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1.
BMC Genomics ; 25(1): 413, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671348

RESUMEN

BACKGROUND: Disulfidptosis is a novel form of programmed cell death induced by high SLC7A11 expression under glucose starvation conditions, unlike other known forms of cell death. However, the roles of disulfidptosis in cancers have yet to be comprehensively well-studied, particularly in ccRCC. METHODS: The expression profiles and somatic mutation of DGs from the TCGA database were investigated. Two DGs clusters were identified by unsupervised consensus clustering analysis, and a disulfidptosis-related prognostic signature (DR score) was constructed. Furthermore, the predictive capacity of the DR score in prognosis was validated by several clinical cohorts. We also developed a nomogram based on the DR score and clinical features. Then, we investigated the differences in the clinicopathological information, TMB, tumor immune landscapes, and biological characteristics between the high- and low-risk groups. We evaluated whether the DR score is a robust tool for predicting immunotherapy response by the TIDE algorithm, immune checkpoint genes, submap analysis, and CheckMate immunotherapy cohort. RESULTS: We identified two DGs clusters with significant differences in prognosis, tumor immune landscapes, and clinical features. The DR score has been demonstrated as an independent risk factor by several clinical cohorts. The high-risk group patients had a more complicated tumor immune microenvironment and suffered from more tumor immune evasion in immunotherapy. Moreover, patients in the low-risk group had better prognosis and response to immunotherapy, particularly in anti-PD1 and anti-CTLA-4 inhibitors, which were verified in the CheckMate immunotherapy cohort. CONCLUSION: The DR score can accurately predict the prognosis and immunotherapy response and assist clinicians in providing a personalized treatment regime for ccRCC patients.


Asunto(s)
Carcinoma de Células Renales , Inmunoterapia , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/terapia , Pronóstico , Neoplasias Renales/genética , Neoplasias Renales/inmunología , Neoplasias Renales/terapia , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Biomarcadores de Tumor/genética , Nomogramas , Regulación Neoplásica de la Expresión Génica , Perfilación de la Expresión Génica , Mutación , Apoptosis
2.
Biol Proced Online ; 26(1): 21, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38969982

RESUMEN

BACKGROUND: The role of tumor inflammatory microenvironment in the advancement of cancer, particularly prostate cancer, is widely acknowledged. ELL-associated factor 2 (EAF2), a tumor suppressor that has been identified in the prostate, is often downregulated in prostate cancer. Earlier investigations have shown that mice with EAF2 gene knockout exhibited a substantial infiltration of inflammatory cells into the prostatic stroma. METHODS: A cohort comprising 38 patients who had been diagnosed with prostate cancer and subsequently undergone radical prostatectomy (RP) was selected. These patients were pathologically graded according to the Gleason scoring system and divided into two groups. The purpose of this selection was to investigate the potential correlation between EAF2 and CD163 using immunohistochemistry (IHC) staining. Additionally, in vitro experimentation was conducted to verify the relationship between EAF2 expression, macrophage migration and polarization. RESULTS: Our study demonstrated that in specimens of human prostate cancer, the expression of EAF2 was notably downregulated, and this decrease was inversely associated with the number of CD163-positive macrophages that infiltrated the cancerous tissue. Cell co-culture experiments revealed that the chemotactic effect of tumor cells towards macrophages was intensified and that macrophages differentiated into tumor-associated macrophages (TAMs) when EAF2 was knocked out. Additionally, the application of cytokine protein microarray showed that the expression of chemokine macrophage migration inhibitory factor (MIF) increased after EAF2 knockout. CONCLUSIONS: Our findings suggested that EAF2 was involved in the infiltration of CD163-positive macrophages in prostate cancer via MIF.

