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1.
Cell Transplant ; 33: 9636897241270401, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39219184

RESUMO

The annual number of human leukocyte antigen (HLA)-haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HCT) is increasing steadily. Comparative studies about haplo-HCT versus HCT with HLA-matched sibling donors (MSD-HCT) have been tried in acute myeloid leukemia and B-cell acute lymphoblastic leukemia/lymphoma (ALL). Few studies were reported in adult T-cell ALL (T-ALL). In this retrospective study, a total of 88 consecutive patients with T-ALL were enrolled who underwent MSD-HCT (n = 24) and haplo-HCT (n = 64) with antithymocyte globulin (ATG)-based graft versus host disease (GVHD) prophylaxis between 2010 and 2022. Median follow-up for survivors was similar (43.5 [range: 7-88] months for MSD-HCT versus 43.5 (range: 6-144) months in the Haplo-HCT group). The 100-day cumulative incidence of grade II to IV acute GVHD (aGVHD) was similar, 33% (95% confidence interval [CI], 16%-52%) after MSD-HCT versus 44% (95% CI, 31%-55%) after haplo-HCT, P = 0.52. The cumulative incidences of grade III-IV aGVHD were 8% (95% CI, 1%-23%) in the MSD-HCT group and 5% (95% CI, 1%-12%) in the haplo-HCT group (P = 0.50). The 2-year cumulative incidence of chronic GVHD (limited and extensive) in the haplo-HCT, 11% (95% CI, 5%-20%) was significantly lower than that in the MSD-HCT group (42% [95% CI, 21%-62%], P = 0.002). The cumulative incidence of 4-year relapse rates (44% versus 37%, P = 0.56) and non-relapse mortality (7% versus 21%, P = 0.08) did not differ between these two groups. There were also no differences in 4-year overall survival (46% versus 47%, P = 0.44) and progression-free survival (49% versus 42%, P = 0.45) between these two groups. On multivariate analysis, using busulfan/fludarabine (BU/Flu) conditioning regimen was found to be associated with worse clinical outcome. Our results suggested that ATG-based haplo-HCT platform could work as an alternative to MSD-HCT for adult patients with T-ALL. Compared with MSD-HCT, haplo-HCT might carry a low risk for cGVHD.


Assuntos
Soro Antilinfocitário , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Irmãos , Humanos , Adulto , Feminino , Masculino , Soro Antilinfocitário/uso terapêutico , Pessoa de Meia-Idade , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto Jovem , Estudos Retrospectivos , Transplante Haploidêntico/métodos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Doença Crônica
2.
Mikrochim Acta ; 191(9): 553, 2024 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-39167246

RESUMO

Single-level biomarker detection has the limitation of insufficient accuracy in cancer diagnosis. Therefore, the strategy of developing highly sensitive, multi-channel biosensors for high-throughput ctDNA determination is critical to improve the accuracy of early diagnosis of clinical tumors. Herein, in order to achieve efficient detection of up to ten targets for early diagnosis of ovarian cancer, a DNA-nanoswitch-based multi-channel (DNA-NSMC) biosensor was built based on the multi-module catalytic hairpin assembly-mediated signal amplification (CHA) and toehold-mediated DNA strand displacement (TDSD) reaction. Only two different fluorescence signals were used as outputs, combined with modular segmentation strategy of DNA-nanoswitch-based reaction platform; the multi-channel detection of up to ten targets was successfully achieved for the first time. The experimental results suggest that the proposed biosensor is a promising tool for simultaneously detecting multiple biomarkers for the early diagnosis of ovarian cancer, offering new strategies for the early screening, diagnosis, and treatment not only for ovarian cancer but also for other cancers.


