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In situ visualization of microRNA (miRNA) in cancer cells and diseased tissues is essential for advancing our comprehension of the onset and progression of associated diseases. Two-photon (TP) imaging, as an imaging technology with high spatiotemporal resolution, deep tissue penetration, and accurate target quantification, has distinctive advantages over single-photon imaging and has attracted increasing attention. Extensive research has been conducted on two-photon dye-doped silica nanoparticles, which exhibit a large two-photon absorption (TPA) cross-section, high fluorescence quantum yield, and excellent biocompatibility. However, the low abundance of RNA in tumor cells leads to insufficient signal output. Based on functional nucleic acid, a catalyzed hairpin self-assembly (CHA) signal amplification strategy, which has simplicity, robustness, and nonenzymatic characteristics, can achieve the amplification of DNA or RNA signals. Here, a two-photon silica nanoamplifier (TP-SNA) utilizing TP dye-doped silica nanoparticles (SiNPs) and functional nucleic acid was constructed, employing triggering catalyzed hairpin self-assembly and fluorescence resonance energy transfer (FRET) for highly sensitive detection and precise TP imaging of endogenous miRNAs in tumor cells and tissues at varying depths. The TP-SNA demonstrated the capability to detect miR-203 with a detection limit of 33 pM. The maximum two-photon tissue penetration depth of the two-photon nanoamplifier was 210 µm. The two-photon nanoamplifier developed in this study makes full use of the advantages of accurate TP ratiometric bioimaging and the CHA signal amplification strategy, which shows good application value for future transformation into clinical diagnosis.
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Transferência Ressonante de Energia de Fluorescência , MicroRNAs , Nanopartículas , Fótons , Dióxido de Silício , Dióxido de Silício/química , MicroRNAs/análise , Humanos , Nanopartículas/química , Corantes Fluorescentes/química , Animais , Camundongos , Células HeLaRESUMO
Photodynamic therapy (PDT) is a significant noninvasive therapeutic modality, but it is often limited in its application due to the restricted tissue penetration depth caused by the wavelength limitations of the light source. Two-photon (TP) fluorescence techniques are capable of having an excitation wavelength in the NIR region by absorbing two NIR photons simultaneously, which offers the potential to achieve higher spatial resolution for deep tissue imaging. Thus, the adoption of TP fluorescence techniques affords several discernible benefits for photodynamic therapy. Organic TP dyes possess a high fluorescence quantum yield. However, the biocompatibility of organic TP dyes is poor, and the method of coating organic TP dyes with silica can effectively overcome the limitations. Herein, based on the TP silica nanoparticles, a functionalized intelligent biogenic missile TP-SiNPs-G4(TMPyP4)-dsDNA(DOX)-Aptamer (TGTDDA) was developed for effective TP bioimaging and synergistic targeted photodynamic therapy and chemotherapy in tumors. First, the Sgc8 aptamer was used to target the PTK7 receptor on the surface of tumor cells. Under two-photon light irradiation, the intelligent biogenic missile can be activated for TP fluorescence imaging to identify tumor cells and the photosensitizer assembled on the nanoparticle surface can be activated for photodynamic therapy. Additionally, this intelligent biogenic missile enables the controlled release of doxorubicin (DOX). The innovative strategy substantially enhances the targeted therapeutic effectiveness of cancer cells. The intelligent biogenic missile provides an effective method for the early detection and treatment of tumors, which has a good application prospect in the real-time high-sensitivity diagnosis and treatment of tumors.
