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Virtual image lenses play essential roles in various optical devices and applications, including vision correction, photography, and scientific instruments. Here, we introduce an approach for creating virtual image Luneburg lenses (LL) on graphene. Remarkably, the graphene plasmonic lens (GPL) exhibits electrically tunable virtual focusing capabilities. The design principle of the tunability is based on the nonlinear relationship between surface plasmon polariton (SPP) wave mode index and chemical potential of graphene. By controlling the gate voltage of graphene, we can achieve continuous tuning of virtual focus. A ray-tracing technique is employed to determine the required gate voltages for various virtual focal lengths. The proposed GPL facilitates adjustable virtual focusing, promising advancements in highly adaptive and transformative nanophotonic devices.
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Motivation: Molecular Regulatory Pathways (MRPs) are crucial for understanding biological functions. Knowledge Graphs (KGs) have become vital in organizing and analyzing MRPs, providing structured representations of complex biological interactions. Current tools for mining KGs from biomedical literature are inadequate in capturing complex, hierarchical relationships and contextual information about MRPs. Large Language Models (LLMs) like GPT-4 offer a promising solution, with advanced capabilities to decipher the intricate nuances of language. However, their potential for end-to-end KG construction, particularly for MRPs, remains largely unexplored. Results: We present reguloGPT, a novel GPT-4 based in-context learning prompt, designed for the end-to-end joint name entity recognition, N-ary relationship extraction, and context predictions from a sentence that describes regulatory interactions with MRPs. Our reguloGPT approach introduces a context-aware relational graph that effectively embodies the hierarchical structure of MRPs and resolves semantic inconsistencies by embedding context directly within relational edges. We created a benchmark dataset including 400 annotated PubMed titles on N6-methyladenosine (m6A) regulations. Rigorous evaluation of reguloGPT on the benchmark dataset demonstrated marked improvement over existing algorithms. We further developed a novel G-Eval scheme, leveraging GPT-4 for annotation-free performance evaluation and demonstrated its agreement with traditional annotation-based evaluations. Utilizing reguloGPT predictions on m6A-related titles, we constructed the m6A-KG and demonstrated its utility in elucidating m6A's regulatory mechanisms in cancer phenotypes across various cancers. These results underscore reguloGPT's transformative potential for extracting biological knowledge from the literature. Availability and implementation: The source code of reguloGPT, the m6A title and benchmark datasets, and m6A-KG are available at: https://github.com/Huang-AI4Medicine-Lab/reguloGPT.
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A graphene plasmonic lens with an electrically tunable focal length is proposed and numerically investigated. The design philosophy of the proposed tunable lens is based on the nonlinear relationship of surface plasmon polariton (SPP) wave index with respect to chemical potential of graphene. By controlling the gate voltage of graphene, the proposed lens can be continuously tuned from a Maxwell Fisheye lens to a Luneburg lens. A ray-tracing method is employed to find out the corresponding gate voltages for various focal lengths. Full-wave EM simulations using COMSOL show that excellent focusing performances can be achieved. This work offers a new way in exploiting active transformational plasmonic elements in the mid-infrared region.
