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1.
Materials (Basel) ; 17(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38591606

RESUMO

Chemical foaming technology is widely used in the preparation of silicone rubber foam and is attributable to its one-step molding capability and eco-friendly production processes. The microrheological properties of silicone rubber play a pivotal role during the foaming process. In this study, Rheolaser Lab (Formulaction, Toulouse, France) was used to conduct in situ examinations for the influence of a crosslinking agent on the microrheological properties of silicone rubber foam for the first time. This study monitors the entire reaction process of silicone rubber foam from liquid to solid, as well as the matching of crosslinking and foaming reactions. Various parameters, including solid-liquid balance, elasticity index, and macroscopic viscosity index, are measured to analyze the microrheological properties of silicone rubber foam. The results show that the silicone rubber foam exhibits good microrheological properties, thereby demonstrating excellent performance at a crosslinking agent content of 2%. Through adjusting the experimental conditions, a sustainable and efficient approach was proposed for better cellular structure control in the industrial preparation of silicone rubber foam.

2.
Sci Rep ; 14(1): 7672, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561377

RESUMO

Lipopolysaccharide (LPS) is known to elicit a robust immune response. This study aimed to investigate the impact of LPS on the transcriptome of human nasal epithelial cells (HNEpC). HNEpC were cultured and stimulated with LPS (1 µg/mL) or an equivalent amount of normal culture medium. Subsequently, total RNA was extracted, purified, and sequenced using next-generation RNA sequencing technology. Differentially expressed genes (DEGs) were identified and subjected to functional enrichment analysis. A protein-protein interaction (PPI) network of DEGs was constructed, followed by Ingenuity Pathway Analysis (IPA) to identify molecular pathways influenced by LPS exposure on HNEpC. Validation of key genes was performed using quantitative real-time PCR (qRT-PCR). A total of 97 DEGs, comprising 48 up-regulated genes and 49 down-regulated genes, were identified. Results from functional enrichment analysis, PPI, and IPA indicated that DEGs were predominantly enriched in chemokine-related signaling pathways. Subsequent qRT-PCR validation demonstrated significant upregulation of key genes in these pathways in LPS-treated HNEpC compared to control cells. In conclusion, LPS intervention profoundly altered the transcriptome of HNEpC, potentially exacerbating inflammatory responses through the activation of chemokine-related signaling pathways.


Assuntos
Perfilação da Expressão Gênica , Lipopolissacarídeos , Humanos , Perfilação da Expressão Gênica/métodos , Lipopolissacarídeos/farmacologia , Transcriptoma , Transdução de Sinais/genética , Células Epiteliais , Quimiocinas/genética , Biologia Computacional/métodos
3.
Front Pharmacol ; 15: 1380277, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628645

RESUMO

Essential oils are potential alternatives to antibiotics for preventing Candida albicans (C. albicans) infection which is responsible for economic losses in the pigeon industry. Cymbopogon martini essential oil (EO) can inhibit pathogens, particularly fungal pathogens but its potential beneficial effects on C. albicans-infected pigeons remain unclear. Therefore, we investigated the impact of C. martini EO on antioxidant activity, immune response, intestinal barrier function, and intestinal microbiota in C. albicans-infected pigeons. The pigeons were divided into four groups as follows: (1) NC group: C. albicans uninfected/C. martini EO untreated group; (2) PC group: C. albicans infected/C. martini EO untreated group; (3) LPA group: C. albicans infected/1% C. martini EO treated group; and (4) HPA group: C. albicans infected/2% C. martini EO treated group. The pigeons were infected with C. albicans from day of age 35 to 41 and treated with C. martini EO from day of age 42 to 44, with samples collected on day of age 45 for analysis. The results demonstrated that C. martini EO prevented the reduction in the antioxidant enzymes SOD and GSH-Px causes by C. albicans challenge in pigeons. Furthermore, C. martini EO could decrease the relative expression of IL-1ß, TGF-ß, and IL-8 in the ileum, as well as IL-1ß and IL-8 in the crop, while increasing the relative expression of Claudin-1 in the ileum and the crop and Occludin in the ileum in infected pigeons. Although the gut microbiota composition was not significantly affected by C. martini EO, 2% C. martini EO increased the abundance of Alistipes and Pedobacter. In conclusion, the application of 2% C. martini EO not only enhanced the level of antioxidant activity and the expression of genes related to intestinal barrier function but also inhibited inflammatory genes in C. albicans-infected pigeons and increased the abundance of gut bacteria that are resistant to C. albicans.

