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Radio-immunotherapy driven by radiation-induced immunogenic cell death (ICD) is emerging as a potential opportunity to address conventional radiotherapy (RT) that is only applicable to localized tumor treatment. However, the effective activation of ICD during RT is severely limited by radiation dose, weak tumor immunogenicity, and radio-resistance caused by tumor microenvironment (TME). Herein, a novel bimetallic hybrid nanoscale coordination nanostimulator is first proposed by phosphate backbone doped with copper ions (Cu2+) and hafnium ions (Hf4+), and then modified with polyvinylpyrrolidone (PVP). The PVPylated Cu/Hf-doped phosphate nanostimulator (denoted as CHP) exhibits effective reprogramming of TME, including depletion of tumor endogenous glutathione (GSH), relief of tumor hypoxia and repolarization of M2 phenotypic macrophages, thus achieving tumor radiosensitization at low X-ray irradiation dose, gradually accumulation of tumor endogenous reactive oxygen species (ROS) and augmenting cuproptosis. In addition, cuproptosis can amplify RT-induced anti-tumor immunity through ICD activation, ultimately resulting in a robust anti-tumor immune response and long-term immunity, evidenced by distant tumor growth inhibition of 4T1-tumor-bearing models. More interestingly, it is discovered that CHP-mediated cuproptosis can be intensifiable during X-ray irradiation. Taken together, this work presents a novel radio-cuproptosis-immunotherapy cascade strategy, offering a new perspective for innovation in the treatment field of breast cancer.
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Manganese ions (Mn2+)-coordinated nanoparticles have emerged as a promising class of antitumor nanotherapeutics, capable of simultaneously disrupting the immunosuppressive tumor microenvironment (TME) and triggering the stimulator of interferon genes (STING) pathway-dependent antitumor immunity. However, the activation of STING signaling by Mn2+-based monotherapies is suboptimal for comprehensive stimulation of antigen presenting cells and reversal of immunosuppression in the TME. Here, we report the design of a Mn2+/CpG oligodeoxynucleotides (ODNs) codecorated black phosphorus nanosheet (BPNS@Mn2+/CpG) platform based on the Mn2+ modification of BPNS and subsequent adsorption of synthetic CpG ODNs. The coordination of Mn2+ significantly improved the stability of BPNS and the adsorption of CpG ODNs. The acidic TME and endosomal compartments can disrupt the Mn2+ coordination, triggering pH-responsive release of CpG ODNs and Mn2+ to effectively activate the Toll-like receptor 9 and STING pathways. As a result, M2-type macrophages and immature dendritic cells were strongly stimulated in the TME, thereby increasing T lymphocyte infiltration and reversing the immunosuppression within the TME. Phototherapy and chemodynamic therapy, utilizing the BPNS@Mn2+/CpG platform, have demonstrated efficacy in inducing immunogenic cell death upon 808 nm laser irradiation. Importantly, the treatment of BPNS@Mn2+/CpG with laser irradiation exhibited significant therapeutic efficacy against the irradiated primary tumor and effectively suppressed the growth of nonirradiated distant tumor. Moreover, it induced a robust immune memory, providing long-lasting protection against tumor recurrence. This study demonstrated the enhanced antitumor potency of BPNS@Mn2+/CpG in multimodal therapy, and its proof-of-concept application as a metal ion-modified BPNS material for effective DNA/drug delivery and immunotherapy.
