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Long nanosecond pulses have been proven to be efficient at enhancing underwater LIBS emission. However, the quantitative analytical capability of underwater long-pulse LIBS has yet to be further revealed. In this work, we investigated the spectral characteristics by irradiating with a laser pulse of 120 ns duration. The alkali and alkaline earth metals Li, K and Ca and the transition element Mn were selected for analysis. It is shown that obvious self-reversal structures were observed in the spectra at high concentrations, making the calibration curves saturated. Correction was performed using the approximate Voigt function fitting method, which significantly improves the linearity of the calibration curves. In addition to the target metal elements, atomic lines of the matrix elements H and O in water were also observed, which can serve as promising internal standards for quantitative analysis. A comparison of the quantification performance with and without the internal standards demonstrates that the use of the internal standards is conducive to improving the robustness of the calibration approaches with higher determination coefficients. More importantly, the underwater LIBS signal stability is improved by more than 3 times, and the prediction error for validation samples is reduced by 2-4 times. The present results suggest that long ns pulses are favorable to significantly improving the qualitative and quantitative performance of underwater single-pulse LIBS, enabling long-pulse LIBS to have great potential to be applied to underwater in situ chemical analysis.
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The sensors with a wide gas pressure detection range are urgently demanded in many industrial applications. Here, we propose a gas pressure sensor based on an all-solid open Fabry-Pérot interferometer, which is prepared by using optical contact bonding to ensure high structural strength and high-quality factor of 8.8 × 105. The applied pressure induces a change in the refractive index of the air, leading to the shift of the resonant spectrum. The pressure is detected by calibrating this shift. The sensor exhibits a pressure sensitivity of 4.20 ± 0.01â nm/MPa in a pressure range of 0 to 10â MPa and has a minimum pressure resolution of 0.005â MPa. Additionally, it shows a lower temperature cross-sensitivity of -0.25 kPa/°C. These findings affirm that the sensor achieves high-sensitivity pressure sensing across a wide detection range. Moreover, owing to its exceptional mechanical strength, it holds great promise for applications in harsh environments, such as high temperature and high pressure.
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The applications of fiber-optic acoustic sensors are expanded to the high-temperature field, but it still faces challenges to realize the wide-band and high-sensitivity acoustic signal detection in high-temperature environments. Here, we propose a miniature membrane-free fiber-optic acoustic sensor based on a rigid Fabry-Pérot (F-P) cavity and construct an acoustic signal detection system. The system can achieve high-sensitivity acoustic detection while maintaining a wide frequency band in temperatures ranging from 20 °C to 200 °C. The prepared F-P cavity based on optical contact technology is the sensitive unit of the sensor, and has a high-quality factor of 8.8×105. Specifically, with the increasing of temperature, the sensitivity gradually increases, and the frequency response range does not change. A maximum sensitivity of 491.2 mV/Pa and a high signal-to-noise ratio of 60.9 dB are achieved at 200 °C. The sensor has an excellent acoustic signal response in the frequency range of 10 Hz-50 kHz with a flatness of ±2 dB. This study is important for the application of the fiber-optic acoustic sensor in high-temperature environments.
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A series of novel nitric oxide (NO)-releasing 5,8-quinolinedione/furoxan hybrids (8a-h and 9a-h) were designed and synthesized through coupling different alkanolamine substituted phenylsulfonyl furoxan with 5,8-quinolinedione. Most compounds displayed high cytotoxic activity against drug-sensitive/-resistant cancer cells. In particular, the IC50 of 9a (0.42 µM) was about 9-fold lower than that of ß-lap (3.69 µM) and 12-fold lower than that of SAHA (5.24 µM) in drug-resistant cancer cells. Also, 9a was demonstrated to selectively inhibit the growth of Bel7402/5-FU cancer cells. Mechanistic studies demonstrated that 9a could serve as an NO donor and nicotinamide quinone oxidoreductase 1 (NQO1) inhibitor (IC50 = 0.8 µM), which could induce the highest level of NO and reactive oxygen species (ROS) in Bel-7402/5-FU cancer cells. Furthermore, 9a could promote tumor cell apoptosis and autophagy via regulation of apoptosis-related protein (Bax, Bcl-2, and Caspase 3) and autophagy-associated proteins (LC3 and p62) in Bel-7402/5-FU cells. Taken together, 9a may be considered as a promising candidate for a further comprehensive study involving drug-resistant hepatocellular carcinoma.
