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To find new anti-UV and whitening agents, 21 fractions isolated from three preparations of ginseng (white, red, and black ginseng) were screened, and their antioxidant effects on AAPH- or H2O2-induced damage were investigated. Furthermore, the protective effect against UV-mediated apoptosis and the tyrosinase inhibitory activity of the targeted fractions were evaluated in vitro and in a zebrafish model. Among all fractions, F10 from white ginseng was selected as having the strongest anti-UV and antimelanogenesis activities. This fraction exhibited excellent inhibitory effects on the pigmentation of zebrafish, which may be due to its potential tyrosinase inhibitory activity. Additionally, the chemical composition of F10 was evaluated by UPLC-MS and NMR instruments. The results indicated that F10 had a carbohydrate content of more than 76%, and the weight-average molecular weight was approximately 239 Da. Disaccharide sucrose was the main active compound in F10. These results suggest that F10 could be used as an ingredient for whitening cosmetics and regarded as an anti-UV filter in the future.
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Particulate matter (PM) contributes to air pollution and primarily originates from unregulated industrial emissions and seasonal natural dust emissions. Fucoxanthin (Fx) is a marine natural pigment from brown macroalgae that has been shown to have various beneficial effects on health. However, the effects of Fx on PM-induced toxicities in cells and animals have not been assessed. In this study, we investigated the anti-inï¬ammatory potential of the Fx-rich fraction (FxRF) of Sargassum fusiformis against PM-mediated inï¬ammatory responses. The FxRF composition was analyzed by rapid-resolution liquid chromatography mass spectrometry. Fx and other main pigments were identified. FxRF attenuated the production of inï¬ammatory components, including prostaglandin E2 (PGE2), cyclooxygenase-2, interleukin (IL)-1ß, and IL-6 from PM-exposed HaCaT keratinocytes. PM exposure also reduced the levels of nitric oxide (NO), tumor necrosis factor-α, inducible nitric oxide synthase (iNOS), and PGE2 in PM-exposed RAW264.7 macrophages. Additionally, the culture medium from PM-exposed HaCaT cells induced upregulation of NO, iNOS, PGE2, and pro-inï¬ammatory cytokines in RAW264.7 macrophages. FxRF also significantly decreased the expression levels of factors involved in inï¬ammatory responses, such as NO, reactive oxygen species, and cell death, in PM-exposed zebrafish embryos. These results demonstrated the potential protective effects of FxRF against PM-induced inflammation both in vitro and in a zebrafish model.
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It is meaningful to study the control problems of nonlinear systems with uncertain parameters and external disturbances, especially for those subject to state constraints. In this paper, a state transformation approach is proposed to address time-varying asymmetric state constraints. By this state transformation, the state constrained problem is transformed into the boundedness problem of the transformed function. When the initial states are in the constrained region, the state constraints can be guaranteed as long as the boundedness of the transformed functions are guaranteed. Compared with the barrier Lyapunov function (BLF) approach, it successfully removes the feasibility test from virtual controllers, and thus broadens its application scope. In addition, for the parametric uncertainties and external disturbances exist in the system simultaneously, the tuning function and the adaptive laws for the upper bounds of disturbances are designed to help realize the control performance of the system. Consequently, a novel tuning function based adaptive backstepping control scheme is given. The designed controller ensures the error signals converge to a small neighbourhood of zero and the asymmetric time-varying constraints on system states are maintained for all the time. Finally, simulation results are given to illustrate the efficacy of the presented control scheme.
