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1.
Cell Commun Signal ; 20(1): 62, 2022 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-35534896

RESUMEN

BACKGROUND: Recent studies have indicated that some members of the tripartite motif (TRIM) proteins function as important regulators for non-small cell lung cancer (NSCLC), However, the regulatory mechanism underpinning aberrant expression of TRIM in NSCLC remains unclear. Here we report that TRIM15 plays important roles in NSCLC progression through modulating Keap1-Nrf2 signaling pathway. METHODS: TRIM15 expression was evaluated by western blot analysis, tissue microarray-based immunohistochemistry analysis. The interactions between TRIM15 and Keap1 were analyzed by co-immunoprecipitation (Co-IP) and immunofluorescence co-localization assay. The correlation between TRIM15 and Keap1 was measured by Co-IP and ubiquitination analysis in vitro. Gain- and lost-of-function experiments were used to detect TRIM15 promotes proliferation and invasion of NSCLC cells both in vitro and vivo. RESULTS: Here, we revealed that TRIM15 was frequently upregulated in NSCLC samples and associated with poor prognosis. Functionally, TRIM15 knockdown resulted in decreased cancer cell proliferation and metastasis, whereas ectopic TRIM15 expression facilitated tumor cancer cell proliferation and metastasis in vitro and in vivo. Moreover, TRIM15 promoted cell proliferation and metastasis depends on its E3 ubiquitin ligase. Mechanistically, TRIM15 directly targeted Keap1 by ubiquitination and degradation, the principal regulator of Nrf2 degradation, leading to Nrf2 escaping from Keap1-mediated degradation, subsequently promoting antioxidant response and tumor progression. CONCLUSIONS: Therefore, our study characterizes the pivotal roles of TRIM15 promotes NSCLC progression via Nrf2 stability mediated by promoting Keap1 ubiquitination and degradation and could be a valuable prognostic biomarker and a potential therapeutic target in NSCLC. Video Abstract.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Proteínas de Unión al ADN , Neoplasias Pulmonares , Transducción de Señal , Ubiquitina-Proteína Ligasas , Carcinoma de Pulmón de Células no Pequeñas/patología , Proteínas de Unión al ADN/metabolismo , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Neoplasias Pulmonares/patología , Factor 2 Relacionado con NF-E2/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo
2.
Molecules ; 27(17)2022 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-36080211

RESUMEN

Polymeric ultrafine fibrous membranes (UFMs) with high thermal stability and high whiteness are highly desired in modern optoelectronic applications. A series of fluoro-containing polyimide (FPI) UFMs with high whiteness, good thermal stability, and good hydrophobicity were prepared via a one-step electrospinning procedure from the organo-soluble FPI resins derived from a fluoro-containing dianhydride, 4,4'-(hexafluoroisopropylidene) diphthalic anhydride (6FDA), and various diamines containing either pendant trifluoromethyl (-CF3) groups or alicyclic units in the side chains. The obtained FPI UFMs, including FPI-1 from 6FDA and 3,5-diaminobenzotrifluoride (TFMDA), FPI-2 from 6FDA and 2'-trifluoromethyl-3,4'-oxydianiline (3FODA), FPI-3 from 6FDA and 1,4-bis[(4-amino-2-trifluoromethyl)phenoxy]benzene (6FAPB), FPI-4 from 4,4'-bis[(4-amino-2-trifluoromethyl)phenoxy]biphenyl (6FBAB), and FPI-5 from 6FDA and 4'-tert-butyl-cyclohexyl-3,5-diaminobenzoate (DABC) showed whiteness indices (WI) higher than 87.00 and optical reflectance values higher than 80% at the wavelength of 457 nm (R457), respectively. The FPI-5 UFM, especially, showed the highest WI of 92.88. Meanwhile, the prepared PI UFMs exhibited good hydrophobic features with water contact angles (WCA) higher than 105°. At last, the PI UFMs exhibited good thermal stability with glass transition temperatures (Tg) higher than 255 °C, and the 5% weight-loss temperatures (T5%) higher than 510 °C in nitrogen.


