RESUMO
Background: This study sought to investigate therapeutic effects of hydrogen-rich saline (HRS) combined with hyperbaric oxygen (HBO2) in an experimental rat model of acute lung injury (ALI). Method: Forty male Sprague-Dawley rats were randomly divided into sham, LPS, LPS + HBO2, LPS + HRS, and LPS + HBO2 + HRS groups. After an intratracheal injection of LPS-induced ALI, the rats were given a single-agent HBO2 or HRS or HBO2 + HRS treatment. The treatments were continued for three days in this experimental rat model of ALI. At the end of experiment, the lung pathological, inflammatory factors, and cell apoptosis in the pulmonary tissue were detected by Tunel method and cell apoptosis rate was calculated accordingly. Results: In the groups treated with HBO2 + HRS, pulmonary pathological data, wet-dry weight ratio, and inflammatory factors of pulmonary tissues and alveolar lavage fluid were significantly superior to those of the sham group (pâº0.05). Cell apoptosis detection revealed that no single agent treatment of HRS or HBO2, or combination treatment, could alleviate all cell apoptosis. HRS combined with HBO2 treatment was superior to single treatment (pâº0.05). Conclusion: HRS or HBO2 single treatment could decrease inflammatory cytokines release in lung tissue, reduce the accumulation of oxidative products and alleviate apoptosis of pulmonary cells, then lead to positive therapeutic effects on ALI induced by LPS. Furthermore, HBO2 combined with HRS treatment presented a synergy effect on cell apoptosis decrease and a decline in inflammatory cytokine release and related inflammatory product generation, compared with a single treatment.
Assuntos
Lesão Pulmonar Aguda , Oxigenoterapia Hiperbárica , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Lipopolissacarídeos/efeitos adversos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/prevenção & controle , Pulmão/patologia , Oxigênio/efeitos adversos , Citocinas , Hidrogênio/uso terapêutico , Hidrogênio/farmacologiaRESUMO
BACKGROUND: This study aimed to establish and validate an easy-to-operate novel scoring system based on simple and readily available clinical indices for predicting the progression of chronic kidney disease (CKD). METHODS: We retrospectively evaluated 1045 eligible CKD patients from a publicly available database. Factors included in the model were determined by univariate and multiple Cox proportional hazard analyses based on the training set. RESULTS: Independent prognostic factors including etiology, hemoglobin level, creatinine level, proteinuria, and urinary protein/creatinine ratio were determined and contained in the model. The model showed good calibration and discrimination. The area under the curve (AUC) values generated to predict 1-, 2-, and 3-year progression-free survival in the training set were 0.947, 0.931, and 0.939, respectively. In the validation set, the model still revealed excellent calibration and discrimination, and the AUC values generated to predict 1-, 2-, and 3-year progression-free survival were 0.948, 0.933, and 0.915, respectively. In addition, decision curve analysis demonstrated that the model was clinically beneficial. Moreover, to visualize the prediction results, we established a web-based calculator ( https://ncutool.shinyapps.io/CKDprogression/ ). CONCLUSION: An easy-to-operate model based on five relevant factors was developed and validated as a conventional tool to assist doctors with clinical decision-making and personalized treatment.
Assuntos
Insuficiência Renal Crônica , Área Sob a Curva , Bases de Dados Factuais , Progressão da Doença , Humanos , Internet , Estudos RetrospectivosRESUMO
Breathing less than 50 kPa of oxygen over time can lead to pulmonary oxygen toxicity (POT). Vital capacity (VC) as the sole parameter for POT has its limitations. In this study we try to find out the changes of acid-base status in a POT rat model. Fifty male rats were randomly divided into five groups, exposed to 230 kPa oxygen for three, six, nine and 12 hours, respectively. Rats exposed to air were used as controls. After exposure the mortality and behavior of rats were observed. Arterial blood samples were collected for acid-base status detection and wet-dry (W/D) ratios of lung tissues were tested. Results showed that the acid-base status in rats exposed to 230 kPa oxygen presented a dynamic change. The primary status was in the compensatory period when primary respiratory acidosis was mixed with compensated metabolic alkalosis. Then the status changed to decompensated alkalosis and developed to decompensated acidosis in the end. pH, PCO2, HCO3-, TCO2, and BE values had two phases: an increase and a later decrease with increasing oxygen exposure time, while PaO2 and lung W/D ratio showed continuously increasing trends with the extension of oxygen exposure time. Lung W/D ratio was significantly associated with PaO2 (r = 0.6385, p = 0.002), while other parameters did not show a significant correlation. It is concluded that acid-base status in POT rats presents a dynamic change: in the compensatory period first, then turns to decompensated alkalosis and ends up with decompensated acidosis status. Blood gas analysis is a useful method to monitor the development of POT.