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Nanopartículas , Neoplasias , Humanos , Oligodesoxirribonucleotídeos/farmacologia , Terapia Combinada , Imunoterapia , Neoplasias/tratamento farmacológico , Microambiente TumoralRESUMO
Background: Radiotherapy is a widely used clinical tool for tumor treatment but can cause systemic toxicity if excessive radiation is administered. Although numerous nanoparticles have been developed as radiosensitizers to reduce the required dose of X-ray irradiation, they often have limitations, such as passive reliance on radiation-induced apoptosis in tumors, and little consider the unique tumor microenvironment that contributes radiotherapy resistance. Methods: In this study, we developed and characterized a novel self-assembled nanoparticle containing dysprosium ion and manganese ion (Dy/Mn-P). We systematically investigated the potential of Dy/Mn-P nanoparticles (NPs) as a reactive oxygen species (ROS) amplifier and radiosensitizer to enhance radiation therapy and modulate the tumor microenvironment at the cellular level. Additionally, we evaluated the effect of Dy/Mn-P on the stimulator of interferon genes (STING), an innate immune signaling pathway. Results: Physicochemical analysis demonstrated the prepared Dy/Mn-P NPs exhibited excellent dispersibility and stability, and degraded rapidly at lower pH values. Furthermore, Dy/Mn-P was internalized by cells and exhibited selective toxicity towards tumor cells compared to normal cells. Our findings also revealed that Dy/Mn-P NPs improved the tumor microenvironment and significantly increased ROS generation under ionizing radiation, resulting in a ~70% increase in ROS levels compared to radiation therapy alone. This enhanced ROS generation inhibited ~92% of cell clone formation and greatly contributed to cytoplasmic DNA exposure. Subsequently, the activation of the STING pathway was observed, leading to the secretion of pro-inflammatory immune factors and maturation of dendritic cells (DCs). Conclusion: Our study demonstrates that Dy/Mn-P NPs can potentiate tumor radiotherapy by improving the tumor microenvironment and increasing endogenous ROS levels within the tumor. Furthermore, Dy/Mn-P can amplify the activation of the STING pathway during radiotherapy, thereby triggering an anti-tumor immune response. This novel approach has the potential to expand the application of radiotherapy in tumor treatment.
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Nanopartículas , Neoplasias , Radiossensibilizantes , Humanos , Espécies Reativas de Oxigênio/metabolismo , Microambiente Tumoral , Neoplasias/radioterapia , Neoplasias/tratamento farmacológico , Radiossensibilizantes/uso terapêutico , Nanopartículas/química , Concentração de Íons de HidrogênioRESUMO
[This retracts the article DOI: 10.7150/ijbs.46986.].
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Portable assays for the rapid identification of lineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to aid large-scale efforts in monitoring the evolution of the virus. Here we report a multiplexed assay in a microarray format for the detection, via isothermal amplification and plasmonic-gold-enhanced near-infrared fluorescence, of variants of SARS-CoV-2. The assay, which has single-nucleotide specificity for variant discrimination, single-RNA-copy sensitivity and does not require RNA extraction, discriminated 12 lineages of SARS-CoV-2 (in three mutational hotspots of the Spike protein) and detected the virus in nasopharyngeal swabs from 1,034 individuals at 98.8% sensitivity and 100% specificity, with 97.6% concordance with genome sequencing in variant discrimination. We also report a compact, portable and fully automated device integrating the entire swab-to-result workflow and amenable to the point-of-care detection of SARS-CoV-2 variants. Portable, rapid, accurate and multiplexed assays for the detection of SARS-CoV-2 variants and lineages may facilitate variant-surveillance efforts.
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COVID-19 , SARS-CoV-2 , Humanos , Bioensaio , COVID-19/diagnóstico , RNA , SARS-CoV-2/genética , FluorescênciaRESUMO
The development and performance of a DNA probe adsorbing Mn2+-modified black phosphorus (BP@Mn2+/DNA) hybrid nanosensor is reported that enables rapid detection of cancer-derived exosomal microRNAs (miRNAs) and exosomes. This two-dimensional (2D) nanosensor can spontaneously penetrate the lipid bilayer of exosome membranes owing to its ultra-thin geometry. Subsequently, the adsorbed probe specifically hybridizes with the target miRNA and then dissociates from the nanosensor surface, generating fluorescent signals. Therefore, the BP@Mn2+/DNA nanosensor can differentiate between colorectal cancer (CRC) cell-derived exosomes and those derived from intestinal epithelial cells through sensing of exosomal miRNAs. Furthermore, when the epithelial cell adhesion molecule (EpCAM) aptamer is adsorbed onto BP@Mn2+ instead of the miRNA probe, the nanosensor is able to distinguish exosomes derived from the plasma of CRC patients from those of healthy controls by the recognition ability of the EpCAM aptamer. By utilizing this nanosensor, we were able to effectively differentiate cancer-derived exosomes through the direct detection of miRNA-21 within the exosomes, as well as the identification of specific exosomal membrane proteins. This nanosensor design paves the way for the development of rapid and efficient cancer-derived exosomal miRNA and exosome biosensing nanoplatforms.
