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1.
Front Mol Neurosci ; 17: 1342233, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38840775

RESUMEN

Introduction: Disrupted in schizophrenia-1 (DISC1) is a scaffolding protein whose mutated form has been linked to schizophrenia, bipolar affective disorders, and recurrent major depression. DISC1 regulates multiple signaling pathways involved in neurite outgrowth and cortical development and binds directly to glycogen synthase kinase-3ß (GSK-3ß). Since ketamine activates GSK-3ß, we examined the impact of ketamine on DISC1 and GSK-3ß expression. Methods: Postnatal day 7 rat pups were treated with ketamine with and without the non-specific GSK-3ß antagonist, lithium. Cleaved-caspase-3, GSK-3ß and DISC1 levels were measured by immunoblots and DISC1 co-localization in neurons by immunofluorescence. Binding of DISC1 to GSK-3ß was determined by co-immunoprecipitation. Neurite outgrowth was determined by measuring dendrite and axon length in primary neuronal cell cultures treated with ketamine and lithium. Results: Ketamine decreased DISC1 in a dose and time-dependent manner. This corresponded to decreases in phosphorylated GSK-3ß, which implicates increased GSK-3ß activity. Lithium significantly attenuated ketamine-induced decrease in DISC1 levels. Ketamine decreased co-immunoprecipitation of DISC1 with GSK-3ß and axonal length. Conclusion: These findings confirmed that acute administration of ketamine decreases in DISC1 levels and axonal growth. Lithium reversed this effect. This interaction provides a link between DISC1 and ketamine-induced neurodegeneration.

2.
BMC Oral Health ; 21(1): 390, 2021 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-34376169

RESUMEN

BACKGROUND: The purpose of this retrospective study was to evaluate the clinical efficacy of mineralized collagen (MC) versus anorganic bovine bone (Bio-Oss) for immediate implant placement in esthetic area. METHODS: Medical records of Department of Oral and Maxillofacial Surgery of Shandong Provincial Hospital were screened for patients who had been treated with immediate implant implantation in the esthetic area using either MC (Allgens®, Beijing Allgens Medical Science and Technology Co., Ltd., China) or Bio-Oss (Bio-Oss®, Geistlich Biomaterials, Wolhusen, Switzerland), between January 2018 and December 2019. All patients fulfilling the in-/exclusion criteria and following followed for a minimum period of 1 year after surgery were enrolled into the presented study. Implant survival rate, radiographic, esthetic and patient satisfactory evaluations were performed. RESULTS: Altogether, 70 patients were included in the study; a total of 80 implants were inserted. All implants had good initial stability. The survival rate of implants was 100% at 1-year follow-up. The differences in horizontal and vertical bone loss between the MC group (0.72 ± 0.26 mm, 1.62 ± 0.84 mm) and the Bio-Oss group (0.70 ± 0.52 mm, 1.57 ± 0.88 mm) were no significant difference statistically no significant 6 months after permanent restoration. Similar results occurred at 12 months after permanent restoration functional loaded. Clinical acceptability defined by pink esthetic score (PES) ≥ 6 (6.07 ± 1.62 vs. 6.13 ± 1.41) was not significantly different between groups. Patient satisfaction estimated by visual analog scale (VAS) was similar (8.56 ± 1.12 vs. 8.27 ± 1.44), and the difference was no significant difference between the two groups. CONCLUSIONS: The biomimetic MC showed a similar behaviour as Bio-Oss not only in its dimensional tissues changes but also in clinical acceptability and patient satisfaction. Within the limitations of this study, these cases show that MC could be considered as an alternative bone graft in IIP.


