Although atopic dermatitis (AD) is known to be a representative skin disorder, it also affects the systemic immune response. In a recent study, myoblasts were shown to be involved in the immune regulation, but the roles of muscle cells in AD are poorly understood. We aimed to identify the relationship between mitochondria and atopy by genome-wide analysis of skeletal muscles in mice. We induced AD-like symptoms using house dust mite (HDM) extract in NC/Nga mice. The transcriptional profiles of the untreated group and HDM-induced AD-like group were analyzed and compared using microarray, differentially expressed gene and functional pathway analyses, and protein interaction network construction. Our microarray analysis demonstrated that immune response-, calcium handling-, and mitochondrial metabolism-related genes were differentially expressed. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology pathway analyses, immune response pathways involved in cytokine interaction, nuclear factor-kappa B, and T-cell receptor signaling, calcium handling pathways, and mitochondria metabolism pathways involved in the citrate cycle were significantly upregulated. In protein interaction network analysis, chemokine family-, muscle contraction process-, and immune response-related genes were identified as hub genes with many interactions. In addition, mitochondrial pathways involved in calcium signaling, cardiac muscle contraction, tricarboxylic acid cycle, oxidation-reduction process, and calcium-mediated signaling were significantly stimulated in KEGG and Gene Ontology analyses. Our results provide a comprehensive understanding of the genome-wide transcriptional changes of HDM-induced AD-like symptoms and the indicated genes that could be used as AD clinical biomarkers.
Animals ; Biomarkers ; Calcium ; Calcium Signaling ; Citric Acid ; Citric Acid Cycle ; Cytokines ; Dermatitis, Atopic ; Gene Ontology ; Genome ; Metabolism ; Mice ; Microarray Analysis ; Mitochondria ; Muscle Cells ; Muscle Contraction ; Muscle, Skeletal ; Myoblasts ; Myocardium ; Oxidation-Reduction ; Protein Interaction Maps ; Pyroglyphidae ; Receptors, Antigen, T-Cell ; Skin

BACKGROUND: The left internal thoracic artery (LITA) has been used as the first conduit of choice in coronary artery bypass grafting (CABG) because of excellent long-term patency and outcomes. However, no studies have examined substances other than nitric oxide that could be beneficial for the bypass conduit, native coronary artery or ischemic myocardium. This study was conducted to evaluate differences in metabolic profiles between the LITA and ascending aorta using gas chromatography-time of flight-mass spectrometry (GC-TOF-MS). METHODS: Twenty patients who underwent CABG using the LITA were prospectively enrolled. Plasma samples were collected simultaneously from the LITA and ascending aorta. GC-TOF-MS based untargeted metabolomic analyses were performed and a 2-step volcano plot analysis was used to identify distinguishable markers from two plasma metabolome profiles. Semi-quantitative and quantitative analyses were performed using GC-TOF-MS and enzyme-linked immunosorbent assay, respectively, after selecting target metabolites based on the metabolite set enrichment analysis. RESULTS: Initial volcano plot analysis demonstrated 5 possible markers among 851 peaks detected. The final analysis demonstrated that the L-cysteine peak was significantly higher in the LITA than in the ascending aorta (fold change = 1.86). The concentrations of intermediate metabolites such as L-cysteine, L-methionine and L-cystine in the ‘cysteine and methionine metabolism pathway' were significantly higher in the LITA than in the ascending aorta (2.0-, 1.4- and 1.2-fold, respectively). Quantitative analysis showed that the concentration of hydrogen sulfide (H2S) was significantly higher in the LITA. CONCLUSION: The plasma metabolome profiles of the LITA and ascending aorta were different, particularly higher plasma concentrations of L-cysteine and H2S in the LITA.
Aorta ; Chromatography, Gas ; Coronary Artery Bypass ; Coronary Vessels ; Cysteine ; Cystine ; Enzyme-Linked Immunosorbent Assay ; Humans ; Hydrogen Sulfide ; Mammary Arteries ; Mass Spectrometry ; Metabolism ; Metabolome ; Metabolomics ; Methionine ; Myocardium ; Nitric Oxide ; Plasma ; Prospective Studies ; Spectrum Analysis

