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ALI(acute lung injury) is a severe respiratory dysfunction caused by various intrapulmonary and extrapulmonary factors. It is primarily characterized by oxidative stress and affects the integrity of the pulmonary barrier. In severe cases, ALI can progress to ARDS(acute respiratory distress syndrome), a condition that poses a serious threat to the lives of affected patients. To date, the etiological mechanisms underlying ALI remain elusive, and available therapeutic options are quite limited. AMPK(AMP-activated protein kinase), an essential serine/threonine protein kinase, performs a pivotal function in the regulation of cellular energy levels and cellular regulatory mechanisms, including the detection of redox signals and mitigating oxidative stress. Meanwhile, Nrf2(nuclear factor erythroid 2-related factor 2), a critical transcription factor, alleviates inflammation and oxidative responses by interacting with multiple signaling pathways and contributing to the modulation of oxidative enzymes associated with inflammation and programmed cell death. Indeed, AMPK induces the dissociation of Nrf2 from Keap1(kelch-like ECH-associated protein-1) and facilitates its translocation into the nucleus to trigger the transcription of downstream antioxidant genes, ultimately suppressing the expression of inflammatory cells in the lungs. Given their roles, AMPK and Nrf2 hold promise as novel treatment targets for ALI. This study aimed to summarise the current status of research on the AMPK/Nrf2 signaling pathway in ALI, encompassing recently reported natural compounds and drugs that can activate the AMPK/Nrf2 signaling pathway to alleviate lung injury, and provide a theoretical reference for early intervention in lung injury and future research on lung protection.
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This corrects the article published in European Journal of Histochemistry 2023;67:3535. doi: 10.4081/ejh.2023.3535.
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Hyperoxia-induced acute lung injury (HALI) is an important complication of clinical oxygen therapy, which is mainly characterized by acute respiratory distress syndrome (ARDS) in adults and broncho-pulmonary dysplasia (BPD) in infants. HALI seriously affects the prognosis and quality of life of patients, so it has received more and more attention. However, the pathogenesis of HALI is complex and unclear, and there is no clear treatment method at present. Non-coding RNA (ncRNA) is an important type of functional RNA transcriptome. Due to the lack of effective open reading frame, ncRNA does not have the function of coding proteins. However, ncRNA can still regulate gene expression at multiple levels and affect the occurrence and development of many diseases. In recent years, a large number of in vitro and in vivo studies have shown that ncRNA is involved in the pathogenesis of HALI and is of great significance. This article reviews the expression and significance of ncRNA in HALI, in order to provide new diagnosis and treatment ideas for the prevention and treatment of HALI.
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Lesión Pulmonar Aguda , Hiperoxia , ARN no Traducido , Humanos , Hiperoxia/complicaciones , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/genética , Lesión Pulmonar Aguda/terapia , ARN no Traducido/genética , AnimalesRESUMEN
Patients who are bedridden are for a long-time prone to develop bedsores, especially in the hip and sacral areas and limbs, which causes eczema, ulcers, infection and other complications, resulting in pain and more medical costs. Therefore, the medical staff of the Second Affiliated Hospital of Zunyi Medical University designed and developed a kind of anti-bedsore turning pad, and has obtained the national utility model patent (ZL 2021 2 3004923.9), which is suitable for various long-term bedridden patients. The anti-bedsore turning pad includes the center axis of the turning pad, and ventilation pad 1 and ventilation pad 2 designed on the left and right of turning pad center axis. Under the ventilation pad 1 and the ventilation pad 2, the air pad 1 and the air pad 2 are respectively designed. There is a bedspread connected with ventilation pad 1 and ventilation pad 2 on the inflatable pad 1 and the inflatable pad 2. Through the design of inflatable pad 1 and inflatable pad 2, the left and right of the anti-bedsore turning pad can be lowered or raised independently, which is convenient for the patient's body to tilt and turn over, and can significantly reduce the number of nursing staff and the burden of nursing staff when turning over. In addition, it is convenient to replace the force site at any time and reduce the occurrence of pressure ulcers caused by long-term pressure on the force site. Through the design of ventilation cushion 1 and ventilation cushion 2, the internal gas flow of the turning pad can be made, and the ventilation between the patient and the turning pad can be kept dry, so as to reduce the occurrence of eczema, ulcers or infection and other complications, and ultimately reduce the occurrence of bedsores. In addition, through the design of the most superficial limb pad, the patient's limb can be appropriately elevated or massaged, which increases the comfort of the patient. The anti-bedsore turning pad is simple and effective, and can be widely used in long-term bedridden patients.