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BACKGROUND: For many years, the role of the microbiome in tumor progression, particularly the tumor microbiome, was largely overlooked. The connection between the tumor microbiome and the tumor genome still requires further investigation. METHODS: The TCGA microbiome and genome data were obtained from Haziza et al.'s article and UCSC Xena database, respectively. Separate WGCNA networks were constructed for the tumor microbiome and genomic data after filtering the datasets. Correlation analysis between the microbial and mRNA modules was conducted to identify oncogenome associated microbiome module (OAM) modules, with three microbial modules selected for each tumor type. Reactome analysis was used to enrich biological processes. Machine learning techniques were implemented to explore the tumor type-specific enrichment and prognostic value of OAM, as well as the ability of the tumor microbiome to differentiate TP53 mutations. RESULTS: We constructed a total of 182 tumor microbiome and 570 mRNA WGCNA modules. Our results show that there is a correlation between tumor microbiome and tumor genome. Gene enrichment analysis results suggest that the genes in the mRNA module with the highest correlation with the tumor microbiome group are mainly enriched in infection, transcriptional regulation by TP53 and antigen presentation. The correlation analysis of OAM with CD8+ T cells or TAM1 cells suggests the existence of many microbiota that may be involved in tumor immune suppression or promotion, such as Williamsia in breast cancer, Biostraticola in stomach cancer, Megasphaera in cervical cancer and Lottiidibacillus in ovarian cancer. In addition, the results show that the microbiome-genome prognostic model has good predictive value for short-term prognosis. The analysis of tumor TP53 mutations shows that tumor microbiota has a certain ability to distinguish TP53 mutations, with an AUROC value of 0.755. The tumor microbiota with high importance scores are Corallococcus, Bacillus and Saezia. Finally, we identified a potential anti-cancer microbiota, Tissierella, which has been shown to be associated with improved prognosis in tumors including breast cancer, lung adenocarcinoma and gastric cancer. CONCLUSION: There is an association between the tumor microbiome and the tumor genome, and the existence of this association is not accidental and could change the landscape of tumor research.
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Neoplasias da Mama , Neoplasias Ovarianas , Feminino , Humanos , Prognóstico , Redes Reguladoras de Genes , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , RNA MensageiroRESUMO
Micro (nano)plastics (MNPs) have become emerging environmental contaminants, yet their toxicity and systemic effects via intranasal exposure remain unclear. This study investigated the in vitro toxicity of thirteen polystyrene MNPs with different surface functionalization (carboxylic (C-PS), amino (A-PS), and bare (PS)) and sizes (20-2000 nm) on human nasal epithelial cells (HNEpCs) at 10-1250 µg/mL as well as their in vivo toxicity to rats via intranasal administration at 125 µg/mL. The in vitro study showed that PS20, PS50, A-PS50, PS500, and A-PS500 significantly inhibited cell viability, which was dependent on particle concentration. A-PS induced higher cytotoxicity than C-PS and PS, and most MNPs inhibited cell proliferation after 24-h. Flow cytometry analysis suggested that PS induced cell apoptosis, while A-PS caused cell necrosis. MNPs were phagocytosed by HNEpCs and entered nucleus. The in vivo study showed that MNPs inhibited dietary behaviors of rats. Histological analysis indicated that PS20, PS200, and A-PS50 thinned out nasal mucosa. Immunohistochemical analysis revealed that exposure to PS20, PS200, and A-PS50 enhanced expression of transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8). Systemic effects including hepatocyte cytoplasmic vacuolation and renal tubule dilatation were observed. The results suggested that nasal inhalation of MNPs may disturb energy metabolism and damage upper respiratory tract, liver, and kidneys.
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Plásticos , Canais de Potencial de Receptor Transitório , Administração Intranasal , Animais , Células Epiteliais , Humanos , Poliestirenos/toxicidade , RatosRESUMO
Nasopharyngeal carcinoma (NPC) is one of the major causes of death in Southern China. Due to the insidious location of NPC, the therapeutic effect of locoregionally advanced NPC is still unsatisfactory. In this work, to improve the treatment efficiency, combining DOC and JS-K to inhibit NPC cells (HNE-1) in vitro was investigated, as well as its possible mechanisms. Moreover, the in vivo effects of DOC and JS-K combination treatment were also evaluated in a xenograft model with HNE-1 cells. In vitro experiments including cell proliferation, migration ability, apoptosis, and expression levels of apoptosis-associated proteins revealed that the combination of DOC and JS-K was able to enhance antitumor effects. In vivo results further confirmed a significant treatment effect without obvious toxicity on mice. The present work provides a promising idea for the treatment of locally advanced NPC.
