RESUMO
Osteoporosis, which manifests as reduced bone mass and deteriorated bone quality, is common in the elderly population. It is characterized by persistent elevation of macrophage-associated inflammation and active osteoclast bone resorption. Currently, the roles of intracellular metabolism in regulating these processes remain unclear. In this study, we initially performed bioinformatics analysis and observed a significant increase in the proportion of M1 macrophages in bone marrow with aging. Further metabolomics analysis demonstrated a notable reduction in the expression of carnitine metabolites in aged macrophages, while carnitine was not detected in osteoclasts. During the differentiation process, osteoclasts took up carnitine synthesized by macrophages to regulate their own activity. Mechanistically, carnitine enhanced the function of Nrf2 by inhibiting the Keap1-Nrf2 interaction, reducing the proteasome-dependent ubiquitination and degradation of Nrf2. In silico molecular ligand docking analysis of the interaction between carnitine and Keap1 showed that carnitine binds to Keap1 to stabilize Nrf2 and enhance its function. In this study, we found that the decrease in carnitine levels in aging macrophages causes overactivation of osteoclasts, ultimately leading to osteoporosis. A decrease in serum carnitine levels in patients with osteoporosis was found to have good diagnostic and predictive value. Moreover, supplementation with carnitine was shown to be effective in the treatment of osteoporosis.
Assuntos
Reabsorção Óssea , Osteoporose , Humanos , Idoso , Osteogênese/genética , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Carnitina/metabolismo , Transdução de Sinais , Osteoclastos/metabolismo , Macrófagos/metabolismo , Reabsorção Óssea/complicações , Reabsorção Óssea/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/genética , Ligante RANK/farmacologiaRESUMO
Cottonseed has a high utilization value due to its luxuriant oil and protein, but low phosphorus (P) in cropland reduces its yield and quality. A limited understanding of the physiological mechanism underlying these results restricted the exploration of P efficient management in cotton cultivation. A 3-year experiment was performed with Lu 54 (low-P sensitive) and Yuzaomian 9110 (low-P tolerant) under 0 (deficient-P), 100 (critical-P), and 200 (excessive-P) kg P2O5 ha-1 in a field having 16.9 mg kg-1 available P to explore the key pathway for P to regulate cottonseed oil and protein formation. P application markedly increased cottonseed oil and protein yields, with the enhanced acetyl-CoA and oxaloacetate contents during 20-26 days post anthesis being a vital reason. Notably, during the crucial period, decreased phosphoenolpyruvate carboxylase activity weakened the carbon allocation to protein, making malonyl-CoA content increase greater than free amino acid; Meanwhile, P application accelerated the carbon storage in oil but retarded that in protein. Consequently, cottonseed oil yield increased more than protein. Oil and protein synthesis in Lu 54 was more susceptible to P, resulting in greater increments in oil and protein yields than Yuzaomian 9110. Based on acetyl-CoA and oxaloacetate contents (the key substrates), the critical P content in the subtending leaf to cotton boll needed by oil and protein synthesis in Lu 54 (0.35%) was higher than Yuzaomian 9110 (0.31%). This study provided a new perception of the regulation of P on cottonseed oil and protein formation, contributing to the efficient P management in cotton cultivation.
Assuntos
Óleo de Sementes de Algodão , Proteínas de Plantas , Óleo de Sementes de Algodão/química , Óleo de Sementes de Algodão/metabolismo , Acetilcoenzima A , Proteínas de Plantas/metabolismo , Gossypium/metabolismoRESUMO
Cottonseed is the main coproduct of cotton production. The carbohydrate metabolism provides carbon substrate for the accumulation of cottonseed kernel biomass which was the basis of cottonseed kernel development. However, the responses of drought stress on carbohydrate metabolism in kernels are still unclear. To address this, two cotton cultivars (Dexiamian 1 and Yuzaomian 9110) were cultivated under three water treatments including soil relative water content (SRWC) at (75 ± 5)% (control), (60 ± 5)% (mild drought) and (45 ± 5)% (severe drought) to investigate the effects of soil drought on cottonseed kernel carbohydrate metabolism and kernel biomass accumulation. Results suggested that drought restrained the accumulation of cottonseed kernel biomass which eventually decreased cottonseed kernel biomass at maturity. In detail, the down-regulation of sucrose phosphate synthase (SPS) activity led to the inhibition of sucrose synthesis, while the up-regulation of invertase (INV) promoted the sucrose decomposite, which reduced the sucrose content eventually under drought. Though hexose content was increased, phosphoenolpyruvic acid (PEP) content was decreased under drought by downregulating 6-phosphofructokinase (PFK) and pyruvate kinase (PK) activities, which hindered the conversion of hexose to PEP. The large decrease of sucrose and PEP contents hindered the accumulation of kernel biomass. The related substances contents and enzyme activities in carbohydrate metabolism of Yuzaomian 9110 were more susceptible to drought stress than Dexiamian 1.
