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We designed and prepared probe W-1 for the detection of H2O2. W-1 showed excellent selectivity for H2O2 and was accompanied by colorimetric signal changes. The excellent linear relationship between fluorescence intensity and H2O2 concentration (0-100 µM) provided favorable conditions for its quantitative detection. In addition, the combination of portable test strips with a smartphone platform provided great convenience for on-site visual detection of H2O2. Moreover, W-1 possessed targeting mitochondria property and could be applied to image the exogenous and endogenous H2O2 in cells to distinguish normal cells and cancer cells. Lastly, W-1 was used for monitoring the H2O2 fluctuation of the diabetic process in mice, and the results showed an increase in H2O2 levels in diabetes. Therefore, the probe provided a tool for understanding the pathological and physiological mechanisms of diabetes by imaging H2O2.
Assuntos
Diabetes Mellitus Experimental , Corantes Fluorescentes , Peróxido de Hidrogênio , Mitocôndrias , Peróxido de Hidrogênio/metabolismo , Animais , Mitocôndrias/metabolismo , Corantes Fluorescentes/química , Camundongos , Humanos , Colorimetria/métodos , Imagem Óptica/métodosRESUMO
The biodiversity of grasslands is important for ecosystem function and health. The protection and mana-gement of grassland biodiversity requires the collection of the information on plant diversity. Hyperspectral remote sensing, with its unique advantages of extensive coverage and high spectral resolution, offers a new solution for long-term monitoring of plant diversity. We first reviewed the development history of hyperspectral remote sensing technology, emphasized its advantages in monitoring grassland plant diversity, and further analyzed its specific applications in this field. Finally, we discussed the challenges faced by hyperspectral remote sensing technology in its applications, such as the complexity of data processing, accuracy of algorithms, and integration with ground-based remote sensing data, and proposes prospects for future research directions. With the advancement of remote sensing technology and the integrated application of multi-source data, hyperspectral remote sensing would play an increasingly important role in grassland ecological monitoring and biodiversity conservation, which could provide scientific basis and technical support for global ecological protection and sustainable development.
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Biodiversidade , Monitoramento Ambiental , Pradaria , Tecnologia de Sensoriamento Remoto , Tecnologia de Sensoriamento Remoto/métodos , Monitoramento Ambiental/métodos , Conservação dos Recursos Naturais/métodos , Imageamento Hiperespectral/métodos , Ecossistema , Poaceae/crescimento & desenvolvimentoRESUMO
Cerebral ischemia/reperfusion (CI/R) usually causes neuroinflammation within the central nervous system, further prompting irreversible cerebral dysfunction. Perilipin 2 (Plin2), a lipid droplet protein, has been reported to exacerbate the pathological process in different diseases, including inflammatory responses. However, the role and mechanism of Plin2 in CI/R injury are unclear. In this study, the rat models of transient middle cerebral artery occlusion followed by reperfusion (tMCAO/R) were established to mimic I/R injury, and we found that Plin2 was highly expressed in the ischemic penumbra of tMCAO/R rats. The siRNA-mediated knockdown of Plin2 significantly decreased neurological deficit scores and reduced infarct areas in rats induced by I/R. Detailed investigation showed that Plin2 deficiency alleviated inflammation of tMCAO/R rats as evidenced by reduced secretion of proinflammatory factors and the blockade of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation. In vitro experiments showed that Plin2 expression was upregulated in mouse microglia subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Plin2 knockdown inhibited OGD/R-induced microglia activation and the accumulation of inflammation-related factors. Taken together, this study demonstrates that lipid droplet protein Plin2 contributes to the pathologic process of CI/R damage by impacting inflammatory response and NLRP3 inflammasome activation. Thus, Plin2 may provide a new therapeutic direction for CI/R injury.
Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Ratos , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos Sprague-Dawley , Perilipina-2/genética , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Isquemia Encefálica/tratamento farmacológico , InflamaçãoRESUMO
Precise molecular engineering of AIEgens-based cationic delivery systems for high transfection efficiency (TE) and effective photodynamic therapy (PDT) holds a huge potential for cancer treatment. Herein, three amphiphiles (DT-C6/8/12-M) consisting of di(triazole-[12]aneN3) (M) and 1,1-dicyano-2-phenyl-2-(4-diphenylamino)phenyl-ethylene (DT) units have been developed to achieve luminescent tracking, efficient TE, and effective PDT in vitro and in vivo. These compounds exhibited strong aggregated induced emission (AIE) at 630 nm and mega Stokes shifts of up to 160 nm. They were able to bind DNA into nanoparticles with suitable sizes, positive surface potential, and good biocompatibility in the presence of DOPE. Among them, vector DT-C12-M/DOPE with n-dodecyl linker achieved a transfection efficiency as high as 42.3 folds that of Lipo2000 in PC-3 cell lines. DT-C12-M/DOPE exhibited the capability of successful endo/lysosomal escape and rapid nuclear delivery of pDNA, and the gene delivery process was clearly monitored via confocal laser scanning microscopy. Moreover, efficient reactive oxygen species (ROS) generation by DT-C12-M upon light irradiation led to effective PDT in vitro . We further show that combination of p53 gene therapy and PDT dramatically enhanced cancer therapeutic outcome in vivo. This "three birds, one stone" strategy offers a novel and promising approach for real-time tracking of gene delivery and better cancer treatment.
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Nanopartículas , Neoplasias , Fotoquimioterapia , DNA/genética , Etilenos , Terapia Genética , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Espécies Reativas de Oxigênio , Triazóis , Proteína Supressora de Tumor p53RESUMO
Objectives: To investigate the effects of a glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide on podocytes, inflammation, and oxidative stress in patients with diabetic nephropathy (DN). Methods: Eighty-four DN patients treated by the department of endocrinology of the Affiliated Hospital of Hebei University during December 2017 and March 2019 were randomly assigned to a control group and a treatment group (n=42, respectively), with the control group prescribed with conventional DN medications and the treatment group receiving liraglutide treatment in addition to the conventional therapy. The course of treatment lasted for 12 weeks. hemoglobin A1c (HbA1C), body mass index (BMI), total cholesterol (TC), triglyceride (TG), urinary albumin excretion rate (UAER), urine podocalyxin (PCX), urine nephrin, as well as inflammation and oxidative stress markers such as tumor necrosis factor α (TNF-α), monocyte chemotactic protein-1 (MCP-1), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were measured pre- and post-treatment for intergroup comparison. Results: After 12 weeks of treatment, HbA1C, BMI, TC, and TG in both groups were reduced in comparison with the pre-treatment levels, with the levels in the treatment group lower than in the control group (p<0.05); reduced levels of UAER, PCX, and nephrin were detected in the two groups, with the treatment group exhibiting a significant reduction in these markers compared with the control group (p<0.05); the 12-week treatment led to decreases in the TNF-α, MCP-1, and MDA levels in both groups, with the decline in the treatment group exceeding that in the control group, whereas both groups had an increased level of GSH-Px, with the level in the treatment group higher than that in the control group, and the differences were statistically significant (p<0.05, respectively). Conclusions: Liraglutide protects the kidneys and improves DN by inhibiting inflammation and oxidative stress, reducing urinary albumin excretion and podocyte damage and supporting renal function in addition to its hypoglycemic properties.
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Gene therapy holds great promise for treatment of gene-associated diseases. However, safe and successful clinical application urgently requires further advancement of constructing efficient delivery systems. Herein, three amphiphilic peptide dendrimers (TTC-L-KRR/KKK/KHH), containing the natural amino acid residues (lysine K, arginine R, and histidine H) and AIE-based photosensitizer (tetraphenylethenethiophene modified cyanoacrylate, TTC) modified with alkyl chain (L), have been designed and prepared for improving therapeutic potency via the combination of gene therapy (GT) and photodynamic therapy (PDT). All three compounds possessed typical aggregation-induced emission (AIE) characteristics and ultralow critical micelle concentrations (CMCs). The liposomes consisting of amphiphilic peptide dendrimers and dioleoylphosphatidylethanolamine (DOPE) can effectively bind DNA into nanoparticles with appropriate sizes, regular morphology and good biocompatibility. Among them, liposomes TTC-L-KKK/DOPE exhibited the highest transfection efficiency up to 5.7-fold as compared with Lipo2000 in HeLa cells. Meanwhile, rapid endocytosis, successful endo/lysosomal escape, gene release and rapid nuclear delivery of DNA revealed the superiority of liposomes TTC-L-KKK/DOPE during gene delivery process. More importantly, efficient reactive oxygen species (ROS) generation by TTC-L-KKK/DOPE led to effective PDT, thus improving therapeutic potency via combining with p53 mediated-gene therapy. Our work brought novel insight and direction for the construction of bio-safe and bio-imaging liposome as the multifunctional nonviral gene vectors for the effective combined gene/photodynamic therapies.
