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1.
Nano Lett ; 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39356651

RESUMEN

High-performance separation materials for oil-water emulsions are crucial to environmental protection and resource recovery; however, most existing fibrous separation materials are subject to large pore size and low porosity, resulting in limited separation performance. Herein, we create high-performance membranes consisting of spherical-beaded nanofibers and nanoarchitectured networks (nano-nets) using electrostatic spinning/netting technology, for water-in-oil emulsion separation. By manipulating the nonequilibrium stretching of jets, spherical-beaded nanofibers capable of generating a robust microelectric field are fabricated as scaffolds, on which charged droplets are induced to eject and phase separate to self-assemble nano-nets with small pores. Benefiting from 3D undulating networks with cavities originating from 2D nano-nets supported by 1D spherical-beaded nanofibers, the membranes exhibit under-oil superhydrophobicity (>152°), a striking separation performance with an efficiency of >99.2% and a flux of 5775 L m-2 h-1, together with wide pressure applicability, antifouling, and reusability. This work may open up new horizons in developing fibrous materials for separation and purification.

2.
Front Med (Lausanne) ; 11: 1446364, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39296893

RESUMEN

Background: As a novel indicator of inflammation, the relationship between the systemic immune-inflammation index (SIRI) and mortality in patients with asthma remains uncertain. Our study aimed to explore the association between SIRI and mortality in asthma patients. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) for US adults from 2001 to 2018 were included in this study. Then, we divided all patients into three groups based on SIRI tertiles and used multivariable weighted Cox regression analysis, smoothing curve fitting, survival curve analysis, and subgroup analysis to investigate the relationship between SIRI and asthma. Results: A total of 6,156 participants were included in the study, with each SIRI tertile consisting of 2052 individuals. Asthma patients with higher SIRI levels were older, had a higher level of education, were more likely to be married, and had a higher chance of being smokers. In Cox proportional-hazards models, the highest SIRI group showed higher hazard ratios (HRs) for all-cause mortality in individuals with asthma after adjusting for potential confounders. The restricted cubic spline analysis indicated a non-linear relationship between SIRI and all-cause mortality. The Kaplan-Meier survival curves showed that patients with higher SIRI levels had a higher risk of all-cause mortality. Subgroup analyses revealed SIRI's association with all-cause mortality across various demographics, including age, sex, race, education levels, smoking status, and marital status. Conclusion: Our study provides evidence for the relationship between SIRI and mortality in asthma patients. SIRI may potentially serve as a predictive tool for evaluating asthma mortality rates.

3.
Front Immunol ; 15: 1420205, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39221244

RESUMEN

Natural Killer (NK) cells play a crucial role as effector cells within the tumor immune microenvironment, capable of identifying and eliminating tumor cells through the expression of diverse activating and inhibitory receptors that recognize tumor-related ligands. Therefore, harnessing NK cells for therapeutic purposes represents a significant adjunct to T cell-based tumor immunotherapy strategies. Presently, NK cell-based tumor immunotherapy strategies encompass various approaches, including adoptive NK cell therapy, cytokine therapy, antibody-based NK cell therapy (enhancing ADCC mediated by NK cells, NK cell engagers, immune checkpoint blockade therapy) and the utilization of nanoparticles and small molecules to modulate NK cell anti-tumor functionality. This article presents a comprehensive overview of the latest advances in NK cell-based anti-tumor immunotherapy, with the aim of offering insights and methodologies for the clinical treatment of cancer patients.


Asunto(s)
Células Asesinas Naturales , Neoplasias , Microambiente Tumoral , Humanos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Neoplasias/terapia , Neoplasias/inmunología , Microambiente Tumoral/inmunología , Animales , Inmunoterapia Adoptiva/métodos , Inmunoterapia/métodos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología
4.
BMC Pulm Med ; 24(1): 298, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918752

