SIRT3 and RORα are two prospective targets against mitophagy during simulated ischemia/reperfusion injury in H9c2 cells.

Autophagy during myocardial ischemia/reperfusion (MI/R) exacerbates cardiomyocyte injury. Melatonin (Mel) alleviates myocardial damage by regulating mitochondrial function and mitophagy, but the role of mitophagy in melatonin-induced cardioprotection remains unclear. This study aimed to explore the roles of sirtuin3 (SIRT3) and retinoid-related orphan nuclear receptor-α (RORα) in mitophagy during simulated ischemia reperfusion (SIR) in H9c2 cells. Our data showed that mitophagy was excessively activated after SIR injury, which was consistent with reduced cell survival, enhanced oxidative responses and mitochondrial dysfunction in H9c2 myocytes. Melatonin greatly enhanced cell viability, reduced oxidative stress and improved mitochondrial function. The effects of melatonin protection were involved in excessive mitophagy inhibition, as demonstrated by the reduced levels of mitophagy-linked proteins, including Parkin, Beclin1, NIX and BNIP3, and the LC3 II/LC3 I ratio and elevations in p62. Additionally, the decreases in SIRT3 and RORα in H9c2 myocytes after SIR were reversed by melatonin, and the above effects of melatonin were eliminated by small interfering RNA (siRNA)-mediated knockdown of SIRT3 and RORα. In brief, SIRT3 and RORα are two prospective targets in the cardioprotection of melatonin against mitophagy during SIR in H9c2 myocytes.

MiR-145-5p reduced ANG II-induced ACE2 shedding and the inflammatory response in alveolar epithelial cells by targeting ADAM17 and inhibiting the AT1R/ADAM17 pathway.

The excessive elevation of angiotensin II (ANG II) is closely associated with the occurrence and development of aortic dissection (AD)-related acute lung injury (ALI), through its binding to angiotensin II receptor type I (AT1R). MiR-145-5p is a noncoding RNA that can be involved in a variety of cellular physiopathological processes. Transfection with miR-145-5p was found to downregulated the expression of A disintegrin and metalloprotease 17 (ADAM17) and reduced the levels of angiotensin-converting enzyme 2 (ACE2) in lung tissue, while concurrently increasing plasma ACE2 levels in the AD combined with ALI mice. ADAM17 was proved to be a target of miR-145-5p. Transfection with miR-145-5p decreased the shedding of ACE2 and alleviated the inflammatory response induced by ANG II through targeting ADAM17 and inhibiting the AT1R/ADAM17 pathway in A549 cells. In conclusion, our present study demonstrates the role and mechanism of miR-145-5p in alleviating ANG II-induced acute lung injury, providing a new insight into miRNA therapy for reducing lung injury in patients with aortic dissection.

Melatonin protects against myocardial ischemia-reperfusion injury by inhibiting excessive mitophagy through the Apelin/SIRT3 signaling axis.

Excessive or uncontrolled mitophagy may result in a drastic shortage of healthy mitochondrial for ATP supply after reperfusion, leading to irreversible myocardial damage. Melatonin, a hormone produced by the pineal gland, has been proven to ameliorate myocardial ischemia-reperfusion (I/R) injury via regulating mitophagy. However, its underlying mechanism has not been fully elucidated. The present study focused on the role of mitophagy in the cardioprotective effects of melatonin by using the myocardial I/R rat model. The rats were pretreated with or without the apelin inhibitor ML221, the sirtuin 3 (SIRT3) inhibitor 3-TYP and then subjected to I/R injury, with melatonin administrated 10 min before reperfusion. The effects of melatonin on myocardial infarct size, biomarkers of myocardial injury, oxidative stress, and mitochondrial function were detected, and the expression of apelin, SIRT3, and mitophagy-related proteins were also measured. Excessive mitophagy was activated after I/R injury and was correlated with oxidative stress and mitochondrial dysfunction. Melatonin pretreatment ameliorated myocardial injury by decreasing oxidative stress, restoring mitochondrial function, and inhibiting excessive mitophagy. However, ML221 or 3-TYP disrupted these beneficial effects of melatonin on I/R injury. Taken together, these results suggest that melatonin pretreatment ameliorates myocardial I/R injury through regulating the apelin/SIRT3 pathway to inhibit excessive mitophagy.