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Eccema , Úlcera por Presión , Humanos , Úlcera por Presión/epidemiología , Úlcera , Respiración , Factores de RiesgoRESUMEN
Aiming at problems such as poor precision of laser processing C/SiC composites, low efficiency of grinding C/SiC composites, and serious wear of grinding wheel, a method of laser-grinding chain processing C/SiC composite groove was proposed in this paper. The method combined the high efficiency characteristic of laser ablating and the high precision characteristic of grinding. The relationship between laser processing parameters and the characteristics of ablative grooves was investigated, and the appropriate laser processing parameters were optimized, and then, to further improve the processing quality of the grooves, the grinding parameters optimization experiments of the grooves of C/SiC composites were carried out. The results showed that the C/SiC composites could be quickly removed by laser processing, and the grooves with relatively good size and shape accuracy could be obtained by laser parameters optimization experiments, but the side wall of the groove still had a certain inclination and the surface quality of the groove was yet poor; meanwhile, the size accuracy, shape accuracy, and surface quality of the grooves were greatly improved by further grinding. In addition, then, through the laser and grinding optimization experiments, the optimized parameters were obtained, where the laser power was 80 W, the scanning speed was 300 mm/s, the scanning frequency was 50 kHz, the scanning spacing was 25 µm, the depth of cut was 30 µm, the liner speed of wheel was 62.832 m/min, and the feed speed was 10 mm/min. With these parameters, the time used to process the groove with the laser-grinding chain was about 23/40 of the grinding process, and the quality of grooves could be guaranteed. Therefore, combined with the optimized process parameters, the laser-grinding chain processing scheme could be used to achieve high efficiency and precision grinding of C/SiC composite grooves.
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The mortality and morbidity rates of ovarian cancer (OC) are high, but the underlying mechanisms of OC have not been characterized. In this study, we determined the role of Rho GTPase Activating Protein 30 (ARHGAP30) in OC progression. We measured ARHGAP30 abundance in OC tissue samples and cells using immunohistochemistry (IHC) and RT-qPCR. EdU, transwell, and annexin V/PI apoptosis assays were used to evaluate proliferation, invasiveness, and apoptosis of OC cells, respectively. The results showed that ARHGAP30 was overexpressed in OC tissue samples and cells. Inhibition of ARHGAP30 suppressed growth and metastasis of OC cells, and enhanced apoptosis. Knockdown of ARHGAP30 in OC cells significantly inhibited the PI3K/AKT/mTOR pathway. Treatment with the PI3K/AKT/mTOR pathway inhibitor buparlisib simulated the effects of ARHGAP30 knockdown on growth, invasiveness, and apoptosis of OC cells. Following buparlisib treatment, the expression levels of p-PI3K, p-AKT, and p-mTOR were significantly decreased. Furthermore, buparlisib inhibited the effects of ARHGAP30 upregulation on OC cell growth and invasiveness. In conclusion, ARHGAP30 regulated the PI3K/AKT/mTOR pathway to promote progression of OC.
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Lesión Pulmonar Aguda , Hiperoxia , Neoplasias Ováricas , ARN Largo no Codificante , Humanos , Femenino , Transducción de Señal , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Largo no Codificante/metabolismo , Potencial de la Membrana Mitocondrial , Serina-Treonina Quinasas TOR/metabolismo , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Células Epiteliales Alveolares/metabolismo , Neoplasias Ováricas/metabolismoRESUMEN
OBJECTIVE: To investigate whether microRNA-21-5p (miR-21-5p) alleviates hyperoxia-induced acute lung injury (HALI) through activating the phosphatidylinositol 3 kinase/serine-threonine protein kinase (PI3K/Akt) signaling pathway by regulating apoptosis of type II alveolar epithelial cell (AEC II). METHODS: Seventy-two male Sprague-Dawley (SD) rats were divided into normozone-controlled group, HALI group, PI3K/Akt signaling pathway inhibitor LY294002+HALI group (LY+HALI group), miR-21-5p overexpression+LY294002+HALI group (miR-21-5p+LY+HALI group), miR-21-5p overexpression+HALI group (miR-21-5p+HALI group), and dimethyl sulfoxide (DMSO)+HALI group by random number table method with 12 rats in each group. Animal models of HALI were prepared using 95% concentrations of oxygen. The animals in the normozone-controlled group were fed normally under normoxia. Transfection of lung tissue by miR-21-5p adeno-associated viral vector AAV6-miR-21-5p was performed by instillation of 200 µL titer (1×1012 TU/mL) through a tracheal catheter 3 weeks prior to modeling. DMSO and LY294002 were administered via the tail vein at 0.3 mg/kg 1 hour before modeling. After 48 hours of modeling, carotid