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Irisin is a muscle factor induced by exercise, generated through the proteolytic cleavage of the membrane protein fibronectin type III domain-containing protein 5 (FNDC-5). Numerous studies have shown that irisin plays a significant role in regulating glucose and lipid metabolism, inhibiting oxidative stress, reducing systemic inflammatory responses, and providing neuroprotection. Additionally, irisin can exert immunomodulatory functions by regulating regulatory T cells (Tregs). Tregs are a highly differentiated subset of mature T cells that play a key role in maintaining self-immune homeostasis and are closely related to infections, inflammation, immune-related diseases, and tumors. Irisin exerts persistent positive effects on Treg cell functions through various mechanisms, including regulating Treg cell differentiation and proliferation, improving their function, modulating the balance of immune cells, increasing the production of anti-inflammatory cytokines, and enhancing metabolic functions, thereby helping to maintain immune homeostasis and prevent immune-related diseases. As an important myokine, irisin interacts with receptors on the cell membrane, activating multiple intracellular signaling pathways to regulate cell metabolism, proliferation, and function. Although the specific receptor for irisin has not been fully identified, integrins are considered potential receptors. Irisin activates various signaling pathways, including AMPK, MAPK, and PI3K/Akt, through integrin receptors, thereby exerting multiple biological effects. These research findings provide important clues for understanding the mechanisms of irisin's action and theoretical basis for its potential applications in metabolic diseases and immunomodulation. This article reviews the relationship between irisin and Tregs, as well as the research progress of irisin in immune-related diseases such as multiple sclerosis, myasthenia gravis, acquired immune deficiency syndrome, type 1 diabetes, sepsis, and rheumatoid arthritis. Studies have revealed that irisin plays an important role in immune regulation by improving the function of Tregs, suggesting its potential application value in the treatment of immune-related diseases.
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Fibronectinas , Linfócitos T Reguladores , Humanos , Fibronectinas/metabolismo , Fibronectinas/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Doenças do Sistema Imunitário/tratamento farmacológico , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/metabolismoRESUMO
Intestinal ischemia-reperfusion injury (IRI) is a potentially severe clinical syndrome after major surgical procedures. In addition to causing intestinal mucosa injury, intestinal IRI further damages distant organs, causing the severity of the condition in patients. So far, effective therapy for intestinal IRI is still absent, and the survival rate of the patients is low. Previous experimental studies have shown that some anesthetics can alleviate intestinal IRI and protect organs while exerting their pharmacological effects, indicating that reasonable perioperative anesthesia management may provide potential benefits for patients to avoid intestinal IRI. These meaningful findings drive scholars to investigate the mechanism of anesthetics in treating intestinal IRI in-depth to discuss the possible new clinical uses. In the present mini-review, we will introduce the protective effects of different anesthetics in intestinal IRI to help us enrich our knowledge in this area.
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Global cerebral ischemia/reperfusion (GCI/R) injury poses a risk for cognitive decline, with neuroinflammation considered pivotal in this process. This study aimed to unravel the molecular mechanisms underlying GCI/R injury and propose a potential therapeutic strategy for associated cognitive deficits. Utilizing bioinformatics analysis of a public microarray profile (GSE30655 and GSE80681) in cerebral ischemic mice, it was observed that neuroinflammation emerged as a significant gene ontology item, with an increase in the expression of thioredoxin-interacting protein (TXNIP) and NLRP3 genes. Experimental models involving bilateral occlusion of the common carotid arteries in mice revealed that GCI/R induced cognitive impairment, along with a time-dependent increase in TXNIP and NLRP3 levels. Notably, TXNIP knockdown alleviated cognitive dysfunction in mice. Furthermore, the introduction of adeno-associated virus injection with TXNIP knockdown reduced the number of activated microglia, apoptosis neurons, and levels of oxidative stress and inflammatory cytokines in the hippocampus. Collectively, these findings underscore the significance of TXNIP/NLRP3 in the hippocampus in exacerbating cognitive decline due to GCI/R injury, suggesting that TXNIP knockdown holds promise as a therapeutic strategy.
