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Photodynamic therapy (PDT) is a well-established treatment modality, typically conducted with single-wavelength irradiation, which may not always be optimal for varying tumor locations and sizes. To address this, photosensitizers with absorption wavelengths ranging from 550 to 760 nm are being explored. Herein, a series of 5,15-diaryltetrabenzoporphyrins (Ar2TBPs) were synthesized. All compounds displayed obvious absorption at 550-700 nm (especially at â¼668 nm), intense fluorescence, efficient generation of singlet oxygen and good photodynamic antitumor effects. Notably, compound I3 (5,15-bis[(4-carboxymethoxy)phenyl]tetrabenzoporphyrin) showed excellent cytotoxicity against Eca-109 cell line upon red light irradiation, with an IC50 value of 0.45 µM, and phototherapeutic index of 25.8. Flow cytometry revealed that I3 could induce distinct cell apoptosis. In vivo studies revealed that compound I3 selectively accumulated at tumor site and exhibited outstanding PDT effect with antitumor activity under single-time administration and light irradiation, and revealed more efficiency than the clinical photosensitizer Verteporfin. These findings underscore the considerable promise of I3 as a robust theranostic agent, offering capabilities in real-time fluorescence imaging and serving as a potent photosensitizer for personalized and precise photodynamic therapy of tumors.
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PURPOSE: Endoscopic sinus surgery (ESS) is now frequently used to treat chronic sinusitis with nasal polyps (CRSwNP), but postoperative recurrence plagues many patients. We aimed to assess the value of the systemic inflammation response index (SIRI) and the systemic immune-inflammatory index (SII) for the prediction of postoperative recurrence in patients with CRSwNP. METHODS: A total of 143 patients with CRSwNP and 76 age- and sex-matched healthy subjects were enrolled. Patients were divided into the recurrence group and the non-recurrence group according to the recurrence of CRSwNP. Univariate and multivariate analyses showed independent risk factors for the recurrence. A receiver operating characteristic curve analysis was conducted to assess the predictive accuracy of the variables and determine the optimal cut-off values. Finally, a survival analysis was conducted. RESULTS: Univariate analysis revealed that age, sex, CRP, EOS, SIRI, SII, NLR, ELR, and Lund-Mackay CT scores were significant predictors of the recurrence of CRSwNP. Multivariate analysis confirmed that SIRI (OR = 1.310, p < 0.001) and Lund-Mackay CT scores (OR = 1.396, p < 0.001) were independent predictors. SIRI (AUC = 0.761, 95% CI: 0.685-0.836) had a certain value in predicting the recurrence of CRSwNP. CONCLUSION: SIRI is a potential predictive marker of the postoperative recurrence of CRSwNP.
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Pólipos Nasais , Rinite , Rinossinusite , Sinusite , Humanos , Estudos Retrospectivos , Pólipos Nasais/complicações , Pólipos Nasais/cirurgia , Pólipos Nasais/epidemiologia , Rinite/complicações , Rinite/cirurgia , Rinite/epidemiologia , Sinusite/complicações , Sinusite/cirurgia , Sinusite/epidemiologia , Doença Crônica , Inflamação , China/epidemiologiaRESUMO
Stratospheric aerosols play an important role in the atmospheric chemical and radiative balance. To detect the stratospheric aerosol layer, a 1064â nm lidar with high resolution and large dynamic range is developed using a superconducting nanowire single-photon detector (SNSPD). Measurements are typically performed at 1064â nm for its sensitivity to aerosol, whereas detectors are limited by low efficiency and high dark count rate (DCR). SNSPDs are characterized by high efficiency in the infrared wavelength domain, as well as low noise and dead time, which can significantly enhance the signal quality. However, it is still challenging to build an SNSPD with both large active area and high count rate. To improve the maximal count rate (MCR) so as to avoid saturation in the near range, a 16-pixel interleaved SNSPD array and a multichannel data acquisition system are developed. As a reference, a synchronous system working at 532â nm is applied. In a continuous comparison experiment, backscatter ratio profiles are retrieved with resolutions of 90 m/3 min, and the 1064â nm system shows better performance, which is sensitive to aerosols and immune to the contamination of the ozone absorption and density of molecule change in the lower stratosphere.