3.
Lab Invest ; 103(12): 100263, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37839637

RESUMEN

In this study, we aimed to explore immune markers predicting locoregional recurrence/distant metastasis (R/M) for patients with esophageal squamous cell carcinoma (ESCC) post-surgical intervention by using a novel high-throughput spatial tool to quantify multiple immune proteins expressed in ESCC and lymphocytes in tumor microenvironment (TME-L). First, formalin-fixed paraffin-embedded tissues from surgical patients with ESCC (n = 94) were constructed on a microarray, which was then divided into discovery (n = 36) and validation cohorts (n = 58). Using a newly developed GeoMx digital spatial profiling tool, 31 immune proteins in paired ESCC and TME-L, morphologically segmented by PANCK and CD45, respectively, from the discovery cohort were quantified, releasing 2,232 variables. Next, the correlation matrix was analyzed using the Corrplot package in R Studio, resulting in 6 closely correlated clusters. The Least Absolute Shrinkage and Selection Operator regression scoring model predictive of R/M risk with superior specificity was successfully established based on the 3 following hierarchically clustered immune proteins: ARG1 in ESCC/PANCK+, STING, and IDO1 in TME-L/CD45+. Moreover, the expression of IDO1 in TME-L, rather than in ESCC, significantly predicted the R/M risk score with an area under curve of 0.9598. In addition, its correlation with R/M status was further validated by dual immunohistochemistry staining of IDO1 and CD45 in discovery and validation cohorts. Above all, our findings not only provide a more accurate scoring approach based on quantitative immune proteins for the prediction of R/M risk, but also propose that IDO1 in TME-L potentially plays a driving role in mediating R/M in ESCC.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Biomarcadores de Tumor , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Pronóstico , Microambiente Tumoral
4.
Cancer Cell Int ; 23(1): 85, 2023 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-37158958

RESUMEN

BACKGROUND: As a novel type of the prevalent post-transcriptional modifications, N7-methylguanosine (m7G) modification is essential in the tumorigenesis, progression, and invasion of many cancers, including bladder cancer (BCa). However, the integrated roles of m7G-related lncRNAs in BCa remain undiscovered. This study aims to develop a prognostic model based on the m7G-related lncRNAs and explore its predictive value of the prognosis and anti-cancer treatment sensitivity. METHODS: We obtained RNA-seq data and corresponding clinicopathological information from the TCGA database and collected m7G-related genes from previous studies and GSEA. Based on LASSO and Cox regression analysis, we developed a m7G prognostic model. The Kaplan-Meier (K-M) survival analysis and ROC curves were performed to evaluate the predictive power of the model. Gene set enrichment analysis (GSEA) was conducted to explore the molecular mechanisms behind apparent discrepancies between the low- and high-risk groups. We also investigated immune cell infiltration, TIDE score, TMB, the sensitivity of common chemotherapy drugs, and the response to immunotherapy between the two risk groups. Finally, we validated the expression levels of these ten m7G-related lncRNAs in BCa cell lines by qRT-PCR. RESULTS: We developed a m7G prognostic model (risk score) composed of 10 m7G-related lncRNAs that are significantly associated with the OS of BCa patients. The K-M survival curves revealed that the high-risk group patients had significantly worse OS than those in the low-risk group. The Cox regression analysis confirmed that the risk score was a significant independent prognostic factor for BCa patients. We found that the high-risk group had higher the immune scores and immune cell infiltration. Furthermore, the results of the sensitivity of common anti-BCa drugs showed that the high-risk group was more sensitive to neoadjuvant cisplatin-based chemotherapy and anti-PD1 immunotherapy. Finally, qRT-PCR revealed that AC006058.1, AC073133.2, LINC00677, and LINC01338 were significantly downregulated in BCa cell lines, while the expression levels of AC124312.2 and AL158209.1 were significantly upregulated in BCa cell lines compared with normal cell lines. CONCLUSION: The m7G prognostic model can be applied to accurately predict the prognosis and provide robust directions for clinicians to develop better individual-based and precise treatment strategies for BCa patients.