4.
Clin Exp Allergy ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639267

RESUMO

BACKGROUND: SERPINB2, a biomarker of Type-2 (T2) inflammatory processes, has been described in the context of asthma. Chronic rhinosinusitis with nasal polyps (CRSwNP) is also correlated with T2 inflammation and elevated 15LO1 induced by IL-4/13 in nasal epithelial cells. The aim of this study was to evaluate the expression and location of SERPINB2 in nasal epithelial cells (NECs) and determine whether SERPINB2 regulates 15LO1 and downstream T2 markers in NECs via STAT6 signalling. METHODS: SERPINB2 gene expression in bulk and single-cell RNAseq database was analysed by bioinformatics analysis. SERPINB2, 15LO1 and other T2 markers were evaluated from CRSwNP and HCs NECs. The colocalization of SERPINB2 and 15LO1 was evaluated by immunofluorescence. Fresh NECs were cultured at an air-liquid interface with or without IL-13, SERPINB2 Dicer-substrate short interfering RNAs (DsiRNAs) transfection, exogenous SERPINB2, 15-HETE recombinant protein and pSTAT6 inhibitors. 15LO1, 15-HETE and downstream T2 markers were analysed by qRT-PCR, western blot and ELISA. RESULTS: SERPINB2 expression was increased in eosinophilic nasal polyps compared with that in noneosinophilic nasal polyps and control tissues and positively correlated with 15LO1 and other downstream T2 markers. SERPINB2 was predominantly expressed by epithelial cells in NP tissue and was colocalized with 15LO1. In primary NECs in vitro, SERPINB2 expression was induced by IL-13. Knockdown or overexpression SERPINB2 decreased or enhanced expression of 15LO1 and 15-HETE in NECs, respectively, in a STAT6-dependent manner. SERPINB2 siRNA also inhibited the expression of the 15LO1 downstream genes, such as CCL26, POSTN and NOS2. STAT6 inhibition similarly decreased SERPINB2-induced 15LO1. CONCLUSIONS: SERPINB2 is increased in NP epithelial cells of eosinophilic CRSwNP (eCRSwNP) and contributes to T2 inflammation via STAT6 signalling. SERPINB2 could be considered a novel therapeutic target for eCRSwNP.

5.
Materials (Basel) ; 17(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38612083

RESUMO

In this paper, ordinary Portland cement, ultrafine cement, polyurethane, and epoxy resin were selected as typical grouting materials. Grouting simulation tests were first conducted to prepare the grouted concrete crack sample. The effect of concrete crack parameters (i.e., crack aperture and roughness), grout water-cement ratio, and grouting pressure on the water-plugging performance of different grouting materials was explored through the impermeability test. The microstructure of grouted concrete cracks was analyzed by means of scanning electron microscopy (SEM) and computed tomography (CT), and the difference in water-plugging performance of different grouting materials was explained at the micro level. The results show that the impermeability of the four grouting materials was ranked as follows: Epoxy resin > polyurethane > ultra-fine cement > ordinary Portland cement. The concrete cracks grouted by epoxy resin have the highest plugging failure water pressure and the lowest permeability, which is the optimal grouting material. The effectiveness of crack grouting in water-plugging was directly proportional to the grouting pressure, provided the pressure did not exceed a certain value. When the pressure surpassed the threshold, the increase in pressure did not have a significant impact on the water plugging performance. For the two cement-based materials, the threshold pressure was 1 MPa, while for the other two chemical grouts, it was 2 MPa. The two cement-based grouts with a water-cement ratio of 0.8 showed optimal water-plugging performance. The water-plugging performance of ordinary Portland cement paste, ultra-fine cement pastes, and polyurethane grout was negatively correlated with crack aperture and positively correlated with crack roughness. However, the water-plugging performance of epoxy resin grout was not affected by crack aperture or roughness.