Objective Quantitative analysis and comparison of the expression of ribonucleic acid （RNA） from frozen organs and formaldehyde-fixed and paraffin-embedded （FFPE） tissues. Methods Frozen specimens of human brain, myocardium and liver tissues as well as FFPE samples at different postmortem intervals were collected and mass concentration of RNA was extracted and detected. Reverse transcription-quantitative polymerase chain reaction （RT-qPCR） technology was used to analyze the amplification efficiency and relative expression of each RNA marker. Results The mass concentration and integrity of RNA extracted from FFPE samples were relatively low compared with frozen specimens. The amplification efficiency of RNA markers was related with RNA species and the length of amplification products. Among them, glyceraldehyde-3-phosphate dehydrogenase （GAPDH） and β-actin （ACTB） with relatively long amplification products failed to achieve optimal amplification efficiency, whereas 5S ribosomal RNA （5S rRNA） achieved ideal amplification efficiency and showed quite stable expression across various tissues, therefore it was chosen as internal reference marker. The expression quantity of GAPDH and ACTB in frozen specimens with longer postmortem intervals and in FFPE samples with relatively long amplification products was decreased. The expressions of tissue-specific microRNAs （miRNAs）, GAPDH and ACTB with relatively short amplification products had consistency in the same tissues and FFPE samples. Conclusion Through standardizing the RT-qPCR experiment, selecting the appropriate RNA marker and designing primers of appropriate product length, RNA expression levels of FFPE samples can be accurately quantified.
DNA Primers ; Formaldehyde ; Gene Expression Profiling ; Humans ; MicroRNAs/analysis* ; Myocardium ; Paraffin Embedding ; RNA/analysis* ; Real-Time Polymerase Chain Reaction/standards*

OBJECTIVETo evaluate the effect of treatment with Qishen Yiqi Dripping Pills (, QSYQ) on myocardial injury and myocardial microvascular function in patients undergoing elective percutaneous coronary intervention (PCI).

METHODSEighty patients undergoing elective PCI were randomly assigned to QSYQ and control groups. The QSYQ group received QSYQ at a dosage of 0.5 g 3 times daily (3-7 days before PCI and then daily for 1 month) and regular medication, which comprised of aspirin, clopidogrel, statin, β-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker in the absence of contradiction. The control group received only the regular medication. The index of microcirculatory resistance (IMR) was measured at maximal hyperemia after PCI. The fractional flow reserve was measured before and after the procedure. Troponin I levels were obtained at baseline and 20-24 h after the procedure.

RESULTSPre-PCI troponin I levels between the two groups were similar (0.028±0.05 vs. 0.022±0.04 ng/mL, P=0.55). However, post- PCI troponin I levels in the QSYQ group were significantly lower than that in the control group (0.11±0.02 vs. 0.16±0.09 ng/mL, P<0.01). IMR values were significantly lower in the QSYQ group as compared to the control group (16.5±6.1 vs. 31.2±16.0, P<0.01). Multivariate analysis identified QSYQ treatment as the only independent protective factor against IMR >32 (odds ratio=0.29, 95% confidence interval: 0.11-0.74, P=0.01).

CONCLUSIONSThe present study demonstrated the benefit of QSYQ in reducing myocardial injury and preserving microvascular function during elective PCI.