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The synthesis of ideal photosensitizers (PSs) is considered to be the most significant bottleneck in photodynamic therapy (PDT). To discover novel PSs with excellent photodynamic anti-tumor activities, a series of novel photosensitizers 5,15-diaryl-10,20-dibromoporphyrins (I1-6) were synthesized by a facile method. Compared with hematoporphyrin monomethyl ether (HMME) as the representative porphyrin-based photosensitizers, it is found that not only the longest absorption wavelength of all compounds was red-shifted to therapeutic window (660 nm) of photodynamic therapy, but also the singlet oxygen quantum yields were significantly increased. Furthermore, all compounds exhibited lower dark toxicity (except I2) and stronger phototoxicity (except I4) against Eca-109 tumor cells than HMME. Among them, I3 possessed the highest singlet oxygen quantum yield (ΦΔ = 0.205), the lower dark toxicity and the strongest phototoxicity (IC50 = 3.5 µM) in vitro. The findings indicated the compounds I3 had the potential to become anti-tumor agents for PDT.
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Neoplasias , Fotoquimioterapia , Porfirinas , Humanos , Fármacos Fotossensibilizantes/química , Oxigênio Singlete/química , Porfirinas/química , Neoplasias/tratamento farmacológicoRESUMO
Coding technology provides new ideas for spatial resolution enhancement of coherent Doppler wind lidar (CDWL). To improve the performance of coding CDWL for ultra-fine-wind field detection, the crosstalk between neighboring laser pulses is analyzed in theory. The strong backscattered signal from aerosols in near field region will interfere with the weak atmospheric signal, making the accuracy of Doppler shift estimation deteriorate seriously. Considering the formation mechanism of crosstalk, a solution based on adaptive field of view (FOV) modulation is proposed to suppress the crosstalk which is validated by numerical simulation and experiment. Dynamic range of the backscatter intensity is controlled from 10â dB to 2â dB within the distance of 50 m to 300 m, thus the crosstalk is accordingly suppressed.
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A multi-frequency differential absorption lidar incorporating a tunable laser and an optical frequency comb is demonstrated for precise spectrum analysis of atmospheric gas. The single frequency tunable laser is stabilized by locking to the optical frequency comb, with a standard deviation of 0.5â MHz. To achieve a high signal-to-noise ratio, a multi-mode superconducting nanowire single-photon detector with an active-area diameter of 50 µm, a quantum efficiency of 31.5%, and dark noise of 100 counts per second is implemented, which enables to avoid the need for high energy lasers. In the experiment, the range-resolved spectrum of atmospheric mixture gases (CO2 and HDO) in a region of 1572.2 - 1572.45â nm is obtained. Results show different partially overlapped absorption of two gases in different seasons, with a stronger influence of HDO on CO2 in summer than in winter. The interactions are taken into account by separating the mixture absorption spectrum (one CO2 line and two HDO lines) with triple-peak Voigt fitting. The retrieved concentrations over 6â km with a range resolution of 120 m and a time resolution of 10 min are compared with in-situ sensors. The uncertainties of the retrieved concentrations are as low as 6.5 µmol/mol (ppm) and 1×10-3 g/kg for CO2 and HDO, respectively.
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A photosensitizer with high phototoxicity, suitable amphipathy and low dark toxicity could play a pivotal role in photodynamic therapy (PDT). In this study, a facile and versatile approach was adopted to synthesize a series of novel fluorinated hematoporphyrin ether derivatives (I1-I5 and II1-II4), and the photodynamic activities of these compounds were studied. Compared to hematoporphyrin monomethyl ether (HMME), all PSs showed preferable photodynamic activity against A549 lung tumor cells. The longest visible absorption wavelength of these compounds was approximately 622 nm. Among them, II3 revealed the highest singlet oxygen yield (0.0957 min-1), the strongest phototoxicity (IC50 = 1.24 µM), the lowest dark toxicity in vitro, and exhibited excellent anti-tumor effects in vivo. So compound II3 could act as new drug candidate for photodynamic therapy.
