RESUMO
Stem cell therapy has shown great potential in treating a wide range of diseases including cancer. The real-time tracking of stem cells with high spatiotemporal resolution and stable imaging signals remains the bottleneck to evaluate and monitor therapeutic outcomes once transplanted into patients. Here, we developed a photosensitive mesenchymal stem cell (MSC) loaded with mesoporous silica-coated gold nanostars (MGNSs) integrated with indocyanine green for spatiotemporal tracking and imaging-guided photothermal therapy (PTT) in treating breast cancers. The MGNS served as a stable imaging probe with multifunctional properties for photoacoustic imaging (PAI), fluorescence imaging, and PT imaging. Owing to the excellent PT stability of MGNSs, long-term three-dimensional (3D) PAI was achieved to monitor stem cells in real time at the tumor site, while the tumor structure was imaged using 3D B-mode ultrasound imaging. PAI revealed that the photosensitive stem cells reached the widest distribution area at the tumor site post 24 h of intratumoral injection, which was further confirmed via two-dimensional (2D) PT and fluorescence imaging. With this optimal cell distribution window, in vivo studies showed that the photosensitive stem cells via both intratumoral and intravenous injections successfully inhibited breast cancer cell growth and decreased the tumor recurrence rate post PTT. Our results support that this photo-integrated platform with stable optical properties is promising to achieve real-time tracking and measure the cell distribution quantitatively with high spatiotemporal resolution for stem cell therapy.
Assuntos
Neoplasias da Mama , Técnicas Fotoacústicas , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Feminino , Ouro/química , Ouro/farmacologia , Humanos , Imagem Multimodal , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Células-Tronco , Nanomedicina Teranóstica/métodosRESUMO
Targeting mitochondria has always been a challenging goal for therapeutic nanoparticle agents due to their heterotypic features and size, which usually lead to a lysosome/endosome endocytosis pathway. To overcome this limitation, in this work, a portfolio targeting strategy combining a small targeting molecule with a biomembrane was developed. Modification of small targeting molecule H2N-TPP on gold nanoparticles (GNPs) could not only facilitate the mitochondrial targeting but could also induce gold nanoparticle assembly. Therefore, the GNPs were endowed with good absorption and photothermal conversion abilities in the near-infrared (NIR) region. Meanwhile, a biomimetic strategy was adopted by wrapping the gold nanoparticle assembly (GNA) with cancer cell membranes (CCMs), which helped the GNA enter the prostatic cancer cell via a homotypic membrane-fusion process to avoid being trapped in endosomes/lysosomes. Thereafter, the GNA remaining in the cytoplasm could reach mitochondria more efficiently via guidance from H2N-TPP molecules. This "biomembrane-small molecule" combination targeting process was evidenced by fluorescence microscopy, and the highly efficient photothermal ablation of prostatic tumors in vivo was demonstrated. This portfolio targeting strategy could be extended to various nanodrugs/agents to realize an accurate subcellular targeting efficiency for cancer treatments or cell detections.
Assuntos
Ouro/química , Ouro/metabolismo , Raios Infravermelhos , Fusão de Membrana , Nanopartículas Metálicas/química , Mitocôndrias/metabolismo , Fototerapia/métodos , Biomimética , Linhagem Celular Tumoral , Endossomos/metabolismo , Humanos , Lisossomos/metabolismoRESUMO
The targeted delivery of nanomedicines into solid tumors remains challenging in cancer treatment. Stem cells with tumortropic migration ability are promising as biocarriers to transport nanomedicines. The transportation of nanomedicines into cancer cells is the key step for tumor targeted delivery via stem cells. In this study, we designed a magnetic nanocube (scMNP) loaded in mesenchymal stem cells for magnetic hyperthermia of prostate cancer, and the delivery and transportation pathways into the cancer cells were fully investigated. The MSCs acted as the carrier of the loaded scMNPs along with the upregulation of CXCR4 for the migration to cancer cells. The therapeutic effect was mainly due to scMNPs via magnetic hyperthermia. Stem cell-derived microvesicles containing scMNPs played an essential role in the crosstalk between stem cells and cancer cells for targeted delivery. Both in vitro and in vivo studies demonstrated that the system showed satisfactory therapeutic efficiency under magnetic hyperthermia therapy. Our investigation presents a comprehensive study of magnetic nanoparticles in combination with MSCs and their extracellular microvesicles and is promising as an effective strategy for magnetic hyperthermia therapy of prostate cancer.