Assuntos
Óleo de Sementes de Algodão , Secas , Biomassa , Solo , Metabolismo dos Carboidratos , Sacarose/metabolismo , Gossypium/metabolismoRESUMO
The reason that immune checkpoint inhibitors have not been widely applied to pancreatic cancer treatment is probably because of low immunogenicity or dense stromal fibrosis. Recently, only pembrolizumab was recommended for DNA mismatch repair deficiency or high microsatellite instability by National Comprehensive Cancer Network guideline. Pancreatic ductal adenocarcinoma (PDAC) accounts for more than 90% of pancreatic cancer, with a poor overall survival rate, the value of immunotherapy for PDAC needs more research. Here, we report a 56-year-old man suffered from PDAC with liver metastasis after radical surgery. The next-generation sequencing result demonstrated that it had remarkably high tumor mutational burden (TMB) of 49.92 Muts/Mb and microsatellite stability. Sintilimab (anti-PD-1) monotherapy was continuously administrated after failure of combined chemotherapy in second line, achieving stable disease within 22 months and few immunotherapy-related adverse events. To our knowledge, this is the first time to report a good outcome achieving 22 months with progression-free survival after PDAC metastasis with monotherapy of sintilimab. TMB may serve as a potential efficacy-related predictor in PDAC patients with sintilimab and help physicians make optimum clinical strategy.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Anticorpos Monoclonais Humanizados , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , DNA , Humanos , Inibidores de Checkpoint Imunológico , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias PancreáticasRESUMO
Cotton, as the fifth-largest oilseed crop, often faces the coupling stress of heat and drought. Still, the effects of combined stress on cottonseed oil synthesis and its closely related carbon metabolism are poorly investigated. To this end, experiments were conducted with two cultivars (Sumian 15 and PHY370WR) under two temperature regimes: ambient temperature (AT) and elevated temperature (ET, which was 2.5°C-2.7°C higher than AT) and three water regimes: optimum soil moisture (soil relative water content [SRWC] at 75% ± 5%), and drought (SD) including SRWC 60% ± 5% and SRWC 45% ± 5%, during 2016-2018. Results showed that ET plus SD decreased cottonseed kernel yield, seed index, kernel weight, and kernel percentage more than either single stress. The content of hexoses, the carbon skeleton source for oil synthesis, was decreased by ET while increased by SD. The combined stress increased the hexose content by increasing the activities of sucrose synthase (SuSy, EC 2.4.1.13) and invertase (Inv, EC 3.2.1.26) and upregulating GhSuSy expression; however, hexose content under combined stress was lower than that under SD alone. Increased oil content under SD was attributed to the high phosphoenolpyruvate carboxylase (PEPCase, EC 4.1.1.31), acetyl-CoA carboxylase (ACCase, EC 6.4.1.2), and diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) activities, whereas the opposite effects were seen under ET. Under combined stress, although ACCase activity decreased, PEPCase and DGAT activities, and GhPEPC-1 and GhDGAT-1 expression upregulated, enhancing carbon flow into oil metabolism and triacylglycerol synthesis, ultimately generating higher oil content.