Assuntos
Antineoplásicos , Neoplasias Hepáticas , Humanos , Óxido Nítrico/metabolismo , Niacinamida/farmacologia , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/metabolismo , Apoptose , Neoplasias Hepáticas/tratamento farmacológico , Fluoruracila/farmacologia , Proliferação de Células , NAD(P)H Desidrogenase (Quinona)RESUMO
A compact fiber-optic Fabry-Perot (F-P) cavity for a sensor is designed based on a sandwich structure, adopting direct bonding of quartz glass. The reflective F-P cavity is manufactured by a fiber optic with a quartz glass ferrule and the sandwich structure with an air cavity, which is achieved by direct bonding of quartz glass. This fabrication process includes plasma surface activation, hydrophilic pre-bonding, high-temperature annealing, and dicing. The cross section of the bonding interface tested by a scanning electron microscope indicates that the sandwich structure is well bonded, and the air cavity is not deformed. Experiments show that the quality factor of the F-P cavity is 2711. Tensile strength testing shows that the bond strength exceeds 35 MPa. The advantage of direct bonding of quartz glass is that high consistency and mass production of the cavity can be realized. Moreover, the cavity is free of problems caused by the mismatch of thermal expansion coefficients between different materials. Therefore, the F-P cavity can be made into a sensor, which is promising in detecting air pressure, acoustic and high temperature.
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Due to the excellent directivity, strong penetrability, and no electromagnetic shielding effect, ultrasonic waves have good potential for wireless energy transmission and information transfer inside and outside of sealed metal devices. However, traditional ultrasonic based energy transmission methods usually result in considerable energy consumption because of the impedance mismatch during the impedance modulation of the communication. This paper presents an optimal design method for efficient energy transfer during ultrasonic communication. The channel equivalent circuit model is established by only using the acoustic-electric channel scattering parameters. According to the equivalent circuit model, the channel impedance matches with a weak mismatch state is performed during the communication. In this way, the impedance modulation effect is ensured with a lower decrease in the energy transmission efficiency. Finally, the simultaneous energy transmission and impedance modulation are carried out through the 11 mm thick 304 stainless steel plate. The transmission power is 37.86 W with a transmission efficiency of 45.75%, and the modulation rate is 10 Kbps. Compared with the traditional methods, our proposed energy transmission efficiency is increased by 17.62%. The results verify the proposed method's effectiveness and the high accuracy of the model. The proposed method has great engineering applications and broad prospects in condition monitoring of metallic environments.
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A micro-fiber-optic acoustic sensor based on the high-quality-factor (high-Q) resonance effect that uses a Fabry-Pérot etalon (FPE) is presented in this study. The device has been demonstrated experimentally to be a high-sensitivity acoustic sensor with a large dynamic range over a wide frequency band. Optical contact technology was used to improve the robustness of the FPE, which consists of two parallel lenses with high reflectivity exceeding 99%. An acoustic signal detection system based on phase modulation spectrum technology was also constructed. A stable and high-Q value of 106 was measured for the FPE. As a result, high sensitivity of 177.6 mV/Pa was achieved. Because of the change in the refractive index of the air when it is modulated by the acoustic waves, a frequency response of 20 Hz-70 kHz with flatness of ±2 dB was obtained and a large dynamic range of 115.3 dB was measured simultaneously. The excellent performance of the device will be beneficial for optical acoustic sensing.