Asunto(s)
Anhídridos , Polímeros , Anhídridos/química , Diaminas/química , Interacciones Hidrofóbicas e Hidrofílicas , Polímeros/química , Temperatura de Transición
3.
J Cell Mol Med ; 23(2): 1458-1469, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30515965

RESUMEN

Lung cancer (LC) is a devastating malignancy with no effective treatments, due to its complex genomic profile. Using bioinformatics analysis and immunohistochemical of lung carcinoma tissues, we show that TRIM59 as a critical oncoprotein relating to LC proliferation and metastasis. In this study, high TRIM59 expression was significantly correlated with lymph node metastasis, distant metastasis, and tumour stage. Furthermore, up-regulation of TRIM59 expression correlated with poorer outcomes in LC patients. Mechanistically, TRIM59 play a key role in promoting LC growth and metastasis through regulation of extracellular-signal regulated protein kinase (ERK) signalling pathway and epithelial-to-mesenchymal transition (EMT)-markers, as validated by loss-of-function studies. In-depth bioinformatics analysis showed that there is preliminary evidence of co-expression of TRIM59 and cyclin dependent kinase 6 (CDK6) in LC. Notably, CDK6 expression significantly decreased when TRIM59 was knocked down in the LC cells. In contrast, exogenous up-regulation of TRIM59 expression also induced significant increases in the expression of CDK6. Moreover, the expression of CDK6 was also inhibited by the ERK signalling inhibitor, U0126. The results of both loss- and gain-of-function studies showed that TRIM59 could regulate the expression of CDK6. Collectively, these data provide evidence that TRIM59 is involved in lung carcinoma growth and progression possibly through the induction of CDK6 expression and EMT process by activation of ERK pathway.


Asunto(s)
Carcinoma/genética , Quinasa 6 Dependiente de la Ciclina/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Neoplasias Pulmonares/genética , Proteínas de Motivos Tripartitos/genética , Biomarcadores de Tumor/genética , Butadienos/farmacología , Carcinoma/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Metástasis de la Neoplasia , Nitrilos/farmacología , Transducción de Señal
4.
Pharmacol Res ; 147: 104381, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31369811

RESUMEN

The Mitochondrial-derived peptide MOTS-c has recently been reported as a 16-amino acid peptide regulating metabolism and homeostasis in different cells. However, its effects on immune cells and bone metabolism are rarely reported. Here we demonstrate that MOTS-c treatment in ultra-high molecular weight polyethylene (UHMWPE) particle-induced osteolysis mouse model alleviated bone erosion and inflammation. MOTS-c increased osteoprotegerin (OPG)/ receptor activator of nuclear factor kappa-B ligand (RANKL) ratio in osteocytes, leading to inhibition of osteoclastogenesis. In primary bone marrow macrophages (BMMs) MOTS-c alleviated STAT1 and NF-κB phosphorylation triggered by UHMWPE particles. Promoting ROS production or suppressing peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) by adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) repression blocked these anti-inflammatory effects of MOTS-c treatment. Taken together, these findings provide evidence that the small peptide inhibits osteoclastogenesis by regulating osteocyte OPG/RANKL secretion and suppressing inflammation via restraining NF-κB and STAT1 pathway. Moreover, its effects on NF-κB activation is dependent on the AMPK-PGC-1α-ROS axis, suggesting its potential use in osteolysis and other inflammation disorders.


Asunto(s)
Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Proteínas Mitocondriales/farmacología , Proteínas Mitocondriales/uso terapéutico , Osteólisis/tratamiento farmacológico , Cráneo/efectos de los fármacos , Animales , Células Cultivadas , Citocinas/genética , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteocitos/efectos de los fármacos , Osteocitos/metabolismo , Osteogénesis/efectos de los fármacos , Osteólisis/inducido químicamente , Osteólisis/metabolismo , Polietileno , Ligando RANK/genética , Ligando RANK/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Cráneo/metabolismo , Cráneo/patología
5.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(2): 134-143, 2019 Feb 28.
Artículo en Zh | MEDLINE | ID: mdl-30837381

