single-nucleus RNA-seq of the nTS at baseline and following allergen challenges reveals that a Dbh + population is preferentially activated. Ablation or chemogenetic inactivation of Dbh + nTS neurons blunted, while chemogenetic activation promoted hyperreactivity. Viral tracing indicates that Dbh + nTS neurons, capable of producing norepinephrine, project to the NA, and NA neurons are necessary and sufficient to relay allergen signals to postganglionic neurons that then directly drive airway constriction. Focusing on transmitters, delivery of norepinephrine antagonists to the NA blunted allergen-induced hyperreactivity. Together, these findings provide molecular, anatomical and functional definitions of key nodes of a canonical allergen response circuit. The knowledge opens the possibility of targeted neural modulation as an approach to control refractory allergen-induced airway constriction.

2.
Tissue Eng Regen Med ; 21(1): 123-135, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37755664

RESUMO

BACKGROUND: Oral submucous fibrosis (OSF) is a chronic disease with carcinogenic tendency that poses a non-negligible threat to human health. Exosomes derived from human adipose mesenchymal stem cells (ADSC-Exo) reduces visceral and cutaneous fibroses, but their role in OSF has received little attention. The aim of this study was to investigate the effects of ADSC-Exo on OSF and elucidate the mechanism. METHODS: In brief, ADSCs were extracted from adipose tissues and subjected to flow cytometry and induction culture. Fibroblasts were isolated from human buccal mucosa and subjected to immunofluorescence. Myofibroblasts were obtained from fibroblasts induced by arecoline and identified. Immunofluorescence assay confirmed that myofibroblasts could take up ADSC-Exo. The effects of ADSC-Exo on the proliferative and migratory capacities of myofibroblasts were examined using the Cell Counting Kit-8 and scratch assay. Real-time quantitative polymerase chain reaction (qPCR) was performed to evaluate mothers against decapentaplegic homolog 2 (Smad2), Smad3, Smad7, collagen type 1 (Col1), Col3, alpha smooth muscle actin (α-SMA), fibronectin, and vimentin. Western blotting was performed to detect phospho (p)-Smad2, Smad2, p-Smad2/3, Smad2/3, Smad7, Col1, Col3, α-SMA, fibronectin, and vimentin. Furthermore, the dual-luciferase reporter assay was performed to prove that miR-181a-5p in ADSC-Exo directly inhibited the expression of Smad2 mRNA to regulate the transforming growth factor beta (TGF-ß) pathway. We also performed qPCR and western blotting to verify the results. RESULTS: ADSC-Exo could promote the proliferation and migration of myofibroblasts, reduce the expressions of p-smad2, Smad2, p-smad2/3, Smad2/3, Col1, αSMA, fibronectin, and vimentin and elevated the levels of Smad7 and Col3. In addition, miR-181a-5p was highly expressed in ADSC-Exo and bound to the 3'-untranslated region of Smad2. ADSC-Exo enriched with miR-181a-5p reduced collagen production in myofibroblasts and modulated the TGF-ß pathway. CONCLUSIONS: ADSC-Exo promoted the proliferative and migratory capacities of myofibroblasts and inhibited collagen deposition and trans-differentiation of myofibroblasts in vitro. miR-181a-5p in exosomes targets Smad2 to regulate the TGF-ß pathway in myofibroblasts. ADSC-Exo perform antifibrotic actions through the miR-181a-5p/Smad2 axis and may be a promising clinical treatment for OSF.


Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Fibrose Oral Submucosa , Humanos , Colágeno Tipo I/metabolismo , Exossomos/metabolismo , Fibronectinas/metabolismo , Fibrose , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fibrose Oral Submucosa/genética , Fibrose Oral Submucosa/terapia , Fibrose Oral Submucosa/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Vimentina/metabolismo
3.
Arch Microbiol ; 205(10): 331, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37698663