Asunto(s)
Sustitutos de Huesos , Implantes Dentales , Animales , Sustitutos de Huesos/uso terapéutico , Bovinos , Colágeno , Implantación Dental Endoósea , Fracaso de la Restauración Dental , Estética Dental , Humanos , Minerales , Estudios Retrospectivos , Resultado del Tratamiento
3.
Regen Biomater ; 7(3): 313-320, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32818060

RESUMEN

To evaluate the clinical efficacy of concentrated growth factors (CGFs) combined with mineralized collagen (MC) in guided bone regeneration (GBR). A retrospective study involving 29 patients treated with GBR technique, which was performed either CGF and MC complexes or MC alone. Implants were inserted simultaneously and cone-beam computed tomography was taken immediately, at 3 and 6 months postoperation. Questionnaires were completed by all patients so as to evaluate the main symptoms and daily activities during the first week after surgery. The outcomes of the two groups were statistically compared. All implants healed uneventfully. Patients in both groups suffered from different levels of discomfort for the reason of swelling, pain and chewing impairment on 1-2 days. Meanwhile, swelling of the Trial group was weaker than the Control group. When compared with the Control group, pain levels in Trial group were more rapidly reduced and patients took fewer analgesics from Day 3. Furthermore, the reconstitution mean value of the graft was thicker at 3 and 6 months in Trial group. CGFs complex with MC were beneficial to relieve the clinical symptoms, promote the peri-implant bone regeneration and shorten the healing time.

4.
ACS Appl Mater Interfaces ; 10(4): 3361-3371, 2018 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-29300454

RESUMEN

Remote and noninvasive modulation of protein activity is essential for applications in biotechnology and medicine. Optical control has emerged as the most attractive approach owing to its high spatial and temporal resolutions; however, it is challenging to engineer light responsive proteins. In this work, a near-infrared (NIR) light-responsive graphene-silica-trypsin (GST) nanoreactor is developed for modulating the bioactivity of trypsin molecules. Biomolecules are spatially confined and protected in the rationally designed compartment architecture, which not only reduces the possible interference but also boosts the bioreaction efficiency. Upon NIR irradiation, the photothermal effect of the GST nanoreactor enables the ultrafast in situ heating for remote activation and tuning of the bioactivity. We apply the GST nanoreactor for remote and ultrafast proteolysis of proteins, which remarkably enhances the proteolysis efficiency and reduces the bioreaction time from the overnight of using free trypsin to seconds. We envision that this work not only provides a promising tool of ultrafast and remotely controllable proteolysis for in vivo proteomics in study of tissue microenvironment and other biomedical applications but also paves the way for exploring smart artificial nanoreactors in biomolecular modulation to gain insight in dynamic biological transformation.


Asunto(s)
Grafito/química , Dióxido de Silicio
5.
Anesth Analg ; 123(4): 1008-17, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27529322

RESUMEN

BACKGROUND: Dexmedetomidine (DEX) has inherent neuroprotective properties that have been attributed to the activation of prosurvival kinases. However, the impact of supraclinical doses of DEX on neuroapoptosis and neuronal viability has not been determined. METHODS: Rat pups and primary neuronal cells were treated with DEX or ketamine (KET) alone or in combination. Neuroapoptosis was measured by cleaved-caspase-3 expression and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining in brain sections. Expression of prosurvival kinases was measured by Western blot. We measured the impact of DEX with and without α1-adrenergic receptor blockade on the viability of primary neuronal cell cultures. RESULTS: Increasing the cumulative dose of DEX resulted in elevated levels of neuroapoptosis in vivo. Low doses increased, whereas high dose decreased phosphorylation of the prosurvival kinases. KET alone and in combination with DEX produced a greater degree of apoptosis and reductions in expression of these protein kinases than DEX alone. Increasing concentrations of DEX decreased, while coadministration of an α1-adrenergic receptor blocker preserved neuronal viability in vitro. CONCLUSIONS: Although DEX is neuroprotective at clinical doses, high cumulative doses and concentrations induce neuroapoptosis, in vivo and in vitro, respectively. Because the current dosing schedules used in humans yield plasma levels that are substantially below concentrations that induce neurotoxicity, low-dose DEX should not be neurotoxic and has the potential to be a neuroprotective adjuvant.


