RESUMEN
Active adjustable terahertz multifunctional devices are crucial for the application of terahertz technology. In this paper, we propose a composite metasurface structure based on an indium antimonide metal octagonal pattern, which achieves different functional switching by controlling the phase state of indium antimonide material under different ambient temperatures. When indium antimonide exhibits in the dielectric state, by stacking and encoding the unit cell, the designed metasurface has the functions of two-beam splitting beam superposition, vortex beam and quarter beam superposition, and dual vortex beam superposition for circularly polarized and linearly polarized wave incidence. When indium antimonide appears in the metallic state, the encoding metasurface alters the modulation function of incident circularly polarized and linearly polarized terahertz waves. This terahertz metasurface provides a new approach for the design of multifunctional devices that can flexibly regulate terahertz wave metasurfaces.
RESUMEN
BACKGROUND: Osteosarcoma (OS) is the most prevalent orthopedic malignancy with a dismal prognosis. Disulfidptosis-related lncRNAs (DRLncs) may be related to the progression of OS, but their potential molecular regulatory role is still unclear. METHODS: Based on the data collected from The Cancer Genome Atlas (TCGA), we conducted correlation analysis and the univariate Cox analysis to screen prognosis-related DRLncs, followed by developing genotyping patterns and corresponding classifier. Subsequently, the survival analysis, enrichment analysis, drug sensitivity analysis and immune infiltration analysis were performed. Afterward, multivariate Cox regression was used to construct a risk model, which was further validated by the receiver operating characteristic (ROC) curve. The aberrant expression of hub DRLncs in OS was validated using the Reverse Transcription Polymerase Chain Reaction (RT-qPCR) assay. RESULTS: We identified 262 DRLncs and eleven prognosis-related DRLncs through filtering. We then constructed two distinct expression patterns of prognosis-related DRLncs and developed a classifier. We obtained 393 differentially expressed genes (DEGs) between different subtypes, which were significantly enriched in biological processes related to the extracellular matrix, integrin binding, focal adhesion, and Wnt signaling pathways. Through immune infiltration analysis, the activated CD4 memory T cells, resting natural killer (NK) cells, M1 macrophages, and resting dendritic cells (DC) were observed to exhibit different abundance in distinct subtypes. In the drug sensitivity analysis, tamoxifen showed a promising effect for drug-resistant OS. Furthermore, we identified five hub DRLncs and constructed a risk model. The RT-qPCR confirmed the aberrant expression of five hub DRLncs in OS. CONCLUSIONS: The present study identified DRLncs in OS, and conducted a comprehensive investigation of DRLncs-related expression patterns, survival status, immune landscape and drug sensitivity to reveal the difference in prognostic, pharmacological and immunological phenotype characteristics between distinct subtypes. Additionally, we developed a risk model to predict the prognosis, and constructed a genotyping classifier to predict the above phenotype characteristics in OS.