RESUMO

Known for its species abundance and evolutionary status complexity, family Roseobacteraceae is an important subject of many studies on the discovery, identification, taxonomic status, and ecological properties of marine bacteria. This study compared and analyzed the phylogenetic, genomic, biochemical, and chemo taxonomical properties of seven species from three genera (Psychromarinibacter, Lutimaribacter, and Maritimibacter) of the family Roseobacteraceae. Moreover, a novel strain, named C21-152T was isolated from solar saltern sediment in Weihai, China. The values of 16S rRNA gene sequence similarity, the average nucleotide identity (ANI), the average amino acid identity (AAI), and the digital DNA-DNA hybridization (dDDH) between genomes of the novel strain and Psychromarinibacter halotolerans MCCC 1K03203T were 97.19, 78.49, 73.45, and 21.90%, respectively. Genome sequencing of strain C21-152T revealed a complete Sox enzyme system related to thiosulfate oxidization as well as a complete pathway for the final conversion of hydroxyproline to α-ketoglutarate. In addition, strain C21-152T was resistant to many antibiotics and had the ability to survive below 13% salinity. This strain had versatile survival strategies in saline environments including salt-in, compatible solute production and compatible solute transport. Some of its physiological features enriched and complemented the knowledge of the characteristics of the genus Psychromarinibacter. Optimum growth of strain C21-152T occurred at 37 â„ƒ, with 5-6% (w/v) NaCl and at pH 7.5. According to the results of the phenotypic, chemotaxonomic characterization, phylogenetic properties and genome analysis, strain C21-152T should represent a novel specie of the genus Psychromarinibacter, for which the name Psychromarinibacter sediminicola sp. nov. is proposed. The type strain is C21-152T (= MCCC 1H00808T = KCTC 92746T = SDUM1063002T).


Assuntos
DNA , Rhodobacteraceae , Mapeamento Cromossômico , Filogenia , RNA Ribossômico 16S/genética , Rhodobacteraceae/classificação
4.
Cancers (Basel) ; 15(4)2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36831685

RESUMO

In today's high-order health examination, imaging examination accounts for a large proportion. Computed tomography (CT), which can detect the whole body, uses X-rays to penetrate the human body to obtain images. Its presentation is a high-resolution black-and-white image composed of gray scales. It is expected to assist doctors in making judgments through deep learning based on the image recognition technology of artificial intelligence. It used CT images to identify the bladder and lesions and then segmented them in the images. The images can achieve high accuracy without using a developer. In this study, the U-Net neural network, commonly used in the medical field, was used to extend the encoder position in combination with the ResBlock in ResNet and the Dense Block in DenseNet, so that the training could maintain the training parameters while reducing the overall identification operation time. The decoder could be used in combination with Attention Gates to suppress the irrelevant areas of the image while paying attention to significant features. Combined with the above algorithm, we proposed a Residual-Dense Attention (RDA) U-Net model, which was used to identify organs and lesions from CT images of abdominal scans. The accuracy (ACC) of using this model for the bladder and its lesions was 96% and 93%, respectively. The values of Intersection over Union (IoU) were 0.9505 and 0.8024, respectively. Average Hausdorff distance (AVGDIST) was as low as 0.02 and 0.12, respectively, and the overall training time was reduced by up to 44% compared with other convolution neural networks.

5.
Small ; 19(20): e2300003, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36807523

RESUMO

Designing highly efficient photocatalysts with rapid migration of photogenerated charges and surface reaction kinetics for the photocatalytic removal of uranium (U(VI)) from uranium mine wastewater remains a significant challenge. Inspired by natural photosynthesis, a biomimetic photocatalytic system is assembled by designing a novel hollow nanosphere MnOx @TiO2 @CdS@Au (MTCA) with loading MnOx and Au nano particles (Au NPs) cocatalysts on the inner and outer surfaces of the TiO2 @CdS. The spatially separated cocatalysts efficiently drive the photogenerated charges to migrate in opposite directions, while the Z-scheme heterogeneous shell further separates the interfacial charges. Theoretical calculation identifies multiple consecutive forward charge transfers without charge recombination within MTCA. Thus, MTCA could efficiently remove 99.61% of U(VI) after 15 min of simulated sunlight irradiation within 3 mmol L-1 NaHCO3 with 0.231 min-1 of the reduction rate constant, outperforming most previously reported photocatalysts. MTCA further significantly removes 91.83% of U(VI) from the natural uranium mining wastewater under sunlight irradiation. This study provides a novel approach to designing an ideal biomimetic photocatalyst for remediating environmental pollution.