Assuntos
Biomarcadores Tumorais , Técnicas Biossensoriais , DNA Tumoral Circulante , Neoplasias Ovarianas , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/sangue , Feminino , Humanos , Técnicas Biossensoriais/métodos , Biomarcadores Tumorais/sangue , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Limite de Detecção
3.
Int Immunopharmacol ; 137: 112493, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38897126

RESUMO

Microglia-mediated neuroinflammation is closely associated with many neurodegenerative diseases. Psoralen has potential for the treatment of many diseases, however, the anti-neuroinflammatory and neuroprotective effects of psoralen have been unclear. This study investigated the anti-neuroinflammatory and neuroprotective effects of psoralen and its regulation of microglial M1/M2 polarization. The LPS-induced mice model was used to test anti-neuroinflammatory effects, regulatory effects on microglia polarization, and neuroprotective effects of psoralen in vivo. The LPS-induced BV2 model was used to test the anti-neuroinflammatory effects and the regulatory effects and mechanisms on microglial M1/M2 polarization of psoralen in vitro. PC12 cell model induced by conditioned medium of BV2 cells was used to validate the protective effects of psoralen against neuroinflammation-induced neuronal damage. These results showed that psoralen inhibited the expression of iNOS, CD86, and TNF-α, and increased the expression of Arg-1, CD206, and IL-10. These results indicated that psoralen inhibited the M1 microglial phenotype and promoted the M2 microglial phenotype. Further studies showed that psoralen inhibited the phosphorylation of Fyn and PKCδ, thereby inhibiting activation of the MAPKs and NF-κB pathways and suppressing the expression of pro-inflammatory cytokines in microglia. Furthermore, psoralen reduced oxidative stress, neuronal damage, and apoptosis via inhibition of neuroinflammation. For the first time, this study showed that psoralen protected neurons and alleviated neuroinflammation by regulating microglial M1/M2 polarization, which may be mediated by inhibition of the Fyn-PKCδ pathway. Thus, psoralen may be a potential agent in the treatment of neuroinflammation-related diseases.


Assuntos
Ficusina , Lipopolissacarídeos , Microglia , Doenças Neuroinflamatórias , Neurônios , Fármacos Neuroprotetores , Proteína Quinase C-delta , Proteínas Proto-Oncogênicas c-fyn , Transdução de Sinais , Animais , Microglia/efeitos dos fármacos , Microglia/metabolismo , Proteínas Proto-Oncogênicas c-fyn/metabolismo , Proteína Quinase C-delta/metabolismo , Camundongos , Ficusina/farmacologia , Ficusina/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Células PC12 , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/imunologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Masculino , Camundongos Endogâmicos C57BL , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Citocinas/metabolismo
4.
Proc Natl Acad Sci U S A ; 121(22): e2319880121, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38768353

RESUMO

Elevated interstitial fluid pressure (IFP) within pathological tissues (e.g., tumors, obstructed kidneys, and cirrhotic livers) creates a significant hindrance to the transport of nanomedicine, ultimately impairing the therapeutic efficiency. Among these tissues, solid tumors present the most challenging scenario. While several strategies through reducing tumor IFP have been devised to enhance nanoparticle delivery, few approaches focus on modulating the intrinsic properties of nanoparticles to effectively counteract IFP during extravasation and penetration, which are precisely the stages obstructed by elevated IFP. Herein, we propose an innovative solution by engineering nanoparticles with a fusiform shape of high curvature, enabling efficient surmounting of IFP barriers during extravasation and penetration within tumor tissues. Through experimental and theoretical analyses, we demonstrate that the elongated nanoparticles with the highest mean curvature outperform spherical and rod-shaped counterparts against elevated IFP, leading to superior intratumoral accumulation and antitumor efficacy. Super-resolution microscopy and molecular dynamics simulations uncover the underlying mechanisms in which the high curvature contributes to diminished drag force in surmounting high-pressure differentials during extravasation. Simultaneously, the facilitated rotational movement augments the hopping frequency during penetration. This study effectively addresses the limitations posed by high-pressure impediments, uncovers the mutual interactions between the physical properties of NPs and their environment, and presents a promising avenue for advancing cancer treatment through nanomedicine.


Assuntos
Sistemas de Liberação de Medicamentos , Líquido Extracelular , Nanopartículas , Pressão , Nanopartículas/química , Líquido Extracelular/metabolismo , Animais , Sistemas de Liberação de Medicamentos/métodos , Camundongos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Linhagem Celular Tumoral , Extravasamento de Materiais Terapêuticos e Diagnósticos , Simulação de Dinâmica Molecular , Antineoplásicos/farmacocinética , Antineoplásicos/administração & dosagem , Antineoplásicos/química
5.
Spectrochim Acta A Mol Biomol Spectrosc ; 308: 123683, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38006864