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Exossomos , MicroRNAs , Neoplasias , Humanos , Exossomos/metabolismo , Molécula de Adesão da Célula Epitelial/metabolismo , Neoplasias/metabolismo , Oligonucleotídeos/metabolismoRESUMO
To develop various biosensors, several 2D nanomaterials adsorb DNA probes (aptamers) via π-π stacking interactions. However, interference from DNA displacement by external non-targeted ligands has precluded their practical applications for specific detection and imaging at high protein concentrations. Metal coordination is an attractive strategy for biomolecular crosslinking and functional molecular self-assembly. Herein, a robust 2D biosensor nanoplatform was developed to enhance DNA adsorption and affinity using Mn2+-modified black phosphorus nanosheets (BPNS@Mn2+) via metal coordination. The Mn2+ can simultaneously coordinate with the lone pair electrons (π bonds) of the BPNS and nucleotide bases to provide binding sites for DNA nucleobases on the BPNS surface, which greatly enhances the stability of the inner BPNS and improves DNA adsorption and affinity. The DNA adsorption mechanism of BPNS@Mn2+ was also characterized, and is extensively discussed. Without any further modification, this BPNS@Mn2+/DNA biosensor specifically detected single-stranded DNA (linear range: 10-200 nM, detection limit: 5.76 nM) and thrombin (linear range: 20-180 nM, detection limit: 2.39 nM) in 100 nM bovine serum albumin solution. The nonspecific ligands in the environment did not affect the detection performance of the robust biosensor. In addition, the expression levels of microRNA-21 can be imaged and analyzed in living cells using this biosensor, which is consistent with the results of the polymerase chain reaction. This study highlights the potential of metal coordination in surface modification and provides new opportunities for biomedical applications of 2D nanomaterials with superior DNA-adsorption capacity, facilitating the development of biosensor design and nucleic acid/drug delivery.
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Técnicas Biossensoriais , MicroRNAs , Ácidos Nucleicos , Adsorção , Técnicas Biossensoriais/métodos , DNA/química , DNA de Cadeia Simples , Oligonucleotídeos , Fósforo , Soroalbumina Bovina , TrombinaRESUMO
STUDY DESIGN: Retrospective study. OBJECTIVE: To present a morphological map of cervical sagittal alignment in basilar invagination (BI), a congenital anomaly of the craniovertebral junction, and contribute to a comprehensive understanding of cervical sagittal alignment in congenital cervical deformities. SUMMARY OF BACKGROUND DATA: Ideal cervical sagittal alignment and surgical targets are debated by scholars. However, most of the literature focuses on the description of cervical sagittal alignment in acquired cervical diseases and normal subjects and few on congenital cervical spine deformities. MATERIALS AND METHODS: This study analyzed cervical spine lateral radiographs of 87 BI patients and 98 asymptomatic subjects. They were analyzed for cranial, cervical spine, and thoracic inlet parameters. RESULTS: Patients with BI manifested significantly larger values for the following parameters than asymptomatic subjects: cranial tilt, cranial incidence angle, sagittal vertical axis (SVA) CGH-C7, C2-C7 angle, cervical tilt, and significantly smaller values for the following parameters: cranial slope, C0-C2 angle, C0-C7 angle, SVA C2-C7, spine tilt, thoracic inlet angle, and neck tilt. In the BI group, SVA C2-C7 was the cervical parameter most strongly correlated with the cranial, cervical spine, and thoracic inlet parameters, and was smaller in BI patients with fusion (atlanto-occipital assimilation) than in those without. CONCLUSION: A significant difference was observed between BI patients and asymptomatic subjects. BI patients have craniums tilted forward and downward, smaller upper cervical lordosis, larger lower cervical lordosis, and smaller thoracic inlet angle. In BI patients, the SVA C2-C7 is an important parameter in cervical sagittal alignment. In both individuals with congenital anomalies of the craniovertebral junction and the asymptomatic population, cervical spine alignment is significantly associated with cranial alignment, particularly thoracic inlet alignment.