6.
IDCases ; 31: e01693, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36704022

RESUMO

Empyema is often caused by Streptococcus anginous species, followed by Streptococcus pneumoniae. The organism Streptococcus gordonii belongs to the Streptococcus mitis group, which rarely causes empyema. We report the case of a 59-year-old man who presented with exertional dyspnea and chest pain on the right side. The image obtained showed effusion on the right side. Streptococcus gordonii was recovered from purulent pleural effusion culture. The patient underwent video-assisted thoracoscopic surgery with decortication, pneumolysis and received antibiotics for 13 days. A total of seven cases were analyzed after combining six cases in the literature and our presented case. The majority of Streptococcus gordonii empyema patients were male (six patients, 86%) and empyema on the right side (five patients, 71%). Common risk factors included poor dental hygiene or recent dental procedure (three patients, 43%), diabetes mellitus (three patients, 43%), and smoking (three patients, 43%). Only a few cases developed empyema-related complications, including bacteremia (one patient, 14%) and spleen abscesses (one patient, 14%). Most patients underwent chest tube insertion (seven patients, 100%) and survived without recurrent empyema (six patients, 86%).

7.
Front Cell Dev Biol ; 10: 942133, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36035989

RESUMO

There is evidence that exosomes derived from the lipoma tissue (Exo-LT) have a stronger capacity to promote the proliferation and migration of adipose-derived stem cells (ADSCs) than those from the adipose tissue (Exo-AT). But the Exo-LT do not have a significant effect on the adipogenic differentiation of the ADSCs. Recently, certain exosomal tRNA-derived fragments (tRFs) have been shown to play a crucial role in the pathogenesis of certain tumors. Therefore, it is necessary to identify the differently expressed tRFs in Exo-LT to further elucidate their molecular functions in lipomas. High-throughput sequencing was performed to examine the tRFs and mRNAs from the all samples belonging to the Exo-LT and Exo-AT groups. Target prediction and bioinformatics analysis were performed to explore their downstream mRNAs and biological functions. In total, 456 differently expressed tRFs and tiRNAs were identified in the Exo-LT group, 12 of which were up-regulated and 12 were down-regulated, respectively. Notably, tRF-1001 was most obviously down-regulated and tRF-3004a was most obviously up-regulated in the Exo-LT group. Moreover, among the target genes of tRF-1001 and tRF-3004a, both JAG2 and VSIG4 were significantly down-regulated in the Exo-LT group, while WNT5A, COL1A1, and PPARGC1A were highly expressed in both the Exo-LT and Exo-AT groups. The significant down-regulation of JAG2 and VSIG4 in the Exo-LT group could be due to the fact that Exo-LT had a stronger capacity to promote the proliferation and migration of ADSCs compared to the Exo-AT. The high expression of WNT5A, COL1A1, and PPARGC1A in both the Exo-LT and Exo-AT groups could be due to the similar ability of Exo-LT and Exo-AT to promote the adipogenic differentiation of ADSCs.

8.
ACS Appl Mater Interfaces ; 14(21): 24766-24774, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35579439

RESUMO

Optimizing the water bonding network in an evaporator is significant for efficient solar-driven vapor generation (SVG). Herein, we report a facile one-pot method to regulate the hydrated structure and wettability in a hierarchical porous hydrogel. An ovalbumin (OVA)-polyacrylamide hydrogel foam was fabricated in a cake-making fashion. Because of the enrichment of amphiphilic OVA at the interface, the hydrophobic walls of the air pores in the foam provide vaporization sites and help reduce parasitic heat loss, while the hydrophilic skeleton with the secondary pores effectively pumps capillary water. Notably, the proportion of intermediate water in the foam reaches 87.6% with the melting point as low as -10 °C. All these features contribute to an exceptional evaporation rate of 3.4-4.5 kg m-2 h-1 under 1 sun and robust SVG performances at high-humidity, weak sunlight, or cold weathers. The strategy of using amphiphilic molecules to optimize the hydrated structures both at the interface and in bulk promises the reasonable design of SVG materials with superior efficiency and weather adaptability.