6.
Stem Cells Int ; 2024: 5388064, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633381

RESUMO

Objectives: Traditional Chinese medicine Cortex Eucommiae has been used to treat bone fracture for hundreds of years, which exerts a significant improvement in fracture healing. Aucubin, a derivative isolated from Cortex Eucommiae, has been demonstrated to possess anti-inflammatory, immunoregulatory, and antioxidative potential. In the present study, our aim was to explore its function in bone regeneration and elucidate the underlying mechanism. Materials and Methods: The effects of Aucubin on osteoblast and osteoclast were examined in mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) and RAW 264.7 cells, respectively. Moreover, the lncRNA H19 and Wnt/ß-catenin signaling were detected by qPCR examination, western blotting, and luciferase activity assays. Using the femur fracture mice model, the in vivo effect of Aucubin on bone formation was monitored by X-ray, micro-CT, histomorphometry, and immunohistochemistry staining. Results: In the present study, Aucubin was found to significantly promote osteogenic differentiation in vitro and stimulated bone formation in vivo. Regarding to the underlying mechanism, H19 was found to be obviously upregulated by Aucubin in MSCs and thus induced the activation of Wnt/ß-catenin signaling. Moreover, H19 knockdown partially reversed the Aucubin-induced osteogenic differentiation and successfully suppressed the activation of Wnt/ß-catenin signaling. We therefore suggested that Aucubin induced the activation of Wnt/ß-catenin signaling through promoting H19 expression. Conclusion: Our results demonstrated that Aucubin promoted osteogenesis in vitro and facilitated fracture healing in vivo through the H19-Wnt/ß-catenin regulatory axis.

7.
Adv Mater ; : e2400858, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38631028

RESUMO

2D materials are burgeoning as promising candidates for investigating nonlinear optical effects due to high nonlinear susceptibilities, broadband optical response, and tunable nonlinearity. However, most 2D materials suffer from poor nonlinear conversion efficiencies, resulting from reduced light-matter interactions and lack of phase matching at atomic thicknesses. Herein, a new 2D nonlinear material, niobium oxide dibromide (NbOBr2) is reported, featuring strong and anisotropic optical nonlinearities with scalable nonlinear intensity. Furthermore, Fabry-Pérot (F-P) microcavities are constructed by coupling NbOBr2 with air holes in silicon. Remarkable enhancement factors of ≈630 times in second harmonic generation (SHG) and 210 times in third harmonic generation (THG) are achieved on cavity at the resonance wavelength of 1500 nm. Notably, the cavity enhancement effect exhibits strong anisotropic feature tunable with pump wavelength, owing to the robust optical birefringence of NbOBr2. The ratio of the enhancement factor along the b- and c-axis of NbOBr2 reaches 2.43 and 5.27 for SHG and THG at 1500 nm pump, respectively, which leads to an extraordinarily high SHG anisotropic ratio of 17.82 and a 10° rotation of THG polarization. The research presents a feasible and practical strategy for developing high-efficiency and low-power-pumped on-chip nonlinear optical devices with tunable anisotropy.

8.
Light Sci Appl ; 13(1): 74, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485915

RESUMO

Photonic quantum computation plays an important role and offers unique advantages. Two decades after the milestone work of Knill-Laflamme-Milburn, various architectures of photonic processors have been proposed, and quantum advantage over classical computers has also been demonstrated. It is now the opportune time to apply this technology to real-world applications. However, at current technology level, this aim is restricted by either programmability in bulk optics or loss in integrated optics for the existing architectures of processors, for which the resource cost is also a problem. Here we present a von-Neumann-like architecture based on temporal-mode encoding and looped structure on table, which is capable of multimode-universal programmability, resource-efficiency, phase-stability and software-scalability. In order to illustrate these merits, we execute two different programs with varying resource requirements on the same processor, to investigate quantum signature of chaos from two aspects: the signature behaviors exhibited in phase space (13 modes), and the Fermi golden rule which has not been experimentally studied in quantitative way before (26 modes). The maximal program contains an optical interferometer network with 1694 freely-adjustable phases. Considering current state-of-the-art, our architecture stands as the most promising candidate for real-world applications.