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Lordose , Platibasia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Humanos , Lordose/diagnóstico por imagem , Pescoço , Radiografia , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate and describe the morphologic features of the C2 pedicle in patients with basilar invagination (BI) for informing the placement of pedicle screws. C2 pedicle screw placement is an important surgical technique for the treatment of atlantoaxial instability in patients with BI. However, no systematic and comprehensive anatomical study of the C2 pedicle in patients with BI has been reported. METHODS: The data from 100 patients diagnosed with BI (BI group) and 100 patients without head or cervical disease (control group) were included in the study. Radiographic parameters, including the pedicle width, length, height, transverse angle, lamina angle, and superior angle, were measured and analyzed on CT images. After summary analysis, the effect of C2-3 congenital fusion on C2 pedicle deformity in patients with BI was also investigated. RESULTS: The width, length, and height of the C2 pedicle of the BI patients were smaller than those of the control group. The pedicle cancellous bone was smaller in the BI group, while no significant difference in cortical bone was observed. In total, 44% of the pedicles were smaller than 4.5 mm in the BI group. Patients with C2-3 congenital fusion presented with smaller pedicle transverse angles and larger pedicle superior angles than those without fusion. Wide variations in the left and right angles of the pedicle were observed in the BI group with atlantoaxial dislocation or atlantooccipital fusion. CONCLUSION: The C2 pedicle in the BI group was thinner than that in the control group due to a smaller cortical bone. Cases of C2-3 congenital fusion, atlantoaxial dislocation, and atlantooccipital fusion displayed variation in the angle of the C2 pedicle.
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Articulação Atlantoaxial , Luxações Articulares , Lesões do Pescoço , Parafusos Pediculares , Platibasia , Fusão Vertebral , Articulação Atlantoaxial/diagnóstico por imagem , Articulação Atlantoaxial/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Humanos , Fusão Vertebral/métodosRESUMO
BACKGROUND: miR-363-3p, the retinoid signaling pathway (RSP), and its associated membrane receptor, stimulated by retinoic acid 6 (STRA6), participate in lung development. We hypothesize that miR-363-3p is involved in lung cell proliferation and apoptosis by regulating the expression of STRA6, and this study was designed to investigate the effect of changes in the expressions of miR-363-3p and the STRA6 gene on the proliferation and apoptosis of rat alveolar type II cells. METHODS: To confirm our hypothesis, we used: a dual-luciferase reporter assay; cell culture and transfection; real-time quantitative polymerase chain reaction (PCR); Western blotting; a cell proliferation assay and flow cytometry analysis of the cell cycle, cell apoptosis, oxidative stress level, and mitochondrial membrane potential. RESULTS: Our results showed that STRA6 is a target gene for miR-363-3p, and when the expression of miR-363-3p increased, the relative messenger RNA (mRNA) expression of STRA6 decreased, which caused a decrease in STRA6 protein synthesis and subsequent inhibition of rat lung alveolar type II cell proliferation. In contrast, inhibiting the expression of miR-363-3p promoted the proliferation of these cells. This study also found that an increased expression of miR-363-3p induced rat lung alveolar type II cell apoptosis led to an increase in the oxidative stress level, decreased mitochondrial membrane potential, and an inducement of G1-phase cell cycle arrest. CONCLUSIONS: In conclusion, miR-363-3p is associated with lung cell proliferation and apoptosis, while miR-363-3p inhibits rat lung alveolar type II cell proliferation by downregulating the expression of STRA6 and induces cell apoptosis by increasing cellular oxidative stress and G1-phase cell cycle arrest.
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To promote the efficient utilization of China's reuse water resources and optimize the allocation of water resources, an analysis of factors influencing the development and utilization of reuse water resources was conducted. The uniqueness and competitiveness of reuse water resources were analyzed, and the driving and constraint mechanisms were revealed. A potential indicator system for the bilateral coordination of the supply and demand of reuse water was also established. Based on redundancy analysis (RDA), key indicators for the prediction of reuse water development and utilization potential were screened. On this basis, a national-scale reuse water development and utilization potential prediction model was constructed (the random effects model, REM). Given some uncertainty in the parameters of the REM model, the confidence interval ranges of the parameters at the 10%-90% quartile levels were identified. The results show that four indicators (ecological water consumption, density of water supply pipelines in built-up areas, fixed asset investment in the construction of reuse water treatment facilities, and total wastewater treatment) are closely related to the development and utilization of reuse water and, hence, are key indicators. The REM for the potential prediction has a high fitting accuracy, which can effectively reflect the fluctuations in the observed values with a maximum fitting error of -8.5%. China's reuse water development and utilization will continue to maintain rapid growth long into the future, reaching 12.9 billion m3 by 2025. This will help optimize national urban water supply structures and improve the reuse rate of regional water resources.