Asunto(s)
Neoplasias Óseas , Regulación Neoplásica de la Expresión Génica , Osteosarcoma , ARN Largo no Codificante , Humanos , Osteosarcoma/genética , Osteosarcoma/inmunología , ARN Largo no Codificante/genética , Pronóstico , Neoplasias Óseas/genética , Neoplasias Óseas/inmunología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/inmunología , Genotipo , Perfilación de la Expresión Génica , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Femenino , MasculinoRESUMEN
BACKGROUND: Steroid-induced avascular necrosis of the femoral head (SANFH) is a typical refractory disease that often progresses irreversibly and has a high disability rate. Numerous studies have confirmed that abnormal osteogenic-adipogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) is one of the major factors of SANFH. However, the mechanism remains to be elucidated. OBJECTIVES: This study aimed to investigate the mechanism and effect of the IFT80/Hedgehog-mediated osteogenic-adipogenic differentiation of BM-MSCs in SANFH. METHODS: Femoral head specimens of SANFH patients and femoral neck fractures (FNF) patients were collected to detect the expression of IFT80, Shh and osteogenic-adipogenic differentiation-related genes by immunohistochemistry (IHC), western blot (WB) and Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR). Based on the rabbit SANFH model, the mRNA expression and protein level of IFT80 and Shh were detected by RT-qPCR and WB. After the osteogenic/adipogenic differentiation based on rabbit BM-MSCs, the IFT80, Gli1, PPAR-γ, and Runx2 expression were detected. Differences in alkaline phosphodiesterase activity, calcium nodule, quantification/distribution of lipid droplets, expression of IFT80/Hedgehog axis, and the level of osteogenic- adipogenic associated factors were determined after IFT80 overexpression. RESULTS: RT-qPCR, WB and IHC revealed that IFT80 and Shh lowly expressed in the osteoblasts and intra-trabecular osteocytes at the edge of trabeculae and in the intercellular matrix of the bone marrow lumen in the SANFH specimens. The Runx2 expression was low, while the PPAR-γ expression was high in both human specimens and animal models of SANFH, suggesting that the balance of osteogenic-adipogenic differentiation was dysregulated. Rabbit BM-MSCs with stable overexpression of IFT80 showed increased alkaline phosphatase activity after induction of osteogenic differentiation, increased calcium nodule production, and decreased adipogenesis after induction of adipogenic differentiation. CONCLUSION: There is a dysregulation of the balance of osteogenic-adipogenic differentiation in SANFH. IFT80 may inhibit adipogenic differentiation while promoting osteogenic differentiation in rabbit BM-MSCs by activating the Hedgehog pathway.
RESUMEN
PURPOSE: There is no consensus in the current literature on the analgesic role of duloxetine after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Thus, we designed this meta-analysis to reveal the analgesic effectiveness and safety of duloxetine in TKA or THA. METHODS: As of October 2022, two authors (L.C. and W.Q.J.) independently searched five main databases (EMBASE, Web of Science, PubMed, Cochrane Library, and Google Scholar) to find relevant studies. Duloxetine vs. placebo in randomized controlled trials (RCTs) for THA or TKA were included. We set perioperative total opioid consumption as the primary outcome. Secondary outcomes included resting or dynamic pain scores over time, gastrointestinal adverse events, neurological adverse events, and other adverse reactions. RESULTS: Eight RCTs with 695 patients were incorporated in our study. This meta-analysis showed high evidence that duloxetine was effective in reducing perioperative opioid consumption (Standard mean difference [SMD] = - 0.50, 95% confidence intervals [CI]: -0.70 to - 0.31, P < 0.00001) and low to moderate evidence that duloxetine could reduce pain within three weeks after surgery. Low to high evidence showed no differences between the two groups for most adverse events. Substantial evidence suggests that duloxetine can reduce nausea and vomiting after surgery (Risk ratio [RR] = 0.69, 95% CI: 0.50 to 0.95, P = 0.02, I2 = 4%). However, moderate evidence suggested that duloxetine might be associated with increased postoperative drowsiness (RR = 1.83, 95% CI: 1.08 to 3.09, P = 0.02, I2 = 0%). CONCLUSION: Duloxetine reduced overall opioid consumption in the perioperative period and relieved pain within three weeks after surgery without increasing the risk of adverse drug events. Duloxetine can be part of a multimodal management regimen in patients with THA and TKA.
Asunto(s)
Analgésicos Opioides , Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Clorhidrato de Duloxetina , Dolor Postoperatorio , Ensayos Clínicos Controlados Aleatorios como Asunto , Clorhidrato de Duloxetina/uso terapéutico , Clorhidrato de Duloxetina/administración & dosificación , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Artroplastia de Reemplazo de Cadera/efectos adversos , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/administración & dosificación , Resultado del Tratamiento , Masculino , FemeninoRESUMEN
With the acceleration of urbanization in recent years, China has witnessed large-scale construction across its provinces, generating massive amounts of construction waste that pose challenges to environmental protection and sustainable development. This study evaluated the impact of construction waste policy intensity on its environmental efficiency. Firstly, the content analysis method was used to analyze the construction waste policy text quantitatively. Second, this study constructed a slack-based measure (SBM) model based on data envelopment analysis (DEA), considering resource input and construction waste output to measure environmental efficiency. Finally, we built and tested an econometric model of how policies affect environmental efficiency using the system generalized method of moments (SYS-GMM). The findings indicate a non-linear U-shaped link between policy intensity and environmental efficiency. Among all five control variables, population density, urbanization level, and technological innovation enhance environmental efficiency, while economic development and highway density will lower it. This study advances the research on construction waste policies and offers some insights for the construction industry to pursue sustainable development.