Assuntos
Óleo de Sementes de Algodão , Secas , Metabolismo dos Carboidratos , Solo , TemperaturaRESUMO
Soil waterlogging and high-temperature events have occurred simultaneously in recent years in the Yangtze River basin cotton belt region of China, negatively affecting the development and quality of cottonseed. This study investigated the effects of the combination of elevated temperature (ET) (34.1/29.0°C) and waterlogging (3 or 6 days) on the accumulation and distribution of oil, protein and carbohydrates in cottonseed during flowering and boll development. The results showed that ET resulted in greater decreases in cottonseed biomass under waterlogging than under control conditions. The combination of waterlogging and ET significantly limited the accumulation of carbohydrates and oil contents. However, ET promoted protein accumulation and compensated for the negative effects of 3-day waterlogging on the final protein content. The combined ET and 6-day waterlogging significantly decreased the final contents of oil and protein by limiting carbon flux and NADPH supply because of the decreased activities of phosphoenolpyruvate carboxylase (PEPC, EC 4.1.1.31) and glucose-6-phosphate dehydrogenase (G6PDH, EC 1.1.1.49). The PEPC activity was correlated more with protein content than oil content. In addition, simultaneous exposure to waterlogging and ET resulted in lower unsaturated fatty acid/saturated fatty acid ratios and essential amino acid/non-essential amino acid ratios than did exposure to the individual factors alone. These findings could provide the theoretical support for the prospective assessment of effects of high temperature and waterlogging stresses on cotton production under climate change, and they can help to develop effective techniques in cotton cultivation.
Assuntos
Óleo de Sementes de Algodão , Folhas de Planta , China , Estudos Prospectivos , TemperaturaRESUMO
The low efficiency homing of nanomaterials in tumors remains a major challenge in nanomedicine. Inspired by the apoptosis targeting properties of phosphatidylserine (PS), a self-amplified apoptosis targeting nanoplatform (MNPs-ZnDPA/ß-Lap) is fabricated combining Zn0.4 Co0.6 Fe2 O4 @Zn0.4 Mn0.6 Fe2 O4 nanoparticles (MNPs) with an excellent magnetic hyperthermia effect, a chemotherapeutic drug of ß-lapachone (ß-Lap) with the promotion of cell apoptosis, and the good apoptosis targeting moiety of Zn(II)-bis(dipicolylamine) (bis-ZnDPA) for PS. In an apoptotic 4T1 xenograft model, MNPs-ZnDPA/ß-Lap can first accumulate in tumors by the EPR effect. The released ß-Lap triggers the apoptosis of cancer cells in the tumor and increases the apoptotic target, which results in amplifying their apoptosis targeting properties. This self-amplified apoptosis targeting efficiency of MNPs-ZnDPA/ß-Lap almost inhibits the growth of tumors with the synergistic magnetic-thermal/chemo therapy, which can offer a significant promise for targeting cancer theranostics.
Assuntos
Hipertermia Induzida , Nanopartículas , Apoptose , Linhagem Celular Tumoral , Fenômenos Magnéticos , Nanomedicina TeranósticaRESUMO
OBJECTIVE: To observe the influence of Xuebijing injection on the inflammatory markers and prognosis of coronavirus disease 2019 (COVID-19) patients. METHODS: Sixty severe COVID-19 patients admitted to Changsha Public Health Treatment Center (North Hospital of the First Hospital of Changsha City) from January to March in 2020 were randomly divided into routine treatment group, Xuebijing 50 mL group and Xuebijing 100 mL group, with 20 cases in each group. The routine treatment group was treated according to the National Health Commission's guide for COVID-19. On the basis of conventional treatment, Xuebijing injection was injected by 50 mL twice a day for 7 days in Xuebijing 50 mL group, while by 100 mL twice a day for 7 days in Xuebijing 100 mL group. The blood routine test, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), acute physiology and chronic health evaluation II (APACHE II) score, 2019 novel coronavirus (2019-nCoV) nucleic acid test and disease classification of three groups before and 8 days after treatment were observed. RESULTS: (1) After treatment, the white blood cell count (WBC) and lymphocyte count (LYM) of three groups increased, meanwhile CRP and ESR decreased. Compared with routine treatment group, the WBC count of Xuebijing 100 mL group after treatment significantly increased (×109/L: 7.12±0.55 vs. 5.67±0.51, P < 0.05), and the levels of CRP and ESR in Xuebijing 50 mL and 100 mL groups significantly decreased [CRP (mg/L): 32.3±4.6, 28.0±6.2 vs. 37.3±5.9; ESR (mm/1 h): 45.9±5.7, 40.5±7.4 vs. 55.3±6.6, all P < 0.05]. Compared with Xuebijing 50 mL group, the increase of WBC, and the decrease of CRP and ESR were more significant in Xuebijing 100 mL group [WBC (×109/L): 7.12±0.55 vs. 5.82±0.49, CRP (mg/L): 28.0±6.2 vs. 32.3±4.6, ESR (mm/1 h): 40.5±7.4 vs. 45.9±5.7, all P < 0.05]. (2) After treatment, the APACHE II score of three groups decreased. In Xuebijing 100 mL group, the APACHE II score after treatment was significantly lower than those in routine treatment and Xuebijing 50 mL groups (12.3±1.5 vs. 16.5±1.6, 15.9±1.4, both P < 0.05). After treatment, the 2019-nCoV nucleic acid test in three groups partly turned negative, with 9 cases in routine treatment group, 8 cases in Xuebijing 50 mL group and 9 cases in Xuebijing 100 mL group, without significant difference (P > 0.05). The conditions of patients in the three groups were improved after treatment, among them, 8 cases in the routine treatment group were transformed into common type, 1 case into critical type; 9 cases and 12 cases of Xuebijing 50 mL group and 100 mL group were transformed into common type respectively. Xuebijing 100 mL group was improved more obviously than Xuebijing 50 mL group and routine treatment group (both P < 0.05). CONCLUSIONS: The Xuebijing injection can effectively improve the inflammatory markers and prognosis of severe COVID-19 patients.