Assuntos
Desequilíbrio Ácido-Base/sangue , Acidose Respiratória/metabolismo , Alcalose Respiratória/metabolismo , Oxigenoterapia Hiperbárica/efeitos adversos , Oxigênio/toxicidade , Desequilíbrio Ácido-Base/etiologia , Animais , Pressão Atmosférica , Bicarbonatos/sangue , Análise Química do Sangue , Gasometria , Dióxido de Carbono/sangue , Oxigenoterapia Hiperbárica/métodos , Pulmão/patologia , Masculino , Modelos Animais , Tamanho do Órgão , Pressão Parcial , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Capacidade VitalRESUMO
The present study was designed to assess the stress responses to a simulation model of the undersea environment that is similar to some undersea working conditions such as submarine rescue, underwater salvage and underwater construction. Restraint, hyperbaric air and immersion were chosen to produce the simulation stress model in rats for four hours. Rats were randomized into five groups: control group, restraint (R) group, hyperbaric air (H) group, restraint plus hyperbaric air (RH) group, and restraint plus hyperbaric air plus immersion (RHI) group. The results showed that the responses to the simulation stress model of the undersea environment induced by R, H, RH and RHI involved the upregulated norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) of the central nervous system (CNS), upregulated adrenocorticotropic hormone (ACTH), corticosterone (CORT) and blood glucose of the neuroendocrine system, upregulated interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) of the immune system, and increased anxiety in rats. Compared with hyperbaric air, restraint tended to activate stronger stress responses. Conclusively, this work established a simulation stress model of the undersea environment induced by restraint, hyperbaric air and immersion. It further provided experimental data of such a model that showed significant activation of the CNS, neuroendocrine and immune systems and anxiety in rats. In this experiment we provided an experimental basis for undersea work such as working aboard a submarine.
Assuntos
Ansiedade/etiologia , Sistema Nervoso Central/metabolismo , Sistema Imunitário/metabolismo , Sistemas Neurossecretores/metabolismo , Estresse Fisiológico/fisiologia , Hormônio Adrenocorticotrópico/metabolismo , Animais , Glicemia/metabolismo , Corticosterona/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Teste de Labirinto em Cruz Elevado , Imersão , Interleucina-1/metabolismo , Interleucina-6 , Masculino , Norepinefrina/metabolismo , Teste de Campo Aberto , Pressão , Distribuição Aleatória , Ratos , Ratos Wistar , Restrição Física , Serotonina/metabolismo , Treinamento por Simulação/métodos , Estresse Psicológico/fisiopatologia , Medicina Submarina , Fator de Necrose Tumoral alfa/metabolismo , Regulação para CimaRESUMO
Exercise plays an important role in the prevention and treatment of chronic liver disease and associated metabolic disorders. A single bout of exercise induces tissue blood flow redistribution, which decreases splanchnic circulation and leads to physiologic hypoxia in the gastrointestinal system and liver. The transcription factor, hypoxia inducible factor-1α (HIF-1α), and its regulator, prolylhydroxylase 2 (PHD2), play pivotal roles in the response to oxygen flux by regulating downstream gene expression levels in the liver. We hypothesized that exercise increases the HIF-1α levels in the liver, and that the hepatic PHD2/HIF-1α axis is involved in postexercise restoration of systemic energy homeostasis. Through constant O2 consumption, CO2 production, food and water intake, and physical activity detection with metabolic chambers, we observed that one 30-min session of swimming exercise enhances systemic energy metabolism in mice. By using the noninvasive bioluminescence imaging ROSA26 oxygen-dependent domain Luc mouse model, we reveal that exercise increases in vivo HIFα levels in the liver. Intraperitoneal injections of the PHD inhibitor, dimethyloxalylglycine, mimicked exercise-induced HIFα increase, whereas the HIF-1α inhibitor, PX-478, blocked this effect. We next constructed liver-specific knockout (LKO) mouse models with albumin- Cre-mediated, hepatocyte-specific Hif1a and Phd2 deletion. Compared with their controls, Hif1a-LKO and Phd2-LKO mice exhibited distinct patterns of hepatic metabolism-related gene expression profiles. Moreover, Hif1a-LKO mice failed to restore systemic energy homeostasis after exercise. In conclusion, the current study demonstrates that a single bout of exercise disrupts systemic energy homeostasis, increasing the HIF-1α levels in the liver. These findings also provide evidence that the hepatic PHD2/HIF-1α axis is involved in postexercise systemic metabolic homeostasis.-Luo, B., Xiang, D., Wu, D., Liu, C., Fang, Y., Chen, P., Hu, Y.-P. Hepatic PHD2/HIF-1α axis is involved in postexercise systemic energy homeostasis.