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Ionizing radiation (IR) confers a survival advantage in tongue squamous cell carcinoma (TSCC), however, IR resistance limits its efficacy. Although Yin Yang 1 (YY1) has been reported to play a role in genotoxic drug resistance by accelerating DNA repair, its role in TSCC radioresistance remains unclear. In this study, we examined YY1 mRNA and protein expression in human tongue cancer samples using qRT-PCR and western blotting, respectively. DNA array data identified YY1 mRNA expression in IR sensitivity or resistance cell lines and tissues. Tongue carcinoma primary cells and CAL27 cells with YY1 stably overexpressed or knocked-down were exposed to IR and evaluated for cell proliferation and apoptosis by CCK8-assay and caspase-3 assay, respectively. We also examined DNA damage- or repair-related indicators, such as YY1, p-H2AX, nuclear PTEN, p-PTEN, and Rad51 through Western blot analysis. Additionally, we explored the mechanism of IR-induced PTEN nuclear translocation by introducing a series of PTEN phosphorylation site mutations and co-IP assay. We observed that YY1 mRNA and protein are highly expressed in TSCC tissues, which was correlated with worse overall survival. Moreover, higher expression of YY1 and Rad51 was observed in radioresistant cells and tissues, overexpression of YY1 led to IR resistance in TSCC cells, whereas YY1 knockdown sensitized TSCC cells to IR. The underlying mechanism showed that the overexpression of YY1 upregulated nuclear PTEN and Rad51 expression, which is essential for DNA repair. IR upregulated YY1, nuclear PTEN, and Rad51; thus, knockdown of YY1 completely blocked IR-induced upregulation of nuclear PTEN/Rad51. IR upregulated PTEN phosphorylation, and mutation of the phosphorylation site of Ser380 nearly completely blocked IR-induced PTEN nuclear translocation. Furthermore, the phosphatase PP2A negatively regulated pS380-PTEN, and knockdown of YY1 completely blocked IR-induced pS380-PTEN through PP2A. In conclusion, knockdown of YY1 enhanced TSCC radiosensitivity through PP2A-mediated dephosphorylation of PTEN Ser380; thus, antagonizing the IR-induced nuclear PTEN/Rad51 axis and targeting YY1 may reverse IR resistance in TSCC.
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Carcinoma de Células Escamosas/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Tolerância a Radiação , Neoplasias da Língua/metabolismo , Fator de Transcrição YY1/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/radioterapia , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Reparo do DNA , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Mutação , PTEN Fosfo-Hidrolase/genética , Fosforilação , Transporte Proteico , Neoplasias da Língua/genética , Neoplasias da Língua/radioterapia , Regulação para Cima , Fator de Transcrição YY1/genéticaRESUMO
OBJECTIVE: To perform the dynamic contrast-enhanced and perfusion magnetic resonance imaging (MRI) of nasopharyngeal carcinoma (NPC) and analyze the correlation with T-staging. METHODS: A total of 46 naïve NPC patients underwent MRI. The parameters of dynamic contrast-enhanced and perfusion MRI included time to peak (TTP), Slopemax and area under the curve (AUC). RESULTS: The increasing period of signal intensity-time curve of all cases was steep. And the perfusion image of AUC could reflect the blood perfusion of tumor tissue. Parameters (TTP/Slopemax/AUC) in different T-staging were T1-staging (60.45/10.59/20 619.56), T2-staging (58.12/12.47/23 037.23), T3-staging (70.61/15.06/26 507.23) and T4-staging (41.72/19.87/30 092.27). Their statistical results were r = -0.247, P > 0.05 and r = 0.859, P < 0.050 and r = 0.963, P < 0.05 respectively. And statistical significance existed in Slopemax, AUC with T-staging. CONCLUSION: Dynamic contrast-enhanced and perfusion MRI can reflect angiogenesis of NPC. And there is a positive correlation between the parameters of dynamic contrast-enhanced and perfusion MRI (Slopemax, AUC) and T-staging.