Assuntos
Dendrímeros , Neoplasias , Fotoquimioterapia , DNA , Dendrímeros/química , Células HeLa , Humanos , Lipossomos/química , Neoplasias/tratamento farmacológico , Neoplasias/genética , Peptídeos/química , TransfecçãoRESUMO
Six amphiphiles (TTC-L-M-1/2/3/4/5/6), each consisting of hydrophilic macrocyclic polyamine triazole-[12]aneN3 (M) and a hydrophobic photosensitizer tetraphenylethenethiophene modified cyanoacrylate (TTC) moiety linked with alkyl chains (L), have been designed and synthesized for synergetic anticancer gene therapy and photodynamic therapy (PDT). These amphiphiles showed strong AIE fluorescence emissions around 600 nm with large Stokes shifts up to 168 nm in an aqueous solution. They were able to condense DNA into nanoparticles with appropriate sizes, positive charges, reversible release, and good biocompatibility. Quantitative and qualitative gene transfection studies indicated that TTC-L-M-4 with a 12 carbon alkyl chain exhibited the best transfection efficiency in HeLa cells, and its transfection efficiency was 4.5-fold that of Lipo2000 in the presence of DOPE. The detailed and efficient delivery process of DNA by TTC-L-M-4 was clearly observed through one- and two-photon fluorescence imaging. Simultaneously, TTC-L-M-4/DOPE was able to deliver siRNA and gene silencing was better than that of Lipo2000. Furthermore, TTC-L-M-4 was able to efficiently generate reactive oxygen species (ROS) for PDT upon light irradiation. It was further demonstrated that combined p53 gene therapy and PDT significantly enhanced cancer therapy in vitro and in vivo. This study provides novel one-for-all organic agents with multiple therapeutic modalities.
Assuntos
Fotoquimioterapia , DNA , Células HeLa , Humanos , Fótons , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologiaRESUMO
Multi-label learning deals with training examples each represented by a single instance while associated with multiple class labels. Due to the exponential number of possible label sets to be considered by the predictive model, it is commonly assumed that label correlations should be well exploited to design an effective multi-label learning approach. On the other hand, class-imbalance stands as an intrinsic property of multi-label data which significantly affects the generalization performance of the multi-label predictive model. For each class label, the number of training examples with positive labeling assignment is generally much less than those with negative labeling assignment. To deal with the class-imbalance issue for multi-label learning, a simple yet effective class-imbalance aware learning strategy called cross-coupling aggregation (COCOA) is proposed in this article. Specifically, COCOA works by leveraging the exploitation of label correlations as well as the exploration of class-imbalance simultaneously. For each class label, a number of multiclass imbalance learners are induced by randomly coupling with other labels, whose predictions on the unseen instance are aggregated to determine the corresponding labeling relevancy. Extensive experiments on 18 benchmark datasets clearly validate the effectiveness of COCOA against state-of-the-art multi-label learning approaches especially in terms of imbalance-specific evaluation metrics.
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BACKGROUND: Photodynamic therapy has been increasingly used to cope with the alarming problem of cancer. Porphyrins and their derivatives are widely used as Potent Photosensitizers (PS) for PDT. However, the hydrophobicity of porphyrins poses a challenge for their use in clinics, while most of the carbon dots (CDs) are known for good biocompatibility, solubility, and pH sensitivity. OBJECTIVE: This study aimed to improve the properties/biocompatibility of the pyropheophorbide-α for PDT. METHODS: The PPa-CD conjugate was synthesized through covalent interaction using amide condensation. The structure of synthesized conjugate was confirmed by TEM, 1HNMR, and FTIR. The absorption and emission spectra were studied. In vitro, cytotoxicity of the conjugate was examined in human esophageal cancer cell line (Eca-109). RESULTS: The results showed that the fluorescence of the drug was increased compared to its precursor. CDbased conjugate could generate ROS as well as enhanced biocompatibility by decreasing cytotoxicity. The conjugated drug also showed pH sensitivity in different solutions. CONCLUSION: The dark toxicity, as well as hemocompatibility, was improved.