9.
Nat Commun ; 15(1): 2329, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485944

RESUMO

Intragrain impurities can impart detrimental effects on the efficiency and stability of perovskite solar cells, but they are indiscernible to conventional characterizations and thus remain unexplored. Using in situ scanning transmission electron microscopy, we reveal that intragrain impurity nano-clusters inherited from either the solution synthesis or post-synthesis storage can revert to perovskites upon irradiation stimuli, leading to the counterintuitive amendment of crystalline grains. In conjunction with computational modelling, we atomically resolve crystallographic transformation modes for the annihilation of intragrain impurity nano-clusters and probe their impacts on optoelectronic properties. Such critical fundamental findings are translated for the device advancement. Adopting a scanning laser stimulus proven to heal intragrain impurity nano-clusters, we simultaneously boost the efficiency and stability of formamidinium-cesium perovskite solar cells, by virtual of improved optoelectronic properties and relaxed intra-crystal strain, respectively. This device engineering, inspired and guided by atomic-scale in situ microscopic imaging, presents a new prototype for solar cell advancement.

10.
J Neurosurg ; : 1-7, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457809

RESUMO

OBJECTIVE: Reducing the incidence of delayed postoperative hemorrhage (DPH) is one of the challenges in the surgical treatment of patients with brain arteriovenous malformations (bAVMs). This study aimed to identify several risk factors for DPH after bAVM resection and evaluate the impact of these risk factors in patients with bAVMs. METHODS: The authors retrospectively reviewed consecutive patients with bAVMs who underwent microsurgical resection between August 2011 and September 2021. Patients were divided into either the DPH group or non-DPH group based on whether they experienced a postoperative intracerebral hemorrhage into the bAVM bed within 14 days after bAVM resection. Factors associated with DPH were assessed using multivariate logistic regression analyses. RESULTS: A total of 1284 consecutive patients with bAVMs were evaluated; DPH events occurred in 18 patients (1.4%). There were several differences in vascular architecture between the two cohorts. A giant nidus, a nidus involved in the eloquent area, a periventricular nidus, and a nidus accompanied by venous ectasia were more likely to be associated with DPH events. The multivariate analysis identified two independent factors associated with DPH: maximum diameter (OR 1.44 per 1-cm increase, 95% CI 1.13-1.83) and periventricular lesion (OR 4.10, 95% CI 1.33-12.59). The area under the receiver operating characteristic curve for the maximum lesion diameter and development of DPH was 0.71 (95% CI 0.58-0.84). The cutoff value for the maximum bAVM diameter was 4.15 cm. Furthermore, patients with a giant bAVM, of which the maximum diameter was ≥ 4.15 cm, had a higher DPH risk after surgery (HR 5.79, 95% CI 2.01-16.67; p < 0.01). The incidence rates of DPH for patients with periventricular lesions were higher than those for patients without periventricular lesions (HR 4.50, 95% CI 1.77-11.40; p < 0.01). CONCLUSIONS: Patients with giant bAVMs or periventricular lesions are at higher risk for DPH after surgery. Strategies such as blood pressure control, preoperative embolization, intraoperative monitoring, and careful patient selection should be considered to reduce the risk of DPH in high-risk patients.

11.
Bioinspir Biomim ; 19(3)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38507791

RESUMO

In this work, we focus on overcoming the challenge of a snake robot climbing on the outside of a bifurcated pipe. Inspired by the climbing postures of biological snakes, we propose an S-shaped rolling gait designed using curve transformations. For this gait, the snake robot's body presenting an S-shaped curve is wrapped mainly around one side of the pipe, which leaves space for the fork of the pipe. To overcome the difficulty in constructing and clarifying the S-shaped curve, we present a method for establishing the transformation between a plane curve and a 3D curve on a cylindrical surface. Therefore, we can intuitively design the curve in 3D space, while analytically calculating the geometric properties of the curve in simple planar coordinate systems. The effectiveness of the proposed gait is verified by actual experiments. In successful configuration scenarios, the snake robot could stably climb on the pipe and efficiently cross or climb to the bifurcation while maintaining its target shape.


