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1.
J Clin Anesth ; 75: 110504, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34509960

RESUMO

STUDY OBJECTIVE: To evaluate the impact of intensive glucose control on diabetic patients undergoing surgery. DESIGN: A systematic review and meta-analysis of randomized controlled trials. PubMed, CENTRAL, EMBASE, ISI Web of Science, and CINAHL databases were searched from inception to 13 December 2020. SETTING: Operating room, postoperative recovery area and ward, up to 30 days after surgery. PATIENTS: Diabetic patients undergoing surgery. INTERVENTIONS: We used Review Manager 5.4 to pool the data with a random-effects model. The quality of evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation system. MEASUREMENTS: The primary outcomes were infectious complications, postoperative mortality, and hypoglycaemia. The secondary outcomes included atrial fibrillation, myocardial infarction, stroke, delirium, renal failure, postoperative mechanical ventilation time, length of intensive care unit (ICU) stay, and hospital stay. MAIN RESULTS: Thirteen studies involving 1582 participants were included. Compared with conventional glucose control, intensive glucose control was associated with a lower risk of infectious complications (risk ratio [RR], 0.35; 95% confidence interval [CI], 0.19-0.63; low-quality evidence), atrial fibrillation (RR, 0.55; 95% CI, 0.42-0.71; high-quality evidence), and renal failure (RR, 0.38; 95% CI, 0.15-0.95; moderate-quality evidence), as well as a shorter length of stay in the ICU (mean difference (MD), -0.55 day; 95% CI, -1.05 to -0.05 days; very-low-quality evidence) and hospital (MD, -1.61 days; 95% CI, -2.78 to -0.44 days; very-low-quality evidence). However, intensive glucose control was associated with a higher risk of hypoglycaemia (RR, 3.00; 95% CI, 1.97-4.55; high-quality evidence). There were no significant differences in postoperative mortality, myocardial infarction, stroke, delirium, or postoperative mechanical ventilation time. CONCLUSIONS: Intensive glucose control in diabetic patients is associated with a reduction in some adverse postoperative outcomes including infectious complications, but also appears to increase the risk of hypoglycaemia. Further well-designed studies may be needed to determine appropriate regimens to reduce hypoglycaemia incidence. PROSPERO REGISTRATION NUMBER: CRD42021226138.

2.
Phys Rev Lett ; 127(8): 082302, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34477404

RESUMO

We derive a set of nontrivial relations between second-order transport coefficients which follow from the second law of thermodynamics upon considering a regime close to uniform rotation of the fluid. We demonstrate that an extension of hydrodynamics by spin variable is equivalent to modifying conventional hydrodynamics by a set of second-order terms satisfying the relations we derived. We point out that a novel contribution to the heat current orthogonal to vorticity and temperature gradient reminiscent of the thermal Hall effect is constrained by the second law.

4.
Neuropharmacology ; 196: 108704, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34252405

RESUMO

Clinically, posttraumatic stress disorder (PTSD) and chronic pain are highly comorbid conditions, but the underlying mechanisms of and therapeutic strategies against PTSD-related pain remain unclear. Our previous studies suggested that dysregulation of neuroinflammation contributes to the development of stress-induced hyperalgesia. Recent studies reported that angiotensin II was a 'stress-related hormone', and could induce glial activation by stimulating the type 1 receptor (AT1R). In the present study, we aimed to investigate whether AT1R blockade could attenuate mechanical allodynia induced by PTSD-like stress. Adult male rats were exposed to single prolonged stress (SPS) to establish a model of PTSD-pain comorbidity. Our results showed that SPS exposure increased the levels of angiotensin II in the hippocampus, prefrontal cortex (PFC) and spinal cord; intraperitoneal injection of losartan attenuated SPS-induced mechanical allodynia, and suppressed SPS-induced glial activation (both microglia and astrocytes) and proinflammatory cytokine expression in the PFC and spinal cord, but not in the hippocampus. We further showed that intrathecal injection of losartan also exerted anti-hyperalgesic effect and suppressed SPS-induced glial activation and proinflammatory cytokine expression in the spinal cord. These results indicated that AT1R blockade by losartan attenuated mechanical allodynia induced by PTSD-like stress, and this may be attributed to the suppression of glial activation and proinflammatory cytokine expression in the spinal cord. Although further research is warranted to verify our findings in female rodents and to assess pharmacological effects of AT1R blockade in PFC and hippocampus, our study suggested the therapeutic potential of targeting AT1R in the treatment of PTSD-related chronic pain.

