RESUMEN
Aggregation-Induced Emission luminogen (AIEgen) possess great potential in enhancing bioimaging-guided radiotherapeutic effects and radioimmunotherapy to improve the therapeutic effects of the tumor with good biosafety. Bacteria as a natural carrier have demonstrated great advantages in tumor targeted delivery and penetration to tumor. Herein, we construct a delivery platform that Salmonella VNP20009 act as an activated bacteria vector loaded the as-prepared novel AIEgen (TBTP-Au, VNP@TBTP-Au), which showed excellent radio-immunotherapy. VNP@TBTP-Au could target and retain AIEgen at the tumor site and deliver it into tumor cells specially, upon X-ray irradiation, much ROS was generated to induce immunogenic cell death via cGAS-STING signaling pathway to evoke immune response, thus achieving efficient radioimmunotherapy of the primary tumor with good biosafety. More importantly, the radioimmunotherapy with VNP@TBTP-Au formatted good abscopal effect that was able to suppress the growth of distant tumor. Our strategy pioneer a novel and simple strategy for the organic combination of bacteria and imaging-guided radiotherapy, and also pave the foundation for the combination with immunotherapy for better therapeutic effects.
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Ions play a vital role in regulating various biological processes, including metabolic and immune homeostasis, which involves tumorigenesis and therapy. Thus, the perturbation of ion homeostasis can induce tumor cell death and evoke immune responses, providing specific antitumor effects. However, antitumor strategies that exploit the effects of multiion perturbation are rare. We herein prepared a pH-responsive nanomodulator by coloading curcumin (CU, a Ca2+ enhancer) with CaCO3 and MnO2 into nanoparticles coated with a cancer cell membrane. This nanoplatform was aimed at reprogramming the tumor microenvironment (TME) and providing an antitumor treatment through ion fluctuation. The obtained nanoplatform, called CM NPs, could neutralize protons by decomposing CaCO3 and attenuating cellular acidity, they could generate Ca2+ and release CU, elevating Ca2+ levels and promoting ROS generation in the mitochondria and endoplasmic reticulum, thus, inducing immunogenic cell death. Mn2+ could decompose the endogenous H2O2 into O2 to relieve hypoxia and enhance the sensitivity of cGAS, activating the cGAS-STING signaling pathway. In addition, this strategy allowed the reprogramming of the immune TME, inducing macrophage polarization and dendritic cell maturation via antigen cross-presentation, thereby increasing the immune system's ability to combat the tumor effectively. Moreover, the as-prepared nanoparticles enhanced the antitumor responses of the αPD1 treatment. This study proposes an effective strategy to combat tumors via the reprogramming of the tumor TME and the alteration of essential ions concentrations. Thus, it shows great potential for future clinical applications as a complementary approach along with other multimodal treatment strategies.
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Nanopartículas , Neoplasias , Humanos , Calcio , Manganeso , Peróxido de Hidrógeno , Compuestos de Manganeso/farmacología , Microambiente Tumoral , Óxidos/farmacología , Inmunoterapia , Neoplasias/tratamiento farmacológico , Línea Celular TumoralRESUMEN
Noncancerous diseases include a wide plethora of medical conditions beyond cancer and are a major cause of mortality around the world. Despite progresses in clinical research, many puzzles about these diseases remain unanswered, and new therapies are continuously being sought. The evolution of bio-nanomedicine has enabled huge advancements in biosensing, diagnosis, bioimaging, and therapeutics. The recent development of aggregation-induced emission luminogens (AIEgens) has provided an impetus to the field of molecular bionanomaterials. Following aggregation, AIEgens show strong emission, overcoming the problems associated with the aggregation-caused quenching (ACQ) effect. They also have other unique properties, including low background interferences, high signal-to-noise ratios, photostability, and excellent biocompatibility, along with activatable aggregation-enhanced theranostic effects, which help them achieve excellent therapeutic effects as an one-for-all multimodal theranostic platform. This review provides a comprehensive overview of the overall progresses in AIEgen-based nanoplatforms for the detection, diagnosis, bioimaging, and bioimaging-guided treatment of noncancerous diseases. In addition, it details future perspectives and the potential clinical applications of these AIEgens in noncancerous diseases are also proposed. This review hopes to motivate further interest in this topic and promote ideation for the further exploration of more advanced AIEgens in a broad range of biomedical and clinical applications in patients with noncancerous diseases.