Asunto(s)
Conservación de los Recursos Naturales , Desarrollo Sostenible , Urbanización , China , Invenciones , Eficiencia , Desarrollo Económico , Política AmbientalRESUMEN
PURPOSE: The purpose of our study is to assess the clinical performance of the DiveScope, a novel handheld histopathologic microscope in rapidly differentiating glioma from normal brain tissue during neurosurgery. METHODS: Thirty-two ex vivo specimens from 18 patients were included in the present study. The excised suspicious tissue was sequentially stained with sodium fluorescein and methylene blue and scanned with DiveScope during surgery. The adjacent tissue was sent to the department of pathology for frozen section examination. They would eventually be sent to the pathology department later for hematoxylin and eosin staining for final confirmation. The positive likelihood ratio, negative likelihood ratio, sensitivity, specificity, and area under the curve of the device were calculated. In addition, the difference in time usage between DiveScope and frozen sections was compared for the initial judgment. RESULTS: The sensitivity and specificity of the DiveScope after analyzing hematoxylin and eosin -staining sections, were 88.29% and 100%, respectively. In contrast, the sensitivity and specificity of the frozen sections histopathology were 100% and 75%, respectively. The area under the curve of the DiveScope and the frozen sections histopathology was not significant ( P =0.578). Concerning time usage, DiveScope is significantly much faster than the frozen sections histopathology no matter the size of tissue. CONCLUSION: Compared with traditional pathological frozen sections, DiveScope was faster and displayed an equal accuracy for judging tumor margins intraoperatively.
Asunto(s)
Glioma , Humanos , Hematoxilina , Eosina Amarillenta-(YS) , Sensibilidad y Especificidad , Coloración y Etiquetado , Glioma/cirugíaRESUMEN
Combined photothermal therapy and nitric oxide (NO)-mediated gas therapy has shown great potential as a cancer treatment. However, the on-demand release of NO at a high concentration presents a challenge owing to the lack of an ideal bio-transducer with a high loading capacity of NO donors and sufficient energy to induce NO release. Here, we present a new 2D BiTiS3 nanosheet that is synthesized, loaded with the NO donor (BNN6), and conjugated with PEG-iRGD to produce a multifunctional bio-transducer (BNN6-BiTiS3-iRGD) for the on-demand production of NO. The BiTiS3 nanosheets not only have a high loading capacity of NO donors (750%), but also exhibit a high photothermal conversion efficiency (59.5%) after irradiation by a 1064-nm laser at 0.5 W/cm2. As a result of the above advantages, the temporal-controllable generation of NO within a large dynamic range (from 0 to 344 µM) is achieved by adjusting power densities, which is among the highest efficiency values reported for NO generators so far. Moreover, the targeted accumulation of BNN6-BiTiS3-iRGD at tumor sites leads to spatial-controllable NO release. In vitro and in vivo assessments demonstrate synergistic NO gas therapy with mild photothermal therapy based on BNN6-BiTiS3-iRGD. Our work provides insights into the design and application of other 2D nanomaterial-based therapeutic platforms.