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Antineoplásicos/uso terapêutico , Éteres/uso terapêutico , Hematoporfirinas/uso terapêutico , Hidrocarbonetos Fluorados/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Células A549 , Animais , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Teoria da Densidade Funcional , Éteres/síntese química , Éteres/efeitos da radiação , Feminino , Hematoporfirinas/síntese química , Hematoporfirinas/efeitos da radiação , Humanos , Hidrocarbonetos Fluorados/síntese química , Hidrocarbonetos Fluorados/efeitos da radiação , Luz , Camundongos Endogâmicos BALB C , Camundongos Nus , Modelos Químicos , Neoplasias/patologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Oxigênio Singlete/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND The long noncoding RNA (lncRNA) HOTTIP is involved in gastric cancer tumorigenesis, papillary thyroid carcinoma, colorectal cancer, lung adenocarcinoma, and hepatocellular carcinoma, but it is unclear how HOTTIP exerts roles in nasopharyngeal carcinoma (NPC). The present study investigated HOTTIP function during NPC development. MATERIAL AND METHODS HOTTIP levels in cancer specimens and cell lines were analyzed using qRT-PCR. HOTTIP function in NPC was determined by Cell Counting Kit-8 (CCK8) and Transwell assay. RESULTS HOTTIP expression was increased in NPC tissues. Higher levels of HOTTIP are correlated with lower survival in NPC patients. HOTTIP silencing suppressed the proliferation, cell cycle, migration, and invasion of NPC cells. HOTTIP served as a sponge for miR-4301. miR-4301 expression was significantly inhibited by HOTTIP in NPC cells. miR-4301 overexpression dramatically inhibited NPC cell proliferation, migration, and invasion. CONCLUSIONS This study showed that HOTTIP acts as an oncogene in NPC by sponging miR-4301.
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Neoplasias Nasofaríngeas/genética , RNA Longo não Codificante/genética , Adulto , Idoso , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica , RNA Longo não Codificante/biossínteseRESUMO
An all-fiber, eye-safe and micro-pulse polarization lidar is demonstrated with a polarization-maintaining structure, incorporating a single superconducting nanowire single-photon detector (SNSPD) at 1.5 µm. The time-division multiplexing technique is used to achieve a calibration-free optical layout. A single piece of detector is used to detect the backscatter signals at two orthogonal states in an alternative sequence. Thus, regular calibration of the two detectors in traditional polarization lidars is avoided. The signal-to-noise ratio of the lidar is guaranteed by using an SNSPD, providing high detection efficiency and low dark count noise. The linear depolarization ratio (LDR) of the urban aerosol is observed horizontally over 48 h in Hefei [N31°50'37'', E117°15'54''], when a heavy air pollution is spreading from the north to the central east of China. Phenomena of LDR bursts are detected at a location where a building is under construction. The lidar results show good agreement with the data detected from a sun photometer, a 532 nm visibility lidar, and the weather forecast information.
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MicroRNA-145 (miR-145) has been implicated in several cancers. However, its role in nasopharyngeal carcinoma (NPC) remains unclear. In this study, we proved that miR-145 was significantly downregulated in NPC and associated with NPC cell metastasis. Moreover, miR-145 suppressed Smad3 by directly binding to the 3'-untranslated region (UTR) of Smad3. Knockdown of Smad3 in NPC cells inhibited cell migration and invasion, which was consistent with the effect of miR-145 in NPC cells. In addition, Smad3 expression was inversely correlated with miR-145 level in clinical NPC samples. Taken together, our findings indicate that miR-145 is a tumour suppressor that affects invasive and metastatic properties of NPC via the miR-145/Smad3 axis, leading us to propose that miR-145 overexpression might be a potential therapeutic strategy of NPC intervention.
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MicroRNAs/genética , Neoplasias Nasofaríngeas/genética , Proteína Smad3/biossíntese , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica/genética , Metástase Neoplásica , Proteína Smad3/genéticaRESUMO
OBJECTIVES: The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposes a substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely related to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA) plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; however, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear. METHODS: The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerase chain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasal polyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genes of miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evaluated using cell migration assay and wound healing assays. RESULTS: miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. In vitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-ß1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression. CONCLUSION: Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study provide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.