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Colorantes Fluorescentes , Neoplasias , Humanos , Nanomedicina Teranóstica/métodos , Nanomedicina , Imagen Óptica/métodos , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológicoRESUMEN
As a prominent class of 2D transition metal dichalcogenides (TMDCs), niobium diselenide nanosheets (NbSe2 NSs) have garnered tremendous interest on account of promising applications pertaining to optoelectronics and energy storage. Although NbSe2 NSs have many unique advantages such as inherent biocompatibility and broad absorption in the NIR region, their biomedical applications have rarely been reported, especially as therapeutic agents for the second near-infrared (NIR-II) range. Herein, a biodegradable nanotherapeutic platform consisting of NbSe2 NSs is designed and demonstrated for NIR-II light-triggered photothermal therapy. NbSe2 NSs synthesized by grinding and liquid exfoliation exhibit superior photothermal conversion efficiency (48.3%) and remarkable photothermal stability in the NIR-II region. In vitro assessment demonstrates that NbSe2 NSs have favorable photothermal cell ablation efficiency and biocompatibility. After intravenous injection in vivo, the NbSe2 NSs accumulate passively in tumor sites to facilitate fluorescence imaging and tumor ablation by NIR-II illumination. Furthermore, as a result of gradual degradation in the physiological environment, NbSe2 NSs can be excreted from the body to avoid potential toxicity caused by long-term retention in vivo. The results reveal a promising NIR-II light-triggered PTT strategy with the aid of NbSe2 NSs and the platform is expected to have large potential in cancer theranostics.
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Neoplasias , Niobio , Humanos , Niobio/farmacología , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológicoRESUMEN
Chemodynamic therapy (CDT) is an emerging treatment that usually employs chemical agents to decompose hydrogen peroxide (H2O2) into hydroxyl radical (â¢OH) via Fenton or Fenton-like reactions, inducing cell apoptosis or necrosis by damaging biomacromolecules such as, lipids, proteins, and DNA. Generally, CDT shows high tumor-specificity and minimal-invasiveness in patients, thus it has attracted extensive research interests. However, the catalytic reaction efficiency of CDT is largely limited by the relatively high pH at the tumor sites. Herein, a 808 nm laser-potentiated peroxidase catalytic/mild-photothermal therapy of molybdenum diphosphide nanorods (MoP2 NRs) is developed to improve CDT performance, and simultaneously achieve effective tumor eradication and anti-infection. In this system, MoP2 NRs exhibit a favorable cytocompatibility due to their inherent excellent elemental biocompatibility. Upon irradiation with an 808 nm laser, MoP2 NRs act as photosensitizers to efficiently capture the photo-excited band electrons and valance band holes, exhibiting enhanced peroxidase-like catalytic activity to sustainedly decompose tumor endogenous H2O2 to â¢OH, which subsequently destroy the cellular biomacromolecules both in tumor cells and bacteria. As demonstrated both in vitro and in vivo, this system exhibits a superior therapeutic efficiency with inappreciable toxicity. Hence, the work may provide a promising therapeutic technique for further clinical applications.