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BACKGROUND/AIMS: Ischemic stroke is a leading cause of long-term disability. To date, there is no effective treatment for stroke. Previous studies have shown that Ginkgo biloba extract has protective effects against neurodegenerative disorders. In this present study, we sought to test the potential protective role of an active component of Ginkgo biloba extract, bilobalide, in a rat model of middle cerebral artery occlusion (MCAO). METHODS: A rat model of MCAO was used to test the potential protective effects of Bilobalide B on stroke protection. TTC staining was performed to evaluate infarct size of the brains. Neurological deficit score was measured to reveal the effects of the treatments on animal behavior and cognition. Immunohistochemical staining and transmission electronic microscope analysis were performed to measure the cellular responses to drug treatment. Western blotting and ELISA were performed. The expression of Cleaved- Casepase 3, Beclin-1, p62 and LC3I/II were quantified, and the Phosphorylation of eNOS and Akt were evaluated. The ratio of Bcl-2/ Bax was determined to reveal the molecular pathways that are involved in the drug treatment. RESULTS: We found that intraperitoneal delivery of various Bilobalide doses during ischemia can protect against brain injury, as evidenced by reduced infarct size and improved neurological scores after surgery. Histochemical analysis revealed that treatment with bilobalide can significantly reduce apoptosis, autophagy, and promote angiogeneis following ischemia/reperfusion injury to the brain. The performence of increased phosphorylation of eNOS and Akt suggested that bilobalide can activate Akt prosurvival and eNOS pathways to promote cell survival and angiogenesis, respectively. CONCLUSIONS: Our results suggested that bilobalide benefits stroke symptoms by reducing cell death pathways and promoting angiogenesis. As such, bilobalide may be a potential agent for improving self-repair after ischemic stroke.
Assuntos
Autofagia/efeitos dos fármacos , Ciclopentanos/farmacologia , Furanos/farmacologia , Ginkgolídeos/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico Sintase Tipo III/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismo por Reperfusão/patologia , Animais , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Caspase 3/metabolismo , Ciclopentanos/uso terapêutico , Modelos Animais de Doenças , Furanos/uso terapêutico , Ginkgolídeos/uso terapêutico , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/prevenção & controle , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Óxido Nítrico/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Single-mode oscillation is crucial to the practicality of optoelectronic oscillator (OEO). Due to the limited by bandwidth and precision of radio frequency (RF) filters, it is difficult to be achieved for the OEO based on the long fiber-optic delay line. So instead of the long fiber-optic delay line, SiO2 optical waveguide ring resonator (OWRR) with high-Q and mode selection is first presented to be applied to OEO. The OEOs based on the minimum loop and SiO2 OWRR are constructed. The oscillation characteristics of the minimum loop OEO and the transmission characteristics of the SiO2 OWRR are simulated by MATLAB, respectively. The filtering effect of the SiO2 OWRR applied to the OEO is verified theoretically by comparing these simulation results. Subsequently, the contrastive experiments of the above two OEOs on oscillation modes are carried out. The oscillation mode spacing of 40.32 MHz and 2.137 GHz are obtained. These results show that the SiO2 OWRR can function as an excellent 'filter' in the minimum loop of the OEO. Moreover, the side mode suppression ratio and the phase noise of the OEO have been improved. Our experimental results demonstrate that the OEO adopting SiO2 OWRR is feasible to achieve the single-mode oscillation and obtain better performance microwave signals.
RESUMO
As an important sensing element, the whispering gallery mode resonator (WGMR) parameters seriously affect the resonant micro-optic gyroscope (RMOG) performance. This work proposes an under-coupling resonator to improve the resonator's Q value and to optimize the coupling coefficient to maximize the RMOG's sensitivity. GeO2-doped silica waveguide-type resonators with different coupling coefficients were simulated, designed, fabricated and tested. An under-coupling ring resonator with a quality factor of 10 million is reported. The RMOG system was built based on this resonator and the scale factor was tested on a uniaxial high-precision rotating platform. Experimental results show that this resonator could improve the RMOG sensitivity by five times.
