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1.
Electrophoresis ; 42(21-22): 2347-2355, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33811361

RESUMO

Electroosmotic flow is an efficient transportation technology driven by applying an external electric field across the microchannel, which has a great potential for future application. This work is presented to study the unsteady electroosmotic flow of viscoelastic fluids combined with a constant pressure gradient and a vertical magnetic field through a parallel plate microchannel. For the reason that the upper and bottom walls of the parallel plate microchannel in microfluidic devices can be made of different materials, this leads to different hydrophobic properties, asymmetric zeta wall potentials, and different slip boundary conditions. The Navier slip model with different slip coefficients at walls is considered. The generalized Maxwell fluid with fractional derivative is adopted for the constitutive equation of the fluid. The analytical and numerical solutions of velocity are derived by employing the integral transform method and finite difference method, respectively. Excellent agreement is found between the numerical solutions and analytical solutions. Finally, the effects of fractional parameter α , relaxation time λ , slip coefficients a and b , the ratio of wall zeta potentials Rξ , Hartmann number Ha , and electrical field strength parameter S on velocity profiles are interpreted graphically in detail.


Assuntos
Eletro-Osmose , Campos Magnéticos
2.
Electrophoresis ; 41(10-11): 769-777, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31901144

RESUMO

In this paper, an investigation of the electroosmotic flow of fractional Oldroyd-B fluids in a narrow circular tube with high zeta potential is presented. The Navier linear slip law at the walls is considered. The potential field is applied along the walls described by the nonlinear Poisson-Boltzmann equation. It's worth noting here that the linear Debye-Hückel approximation can't be used at the condition of high zeta potential and the exact solution of potential in cylindrical coordinates can't be obtained. Therefore, the Matlab bvp4c solver method and the finite difference method are employed to numerically solve the nonlinear Poisson-Boltzmann equation and the governing equations of the velocity distribution, respectively. To verify the validity of our numerical approach, a comparison has been made with the previous work in the case of low zeta potential and the excellent agreement between the solutions is clear. Then, in view of the obtained numerical solution for the velocity distribution, the numerical solutions of the flow rate and the shear stress are derived. Furthermore, based on numerical analysis, the influence of pertinent parameters on the potential distribution and the generation of flow is presented graphically.


Assuntos
Eletro-Osmose , Modelos Químicos , Algoritmos , Simulação por Computador , Elasticidade , Viscosidade
3.
Cephalalgia ; 36(10): 943-50, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26590611

RESUMO

AIMS: Our studies investigated the location of oxytocin receptors in the peripheral trigeminal sensory system and determined their role in trigeminal pain. METHODS: Oxytocin receptor expression and co-localization with calcitonin gene-related peptide was investigated in rat trigeminal ganglion using immunohistochemistry. Enzyme-linked immunosorbent assay was used to determine the effects of facial electrocutaneous stimulation and adjuvant-induced inflammation of the temporomandibular joint on oxytocin receptor expression in the trigeminal ganglion. Finally, the effects of oxytocin on capsaicin-induced calcitonin gene-related peptide release from dural nociceptors were investigated using isolated rat dura mater. RESULTS: Oxytocin receptor immunoreactivity was present in rat trigeminal neurons. The vast majority of oxytocin receptor immunoreactive neurons co-expressed calcitonin gene-related peptide. Both electrocutaneous stimulation and adjuvant-induced inflammation led to a rapid upregulation of oxytocin receptor protein expression in trigeminal ganglion neurons. Oxytocin significantly and dose-dependently decreased capsaicin-induced calcitonin gene-related peptide release from dural nociceptors. CONCLUSION: Oxytocin receptor expression in calcitonin gene-related peptide containing trigeminal ganglion neurons, and the blockade of calcitonin gene-related peptide release from trigeminal dural afferents suggests that activation of these receptors may provide therapeutic benefit in patients with migraine and other primary headache disorders.


