RESUMEN
Histone lysine N-methyltransferase 2C (KMT2C) is involved in transcriptional regulation and DNA damage repair. Mutations in KMT2C have been implicated in the progression, metastasis, and drug resistance of multiple cancer types. However, the roles of KMT2C in the regulation of tumor prognosis, immune cell infiltration and the immune microenvironment in these multiple cancer types remain unclear. Therefore, in the present study, data from The Cancer Genome Atlas and Genotype-Tissue Expression databases were used for KMT2C expression analyses. Kaplan-Meier and univariate Cox regression analyses were also performed to investigate the prognostic role of KMT2C. In addition, Gene Set Enrichment Analysis (GSEA) was conducted to study the KMT2C-related signaling pathways. Tumor immune estimation resource 2 and single-sample GSEA were conducted to investigate the correlation between KMT2C expression and immune cell infiltrations, and Spearman's analysis was conducted to study the correlations among KMT2C, tumor mutational burden, microsatellite instability, immune regulators, chemokines and immune receptors. Immunohistochemistry of patient kidney tumor samples was performed to verify the correlation between KMT2C and programmed death-ligand 1 (PD-L1) expression. Finally, RNA interference, wound healing and colony formation assays were conducted to evaluate the effects of KMT2C expression on cell proliferation and metastasis. The results of the present study demonstrated that KMT2C was highly expressed in multiple cancer types, was a protective factor in kidney renal clear cell carcinoma and ovarian serous cystadenocarcinoma, and a risk factor for lung squamous cell carcinoma and uveal melanoma. In addition, KMT2C levels were negatively correlated with immune-activated pathways and the infiltration of immune cells, and positively correlated with inhibitory immune factors and tumor angiogenesis. Patients with low KMT2C expression had higher objective response rates to immunotherapy, and drug sensitivity analysis indicated that topoisomerase, histone deacetylase, DOT1-like histone H3K79 methyltransferase and G9A nuclear histone lysine methyltransferase inhibitors could potentially be used to treat tumors with high KMT2C expression levels. Finally, the KMT2C and PD-L1 expression levels were shown to be positively correlated, and KMT2C knockdown markedly promoted the proliferation and invasion capacities of A549 cells. In conclusion, the present study revealed that low KMT2C expression may be a promising biomarker for predicting the response of patients with cancer to immunotherapy. Conversely, high KMT2C expression was shown to promote tumor angiogenesis, which may contribute to the formation of the immunosuppressive tumor microenvironment.
RESUMEN
The achievement of both efficiency and stability in perovskite solar cells (PSCs) remains a challenging and actively researched topic. In particular, among different environmental factors, ultraviolet (UV) photons play a pivotal role in contributing to device degradation. In this work, by harvesting simultaneously both the optical and the structural properties of bottom-up-synthesized colloidal carbon quantum dots (CQDs), a cost-effective means is provided to circumvent the UV-induced degradation in PSCs without scarification on their power conversion efficiencies (PCEs). By exploring and optimizing the number of CQDs and the different locations/interfaces of the solar cells where CQDs are applied, a synergetic configuration is achieved where the photovoltaic performance drop due to optical loss is completely compensated by the increased perovskite crystallinity due to interfacial modification. As a result, on the optimized configurations where CQDs are applied both on the exterior front side as an optical layer and at the interface between the electron transport layer and the perovskite absorber, unencapsulated PSCs with PCEs >20% are fabricated which can maintain up to ≈94% of their initial PCE after 100 h of degradation in ambient air under continuous UV illumination (5 mW cm-2).