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Ischemic heart disease is a leading cause of death in human population and protection of myocardial infarction (MI) associated with ischemia-reperfusion (I/R) remains a challenge. MG53 is an essential component of the cell membrane repair machinery that protects injury to the myocardium. We investigated the therapeutic value of using the recombinant human MG53 (rhMG53) protein for treatment of MI. Using Langendorff perfusion of isolated mouse heart, we found that I/R caused injury to cardiomyocytes and release of endogenous MG53 into the extracellular solution. rhMG53 protein was applied to the perfusion solution concentrated at injury sites on cardiomyocytes to facilitate cardioprotection. With rodent models of I/R-induced MI, we established the in vivo dosing range for rhMG53 in cardioprotection. Using a porcine model of angioplasty-induced MI, the cardioprotective effect of rhMG53 was evaluated. Intravenous administration of rhMG53, either prior to or post-ischemia, reduced infarct size and troponin I release in the porcine model when examined at 24h post-reperfusion. Echocardiogram and histological analyses revealed that the protective effects of rhMG53 observed following acute MI led to long-term improvement in cardiac structure and function in the porcine model when examined at 4weeks post-operation. Our study supports the concept that rhMG53 could have potential therapeutic value for treatment of MI in human patients with ischemic heart diseases.
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Cardiotônicos/farmacologia , Proteínas de Transporte/farmacologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Proteínas Recombinantes/farmacologia , Animais , Cardiotônicos/administração & dosagem , Cardiotônicos/farmacocinética , Proteínas de Transporte/administração & dosagem , Proteínas de Transporte/farmacocinética , Modelos Animais de Doenças , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Técnicas In Vitro , Masculino , Camundongos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/mortalidade , Miocárdio/metabolismo , Miocárdio/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacocinética , Transdução de Sinais/efeitos dos fármacos , Suínos , Proteínas com Motivo TripartidoRESUMO
INTRODUCTION: Ischemia-reperfusion injury (I-R) in skeletal muscle requires timely treatment. METHODS: Rodent models of I-R injury were used to test the efficacy of recombinant human MG53 (rhMG53) protein for protecting skeletal muscle. RESULTS: In a mouse I-R injury model, we found that mg53,-/- mice are more susceptible to I-R injury. rhMG53 applied intravenously to the wild-type mice protected I-R injured muscle, as demonstrated by reduced CK release and Evans blue staining. Histochemical studies confirmed beneficial effects of rhMG53. Of interest, rhMG53 did not protect against I-R injury in rat skeletal muscle. This was likely due to the fact that the plasma level of endogenous MG53 protein is high in rats. CONCLUSIONS: Our data suggest that rhMG53 may be a potential therapy for protection against muscle trauma. A mouse model appears to be a better choice than a rat model for evaluating potential treatments for protecting skeletal muscle.
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Proteínas de Transporte/uso terapêutico , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/lesões , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Proteínas de Transporte/farmacologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético/patologia , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/patologia , Proteínas com Motivo TripartidoRESUMO
AIM: The herbal prescription Chang'an II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Chang'an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model. METHODS: A rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g · kg(-1) · d(-1), ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4(+) and CD8(+) cells were counted and IL-1ß and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier. RESULTS: PI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang'an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4(+)/CD8(+) cell ratio in lamina propria and submucosa, and increased IL-1ß and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment reversed PI-IBS-induced changes in CD4(+)/CD8(+) cell ratio and expression of IL-1ß and IL-4. CONCLUSION: Chang'an II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects.