Assuntos
Transtornos da Cefaleia/metabolismo , Nociceptores/metabolismo , Receptores de Ocitocina/biossíntese , Gânglio Trigeminal/metabolismo , Animais , Peptídeo Relacionado com Gene de Calcitonina/análise , Peptídeo Relacionado com Gene de Calcitonina/biossíntese , Peptídeo Relacionado com Gene de Calcitonina/genética , Regulação da Expressão Gênica , Transtornos da Cefaleia/genética , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Ocitocina/análise , Receptores de Ocitocina/genética , Resultado do Tratamento , Gânglio Trigeminal/química
4.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(9): 3014-9, 2016 Sep.
Artigo em Zh | MEDLINE | ID: mdl-30085496

RESUMO

By using doppler asymmetric spatial heterodyne spectroscopy and doppler effect, the wind speed can be achieved through detecting the interferogram of airglow in the upper atmosphere. This paper mainly analyses the data processing method of the interferogram and then derive the interferometer phase in order to get the wind speed. Comparing with the traditional spatial heterodyne spectroscopy, not only the noise and error of the system should be taken into consideration, but the window function that used to isolate the spectrum has a great influence during the data processing. Then the effect of window type and window width on phase difference of interferogram and the wind error curve are simulated through software. On basis of this the wind error curve under the noise of system and flat field factor are simulated by choosing appropriate window function. The window function simulation indicates that although the joining of window leads to a distortion of the interferogam and phase, the wind speed error can be less than 0.5% with Hanning window in the appropriate optical path difference. The noise of the system simulation indicates that the wind speed error increases with the noise, so it is necessary to control the system noise and preprocess the sampling data. The research on data processing method has great theoretical significance and practical value for designing the system parameter and improving the precision of spatial heterodyne wind detection.

5.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(7): 2291-5, 2016 Jul.
Artigo em Zh | MEDLINE | ID: mdl-30036014

RESUMO

Restrictive relationship exists between spectral resolution, spectral range and number of pixels of traditional Spatial Heterodyne Spectroscopy (SHS). The main difference between Asymmetric Spatial Heterodyne Spectroscopy (ASHS) and SHS accelerates the space of one grating from the beamsplitter. It greatly increases spectral resolution while system parameters remain unchanged. First of all, this paper elaborates the fundamentals of the ASHS, the derived formulas of the system parameters and theoretical relationship between grating offset and the spectral resolution increases. As an important parameter of the ASHS, offset is restricted by the pixel number of short double side interferogram and the spectral resolution requirements. According to the experimental breadboard parameters of laboratory, the selection principle and the results of the offset are presented. In the case of the same device parameters, two types of theoretical performance parameters are calculated. The simulation is carried out. The results show that two of them have the same spectral range, but the ASHS has a higher spectral resolution. The relationship between resolution and offset increased consistent with theoretical calculation. Finally the ASHS breadboard is calibrated with the monochromatic light scanning method. The derived spectral range and resolution are in good agreement with the theoretical value.

6.
AAPS PharmSciTech ; 16(5): 1051-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25652729

RESUMO

AJS is the code name of an untitled novel medicative compound synthesized by the Tasly Holding Group Company (Tianjin, China) based on the structure of cinnamamide, which is one of the Biopharmaceutics Classification System (BCS) class II drugs. The drug has better antidepressant effect, achieved by acting on the 5-hydroxytryptamine receptor. However, the therapeutic effects of the drug are compromised due to its poor water solubility and lower bioavailability. Herein, a self-microemulsifying drug delivery system (SMEDDS) was developed to improve its solubility and oral bioavailability. AJS-SMEDDS formulation was optimized in terms of drug solubility in the excipients, droplet size, stability, and drug precipitation using a pseudo-ternary diagram. The pharmacokinetic study was performed in rats, and the drug concentration in plasma samples was assayed using the high-performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-MS/MS) method. The optimized formulation for SMEDDS has a composition of castor oil 24.5%, Labrasol 28.6%, Cremphor EL 40.8%, and Transcutol HP 2.7% (co-surfactant). No drug precipitation or phase separation was observed from the optimized formulation after 3 months of storing at 25°C. The droplet size of microemulsion formed by the optimized formulation was 26.08 ± 1.68 nm, and the zeta potential was -2.76 mV. The oral bioavailability of AJS-SMEDDS was increased by 3.4- and 35.9-fold, respectively, compared with the solid dispersion and cyclodextrin inclusion; meanwhile, the C max of AJS-SMEDDS was about 2- and 40-fold as great as the two controls, respectively. In summary, the present SMEDDS enhanced oral bioavailability of AJS and was a promising strategy to orally deliver the drug.