Assuntos
Neoplasias , Fotoquimioterapia , Porfirinas , Carbono/química , Linhagem Celular Tumoral , Humanos , Concentração de Íons de Hidrogênio , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/farmacologiaRESUMO
The development of cationic polymers as non-viral gene vectors has been hurdled by their high toxicity, thus degradable and biocompatible polymers are urgently demanded. Herein, five polyesters (B3a-B3e) were synthesized based on the ring-opening copolymerization between α-allyl-δ-valerolactone and δ-valerolactone derivatives decorated with alkyl or alkoxyl chains of different lengths, followed by the modification with 1,5,9-triazacyclododecyl ([12]aneN3) through thiol-ene click reactions. The five polyesters effectively condensed DNA into nanoparticles. Of them, B3a with a shorter alkyl chain and B3d with more positive charged units showed stronger DNA condensing performance and can completely retard the migration of DNA at N/P = 1.6 in the presence of DOPE. B3b/DOPE with a longer alkyl chain exhibited the highest transfection efficiency in HeLa cells with 1.8 times of 25 kDa PEI, while B3d/DOPE with more positive charged units exhibited highest transfection efficiency in A549 cells with 2.3 times of 25 kDa PEI. B3b/DOPE and B3d/DOPE successfully delivered pEGFP into zebrafish, which was superior to 25 kDa PEI (1.5 folds and 1.1 folds, respectively). The cytotoxicity measurements proved that the biocompatibility of these polyesters was better than 25 kDa PEI, due to their degradable property in acid environment. The results indicated that these cationic polyesters can be developed as potential non-viral gene vectors for DNA delivery.
Assuntos
DNA/genética , Técnicas de Transferência de Genes , Lactonas/química , Nanopartículas/química , Poliésteres/química , Cátions/química , Cátions/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Vetores Genéticos/química , Humanos , Estrutura Molecular , Plasmídeos/genética , Poliésteres/farmacologia , Polimerização , Relação Estrutura-AtividadeRESUMO
Two-photon fluorescent Acenaphtho[1,2-b]quinoxaline (ANQ) and the hydrophilic di-(triazole-[12]aneN3) moieties were combined through an alkyl chain (ANQ-A-M) or a ß-hairpin motif with two aromatic γ-amino acid residues (ANQ-H-M) to explore their capabilities for in vitro and in vivo gene delivery and tracing. ANQ-A-M and ANQ-H-M showed the same maximum absorption at 420 nm, and their fluorescent intensities around 650 nm were varied in different solvents and became poor in the protic solvents. Gel electrophoresis assays indicated that both compounds completely retarded the migration of pDNA at 20 µM in the presence of DOPE. However, the DNA condensation with ANQ-H-M was not reversible, and the particle size of the corresponding complexes were larger indicated from the SEM and DLS measurements. In vitro transfections indicated ANQ-A-M/DOPE achieved Luciferase and GFP expressions were to be 7.9- and 5.7-fold of those by Lipo2000 in A549 cells respectively. However, ANQ-H-M showed very poor transfection efficiency in Luciferase expression. With the help of single/two-photon fluorescence imaging it clearly demonstrated that the successful transfection of ANQ-A-M was attributed to its cellular uptake, apparent lysosomal escape, and reversible release of DNA; and the poor transfection of ANQ-H-M was resulted from the aggregation of the DNA complexes which prevented them from the cellular uptake, and also the strong binding ability which is not easy to release DNA. ANQ-A-M/DOPE also exhibited robust gene silencing (83% knockdown of Luciferase) and GFP expression (2.47-fold higher) efficiency compared with Lipo2000 in A549 and zebrafish, respectively. The work demonstrated that the linkage structure between fluorescent and di(triazole-[12]aneN3) played the important role for their gene delivery performance, and that ANQ-A-M represents a vector with the strong transfection efficiency in vitro and in vivo as well as the efficient real time bioimaging properties, which is potential for the development in biomedical research.