Development and validation of a risk prediction model for postoperative gastrointestinal complications in patients undergoing aortic arch surgery.

BACKGROUND: Postoperative gastrointestinal complications (GICs) were potentially fatal to patients who underwent aortic arch surgery. The aim of this study was to construct a prediction model of GICs. METHODS: We retrospectively studied the medical records of 3063 patients who underwent aortic arch surgery. Patients were randomly divided into derivation and validation cohorts at a ratio of 4:1. A nomogram was constructed in the derivation cohort. RESULTS: A total of 157 patients with GICs were identified. In the derivation cohort, multivariate analysis identified six predictors of GICs including hypertension, ASA classification, preinduction MAP, aortic cross-clamp time, CPB time, and intraoperative transfusion of red blood cells. Compared with the patients without GICs, the patients with GICs had higher mortality, and longer ICU and hospital stays. We also divided the patients into four intervals according to the risk of GICs. CONCLUSIONS: This study developed a reliable prediction model of GICs after aortic arch surgery. This prediction model had been well verified in our research centre, and further external verification was required before it can be recommended for clinical application.

Melatonin or its analogs as premedication to prevent emergence agitation in children: a systematic review and meta-analysis.

BACKGROUND: Emergence agitation (EA) is a prevalent complication in children following general anesthesia. Several studies have assessed the relationship between melatonin or its analogs and the incidence of pediatric EA, yielding conflicting results. This meta-analysis aims to assess the effects of premedication with melatonin or its analogs on preventing EA in children after general anesthesia. METHODS: PubMed, EMBASE, the Cochrane Library, ProQuest Dissertations & Theses Global, Web of Science, CNKI, Wanfang Data, clinicaltrials.gov, and WHO International Clinical Trials Registry Platform were searched until 25 November 2022. We included randomized controlled trials that assessed EA in patients less than 18 years old who underwent general anesthesia. We excluded studies that did not use a specific evaluation to assess EA. RESULTS: Nine studies (951 participants) were included in this systematic review. Melatonin significantly reduced the incidence of EA compared with placebos (risk ratio 0.40, 95% CI 0.26 to 0.61, P < 0.01) and midazolam (risk ratio 0.48, 95% CI 0.32 to 0.73, P < 0.01). Dexmedetomidine remarkably decreased the incidence of EA compared with melatonin (risk ratio 2.04, 95% CI 1.11 to 3.73, P = 0.02). CONCLUSIONS: Melatonin premedication significantly decreases the incidence of EA compared with placebos and midazolam. Dexmedetomidine premedication has a stronger effect than melatonin in preventing EA. Nevertheless, further studies are warranted to reinforce and validate the conclusion on the efficacy of melatonin premedication in mitigating EA in pediatric patients.

Melatonin and ferroptosis: Mechanisms and therapeutic implications.

Ferroptosis, a regulated form of cell death, is characterized by iron-dependent lipid peroxidation leading to oxidative damage to cell membranes. Cell sensitivity to ferroptosis is influenced by factors such as iron overload, lipid metabolism, and the regulation of the antioxidant system. Melatonin, with its demonstrated capacity to chelate iron, modulate iron metabolism proteins, regulate lipid peroxidation, and regulate antioxidant systems, has promise as a potential therapeutic agent in mediating ferroptosis. The availability of approved drugs targeting ferroptosis is limited; therefore, melatonin is a candidate for broad application due to its safety and efficacy in attenuating ferroptosis in noncancerous diseases. Melatonin has been demonstrated to attenuate ferroptosis in cellular and animal models of noncancerous diseases, showcasing effectiveness in organs such as the heart, brain, lung, liver, kidney, and bone. This review outlines the molecular mechanisms of ferroptosis, investigates melatonin's potential effects on ferroptosis, and discusses melatonin's therapeutic potential as a promising intervention against diseases associated with ferroptosis. Through this discourse, we aim to lay a strong foundation for developing melatonin as a therapeutic strategy to modulate ferroptosis in a variety of disease contexts.

The risk factors of postoperative hypoxemia in patients with Stanford type A acute aortic dissection.

