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In recent years, supramolecular hydrogels have made groundbreaking research progress in biomedical fields such as drug delivery, biosensing, imaging analysis, and tissue engineering. Peptides, with their unique characteristics of facile preparation, low immunogenicity and easy biodegradability, are commonly used as building blocks of supramolecular hydrogels. Peptide-based supramolecular hydrogels loaded with drugs, prepared via physical means or covalent crosslinking, exhibit unique three-dimensional network structures and strong water retention capacities. These properties enhance drug bioavailability and reduce side effects, enabling drug accumulation and responsive release at disease sites, significantly improving the therapeutic efficacy. Here, we review recent advancements in peptide-based supramolecular hydrogels and their biotherapeutic applications, including chemotherapy, photothermal therapy, photodynamic therapy, immunotherapy, gene therapy, antibacterial and anti-inflammatory treatments, and other biological applications. This review aims to provide new inspiration for the development of biomaterials in the therapeutic field and provide more personalized options for disease treatment. Additionally, challenges and limitations in this field are briefly discussed.
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Cesium oxide (CsOx) nanostructures grown on Au(111) behave as active centers for the CO2 binding and hydrogenation reactions. The morphology and reactivity of these CsOx systems were investigated as a function of alkali coverage using scanning tunneling microscopy (STM), ambient pressure X-ray photoelectron spectroscopy (AP-XPS), and density functional theory (DFT) calculations. STM results show that initially (0.05-0.10 ML) cesium oxide clusters (Cs2O2) grow at the elbow sites of the herringbone of Au(111), subsequently transforming into two-dimensional islands with increasing cesium coverage (>0.15 ML). XPS measurements reveal the presence of suboxidic (CsyO; y ≥ 2) species for the island structures. The higher coverages of cesium oxide nanostructures contain a lower O/Cs ratio, resulting in a stronger binding of CO2. Moreover, the O atoms in the CsyO structure undergo a rearrangement upon the adsorption of CO2 which is a reversible phenomenon. Under CO2 hydrogenation conditions, the small Cs2O2 clusters are hydroxylated, thereby preventing the adsorption of CO2. However, the hydroxylation of the higher coverages of CsyO did not prevent CO2 adsorption, and adsorbed CO2 transformed to HCOO species that eventually yield HCOOH. DFT calculations further confirm that the dissociated H2 attacks the C in the adsorbate to produce formate, which is both thermodynamically and kinetically favored during the CO2 reaction with hydroxylated CsyO. These results demonstrate that cesium oxide by itself is an excellent catalyst for CO2 hydrogenation that could produce formate, an important intermediate for the generation of value-added species. The role of the alkali oxide nanostructures as active centers, not merely as promoters, may have broad implications, wherein the alkali oxides can be considered in the design of materials tuned for specific applications in heterogeneous catalysis.
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Interest in macrocycles as potential therapeutic agents has increased rapidly. Macrocyclization of bioactive acyclic molecules provides a potential avenue to yield novel chemical scaffolds, which can contribute to the improvement of the biological activity and physicochemical properties of these molecules. In this study, we propose a computational macrocyclization method based on Transformer architecture (which we name Macformer). Leveraging deep learning, Macformer explores the vast chemical space of macrocyclic analogues of a given acyclic molecule by adding diverse linkers compatible with the acyclic molecule. Macformer can efficiently learn the implicit relationships between acyclic and macrocyclic structures represented as SMILES strings and generate plenty of macrocycles with chemical diversity and structural novelty. In data augmentation scenarios using both internal ChEMBL and external ZINC test datasets, Macformer display excellent performance and generalisability. We showcase the utility of Macformer when combined with molecular docking simulations and wet lab based experimental validation, by applying it to the prospective design of macrocyclic JAK2 inhibitors.