Assuntos
Betacoronavirus , Infecções por Coronavirus , Medicamentos de Ervas Chinesas/uso terapêutico , Pandemias , Pneumonia Viral , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Humanos , Pneumonia Viral/tratamento farmacológico , SARS-CoV-2 , Tratamento Farmacológico da COVID-19RESUMO
Although exogenous melatonin can enhance the drought tolerance of plants, reports on the role of melatonin in drought tolerance in male reproductive organs are limited. To explore this, a pot experiment was conducted with cotton cultivar Yuzaomian 9110 to study the effects of exogenous melatonin (100, 200, and 1000 µM) on male fertility and related carbohydrate metabolism in anther under drought. Results showed that drought inhibited the translocation of carbon assimilates to anthers, however, melatonin application (100 and 200 µM) significantly improved the translocation of carbon assimilates to drought-stressed anthers. Drought reduced the deposition of starch, the hydrolysis of sucrose into hexoses, the generation of adenosine triphosphate (ATP) in anthers, restricting pollen viability and germination. Nevertheless, the appropriate melatonin concentrations (100 and 200 µM) increased the starch accumulation by enhancing ADP-glucose pyrophosphorylase and soluble starch synthases activities and accelerated the hydrolysis of sucrose by increasing sucrose synthase, acid and alkaline invertases activities in drought-stressed anthers. Appropriate melatonin concentrations (100 and 200 µM) also could help to generate more ATP for reproductive activities of drought-stressed anthers, finally increasing the pollen viability and germination of drought-stressed plants. These findings suggest that drought inhibited male fertility of cotton, but a precise melatonin application could regulate the carbohydrate balance of drought-stressed anthers to improve male fertility. This is the first report demonstrating the important role of exogenous melatonin in improving male fertility under drought conditions by regulating the carbohydrate metabolism in the male part of cotton.
Assuntos
Metabolismo dos Carboidratos , Secas , Gossypium , Melatonina , Pólen , Metabolismo dos Carboidratos/efeitos dos fármacos , Fertilidade/efeitos dos fármacos , Gossypium/efeitos dos fármacos , Melatonina/farmacologia , Pólen/efeitos dos fármacosRESUMO
Targeted theranostic platform that integrates multi-modal imaging and therapeutic function is emerging as a promising strategy for earlier detection and precise treatment of cancer. Herein, we designed targeted gold-nanoshelled poly (lactic-co-glycolic acid) (PLGA) magnetic hybrid nanoparticles carrying anti-human epidermal growth factor receptor 2 (Her2) antibodies (Her2-GPH NPs) for dual-modal ultrasound (US)/magnetic resonance (MR) imaging and photothermal therapy of breast cancer. The agent was fabricated by coating gold nanoshell around PLGA nanoparticles co-loaded with perfluorooctyl bromide (PFOB) and superparamagnetic iron oxide nanoparticles (SPIOs), followed by conjugating with anti-Her2 antibodies. Cell-targeting studies demonstrated receptor-mediated specific binding of the agent to Her2-positive human breast cancer SKBR3 cells, and its binding rate was significantly higher than that of Her2-negative cells (P < 0.001). In vitro, the agent had capabilities for contrast-enhanced US imaging as well as T2-weighted MR imaging with a relatively high relaxivity (r2 = 441.47 mM-1 s-1). Furthermore, the Her2 functionalization of the agent prominently enhanced the US/MR molecular imaging effect of targeted cells by cell-specific binding. Live/dead cell assay and targeted photothermal cytotoxicity experiments confirmed that Her2-GPH NPs could serve as effective photoabsorbers to specifically induce SKBR3 cell death upon near-infrared laser irradiation. In summary, Her2-GPH NPs were demonstrated to be novel targeted theranostic agents with great potential to facilitate early non-invasive diagnosis and adjuvant therapy of breast cancer.