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Aumento da Imagem , Angiografia por Ressonância Magnética/métodos , Neoplasias Nasofaríngeas/patologia , Adulto , Carcinoma , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Estadiamento de Neoplasias , Adulto JovemRESUMO
1. In the present study, the temporal and concentration-dependent cardioprotective effects of rapamycin against ischaemia-reperfusion (I/R) injury, as well as the underlying mechanisms, were investigated. 2. Rat Langendorff-perfused isolated hearts were exposed to 40 min global ischaemia followed by 120 min reperfusion. Hearts were perfused with different concentrations of rapamycin before and after ischaemia. Myocardial injury was assessed in terms of infarct size and the release of lactate dehydrogenase (LDH) and creatine kinase (CK). The phosphorylation of Akt, extracellular signal-regulated kinase (ERK) 1/2 and endothelial nitric oxide synthase (eNOS) was determined at the end of reperfusion. 3. When administered prior to ischaemia, 25, 50 and 100 nmol/L rapamycin significantly reduced infarct size compared with control (40.1 ± 1.5, 26.3 ± 4.1 and 21.2 ± 3.4 vs 52.5 ± 4.5%, respectively) without affecting the recovery of ventricular function. No reduction in infarct size was observed when 50 nmol/L rapamycin was administered 10 or 120 min into the reperfusion period. 4. Rapamycin (50 nmol/L) enhanced the phosphorylation of Akt kinase but did not affect the phosphorylation of ERK1/2 or eNOS at the end of reperfusion. The cardioprotective effect of rapamycin was blocked by the phosphatidylinositol 3-kinase (Akt) inhibitor LY294002 (15 nmol/L). 5. In conclusion, rapamycin mediates cardioprotection prior to ischaemia and after reperfusion. This protection may involve activation of the phosphatidylinositol 3-kinase pathway.
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Cardiotônicos/farmacologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle , Sirolimo/farmacologia , Algoritmos , Animais , Creatina Quinase/metabolismo , Avaliação Pré-Clínica de Medicamentos , Hemodinâmica/efeitos dos fármacos , Técnicas In Vitro , L-Lactato Desidrogenase/metabolismo , Masculino , Infarto do Miocárdio/patologia , Tamanho do Órgão/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVES: The purpose of this study was to investigate potential roles of rapamycin, a macrocytic lactone produced by Streptomyces hygroscopicus, in myocardial ischemia/reperfusion (I/R) injury. METHODS: Male Wistar rats were pretreated with three different doses of rapamycin (0.25, 2, and 5 mg/kg). Then, isolated rat hearts were exposed to 40 min of global ischemia followed by 120 min of reperfusion using a Langendorff apparatus. Western blot analysis was used to examine changes in the expression levels of ERK1/2 and Akt kinases and LC3 -II/I (a marker of autophagy). The area of myocardial infarction and cardiac function were evaluated. RESULTS: Our results demonstrated that rapamycin mediates cardioprotection in a dose-dependent manner in isolated rat hearts during myocardial I/R injury. Significant a autophagy was induced by rapamycin during I/R. Both, the mitochondrial K(ATP)-channel blocker 5-hydroxydecanoate (5-HD) and the PI3K inhibitor LY294002 (LY) abolished the protection afforded by rapamycin completely, while the inhibitors alone did not influence the infarct size in control hearts. However, the ERK1/2 inhibitor PD98059(PD) and the blocker of autophagy 3-methyladenine (3-MA) had no effect on rapamycin-mediated cardioprtection. CONCLUSIONS: Cardioprotection afforded by rapamycin involves the PI3K pathway and the activation of mitochondrial K(ATP)-channels, but is independent of rapamycin-induced autophagy. This study may have significant impact on clinical practice.