Assuntos
Locomoção , Robótica , Robótica/métodos , Biomimética/métodos , Marcha
12.
Int J Biol Macromol ; 264(Pt 2): 130552, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38442835

RESUMO

Resistant starch from rice was prepared using high-pressure homogenization and branched chain amylase treatment. The yield, starch external structure, thermal properties, and crystal structure of rice-resistant starch prepared in different ways were investigated. The results showed that the optimum homogenizing pressure was 90 MPa, the optimum digestion time was 4 h, the optimum concentration of branched-chain amylase was 50 U/g and the yield of resistant starch was 38.58 %. Scanning electron microscopy results showed a rougher surface and more complete debranching of the homogenized coenzyme rice-resistant starch granules. FT-IR and X-ray diffraction results showed that the homogenization treatment exhibited a spiral downward trend on rice starch relative crystallinity and a spiral upward trend on starch debranching and recrystallization. The 4-week dietary intervention in db/db type 2 diabetic mice showed that homogeneous coenzyme rice-resistant starch had a better glycemic modulating effect than normal debranched starch and had a tendency to interfere with the index of liver damage in T2DM mice. Additionally, homogeneous coenzyme rice-resistant starch proved more effective in improving intestinal flora disorders and enhancing the abundance of probiotics in T2DM mice.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Oryza , Camundongos , Animais , Amido Resistente , Glicemia , Oryza/química , Espectroscopia de Infravermelho com Transformada de Fourier , Amido/química , Difração de Raios X , Amilases
13.
J Pharm Biomed Anal ; 243: 116077, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38460276

RESUMO

BACKGROUND: Dendrobium officinale Kimura et Migo (DO), a valuable Chinese herbal medicine, has been reported to exhibit potential effects in the prevention and treatment of lung cancer. However, its material basis and mechanism of action have not been comprehensively analyzed. PURPOSE: The objective of this study was to preliminarily elucidate the active components and pharmacological mechanisms of DO in treating lung cancer, according to UPLC-Q/TOF-MS, HPAEC-PAD, network pharmacology, molecular docking, and experimental verification. METHODS: The chemical components of DO were identified via UPLC-Q/TOF-MS, while the monosaccharide composition of Dendrobium officinale polysaccharide (DOP) was determined by HPAEC-PAD. The prospective active constituents of DO as well as their respective targets were predicted in the combined database of Swiss ADME and Swiss Target Prediction. Relevant disease targets for lung cancer were searched in OMIM, TTD, and Genecards databases. Further, the active compounds and potential core targets of DO against lung cancer were found by the C-T-D network and the PPI network, respectively. The core targets were then subjected to enrichment analysis in the Metascape database. The main active compounds were molecularly docked to the core targets and visualized. Finally, the viability of A549 cells and the relative quantity of associated proteins within the major signaling pathway were detected. RESULTS: 249 ingredients were identified from DO, including 39 flavonoids, 39 bibenzyls, 50 organic acids, 8 phenanthrenes, 27 phenylpropanoids, 17 alkaloids, 17 amino acids and their derivatives, 7 monosaccharides, and 45 others. Here, 50 main active compounds with high degree values were attained through the C-T-D network, mainly consisting of bibenzyls and monosaccharides. Based on the PPI network analysis, 10 core targets were further predicted, including HSP90AA1, SRC, ESR1, CREBBP, MAPK3, AKT1, PIK3R1, PIK3CA, HIF1A, and HDAC1. The results of the enrichment analysis and molecular docking indicated a close association between the therapeutic mechanism of DO and the PI3K-Akt signaling pathway. It was confirmed that the bibenzyl extract and erianin could inhibit the multiplication of A549 cells in vitro. Furthermore, erianin was found to down-regulate the relative expressions of p-AKT and p-PI3K proteins within the PI3K-Akt signaling pathway. CONCLUSIONS: This study predicted that DO could treat lung cancer through various components, multiple targets, and diverse pathways. Bibenzyls from DO might exert anti-lung cancer activity by inhibiting cancer cell proliferation and modulating the PI3K-Akt signaling pathway. A fundamental reference for further studies and clinical therapy was given by the above data.