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Imagem Óptica , Fotoquimioterapia , Fótons , Fármacos Fotossensibilizantes , Humanos , Animais , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Camundongos , Nanopartículas/química , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Dióxido de Silício/química , Aptâmeros de Nucleotídeos/química , Corantes Fluorescentes/química , Neoplasias/tratamento farmacológico , Neoplasias/diagnóstico por imagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Camundongos Nus , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB CRESUMO
The discovery of reliable biomarkers is essential for early diagnosis, treatment, and prognosis assessment of diseases. Many research studies have shown that circRNA is a potential biomarker for diagnosis and prognosis of diseases. However, in situ monitoring circRNA in live cells is still a challenge at present, which brings a major limitation to the development and verification of circRNA as a disease biomarker. In this study, a catalytic hairpin assembly (CHA) reaction-based DNA octahedral amplifier (DOA) was developed for fluorescence resonance energy transfer (FRET) detection and bioimaging of circRNA in living cells. The DOA was first produced by self-assembling a DNA octahedron with six customized single-stranded DNAs, and two hairpins H1 (Cy3) and H2 (Cy5) were then hybridized to four vertices of the DNA octahedron. Idiopathic pulmonary fibrosis (IPF)-related circHIPK3 was used as the target. Once the CHA reaction from H1 and H2 on DOA was activated by a sequence-specific back-splice junction (BSJ) of circHIPK3, a significant FRET signal can be obtained from Cy3 to Cy5. The circHIPK3 was subsequently released to cause the next CHA reaction. Because the DOA has the advantages of the spatial-confinement effect, resistance to nuclease degradation and easy penetration into cells, rapid and excellent signal amplification FRET detection and bioimaging of endogenous circHIPK3 can be achieved in various cells. This study provides a high-precision assay platform to explore the possibility of using circRNA as a biomarker, and it is valuable for circRNA-related early diagnosis and treatment of diseases.
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Técnicas Biossensoriais , Carbocianinas , MicroRNAs , MicroRNAs/genética , RNA Circular/genética , DNA/genética , Biomarcadores , Técnicas Biossensoriais/métodos , Limite de DetecçãoRESUMO
AIMS: Microtubule inhibitors are widely used in first line cancer therapy, though drug resistance often develops and causes treatment failure. Colchicine binds to tubulins and inhibits tumor growth, but is not approved for cancer therapy due to systemic toxicity. In this study, we aim to improve the therapeutic index of colchicine through structural modification. METHODS: The methoxyl group of the tropolonic ring in colchicine was replaced with amino groups. The cross-resistance of the derivatives with paclitaxel and vincristine was tested. Antitumor effects of target compounds were tested in vivo in A549 and paclitaxel-resistant A549/T xenografts. The interaction of target compounds with tubulins was measured using biological and chemical methods. RESULTS: Methylamino replacement of the tropolonic methoxyl group of colchicine increases, while demethylation loses, selective tubulin binding affinity, G2/M arrest and antiproliferation activity. Methylaminocolchicine is more potent than paclitaxel and vincristine to inhibit tumor growth in vitro and in vivo without showing cross-resistance to paclitaxel. Methylaminocolchicine binds to tubulins in unique patterns and inhibits P-gp with a stable pharmacokinetic profile. CONCLUSION: Methylanimo replacement of the tropolonic methoxyl group of colchicine increases antitumor activity with improved therapeutic index. Methylaminocolchicine represents a new type of mitotic inhibitor with the ability of overcoming paclitaxel and vincristine resistance.
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Antineoplásicos , Neoplasias , Humanos , Paclitaxel/farmacologia , Paclitaxel/química , Paclitaxel/uso terapêutico , Colchicina/farmacologia , Colchicina/química , Colchicina/metabolismo , Tubulina (Proteína) , Vincristina/farmacologia , Vincristina/uso terapêutico , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral , Antineoplásicos/uso terapêuticoRESUMO
The Advanced Geostationary Radiation Imager (AGRI) sensor on board the geostationary satellite Fengyun-4B (FY-4B) is capable of capturing particles in different phases in the atmospheric environment and acquiring aerosol observation data with high spatial and temporal resolution. To understand the quality of the Land Aerosol (LDA) product of AGRI and its application prospects, we conducted a comprehensive evaluation of the AGRI LDA AOD. Using the 550 nm AGRI LDA AOD (550 nm) of nearly 1 year (1 October 2022 to 30 September 2023) to compare with the Aerosol Robotic Network (AERONET), MODIS MAIAC, and Himawari-9/AHI AODs. Results show the erratic algorithmic performance of AGRI LDA AOD, the correlation coefficient (R), mean error (Bias), root mean square error (RMSE), and the percentage of data with errors falling within the expected error envelope of ±(0.05+0.15×AODAERONET) (within EE15) of the LDA AOD dataset are 0.55, 0.328, 0.533, and 34%, respectively. The LDA AOD appears to be overestimated easily in the southern and western regions of China and performs poorly in the offshore areas, with an R of 0.43, a Bias of 0.334, a larger RMSE of 0.597, and a global climate observing system fraction (GCOSF) percentage of 15% compared to the inland areas (R = 0.60, Bias = 0.163, RMSE = 0.509, GCOSF = 17%). Future improvements should focus on surface reflectance calculation, water vapor attenuation, and more suitable aerosol model selection to improve the algorithm's accuracy.