Assuntos
Compostos de Anilina/química , DNA/genética , Corantes Fluorescentes/química , Técnicas de Transferência de Genes , Imagem Óptica , Fótons , Quinoxalinas/química , RNA Interferente Pequeno/genética , Compostos de Anilina/síntese química , Corantes Fluorescentes/síntese química , Vetores Genéticos/síntese química , Vetores Genéticos/química , Quinoxalinas/síntese químicaRESUMO
Although a plethora of gene carriers have been developed for potential gene therapy, imageable stimuli-responsive gene vectors with fast access to the nucleus, high biocompatibility, and transfection efficiency are still scarce. Herein, we report the design and synthesis of four dendrite-shaped cationic liposomes, MPA-HBI-R/DOPE (R: n-butyl, 1; n-octyl, 2; n-dodecyl, 3; palmyl, 4), prepared via esterification of 4-alkoxybenzylideneimidazolinone containing aliphatic chains of different lengths (HBI-R), the green fluorescent protein (GFP) chromophore, with a di[12]aneN3 unit. Liposomes were fabricated via the self-assembly of MPA-HBI-R, assisted with 1,2-dioleoyl-sn-glycerol-3-phosphorylethanolamine (DOPE). These liposomes (MPA-HBI-R/DOPE) exhibited efficient DNA condensation, pH-responsive degradation, excellent cellular biocompatibility (up to 150 µM), and high transfection efficiency. Molecular docking experiments were also used to verify the optimal interaction between MPA-HBI-R and DNA, as well as the fluorescence enhancements. In particular, MPA-HBI-2/DOPE delivered DNA into the nucleus in less than an hour, and its luciferase transfection activity was more than 10 times that by Lipo2000, across multiple cell lines. The GFP chromophore conjugation allowed trackable intracellular delivery and release of DNA in real time via fluorescence imaging. Furthermore, efficient red fluorescent protein (RFP) transfection in zebrafish, with an efficiency of more than 6 times that by Lipo2000, was also achieved. The results not only realized, for the first time, the combination of gene delivery and GFP-simulated light emission, allowing fluorescent tracking and highly efficient gene transfection, but also offered valuable insights into the use of biomimetic chromophore for the development of the next-generation nonviral vectors.
Assuntos
Lipossomos , Luminescência , Animais , DNA/genética , Proteínas de Fluorescência Verde/genética , Simulação de Acoplamento Molecular , Transfecção , Peixe-Zebra/genéticaRESUMO
Although a plethora of nonviral gene vectors have been developed for potential gene therapy, imageable gemini surfactants with stimuli-responsiveness and high transfection efficiency are still scarce for gene delivery. Herein, three gemini amphiphiles (DEDPP-4/8/12) consisting of an aggregation-induced emission (AIE) central fluorophore: 5,6-diphenylpyrazine-2,3-diester (DEDPP), decorated with triazole-[12]aneN3 as the hydrophilic moiety and alkyl chains of various lengths as the hydrophobic moiety, were designed and synthesized for trackable gene delivery via optical imaging. All three amphiphiles exhibited ultralow critical micelle concentrations (CMCs) (up to 3.40 × 10-6 M), prominent two-photon absorption properties, and solvatochromic fluorescence. Gel electrophoresis assays demonstrated that the migration of plasmid DNA was completely retarded after condensation with these gemini amphiphiles at low concentrations (up to 10 µM). In addition, the ester bond in these amphiphiles may facilitate vector degradation and DNA release, in response to esterase and the acidic environment inside cells. Upon self-assembly with DOPE to form liposomes, DEDPP-8/DOPE achieved the best transfection efficiency in four cell lines, and the transfection efficiency of DEDPP-8/DOPE in HeLa cell lines was 23.5-fold higher than that of Lipo2000, which is unusually high for small organic molecule-based nonviral vectors. Furthermore, excellent transfection efficiency of DEDPP-8/DOPE was obtained in the presence of serum, and the red fluorescence protein (RFP) gene was successfully transfected in zebrafish embryos. Both one- and two-photon fluorescence imaging clearly demonstrated the delivery process of plasmid DNA. This study demonstrated that gemini-type amphiphiles composed of a two-photon fluorophore core conjugated with triazole-[12]aneN3 via an ester bond afforded an unprecedentedly high transfection efficiency with excellent biocompatibility, which may provide new insights for the design and development of multifunctional nonviral gene vectors for imageable gene delivery.