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BACKGROUND: Depression is one of the most common mental diseases and the leading cause of disability worldwide. A dysfunctional gut microbiota-brain axis is one of the main pathological bases of depression. Irisin, an exercise-related myokine, reduces depression-like behaviors and may guide the relief of depressive symptoms by exercise. However, its underlying mechanism remains unclear. METHODS: Fibronectin type III domain containing 5 (Fndc5)/Irisin was knocked out in male wide-type C57BL/6N mice using CRISPR-cas9. The depression and anxiety symptoms were examined in irisin knockout and control mice with or without chronic unpredictable mild stress by sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST). Fecal microbiota was assessed by 16S rRNA sequencing and microbiota-related metabolites using liquid chromatography with tandem mass spectrometry. Differential metabolites were analyzed with the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. RESULTS: The knockout mice showed anxiety- and depression-like behaviors and altered diversity and richness of gut microbiota. At the phylum level, these mice had decreased Firmicutes and increased Bacteroidota populations, while at the genus level, they exhibited a low relative abundance of Lactobacillus and Bifidobacterium. Moreover, knocking out of Irisin gene in these mice significantly reduced N-desmethyl-mifepristone (RU 42633) and elevated (-)-stercobilin levels. The KEGG results showed that the microbiota-related metabolites affected by irisin mainly clustered into arginine and proline metabolism and affected the mechanistic target of rapamycin kinase (mTOR) signaling pathway. CONCLUSION: Our findings show that Fndc5/irisin deficiency causes depression in mice by inducing dysbiosis of gut microbiota and changes in microbiota-related metabolites.
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Microbioma Gastrointestinal , Animais , Masculino , Camundongos , Depressão/metabolismo , Disbiose , Fibronectinas , Microbioma Gastrointestinal/genética , Camundongos Endogâmicos C57BL , RNA Ribossômico 16SRESUMO
BACKGROUND & OBJECTIVE: We aimed to evaluate the effect of sitaxentan on renal microvascular perfusion via application of ultrasound microbubble contrast. METHODS: Male beagles were randomly divided into: Sham, cardiopulmonary bypass (CPB) and sitaxentan-infused (Sit) groups (nâ=â6). The ascending slope rate (ASR), area under the curve (AUC), derived peak intensity, and time to peak (TTP) were obtained via ultrasound microbubble contrast before CPB (T1), after 1âh CPB (T2), at end of CPB (T3), and 2âh after CPB (T4). RESULTS: Compared with the Sham group, the CPB group had lower ASR of the renal cortex and medulla at T2 - 4, higher AUC and TTP at T3 - 4, and lower derived peak intensity at T4. The ASR at T2 - 4 in the Sit group was lower, TTP was higher at T2 - 4, and AUC was higher at T3 - 4 (Pâ<â0.05). Compared with the CPB group, the Sit group had higher ASR of the renal cortex and medulla at T3 - 4 and AUC and TTP at T3 - 4 (Pâ<â0.05). Compared with that at T1, the ASR of the renal cortex and medulla at T2 - 4 in the CPB group was lower, and AUC and TTP were higher at T3 - 4. The ASR of the renal cortex and medulla at T2 - 4 in the Sit group was lower, TTP was higher at T2 - 4, and AUC was higher at T4 (Pâ<â0.05). CONCLUSIONS: Ultrasound microbubble contrast could be effectively used to evaluate renal microvascular perfusion peri-CPB in beagles, which was prone to decrease and could be improved via pretreatment with sitaxentan.
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Ponte Cardiopulmonar , Microbolhas , Animais , Cães , Masculino , Ponte Cardiopulmonar/efeitos adversos , Meios de Contraste , Rim/diagnóstico por imagem , Rim/irrigação sanguínea , Perfusão , UltrassonografiaRESUMO
The association of intra-operative mechanical power (MP) with post-operative pulmonary complications (PPCs) has been described before, but it is uncertain whether the potential inherent bias can limit the use of this parameter, particularly in the context of one-lung ventilation. This single-center study aims to investigate the effect of MP during one-lung ventilation (OLV), and the risks of PPCs in patients undergoing thoracoscopic lobectomy. This prospective observational study is being conducted in an academic tertiary hospital in mainland China. Participants diagnosed with lung cancer, and aged 50 to 80 years are eligible. Video-assisted thoracoscopic surgery (VATS) lobectomy is performed for all patients. The primary outcome is the occurrence of PPCs over 5 consecutive days after the surgery, or until discharge from the hospital. Secondary outcomes include the composite conditions of PPCs, in-hospital stay, systematic inflammation tested by blood samples, and changes in aeration compartments in the ventilated lung as assessed by CT scans. We aim to evaluate the association of mean MP and the temporal patterns in the trend of MP during OLV with the occurrence of PPCs. A total of 120 patients will be enrolled in this study. The study protocol has received approval from the Ethics Committee of the affiliated hospital of Southwest Medical University, China (Reference number: KY2022162). The findings will be made available to the funder and researchers via scientific conferences and peer-reviewed publications. This controlled trial was approved by the Ethics Committee of Southwest Medical University(ChiCTR2200062173), and registered in the Chinese Clinical Trial Register website ( http://www.chictr.org.cn/edit.aspx?pid=172533&htm=4 , ChiCTR2200062173). A written consent was obtained from each patient.