Assuntos
Antidepressivos/farmacocinética , Cinamatos/farmacocinética , Portadores de Fármacos , Sistemas de Liberação de Medicamentos/instrumentação , Administração Oral , Animais , Antidepressivos/administração & dosagem , Antidepressivos/sangue , Antidepressivos/química , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Cinamatos/administração & dosagem , Cinamatos/sangue , Cinamatos/química , Composição de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Emulsões , Nanopartículas , Ratos Wistar , Solubilidade , Espectrometria de Massas por Ionização por Electrospray , Tensoativos/química , Espectrometria de Massas em Tandem , Temperatura , Viscosidade
7.
J Virol ; 87(5): 2791-802, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23269807

RESUMO

The tropism of herpes simplex virus (HSV-1) for human sensory neurons infected in vivo was examined using dorsal root ganglion (DRG) xenografts maintained in mice with severe combined immunodeficiency (SCID). In contrast to the HSV-1 lytic infectious cycle in vitro, replication of the HSV-1 F strain was restricted in human DRG neurons despite the absence of adaptive immune responses in SCID mice, allowing the establishment of neuronal latency. At 12 days after DRG inoculation, 26.2% of human neurons expressed HSV-1 protein and 13.1% expressed latency-associated transcripts (LAT). Some infected neurons showed cytopathic changes, but HSV-1, unlike varicella-zoster virus (VZV), only rarely infected satellite cells and did not induce fusion of neuronal and satellite cell plasma membranes. Cell-free enveloped HSV-1 virions were observed, indicating productive infection. A recombinant HSV-1-expressing luciferase exhibited less virulence than HSV-1 F in the SCID mouse host, enabling analysis of infection in human DRG xenografts for a 61-day interval. At 12 days after inoculation, 4.2% of neurons expressed HSV-1 proteins; frequencies increased to 32.1% at 33 days but declined to 20.8% by 61 days. Frequencies of LAT-positive neurons were 1.2% at 12 days and increased to 40.2% at 33 days. LAT expression remained at 37% at 61 days, in contrast to the decline in neurons expressing viral proteins. These observations show that the progression of HSV-1 infection is highly restricted in human DRG, and HSV-1 genome silencing occurs in human neurons infected in vivo as a consequence of virus-host cell interactions and does not require adaptive immune control.


Assuntos
Gânglios Espinais/virologia , Herpes Simples/virologia , Herpesvirus Humano 1/fisiologia , Imunodeficiência Combinada Severa/virologia , Tropismo Viral , Aciclovir/administração & dosagem , Aciclovir/análogos & derivados , Aciclovir/farmacologia , Animais , Gânglios Espinais/patologia , Expressão Gênica , Herpes Simples/tratamento farmacológico , Herpes Simples/metabolismo , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/metabolismo , Herpesvirus Humano 3 , Humanos , Luciferases/biossíntese , Camundongos , Camundongos SCID , Células Satélites Perineuronais/virologia , Transplante Heterólogo , Valaciclovir , Valina/administração & dosagem , Valina/análogos & derivados , Valina/farmacologia , Proteínas Virais/metabolismo , Latência Viral , Replicação Viral
8.
Heart Lung Circ ; 23(9): 847-51, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24801447

RESUMO

OBJECTIVE: This study aimed to investigate feasibility and safety of minimally invasive video-assisted surgery for double-valve (mitral and aortic) replacement through right anterolateral minithoracotomy. METHODS: Between February 2011 and April 2013, 60 patients with combined valvular disease underwent double valve replacement, 26 of them by minimally invasive video-assisted surgery through right anterolateral minithoracotomy (study group) and 34 by median sternotomy (control group). Peripheral cardiopulmonary bypass (CPB) was established through right femoral artery and vein. The incision was made around the right breast approximately 5 cm in length. Pericardiotomy, bicaval occlusion, atriotomy and aortotomy, and double valve replacement were performed with thoracoscope. RESULTS: In the study group, times of CPB and aortic cross-clamp were 146.5 ± 40.5 min and 91.5 ± 23.4 min, respectively, which were significantly different from those in the control group, 115.4 ± 26.5 min and 75.4 ± 16.5 min (P<0.05). Thoracic drainage in the study group was significantly lower than the control group, 587 ± 245 ml (study group) versus 756 ± 267 ml (control group) (P<0.05). Length of ICU and postoperative hospital stay were shorter in the study group, 1.9 ± 0.8 and 8.7 ± 4.5 days versus 2.8 ± 1.3 and 11.2 ± 5.6 days in the control group (P<0.05), respectively. There was no statistical difference in the postoperative results of TTE (transthoracic echocardiography) (P>0.05). All patients recovered smoothly with follow-up of six months to two years, with no severe complications. CONCLUSIONS: Minimally invasive video-assisted procedure through right anterolateral minithoracotomy is a new promising approach for double valve replacement. Our study suggested that this approach was feasible, safe and had cosmetic effects.