Aged ; Coronary Angiography ; Coronary Circulation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Male ; Microvessels ; diagnostic imaging ; drug effects ; physiopathology ; Middle Aged ; Multivariate Analysis ; Myocardium ; pathology ; Percutaneous Coronary Intervention ; Pilot Projects ; Troponin I ; blood

PURPOSE: Children born with single ventricle physiology demonstrate poor growth rate and suffer from malnutrition, which lead to increased morbidity and mortality in this population. We assume that an anabolic steroid, oxandrolone, will promote growth in these infants by improving myocardial energy utilization. The purpose of this paper is to study the efficacy of oxandrolone on myocardial energy consumption in these infants. MATERIALS AND METHODS: We modeled single ventricle physiology in a lamb by prenatally shunting the aorta to the pulmonary artery and then postnatally, we monitored cardiac energy utilization by quantitatively measuring the first order reaction rate constant, kf of the creatine-kinase reaction in the heart using magnetization transfer 31P magnetic resonance spectroscopy, home built 1H/31P transmit/receive double tuned coil, and transmit/receive switch. We also performed cine MRI to study the structure and dynamic function of the myocardium and the left ventricular chamber. The spectroscopy data were processed using home-developed python software, while cine data were analyzed using Argus software. RESULTS: We quantitatively measured both the first order reaction rate constant and ejection fraction in the control, shunted, and the oxandrolone-treated lambs. Both kf and ejection fraction were found to be more significantly reduced in the shunted lambs compared to the control lambs, and they are increased in oxandrolone-treated lambs. CONCLUSION: Some improvement was observed in both the first order reaction rate constant and ejection fraction for the lamb treated with oxandrolone in our preliminary study.
Aorta ; Boidae ; Child ; Evaluation Studies as Topic ; Heart ; Humans ; Infant ; Magnetic Resonance Imaging, Cine ; Magnetic Resonance Spectroscopy ; Malnutrition ; Mortality ; Myocardium ; Oxandrolone ; Physiology ; Pulmonary Artery ; Spectrum Analysis

OBJECTIVE: To investigate the effect of tea polyphenols on cardiac function in rats with diabetic cardiomyopathy, and the mechanism by which tea polyphenols regulate autophagy in diabetic cardiomyopathy. METHODS: Sixty Sprague-Dawley (SD) rats were randomly divided into six groups: a normal control group (NC), an obesity group (OB), a diabetic cardiomyopathy group (DCM), a tea polyphenol group (TP), an obesity tea polyphenol treatment group (OB-TP), and a diabetic cardiomyopathy tea polyphenol treatment group (DCM-TP). After successful modeling, serum glucose, cholesterol, and triglyceride levels were determined; cardiac structure and function were inspected by ultrasonic cardiography; myocardial pathology was examined by staining with hematoxylin-eosin; transmission electron microscopy was used to observe the morphology and quantity of autophagosomes; and expression levels of autophagy-related proteins LC3-II, SQSTM1/p62, and Beclin-1 were determined by Western blotting. RESULTS: Compared to the NC group, the OB group had normal blood glucose and a high level of blood lipids; both blood glucose and lipids were increased in the DCM group; ultrasonic cardiograms showed that the fraction shortening was reduced in the DCM group. However, these were improved significantly in the DCM-TP group. Hematoxylin-eosin staining showed disordered cardiomyocytes and hypertrophy in the DCM group; however, no differences were found among the remaining groups. Transmission electron microscopy revealed that the numbers of autophagosomes in the DCM and OB-TP groups were obviously increased compared to the NC and OB groups; the number of autophagosomes in the DCM-TP group was reduced. Western blotting showed that the expression of LC3-II/I and Beclin-1 increased obviously, whereas the expression of SQSTM1/p62 was decreased in the DCM and OB-TP groups (P<0.05). CONCLUSIONS Tea polyphenols had an effect on diabetic cardiomyopathy in rat cardiac function and may alter the levels of autophagy to improve glucose and lipid metabolism in diabetes.
Animals ; Autophagy ; drug effects ; Beclin-1 ; analysis ; Blood Glucose ; analysis ; Body Weight ; Diabetic Cardiomyopathies ; drug therapy ; pathology ; physiopathology ; Lipids ; blood ; Male ; Myocardium ; pathology ; Polyphenols ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Tea ; chemistry