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Antibacterianos/farmacologia , Autofagia/efeitos dos fármacos , Cardiotônicos , Canais KATP/metabolismo , Mitocôndrias Cardíacas/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Proteína Oncogênica v-akt/fisiologia , Fosfatidilinositol 3-Quinases/fisiologia , Sirolimo/farmacologia , Animais , Western Blotting , Circulação Coronária/efeitos dos fármacos , Testes de Função Cardíaca , Hemodinâmica/efeitos dos fármacos , Técnicas In Vitro , Masculino , Mitocôndrias Cardíacas/efeitos dos fármacos , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Proteína Oncogênica v-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Ratos WistarRESUMO
OBJECTIVE: To investigate the impact of statin use on coronary flow reserve (CFR) in patients with slow coronary flow. METHODS: A total of 91 patients with chest pain and coronary slow flow but normal coronary angiography were included in this study, patients were divided into statin group (atorvastatin 20 mg/d for 8 weeks, n = 51) and non-statin group (n = 40), 26 healthy subjects with normal angiography and negative exercise ECG test served as normal controls. Blood cholesterol was measured. Doppler coronary flow velocity and Doppler reserve measurement of distal left anterior descending were recorded at rest and adenosine infusion (140 microgxkg(-1)xmin(-1)) induced hyperemia state, CFR was calculated by the ratio of maximal hyperemia and baseline peak diastolic coronary flow velocity (hCFV and bCFV) before and after atorvastatin treatment. RESULTS: (1) Eight weeks later, total cholesterol and LDL-C levels were significantly lower in statin group than in non-statin group and control group [TC (3.83 +/- 0.80) mmol/L vs. (5.30 +/- 1.18) mmol/L vs. (5.32 +/- 1.17) mmol/L, P < 0.05; LDL-C (2.26 +/- 0.64) mmol/L vs. (3.28 +/- 0.85) mmol/L vs. (3.30 +/- 0.82) mmol/L, P < 0.05]. (2)Baseline CFR levels were significantly lower in statin group and non-statin group than that in control group (2.32 +/- 0.30 vs. 2.25 +/- 0.33 vs. 3.15 +/- 0.34, P < 0.05). Compared with non-statin group and statin group before treatment, 8 weeks statin treatment was associated with reduced bCFV [(26.06 +/- 3.22) cm/s vs. (29.02 +/- 3.36) cm/s and (26.06 +/- 3.22) cm/s vs. (28.43 +/- 3.40) cm/s, P < 0.05], increased hCFV [(77.63 +/- 8.96) cm/s vs. (65.17 +/- 7.22) cm/s and (77.63 +/- 8.96) cm/s vs. (64.58 +/- 6.26) cm/s, P < 0.05] and increased CFR (3.07 +/- 0.29 vs. 2.28 +/- 0.35 and 3.07 +/- 0.29 vs. 2.32 +/- 0.30, P < 0.05). bCFV, hCFV and CFR of statin group post treatment were similar to those of controls (P > 0.05). CONCLUSION: Patients with coronary slow flow were associated with lower CFR which could be significantly improved by statin therapy.
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Anticolesterolemiantes/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/fisiopatologia , Ácidos Heptanoicos/uso terapêutico , Pirróis/uso terapêutico , Adulto , Idoso , Atorvastatina , Feminino , Reserva Fracionada de Fluxo Miocárdico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A beta-diketone ligand 4,4,5,5,5-pentafluoro-1-(2-naphthyl)-1,3-butanedione (Hpfnp), which contains a pentafluoroalkyl chain, was synthesized as the main sensitizer for synthesizing new near-infrared (NIR) luminescent Ln(pfnp)(3)phen (phen = 1,10-phenanthroline) (Ln = Er, Nd, Yb, Sm) complexes. At the same time, a series of lanthanide complexes covalently bonded to xerogels by the ligand 5-(N,N-bis-3-(triethoxysilyl)propyl)ureyl-1,10-phenanthroline (phen-Si) were synthesized in situvia a sol-gel process. [The obtained materials are denoted as xerogel-bonded Ln complexes (Ln = Er, Nd, Yb, Sm).] The single crystal structures of the Ln(pfnp)(3)phen complexes were determined. The properties of these complexes and the corresponding xerogel materials were investigated by Fourier-transform infrared (FTIR), diffuse reflectance (DR), and field-emission scanning electron microscopy (FE-SEM). After ligand-mediated excitation of these complexes and the corresponding xerogel materials they all show the characteristic NIR luminescence of the corresponding Ln(3+) ion. This is attributed to efficient energy transfer from the ligands to the Ln(3+) ion (the so-called "antenna effect").