Assuntos
Homeostase/genética , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Fígado/metabolismo , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Animais , Linhagem Celular Tumoral , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Camundongos Transgênicos , Oxigênio/metabolismo , Prolil Hidroxilases/genética , RNA Mensageiro/genéticaRESUMO
Plants often develop the capacity to tolerate moderate and reversible environmental stresses, such as drought, and to re-establish normal development once the stress has been removed. An example of this phenomenon is provided by cut rose (Rosa hybrida) flowers, which experience typical reversible dehydration stresses during post-harvest handling after harvesting at the bud stages. The molecular mechanisms involved in rose flower dehydration tolerance are not known, however. Here, we characterized a dehydration- and abscisic acid (ABA)-induced ferritin gene (RhFer1). Dehydration-induced free ferrous iron (Fe2+ ) is preferentially sequestered by RhFer1 and not transported outside of the petal cells, to restrict oxidative stresses during dehydration. Free Fe2+ accumulation resulted in more serious oxidative stresses and the induction of genes encoding antioxidant enzyme in RhFer1-silenced petals, and poorer dehydration tolerance was observed compared with tobacco rattle virus (TRV) controls. We also determined that RhABF2, an AREB/ABF transcription factor involved in the ABA signaling pathway, can activate RhFer1 expression by directly binding to its promoter. The silencing of RhABF2 decreased dehydration tolerance and disrupted Fe homeostasis in rose petals during dehydration, as did the silencing of RhFer1. Although both RhFer1 and Fe transporter genes are induced during flower natural senescence in plants, the silencing of RhABF2 or RhFer1 accelerates the petal senescence processes. These results suggest that the regulatory module RhABF2/RhFer1 contributes to the maintenance of Fe levels and enhances dehydration tolerance through the action of RhFer1 locally sequestering free Fe2+ under dehydration conditions, and plays synergistic roles with transporter genes during flower senescence.
Assuntos
Ferritinas/metabolismo , Ferro/metabolismo , Rosa/genética , Fatores de Transcrição/metabolismo , Ácido Abscísico/metabolismo , Desidratação , Secas , Ferritinas/genética , Flores/citologia , Flores/genética , Flores/fisiologia , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas/genética , Rosa/citologia , Rosa/fisiologia , Estresse Fisiológico , Fatores de Transcrição/genéticaRESUMO
Statins, which are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase competitive inhibitors, not only lower blood cholesterol but also exert pleiotropic and beneficial effects in various diseases. However, the effects of statins on acute lung injury (ALI) induced by hyperbaric oxygen (HBO) have not been investigated. The present study is the first to investigate the effects of simvastatin in ALI induced by HBO in 8- to 9-wk-old C57BL/6 mice exposed to 0.23 MPa [=2.3 atmosphere absolute (ATA)] hyperoxia (≥95% O2) for 6 h. Mice were either given simvastatin (20 mg·kg·-1·day-1) in saline or a saline vehicle for 3 days before oxygen exposure. Lung tissue, serum, and bronchoalveolar lavage fluid (BALF) were collected for analysis of proapoptotic proteins, low-density lipoprotein cholesterol (LDL-C) levels, and lung inflammation. Simvastatin treatment significantly reduced lung permeability, serum LDL-C levels, tissue apoptosis, and inflammation. However, simvastatin treatment had no effect on antioxidant enzyme activity, nicotinamide adenine dinucleotide phosphate oxidase 4 (NADPH4) expression, and Akt phosphorylation levels. Furthermore, we investigated the role of endothelial nitric oxide synthase (eNOS) in simvastatin protection through inhibiting eNOS activity with NG-nitro-l-arginine methyl ester (l-NAME; 20 mg/kg). Results showed that the beneficial effects of simvastatin on ALI induced by HBO (antiinflammatory, antiapoptotic, lipid lowering, and reduction in lung permeability) were reversed. These results showed that simvastatin curbs HBO-induced lung edema, permeability, inflammation, and apoptosis via upregulating eNOS expression and that simvastatin could be an effective therapy to treat prolonged HBO exposure.
Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Anticolesterolemiantes/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Oxigenoterapia Hiperbárica/efeitos adversos , Óxido Nítrico Sintase Tipo III/metabolismo , Sinvastatina/farmacologia , Lesão Pulmonar Aguda/enzimologia , Lesão Pulmonar Aguda/etiologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Ativação TranscricionalRESUMO
Nuclear factor kappa B (NF-κB) is the critical transcriptional factor in the pathogenesis of acute lung injury (ALI). NF-κB regulates the expression changes of inflammatory factors such as tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß) and interleukin 6 (IL-6). In a previous study we showed that decompression sickness (DCS) caused by simulated unsafe fast buoyancy ascent escape (FBAE) could result in ALI, which was characterized by expression changes of inflammatory factors in rat lung tissue. The purpose of the present work was to study the roles of NF-κB and TNF-α in the process of DCS-induced rat lung injury caused by simulated unsafe FBAE. The research methods aimed to detect the rat lung tissue messenger ribonucleic acid (mRNA) and protein level variations of NF-κB, inhibitory ×B (I×B), TNF-α, IL-1ß, IL-6, IL-10 and IL-13 by using pretreatment of the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) and TNF-α antibody (Ab). Our experimental results demonstrated that PDTC could improve the survival rate of the rats with DCS caused by unsafe FBAE more effectively than TNF-α Ab. However, the inhibition of TNF-α Ab on the nuclear translocated protein expression of NF-κB was more effective than PDTC. Both PDTC and TNF-α Ab can abrogate the increment of the rat lung tissue mRNA levels of TNF-α, IL-1ß, IL-6 and protein levels of NF-κB, TNF-α, IL-1ß effectively and increase the rat lung tissue content of I×B significantly. In conclusion, TNF-α-mediated NF-κB signaling may be one of the critical signaling pathways in the pathogenesis of DCS-induced rat lung injury caused by simulated unsafe FBAE. PDTC may ameliorate this type of injury partly through inhibiting the NF-κB pathway.
Assuntos
Lesão Pulmonar Aguda/metabolismo , Antioxidantes/farmacologia , Doença da Descompressão/complicações , Interleucinas/metabolismo , NF-kappa B/metabolismo , Pirrolidinas/farmacologia , Tiocarbamatos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/patologia , Animais , Interleucina-10/metabolismo , Interleucina-13/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Masculino , NF-kappa B/antagonistas & inibidores , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Taxa de Sobrevida , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
The pentacyclic triterpenoid corosolic acid was metabolized by Cunninghamella echinulata CGMCC 3.2000 to its C-24 aldehyde group metabolite and five other hydroxylated metabolites: madasiatic acid (2), 2α, 3ß, 7ß-trihydroxyurs-12-en-28-oic acid (3), 2α, 3ß, 15α-trihydroxyurs-12-en-28-oic acid (4), 2α, 3ß, 6ß, 7ß-tetrahydroxyurs-12-en-28-oic acid (5), 2α, 3ß, 7ß, 15α-tetrahydroxyurs-12-en-28-oic acid (6), and 2α, 3ß,7ß-trihydroxy-24-al-urs-12-en-28-oic acid (7); compounds 3, 5, and 7 were new compounds. The α-glucosidase inhibitory effects of the metabolites were also evaluated.