RESUMEN

BACKGROUND: End-expiratory lung volume (EELV) has been observed to decrease in acute respiratory distress syndrome (ARDS). Yet, research investigating EELV in patients with COVID-19 associated ARDS (CARDS) remains limited. It is unclear whether EELV could serve as a potential metric for monitoring disease progression and identifying patients with ARDS at increased risk of adverse outcomes. STUDY DESIGN AND METHODS: This retrospective study included mechanically ventilated patients diagnosed with CARDS during the initial phase of epidemic control in Shanghai. EELV was measured using the nitrogen washout-washin technique within 48 h post-intubation, followed by regular assessments every 3-4 days. Chest CT scans, performed within a 24-hour window around each EELV measurement, were analyzed using AI software. Differences in patient demographics, clinical data, respiratory mechanics, EELV, and chest CT findings were assessed using linear mixed models (LMM). RESULTS: Out of the 38 patients enrolled, 26.3% survived until discharge from the ICU. In the survivor group, EELV, EELV/predicted body weight (EELV/PBW) and EELV/predicted functional residual capacity (EELV/preFRC) were significantly higher than those in the non-survivor group (survivor group vs. non-survivor group: EELV: 1455 vs. 1162 ml, P = 0.049; EELV/PBW: 24.1 vs. 18.5 ml/kg, P = 0.011; EELV/preFRC: 0.45 vs. 0.34, P = 0.005). Follow-up assessments showed a sustained elevation of EELV/PBW and EELV/preFRC among the survivors. Additionally, EELV exhibited a positive correlation with total lung volume and residual lung volume, while demonstrating a negative correlation with lesion volume determined through chest CT scans analyzed using AI software. CONCLUSION: EELV is a useful indicator for assessing disease severity and monitoring the prognosis of patients with CARDS.


Asunto(s)
COVID-19 , Mediciones del Volumen Pulmonar , Síndrome de Dificultad Respiratoria , Tomografía Computarizada por Rayos X , Humanos , COVID-19/complicaciones , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/terapia , China , Anciano , Mediciones del Volumen Pulmonar/métodos , SARS-CoV-2 , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Respiración Artificial , Adulto
5.
Biofabrication ; 16(2)2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38442726

RESUMEN

Stem cell therapy, achieved using mesenchymal stem cells (MSCs), has been highlighted for the treatment of liver fibrosis. Infusion into the circulatory system is a traditional application of MSCs; however, this approach is limited by phenotypic drift, stem cell senescence, and vascular embolism. Maintaining the therapeutic phenotype of MSCs while avoiding adverse infusion-related reactions is the key to developing next-generation stem cell therapy technologies. Here, we propose a bioreactor-based MSCs therapy to avoid cell infusion. In this scheme, 5% liver fibrosis serum was used to induce the therapeutic phenotype of MSCs, and a fluid bioreactor carrying a co-culture system of hepatocytes and MSCs was constructed to produce the therapeutic medium. In a rat model of liver fibrosis, the therapeutic medium derived from the bioreactor significantly alleviated liver fibrosis. Therapeutic mechanisms include immune regulation, inhibition of hepatic stellate cell activation, establishment of hepatocyte homeostasis, and recovery of liver stem cell subsets. Overall, the bioreactor-based stem cell therapy (scheme) described here represents a promising new strategy for the treatment of liver fibrosis and will be beneficial for the development of 'cell-free' stem cell therapy.


Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Ratas , Animales , Hígado , Cirrosis Hepática/terapia , Cirrosis Hepática/patología , Hepatocitos , Fibrosis
6.
Cell Mol Biol (Noisy-le-grand) ; 69(12): 111-117, 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38063110

RESUMEN

Nasopharyngeal carcinoma (NPC) originates from the nasopharyngeal epithelium. hsa_circ_0135761 (circEFR3A), a newly identified circRNA, presented elevation in NPC via high-throughput sequencing. This study aimed to clarify the molecular mechanism of circEFR3A in the carcinogenesis of NPC. Based on RT-qPCR, subcellular fractionation, RNase R digestion and actinomycin D assays, we evaluated circEFR3A expression characteristics in NPC cells. We found that the circEFR3A was located in the cytoplasm of NPC cells, presented upregulation and stably expressed in NPC cells. Loss-of-function assays clarified the effects of circEFR3A on NPC cell malignant behaviors. The results demonstrated that circEFR3A knockdown facilitated NPC cell apoptosis but repressed NPC cell proliferation and migration. Furthermore, the regulatory mechanism of circEFR3A in NPC was explored. Bioinformatics and mechanism experiments revealed that cicrEFR3A positively modulated EFR3A by competitively binding with miR-654-3p in NPC cells. Additionally, rescue assays showed that the suppressive effects of cicrEFR3A knockdown on NPC cell proliferation, migration and apoptosis were countervailed by EFR3A upregulation. Xenograft tumor-bearing mouse models were established to investigate the role of cicrEFR3A in NPC tumorigenesis in vivo, and the results indicated that circEFR3A silencing suppressed tumor growth in mice. In conclusion, circEFR3A is highly expressed and functions as an oncogene in NPC progression. circEFR3A facilitates NPC cell proliferation and migration by binding to miR-654-3p to upregulate EFR3A, providing a potential new direction for seeking therapeutic plans for NPC.