Assuntos
Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Toracotomia/métodos , Idoso , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Ponte Cardiopulmonar , Cuidados Críticos , Ecocardiografia , Feminino , Doenças das Valvas Cardíacas/diagnóstico por imagem , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Esternotomia , Fatores de Tempo
9.
Heart Lung Circ ; 22(2): 88-91, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23122742

RESUMO

BACKGROUND: Totally thoracoscopic operation provides minimally invasive alternative for patients with atrial septal defect. In this study, we report the mid-term follow-up results of 45 patients with atrial septal defect who underwent totally thoracoscopic operation and discuss the feasibility and safety of this new technique. METHODS: From January 2010 to February 2012, 45 patients with atrial septal defect underwent totally thoracoscopic closure as an alternative to traditional median sternotomy surgery. The mean age of the patients was 33.2±12.5 years (range 6.3-61.5 years), and mean weight was 55.7±11.1 kg (range 30.5-80 kg). Based on echocardiography the mean size of the atrial septal defect was 16.0±10.8mm (range 13-39 mm). RESULTS: All patients underwent totally thoracoscopic repair. Twenty-five patients with a pericardial patch and 20 patients were sutured directly. Five patients underwent concomitant tricuspid valvuloplasty with Kay technique. No death, reoperation or complete atrioventricular block occurred. The mean time of cardiopulmonary bypass was 70.5±20.6 min (range 31.0-153.0 min), the mean time of aortic cross-clamp was 28.8±13.3 min (range 0.0-80.0 min) and the mean time of operation was 155.8±36.8 min (range 65.0-300.0 min). Postoperative mechanical ventilation averaged 5.1±2.8h (range 3.6-12.6h), and the duration of intensive care unit stay 20.0±5.6h (range 16.2-25 h). The mean volume of blood drainage was 156±36 ml (range 51-800 ml). No death, residual shunt, lung atelectasis or moderate tricuspid regurgitation was found at three-month follow-up. CONCLUSION: Totally thoracoscopic repair is feasible and safe for patients with ASD, even with or without tricuspid regurgitation however more clinical data is needed in the future study.


Assuntos
Comunicação Interatrial/cirurgia , Duração da Cirurgia , Toracoscopia/métodos , Adolescente , Adulto , Idoso , Valvuloplastia com Balão , Criança , Feminino , Seguimentos , Comunicação Interatrial/diagnóstico por imagem , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/etiologia , Respiração Artificial , Toracoscopia/efeitos adversos , Fatores de Tempo , Valva Tricúspide/cirurgia , Ultrassonografia , Adulto Jovem
10.
Pediatr Cardiol ; 33(8): 1355-61, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22576768

RESUMO

The ventricular septal defect (VSD) is the most common type of congenital heart disease (CHD). The morbidity and mortality of CHD patients are significantly higher due to late cardiac complications, likely caused by genetic defects. Mutations in cardiac transcription factor genes such as GATA-4, TBX5, and NKX2-5 have been implicated in CHD cases. The NKX2-5 gene, a homeobox gene, is expressed in the developing heart and the adult heart. Because NKX2-5 is a dosage-sensitive regulator during embryonic development, the authors hypothesized that the expression levels of the NKX2-5 gene rather than the mutant protein may play important roles in CHD. In this study, the promoter regions and exon regions of the NKX2-5 gene were bidirectionally sequenced in large cohorts of VSD patients and healthy control subjects. The results showed that a novel sequence variant (g.4574c>deletion), found only in one VSD patient, and a single nucleotide polymorphism (rs118026695), the frequency of which was significantly higher in VSD patients, were identified within the promoter region. Functional analysis confirmed that these sequence variants significantly enhanced the transcriptional activities of the NKX2-5 gene promoter, altering the expression of the NKX2-5 gene and the cardiac gene regulatory network. In addition, a synonymous mutation in the second exon of the NKX2-5 gene was identified in one VSD patient, which may affect the translation process. Therefore, the authors' data provide supportive evidence that mutations in the coding region of the NKX2-5 gene and sequence variants within its promoter region may be among the contributors to the CHD etiology.


