RESUMEN
Biogenic amines (BAs) are a family of nitrogen-bearing natural organic molecules with at least one primary amine, which play an important role in living organisms. Elevated concentration of BAs may cause neuron disorder, Parkinson's disease and many other diseases. Therefore, it is essential to monitor BAs in living organisms. Herein, we reported a resorufin-based fluorescence probe for sensing of various BAs. Upon nucleophilic substitution reaction with BAs, the probe released resorufin, affording to strong fluorescence emission at 592 nm with rapid response (<8 min), good selectivity and a low detection limit (LOD = 0.47 µM). The probe has low cytotoxicity and good membrane permeability, and has been successfully used to visualize BAs in living cells and zebrafish with good performance.
RESUMEN
Lung ischemia-reperfusion injury (LIRI) is a severe multifaceted pathological condition that can lead to poor patient outcome where oxidative stress and the resulting inflammatory response can trigger and exacerbate tissue damage in LIRI patients. Sirtuin3 (SIRT3), a member of the sirtuin family, protects against oxidative stress-related diseases. However, it remains unclear if and how SIRT3 alleviates lung injury induced by ischemia/reperfusion (I/R). Our previous study showed that lung tissue structures were severely damaged at 6 h after lung I/R in mice, however, repair of the injured lung tissue was significant at 24 h. In this study, we found that both SIRT3 mRNA and protein levels were markedly increased at 24 h after lung I/R in vivo. Meanwhile, inhibition of SIRT3 aggravated lung injury and inflammation, augmented mitochondrial fission and oxidative stress and increased Hypoxia-inducible factor-1α (HIF-1α) expression in vivo. The results suggest that SIRT3 may be an upstream regulator of HIF-1α expression. Knockdown of SIRT3 resulted in excessive mitochondrial fission and increased oxidative stress in vitro, and we found that knocking down the expression of HIF-1α alleviated these changes. This suggests that the SIRT3-HIF-1α signaling pathway is involved in regulating mitochondrial function and oxidative stress. Furthermore, inhibition of dynamin-related protein 1 (Drp-1) by the inhibitor of mitophagy, Mdivi-1, blocked mitochondrial fission and alleviated oxidative stress in vitro. Taken together, our results demonstrated that downregulation of SIRT3 aggravates LIRI by increasing mitochondrial fission and oxidative stress. Activation of SIRT3 inhibits mitochondrial fission and this mechanism may serve as a new therapeutic strategy to treat LIRI.
Asunto(s)
Lesión Pulmonar , Daño por Reperfusión , Sirtuina 3 , Sirtuinas , Animales , Apoptosis , Regulación hacia Abajo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Pulmón/patología , Ratones , Dinámicas Mitocondriales , Estrés Oxidativo , ARN Mensajero/metabolismo , Daño por Reperfusión/patología , Sirtuina 3/genética , Sirtuina 3/metabolismo , Sirtuinas/genética , Sirtuinas/metabolismoRESUMEN
Ventilator-induced lung injury (VILI) is one of the most common complications of mechanical ventilation and can severely affect health. VILI appears to involve excessive inflammatory responses, but its pathogenesis has not yet been clarified. Since interleukin-17 (IL-17) plays a critical role in the immune system and the development of infectious and inflammatory diseases, we investigated here whether it plays a role in VILI. In a mouse model of VILI, mechanical ventilation with high tidal volume promoted the accumulation of lung neutrophils, leading to increased IL-17 levels in the lung, which in turn upregulated macrophage chemoattractant protein-1 via p38 mitogen-activated protein kinase. Depletion of neutrophils decreases the production IL-17 in mice and inhibition of IL-17 significantly reduced HTV-induced lung injury and inflammatory response. These results were confirmed in vitro using RAW264.7 macrophage cultures. Our results suggest that IL-17 plays a pro-inflammatory role in VILI and could serve as a new target for its treatment.
Asunto(s)
Quimiocina CCL2/fisiología , Interleucina-17/fisiología , Neutrófilos/fisiología , Lesión Pulmonar Inducida por Ventilación Mecánica/etiología , Proteínas Quinasas p38 Activadas por Mitógenos/fisiología , Animales , Interleucina-17/antagonistas & inhibidores , Masculino , Ratones , Ratones Endogámicos C57BL , Células RAW 264.7 , Respiración Artificial/efectos adversos , Transducción de Señal/fisiologíaRESUMEN
Hepatocellular carcinoma (HCC), a common type of human malignancies, leads to increasing incidence and fairly high mortality. An increasing number of studies have verified that long noncoding RNAs (lncRNAs) played key roles in the development of multiple human cancers. As a biomarker, SLC16A1-AS1 has been reported in non-small cell lung cancer (NSCLC) and oral squamous cell carcinoma (OSCC). Thus, we decided to investigate whether SLC16A1-AS1 exerts its biological function in HCC. In this study, we discovered that SLC16A1-AS1 was obviously downregulated in HCC tissues and cells. Overexpression of SLC16A1-AS1 inhibited HCC cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) process as well as promoted cell apoptosis. Moreover, SLC16A1-AS1 was confirmed to enhance the radiosensitivity of HCC cells. Molecular mechanism exploration suggested that SLC16A1-AS1 served as a sponge for miR-301b-3p and CHD5 was the downstream target gene of miR-301b-3p in HCC cells. Rescue assays implied that CHD5 knockdown could recover the effects of SLC16A1-AS1 overexpression on HCC cellular processes. In brief, our study clarified that SLC16A1-AS1 acted as a tumor suppressor in HCC by targeting the miR-301b-3p/CHD5 axis, which may be a promising diagnostic biomarker and provide promising treatment for HCC patients.