RESUMEN

OBJECTIVE: To investigate the effects of airway epithelial cells on macrophages chemotaxis and inflammatory cytokine expression under hypoxic conditions.
 Methods: Human bronchial epithelial cells (HBE) treated with different concentrations (0, 100, 200, 400, 800 µmol/L) of CoCl2 or transfected with HIF-1α siRNA were co-cultured with THP-1-derived M1 macrophages or M2 macrophages. The chemotactic effects on macrophages were analyzed by Transwell assay. The levels of TNF-α, IFN-γ, IL-4, IL-13 and IL-10 in the supernatants of macrophages were detected by ELISA, and HIF-1α or Cav-1 mRNA expression in HBE or macrophages was detected by RT-qPCR.
 Results: HBE cells promoted macrophages chemotaxis in a time- and concentration-dependent manner. Compared to un-transfected group, the chemotactic ability of HBE transfected with HIF-1α siRNA was significantly weakened (P<0.01). Under the same culture conditions, the chemotaxis of M2 macrophages was greater than that in THP1-derived M1 macrophages. The concentrations of TNF-α, IFN-γ, IL-4, IL-13 and IL-10 in the supernatants of macrophages were increased in a time-and concentration-dependent manner. The concentrations of TNF-α and IFN-γ were increased further after co-culturing for 8 and 12 h; while IL-4, IL-13 and IL-10 concentrations were increased further during 24 h of co-culture. The levels of cytokines in the supernatants of macrophages co-cultured with HBE and transfected with HIF-1α siRNA were significantly lower than those in un-transfected cells (P<0.05 or P<0.01). The reduction of TNF-α or IFN-γ was more obvious. The expression of HIF-1α or Cav-1 mRNA in HBE or macrophages was increased in a concentration-dependent manner after 8 or 12 h co-culture, which was significantly reduced when HBE was transfected with HIF-1α siRNA.
 Conclusion: Airway epithelial cells can enhance macrophages chemotaxis and pro-inflammatory cytokines expressions under hypoxic condition. HIF-1α and Cav-1 may be the important mediators in these processes.


Asunto(s)
Quimiotaxis , Hipoxia de la Célula , Citocinas , Células Epiteliales , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia , Macrófagos
6.
J Imaging ; 10(9)2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39330436

RESUMEN

Methods based on deep learning have achieved great success in the field of video action recognition. When these methods are applied to real-world scenarios that require fine-grained analysis of actions, such as being tested on a tea ceremony, limitations may arise. To promote the development of fine-grained action recognition, a fine-grained video action dataset is constructed by collecting videos of tea ceremony actions. This dataset includes 2745 video clips. By using a hierarchical fine-grained action classification approach, these clips are divided into 9 basic action classes and 31 fine-grained action subclasses. To better establish a fine-grained temporal model for tea ceremony actions, a method named TSM-ConvNeXt is proposed that integrates a TSM into the high-performance convolutional neural network ConvNeXt. Compared to a baseline method using ResNet50, the experimental performance of TSM-ConvNeXt is improved by 7.31%. Furthermore, compared with the state-of-the-art methods for action recognition on the FineTea and Diving48 datasets, the proposed approach achieves the best experimental results. The FineTea dataset is publicly available.

7.
Sci Rep ; 14(1): 22301, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39333631

RESUMEN

In this study, the corrosion electrochemistry and corrosion behavior of two steels were studied under the simulated alumina production conditions. The corrosion rate of 16Mn steel is greater than that of Q235 steel. The effect of S2- concentration on corrosion rate was significantly higher than that of S2O32-. The synergistic corrosion rates of Q235 and 16Mn steels increase at first and then decrease with the sulfur content, and the peak value appears when the concentration of S2- and S2O32- is 4 g/L and 3 g/L respectively. There are two main types of corrosion products: one is surface octahedral grain, which is composed of Fe2O3, Fe3O4 and Al2O3.The other is the interlayer corrosion between the surface layer and the matrix, which is composed of FeS, FeS2 and NaFeO2.The formation mechanism of the corrosion and corrosion mechanism were obtained by analyzing the phenomenon of ion competitive adsorption. Further validation and analysis of ion competition adsorption phenomenon were conducted using first-principles calculations based on density functional theory (DFT). The formation of corrosion products on the steel surface was investigated at an ion level, and the adsorption energies of OH- and S2- at the top site of Fe(110) surface were calculated. It was found that S2- is more likely to be adsorbed on the Fe(110) surface compared to OH-. The corrosion mechanism of steel is discussed preliminarily.

