Apelin receptor inhibition in ischemia-reperfused mouse hearts protected by endogenous n-3 polyunsaturated fatty acids.

Background: While the protective effects of n-3 polyunsaturated fatty acids (PUFAs) on cardiac ischemia-reperfusion (IR) injury have been previously reported, limited data are available regarding how these fatty acids affect membrane receptors and their downstream signaling following IR injury. We aimed to identify potential receptors activated by n-3 PUFAs in IR hearts to understand the regulatory mechanisms of these receptors. Methods: We used fat-1 mice, which naturally have elevated levels of n-3 PUFAs, and C57BL/6J mice as a control group to create a myocardial IR injury model through Langendorff perfusion. We assessed the impact of endogenous n-3 PUFAs on left ventricular function, myocardial infarct size, myocardial apoptosis, and ATP production. RNA sequencing (RNA-seq) and bioinformatics analysis were conducted to identify molecular targets affected by n-3 PUFAs. Based on these analyses we then treated IR hearts of WT and fat-1 mice with an antagonist (ML221) or an agonist (apelin-13) for the predicted receptor to assess cardiac contractile function and intracellular signaling pathways. An in vitro hypoxia-reoxygenation (HR) model was also used to confirm the effects of n-3 PUFAs on the examined intracellular signaling pathways. Results: Endogenous n-3 PUFAs protected cardiac structure and function in post-IR hearts, and modulated phosphorylation patterns in the PI3K-AKT-mTOR signaling pathways. RNA-seq analysis revealed that n-3 PUFAs affected multiple biological processes as well as levels of the apelin receptor (APLNR). Consistent with a role for the PLNNR, ML221 synchronized the activation of the PI3K-AKT-mTOR signaling axis, suppressed the expression of PKCδ and phosphorylated p38α, upregulated PKCε expression, upregulated or restored the phosphorylation of myofilaments, and prevented myocardial injury and contractile dysfunction in WT IR hearts. By contrast, apelin-13 disrupted the PI3K-AKT-mTOR signaling axis in post-IR fat-1 hearts. The phosphorylation signaling targeted by APLNR inhibition in post-IR fat-1 hearts was also observed after treating HR cells with eicosatetraenoic acid (EPA). Conclusion: Endogenous n-3 PUFAs protect against post-IR injury and preserve cardiac contractile function possibly through APLNR inhibition. This inhibition synchronizes the PI3K-AKT-mTOR axis, suppresses detrimental phosphorylation signaling, and restores or increases myofilament phosphorylation in post-IR hearts. The beneficial effects observed in fat-1 transgenic mouse hearts can be attributed, at least in part, to elevated EPA levels. This study is the first to demonstrate that n-3 PUFAs protect hearts against IR injury through APLNR inhibition.

Innovative Animal Models Of Cardiac Remodeling: Development And Evaluation.

ARTICLES DISCUSSED: Liao, R. et al. Generation and characterization of right ventricular myocardial infarction induced by permanent ligation of the right coronary artery in mice. Journal of Visualized Experiments. (180), e63508 (2022). Li, X. et al. Establishment and evaluation of a porcine vein graft disease model. Journal of Visualized Experiments. (185), e63896 (2022). Lu, A. et al. Viral transgene expression in rodent hearts and the assessment of cardiac arrhythmia risk. Journal of Visualized Experiments. (185), e64073 (2022). Wang, Y., Gao, H., Li, Y., Sun, H., Liu, L. Estimating bilateral atrial function by cardiovascular magnetic resonance feature tracking in patients with paroxysmal atrial fibrillation. Journal of Visualized Experiments. (185), e63598 (2022). Wu, J. et al. Surgically induced cardiac volume overload by aortic regurgitation in mouse. Journal of Visualized Experiments. (186), e63579 (2022). Li, X. et al. A surgical model of heart failure with preserved ejection fraction in Tibetan minipigs. Journal of Visualized Experiments. (180), e63526 (2022). Wang, M. et al. Improved renal denervation mitigated hypertension induced by angiotensin II infusion. Journal of Visualized Experiments. (183), e63719 (2022). Xia, Y. et al. Investigating the pathogenesis of MYH7 mutation Gly823Glu in familial hypertrophic cardiomyopathy using a mouse model. Journal of Visualized Experiments. (186), e63949 (2022).