Assuntos
Comunicação Interventricular/genética , Proteínas de Homeodomínio/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Éxons , Feminino , Proteína Homeobox Nkx-2.5 , Humanos , Lactente , Masculino , Mutação/genética , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , Deleção de Sequência/genética
11.
Opt Express ; 19(27): 26429-43, 2011 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-22274228

RESUMO

A simple yet accurate parameterization of spectral and broadband ocean surface albedo has been developed. To facilitate the parameterization and its applications, the albedo is parameterized for the direct and diffuse incident radiation separately, and then each of them is further divided into two components: the contributions from surface and water, respectively. The four albedo components are independent of each other, hence, altering one will not affect the others. Such a designed parameterization scheme is flexible for any future update. Users can simply replace any of the adopted empirical formulations (e.g., the relationship between foam reflectance and wind speed) as desired without a need to change the parameterization scheme. The parameterization is validated by in situ measurements and can be easily implemented into a climate or radiative transfer model.


Assuntos
Luz , Modelos Químicos , Fotometria/métodos , Espalhamento de Radiação , Energia Solar , Água/química , Simulação por Computador , Oceanos e Mares
12.
Guang Pu Xue Yu Guang Pu Fen Xi ; 31(1): 272-6, 2011 Jan.
Artigo em Zh | MEDLINE | ID: mdl-21428104

RESUMO

Multispectral area CCD camera based on liquid crystal tunable filter (LCTF) is a new spectral imaging system, which could record image of one wavelength on the area CCD by utilizing electrically controlled birefringence of liquid-crystal and interference principle of polarized light. Because of the special working principle of LCTF and frame transfer area CCD, the existing radiometric calibration method can not meet the precision need of remote sensing application if it is used for LCTF-camera. An improved radiometric calibration method is proposed, in which the camera performance test and calibration experiment are carried out relying on the devices of integrating sphere and standard detector, and the absolute calibration coefficient is calculated via correcting frame transfer smear and improving data process algorithm. Then the validity of the laboratory calibration coefficient is checked by a field validation experiment. Experimental result indicates that the calibration coefficient is valid, and the radiation information on the ground could be accurately inverted from the calibrated image data. With the resolution of radiometric calibration of LCTF-camera and the improvement of calibration precision, the application field of the image data acquired by the camera would be extended effectively.

13.
Guang Pu Xue Yu Guang Pu Fen Xi ; 31(7): 1884-8, 2011 Jul.
Artigo em Zh | MEDLINE | ID: mdl-21942044

RESUMO

The content of total nitrogen in the waters is an important index to measure lake water quality, and the technique of remote sensing plays a large role in quantitatively monitoring the dynamic change and timely grasping the status of lake pollution. Taking Chaohu as an example, quantitative inversion models of total nitrogen were established by multivariable regression Kriging under analyzing of an correlation between total nitrogen and chlorophyll-a or suspended solids by HIS hyperspectral remote sensing data of HJ-1A satellite. The result shows that the correlation of 0.76 was discovered between total nitrogen and the multiple combination with band 72, band 79 and band 97, while the correlation could be increased to 0.83 by applying combined model of multiple linear regression and ordinary Kriging. The optimization of the residuals of the conventional regression model can improve the accuracy of the inversion effectively. These results also provide useful exploration for further establishing a common model of quantitative inversion of lake total nitrogen concentration.