8.
Artículo en Inglés | MEDLINE | ID: mdl-39226206

RESUMEN

Ultrasound image super-resolution (SR) aims to transform low-resolution images into high-resolution ones, thereby restoring intricate details crucial for improved diagnostic accuracy. However, prevailing methods relying solely on image modality guidance and pixel-wise loss functions struggle to capture the distinct characteristics of medical images, such as unique texture patterns and specific colors harboring critical diagnostic information. To overcome these challenges, this paper introduces the Multi-Modal Regularized Coarse-to-fine Transformer (M2Trans) for Ultrasound Image SR. By integrating the text modality, we establish joint image-text guidance during training, leveraging the medical CLIP model to incorporate richer priors from text descriptions into the SR optimization process, enhancing detail, structure, and semantic recovery. Furthermore, we propose a novel coarse-to-fine transformer comprising multiple branches infused with self-attention and frequency transforms to efficiently capture signal dependencies across different scales. Extensive experimental results demonstrate significant improvements over state-of-the-art methods on benchmark datasets, including CCA-US, US-CASE, and our newly created dataset MMUS1K, with a minimum improvement of 0.17dB, 0.30dB, and 0.28dB in terms of PSNR. Our code and dataset will be available at: https://github.com/eezkni/M2Trans.

9.
IEEE Trans Image Process ; 32: 6090-6101, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37922166

RESUMEN

It is challenging to generate temporal action proposals from untrimmed videos. In general, boundary-based temporal action proposal generators are based on detecting temporal action boundaries, where a classifier is usually applied to evaluate the probability of each temporal action location. However, most existing approaches treat boundaries and contents separately, which neglect that the context of actions and the temporal locations complement each other, resulting in incomplete modeling of boundaries and contents. In addition, temporal boundaries are often located by exploiting either local clues or global information, without mining local temporal information and temporal-to-temporal relations sufficiently at different levels. Facing these challenges, a novel approach named multi-level content-aware boundary detection (MCBD) is proposed to generate temporal action proposals from videos, which jointly models the boundaries and contents of actions and captures multi-level (i.e., frame level and proposal level) temporal and context information. Specifically, the proposed MCBD preliminarily mines rich frame-level features to generate one-dimensional probability sequences, and further exploits temporal-to-temporal proposal-level relations to produce two-dimensional probability maps. The final temporal action proposals are obtained by a fusion of the multi-level boundary and content probabilities, achieving precise boundaries and reliable confidence of proposals. The extensive experiments on the three benchmark datasets of THUMOS14, ActivityNet v1.3 and HACS demonstrate the effectiveness of the proposed MCBD compared to state-of-the-art methods. The source code of this work can be found in https://mic.tongji.edu.cn.

10.
IEEE Trans Pattern Anal Mach Intell ; 45(7): 8634-8645, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37015429

RESUMEN

As a technically challenging topic, visual storytelling aims at generating an imaginary and coherent story with narrative multi-sentences from a group of relevant images. Existing methods often generate direct and rigid descriptions of apparent image-based contents, because they are not capable of exploring implicit information beyond images. Hence, these schemes could not capture consistent dependencies from holistic representation, impairing the generation of reasonable and fluent stories. To address these problems, a novel knowledge-enriched attention network with group-wise semantic model is proposed. Three main novel components are designed and supported by substantial experiments to reveal practical advantages. First, a knowledge-enriched attention network is designed to extract implicit concepts from external knowledge system, and these concepts are followed by a cascade cross-modal attention mechanism to characterize imaginative and concrete representations. Second, a group-wise semantic module with second-order pooling is developed to explore the globally consistent guidance. Third, a unified one-stage story generation model with encoder-decoder structure is proposed to simultaneously train and infer the knowledge-enriched attention network, group-wise semantic module and multi-modal story generation decoder in an end-to-end fashion. Substantial experiments on the visual storytelling datasets with both objective and subjective evaluation metrics demonstrate the superior performance of the proposed scheme as compared with other state-of-the-art methods. The source code of this work can be found in https://mic.tongji.edu.cn.