Asunto(s)
MicroARNs , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , ARN Circular , Animales , Humanos , Ratones , Carcinogénesis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , ARN Circular/genética
7.
Am J Cancer Res ; 13(6): 2488-2503, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37424803

RESUMEN

Splicing factor proline- and glutamine-rich (SFPQ) regulates transcripts in skeletal muscle metabolism and tumorigenesis. As osteosarcoma (OS) is the most common malignant bone tumor characterized by genome instability, such as MYC amplification, this study aimed to investigate the role and mechanism of SFPQ in OS. Expression of SFPQ in OS cell lines and human OS tissues was detected using quantitative real-time PCR, western blot, and fluorescence in situ hybridization (FISH) analyses. The oncogenic role of SFPQ in OS cells and murine xenograft models and the underlying mechanism of SFPQ on the c-Myc signaling pathway were assessed in vitro and in vivo. Results showed that SFPQ expression was upregulated and correlated with poor prognosis in OS patients. SFPQ overexpression promoted the malignant biological behavior of OS cells, while its knockdown markedly reduced the oncogenic function of OS. Additionally, depletion of SFPQ inhibited OS growth and bone destruction in nude mice. SFPQ overexpression induced malignant biological behaviors, which could be rescued by the depletion of c-Myc. These results suggest an oncogenic role of SFPQ in OS, possibly through the c-Myc signaling pathway.

8.
J Nutr Biochem ; 120: 109416, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37451475

RESUMEN

Leptin is a nutritional cytokine, and it is closely related to the progression of cancer. However, the detailed effect of leptin in lung cancer remains poorly known. We found leptin-induced A549 cell proliferation, migration, and invasion, which was reversed by epigallocatechin gallate (EGCG) from green tea. Currently, we found that leptin-triggered M2 polarization of tumor-associated macrophages was inhibited by EGCG. Then, to investigate the underlying mechanism effect of leptin on A549 cells was studied. Aberrant activities of STAT1 are implicated in cancer development. Based on the cancer genome atlas data, STAT1 acted as an oncogene in lung cancer and EGCG greatly reduced STAT1 expression in A549 cells. Ferroptosis is an iron-dependent nonapoptotic cell death. STAT1 served as a transcriptional activator for SLC7A11. EGCG restrained lung cancer cell growth induced by leptin via targeting STAT1-SLC7A11 mediated ferroptosis. A high-fat diet (HFD) feeding condition was combined with a multi-dose urethane-induced lung tumorigenesis model using C57BL/6J mice. Obesity was induced with a 60 kcal% HFD feeding. Serum leptin levels increased in urethane-administered and HFD-fed mice. Compared to the control diet-fed mice, the HFD-fed mice exhibited increased lung tumor burden and typical pro-tumorigenic STAT1 activation in lung tissues after urethane administration. In addition, HFD alters the gut microbiome by decreasing the abundance of Clostridia and by increasing the abundance of Deltaproteobacteria and Epsilonproteobacteria while EGCG exhibited a reversed effect. These findings suggested that leptin promoted the development of lung tumorigenesis in vitro and in vivo via mediating activation of the STAT-SLC7A11 pathway and gut microbiota.