RESUMO
Magnetic nanoparticles have gained much interest for theranostics benefited from their intrinsic integration of imaging and therapeutic abilities. Herein, c(RGDyK) peptide PEGylated Fe@Fe3 O4 nanoparticles (RGD-PEG-MNPs) are developed for photoacoustic (PA)-enabled self-guidance in tumor-targeting magnetic hyperthermia therapy in vivo. In the αv ß3 -positive U87MG glioblastoma xenograft model, the PA signal of RGD-PEG-MNPs reaches its maximum in the tumor at 6 h after intravenous administration. This signal is enhanced by 2.2-folds compared to that of the preinjection and is also 2.2 times higher than that in the blocking group. It demonstrates the excellent targeting property of RGD-PEG-MNPs. With the guidance of the PA, an effective magnetic hyperthermia to tumor is achieved using RGD-PEG-MNPs.
Assuntos
Glioblastoma/terapia , Hipertermia Induzida/métodos , Magnetoterapia/métodos , Nanopartículas de Magnetita , Técnicas Fotoacústicas/métodos , Nanomedicina Teranóstica/métodos , Animais , Linhagem Celular Tumoral , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Camundongos Endogâmicos BALB C , Camundongos Nus , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
We report a pH-responsive photothermal ablation agent (pH-PTT) based on cyanine dyes for photothermal therapy (PTT). The nanoparticles formed by BSA and pH-PTT preferentially accumulated in the Golgi apparatus of cancer cells compared to normal cells, and thus can be specifically activated by the acidic Golgi apparatus in cancer cells for effective PTT both ex vivo and in vivo.
Assuntos
Carbocianinas/química , Corantes/química , Complexo de Golgi/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Processos Fotoquímicos , Temperatura , Carbocianinas/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Corantes/farmacologia , Complexo de Golgi/química , Complexo de Golgi/efeitos dos fármacos , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas/química , Imagem Óptica , FototerapiaRESUMO
To evaluate the role of potassium (K) in maintaining nitrogen metabolism and osmotic adjustment development of cotton functional leaves to sustain growth under soil drought and rewatering conditions, the plants of two cotton cultivars Siza 3 (low-K sensitive) and Simian 3 (low-K tolerant), were grown under three different K rates (K0, K1, and K2; 0, 150, and 300kgK2Oha-1, respectively) and exposed to drought stress with 40±5% soil relative water content (SRWC). The drought stress was applied at flowering stage by withholding water for eight days followed by rewatering to a well-watered level (75±5% SRWC). The results showed that drought-stressed plants of both cultivars showed a decrease in leaf relative water content (RWC) and osmotic potential in the functional leaves and developed osmotic adjustment with an increase in the contents of free amino acids, soluble sugars, inorganic K, and nitrate as compared to well-watered plants. In drought-stressed plants, nitrogen-metabolizing enzyme activities of nitrogen reductase (NR), glutamine synthetase (GS), and glutamate synthase (GOGAT) were diminished significantly (P≤0.05) along with decreased chlorophyll content and soluble proteins. However, drought-stressed plants under K application not only exhibited higher osmotic adjustment with greater accumulation of osmolytes but also regulated nitrogen metabolism by maintaining higher enzyme activities, soluble proteins, and chlorophyll content in functional leaves as compared to the plants without K application. Siza 3 showed better stability in enzyme activities and resulted in 89% higher seed cotton yield under K2 as compared to K0 in drought-stressed plants, whereas this increase was 53% in the case of Simian 3. The results of the study suggested that K application enhances cotton plants' potential for sustaining high nitrogen-metabolizing enzyme activities and related components to supplement osmotic adjustment under soil drought conditions.