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Neoplasias Pulmonares , Ventilação Monopulmonar , Humanos , Neoplasias Pulmonares/cirurgia , Estudos Observacionais como Assunto , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou maisRESUMO
Our previous study showed that the plasma microRNA-221-3p level could serve as a biomarker for major depression or mood. This study aimed to further investigate the role of plasma microRNA-221-3p level in postoperative cognitive dysfunction (POCD). Patients undergoing non-cardiac surgery were randomly assigned according to the inclusion and exclusion criteria. POCD was diagnosed by the Z score method. The relative level of plasma microRNA-221-3p was decided by quantitative real-time polymerase chain reaction. Multiple logistic regression analysis and receiver operating characteristic(ROC) curves were used for the analysis of plasma microRNA-221-3p prediction performance for POCD. At 7 days post-surgery, the rate of POCD was 34.04%. Patients in the POCD group had a higher preoperative depression score, older age, and longer operation duration than that in the NPOCD group. The relative level of plasma microRNA-221-3p in the POCD group was 1.78 and 2.73 times higher than that in the NPOCD group at 1 day before and 7 days after the surgery, respectively. The relative content of plasma microRNA-221-3p at 7 days after operation was an independent risk factor for POCD. The ROC curves showed that the area under the curve was 0.938 for plasma microRNA-221-3p at postoperative 7 days, and the threshold for POCD detection was 12.33 with a sensitivity and specificity of 81.3% and 96.3%, respectively. Our results indicate that the plasma postoperative microRNA-221-3p levels could be an effective predictor for POCD after non-cardiac surgery.
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MicroRNAs , Complicações Cognitivas Pós-Operatórias , Biomarcadores , Humanos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Curva ROCAssuntos
Corpos Estranhos , Sanguessugas , Animais , Corpos Estranhos/diagnóstico por imagem , Humanos , TraqueiaRESUMO
INTRODUCTION: Sepsis is a kind of maladjustment response to bacterial infection and activation of coagulation, which can induce neuromuscular dysfunction. However, there is scarce of experimental evidence about the relationship between Schwann cells (SCs) and sepsis in neuromuscular dysfunction. We therefore set out to identify the potential role of SCs in sepsis-induced neuromuscular dysfunction and to explore the underlying molecular mechanism. METHODS: Primary SCs were isolated from the left hind limb sciatic nerve of sepsis mice, which was constructed by cecal ligation and puncture. Then, the SCs were infected with adenovirus encoding toll-like receptor 4 (TLR4), MyD88, or IL-1R (with lipopolysaccharide stimulation), and the Raw 264.7 macrophages were injected with adenovirus with CCR2 silencing (with mMCP-1 stimulation). Further investigation of the interleukin 1 beta (IL-1ß) and macrophage cationic peptide 1 (MCP-1) expressions, we followed reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay techniques, the F4/80 and Ki67 expressions was observed by immunofluorescence staining, while the expressions of CCR2, FAK/p-FAK, nuclear factor-κB (NFκB)/p-NFκB, and ERK1/2/p-ERK1/2 were determined by Western blot analysis. Last, but not the least, the cell migration ability and cell proliferation ability were detected by Transwell assay and Flow cytometry respectively. RESULTS: Our results showed that in sepsis mice, the TLR4/MyD88/ERK pathway was activated in SCs, which triggered the cells to secrete IL-1ß and MCP-1. The secreted IL-1ß bound with IL-1ß receptor on the surface of SCs, thereby activating the IL-1ß/IL-1R/MyD88/ERK pathway and further promoting the secretion of MCP-1 by SCs. MCP-1 was found to bind to CCR2 on the surface of Raw264.7 macrophages to activate the TLR4/MyD88/ERK pathway which caused the inhibition of neuromuscular function. CONCLUSION: Sepsis significantly promotes the infiltration of macrophages by activating the TLR4/MyD88 pathway in SCs, thereby impeding neuromuscular function. Consistently, our study provides a novel concept in the area of neuromuscular dysfunction therapeutics following sepsis.