Asunto(s)
Apoptosis/efectos de los fármacos , Dexmedetomidina/administración & dosificación , Dexmedetomidina/toxicidad , Neuronas/efectos de los fármacos , Animales , Animales Recién Nacidos , Apoptosis/fisiología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Femenino , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/toxicidad , Neuronas/patología , Neuronas/fisiología , Embarazo , Ratas , Ratas Sprague-Dawley
6.
J Neurol Sci ; 366: 127-134, 2016 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-27288790

RESUMEN

Since Alzheimer's disease (AD) is becoming the prevalent dementia in the whole world, more underlying mechanisms are emerging. Long time has the transcription factor NF-κB been identified to participate in AD pathogenesis, various studies have focused on the causes and effects of AD that are linked to NF-κB. In this review we discuss diverse environmental stimuli including oxidative stress, neuroinflammation and metabolism, involved signaling pathways such as PI3K/AKT, MAPK and AGE/RAGE/GSK-3 and newly found ncRNAs that mediate neuron toxicity or neuron protection through NF-κB activation and the following response associated with the same factors in AD. These may provide future orientation of investigation at transcription level and support efficient treatment to AD by a better understanding of the upstream regulators and downstream effectors of NF-κB.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , FN-kappa B/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Animales , Humanos
7.
Gene ; 575(1): 1-8, 2016 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-26341058

RESUMEN

Hypoxic regions are common in solid tumors and have an impact on tumor progression and on the therapeutic response. However, the underlying mechanism for hypoxic tumor microenvironment has not been entirely elucidated. Recently, long noncoding RNAs (lncRNAs) are being increasingly recognized to contribute to carcinogenesis through diverse mechanisms. To date, several lncRNAs have been described in hypoxia-associated cancer process, implying a potential role in maintaining cellular homeostasis and enabling an adaptive survival under hypoxic stress conditions. While it has been widely accepted that a complex cellular network of gene products, such as protein and miRNA, take part in hypoxic cancer progression, it remains largely elusive how lncRNAs participate in it. In this review, we introduce an update view of lncRNAs, focusing on hypoxia-related lncRNAs. We hereby summarize the cause and consequence of hypoxia-modulated lncRNAs in cancer as well as their functional mechanisms, highlighting the specific roles of lncRNAs in hypoxia response in cancer.


Asunto(s)
Neoplasias/metabolismo , ARN Largo no Codificante/metabolismo , ARN Neoplásico/metabolismo , Animales , Hipoxia de la Célula , Humanos , Neoplasias/genética , ARN Largo no Codificante/genética , ARN Neoplásico/genética
8.
Int J Biochem Cell Biol ; 70: 140-8, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26615762

RESUMEN

Nuclear factor κB is a key mediator of inflammation during conditions of hypoxia. Here, we used models of hypoxic pre-conditioning as mechanism to decrease nuclear factor κB activity induced by hypoxia. Our initial studies suggested that Disrupted in Schizophrenia-1 may be induced by hypoxic pre-conditioning and possibly involved in the regulation of nuclear factor κB. In this study we used Disrupted in Schizophrenia-1 exogenous over-expression and knock-down to determine its effect on ataxia telangiectasia mutated--nuclear factor κB activation cascade. Our results demonstrated that hypoxic pre-conditioning significantly increased the expression of Disrupted in Schizophrenia-1 at mRNA and protein levels both in vitro and in vivo. Over-expression of Disrupted in Schizophrenia-1 significantly attenuated the hypoxia-mediated ataxia telangiectasia mutated phosphorylation and prevented its cytoplasm translocation where it functions to activate nuclear factor κB. We further determined that Disrupted in Schizophrenia-1 activated the protein phosphatase 2A, preventing the phosphorylation of ataxia telangiectasia mutated serine-1981, the main regulatory site of ataxia telangiectasia mutated activity. Cellular levels of Disrupted in Schizophrenia-1 protein significantly decreased nuclear factor κB activation profiles and pro-inflammatory gene expression. Taken together, these results demonstrate that hypoxic pre-conditioning decreases the activation of nuclear factor κB through the transcriptional induction of Disrupted in Schizophrenia-1.