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OBJECTIVE: To evaluate the clinical efficacy of a combined in-office cold light bleaching and night-guard vital bleaching (NGVB) system for treating tetracycline stained teeth (TST). METHODS: 90 patients with light, medium and heavy TST were randomly and evenly divided into 3 groups. 30 patients with 472 TST from the treatment group were treated with in-office cold light bleaching and NGVB, 30 patients with 466 TST from the control group 1 were treated with in-office cold light bleaching and 30 patients with 469 TST from control group 2 were treated with NGVB. At the time of treatment completion, after half a year and after one year, Vitalescence esthetic restorative masters shade guide was used to record the change of color. Bleaching efficacy and course of treatment were calculated, and lightening stability were evaluated. RESULTS: 1) Three groups had satisfied lightening efficacy for light TST with 100% bleaching efficacy. The overall efficacy of treatment group and control group 2 were superior to the in-office cold light bleaching system (P < 0.05). Though there was no significant lightening efficacy difference between the treatment group and control group 2 (P > 0.05), the periods of treatment of the treatment group for light, medium and heavy TST were shortened by 43%, 46% and 49%, respectively, compared to the control group 2. 2) All three groups' treatment efficacy for light, medium and heavy TST became weaker progressively (P < 0.05). 3) For the treatment efficacy between the time of treatment completion and after half a year and one year, there was significant statistical difference (P < 0.01) for the control group 1, while there was no significant difference for both the treatment group and the control group 2 (P > 0.05). Both treatment group and control group 2 had better performance in treatment stability than control group 1. CONCLUSION: In treating the light and medium tetracycline stained teeth, the combined in-office cold light bleaching and NGVB system can achieve a more satisfied whitening result in much shorter period, and significantly enhance the long term whitening stability.
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Tetraciclina , Clareamento Dental , Adulto , Antibacterianos , Cor , Humanos , Peróxidos , Resultado do Tratamento , UreiaRESUMO
OBJECTIVE: To evaluate the effects of oxidative stress on the protein expression of atrial calpain I and pathohistological and ultrastructural changes of atrial myocardium in atrial fibrillation (AF). METHODS: Twenty dogs were all implanted with pacemaker in a subcutaneous pocket and attached to a screw-in epicardial lead in right atrial appendage. They were randomly divided into 3 groups: sham-operation group (n = 6 without pacing), control group (n = 7 per minutes for 6 weeks), and probucol group (n = 7, pacing 1 week after recovery for 6 weeks, and administration of probucol 100 mg x kg(-1) x d(-1) 1 week before pacing till the end of pacing). One thin silicon plaque containing 4 pairs of electrodes were sutured to the right atrium. The dogs in control group, probucol group were paced at 400 beats per minutes for 6 weeks. Then the dogs were killed with their hearts taken out. The expression of atrial calpain I was measured by Western-blotting and immunohistochemistry. The pathohistological and ultrastructural changes in atrial tissue were tested by light and electron microscopy. The inducibility and duration of AF were measured in the control group and probucol group. The indexes of oxidative stress total anti-oxidation capability (T-AOC), malonyldiadehyde (MDA), and scavenging activities of superoxide anion (O2-) radical were measured by colorimetric method. RESULTS: The percentage of myolysis in the left and right atria of the control group were (53.6 +/- 11.8)% and. (58.5 +/- 9.2)% respectively, significantly higher than those of the sham operation group [(4.4 +/- 3.1)% and (4.1 +/- 2.9)% respectively, both P < 0.01]. The percentage of myolysis in the left and right atria of the probucol group were (12.3 +/- 3.2)% and (12.0 +/- 2.6)% respectively, both significantly lower than those of the control group (both P < 0.01). The protein expression of calpain I of the control group was significantly higher than that of the sham-operation group, and the protein expression of calpain I of the probucol group was significantly lower than that of the control group. The AF inducibility rate after pacing of the probucol group was 60%, significantly lower than that of the control group (92.9%, P < 0.01). The average AF duration time after pacing of the probucol group was (601 +/- 328) s, significantly shorter than that of the control group (1458 +/- 498) s. The indexes of oxidative stress in probucol group were lower than the level in control group. The MDA levels of the probucol group was (3.08 +/- 0.20) mmol/mg protein, significantly lower than that of the control group (4.15 +/- 0.23) mmol/mg protein). The anti-O2- and T-AOC level of the probucol group were 279 +/- 20 U/g protein and 30.5 +/- 1.3 nmol/mg protein, both significantly higher than those of the control group (215 +/- 16 U/g protein and 25.6 +/- 1.5 nmol/mg protein respectively, both P < 0.01). There were more sarcomere vacuolization and dissolution in atrial myocytes in the control group than in the sham operation group. And the pathohistological and ultrastructural changes of the probucol were lighter than those of the control group. CONCLUSION: Probucol prevents the pathohistological and ultrastructural changes in atrial myocardium by inhibiting calpain I expression, thus suppressing atrial structural remodeling, and preventing the induction and promotion of AF.