Asunto(s)
Técnicas Biosensibles , Nanopartículas , Neoplasias , Animales , Óxido Nítrico , Bitis , Luz , Fototerapia , Línea Celular Tumoral , Neoplasias/terapia , Neoplasias/patologíaRESUMEN
The photothermal performance of black phosphorus (BP) in the near infrared (NIR)-II bio-window (1000-1500 nm) is low, which limits its biomedical applications. Herein, ultrasmall nickel phosphide quantum dots (Ni2 P QDs) are synthesized with BP quantum dots (BPQDs) as the template by topochemical transformation. The size of Ni2 P QDs is ≈3.5 nm, similar to that of BPQDs, whereas the absorption and photothermal conversion efficiency of Ni2 P QDs at 1064 nm (43.5%) are significantly improved compared with those of BPQDs. To facilitate in vivo applications, an Ni2 P QDs-based liposomal nano-platform (Ni2 P-DOX@Lipo-cRGD) is designed by incorporation of Ni2 P QDs and doxorubicin (DOX) into liposomal bilayers and the interior, respectively. The encapsulated DOX is responsively released from liposomes upon 1064-nm laser irradiation owing to the photothermal effect of Ni2 P QDs, and the drug release rate and amount are controlled by the light intensity and exposure time. In vivo, experiments show that Ni2 P-DOX@Lipo-cRGD has excellent tumor target capability and biocompatibility, as well as complete tumor ablation through the combination of photothermal therapy and chemotherapy. The work provides a new paradigm for the NIR-II transformation of nano-materials and may shed light on the construction of multifunctional nano-platforms for cancer treatment.
Asunto(s)
Neoplasias , Puntos Cuánticos , Humanos , Fototerapia , Fósforo , Doxorrubicina , Liposomas , Neoplasias/tratamiento farmacológicoRESUMEN
Cascaded inverse fast Fourier transform/fast Fourier transform (IFFT/FFT)-based multi-channel aggregation/de-aggregation offers a promising solution in constructing highly desirable flexible optical transceivers for considerably improving optical networks' elasticity, flexibility, and adaptability. However, the multi-channel aggregation operation unavoidably results in generated signals having high peak-to-average power ratios (PAPRs). To solve this technical challenge, this paper first explores the PAPR characteristics of the corresponding flexible transceivers in optical back-to-back (B2B) and 20 km intensity modulation and direct detection (IMDD) transmission systems, and then numerically investigates the feasibility and effectiveness of utilizing the conventional clipping techniques in reducing their PAPR reductions. The results show that the last IFFT operation size is the primary factor determining the PAPRs rather than the channel count and modulation format. For a given last IFFT operation size, the optimal clipping ratio can be identified, which is independent of channel count. With the identified optimal clipping ratio, when the channel count is >4, every two-channel increase in the channel count can only lead to <1.2 Gb/s decreases in the maximum aggregated signal transmission capacity.
RESUMEN
Cellular apoptosis is a central mechanism leveraged by chemotherapy to treat human cancers. 5-Methylcytosine (m5C) modifications installed on both DNA and mRNA are documented to regulate apoptosis independently. However, the interplay or crosstalk between them in cellular apoptosis has not yet been explored. Here, we reported that promoter methylation by DNMT1 coordinated with mRNA methylation by NSun2 to regulate osteosarcoma cell apoptosis. DNMT1 was induced during osteosarcoma cell apoptosis triggered by chemotherapeutic drugs, whereas NSun2 expression was suppressed. DNMT1 was found to repress NSun2 expression by methylating the NSun2 promoter. Moreover, DNMT1 and NSun2 regulate the anti-apoptotic genes AXL, NOTCH2, and YAP1 through DNA and mRNA methylation, respectively. Upon exposure to cisplatin or doxorubicin, DNMT1 elevation drastically reduced the expression of these anti-apoptotic genes via enhanced promoter methylation coupled with NSun2 ablation-mediated attenuation of mRNA methylation, thus rendering osteosarcoma cells to apoptosis. Collectively, our findings establish crosstalk of importance between DNA and RNA cytosine methylations in determining osteosarcoma resistance to apoptosis during chemotherapy, shedding new light on future treatment of osteosarcoma, and adding additional layers to the control of gene expression at different epigenetic levels.