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Anti-Inflamatórios/farmacologia , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Fármacos Gastrointestinais/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Síndrome do Intestino Irritável/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Comportamento Animal/efeitos dos fármacos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Colite/induzido quimicamente , Colite/imunologia , Colite/metabolismo , Colite/patologia , Colite/psicologia , Colo/imunologia , Colo/metabolismo , Colo/ultraestrutura , Modelos Animais de Doenças , Combinação de Medicamentos , Fezes/química , Comportamento Alimentar/efeitos dos fármacos , Preferências Alimentares/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-4/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/ultraestrutura , Síndrome do Intestino Irritável/induzido quimicamente , Síndrome do Intestino Irritável/imunologia , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/patologia , Síndrome do Intestino Irritável/psicologia , Masculino , Medicina Tradicional Chinesa , Atividade Motora/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Ratos Sprague-Dawley , Ácido TrinitrobenzenossulfônicoRESUMO
AIM: To investigate the effects of ginsenoside Rd (Rd) on neurogenesis in rat brain after ischemia/reperfusion injury (IRI). METHODS: Male SD rats were subjected to transient middle cerebral artery occlusion (MCAO) followed by reperfusion. The rats were injected with Rd (1, 2.5, and 5 mg·kg(-1)·d(-1), ip) from d 1 to d 3 after MCAO, and with BrdU (50 mg·kg(-1)·d(-1), ip) from d 3 to d 6, then sacrificed on 7 d. The infarct size and neurological scores were assessed. Neurogenesis in the brains was detected by BrdU, DCX, Nestin, and GFAP immunohistochemistry staining. PC12 cells subjected to OGD/reperfusion were used as an in vitro model of brain ischemia. VEGF and BDNF levels were assessed with ELISA, and Akt and ERK phosphorylation was measured using Western blotting. RESULTS: Rd administration dose-dependently decreased the infarct size and neurological scores in the rats with IRI. The high dose of Rd 5 (mg·kg(-1)·d(-1)) significantly increased Akt phosphorylation in ipsilateral hemisphere, and markedly increased the number of BrdU/DCX and Nestin/GFAP double-positive cells in ischemic area, which was partially blocked by co-administration of the PI3 kinase inhibitor LY294002. Treatment with Rd (25, 50, and 100 µmol/L) during reperfusion significantly increased the expression of VEGF and BDNF in PC12 cells with IRI. Furthermore, treatment with Rd dose-dependently increased the phosphorylation of Akt and ERK, and significantly decreased PC12 cell apoptosis, which were blocked by co-application of LY294002. CONCLUSION: Rd not only attenuates ischemia/reperfusion injury in rat brain, but also promotes neurogenesis via increasing VEGF and BDNF expression and activating the PI3K/Akt and ERK1/2 pathways.
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Encéfalo/irrigação sanguínea , Ginsenosídeos/uso terapêutico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Ataque Isquêmico Transitório/tratamento farmacológico , Neurogênese/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Encéfalo/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína Duplacortina , Ginsenosídeos/química , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Ataque Isquêmico Transitório/metabolismo , Ataque Isquêmico Transitório/patologia , Sistema de Sinalização das MAP Quinases , Masculino , Panax/química , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Melatonin, a natural product of the pineal gland, has been shown to protect against ischemic stroke, but the molecular mechanisms underlying its protective function are not fully understood. In the present study, we tested whether melatonin could protect against ischemia-reperfusion (I/R) injury to rat brain by targeting the autophagy pathway. The I/R brain injury was induced by the established rat transient middle cerebral artery occlusion model. We found intraperitoneal injection of melatonin can ameliorate rat brain injury as evidenced by multiple morphological and behavioral criteria, such as infarct size, neurological score, serum creatine kinase, and lactate dehydrogenase content, as well as pyknotic-positive cells. Further studies revealed that the beneficial effects of melatonin is through targeting the autophagy pathway by inhibiting expression of beclin-1 and conversion of LC3, as well as activating the PI3K/Akt pro-survival pathway. To further confirm this finding, the autophagy pathway was activated by lentiviral mediated beclin-1 delivery and the PI3K/Akt pathway was inhibited by a pharmacological inhibitor, LY294002. In both manipulations, the beneficial effects of melatonin were greatly abolished. Taken together, our study suggested melatonin plays a protective role against I/R brain injury by inhibiting autophagy and activating the PI3K/Akt pro-survival pathway.