artery blood was collected to detect oxygenation index (OI) and respiratory index (RI), and real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect miR-21-5p expression. Lung tissue was collected, and the levels of inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-1ß) were measured by enzyme-linked immunosorbent assay (ELISA), and the ratio of pulmonary wet/dry weight (W/D) was determined, and the pathological changes of lung histopathology were observed under the light microscopy after hematoxylin-eosin (HE) staining. Each group was purified AEC II cells from 6 rats, the apoptosis rate was detected by flow cytometry, and the expression levels of phosphatase and tensin homologous gene (PTEN), and proteins from the PI3K/Akt signaling pathway were detected by Western blotting. RESULTS: Compared with the normozone-controlled group, alveolar septal thickening and massive inflammatory cell infiltration were found after hyperoxia exposure, RI, inflammatory factors, lung W/D ratio, pathological score, AEC II cells early apoptosis rate, PTEN protein expression and phosphorylation level of Akt were increased, while OI and miR-21-5p expression were decreased, indicating the successful preparation of the model. After pretreatment, LY294002 could aggravate the pathological injury of lung tissue in HALI rats, RI, inflammatory factors and lung W/D ratio were further increased, and OI was further reduced compared with HALI group. At the same time, it could promote the AEC II cell apoptosis, further up-regulate the expression of PTEN, and reduce the phosphorylation of Akt. However, miR-21-5p pretreatment could negatively regulate PTEN, activate PI3K/Akt signal pathway, inhibit AEC II cell apoptosis, and reduce HALI, which was shown by the decreased level of inflammatory factors in miR-21-5p+LY+HALI group compared with LY+HALI group [TNF-α (µg/L): 100.33±3.48 vs. 116.55±2.53, IL-6 (ng/L): 141.06±3.70 vs. 161.31±3.59, IL-1ß (µg/L): 90.82±3.69 vs. 112.23±2.87, all P < 0.05], RI, lung injury pathology score, lung W/D ratio, and AEC II cell early apoptosis rate were significantly decreased [RI: 0.81±0.02 vs. 1.05±0.07, pathology score: 0.304±0.008 vs. 0.359±0.007, lung W/D ratio: 5.29±0.03 vs. 5.52±0.08, apoptosis rate: (27.20±2.34)% vs. (34.17±1.49)%, all P < 0.05], OI and expressions of miR-21-5p were significantly increased [OI (mmHg, 1 mmHg ≈ 0.133 kPa): 266.71±2.75 vs. 230.12±4.04, miR-21-5p (2-ΔΔCt): 2.21±0.13 vs. 0.33±0.03, both P < 0.05], and PTEN protein expression in AEC II cell was significantly reduced (PTEN/GAPDH: 0.50±0.06 vs. 0.93±0.06, P < 0.05), and phosphorylation level of Akt was significantly increased [phosphorylated Akt (p-Akt) protein (p-Akt/GAPDH): 0.86±0.05 vs. 0.56±0.06, P < 0.05]. CONCLUSIONS: miR-21-5p attenuates HALI by inhibiting AEC II cell apoptosis, possibly through negative regulation of PTEN to activate PI3K/Akt signaling pathway.
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Lesión Pulmonar Aguda , Hiperoxia , MicroARNs , Ratas , Masculino , Animales , Células Epiteliales Alveolares/metabolismo , Ratas Sprague-Dawley , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Hiperoxia/complicaciones , Factor de Necrosis Tumoral alfa , Interleucina-6 , Fosfatidilinositol 3-Quinasas/metabolismo , Dimetilsulfóxido , Transducción de Señal , Proteínas Serina-Treonina Quinasas/metabolismo , Apoptosis , MicroARNs/metabolismoRESUMEN
In order to machine the tungsten alloy with high efficiency, low damage and precision, laser ablation texture technology and precision grinding technology were combined to carry out grinding experiments of tungsten alloy and laser ablation texture-assisted grinding experiments. The advantages of laser ablation texture-assisted grinding tungsten alloy were investigated by comparing of the surface morphology, grinding force and surface roughness between ordinary grinding and laser ablative texture-assisted grinding. The results demonstrate that the surface morphology of ordinary grinding tungsten alloy was poor, the surface roughness was relatively high and the grinding force was relatively large. The surface morphology of the laser ablation texture-assisted grinding tungsten alloy processed by laser ablation texture was improved, the surface roughness decreased by 0.023 µm-0.204 µm, the normal force decreased by 49.91-59.46% and the tangent force decreased by 44.11-58.49%. Meantime, for the area ratio of texture A being the most, the grinding effect was related to the area ratio of texture, and the lowest grinding force and the best surface quality were observed on the tungsten alloy with the laser ablated texture A; the grinding forces and roughness of the other textures' workpiece was similar and close because of their similar area ratios. The results demonstrate that laser ablation texture-assisted grinding of tungsten alloy could improve machining quality and reduce grinding force, which would provide guidance for realizing the high efficiency and precision machining of tungsten alloy.