Hypoxemia is one of the most common complications in patients after Stanford type A acute aortic dissection surgery. The aim of this study was to investigate the association of circulating ANG II level with postoperative hypoxemia and to identify the risk factors for postoperative hypoxemia in Stanford type A acute aortic dissection patients. In this study, 88 patients who underwent Stanford type A acute aortic dissection surgery were enrolled. Postoperative hypoxemia is defined by the oxygenation index (OI). Perioperative clinical data were collected and the serum ANG II and sACE2 levels were measured. The differences in the basic characteristics, intraoperative details, biochemical parameters, laboratory test data and clinical outcomes were compared between the hypoxemia group and the non-hypoxemia group by univariate analysis. Multivariate logistic regression analysis was performed on the variables with P < .1 in univariate analysis or that were considered clinically important to identify risk factors for postoperative hypoxemia. Twenty-five patients (28.4%) were considered to have postoperative hypoxemia (OI ≤ 200 mm Hg). The ANG II concentration remained a risk factor associated with postoperative hypoxemia [OR = 1.018, 95% CI (1.003-1.034), P = .022]. The other risk factors remaining in the logistic regression model were BMI [OR = 1.417, 95% CI (1.159-1.733), P = .001] and cTnI [OR = 1.003, 95% CI (1.000-1.005), P = .032]. Elevated levels of ANG II, BMI and cTnI are risk factors for postoperative hypoxemia in patients with Stanford type A acute aortic dissection.

A New Aspect of Penehyclidine Hydrochloride in Alleviating Myocardial Ischemia-Reperfusion Injury: Ferroptosis.

Penehyclidine hydrochloride (PHC) is an anticholinergic drug with cardioprotective effects. Ferroptosis is closely related to myocardial ischaemia-reperfusion injury (MIRI). In the present study, MIRI was induced in rats by left anterior descending coronary artery ligation. PHC pretreatment increased haemodynamic parameters and histopathological damage and reduced myocardial infarction size in the MIRI model. PHC pretreatment also inhibited ferroptosis, which was characterized by the decreased levels of Fe2+, 4-hydroxynonenal and ACSL4, and increased levels of GPX4, GSH-Px and GST. In response to 6 h of oxygen-glucose deprivation and 18 h of reoxygenation, PHC pretreatment had the same effects on these factors in H9c2 cells and reduced lipid ROS levels. Furthermore, ACSL4 overexpression reversed the protective effects of PHC on H9c2 cells. These results indicated that PHC inhibited MIRI through ACSL4-mediated ferroptosis. This study demonstrated that PHC could inhibit ferroptosis in MIRI and the relationship among PHC, ACSL4, ferroptosis and MIRI. This study demonstrated the inhibitory effect of PHC on ferroptosis and showed that PHC affects MIRI through ACSL4-mediated ferroptosis in vivo and in vitro.

Risk Factors and Early Outcomes for Gastrointestinal Complications in Patients Undergoing Open Surgery for Type A Aortic Dissection.

BACKGROUND: Gastrointestinal complications need to be paid more attention, especially in critically ill patients. The purpose of this study was to identify the risk factors and short-term outcomes of gastrointestinal complications after open surgery for type A aortic dissection. METHODS: A retrospective single-institutional study including patients who underwent open surgery for type A aortic dissection during 2012-2020 was conducted. Univariate analysis and logistic regression analysis were used to identify risk factors associated with gastrointestinal complications. The related clinical outcomes were compared between the patients with and without gastrointestinal complications. RESULTS: Among the 2746 patients, 150 developed gastrointestinal complications. The development of gastrointestinal complications contributed to the higher rate of mortality (P = .008), longer stay in the intensive care unit (P < .001), and longer hospital stay (P < .001). Logistic regression analysis showed that age (odds ratio [OR] 1.020; 95% confidence interval [CI] 1.005-1.057; P = .011), American Society of Anesthesiologists classification greater than grade III (OR 1.724; 95%CI 1.179-2.521, P = .005), pre-induction mean arterial pressure (OR 0.978; 95%CI 0.965-0.990, P = .001), aortic cross-clamp time (OR 1.012; 95%CI 1.005-1.019, P = .001), cardiopulmonary bypass time (OR 1.007; 95%CI 1.002-1.011, P = .002), and intraoperative transfusion of red blood cells (OR 1.214; 95%CI 1.122-1.314, P = .001) were independent risk factors for gastrointestinal complications. CONCLUSIONS: The incidence of gastrointestinal complications after open surgery for type A aortic dissection was 5.5%, resulting in increased mortality and prolonged hospital stay. It is necessary to take suitable strategies to reduce the incidence of gastrointestinal complications.