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Molibdeno/química , Neoplasias de la Boca/terapia , Nanotubos/química , Peroxidasa/metabolismo , Terapia Fototérmica/métodos , Animales , Línea Celular Tumoral , Terapia Combinada , Difosfatos/química , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: Dcf1 has been demonstrated to play vital roles in many CNS diseases, it also has a destructive role on cell mitochondria in glioma cells and promotes the autophagy. Hitherto, it is unclear whether the viability of glioblastoma cells is affected by Dcf1, in particular Dcf1 possesses broad localization on different organelles, and the organelles interaction frequently implicated in cancer cells survival. METHODS: Surgically excised WHO grade IV human glioblastoma tissues were collected and cells isolated for culturing. RT-PCR and DNA sequencing assay to estimate the abundance and mutation of Dcf1. iTRAQ sequencing and bioinformatic analysis were performed. Subsequently, immunoprecipitation assay to evaluate the degradation of HistoneH2A isomers by UBA52 ubiquitylation. Transmission electron microscopy (TEM) was applied to observe the structure change of mitochondria and autophagosome. Organelle isolated assay to determine the distribution of protein. Cell cycle and apoptosis were evaluated by flow cytometric assays. RESULTS: Dcf1 was downregulated in WHO grade IV tumor without mutation, and overexpression of Dcf1 was found to significantly regulate glioblastoma cells. One hundred and seventy-six differentially expressed proteins were identified by iTRAQ sequencing. Furthermore, we confirmed that overexpression of Dcf1 destabilized the structure of the nucleosome via UBA52 ubiquitination to downregulate HistoneH2A.X but not macroH2A or HistoneH2A.Z, decreased the mitochondrial DNA copy number and inhibited the mitochondrial biogenesis, thus causing mitochondrial destruction and dysfunction in order to supply cellular energy and induce mitophagy preferentially but not apoptosis. Dcf1 also has disrupted the integrity of lysosomes to block autolysosome degradation and autophagy and to increase the release of Cathepsin B and D from lysosomes into cytosol. These proteins cleaved and activated BID to induce glioblastoma cells apoptosis. CONCLUSIONS: In this study, we demonstrated that unmutated Dcf1 expression is negatively related to the malignancy of glioblastoma, Dcf1 overexpression causes nucleosomes destabilization, mitochondria destruction and dysfunction to induce mitophagy preferentially, and block autophagy by impairing lysosomes to induce apoptosis in glioblastoma.
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Apoptosis , Autofagia , Glioblastoma/genética , Glioblastoma/patología , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Histonas/genética , Humanos , Lisosomas/patología , Proteínas de la Membrana/fisiología , Mitocondrias/patología , Mitofagia , Proteínas del Tejido Nervioso/fisiología , Nucleosomas/patología , Biogénesis de OrganelosRESUMEN
INTRODUCTION: Excessive production of reactive oxygen species (ROS) to induce high oxidative stress is one of the main causes of colitis; thus, it has been regarded as a therapeutic target for colitis treatment. And the nanomaterial-based therapeutic strategies are effective against colitis. However, the previous elaborately designed materials exhibit limited application due to the uncertain biocompatibility and complicated manufacturing processes. METHODS: In this study, the highly monodisperse hollow CeO2 nanoparticles (H-CeO2) with uniform morphology were obtained by in situ growing CeO2 on solid silica nanoparticles and subsequently removing the silica core. The H-CeO2 was further modified with PEG, which owned excellent biological stability and biocompatibility. The experimental model of colitis induced by dextran sulfate sodium (DSS) was used to investigate the anti-inflammatory effect of H-CeO2-PEG. RESULTS: The H-CeO2-PEG showed good ROS scavenging efficacy and decreased the levels of proinflammatory cytokines (IL-6, IL-1ß, IL-18, and TNF-α) in DSS-induced colitis mice. Furthermore, H-CeO2-PEG inhibited the activation of the MAPK signalling pathway to alleviate colitis. CONCLUSION: This study reveals the therapeutic effects of CeO2-based nanomedicine toward colitis and elucidates the specific signalling pathway involved, which provides potential alternative therapeutic options for patients with inflammation tissue.
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Colitis , Animales , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Sulfato de Dextran , Humanos , Inflamación , Ratones , Estrés Oxidativo , Especies Reactivas de OxígenoRESUMEN
Nanomaterial-based photothermal and photocatalytic therapies are effective against various types of cancers. However, combining two or more materials is considered necessary to achieve the synergistic anticancer effects of photothermal and photocatalytic therapy, which made the preparation process complicated. Herein, the authors describe simple 2D titanium diselenide (TiSe2 ) nanosheets (NSs) that can couple photothermal therapy with photocatalytic therapy. The TiSe2 NSs are prepared using a liquid exfoliation method. They show a layered structure and possess high photothermal conversion efficiency (65.58%) and good biocompatibility. Notably, upon near-infrared irradiation, these NSs exhibit good photocatalytic properties with enhanced reactive oxygen species generation and H2 O2 decomposition in vitro. They can also achieve high temperatures, with heat improving their catalytic ability to further amplify oxidative stress and glutathione depletion in cancer cells. Furthermore, molecular mechanism studies reveal that the synergistic effects of photothermal and enhanced photocatalytic therapy can simultaneously lead to apoptosis and necrosis in cancer cells via the HSP90/JAK3/NF-κB/IKB-α/Caspase-3 pathway. Systemic exploration reveals that the TiSe2 NSs has an appreciable degradation rate and accumulates passively in tumor tissue, where they facilitate photothermal and photocatalytic effects without obvious toxicity. Their study thus indicates the high potential of biodegradable TiSe2 NSs in synergistic phototherapy for cancer treatment.