Asunto(s)
Neoplasias Óseas , Osteosarcoma , Humanos , Metilación , ARN Mensajero/genética , Citosina , ADN , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/genética , Apoptosis/genéticaAsunto(s)
Enfermedad de la Arteria Coronaria , Hiperlipoproteinemia Tipo II , Humanos , Enfermedad de la Arteria Coronaria/epidemiología , Anticuerpos Monoclonales Humanizados , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genéticaRESUMEN
BACKGROUND: Steroid-induced Avascular Necrosis of the Femoral Head (SANFH) is a condition characterized by the necrosis of the femoral head caused by long-term or high-dose hormone usage. Studies have shown that the PI3K/AKT pathway plays a crucial regulatory role in the development of SANFH. The aim of this study is to determine how external environmental factors induce changes in endogenous hormone levels, how these changes lead to steroid-induced femoral head necrosis, and the interrelationship between the changes in PIK3R5 promoter methylation levels and the regulation of the associated signaling pathways. METHODS: Femoral head samples underwent molecular sequencing analysis. Candidate genes were screened by differential gene analysis and functional enrichment analysis.Methylation level of candidate gene PIK3R5 was verified by methylation-specific PCR(MS-PCR). SANFH model was constructed in New Zealand white rabbits, and the model results were verified by magnetic resonance imaging (MRI) and haematoxylin-eosin (HE) staining.The expression of PIK3R5, PI3K and AKT in rabbit models and human specimens was verified by real-time fluorescence quantitative PCR(RT-qPCR) and Western Blot(WB), respectively. RESULTS: Human femoral head sequencing results indicate distinct differences in the methylation level and mRNA expression of PIK3R5 in SANFH. MS-PCR results showed the methylation level of SANFH patients was significantly higher than that of the control group (P < 0.01). The RT-qPCR results showed that PIK3R5 and PI3K expression levels in the SANFH group were lower than those in the control group (P < 0.05), and the WB experiment results were consistent with the RT-qPCR results. The MRI and HE staining results showed that the rabbit model of SANFH was successfully constructed, and the results of RT-qPCR and WB were consistent with the results of human tissues. CONCLUSION: During the occurrence and development of SANFH, PIK3R5 gene regulates the PI3K/AKT pathway through methylation modification, promotes the oxidative stress response of cells, and accelerates the disease process.
Asunto(s)
Necrosis de la Cabeza Femoral , Humanos , Animales , Conejos , Necrosis de la Cabeza Femoral/inducido químicamente , Necrosis de la Cabeza Femoral/genética , Necrosis de la Cabeza Femoral/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/farmacología , Metilación , Cabeza Femoral/metabolismo , Cabeza Femoral/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/farmacología , Esteroides/toxicidad , Esteroides/metabolismo , Hormonas/metabolismoRESUMEN
During the last decades, the ever-increasing incidence of various diseases, like cancer, has led to a high rate of death worldwide. On the other hand, conventional modalities (such as chemotherapy and radiotherapy) have not indicated enough efficiency in the diagnosis and treatment of diseases. Thus, potential novel approaches should be taken into consideration to pave the way for the suppression of diseases. Among novel approaches, biomaterials, like chitosan nanoparticles (CS NPs, N-acetyl-glucosamine and D-glucosamine), have been approved by the FDA for some efficient pharmaceutical applications. These NPs owing to their physicochemical properties, modification with different molecules, biocompatibility, serum stability, less immune response, suitable pharmacokinetics and pharmacodynamics, etc. have received deep attention among researchers and clinicians. More importantly, the impact of CS polysaccharide in the synthesis, preparation, and delivery of metallic NPs (like gold, silver, and magnetic NPs), and combination of CS with these metallic NPs can further facilitate the diagnosis and treatment of diseases. Metallic NPs possess some features, like converting NIR photon energy into thermal energy and anti-microorganism capability, and can be a potential candidate for the diagnosis and treatment of diseases in combination with CS NPs. These combined NPs would be efficient pharmaceuticals in the future.