Isoflurane Preconditioning May Attenuate Cardiomyocyte Injury Induced by Hypoxia/Reoxygenation Possibly by Regulating miR-363-3p.

This study attempted to explore whether miR-363-3p play a role in the isoflurane (ISO)-mediated protective effect of cardiomyocyte injury induced by hypoxia/reoxygenation (H/R). A myocardial cell injury model was established, and the different preconditioning ISO concentrations were screened and determined. The miR-363-3p level was detected by RT-qPCR. The effects of miR-363-3p on proliferation and apoptosis of H9c2 cells were detected by CCK-8 assay and flow cytometry. Myocardial injury indexes were determined by enzyme-linked immunosorbent assay (ELISA). The interaction of miR-363-3p with the 3'-UTR of the KLF2 gene was confirmed by luciferase reporter gene assay. ISO pretreatment can reduce the up-regulation of miR-363-3p after H/R injury. ISO pretreatment reduces the inhibition of cell viability and the promotion of cell apoptosis induced by H/R stimuli, while the overexpression of miR-363-3p counteracts the protective effect of ISO pretreatment. Meanwhile, ISO pretreatment also reduced the level of markers of H/R-induced myocardial injury. Moreover, luciferase reporter analysis showed that KLF2 was the downstream target gene of miR-363-3p. ISO pretreatment may alleviate H/R-induced cardiomyocyte injury by regulating miR-363-3p.

Temporal effect of melatonin posttreatment on anoxia/reoxygenation injury in H9c2 cells.

Melatonin has been proven to reduce myocardial ischemia-reperfusion (MI/R) injury. However, in most studies, melatonin was administered before MI/R, thus, the results lack clinical significance in patients with acute myocardial infarction. We hypothesize that melatonin posttreatment at different times has different curative effects. Administered of Melatonin (150 µM) at different times after the onset of reoxygenation (t = -15, 0, 5, 10, 15, and 30 min). Cellular apoptosis, oxidative stress, and mitochondrial function were assessed. Mitophagy-related protein levels, mitochondrial membrane potential (MMP), and mitochondrial permeability transition pore (mPTP) activity were also measured. A/R injury upregulated mitophagy, which was associated with increased cellular apoptosis, oxidative stress, and mitochondrial dysfunction. Melatonin posttreatment (t = -15, 0, 5, 10, 15, and 30 min) significantly inhibited excessive mitophagy after A/R injury, reduced cellular apoptosis and oxidative stress, restored mitochondrial function and MMP, and restrained mPTP opening. The therapeutic time window in which melatonin posttreatment protected H9c2 cells against A/R injury was large (from -15 to 30 min after the onset of reperfusion), but the earlier the melatonin administration was, the better its protective effect was. This mechanism is likely due to a reduction in mPTP activity and MMP collapse, which lead to the inhibition of mitophagy.

Effects of Long Noncoding RNA H19 on Isoflurane-Induced Cognitive Dysregulation by Promoting Neuroinflammation.

INTRODUCTION: Isoflurane (ISO) may cause neuronal apoptosis and synaptic disorder during development, and damage long-term learning and memory function. This observation aimed to study the function of H19 in vitro and in vivo tests and the further mechanism was identified. METHODS: ISO cell models and rat models were established and reactive oxygen species (ROS) identified. The viability and apoptosis of HT22 cells were detected by the MTT and flow cytometer. Morris water maze test was conducted to analyze the neurotoxicity of ISO on spatial learning and memory ability. Quantitative PCR was the method to verify the expression of H19. The concentration of inflammatory indicators was identified by enzyme-linked immunosorbent assay. RESULTS: 1.5% and 2% ISO led to the neurotoxicity of HT22 cells and increased expression of H19. Silenced H19 meliorated these adverse impacts of ISO. Interference of H19 exerted neuroprotective roles by repressing modified neurological severity score, inhibiting escape latency, elevating distance and time of target area, and controlling ROS and inflammation. MiR-17-5p might be a promising competing endogenous RNA of H19. The expression of miR-17-5p was reduced in the ISO group and reversed by the absence of H19. CONCLUSION: Our results of in vitro and in vivo assay indicated that the absence of HT22 is a neuroprotective regulator of cognition and inflammation by accumulating miR-17-5p.