Effects of Workplace Ostracism on Burnout among Nursing Staff during the COVID-19 Pandemic, Mediated by Emotional Labor.

This study investigated the effects of workplace ostracism on emotional labor and burnout among current nursing staff during the COVID-19 pandemic, as well as the relationship between the surface acting and deep acting of emotional labor as the mediators of workplace ostracism and burnout. The sample for this study consisted of 250 nursing staff recruited from Taiwanese medical institutions, and the questionnaire was divided into two stages. The first stage included questions about ostracism and personal data, and then two months later the same respondents completed part two of the questionnaire regarding emotional labor and burnout, which solved the problem of common-method variance (CMV). The results of this study indicate that ostracism had a positive and significant effect on burnout and surface acting, but its negative effect on deep acting was not supported. While surface acting showed partial mediation between ostracism and burnout, deep acting did not have a significant mediating effect between ostracism and burnout. These results can provide a reference for practice and researchers.

TAK1 Activation by NLRP3 Deficiency Confers Cardioprotection Against Pressure Overload-Induced Cardiomyocyte Pyroptosis and Hypertrophy.

A comprehensive view of the role of NLRP3/caspase-1/GSDMD-mediated pyroptosis in pressure overload cardiac hypertrophy is presented in this study. Furthermore, mitigation of NLRP3 deficiency-induced pyroptosis confers cardioprotection against pressure overload through activation of TAK1, whereas this salutary effect is abolished by inhibition of TAK1 activity, highlighting a previously unrecognized reciprocally regulatory role of NLRP3-TAK1 governing inflammation-induced cell death and hypertrophic growth. Translationally, this study advocates strategies based on inflammation-induced cell death might be exploited therapeutically in other inflammatory and mechanical overload disorders, such as myocardial infarction and mitral regurgitation.

Are virtual anime endorsers a new type of endorser? Examining product involvement as a moderating role.

Virtual anime endorsement has been prevalent as an advertising strategy, and many companies invest massive amounts of money into virtual endorsements. While previous studies have found that endorser-product congruence is related to consumer brand attitude and purchase intention, it is not known whether moderate incongruence between a virtual anime endorser and a product has a positive influence on brand attitude and purchase intention. This study developed a 1 × 2 experiment to investigate the influences of virtual anime endorser-product congruence and moderate the endorser-product incongruence on consumer brand attitude and purchase intention. Product involvement played a key moderating role in the relationships of virtual anime endorser-product congruence and the endorser-product incongruence with consumer attitudes. A total of 919 participants were recruited from animation-related venues and stores in Taiwan. The findings of this study validated the interaction effects of virtual anime endorser-product congruence and incongruence on these two consumer responses, i.e., brand attitude and purchase intention. This study further investigated the moderating effect of product involvement in the relationships of virtual anime endorser-product congruence and moderate the endorser-product incongruence with consumer responses. The findings of this study provide a valuable reference regarding endorsers and product patterns through which enterprises can maximize their value.

Examine the relationships between health-related quality of life, achievement motivation and job performance: the case of Taiwan hospitality industry.

BACKGROUND: Employees are considered as one of the most important assets in many organizations, and their health well-being is critical to help achieve a sustainable and motivated workforce that is committed to delivering quality hospitality services through enhanced performance and productivity. Given the extent of the challenges and impact presented by the COVID-19 pandemic to the hospitality industry, it is timely to gain further insights on employees' health well-being. The key purpose of this study is to examine the relationships between health-related quality of life, achievement motivation and job performance in the Taiwan hospitality industry, to acquire a better understanding of their relationships through the job performance pathway models. METHODS: This study has used a purposeful sampling technique to select the 10 highest-earning hospitality companies in Taiwan. A total of 292 questionnaires were collected from the employees of these hospitality companies. Based on the multi-dimensional concept of health-related quality of life (HRQoL), the relationships between the five key dimensions (i.e. psychological health, physical health, social health, achievement motivation, and job performance) were examined. To measure these dimensions, the survey questions were adapted from previous research such as the World Health Organization's WHOQOL-BREF scale, Minnesota Satisfaction Questionnaire. Partial least squares - Structural Equation Modeling method was used to explore these dimensions, and two job performance pathway models (for manager and staff) were subsequently developed. RESULTS AND CONCLUSIONS: Findings showed that psychological health directly affected the manager's job performance and physical health had a similar effect through social health. While psychological health had not affected the staff's job performance, but it could affect achievement motivation through both direct and indirect effects of social health. The pathway models that were developed indicated that the manager's job performance was mainly affected by psychological health and social health, whereas the key dimension that had affected the staff's job performance was achievement motivation.