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Neoplasias Nasofaríngeas , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Humanos , Camundongos , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The treatment and healing of infected skin lesions is one of the major challenges in surgery. To solve this problem, collagen I (Col-I) and the antibacterial agent hydroxypropyltrimethyl ammonium chloride chitosan (HACC) were composited into the bacterial cellulose (BC) three-dimensional network structure by a novel membrane-liquid interface (MLI) culture, and a Col-I/HACC/BC (CHBC) multifunctional dressing was designed. The water absorption rate and water vapor transmission rate of the obtained CHBC dressing were 35.78 ± 2.45 g/g and 3084 ± 56 g m-2·day-1, respectively. The water retention of the CHBC dressing was significantly improved compared with the BC caused by the introduced Col-I and HACC. In vitro results indicated that the combined advantages of HACC and Col-I confer on CHBC dressings not only have outstanding antibacterial properties against Staphylococcus aureus (S. aureus) compared with BC and CBC, but also exhibit better cytocompatibility than BC and HBC to promote the proliferation and spread of NIH3T3 cells and HUVECs. Most importantly, the results of in vivo animal tests demonstrated that the CHBC dressings fully promoted wound healing for 8 days and exhibited shorter healing times, especially in the case of wound infection. Excellent skin regeneration effects and higher expression levels of collagen during infection were also shown in the CHBC group. We believe that CHBC composites with favorable multifunctionality have potential applications as wound dressings to treat infected wounds.
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Background: Helicobacter pylori infection is the strongest known risk factor for gastric cancer. The Hippo signaling pathway controls organ size and maintains tissue homeostasis by coordinately regulating cell growth and proliferation. Here, we demonstrate the interactive role of TAZ, the transcriptional coactivator of the Hippo pathway, and beta-catenin in promoting the pathogenesis of H. pylori infection. Methods: TAZ expression was evaluated in human gastric tissues and H. pylori-infected insulin-gastrin (INS-GAS) mice. Western blot, immunofluorescence, immunohistochemistry, and RT-PCR assays were performed. Coimmunoprecipitation was performed to examine the interaction between TAZ and ß-catenin. TAZ and ß-catenin were silenced using small interfering RNAs. HA-ß-catenin and Flag-TAZ were constructed. Results: Increased TAZ was noted in human gastric cancer tissues compared to chronic gastritis tissues and in H. pylori-positive gastritis tissues compared to H. pylori-negative gastritis tissues. In addition, H. pylori infection induced TAZ expression and nuclear accumulation in the gastric tissue of INS-GAS mice and cultured gastric epithelial cells, which was dependent on the virulence factor CagA. Moreover, TAZ or ß-catenin knockdown significantly suppressed H. pylori infection-induced cell growth, survival, and invasion. Furthermore, the interactive regulation of TAZ and ß-catenin activation was revealed. Finally, ß-catenin was required for H. pylori-induced TAZ activation. Conclusion: These findings suggest the existence of a positive feedback loop of activation between TAZ and ß-catenin that could play an important role in CagA+ H. pylori infection-induced gastric carcinogenesis. TAZ inhibition represents a potential target for the prevention of H. pylori infection-associated gastric cancer.
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Gastric cancer (GC) is a leading cause of mortality and morbidity worldwide. We assessed the expression patterns of DNA damage response (DDR)-related markers, including ATM, CHK2, p-p53 (S15), Rad51, and BRCA2 and autophagy-related proteins including p62 and Beclin-1 in 153 GC specimens using immunohistochemistry staining. GC tissues showed lower levels of ATM, CHK2, p-p53, BRCA2, and higher levels of Rad51 compared to adjacent normal tissues. The autophagy-related protein p62 was upregulated, whereas Beclin-1 was downregulated in human GC groups. Additionally, different statuses of DDR pathways and autophagy characterized by protein expression were associated with overall survival. Our results indicated that the impairment of DNA damage and autophagy may be implicated in gastric cancer progression and its clinical prognosis.