Melatonin postconditioning ameliorates anoxia/reoxygenation injury by regulating mitophagy and mitochondrial dynamics in a SIRT3-dependent manner.

Ischaemia/reperfusion (I/R) injury is accompanied by excessive mitochondrial autophagy (mitophagy) and an imbalance in mitochondrial dynamics. Melatonin has been reported to alleviate I/R injury by regulating mitophagy and mitochondrial dynamics. However, the underlying mechanism associated with this activity is not fully understood. The goal of the present study was to investigate whether and how melatonin administration at the beginning of reoxygenation exerts protective effects by regulating mitophagy and mitochondrial dynamics. H9c2 cells were transfected with sirtuin 3 (SIRT3)-targeting siRNA and then subjected to anoxia/reoxygenation (A/R) injury, with melatonin (150 µM) administered at the onset of reoxygenation. Biomarkers related to cellular apoptosis, oxidative stress, mitochondrial function, mitophagy and mitochondrial dynamics were assessed, and the expression and activity of SIRT3 was also measured. Mitochondrial fission and mitophagy were activated after A/R injury and were accompanied by cellular apoptosis, oxidative stress, and mitochondrial dysfunction. However, melatonin postconditioning inhibited excessive mitochondrial fission and mitophagy, promoted mitochondrial fusion, restored mitochondrial function and reduced cellular apoptosis, and the mitophagy inhibitor 3-methyladenine (3-MA) also attenuated A/R-induced apoptosis. Moreover, the A/R-induced decreases in SIRT3 and manganese superoxide dismutase (SOD2) activities were ameliorated by melatonin. However, SIRT3 silencing abolished the beneficial effects of melatonin, eliminated the inhibitory effects of melatonin on mitochondrial fission and mitophagy, and reversed the melatonin-induced increase in SOD2 activity. These results indicate that melatonin postconditioning protects H9c2 cells from A/R injury by inhibiting excessive mitophagy and maintaining the balance of mitochondrial fission and fusion in a SIRT3-dependent manner.

Effects of different ventilation on cerebral oxygen saturation and cerebral blood flow before and after modified ultrafiltration in infants during ventricular septal defect repair.

OBJECTIVE: To analyse the changes of different ventilation on regional cerebral oxygen saturation and cerebral blood flow in infants during ventricular septal defect repair. METHODS: Ninety-two infants younger than 1 year were enrolled in the study. End-expiratory tidal pressure of carbon dioxide was maintained at 40-45 and 35-39 mmHg in relative low and high ventilation groups. Regional cerebral oxygen saturation and flow velocity of the middle cerebral artery were recorded after anaesthesia (T0), cut pericardium (T1), separation from cardiopulmonary bypass (T2), the end of modified ultrafiltration, (T3) and at the end of operation (T4). RESULTS: The relative low ventilation group exhibited a significantly high regional cerebral oxygen saturation at each time point except for T2 (T0:77 ± 4, T1:76 ± 5, T3:76 ± 8, T4:76 ± 8, respectively, p < 0.001). Flow velocity of the middle cerebral artery in the relative low ventilation group was higher compared to the relative high ventilation group at each time point except for T2 (T0:53 ± 14, T1:54 ± 15, T3:53 ± 17, T4:52 ± 16, respectively, p < 0.001). Between the two groups, T2 showed the lowest middle cerebral artery flow velocity (relative low ventilation: 39 ± 15, relative high ventilation: 39 ± 11, p < 0.001). CONCLUSION: The infants' regional cerebral oxygen saturation and middle cerebral artery flow velocity performed better in the range of 40-45 mmHg end-expiratory tidal pressure of carbon dioxide during CHD surgery. Modified ultrafiltration increased cerebral oxygen saturation. It was important to regulate ventilation in order to balance cerebral oxygen in infants.

Effect of Melatonin on Postoperative Pain and Perioperative Opioid Use: A Meta-analysis and Trial Sequential Analysis.