5.
Proc Natl Acad Sci U S A ; 117(35): 21052-21057, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32817562

RESUMEN

Anchoring nanoscale building blocks, regardless of their shape, into specific arrangements on surfaces presents a significant challenge for the fabrication of next-generation chip-based nanophotonic devices. Current methods to prepare nanocrystal arrays lack the precision, generalizability, and postsynthetic robustness required for the fabrication of device-quality, nanocrystal-based metamaterials [Q. Y. Lin et al. Nano Lett. 15, 4699-4703 (2015); V. Flauraud et al., Nat. Nanotechnol. 12, 73-80 (2017)]. To address this challenge, we have developed a synthetic strategy to precisely arrange any anisotropic colloidal nanoparticle onto a substrate using a shallow-template-assisted, DNA-mediated assembly approach. We show that anisotropic nanoparticles of virtually any shape can be anchored onto surfaces in any desired arrangement, with precise positional and orientational control. Importantly, the technique allows nanoparticles to be patterned over a large surface area, with interparticle distances as small as 4 nm, providing the opportunity to exploit light-matter interactions in an unprecedented manner. As a proof-of-concept, we have synthesized a nanocrystal-based, dynamically tunable metasurface (an anomalous reflector), demonstrating the potential of this nanoparticle-based metamaterial synthesis platform.


Asunto(s)
Coloides/química , Cristalización/métodos , Nanopartículas del Metal/química , Anisotropía , ADN/química , Oro/química , Tamaño de la Partícula , Propiedades de Superficie
6.
Nano Lett ; 18(4): 2645-2649, 2018 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-29570302

RESUMEN

Multiplexed surface encoding is achieved by positioning two different sizes of gold nanocubes on gold surfaces with precisely defined locations for each particle via template-confined, DNA-mediated nanoparticle assembly. As a proof-of-concept demonstration, cubes with 86 and 63 nm edge lengths are assembled into arrangements that physically and spectrally encrypt two sets of patterns in the same location. These patterns can be decrypted by mapping the absorption intensity of the substrate at λ = 773 and 687 nm, respectively. This multiplexed encoding platform dramatically increases the sophistication and density of codes that can be written using colloidal nanoparticles, which may enable high-security, high-resolution encoding applications.


Asunto(s)
ADN/química , Oro/química , Nanopartículas/química , Nanotecnología/métodos , Nanopartículas/ultraestructura , Tamaño de la Partícula , Propiedades de Superficie
7.
Small ; 14(44): e1802742, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30251440

RESUMEN

Template-based strategies are becoming increasingly important for controlling the position of nanoparticle-based (NP-based) structures on surfaces for a wide variety of encoding and device fabrication strategies. Thus, there is an increasing need to understand the behavior of NPs in confined spaces. Herein, a systematic investigation of the diffusion and adsorption properties of DNA-modified NPs is presented in lithographically defined, high-aspect-ratio pores using a template-confined, DNA-mediated assembly. Leveraging the sequence-specific binding affinity of DNA, it is discovered that although NP adsorption in deep polymer pores follows a traditional Langmuir adsorption model when under thermodynamic control, such NPs kinetically follow Fick's classical law of diffusion. Importantly, these observations allow one to establish design rules for template-confined, DNA-mediated NP assembly on substrates based on pore dimensions, NP size and shape, NP concentration, temperature, and time. As a proof-of-concept example, these design rules are used to engineer a vertical, four-layer assembly consisting of individual octahedral NPs stacked on top of one another, with in-plane positioning defined by pores generated by e-beam lithography.


Asunto(s)
Oro/química , Nanopartículas del Metal/química , Adsorción , Cinética , Polímeros/química , Termodinámica
8.
Anal Bioanal Chem ; 410(28): 7489-7498, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30232524

RESUMEN

A high serum HER-2 extracellular domain (sHER-2 ECD) level has a reverse association with tumor behaviors. In this study, a portable platform for the disease biomarker sHER-2 ECD detection has been established using a pressure-based bioassay. The pressure bioassay consists of a monoclonal antibody immobilized on an eight-well strip, the analyte HER-2, and another monoclonal antibody labeled with the Pt nanoparticles (PtNPs), which have the catalytic ability to decompose H2O2 into H2O and O2(g). The increased pressure due to O2(g) generation is measured by a hand-held pressure meter. A total of 34 serum samples were collected to validate the performance of the pressure bioassay. The results showed that the pressure bioassay platform of HER-2 had a dynamic range from 2 to 50 ng/mL with a limit of detection (LOD) of 2 ng/mL, which was consistent with the ELISA result. In the real serum samples, there was a significant correlation between sHER-2 ECD level and several clinicopathological parameters, especially tissue HER-2 status. Furthermore, the sHER-2 ECD level was found to decrease after targeted therapy in a patient with tHER-2 positive. Overall, this bioassay can facilitate breast cancer diagnosis and prognosis in clinical scenarios and resource-limited areas.