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Mitophagy is the selective degradation of damaged mitochondria, and it is of great significance to maintain the normal quantity and quality of mitochondria to ensure cell homeostasis and survival. Necroptosis is a type of programmed cell necrosis that can be induced by excessive mitophagy. Reactive oxygen species (ROS) are produced mainly by mitochondria and can damage mitochondria. Hyperoxic acute lung injury (HALI) is a serious complication of clinical oxygen therapy, and its pathogenesis is not clear. Existing studies have shown that mitophagy and necroptosis are involved in the occurrence of HALI. There are many mechanisms regulating mitophagy and necroptosis, including tumor necrosis factor-α (TNF-α), E3 ubiquitin protein ligase (PINK1/Parkin) protein pathway encoded by PTEN-induced kinase 1/PARK2 gene, phosphoglycerate mutase 5 (PGAM5), etc. PGAM5 has been proved to be a key factor linking mitophagy and necroptosis. Previous studies of our team found that the mechanism of microRNA-21-5p (miR-21-5p) alleviating HALI was related to its pGAM5-mediated inhibition of mitophagy, but the mechanism of PGAM5-mediated mitophagy and necroptosis remains unclear. Therefore, this paper reviews the targets of PGAM5-mediated mitophagy and necroptosis, in order to find clues of lung protection of pGAM5-mediated mitophagy and necroptosis in HALI, and provide theoretical basis for subsequent basic research.
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MicroARNs , Mitofagia , Humanos , Mitofagia/genética , Necroptosis , Necrosis , Oxígeno , Fosfoglicerato Mutasa , Fosfoproteínas Fosfatasas/genética , Fosfoproteínas Fosfatasas/metabolismo , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factor de Necrosis Tumoral alfa , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
BACKGROUND: Severe sepsis, a major health problem worldwide, has become one of the leading causes of death in ICU patients. Further study on the pathogenesis and treatment of acute kidney injury (AKI) is of great significance to reduce high mortality rate of sepsis. In this study, the mechanism by which ubiquitin specific peptidase 10 (USP10) reduces sepsis-induced AKI was investigated. Ligation and perforation of cecum (CLP) was employed to establish C57BL/6 mouse models of sepsis. Hematoxylin-eosin (H&E) staining was performed to detect renal injury. The concentrations of serum creatinine (Cr), urea nitrogen (BUN) and cystatin C (Cys C) were determined using a QuantiChrom™ Urea Assay kit. RT-qPCR and western blot were conducted to assess the USP10 expression level. DHE staining was used to detect reactive oxygen species (ROS) levels. H2O2, MDA and SOD levels were assessed using corresponding colorimetric kits. Western blot was used to examine the expression levels of Bcl-2, Bax, cleaved caspase-3, Sirt6, Nrf2 and HO-1. MTT assay was used to determine cell viability, whereas TUNEL staining and flow cytometry were used to assess cell apoptosis. RESULTS: In this study, we found that USP10 was decreased in CLP-induced mouse renal tissues. We identified that USP10 alleviated renal dysfunction induced by CLP. Moreover, USP10 was found to reduce oxidative stress, and abated LPS-induced renal tubular epithelial cell injury and apoptosis. Finally, we discovered that USP10 promoted activation of the NRF2/HO-1 pathway through SIRT6 and attenuated LPS-induced renal tubular epithelial cell injury. CONCLUSIONS: This study found that USP10 activates the NRF2/ARE signaling through SIRT6. USP10 alleviates sepsis-induced renal dysfunction and reduces renal tubular epithelial cell apoptosis and oxidative stress.