Asunto(s)
Células Epiteliales/metabolismo , Hipoxia/genética , FN-kappa B/genética , Proteínas del Tejido Nervioso/genética , ARN Mensajero/genética , Animales , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Hipoxia de la Célula/genética , Línea Celular Tumoral , Células Epiteliales/patología , Regulación de la Expresión Génica , Células HeLa , Humanos , Hipoxia/metabolismo , Hipoxia/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Mutación , FN-kappa B/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Fosforilación , Proteína Fosfatasa 2/genética , Proteína Fosfatasa 2/metabolismo , Transporte de Proteínas , ARN Mensajero/metabolismo , Serina/metabolismo , Transducción de Señal
9.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(7): 2031-5, 2016 Jul.
Artículo en Chino | MEDLINE | ID: mdl-30035870

RESUMEN

Osteoarthritis is a common arthritis disease caused by cartilage tissue damage and degeneration, which is one of the large epidemics that affect human health. The early detection of the pathological changes of articular cartilage can greatly improve the cure rate of disease, but the relevant clinical diagnosis technology has not been developed. In recent years, the applications and researches of terahertz technology are increasingly valued and it has drawn great attention in the field of medicine. Compared with traditional methods, the terahertz radiation is low-energy and non-ionizing whose spectral-fingerprinting capability is well-known in the biological world. Meanwhile, THz technology has a great potential in diagnosis of articular cartilage early degeneration. This paper briefly introduces the physiological and pathological conditions of the articular cartilage, the current clinical techniques of articular cartilage detection. It mainly summarizes the terahertz technology used for detecting articular cartilage, including detection of animal and human cartilage respectively. At last, the challenges and development prospects of terahertz technology in articular cartilage detection are discussed.


Asunto(s)
Cartílago Articular , Animales , Humanos , Osteoartritis , Radiación Terahertz
10.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(4): 919-23, 2016 Apr.
Artículo en Chino | MEDLINE | ID: mdl-30048082

RESUMEN

Epoxy resin is an important adhesive applied in the manufacturing processes of fiber reinforced polymer (FRP) composites. Terahertz (THz) time-domain spectroscopy (TDS) technology is an effective supplementary method for nondestructive evaluation (NDE) of FRP composites. As one of the most important parameters for epoxy resin, different curing temperature can affect the properties of epoxy resin. In this paper, we carry out systematic investigations on THz transmission properties of epoxy resin cured respectively under room temperature and high temperature with THz TDS technology. At the same time, the authors extract the refractive indices and absorption coefficients of epoxy resin, and make comparisons d. As shown in the experiments, the epoxy resin samples cured under room temperature have no bubble, whereas there are some micro-bubbles in the samples cured under high temperature, which reduce the sample density. Hence, the refractive index and absorption coefficient of epoxy resin cured under room temperature are both greater than those cured under high temperature. The difference of refractive index of different samples cured under the same condition is not significant. In addition, the difference of absorption coefficient of different samples cured under room temperature is also slight. However, the difference of absorption coefficient of different samples cured under high temperature gradually increase within the frequency from 0.6 to 1.5 THz, which is mainly due to the heterogeneous distribution of the bubbles in the different samples cured under high temperature. Moreover, the absorption coefficient of epoxy resin prepared under both curing temperatures gradually increases with the frequency, and there is no obvious absorption peak. Finally, because of the existence of Fabry-Pérot interference, the power transmission ratio of thicker epoxy resin samples may be greater than thinner samples at the resonant frequency. This research is of great significance for the THz NDE of FRP composites.

11.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(11): 3449-54, 2016 Nov.
Artículo en Chino | MEDLINE | ID: mdl-30198240

RESUMEN

Optical parameters which macroscopically characterize optical properties of materials indirectly reflect microscopic peculiarities of materials. Accurate extractions of optical parameters are significant for the research of microscopic behavior and macroscopic responses of materials. In recent years, as a new spectral analysis method, terahertz time-domain spectroscopy (THz-TDS) technology has become a research hotspot. Due to the low THz radiation energy and narrow pulse width (picosecond range), THz-TDS technology is nondestructive with high-temporal-resolution when being used to extract optical parameters of samples. This paper summarizes optical parameters extraction methods by using THz transmission and reflection spectroscopy technology, emphatically introduces several classic methods and analyses, along with their respective merits and demerits, and finally discusses the challenges of THz-TDS technology in optical parameters extraction. In conclusion, the transmission methods are adaptive for measuring substances which slightly absorb terahertz radiation, whereas the reflection methods are suitable for measuring materials with strong absorption capacity.