Asunto(s)
Neoplasias de la Mama/sangre , Receptor ErbB-2/sangre , Anticuerpos Monoclonales , Bioensayo/métodos , Biomarcadores de Tumor/sangre , Femenino , Humanos , Presión , Receptor ErbB-2/química
9.
J Am Chem Soc ; 138(28): 8722-5, 2016 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-27402303

RESUMEN

DNA surface ligands can be used as programmable "bonds" to control the arrangement of nanoparticles into crystalline superlattices. Here, we study the intrinsic responsiveness of these DNA bonds to changes in local dielectric constant (εr) as a new approach to dynamically modulate superlattice structure. Remarkably, ethanol (EtOH) addition can be used to controllably tune DNA bond length from 16 to 3 nm and to increase bond stability by >40 °C, while retaining long-range order and crystal habit. Interestingly, we find that these structural changes, which involve the expansion and contraction of crystals by up to 75% in volume, occur in a cooperative fashion once a critical percentage of EtOH is reached. These results provide a facile and robust approach to create stimuli-responsive lattices, to access high volume fractions, and to improve thermal stability.

10.
Nano Lett ; 15(7): 4699-703, 2015 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-26046948

RESUMEN

Control of both photonic and plasmonic coupling in a single optical device represents a challenge due to the distinct length scales that must be manipulated. Here, we show that optical metasurfaces with such control can be constructed using an approach that combines top-down and bottom-up processes, wherein gold nanocubes are assembled into ordered arrays via DNA hybridization events onto a gold film decorated with DNA-binding regions defined using electron beam lithography. This approach enables one to systematically tune three critical architectural parameters: (1) anisotropic metal nanoparticle shape and size, (2) the distance between nanoparticles and a metal surface, and (3) the symmetry and spacing of particles. Importantly, these parameters allow for the independent control of two distinct optical modes, a gap mode between the particle and the surface and a lattice mode that originates from cooperative scattering of many particles in an array. Through reflectivity spectroscopy and finite-difference time-domain simulation, we find that these modes can be brought into resonance and coupled strongly. The high degree of synthetic control enables the systematic study of this coupling with respect to geometry, lattice symmetry, and particle shape, which together serve as a compelling example of how nanoparticle-based optics can be useful to realize advanced nanophotonic structures that hold implications for sensing, quantum plasmonics, and tunable absorbers.


Asunto(s)
ADN/química , Oro/química , Nanopartículas del Metal/química , Dispositivos Ópticos , Diseño de Equipo , Nanopartículas del Metal/ultraestructura , Nanotecnología , Hibridación de Ácido Nucleico , Óptica y Fotónica/instrumentación , Fotones
11.
J Am Chem Soc ; 137(28): 9167-73, 2015 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-26144242

RESUMEN

Alloy nanoparticles are important in many fields, including catalysis, plasmonics, and electronics, due to the chemical and physical properties that arise from the interactions between their components. Typically, alloy nanoparticles are made by solution-based synthesis; however, scanning-probe-based methods offer the ability to make and position such structures on surfaces with nanometer-scale resolution. In particular, scanning probe block copolymer lithography (SPBCL), which combines elements of block copolymer lithography with scanning probe techniques, allows one to synthesize nanoparticles with control over particle diameter in the 2-50 nm range. Thus far, single-element structures have been studied in detail, but, in principle, one could make a wide variety of multicomponent systems by controlling the composition of the polymer ink, polymer feature size, and metal precursor concentrations. Indeed, it is possible to use this approach to synthesize alloy nanoparticles comprised of combinations of Au, Ag, Pd, Ni, Co, and Pt. Here, such structures have been made with diameters deliberately tailored in the 10-20 nm range and characterized by STEM and EDS for structural and elemental composition. The catalytic activity of one class of AuPd alloy nanoparticles made via this method was evaluated with respect to the reduction of 4-nitrophenol with NaBH4. In addition to being the first catalytic studies of particles made by SPBCL, these proof-of-concept experiments demonstrate the potential for SPBCL as a new method for studying the fundamental science and potential applications of alloy nanoparticles in areas such as heterogeneous catalysis.