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Fibrilação Atrial/patologia , Miocárdio/patologia , Estresse Oxidativo , Animais , Fibrilação Atrial/metabolismo , Calpaína/biossíntese , Modelos Animais de Doenças , Cães , Feminino , Átrios do Coração , Masculino , Microscopia Eletrônica de Transmissão , Miocárdio/metabolismo , Miocárdio/ultraestruturaRESUMO
A novel mesoporous material covalently bonded with 8-hydroxyquinoline (HQ) was synthesized (designated as Q-SBA-15). The 5-formyl-8-hydroxyquinoline grafted to (3-aminopropyl)triethoxysilane, that is, alkoxysilane modified 8-hydroxyquinoline (Q-Si), was used as one of the precursors for the preparation of the Q-SBA-15 material. On the basis of the other function of the Q-Si of coordinating to lanthanide (Ln) ions, for the first time, the LnQ 3 complexes (Ln = Er, Nd, Yb) have been covalently bonded to the SBA-15 materials. The derivative materials, denoted as LnQ 3-SBA-15, were characterized by field emission scanning electron microscopy (FE-SEM), powder X-ray diffraction (XRD), transmission electron microscopy (TEM), nitrogen adsorption-desorption, and fluorescence spectra. Upon excitation at the ligands absorption bands, all of these materials show the characteristic near-infrared (NIR) luminescence of the corresponding lanthanide ions through the intramolecular energy transfer from the ligands to the lanthanide ions. The NIR luminescence of these mesoporous materials was compared with that of the corresponding pure LnQ 3 complexes and discussed in detail.
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A new class of bifunctional architecture combining the useful functions of superparamagnetism and terbium complex luminescence into one material has been prepared via two main steps by a modified Stöber method and the layer-by-layer (LbL) assembly technique. The obtained bifunctional nanocomposites exhibit superparamagnetic behavior, high fluorescence intensity, and color purity. The architecture has been characterized by field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), UV-vis absorption and emission spectroscopy, X-ray diffraction, and superconducting quantum interference device (SQUID) magnetometry.
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Elementos da Série dos Lantanídeos/química , Luminescência , Magnetismo , Nanocompostos/química , Compostos Organometálicos/síntese química , Dióxido de Silício/química , Térbio/química , Medições Luminescentes , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Nanocompostos/ultraestrutura , Espectrofotometria Ultravioleta , Temperatura , Fatores de Tempo , Difração de Raios XRESUMO
OBJECTIVE: To explore the effects of adenovirus vector-mediated gene transfer of ICOSIg fusion protein on experimental autoimmune myocarditis (EAM) in Lewis rats. METHODS: Expression vector containing ICOSIg (p-Adeno-ICOSIg) was constructed by fusion of human ICOS and IgGFc segment. Adenovirus vector was digested by PacI enzyme and transfected into HEK 293 cells. Adenovirus expressing ICOSIg was produced. EGFP was constructed into adenovirus vector and used as control. EAM was induced in Lewis rats by injection of porcine cardiac myosin. All immunized Lewis rats were divided into 4 groups. Group A (n = 15) and B (n = 15) received adenovirus containing ICOSIg on day 0 and day 14 respectively to study the effects of costimulatory molecules gene therapy on T cell activation and inflammation; group C (n = 10) and group D (n = 10) received adenovirus containing EGFP on day 0 and day 14 respectively as controls. Group E (n = 10) was normal controls that did not receive immunization. On day 28, all rats were killed after echocardiography examination. Histopathological examination was performed to observe myocardial inflammation. Protein levels of ICOS, ICOSL, B7-1 and B7-2 were detected by Western blot. INF-gamma, IL-2 and IL-4 mRNA were determined by realtime RT-PCR. RESULTS: On day 28, cardiac function was significantly improved and myocardial inflammation significantly attenuated in group B compared to group A, C and D (all P < 0.05). B7-1 expression at protein level was significantly lower in group B than that of group C (P < 0.05). ICOS and ICOSL expressions at protein level were significantly decreased in both group A and B compared with group C and D (P < 0.05). IFN-gamma mRNA level significantly decreased and IL-4 mRNA significantly increased in group A and B compared to group C and D (P < 0.05). CONCLUSIONS: Blockade of costimulatory pathway with gene therapy of ICOSIg alleviated autoimmune inflammatory damage and improved cardiac function in Lewis rats with EAM. Down-regulated costimulatory molecules in the myocardium and reduced inflammatory cytokine secretion might be responsible for the beneficial effects of ICOSIg in this model.