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Fator 88 de Diferenciação Mieloide/metabolismo , Células de Schwann/patologia , Sepse/metabolismo , Sepse/patologia , Receptor 4 Toll-Like/metabolismo , Animais , Proliferação de Células , Quimiocina CCL2/metabolismo , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/fisiologia , Células de Schwann/metabolismo , Sepse/complicaçõesRESUMO
Intestinal ischemia/reperfusion (I/R) can cause multiple organ damage with extremely high morbidity and mortality. Melatonin has anti-inflammatory, anti-oxidative and anti-apoptotic effects against various diseases. This study aimed to explore whether melatonin had a protective effect against intestinal I/R-induced neuroinflammation and cognitive dysfunction, and investigate its potential mechanisms. In this study, melatonin was administered to the rats with intestinal I/R, then histological changes in intestine and brain (frontal cortex and hippocampal CA1 area) tissues and cognitive function were detected, respectively. The encephaledema and blood-brain barrier (BBB) permeability were observed. Moreover, the alterations of proinflammatory factors (tumor necrosis factor-α, interleukin-6 and interleukin-1ß), oxidative response (malondialdehyde, superoxide dismutase, and reactive oxygen species), apoptosis and proteins associated with inflammation,including Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88) and phosphorylated nuclear factor kappa beta (NF-κB), and apoptosis (cleaved caspase-3) in brain tissues were examined. Furthermore, the expressions of TLR4, Myd88, and microglial activity were observed by multiple immunofluorescence staining. The results showed that intestinal I/R-induced abnormal neurobehavior and cerebral damage were ameliorated after melatonin treatment, which were demonstrated by improved cognitive dysfunction and aggravated histology. Furthermore, melatonin decreased the levels of proinflammatory factors and oxidative stress in plasma, intestine and brain tissues, attenuated apoptotic cell, and inhibited the expressions of related proteins and the immunoreactivity of TLR4 or Myd88 in microglia in brain tissues. These findings showed that melatonin might relieve neuroinflammation and cognitive dysfunction caused by intestinal I/R, which could be, at least partially, related to the inhibition of the TLR4/Myd88 signaling in microglia.
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Anti-Inflamatórios/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Enteropatias/tratamento farmacológico , Melatonina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/imunologia , Encéfalo/patologia , Disfunção Cognitiva/imunologia , Disfunção Cognitiva/patologia , Citocinas/imunologia , Enteropatias/imunologia , Enteropatias/patologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/imunologia , Intestino Delgado/patologia , Masculino , Melatonina/farmacologia , Fator 88 de Diferenciação Mieloide/imunologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/patologia , Receptor 4 Toll-Like/imunologiaRESUMO
With the increasing demand for electricity transmission and distribution, single-phase grounding accidents, which cause great economic losses and casualties, have occurred frequently. In this study, a Bayesian network (BN)-based risk assessment model for representing single-phase grounding accidents is proposed to examine accident evolution from causes to potential consequences. The Bayesian network of single-phase grounding accidents includes 21 nodes that take into account the influential factors of environment, management, equipment and human error. The Bow-tie method was employed to build the accident evolution path and then converted to a BN. The BN conditional probability tables are determined with reference to historical accident data and expert opinion obtained by the Delphi method. The probability of a single-phase grounding accident and its potential consequences in normal conditions and three typical accident scenarios are analyzed. We found that "Storm" is the most critical hazard of single-phase grounding, followed by "Aging" and "Icing". This study could quantitatively evaluate the single-phase grounding accident in multi-hazard coupling scenarios and provide technical support for occupational health and safety management of power transmission lines.