A Surgical Model of Heart Failure with Preserved Ejection Fraction in Tibetan Minipigs.

More than half of heart failure (HF) cases are classified as heart failure with preserved ejection fraction (HFpEF) worldwide. Large animal models are limited for investigating the fundamental mechanisms of HFpEF and identifying potential therapeutic targets. This work provides a detailed description of the surgical procedure of descending aortic constriction (DAC) in Tibetan minipigs to establish a large animal model of HFpEF. This model used a precisely controlled constriction of the descending aorta to induce chronic pressure overload in the left ventricle. Echocardiography was used to evaluate the morphological and functional changes in the heart. After 12 weeks of DAC stress, the ventricular septum was hypertrophic, but the thickness of the posterior wall was significantly reduced, accompanied by dilation of the left ventricle. However, the LV ejection fraction of the model hearts was maintained at >50% during the 12-week period. Furthermore, the DAC model displayed cardiac damage, including fibrosis, inflammation, and cardiomyocyte hypertrophy. Heart failure marker levels were significantly elevated in the DAC group. This DAC-induced HFpEF in minipigs is a powerful tool for investigating molecular mechanisms of this disease and for preclinical testing.

Differential mRNA Expression and Circular RNA-Based Competitive Endogenous RNA Networks in the Three Stages of Heart Failure in Transverse Aortic Constriction Mice.

Background: The murine transverse aortic constriction (TAC) model is frequently used to investigate molecular mechanisms underlying heart failure. However, limited data is available regarding the expression of mRNAs and circRNAs in murine heart failure progression induced by pressure overload. Methods: Transverse aortic constriction was used to induce pressure overload for 2, 4, and 8 weeks in mice. Echocardiographic measurements in B-mode and M-mode, as well as blood flow Doppler data were collected in mice without (sham) and with (2W-, 4W-, and 8W-post-TAC) pressure load. Hearts were excised and morphology, cardiomyocyte size, and fibrosis were determined. RNA sequencing, circRNA microarray, functional mRNA enrichment analysis, hub gene identification, target miRNA interaction, and competitive endogenous RNA (ceRNA) network construction were conducted. Results: Heart weight, cardiomyocyte hypertrophy, and fibrosis gradually increased over time in the hearts with pressure overload. The 2W-post-TAC hearts displayed concentric hypertrophy, thickened left ventricular walls, and increased EF and FS. The 4W-post-TAC hearts were characterized by preserved EF and FS, dilated atria, and increased left ventricle (LV) systolic volume. The 8W-post-TAC hearts presented with ventricular and atrial dilation, increased LV systolic and diastolic volume, reduced EF and FS, and increased ejection time (MV ET). mRNA expression analysis suggested that cardiac remodeling, immune response dysregulation, and metabolic disorder were the key cellular events in heart failure progression. Depression in chemotaxis and mitochondrial function were predicted in 4W- and 8W-post-TAC myocardia, respectively. A ceRNA network analysis demonstrated that the circRNAs targeted the expression of genes enriched in metabolism dysregulation in the 2W-post-TAC hypertrophic hearts, while they targeted genes enriched in cardiac remodeling in the 4W-post-TAC EF-preserved hearts and in the suppression of oxidative phosphorylation and cardiac contraction in the 8W-post-TAC EF-reduced hearts. Conclusion: Our work empirically demonstrates that distinctive features of heart failure, including ventricular hypertrophy, heart failure with preserved EF (HFpEF), and heart failure with reduced EF (HFrEF) are present in the murine pressure overload models. The three stages of heart failure vary in terms of mRNA and circRNA expression, as well as ceRNA regulation in a manner consistent with their structural, functional, and pathological differences.