6.
J Mol Diagn ; 23(9): 1174-1184, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34182124

RESUMO

Liver cancer is the fifth-most common cancer worldwide, with the third-highest rate of cancer-related mortality. Hepatocellular carcinoma (HCC) is the leading pathologic subtype, contributing 85% to 90% of cases of primary liver cancer. Most HCC patients are diagnosed at an advanced stage at which treatment is not curative. This study assessed the performance of a newly developed blood-based assay that utilizes genomic features and protein markers for the early detection of HCC. Two cancer-associated hallmarks, copy-number aberrations (CNA) and fragment size (FS), were characterized by shallow whole-genome sequencing of cell-free DNA and utilized to differentiate cancer patients from healthy subjects. As a clinically implemented biomarker of HCC, plasma α-fetoprotein (AFP) was also used with the genomic surrogates to optimize the detection of HCCs. The sensitivity of AFP ≥20.0 µg/L in detecting HCC was 57.9%. The combined genomic classifier CNA + FS via cell-free DNA shallow whole-genome sequencing identified nearly half of AFP-negative HCC patients (43.8%). By integrating CNA, FS as well as AFP (HCCseek), 75.0% sensitivity was achieved at 98.0% specificity, resulting in 92.6% accuracy, with 58.6% sensitivity in stage I HCC. The quantitative output of HCCseek was correlated with the severity of the disease (tumor size, stage, and recurrence-free survival). In summary, this study describes an efficient, noninvasive, and cost-effective method to detect HCC.

7.
Neurosci Biobehav Rev ; 127: 37-53, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33894241

RESUMO

Brain diseases, including neurodegenerative, cerebrovascular and neuropsychiatric diseases, have posed a deleterious threat to human health and brought a great burden to society and the healthcare system. With the development of medical technology, vagus nerve stimulation (VNS) has been approved by the Food and Drug Administration (FDA) as an alternative treatment for refractory epilepsy, refractory depression, cluster headaches, and migraines. Furthermore, current evidence showed promising results towards the treatment of more brain diseases, such as Parkinson's disease (PD), autistic spectrum disorder (ASD), traumatic brain injury (TBI), and stroke. Nonetheless, the biological mechanisms underlying the beneficial effects of VNS in brain diseases remain only partially elucidated. This review aims to delve into the relevant preclinical and clinical studies and update the progress of VNS applications and its potential mechanisms underlying the biological effects in brain diseases.


Assuntos
Lesões Encefálicas Traumáticas , Doença de Parkinson , Acidente Vascular Cerebral , Estimulação do Nervo Vago , Humanos , Nervo Vago
8.
World J Gastroenterol ; 27(7): 561-575, 2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33642829

RESUMO

Although coronavirus (CoV) infection is often characterized by respiratory symptoms, the virus can also result in extrapulmonary symptoms, especially the symptoms related to the digestive system. The outbreak of coronavirus disease 2019 (COVID-19) is currently the world's most pressing public health threat and has a significant impact on civil societies and the global economy. The occurrence of digestive symptoms in patients with COVID-19 is closely related to the development and prognosis of the disease. Moreover, thus far, there are no specific antiviral drug or vaccine approved for the treatment or prevention of COVID-19. Therefore, we elaborate on the effects of CoVs on the digestive system and the potential underlying mechanisms.


Assuntos
Infecções por Coronavirus/complicações , Doenças do Sistema Digestório/virologia , Interações Hospedeiro-Patógeno , SARS-CoV-2/fisiologia , Humanos
10.
J Clin Anesth ; 69: 110157, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33296787