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PURPOSE: The purpose of this study is to evaluate the potential advantages of thoracoscopic versus open resection for symptomatic congenital pulmonary airway malformation (CPAM) in neonates. METHODS: A retrospective review of the medical records of neonates (age ≤ 28 days) who underwent surgery for symptomatic CPAM from 2010 to 2020. RESULTS: Of the 24 patients, 14 patients underwent thoracoscopic resection and 10 patients underwent open resection. 4 patients with CPAM located in the upper or middle lobes underwent lobectomy, and 20 underwent lung-preserving wedge resection in the lower lobe. Between the two groups, there were no statistically significant differences in related preoperative variables, including gestational age at birth, body weight, head circumference, lesion size, cystic adenomatoid malformation volume ratio (CVR), and age at operation (P > .05). The differences in intraoperative variables were statistically significant. The length of the surgical incision was significantly shorter in thoracoscopic resection group than in open resection group (1.4 cm [1.3-1.8] vs. 6.0 cm [5.0-8.0], P = .000), along with significantly less operative blood loss (3 ml [1-6] vs. 5 ml [2-10], P = .030) but significantly longer operation time (159 min [100-220] vs. 110 min [70-170], P = .003). Regarding postoperative variables, ventilator days, duration of chest tube use and length of hospital stay were not statistically significant (P > .05). CONCLUSION: Both thoracoscopic and open resection for symptomatic CPAM achieve good clinical outcomes, even in neonates. Thoracoscopic resection has minimal aesthetic effects and does not increase the risk of surgical or postoperative complications. Lung-preserving resection may be feasible for neonatal CPAM surgery.
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Malformação Adenomatoide Cística Congênita do Pulmão/cirurgia , Tempo de Internação/estatística & dados numéricos , Toracoscopia/métodos , Toracotomia/métodos , Perda Sanguínea Cirúrgica , Feminino , Humanos , Recém-Nascido , Masculino , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Toracoscopia/efeitos adversos , Toracotomia/efeitos adversos , Resultado do TratamentoRESUMO
Insulin-like growth factor binding protein 4-1 (IGFBP4-1), a new long noncoding RNA (lncRNA), has been reported to contribute to tumorigenesis and has been suggested to be a poor prognostic marker in human lung cancer. However, there still lacks basic studies that investigated the biological role of IGFBP4-1 in bladder urothelial carcinoma to date. In this study, we investigated the relationship between IGFBP4-1 expression and prognosis in patients with bladder cancer. Cell proliferation, cell cycle and cell apoptosis assays were performed to assess IGFBP4-1 function by up-regulating or down-regulating IGFBP4-1 in bladder cancer cells. A xenograft mice model was used to validate the in vitro results. Blockade of Janus kinase-signal transducer and activator of transcription pathway (JAK/STAT) was used to evaluate JAK/STAT signaling activity. The results showed that IGFBP4-1 was overexpressed in bladder cancer tissues compared with that in normal bladder tissues, and its expression level was positively correlated with poor prognosis in bladder cancer patients. Overexpression of IGFBP4-1 markedly promoted cell proliferation and cell cycle progression, and inhibited cell apoptosis, while knockdown of IGFBP4-1 notably suppressed the proliferation, promoted cell apoptosis, and induced cell cycle arrest at the G0/G1 phase. Mechanistically, we revealed that IGFBP4-1 promotes the activation of the JAK/STAT pathway in bladder cancer cells. Moreover, the JAK/STAT inhibitor dramatically blocked the tumor-promoting activity of IGFBP4-1. Tumor growth in vivo was also suppressed by knocking down of IGFBP4-1. In conclusion, IGFBP4-1 promoted bladder cancer progression by activating the JAK/STAT signaling pathway. These findings suggest that IGFBP4-1 exhibits an oncogenic role in the development of human bladder cancer.