A Porcine Model of Heart Failure With Preserved Ejection Fraction Induced by Chronic Pressure Overload Characterized by Cardiac Fibrosis and Remodeling.

Heart failure is induced by multiple pathological mechanisms, and current therapies are ineffective against heart failure with preserved ejection fraction (HFpEF). As there are limited animal models of HFpEF, its underlying mechanisms have not yet been elucidated. Here, we employed the descending aortic constriction (DAC) technique to induce chronic pressure overload in the left ventricles of Tibetan minipigs for 12 weeks. Cardiac function, pathological and cellular changes, fibrotic signaling activation, and gene expression profiles were explored. The left ventricles developed concentric hypertrophy from weeks 4 to 6 and transition to dilation starting in week 10. Notably, the left ventricular ejection fraction was maintained at >50% in the DAC group during the 12-week period. Pathological examination, biochemical analyses, and gene profile analysis revealed evidence of inflammation, fibrosis, cell death, and myofilament dephosphorylation in the myocardium of HFpEF model animals, together with gene expression shifts promoting cardiac remodeling and downregulating metabolic pathways. Furthermore, we noted the activation of several signaling proteins that impact cardiac fibrosis and remodeling, including transforming growth factor-ß/SMAD family members 2/3, type I/III/V collagens, phosphatidylinositol 3-kinase, extracellular signal-regulated kinase, matrix metalloproteinases 2 and 9, tissue inhibitor of metalloproteinases 1 and 2, interleukins 6 and 1ß, and inhibitor of κBα/nuclear factor-κB. Our findings demonstrate that this chronic pressure overload-induced porcine HFpEF model is a powerful tool to elucidate the mechanisms of this disease and translate preclinical findings.

Aged Monkeys Fed a High-Fat/High-Sugar Diet Recapitulate Metabolic Disorders and Cardiac Contractile Dysfunction.

Aged nonhuman primate (NHP) models are of great value for studying the pathology of metabolic heart diseases and developing therapeutic strategies. In this study, aged male cynomolgus monkeys were fed a regular diet or a high-fat/high-sugar diet (HFSD) for 8 months. Metabolic disorders were diagnosed by 1H-NMR and serum biochemistry, and cardiac function was evaluated by echocardiography. Our results showed that serum metabolic profiles were altered in aged monkeys fed a HFSD, in line with aortic tissue damage, cardiac remodeling, and contractile dysfunction. This aged monkey model significantly increased expression of proinflammatory cytokines and altered expression and phosphorylation of intracellular signaling proteins in the heart, as compared to aged monkeys on a regular diet. Furthermore, the animals demonstrated increased phosphorylation of cardiac myofilament proteins which are causatively associated with decreased myofilament contractility. We conclude that the aged monkey model fed a HFSD exhibits metabolic disorders and cardiac contractile dysfunction.

Cardioprotective Effects of n-3 Polyunsaturated Fatty Acids: Orchestration of mRNA Expression, Protein Phosphorylation, and Lipid Metabolism in Pressure Overload Hearts.