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Disbiosis/etiología , Hiperoxia/complicaciones , Animales , Modelos Animales de Enfermedad , Disbiosis/fisiopatología , Hiperoxia/fisiopatología , Masculino , Microbiota/efectos de los fármacos , Oxígeno/administración & dosificación , Oxígeno/efectos adversos , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Fulminant lupus myocarditis is a rare but fatal manifestation of systemic lupus erythematosus. Aggressive immunosuppressive treatments are important in its successful management. However, they can significantly damage the immunity and are associated with a considerable risk of infection development and spread. We present a rare and complicated case of a 20-year-old female diagnosed with fulminant lupus myocarditis accompanied by pneumonia. The patient was successfully treated with plasma exchange (PE) for fulminant lupus myocarditis. CASE SUMMARY: A 20-year-old Chinese woman presented to the Hematology Department complaining of fatigue and knee pain. Blood test showed anemia and thrombocytopenia. On the second day of hospitalization, she was transferred to the ICU due to dyspnea and hypotension. Autoimmune profiles showed hypocomplementemia and positive antinuclear antibodies. Computer tomography showed an enlarged heart and pneumonia. Ultrasound revealed an enlarged heart with a low left ventricular ejection fraction. Fulminant lupus myocarditis with cardiogenic shock was initially considered. Due to the accompanying pneumonia, aggressive immunosuppression was contraindicated. Her cardiac function remained critical after the initial therapy of intravenous immunoglobulin and corticosteroids at a conventional dose, but she responded well to later PE therapy plus corticosteroids administration. The patient fully recovered with normal cardiac function. CONCLUSION: This case indicates that PE is a valuable treatment choice without adverse effects of immunosuppression in patients with fulminant lupus myocarditis and coexisting infection.
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Hyperoxia-induced acute lung injury (HALI) is a severe side effect of refractory hypoxemia treatment, for which no effective therapeutic strategy is available. Here, we found that the lung miR-21-5p level was significantly decreased in the rats subjected to hyperoxia. Further, we presented evidence that miR-21-5p was a crucial regulator of mitophagy and mitochondrial dysfunction. Moreover, it proved that miR-21-5p regulated hyperoxia-induced mitophagy and mitochondrial dysfunction by directly binding to the target gene PGAM5. In conclusion, for the first time, we found that miR-21-5p could directly suppress mitophagy and mitochondrial damage during HALI formation.
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Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/genética , Hiperoxia/complicaciones , MicroARNs/metabolismo , Proteínas Mitocondriales/metabolismo , Mitofagia/genética , Fosfoproteínas Fosfatasas/metabolismo , Lesión Pulmonar Aguda/patología , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/patología , Animales , Masculino , Mitocondrias/metabolismo , Modelos Biológicos , Ratas Sprague-DawleyRESUMEN
Inhibiting apoptosis of type II alveolar epithelial cells (AEC II) is an effective way to decrease hyperoxic acute lung injury (HALI); however, the specific underlying molecular mechanisms have not yet been fully elucidated. Although miRNA215p has previously been reported to decrease H2O2induced AEC II apoptosis by targeting PTEN in vitro, whether miR215p can decrease HALI in vivo and the downstream molecular mechanisms remain unclear. In the present study, rats were endotracheally administered with an miR215pencoding (AAV6miR215p) or a negative control adenovirus vector, and then a HALI model was established by exposure to hyperoxia. At 3 weeks following the administration of AAV6miR215p, the severity of HALI was decreased, as evidenced by the improved outcome of the oxygenation index, respiratory index, wet/dry weight ratio and pathological scores of the HALI lungs. To further investigate the underlying mechanisms, AEC II cells were isolated from the lungs of the experimental rats and cultured. The expression levels of miR215p and its target gene, PTEN, were detected, as well as the levels of phosphorylated and total AKT. In addition, the apoptosis rate of AEC II was detected by flow cytometry. The results demonstrated that AAV6miR215p administration increased the miR215p levels in primary AEC II cells, while it decreased the expression levels of PTEN. miR215p overexpression also increased AKT phosphorylation in AEC II cells from the HALI lungs compared with that of the HALI alone group and the control virus group. The present study indicated that miR215p ameliorated HALI in vivo, which may have resulted from the inhibition of PTEN/AKTinduced apoptosis of AEC II cells. These findings suggest that miR215p and PTEN/AKT signaling might serve as potential targets for HALI treatment.