RESUMEN
Several microRNAs (miRNAs) are expressed at lower levels in specific tumors, e.g., miR-let-7a in non-small cell lung cancer (NSCLC). This makes it challenging to analyze their lower abundance versus specifically elevated miRNAs. Here, we describe a novel fluorescent biosensor for the highly selective and sensitive detection of miR-let-7a constructed by combining miRNA screening assisted by a duplex-specific nuclease (DSN) with CRISPR-Cas12a system signal amplification. We meticulously designed a mismatch in the first three to four bases at the 5'-end of the capture DNA to improve the signal-to-noise ratio of the CRISPR-Cas12a system. Within this "DSN-mismatched CRISPR" fluorescence strategy, miR-let-7a was accurately screened by DSN-assisted cleavage, and the mismatched capture DNA unbound to target miRNA could trigger the CRISPR-Cas12a system to produce a mass of trans-cleave fluorescence signals. This "turn-off" approach was suitable for detecting decreased levels of miRNAs. This approach can not only discriminate the single-base mismatched let-7 family but also reach a limit of detection at 64.17 fM as well as be quantified from 100 fM to 500 pM. The miR-let-7a levels were then measured in clinical serum samples from healthy volunteers and patients with NSCLC. This study holds promise for the development of a universal under-expressed miRNA assay for early diagnosis and treatment of cancers.
Asunto(s)
Técnicas Biosensibles , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , MicroARNs/genética , ADN , ColorantesRESUMEN
It has been reported that CDK8 plays a key role in acute myeloid leukaemia. Here, a total of 40 compounds were rational designed and synthesised based on the previous SAR. Among them, compound 12 (3-(3-(furan-3-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide) showed the most potent inhibiting activity against CDK8 with an IC50 value of 39.2 ± 6.3 nM and anti AML cell proliferation activity (molm-13 GC50 = 0.02 ± 0.01 µM, MV4-11 GC50 = 0.03 ± 0.01 µM). Mechanistic studies revealed that this compound 12 could inhibit the phosphorylation of STAT-1 and STAT-5. Importantly, compound 12 showed relative good bioavailability (F = 38.80%) and low toxicity in vivo. This study has great significance for the discovery of more efficient CDK8 inhibitors and the development of drugs for treating AML in the future.
Asunto(s)
Leucemia Mieloide Aguda , Humanos , Disponibilidad Biológica , Leucemia Mieloide Aguda/tratamiento farmacológico , Fosforilación , Quinasa 8 Dependiente de CiclinaRESUMEN
Copper-induced cell death, also known as cuproptosis, is distinct from other types of cell death such as apoptosis, necrosis, and ferroptosis. It can trigger the accumulation of lethal reactive oxygen species, leading to the onset and progression of aging. The significant increases in copper ion levels in the aging populations confirm a close relationship between copper homeostasis and vascular aging. On the other hand, vascular aging is also closely related to the occurrence of various cardiovascular diseases throughout the aging process. However, the specific causes of vascular aging are not clear, and different living environments and stress patterns can lead to individualized vascular aging. By exploring the correlations between copper-induced cell death and vascular aging, we can gain a novel perspective on the pathogenesis of vascular aging and enhance the prognosis of atherosclerosis. This article aims to provide a comprehensive review of the impacts of copper homeostasis on vascular aging, including their effects on endothelial cells, smooth muscle cells, oxidative stress, ferroptosis, intestinal flora, and other related factors. Furthermore, we intend to discuss potential strategies involving cuproptosis and provide new insights for copper-related vascular aging.