11.
IEEE Trans Image Process ; 32: 2827-2842, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37186533

RESUMEN

Convolutional Neural Networks (CNNs) dominate image processing but suffer from local inductive bias, which is addressed by the transformer framework with its inherent ability to capture global context through self-attention mechanisms. However, how to inherit and integrate their advantages to improve compressed sensing is still an open issue. This paper proposes CSformer, a hybrid framework to explore the representation capacity of local and global features. The proposed approach is well-designed for end-to-end compressive image sensing, composed of adaptive sampling and recovery. In the sampling module, images are measured block-by-block by the learned sampling matrix. In the reconstruction stage, the measurements are projected into an initialization stem, a CNN stem, and a transformer stem. The initialization stem mimics the traditional reconstruction of compressive sensing but generates the initial reconstruction in a learnable and efficient manner. The CNN stem and transformer stem are concurrent, simultaneously calculating fine-grained and long-range features and efficiently aggregating them. Furthermore, we explore a progressive strategy and window-based transformer block to reduce the parameters and computational complexity. The experimental results demonstrate the effectiveness of the dedicated transformer-based architecture for compressive sensing, which achieves superior performance compared to state-of-the-art methods on different datasets. Our codes is available at: https://github.com/Lineves7/CSformer.

12.
PLoS One ; 18(4): e0282866, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37079570

RESUMEN

BACKGROUND: Diabetic retinopathy (DR) is one of the most common complications of diabetes and has become a major global cause of blindness. Curcumin, an extract of Curcuma longa (turmeric), is effective in preventing and treating diabetes. Recent studies have shown that curcumin can delay DR development. However, there has been no systematic review of its treatment of DR. This study will conduct a systematic review and meta-analysis of currently published randomized controlled trials (RCT) of curcumin for treating DR patients to evaluate its efficacy and safety. METHODS: We will search the relevant studies of curcumin in the treatment of DR in PubMed, Medline, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang databases from their respective inception dates to May 2022. A meta-analysis of the data extracted from qualified RCTs will be conducted, including the progression of DR, visual acuity, visual field, macular edema, quality of life, and adverse events. The meta-analysis will be performed using Review Manager 5.4.1 software, and the results will be based on either random-effects or fixed-effects models, depending on the heterogeneity. The Grading of Recommendations, Development, and Evaluation (GRADE) system will be used to evaluate the reliability and quality of evidence. RESULTS: The results of this study will provide sound and high-quality evidence for the efficacy and safety of curcumin in the treatment of DR. CONCLUSION: This study will be the first meta-analysis to comprehensively assess the efficacy and safety of curcumin in the treatment of DR and will provide helpful evidence for the clinical management of this disease. SYSTEMATIC REVIEW REGISTRATION: INPLASY202250002.


Asunto(s)
Curcumina , Diabetes Mellitus , Retinopatía Diabética , Medicamentos Herbarios Chinos , Humanos , Curcumina/efectos adversos , Retinopatía Diabética/tratamiento farmacológico , Revisiones Sistemáticas como Asunto , Metaanálisis como Asunto , Medicamentos Herbarios Chinos/uso terapéutico , Diabetes Mellitus/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto
13.
Membranes (Basel) ; 13(7)2023 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-37505055

RESUMEN

Due to the low boiling point of helium, the nitrogen-rich off gas of the nitrogen rejection unit (NRU) in the liquefied natural gas (LNG) plant usually contains a small amount of CH4, approximately 1-4% He, and associated gases, such as H2. However, it is difficult to separate hydrogen and helium. Here, we propose two different integrated processes coupled with membrane separation, pressure swing adsorption (PSA), and the electrochemical hydrogen pump (EHP) based on different sequences of hydrogen gas removal. Both processes use membrane separation and PSA in order to recover and purify helium, and the EHP is used to remove hydrogen. The processes were strictly simulated using UniSim Design, and an economic assessment was conducted. The results of the economic assessment show that flowsheet #2 was more cost-effective due to the significant reduction in the capacity of the compressor and PSA because of the pre-removal of hydrogen. Additionally, using the response surface methodology (RSM), a Box-Behnken design experiment was conducted, and an accurate and reliable quadratic response surface regression model was fitted through variance analysis. The optimized operating parameters for the integrated process were determined as follows: the membrane area of M101 was 966.6 m2, the permeate pressure of M101 was 100 kPa, and the membrane area of M102 was 41.2 m2. The maximum recovery fraction was 90.66%, and the minimum cost of helium production was 2.21 $/kg. Thus, proposed flowsheet #2 has prospects and value for industrial application.