14.
J Immunother Cancer ; 9(12)2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34887262

RESUMO

BACKGROUND: Stimulating antitumor immunity by blocking programmed death-1 (PD-1) or its ligand (programmed death-ligand 1 (PD-L1) is a promising antitumor therapy. However, numerous patients respond poorly to PD-1/PD-L1 blockade. Unresponsiveness to immune-checkpoint blockade (ICB) can cast significant challenges to the therapeutic options for patients with hard-to-treat tumors. There is an unmet clinical need to establish new therapeutic approaches for mitigating ICB unresponsiveness in patients. In this study, we investigated the efficacy and role of low-dose antineoplastic agent SN-38 or metformin in sensitizing unresponsive tumors to respond to ICB therapy. METHODS: We assessed the significant pathological relationships between PD-L1 and FOXO3 expression and between PD-L1 and c-Myc or STAT3 expression in patients with various tumors. We determined the efficacy of low-dose SN-38 or metformin in sensitizing unresponsive tumors to respond to anti-PD-1 therapy in a syngeneic tumor system. We deciphered novel therapeutic mechanisms underlying the SN-38 and anti-PD-1 therapy-mediated engagement of natural killer (NK) or CD8+ T cells to infiltrate tumors and boost antitumor immunity. RESULTS: We showed that PD-L1 protein level was inversely associated with FOXO3 protein level in patients with ovarian, breast, and hepatocellular tumors. Low-dose SN-38 or metformin abrogated PD-L1 protein expression, promoted FOXO3 protein level, and significantly increased the animal survival rate in syngeneic mouse tumor models. SN-38 or metformin sensitized unresponsive tumors responding to anti-PD-1 therapy by engaging NK or CD8+ T cells to infiltrate the tumor microenvironment (TME) and secret interferon-γ and granzyme B to kill tumors. SN-38 suppressed the levels of c-Myc and STAT3 proteins, which controlled PD-L1 expression. FOXO3 was essential for SN38-mediated PD-L1 suppression. The expression of PD-L1 was compellingly linked to that of c-Myc or STAT3 in patients with the indicated tumors. CONCLUSION: We show that SN-38 or metformin can boost antitumor immunity in the TME by inhibiting c-Myc and STAT3 through FOXO3 activation. These results may provide novel insight into ameliorating patient response to overarching immunotherapy for tumors.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Linfócitos T CD8-Positivos/imunologia , Carcinoma Hepatocelular/tratamento farmacológico , Proteína Forkhead Box O3/metabolismo , Inibidores de Checkpoint Imunológico/farmacologia , Células Matadoras Naturais/imunologia , Neoplasias Ovarianas/tratamento farmacológico , Animais , Apoptose , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proliferação de Células , Feminino , Proteína Forkhead Box O3/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imunoterapia , Irinotecano/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inibidores da Topoisomerase I/farmacologia , Células Tumorais Cultivadas , Microambiente Tumoral
15.
Anesthesiology ; 113(4): 945-56, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20823759

RESUMO

BACKGROUND: Surgical injury induces production and release of inflammatory mediators in the vicinity of the wound. They in turn trigger nociceptive signaling to produce hyperalgesia and pain. Interleukin-1ß plays a crucial role in this process. The mechanism regulating production of this cytokine after incision is, however, unknown. Caspase-1 is a key enzyme that cleaves prointerleukin-1ß to its active form. We hypothesized that caspase-1 is a crucial regulator of incisional interleukin-1ß levels, nociceptive sensitization, and inflammation. METHODS: These studies employed a mouse hind paw incisional model. Caspase-1 was blocked using the selective inhibitors Ac-YVAD-CMK and VRTXSD727. Nociceptive sensitization, edema, and hind paw warmth were followed in intact animals whereas caspase-1 activity, cytokine, and prostaglandin E2 levels were assessed in homogenized skin. Confocal microscopy was used to detect the expression of caspase-1 near the wounds. RESULTS: Analysis of enzyme activity demonstrated that caspase-1 activity was significantly increased in periincisional skin. Pretreatment with Ac-YVAD-CMK significantly reduced mechanical allodynia and thermal hyperalgesia. Repeated administration of this inhibitor produced robust analgesia, especially to mechanical stimulation. Administration of VRTXSD727 provided qualitatively similar results. Caspase-1 inhibition also reduced edema and the normally observed increase in paw warmth around the wound site. Correspondingly, caspase-1 inhibition significantly reduced interleukin-1ß as well as macrophage-inflammatory protein 1α, granulocyte colony-stimulating factor, and prostaglandin E2 levels near the wound. The expression of caspase-1 was primarily observed in keratinocytes in the epidermal layer and in neutrophils deeper in the wounds. CONCLUSIONS: The current study demonstrates that the inhibition of caspase-1 reduces postsurgical sensitization and inflammation, likely through a caspase-1/interleukin-1ß-dependent mechanism.