Assuntos
Cunninghamella/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , Triterpenos/farmacologia , Biotransformação , Diabetes Mellitus/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/química , Hipoglicemiantes/química , Estrutura Molecular , Estereoisomerismo , Triterpenos/química , alfa-Glucosidases/efeitos dos fármacos , alfa-Glucosidases/metabolismoRESUMO
Decompression sickness (DCS) is a specific diving injury which sometimes may be life-threatening. Previous studies suggested that simvastatin (SIM) can protect against pathological inflammation and tissue damage. This study aimed to investigate whether SIM pretreatment could exert its beneficial effects on DCS. SIM was administered orally to adult male Sprague-Dawley rats for two weeks (2 mg/kg/day), then rats were subjected to a simulated dive at 700 kPa air pressure for 100 minutes before rapid decompression. After 30 minutes of symptom observation, lung tissue and blood samples were collected for further analysis. Compared to the vehicle-control, SIM pretreatment significantly decreased the incidence of DCS and ameliorated all parameters of pulmonary injuries, including lung dry/wet weight ratio, bronchoalveolar lavage fluid protein concentration, lung tissue malondialdehyde level and morphology. Moreover, SIM pretreatment abolished increases in systemic and pulmonary inflammation by reducing tumor necrosis factor-α levels in blood plasma and lung tissue. The results indicate that SIM may offer a novel pharmacological protection against injuries in DCS rats by inhibiting inflammatory responses. Further study is needed to understand the exact mechanisms.
Assuntos
Doença da Descompressão/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Sinvastatina/uso terapêutico , Adiposidade , Administração Oral , Animais , Líquido da Lavagem Broncoalveolar/química , Descompressão/métodos , Doença da Descompressão/epidemiologia , Doença da Descompressão/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Incidência , Inflamação/prevenção & controle , Lipídeos/sangue , Pulmão/química , Pulmão/patologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/prevenção & controle , Masculino , Malondialdeído/análise , Tamanho do Órgão , Pneumonia/prevenção & controle , Edema Pulmonar/diagnóstico , Ratos , Ratos Sprague-Dawley , Sinvastatina/administração & dosagem , Fator de Necrose Tumoral alfa/análiseRESUMO
Fast buoyancy ascent escape is one of the major naval submarine escape maneuvers. Decompression sickness (DCS) is the major bottleneck to increase the depth of fast buoyancy ascent escape. Rapid decompression induces the release of inflammatory mediators and results in tissue inflammation cascades and a protective anti-inflammatory response. In our previous study, we found that DCS caused by simulated fast buoyancy ascent escape could induce acute lung injury (ALI) and the expression changes of the proinflammatory cytokines: tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß and IL-6 in rat lung tissue. In order to study the expression change characteristics of TNF-α, IL-1ß, IL-6, IL-10 and IL-13 in the rat lung of DCS caused by simulated fast buoyancy ascent escape, we detected the rat lung mRNA and protein levels of TNF-α, IL-1ß, IL-6, IL-10 and IL-13 at 0.5 hour after DCS caused by simulated fast buoyancy ascent escape (fast escape group), compared with the normal control group (control group) and diving DCS (decompression group). We observed that DCS caused by simulated fast buoyancy ascent escape could increase the mRNA levels of TNF-α, IL-1ß, IL-6, IL-10, and the protein levels of TNF-α, IL-10 in rat lung tissue. At the same time, we found that the protein level of IL-13 was also downregulated in rat lung tissue. TNF-α, IL-10 and IL-13 may be involved in the process of the rat lung injury of DCS caused by simulated fast buoyancy ascent escape. In conclusion, the expression changes of inflammatory factors in the rat lung of DCS caused by simulated fast buoyancy ascent escape were probably different from that in the rat lung of diving DCS, which indicated that the pathological mechanism of DCS caused by simulated fast buoyancy ascent escape might be different from that of diving DCS.
Assuntos
Doença da Descompressão/metabolismo , Interleucinas/metabolismo , Pulmão/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Doença da Descompressão/etiologia , Doença da Descompressão/mortalidade , Doença da Descompressão/patologia , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-13/genética , Interleucina-13/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucinas/genética , Pulmão/patologia , Masculino , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Medicina Submarina , Fatores de Tempo , Fator de Necrose Tumoral alfa/genéticaRESUMO
Fast buoyancy ascent escape is the general submarine escape manner adopted by the majority of naval forces all over the world. However, if hyperbaric exposure time exceeds the time limit, fast buoyancy ascent escape has a high risk to result in decompression sickness (DCS). Tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 have been all implicated in the process of inflammation associated with acute lung injury (ALI). Our work demonstrated that DCS caused by simulated fast buoyancy ascent escape could induce ALß in the rat model. The purpose of the present work was to study the expression changes of TNF-α, IL-1ß and IL-6 in the rat lung affected by DCS caused by simulated fast buoyancy ascent escape. The lung tissue mRNA levels of TNF-α, Il-1ß and Il-6 were significantly increased at 0.5 hour after DCS caused by simulated fast buoyancy ascent escape. The lung contents of TNF-α, IL-1ß and IL-6 were at an expression peak at 0.5 hour, although showing no statistical difference when compared with the normal control group. In conclusion, the rat lung expression variations of TNF-α, IL-1ß and IL-6 are the most obvious at 0.5 hour within 24 hours after the lung injury by DCS caused by simulated fast buoyancy ascent escape.