14.
IEEE Trans Image Process ; 32: 5933-5947, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37903048

RESUMEN

Dynamic point cloud is a volumetric visual data representing realistic 3D scenes for virtual reality and augmented reality applications. However, its large data volume has been the bottleneck of data processing, transmission, and storage, which requires effective compression. In this paper, we propose a Perceptually Weighted Rate-Distortion Optimization (PWRDO) scheme for Video-based Point Cloud Compression (V-PCC), which aims to minimize the perceptual distortion of reconstructed point cloud at the given bit rate. Firstly, we propose a general framework of perceptually optimized V-PCC to exploit visual redundancies in point clouds. Secondly, a multi-scale Projection based Point Cloud quality Metric (PPCM) is proposed to measure the perceptual quality of 3D point cloud. The PPCM model comprises 3D-to-2D patch projection, multi-scale structural distortion measurement, and fusion model. Approximations and simplifications of the proposed PPCM are also presented for both V-PCC integration and low complexity. Thirdly, based on the simplified PPCM model, we propose a PWRDO scheme with Lagrange multiplier adaptation, which is incorporated into the V-PCC to enhance the coding efficiency. Experimental results show that the proposed PPCM models can be used as standalone quality metrics, and they are able to achieve higher consistency with the human subjective scores than the state-of-the-art objective visual quality metrics. Also, compared with the latest V-PCC reference model, the proposed PWRDO-based V-PCC scheme achieves an average bit rate reduction of 13.52%, 8.16%, 10.56% and 9.54%, respectively, in terms of four objective visual quality metrics for point clouds. It is significantly superior to the state-of-the-art coding algorithms. The computational complexity of the proposed PWRDO increases by 1.71% and 0.05% on average to the V-PCC encoder and decoder, respectively, which is negligible. The source codes of the PPCM and PWRDO schemes are available at https://github.com/VVCodec/PPCM-PWRDO.

15.
J Exp Clin Cancer Res ; 42(1): 275, 2023 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-37865804

RESUMEN

BACKGROUND: Alterations in several tripartite motif-containing (TRIM) family proteins have been implicated in the pathogenesis of lung cancer. TRIM28, a member of the TRIM E3 ligase family, has been associated with tumorigenesis, cell proliferation, and inflammation. However, little is known about TRIM28 expression and its role in the immune microenvironment of non-small cell lung cancer (NSCLC). METHODS: We assessed the clinical significance of TRIM28 in tissue microarrays and TCGA cohorts. We investigated the function of TRIM28 in syngeneic mouse tumor models, the KrasLSL-G12D/+; Tp53fl/fl (KP) mouse model, and humanized mice. Immune cell composition was analyzed using flow cytometry and immunohistochemistry. RESULTS: Our findings revealed a positive correlation between TRIM28 expression and the infiltration of suppressive myeloid-derived suppressor cells (MDSCs) in NSCLC. Moreover, silencing TRIM28 enhanced the efficacy of anti-PD-1 immunotherapy by reshaping the inflamed tumor microenvironment. Mechanistically, we demonstrated that TRIM28 could physically interact with receptor-interacting protein kinase 1 (RIPK1) and promote K63-linked ubiquitination of RIPK1, which is crucial for sustaining activation of the NF-κB pathway. Mutagenesis of the E3 ligase domain corroborated the essential role of E3 ligase activity in TRIM28-mediated NF-κB activation. Further experiments revealed that TRIM28 could upregulate the expression of CXCL1 by activating NF-κB signaling. CXCL1 could bind to CXCR2 on MDSCs and promote their migration to the tumor microenvironment. TRIM28 knockdown increased responsiveness to anti-PD-1 therapy in immunocompetent mice, characterized by increased CD8+T tumor-infiltrating lymphocytes and decreased MDSCs. CONCLUSION: The present study identified TRIM28 as a promoter of chemokine-driven recruitment of MDSCs through RIPK1-mediated NF-κB activation, leading to the suppression of infiltrating activated CD8+T cells and the development of anti-PD-1 resistance. Understanding the regulation of MDSC recruitment and function by TRIM28 provides crucial insights into the association between TRIM28 signaling and the development of an immunosuppressive tumor microenvironment. These insights may inform the development of combination therapies to enhance the effectiveness of immune checkpoint blockade therapy in NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Células Supresoras de Origen Mieloide , Humanos , Ratones , Animales , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , FN-kappa B/metabolismo , Modelos Animales de Enfermedad , Microambiente Tumoral , Proteína 28 que Contiene Motivos Tripartito/genética , Proteína 28 que Contiene Motivos Tripartito/metabolismo
16.
Membranes (Basel) ; 13(4)2023 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-37103871