Assuntos
Calcitriol/análogos & derivados , Corantes Fluorescentes/química , Técnicas de Transferência de Genes , Imagem Óptica , Pirazinas/química , Tensoativos/química , Calcitriol/síntese química , Calcitriol/química , Células Cultivadas , Corantes Fluorescentes/síntese química , Células HEK293 , Humanos , Estrutura Molecular , Tamanho da Partícula , Fótons , Pirazinas/síntese química , Propriedades de Superfície , Tensoativos/síntese químicaRESUMO
With the aim to develop a novel multifunctional gene delivery system that may overcome the common barriers of gene transfection, near-infrared fluorescent triphenylamine-pyrazine was modified with a DNA condensing triazole-[12]aneN3 moiety through different length alkyl ester linkages to afford three new non-viral gene vectors, TDM-A/B/C. All compounds showed prominent solvatochromic fluorescence (Stokes shift of up to 383 nm) and two-photon absorption properties (σ2P to 101 GM), and exhibited strong aggregation-induced emission (AIE). Gel electrophoresis demonstrated that plasmid DNA was completely condensed at a concentration of 10 µM (TDM-A), 14 µM (TDM-B) and 16 µM (TDM-C), and released in esterase and acidic environment. SEM demonstrated that the three compounds were able to self-assemble and co-aggregate with DNA to form regular nanoparticles. Experiments demonstrated that TDM-A/B/C was able to integrate with DNA through electrostatic interactions and supramolecular stacking, and the short alkyl linkage favored the strong interaction with DNA. Among the three compounds, TDM-B showed the best luciferase and GFP transfection activities in the presence of DOPE, which were 156% and 310% higher than those of Lipo2000, respectively. The transfection process of DNA was clearly traced through one- and two-photon fluorescence microscopy imaging. Cellular uptake inhibition assay indicated that the DNA complex entered the cell mainly via clathrin-independent endocytosis. Furthermore, the in vivo transfection experiments of TDM-B/DOPE were successfully implemented in zebra fish embryos, and the GFP gene expression level was superior to that of Lipo2000 (200%). Finally, this study clearly unraveled that the length of the alkyl linkage affected the DNA condensation and transfection activity, which can serve as a base for the future rational design of non-viral gene vectors.
Assuntos
Compostos de Anilina/química , Compostos Macrocíclicos/química , Imagem Óptica , Fótons , Poliaminas/química , Pirazinas/química , Compostos de Anilina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células HEK293 , Células HeLa , Humanos , Lipossomos/química , Compostos Macrocíclicos/farmacologia , Microscopia de Fluorescência , Estrutura Molecular , Tamanho da Partícula , Poliaminas/farmacologia , Pirazinas/farmacologia , Propriedades de Superfície , Células Tumorais CultivadasRESUMO
Tumor targeting provided more effective gene therapy. Bcl-2 is an oncogene, and Bcl-2 small interfering RNA (Bcl-2 siRNA) can inhibit its expression. Here, a fluorescent and gene-loading capacity vector DPL, derived from diketopyrrolopyrrole (DPP), was developed for Bcl-2 siRNA-targeted delivery and tumor imaging in vitro and in vivo. The vector DPL showed a significant emission enhancement after interacting with siRNA, which was used to track the gene transfer process. Compared to commercial transfection reagent Lipo 2000, DPL obviously downregulated the Bcl-2 protein expression and exhibited excellent antitumor efficacy with less Bcl-2 siRNA. Importantly, DPL can target tumors to transport Bcl-2 siRNA to tumor sites in vivo based on the enhanced permeability and retention (EPR) effect for effective in vivo tumor therapy. This work inspired us to design and synthesize a multifunctional gene vector for tumor targeting and gene therapy.