Asunto(s)
Cobre , Células Endoteliales , Cobre/farmacología , Muerte Celular , Apoptosis , HomeostasisRESUMEN
Products made from allogeneic tissue are largely used in clinical treatment due to its wide source compared with autologous tissue, causing less secondary trauma of patients and the good biocompatibility. Various organic solvents and other substances introduced in the production process of allogeneic products will leach down into the human through clinical treatment, thus bringing varying degrees of harm to patients. Therefore, it is very necessary to detect and control the leachables in such products. Based on the classification and summary of leachable substances existing in the allogeneic products, the preparation of extract and the establishment of the detection techniques for known and unknown leachable are briefly introduced in this study, in order to provide research method for the study of leachable substances of allogeneic products.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Humanos , Embalaje de MedicamentosRESUMEN
Synovial angiogenesis is essential for the development of rheumatoid arthritis (RA). Human vascular endothelial growth factor receptor 2 tyrosine kinase (VEGFR2) is a direct target gene that is notably elevated in RA synovium. Herein, we report the identification of indazole derivatives as a novel class of potent VEGFR2 inhibitors. The most potent compound, compound 25, displayed single-digit nanomolar potency against VEGFR2 in biochemical assays and achieved good selectivity for other protein kinases in the kinome. In addition, compound 25 dose-dependently inhibited the phosphorylation of VEGFR2 in Human Umbilical Vein Endothelial Cells (HUVECs) and showed an anti-angiogenic effect, as evidenced by the inhibition of capillary-like tube formation in vitro. Moreover, compound 25 reduced the severity and development of adjuvant-induced arthritis in rats by inhibiting synovial VEGFR2 phosphorylation and angiogenesis. Overall, these findings provide evidence that compound 25 is a leading potential drug candidate for anti-arthritic and anti-angiogenic therapy.
Asunto(s)
Artritis Reumatoide , Transducción de Señal , Ratas , Humanos , Animales , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proliferación Celular , Neovascularización Patológica/tratamiento farmacológico , Células Endoteliales de la Vena Umbilical Humana , Artritis Reumatoide/tratamiento farmacológicoRESUMEN
BACKGROUND: Emerging studies indicated that circular RNA hsa_circ_ 0023404 and its target miR-217/MARK1 axis play a critical role in cancer progression such as non-small cell lung cancer and cervical cancer. However, the role of hsa_circ_0023404/miR-217/MARK1 involved in endometrial cancer (EC) was not investigated yet. The aim of this study is to investigate the functions of hsa_circ_0023404 in endometrial cancer (EC) and the potential molecular mechanism. METHODS: We used RT-qPCR and Western blot approach to detect the expressed levels of related genes in EC cell lines. Transfected siRNAs were applied to knockdown the level of related mRNA in cells. Cell proliferation by CCK-8 assay and colony formation assay were applied to detect cell proliferation. Transwell migration and invasion assay was for detecting the migration and invasion of the cells. RESULTS: RT-qPCR showed that the levels of hsa_circ_0023404 and MARK1 mRNA were upregulated, but mirR-217 was decreased in three endometrial cancer cell lines. Knockdown of hsa_circ_0023404 by siRNA markedly increased the level of miR-217 and reduced the proliferation of the Ishikawa cells. It also inhibited the cell migration and invasion. Anti-miR-217 can reverse the promoted proliferation, migrations and invasion of Ishikawa cells mediated by si-circ_0023404. si-MARK1 restored the inhibited cell proliferation, migration and invasion of the co-transfected Ishikawa cells with si- circ_0023404 and anti-miR-217. CONCLUSION: hsa_circ_0023404 exerts a tumor-promoting role in endometrial cancer by regulating miR-217/MARK1 axis. hsa_circ_0023404 inhibit miR-217 as sponge which inhibit endometrial cancer cell growth and metastasis. MARK1 is downstream target of miR217 and upregulated by hsa_circ_ 0023404/miR-217 axis and involved in the endometrial cancer progression.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Endometriales , Neoplasias Pulmonares , MicroARNs , Femenino , Humanos , ARN Circular/genética , Antagomirs , Carcinoma de Pulmón de Células no Pequeñas/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , Proliferación Celular/genética , Movimiento Celular/genética , Neoplasias Endometriales/genética , ARN Interferente Pequeño , ARN Mensajero , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 1 Activada por Mitógenos/metabolismoRESUMEN
Recent attempts to improve solar cell performance by increasing their spectral absorption interval incorporate up-converting fluorescent nanocrystals on the structure. These nanocrystals absorb low energy light and emit higher energy photons that can then be captured by the solar cell active layer. However, this process is very inefficient and it needs to be enhanced by different strategies. In this work, we have studied the effect of nanostructuration of perovskite thin films used in the fabrication of hybrid solar cells on their local optical properties. The perovskite surface was engraved with a focused ion beam to form gratings of one-dimensional grooves. We characterized the surfaces with a fluorescence scanning near-field optical microscope, and obtained maps showing a fringe pattern oriented in a direction parallel to the grooves. By scanning structures as a function of the groove depth, ranging from 100 nm to 200 nm, we observed that a 3-fold luminescence enhancement could be obtained for the deeper ones. Near-field luminescence was found to be enhanced between the grooves, not inside them, independent of the groove depth and the incident polarization direction. This indicates that the ideal position of the nanocrystals is between the grooves. In addition, we also studied the influence of the inhomogeneities of the perovskite layer and we observed that roughness tends to locally modify the intensity of the fringes and distort their alignment. All the experimental results are in good agreement with numerical simulations.