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Nanopartículas , Neoplasias , Humanos , Rayos Infrarrojos , Fototerapia , TitanioRESUMEN
While promising, the efficacy of aggregation-induced emission (AIE)-based photodynamic therapy (PDT) is limited by several factors including limited depth of laser penetration and intratumoral hypoxia. In the present study, a novel bacteria-based AIEgen (TBP-2) hybrid system (AE) is developed, that is able to facilitate the hypoxia-tolerant PDT treatment of orthotopic colon tumors via an interventional method. For this approach, an interventional device is initially designed, composed of an optical fiber and an endoscope, allowing for clear visualization of the position of the orthotopic tumor within the abdominal cavity. It is then possible to conduct successful PDT treatment of this hypoxic tumor via laser irradiation, as the TBP-2 is able to generate hydroxyl radicals (â¢OH) via a type I mechanism within this hypoxic microenvironment. Moreover, this interventional approach is proved to significantly impair orthotopic colon cancer growth and overcame PDT defects. This study is the first report involving such an interventional PDT strategy to knowledge, and it has the potential to complement other treatment modalities while also highlighting novel approaches to the design of hybrid AIEgen systems.
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Bacterias/metabolismo , Neoplasias del Colon/terapia , Hipoxia/metabolismo , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Microambiente Tumoral , Animales , Modelos Animales de Enfermedad , Endoscopía Gastrointestinal/métodos , Ratones , Fotoquimioterapia/instrumentación , Fármacos Fotosensibilizantes/metabolismoRESUMEN
Microalgae have received significant attention as potential next-generation microbiologic cell factories for biofuels. However, the production of microalgal biofuels is not yet sufficiently cost-effective for commercial applications. To screen higher lipid-producing strains, heavy carbon ion beams are applied to induce a genetic mutant. An RNA-seq technology is used to identify the pathways and genes of importance related to photosynthesis and biofuel production. The deep elucidation of photosynthesis and the fatty acid metabolism pathway involved in lipid yield is valuable information for further optimization studies. This study provided the photosynthetic efficiency and transcriptome profiling of a unicellular microalgae, Scenedesmus obliqnus mutant SO120G, with enhanced lipid production induced by heavy carbon ion beams. The lipid yield (52.5 mg L-1) of SO120G mutant were enhanced 2.4 fold compared with that of the wild strain under the nitrogen deficient condition. In addition, the biomass and growth rate were 57% and 25% higher, respectively, in SO120G than in the wild type, likely owing to an improved maximum quantum efficiency (Fv/Fm) of photosynthesis. As for the major pigment compositions, the content of chlorophyll a and carotenoids was higher in SO120G than in the wild type. The transcriptome data confirmed that a total of 2077 genes with a change of at least twofold were recognized as differential expression genes (DEGs), of which 1060 genes were up-regulated and 1017 genes were down-regulated. Most of the DEGs involved in lipid biosynthesis were up-regulated with the mutant SO120G. The expression of the gene involved in the fatty acid biosynthesis and photosynthesis of SO120G was upregulated, while that related to starch metabolism decreased compared with that of the wild strain. This work demonstrated that heavy-ion irradiation is an promising strategy for quality improvement. In addition, the mutant SO120G was shown to be a potential algal strain for enhanced lipid production. Transcriptome sequencing and annotation of the mutant suggested the possible genes responsible for lipid biosynthesis and photosynthesis, and identified the putative target genes for future genetic manipulation and biotechnological applications.