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Carcinoma/metabolismo , Proteína 4 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Janus Quinases/metabolismo , Fatores de Transcrição STAT/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Animais , Apoptose , Carcinoma/genética , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Bases de Dados Genéticas , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteína 4 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Janus Quinases/genética , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Neoplasias Experimentais , RNA Longo não Codificante , Fatores de Transcrição STAT/genética , Regulação para Cima , Neoplasias da Bexiga Urinária/genéticaRESUMO
Lung hypoplasia is the main cause of congenital diaphragmatic hernia (CDH)-associated death but pathogenesis remains unclear. MiR-455-5p is involved in lung hypoplasia. We hypothesized that nitrofen causes abnormal miR-455-5p expression during lung development and designed this study to determine the relationship between miR-455-5p, stimulated by retinoic acid 6 (STRA6), and retinol in a nitrofen-induced CDH with lung hypoplasia rat model. Nitrofen or olive oil was administered to Sprague-Dawley rats by gavage on day 9.5 of gestation, and the rats were divided into a nitrofen group and a control group (n = 6). The left lung of fetuses was dissected on day 15.5. The expression of miR-455-5p or STRA6 messenger RNA (mRNA) was determined by quantitative real-time polymerase chain reaction. Average integrated optical density (IOD) of STRA6 protein was determined by immunofluorescence histochemistry. The average retinol level was detected by enzyme-linked immunosorbent assay (n = 6 lungs, respectively). Compared with the control group, the nitrofen group exhibited significantly increased miR-455-5p expression levels (29.450 ± 9.253 vs 5.955 ± 2.330; P = .00045) and significantly decreased STRA6 mRNA levels (0.197 ± 0.097 vs 0.588 ± 0.184; P = .0047). In addition, the average IOD of the STRA6 protein was significantly lower in the nitrofen group (805.643 ± 291.182 vs 1616.391 ± 572.308, P = .015), and the average retinol level was significantly reduced (4.013 ± 0.195 vs 5.317 ± 0.337 µg/L, P = .000). In summary, the overexpression of miR-455-5p affected retinol absorption by downregulating STRA6 in the nitrofen-induced CDH with lung hypoplasia rat model, and this downregulation may be one cause of CDH with lung hypoplasia.
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Hérnias Diafragmáticas Congênitas/genética , Hérnias Diafragmáticas Congênitas/metabolismo , Pulmão/metabolismo , Proteínas de Membrana/genética , Vitamina A/metabolismo , Vitaminas/metabolismo , 2,4-Dinitrofenol , Animais , Regulação para Baixo , Feminino , Hérnias Diafragmáticas Congênitas/induzido quimicamente , Pulmão/patologia , Masculino , Ratos Sprague-DawleyRESUMO
miR-455-5p and retinoid signaling pathway and its membrane receptor, STRA6, are associated with lung development. Software copredictions indicate that the miRNA upstream of the STRA6 gene is miR-455-5p. We hypothesized that miR-455-5p participates in rat lung alveolar Type II cell proliferation by targeting STRA6 and designed this study to investigate the effects of miR-455-5p overexpression on rat lung alveolar Type II cells. Dual luciferase reporter gene assay was utilized to confirm the relationship between miR-455-5p and STRA6. An miR-455-5p-expressing adenoviral vector was constructed and transfected into rat lung alveolar Type II cells. STRA6 protein expression was detected in rat lung alveolar Type II cells by Western blotting at 72 hr posttransfection. Retinol concentration was detected by ELISA at 72 hr posttransfection. The cell proliferation was detected by CCK8 assay at 24, 48, and 72 hr posttransfection. Our results showed that STRA6 is a target gene of miR-455-5p. STRA6 protein expression was significantly lower in the miR-455-5p-overexpression group than in the NC group (0.615 ± 0.131 vs. 0.958 ± 0.246, P = 0.029). Similar results were observed for retinol concentration (2.985 ± 0.061 vs. 3.949 ± 0.118, P = 0.000). Rat lung alveolar Type II cell proliferation was lower in the miR-455-5p-overexpression group than in the NC group at 24, 48, and 72 hr posttransfection (24 hr: 0.280 ± 0.184 vs. 1.354 ± 0.169 P = 0.026; 48 hr: 0.881 ± 0.016 vs. 1.992 ± 0.050 P = 0.001; 72 hr: 2.105 ± 0.148 vs. 2.937 ± 0.079 P = 0.016). In summary, miR-455-5p is associated with lung development. miR-455-5p overexpression downregulates STRA6, leading to reduced retinol concentration and rat lung alveolar Type II cell proliferation. Anat Rec, 302:2062-2069, 2019. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.