RESUMO

Detecting heavy metal copper ions in lubricating oil holds immense significance for assessing mechanical wear and predicting mechanical failure. While perovskite nanocrystals offer high sensitivity in detecting copper ions, traditional lead halide perovskites suffer from lead toxicity defects. Lead-free perovskites, like Cs2NaInCl6, avoid the issue of lead toxicity but display lower luminescence intensity due to the presence of forbidden optical transitions. To address these issues, this study synthesized Cs2NaInCl6 nanocrystals (NCs) co-doped with Sb3+ and Tb3+ ions for copper ions detection in lubricating oil. The introduction of Sb3+ effectively reduced the band gap of the Cs2NaInCl6 host, creating an energy transfer pathway for Tb3+ emission via self-trapped excitations (STEs). Moreover, the doping of Tb3+ ions resulted in the suppression of STEs emission due to electron transfer from STEs to Tb3+. The emission of Tb3+ increased initially and then decreased with the increasing Tb3+ concentration, peaking at 40 %. Finally, Cs2NaInCl6: 2.5 %Sb3+, 40 %Tb3+ NCs were employed as probes for copper ions detection, exhibiting superior sensitivity and selectivity compared to similar probes. The presence of copper ions introduced competition between copper and Tb3+ for electrons from STEs, consequently leading to the quenching of multiple emission intensities associated with STEs and Tb3+. This method shows promising potential in predicting mechanical failure.

6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(5): 1501-1508, 2023.
Artigo em Chinês | MEDLINE | ID: mdl-37846708

RESUMO

OBJECTIVE: To investigate the clinical features of transplant-associated thrombotic microangiopathy (TA-TMA) and the prognostic value of different prognostic risk models for TA-TMA. METHODS: The clinical characteristics of 32 TA-TMA patients diagnosed at the First Medical Center of the PLA General Hospital from January 2018 to February 2022 in terms of short-term prognosis and influencing factors were retrospectively analyzed. In addition, the risk population composition ratio, treatment response, and overall survival between the BATAP risk model and the TMA index model were compared, as well as the efficacy of two prognostic risk models for predicting death in patients with TA-TMA. RESULTS: Independent risk factors affecting the short-term prognosis of TA-TMA include III-IV aGVHD prior to TA-TMA diagnosis (P=0.001), renal or neurological dysfunction (P=0.006), and Hb<70 g/L (P=0.043). In the TMA index model, treatment response was worst in the high-risk group (P=0.008), while there was no significant difference in treatment response between different risk groups in the BATAP model (P=0.105). In the BATAP model, there was a statistically significant difference in the OS between the three groups of low risk, intermediate risk, and high risk (87.5% vs 61.1% vs 16.7%, χ2=6.7, P=0.014). In the TMA index model, there was a statistically significant difference in the OS between the three groups of low risk, intermediate risk, and high risk (77.8% vs 45.5% vs 0.0%, χ2=7.3, P=0.017). The area under the ROC curve (AUC) of the TMA index model was 0.745 (95%CI: 0.56-0.88, P<0.05), and the AUC of the BATAP model was 0.743 (95%CI: 0.56-0.88, P<0.05), indicating that both prognostic risk models have good predictive value. CONCLUSION: The short-term prognosis of TA-TMA patients might be accurately determined using both the BATAP model and the TMA index model. When predicting the efficacy of TA-TMA in different risk groups, the TMA index model may perform better than the BATAP model.

7.
Food Chem ; 428: 136703, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37423103

RESUMO

The synergistic effect of the initial state of the enzyme and pressure level on the denaturation of PPO has not been clear yet, but it significantly affects the application of high hydrostatic pressure (HHP) in the enzyme-containing food processing. Solid (S-) and low/high concentration liquid (LL-/HL-) polyphenol oxidase (PPO) was used as the study object, and the microscopic conformation, molecular morphology and macroscopic activity of PPO under HHP treatments (100-400 MPa, 25 °C/30 min) were investigated by spectroscopic techniques. The results show that the initial state has a significant effect on the activity, structure, active force and substrate channel of PPO under pressure. The effec can be ranked as follows: physical state > concentration > pressure, S-PPO > LL-PPO > HL-PPO. High concentration has a weakening effect on the pressure denaturation of the PPO solution. Under high pressure, the α-helix and concentration factors play a crucial role in stabilizing the structure.