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Lily is a popular flower worldwide due to its elegant appearance and pleasant fragrance. Floral volatiles of lily are predominated by monoterpenes and benzenoids. While a number of genes for monoterpene biosynthesis have been characterized, the molecular mechanism underlying floral benzenoid formation in lily remains unclear. Here, we report on the identification and characterization of a novel BAHD acyltransferase gene that contributes to the biosynthesis of two related floral scent benzoate esters, ethyl benzoate and methyl benzoate, in the scented Lilium oriental hybrid 'Siberia'. The emission of both methyl benzoate and ethyl benzoate in L. 'Siberia' was found to be tepal-specific, floral development-regulated and rhythmic. Through transcriptome profiling and bioinformatic analysis, a BAHD acyltransferase gene designated LoAAT1 was identified as the top candidate gene for the production of ethyl benzoate. In vitro enzyme assays and substrate feeding assays provide substantial evidence that LoAAT1 is responsible for the biosynthesis of ethyl benzoate. It was interesting to note that in in vitro enzyme assay, LoAAT1 can also catalyze the formation of methyl benzoate, which is typically formed by the action of benzoic acid methyltransferase (BAMT). The lack of an expressed putative BAMT gene in the flower transcriptome of L. 'Siberia', together with biochemical and expression evidence, led us to conclude that LoAAT1 is also responsible for, or at least contributes to, the biosynthesis of the floral scent compound methyl benzoate. This is the first report that a member of the plant BAHD acyltransferase family contributes to the production of both ethyl benzoate and methyl benzoate, presenting a new mechanism for the biosynthesis of benzoate esters.
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Geometric deep learning has sparked a rising interest in computer graphics to perform shape understanding tasks, such as shape classification and semantic segmentation. When the input is a polygonal surface, one has to suffer from the irregular mesh structure. Motivated by the geometric spectral theory, we introduce Laplacian2Mesh, a novel and flexible convolutional neural network (CNN) framework for coping with irregular triangle meshes (vertices may have any valence). By mapping the input mesh surface to the multi-dimensional Laplacian-Beltrami space, Laplacian2Mesh enables one to perform shape analysis tasks directly using the mature CNNs, without the need to deal with the irregular connectivity of the mesh structure. We further define a mesh pooling operation such that the receptive field of the network can be expanded while retaining the original vertex set as well as the connections between them. Besides, we introduce a channel-wise self-attention block to learn the individual importance of feature ingredients. Laplacian2Mesh not only decouples the geometry from the irregular connectivity of the mesh structure but also better captures the global features that are central to shape classification and segmentation. Extensive tests on various datasets demonstrate the effectiveness and efficiency of Laplacian2Mesh, particularly in terms of the capability of being vulnerable to noise to fulfill various learning tasks.
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BACKGROUND: The present work was conducted to screen the potential biomarkers affecting nasopharyngeal carcinoma (NPC) progression through RNA-sequencing (RNA-seq), bioinformatic analysis and functional experiments. MATERIALS AND METHODS: Six normal samples and five NPC clinical samples were collected for RNA-seq analysis. The expression levels in both groups were determined through student's t-test. We identified genes of P < 0.01 as the differentially expressed genes (DEGs). In addition, gene set enrichment analysis (GSEA) was conducted. Afterwards, STRING V10 database was employed to extract protein interactions among the DEGs. Later, we established a protein-protein interaction (PPI) network, and used the Cytoscape software for network visualization. qRT-PCR was conducted to verify hub genes from clinical samples. Then, the function of CXCL10 in cell proliferation, apoptosis, invasion and migration was evaluated. RESULTS: A total of 2024 DEGs were identified, among which, 1449 were down-regulated and 575 were up-regulated. The PPI was constructed, and the hub genes including Insulin Like Growth Factor 1 (IGF1), C-X-C Motif Chemokine Ligand 10 (CXCL10), Interleukin 13 (IL13), Intercellular Adhesion Molecule 1 (ICAM1), G Protein Subunit Gamma Transducin 1 (GNGT1), Matrix Metallopeptidase 1 (MMP1), Neurexin 1 (NRXN1) and Matrix Metallopeptidase 3 (MMP3) were obtained. The expression levels of CXCL10, IGF1, MMP3, MMP1, ICAM1, and IL-13 were significantly up-regulated in tumor tissues. High expression levels of CXCL10, MMP3 and ICAM1 predicted poor prognosis of NPC patients. CXCL10 silencing suppressed NPC cell proliferation and migration. CONCLUSIONS: CXCL10 may serve as a potential key gene affecting NPC genesis and progression.