12.
Biochemistry ; 54(43): 6555-66, 2015 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-26465056

RESUMEN

The Hippo pathway was originally identified and named through screening for mutations in Drosophila, and the core components of the Hippo pathway are highly conserved in mammals. In the Hippo pathway, MST1/2 and LATS1/2 regulate downstream transcription coactivators YAP and TAZ, which mainly interact with TEAD family transcription factors to promote tissue proliferation, self-renewal of normal and cancer stem cells, migration, and carcinogenesis. The Hippo pathway was initially thought to be quite straightforward; however, recent studies have revealed that YAP/TAZ is an integral part and a nexus of a network composed of multiple signaling pathways. Therefore, in this review, we will summarize the latest findings on events upstream and downstream of YAP/TAZ and the ways of regulation of YAP/TAZ. In addition, we also focus on the crosstalk between the Hippo pathway and other tumor-related pathways and discuss their potential as therapeutic targets.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Neoplasias/metabolismo , Factores de Transcripción/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Regulación de la Expresión Génica , Proteínas Hedgehog/metabolismo , Humanos , Hipoxia/metabolismo , Sistema de Señalización de MAP Quinasas , Ácido Mevalónico/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Modelos Biológicos , Neoplasias/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Procesamiento Proteico-Postraduccional , Proteínas Serina-Treonina Quinasas/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Receptores Androgénicos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Notch/metabolismo , Transducción de Señal , Proteínas Smad/metabolismo , Factores de Transcripción/genética , Vía de Señalización Wnt
13.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(12): 3319-24, 2015 Dec.
Artículo en Chino | MEDLINE | ID: mdl-26964202

RESUMEN

Polymethacrylimide (PMI) foam composite has many excellent properties. Currently, PMI is heat-resistant foam, with the highest strength and stiffness. It is suitable as a high-performance sandwich structure core material. It can replace the honeycomb structure. It is widely used in aerospace, aviation, military, marine, automotive and high-speed trains, etc. But as new sandwich materials, PMI performance testing in the THz band is not yet visible. Based on the Terahertz (THz) time-domain spectroscopy technique, we conducted the transmission and reflection experiments, got the time domain waveforms and power density spectrum. And then we analyzed and compared the signals. The MATALB and Origin 8. 0 was used to calculate and obtain the transmittance (transfer function), absorptivity Coefficient, reflectance and the refractive index of the different thickness Degussa PMI (Model: Rohacell WF71), which were based on the application of the time-domain and frequency-domain analysis methods. We used the data to compared with the THz refractive index and absorption spectra of a domestic PMI, Baoding Meiwo Technology Development Co. , Ltd. (Model: SP1D80-P-30). The result shows that the impact of humidity on the measurement results is obvious. The refractive index of PMI is about 1. 05. The attenuation of power spectrum is due to the signal of the test platform is weak, the sample is thick and the internal scattering of PMI foam microstructure. This conclusion provides a theoretical basis for the THz band applications in the composite PMI. It also made a good groundwork for THz NDT (Non-Destructive Testing, NDT) technology in terms of PMI foam composites.

14.
Endocrine ; 49(2): 385-95, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25542183

RESUMEN

Fibroblast growth factor 21 (FGF-21) is a major paracrine and endocrine regulator of metabolic homeostasis. Here we demonstrate that FGF-21 is also a potent mediator of innate immunity. Double-staining flow cytometry identified neutrophils and monocytes as the main sources of FGF-21 among circulating leukocytes. Functional assays showed that FGF-21 stimulates phagocytosis and production of reactive oxygen species in neutrophil-like HL-60 cells and monocytic THP-1 cells. The mechanism of action of FGF-21 was observed to involve FGF receptor activation, signal transduction through the PI3K/Akt pathway, and stimulation of NADPH oxidase activity. This study indicates that FGF-21 could be an attractive target for the management of inflammatory disorders.