Assuntos
Bibenzilas , Dendrobium , Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Fenol , Neoplasias Pulmonares/tratamento farmacológico , Farmacologia em Rede , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-akt , Monossacarídeos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
14.
J Neurointerv Surg ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38471763

RESUMO

BACKGROUND: The hemodynamics of brain arteriovenous malformations (AVMs) may have implications for hemorrhage. This study aimed to explore the hemodynamics of ruptured AVMs by direct microcatheter intravascular pressure monitoring (MIPM) and indirect quantitative digital subtraction angiography (QDSA). METHODS: We recruited patients with AVMs at a tertiary neurosurgery center from October 2020 to March 2023. In terms of MIPM, we preoperatively super-selected a predominant feeding artery and main draining vein through angiography to measure intravascular pressure before embolization. In processing of QDSA, we adopted previously standardized procedure for quantitative hemodynamics analysis of pre-embolization digital subtraction angiography (DSA), encompassing main feeding artery, nidus, and the main draining vein. Subsequently, we investigated the correlation between AVM rupture and intravascular pressure from MIPM, as well as hemodynamic parameters derived from QDSA. Additionally, we explored the interrelationships between hemodynamic indicators in both dimensions. RESULTS: After strict screening of patients, our study included 10 AVMs (six ruptured and four unruptured). We found that higher transnidal pressure gradient (TPG) (53.00±6.36 vs 39.25±8.96 mmHg, p=0.042), higher feeding artery pressure (FAP) (72.83±5.46 vs 65.00±6.48 mmHg, p=0.031) and higher stasis index of nidus (3.54±0.73 vs 2.43±0.70, p=0.043) were significantly correlated with AVM rupture. In analysis of interrelationships between hemodynamic indicators in both dimensions, a strongly positive correlation (r=0.681, p=0.030) existed between TPG and stasis index of nidus. CONCLUSIONS: TPG and FAP from MIPM platform and nidus stasis index from QDSA platform were correlated with AVM rupture, and both were positively correlated, suggesting that higher pressure load within nidus may be the central mechanism leading to AVM rupture.

15.
Life (Basel) ; 14(2)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38398700

RESUMO

The mammary gland of mammals can generate numerous bioactive proteins. To express the human amylin protein in the mammary glands of domestic animals, we engineered a transgenic mammary gland bioreactor. For this study, we produced transgenic mice through prokaryotic microinjection. RT-PCR, qPCR, and Western blotting confirmed the presence of transgenes in the mice. The ELISA assay indicated an amylin yield of approximately 1.44 µg/mL in the mice milk. Further research revealed that consuming milk containing amylin resulted in a slight, but insignificant enhancement in food consumption, blood sugar equilibrium, and glucose tolerance. The influence of amylin-fortified milk on the abundance of fecal strains in mice was examined, and a significant difference in the quantity of strains needed for fatty acid synthesis and metabolism was discovered. The amylin protein gathered from humans is safe to consume, as no harmful effects were detected in the mice. Our study examined the production of human amylin using a new safety strategy that could potentially alleviate diabetic symptoms in the future through oral administration of milk containing amylin.