Asunto(s)
Aleaciones/química , Nanopartículas del Metal/química , Metales/química , Nanotecnología/métodos , Catálisis , Cobalto/química , Oro/química , Nanopartículas del Metal/ultraestructura , Níquel/química , Nitrofenoles/química , Oxidación-Reducción , Paladio/química , Platino (Metal)/química , Polímeros/química , Plata/química
12.
Small ; 11(8): 913-8, 2015 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-25315252

RESUMEN

A novel, apertureless, cantilever-free pen array can be used for dual scanning photochemical and molecular printing. Serial writing with light is enabled by combining self-focusing pyramidal pens with an opaque backing between pens. The elastomeric pens also afford force-tuned illumination and simultaneous delivery of materials and optical energy. These attributes make the technique a promising candidate for maskless high-resolution photopatterning and combinatorial chemistry.


Asunto(s)
Nanotecnología/métodos , Polímeros/química , Impresión/métodos , Técnicas Químicas Combinatorias , Diseño de Equipo , Tinta , Luz , Nanopartículas del Metal/química , Microscopía Fluorescente , Nanotecnología/instrumentación , Óptica y Fotónica , Tamaño de la Partícula , Impresión/instrumentación , Propiedades de Superficie , Rayos Ultravioleta
13.
Lipids Health Dis ; 14: 76, 2015 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-26199022

RESUMEN

BACKGROUND: Metabolic syndrome (MetS) is an important risk factor for cerebral ischemic stroke, yet previous studies on the relationship between MetS or its components and acute cerebral infarction have been inconsistent. This study aims to evaluate the effects of MetS and its components on the short-term prognosis of patients with acute ischemic stroke. METHODS: Subjects with ischemic stroke of <7-day duration (530 cases) were enrolled. MetS was defined based on the modified criteria of the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. Demographic data, vascular risk factors, National Institutes of Health Stroke Scale score, the results of physical, laboratory and imaging examinations and clinical outcomes at 30 and 90 days were recorded. Using univariate analysis, we compared different baseline characteristics between patients with MetS and those without MetS. Further, we assessed MetS and its 5 components on the contribution to short-term prognosis of ischemic stroke with multiple logistic regression models after adjusting for age and sex. RESULTS: The prevalence of MetS among the patients with acute ischemic stroke in the study is 58.3%, with more in females (70.3%) than in males (49.7%, p < 0.001). As expected, among the MetS components, elevated waist circumference, elevated triglyceride, high fasting blood glucose and low high density lipoprotein cholesterol (HDL-C) were significantly more prevalent in patients with MetS than those without MetS (all p < 0.001). There was no correlation between MetS itself and the short-term prognosis of acute ischemic stroke. Only hyperglycemia in the serum was shown to have impact on poor functional outcomes in 30 and 90 days after the onset of stroke. CONCLUSIONS: The occurrence of MetS among patients with acute ischemic stroke in our study is 58.3%. MetS itself may not be predictive for the short-term prognosis of patients, while hyperglycemia is a significant predictor for poor functional outcomes in our study.