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Bioimaging is widely used in various fields of modern medicine. Fluorescence imaging has the advantages of high sensitivity, high selectivity, noninvasiveness, in situ imaging, and so on. However, one-photon (OP) fluorescence imaging has problems, such as low tissue penetration depth and low spatiotemporal resolution. These disadvantages can be solved by two-photon (TP) fluorescence imaging. However, TP imaging still uses fluorescence intensity as a signal. The complexity of organisms will inevitably affect the change of fluorescence intensity, cause false-positive signals, and affect the accuracy of the results obtained. Fluorescence lifetime imaging (FLIM) is different from other kinds of fluorescence imaging, which is an intrinsic property of the material and independent of the material concentration and fluorescence intensity. FLIM can effectively avoid the fluctuation of TP imaging based on fluorescence intensity and the interference of autofluorescence. Therefore, based on silica-coated gold nanoclusters (AuNCs@SiO2) combined with nucleic acid probes, the dual-mode nanoprobe platform was constructed for TP and FLIM imaging of intracellular endogenous miRNA-21 for the first time. First, the dual-mode nanoprobe used a dual fluorescence quencher of BHQ2 and graphene oxide (GO), which has a high signal-to-noise ratio and anti-interference. Second, the dual-mode nanoprobe can detect miR-21 with high sensitivity and selectivity in vitro, with a detection limit of 0.91 nM. Finally, the dual-mode nanoprobes performed satisfactory TP fluorescence imaging (330.0 µm penetration depth) and FLIM (τave = 50.0 ns) of endogenous miR-21 in living cells and tissues. The dual-mode platforms have promising applications in miRNA-based early detection and therapy and hold much promise for improving clinical efficacy.
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Rapid, simultaneous, and sensitive detection of biomolecules has important application prospects in disease diagnosis and biomedical research. However, because the content of intracellular endogenous target biomolecules is usually very low, traditional detection methods can't be used for effective detection and imaging, and to enhance the detection sensitivity, signal amplification strategies are frequently required. The hybridization chain reaction (HCR) has been used to detect many disease biomarkers because of its simple operation, good reproducibility, and no enzyme involvement. Although HCR signal amplification methods have been employed to detect and image intracellular biomolecules, there are still false positive signals. Therefore, a target-triggered enzyme-free amplification system (GHCR system) was developed, as a fluorescent AND-gated sensing platform for intracellular target probing. The false positive signals can be well avoided and the accuracy of detection and imaging can be improved by using the design of the AND gate. Two cancer markers, GSH and miR-1246, were used as two orthogonal inputs for the AND gated probe. The AND-gated probe only works when GSH and miR-1246 are the inputs at the same time, and FRET signals can be the output. In addition to the use of AND-gated imaging, FRET-based high-precision ratiometric fluorescence imaging was employed. FRET-based ratiometric fluorescent probes have a higher ability to resist interference from the intracellular environment, they can avoid false positive signals well, and they are expected to have good specificity. Due to the advantages of HCR, AND-gated, and FRET fluorescent probes, the GHCR system exhibited highly efficient AND-gated FRET bioimaging for intracellular endogenous miRNAs with a lower detection limit of 18 pM, which benefits the applications of ratiometric intracellular biosensing and bioimaging and offers a novel concept for advancing the diagnosis and therapeutic strategies in the field of cancer.