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Aprendizado Profundo , Inibidores de Janus Quinases , Compostos Macrocíclicos , Simulação de Acoplamento Molecular , Compostos Macrocíclicos/farmacologia , Compostos Macrocíclicos/química , Descoberta de Drogas/métodosRESUMO
Vibrio vulnificus is a facultative anaerobic, alkalophilic, halophilic, mesophilic, Gram-negative bacterium that can cause severe wound infection, sepsis and diarrhea. This paper reported a case of 85-year-old male patient infected with Vibrio vulnificus due to being stabbed by a sea shrimp. This patient also had diabetes with a long history of alcoholism. Due to bacterial pathogenicity and the patient's underlying diseases, his condition deteriorated rapidly. Based on the rapid diagnosis of Vibrio vulnificus using the next-generation sequencingï¼NGSï¼technology and blood culture method, as well as the selection of the most effective antibiotics via drug sensitivity test, this patient underwent precise antimicrobial treatment, thorough debridement and drainage within the shortest possible time, and thus the prognosis of this patient was greatly improved. In this paper, we have systematically explored the epidemiology, clinical features, diagnosis and treatment of Vibrio vulnificus infection, thus providing a practical reference for the clinicians to quickly identify and treat possible Vibrio vulnificus infection in diabetic patients after contacting with sea water or seafood.
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BACKGROUND: Hydrocortisone (HYD) has been suggested as a drug for anti-sepsis treatment, but its clinical efficacy remains controversial. This study aims to evaluate the function of HYD in sepsis-induced acute kidney injury (AKI) and the molecules involved. METHODS: A mouse model of sepsis was induced by cecal ligation and puncture (CLP) and treated with HYD. The kidney injury biomarkers and inflammatory cytokines in serum samples were determined. The pathological changes in mouse kidney tissues were examined by histological staining. Differentially expressed genes after HYD treatment were screened by microarray analysis. Expression of heat shock transcription factor 1 (HSF1) in the serum samples of septic patients and mouse kidney tissues after HYD treatment was determined. The downstream targets of HSF1 were bioinformatically predicted. Gain- and loss-of-function assays of HSF1 and exportin 1 (XPO1) were performed to validate their functions in AKI. RESULTS: CLP increased the levels of blood urea nitrogen and serum creatinine and the serum levels of pro-inflammatory cytokines. The levels of these biomarkers and the pathological changes and symptoms in mice induced by CLP were significantly alleviated by HYD treatment. HYD elevated the expression of HSF1, which was initially suppressed by CLP in mice. HSF1 bound to XPO1 promoter to suppress its transcription. Downregulation of HSF1 blocked the protective effects of HYD, but further suppression of XPO1 restored the function of HYD and ameliorated the kidney injury in mice. CONCLUSION: This study demonstrates that HYD alleviates sepsis-induced acute kidney injury through HSF1-mediated transcriptional suppression of XPO1.
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Injúria Renal Aguda , Sepse , Animais , Camundongos , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , Biomarcadores/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Hidrocortisona/farmacologia , Hidrocortisona/uso terapêutico , Rim/patologia , Sepse/complicações , Sepse/tratamento farmacológico , Humanos , Proteína Exportina 1RESUMO
In industrial catalysis, alkali cations are frequently used to promote activity or selectivity. Scanning tunneling microscopy, ambient-pressure X-ray photoelectron spectroscopy, and density-functional calculations were used to study the structure and reactivity of potassium oxides in contact with the Au(111) surface. Three different types of oxides (K2 O2 , K2 O and KOy with y<0.5) were observed on top of the gold substrate at 300-525â K. Initially, small aggregates of K2 O2 /K2 O (1-2â nm in size) were seen at the elbows of the herringbone structure. After increasing the K coverage (>0.15â ML), large islands of the oxide (20-40â nm in size) appeared. These islands contained a mixture of K2 O and KOy (y<0.5). A key correlation was found involving the structure, oxidation state, and chemical activity of the alkali oxide. The small aggregates of potassium oxide had a very high catalytic activity for the oxidation of CO, being much more than plain promoters.
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Introduction: Alzheimer's disease (AD) is the most frequent cause of dementia and still lacks effective therapy. Clinical signs of AD include low levels of endogenous melanocortins (MCs) and previous studies have shown that treatment with MC analogs induces neuroprotection in the early stages of AD. Methods: We investigated the neuroprotective role of MCs in two transgenic mouse models of severe AD using 5 and 7 month-old (mo) 5XFAD mice and 9 and 12 mo 3xTg mice. These mice were subjected to a chronic stimulation of MC receptors (MCRs) with MC analogue Nle4-D-Phe7-α-melanocyte stimulating hormone (NDP-α-MSH, 340 µg/kg, i.p.). Mouse behavior and ex-vivo histological and biochemical analyses were performed after 50 days of treatment. Results: Our analysis demonstrated an improvement in cognitive abilities of AD mice at late stage of AD progression. We also showed that these protective effects are associated with decreased levels of hyperphosphorylated Tau but not with Aß burden, that was unaffected in the hippocampus and in the cortex of AD mice. In addition, an age-dependent NDP effect on glial reactivity was observed only in 3xTg mice whereas a global downregulation of p38 mitogen-activated protein kinase was selectively observed in 7 mo 5XFAD and 14 mo 3xTg mice. Conclusion: Our results suggest that MCR stimulation by NDP-α-MSH could represent a promising therapeutic strategy in managing cognitive decline also at late stage of AD, whereas the effects on neuroinflammation may be restricted to specific stages of AD progression.