RESUMEN

Two-dimensional (2D) nanomaterials, due to their high aspect ratio and high specific surface area, which provide a more tortuous pathway for larger gas molecules, are frequently used in membrane separation. However, in mixed-matrix membranes (MMMs), the high aspect ratio and high specific surface area of 2D fillers can increase transport resistance, thereby reducing the permeability of gas molecules. In this work, we combine boron nitride nanosheets (BNNS) with ZIF-8 nanoparticles to develop a novel material, ZIF-8@BNNS, to improve both CO2 permeability and CO2/N2 selectivity. Growth of ZIF-8 nanoparticles on the BNNS surface is achieved using an in-situ growth method where the amino groups of BNNS are complexed with Zn2+, creating gas transmission pathways that accelerate CO2 transmission. The 2D-BNNS material acts as a barrier in MMMs to improve CO2/N2 selectivity. The MMMs with a 20 wt.% ZIF-8@BNNS loading achieved a CO2 permeability of 106.5 Barrer and CO2/N2 selectivity of 83.2, surpassing the Robeson upper bound (2008) and demonstrating that MOF layers can efficiently reduce mass transfer resistance and enhance gas separation performance.

17.
Membranes (Basel) ; 13(9)2023 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-37755203

RESUMEN

Mixed matrix membranes (MMMs) generally have some fatal defects, such as poor compatibility between the two phases leading to non-selective pores. In this work, PIM-1 was chosen as the polymer matrix, and UiO-66 modified with amidoxime (UiO-66-AO) was used as the filler to prepare the MMMs. In the MMMs, the amino and hydroxyl groups on UO-66-AO form a rich hydrogen bond network with the N and O atoms in the polymer PIM-1 chain to improve the compatibility between the polymer matrix and the filler. In addition, the selective adsorption of CO2 by the amidoxime group can promote the transport of CO2 in the membrane, which enhances the gas selectivity. The CO2 permeability and CO2/N2 selectivity of UiO-66-AO@PIM-1 MMMs are increased by 35.2% and 45.2% compared to pure PIM-1 membranes, reaching 7535.5 Barrer and 26.9, surpassing the Robeson Upper Bound (2008) and close to the 2019 Upper Bound. After 38 days of the aging experiment, the CO2 permeability is approximately 74% of the original. The results show that the addition of UiO-66-AO has an obvious effect on improving the aging properties of the membrane. The UiO-66-AO@PIM-1 MMMs have a bright prospect for CO2 separation in the future.

18.
Food Chem Toxicol ; 165: 113061, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35489465

RESUMEN

The mycotoxin zearalenone (ZEA) in food and feed seriously harms human and animal health. How to reduce its toxicity is an important direction of current research on food safety. This study aim to assess the effects of procyanidins (PC) on cell apoptosis caused by ZEA and to clarify the role of Nrf2 in the process. Swine testicle (ST) cells were treated with ZEA (57.5 µmol/L) and/or PC (10 mg/L) for 24 h. Cell viability was detected by CCK-8 assay. Cell apoptosis and the level of ROS were detected by flow cytometry. The expression levels of mRNA and protein was detected by qRT-PCR and western blotting. Our results showed that ZEA reduced the antioxidant capacity of the ST cells, induced the cell apoptosis and inhibited the gene and protein expression of Nrf2 and its downstream genes (ho-1,nqo1), while PC improved the cell antioxidant capacity, reduced the degree of ZEA-induced cell apoptosis and promoted the gene and protein expression of Nrf2 and its downstream genes. However, when the Nrf2 small molecule inhibitor ML385 was added, the ability of PC to inhibit ZEA-induced cell apoptosis and promote the expression of Nrf2 and its downstream genes were decreased. Our results demonstrated that ZEA induced oxidative stress and apoptosis of ST cells, which were alleviated by PC intervention via activating Nrf2 signaling pathway. This finding of this study provided a molecular basis for the clinical application of PC to prevent ZEN-caused reproductive toxicity.