Assuntos
Caspase 1/fisiologia , Inflamação/patologia , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Animais , Biomarcadores , Temperatura Corporal/efeitos dos fármacos , Inibidores de Caspase , Quimiocina CCL3/metabolismo , Dinoprostona/metabolismo , Edema/patologia , Fator Estimulador de Colônias de Granulócitos/líquido cefalorraquidiano , Membro Posterior/patologia , Temperatura Alta , Hiperalgesia/fisiopatologia , Imuno-Histoquímica , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Dor/psicologia , Medição da Dor , Limiar da Dor/fisiologia , Pele/metabolismo
16.
Anesth Analg ; 111(6): 1525-33, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20889942

RESUMO

BACKGROUND: Wound healing is a multistep, complex process that involves the coordinated action of multiple cell types. Conflicting results have been obtained when conventional methods have been used to study wound biology. Therefore, we analyzed the wound response in a mouse genetic model. METHODS: We analyzed inflammatory mediators produced within incisional wounds induced in 16 inbred mouse strains. Computational haplotype-based genetic analysis of inter-strain differences in the level of production of 2 chemokines in wounds was performed. An in vitro experimental analysis system was developed to investigate whether interleukin (IL)-1 could affect chemokine production by 2 different types of cells that are present within wounds. RESULTS: The level of 2 chemokines, keratinocyte-derived chemokine (KC) and macrophage inflammatory protein 1α, exhibited very large (75- and 463-fold, respectively) interstrain differences within wound tissue across this inbred strain panel. Genetic variation within Nalp1, an inflammasome component that regulates IL-1 production, correlated with the interstrain differences in KC and macrophage inhibitory protein 1α production. Consistent with the genetic correlation, IL-1ß was shown to stimulate KC production by murine keratinocyte and fibroblast cell lines in vitro. CONCLUSIONS: Genetic variation within Nalp1 could contribute to interstrain differences in wound chemokine production by altering the amount of IL-1 produced.


Assuntos
Quimiocina CCL3/metabolismo , Quimiocinas/metabolismo , Procedimentos Cirúrgicos Dermatológicos , Mediadores da Inflamação/metabolismo , Interleucina-1/metabolismo , Cicatrização , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Células Cultivadas , Quimiocina CCL3/genética , Quimiocinas/genética , Genômica , Haplótipos , Imuno-Histoquímica , Interleucina-1/genética , Interleucina-1alfa/metabolismo , Interleucina-1beta/metabolismo , Queratinócitos/imunologia , Macrófagos Peritoneais/imunologia , Camundongos , Camundongos Endogâmicos , Fenótipo , Pele/imunologia , Especificidade da Espécie , Fatores de Tempo , Cicatrização/genética
17.
Anesth Analg ; 111(6): 1534-42, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20889944

RESUMO

BACKGROUND: In the accompanying paper, we demonstrate that genetic variation within Nalp1 could contribute to interstrain differences in wound chemokine production through altering the amount of interleukin (IL)-1 produced. We further investigate the role of IL-1 in incisional wound biology and its effect on wound chemokine production in vivo and whether this mechanism could be active in human subjects. METHODS: A well-characterized murine model of incisional wounding was used to assess the in vivo role of IL-1 in wound biology. The amount of 7 different cytokines/chemokines produced within an experimentally induced skin incision on a mouse paw and the nociceptive response was analyzed in mice treated with an IL-1 inhibitor. We also investigated whether human IL-1ß or IL-1α stimulated the production of chemokines by primary human keratinocytes in vitro, and whether there was a correlation between IL-1ß and chemokine levels in 2 experimental human wound paradigms. RESULTS: Administration of an IL-1 receptor antagonist to mice decreased the nociceptive response to an incisional wound, and reduced the production of multiple inflammatory mediators, including keratinocyte-derived chemokine (KC) and macrophage inhibitory protein (MIP)-1α, within the wounds. IL-1α and IL-1ß stimulated IL-8 and GRO-α (human homologues of murine keratinocyte-derived chemokine) production by primary human keratinocytes in vitro. IL-1ß levels were highly correlated with IL-8 in human surgical wounds, and at cutaneous sites of human ultraviolet B-induced sunburn injury. CONCLUSIONS: IL-1 plays a major role in regulating inflammatory mediator production in wounds through a novel mechanism; by stimulating the production of multiple cytokines and chemokines, it impacts clinically important aspects of wound biology. These data suggest that administration of an IL-1 receptor antagonist within the perioperative period could decrease postsurgical wound pain.