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Doença de Alzheimer , Disfunção Cognitiva , Receptor Tipo 4 de Melanocortina , Animais , Camundongos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Cognição , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Camundongos Transgênicos , Receptor Tipo 4 de Melanocortina/agonistasRESUMO
In this study, the preparation and desulfurization application of MnO2 and pyrolusite blending-modified activated cokes (ACM and ACP) were studied. Thermodynamic calculation shows that the blended metal oxides could be reacted with the solid carbon and gaseous products H2, CO, and CO2 for activation. The physicochemical properties of the blending-modified ACP and ACM responded considerably differently to preparation conditions. The blended metal oxide significantly improved the mesoporous structure of the modified activated cokes, as well as the surface acidic and basic functional groups. Different metal oxides played different roles in the pore structure and surface functional group evolution, and the current investigation indicates that MnO2 is more favorable than pyrolusite. The enhanced acidic and basic functional groups, coupled with the catalysis of metal oxides, improved the desulfurization performance of the modified activated cokes. The sulfur capacities of the prepared ACP and ACM were 47.9-208.9 and 119.4-205.9 mg/g, respectively, which were much greater than the sulfur capacity of the fresh activated coke.
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The efficient conversion of carbon dioxide, a major air pollutant, into ethanol or higher alcohols is a big challenge in heterogeneous catalysis, generating great interest in both basic scientific research and commercial applications. Here, we report the facilitated methanol synthesis and the enabled ethanol synthesis from carbon dioxide hydrogenation on a catalyst generated by codepositing Cs and Cu on a ZnO(0001Ì ) substrate. A combination of catalytic testing, X-ray photoelectron spectroscopy (XPS) measurements, and calculations based on density functional theory (DFT) and kinetic Monte Carlo (KMC) simulation was used. The results of XPS showed a clear change in the reaction mechanism when going from Cs/Cu(111) to a Cs/Cu/ZnO(0001Ì ) catalyst. The Cs-promoting effect on C-C coupling is a result of a synergy among Cs, Cu, and ZnO components that leads to the presence of CHx and CHyO species on the surface. According to the DFT-based KMC simulations, the deposition of Cs introduces multifunctional sites with a unique structure at the Cu-Cs-ZnO interface, particularly being able to promote the interaction with CO2 and thus the methanol synthesis predominantly via the formate pathway. More importantly, it tunes the CHO binding strongly enough to facilitate the HCOOH decomposition to CHO via the formate pathway, but weakly enough to allow further hydrogenation to methanol. The fine-tuning of CHO binding also enables a close alignment of a CHO pair to facilitate the C-C coupling and eventually ethanol synthesis. Our study opens new possibilities to allow the highly active and selective conversion of carbon dioxide to higher alcohols on widely used and low-cost Cu-based catalysts.
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Intracellular Aß (iAß) expression, extracellular Aß (eAß) plaque formation and microglial reactivity are characteristic neuropathological events of Alzheimer's disease (AD) and have been detected in several transgenic mouse models of this disease. In this work we decided to investigate the early (2-7 months of age) development of these phenomena at both regional and cellular levels in 5XFAD mice, a severe transgenic mouse model of AD. We demonstrated that 1) Aß pathology develops in many but not all brain regions, 2) iAß is transient and almost always followed by eAß in grey matter regions, and the respective levels are roughly proportional, and 3) in about 1/3 of the grey matter regions with Aß pathology and in several white matter regions, eAß plaques can appear where no iAß-positive structures were detected. We also showed that male and female mice share a similar regional and cellular pattern of Aß pathology development that is more prominent in females. Early iAß is associated to the activation of microglia, while subsequent formation of eAß plaques is associated with markedly increased density of microglial cells that acquire a characteristic clustered phenotype. Present analysis is relevant to set a reference for pathophysiological studies and to define specific targets for the test of therapeutic interventions in this widely used AD transgenic model.