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Neoplasias Gástricas , Autofagia , Proteína Beclina-1/genética , Dano ao DNA , Humanos , Prognóstico , Neoplasias Gástricas/genéticaRESUMO
BACKGROUND: There is increasing evidence that the eradication of Helicobacter pylori leads to the regression of gastric hyperplastic polyps (GHPs). We performed a systematic review with a meta-analysis of randomized controlled trials and observational studies that assessed the effects of eradication. MATERIALS AND METHODS: We searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies with a combination of the terms "Helicobacter pylori" and "polyps." The risk ratio was used to compare the effect of H. pylori eradication/treatment on GHP. We also calculated the pooled disappearance rate of GHP in the H. pylori eradication/treatment group and persistent infection group. RESULTS: We analyzed data from 6 studies, including 3 RCTs. A total of 58/394 patients were included in the H. pylori treatment/successful eradication group, and 57/302 patients were included in the H. pylori untreated/persistent infection group. The pooled rate of GHP elimination after H. pylori treatment/successful eradication was 59% (95% CI, 43%-75%)/79% (95% CI, 72%-86%). H. pylori treatment/successful eradication significantly increased the GHP elimination rate [ITT: (pooled rate: 58% vs. 0%, RR =22.24, 95% CI, 4.51- 109.78, p = 0.0001), PP: (pooled rate: 65% vs. 0%, RR =22.25, 95% CI, 4.52- 109.37, p = 0.0001)/(pooled rate: 79% vs. 9%, RR =26.87, 95% CI, 1.34-540.5, p = 0.03)]. CONCLUSIONS: Our meta-analysis showed that after the eradication of H. pylori, most GHPs are eliminated. Moreover, the treatment/successful eradication of H. pylori increased the GHP elimination rate by more than 20 times that in the control group.
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Pólipos Adenomatosos , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Pólipos Adenomatosos/tratamento farmacológico , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Humanos , Razão de Chances , Neoplasias Gástricas/tratamento farmacológicoRESUMO
Chronic rhinosinusitis (CRS) is a rather prevalent condition with a chronic inflammatory process, which is hard to cure. Herein, a new antibacterial drug, nitric oxide (NO), was used for the attempt on CRS therapy. To achieve this, a star copolymer (ß-CD-PAMAM) consisting of the ß-cyclodextrin (ß-CD) core and seven PAMAM-G3 arms, which was designed as a low-cytotoxicity and high NO loading carrier, were synthesized and characterizied. The obtained ß-CD-PAMAM/NONOate showed the effect in inhibiting and dispersing the biofilm of S. aureus, as well as the effective antibacterial performance, implying the promising application in CRS treatment. The in vivo assay confirmed that ß-CD-PAMAM/NONOate displayed excellent therapy effect on CRS and significantly improved the symptoms of the experimental rats, which was no significant different in therapy effect with the clinical Rhinocort. Incorporated with its little toxicity in vitro and in vivo, the ß-CD-PAMAM/NONOate was suggested a promising application in CRS therapy.
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Doença Crônica/tratamento farmacológico , Dendrímeros/farmacologia , Óxido Nítrico/farmacologia , Poliaminas/farmacologia , Sinusite/tratamento farmacológico , beta-Ciclodextrinas/farmacologia , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Sinusite/microbiologia , Staphylococcus aureus/efeitos dos fármacosRESUMO
BACKGROUND: Osteosarcoma is one of the most common malignant bone tumors with the annual global incidence of approximately four per million. Upregulated gene 4 (URG4) expression in the osteosarcoma tissue is closely associated with recurrence, metastasis, and poor prognosis of osteosarcoma. However, the biological function and underlying mechanisms of URG4 in osteosarcoma have not been elucidated. This study aimed to explore the expression and underlying mechanism of URG4 in osteosarcoma. METHODS: The expression level of URG4 in osteosarcoma and normal tissues was compared using immunohistochemistry (IHC). PCR and western blotting (WB) techniques are used to detect URG4 mRNA and protein levels. Wound healing and Transwell analysis to assess the effect of URG4 on osteosarcoma cell migration and invasion. Cell Counting Kit-8 assay and colony proliferation assay were performed to evaluate the effects of silencing URG4 on the inhibition of cell proliferation. The cell cycle distribution was detected by flow cytometry, and a xenograft mouse model was used to verify the function of URG4 in vivo. RESULTS: URG4 was found to be highly expressed in osteosarcoma tissues and cells, and its high expression was correlated with advanced Enneking stage, large tumor size, and tumor metastasis in osteosarcoma patients. The proliferation in osteosarcoma cell lines and cell cycle in the S phase was suppressed when siRNA was used to downregulate URG4. URG4 promoted cell proliferation and tumorigenesis in vitro and in vivo. WB verified that URG4 promotes cell proliferation in osteosarcoma via pGSK3ß/ß-catenin/cyclinD1 signaling. CONCLUSION: URG4, which is high-expressed in osteosarcoma, promotes cell cycle progression via GSK3ß/ß-catenin/cyclin D1 signaling pathway and may be a novel biomarker and potential target for the treatment of osteosarcoma.