RESUMEN
With the rapid development of my country's hemodialysis industry, the application of hemodialysis machines has become more and more extensive, but at the same time, the quality control technology of hemodialysis machines is not perfect. Especially for a wide range of leachable substances in dialyzers, there are few studies and detection methods. This study first briefly describes the development of hemodialyzers, and then expounds the common types of leachables, extraction methods, and chromatography and mass spectrometry conditions. It is summarized that the research plan of leachable substances is to determine the type first, then formulate the extraction plan, and then establish the detection method. Finally, we look forward to the research prospects of hemodialyzer leachables, and point out that with the deepening and extensive development of research, it can further promote the healthy development of the hemodialyzer industry.
Asunto(s)
Fallo Renal Crónico , Riñones Artificiales , Humanos , Fallo Renal Crónico/terapia , Diálisis RenalRESUMEN
MicroRNA (miRNA/miR)-409-5p has been reported to be implicated in prostate and breast cancers; however, its functional role in ovarian cancer (OC) remains unclear. Therefore the aim of the present study was to investigate the clinical significance and biological function of miR-409-5p in OC. Here, reverse transcription-quantitative PCR analysis was performed to detect miR-409-5p expression in OC tissues and cell lines. The association between miR-409-5p expression and the clinicopathological characteristics of patients with OC was assessed using the Fisher's exact test. Furthermore, the Cell Counting Kit-8 assay was performed to assess cell proliferation. Cell cycle distribution and apoptosis were evaluated via flow cytometric analysis, and the target gene of miR-409-5p was validated via the dual-luciferase reporter assay. The results demonstrated that miR-409-5p expression was significantly downregulated in OC tissues and cell lines compared with adjacent normal tissues and epithelial cells, respectively. In addition, low miR-409-5p expression was significantly associated with tumor size (P=0.044) and the International Federation of Gynecology and Obstetrics staging system (P=0.005). Notably, overexpression of miR-409-5p suppressed cell proliferation, and induced G2/M phase arrest and apoptosis of OC cells. Mechanistically, discs large-associated protein 5 (DLGAP5) was identified as a novel target of miR-409-5p, which was negatively regulated by miR-409-5p. DLGAP5 expression was significantly upregulated in OC tissues and cell lines compared with adjacent normal tissues and epithelial cells, respectively. Furthermore, overexpression of DLGAP5 reversed the effects of miR-409-5p on SKOV-3 cell proliferation, and G2/M phase and apoptosis. Taken together, these results suggest that miR-409-5p acts as a tumor suppressor in OC by modulating DLGAP5 expression.
RESUMEN
Osteoporosis is a bone metabolic disease characterized by reduced bone mass and deterioration of bone tissue microarchitecture, leading to enhanced skeletal fragility and susceptibility to fracture. Unbalanced bone remodeling is the primary pathogenetic factor of osteoporosis, in which osteoclast-mediated bone resorption exceeds osteoblast-mediated bone formation. Bisphosphonates and calcitonin are among the drugs commonly used to treat osteoporosis, in addition to the bone nutrients vitamin D and calcium supplements. The current treatments effectively prevent further bone loss by inhibiting the excessive activation of osteoclasts, accompanied by various degrees of side effects. Iron, one of the trace elements essential for life activities, has recently been recognized as an independent risk factor for osteoporosis. Abnormal iron metabolism increases the incidence of many bone diseases, especially osteoporosis. Iron metabolism does play a key role in bone homeostasis. Ferroptosis is a novel form of cell death that has been discovered in recent years. Its main features include iron overload and the accumulation of ROS. And lipid peroxidation is the key. There are increasing shreds of evidence that ferroptosis is involved in the occurrence and development of osteoporosis, and its regulation can effectively prevent osteoporosis. Therefore, this review further elucidates the role of ferroptosis in osteoporosis based on the mechanism and its relationship with osteoporosis and provides a new idea for treating osteoporosis.