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Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Córtex Cerebral/patologia , Placa Amiloide/patologia , Doença de Alzheimer/genética , Doença de Alzheimer/imunologia , Peptídeos beta-Amiloides/análise , Animais , Córtex Cerebral/citologia , Córtex Cerebral/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Microglia/imunologia , Microglia/metabolismo , Microglia/patologia , Placa Amiloide/genética , Placa Amiloide/imunologia , Fatores SexuaisRESUMO
The data-driven approach to sustainable urban development is becoming increasingly popular among the cities across the world. This is due to cities' attention in supporting smart and sustainable urbanism practices. In an era of digitalization of urban services and processes, which is upon us, platform urbanism is becoming a fundamental tool to support smart urban governance, and helping in the formation of a new version of cities-i.e., City 4.0. This new version utilizes urban dashboards and platforms in its operations and management tasks of its complex urban metabolism. These intelligent systems help in maintaining the robustness of our cities, integrating various sensors (e.g., internet-of-things) and big data analysis technologies (e.g., artificial intelligence) with the aim of optimizing urban infrastructures and services (e.g., water, waste, energy), and turning the urban system into a smart one. The study generates insights from the sensor city best practices by placing some of renowned projects, implemented by Huawei, Cisco, Google, Ericsson, Microsoft, and Alibaba, under the microscope. The investigation findings reveal that the sensor city approach: (a) Has the potential to increase the smartness and sustainability level of cities; (b) Manages to engage citizens and companies in the process of planning, monitoring and analyzing urban processes; (c) Raises awareness on the local environmental, social and economic issues, and; (d) Provides a novel city blueprint for urban administrators, managers and planners. Nonetheless, the use of advanced technologies-e.g., real-time monitoring stations, cloud computing, surveillance cameras-poses a multitude of challenges related to: (a) Quality of the data used; (b) Level of protection of traditional and cybernetic urban security; (c) Necessary integration between the various urban infrastructure, and; (d) Ability to transform feedback from stakeholders into innovative urban policies.
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Post-combustion flue gas desulfurization and denitrification technologies are essential in achieving the full compliance of fine particulate matter (PM2.5, aerodynamic diameter less than 2.5 µm) air quality standards by 2030 in China as sulfur dioxide (SO2) and nitrogen oxides (NOX) are the main precursors of PM2.5. Some studies have addressed the performance evaluation of desulfurization technology, but none included the water-soluble ions (sulfate (SO42-), nitrate (NO3-), etc.) as an indicator nor accounted for uncertainty involved. In this study, we present a multilevel fuzzy method that integrates the analytic hierarchy process with fuzzy theory, defines SO42-concentration as a new environmental indicator, and is supplemented with an uncertainly analysis and apply the method for the techno-economic and environmental evaluation of desulfurization and denitrification technologies in six typical enterprises (including two power plants and three industrial production plants and a waste incineration plant) in Chengdu, China. The evaluation shows that first, the fluctuating desulfurization rate and the dosage leads to changed ranking of the economic and technical secondary evaluation results, with the overall comprehensive evaluation ranks unchanged. Second, from the perspective of environmental protection agency and the public, if the environmental indicators are empowered, the lower the SO42-concentration of an enterprise, the better its evaluation ranking will be and vice versa. Third, if we re-empower from the perspective of the enterprise, under the condition that the technical feasibility is met and the environmental indicators are basically up to standard, the low-cost removing process is more likely to be the tendency of the enterprise. In summary, the findings of the study have led to the conclusions that (1) for the power industry, the integration of desulfurization, denitrification, and dedusting technologies should be promoted rigorously; (2) the non-power industry should continue the end-of-pipe treatment and environmental protection regulatory policies of the power industry; and (3) the energy industry structure should be optimized with enhanced end-of-pipe control technologies to achieve deep reduction of air pollutants.
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Poluentes Atmosféricos , Desnitrificação , Poluentes Atmosféricos/análise , China , Material Particulado/análise , Dióxido de Enxofre/análiseRESUMO
Highly selective oxidation of methane to methanol has long been challenging in catalysis. Here, we reveal key steps for the pro-motion of this reaction by water when tuning the selectivity of a well-defined CeO2/Cu2O/Cu(111) catalyst from carbon monoxide and carbon dioxide to methanol under a reaction environment with methane, oxygen, and water. Ambient-pressure x-ray photoelectron spectroscopy showed that water added to methane and oxygen led to surface methoxy groups and accelerated methanol production. These results were consistent with density functional theory calculations and kinetic Monte Carlo simulations, which showed that water preferentially dissociates over the active cerium ions at the CeO2-Cu2O/Cu(111) interface. The adsorbed hydroxyl species blocked O-O bond cleavage that would dehydrogenate methoxy groups to carbon monoxide and carbon dioxide, and it directly converted this species to methanol, while oxygen reoxidized the reduced surface. Water adsorption also displaced the produced methanol into the gas phase.