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Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Biologia Computacional , Progressão da Doença , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Interleucina-13/genética , Interleucina-13/metabolismo , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , RNA-SeqRESUMO
PURPOSE: Hsa_circ_0007637 was discovered to be differentially expressed in nasopharyngeal carcinoma (NPC). However, the exact function and mechanism of Hsa_circ_0007637 on NPC have not been studied. This study firstly researched the function and mechanism of Hsa_circ_0007637 on NPC progression. METHODS: Hsa_circ_0007637, miR-636 and TPD52 expressions in 80 NPC patients were detected by quantitative real-time polymerase chain reaction. Hsa_circ_0007637 effect on NPC cell proliferation, apopticosis, invasion and migration was investigated by cell counting kit-8 assay, flow cytometry, transwell experiment and wound healing assay accordingly. Dual-luciferase reporter gene assay, RNA immunoprecipitation experiment and RNA fluorescence in situ hybridization experiment were performed to identify the binding between Hsa_circ_0007637 and miR-636. Dual-luciferase reporter gene assay and RNA pull down assay were conducted to verify the binding between miR-636 and TPD52. TPD52 protein expression in NPC cells was determined by Western blot. In vivo study was performed using nude mice. Immunohistochemistry was performed to assess TPD52 and Ki67 expression in tissues. RESULTS: Hsa_circ_0007637 was overexpressed in NPC tissues and cells. High Hsa_circ_0007637 expression predicted a poor outcome for NPC patients. Hsa_circ_0007637 knockdown decreased proliferation, invasion, migration and increased apoptosis of NPC cells (P < 0.01). Hsa_circ_0007637 could enhance TPD52 expression via sponging miR-636. miR-636 overexpression or TPD52 knockdown weakened the promoting effect of Hsa_circ_0007637 on NPC cells malignant phenotype (P < 0.01). Hsa_circ_0007637 knockdown suppressed NPC cells growth in vivo (P < 0.01). CONCLUSION: Hsa_circ_0007637 facilitates NPC progression by sponging miR-636/TPD52 axis.
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Spectroscopy is a well-established nonintrusive tool that has played an important role in identifying and quantifying substances, from quantum descriptions to chemical and biomedical diagnostics. Challenges exist in accurate spectrum analysis in free space, which hinders us from understanding the composition of multiple gases and the chemical processes in the atmosphere. A photon-counting distributed free-space spectroscopy is proposed and demonstrated using lidar technique, incorporating a comb-referenced frequency-scanning laser and a superconducting nanowire single-photon detector. It is suitable for remote spectrum analysis with a range resolution over a wide band. As an example, a continuous field experiment is carried out over 72 h to obtain the spectra of carbon dioxide (CO2) and semi-heavy water (HDO, isotopic water vapor) in 6 km, with a range resolution of 60 m and a time resolution of 10 min. Compared to the methods that obtain only column-integrated spectra over kilometer-scale, the range resolution is improved by 2-3 orders of magnitude in this work. The CO2 and HDO concentrations are retrieved from the spectra acquired with uncertainties as low as ±1.2% and ±14.3%, respectively. This method holds much promise for increasing knowledge of atmospheric environment and chemistry researches, especially in terms of the evolution of complex molecular spectra in open areas.
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INTRODUCTION: Olfactory ensheathing cell is a unique kind of glia cells, which can promote axon growth. Little is known about the differences between olfactory mucosa olfactory ensheathing cells and olfactory bulb olfactory ensheathing cells in the capability to promote nerve regeneration. OBJECTIVE: To study the recovery of the rat facial nerve after olfactory ensheathing cells transplantation, and to compare the differences between the facial nerve regeneration of olfactory mucosa-olfactory ensheathing cells and olfactory bulb olfactory bulb olfactory ensheathing cells transplantation. METHODS: Institutional ethical guideline was followed (201510129A). Olfactory mucosa-olfactory ensheathing cells and olfactory bulb olfactory ensheathing cells were cultured and harvested after 7 days in vitro. 36 Sprague Dawley male rats were randomly divided into three different groups depending on the transplanting cells: Group A: olfactory mucosa-olfactory ensheathing cells; Group B: olfactory bulb olfactory ensheathing cells; Group C: DF-12 medium/fetal bovine serum. The main trunk of the facial nerve was transected and both stumps were inserted into a polylactic acid/chitosan conduit, then the transplanted cells were injected into the collagen in the conduits. After 4 and 8 weeks after the transplant, the rats of the three groups were scarified and the facial function score, facial nerve evoked potentials, histology analysis, and fluorescent retrograde tracing were tested and recorded, respectively, to evaluate the facial nerve regeneration and to analysis the differences among the three groups. RESULTS: Olfactory ensheathing cells can promote the facial nerve regeneration. Compared with olfactory bulb olfactory ensheathing cells, olfactory mucosa olfactory ensheathing cells were more effective in promoting facial nerve regeneration, and this difference was more significant 8 weeks after the transplantation than 4 weeks. CONCLUSION: We discovered that olfactory ensheathing cells with nerve conduit could improve the facial nerve recovery, and the olfactory mucosa olfactory ensheathing cells are more effective for facial nerve regeneration compared with olfactory bulb olfactory ensheathing cells 8 weeks after the transplantation. These results could cast new light in the therapy of facial nerve defect, and furnish the foundation of auto-transplantation of olfactory mucosa olfactory ensheathing cells in periphery nerve injury.