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Pesquisa Biomédica , MicroRNAs , Neoplasias , Humanos , Corantes Fluorescentes , Reprodutibilidade dos Testes , MicroRNAs/genética , Neoplasias/diagnóstico por imagemRESUMO
Phenol and its derivatives are the most used polymerization inhibitors for vinyl-based monomers. Here, we reported a novel catalytic system composed of mussel inspired adhesive moiety, catechol, in combination with iron oxide nanoparticles (IONPs) to generate hydroxyl radical (â¢OH) at pH 7.4. Catechol-containing microgel (DHM) was prepared by copolymerizing dopamine methacrylamide (DMA) and N-hydroxyethyl acrylamide (HEAA), which generated superoxide (â¢O2-) and hydrogen peroxide (H2O2) as a result of catechol oxidation. In the presence of IONPs, the generated reactive oxygen species were further converted to â¢OH, which initiated free radical polymerization of various water-soluble acrylate-based monomers including neutral (acrylamide, methyl acrylamide, etc.), anionic (2-acrylamido-2-methyl-1-propanesulfonic acid sodium salt), cationic ([2-(methacryloyloxy)ethyl]trimethylammonium chloride), and zwitterionic (2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide) monomers. Compared with the typical free radical initiating systems, the reported system does not require the addition of extra initiators for polymerization. During the process of polymerization, a bilayer hydrogel was formed in situ and exhibited the ability to bend during the process of swelling. The incorporation of IONPs significantly enhanced magnetic property of the hydrogel and the combination of DHM and IONPs also improved the mechanical properties of these hydrogels.
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Phytoremediation by intercropping is a potential method to realize both production and remediation. Maize and peanut are the main crops planted in arsenic(As) contaminated areas in south China and vulnerable to As pollution. Experiments were conducted on arsenic-polluted soil with low As-accumulating maize monoculture (M), peanut monoculture (P), and intercropping with different distances between the maize and peanut (0.2 m, 0.35 m, and 0.5 m, recorded as MP0.2, MP0.35, and MP0.5, respectively). The results indicated that the As content in the maize grains and peanut lipids in the intercropping system decreased significantly, meeting the food safety standard of China (GB 2762-2017). Moreover, the land equivalent ratio (LER) and heavy metal removal equivalence ratio (MRER) of all intercropping treatments were greater than 1, indicating that this intercropping agrosystem has the advantage of production and arsenic removal, among which the yield and LER of MP0.35 treatment were the highest. Additionally, the bioconcentration factors (BCF) and translocation factor (TF) of MP0.2 increased by 117.95% and 16.89%, respectively, indicating that the root interaction affected the absorption of As in soil by crops. This study preliminarily demonstrated the feasibility of this intercropping system to safely use and remedy arsenic-contaminated farmland during production.
Phytoremediation by intercropping is a potential method to realize both production and remediation. Maize and peanuts are the main crops planted in As-contaminated areas and easily polluted by As. This study preliminarily demonstrated the feasibility of this intercropping system to safely use and remedy arsenic-contaminated farmland during production.
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Arsênio , Poluentes do Solo , Agricultura/métodos , Arachis , Zea mays , Biodegradação Ambiental , Solo , Produtos Agrícolas , Poluentes do Solo/análiseRESUMO
The COVID-19, caused by SARS-CoV-2, is threatening public health, and there is no effective treatment. In this study, we have implemented a multi-targeted anti-viral drug design strategy to discover highly potent SARS-CoV-2 inhibitors, which simultaneously act on the host ribosome, viral RNA as well as RNA-dependent RNA polymerases, and nucleocapsid protein of the virus, to impair viral translation, frameshifting, replication, and assembly. Driven by this strategy, three alkaloids, including lycorine, emetine, and cephaeline, were discovered to inhibit SARS-CoV-2 with EC50 values of low nanomolar levels potently. The findings in this work demonstrate the feasibility of this multi-targeting drug design strategy and provide a rationale for designing more potent anti-virus drugs.