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Autofagia/efeitos dos fármacos , Ataque Isquêmico Transitório/tratamento farmacológico , Ataque Isquêmico Transitório/prevenção & controle , Melatonina/administração & dosagem , Melatonina/farmacologia , Fármacos Neuroprotetores , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia/fisiologia , Proteína Beclina-1 , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Injeções Intraperitoneais , Ataque Isquêmico Transitório/genética , Masculino , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genéticaRESUMO
Protocatechuic acid (PCA), a phenolic compound and one of the main metabolites of complex polyphenols, has been found to possess various biological activities, and it may have a potential in the treatment of ischemic heart diseases. This study explored the cardioprotective effect of PCA on myocardial ischemia/reperfusion (MI/R) injury and the underlying mechanisms. In an in vivo rat model of MI/R injury, myocardial infarct size, serum TNF-a level, and platelet aggregation were measured. In a primary neonatal rat cardiomyocyte model of hypoxia/ reoxygenation (H/R) injury, the apoptotic rate, expressions of cleaved caspase-3, and phosphorylated Akt were observed. We found that PCA significantly reduced myocardial infarct size, serum TNF-a level, and platelet aggregation. In vitro experiments revealed that PCA significantly inhibited the apoptotic rate and the expression of cleaved caspase-3, and it upregulated the expression of phosphorylated Akt in cardiomyocytes subjected to H/R injury. Our results suggest that PCA can provide a significant protection against MI/R injury, which may be at least partially attributed to its inhibitions against injury induced by MI/R including the inflammatory response, platelet aggregation, and cardiomyocytes apoptosis.
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Cardiotônicos , Hidroxibenzoatos/farmacologia , Hidroxibenzoatos/uso terapêutico , Isquemia Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Masculino , Isquemia Miocárdica/sangue , Isquemia Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Agregação Plaquetária/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Ratos Wistar , Fator de Necrose Tumoral alfa/sangueRESUMO
OBJECTIVE: To study the protective effect of rosmarinic acid (Ros A) on the primary cardiomyocyte hypoxia/reoxygenation (H/R) injury. METHOD: Primary cardiomyocytes of rats were cultured in vitro to establish the H/R injury of cardiomyocytes and observe the changes in the cell viability and LDH leakage. The changes in ATP content and ROS in cardiomyocytes were measured by using chemiluminescence and fluorescent probe technique. The effects of rosmarinic acid on the apoptosis of cardiomyocytes, cleaved-caspase 3, Akt and p-Akt protein expression were further detected by flow cytometry and western blot analysis. RESULT: According to the experimental results, Ros A at doses of 25, 50, 100 mg x L(-1) could inhibit the decrease in H/R-induced cell viability, LDH leakage and excessive ROS generation, and maintain the ATP level in cells. Ros A at doses of 50, 100 mg x L(-1) could remarkably inhibit the H/R-induced cardiomyocyte apoptosis and down-regulate the expression of cleaved caspase-3. Moreover, Ros A at doses of 100 mg x L(-1) could significantly up-regulate the expression of p-Akt. CONCLUSION: Ros A has the significant effect in resisting the cardiomyocyte H/R injury, improve cardiomyocyte energy metabolism and reduce cell apoptosis, which is related to the activation of Akt pathway.
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Cinamatos/farmacologia , Depsídeos/farmacologia , Hipóxia/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Oxigênio/metabolismo , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Rosmarinus/química , Trifosfato de Adenosina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Hipóxia Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Hipóxia/genética , Hipóxia/fisiopatologia , Hipóxia/prevenção & controle , Masculino , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Ácido RosmarínicoRESUMO