Asunto(s)
Isquemia Encefálica/complicaciones , Hospitales , Síndrome Metabólico/complicaciones , Accidente Cerebrovascular/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento
14.
Int J Mol Sci ; 16(9): 21897-910, 2015 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-26378521

RESUMEN

The general control of nucleotide synthesis 5 (GCN5), which is one kind of lysine acetyltransferases, regulates a number of cellular processes, such as cell proliferation, differentiation, cell cycle and DNA damage repair. However, its biological role in human glioma development remains elusive. In the present study, we firstly reported that GCN5 was frequently overexpressed in human glioma tissues and GCN5 was positively correlated with proliferation of cell nuclear antigen PCNA and matrix metallopeptidase MMP9. Meanwhile, down-regulation of GCN5 by siRNA interfering inhibited glioma cell proliferation and invasion. In addition, GCN5 knockdown reduced expression of p-STAT3, p-AKT, PCNA and MMP9 and increased the expression of p21 in glioma cells. In conclusion, GCN5 exhibited critical roles in glioma development by regulating cell proliferation and invasion, which suggested that GCN5 might be a potential molecular target for glioma treatment.


Asunto(s)
Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Factores de Transcripción p300-CBP/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Expresión Génica , Técnicas de Silenciamiento del Gen , Silenciador del Gen , Glioma/genética , Glioma/patología , Humanos , Inmunohistoquímica , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Antígeno Nuclear de Célula en Proliferación/genética , Antígeno Nuclear de Célula en Proliferación/metabolismo , Factores de Transcripción p300-CBP/genética
15.
Oncol Lett ; 28(1): 320, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38807668

RESUMEN

Gliomas are highly malignant and invasive tumors lacking clear boundaries. Previous bioinformatics and experimental analyses have indicated that F-box and leucine-rich repeat protein 6 (FBXL6), a protein crucial for the cell cycle and tumorigenesis, is highly expressed in certain types of tumors. The high expression level of FBXL6 is reported to promote tumor growth and adversely affect patient survival. However, the molecular mechanism, prognostic value and drug sensitivity of FBXL6 in glioma remain unclear. To address this, the present study analyzed FBXL6 expression in gliomas, utilizing data from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. Analysis of FBXL6 mRNA expression levels, combined with patient factors such as age, sex and tumor grade using Kaplan-Meier plots and nomograms, demonstrated a strong correlation between FBXL6 expression and glioma progression. Co-expression networks provided further insights into the biological function of FBXL6. Additionally, using CIBERSORT and TISDB tools, the correlation between FBXL6 expression correlation tumor-infiltrating immune cells and immune genes was demonstrated to be statistically significant. These findings were validated by examining FBXL6 mRNA and protein levels in glioma tissues using various techniques, including western blot, reverse transcription-quantitative PCR and immunohistochemistry. These assays demonstrated the role of FBXL6 in glioma progression. Furthermore, drug sensitivity analysis demonstrated a strong correlation between FBXL6 expression and various drugs, which indicated that FBXL6 may potentially act as a future promising therapeutic target in glioma treatment. Therefore, the present study identified FBXL6 as a diagnostic and prognostic marker in patients with gliomas and highlighted its potential role in glioma progression.

16.
Adv Sci (Weinh) ; 11(20): e2308131, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38498770

RESUMEN

To evade immune surveillance, tumor cells express ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) on the surface of their membrane, which degrades extracellular cyclic GMP-AMP (cGAMP), thereby inhibiting the cyclic GMP-AMP synthase (cGAS) stimulator of interferon gene (STING) DNA-sensing pathway. To fully understand this tumor stealth mechanism, it is essential to determine whether other forms of ENPP1 with hydrolytic cGAMP activity also are present in the tumor microenvironment to regulate this innate immune pathway. Herein, it is reported that various tumor-derived exosomes carry ENPP1, and can hydrolyze synthetic 2'3'-cGAMP and endogenous 2'3'-cGAMP produced by cells to inhibit cGAS-STING pathway in immune cells. Moreover, tumor exosomal ENPP1 also can hydrolyze 2'3'-cGAMP bound to LL-37 (an effective transporter of 2'3'-cGAMP) to inhibit STING signaling. Furthermore, high expression of ENPP1 in exosomes is observed isolated from human breast and lung cancer tissue, and tumor exosomal ENPP1 inhibited the immune infiltration of CD8+ T cells and CD4+ T cells. The results elucidate the essential function of tumor exosomal ENPP1 in the cGAS-STING pathway, furthering understanding of the crosstalk between the tumor cells and immune system.