Asunto(s)
Microbioma Gastrointestinal , Neoplasias Pulmonares , Ratones , Animales , Leptina/farmacología , Ratones Endogámicos C57BL , Obesidad/metabolismo , Pulmón/metabolismo , Carcinogénesis , Uretano/farmacología , Dieta Alta en Grasa
9.
Clin Epigenetics ; 15(1): 92, 2023 05 26.
Artículo en Inglés | MEDLINE | ID: mdl-37237385

RESUMEN

BACKGROUND: Epigenetic dysregulation is essential to the tumorigenesis of oral squamous cell carcinoma (OSCC). SET and MYND domain-containing protein 3 (SMYD3), a histone lysine methyltransferase, is implicated in gene transcription regulation and tumor development. However, the roles of SMYD3 in OSCC initiation are not fully understood. The present study investigated the biological functions and mechanisms involved in the SMYD3-mediated tumorigenesis of OSCC utilizing bioinformatic approaches and validation assays with the aim of informing the development of targeted therapies for OSCC. RESULTS: 429 chromatin regulators were screened by a machine learning approach and aberrant expression of SMYD3 was found to be closely associated with OSCC formation and poor prognosis. Data profiling of single-cell and tissue demonstrated that upregulated SMYD3 significantly correlated with aggressive clinicopathological features of OSCC. Alterations in copy number and DNA methylation patterns may contribute to SMYD3 overexpression. Functional experimental results suggested that SMYD3 enhanced cancer cell stemness and proliferation in vitro and tumor growth in vivo. SMYD3 was observed to bind to the High Mobility Group AT-Hook 2 (HMGA2) promoter and elevated tri-methylation of histone H3 lysine 4 at the corresponding site was responsible for transactivating HMGA2. SMYD3 also was positively linked to HMGA2 expression in OSCC samples. Furthermore, treatment with the SMYD3 chemical inhibitor BCI-121 exerted anti-tumor effects. CONCLUSIONS: Histone methyltransferase activity and transcription-potentiating function of SMYD3 were found to be essential for tumorigenesis and the SMYD3-HMGA2 is a potential therapeutic target in OSCC.


Asunto(s)
N-Metiltransferasa de Histona-Lisina , Neoplasias de la Boca , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Carcinogénesis/genética , Línea Celular Tumoral , Transformación Celular Neoplásica/genética , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas/metabolismo , Neoplasias de la Boca/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética
10.
Hum Cell ; 36(1): 276-285, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36163585

RESUMEN

Macrophages represent the major population in the tumor microenvironment (TME). Recent studies have demonstrated circular RNAs (circRNAs) are implicated in the development and progression of different immune responses and immune diseases. However, the role of circRNAs in the development of tumor-associated macrophages (TAM) remains unknown. Here, we used the circRNA sequencing to identify the differentially expressed circRNAs (DEcircRNAs) in TAM-like cell induced by culture medium of colorectal cancer cell lines. Of note, the expression of circMERTK was remarkably overexpressed in TAMs. The ISH assay displayed that the expressions of circMERTK were mainly overlapped with macrophages marker CD68, and the abundance of circMERTK in CRC tissues was much higher than that in matched normal tissues. Functionally, circMERTK knockdown resulted in attenuated CD8+ T cell apoptosis in the co-culture assay, indicating that circMERTK could have an impact on the immunosuppressive activity of TAM-like cell. Mechanically, TAM-like cell could exert immunosuppressive activity via circMERTK/miR-125a-3p/IL-10 axis. These data suggested that circMERTK could play an important role in TAM activation, and may serve as a potential therapeutic target for CRC.


Asunto(s)
Neoplasias Colorrectales , MicroARNs , Humanos , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/patología , ARN Circular/genética , ARN Circular/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Macrófagos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , MicroARNs/genética , MicroARNs/metabolismo , Microambiente Tumoral/genética
11.
Cell Mol Biol (Noisy-le-grand) ; 68(7): 171-176, 2022 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-36495500

RESUMEN

Glioma is a malignant tumor originating from the central nervous system. Glioma is the incidence rate of the central nervous system in adults. Nanotechnology has been widely used in drug delivery in vivo, achieving targeted drug delivery through surface modification. At the same time, the samples measured by NMR have no bias to all compounds, and there is no need for specific internal standards for quantification. Therefore, based on the use of nuclear magnetic resonance technology, this paper analyzed the inhibitory effect of nano-targeted micelles combined with in vitro radiotherapy on glioma. The results show that the coupling constants of ß - CH3 of Ala and ß - CH3 of Lac are close. It is difficult to distinguish the spectral lines of Ala and Lae by 1.5T NMR. DHA-PLys(s-s)P can efficiently deliver drugs across BBB and into brain parenchymal cells to release drugs. Due to its increased stability in the systemic circulation, DHA-PLys(s-s)P can help to improve drug delivery efficiency. The DNA damage of U87 and U251 cells was more serious than that of C6 cells. There was a positive correlation between DNA damage and Cho/Cr ratio, indicating that nano-targeted micelles combined with in vitro radiotherapy have an inhibitory effect on glioma.


Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Micelas , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Glioma/tratamiento farmacológico , Glioma/radioterapia , Glioma/patología , Espectroscopía de Resonancia Magnética , Tecnología
12.
Front Oncol ; 12: 819051, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36212475

RESUMEN

Background: Substantial evidence suggests that receptor tyrosine kinases (RTKs) are overexpressed in tumors; however, few studies have focused on the prognostic value of RTKs in melanoma. Objectives: The objective of this study is to evaluate the association between overexpression of RTKs and survival in melanoma patients based on immunohistochemistry (IHC) analysis. Methods: Our review is registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number CRD42021261460. Seven databases were searched, and data were extracted. We used IHC to measure the association between overexpression of RTKs and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and clinicopathology in melanoma patients. Pooled analysis was conducted to assess the differences between Hazard Ratios along with 95% confidence intervals. Results: Of 5,508 publications examined following the database search, 23 publications were included in this study, which included data from a total of 2,072 patients. Vascular endothelial growth factor receptor 2 (VEGF-R2) overexpression was associated with worse OS and DFS in melanoma. Furthermore, there was an association between OS and the expression of several RTKs, including epidermal growth factor receptor (EGFR), mesenchymal-epithelial transition factor (MET), vascular endothelial growth factor receptor 1 (VEGF-R1), and insulin-like growth factor 1 receptor (IGF-1R). There were no significant correlations between EGFR overexpression and worse DFS or PFS. EGFR overexpression was associated with worse OS cutaneous and nasal melanoma, but not uveal melanoma. However, MET overexpression was related to worse OS in both cutaneous and uveal melanoma. Furthermore, EGFR overexpression was associated with a worse OS in Europe compared to other geographic areas. Moreover, EGFR and MET overexpression showed significant prognostic value in patients with the cut-off "≥10% staining". Conclusions: Our findings build concrete evidence that overexpression of RTKs is associated with poor prognosis and clinicopathology in melanoma, highlighting RTK expression has the potential to inform individualized combination therapies and accurate prognostic evaluation.

13.
Cancer Manag Res ; 14: 2323-2337, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35958946

RESUMEN

Background: Gastric cancer (GC) is a common type of gastrointestinal tumor in the world. Transfer RNA (tRNA) derived fragments (tsRNAs) implicate various cancers, but their roles in GC remain unclear. Our study aimed to investigate the potential biological functions and molecular mechanisms of tsRNAs in GC. Methods: Differentially expressed tsRNAs were identified using high-throughput sequencing. The expression levels of tsRNAs were validated in 62 paired GC tissues and adjacent normal tissues using RT-qPCR. In vitro functional assays were used to evaluate the influences of tsRNAs on GC cells. The potential mechanisms underlying tsRNAs were explored using bioinformatics analysis,RT-qPCR, RNA immunoprecipitation assays and Western blot. Results: We found that tiRNA-Val-CAC-001 was downregulated in GC tissues and cells, and demonstrated that tiRNA-Val-CAC-001 was a tsRNA sheared from mature tRNA-Val and mainly localized in the cytoplasm. tiRNA-Val-CAC-001 overexpression inhibited metastasis and proliferation but promoted apoptosis of GC cells; nevertheless, tiRNA-Val-CAC-001 knockdown increased metastasis and proliferation and reduced apoptosis (P<0.05). GO and KEGG analyses indicated tiRNA-Val-CAC-001 may exert its effects via Wnt/ß-catenin signaling pathway by targeting LRP6. Following experiments showed that tiRNA-Val-CAC-001 could downregulated the protein levels of LRP6 and ß-catenin, but up-regulated p-ß-catenin, which confirmed the findings in bioinformatics analysis. Conclusion: In conclusion, tiRNA-Val-CAC-001 works as a cancer suppressor in GC by targeting LRP6 via Wnt/ß-catenin signaling pathway. tiRNA-Val-CAC-001 may serve as a therapy target and a biomarker of GC in the future. Key Points: tiRNA-Val-CAC-001 is downregulated in gastric cancer tissues and cell lines, tiRNA-Val-CAC-001 has potential to become a novel diagnostic biomarker in gastric cancer, and tiRNA-Val-CAC-001 regulates gastric cancer cells by targeting LRP6.