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Terapia Genética , Vetores Genéticos/genética , Neoplasias/genética , Neoplasias/terapia , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Interferente Pequeno/genética , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Marcação de Genes , Vetores Genéticos/metabolismo , Humanos , Camundongos , Neoplasias/metabolismo , Neoplasias/fisiopatologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Interferente Pequeno/metabolismo , TransfecçãoRESUMO
Three nonviral gene vectors, TPA-BI-A/B/C, have been designed and synthesized by the combination of one or two hydrophilic [12]aneN3 moieties and two-photon fluorescent triphenylamine-benzylideneimidazolone (TPA-BI) units through different ester linkage. Spectroscopic characterization demonstrated that TPA-BI-A/B/C had strong aggregation-induced emissions (AIE), large Stokes shifts (230, 284, and 263 nm), and large two-photon absorption cross sections (δ2PA) (67, 592, and 80 GM). Gel electrophoresis indicated that the three compounds completely condensed DNA at 15 µM in the presence of DOPE, and showed the lipase- and pH-triggered reversible release of DNA and the fluorescent recognition of the different lengths of ssDNA and dsDNA. The optimal TPA-BI-C/DOPE-mediated luciferase and GFP activity was 146% and 290% higher than those of Lipo2000. The transfection process of DNA could be traced clearly through one- and two-photon fluorescence spectra, and displayed in a 3D-video. TPA-BI-C/DOPE successfully transfected the GFP gene into zebrafish, which was superior to Lipo2000 (192%). In conclusion, TPA-BI-C/DOPE is the first nonviral gene vector with the abilities of pH/lipase enzyme responsiveness, one/two-photon fluorescent tracking of intracellular delivery of DNA, and successful transfection in vivo and in vitro, even better than Lipo2000.
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Corantes Fluorescentes , Técnicas de Transferência de Genes , Vetores Genéticos , Fosfatidiletanolaminas , Células A549 , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Vetores Genéticos/química , Vetores Genéticos/genética , Vetores Genéticos/farmacologia , Humanos , Microscopia de Fluorescência por Excitação Multifotônica , Fosfatidiletanolaminas/sangue , Fosfatidiletanolaminas/farmacologiaRESUMO
Vapor transportation is the core process in growing transition-metal dichalcogenides (TMDCs) by chemical vapor deposition (CVD). One inevitable problem is the spatial inhomogeneity of vapors. The non-stoichiometric supply of transition-metal precursors and chalcogens leads to poor control in the products' location, morphology, crystallinity, uniformity and batch to batch reproducibility. The vapor-liquid-solid (VLS) growth method often involves molten precursors (e.g., non-volatile Na2MoO4) at growth temperatures higher than their melting points. The liquid Na2MoO4 can precipitate out solid MoS2 monolayers when saturated with sulfur vapor. Taking advantage of the VLS growth, we attained three kinds of important achievements: (i) a 4-inch-wafer-scale uniform growth of MoS2 flakes on SiO2/Si substrates, (ii) a 2-inch-wafer-scale growth of continuous MoS2 film with the grain size exceeding 100 µm on sapphire substrates, and (iii) a patterned (site-controlled) growth of MoS2 flakes and films. We clarified that the VLS growth thus paves a new way for the high-efficient and scalable synthesis of two-dimensional TMDC monolayers.
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Oligoamide molecular strands with hydrogen-bonding sequences DADDAD and guanidine (O-1) or 1,5,9-triazacyclododecane ([12]aneN3 ; O-2) side chains and oligoamides with hydrogen-bonding sequences ADAADA and octyl moieties (O-3), were synthesized. Two duplexes (D-1 and D-2) were prepared by conjugating the hydrophilic O-1 or O-2 and hydrophobic O-3 through sequence-specific hydrogen-bond association and cross-linked disulfide bonds. Electrophoresis measurements indicated that O-1, O-2, D-1, and D-2 were able to completely retard the DNA mobiliy at concentrations of 30, 30, 10, and 20â µM, respectively. Reversible DNA release in O-1 and O-2 complexes can be achieved in the presence of heparin sodium, whereas the presence of GSH greatly improved DNA release in D-1 and D-2 complexes. The particles formed were in a size range of 50-170â nm with positively charged surfaces. D-1 and D-2 transfected pEGFP-N1 into HeLa cells successfully.