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Antivirais/farmacologia , Desenho de Fármacos , SARS-CoV-2/efeitos dos fármacos , Animais , Antivirais/síntese química , Antivirais/química , Linhagem Celular , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Acrolein (ACR) is a metabolic byproduct in vivo and a ubiquitous environmental toxicant. It is implicated in the initiation and development of many diseases through multiple mechanisms, including the induction of oxidative stress. Currently, our understanding of the body defense mechanism against ACR toxicity is still limited. Given that hydrogen sulfide (H2S) has strong antioxidative actions and it shares several properties of ACR scavenger glutathione (GSH), we, therefore, tested whether H2S could be involved in ACR detoxification. Taking advantage of two cell lines that produced different levels of endogenous H2S, we found that the severity of ACR toxicity was reversely correlated with H2S-producing ability. In further support of the role of H2S, supplementing cells with exogenous H2S increased cell resistance to ACR, whereas inhibition of endogenous H2S sensitized cells to ACR. In vivo experiments showed that inhibition of endogenous H2S with CSE inhibitor markedly increased mouse susceptibility to the toxicity of cyclophosphamide and ACR, as evidenced by the increased mortality and worsened organ injury. Further analysis revealed that H2S directly reacted with ACR. It promoted ACR clearance and prevented ACR-initiated protein carbonylation. Collectively, this study characterized H2S as a presently unrecognized endogenous scavenger of ACR and suggested that H2S can be exploited to prevent and treat ACR-associated diseases.
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Sulfeto de Hidrogênio , Acroleína/toxicidade , Animais , Antioxidantes , Glutationa/metabolismo , Sulfeto de Hidrogênio/toxicidade , Camundongos , Estresse OxidativoRESUMO
As one of the main environmental pollutants and occupational hazards, nickel has been reported to have mutagenic, carcinogenic, and teratogenic properties, as well as reproductive toxicity. However, how nickel affects human reproduction is still unclear. In this study, the toxicity of nickel on human sperm and the underlying mechanisms were evaluated in vitro. We found that NiCl2 (10, 50, and 250 µM) impaired sperm total motility and progressive motility in a dose- and time-dependent manner. In addition, sperm hyperactivation and the ability of human sperm to penetrate a viscous medium were found to be compromised after nickel exposure. Mechanically, NiCl2 significantly inhibited the basal intracellular Ca2+ signaling. Besides, reactive oxygen species (ROS), superoxide, and malondialdehyde levels were increased in human sperm after exposure to different concentrations of NiCl2. Consistently, eliminating excess ROS by N-acetyl-L-cysteine or tocopherol significantly alleviated nickel-impaired sperm motility. Taken together, these results revealed that nickel could compromise sperm functions by interfering with Ca2+ signaling and inducing excessive oxidative stress. These findings suggest that, in the high and occupational nickel exposure environments, the contribution of nickel toxicity to the males who wish to preserve their fertility is worthy of careful evaluation.
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Níquel , Motilidade dos Espermatozoides , Humanos , Masculino , Níquel/toxicidade , Espécies Reativas de Oxigênio , Reprodução , EspermatozoidesRESUMO
Toad venom contains a large number of bufadienolides, which have a variety of pharmacological activities, including antitumor, cardiovascular, anti-inflammatory, analgesic and immunomodulatory effects. The strong antitumor effect of bufadienolides has attracted considerable attention in recent years, but the clinical application of bufadienolides is limited due to their low solubility and poor bioavailability. In order to overcome these shortcomings, many strategies have been explored, such as structural modification, solid dispersion, cyclodextrin inclusion, microemulsion and nanodrug delivery systems, etc. In this review, we have tried to summarize the pharmacological activities and structure-activity relationship of bufadienolides. Furthermore, the strategies for solubility and bioavailability enhancement of bufadienolides also are discussed. This review can provide a basis for further study on bufadienolides.
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Bufanolídeos/química , Bufanolídeos/farmacocinética , Venenos de Anfíbios/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacocinética , Disponibilidade Biológica , Bufanolídeos/administração & dosagem , Sistemas de Liberação de Medicamentos , Humanos , Estrutura Molecular , Solubilidade , Relação Estrutura-AtividadeRESUMO
The thermal performance of a deep UV LED package in three different chip on board (COB) substrates was studied by finite element simulation. The relationship between the temperature of each component in different COB substrates and the packaging density of the deep UV LED was analyzed. Having the same size of a 1313 COB substrate, this study indicates that the aluminum substrate can adapt to a 0.38 W/mm2 packaging density at a maximum owing to the existence of an insulation layer, which has a low thermal conductivity. However, an alumina ceramic substrate can be adapted to a 0.94 W/mm2 packaging density. Aluminum nitride ceramic can meet the demand for a higher packaging density; however, the cost is a key factor which cannot be ignored for large-scale applications. The results of this study provide detailed suggestions for researchers and industrial use for the selection of COB substrates packaged with deep UV LED according to different packaging densities, which have a higher practical application value.