RESUMEN
Numerous studies have been conducted on fiber-reinforced concrete; however, comparative investigations specifically focusing on the utilization of fibers in CLSM remain limited. In this study, we conducted a systematic investigation into the mechanical properties of controlled low-strength material (CLSM) by manipulating the length and doping amount of fibers as control variables. The 7-day compressive strength (7d-UCS), 28-day compressive strength (28d-UCS), and 28-day splitting strength of CLSM were employed as indicators to evaluate the material's performance. Based on our comprehensive analysis, the following conclusions were drawn: (1) A positive correlation was observed between fiber length and material strength within the range of 0-6 mm, while conversely, a negative correlation was evident. Similarly, when the fiber doping was within the range of 0-0.3%, a positive correlation was identified between material strength and fiber doping. However, the strength of CLSM decreased when fiber doping exceeded 0.3%. (2) SEM and PCAS analyses provided further confirmation that the incorporation of fibers effectively reduced the porosity of the material by filling internal pores and interacting with hydration products, thereby forming a mesh structure. Overall, this study offers valuable insights into the manipulation of fiber length and doping amount to optimize the mechanical properties of CLSM. The findings have important implications for the practical application of CLSM, particularly in terms of enhancing its strength through fiber incorporation.
RESUMEN
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease closely related to inflammation. Cuproptosis is a newly discovered unique type of cell death, and it has been found that it may play an essential role in the occurrence and development of RA. Therefore, we intend to explore the potential association between cuproptosis-related genes (CRGs) and RA to provide a new biomarker for the treatment and prognosis of RA. Methods: Download GSE93777 datasets from the GEO database. Variance analysis was performed on the CRGs that had been reported. Then, the random forest (RF) model and nomogram of differentially expressed CRGs were constructed, and the ROC curve was used to evaluate the accuracy of the diagnostic model. Next, RA patients were subtyped by consensus clustering, and immune infiltration was analyzed in each subgroup to confirm the correlation between CRGs and abundance of immune cells. The expression levels of CRGs were verified by qRT-PCR. Results: Eight differentially expressed CRGs (DLST, DLD, PDHB, PDHA1, ATP7A, CDKN2A, LIAS, DLAT) were screened out by differential analysis to construct an RF model. The ROC curve proved that this model had good diagnostic accuracy. Based on the above eight significant CRGs, a nomogram was built to predict effective and high-precision results. The consensus clustering method identified two CRG patterns. Most of the immune cells were enriched in cluster A, indicating that cluster A may be related to the development of RA. Finally, qRT-PCR verified the expression of eight key genes, further confirming our findings. Conclusion: The diagnosis model of RA based on the above eight CRGs has excellent diagnostic potential. Based on these, patients can be divided into two different molecular subtypes; it is expected to develop a new treatment strategy for RA.
Asunto(s)
Apoptosis , Artritis Reumatoide , Enfermedades Autoinmunes , Humanos , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/genética , Muerte Celular , Análisis por Conglomerados , Inflamación , CobreRESUMEN
Development of specific signal reporters with signal amplification effect are highly needed for sensitive and accurate detection of pathogen. Herein, we design a colorimetric immunosensing nanosystem based on liposome encapsulated quantum dots-sized MnO2 nanozyme (MnO2QDs@Lip) as a signal reporter for ultrasensitive and fast detection of SARS-CoV-2 antigen. The pathogenic antigens captured and separated by antibody-conjugated magnetic beads (MBs) are further connected with antibody-modified MnO2QDs@Lip to form a sandwich-like immunocomplex structure. After triggered release, MnO2 QDs efficiently catalyze colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB, which can be qualitatively observed by naked eyes and quantitatively analyzed by UV-Vis spectra or smartphone platforms. By taking advantages of immuno-magnetic separation, excellent peroxidase-like catalytic activity of MnO2 QDs, and high encapsulation efficiency of MnO2QDs@Lip, ultrasensitive detection of SARS-CoV-2 antigen ranging from 0.1 pg/mL to 100 ng/mL is achieved within 20 min. The limit of detection (LOD) is calculated to be 65 fg/mL in PBS buffer. Furthermore, real clinical samples of SARS-CoV-2 antigens can be effectively identified by this immunosensing nanosystem with excellent accuracy. This proposed detection nanosystem provides a strategy for simple, rapid and ultrasensitive detection of pathogens and may shed light on the development of new POCT detection platforms for early diagnosis of pathogens and surveillance in public health.