Asunto(s)
Carcinoma Hepatocelular , Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Hepáticas , Neoplasias Pulmonares , MicroARNs , Transportadores de Ácidos Monocarboxílicos , Neoplasias de la Boca , Simportadores , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Proliferación Celular , ADN Helicasas , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , MicroARNs/genética , Transportadores de Ácidos Monocarboxílicos/fisiología , Proteínas del Tejido Nervioso , Tolerancia a Radiación/genética , Simportadores/fisiologíaRESUMEN
Lymphocyte antigen 6Chigh (Ly-6Chigh) inflammatory monocytes, as novel mononuclear cells in the innate immune system, participate in infectious diseases. In this study, we investigated the potential role of these monocytes in ventilator-induced lung injury (VILI) and the possible mechanism involved in their migration to lung tissue. Our results showed that mechanical ventilation with high tidal volume (HTV) increased the accumulation of Ly-6Chigh inflammatory monocytes in lung tissues and that blocking CC chemokine receptor 2 (CCR2) could significantly reduce Ly-6Chigh inflammatory-monocyte migration and attenuate the degree of inflammation of lung tissues. In addition, inhibition of p38 mitogen-activated protein kinase (p38 MAPK) activity could decrease the secretion of monocyte chemoattractant protein 1 (MCP-1), which in turn decreased the migration of Ly-6Chigh inflammatory monocytes into lung tissue. We also demonstrated that high ventilation caused Ly-6Chigh inflammatory monocytes in the bone marrow to migrate into and aggregate in the lungs, creating inflammation, and that the mechanism was quite different from that of infectious diseases. Ly-6Chigh inflammatory monocytes might play a pro-inflammatory role in VILI, and blocking their infiltration into lung tissue might become a new target for the treatment of this injury.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Quimiocina CCL2/metabolismo , Monocitos/inmunología , Lesión Pulmonar Inducida por Ventilación Mecánica/inmunología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Antígenos Ly/metabolismo , Benzoxazinas/farmacología , Benzoxazinas/uso terapéutico , Médula Ósea/inmunología , Médula Ósea/patología , Movimiento Celular/efectos de los fármacos , Movimiento Celular/inmunología , Modelos Animales de Enfermedad , Humanos , Imidazoles/farmacología , Imidazoles/uso terapéutico , Pulmón/citología , Pulmón/inmunología , Pulmón/patología , Ratones , Monocitos/metabolismo , Piridinas/farmacología , Piridinas/uso terapéutico , Receptores CCR2/antagonistas & inhibidores , Receptores CCR2/metabolismo , Compuestos de Espiro/farmacología , Compuestos de Espiro/uso terapéutico , Volumen de Ventilación Pulmonar , Lesión Pulmonar Inducida por Ventilación Mecánica/diagnóstico , Lesión Pulmonar Inducida por Ventilación Mecánica/tratamiento farmacológico , Lesión Pulmonar Inducida por Ventilación Mecánica/patología , Ventiladores Mecánicos/efectos adversos , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidoresRESUMEN
AIM: This review was performed to investigate the effect of ondansetron on the prevention of propofol injection pain. METHODS: PubMed, Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched for randomized controlled trials (RCTs) of ondansetron in preventing the pain on injection of propofol. Then, RevMan 5.2 was adopted to conduct a meta-analysis on propofol injection pain. RESULTS: Ten RCTs, totaling 782 patients, were included in this analysis. The meta-analysis showed that: 1) compared with the control group, the ondansetron group was related to a decreasing incidence of propofol injection pain, and it was statistically significant (risk ratio [RR] = 0.41, 95% confidence interval [CI, 0.34, 0.49], P < 0.00001); 2) compared with the incidence of propofol injection pain in the lidocaine group, there was no difference and no statistical significance (RR = 1.28, 95% CI [0.85, 1.93], P = 0.25); 3) no statistically significant differences were found between the ondansetron and magnesium sulfate groups in the incidence of propofol injection pain (RR = 1.20, 95% CI [0.87, 1.66], P = 0.27); and 4) the incidence of ondansetron group igniting moderate pain (RR = 0.37, 95% CI [0.26, 0.52], P < 0.00001) and severe pain (RR = 0.27, 95% CI [0.17, 0.43] P < 0.00001) was less likely to occur during the injection of propofol compared with the control group, but there was no difference between the ondansetron and control groups in the incidence of mild propofol injection pain (RR = 0.83, 95% CI [0.63, 1.10], P = 0.20). CONCLUSION: Ondansetron can effectively prevent propofol injection pain, and the effect is similar to that of magnesium sulfate and lidocaine.