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Antígenos de Diferenciação de Linfócitos T/genética , Doenças Autoimunes/terapia , Terapia Genética , Fragmentos Fc das Imunoglobulinas/genética , Miocardite/terapia , Adenoviridae/genética , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Modelos Animais de Doenças , Técnicas de Transferência de Genes , Vetores Genéticos , Proteína Coestimuladora de Linfócitos T Induzíveis , Masculino , Miocardite/imunologia , Miocardite/patologia , Ratos , Ratos Endogâmicos Lew , Proteínas Recombinantes de Fusão/genéticaRESUMO
The near-infrared (NIR) luminescent lanthanide ions, such as Er(III), Nd(III), and Yb(III), have been paid much attention for the potential use in the optical communications or laser systems. For the first time, the NIR-luminescent Ln(dbm)(3)phen complexes have been covalently bonded to the ordered mesoporous materials MCM-41 and SBA-15 via a functionalized phen group phen-Si (phen-Si = 5-(N,N-bis-3-(triethoxysilyl)propyl)ureyl-1,10-phenanthroline; dbm = dibenzoylmethanate; Ln = Er, Nd, Yb). The synthesis parameters X = 12 and Y = 6 h (X denotes Ln(dbm)(3)(H(2)O)(2)/phen-MCM-41 molar ratio or Ln(dbm)(3)(H(2)O)(2)/phen-SBA-15 molar ratio and Y is the reaction time for the ligand exchange reaction; phen-MCM-41 and phen-SBA-15 are phen-functionalized MCM-41 and SBA-15 mesoporous materials, respectively) were selected through a systematic and comparative study. The derivative materials, denoted as Ln(dbm)(3)phen-MCM-41 and Ln(dbm)(3)phen-SBA-15 (Ln = Er, Nd, Yb), were characterized by powder X-ray diffraction, nitrogen adsorption/desorption, Fourier transform infrared (FT-IR), elemental analysis, and fluorescence spectra. Upon excitation of the ligands absorption bands, all these materials show the characteristic NIR luminescence of the corresponding lanthanide ions through the intramolecular energy transfer from the ligands to the lanthanide ions. The excellent NIR-luminescent properties enable these mesoporous materials to have potential uses in optical amplifiers (operating at 1.3 or 1.5 mum), laser systems, or medical diagnostics. In addition, the Ln(dbm)(3)phen-SBA-15 materials show an overall increase in relative luminescent intensity and lifetime compared to the Ln(dbm)(3)phen-MCM-41 materials, which was explained by the comparison of the lanthanide ion content and the pore structures of the two kinds of mesoporous materials in detail.
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The crystal structures of ternary Ln(DBM)(3)phen complexes (DBM = dibenzoylmethane, phen = 1,10-phenanthroline, and Ln = Nd, Yb) and their in situ syntheses via the sol-gel process are reported. The properties of the Ln(DBM)(3)phen complexes and their corresponding Ln(3+)/DBM/phen-co-doped luminescent hybrid gels obtained via an in situ method (Ln-D-P gel) have been studied. The results reveal that the lanthanide complexes are successfully in situ synthesized in the corresponding Ln-D-P gels. Both Ln(DBM)(3)phen complexes and Ln-D-P gels display sensitized near-infrared (NIR) luminescence upon excitation at the maximum absorption of the ligands, which contributes to the efficient energy transfer from the ligands to the Ln(3+) ions (Ln = Nd, Yb), an antenna effect. The radiative properties of the Nd(3+) ion in a Nd-D-P gel are discussed using Judd-Ofelt analysis, which indicates that the (4)F(3/2) --> (4)I(11/2) transition of the Nd(3+) ion in the Nd-D-P gel can be considered as a possible laser transition.