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Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Proteínas de Neoplasias/metabolismo , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Adolescente , Adulto , Animais , Técnicas de Cultura de Células , Ciclo Celular , Proliferação de Células , Ciclina D1/metabolismo , Modelos Animais de Doenças , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transdução de Sinais , Adulto Jovem , beta Catenina/metabolismoRESUMO
To obtain a high-efficiency drug and gene co-delivery system to HNE-1 tumor therapy, a polymeric prodrug (PAAs-MTX) with chemotherapeutic sensibilization was synthesized consisting of a GSH-response hyperbranched poly(amido amine) (PAAs) and an antitumor drug of methotrexate (MTX). Then, the targeting molecule to HNE-1 cells, transferrin (Tf), was conjugated to form the Tf-PAAs-MTX. This polymeric prodrug could deliver MMP-9 shRNA plasmid (pMMP-9) again to form the drug and gene co-delivery system of Tf-PAAs-MTX/pMMP-9. The co-delivery system showed the effective drug and gene delivery ability with high cytotoxicity and gene transfection efficiency to HNE-1 cells. Besides that, Tf-PAAs-MTX also showed the chemotherapeutic sensibilization effect, the formulation containing PAAs segments showed much higher cytotoxicity than that of free MTX. Benefiting from the sensibilization effect and MTX/pMMP-9 co-delivery strategy, this Tf-PAAs-MTX/pMMP-9 co-delivery system exhibited the significantly improved therapeutic efficacy to HNE-1 tumor in a combined manner which was confirmed by in vitro and in vivo assays. Moreover, its biocompatibility, especially the blood compatibility was analyzed. This polymeric prodrug provided an easily delivery system combining the drug/gene co-delivery, chemotherapeutic sensibilization and targeting into one single platform, which showed a promising application in nasopharyngeal carcinoma therapy.
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Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Técnicas de Transferência de Genes , Metaloproteinase 9 da Matriz/administração & dosagem , Metotrexato/administração & dosagem , Carcinoma Nasofaríngeo/terapia , Plasmídeos/administração & dosagem , Poliaminas/química , Pró-Fármacos/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Células 3T3 , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Terapia Combinada , Metaloproteinase 9 da Matriz/genética , Metotrexato/uso terapêutico , Camundongos , Camundongos Nus , Plasmídeos/genética , Pró-Fármacos/uso terapêutico , RNA Interferente Pequeno/genética , Transfecção , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A drug and gene co-delivery system with chemotherapeutic sensibilization was prepared and used for nasopharyngeal carcinoma therapy. For this purpose, the graphene oxide (GO) was conjugated with the redox hyperbranched poly(amido amine) (HPAA) and then the targeting molecule, transferrin (Tf), was also conjugated. The obtained Tf-HPAA-GO could co-deliver docetaxel (DOC) and MMP-9 shRNA plasmid (pMMP-9) effectively and showed the targeting effect to HNE-1 cells. The co-delivery system showed the effective drug and gene delivery ability with high cytotoxicity and gene transfection efficiency. Besides that, Tf-HPAA-GO/DOC also showed the chemotherapeutic sensibilization effect, the formulation containing HPAA segments showed much higher cytotoxicity than free DOC. Benefiting from the sensibilization effect and DOC/pMMP-9 co-delivery strategy, this Tf-HPAA-GO/DOC/pMMP-9 co-delivery system exhibited the significantly improved therapeutic efficacy to HNE-1 tumor in a combined manner which was confirmed by in vitro and in vivo assays. This strategy provided an easily delivery system combining the drug/gene co-delivery, chemotherapeutic sensibilization, and targeting into one single platform, which showed a promising application in cancer therapy.