Assuntos
Doença da Descompressão/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Pulmão/metabolismo , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Doença da Descompressão/patologia , Interleucina-1beta/genética , Interleucina-6/genética , Pulmão/patologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Medicina Submarina , Fatores de Tempo , Fator de Necrose Tumoral alfa/genéticaRESUMO
Recent studies have demonstrated that peroxisome proliferator-activated receptor-beta/delta (PPAR-ß/δ) has a protective effect during lung injury induced by bleomycin and polymicrobial sepsis, but its function in pulmonary oxygen toxicity is unknown. In this study, we used GW0742, a PPAR-ß/δ agonist, and GSK0660, a PPAR-ß/δ antagonist, to test the role of PPAR-ß/δ in lung injury due to hyperbaric oxygen (HBO2) exposure. Lung injury was induced in rats by HBO2 exposure (2.3 ATA, 100%O2, 8 hours). Sixty male Sprague-Dawley rats were randomly divided into 6 groups: air+vehicle, air+GW0742, air+GSK0660, HBO2+vehicle, HBO2+GW0742, and HBO2+GSK0660. Rats were injected with vehicle or GW0742 (0.3 mg/kg, i.p.) or GSK0660 (1 mg/kg, i.p.) at 1 hour, 6 hours, and 12 hours before either air or oxygen exposure. Administration of GW0742 to rats exposed to HBO2 significantly reduced the observed lung injury, extravascular lung water, total protein levels in bronchoalveolar lavage fluid, and the levels of iNOS and nNOS in the lungs when compared to untreated rats exposed to HBO2. Treatment of rats with GSK0660 exacerbated lung injury and elevated the levels of nNOS and eNOS in the lungs. In addition, nNOS and eNOS knock-out mice were examined. The results indicated that after HBO2 exposure, the lung injury was obviously decreased in the nNOS(-/-)+GSK0660 mice compared to the wild-type +GSK0660 mice; furthermore, administration of GSK0660 significantly elevated the lung injury in the eNOS(-/-) mice. Collectively, these data indicate that PPAR-ß/δ activation can protect against pulmonary oxygen toxicity in the lungs of rats through changes in the expression of NOS.
Assuntos
Lesão Pulmonar Aguda/etiologia , Óxido Nítrico Sintase/metabolismo , Oxigênio/efeitos adversos , PPAR delta/metabolismo , PPAR beta/metabolismo , Lesão Pulmonar Aguda/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , PPAR delta/agonistas , PPAR delta/antagonistas & inibidores , PPAR beta/agonistas , PPAR beta/antagonistas & inibidores , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Sulfonas , Tiazóis , Tiofenos , Regulação para CimaRESUMO
OBJECTIVE: To observe MMP9 expression in rat lungs under different degrees of hyperbaric oxygen (HBO2) exposure and to observe the relationship of tissue damage and apoptosis rate in the lung tissue. METHODS: 40 Sprague Dawley (SD) rats were randomly divided into five groups: 250 kPa oxygen exposure for two-, four-, six- and eight-hour exposures and a "normal group," each n = 8. After hyperbaric oxygen treatment, the rats were euthanized immediately to collect lung tissue. We used HE staining to detect the pathological changes and immunohistochemistry to detect in situ expression of matrix metalloproteinase 9 (MMP9). Then we tested the expression level of caspase 3 in lung tissue by Western Blot. To understand the antioxidant capacity changes, we detected superoxide dismutase (SOD) activities and malondialdehyde (MDA) contents in lung tissue during HBO2 exposure. Finally, we exposed MMP9 knockout or wild-type mice under hyperbaric oxygen for six hours, and detected the pathological changes with HE staining. RESULT: Lung tissue damage changed gradually under different degrees of hyperbaric oxygen exposure, but eased in the six-hour group. However, MMP9 expression decreased initially and then was upregulated until it reached the peak after six hours of exposure; it then reduced significantly after an eight-hour exposure. Active caspase 3 reached the highest level after eight hours. While SOD activity was upregulated only after six hours of HBO2 exposure, MDA content increased after eight hours of exposure. CONCLUSIONS: MMP9 expression was elevated after exposure to hyperbaric oxygen. This is a compensatory mechanism of the body's antioxidant response by regulating the inflammatory response. This in turn helps to reduce the apoptosis rate and protects lung tissue from oxygen toxicity.