Background: Pressure overload can result in dilated cardiomyopathy. The beneficial effects of n-3 polyunsaturated fatty acids (n-3 PUFAs) on heart disorders have been widely recognized. However, the molecular mechanisms underlying their protective effects against cardiomyopathy remain unclear. Methods: Pressure overload in mice induced by 8 weeks of transverse aortic constriction was used to induce dilated cardiomyopathy. A transgenic fat-1 mouse model carrying the n-3 fatty acid desaturase gene fat-1 gene from Caenorhabditis elegans was used to evaluate the mechanism of n-3 PUFAs in this disease. Echocardiography, transmission electron microscopy, and histopathological analyses were used to evaluate the structural integrity and function in pressure overloaded fat-1 hearts. mRNA sequencing, label-free phosphoprotein quantification, lipidomics, Western blotting, RT-qPCR, and ATP detection were performed to examine the effects of n-3 PUFAs in the heart. Results: Compared with wild-type hearts, left ventricular ejection fraction was significantly improved (C57BL/6J [32%] vs. fat-1 [53%]), while the internal diameters of the left ventricle at systole and diastole were reduced in the fat-1 pressure overload hearts. mRNA expression, protein phosphorylation and lipid metabolism were remodeled by pressure overload in wild-type and fat-1 hearts. Specifically, elevation of endogenous n-3 PUFAs maintained the phosphorylation states of proteins in the subcellular compartments of sarcomeres, cytoplasm, membranes, sarcoplasmic reticulum, and mitochondria. Moreover, transcriptomic analysis predicted that endogenous n-3 PUFAs restored mitochondrial respiratory chain function that was lost in the dilated hearts, and this was supported by reductions in detrimental oxylipins and protection of mitochondrial structure, oxidative phosphorylation, and ATP production. Conclusions: Endogenous n-3 PUFAs prevents dilated cardiomyopathy via orchestrating gene expression, protein phosphorylation, and lipid metabolism. This is the first study provides mechanistic insights into the cardioprotective effects of n-3 PUFAs in dilated cardiomyopathy through integrated multi-omics data analysis.

Effect of mesenchymal stem cells transplantation on the changes of oligodendrocyte lineage in rat brain with experimental autoimmune encephalomyelitis.

OBJECTIVE: To explore the effect of bone marrow mesenchymal stem cells (BM-MSCs) transplantation on the changes of oligodendrocyte lineage in brain of experimental autoimmune encephalomyelitis (EAE) rats. METHODS: The animals were divided into normal control group, EAE model group (EAE group), cell culture medium injection treatment group (placebo treatment group), and MSCs treatment group (treatment group). The changes of A2B5-, O4-, and CNPase-positive cells in oligodendrocyte lineage in rat brain were observed after 1, 3, 7, 14, 21, and 28 days. RESULTS: The number of A2B5-positive cells in rat brain of the treatment group at each time point was significantly more than that of the EAE and placebo treatment groups, and most obvious at 14 days. The O4-positive cells number at each time point in the treatment group was significantly increased compared with the EAE and placebo treatment groups, and most obvious at 14 days. The CNPase-positive cells number at each time point in the treatment group was significantly increased compared with the EAE and placebo treatment groups, and most obvious at 14 days. CONCLUSIONS: MSCs treatment can increase cells expression in oligodendrocyte lineage, which laying a solid foundation for myelin regeneration.

Slit2 Protects Hearts Against Ischemia-Reperfusion Injury by Inhibiting Inflammatory Responses and Maintaining Myofilament Contractile Properties.

BACKGROUND: The secreted glycoprotein Slit2, previously known as an axon guidance cue, has recently been found to protect tissues in pathological conditions; however, it is unknown whether Slit2 functions in cardiac ischemia-reperfusion (IR) injury. METHODS: Langendorff-perfused isolated hearts from Slit2-overexpressing (Slit2-Tg) mice and C57BL/6J mice (background strain) were subjected to 20 min of global ischemia followed by 40 min of reperfusion. We compared Slit2-Tg with C57BL/6J mice in terms of left ventricular function and infarct size of post-IR hearts along with tissue histological and biochemical assessments (mRNA and protein expression, phosphorylation status, and myofilament contractile properties). RESULTS: Slit2 played cardioprotective roles in maintaining contractile function and reducing infarct size in post-IR hearts. IR increased the expression of the Slit2 receptor Robo4 and the membrane receptor Slamf7, but these increases were suppressed by Slit2 overexpression post IR. This suppression was associated with inhibition of the nuclear translocation of NFκB p65 and reductions in IL-1ß and IL-18 release into perfusates. Furthermore, Slit2 overexpression attenuated the increases in myofilament-associated PKCs and phosphorylation of cTnI at Ser43 in the post-IR myocardium. The myofilament calcium sensitivity and actomyosin MgATPase activity were preserved in the post-IR Slit2 myocardium. CONCLUSION: Our work demonstrates that Slit2 inhibits inflammatory responses and maintains myofilament contractile properties, thus contributing, at least in part, to the prevention of structural and functional damage during IR.

Ketogenic diet effects on 52 children with pharmacoresistant epileptic encephalopathy: A clinical prospective study.