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Regulación de la Expresión Génica de las Plantas , Metabolismo de los Lípidos/genética , Mutación , Fotosíntesis/genética , Scenedesmus/genética , Scenedesmus/metabolismo , Transcriptoma , Biomasa , Metabolismo de los Hidratos de Carbono , Clorofila A/metabolismo , Biología Computacional/métodos , Metabolismo Energético , Perfilación de la Expresión Génica , Redes y Vías Metabólicas , Proteínas de Plantas/metabolismo , Almidón/metabolismoRESUMEN
Myelination is extremely important in achieving neural function. Hypomyelination causes a variety of neurological diseases. However, little is known about how hypomyelination occurs. Here we investigated the effect of dendritic cell factor 1(Dcf1) on myelination, using in vitro and in vivo models and found that Dcf1 is essential for normal myelination, motor coordination and balance. Lack of Dcf1 downregulated myelin-associated proteins, such as myelin basic protein (MBP), myelin associated glycoprotein (MAG), and 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the hippocampus and corpus callosum of Dcf1-null mice, as a result, the myelin sheath of these mice became thinner. Transmission electron microscopy revealed hypomyelination in Dcf1-deficient mice. Motor coordination and balance tests confirmed impaired neurological function in Dcf1-null mice. Gain-of-function analysis via In utero electroporation showed that hypomyelination could be rescued by re-expression of Dcf1 in Dcf1-null mouse brain. Dcf1-null mice exhibited a phenotype similar to that of cuprizone-induced demyelinated mice, thereby supporting the finding of hypomyelination caused by Dcf1 knockout. Mechanistically, we further revealed that insufficient Dcf1 leads to hyperactivation of the Wnt/ß-catenin signaling pathway. Our work describes the role of Dcf1 in maintaining normal myelination, and this could help improve the current understanding of hypomyelination and its pathogenesis.
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Enfermedades Desmielinizantes/genética , Proteínas de la Membrana/genética , Vaina de Mielina/genética , Proteínas del Tejido Nervioso/genética , Vía de Señalización Wnt/genética , Animales , Cuerpo Calloso/metabolismo , Cuprizona , Enfermedades Desmielinizantes/inducido químicamente , Enfermedades Desmielinizantes/psicología , Regulación hacia Abajo/genética , Electroporación , Hipocampo/metabolismo , Masculino , Ratones , Ratones Noqueados , Proteínas de la Mielina/biosíntesis , Equilibrio Postural , Desempeño PsicomotorRESUMEN
Chronic obstructive pulmonary disease (COPD) is an intractable disease involving a sticky mucus layer and nanoagents with mucus-penetrating capability offer a new way to deliver drugs. However, drug release from nanovehicles requires optimization to enhance the therapeutic effects of COPD therapy. Herein, black phosphorus quantum dots (BPQDs) are combined with PEGylated chitosan nanospheres containing the antibiotic amikacin (termed PEG@CS/BPQDs-AM NPs). As a drug-delivery system, the hydrophilicity of PEG and positive charge of CS facilitate the penetration of nanovehicles through the mucus layer. The nanovehicles then adhere to the mucous membrane. Furthermore, the BPQDs degrade rapidly into nontoxic PO43- and acidic H+ , thereby promoting the dissociation of PEGylated CS nanospheres, accelerating the release of AM, decreasing the vitality of biofilms for ease of eradication. Our results reveal that drug delivery mediated by BPQDs is a feasible and desirable strategy for precision medicine and promising for the clinical therapy of COPD.
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Portadores de Fármacos , Nanopartículas , Fósforo/química , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Puntos Cuánticos/química , Animales , Antibacterianos/uso terapéutico , Liberación de Fármacos , Humanos , Ratones , Moco/efectos de los fármacosRESUMEN
Effects of turbulent energy dissipation rate (increased from 1.28 × 10-6 to 1.67 × 10-5 m2 s-3) on Scenedesmus obliquus biomass and lipid accumulation at different aeration rates (0.3, 0.6, 0.9, 1.2, and 1.5 L min-1) were investigated. The turbulent energy dissipation rate was calculated by CFD model simulation. When the turbulent energy dissipation rate increased to 7.30 × 10-6 m2 s-3, the biomass and lipid productivity increased gradually, and finally reached their maximum values of 1.11 × 107 cells mL-1 and 16.0 mg L-1 day-1, respectively. When it exceeded 7.30 × 10-6 m2 s-3, the biomass and lipid productivity showed a decreasing trend. Therefore, the most favorable turbulent energy dissipation rate for S. obliquus growth and lipid accumulation was 7.30 × 10-6 m2 s-3.