Asunto(s)
Técnicas Biosensibles , Colorimetría , Inmunoensayo , SARS-CoV-2 , Colorimetría/métodos , Técnicas Biosensibles/métodos , Inmunoensayo/métodos , Liposomas/química , Antígenos Virales/análisis , Antígenos Virales/inmunología , SARS-CoV-2/química , SARS-CoV-2/inmunología , NanopartículasRESUMEN
BACKGROUND: Osteosarcoma (OS) is the most prevalent orthopedic malignancy with a dismal prognosis. The high iron absorption rate in OS cells of patients suggests that ferroptosis may be related to the progression of OS, but its potential molecular regulatory role is still unclear. Based on the ability to couple with exosomes for targeted delivery of signals, exosome-derived micro ribonucleic acids (miRNAs) can potentially serve as diagnostic biomarkers for OS. METHODS: We identified ferroptosis-related miRNAs and messenger ribonucleic acids(mRNAs) in OS using bioinformatics analysis and performed survival analysis. Then we measured miRNA expression levels through exosome microarray sequencing, and used RT-qPCR and IHC to verify the expression level of miR-144-3p and ZEB1. Stable gene expression cell lines were fabricated for in vitro experiments. Cell viability, migration and invasion were determined by CCK-8 and transwell experiment. Use the corresponding reagent kit to detect GSH/GSSG ratio, Fe2+ level, MDA level and ROS level, and measure the expression levels of GPX4, ACSL4 and xCT through RT-qPCR and WB. We also constructed nude mice model for in vivo experiments. Finally, the stability of the miRNA/mRNA axis was verified through functional rescue experiments. RESULTS: Low expression of miR-144-3p and high expression of ZEB1 in OS cell lines and tissues was observed. Overexpression of miR-144-3p can promote ferroptosis, reduce the survival ability of OS cells, and prevent the progression of OS. In addition, overexpression of miR-144-3p can downregulate the expression of ZEB1 in cell lines and nude mice. Knockdown of miR-144-3p has the opposite effect. The functional rescue experiment validated that miR-144-3p can regulate downstream ZEB1, and participates in the occurrence and development of OS by interfering with redox homeostasis and iron metabolism. CONCLUSIONS: MiR-144-3p can induce the occurrence of ferroptosis by negatively regulating the expression of ZEB1, thereby inhibiting the proliferation, migration, and invasion of OS cells.
Asunto(s)
Neoplasias Óseas , Exosomas , Ferroptosis , MicroARNs , Osteosarcoma , Animales , Ratones , Neoplasias Óseas/patología , Línea Celular Tumoral , Proliferación Celular/genética , Exosomas/metabolismo , Ferroptosis/genética , Hierro , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , Osteosarcoma/patología , HumanosRESUMEN
As a common tumor with high incidence, osteosarcoma possesses extremely poor prognosis and high mortality. Improving the survival of osteosarcoma patients is still a great challenge due to the precipice of advancement in treatment. In this study, a combination strategy of gene therapy and photothermal therapy (PTT) is developed for efficient treatment of osteosarcoma. Two-dimensional (2D) FePS3 nanosheets are synthesized and functionalized by poly-L-lysine-PEG-folic acid (PPF) to fabricate a multifunctional nanoplatform (FePS@PPF) for further loading microRNAs inhibitor, miR-19a inhibitor (anti-miR-19a). The photothermal conversion efficiency of FePS@PPF is up to 47.1% under irradiation by 1064 nm laser. In vitro study shows that anti-miR-19a can be efficiently internalized into osteosarcoma cells through the protection and delivery of FePS@PPF nanaocarrier, which induces up-regulation of PTEN protein and down-regulation p-AKT protein. After intravenous injection, the FePS@PPF nanoplatform specifically accumulates to tumor site of osteosarcoma-bearing mice. The in vitro and in vivo investigations reveal that the combined PTT-gene therapy displays most significant tumor ablation compared with monotherapy. More importantly, the good biodegradability promotes FePS@PPF to be cleared from body avoiding potential toxicity of long-term retention. Our work not only develops a combined strategy of NIR-II PTT and gene therapy mediated by anti-miR-19a/FePS@PPF but also provides insights into the design and applications of other nanotherapeutic platforms.