Asunto(s)
Proantocianidinas , Zearalenona , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Apoptosis , Masculino , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Proantocianidinas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Porcinos , Testículo/metabolismo , Zearalenona/metabolismo
19.
Materials (Basel) ; 15(18)2022 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-36143653

RESUMEN

Wholly aromatic polyimide (PI) films with good solution processability, light colors, good optical transparency, high storage modulus, and improved heat resistance were prepared and characterized. For this purpose, a multi-component copolymerization methodology was performed from a fluoro-containing dianhydride, 4,4'-(hexafluoroisopropylidene)diphthalic anhydride (6FDA), a rigid dianhydride, 3,3',4,4'-biphenyltetracarboxylic dianhydride (BPDA), and a fluoro-containing diamine, 2,2'-bis(trifluoromethyl)-4,4'-bis [4-(4-amino-3-methyl)benzamide]biphenyl (MABTFMB). One homopolymer, FPI-1 (6FDA-MABTFMB), and five copolymers, FPI-2~FPI-6, containing the BPDA units from 10 mol% to 50 mol% in the dianhydride moieties, were prepared, respectively. The derived PI resins showed good solubility in the polar aprotic solvents, such as N-methyl-2-pyrrolidone (NMP) and N,N-dimethylacetamide (DMAc). The flexible PI films obtained by the solution casting procedure showed good optical properties with the transmittances higher than 74.0% at the wavelength of 450 nm. The PI films exhibited excellent thermal properties, including 5% weight loss temperatures (T5%) over 510 °C, together with glass transition temperatures (Tg) over 350.0 °C according to the peak temperatures of the loss modulus in dynamical mechanical analysis (DMA) measurements. The FPI-6 film also showed the lowest linear coefficient of thermal expansion (CTE) value of 23.4 × 10-6/K from 50 to 250 °C according to the thermomechanical analysis (TMA) measurements, which was obviously lower than that of FPI-1 (CTE = 30.6 × 10-6/K).

20.
Environ Sci Pollut Res Int ; 28(47): 67779-67787, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34264493

RESUMEN

Zearalenone (ZEA) is a mycotoxin with estrogenic activity whose main effect is to impair the reproductive systems of animals. It leads to reproductive disorders in livestock and thus causes serious losses to agriculture and animal husbandry. This study aims to examine whether ZEA induces toxicity in Leydig cells through the PI3K/AKT signaling pathway and also to investigate the role played by the upstream phosphatase and tensin homolog (PTEN) gene. An adenovirus vector model was constructed to interfere with the PTEN gene to investigate whether ZEA promotes the apoptosis of TM3 cells through the PI3K/AKT pathway. Apoptosis was detected cytometrically and the protein expression levels of PTEN, AKT, p-AKT, Bax, and Bcl-2 were evaluated via western blot analysis. The results show that ZEA induces apoptosis of TM3 cells. PTEN expression is significantly increased (P < 0.01), Bax expression is increased (P < 0.05), AKT and p-AKT expression of anti-apoptotic protein is significantly decreased (P < 0.01), and Bcl-2 protein expression is decreased (P < 0.05) in the ZEA group compared with the control group. In the shRNA+ZEA group, the expression levels of PTEN and Bax proteins are significantly decreased (P < 0.01), AKT protein is significantly increased (P < 0.01), and p-AKT protein is increased (P < 0.05) compared with the ZEA group. This study thus demonstrates that ZEA promotes apoptosis of TM3 cells by targeting PTEN and thus inhibiting the PI3K/AKT signal pathway.


Asunto(s)
Proteínas Proto-Oncogénicas c-akt , Zearalenona , Animales , Apoptosis , Células Intersticiales del Testículo/metabolismo , Masculino , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Tensinas , Zearalenona/toxicidad
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