Assuntos
Gossypium/metabolismo , Nitrogênio/metabolismo , Potássio/farmacologia , Secas , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/genética , Gossypium/efeitos dos fármacos , Osmose/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismoRESUMO
By using a solvothermal method in the presence of polyethylene glycol (PEG), BaGdF5 nanoparticles are firmly attached on the surface of graphene oxide (GO) nanosheets to form the GO/BaGdF5/PEG nanocomposites. The resulting GO/BaGdF5/PEG shows low cytotoxicity, positive magnetic resonance (MR) contrast effect and better X-ray attenuation property than Iohexol, which enables effective dual-modality MR and X-ray computed tomography (CT) imaging of the tumor model in vivo. The enhanced near-infrared absorbance, good photothermal stability and efficient tumor passive targeting of GO/BaGdF5/PEG result in the highly efficient photothermal ablation of tumor in vivo after intravenous injection of GO/BaGdF5/PEG and the following 808-nm laser irradiation (0.5 W/cm(2)). The histological and biochemical analysis data reveal no perceptible toxicity of GO/BaGdF5/PEG in mice after treatment. These results indicate potential application of GO/BaGdF5/PEG in dual-modality MR/CT imaging and photothermal therapy of cancers.
Assuntos
Bário/farmacologia , Fluoretos/farmacologia , Grafite/farmacologia , Hipertermia Induzida , Imagem Multimodal , Nanocompostos/química , Óxidos/farmacologia , Fototerapia , Animais , Compostos de Bário/farmacologia , Morte Celular/efeitos dos fármacos , Gadolínio/farmacologia , Células HeLa , Humanos , Imageamento por Ressonância Magnética , Camundongos , Camundongos Nus , Nanocompostos/ultraestrutura , Neoplasias/patologia , Polietilenoglicóis/química , Soluções , Espectroscopia de Infravermelho com Transformada de Fourier , Espectroscopia de Luz Próxima ao Infravermelho , Tomografia Computadorizada por Raios X , Difração de Raios XRESUMO
Photothermal therapy has attracted significant attention as a minimally invasive therapy methodology. In this work, we report PEGylated nickel carbide nanocrystals (Ni3C NCs) as an efficient photothermal agent for the first time. The nanoparticles exhibit a broad absorption from the visible to the near-infrared regions and a rapid rise in temperature when irradiated by an 808 nm laser even at a concentration of 100 µg mL(-1). In vitro and in vivo cytotoxicity assays demonstrate they have good biocompatibility, which lays an important foundation for their biological application. In vitro studies reveal the efficient damage of cancer cells by the exposure of 808 nm laser with a power density of 0.50 W cm(-2). Furthermore, hematoxylin and eosin (H & E) and terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling (TUNEL) staining of tumor slices confirmed the obvious destruction of cancer cells in vivo by an 808 nm laser (0.50 W cm(-2)) after only a 5 min application. Our work may open up a new application domain for transition metal carbides for biomedicine.
Assuntos
Carbono/química , Lasers , Nanopartículas/química , Neoplasias/terapia , Níquel/química , Fototerapia , Polietilenoglicóis/química , Espectroscopia de Luz Próxima ao Infravermelho , Animais , Materiais Biocompatíveis/química , Células HeLa , Humanos , Marcação In Situ das Extremidades Cortadas , Ligantes , Metais/química , Camundongos , Camundongos Nus , Microscopia Confocal , Transplante de Neoplasias , Neoplasias/tratamento farmacológico , Fotoquímica , RatosRESUMO
The development of photothermal agents (PTAs) with good stability, low toxicity, highly targeting ability and photothermal conversion efficiency is an essential pre-requisite to near-infrared photothermal therapy (PTT) in vivo. Herein, we report the readily available PEGylated Fe@Fe3O4 NPs, which possess triple functional properties in one entity - targeting, PTT, and imaging. Compared to Au nanorods, they exhibit comparable photothermal conversion efficiency (â¼20%), and much higher photothermal stability. They also show a high magnetization value and transverse relaxivity (â¼156 mm(-1) s(-1)), which should be applied for magnetic targeting MRI. With the Nd-Fe-B magnet (0.5 T) beside the tumour for 12 h on the xenograft HeLa tumour model, PEGylated Fe@Fe3O4 NPs exhibit an obvious accumulation. In tumour, the intensity of MRI signal is â¼ three folds and the increased temperature is â¼ two times than those without magnetic targeting, indicating the good magnetic targeting ability. Notably, the intrinsic high photothermal conversion efficiency and selective magnetic targeting effect of the NPs in tumour play synergistically in highly efficient ablation of cancer cells in vitro and in vivo.