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Primary lung cancer presents as nephrotic syndrome firstly is a rare condition. Few data are available to address this question because of its seldom. Herein we present one case of primary lung cancer which showing nephrotic syndrome as first manifestation and review the literature.
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Integrin αvß3, which is selectively targeted by cyclic arginine-glycine-aspartic acid (cRGD) peptides, is significantly upregulated in tumors. Previous studies showed that small interfering RNA (siRNA) modified with cRGD (cRGD-siRNA) could significantly inhibit tumor growth through RNAi with oncogene expression. However, cRGD-siRNA is partially reabsorbed and trapped in the kidneys, causing renal injury in an unpredictable manner. This study aimed to investigate the influence of Gelofusine on tubulointerstitial injury induced by cRGD-siRNA in vitro and in vivo. The effect of Gelofusine on the distribution of cRGD-siRNA in tumor-bearing nude mice and wild-type mice was also explored. We found that Gelofusine inhibited apoptosis and activation of the innate immune response of human tubular epithelial cells induced by cRGD-siRNA in vitro. In addition, co-injection of Gelofusine efficiently reduced renal retention of cRGD-siRNA without affecting its tumor targeting in vivo. Further in vivo studies indicated that Gelofusine significantly attenuated tubulointerstitial injury induced by cRGD-siRNA through regulating Toll-like receptor 3 (TLR3)-mediated activation of the nuclear factor κ B (NF-κB) and caspase-3 apoptotic pathway. In conclusion, Gelofusine, acting as a novel and effective renal protective agent, could form a compound preparation with siRNA drugs for future clinical applications.
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China has become the largest generator of municipal solid waste (MSW) in the world with its rapid urbanization, population growth and raising living standard. Among diverse solid waste disposal technologies, MSW incineration has been becoming an attractive choice. In terms of systematic point, an integrated MSW incineration system should include an incineration subsystem and a bottom ash (BA) disposal subsystem. This paper employed an extend emergy assessment method with several improved indicators, which considers the emissions' impact, to evaluate the comprehensive performances of an integrated MSW incineration system. One existing incineration plant in Yibin City, Sichuan Province, China, as a case study, is evaluated using the proposed method. Three alternative scenarios (scenario A: the incineration subsystemâ¯+â¯the BA landfill subsystem; scenario B: the incineration subsystemâ¯+â¯the concrete paving brick production subsystem using BA as raw material; scenario C: the incineration subsystemâ¯+â¯the non-burnt wall brick production subsystem using BA as raw material) were compared. The study results reveal that the ratio of positive output is 1.225, 2.861 and 1.230, the improved environmental loading ratio is 2.715, 2.742 and 1.533, and the improved environmental sustainability index is 0.451, 1.043 and 0.803 for scenario A, B and C respectively. Therefore, reuse of BA can enhance the sustainability level of this integrated system greatly. Comparatively, scenario B has the best comprehensive performance among the three scenarios. Finally, some targeted recommendations are put forward for decision-making.
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Conservação de Recursos Energéticos , Incineração , Resíduos Sólidos , China , Eliminação de Resíduos , Instalações de Eliminação de ResíduosRESUMO
Based on successful targeting to the αvß3 integrin of cyclic arginine-glycine-aspartic acid (cRGD), cRGD-conjugated small interfering RNA (siRNA) exhibits tumor targeting and has become a new treatment strategy for solid tumors. However, the nephrotoxicity caused by its renal retention limits its clinical application. Here, we evaluated the protective effect of Gelofusine against cRGD-conjugated siRNA-induced nephrotoxicity in mice. Male Kunming mice (six per group) were either co-injected with Gelofusine and cRGD-siRNA or injected with cRGD-siRNA alone. After administration of these treatments five times, creatinine and blood urea nitrogen (BUN) levels were determined. Hematoxylin-eosin staining (HE staining) and transferase dUTP nick end labeling (TUNEL) analysis were used to compare the difference in renal damage between the groups. Additionally, fluorescence imaging was used to observe the distribution of cRGD-siRNA in vivo. The group co-injected with Gelofusine and cRGD-siRNA displayed lower creatinine and BUN levels than the cRGD-siRNA-alone group and showed less renal damage upon HE staining and TUNEL analysis. Gelofusine decreased the retention time and accelerated the elimination of cRGD-siRNA from the organs, as observed in the fluorescence images. These data indicate that Gelofusine significantly increased the excretion of cRGD-conjugated siRNA and reduced the associated renal damage.