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Optical assembly as a multiple optical trapping technique enables patterned arrangements of matter ranging from atoms to microparticles for diverse applications in biophysics, quantum physics, surface chemistry, and cell biology. Optical potential energy landscapes based on evanescent fields are conventionally employed for optical assembly of subwavelength particles, but are typically limited to predefined patterns and lacking in tunability. Here we present a microfiber photonic crystal cavity applicable for tunable optical assembly of subwavelength particles along a flexible path. This is enabled by excellent mechanical flexibility of the microfiber cavity as well as its broadband photonic crystal reflectors. By virtue of the broadband reflectors, the lattice constant of the assembled particles is precisely tunable via altering the wavelength of input light. Three-dimensional optical assembly is also realized by making use of the high-order transverse mode of the microfiber cavity. Moreover, the optical assembly process is detectable by simply monitoring the reflection/transmission spectrum of the microfiber cavity. The design of the microfiber cavity heralds a new way for tunable optical assembly of subwavelength particles, potentially applicable for development of tunable photonic crystals, metamaterials, and sensors.
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The centromere, in which kinetochore proteins are assembled, plays an important role in the accurate congression and segregation of chromosomes during cell mitosis. Although the function of the centromere and kinetochore is conserved from monocentric to holocentric, the DNA sequences of the centromere and components of the kinetochore are varied among different species. Given the lack of core centromere protein A (CENP-A) and CENP-C in the lepidopteran silkworm Bombyx mori, which possesses holocentric chromosomes, here we investigated the role of CENP-N, another important member of the centromere protein family essential for kinetochore assembly. For the first time, cellular localization and RNA interference against CENP-N have confirmed its kinetochore function in silkworms. To gain further insights into the regulation of CENP-N in the centromere, we analyzed the affinity-purified complex of CENP-N by mass spectrometry and identified 142 interacting proteins. Among these factors, we found that the chaperone protein heat shock cognate 70 (HSC70) is able to regulate the stability of CENP-N by prohibiting ubiquitin-proteasome pathway, indicating that HSC70 could control cell cycle-regulated degradation of CENP-N at centromeres. Altogether, the present work will provide a novel clue to understand the regulatory mechanism for the kinetochore activity of CENP-N during the cell cycle.
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Bombyx/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Insetos/metabolismo , Cinetocoros/metabolismo , Animais , Bombyx/genética , Proteínas Cromossômicas não Histona/genética , Proteínas de Choque Térmico HSP70/genética , Proteínas de Insetos/genética , Estabilidade ProteicaRESUMO
Glioblastoma multiforme (GBM) is the most lethal brain malignancy which involves multi-gene abnormality. Unfortunately, effective therapy against GBM remains lacking. Previously, we found that NRP-1 and its downstream NRP-1/GIPC1 pathway played an important role in GBM. In our study, we further investigated the upstream signaling of NRP-1 to understand how it is regulated. First, we identified that hsa-miR-124-3p was miRNA differentially expressed in GBM and in normal brain tissues by high-throughput sequencing. Then, by dual luciferase reporter gene, we found miR-124-3p can specially bind to the 3'UTR region of the NRP-1 thus suppresses its expression. Moreover, miR-124-3p overexpression significantly inhibited GBM cell proliferation, migration and tumor angiogenesis which resulted in GBM apoptosis and cell cycle arrest, putatively via NRP-1 mediated PI3K/Akt/NFκB pathways activation in GBM cells. Meanwhile, miR-124-3p overexpression also suppressed tumor growth and reduced tumor angiogenesis when targeted by NRP-1 in a PDX model. Furthermore, NRP-1 mAb exerted synergistic inhibitory effects with miR-124-3p overexpression in GBM. Thus, we discovered that miR-124-3p acts as the upstream suppressor of NRP-1 which promotes GBM cell development and growth by PI3K/Akt/NFκB pathway. The miR-124-3p/NRP-1/GIPC1 pathway as a new pathway has a vital role in GBM, and it could be considered as the potential target for malignant gliomas in future.