OBJECTIVES: We performed this meta-analysis in order to assess the effect of melatonin on postoperative pain and perioperative opioid consumption. METHODS: We systematically searched PubMed, EMBASE, and the Cochrane Library until October 2019 for studies concerning the effect of melatonin vs. placebo on postoperative pain. We also searched for grey literature in ClnicalTrials.gov and grey literature databases, including OpenGrey and Grey Literature Report. We performed a meta-analysis of postoperative pain scores, perioperative opioid use, the number of patients with analgesic requirements, the time to the first analgesic requirement, length of hospital stay, and common reported adverse events of melatonin. RESULTS: According to the inclusion and exclusion criteria, 15 studies with a total of 1,102 patients were included in the final analysis. Melatonin was significantly associated with decreased VAS score (24 hours postoperatively) compared to placebo (trial sequential analysis = conclusive; mean difference [MD] -0.86; 95% confidence interval [CI] -1.38, -0.34; P = 0.001). Patients randomly assigned to melatonin were administered less postoperative opioids than patients in the control groups (trial sequential analysis = inconclusive; MD -3.33 mg; 95% CI -5.28, -1.38; P = 0.0008). The need for analgesic requirements was significantly decreased in the melatonin group. Patients who received melatonin had a significantly longer time to the first analgesic requirement. Compared to the placebo group, there were no significant differences in terms of length of hospital stay, dizziness, headache, paresthesia, and nausea. CONCLUSIONS: Given the low quality of evidence, minor degree of VAS score reduction, and inconclusive trial sequential analysis of postoperative opioid consumption, this meta-analysis neither supports nor opposes the effect of melatonin on postoperative pain.

Age-related cerebrovascular carbon dioxide reactivity in children with ventricular septal defect younger than 3 years.

BACKGROUND: Impaired cerebrovascular reactivity to carbon dioxide was proposed to contribute to neurological morbidity in children undergoing cardiac surgery. The objective of this study was to assess carbon dioxide reactivity and regional cerebral oxygen saturation in children younger than 3 years. METHODS: This study enrolled children younger than 3 years undergoing ventricular septal defect repair. The cohort was divided into three age groups: younger than 6 months, 6-12 months, and 12-36 months. Under steady-state anesthesia, carbon dioxide reactivity was calculated by measuring changes in middle cerebral artery blood flow velocity using transcranial Doppler sonography. Regional cerebral oxygen saturation changes were measured by near-infrared spectroscopy while endtidal carbon dioxide pressure was adjusted from 30 to 45 mm Hg. RESULTS: Carbon dioxide reactivity showed a statistically significant increasing relationship with age (younger than 6 months group: 4.42% ± 2.73%, 6-12 months group: 5.86% ± 1.91%, 12-36 months group: 7.58% ± 1.49%; P < .001). Regional cerebral oxygen saturation showed a statistically significant increasing relationship with age (younger than 6 months group: 65% ± 6%, 6-12 months group: 68% ± 5%, 12-36 months group: 70% ± 5%; P = .027). Regional cerebral oxygen saturation showed a statistically significant increasing relationship with endtidal carbon dioxide pressure in all children (P < .001). CONCLUSION: Abnormal carbon dioxide reactivity is prevalent in children younger than 3 years and the degree varies according to age.

Medium- and long-chain triglyceride propofol reduces the activity of acetyl-coenzyme A carboxylase in hepatic lipid metabolism in HepG2 and Huh7 cells.

Medium- and long-chain triglyceride (MCT/LCT) propofol is widely used as an intravenous anesthetic, especially in the intensive care unit. The present study aimed to assess whether MCT/LCT propofol is safe in the hyperlipidemic population for long-term use. Free fatty acids (FFAs) were used to establish high-fat stimulation of HepG2 and Huh7 cells. Subsequently, these cells were treated with propofol at the concentration of 0, 4, or 8 µg/ml for 24 and 48 h. The results indicated that the cell viability was notably decreased when the cells were stimulated with 2 mmol/L FFAs and treated with 12 µg/ml MCT/LCT propofol. Accordingly, we chose 2 mmol/L FFAs along with 4 and 8 µg/ml MCT/LCT propofol for the subsequent experiments. Four and 8 µg/ml MCT/LCT propofol inhibited FFA-induced lipid accumulation in the cells and significantly reversed acetyl coenzyme A carboxylase (ACC) activity. In addition, MCT/LCT propofol not only significantly promoted the phosphorylation of AMPK and ACC, but also reversed the FFA-induced decreased phosphorylation of AMPK and ACC. In conclusion, MCT/LCT propofol reverses the negative effects caused by FFAs in HepG2 and Huh7 cells, indicating that MCT/LCT propofol might positively regulate lipid metabolism.