9.
Chemistry ; 28(36): e202201006, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35470509

RESUMO

There is little investigation into the impact of molecular conformation on device efficiency and degradation of boron-nitrogen thermally activated delayed fluorescence emitters (BN-TADF). Herein, three highly-efficient green BN-TADF emitters have been designed to unveil the impact of peripheral phenyl groups on device efficiencies and lifetimes. Compared to BN-PhOH with the lowest EQEmax of 19 %, BN-PhOCH3 and BN-PhN(CH3 )2 have achieved strongly enhanced EQEmax of 25.6 % and 24.1 %, respectively. Importantly, the device lifetimes (LT50 ) are dramatically improved from 1.7 h of BN-PhOH to 4.4 h of BN-PhOCH3 and 7.7 h of BN-PhN(CH3 )2 without encapsulation. According to in situ Raman spectroscopy and simulations, BN-PhN(CH3 )2 of less conformation change after aging exhibits the best photostability. It is proposed that the torsion angle change between the BN core and the peripheral phenyl group results in BN-TADF degradation. This knowledge means precisely tuning peripheral groups of BN-TADF can achieve both higher device efficiencies and longer lifetimes.

10.
Dev Cell ; 57(7): 839-853.e6, 2022 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-35303432

RESUMO

Although increased neuropeptides are often detected in lungs that exhibit respiratory distress, whether they contribute to the condition is unknown. Here, we show in a mouse model of neuroendocrine cell hyperplasia of infancy, a pediatric disease with increased pulmonary neuroendocrine cells (PNECs), excess PNEC-derived neuropeptides are responsible for pulmonary manifestations including hypoxemia. In mouse postnatal lung, prolonged signaling from elevated neuropeptides such as calcitonin gene-related peptide (CGRP) activate receptors enriched on endothelial cells, leading to reduced cellular junction gene expression, increased endothelium permeability, excess lung fluid, and hypoxemia. Excess fluid and hypoxemia were effectively attenuated by either prevention of PNEC formation, inactivation of CGRP gene, endothelium-specific inactivation of CGRP receptor gene, or treatment with CGRP receptor antagonist. Neuropeptides were increased in human lung diseases with excess fluid such as acute respiratory distress syndrome. Our findings suggest that restricting neuropeptide function may limit fluid and improve gas exchange in these conditions.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Neuropeptídeos , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Células Endoteliais/metabolismo , Humanos , Hipóxia/metabolismo , Pulmão/metabolismo , Camundongos , Neuropeptídeos/metabolismo
11.
Am J Physiol Lung Cell Mol Physiol ; 322(1): L50-L63, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34755535

RESUMO

Known as the gas exchange organ, the lung is also critical for responding to the aerosol environment in part through interaction with the nervous system. The diversity and specificity of lung innervating neurons remain poorly understood. Here, we interrogated the cell body location and molecular signature and projection pattern of lung innervating sensory neurons. Retrograde tracing from the lung coupled with whole tissue clearing highlighted neurons primarily in the vagal ganglia. Centrally, they project specifically to the nucleus of the solitary tract in the brainstem. Peripherally, they enter the lung alongside branching airways. Labeling of nociceptor Trpv1+ versus peptidergic Tac1+ vagal neurons showed shared and distinct terminal morphology and targeting to airway smooth muscles, vasculature including lymphatics, and alveoli. Notably, a small population of vagal neurons that are Calb1+ preferentially innervate pulmonary neuroendocrine cells, a demonstrated airway sensor population. This atlas of lung innervating neurons serves as a foundation for understanding their function in lung.


Assuntos
Pulmão/inervação , Células Receptoras Sensoriais/fisiologia , Células Epiteliais Alveolares/metabolismo , Animais , Tronco Encefálico/fisiologia , Calbindinas/metabolismo , Perfilação da Expressão Gênica , Integrases/metabolismo , Pulmão/irrigação sanguínea , Camundongos , Modelos Biológicos , Músculo Liso/fisiologia , Células Neuroendócrinas/metabolismo , Gânglio Nodoso/fisiologia , Traqueia/inervação , Nervo Vago/fisiologia
12.
ACS Appl Mater Interfaces ; 13(22): 26590-26600, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34047185

RESUMO

Maintaining the human body's comfort is a predominant requirement of functional textiles, but there are still considerable drawbacks to design an intelligent textile with proper moisture absorption and evaporation properties. Herein, we develop moisture-wicking and solar-heated coaxial fibers with a bark-like appearance for fabric comfort management. The cortex layer of coaxial fibers can absorb moisture via the synergistic effect of the hierarchical roughness and the hydrophilic polymeric matrix. The core layer containing zirconium carbide nanoparticles can assimilate energy from the body and sunlight, which raises the surface temperature of the material and accelerates moisture evaporation. The resulting coaxial fiber-based membrane exhibits an excellent droplet diffusion radius of 2.73 cm, an excellent wicking height of 6.97 cm, and a high surface temperature of 61.7 °C which is radiated by simulated sunlight. Moreover, the designed fabric also exhibits a significant UV protection factor of 2000. Overall, the successful synthesis of such fascinating fibrous membranes enables the rapid removal of sweat from the human body textile, providing a suitable and comfortable microenvironment for the human body.