16.
Biomaterials ; 306: 122483, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38330742

RESUMO

Bromodomain-containing protein 4 (BRD4) is the most well-studied BET protein that is important for the innate immune response. We recently revealed that targeting BRD4 triggers apoptosis in tumor-associated macrophages, but its role in synovial macrophages and joint inflammation is largely unknown. Herein, we demonstrated that BRD4 was highly expressed in the iNOS-positive M1 macrophages in the human and mouse osteoarthritis (OA) synovium, and conditional knockout of BRD4 in the myeloid lineage using Lyz2-cre; BRD4flox/flox mice significantly abolished anterior cruciate ligament transection (ACLT)-induced M1 macrophage accumulation and synovial inflammation. Accordingly, we successfully constructed apoptotic body-inspired phosphatidylserine-containing nanoliposomes (PSLs) loaded with the BRD4 inhibitor JQ1 to regulate inflammatory macrophages. JQ1-loaded PSLs (JQ1@PSLs) exhibited a higher cellular uptake by macrophages than fibroblast-like synoviocytes (FLSs) in vitro and in vivo, as well as the reduction in proinflammatory M1 macrophage polarization. Intra-articular injections of JQ1@PSLs showed prolonged retention within the joint, and remarkably reduced synovial inflammation and joint pain via suppressing M1 polarization accompanied by reduced TRPA1 expression by targeted inhibition of BRD4 in the macrophages, thus attenuating cartilage degradation during OA development. The results show that BRD4-inhibiting JQ1@PSLs can targeted-modulate macrophage polarization, which opens a new avenue for efficient OA therapy via a "Trojan horse".


Assuntos
Osteoartrite , Fatores de Transcrição , Animais , Humanos , Camundongos , Proteínas que Contêm Bromodomínio , Proteínas de Ciclo Celular/metabolismo , Inflamação/metabolismo , Macrófagos/metabolismo , Proteínas Nucleares/metabolismo , Osteoartrite/metabolismo , Membrana Sinovial/metabolismo , Fatores de Transcrição/metabolismo
17.
Food Chem ; 445: 138765, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38367562

RESUMO

This study aimed to reveal the effects and regulatory mechanism of dietary NDF on the performance of pigs by multi-omics analysis. Results showed that 16 % dietary NDF significantly improved meat quality, increased flavor amino acid content, and reduced backfat thickness and the feed-to-gain ratio. 16S rDNA sequencing showed that 16 % NDF significantly increased the abundance of Akkermansia, Lachnoclostridium, and Ruminococcus. Transcript analysis showed that genes related to muscle development and lipid metabolism were significantly modified. Metabonomic analysis showed that 16 % NDF significantly increased amino and fatty acid related metabolites. Correlation analysis suggested that 16 % NDF treatment may alter the gut microbiota and metabolites, regulate the expression of genes related to lipid and amino metabolism, and ultimately affect the flavor and performance of pigs. This study provides a novel understanding about the effect and regulatory mechanism of NDF supplements on the finishing pigs and a relevant reference for the improvement of diet formulation.


Assuntos
Aminoácidos , Detergentes , Suínos/genética , Animais , Aminoácidos/metabolismo , Multiômica , Composição Corporal , Suplementos Nutricionais , Dieta/veterinária , Carne/análise , Ração Animal/análise
18.
Cell Mol Life Sci ; 81(1): 96, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372748

RESUMO

Activation of hepatic stellate cells (HSCs) has been demonstrated to play a pivotal role in the process of liver fibrogenesis. In this study, we observed a decrease in the expression of KIF18A in fibrotic liver tissues compared to healthy liver tissues, which exhibited a negative correlation with the activation of HSCs. To elucidate the molecular mechanisms underlying the involvement of KIF18A, we performed in vitro proliferation experiments and established a CCl4-induced liver fibrosis model. Our results revealed that KIF18A knockdown enhanced HSCs proliferation and reduced HSCs apoptosis in vitro. Mouse liver fibrosis grade was evaluated with Masson's trichrome and alpha-smooth muscle actin (α-SMA) staining. In addition, the expression of fibrosis markers Col1A1, Stat1, and Timp1 were detected. Animal experiments demonstrated that knockdown of KIF18A could promote liver fibrosis, whereas overexpression of KIF18A alleviated liver fibrosis in a CCl4-induced mouse model. Mechanistically, we found that KIF18A suppressed the AKT/mTOR pathway and exhibited direct binding to TTC3. Moreover, TTC3 was found to interact with p-AKT and could promote its ubiquitination and degradation. Our findings provide compelling evidence that KIF18A enhances the protein binding between TTC3 and p-AKT, promoting TTC3-mediated ubiquitination and degradation of p-AKT. These results refine the current understanding of the mechanisms underlying the pathogenesis of liver fibrosis and may offer new targets for treating this patient population.