Assuntos
Catecol Oxidase , Manipulação de Alimentos , Catecol Oxidase/química , Manipulação de Alimentos/métodos , Pressão Hidrostática
8.
Drug Discov Today ; 27(3): 822-830, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34767960

RESUMO

The prevalence of obesity is a major cause of many chronic metabolic disorders, including type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and cancer. Insulin resistance is often associated with metabolic unhealthy obesity (MUO). Therapeutic approaches aiming to improve insulin sensitivity are believed to be central for the prevention and treatment of MUO. However, current antiobesity drugs are reported as multitargeted and their insulin-sensitizing effects remain unclear. In this review, we discuss current understanding of the mechanisms of insulin resistance from the aspects of endocrine disturbance, inflammation, oxidative, and endoplasmic reticulum stress (ERS). We then summarize the antiobesity drugs, focusing on their effects on insulin sensitivity. Finally, we discuss strategies for obesity treatment.


Assuntos
Fármacos Antiobesidade , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Fármacos Antiobesidade/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Insulina/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo
9.
Postgrad Med ; 133(7): 822-829, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34281466

RESUMO

BACKGROUND: Recent studies have identified monocyte to high-density lipoprotein ratio (MHR) as a simple, practical surrogate of atherosclerosis. Considering atherosclerosis is a major mechanism of coronary heart disease (CHD). The present study aims to evaluate the association between MHR and the prevalence of CHD. METHODS AND RESULTS: The present cross-sectional work included 6442 participants (mean age: 59.57 years, 60.2% females), all of them were included from rural areas of northern China between October 2019 to April 2020. MHR was acquired as monocytes count divided by high-density lipoprotein concentration. Prevalent CHD researched 3.14%. After adjustment of sex, age, current drinking and smoking, BMI, WC, diabetes, hypertension, LDL-C, TG, eGFR, lipid-lowering therapy and cerebrovascular disease history, each standard deviation increase of MHR cast a 39.5% additional CHD risk. Furthermore, the top quartile of MHR had an additional 89.0% CHD risk than the bottom quartile. Besides, smooth curve fitting revealed a linear pattern of the association. Additionally, the stratified evaluation showed a robust correlation among the subgroups divided by CHD risk factors. Finally, area under the curve demonstrated an advancement when including MHR into common CHD risk factors (0.744 vs 0.761, p < 0.001). Consistently, reclassification analysis indicated the improvement from MHR (all P = 0.003). CONCLUSION: Our work suggests the robust and linear relationship between MHR and the prevalent CHD in a general population, providing epidemiological evidence for laboratory studies. More importantly, the findings implicate the efficacy of MHR to be a potential indicator to identify the prevalent CHD.


Assuntos
Doença das Coronárias/sangue , Lipoproteínas HDL/análise , Monócitos/citologia , Idoso , Aterosclerose/sangue , China , Comorbidade , Estudos Transversais , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade
10.
CNS Neurosci Ther ; 27(11): 1313-1326, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34255932

RESUMO

AIMS: Chronification of postoperative pain is a common clinical phenomenon following surgical operation, and it perplexes a great number of patients. Estrogen and its membrane receptor (G protein-coupled estrogen receptor, GPER) play a crucial role in pain regulation. Here, we explored the role of GPER in the rostral ventromedial medulla (RVM) during chronic postoperative pain and search for the possible mechanism. METHODS AND RESULTS: Postoperative pain was induced in mice or rats via a plantar incision surgery. Behavioral tests were conducted to detect both thermal and mechanical pain, showing a small part (16.2%) of mice developed into pain persisting state with consistent low pain threshold on 14 days after incision surgery compared with the pain recovery mice. Immunofluorescent staining assay revealed that the GPER-positive neurons in the RVM were significantly activated in pain persisting rats. In addition, RT-PCR and immunoblot analyses showed that the levels of GPER and phosphorylated µ-type opioid receptor (p-MOR) in the RVM of pain persisting mice were apparently increased on 14 days after incision surgery. Furthermore, chemogenetic activation of GPER-positive neurons in the RVM of Gper-Cre mice could reverse the pain threshold of pain recovery mice. Conversely, chemogenetic inhibition of GPER-positive neurons in the RVM could prevent mice from being in the pain persistent state. CONCLUSION: Our findings demonstrated that the GPER in the RVM was responsible for the chronification of postoperative pain and the downstream pathway might be involved in MOR phosphorylation.