Assuntos
Materiais Biomiméticos/química , Nanopartículas/química , Casca de Planta/química , Luz Solar , Suor/química , Têxteis/normas , Água/química , Ação Capilar , Humanos , Têxteis/análise , Zircônio/química
13.
Dev Cell ; 55(2): 123-132, 2020 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-33108755

RESUMO

Pulmonary neuroendocrine cells (PNECs) are rare airway epithelial cells that also uniquely harbor neuronal and endocrine characteristics. In vitro data indicate that these cells respond to chemical or mechanical stimuli by releasing neuropeptides and neurotransmitters, implicating them as airway sensors. Emerging in vivo data corroborate this role and demonstrate that PNECs are important for lung response to signals, such as allergens. With close proximity to steady-state immune cells and innervating nerves, PNECs, as prototype tissue-resident neuroendocrine cells, are at the center of a neuro-immune module that enables the fundamental ability of an organ to sense and respond to the environment.


Assuntos
Células Epiteliais/metabolismo , Epitélio/metabolismo , Pulmão/metabolismo , Células Neuroendócrinas/metabolismo , Animais , Células Epiteliais/imunologia , Epitélio/imunologia , Humanos , Pulmão/imunologia , Células Neuroendócrinas/imunologia , Neuropeptídeos/metabolismo
14.
RSC Adv ; 10(46): 27512-27522, 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35516954

RESUMO

Compared with previous textiles possessing a hierarchical roughness structure for accelerating moisture evaporation, the use of Joule-heating to prepare heatable textiles is a more novel and useful way to achieve ultra-fast evaporation. Herein, we report an assembly strategy to create a functional non-woven (NW) fabric for directional moisture transportation and ultra-fast evaporation, ameliorating previous shortcomings. The resulting functional NW fabric reaches a sheet resistance of 1.116 Ω â–¡-1, and the increased surface temperature (76.1 °C) induced by a low voltage (5 V) further results in an excellent ultra-fast evaporation rate (3.42 g h-1). Also, the moisture is transported to the outer surface of the designed fabric and spreads onto this surface. This desirable property can expand the contact area between sweat and the heatable fabric, further improving the evaporation efficiency, while maintaining the dry state of human skin. Generally, this functional textile with remarkable moisture management capabilities could be applied in winter outdoor sportswear to maintain human comfort.

15.
Mol Ther Nucleic Acids ; 16: 650-662, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31121477

RESUMO

Lymph nodes are important peripheral immune organs in which numerous important immune responses occur. During the process of lymphatic metastasis, lymph nodes are also sites through which tumor cells must pass. Therefore, it is essential to develop a drug delivery system that can specifically transfer immunostimulatory medicine into lymph nodes to block lymphatic metastasis. Here, we developed a nucleic acid drug delivery system containing cationic agarose (C-agarose) and CpG oligodeoxynucleotides. C-agarose has a high affinity for Siglec-1 on the surface of lymph node sinus macrophages, which have a high specificity for targeting lymph nodes. Subcutaneous implantation of C-agarose+CpG gel caused the accumulation of CpG in the lymph node sinus macrophages and generated antitumor immune responses in the lymph node. C-agarose+CpG gel treatment decreased the metastasis size in the tumor-draining lymph node (TDLN) and lung metastatic nodules and suppressed tumor growth in both a mouse 4T1 breast cancer model and a B16F10 melanoma model. On this basis, this study proposes a nonsurgical invasive lymph node targeting immunotherapy concept that may provide a new approach for antitumor metastasis.