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Microalgas , Scenedesmus , Biocombustibles , Biomasa , Lípidos , FotosíntesisRESUMEN
Cisplatin is the most commonly used chemotherapeutic drug for nasopharyngeal carcinoma (NPC), while its side effects are often intolerable. Lobaplatin, as an effective third-generation platinum with fewer adverse reactions and less platinum cross-resistance, has been considered as a good alternative to cisplatin after cisplatin's failure (relapse or metastasis) in the treatment of NPC. However, the anti-NPC mechanism of lobaplatin remains largely unknown. In present study, 50% inhibiting concentration (IC50) of lobaplatin for NPC cells is found to be similar to that of cisplatin. 10 µM and 20 µM lobaplatin caused obvious gasdermin-E (GSDME)-mediated pyroptosis by activating caspase-3. Moreover, we found lobaplatin induced proteasomal degradation of cell inhibitor of apoptosis protein-1/2 (cIAP1/2). And these pyroptotic phenomena could be suppressed by the recovery of cIAP1/2, suggesting that cIAP1/2 are critical in lobaplatin-induced pyroptosis. Further inhibition of cIAP1/2 by birinapant (an antagonist of cIAP1/2) dramatically enhanced pyroptosis induced by lobaplatin in vitro and in vivo, which was consistent with the combination with cisplatin. Importantly, this synergistic pyroptotic effect were suppressed by the inhibition of Ripoptosome (RIPK1/Caspase-8/FADD), reactive oxygen species (ROS) and caspase-3 cleavage, and were independent of phosphorylation of JNK and NF-κB signal. Our data reveal that cIAP1/2 play important roles in lobaplatin-induced NPC cell pyroptosis, and this anti-NPC effect can be significantly potentiated by cIAP1/2 antagonist birinapant through regulating the formation of Ripoptosome and the generation of ROS. These study provides a possibility to further reduce the platinum-related adverse events and chemoresistance of lobaplatin while maintaining satisfactory anti-NPC efficacy.
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Ciclobutanos/farmacología , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/metabolismo , Compuestos Organoplatinos/farmacología , Piroptosis/efectos de los fármacos , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Proteína 3 que Contiene Repeticiones IAP de Baculovirus/antagonistas & inhibidores , Proteína 3 que Contiene Repeticiones IAP de Baculovirus/metabolismo , Caspasa 8/metabolismo , Línea Celular Tumoral , Ciclobutanos/administración & dosificación , Dipéptidos/administración & dosificación , Dipéptidos/farmacología , Proteína de Dominio de Muerte Asociada a Fas/metabolismo , Femenino , Humanos , Indoles/administración & dosificación , Indoles/farmacología , Proteínas Inhibidoras de la Apoptosis/antagonistas & inhibidores , Proteínas Inhibidoras de la Apoptosis/metabolismo , Ratones Endogámicos BALB C , Carcinoma Nasofaríngeo/patología , Compuestos Organoplatinos/administración & dosificación , Piroptosis/fisiología , Especies Reactivas de Oxígeno/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
As new 2D layered nanomaterials, Bi2 O2 Se nanoplates have unique semiconducting properties that can benefit biomedical applications. Herein, a facile top-down approach for the synthesis of Bi2 O2 Se quantum dots (QDs) in a solution is described. The Bi2 O2 Se QDs with a size of 3.8 nm and thickness of 1.9 nm exhibit a high photothermal conversion coefficient of 35.7% and good photothermal stability. In vitro and in vivo assessments demonstrate that the Bi2 O2 Se QDs possess excellent photoacoustic (PA) performance and photothermal therapy (PTT) efficiency. After systemic administration, the Bi2 O2 Se QDs accumulate passively in tumors enabling efficient PA imaging of the entire tumors to facilitate imaging-guided PTT without obvious toxicity. Furthermore, the Bi2 O2 Se QDs which exhibit degradability in aqueous media not only have sufficient stability during in vivo circulation to perform the designed therapeutic functions, but also can be discharged harmlessly from the body afterward. The results reveal the great potential of Bi2 O2 Se QDs as a biodegradable multifunctional agent in medical applications.