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Injúria Renal Aguda/prevenção & controle , Rim/efeitos dos fármacos , Poligelina/uso terapêutico , RNA Interferente Pequeno/imunologia , Eliminação Renal/efeitos dos fármacos , Injúria Renal Aguda/imunologia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Humanos , Integrina alfaVbeta3/genética , Rim/metabolismo , Masculino , Camundongos , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/química , Peptídeos Cíclicos/toxicidade , Poligelina/farmacologia , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , Distribuição TecidualRESUMO
The epidermal growth factor receptor (EGFR) is an important anti-tumor target. The development of novel molecular-targeted anti-tumor drugs that can target the interior of tumor cells and specifically silence EGFR expression is valuable and promising. In this work, a promising anti-tumor conjugate comprising methoxy-modified EGFR siRNA and cyclic arginine-glycine-aspartic acid (cRGD) peptides, which selectively bind to αvß3 integrins, was synthesized and examined. To prepare cRGD-EGFR siRNA (cRGD-siEGFR), cRGD was covalently conjugated to the 5'-end of an siRNA sense strand using a thiol-maleimide linker. The cellular uptake and cytotoxicity of cRGD-siEGFR in vitro were tested using an αvß3-positive U87MG cell line. In vivo bio-distribution, anti-tumor activity, immunogenicity and toxicity were investigated in a nude mouse tumor model through repeated i.v. administration of cRGD-siEGFR (7 times over a 48 h interval). Analyses of in vitro data showed that cRGD-siEGFR silenced EGFR expression effectively, with high tumor targeting ability. Administration of cRGD-siEGFR to tumor-bearing nude mice led to significant inhibition of tumor growth, obvious reduction of EGFR expression and down-regulation of EGFR mRNA and protein in tumor tissue. Furthermore, serum biochemistry and pathological section evaluation did not indicate any serious toxicity of cRGD-siEGFR in vivo. cRGD-siEGFR is likely a promising candidate with high targeting ability, substantial anti-tumor effects and low toxicity in vitro and in vivo.
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Neoplasias Encefálicas/terapia , Receptores ErbB/metabolismo , Técnicas de Transferência de Genes , Glioblastoma/terapia , Peptídeos Cíclicos/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Terapêutica com RNAi/métodos , Animais , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/metabolismo , Integrina alfaVbeta3/metabolismo , Ligantes , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Interferente Pequeno/genética , Fatores de Tempo , Distribuição Tecidual , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
In recent years, long noncoding RNAs (lncRNAs) have been shown to have critical roles in a broad range of cell biological processes. However, the activities of lncRNAs during ischemic stroke remain largely unknown. In this study, we carried out a genome-wide lncRNA microarray analysis in rat brains with ischemia/reperfusion (I/R) injury. The results revealed the differential expression of a subset of lncRNAs. Through the construction of lncRNA-mRNA co-expression networks, we identified lncRNA-N1LR as a novel I/R-induced lncRNA. The functions of lncRNA-N1LR were assessed by silencing and overexpressing this lncRNA in vitro and in vivo. We found that lncRNA-N1LR enhanced cell cycle progression and cell proliferation, and inhibited apoptosis in N2a cells subjected to in vitro ischemia (oxygen-glucose deprivation/reoxygenation, OGD/R). Furthermore, we showed that lncRNA-N1LR reduced neuronal apoptosis and neural cell loss in I/R-induced mouse brains. Mechanistically, we discovered that lncRNA-N1LR promoted neuroprotection probably through the inhibition of p53 phosphorylation on serine 15 in a manner that was independent of its location-associated gene Nck1. In summary, our results indicated that lncRNA-N1LR promoted neuroprotection against ischemic stroke probably by inactivating p53. Thus, we propose that lncRNA-N1LR may serve as a potential target for therapeutic intervention following ischemic brain injury.