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Acidentes , Fontes de Energia Elétrica , Gestão da Segurança , Acidentes/estatística & dados numéricos , Acidentes de Trabalho/estatística & dados numéricos , Teorema de Bayes , Fontes de Energia Elétrica/estatística & dados numéricos , Humanos , Probabilidade , Medição de RiscoRESUMO
In recent years, concerns about the safety of laboratories have been caused by several serious accidents in school laboratories. Gas leaks in the laboratory are often difficult to detect and cause serious consequences. In this study, a comprehensive model based on the Bayesian network is established for the assessment of the gas leaks evolution process and consequences in school laboratories. The model can quantitatively evaluate the factors affecting the probability and consequences of gas leakage. The results show that a model is an effective tool for assessing the risk of gas leakage. Among the various factors, the unsafe behavior of personnel has the greatest impact on the probability of gas leakage, and the concentration of toxic and harmful gases is the main factor affecting the consequences of accidents. Since the probability distribution of each node is obtained based on the experience of experts, there is a deviation in the quantitative calculation of the probability of gas leakage and consequences, but does not affect the risk analysis. This study could quantitatively assess the probability and consequences of gas leakage in the laboratory, and identify vulnerabilities, which helps improve the safety management level of gas in the school laboratory and reducing the possibility of gas leakage posing a threat to personal safety.
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Acidentes , Gás Natural , Instituições Acadêmicas , Teorema de Bayes , Laboratórios , Medição de Risco , Gestão da SegurançaRESUMO
Sepsis is a serious and elusive syndrome caused by infection, which is accompanied by a high mortality worldwide. Recent evidence has documented the regulatory role of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) during the inflammatory process, the effects of which in the development of sepsis have become the focus of the current study. An in vivo mouse model and in vitro cell model of sepsis induced by lipopolysaccharide (LPS) were developed. High expression of lncRNA MALAT1 along with low expression of breast cancer susceptibility gene 1 (BRCA1) were identified in septic mice and human skeletal muscle cells of sepsis. Then, lncRNA MALAT1 expression was altered in vivo and in vitro to examine serum levels of inflammatory factors, as well as skeletal muscle cell apoptosis. lncRNA MALAT1 was noted to regulate the expression and export from the nucleus of BRCA1 by recruiting zeste homolog 2 (EZH2) in skeletal muscle cells of sepsis. Silencing lncRNA MALAT1 resulted in reduced serum levels of interleukin (IL)-6, IL-8, and tumor necrosis factor alpha (TNF-α), neutrophil migration, skeletal muscle cell apoptosis, and AKT-1 phosphorylation. Taken together, lncRNA MALAT1 interacting with EZH2 stimulated AKT-1 phosphorylation and decreased BRCA1 expression, consequently aggravating the progression of sepsis, highlighting a promising therapeutic option for sepsis.
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OBJECTIVE: To test the hypothesis that patient-controlled analgesia (PCA) contributes to improvement of hemorheology in patients undergoing hip arthroplasty. METHODS: 120 patients, aged 60â-â75 years old, undergoing hip arthroplasty under spinal anesthesia, were randomly divided into group PCA (n = 60) and control group (n = 60). Patients in PCA group received PCA in postoperative 3 days. Blood samples from the median cubital vein were collected at five time points: before anesthesia (T1), after surgery (T2), 6 h after surgery (T3), 24 h after surgery (T4), 48 h after surgery (T5). Hemorheological parameters were measured, including whole blood viscosity at a high shear rate (Hηb), whole blood viscosity at a low shear rate (Lηb), reduced viscosity (ηr), plasma viscosity (ηp), hematocrit (Hct), erythrocyte aggregation index(EAI) and erythrocyte deformation index (EDI). Noninvasive blood pressure and heart rate at T1-5 and pain scoring of visual analogue scale (VAS) score at T2-5 were recorded. RESULTS: (1) Compared with T1, Hηb, Lηb, ηp, ηr decreased significantly at T3-5 with EAI decreased significantly at T5 in group PCA (p < 0.05), EDI increased significantly at T5 in group C (p < 0.05). (2) Compared with group C, Hηb, Lηb, ηp, ηr, EAI decreased significantly at T5 with Lηb concurrently decreased at T4 in group PCA (p < 0.05). CONCLUSION: Postoperative pain may increase blood viscosity in patients undergoing hip arthroplasty, mainly via plasma viscosity, erythrocyte aggregation and rigidity, and which could be improved by postoperative PCA.