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Antineoplásicos/administração & dosagem , Docetaxel/administração & dosagem , Grafite/administração & dosagem , Metaloproteinase 9 da Matriz/genética , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Transferrina/administração & dosagem , Células 3T3 , Aminas/síntese química , Aminas/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Terapia Combinada , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Terapia Genética , Glutationa/metabolismo , Grafite/química , Inibidores de Metaloproteinases de Matriz/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/metabolismoRESUMO
Due to the increasing incidence of tumor metastasis and multidrug resistance, even though a combined use of chemotherapy and radiotherapy is introduced, the 5-year average survival rate of an advanced nasopharyngeal carcinoma (NPC) patient still remains low. Hence, targeted slow-release anticancer drugs represent a potential therapy for advanced NPC. In this study, pH and redox dual stimulation-responsive folate-targeted folic acid - ß-cyclodextrin - hyperbranched poly(amido amine)s (FA-DS-PAAs) nanocarriers for codelivery of docetaxel (DOC) and tissue factor pathway inhibitor 2 (TFPI-2) for NPC therapy are discussed. Physical and chemical properties, in vitro DOC-release properties, folic acid (FA)-targeting, transfection, Western blotting, DOC and TFPI-2 codelivery, therapeutic properties, targeted inhibition, and biocompatibility, in vivo FA-targeting, toxicity, and therapeutic properties of FA-DS-PAAs/DOC/TFPI2 nanoparticles are evaluated. The results indicate that the 200 nm low-toxicity FA-DS-PAAs/DOC/TFPI2 nanoparticles could enhance TFPI2 gene expression, make cancer cells more sensitive to DOC, induce cell apoptosis, and reduce cell invasion more effectively compared with monochemotherapy. With respect to the targeted release of drugs (DOC and TFPI2) in tumor cells, FA-DS-PAAs/DOC/TFPI2 is associated with the slowest growth rate of tumor and the smallest volume of tumor, so this study demonstrates the best synergetic antitumor effect. We anticipate that this study is important because it not only provides a potential new therapy approach for NPC but also paves the preclinical way for potential application of FA-DS-PAAs/DOC/TFPI2.
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Transferrin-functionalized chitosan-graft-poly(l-lysine) dendrons (CS-PLLD-Tf) were synthesized in this work and then used to deliver the MMP-9 shRNA plasmid to HNE-1 cells for gene therapy. The obtained CS-PLLD-Tf displayed excellent gene transfection in vitro, verifying the strategy of constructing a high-efficiency gene carrier by conjugating the multiple low generation PLLDs to one molecule of CS to form a copolymer. Particularly, CS-PLLD-Tf showed much higher gene transfection efficiency than PEI-25k and CS-PLLD in the presence of serum, and more than 40% HNE-1 cells were transfected. This result led to an obvious decrease in MMP-9 protein expression and the apoptosis of HNE-1 cells as well as inhibition of the growth and invasion of HNE-1 tumors. The in vivo anti-tumor assay showed that CS-PLLD-Tf delivered the MMP-9 plasmid effectively and the tumor volume decreased more than 77% compared with the PBS control group. Moreover, CS-PLLD-Tf displayed higher bioavailability and good biocompatibility such as lower cytotoxicity, excellent blood compatibility and non-toxicity to organs, suggesting a potential application in gene therapy of tumors.