RESUMO

STUDY OBJECTIVE: To compare the effect of sedation protocols with and without dexmedetomidine on delirium risk and duration in adult patients in intensive care units (ICUs). DESIGN: A meta-analysis of randomized controlled trials. REVIEW METHODS: We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and ISI Web of Science from inception to September 3, 2020. We included studies comparing the effect of dexmedetomidine-based sedation on delirium risk with non-dexmedetomidine-based sedation in adult patients in ICUs. We pooled the data using a random-effects model using Review Manager 5.2, and assessed publication bias using Stata 11.0. The quality of evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation system. MAIN RESULTS: We included 36 studies involving 9623 participants. The use of dexmedetomidine was associated with reduced risk of delirium (risk ratio [RR], 0.63; 95% confidence interval [CI], 0.54-0.75; very low-quality evidence), but higher incidences of hypotension and bradycardia during hospital stay. Dexmedetomidine was also associated with shorter durations of ICU stay, hospital stay and mechanical ventilation. Dexmedetomidine did not affect ICU mortality (RR, 1.01; 95% CI, 0.89-1.14; low-quality evidence), hospital mortality (RR, 1.01; 95% CI, 0.91-1.12; very low-quality evidence), or 30-day mortality (RR, 0.77; 95% CI, 0.58-1.01; moderate-quality evidence), or duration of delirium (mean difference, -0.74 days; 95% CI, -1.83 to 0.36 days; very low-quality evidence). We identified publication bias for risk and duration of delirium, length of ICU stay, and hospital stay. CONCLUSIONS: Low- or very low-quality evidence suggests that dexmedetomidine was associated with a clinically-small reduction of delirium risk, ICU/hospital stay and mechanical ventilation duration, but were not associated with improved mortality or shorter delirium duration in ICU patients. These findings were inconclusive because of publication bias, heterogeneity, and limited sample size. Significant adverse effects of dexmedetomidine include hypotension and bradycardia. PROSPERO registration number: CRD42018095358.

11.
Oxid Med Cell Longev ; 2020: 4635163, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33381265

RESUMO

Postoperative cognitive dysfunction (POCD) is a sever postsurgical neurological complication in the elderly population. As the global acceleration of population ageing, POCD is proved to be a great challenge to the present labor market and healthcare system. In the present study, our findings showed that tau acetylation mediated by SIRT1 deficiency resulted in tau hyperphosphorylation in the hippocampus of the aged POCD model and consequently contributed to cognitive impairment. Interestingly, pretreatment with resveratrol almost restored the expression of SIRT1, reduced the levels of acetylated tau and hyperphosphorylated tau in the hippocampus, and improved the cognitive performance in the behavioral tests. What is more, we observed that microglia-derived neuroinflammation resulting from SIRT1 inhibition in microglia probably aggravated the tau acetylation in cultured neurons in vitro. Our findings supported the notion that activation SIRT1 provided dually beneficial effect in the aged POCD model. Taken together, our findings provided the initial evidence that tau acetylation was associated with cognitive impairment in the aged POCD model and paved a promising avenue to prevent POCD by inhibiting tau acetylation in a SIRT1-dependent manner.


Assuntos
Disfunção Cognitiva/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Resveratrol/farmacologia , Proteínas tau/metabolismo , Acetilação/efeitos dos fármacos , Acetiltransferases/metabolismo , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Envelhecimento/psicologia , Anestesia/efeitos adversos , Animais , Células Cultivadas , Cognição/efeitos dos fármacos , Cognição/fisiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Ativação Enzimática/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos , Complicações Pós-Operatórias/metabolismo , Complicações Pós-Operatórias/psicologia , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Resveratrol/uso terapêutico , Sirtuína 1/metabolismo , Procedimentos Cirúrgicos Operatórios/efeitos adversos
12.
Am J Transl Res ; 12(10): 6655-6664, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194062

RESUMO

Few studies have reported the implications of performing endotracheal intubation for critically ill COVID-19 patients admitted to intensive care units (ICUs). Therefore, this study aimed to summarize the outcomes of COVID-19 patients in the ICU following endotracheal intubation and provide a clinical reference for the high-risk procedure. From February 1 to February 18, 2020, we enrolled 59 critically ill COVID-19 patients who received emergency endotracheal intubation in the ICUs of Tongji Hospital. We recorded demographic information, laboratory parameters, comorbidities, changes in vital signs pre- and post-intubation, the airway grade, intubation success rate using three types of laryngoscopes, and the experience of intubators. Follow-up evaluations were performed for all proceduralists to monitor nosocomial infections. The majority of the patients requiring intubation were elderly and had at least one comorbidity. Of the patients, 86.4% developed hypoxia before intubation. The first and second attempts of successful endotracheal intubation with the Macintosh laryngoscope (70.0% and 83.3%), Airtraq videolaryngoscope (93.5% and 80%), and UE videolaryngoscope (88.9% and 100%) were performed. Notably, SpO2 <93% and hypotension were observed 3 min after intubation in 32.2% and 39% patients, respectively. With the proper use of personal protective equipment (PPE), no nosocomial infections were observed among proceduralists. Full PPE increased the occurrence of fogging on goggles and myopia glasses. Overall, a higher success rate of intubation was achieved by senior intubators using a videolaryngoscope. Although inconvenient, appropriate ensembles of PPE could prevent nosocomial infections.