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Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/patologia , Neovascularização Patológica/genética , Neuropilina-1/genética , Interferência de RNA , Regiões 3' não Traduzidas , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Encéfalo/metabolismo , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Perfilação da Expressão Gênica , Glioblastoma/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Proteína Oncogênica v-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , TranscriptomaRESUMO
Vacuolar-type ATPase (V-ATPase) is a type of hydrogen ion transporter located in the vesicular membrane-like system, which mediates active transport and intracellular acidification in various compartments. In mammals, V-ATPase has been reported to play a key role in cell proliferation and apoptosis. The studies of V-ATPase in silkworm mainly focus on the acidification regulation of midgut and silk gland and immune resistance. However, there are few reports about the function of silkworm V-ATPase on cell proliferation, autophagy, and apoptosis. Thus, the function of V-ATPase in a cell line of Bombyx mori (BmE) was investigated by treating the cell line with bafilomycin A1, a specific inhibitor of V-ATPase. Cell counting kit 8 (CCK8) and flow cytometry analysis showed that bafilomycin A1 treatment decreased the cell proliferation activity, affected the cell cycle progression and induced cell apoptosis. LysoTracker Red staining showed that the target of bafilomycin A1 is lysosome. The expression of all autophagy-related genes ( BmATG5, BmATG6, and BmATG8) decreased, indicating that cell autophagy was inhibited. The analysis of the apoptosis pathway demonstrated that inhibiting the activity of V-ATPase of BmE cells could promote mitochondria to release cytochrome C, inhibit the expression of BmIAP, and activate the caspase cascade to induce apoptosis. All these findings systematically illustrate the effects of V-ATPase on the proliferation, autophagy, and apoptosis in BmE cells, and provide new ideas and a theoretical basis for further study on the function of V-ATPase in BmE.
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Bombyx/enzimologia , ATPases Vacuolares Próton-Translocadoras/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Proteínas de Insetos/metabolismo , Macrolídeos/farmacologia , ATPases Vacuolares Próton-Translocadoras/antagonistas & inibidoresRESUMO
A single-walled carbon nanohorn (SWCNH) has been used to construct a molecularly imprinted electrochemical sensor for the first time. Kanamycin, a widely used aminoglycoside antibiotic, is used as a representative analyte to test the detection strategy. The kanamycin sensor was constructed by the electropolymerization of a molecularly imprinted poly-o-phenylenediamine film on a SWCNH modified glassy carbon electrode. The sensor was investigated in the presence or absence of kanamycin by cyclic voltammetry to verify the changes in the redox peak currents of K3Fe(CN)6. The sensor exhibits a linear range of 0.1-50 µM with a detection limit of 0.1 µM. It also shows high recognition ability, indicating that the SWCNH-based molecularly imprinted sensor is promising.
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The Internet of Things (IoT) has revolutionized the connectivity of physical devices, leading to an exponential increase in multimedia wireless traffic and creating substantial demand for radio spectrum. Given the inherent scarcity of available spectrum, Cognitive Radio (CR)-assisted IoT emerges as a promising solution to optimize spectrum utilization through cooperation between cognitive and IoT nodes. Unlicensed IoT nodes can opportunistically access licensed spectrum bands without causing interference to licensed users. However, energy constraints may lead to reduced cooperation from IoT nodes during the search for vacant channels, as they aim to conserve battery life. To address this issue, we propose a Punishment-reward-based Cooperative Sensing and Data Forwarding (PR-CSDF) approach for IoT data transmission. Our method involves two key steps: (1) distributing sensing tasks among IoT nodes and (2) enhancing cooperation through a reward and punishment strategy. Evaluation results demonstrate that both secondary users (SUs) and IoT nodes achieve significant utility gains with the proposed mechanism, providing strong incentives for cooperative behaviour.