14.
Am J Cancer Res ; 12(7): 3464-3478, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35968334

RESUMEN

Cyclin D2 (CCND2) is abnormally overexpressed in many tumor types and has been associated with tumor cell proliferation. Although the important role of miR-1297 is well established, the molecular mechanism between CCND2 and miR-1297 in osteosarcoma (OS) has not been determined. In the present study, we found CCND2 was highly expressed in OS cells, and its downregulation suppressed cell proliferation, resulting in G1 phase cell cycle arrest. In contrast, miR-1297 was lowly expressed in OS compared to normal tissue. Several data platforms predicted that CCND2 was a target of miR-1297, which was validated by a dual-luciferase reporter assay that revealed miR-1297 could bind with CCND2-3'UTR. miR-1297 overexpression greatly inhibited CCND2 protein expression and exerted the same phenotypic effect as CCND2 downregulation in OS cells. Furthermore, miR-1297 inhibition could also be rescued by CCND2. Nude mice injected cells stable overexpressing miR-1297 OS cells showed lower size and tumor weight. Moreover, lower fluorescence activity recorded by in vivo imaging system and bone erosion revealed by microCT in the miR-1297 group demonstrated miR-1297 inhibited OS tumor growth via CCND2. Our findings demonstrated that miR-1297 can inhibit proliferation and tumor growth in OS by directly targeting CCND2, which indicates that miR-1297 may represent a novel therapeutic target for OS.

15.
Cell Mol Biol Lett ; 27(1): 44, 2022 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-35672694

RESUMEN

BACKGROUND: Obstructive sleep apnea is associated with increased lung cancer incidence and mortality. Cancer stem cells (CSCs) are characterized by their self-renewing ability, which contributes to metastasis, recurrence, and drug resistance. ATPase family AAA domain-containing protein 2 (ATAD2) induces malignancy in different types of tumors. However, a correlation between ATAD2 expression and CSCs in lung cancer has not yet been reported. METHODS: The relative messenger RNA (mRNA) levels of ATAD2, CD44, CD133, and hypoxia-inducible factor (HIF)-1α were determined using reverse-transcription quantitative polymerase chain reaction. ATAD2 protein levels were determined using Western blotting. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine (EdU), and colony formation assays were performed to analyze the proliferation of lung cancer cells. Transwell migration and invasion assays were performed to evaluate cell migration and invasion, respectively. Tumor sphere formation analysis was used to determine tumor spheroid capacity. The link between ATAD2 and HIF-1α was verified using a dual-luciferase reporter assay. Immunofluorescence staining was performed to assess mitochondrial reactive oxygen species (mtROS) production. Flow cytometry analysis was conducted to determine the CD133 and CD44 positive cell ratio. RESULTS: We evaluated the relative expression of ATAD2 in four lung cancer cell lines (A549, SPC-A1, H460, and H1299 cells) and found increased mRNA and protein levels of ATAD2 in lung cancer samples. ATAD2 overexpression was a poor prognostic factor for lung cancer patients. Loss of ATAD2 reduced lung cancer cell viability and proliferation. Additionally, ATAD2 knockdown repressed lung cancer cell migration, invasion, stem-cell-like properties, and mtROS production. Chronic intermittent hypoxia (CIH)-induced HIF-1α expression significantly activated ATAD2 during lung cancer progression. CONCLUSIONS: This study found that CIH induced HIF-1α expression, which acts as a transcriptional activator of ATAD2. The present study also suggests a novel mechanism by which the integrity of CIH-triggered HIF-1α/ATAD2 may determine lung cancer aggressiveness via the interplay of mtROS and stemness in lung cancer cells.