MiR-183-5p protects rat hearts against myocardial ischemia/reperfusion injury through targeting VDAC1.

MicroRNAs have been reported to be implicated in myocardial ischemia/reperfusion (I/R) injury. The purpose of this study was to investigate the effect of miR-183-5p on I/R injury. Overexpression of miR-183-5p by agomiR transfection alleviated cardiac dysfunction and significantly reduced the infarct size in rats with myocardial I/R. MiR-183-5p also alleviated myocardial apoptosis with reduced apoptotic cells and lower levels of apoptosis associated proteins. in vitro experiments were conducted on rat H9c2 cells treated with anoxia/reoxygenation (A/R). Annexin V/propidium iodide (PI) staining and flow cytometry reported that the ratio of apoptotic cells decreased by miR-183-5p transfection before A/R treatment. Moreover, according to binding sequence prediction and Dual luciferase reporter assay, we explored that voltage-dependent anion channel 1 (VDAC1), which aggravates myocardial injury and apoptosis reported in our former research, was a target of miR-183-5p. In conclusion, miR-183-5p can efficiently attenuate I/R injury and miR-183-5p may exert its effect through repressing VDAC1 expression.

Effects of acute hypercapnia on cognitive function in patients undergoing bronchoscope intervention.

BACKGROUND: There are multiple studies that have revealed that hypercapnia possessed neuroprotection, the conclusive cognitive impacts of permissive hypercapnia in medicine is still unclear. METHODS: A total of 102 patients registered for this research work had accomplished cognitive tests; with 64 patients possessing moderate hypercapnia all through bronchoscope intervention (BI). Thirty-six patients completed collection of blood specimens. Every patient underwent the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) a day before the surgery (T0), as well as at 7 days (T7). Serum specimens were used to measure levels of S100B, neuron-specific enolase (NSE), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), superoxide dismutase (SOD) prior to the administration of anesthesia (T0), one day (T1) and seven days (T7) after surgery. RESULTS: In comparison with the preoperative MMSE scores, Group Hypercapnia (Group H) on 7 days after surgery, exhibited a significant increased score (P=0.00). In comparison with the preoperative MoCA scores, Group H on 7 days after surgery exhibited a significant increased score (P=0.00). Meanwhile, the MoCA scores in Group H exhibited considerably higher elevation as compared with that in the Group Control (Group C) (P=0.01). No substantial differences were observed in serum S100B and NSE levels between Group H and Group C (P=0.23, P=0.14). Serum IL-6, TNF-α, SOD and MDA levels shared similarity between two groups. CONCLUSIONS: Mild and moderate hypercapnia augmented cognitive activity with the help of MMSE tests and MoCA tests, whereby the latent reasons were not sure. As suggested by this study, hypercapnia up to 100 mmHg during BI was less likely to affect cognitive function adversely.

RhoA/rho-kinase, nitric oxide and inflammatory response in LIMA during OPCABG with isoflurane preconditioning.

BACKGROUND: Grafting vessel with LIMA to the left anterior descending coronary artery plays a most important role in the long-term prognosis of OPCABG surgery. The aim of this study was to compare the effects of isoflurane preconditioning on miRs and mRNAs levels in the left internal mammary arterie (LIMA) graft with propofol in patients undergoing off-pump coronary artery bypass surgery (OPCABG). METHODS: Patients were randomly assigned to receive either propofol (n = 15), or interrupted isoflurane (n = 15). In group P, propofol administration was continued at 3-5 mg/kg/h intravenous injection for the duration of surgery. Five minutes prior to incision, patients of the isoflurane group (group Iso) received 2 cycles of 1 MAC isoflurane. RESULTS: miR-221 were significantly lower in group Iso (P < 0 .05). E-selectin mRNA, RhoA mRNA and ROK mRNA were significantly lower at specimens of LIMA in group Iso compared with those in group P patients (P < 0 .05). The expression of NOS3 mRNA was significantly higher in group Iso patients (P < 0 .05). CONCLUSION: Our findings provide some insight that prior interrupted isoflurane administration could regulate miR-221, and downstream effectors (mRNAs) and resulted in actual attenuation of inflammation and spasm of LIMA in patients undergoing OPCABG surgery. TRIAL REGISTRATION: NCT No. ( ClinicalTrials.gov ): NCT02678650; Registration date: January 23, 2016.