13.
Sensors (Basel) ; 20(22)2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33207813

RESUMO

Recently, more and more smart homes have become one of important parts of home infrastructure. However, most of the smart home applications are not interconnected and remain isolated. They use the cloud center as the control platform, which increases the risk of link congestion and data security. Thus, in the future, smart homes based on edge computing without using cloud center become an important research area. In this paper, we assume that all applications in a smart home environment are composed of edge nodes and users. In order to maximize the utility of users, we assume that all users and edge nodes are placed in a market and formulate a pricing resource allocation model with utility maximization. We apply the Lagrangian method to analyze the model, so an edge node (provider in the market) allocates its resources to a user (customer in the market) based on the prices of resources and the utility related to the preference of users. To obtain the optimal resource allocation, we propose a pricing-based resource allocation algorithm by using low-pass filtering scheme and conform that the proposed algorithm can achieve an optimum within reasonable convergence times through some numerical examples.

15.
J Neurol ; 267(8): 2179-2184, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32458193

RESUMO

Coronavirus disease 2019 (COVID-19), a disease caused by the novel betacoronavirus (SARS-CoV-2), has become a global pandemic threat. The potential involvement of COVID-19 in central nervous system (CNS) has attracted considerable attention due to neurological manifestations presented throughout the disease process. In addition, SARS-CoV-2 is structurally similar to SARS-CoV, and both bind to the angiotensin-converting enzyme 2 (ACE2) receptor to enter human cells. Thus, cells expressing ACE2, such as neurons and glial cells may act as targets and are thus vulnerable to SARS-CoV-2 infection. Here, we have reviewed the neurological characteristics of COVID-19 and summarized possible mechanisms of SARS-CoV-2 invasion of the CNS. COVID-19 patients have presented with a number of different neurological symptoms such as headache, dizziness, hyposmia, and hypogeusia during the course of illness. It has also been reported recently that some cases of COVID-19 have presented with concurrent acute cerebrovascular disease (acute ischemic stroke, cerebral venous sinus thrombosis, cerebral hemorrhage, subarachnoid hemorrhage), meningitis/encephalitis, acute necrotizing hemorrhagic encephalopathy, and acute Guillain-Barré syndrome. Furthermore, SARS-CoV-2 RNA detected in a cerebrospinal fluid specimen of a patient with COVID-19 have provided direct evidence to support the theory of neurotropic involvement of SARS-CoV-2. However, the underlying neurotropic mechanisms of SARS-CoV-2 are yet to be established. SARS-CoV-2 may affect CNS through two direct mechanisms (hematogenous dissemination or neuronal retrograde dissemination) or via indirect routes. The underlying mechanisms require further elucidation in the future.


Assuntos
Betacoronavirus , Encéfalo/metabolismo , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/metabolismo , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/metabolismo , Pneumonia Viral/epidemiologia , Pneumonia Viral/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Barreira Hematoencefálica/virologia , Encéfalo/patologia , Encéfalo/virologia , COVID-19 , Infecções por Coronavirus/diagnóstico , Tontura/diagnóstico , Tontura/epidemiologia , Tontura/metabolismo , Encefalite/diagnóstico , Encefalite/epidemiologia , Encefalite/metabolismo , Cefaleia/diagnóstico , Cefaleia/epidemiologia , Cefaleia/metabolismo , Humanos , Doenças do Sistema Nervoso/diagnóstico , Pandemias , Pneumonia Viral/diagnóstico , SARS-CoV-2
16.
Oxid Med Cell Longev ; 2020: 9018624, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32148659