Asunto(s)
Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Pulmonares , ATPasas Asociadas con Actividades Celulares Diversas/genética , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proteínas de Unión al ADN/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Neoplasias Pulmonares/patología , Células Madre Neoplásicas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo
16.
Front Optoelectron ; 15(1): 45, 2022 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-36637682

RESUMEN

Broadband optical frequency comb (OFC) generation based on a single electro-absorption modulator (EAM) is proposed. The EAM is driven by a radio frequency (RF) multi-frequency signal generated by a multiplication coupler composed of an electrical power splitter and an arithmetic circuit. Thus the number of comb-lines of the generated OFC can be increased. A complete theoretical model of OFC generation by an EAM driven by nth power of the RF source is established, and the performance of the OFC is analyzed by using OptiSystem software. The results show that, the number of comb-lines of the OFC is positively correlated with the number of multiplication of the RF source signal. The frequency spacing of the comb-lines is twice the frequency of the RF source signal and is tunable by adjusting the frequency of the RF source signal. Increasing chirp factor and modulation index of EAM could increase the number of comb-lines of the generated OFC. The amplitude of the RF source signal had little impact on the flatness of the OFC and the average OFC power. The scheme developed is not only simple and low-cost, but also can produce a large number of comb-lines.

17.
Respir Res ; 22(1): 320, 2021 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-34949193

RESUMEN

BACKGROUND: Growing evidence suggests that cancer stem cells (CSCs) are responsible for cancer initiation in tumors. Bach1 has been identified to contribute to several tumor progression, including lung cancer. The role of Bach1 in CSCs remains poorly known. Therefore, the function of Bach1 on lung CSCs was focused currently. METHODS: The expression of Bach1, CD133, CD44, Sox2, Nanog and Oct4 mRNA was assessed using Real-Time Quantitative Reverse Transcription PCR (RT-qPCR). Protein expression of Bach1, CD133, CD44, Sox2, Nanog, Oct4, p53, BCL2, BAX, p-p38, p-AKT1, c-Fos and c-Jun protein was analyzed by western blotting. 5-ethynyl-29-deoxyuridine (EdU), colony formation, Flow cytometry analysis and transwell invasion assay were carried out to analyze lung cancer cell proliferation, apoptosis and invasion respectively. Tumor sphere formation assay was utilized to evaluate spheroid capacity. Flow cytometry analysis was carried out to isolate CD133 or CD44 positive lung cancer cells. The relationship between Bach1 and CD44 was verified using ChIP-qPCR and dual-luciferase reporter assay. Xenograft tumor tissues were collected for hematoxylin and eosin (HE) staining and IHC analysis to evaluate histology and Ki-67. RESULTS: The ratio of CD44 + CSCs from A549 and SPC-A1 cells were significantly enriched. Tumor growth of CD44 + CSCs was obviously suppressed in vivo compared to CD44- CSCs. Bach1 expression was obviously increased in CD44 + CSCs. Then, via using the in vitro experiment, it was observed that CSCs proliferation and invasion were greatly reduced by the down-regulation of Bach1 while cell apoptosis was triggered by knockdown of Bach1. Loss of Bach1 was able to repress tumor-sphere formation and tumor-initiating CSC markers. A repression of CSCs growth and metastasis of shRNA-Bach1 was confirmed using xenograft models and caudal vein injection. The direct interaction between Bach1 and CD44 was confirmed by ChIP-qPCR and dual-luciferase reporter assay. Furthermore, mitogen-activated protein kinases (MAPK) signaling pathway was selected and we proved the effects of Bach1 on lung CSCs were associated with the activation of the MAPK pathway. As manifested, loss of Bach1 was able to repress p-p38, p-AKT1, c-Fos, c-Jun protein levels in lung CSCs. Inhibition of MAPK signaling remarkably restrained lung CSCs growth and CSCs properties induced by Bach1 overexpression. CONCLUSION: In summary, we imply that Bach1 demonstrates great potential for the treatment of lung cancer metastasis and recurrence via activating CD44 and MPAK signaling.


Asunto(s)
Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/deficiencia , Regulación Neoplásica de la Expresión Génica/fisiología , Receptores de Hialuranos/biosíntesis , Neoplasias Pulmonares/metabolismo , Células Madre Neoplásicas/metabolismo , Fenotipo , Células A549 , Animales , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/antagonistas & inhibidores , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Proliferación Celular/fisiología , Técnicas de Silenciamiento del Gen/métodos , Humanos , Receptores de Hialuranos/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Ratones Desnudos , Células Madre Neoplásicas/patología , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
18.
Am J Transl Res ; 13(11): 12264-12284, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34956452