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Células Epiteliais Alveolares/citologia , Proliferação de Células , Proteínas de Membrana/metabolismo , MicroRNAs/genética , Alvéolos Pulmonares/citologia , Células Epiteliais Alveolares/metabolismo , Animais , Apoptose , Células Cultivadas , Proteínas de Membrana/genética , Alvéolos Pulmonares/metabolismo , Ratos , Transdução de SinaisRESUMO
Neuroblastoma is one of the most malignant solid tumors in infants and young children. No more than 40% of neuroblastoma patients can survive for longer than five years after it has been diagnosed. XPC protein is a pivotal factor that recognizes DNA damage and starts up the nucleotide excision repair (NER) in mammalian cells. This makes up the first group to defend against the cancer. Previous studies have identified that XPC gene polymorphisms were associated with various types of cancer. However, the associations between XPC gene polymorphisms and neuroblastoma risk have not yet been studied. We investigated the associations between three XPC gene polymorphisms (rs2228001 A>C, rs2228000 C>T, and rs2229090 G>C) and neuroblastoma risk with 256 neuroblastoma patients and 531 healthy controls in a Chinese Han population. Odds ratios and 95% confidence intervals were used to access the association between these three polymorphisms and neuroblastoma risk. No significant association was detected between these three polymorphisms and neuroblastoma risk in the overall analysis as well as in the stratification analysis. These results suggest that none of these three polymorphisms may be associated with the risk of neuroblastoma in the Chinese Han population.
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Povo Asiático/genética , Proteínas de Ligação a DNA/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Neuroblastoma/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Feminino , Frequência do Gene/genética , Humanos , Masculino , Medição de RiscoRESUMO
OBJECTIVE: To explore the effects of NF-E2-related factor-2 (NRF2)-617C/A promoter polymorphism on NRF2 expression as well as lipopolysaccharide-induced inflammatory responses in macrophages. METHODS: NRF2-617C/A promoter fragments were synthesized by chemical method and cloned into a pUC57 vector. The dul-luciferase reporter assay was employed to determine the activity of promoters. Then recombinant adenoviral vectors were constructed and transfected into macrophages. The expression of Nrf2 was examined by Western blotting and reverse transcription (RT)-PCR. The expressions of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) in macrophages after the stimulation of LPS were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The activity of NRF2-617C promoter-luciferase reporter (FLuc/RLuc activity ratio) was significantly higher than that of NRF2-617A group (0.584 ± 0.016 vs 0.258 ± 0.018, P < 0.05).The NRF2 protein and mRNA levels in -617C group were much higher than those of 617A group (1.123 ± 0.080 vs 0.951 ± 0.057,1.889 ± 0.031 vs 1.647 ± 0.323, both P < 0.05). After the stimulation of LPS, the NRF2 protein expression in macrophages significantly increased (0.584 ± 0.016 vs 0.258 ± 0.018, P < 0.05). Compared with -617A group, there was a significantly higher expression of NRF2 in -617C group (0.671 ± 0.033 vs 0.751 ± 0.014, P < 0.05). Additionally, the productions of IL-6 and IL-10 in -617C group were markedly lower than those in -617A group as well as IL-6/IL-10 (both P < 0.05). However, no significant difference existed in the levels of TNF-α between -617C and -617A groups (P > 0.05). CONCLUSIONS: The -617C/A promoter polymorphism of NRF2 may influence the NRF2 expression. And it appears to be associated with the LPS-induced inflammatory responses in macrophages.
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Inflamação , Macrófagos/patologia , Fator 2 Relacionado a NF-E2/genética , Células Cultivadas , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos , Macrófagos/metabolismo , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Fator de Necrose Tumoral alfa/metabolismoRESUMO
This study examined the association of pregnancy with urolithiasis and provided new insights into urolithiasis in pregnancy. A total of 462 subjects were studied from January 2004 to December 2009 in Foshan Maternal and Child Health Hospital, China. Among the 462 subjects, 162 cases of urolithiasis during pregnancy (UPG) were selected as the observation group, 150 cases of no urolithiasis during pregnancy (NUPG) served as pregnancy control group, and 150 cases of no pregnancy (NPG) at reproductive age who took part in physical examination were randomly assigned into non-pregnant control group. At the same time, the patients in observation group were divided into the following sub-groups: no symptomatic urinary calculus (NSUC) and symptomatic urinary calculus (SUC) groups; SUC group was further divided into surgical intervention (SI) and conservative management (CM) groups. The general information and the data of blood and urine were collected and compared among the groups. The results showed that the incidence of urinary calculi in pregnant women was lower than that in non-pregnant women, the formation of urinary stone was associated with the change of metabolism of protein and sugar in pregnant women, and the surgical intervention was a practicable alternative to treat the clinical intractable symptomatic urinary calculi in pregnancy.