Objective: To evaluate the clinical impact of ketogenic diet (KD) on children with pharmacoresistant epileptic encephalopathy. Methods: In all, 52 children with pharmacoresistant epileptic encephalopathy that diagnosed in our hospital from July 2012 to June 2015 were selected, including West syndrome 38 cases, Lennox-Gastaut Syndrome 7 cases, Doose Syndrome 1 case, and Dravet syndrome 6 cases, and the effect, compliance, adverse reactions, electroencephalogram (EEG), and cognitive function were analyzed. Modified Johns Hopkins protocol was used to initiate KD, and Engel scale was used to evaluate the effect, and evaluated the effect of KD on the cognition, language, and motor function. Results: At 12 weeks of KD treatment, the patients achieved I, II, III, and IV grade effect were accounted for 26.9% (14/52 cases), 17.3% (9/52 cases), 11.5% (6/52 cases), and 44.2% (23/52 cases), respectively, according to Engel scale. KD has different effect on different epileptic syndromes, best effect on Doose syndromes of 100%, and better effect on West syndrome with the effect rate of 57.9%, and the total effect number was 22 cases. The reduction of epileptiform discharges in the awake state before KD treatment was correlated with the seizure time after 3 months of KD treatment (r = .330, p = .017). The cognitive function of 23 patients was improved, 12 patients had language improvement, and the motor function was improved in 10 patients. In all, 23 patients had adverse reactions, and all patients were tolerated and improved. Conclusion: KD has certain effect on children with pharmacoresistant epileptic encephalopathy, and it can reduce interictal epileptic discharge frequency, and improve the background rhythm of EEG. The reduction of epileptiform discharges in awake state is in favor of the reduction of seizures frequency, thus increasing the efficacy, and improve the cognitive function, language, and motor function to varying degrees, combined with less adverse reaction, which is worthy of clinical application.

[High-frequency echocardiography for assessment of regional wall motion abnormality and cardiac function in mice with myocardial infarction].

OBJECTIVE: To evaluate the value of high-frequency echocardiography in assessing cardiac structure and function in a mouse model of myocardial infarction. METHODS: Twenty-five C57BL/6 mice were randomly divided into sham-operated group (n=10) and myocardial infarction model group (n=15) established by ligation of the left anterior descending artery. The cardiac structure, regional wall motion and cardiac function of mice were examined with pulsed wave Doppler (PWD), tissue Doppler imaging (TDI), EKV and M-mode echocardiography 3 days before and at 1 week after the operation. The histological changes and myocardial structure of the heart were observed at 1 week after the operation. RESULTS: High-frequency echocardiography and HE staining detected obvious myocardial infarction in the mice in the model group. Compared with the sham-operated mice, the mice with myocardial infarction showed significant left ventricular expansion, obvious thinning of the ventricular wall, and significantly decreased ventricular systolic function and diastolic function with regional wall motion abnormality and ventricular remodeling. CONCLUSION: s 2D-type echocardiography combined with M-mode, PWD, TDI and EKVTM for allows accurate and sensitive detection of the loci and severity of myocardial infarction to provide important evidence for clinical diagnosis and treatment of myocardial infarction.

Inhibition of Soluble Epoxide Hydrolase Limits Mitochondrial Damage and Preserves Function Following Ischemic Injury.