RESUMEN

Osteosarcoma is a primary malignant bone tumor that occurs frequently in children and adolescents and has a propensity for drug resistance, recurrence, and metastasis. The purpose of this study was to identify potential target genes to predict metastasis and survival in patients with osteosarcoma. We analyzed gene expression profiles and corresponding clinical data of patients with osteosarcoma in the Gene Expression Omnibus database and identified 202 genes that were differentially expressed between osteosarcoma cells and normal osteoblasts. Univariate and multivariable Cox regression analyses identified four risk genes that affected osteosarcoma prognosis: MCAM, ENPEP, LRRC1, and CPE. Independent prognostic analyses and clinical correlation studies showed that the four risk genes constituted an independent prognostic signature that correlated with survival and clinical parameters including age and distant metastasis. In a single-sample Gene Set Enrichment Analysis, risk scores based on the prognostic signature correlated with tumor infiltration by immune cells and immune functions in osteosarcoma. A subsequent analysis showed that the expression levels of the four genes in the prognostic signature were predictive of overall survival and metastasis-free survival of patients with osteosarcoma. Furthermore, Human Cancer Metastasis Database and qRT-PCR analyses demonstrated that the four risk genes are overexpressed in osteosarcoma tissues and cell lines. In summary, we developed and validated a four-gene prognostic signature that may be useful in osteosarcoma diagnosis and metastasis prediction.

19.
Front Genet ; 12: 780780, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34899864

RESUMEN

Osteosarcoma is a common malignant bone tumor with a propensity for drug resistance, recurrence, and metastasis. A growing number of studies have elucidated the dual role of pyroptosis in the development of cancer, which is a gasdermin-regulated novel inflammatory programmed cell death. However, the interaction between pyroptosis and the overall survival (OS) of osteosarcoma patients is poorly understood. This study aimed to construct a prognostic model based on pyroptosis-related genes to provide new insights into the prognosis of osteosarcoma patients. We identified 46 differentially expressed pyroptosis-associated genes between osteosarcoma tissues and normal control tissues. A total of six risk genes affecting the prognosis of osteosarcoma patients were screened to form a pyroptosis-related signature by univariate and LASSO regression analysis and verified using GSE21257 as a validation cohort. Combined with other clinical characteristics, including age, gender, and metastatic status, we found that the pyroptosis-related signature score, which we named "PRS-score," was an independent prognostic factor for patients with osteosarcoma and that a low PRS-score indicated better OS and a lower risk of metastasis. The result of ssGSEA and ESTIMATE algorithms showed that a lower PRS-score indicated higher immune scores, higher levels of tumor infiltration by immune cells, more active immune function, and lower tumor purity. In summary, we developed and validated a pyroptosis-related signature for predicting the prognosis of osteosarcoma, which may contribute to early diagnosis and immunotherapy of osteosarcoma.

20.
Rev Sci Instrum ; 92(10): 104701, 2021 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-34717402

RESUMEN

Aiming at developing a megavolt ultrafast bypass switch (UFBPS) that operates at a very low working coefficient, an enhanced plasma injection (EPI) method was proposed, which ejected high-density plasmas up to several centimeters in height in a high-pressure SF6 and thus has an extremely strong triggering ability. The EPI method employed a thin polytetrafluoroethylene microcavity embedded inside the ground electrode and a metal wire electrically exploded inside the microcavity, generating a high-density metal vapor plasma that was rapidly ejected outward from the nozzle and inducing a breakdown of the residual gas gap. In this study, the ejected plasma properties by EPI and main influencing factors were examined and the EPI triggering ability was experimentally verified. The results showed that EPI evolution presented three stages: ellipsoid-shaped, mushroom-shaped, and dissipation stages. In 0.5-MPa SF6, when the trigger energy was 960 J and the exploded aluminum wire was 300 µm in radius, the EPI maximum height reached over 9 cm within 0.7 ms, with an initial evolution velocity >800 m/s. Then, an EPI cavity array was set to repetitively trigger a 10 cm-magnitude SF6 gas gap at 0.5 MPa, with a theoretical breakdown voltage >2 MV. The gas gap was successfully triggered with an average trigger delay of 538 µs when a DC 100 kV voltage (undervoltage ratio <5%) was applied. These results indicated that EPI was an effective method for triggering megavolt-magnitude high-pressure SF6 gas gaps at a low undervoltage ratio and meeting the submillisecond trigger requirement of the UFBPS.

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