Assuntos
Apoptose , Oxigenoterapia Hiperbárica , Pulmão/enzimologia , Metaloproteinase 9 da Matriz/metabolismo , Animais , Caspase 3/metabolismo , Técnicas de Inativação de Genes , Pulmão/metabolismo , Pulmão/patologia , Masculino , Malondialdeído/metabolismo , Metaloproteinase 9 da Matriz/genética , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Fatores de Tempo , Regulação para CimaRESUMO
Conductive hydrogels have been widely used as sensors owing to their tissue-like properties. However, the synthesis of conductive hydrogels with highly adjustable mechanical properties and multiple functions remains difficult to achieve yet highly needed. In this study, lignin hydrogel characterized by frost resistance, UV resistance, high conductivity, and highly adjustable mechanical properties without forming by-products was prepared through a rapid in-situ polymerization of acrylic acid/zinc chloride (AA/ZnCl2) aqueous solution containing lignin extract induced by the reversible quinone-catechol redox of the ZnCl2-lignin system at room temperature. Results revealed that the PAA/ZnCl2/lignin hydrogel exhibited mechanical properties with tensile stress (ranging from 0.08 to 3.28 MPa), adhesion to multiple surfaces (up to 62.05 J m-2), excellent frost resistance (-70-20 °C), UV resistance, and conductivity (0.967 S m-1), which further endow the hydrogel as potential strain and temperature sensor with wide monitor range (0-300 %), fatigue resistance, and quick response (70 ms for 150 % strain). This study proposed and developed a green, simple, economical, and efficient processing method for a hydrogel sensor in flexible wearable devices and man-machine interaction fields.
Assuntos
Hidrogéis , Lignina , Humanos , Polimerização , Condutividade Elétrica , QuinonasRESUMO
Underwater exercise is becoming increasingly prevalent, during which brain function is necessary but is also at risk. However, no study has explored how prolonged exercise affect the brain in underwater environment. Previous studies have indicated that excessive exercise in common environment causes brain dysfunction but have failed to provide appropriate interventions. Numerous evidence has indicated the neuroprotective effect of hyperbaric oxygen preconditioning (HBO-PC). The objective of this study was to investigate the cognitive effect of prolonged underwater exercise (PUE) and to explore the potential neuroprotective effect of HBO-PC in underwater environment. Rats swimming for 3â¯h in a simulated hyperbaric chamber (2.0 ATA) was used to establish the PUE animal model and HBO-PC (2.5 ATA for 1, 3,5 times respectively) was administrated before PUE. The results demonstrated that PUE triggers anxiety-like behaviors, cognitive impairment accompanied by hippocampal dysfunction, microglia activation and neuroinflammation. Conversely, 3 HBO-PC rescued anxiety-like behaviors and cognitive impairment. Mechanistically, 3 HBO-PC reduced microglia activation and switched the activated microglia from a pro-inflammatory to neuroprotective phenotype. These findings illustrated that PUE induces anxiety-like behaviors and cognitive impairment and HBO-PC of proper frequency may provide an appropriate and less invasive intervention for protecting the brain in underwater exercise.