RESUMO

Various lines of evidence suggest that neonatal exposure to general anesthetics, especially repeatedly, results in neuropathological brain changes and long-term cognitive impairment. Although progress has been made in experimental models, the exact mechanism of GA-induced neurotoxicity in the developing brain remains to be clarified. Sirtuin 1 (SIRT1) plays an important role in synaptic plasticity and cognitive performance, and its abnormal reduction is associated with cognitive dysfunction in neurodegenerative diseases. However, the role of SIRT1 in GA-induced neurotoxicity is unclear to date. In this study, we found that the protein level of SIRT1 was inhibited in the hippocampi of developing mice exposed to sevoflurane. Furthermore, the SIRT1 inhibition in hippocampi was associated with brain-derived neurotrophic factor (BDNF) downregulation modulated by methyl-cytosine-phosphate-guanine-binding protein 2 (MeCP2) and cAMP response element-binding protein (CREB). Pretreatment of neonatal mice with resveratrol nearly reversed the reduction in hippocampal SIRT1 expression, which increased the expression of BDNF in developing mice exposed to sevoflurane. Moreover, changes in the levels of CREB and MeCP2, which were considered to interact with BDNF promoter IV, were also rescued by resveratrol. Furthermore, resveratrol improved the cognitive performance in the Morris water maze test of the adult mice with exposure to sevoflurane in the neonatal stage, without changing motor function in the open field test. Taken together, our findings suggested that SIRT1 deficiency regulated BDNF signaling via regulation of the epigenetic activity of MeCP2 and CREB, and resveratrol might be a promising agent for mitigating sevoflurane-induced neurotoxicity in developing mice.


Assuntos
Antioxidantes/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Síndromes Neurotóxicas/tratamento farmacológico , Resveratrol/uso terapêutico , Sevoflurano/efeitos adversos , Sirtuína 1/metabolismo , Animais , Antioxidantes/farmacologia , Humanos , Masculino , Camundongos , Resveratrol/farmacologia
17.
Atherosclerosis ; 297: 47-54, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32078829

RESUMO

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease when aortic rupture occurs, especially for elders. There is an urgent need to understand the mechanisms of AAA formation and development at molecular level. Our previous study showed that disintegrin and metalloprotease 10 (ADAM10) played an important role in abdominal aortic aneurysm formation. In this study, we investigated the effects of another ADAM protein (ADMA9) in AAA formation. METHOD AND RESULTS: Using AngII treated human aortic smooth muscle cells (HASMCs) and human aortic endothelial cells (hAoECs) as in vitro AAA model and murine AAA model, ADAM9 was overexpressed suggesting that ADAM9 may play important roles in AAA formation. Further investigation showed that ADAM9 induced inflammation leading to increased macrophage infiltration. ADAM9 was also found to induce cell apoptosis. AKT/NF-κB pathway was activated in murine AAA. Bioinformatic analysis showed that the 3' UTR of ADMA9 was a potential target of miR-126. We investigated the potential of using miR-126 to modulate ADAM9 expression. The expression level of miR-126 was decreased and inversely correlated with the expression of ADAM9 in the in vitro AAA model. Further investigation showed that miR-126 negatively regulated gene expression of ADAM9 and suppressed the production of inflammatory cytokines. miR-126 was also found to improve cell survival and significantly reduce AAA formation in murine AAA. CONCLUSIONS: Our data revealed a link between ADAM9 and AAA formation, providing an approach to control AAA development using miR-126, possibly through modulation of the expression level of ADAM9.


Assuntos
Proteínas ADAM/metabolismo , Aorta Abdominal/enzimologia , Aneurisma da Aorta Abdominal/enzimologia , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Proteínas ADAM/genética , Angiotensina II , Animais , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/patologia , Apoptose , Sítios de Ligação , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/enzimologia , Células Endoteliais/patologia , Regulação Enzimológica da Expressão Gênica , Macrófagos/enzimologia , Macrófagos/patologia , Masculino , Proteínas de Membrana/genética , Camundongos Knockout para ApoE , MicroRNAs/genética , Músculo Liso Vascular/enzimologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/enzimologia , Miócitos de Músculo Liso/patologia , Transdução de Sinais
18.
Adv Sci (Weinh) ; 7(4): 1902600, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32076591

RESUMO

Intrathecal injection, drugs transporting along perivascular spaces, represents an important route for maintaining blood-brain barrier (BBB) integrity after cerebral ischemia/reperfusion (I/R) injury. However, after being directly injected into cerebrospinal fluid (CSF), the temporal and spatial changes in the distribution of therapeutic protein drugs have remained unknown. Here, with positron emission tomography (PET) imaging, the uptake of 89Zr-agrin is noninvasively and dynamically monitored. These data demonstrate the time-activity curve of drugs in the brain subregions and their spatial distribution in different organs after intrathecal administration. Furthermore, agrin treatment effectively inhibits BBB disruption by reducing the loss of tight-junctional proteins. Importantly, the infarct volume is reduced; the number of apoptotic neurons is decreased; and neurological function is improved in mouse I/R injury models. Thus, intrathecal injection of agrin provides the basis for a new strategy to research and develop protein drugs for reducing the aggravation of I/R injury.