AIMS: Myocardial ischemia can result in marked mitochondrial damage leading to cardiac dysfunction, as such identifying novel mechanisms to limit mitochondrial injury is important. This study investigated the hypothesis that inhibiting soluble epoxide hydrolase (sEH), responsible for converting epoxyeicosatrienoic acids to dihydroxyeicosatrienoic acids protects mitochondrial from injury caused by myocardial infarction. METHODS: sEH null and WT littermate mice were subjected to surgical occlusion of the left anterior descending (LAD) artery or sham operation. A parallel group of WT mice received an sEH inhibitor, trans-4-[4-(3-adamantan-1-y1-ureido)-cyclohexyloxy]-benzoic acid (tAUCB; 10 mg/L) or vehicle in the drinking water 4 days prior and 7 days post-MI. Cardiac function was assessed by echocardiography prior- and 7-days post-surgery. Heart tissues were dissected into infarct, peri-, and non-infarct regions to assess ultrastructure by electron microscopy. Complexes I, II, IV, citrate synthase, PI3K activities, and mitochondrial respiration were assessed in non-infarct regions. Isolated working hearts were used to measure the rates of glucose and palmitate oxidation. RESULTS: Echocardiography revealed that tAUCB treatment or sEH deficiency significantly improved systolic and diastolic function post-MI compared to controls. Reduced infarct expansion and less adverse cardiac remodeling were observed in tAUCB-treated and sEH null groups. EM data demonstrated mitochondrial ultrastructure damage occurred in infarct and peri-infarct regions but not in non-infarct regions. Inhibition of sEH resulted in significant improvements in mitochondrial respiration, ATP content, mitochondrial enzymatic activities and restored insulin sensitivity and PI3K activity. CONCLUSION: Inhibition or genetic deletion of sEH protects against long-term ischemia by preserving cardiac function and maintaining mitochondrial efficiency.

Cerebral infarction after mild head trauma in children.

We conducted this retrospective, case record review to determine the risk factors and clinical features associated with cerebral infarction after mild head trauma in children. The median age of the cohort was 2.18 years (range, 6 mo-8 y). Most (26/29) of the patients developed the neurological symptoms and signs within 72 hours after trauma, 51.7% within 30 minutes. The first symptoms included hemiparesis (20), facial paresis (7), and convulsion (7). 86.21% of the lesions lay in basal ganglia region. Pre-existing basal ganglia calcification was identified in 13 as a risk factor.

Clinical features and risk factors of cerebral infarction after mild head trauma under 18 months of age.

Mild head trauma can cause cerebral infarction in children younger than 18 months of age, yet the pathogenesis, clinical characteristics, and risk factors are not fully understood. Data of 16 cases between August 2008 and September 2011, including clinical manifestations and imaging and laboratory findings were collected and analyzed. All patients had the history of mild head trauma. The median age of the cohort was 13.5 months (range 6 months to 18 months). All children developed neurologic symptoms and signs within 72 hours after trauma, 62.5% (10/16) within 30 minutes. The first symptoms included hemiparesis (9/16), facial paresis (4/16), and convulsion (6/16). Overall, 93.75% (15/16) of the lesions were in the basal ganglia region. Two risk factors were identified, basal ganglia calcification in 10 and cytomegalovirus infection in eight. After conservative therapy, the neurologic deficits recovered to some extent. Cerebral infarction after mild head trauma in children younger than 18 months of age may take place, especially under the circumstances of basal ganglia calcification or cytomegalovirus infection.

Leukemia inhibitory factor inhibits the proliferation of primary rat astrocytes induced by oxygen-glucose deprivation.

Leukemia inhibitory factor (LIF) is a neuroprotective cytokine that is necessary for the normal development of astrocytes. Oxygen-glucose deprivation (OGD) can induce astrocyte proliferation by increasing hypoxia-inducible factor alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF). Here, we studied whether LIF affects the proliferation of cultured primary rat astrocytes under OGD conditions by measuring EdU incorporation into astrocyte DNA and the expression of proliferating cell nuclear antigen (PCNA) mRNA and protein. Our findings show that low concentrations of LIF (5 and 10 ng/mL) significantly decreased EdU incorporation and downregulated the expression of PCNA mRNA and PCNA protein in astrocytes subjected to OGD. A low concentration of LIF (10 ng/mL) clearly inhibited astrocyte proliferation induced by OGD, while a higher concentration (50 ng/mL) had no effect. To investigate the mechanism of this inhibition by LIF (10 ng/mL), the expression of 3 related genes (LIF receptor, HIF-1alpha, and VEGF) was assessed using real-time PCR; VEGF protein expression was measured by Western blot. Our results indicate that LIFR mRNA was downregulated in astrocytes subjected to OGD. Interestingly, treatment with LIF further reduced LIFR mRNA expression in these cells. LIF treatment also decreased the expression of HIF-1alpha mRNA, VEGF mRNA, and VEGF protein induced by OGD. Low concentrations of LIF were observed to inhibit astrocyte proliferation induced by OGD.