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Maintaining cognitive integrity is crucial during underwater operations, which can significantly impact work performance and risk severe accidents. However, the cognitive effects of underwater operations and their underlying mechanism remain elusive, posing great challenges to the medical protection of professionals concerned. Here, we found that a single underwater operation session affects cognition in a time-dependent model. Prolonged exposure elicits significant cognitive impairment and hippocampal dysfunction, accompanied by increased neuroinflammation. Furthermore, RNA sequencing (RNA-seq) analysis revealed the involvement of neuroinflammation and highlighted the critical role of CCR3. Knockdown of CCR3 significantly rescued cognitive impairment and hippocampal dysfunction and reversed the upregulation of pro-inflammatory cytokines, by switching the activated microglia from a pro-inflammatory to a neuroprotective phenotype. Taken together, these results highlighted the time-dependent effects of a single underwater operation session on cognitive function. Knocking down CCR3 can attenuate neuroinflammation by regulating polarization of activated microglia, thereby alleviating prolonged underwater operations-induced cognitive impairment.
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Cellulose, as a biomass resource, has attracted increasingly attention and extensive research by virtue of its widely sources, ideal degradability, good mechanical properties and easy modification due to its rich hydroxyl groups. Nevertheless, it is still a challenge to attain high performance cellulose-based composite film materials with diverse functional combinations. In this work, we developed a multifunctional cellulose-based film via a facile impregnation-curing strategy. Here, benzoxazine resin (BR) is used as an optically functional component to endow the microfibrillated cellulose (MFC) film with powerful light management capabilities including UV and blue light double shielding, high transmittance, and high haze. Meanwhile, the introduction of tannic acid (TA) substantially enhanced the mechanical properties of the film, including tensile strength and toughness, by constructing energy-sacrificial bonds. An effective self-healing of the film was achieved by controlling the degree of BR curing. The final films exhibited 98.24â¯% UV shielding and 89.98â¯% blue light blocking, good mechanical properties including a tensile strength of 202.21â¯MPa and tensile strain of 7.1â¯%, as well as desirable thermal healing properties supported by incompletely cured BR. This work may provide new insights into the high-value utilization of biomass resources.
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The increased use and expansion of biomass applications offer a viable approach to diminish reliance on petroleum-derived resources and promote carbon neutrality. Cellulose, being the most abundant natural polymer on Earth, has garnered considerable attention. This study introduces a straightforward method to fabricate a cellulose-based multifunctional composite film designed for efficient light management, specifically featuring flame retardant and thermal-healing capabilities. The film incorporates a microfibrillated cellulose (MFC) matrix with functional components, namely benzoxazine resin (BR) and 2-hydroxyethyl methacrylate phosphate (HEMAP). Utilizing dynamic covalent crosslinking, the composite films exhibit satisfactory self-healing properties. The combined effects of BR and HEMAP contribute to the effective flame retardancy of the composite film. Furthermore, the resulting film shields ultraviolet and blue light, offering comfortable interior lighting by mitigating harsh light and extending light propagation. The film also demonstrates favorable water resistance and high tensile strength. The exceptional multifunctional properties, coupled with its safety and extended service life, position it as a potential optical management film for smart building materials.
Assuntos
Celulose , Retardadores de Chama , Polímeros , Benzoxazinas , BiomassaRESUMO
Bacopaside I (BSI) is a natural compound that is difficult to absorb orally but has been shown to have antidepressant effects. The microbiota-gut-brain axis is involved in the development of depression through the peripheral nervous system, endocrine system, and immune system and may be a key factor in the effect of BSI. Therefore, this study aimed to investigate the potential mechanism of BSI in the treatment of depression via the microbiota-gut-brain axis and to validate it in a fecal microbiota transplantation model. The antidepressant effect of BSI was established in CUMS-induced mice using behavioral tests and measurement of changes in hypothalamicpituitaryadrenal (HPA) axis-related hormones. The improvement of stress-induced gut-brain axis damage by BSI was observed by histopathological sections and enzyme-linked immunosorbent assay (ELISA). 16 S rDNA sequencing analysis indicated that BSI could modulate the abundance of gut microbiota and increase the abundance of probiotic bacteria. We also observed an increase in short-chain fatty acids, particularly acetic acid. In addition, BSI could modulate the disruption of lipid metabolism induced by CUMS. Fecal microbiota transplantation further confirmed that disruption of the microbiota-gut-brain axis is closely associated with the development of depression, and that the microbiota regulated by BSI exerts a partial antidepressant effect. In conclusion, BSI exerts antidepressant effects by remodeling gut microbiota, specifically through the Lactobacillus and Streptococcus-acetic acid-neurotrophin signaling pathways. Furthermore, BSI can repair damage to the gut-brain axis, regulate HPA axis dysfunction, and maintain immune homeostasis.