Assuntos
Hipertermia Induzida , Células-Tronco Mesenquimais , Neoplasias da Próstata , Linhagem Celular Tumoral , Humanos , Magnetismo , MasculinoRESUMO
Precise induction and monitoring of cell apoptosis are significant for cancer treatment. This study aims to develop a gold nanoparticle (GNP)-based nanoprobe, which could simultaneously induce and monitor the apoptosis of melanoma cells in situ and realize a precise control of photothermal therapeutic dose. The GNS-TAT-Cy5 nanoprobe was obtained through the formation of Au-S bonds between GNS-TAT and Cy5-tagged caspase-3 specific peptides (Cy5-DEVD). The fluorescence of Cy5 was quenched by the GNS due to the nanosurface energy transfer effect. Upon laser irradiation, activated caspase-3 cleaved the substrate peptide and Cy5 was released from the nanoprobe, leading to a significant fluorescence turn on signal for sensitive and continuous analysis of caspase 3 activity in vitro and in vivo. Therefore, the GNS-TAT-Cy5 nanoprobe can serve as a precise theranostic platform via regulating the photothermal dose and achieved regulation and detection of apoptosis related to caspase-3 for melanoma.
Assuntos
Ouro/química , Melanoma/terapia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Animais , Apoptose , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Feminino , Humanos , Camundongos , FototerapiaRESUMO
OBJECTIVE: To explore the features of Traditional Chinese Medicine (TCM) syndromes in male infertility using computer-based analyses. METHODS: Latent class analysis was used to analyze the TCM syndrome data from 813 patients with male infertility and establish a latent tree model. RESULTS: A latent tree model with a Bayesian information criterion score of -11 263 was created. This model revealed that the characteristics of basic TCM syndromes in patients with male infertility were kidney Yang deficiency, kidney Qi deficiency, spleen Yang deficiency, liver Qi stagnation, Qi stagnation and blood stasis, and dump-heat; moreover, most patients with male infertility had complex syndromes (spleen-kidney Yang deficiency and liver Qi stagnation) rather than simple single syndromes. CONCLUSION: The hidden tree model analysis revealed the objective and quantitative complex relationships between the TCM symptoms of male infertility, and obtained the quantification and objective evidence of TCM syndromes in male infertility.
Assuntos
Infertilidade Masculina/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Infertilidade Masculina/fisiopatologia , Rim/fisiopatologia , Fígado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Baço/fisiopatologia , Deficiência da Energia Yang/diagnóstico , Deficiência da Energia Yang/fisiopatologia , Adulto JovemRESUMO
Larger, and deeper, root systems of new maize varieties, compared to older varieties, are thought to have enabled improved acquisition of soil resources and, consequently, greater grain yields. To compare the spatial distributions of the root systems of new and old maize varieties and their relationships with spatial variations in soil concentrations of available nitrogen (N), phosphorus (P) and potassium (K), two years of field experiments were performed using six Chinese maize varieties released in different eras. Vertical distributions of roots, and available N, P and K in the 0-60 cm soil profile were determined in excavated soil monoliths at silking and maturity. The results demonstrated that new maize varieties had larger root dry weight, higher grain yield and greater nutrient accumulation than older varieties. All varieties had similar total root length and vertical root distribution at silking, but newer varieties maintained greater total root length and had more roots in the 30-60 cm soil layers at maturity. The spatial variation of soil mineral N (Nmin) in each soil horizon was larger than that of Olsen-P and ammonium-acetate-extractable K, and was inversely correlated with root length density (RLD), especially in the 0-20 cm soil layer. It was concluded that greater acquisition of mineral nutrients and higher yields of newer varieties were associated with greater total root length at maturity. The negative relationship between RLD and soil Nmin at harvest for all varieties suggests the importance of the spatial distribution of the root system for N uptake by maize.