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Lesión Pulmonar Aguda/metabolismo , Células Epiteliales Alveolares/metabolismo , Apoptosis/fisiología , Hiperoxia/metabolismo , MicroARNs/metabolismo , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Lesión Pulmonar Aguda/patología , Animales , Modelos Animales de Enfermedad , Femenino , Pulmón/patología , Masculino , Fosfohidrolasa PTEN/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
OBJECTIVE: To investigate the effect of overexpression of microRNA-21-5p (miR-21-5p) on early apoptosis of type II alveolar epithelial cells (AEC II) in rats with hyperoxic acute lung injury (HALI). METHODS: The Sprague-Dawley (SD) rats were randomly divided into four groups: control group (CON group), hyperoxia group (H group), overexpression group (OE group) and empty vector group (EV group), with 20 rats in each group. HALI animal model was made by inhaling high concentration oxygen (oxygen concentration ≥ 90%); CON group was arranged to inhale room air. The miR-21-5p adeno-associated virus-6 (AAV-6) overexpression vectors or empty vectors were dripped into the lungs of OE group and EV group through tracheal tube, respectively. The hyperoxia model was prepared after 3 weeks of feeding. At 0, 24, 48 and 60 hours after making model, 5 rats were selected to detect lung injury parameters: oxygenation index (OI), respiratory index (RI), wet/dry ratio (W/D), pathological injury score of lung tissue; real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-21-5p in AEC II, and flow cytometry was used to detect the early apoptotic rate of AEC II. RESULTS: (1) The lung injury parameters: in H group, the OI gradually decreased with time, but the RI, lung W/D ratio and pathological score increased gradually with time, the difference between CON group was statistically significant at 24 hours [OI (mmHg, 1 mmHg = 0.133 kPa): 336.04±5.79 vs. 400.22±19.70, RI: 0.20±0.02 vs. 0.10±0.06, lung W/D ratio: 5.04±0.09 vs. 4.85±0.09, lung tissue pathological score: 0.13±0.01 vs. 0.07±0.01, all P < 0.05]. It indicated that HALI model could be successfully established by inhaling high concentration oxygen continuously. (2) The expression of miR-21-5p: the miR-21-5p was gradually increased in H, OE and EV groups, and the expression of miR-21-5p was significantly higher than that in CON group at 24, 48 and 60 hours. Compared with H group, the expression of miR-21-5p was significantly increased further in OE group at 0, 24, 48 and 60 hours (2-ΔΔCt: 3.75±0.11 vs. 0.98±0.14, 3.98±0.12 vs. 1.18±0.13, 4.28±0.18 vs. 1.49±0.06, 4.66±0.12 vs. 1.80±0.12, all P < 0.05). (3) The early apoptosis of AEC II: the early apoptosis rate gradually increased with time in H, OE and EV groups, and the early apoptosis of AEC II was significantly higher than that in CON group at 24, 48 and 60 hours. Compared with H group, the early apoptosis rate was significantly decreased in OE group at 24, 48 and 60 hours [(1.22±0.63)% vs. (2.84±0.59)%, (5.76±0.18)% vs. (13.10±2.01)%, (29.48±0.48)% vs. (49.04±1.36)%, all P < 0.05]. (4) There was no significant difference in the expression of miR-21-5p and the early apoptosis of AEC II cells between EV group and H group at each time point. CONCLUSIONS: Overexpression of miR-21-5p could inhibit the early apoptosis of AECII in rats with HALI.
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Lesión Pulmonar Aguda , Hiperoxia , MicroARNs/metabolismo , Células Epiteliales Alveolares , Animales , Apoptosis , Pulmón , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyRESUMEN
Hyperoxia-induced acute lung injury (HALI) is a kind of iatrogenic pulmonary dysfunction caused by the prolonged exposure to high concentrations of oxygen, which is commonly seen in the treatment of refractory hypoxemia. Agmatine (AGM), a biogenic amine metabolite of l-arginine, induces a variety of physiological and pharmacological effects in the body. In this study, we investigated the protective effect of AGM on hyperoxia-induced lung injury and explored the underlying mechanism. A series of methods were used including flow cytometry, tunnel assay, dual-luciferase reporter assay, qRT-PCR and Western blotting. The results indicate that AGM can protect hyperoxia-induced lung injury. Further studies suggest that AGM decreased the upregulated expression of lncRNA gadd7 caused by hyperoxia and due to the presence of the competitive binding of lncRNA gadd7 and MFN1 to miR-125a, AGM indirectly decreased MFN1 protein expression to inhibit the cells apoptosis. In conclusion, AGM protects hyperoxia-induced lung injury by decreasing the expression of lncRNA gadd7 to regulate MFN1 expression.