Assuntos
Dor Crônica/genética , Bulbo/efeitos dos fármacos , Dor Pós-Operatória/genética , Receptores de Estrogênio/genética , Receptores Acoplados a Proteínas G/genética , Animais , Dor Crônica/fisiopatologia , Hiperalgesia/psicologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Medição da Dor , Dor Pós-Operatória/fisiopatologia , Ratos , Ratos Sprague-Dawley , Receptores Opioides mu/efeitos dos fármacos , Receptores Opioides mu/genética
11.
Chem Commun (Camb) ; 57(42): 5179-5182, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-33908488

RESUMO

Herein, a novel co-catalytic ferrocene/hemin/G-quadruplexes/Fe3O4 nanoparticles (Fc/HGQs/Fe3O4) nanocomposite was synthesized to significantly magnify the electrochemical signal of ferrocene (Fc) using the synergistic catalysis of hemin/G-quadruplexes (HGQs) and Fe3O4 nanoparticles as hydrogen peroxide enzyme mimics for the construction of ultrasensitive electrochemical biosensors. The fabricated electrochemical biosensor can achieve ultrasensitive detection of miRNA-155 ranging from 0.1 fM to 1 nM, as well as a limit of detection of 74.8 aM. This strategy provides a new route to exploring efficient signal labels for signal amplification and provides an impetus to find novel methods for the construction of biosensors for biological detection and the early clinic diagnosis of diseases.


Assuntos
Técnicas Biossensoriais/métodos , Óxido Ferroso-Férrico/química , Compostos Ferrosos/química , Quadruplex G , Metalocenos/química , Nanocompostos/química , Linhagem Celular Tumoral , Técnicas Eletroquímicas , Hemina/química , Humanos , Limite de Detecção , MicroRNAs
12.
Aging (Albany NY) ; 12(16): 16368-16389, 2020 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-32862153

RESUMO

This study aimed to evaluate the role of FRT in ROS/DNA regulation with or without PARP-1 in radiation-injured thymus cells. The administration of FRT to PARP-1-/- (KO) mice demonstrated that FRT significantly increased the viability of thymus cells and decreased their rate of apoptosis through PARP-1. Radiation increased the levels of ROS, γ-H2AX and 53BP1, and induced DNA double strand breaks. Compared with wild type (WT) mice, levels of ROS, γ-H2AX and 53BP1 in KO mice were much less elevated. The FRT treatment groups also showed little reduction in these indicators in KO mice compared with WT mice. The results of the KO mice study indicated that FRT reduced ROS activation through inhibition of PARP-1. Furthermore, FRT reduced the concentrations of γ-H2AX by decreasing ROS activation. However, we found that FRT did not regulate 53BP1, a marker of DNA damage, because of its elimination of ROS. Levels of apoptosis-inducing factor (AIF), exhibited no significant difference after irradiation in KO mice. To summarize, ROS suppression by PARP-1 knockout in KO mice highlights potential therapeutic target either by PARP-1 inhibition combined with radiation or by treatment with a drug therapy alone. AIF-induced apoptosis could not be activated in KO mice.


Assuntos
Antioxidantes/farmacologia , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Flavonoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Poli(ADP-Ribose) Polimerase-1/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Rosa , Timo/efeitos dos fármacos , Animais , Antioxidantes/isolamento & purificação , Apoptose/efeitos dos fármacos , Fator de Indução de Apoptose/metabolismo , Células Cultivadas , Flavonoides/isolamento & purificação , Histonas/metabolismo , Camundongos Knockout , Estresse Oxidativo/efeitos da radiação , Poli(ADP-Ribose) Polimerase-1/deficiência , Poli(ADP-Ribose) Polimerase-1/genética , Rosa/química , Timo/metabolismo , Timo/patologia , Timo/efeitos da radiação , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo
13.
Biosens Bioelectron ; 149: 111848, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31726271