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Artroplastia de Quadril , Idoso , Analgesia Controlada pelo Paciente , Hemorreologia , Humanos , Pessoa de Meia-Idade , Dor Pós-OperatóriaRESUMO
BACKGROUND: Continuous positive airways pressure (CPAP) with a CPAP machine and mask has been shown to be more effective at minimising hypoxaemia than other devices under deep sedation. However, the efficacy of a new and simple CPAP device for spontaneously breathing obese patients during colonoscopy is unknown. OBJECTIVE: We hypothesised that oxygenation and ventilation in obese patients under deep sedation during colonoscopy using CPAP via a new nasal mask (SuperNO2VA) would be better than routine care with oxygen supplementation via a nasal cannula. DESIGN: Randomised study. SETTING: Single-centre, June 2017 to October 2017. PATIENTS: A total of 174 patients were enrolled and randomly assigned to Mask group or Control group. Thirty-eight patients were excluded and data from 136 patients underwent final analysis. INTERVENTION: Patients in the Mask group were provided with nasal CPAP (10âcmH2O) at an oxygen flow rate of 15âlâmin. In the Control group, patients were given oxygen via a nasal cannula at a flow rate of 5âlâmin. MAIN OUTCOME MEASURES: The primary outcome was elapsed time from anaesthesia induction to the first airway intervention. RESULTS: The elapsed time from anaesthesia induction to the first airway intervention was 19â±â10âmin in the Mask group (n=63) vs. 10â±â12âmin in the Control group (n=73, Pâ<â0.001). In all, 87.5% (56/64) of patients achieved the target CPAP value. More patients in the Control group (63%) received airway intervention than in the Mask group (22%) (Pâ<â0.001). Hypoxaemia (pulse oximeter oxygen saturation, SpO2â<â90%) occurred more frequently in the Control group (22%) than in the Mask group (5%) (Pâ=â0.004). Minute ventilationPostinduction/minute ventilationBaseline and minute ventilationProcedure-end/minute ventilationBaseline was lower in the Control group than in the Mask group (Pâ=â0.007 and 0.001, respectively). CONCLUSION: Application of a nasal mask at a target CPAP of 10âcmH2O improves ventilation and decreases the frequency and severity of hypoxaemia. TRIAL REGISTRATION: NCT03139448, registered at ClinicalTrials.gov.
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Pressão Positiva Contínua nas Vias Aéreas/instrumentação , Sedação Profunda/efeitos adversos , Hipóxia/prevenção & controle , Obesidade/complicações , Oxigênio/administração & dosagem , Adolescente , Adulto , Cânula , Colonoscopia/efeitos adversos , Feminino , Humanos , Hipóxia/diagnóstico , Hipóxia/etiologia , Masculino , Máscaras , Oximetria , Oxigênio/sangue , Dor Processual/etiologia , Dor Processual/prevenção & controle , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
Sepsis is a systemic inflammatory response syndrome resulting from infection. This study aimed at exploring the role of microRNA-140 (miR-140) in septic mice. Wnt family member 11 (WNT11) was verified to be a target gene of miR-140 after bioinformatic prediction and dual luciferase reporter gene assay. Importantly, miR-140 negatively regulated WNT11. We initially induced the model of sepsis by endotoxin, and then ectopic expression and knockdown experiments were performed to explore the functional role of miR-140 in sepsis. Additionally, cross-sectional areas of muscle fiber, lactic acid production, 3-methylhistidine (3-MH) and tyrosine (Tyr) production in extensor digitorium longus (EDL) muscles, and serum levels of inflammatory factors were examined. The effect of miR-140 on the expression of WNT signaling pathway-related and apoptosis-related factors in skeletal muscle tissue was determined. The experimental results indicated that upregulated miR-140 or silenced WNT11 increased cross-sectional areas of muscle fiber while decreasing lactic acid production, skeletal muscle cell apoptosis [corresponding to downregulated B cell lymphoma 2 (Bcl-2)-associated X protein (Bax) and caspase-3 and upregulated Bcl-2], and the proteolytic rate of Tyr and 3-MH. Also, overexpressed miR-140 or silenced WNT11 reduced inflammation as reflected by decreased serum levels of IL-6, IL-10, and TNF-α. Furthermore, overexpression of miR-140 was shown to suppress the activation of the WNT signaling pathway, accompanied by decreased expression of WNT11, ß-catenin, and GSK-3ß. Taken together, upregulation of miR-140 could potentially inhibit skeletal muscle lactate release, an indirect measure of glycolysis, and atrophy in septic mice through suppressing the WNT signaling pathway via inhibiting WNT11 expression.