OBJECTIVE: To observe the effect of Huatuo Zaizao extractum (HTZZ) on focal cerebral ischemia/reperfusion (I/R) neurogenesis in rats induced by middle cerebral artery occlusion (MCAO) and its mechanism. METHOD: Totally 55 healthy adult male Sprague-Dawley rats were divided into the sham operation group, the MCAO model group and HTZZ high, middle and low dose groups (5, 2.5, 1.25 g x kg(-1)), with 11 rats in each group, and orally administered with drugs. The focal cerebral ischemia model was established by performing a middle cerebral artery occlusion (MCAO, 90 min) followed by a seven-day reperfusion (once a day). The neurogenesis and expressions of extracellular signal-regulated kinase (ERK) and cAMP response element binding protein (CREB) were detected by the immunofluorescent staining. The enzyme linked immunosorbent assay (ELISA) was adopted to determine the vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF). RESULT: MCAO (90 min) followed by a seven-day reperfusion resulted in the significant increase in the number of penumbra cortex newborn neurons (BrdU(+) -NeuN(+)), which was accompanied by the growth of ERK and CREB phosphorylation and VEGF and BDNF levels. HTZZ could promote the generation of newborn neurons (BrdU(+)-NeuN(+)) and the ERK and CREB phosphorylation and increase VEGF and BDNF levels at the ischemic side. CONCLUSION: HTZZ could promote the neurogenesis, which may be the interventional targets of effective traditional Chinese medicine Huatuo Zaizao extractum in promoting the self-repair function of the cerebral ischemic areas.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Neurônios/citologia , Animais , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Humanos , Masculino , Neurogênese/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Reperfusão , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
To establish neonatal rat cardiac fibroblast inflammatory secretion model by using LPS 100 microg x L(-1) combined with ATP 5 mmol x L(-1), in order to study the inhibitory effect of quercetin on the secretion of inflammatory factors TNF-alpha, IL-1beta and IL-6 of cardiac fibroblasts, further investigate the effect of quercetin on the protein expression of p-NF-kappaB p65 (S276) and p-Akt (S473) by western blot, and discuss the inhibitory effect of quercetin on the inflammatory secretion of cardiac fibroblasts. According to the findings, quercetin with the concentrations between 51.74 micromol x L(-1) and 827.81 micromol x L(-1) had no significant effect on the activity of cardiac fibroblasts. Quercetin with the concentrations of 82.78, 41.39, 20.70 micromol x L(-1) could notably inhibit the increase of TNF-alpha and IL-1beta induced by LPS 100 microg x L(-1) for 3 h and then ATP 5 mmol x L(-1) for 36 h (P < 0.01 or P < 0.05). Quercetin with the concentrations of 82.78, 41.39 micromol x L(-1) could notably inhibit the increase of IL-6 induced LPS 100 microg x L(-1) for 3 h and then ATP 5 mmol x L(-1) for 36 h (P < 0.05), without any notable effect of quercetin with the concentration of 20.70 micromol x L(-1). Quercetin with the concentrations of 82.78, 41.39, 20. 70 micromol x L(-1) could notably inhibit the NF-kappaB p65 (S276) activation induced by LPS 100 microg x L(-1) for 3 h and then ATP 5 mmol x L(-1) for 15 min, with the most significant effect in 20.70 micromol x L(-1). Quercetin with the concentrations of 82.78, 41.39, 20.70 micromol x L(-1) could notably inhibit the increase of p-Akt(473) expression induced by LPS 100 microg x L(-1) for 3 h and then ATP 5 mmol x L(-1) for 240 min (P < 0.05). Therefore, this study believes that quercetin could attenuate the secretion of inflammatory factors TNF-alpha, IL-1beta and IL-6 of cardiac fibroblasts by inhibiting the activation of NF-kappaB p65 (S276) and Akt (473).
Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Fibrose Endomiocárdica/tratamento farmacológico , Fibroblastos/efeitos dos fármacos , Quercetina/administração & dosagem , Animais , Células Cultivadas , Fibrose Endomiocárdica/genética , Fibrose Endomiocárdica/imunologia , Feminino , Fibroblastos/imunologia , Coração/efeitos dos fármacos , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/imunologia , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
In the field of in situ measurement of high-temperature pressure, fiber-optic Fabry-Perot pressure sensors have been extensively studied and applied in recent years thanks to their compact size and excellent anti-interference and anti-shock capabilities. However, such sensors have high technological difficulty, limited pressure measurement range, and low sensitivity. This paper proposes a fiber-optic Fabry-Perot pressure sensor based on a membrane-hole-base structure. The sensitive core was fabricated by laser cutting technology and direct bonding technology of three-layer sapphire and develops a supporting large-cavity-length demodulation algorithm for the sensor's Fabry-Perot cavity. The sensor exhibits enhanced sensitivity, a simplified structure, convenient preparation procedures, as well as improved pressure resistance and anti-harsh environment capabilities, and has large-range pressure sensing capability of 0-10 MPa in the temperature range of 20-370 °C. The sensor sensitivity is 918.9 nm/MPa, the temperature coefficient is 0.0695 nm/(MPaâ°C), and the error over the full temperature range is better than 2.312%.