19.
Biomed Res Int ; 2020: 7380172, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31998797

RESUMO

General anesthetic (GA) is used clinically to millions of young children each year to facilitate surgical procedures, relieve perioperative stress, and provide analgesia and amnesia. During recent years, there is a growing concern regarding a causal association between early life GA exposure and subsequently long-term neurocognitive abnormalities. To address the increasing concern, mounting preclinical studies and clinical trials have been undergoing. Until now, nearly all of the preclinical findings show that neonatal exposure to GA causally leads to acute neural cell injury and delayed cognitive impairment. Unexpectedly, several influential clinical findings suggest that early life GA exposure, especially brief and single exposure, does not cause adverse neurodevelopmental outcome, which is not fully in line with the experimental findings and data from several previous cohort trials. As the clinical data have been critically discussed in previous reviews, in the present review, we try to analyze the potential factors of the experimental studies that may overestimate the adverse effect of GA on the developing brain. Meanwhile, we briefly summarized the advance in experimental research. Generally, our purpose is to provide some useful suggestions for forthcoming preclinical studies and strengthen the powerfulness of preclinical data.


Assuntos
Anestesia Geral/efeitos adversos , Anestésicos Gerais , Encéfalo , Síndromes Neurotóxicas , Anestésicos Gerais/efeitos adversos , Anestésicos Gerais/uso terapêutico , Animais , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Encéfalo/patologia , Criança , Humanos , Neurônios/metabolismo , Neurônios/patologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia
20.
Eur J Vasc Endovasc Surg ; 59(1): 98-107, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31744785

RESUMO

OBJECTIVE: This study aimed to investigate the effect of long non-coding RNA (lncRNA) DLGAP1 antisense RNA 1 (DLGAP1-AS1) on vascular endothelial cell (VEC) injury via the phosphoinositide 3-kinase (PI3K)/Akt pathway in rat models of acute lower limb ischaemia-reperfusion (I/R). METHODS: Differentially expressed lncRNAs related to I/R were screened using the gene expression omnibus database. Acute lower limb I/R models were induced in male Wistar rats, in which the regulatory mechanisms of DLGAP1-AS1 silencing were analysed after the treatment of small interfering RNA (siRNA) against DLGAP1-AS1 or an inhibitor of the PI3K/Akt pathway. The relationship between DLGAP1-AS1 and the PI3K/Akt pathway was analysed. The levels of tumour necrosis factor (TNF)-α and vascular cell adhesion molecule-1 (VCAM-1), as well as malondialdehyde (MDA) concentration and creatine kinase (CK) activity, were measured. The number of circulating endothelial cells (CECs) and apoptosis of VECs were identified. RESULTS: Microarray based analysis indicated that DLGAP1-AS1 was highly expressed in I/R, which was further confirmed by detection of expression in rat models of acute lower limb I/R. Notably, the treatment of siRNA against DLGAP1-AS1 led to the activation of the PI3K/Akt pathway. In response to siRNA against DLGAP1-AS1, the levels of TNF-α and VCAM-1 were decreased, and MDA concentration and CK activity was downregulated. Reduced CEC numbers and suppressed VEC apoptosis were also observed. CONCLUSION: DLGAP1-AS1 silencing could further suppress the oxidative stress, exert an anti-apoptosis effect, and reduce inflammatory reaction, whereby VEC injury is alleviated by activation of the PI3K/Akt pathway in rats with acute lower limb I/R.


Assuntos
Apoptose/genética , Células Endoteliais/patologia , RNA Longo não Codificante/metabolismo , Traumatismo por Reperfusão/genética , Transdução de Sinais/genética , Animais , Proliferação de Células/genética , Modelos Animais de Doenças , Regulação para Baixo , Humanos , Masculino , Estresse Oxidativo/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologia
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