Asunto(s)
Conservadores de la Densidad Ósea , Ferroptosis , Osteoporosis , Densidad Ósea , Conservadores de la Densidad Ósea/farmacología , Conservadores de la Densidad Ósea/uso terapéutico , Humanos , Hierro/metabolismo , Hierro/uso terapéutico , Osteoporosis/tratamiento farmacológico , Osteoporosis/metabolismoRESUMEN
Polypyrrole (PPy) is a conductive polymer and widely applied in different applications owing to its broadband absorption in the UV-visible, near-infrared (NIR), and short-wave-infrared (SWIR) spectrum, excellent conductivity, and strong photothermal effect. In this work, we explored for the first time the photothermal effect of PPy nanoparticles (PPy-NPs) in a photothermal-induced detector structure and developed a new type of air-stable hybrid PPy-NPs/Pt photodetector (PD) with NIR/SWIR sensitivity. By combining PPy-NPs with a platinum (Pt)-resistive pattern, we fabricated PPy-NPs/Pt PDs that are sensitive to illumination in the wavelength range from 800 to 2000 nm. Under the illumination of λ = 1.5 µm, the maximum photoresponsivity was measured to be â¼1.3 A/W with a 131 µs photoresponse rise time. Owing to the excellent material stability from both PPy-NPs and the Pt pattern, the current photodetectors show long-term stable photoresponsivity when they were stored in air without encapsulation. The results suggest that the PPy-NPs/Pt hybrid PDs are promising candidates for a new type of low-cost and broadband due to their multiple advantages such as free of toxic heavy metals, air stability, and solution processing.
RESUMEN
Microwave photoconductive switches, allowing an optical control on the magnitude and phase of the microwave signals to be transmitted, are important components for many optoelectronic applications. In recent years, there are significant demands to develop photoconductive switches functional in the short-wave-infrared spectrum window (e.g.λ = 1.3-1.55µm) but most state-of-the-art semiconductors for photoconductive switches cannot achieve this goal. In this work, we propose a novel approach, by the use of solution-processed colloidal upconversion nanocrystals deposited directly onto low-temperature-grown gallium arsenide (LT-GaAs), to achieve microwave photoconductive switches functional atλ = 1.55µm illumination. Hybrid upconversion Er3+-doped NaYF4nanocrystal/LT-GaAs photoconductive switch was fabricated. Under a continuous waveλ = 1.55µm laser illumination (power density â¼ 12.9 mWµm-2), thanks to the upconversion energy transfer from the nanocrystals, a more than 2-fold larger value in decibel was measured for the ON/OFF ratio on the hybrid nanocrystal/LT-GaAs device by comparison to the control device without upconversion nanoparticles. A maximum ON/OFF ratio reaching 20.6 dB was measured on the nanocrystal/LT-GaAs hybrid device at an input signal frequency of 20 MHz.
RESUMEN
Considerable researches implicate that the circadian clock regulates the responsive rhythms of organs and sets the orderly aging process of cells indirectly. It influences an array of diverse biological process including intestinal flora, peripheral inflammatory responses, and redox homeostasis. People with sleep disoders and other kinds of circadian disruptions are prone to have vascular aging earlier. Meanwhile, those people are always faced with chronic vascular inflammation. It has not been elucidated that the specific mechanism of the interaction between the circadian system and early vascular aging. To explore the biphasic relationship between vascular aging and the circadian system, we summarize what is linking circadian clock with early vascular aging through four major prospect: inflammatory process, oxidative stress response, intestinal flora, and cellular senescence. Meanwhile, we discuss the hypothesis that the deterioration of circadian rhythms may exacerbate the process of early vascular aging, leading to the cardiovascular diseases. It will help us to provide new ideas for understanding the process of vascular aging and exploring the possible ways to design personalized chronotherapies.