RESUMO

In this work, a novel DNA circle capture probe with multiple target recognition domains was designed to develop an electrochemical biosensor for ultrasensitive detection of microRNA-21 (miRNA-21) and miRNA-155 simultaneously. The DNA circle capture probe was anchored at the top of the tetrahedron DNA nanostructure (TDN) to simultaneously recognize miRNA-21 and miRNA-155 through multiple target recognition domains under the assistance of Helper strands, which could trigger mimetic proximity ligation assay (mPLA) for capturing the beacons ferrocene (Fc)-A1 and methylene blue (MB)-A2 to achieve multiple miRNAs detection. In this way, the local reaction concentration could be enhanced and avoid the interference of various capture probes compared with the traditional multiplexed electrochemical biosensor with the use of different capture probes, resulting in the significantly improvement of detection sensitivity. As a result, this proposed biosensor showed wide linearity ranging from 0.1 fM to 10 nM with detection limits of miRNA-21 and miRNA-155 as 18.9 aM and 39.6 aM respectively, which also could be applied in the simultaneously detection of miRNA-21 and miRNA-155 from cancer cell lysates. The present strategy paved a new path in the design of capture probes for achieving more efficient and sensitive multiple biomarkers detections and possessed the potential applications in clinical diagnostic of diseases.


Assuntos
Técnicas Biossensoriais , MicroRNAs/isolamento & purificação , Neoplasias/diagnóstico , Sondas de DNA/química , Técnicas Eletroquímicas , Humanos , Limite de Detecção , MicroRNAs/química , Neoplasias/genética
14.
Mikrochim Acta ; 185(10): 454, 2018 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-30209588

RESUMO

Accurate detection of temperature and oxygen concentration at the cellular level is important in tumor diagnosis. Multifunctional nanocomposites are described that consist of upconversion luminescent nanoparticles capped with mesoporous silica and loaded with an oxygen-sensitive luminescent ruthenium complex. The nanocomposites of type NaYF4:Yb,Er@NaYF4@mSiO2-Ru have two modes of operation: Its red downconversion luminescence (at excitation/emission peaks of 455/606 nm) is quenched by oxygen (O2), and this is used to sense and image O2. The green upconversion luminescence (typically acquired at excitation/emission wavelengths of 980/525 and 544 nm), in turn, is used to measure temperature. The nanocomposites were then applied to dual mode in-vitro imaging of temperature and O2 in hepatocellular carcinoma cells (HepG-2). Graphical abstract A new multifunctional nanocomposite of mesoporous silica coating NaYF4:Yb,Er@NaYF4 upconversion nanopaticless loaded with ruthenium (II) complex has been designed with both green upconversion and red downconversion luminescence for temperature detection, oxygen sensing and dual mode cell imaging.

15.
Apoptosis ; 23(9-10): 470-483, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29995207

RESUMO

The present study evaluated the protective effect of the natural compound flavonoids of Rosa roxburghii Tratt (FRT) against γ-radiation-induced apoptosis and inflammation in mouse thymus cells in vivo and in vitro. Thymus cells and mice were exposed to 60Co γ-ray at a dose of 6 Gy. The radiation treatment induced significant cell apoptosis and inflammation. Radiation increased the expressions of cleaved caspase 3/8-10, AIF, and PARP-1, and FRT could mitigate their activation and inhibit subsequent apoptosis in the thymus both in vitro or in vivo. Irradiation increased the mRNA expression of ICAM-1/VCAM-1, IL-1α/IL-6 and TNF-α/NF-κB. Our results also indicated that FRT alleviated gene expression of some inflammatory factors such as ICAM-1/VCAM-1, TNF-α/NF-κB, but not IL-1α/IL-6. Irradiation increased the protein expression levels of ICAM-1/VCAM-1, IL-1α/IL-6 and TNF-α/NF-Κb, and our results also indicated that FRT alleviated protein level expression of certain inflammatory factors such as ICAM-1, IL-1α/IL-6, TNF-α/NF-κB, but not VCAM-1. Our results suggested that FRT enhanced radioprotection at least partially by regulating caspase 3/8-10, AIF, and PARP-1 to reduce apoptosis and by regulating ICAM-1, IL-1α/IL-6, TNF-α/NF-κB to reduce inflammation.