Asunto(s)
Factores de Crecimiento de Fibroblastos/fisiología , Inmunidad Innata/fisiología , NADPH Oxidasas/metabolismo , Neutrófilos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Adulto , Animales , Femenino , Humanos , Masculino , Ratones , Monocitos/metabolismo , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Adulto Joven
15.
Cancer Biol Ther ; 15(9): 1226-38, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24971746

RESUMEN

Recombinant Newcastle disease virus (rNDV) have shown oncolytic therapeutic efficacy in preclinical studies and are currently in clinical trials. In this study, we have evaluated the possibility to enhance the cancer therapeutic potential of NDV by means of inserting both interleukin-2 (IL-2) and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) delivered by rNDV. We demonstrated that rNDV expressing TRAIL (rNDV-TRAIL) or both human IL-2 and TRAIL (rNDV-IL-2-TRAIL) significantly enhanced inherent anti-neoplastic of rNDV by inducing apoptosis. And we showed that apoptosis-related genes mRNA expression was increased after treated with rNDV-TRAIL or rNDV-IL-2-TRAIL compared with rNDV and rNDV-IL-2. We also demonstrated that both rNDV-IL-2 and rNDV-IL-2-TRAIL induced proliferation of the CD4(+) and CD8(+) in treated mice and elicited expression of TNF-α and IFN-γ antitumor cytokines. These mice treated with oncolytic agents exhibited significant reduction in tumor development compared with mice treated with the parental virus. In addition, experiments in both hepatocellular carcinoma and melanoma-bearing mice demonstrated that the genetically engineered rNDV-IL-2-TRAIL exhibited prolonged animals' survival compared with rNDV, rNDV-IL-2, and rNDV-TRAIL. In conclusion, the immunotherapy and oncolytic virotherapy properties of NDV can be enhanced by the introduction of IL-2 and TRAIL genes, whose products initiated a broad cascade of immunological affects and induced tumor cells apoptosis in the microenvironment of the immune system.


Asunto(s)
Carcinoma Hepatocelular/terapia , Interleucina-2/metabolismo , Neoplasias Hepáticas/terapia , Melanoma/terapia , Virus de la Enfermedad de Newcastle/genética , Virus Oncolíticos/genética , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Animales , Apoptosis , Proteínas Reguladoras de la Apoptosis/metabolismo , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Carcinoma Hepatocelular/inmunología , Línea Celular , Proliferación Celular , Embrión de Pollo , Femenino , Ingeniería Genética , Humanos , Interferón gamma/metabolismo , Interleucina-2/genética , Neoplasias Hepáticas/inmunología , Melanoma/inmunología , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Virus de la Enfermedad de Newcastle/metabolismo , Viroterapia Oncolítica , Virus Oncolíticos/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Factor de Necrosis Tumoral alfa/metabolismo
16.
Yao Xue Xue Bao ; 49(3): 322-8, 2014 Mar.
Artículo en Chino | MEDLINE | ID: mdl-24961102

RESUMEN

In order to obtain the lead compound for treatment of rheumatoid arthritis (RA), in this study, therapeutic efficacy of three bispecific antibodies (BsAB-1, BsAB-2 and BsAB-3) against both hIL-1beta and hIL-17 were compared on CIA model mice. First, by ELISA method we compared the binding capacity of the three bispecific antibodies to the two antigens. The results showed that all three antibodies could simultaneously bind both antigens, among these antibodies, BsAB-1 was superior over BsAB-2 and BsAB-3. CIA model was established with chicken type II collagen (CII) and developed RA-like symptoms such as ankle swelling, skin tight, hind foot skin hyperemia. The CIA mice were treated with three antibodies once every two days for total of 29 days. Compared with the CIA model mice, the RA-like symptoms of the antibody treated-mice significantly relieved, while the BsAB-1 treated-mice were almost recovered. CII antibody level in the serum and cytokines (IL-2, IL-1beta, IL-17A and TNF-alpha) expression in the spleen were examined. Compared with the CIA model mice, all three antibodies could significantly reduce CII antibody and cytokine expression levels. BsAB-1 antibody was more potent than BsAB-2 and BsAB-3. In summary, BsAB-1 is superior over BsAB-2 and BsAB-3 in amelioration of RA symptoms and regulation of CII antibody production and pro-inflammatory cytokine expression, therefore, BsAB-1 can be chosen as a lead compound for further development of drug candidate for treatment of RA.