Assuntos
Quimiocinas/metabolismo , Procedimentos Cirúrgicos Dermatológicos , Mediadores da Inflamação/metabolismo , Interleucina-1/metabolismo , Queratinócitos/imunologia , Cicatrização , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Células Cultivadas , Cesárea , Quimiocina CCL3/metabolismo , Quimiocina CXCL1/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Interleucina-1alfa/metabolismo , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dor Pós-Operatória/imunologia , Dor Pós-Operatória/prevenção & controle , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Pele/efeitos dos fármacos , Pele/imunologia , Pele/efeitos da radiação , Queimadura Solar/imunologia , Fatores de Tempo , Pesquisa Translacional Biomédica , Cicatrização/efeitos dos fármacos
18.
Guang Pu Xue Yu Guang Pu Fen Xi ; 30(6): 1683-7, 2010 Jun.
Artigo em Zh | MEDLINE | ID: mdl-20707176

RESUMO

Spatial heterodyne spectroscopy (SHS) is a novel method for hyperspectral analysis, but the calibration methods have not been thoroughly studied. The present paper gives some basic theories of SHS, and investigates the laboratory calibration methods, including spectral calibration and radiometric calibration. According to emission lines and the relation between detector size and system bandwidth, we designed the spectral calibration plan for SHS, which uses tunable laser and halogen lamp. Experiments show that the actual spectral range and resolution of our instrument is the same as it was designed, and the spectral shift is less by stability testing. For radiometric calibration, we measured the system's stability by using integrating sphere, and its responses were also calibrated by using standard lamp and diffuser. The experimental results, after validation, proved that our method can be used for SHS calibration. This is a fundamental work for quantified retrieval.

19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 29(3): 848-52, 2009 Mar.
Artigo em Zh | MEDLINE | ID: mdl-19455841

RESUMO

Spatial heterodyne spectroscopy (SHS) is a new spectroscopic technique which can achieve high spectral resolution. The basic concepts of spatial heterodyne spectrometer was described. A method of data processing for interferogram of spatial heterodyne spectrometer was presented based on its characteristics. First order difference was performed for eliminating the baseline of interferogram. The triangular function was chosen as apodization function. The process of phase correction for Fourier transform spectrum is described. The wavelength calibration curve of SHS experimental system was obtained by measuring sodium light double line and mercury light double line. The spectral inversion accuracy of spatial heterodyne spectrometer can be effectively improved by use of this method.

20.
J Nanosci Nanotechnol ; 19(12): 7551-7556, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31196260

RESUMO

Cardiovascular disease is an important problem in developed countries and the effective target of treatment should be further developed. ETB receptor is one of receptor of ET system, which may affect the function of vascular smooth muscle cell via NO released. In order to clarify the theory, we had cell culture with or without ET-1 treatment. Flow cytometry had been used to prove cell apoptosis and transwell assay had been used to detect the ability of cell migration. The expression of ET-1, ICAM-1, VCAM-1, MMP-9 and CRP were detected by using qRT-PCR and Western blot assay. After we had found that RES-701-1 one of ETB receptor antagonists can induced VSMC apoptosis and migration. Also RES-701-1 can down regulated ICAM-1, VCAM-1, MMP-9 and CRP while ET-1 was the opposite. In a conclusion ETB receptor is one of the role target to mediate vascular smooth muscle cell through the ET system and it may be a significant treating target in cardiovascular disease in the future.


Assuntos
Endotelina-1 , Músculo Liso Vascular , Receptor de Endotelina B , Movimento Celular , Endotelina-1/genética , Endotelina-1/farmacologia , Humanos , Receptor de Endotelina B/genética
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