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Glicólise , MicroRNAs/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Sepse/metabolismo , Proteínas Wnt/metabolismo , Via de Sinalização Wnt , Animais , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Células Cultivadas , Citocinas/sangue , Modelos Animais de Doenças , Regulação para Baixo , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Mediadores da Inflamação/sangue , Ácido Láctico/metabolismo , Lipopolissacarídeos , Masculino , Metilistidinas/metabolismo , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Músculo Esquelético/patologia , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/genética , Atrofia Muscular/patologia , Sepse/induzido quimicamente , Sepse/genética , Sepse/patologia , Tirosina/metabolismo , Proteínas Wnt/genética , beta Catenina/genética , beta Catenina/metabolismoRESUMO
Sepsis-induced skeletal muscle atrophy is a pathological condition characterized by the loss of strength and muscle mass. Cytokine-induced apoptosis and impaired myogenesis play key roles in the development of this condition. However, the complete underlying mechanism remains largely unknown. Neuregulins are glial growth factors essential for myogenesis that regulate muscle metabolism. We investigated the role of neuregulin-1ß (NRG-1ß) in sepsis-induced apoptosis and myogenesis in skeletal muscle using a serum-based in vitro sepsis model. C2C12 myoblasts were differentiated by treatment with proliferative medium for 7 days. Then, cells were treated with 2% sham mouse serum, 1 nM NRG-1ß in 2% sham mouse serum, 2% septic mouse serum (SMS), or 1 nM NRG-1ß in 2% SMS. Exposure to SMS induced apoptosis, impaired myogenesis, and downregulated PPARγ. NRG-1ß co-incubation remedied all these effects and inhibited NF-κB transcriptional activity. A specific PPARγ antagonist (GW9662) was also administered as a 2-h pretreatment to block PPARγ-mediated signaling and appeared to attenuate the effects of NRG-1ß. Taken together, our results demonstrate that NRG-1ß functions via a PPARγ/NF-κB-dependent pathway to modulate myogenesis and protect against apoptosis in SMS-treated C2C12 myotubes.
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Desenvolvimento Muscular/efeitos dos fármacos , Neuregulina-1/fisiologia , Animais , Apoptose/efeitos dos fármacos , Atrofia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Regulação da Expressão Gênica/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Desenvolvimento Muscular/genética , Desenvolvimento Muscular/fisiologia , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético , Mioblastos/metabolismo , NF-kappa B/metabolismo , Neuregulina-1/genética , PPAR gama/metabolismo , Sepse/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Efficient air removal from a vascular access line is a key step to prevent air embolism. Existing devices, especially for rapid infusers, are far from optimum. In this study, we developed a novel device, vascular access line air removal device (VALARD), and compared its efficiency of air removal and pause time of forward bulk flow with a commonly used device, the Belmont pump. Part I experiment, saline was infused at a forward bulk flow rate of 250, 500, and 750 mL/min. Meanwhile, air was introduced into the infusion line at a rate of 5, 10, and 15 mL/min for each bulk flow rate. Air bubbles > 10 µL downstream from either the VALARD or the Belmont pump and the fraction of pause time of the forward bulk flow were determined. Part II experiment, 120 mL of air was rapidly introduced into the VALARD at a bulk flow rate of about 500 mL/min. Air bubbles > 10 µL downstream from the VALARD, fraction of pause time of the forward bulk flow, and the transit time of the 120 mL of air at the working chamber were recorded. The VALARD: no air bubbles > 10 µL were detected during any tested combination of air injection and bulk flow rates without pause of forward flow. The Belmont pump: air bubbles > 10 µL were detected in 60% of the tests with pause of the forward flow. The VALARD eliminates air efficiently without pause of the forward bulk flow. Further clinical trials are needed to compare the VALARD with other devices and to assess its efficiency, safety, and user friendliness.