Assuntos
Ferro/uso terapêutico , Nanopartículas de Magnetita/uso terapêutico , Neoplasias/diagnóstico , Neoplasias/terapia , Animais , Células HeLa , Humanos , Hipertermia Induzida/métodos , Raios Infravermelhos , Ferro/química , Imageamento por Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Camundongos Nus , Fototerapia/métodos , Polietilenoglicóis/química , Polietilenoglicóis/uso terapêutico , RatosRESUMO
We report here a facile thermal decomposition approach to creating tungsten oxide nanorods (WO2.9 NRs) with a length of 13.1 ± 3.6 nm and a diameter of 4.4 ± 1.5 nm for tumor theranostic applications. The formed WO2.9 NRs were modified with methoxypoly(ethylene glycol) (PEG) carboxyl acid via ligand exchange to have good water dispersability and biocompatibility. With the high photothermal conversion efficiency irradiated by a 980 nm laser and the better X-ray attenuation property than clinically used computed tomography (CT) contrast agent Iohexol, the formed PEGylated WO2.9 NRs are able to inhibit the growth of the model cancer cells in vitro and the corresponding tumor model in vivo, and enable effective CT imaging of the tumor model in vivo. Our "killing two birds with one stone" strategy could be extended for fabricating other nanoplatforms for efficient tumor theranostic applications.
Assuntos
Nanotecnologia , Nanotubos/química , Óxidos/química , Tungstênio/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Modelos Animais de Doenças , Células HeLa , Humanos , Hipertermia Induzida , Camundongos , Nanotubos/ultraestrutura , Neoplasias/diagnóstico , Neoplasias/terapia , Fototerapia , Polietilenoglicóis/química , Tocoferóis , Tomografia Computadorizada por Raios X , Difração de Raios X , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A rhodamine B derivative 4 containing a highly electron-rich S atom has been synthesized as a fluorescence turn-on chemodosimeter for Cu(2+). Following Cu(2+)-promoted ring-opening, redox and hydrolysis reactions, comparable amplifications of absorption and fluorescence signals were observed upon addition of Cu(2+); this suggests that chemodosimeter 4 effectively avoided the fluorescence quenching caused by the paramagnetic nature of Cu(2+). Importantly, 4 can selectively recognize Cu(2+) in aqueous media in the presence of other trace metal ions in organisms (such as Fe(3+), Fe(2+), Cu(+), Zn(2+), Cr(3+), Mn(2+), Co(2+), and Ni(2+)), abundant cellular cations (such as Na(+), K(+), Mg(2+), and Ca(2+)), and the prevalent toxic metal ions in the environment (such as Pb(2+) and Cd(2+)) with high sensitivity (detection limit < or =10 ppb) and a rapid response time (< or =1 min). Moreover, by virtue of the chemodosimeter as fluorescent probe for Cu(2+), confocal and two-photon microscopy experiments revealed a significant increase of intracellular Cu(2+) concentration and the subcellular distribution of Cu(2+), which was internalized into the living HeLa cells upon incubation in growth medium supplemented with 50 muM CuCl(2) for 20 h.
Assuntos
Cobre/química , Cobre/metabolismo , Corantes Fluorescentes/química , Cátions Bivalentes , Linhagem Celular Tumoral , Sobrevivência Celular , Fluorescência , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Sensibilidade e Especificidade , Fatores de TempoRESUMO
Treatment of hyperthyroidism, a common clinical condition that can have serious manifestations in the elderly, has remained essentially unchanged for >30 years. Directly antagonizing the effect of the thyroid hormone at the receptor level may be a significant improvement for the treatment of hyperthyroid patients. We built a computer model of the thyroid hormone receptor (TR) ligand-binding domain in its predicted antagonist-bound conformation and used a virtual screening algorithm to select 100 TR antagonist candidates out of a library of >250,000 compounds. We were able to obtain 75 of the compounds selected in silico and studied their ability to act as antagonists by using cultured cells that express TR. Fourteen of these compounds were found to antagonize the effect of T3 on TR with IC50s ranging from 1.5 to 30 microM. A small virtual library of compounds, derived from the highest affinity antagonist (1-850) that could be rapidly synthesized, was generated. A second round of virtual screening identified new compounds with predicted increased antagonist activity. These second generation compounds were synthesized, and their ability to act as TR antagonists was confirmed by transfection and receptor binding experiments. The extreme structural diversity of the antagonist compounds shows how receptor-based virtual screening can identify diverse chemistries that comply with the structural rules of TR antagonism.