Asunto(s)
Exosomas , Proteínas de la Membrana , Nucleótidos Cíclicos , Nucleotidiltransferasas , Hidrolasas Diéster Fosfóricas , Pirofosfatasas , Transducción de Señal , Nucleótidos Cíclicos/metabolismo , Pirofosfatasas/metabolismo , Pirofosfatasas/genética , Transducción de Señal/genética , Hidrolasas Diéster Fosfóricas/metabolismo , Hidrolasas Diéster Fosfóricas/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Humanos , Nucleotidiltransferasas/metabolismo , Nucleotidiltransferasas/genética , Exosomas/metabolismo , Exosomas/genética , Ratones , Animales , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/inmunología , Línea Celular Tumoral , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética
17.
J Clin Immunol ; 33(2): 378-87, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23100145

RESUMEN

OBJECTIVE: The purpose of this study is to examine autoantibody profile of systemic lupus erythematosus (SLE) patients with lupus nephritis (LN) and to establish the correlation between the antibody reactivity and disease activity of LN. METHODS: Autoantibodies and serological parameters were measured and analyzed in 589 SLE patients. The associations of the co-positivity of anti-dsDNA, -nucleosome and -histone antibodies (3-pos) with clinical, serological and outcome parameters were analyzed. RESULTS: At the study entry, the prevalence for anti-dsDNA (61.52 % vs. 34.11 %, P < 0.0001), anti-nucleosome (56.09 % vs. 37.21 %, P = 0.0002) and anti-histone (49.35 % vs. 33.33 %, P = 0.0013) antibodies in patients with LN were significantly higher than that in patients without LN. Patients with 3-pos had a higher proportion of proliferative renal lesions (class III + IV). The incidence of a poor renal outcome (7.14 % vs. 2.52 %, P = 0.0174) in LN patients with 3-pos was significantly higher than those without 3-pos. Moreover, the rate of remission (73.63 % vs. 82.37 %, P = 0.0245) was significantly reduced and recurrence increased (58.90 % vs. 23.44 %, P < 0.0001) in 3-pos patients as compared to that in non 3-pos within the LN group. CONCLUSION: Our data indicate a strong association between the 3-pos and renal disease activities, especially proliferative glomerulonephritis. The ability of 3-pos to predict renal flares may lead to major additional benefits in the follow-up of these patients.


Asunto(s)
Anticuerpos Antinucleares/inmunología , Autoanticuerpos/inmunología , Histonas/inmunología , Nefritis Lúpica/inmunología , Nucleosomas/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antinucleares/sangre , Autoanticuerpos/sangre , Biomarcadores/sangre , Niño , Femenino , Glomerulonefritis Membranoproliferativa/inmunología , Glomerulonefritis Membranoproliferativa/patología , Humanos , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/epidemiología , Nefritis Lúpica/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estudios Seroepidemiológicos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto Joven
18.
Rheumatol Int ; 33(11): 2757-61, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23801380

RESUMEN

Several molecular epidemiological studies have been conducted in recent years to evaluate a possible association between the interferon regulatory factor 5 (IRF5) rs2004640 polymorphism and rheumatoid arthritis risk in diverse populations. However, the results remain conflicting rather than conclusive. Our aim was to assess associations of IRF5 gene polymorphisms with rheumatoid arthritis risk. Meta-analysis was performed on six published case-control studies (from eight countries) that included 4,818 cases of rheumatoid arthritis and 4,316 controls. The rs2004640-T allele was associated with a significantly increased risk of rheumatoid arthritis when the dominant genetic model was applied (T/T + T/G versus G/G: P = 0.003, OR = 1.14, 95% CI 1.05-1.25). Upon stratified analysis by ethnicity, the rs2004640 polymorphism was associated with an increased rheumatoid arthritis risk in Caucasians when the homozygotic contrast model was employed(T/T versus G/G: P = 0.03, OR = 1.25, 95% CI 1.02-1.53) and this was also the case when the dominant genetic model was used (T/T + T/G versus G/G: P = 0.04, OR = 1.20, 95% CI 1.01-1.42), whereas, in Asian populations, only the dominant genetic model was associated with an increased rheumatoid arthritis risk (T/T + T/G versus G/G: P = 0.02, OR = 1.14, 95% CI 1.02-1.26). The results suggest that the IRF5 rs2004640 polymorphism is associated with rheumatoid arthritis especially when the dominant genetic model is applied.