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Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/etiología , Agmatina/uso terapéutico , Hiperoxia/complicaciones , Sustancias Protectoras/uso terapéutico , ARN Largo no Codificante/genética , Lesión Pulmonar Aguda/genética , Animales , Células Cultivadas , Hiperoxia/genética , Masculino , Ratas Sprague-Dawley , Regulación hacia Arriba/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate the effect of heme oxygenase-1 (HO-1) on the apoptosis of type II alveolar epithelial cells (AEC-II) in rats with hyperoxia-induced acute lung injury (HALI). METHODS: Twenty-four healthy male Sprague-Dawley (SD) rats were randomly divided into 4 groups (n = 6): control group, HALI group, HO-1 group, and HO-1 inhibition group. The control group was fed in the room air; the HALI group was fed in the hyperoxia box (the oxygen concentration was more than 90%, the temperature was kept at 25-27 centigrade, the humidity was maintained at 50%-70%, and the CO2 concentration was less than 0.5%); the HO-1 group was fed in the hyperoxia box after HO-1 (0.2 µmol/L) treatment; and the HO-1 inhibition group was fed in the hyperoxia box after treatment with zinc protoporphyrin IX (20 µmol/L). After 48 hours of hyperoxia treatment, rats were sacrificed, left upper lung tissue was stained with hematoxylin-eosin (HE) and the pathological changes of lung tissue were observed under light microscope. The ratio of wet/dry weight (W/D) was measured in the lower left lung. AEC II was extracted from the right lung tissue, the apoptosis rate was detected by flow cytometry, and the expressions of apoptosis-related proteins Bcl-2 and caspase-3 were detected by Western Blot. RESULTS: (1) It was shown by light microscopy that the lung tissue structure of the control group was clear. In HALI group and HO-1 inhibitor group, the lung tissue structure was disordered, alveolar wall was broken and fused into pulmonary alveoli, alveolar septum was obviously swollen and widened, a large number of inflammatory cells infiltrated, and edema fluid and inflammatory cells appeared in alveolar cavity. The pathological changes of lung tissue in HO-1 group were significantly less than those in HALI group. (2) Compared with the control group, the lung W/D ratio, the apoptosis rate of AEC II and the expression of Bcl-2 protein in the HALI group and the HO-1 inhibitor group were significantly increased, and the expression of caspase-3 was significantly decreased [lung W/D ratio: 4.61±0.41 vs. 3.68±0.45, apoptosis rate of AEC II: (42.44±0.93)% vs. (24.74±0.64)%, Bcl-2 (integral absorbance): 0.72±0.18 vs. 0.41±0.12, caspase-3 (integral absorbance): 1.32±0.32 vs. 1.81±0.69, all P < 0.05]. Compared with the HALI group, the lung W/D ratio, the apoptosis rate of AEC II, the expression of Bcl-2 protein in HO-1 group were significantly decreased, and the expression of caspase-3 was significantly increased [lung W/D ratio: 3.82±0.28 vs. 4.61±0.41, apoptosis rate of AEC II: (26.67±1.58)% vs. (42.44±0.93)%, Bcl-2 (integral absorbance): 0.39±0.08 vs. 0.72±0.18, caspase-3 (integral absorbance): 1.78±0.46 vs. 1.32±0.32, all P < 0.05]. There was no significant difference between HO-1 inhibitor group and HALI group. CONCLUSIONS: HO-1 can reduce the apoptosis rate of AEC II in rats with HALI, which may be related to the expressions of apoptosis related proteins Bcl-2 and caspase-3.
Asunto(s)
Células Epiteliales Alveolares/enzimología , Apoptosis/efectos de los fármacos , Hemo-Oxigenasa 1/farmacología , Lesión Pulmonar Aguda/etiología , Animales , Hiperoxia/complicaciones , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Hyperoxiainduced acute lung injury (HALI) as one of the most common complications in patents on mechanical ventilation, and there are no efficient methods to overcome this at present. It was hypothesized that microRNA 215p(miR215p) can promote the survival of type II alveolar epithelial cells (AECII), alleviating HALI. The present study aimed to combine gene chip analysis with the overexpression miR215p to develop a novel therapeutic option for HALI. It was found that AECII apoptosis was an important pathogenic event in the development of HALI, and the overexpression of miR215p prevented HALI, associated with reducing AECII apoptosis. These results were obtained using adenoviral/lentiviral vectors, which overexpressed miR215p, to transfect AECII cells in vitro and in vivo. It was found that the overexpression of miR215p reduced the apoptotic rate of the AECII cells. In addition, miR215p decreased the ratio of Bcell lymphoma 2 (Bcl2)associated X protein/Bcl2 and the expression of caspase3. It was also revealed that the overexpression of miR215p alleviated acute lung injury in adult rats exposed to a hyperoxic environment. These results suggest that miR215p may become a novel therapeutic option for patients with HALI, by protecting AECII cells from apoptosis.