16.
RSC Adv ; 9(29): 16754-16766, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35516382

RESUMO

Directional water transport in garment materials plays a pivotal role in maintaining human thermal and wet comfort. In the present work, a new type of multilayer fibrous mat with the specific function of directional water transport was prepared via the combination of melt-electrospinning and solution-electrospinning. The polypropylene (PP) fibrous layer prepared by melt-electrospinning technology was located in the inner layer (next to the skin), while the polyacrylonitrile-containing hydrophilic nano-silica particles (PAN-SiO2) layer with remarkable hydrophilicity was located in the outer layer, which could effectively transport water to the outer surface of the composites. Treatment of the as-prepared PAN-SiO2/PP with an alkaline aqueous solution of dopamine not only increased the wettability of the PP layer, but also further improved the hydrophilicity of PAN-SiO2. A layer of cotton woven mesh was added between the TPP layer and TPAN-SiO2 to form a sandwich structure in order to accelerate water transport in the bilayered fibrous mats. The directional water transport, mechanical flexibility, and permeability of the prepared multilayered superfine fibrous mat were characterized systematically. The experimental results exhibited that TPAN-SiO2/cotton mesh/TPP exhibited an excellent accumulative one-way transport index (AOTI, 1071%), remarkable overall moisture management capacity (OMMC, 0.88), and reasonably high water vapor transport rate (WVT, 11.6 kg d-1 m-2), indicating it is a promising candidate for the development of novel textile materials for use in the field of sportswear for fast sweat release applications.

17.
Biochem Pharmacol ; 155: 275-287, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30028990

RESUMO

Hyperactivated macrophages play a key role in the initiation and perpetuation of mucosal inflammation in Crohn's disease (CD). Increasing evidence suggests that the basic helix-loop-helix (bHLH) repressor Twist1 can suppress activation of nuclear factor-κB (NF-κB) and the subsequent production of TNF-α, which are both essential elements of macrophage activation. Thus, developing novel therapeutic strategies to enhance Twist1 expression and to inhibit macrophage activation may be beneficial for CD treatment. In the present study, a series of trifluoroethyl thiazolo[3,2-b][1,2,4]triazole derivatives were used to investigate their potential anti-inflammatory activities and the underlying mechanism. In a biological activity screen, compound 7# (Thiazolo[3,2-b][1,2,4]triazole-5-methanamine, 6-phenyl-α-(trifluoromethyl)-, (αR)-, TT-TFM) suppressed the activation of macrophages. Consistent with the in vitro data, TT-TFM protected against 2,4,6-trinitrobenzene sulfonic acid (TNBS), dextran sulfate sodium (DSS)-induced acute colitis and IL-10 knockout (KO) chronic colitis, as judged by body weight changes and colonic pathological damage. A mechanistic study based on microarray analysis and gene interference experiments indicated that TT-TFM exerted anti-inflammatory effects by enhancing Twist1 expression and subsequently blocking the NF-κB/TNF-α pathway. In addition, pretreatment with lentiviruses encoding shRNA targeting Twist1 could abolish the therapeutic effect of TT-TFM in TNBS colitis. Ultimately, TT-TFM showed anti-colitis activity by reducing NF-κB activation and the TNF-α level by promoting Twist1 expression; thus, TT-TFM may offer a therapeutic strategy for CD patients.


Assuntos
Colite/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Proteínas Nucleares/biossíntese , Transdução de Sinais/fisiologia , Triazóis/química , Triazóis/uso terapêutico , Proteína 1 Relacionada a Twist/biossíntese , Animais , Células Cultivadas , Colite/tratamento farmacológico , Feminino , Ativação de Macrófagos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Knockout , Proteínas Nucleares/agonistas , Transdução de Sinais/efeitos dos fármacos , Triazóis/farmacologia , Trifluoretanol/química , Trifluoretanol/farmacologia , Trifluoretanol/uso terapêutico , Proteína 1 Relacionada a Twist/agonistas
18.
Asian-Australas J Anim Sci ; 31(8): 1230-1237, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29514435