Assuntos
Apoptose/efeitos dos fármacos , Flavonoides/administração & dosagem , Inflamação/tratamento farmacológico , Rosa/química , Animais , Apoptose/genética , Apoptose/efeitos da radiação , Caspase 3/genética , Flavonoides/química , Raios gama/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Inflamação/patologia , Molécula 1 de Adesão Intercelular/genética , Camundongos , NF-kappa B/genética , Transdução de Sinais/efeitos dos fármacos , Timo/efeitos dos fármacos , Timo/patologia , Fator de Transcrição RelA/genética , Fator de Necrose Tumoral alfa/genética
16.
J Cell Biochem ; 119(4): 3519-3527, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29144017

RESUMO

It was found that the expression level of miR-147a was significantly increased and the pathway of PI3K/AKT was dramatically inhibited after radiation. In view of the relationship between miRNA and target genes, we put forward the question, what is the relationship between PI3K/AKT and miR-147a? In order to find the answer to the question, we used bioinformatics techniques to analyze the relationship between miR-147 (a or b) and PI3K/AKT signaling pathway. miR-147a overexpression plasmid and PDPK1 3'UTR luciferase reporter gene plasmid were constructed. Dual luciferase reporter gene system validation experiments were carried out on miR-147a and PDPK1 relationship. The verification experiments were also carried out. Bioinformatics analysis showed that there is a miR-147a binding site in the non-coding region (3'UTR) of PDPK1. In the experimental groups transfected with wild type PDPK1 gene of 3'UTR plasmid, the luciferase activity decreased (or increased) significantly in miR-147a (or inhibitor) group compared with miR-NC (or anti-miR-NC); There was no significant difference between the miR-147a group (or inhibitor) and the miR-NC group (or anti-miR-NC) in the transfection of PDPK1-3'UTR-Mut gene vector. PDPK1 was a target gene for direct regulation of miR-147a downstream. Verifying test results showed that the expression of PDPK1 mRNA and protein was reduced after overexpression of miR-147a, which was up-regulated after silencing miR-147a in TC, and V79 cells. These results suggest that miR-147a could be involved in the regulation of PDPK1 transcription by binding to the target site in PDPK1 mRNA 3'UTR, and then regulated AKT.


Assuntos
Proteínas Quinases Dependentes de 3-Fosfoinositídeo/genética , Proteínas Quinases Dependentes de 3-Fosfoinositídeo/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Regiões 3' não Traduzidas/genética , Animais , Células Cultivadas , Biologia Computacional , Cricetinae , Células HEK293 , Humanos , Immunoblotting , Camundongos , Ligação Proteica/efeitos da radiação , Transdução de Sinais/efeitos dos fármacos
17.
Sci Rep ; 7(1): 11849, 2017 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-28928385

RESUMO

To realize photothermal therapy (PTT) of cancer/tumor both the photothermal conversion and temperature detection are required. Usually, the temperature detection in PTT needs complicated instruments, and the therapy process is out of temperature control in the present investigations. In this work, we attempt to develop a novel material for achieving both the photothermal conversion and temperature sensing and control at the same time. To this end, a core-shell structure with NaYF4:Er3+/Yb3+ core for temperature detection and NaYF4:Tm3+/Yb3+ shell for photothermal conversion was designed and prepared. The crystal structure and morphology of the samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Furthermore, the temperature sensing properties for the NaYF4:Er3+/Yb3+ and core-shell NaYF4:Er3+/Yb3+@NaYF4:Tm3+/Yb3+ nanoparticles were studied. It was found that the temperature sensing performance of the core-shell nanoparticles did not become worse due to coating of NaYF4:Tm3+/Yb3+ shell. The photothermal conversion behaviors were examined in cyclohexane solution based on the temperature response, the NaYF4:Er3+/Yb3+@NaYF4:Tm3+/Yb3+ core-shell nanoparticles exhibited more effective photothermal conversion than that of NaYF4:Er3+/Yb3+ nanoparticles, and a net temperature increment of about 7 °C was achieved by using the core-shell nanoparticles.