Asunto(s)
Artritis Reumatoide/genética , Predisposición Genética a la Enfermedad , Factores Reguladores del Interferón/genética , Polimorfismo de Nucleótido Simple , Alelos , Pueblo Asiatico/genética , Frecuencia de los Genes , Haplotipos , Humanos , Modelos Genéticos , Población Blanca/genética
19.
Front Mol Biosci ; 10: 1115091, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37091865

RESUMEN

Cuproptosis is a novel form of cell death linked to mitochondrial metabolism and is mediated by protein lipoylation. The mechanism of cuproptosis in many diseases, such as psoriasis, remains unclear. In this study, signature diagnostic markers of cuproptosis were screened by differential analysis between psoriatic and non-psoriatic patients. The differentially expressed cuproptosis-related genes (CRGs) for patients with psoriasis were screened using the GSE178197 dataset from the gene expression omnibus database. The biological roles of CRGs were identified by GO and KEGG enrichment analyses, and the candidates of cuproptosis-related regulators were selected from a nomogram model. The consensus clustering approach was used to classify psoriasis into clusters and the principal component analysis algorithms were constructed to calculate the cuproptosis score. Finally, latent diagnostic markers and drug sensitivity were analyzed using the pRRophetic R package. The differential analysis revealed that CRGs (MTF1, ATP7B, and SLC31A1) are significantly expressed in psoriatic patients. GO and KEGG enrichment analyses showed that the biological functions of CRGs were mainly related to acetyl-CoA metabolic processes, the mitochondrial matrix, and acyltransferase activity. Compared to the machine learning method used, the random forest model has higher accuracy in the occurrence of cuproptosis. However, the decision curve of the candidate cuproptosis regulators analysis showed that patients can benefit from the nomogram model. The consensus clustering analysis showed that psoriasis can be grouped into three patterns of cuproptosis (clusterA, clusterB, and clusterC) based on selected important regulators of cuproptosis. In advance, we analyzed the immune characteristics of patients and found that clusterA was associated with T cells, clusterB with neutrophil cells, and clusterC predominantly with B cells. Drug sensitivity analysis showed that three cuproptosis regulators (ATP7B, SLC31A1, and MTF1) were associated with the drug sensitivity. This study provides insight into the specific biological functions and related mechanisms of CRGs in the development of psoriasis and indicates that cuproptosis plays a non-negligible role. These results may help guide future treatment strategies for psoriasis.

20.
Mar Pollut Bull ; 186: 114347, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36436274

RESUMEN

In this study, polyaluminum sulfate (PAS) coagulant was selected to evaluate the coagulation performance of polystyrene microplastics. Overall, polystyrene removal efficiency was 90.4 % at the optimal dosage of 7.5 g/L of PAS. In addition to the type of coagulants (e.g. polyaluminum chloride, iron(III) chloride, and polyferric sulfate), surface characteristics such as densities, particle sizes, morphologies, adsorbed substances, and functional groups can also significantly impact the coagulation performance. The coagulation ratios are reduced to (2.6 ± 0.1)% when the densities of microplastics decrease. Aging treatments involving NaOH, H2SO4, NaClO, CH3OH, and O3 promoted coagulation, whereas UV and Na2S2O3 treatments inhibited (64.1 ± 9.7)% and (79.3 ± 8.0)% of polystyrene removals, respectively. In contrast, Fe(NO3)3 treatment did not affect the removal ratio. Further characterization of polystyrene before and after coagulation exemplified that the functional groups (CO, CO, and CH) and the rough surfaces of PAS provided adsorption and interception sites for hydrolysis products of the PAS.


Asunto(s)
Compuestos Férricos , Purificación del Agua , Microplásticos , Poliestirenos , Plásticos , Hierro , Sulfatos , Floculación
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