Asunto(s)
Anticuerpos Biespecíficos/uso terapéutico , Artritis Experimental/terapia , Artritis Reumatoide/terapia , Animales , Anticuerpos/metabolismo , Anticuerpos Biespecíficos/inmunología , Reacciones Antígeno-Anticuerpo , Artritis Experimental/inducido químicamente , Artritis Experimental/metabolismo , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/metabolismo , Colágeno Tipo II/inmunología , Interleucina-17/metabolismo , Interleucina-1beta/metabolismo , Interleucina-2/metabolismo , Masculino , Ratones , Bazo/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
17.
Arch Toxicol ; 87(10): 1797-808, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23536271

RESUMEN

ß-Ionone is an end ring analog of ß-carotenoid which has been shown to possess potent anti-proliferative activity both in vitro and in vivo. To investigate the possible inhibitory effects of ß-ionone, we studied cell growth characteristics, DNA synthesis, cell cycle progression, as well as mitogen-activated protein kinases (MAPKs) pathways in the human gastric adenocarcinoma cancer cell line (SGC-7901). Our results show that cell growth and DNA synthesis were inhibited, and the cell cycle was arrested at the G0/G1 phase in a dose-dependent manner in cells treated with ß-ionone (25, 50, 100 and 200 µmol/L) for 24 h. We found that the ß-ionone significantly decreased the extracellular signal-regulated kinase protein expression and significantly increased the levels of p38 and Jun-amino-terminal kinase protein expression (P < 0.01). ß-Ionone also inhibited cell cycle-related proteins of Cdk4, Cyclin B1, D1 and increased p27 protein expression in SGC-7901 cells. These results suggested that the cell cycle arrest observed may be regulated through a MAPK pathway by transcriptional down-regulation of cell cycle proteins. These results demonstrate potent ability of ß-ionone to arrest cell cycle of SGC-7901 cells and decrease proliferation.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Norisoprenoides/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/patología , Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , ADN/biosíntesis , ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Humanos , Norisoprenoides/administración & dosificación , Fase de Descanso del Ciclo Celular/efectos de los fármacos , Neoplasias Gástricas/patología
18.
Arch Toxicol ; 87(3): 481-90, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23100158

RESUMEN

ß-ionone has been shown to hold potent anti-proliferative and apoptosis induction properties in vitro and in vivo. To investigate the effects of ß-ionone on apoptosis initiation and its possible mechanisms of action, we qualified cell apoptosis, proteins related to apoptosis and a phosphatidylinositol 3-kinase (PI3K)-AKT pathway in human gastric adenocarcinoma cancer SGC-7901 cells. The results demonstrated that ß-ionone-induced apoptosis in a dose-dependent manner in SGC-7901 cells treated with ß-ionone (25, 50, 100 and 200 µmol/L) for 24 h. ß-ionone was also shown to induce the expression of cleaved-caspase-3 and inhibit bcl-2 expression in SGC-7901 cells in a dose-dependent manner. The significantly decreased levels of p-PI3K and p-AKT expression were observed in SGC-7901 cells after ß-ionone treatments in a time- and dose-dependent manner (P < 0.01). Thus, the apoptosis induction in SGC-7901 cells by ß-ionone may be regulated through a PI3K-AKT pathway. These results demonstrate a potential mechanism by which ß-ionone to induce apoptosis initiation in SGC-7901 cells.