Asunto(s)
Relojes Circadianos , Ritmo Circadiano , Estrés Oxidativo , SueñoRESUMEN
Osteopontin (OPN) is an important protein for mediating cell behaviour on biomaterials. However, the interactions between the chemical groups on the biomaterial surface and OPN still need to be further clarified, which has restricted the application of OPN in biomaterial functionalization. In the present study, we developed different self-assembled monolayers (SAMs) with specific chemical groups, including SAMs-OH, SAMs-OEG, SAMs-COOH, SAMs-NH2, and SAMs-PO3H2, to study the behavior of OPN on these SAMs. The results showed that SAMs-NH2 could strongly adsorb OPN, and the amount of protein was highest on this material. Meanwhile, the lowest amount of OPN was present on SAMs-OEG. Interestingly, the unit-mass trend of bound OPN monoclonal antibodies (mAbs) on the SAMs was opposite to the OPN adsorption trend: lowest on SAMs-NH2 but highest on SAMs-OEG. In vitro cell assay results showed that mouse bone marrow mesenchymal stem cells (mBMSCs) on SAMs-COOH, SAMs-NH2, and SAMs-PO3H2 with pre-adsorbed OPN showed promoted behaviour, in terms of spreading, viability, and the expression levels of αv and ß3 genes, compared with the other two SAMs, demonstrating the higher bioactivity of the adsorbed OPN. We believe that our findings will have great potential for developing OPN-activated biomaterials.
RESUMEN
Metal halide perovskites are promising contenders for next-generation photovoltaic applications due to their remarkable photovoltaic efficiency and their compatibility with solution-processed fabrication. Among the various strategies to control the crystallinity and the morphology of the perovskite active layer and its interfaces with the transport layers, fabrication of perovskite solar cells from precursor solutions with a slight excess of PbI2 has become very common. Despite this, the role of such excess PbI2 is still rather controversial, lacking consensus on its effect on the bulk and interface properties of the perovskite layer. In this work, we investigate the effect of removing the excess PbI2 from the surface of a triple-cation mixed-halide Cs0.05(FA0.83MA0.17)0.95Pb(I0.83Br0.17)3 perovskite layer by four different organic salts on their photovoltaic performance and stability. We show that treatments with iodide salts such as methylammonium iodide (MAI) and formamidinium iodide (FAI) can lead to the strongest beneficial effects on solar cell efficiency, charge recombination suppression, and stability while non-iodide salts such as methylammonium bromide (MABr) and methylammonium chloride (MACl) can also provide improvement in terms of charge recombination suppression and stability to a moderate extent in comparison to the untreated sample. Under optimized conditions and continuous solar illumination, the MAI- and FAI-treated devices maintained 81 and 86% of their initial power conversion efficiency (PCEs), respectively, after 100 h of continuous illumination (versus 64% for the untreated solar cell with excess PbI2). Our study demonstrates that eliminating excess PbI2 at the perovskite/hole transport layer (HTL) interface by treating the perovskite surface with organic salts is a simple and efficient route to enhance the efficiency, and in particular the stability of perovskite solar cells.