Assuntos
Portadores de Fármacos/química , Portadores de Fármacos/síntese química , Técnicas de Transferência de Genes , Glutationa/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Nylons/química , Nylons/síntese química , Técnicas de Química Sintética , DNA/química , DNA/genética , Portadores de Fármacos/metabolismo , Células HeLa , Humanos , Ligação de Hidrogênio , Nylons/metabolismo , OxirreduçãoRESUMO
OBJECTIVE: To explore the association of insulin resistance and ß cell function with lipid metabolism in middle-aged and elderly Hui and Han populations. METHODS: A total of 1000 subjects age over 40 years were recruited from five urban communities in Yinchuan and Wuzhong cities of Ningxia. The composition ratio between Hui and Han nationality was 1:2. A questionnaire-based survey was performed. Physical examinations were carried out to measure the height, body mass, waistline, and hipline. The levels of triglyceride (TG), total cholesterol (TC), blood uric acid (BUA), fasting blood glucose and insulin were measured. The boby mass index (BMI), waist-hip ratio (WHR), and secretion related index including insulin resistance index (IR), insulin sensitivity index (IAI), and beta cell function index (HBCI) were calculated. RESULTS: The BMI, WHR, IAI, HBCI, and the prevalence rate of diabetes in Hui nationality were significantly higher than those in Han nationality (P<0.01). The levels of BUA, fasting blood glucose, TC, and IR in Han nationality were significantly lower than those in Hui nationality (P<0.01). In Hui populations, TG, BMI, WHR, and BUA were positively correlated with IR (r=0.234, r=0.193, r=0.143, and r=0.129, respectively; P<0.01) and were negatively correlated with IAI (r=-0.234, r=-0.193, r=-0.143, r=-0.129, respectively; P<0.01), whereas TC was negatively correlated with HBCI (r=-0.169, P<0.01). In Han populations, TC, TG, BMI, WHR, and BUA were positively correlated with IR (r=0.140, r=0.257, r=0.288, r=0.163, r=0.104, P<0.01) and negatively correlated with IAI (r=-0.140, r=-0.257, r=-0.288, r=-0.163, and r=-0.104, P<0.01), whereas BMI was negatively correlated with HBCI (r=-0.111, P<0.01). After the influential factors such as gender, nationality, and age were adjusted, the TC, TG, BMI, WHR, BUA levels were positively correlated with IR (r=0.109, r=0.256, r=0.253, r=0.139, and r=0.142, P<0.01) and negatively correlated with IAI (r=-0.109, r=-0.256, r=-0.253, r=-0.139, and r=-0.142, P<0.01). TC and BMI were negatively correlated with HBCI (r=-0.113, r=-0.086, P<0.01). TG and BMI were independently associated with IR and IAI (r=0.218, r=0.182, r=-0.218, r=-0.182), while TC and BMI were independently associated with HBCI (r=-0.113, r=-0.086). CONCLUSIONS: The distributions of TC, TG, BMI, WHR, BUA, IR, IAI, and HBCI differ between Han and Hui populations. The development of insulin resistance is closely related with the increased levels of TC, TG, BMI, WHR, and BUA. However, the HBCI increases with the increased level of TC and BMI. TG and BMI may be related with insulin resistance. Also, TC and BMI may affect the secretion function of ß cells.
Assuntos
Resistência à Insulina , Células Secretoras de Insulina/citologia , Metabolismo dos Lipídeos , Idoso , Povo Asiático , Glicemia/análise , Índice de Massa Corporal , Colesterol/sangue , Etnicidade , Humanos , Insulina/sangue , Pessoa de Meia-Idade , Triglicerídeos/sangue , Ácido Úrico/sangueRESUMO
Self-organizing n-type hexaazatrinaphthylenes (HATNAs) with various bay-located side chains have been synthesized. The HATNA derivatives are able to form long-range molecular columns with self-directed growth directions. In particular, alkyl-substituted HATNAs showed in-plane molecular columns with axes parallel to substrates, whereas the columnar orientation of the HATNAs with alkylethynyl or alkylthio groups strongly depended on the length of the introduced side chains. Interestingly, the derivative with octylthio chains exhibited out-of-plane molecular columns, in which electron mobility of up to 10(-3) â cm(2) V(-1) s(-1) was determined through the time-of-flight technique, highlighting the fact that such molecular columns based on bay-substituted HATNAs are promising n-type semiconductors for device applications.