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The co-delivery of a drug and a target gene has become a primary strategy in cancer therapy. Based on our previous study, a synthesized starshaped copolymer consisting of ßcyclodextrin (CD) and a poly(Llysine) dendron (PLLD) was used to co-deliver docetaxel (DOC) and matrix metalloproteinase 9 (MMP9) small interfering RNA, via CDPLLD/DOC/MMP9 complexes, into mice implanted with HNE1 human nasopharyngeal carcinoma (NPC) tumor cells in vivo. Unlike the commonly used amphiphilic copolymer micelles, the obtained CD derivative may be used directly for a combined delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vivo assays demonstrated that CDPLLD/DOC/MMP9 inhibited HNE1 tumor growth and decreased proliferating cell nuclear antigen expression levels, indicating a potential strategy for NPC therapy. In addition, the distribution of DOC and MMP9 was investigated; CDPLLD/DOC/MMP9 complexes were phagocytized in reticuloendothelial systems, including the liver and spleen, which requires further study. Furthermore, the complexes did not cross the bloodbrain barrier due to their large molecular size, suggesting they may be relatively safe. Additionally, the complexes mediated increased DOC concentrations with prolonged blood circulation and EGFP expression in HNE1 tumors. These results suggest the future potential application of CD-PLLD/DOC/MMP-9 for NPC therapy.
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Carcinoma/tratamento farmacológico , Portadores de Fármacos/química , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Nasofaríngeas/tratamento farmacológico , RNA Interferente Pequeno/metabolismo , Taxoides/uso terapêutico , Animais , Carcinoma/patologia , Linhagem Celular Tumoral , Docetaxel , Humanos , Metaloproteinase 9 da Matriz/química , Metaloproteinase 9 da Matriz/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Polilisina/química , Antígeno Nuclear de Célula em Proliferação/metabolismo , RNA Interferente Pequeno/química , Taxoides/química , Transplante Heterólogo , beta-Ciclodextrinas/químicaRESUMO
Controlling the loss of graphene can be used in the field of transformation optics. We propose a new concept of electromagnetic fence on a monolayer graphene surface plasmon polariton platform. Using a Dot-Density-Renderer quasicrystal metasurface, we can simulate the absorption of gradient index optics structures. Numerical simulations show that the incident waves to our designed electromagnetic fence are trapped toward the central lines and quickly absorbed by the high-loss region. Two basic types of electromagnetic fence and its composite structures have been designed and analyzed, which exhibit excellent broadband absorbing performances at 8 THz-12 THz. Because of its advantages in controlling the soft-boundary effects and easy manufacturing characteristics, the proposed electromagnetic fence seems very promising for THz-frequency-transformation plasmonics applications.
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The co-delivery of drug and gene has become the primary strategy in cancer therapy. Based on our previous work, to co-deliver docetaxel (DOC) and MMP-9 siRNA more efficiently for HNE-1 nasopharyngeal carcinoma therapy, a folate-modified star-shaped copolymer (FA-CD-PLLD) consisting of ß-cyclodextrin (CD) and poly(L-lysine) dendron (PLLD) was synthesized, and then used for DOC and MMP-9 co-delivery. Different from commonly used amphiphilic copolymers micelles, the obtained CD derivative could be used directly for the combinatorial delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vitro and in vivo assays are carried out to confirm the effectiveness of the target strategy and combined treatment. It was found that the conjugation of CD-PLLD with FA could enhance the DOC/MMP-9 delivery effect obviously, inducing a more significant apoptosis and decreasing invasive capacity of HEN-1 cells. In vivo assays showed that FA-CD-PLLD/DOC/MMP-9 could inhibit HNE-1 tumor growth and decrease PCNA expression effectively, indicating a promising strategy for nasopharyngeal carcinoma therapy. Moreover, the in vivo distribution of DOC and MMP-9, blood compatibility and toxicity are also explored.