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Bismuto/uso terapéutico , Neoplasias/terapia , Compuestos de Organoselenio/uso terapéutico , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Puntos Cuánticos , Bismuto/química , Línea Celular Tumoral , Humanos , Compuestos de Organoselenio/química , Difracción de Polvo , Compuestos de Selenio , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja CortaRESUMEN
Neuroblastoma (NB) is the most common extracranial solid tumor that affects mainly children and has extremely high mortality and recurrence rates. A previous study revealed that dendritic cell factor 1 (DCF1), also called transmembrane protein 59, could activate apoptosis in glioma cells. In the present study, we applied immunofluorescence, western blot analysis, flow cytometry and cell tumorigenicity to investigate the DCF1 mechanisms involved in NB apoptosis. DCF1 was overexpressed in Neuro-2a and SK-N-SH cells through instantaneous transfection. The data revealed that overexpression of DCF1 could inhibit cell proliferation, migration, invasion and promote cell apoptosis in vitro, and suppress NB growth in vivo. The ERK1/2 signaling pathway, which promotes cell survival, was the target of DCF1 in neuroblastoma cells. All the results indicated that DCF1 could be a potential therapeutic target for the understanding and treatment of NB.
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Sistema de Señalización de MAP Quinasas , Proteínas de la Membrana/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neuroblastoma/metabolismo , Neuroblastoma/patología , Animales , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Trasplante de NeoplasiasRESUMEN
ADP-ribosylation factor-like3 (ARL3) is a member of the ADP-ribosylation factor family of GTP-binding proteins that plays important role in regulating Ciliary trafficking. It ubiquitously expressed in normal tissues and tumor cell lines. However, the location and function of ARL3 in organelles are rarely known. In this study, we explored ARL3 subcellular localization in an all-round way in HEK293T, Neuro-2A and U251â¯cells by density gradient centrifugation and immunofluorescence. The results showed that ARL3 is expressed in most of organelles, and an iodixonal step gradient was further confirmed that ARL3 is mainly localized to the mitochondria, endosomes, lysosomes, and proteasome. By molecular functional analysis, we observed that ARL3 promotes the aggregation of GFP-LC3, up-regulation of LC3-II/LC3-I and down-regulation of SQSMT1/BECN1, and knocking down of ARL3 inbibits autophagy, which suggested that ARL3 is necessary for autophagy. this study presents a comprehensive evaluation of the subcellular localization for ARL3 and provides important on understanding the functions of ARL3.
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Factores de Ribosilacion-ADP/metabolismo , Autofagia , Orgánulos/metabolismo , Agregado de Proteínas , Factores de Ribosilacion-ADP/genética , Técnicas de Silenciamiento del Gen , Células HEK293 , Humanos , Orgánulos/genéticaRESUMEN
Dendritic cell factor 1 (DCF1) is a transmembrane protein that plays important roles in regulating neural stem cell differentiation and dendritic spine formation. Apart from its cytoplasmic functions, DCF1 plays a role in autophagy during the regulation of amyloid precursor proteins. However, the subcellular localization of DCF1 remains unknown. Therefore, in this study, DCF1 tagged with green fluorescent protein was transiently expression in HelaS3 and HEK293T cells. The results showed that DCF1 was widely expressed in different organelles, including the mitochondria, Golgi apparatus, endoplasmic reticulum, endosomes and lysosomes. An iodixanol step gradient further confirmed that DCF1 is localized to the mitochondria, endosomes, lysosomes, endoplasmic reticulum, and proteasome. Finally, functional analysis of the mitochondria revealed that DCF1 affected the expression and localization of MGST1. This study presents a comprehensive evaluation of the subcellular localization of DCF1, which provides important information on complex functions mediated by DCF1.