Assuntos
Hipertermia Induzida , Nanopartículas , Fototerapia , Animais , Érbio/química , Fluoretos/química , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Termômetros , Itérbio/química , Ítrio/química
18.
Biomaterials ; 138: 69-79, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28554009

RESUMO

Detection and isolation of circulating tumor cells (CTCs) play a pivotal role in the diagnosis and prognosis of cancer, while the high capture efficiency and purity of CTCs are difficult to achieve simultaneously among the various isolation methods. In this work, we designed an inverted microchip integrating silicon nanowires (SiNWs) and multifunctional magnetic nanocomposites (Fe3O4@C6/Ce6@silane, Coumarin 6 (C6), Chlorin e6 (Ce6)) for enhanced capture efficiency and purity of CTCs. The Fe3O4@C6/Ce6@silane conjugated with antibody can label the CTCs and pull them to the upside SiNWs capture surface by the upward magnetic field with high purity. This inverted structure was also featured with real-time detection and photodynamic therapy (PDT) of CTCs with the confocal laser scanning microscope (CLSM). The results indicate the important role of the composites labels and the magnetic field, which greatly improves the capture purity of the CTCs to 90%. Meanwhile, capture efficiency of CTCs achieve to 90.3% in culture medium and 82% in blood with 2 mL/h flow rate, respectively. Based on the structure of the device and composites, the captured CTCs could be directly inactivated by the in situ photodynamic therapy in the capture process which holds positive impact to block cancer spread.


Assuntos
Antineoplásicos/uso terapêutico , Separação Celular/métodos , Nanopartículas de Magnetita/química , Técnicas Analíticas Microfluídicas , Neoplasias/diagnóstico , Células Neoplásicas Circulantes/química , Anticorpos Imobilizados/química , Antineoplásicos/síntese química , Clorofilídeos , Cumarínicos/química , Células HeLa , Humanos , Dispositivos Lab-On-A-Chip , Células MCF-7 , Campos Magnéticos , Microscopia Confocal , Nanoconjugados/química , Nanofios/química , Neoplasias/patologia , Fotoquimioterapia , Porfirinas/química , Silanos/química , Silício/química
19.
J Hazard Mater ; 327: 35-43, 2017 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-28038430

RESUMO

Degradation of mechanically sorted organic fraction (MSOF) of municipal solid waste in composting facilities is among the major contributors of volatile compounds (VCs) generation and emission, causes nuisance problems and health risks on site as well as in the vicinages. The aim of current study was to determine the seasonal (summer and winter) variation and human health risk assessment of VCs in the ambient air of different processing units in MSOF at composting plant in China. Average concentration of VCs was 58.50 and 138.03mg/m3 in summer and winter respectively. Oxygenated compounds were found to be the highest concentration (46.78-91.89mg/m3) with ethyl alcohol as the major specie (43.90-85.31mg/m3) in the two seasons respectively. Nevertheless, individual non-carcinogenic (Hazard relation i.e HR<1) and carcinogenic risk (CR<1.0E-04) of the quantified VCs were within acceptable limit except naphthalene at biofilter unit. In addition, cumulative non-carcinogenic risk exceeded from the threshold limit both in summers and winters in all units except at biofilter unit during winter. Furthermore cumulative carcinogenic risk also exceeded at same unit during the summer season. Therefore special attention should be made to minimize cumulative non-carcinogenic and carcinogenic risk as people are well exposed to mixture of compounds, not to individual.


Assuntos
Compostagem , Eliminação de Resíduos , Resíduos Sólidos/análise , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/toxicidade , Ar/análise , Poluentes Ocupacionais do Ar/análise , Poluentes Ocupacionais do Ar/toxicidade , Algoritmos , Carcinógenos/toxicidade , China , Monitoramento Ambiental , Humanos , Naftalenos/toxicidade , Medição de Risco , Estações do Ano
20.
Sci Rep ; 6: 23406, 2016 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-27001460

RESUMO

A paper-based upconversion fluorescence resonance energy transfer assay device is proposed for sensitive detection of CEA. The device is fabricated on a normal filter paper with simple nano-printing method. Upconversion nanoparticles tagged with specific antibodies are printed to the test zones on the test paper, followed by the introduction of assay antigen. Upconversion fluorescence measurements are directly conducted on the test zones after the antigen-to-antibody reactions. Furthermore, a multi-channel test paper for simultaneous detection of multiple cancer biomarkers was established by the same method and obtained positive results. The device showed high anti-interfere, stability, reproducible and low detection limit (0.89 ng/mL), moreover it is very easy to fabricate and operate, which is a promising prospect for a clinical point-of-care test.


Assuntos
Biomarcadores Tumorais/metabolismo , Técnicas Biossensoriais , Transferência Ressonante de Energia de Fluorescência , Papel , Limite de Detecção , Microscopia Eletrônica de Transmissão , Reprodutibilidade dos Testes
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