RESUMEN
OBJECTIVE: To evaluate the effects of urinary kallidinogenase on subarachnoid hemorrhage (SAH) in rabbits. METHODS: Rabbits symptomatic cerebral vasospasm model was built though Endo method, among the 40 rabbits, 8 died or had severe nervous system syndrome, the other 32 were randomly divided into 4 groups:group A, control group, injection of normal saline to the cisterna magna;group B, subarachnoid hemorrhage;group C, injection of human urinary tissue kallikreins;group D, treated with Nimodipine. The behavior scores, neurological scores and cerebral angiography changes were observed. RESULTS: Food intake obviously decreased and neurological deficit were seen in group B, while which were attenuated in group C and group D, and group A was normal. Comparing the diameter of basilar artery was (1.9 +/- 0.3) mm before SAH, the diameter of group B 4 d later was (1.5 +/- 0.3) mm, 7 d later (1.4 +/- 0.3) mm, the difference was significant (P < 0.05). Comparing with group C on the day 4th and 7th, the diameters of basilar artery were significantly different (P < 0.001). Comparing with group D on the day 4th, 7th and 14th, there was no obvious improvement. CONCLUSION: Urinary kallidinogenase and Nimodipine can obviously alleviate symptomatic cerebral vasospasm in rabbits remarkably, but the former's effect of attenuating vasospasm is better than that of Nimodipine.
Asunto(s)
Calicreínas de Tejido/uso terapéutico , Vasodilatadores/uso terapéutico , Vasoespasmo Intracraneal/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Nimodipina/uso terapéutico , Conejos , Distribución AleatoriaRESUMEN
OBJECTIVE: To study the effects of human tissue kallikrein (HTK) on symptomatic cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). METHODS: Forty rabbits underwent occlusion of bilateral carotid. Two weeks later the 28 surviving rabbits were randomly divided into to 4 groups: shamed-operation group (n = 8) undergoing injection of normal saline into the cisterna magna on day 1 and day 3, SAH group (n = 6) undergoing injection of nonheparinized autologous arterial blood into the cisterna magna, HTK therapy group (n = 6) undergoing blood injection into the cisterna magna and then injection of HTK via ear marginal vein daily for 3 days, and nimodipine (ND) therapy group (n = 6) undergoing blood injection into the cisterna magna and then injection of ND via ear marginal vein. 3-dimension-CT angiography (3-D CTA) was used to measure the basilar artery diameter on D(0) and D(5). On D(6) the rabbits were killed with their basilar arteries taken out to undergo light microscopic examination. RESULTS: Blood could be seen in the basis cephalic of the 3 groups undergoing blood injection. 3-D CTA showed that arteriospasm was seen in the SAH and ND groups but not in the HTK group. Microscopy showed obvious pathological changes in basilar artery in the SAH and ND groups but not in the HTK group. CONCLUSION: HTK given early after SAH effectively alleviates the symptomatic cerebral vasospasm.
Asunto(s)
Calicreínas de Tejido/uso terapéutico , Vasoespasmo Intracraneal/terapia , Animales , Transfusión Sanguínea/métodos , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Conejos , Hemorragia Subaracnoidea/terapia , Calicreínas de Tejido/administración & dosificación , Resultado del Tratamiento , Vasoespasmo Intracraneal/patologíaRESUMEN
OBJECTIVE: To observe the effect of transcutaneous acupoint electrical stimulation (TAES) on brain tissue oxygen and glucose metabolism of the brain tissue in peri-operative period of the craniocerebral operation. METHODS: Fifty patients scheduled for neuro-surgery were randomly assigned to the treatment group and the control group equally. Anesthesia applied after induction on all patients was continuous sevoflurane inhalation and intermittent intravenous injection of sulfenany and vecurnium bromide, but to the treatment group TASE was applied additionally from 30 min before anesthesia to the end of operation. Blood samples were taken from artery and jugular venous bulb at different time points, i. e. before induction (T0) , before skin incision (T1) , at the end of operation (T2) , and 10 min after extubation (T3) , for blood-gas analysis. The difference of oxygen, glucose and lactate contents between blood samples of arterial and jugular bulb (Da-jvO2, Da-jvGlu and Da-jvLac) at respective time point were determined and calculated. RESULTS: Da-jvO2 decreased in both group at T1, T2 and T3, and all lower than that at T0 (P < 0.05 or P < 0.01), but significant difference was shown in comparison of the index at T2 and T3 with the same time points in the control group in the treatment group (P < 0.05 or P < 0.01) , and that between groups at T2 and T3 (P < 0.01). Da-jvGlu in the treatment group decreased at T2 and T3 (P < 0.05), but keep unchanged relatively in the control group before and after anesthesia, inter-group comparison showed it was lower at T2 and T3 in the treatment group than that in the control group respectively (P < 0.05). Da-jvGlu in the treatment group at T1, T2, and T3 were all lower than that at the same time points (P < 0. 01). CONCLUSION: TAES can significantly decrease the oxygen and glucose metabolism of the brain tissue in the perioperative period of the craniocerebral operation.