Asunto(s)
Adenocarcinoma/enzimología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Norisoprenoides/farmacología , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas/enzimología , Adenocarcinoma/patología , Caspasa 3/metabolismo , Línea Celular Tumoral , Forma del Núcleo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Neoplasias Gástricas/patología , Factores de Tiempo
19.
Anesthesiology ; 117(1): 64-71, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22617253

RESUMEN

BACKGROUND: Ketamine induces neuroapoptosis in neonatal rodents. However, these experimental paradigms were performed without concurrent noxious stimulation, a condition that does not reflect the interaction of anesthesia and surgical stimulation. Noxious stimulation with and without concurrent analgesic drugs has been shown to have divergent patterns of neuronal activation and cell death. We hypothesized that concurrent noxious stimulation would attenuate ketamine-induced caspase-3 activation. METHODS: Postnatal day 7 Sprague-Dawley rat pups were randomized to a 6-h exposure to ketamine with and without peripheral noxious stimulation by intraplantar injection of complete Freund's adjuvant. A cohort of naïve rat pups with and without complete Freund's adjuvant injections served as control subjects. Neuroapoptosis was measured by cleaved caspase-3 expression and terminal deoxynucleotidyl-transferase mediated 2'-deoxyuridine 5'-triphosphate nick end labeling staining. In order to determine if concurrent noxious simulation altered the expression of cell survival and cell cycle proteins, levels of protein kinase B and glycogen synthase kinase-3ß and cyclin D1 were measured. RESULTS: Ketamine induced a significant increase in cleaved caspase-3 expression and terminal deoxynucleotidyl-transferase mediated 2'-deoxyuridine 5'-triphosphate nick end labeling staining with increases in cyclin D1 levels. Concurrent noxious stimulation with ketamine attenuated caspase-3 activation and maintained cyclin D1 levels. Phosphorylation of protein kinase B and glycogen synthase kinase-3ß was not definitively altered under these conditions. CONCLUSION: The administration of ketamine with concurrent noxious stimulation results in the attenuation of the neuroapoptotic response. These findings suggest that concurrent surgery and procedural pain attenuates ketamine-induced neuroapoptosis.


Asunto(s)
Apoptosis/efectos de los fármacos , Encéfalo/efectos de los fármacos , Ketamina/farmacología , Dolor/fisiopatología , Animales , Encéfalo/patología , Caspasa 3/metabolismo , Ciclina D1/análisis , Adyuvante de Freund/farmacología , Glucógeno Sintasa Quinasa 3/análisis , Glucógeno Sintasa Quinasa 3 beta , Proteínas Proto-Oncogénicas c-akt/análisis , Ratas , Ratas Sprague-Dawley
20.
Can J Ophthalmol ; 46(6): 521-7, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22153640

RESUMEN

OBJECTIVE: To examine possible differences in success rates of primary dacryocystorhinostomy (DCR) with and without silicone intubation, and to find out whether the use of silicone tubes is beneficial. DESIGN: A literature search was conducted in the PubMed, EMBASE, and Cochrane Controlled Trials Register to identify potentially relevant controlled trials. METHODS: Language was restricted to English. The surgical techniques were categorized into external DCR (EX-DCR), endonasal laser-assisted DCR (LA-DCR), and nonlaser endoscopic endonasal DCR techniques (EN-DCR). The main outcome measure was success rates after DCR-with and DCR-without silicone intubation. The statistical analysis was carried out using a RevMan 5.0 software. RESULTS: Of 188 retrieved trials from the electronic database, 9 trials (5 randomized controlled trials and 4 cohort studies) involving 514 cases met our inclusion criteria. There was no statistically significant heterogeneity between the studies. The pooled risk ratio was 0.99, with a 95% confidence interval (0.91-1.08). There was no significant difference in the success rates between the DCR with and without silicone intubation (p = 0.81). Sensitivity analysis and subgroups analyses suggested that the result was comparatively reliable. CONCLUSIONS: Based on this meta-analysis that included 5 randomized controlled trials and 4 cohort studies, no benefit was found for silicone tube intubation in primary DCR. Further well-organized, prospective, randomized studies involving larger patient numbers are required.


Asunto(s)
Dacriocistorrinostomía , Intubación , Obstrucción del Conducto Lagrimal/terapia , Conducto Nasolagrimal/cirugía , Stents , Bases de Datos Factuales , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Siliconas , Resultado del Tratamiento
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