RESUMO

OBJECTIVE: The present study was undertaken to determine an optimal balance between the amount of physically effective neutral detergent fiber (peNDF) to metabolizable glucose (MG) on rumen fermentation, blood metabolites and growth performance of 8 to 10-month-old heifers. METHODS: A total of 15 healthy Holstein heifers weighing an average of 256 kg (8 month of age) were randomly assigned to three groups of five. Treatment diets consisted of the following three peNDF8.0/MG levels: 1.46 (Treatment A), 1.74 (Treatment B), and 2.08 (Treatment C). RESULTS: The results showed that the ratio of peNDF8.0/MG affected rumen fermentation, blood metabolites and growth performance of heifers. The average daily gain of heifers tended to decrease as the ratio of peNDF8.0/MG increased (p = 0.07). The concentrations of blood urea nitrogen, triglyceride, and cholesterol increased significantly (p<0.05), while the high-density lipoprotein concentration decreased (p<0.05). After feeding 2 h and 4 h, insulin concentration in Treatment A was greater than Treatment C (p<0.05). Propionate concentration had decreasing trend (p = 0.07); acetate to propionate ratio and non-glucogenic to glucogenic volatile fatty acid (NGR) increased significantly (p<0.05). In addition, the digestibility of dry matter, crude protein, neutral detergent fiber, and acid detergent fiber decreased significantly (p<0.05). CONCLUSION: The present investigation indicated that dietary peNDF8.0/MG ratio can affect the growth and development, blood metabolites, rumen fermentation and apparent digestibility of heifers, and the optimal dietary peNDF8.0/MG ratio for 8 to 10-month-old heifers in the present study was 1.46.

19.
Science ; 360(6393)2018 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-29599193

RESUMO

Pulmonary neuroendocrine cells (PNECs) are rare airway epithelial cells whose function is poorly understood. Here we show that Ascl1-mutant mice that have no PNECs exhibit severely blunted mucosal type 2 response in models of allergic asthma. PNECs reside in close proximity to group 2 innate lymphoid cells (ILC2s) near airway branch points. PNECs act through calcitonin gene-related peptide (CGRP) to stimulate ILC2s and elicit downstream immune responses. In addition, PNECs act through the neurotransmitter γ-aminobutyric acid (GABA) to induce goblet cell hyperplasia. The instillation of a mixture of CGRP and GABA in Ascl1-mutant airways restores both immune and goblet cell responses. In accordance, lungs from human asthmatics show increased PNECs. These findings demonstrate that the PNEC-ILC2 neuroimmunological modules function at airway branch points to amplify allergic asthma responses.


Assuntos
Asma/imunologia , Asma/patologia , Pulmão/patologia , Células Neuroendócrinas/imunologia , Células Neuroendócrinas/patologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/deficiência , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Citocinas/biossíntese , Modelos Animais de Doenças , Células Epiteliais/imunologia , Células Epiteliais/patologia , Feminino , Células Caliciformes/patologia , Humanos , Hiperplasia , Camundongos , Ácido gama-Aminobutírico/biossíntese , Ácido gama-Aminobutírico/metabolismo
20.
Asian-Australas J Anim Sci ; 31(8): 1205-1212, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29381900

RESUMO

OBJECTIVE: The aim of this experiment was to evaluate the effects of different dietary ratio of metabolizable glucose (MG) to metabolizable protein (MP) on growth performance, blood metabolites, rumen fermentation parameters and the ruminal microbial community of 8 to 10-month-old heifers. METHODS: A total of 24 Holstein heifers weighing an average of 282.90 kg (8 month of age) were randomly assigned to four groups of six. The heifers were fed one of four diets of different dietary MG/MP (0.97, 1.07, 1.13, and 1.26). RESULTS: The results showed that the ratio of MG/MP affected the growth performance, blood metabolites, rumen fermentation parameters and the ruminal microbial community of heifers. The average daily gain of heifers was enhanced by increasing the ratio of MG/MP (p<0.05). The concentration of blood urea nitrogen, cholesterol, and low density lipoprotein cholesterol as well as the concentration of total volatile fatty acid in the rumen fluid of heifers decreased with the improvement in the ratio of dietary MG/MP (p<0.05). However, the relative amount of Ruminococcus albus and Butyrivibrio fibrisolvens in the rumen of heifers was increased significantly (p<0.05) when the dietary MG/MP increased. At the same time, with the improvement in dietary MG/MP, the amount of Fibrobacter succinogenes increased (p = 0.08). CONCLUSION: A diet with an optimal ratio (1.13) of MG/MP was beneficial for the improvement of growth, rumen fermentation, dietary protein and energy utilization of 8 to 10-month-old dairy heifers in this experiment.

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