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Nervo Facial , Regeneração Nervosa , Animais , Masculino , Bulbo Olfatório , Mucosa Olfatória , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: This study aimed to investigate the expression and biological function of miR-141-3p in nasopharyngeal carcinoma (NPC) via targeting neoplasm metastasis 1 (NME1). MATERIALS AND METHODS: The expression of miR-141-3p and NME1 in 5-8F, C666-1, CNE-1, CNE-2, 6-10B and NP69 nasopharyngeal epithelial cells were detected using real-time Polymerase Chain Reaction (real-time PCR) and western blot, respectively. Cell proliferation was detected using Cell Counting Kit-8 (CCK-8), and the metastasis was detected using Transwell. The binding of miR-141-3p to NME1 was detected by dual luciferase reporter gene detection system. The effects of miR-141-3p on tumor growth were also determined in vivo. RESULTS: The results showed that the expression of miR-141-3p significantly increased in various tumor cell lines and the expression of NME1 was higher in NP69 cells and lower in 5-8F cells, which had significant negative correlation. Furthermore, the expression of NME1 was significantly reduced after transfection of miR-141-3p and miR-141-3p promoted cell proliferation and metastasis. The double luciferase reporter gene detection system confirmed that NME1 was the target gene of miR-141-3p. Knockout of NME1 promoted the proliferation and metastasis of NP69 or 6-10B cells and the activation of p-Akt, which were abrogated by miR-141-3p. In vivo, the tumor volumes and weights in the miR-141-3p group significantly increased followed by down-regulation of NME1 and activation of p-Akt. CONCLUSIONS: We confirmed that miR-141-3p promotes the proliferation and metastasis of NPC by targeting NME1.
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Biomarcadores Tumorais/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Nucleosídeo NM23 Difosfato Quinases/metabolismo , Carcinoma Nasofaríngeo/secundário , Neoplasias Nasofaríngeas/patologia , Animais , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nucleosídeo NM23 Difosfato Quinases/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Photodynamic therapy (PDT) has been developed as a promising therapeutic method in cancer treatment. The discovery of effective photosensitizer, which is the key factor of PDT, is highly desired. This paper reports the synthesis of novel chlorin derivatives, 5,10,15,20-tetraphenyl-[2:3]-[(methoxycarbonyl, carboxy)methano] chlorin I and 5,10,15,20-tetraphenyl-[2:3]- {[methoxycarbonyl, (2-hydroxyethyl)amide]methano}chlorin II. Their structures were characterized with UV-vis, 1HNMR, 13CNMR and HRMS spectroscopies. Photophysical and photochemical experiments results showed that compound I and II had an absorption maximum around 650 nm, with molar extinction coefficients of 1 × 104 M-1 cm-1. They had strong fluorescence emission in 650-660 nm upon excitation with 419-422 nm light. ESR showed that singlet oxygen was produced upon irradiation of compounds with 650 nm light in the presence of molecular oxygen. The photo-bleaching test indicated that the structure of compounds was stable. These new compounds exhibit excellent anti-tumor effects and lower toxicity compared to m-THPC in vitro and in vivo. Compound I and II had high tumor selectivity, which could induced tumor cells shrinkage and necrosis under 650 nm laser irradiation. Flow cytometry revealed that the compounds might mediate PDT effect at late apoptotic phase. These results make these compound I and II promising candidates for future study in photo-diagnosis and photodynamic therapy of cholangiocarcinoma.