Assuntos
Minerais/análise , Nitrogênio/análise , Raízes de Plantas/anatomia & histologia , Solo/química , Zea mays/anatomia & histologia , Biomassa , Fertilizantes , Fósforo/análise , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Brotos de Planta/anatomia & histologia , Potássio/análise , Zea mays/classificação , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismoRESUMO
<p><b>OBJECTIVE</b>To study the syndrome evolution law of Chinese medicine (CM) in the patients with gastric mucosal dysplasia.</p><p><b>METHODS</b>Three hundred and twenty four gastric mucosal dysplasia patients with deficiency and excess correlation syndromes were enrolled by a multi-center collaboration for two years' clinical follow-up to detect the levels of tumor supplied group of factors (TSGF) and carcino-embryonic antigen (CEA).</p><p><b>RESULTS</b>Among the 324 cases, 29 cases turned cancer in the two years, and the canceration rate was 9.0%. The three syndromes with higher canceration rate were the damp-heat accumulating Wei syndrome concurring or combining with asthenia-cold in Pi and Wei syndrome for 16.7%; stagnation in Wei collaterals syndrome concurring or combining with asthenia of both qi and yin syndrome for 13.2%; stagnation of Gan and Wei qi syndrome concurring or combining with asthenia-cold in Pi and Wei syndrome for 8.0%, respectively. Among the three syndromes, the highest level of TSGF occurred in the former two syndromes. In the half year before carcinogenesis, the syndromes of the patients took on deficiency and excess concurrent syndromes, and the deficiency syndromes involving the qi and blood deficiency syndrome and the Shen deficiency syndrome accounting for 48.0%.</p><p><b>CONCLUSIONS</b>Gastric mucosal dyspalsia canceration syndromes took on the polymorphism of excess and deficiency concurrent syndromes and had the characteristics of deficiency syndromes involving qi and blood deficiency syndrome and Shen-yin-yang deficiency syndrome.</p>
Assuntos
Humanos , Biomarcadores Tumorais , Metabolismo , Antígeno Carcinoembrionário , Metabolismo , Mucosa Gástrica , Metabolismo , Patologia , Gastroscopia , Hiperplasia , Medicina Tradicional Chinesa , Lesões Pré-Cancerosas , Metabolismo , Patologia , Neoplasias Gástricas , Diagnóstico , Patologia , SíndromeRESUMO
The 150 samples of pu'er tea collected from the main producing area of Yunnan were detected by ICP-AES method, to investigate the current safety status of pu'er tea rare earth elements. The rare earth elements contents were found to be in the range 0.26-4.07 mg x kg(-1) in all detected samples, with the 43.0% samples exceeding the maximum levels of contaminants of 2 mg x kg(-1) set by GB 2762-2005 "Maximum levels of contaminants in foods". There was a significant difference between ripened tea rare earth elements and raw tea's from the same sources, which affected some ripened tea quality at last. There was a significant difference among the rare earth elements contents of the pu'er tea main producing areas, and the condition of pu'er tea quality and safety controlling was not optimistic at individual producing areas.
Assuntos
Análise de Alimentos/métodos , Metais Terras Raras/análise , Chá/química , China , Espectrofotometria AtômicaRESUMO
The mistakes in English abstracts of medical literatures influence the international communication of medical information. The misuse of words, grammar mistakes, and improper expressions are common problems. Moreover, nonstandard expressions also include the names of Chinese herbal medicines, numbers, punctuations, and so on.
Assuntos
Indexação e Redação de Resumos , Publicações Periódicas como Assunto , TraduçõesRESUMO
<p><b>OBJECTIVE</b>To observe whether the dopaminergic neuroprotective effect of (-)-epigallocatechin gallate (EGCG) is associated with its inhibition of microglial cell activation in vivo.</p><p><b>METHODS</b>The effects of EGCG at different doses on dopaminergic neuronal survival were tested in a methyl-4-phenyl-pyridinium (MPP+)-induced dopaminergic neuronal injury model in the primary mesencephalic cell cultures. With unbiased stereological method, tyrosine hydroxylase-immunoreactive (TH-ir) cells were counted in the A8, A9 and A10 regions of the substantia nigra (SN) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57BL/6 mice. The effect of EGCG on microglial activation in the SN was also investigated.</p><p><b>RESULTS</b>Pretreatment with EGCG (1 to 100 micromol/L) significantly attenuated MPP+-induced TH-ir cell loss by 22.2% to 80.5% in the mesencephalic cell cultures. In MPTP-treated C57BL/6 mice, EGCG at a low concentration (1 mg/kg) provided significant protection against MPTP-induced TH-ir cell loss by 50.9% in the whole nigral area and by 71.7% in the A9 region. EGCG at 5 mg/kg showed more prominent protective effect than at 1 or 10 mg/kg. EGCG pretreatment significantly inhibited microglial activation and CD11b expression induced by MPTP.</p><p><b>CONCLUSION</b>EGCG exerts potent dopaminergic neuroprotective activity by means of microglial inhibition, which shed light on the potential use of EGCG in treatment of Parkinson's disease.</p>