Assuntos
Células Estreladas do Fígado , Cinesinas , Cirrose Hepática , Animais , Humanos , Camundongos , Cinesinas/genética , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TOR , Ubiquitina-Proteína Ligases
19.
Int J Biol Macromol ; 263(Pt 2): 130161, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38367791

RESUMO

Snail mucus is rich in proteins and polysaccharides, which has been proved to promote wound healing in mice in our previous research. The aim of this study was to investigate the effective component in snail mucus that can exert the wound healing potential and its structural characterization. Here, the glycoprotein from the snail mucus (SM1S) was obtained by DEAE-Sepharose Fast Flow and Sephacryl S-300 columns. The structural characteristics of SM1S were investigated via chromatographic techniques, periodic acid oxidation, FT-IR spectroscopy and NMR spectroscopy. Results showed that SM1S was a glycoprotein with a molecular weight of 3.8 kDa (83.23 %), consists of mannose, glucuronic acid, glucose, galactose, xylose, arabinose, fucose at a ratio of 13.180:4.875:1043.173:7.552:1:3.501:2.058. In addition, the periodic acid oxidation and NMR analysis showed that SM1S contained 1,6-glycosidic bonds, and might also contain 1 â†’ 4 and 1 â†’ 2 glycosidic or 1 â†’ 3 glycosidic bonds. Furthermore, the migration experiment of human skin fibroblasts in vitro suggested that SM1S had a good effect to accelerate the scratch healing of cells. This study suggested that SM1S may be a prospective candidate as a natural wound dressing for the development of snail mucus products.


Assuntos
Glicoproteínas , Polissacarídeos , Caramujos , Animais , Humanos , Camundongos , Espectroscopia de Infravermelho com Transformada de Fourier , Ácido Periódico , Polissacarídeos/farmacologia , Polissacarídeos/química , Cicatrização
20.
Animals (Basel) ; 14(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38338075

RESUMO

The gut microbiota establishment in young ruminants has a profound impact on their adult production performance. However, the critical phase for the succession of the gut microbial composition and metabolic profiles of juvenile sika deer still needs to be further investigated. Here, we analyzed the fecal microbiota and metabolites of juvenile sika deer during the birth (D1), transition (D42), and rumination (D70) periods based on 16S rRNA sequencing and gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS). The results showed that the fecal bacteria and metabolites composition were significantly different in D1 compared to D42 and D70, and the number of OTUs and the Shannon index were significantly higher in D70 than in D1 (p < 0.05). The relative abundances of Lactobacillus, Lactococcus, and Lachnoclostridium showed a significant increase in D1 compared to D42 and D70, whereas the relative abundances of Ruminococcaceae UCG-005, Ruminococcaceae UCG-010, Ruminococcaceae UCG-014, Christensenellaceae R-7, and Eubacterium coprostanoligenes group were significantly decreased in D1 compared to D42 and D70 (p < 0.05). The amounts of serine, phenylalanine, aspartic acid, ornithine, citrulline, creatine, isoleucine, galactose, and ribose in the feces were significantly higher in D1 compared to D42 and D70. In contrast, the concentrations of cortexolone, resveratrol, piceatannol, fumaric acid, alpha-ketoglutarate, glycerol, uracil-5-carboxylic acid, and maleic acid were significantly decreased in D1. The enrichment analysis showed that amino acid metabolism and carbohydrate metabolism were significantly changed in D1 compared to D42 and D70. The glycine, serine and threonine metabolism; alanine, aspartate and glutamate metabolism; arginine biosynthesis; glyoxylate and dicarboxylate metabolism; citrate cycle; and pyruvate metabolism were significantly enriched across the three periods (p < 0.05). In conclusion, our results suggested that the birth-transition period is a critical phase for the gut bacterial community and metabolic function shift in juvenile sika deer.

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