Asunto(s)
Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/metabolismo , Células Epiteliales Alveolares/metabolismo , Apoptosis/genética , Hiperoxia/complicaciones , Hiperoxia/metabolismo , MicroARNs/genética , Lesión Pulmonar Aguda/patología , Lesión Pulmonar Aguda/fisiopatología , Células Epiteliales Alveolares/patología , Células Epiteliales Alveolares/ultraestructura , Animales , Biomarcadores , Biopsia , Modelos Animales de Enfermedad , Femenino , Perfilación de la Expresión Génica , Masculino , Ratas , Reproducibilidad de los Resultados , Pruebas de Función RespiratoriaRESUMEN
OBJECTIVE: To investigate the influence of continuous veno-venous hemofiltration (CVVH) on cardiac output (CO) value and parameters of hemodynamics monitored by transpulmonary thermodilution technique in critical patients. METHODS: A prospective cohort study was conduced. Sixty-two critical patients admitted to intensive care unit (ICU) of Zunyi Medical College Affiliated Hospital from January 2011 to October 2015 were enrolled. All of the patients received CVVH through femoral vein puncture catheter. The CO value was monitored before CVVH operation, immediately after CVVH operation (8?centigrade normal saline was injected immediately after the output of blood from the arterial end), 5 minutes after operation, the time at the sudden interruption (press pause key after 10 minutes of operation) and resumed immediately, 15 minutes and 30 minutes after operation by pulse-indicated continuous cardiac output (PiCCO) with transpulmonary thermodilution method. The changes in heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), and blood temperature were observed at all time points. RESULTS: From CVVH before start to 5 minutes thereafter, CO values were not significantly changed in patients, fluctuating in 6.96 (7.33, 8.67)-6.98 (6.43, 7.45) L/min. When CVVH was suddenly interrupted, CO value was immediately increased to the peak 8.04 (7.36, 8.77) L/min, which showed statistically significant difference as compared with other time points (all P < 0.01). Immediately after the CVVH recovery from interruption, the CO value dropped to 4.71 (4.14, 7.26) L/min, and it was significantly lower than those at other time points (all P < 0.01). With the CVVH recovery, the patients' CO value was gradually restored to the stable operation ahead of interruption [4.71 (4.14, 7.26)-6.85 (6.08, 7.26) L/min]. During CO monitoring, HR, MAP, CVP and blood temperature of the patients were at the same level, and no significant changes were founded. CONCLUSIONS: CVVH interruption of immediate PiCCO monitoring CO value were significantly increased, immediately after the CVVH recovery the CO value were significantly reduced, and the normal operation of CVVH did not affect the CO value monitoring. Hemodynamics and blood temperature of all patients were stable during CVVH.
Asunto(s)
Gasto Cardíaco , Hemofiltración , Monitoreo Fisiológico , Termodilución , Presión Arterial , Presión Venosa Central , Frecuencia Cardíaca , Hemodinámica , Humanos , Unidades de Cuidados Intensivos , Estudios ProspectivosRESUMEN
Total synthesis of naturally occurring spirobisnaphthalene palmarumycin CP17 and its methoxy analogues was first achieved through Friedel-Crafts acylation, Wolff-Kishner reduction, intramolecular cyclization, ketalization, benzylic oxidation, and demethylation using the inexpensive and readily available methoxybenzene, 1,2-dimethoxybenzene and 1,4-dimethoxybenzene and 1,8-dihydroxynaphthalene as raw materials. Demethylation with (CH3)3SiI at ambient temperature resulted in ring A aromatization and acetal cleavage to give rise to binaphthyl ethers. The antifungal activities of these spirobisnaphthalene derivatives were evaluated, and the results revealed that 5 and 9b exhibit EC50 values of 9.34 µg/mL and 12.35 µg/mL, respectively, against P. piricola.