RESUMEN
The telecommunication wavelength of λ = 1.5 µm has been playing an important role in various fields. In particular, performing photodetection at this wavelength is challenging, demanding more performance stability and lower manufacturing cost. In this work, upconversion nanoparticle (UCNP)/Si hybrid photodetectors (hybrid PDs) are presented, made by integrating solution-processed Er3+-doped NaYF4 upconversion nanoparticles (UCNPs) onto a silicon photodetector. After optimization, we demonstrated that a layer of UCNPs can well lead to an effective spectral sensitivity extension without sacrificing the photodetection performance of the Si photodetector in the visible and near-infrared (near-IR) spectrum. Under λ = 1.5 µm illumination, the hybrid UCNPs/Si-PD exhibits a room-temperature detectivity of 6.15 × 1012 Jones and a response speed of 0.4 ms. These UCNPs/Si-PDs represent a promising hybrid strategy in the quest for low-cost and broadband photodetection that is sensitive in the spectrum from visible light down to the short-wave infrared.
RESUMEN
Objective: To investigate the effects of Apatinib on the "stemness" of lung cancer cells in vivo and to explore its related mechanisms. Methods: A xenograft model of lung cancer cells A549 was established in nude mice and randomized into a control group (n = 4) and an Apatinib group (n = 4). Tumor tissues were harvested after 2 weeks, and mRNA was extracted to detect changes in stemness-related genes (CD133, EPCAM, CD13, CD90, ALDH1, CD44, CD45, SOX2, NANOG, and OCT4) and Wnt/ß-catenin, Hedgehog, and Hippo signal pathways. Results: Compared with the control group, the volume and weight of nude mice treated with Apatinib were different and had statistical significance. Apatinib inhibited the expressions of ABCG2, CD24, ICAM-1, OCT4, and SOX2 and upregulated the expressions of CD44, CD13, and FOXD3. Apatinib treatment also inhibited the Wnt/ß-catenin, Hedgehog, and Hippo signaling pathways. Conclusion: Apatinib suppressed the growth of non-small-cell lung cancer cells by repressing the stemness of lung cancer through the inhibition of the Hedgehog, Hippo, and Wnt signaling pathways.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/genética , Proliferación Celular/efectos de los fármacos , Neoplasias Pulmonares/genética , Células Madre Neoplásicas/efectos de los fármacos , Piridinas/farmacología , Células A549 , Animales , Antígenos CD13/efectos de los fármacos , Antígenos CD13/genética , Antígenos CD13/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proteínas Hedgehog/efectos de los fármacos , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Vía de Señalización Hippo , Humanos , Receptores de Hialuranos/efectos de los fármacos , Receptores de Hialuranos/genética , Receptores de Hialuranos/metabolismo , Neoplasias Pulmonares/metabolismo , Ratones , Ratones Desnudos , Células Madre Neoplásicas/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/efectos de los fármacos , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Proteínas Serina-Treonina Quinasas/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Factores de Transcripción SOXB1/efectos de los fármacos , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Transducción de Señal , Vía de Señalización Wnt/efectos de los fármacos , Vía de Señalización Wnt/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Organic-inorganic hybrid perovskite solar cells have attracted much attention due to their high power conversion efficiency (>25%) and low-cost fabrication. Yet, improvements are still needed for more stable and higher-performing solar cells. In this work, a series of TiO2 nanocolumn photonic structures have been intentionally fabricated on half of the compact TiO2-coated fluorine-doped tin oxide substrate by glancing angle deposition with magnetron sputtering, a method particularly suitable for industrial applications due to its high reliability and reduced cost when coating large areas. These vertically aligned nanocolumn arrays were then applied as the electron transport layer into triple-cation lead halide perovskite solar cells based on Cs0.05(FA0.83MA0.17)0.95Pb(I0.83Br0.17)3. By comparison to solar cells built onto the same substrate without nanocolumns, the use of TiO2 nanocolumns can significantly enhance the power conversion efficiency of the perovskite solar cells by 7% and prolong their shelf life. Here, detailed characterizations on the morphology and the spectroscopic aspects of the nanocolumns, their near-field and far-field optical properties, solar cells characteristics, as well as the charge transport properties provide mechanistic insights on how one-dimensional TiO2 nanocolumns affect the performance of perovskite halide solar cells in terms of charge transport, light harvesting, and stability, knowledge necessary for the future design of higher-performing and more stable perovskite solar cells.