OBJECTIVE: This article investigated the changes of some biochemical markers and cardiac function in chronic heart failure (CHF), and provided the basis for the diagnosis of CHF. METHODS: New Zealand rabbit CHF model was established using adriamycin (ADR). Twenty New Zealand rabbits were randomly divided into model group (=15) and control group (=5), injected with ADR and saline solution the ear vein respectively, 2 times a week, lasting for 8 weeks. After that, myocardial enzymes, carotid artery pressure, echocardiogram (ECG) and phonocardiogram (PCG) of all New Zealand rabbits were detected and recorded. RESULTS: Compared with control group, all parameters of the model group were changed significantly (<0.05). CONCLUSIONS CHF leads to myocardial damage in New Zealand rabbits, decreased systolic and diastolic function, cardiac reserve index can be used to assess cardiac function.
Animals ; Biomarkers ; analysis ; Blood Pressure ; Carotid Arteries ; physiopathology ; Chronic Disease ; Doxorubicin ; Electrocardiography ; Heart Failure ; chemically induced ; physiopathology ; Myocardium ; enzymology ; Phonocardiography ; Rabbits ; Random Allocation

OBJECTIVETo study the effect of calcium-sensing receptor (CaSR) agonists and antagonists on the expression of CaSR in neonatal mice with persistent pulmonary hypertension (PPHN), and to clarify the role of CaSR in neonatal mice with PPHN.

METHODSForty-nine neonatal mice were randomly divided into four groups: control (n=10), hypoxia (PPHN; n=11), agonist (n=13), and antagonist (n=15). The mice in the PPHN, agonist, and antagonist groups were exposed to an oxygen concentration of 12%, and those in the control group were exposed to the air. The mice in the agonist and antagonist groups were intraperitoneally injected with gadolinium chloride (16 mg/kg) and NPS2390 (1 mg/kg) respectively once daily. Those in the PPHN and the control groups were given normal saline daily. All the mice were treated for 14 consecutive days. Hematoxylin and eosin staining and immunohistochemistry were used to observe the changes in pulmonary vessels. Laser confocal microscopy was used to observe the site of CaSR expression and measure its content in lung tissues. qRT-PCR and Western blot were used to measure the mRNA and protein expression of CaSR in lung tissues.

RESULTSCompared with the control group, the PPHN group had significant increases in the pulmonary small artery wall thickness and the ratio of right to left ventricular wall thickness (P<0.05), which suggested that the model was successfully prepared. Compared with the control group, the PPHN group had a significant increase in the mRNA and protein expression of CaSR (P<0.05), and the agonist group had a significantly greater increase (P<0.05); the antagonist group had a significant reduction in the mRNA and protein expression of CaSR (P<0.05).

CONCLUSIONSCaSR may play an important role in the development of PPHN induced by hypoxia in neonatal mice.

Animals ; Hypoxia ; complications ; Lung ; pathology ; Mice ; Myocardium ; pathology ; Persistent Fetal Circulation Syndrome ; etiology ; pathology ; Pulmonary Artery ; pathology ; RNA, Messenger ; analysis ; Receptors, Calcium-Sensing ; analysis ; genetics ; physiology

OBJECTIVETo investigate the myocardial protective effect of L-carnitine in children with hand, foot and mouth disease (HFMD) caused by Coxsackie A16 virus and possible mechanisms.

METHODSA total of 60 HFMD children with abnormal myocardial enzyme after Coxsackie A16 virus infection were enrolled and randomly divided into L-carnitine group and fructose-1,6-diphosphate group (fructose group), with 30 children in each group. The two groups were given L-carnitine or fructose diphosphate in addition to antiviral and heat clearance treatment. Another 30 healthy children who underwent physical examination were enrolled as control group. The changes in myocardial zymogram, malondialdehyde (MDA), superoxide dismutase (SOD), and apoptosis factors sFas and sFasL after treatment were compared between groups.

RESULTSThere was no significant difference in treatment response between the L-carnitine group and the fructose group (P>0.05). One child in the fructose group progressed to critical HFMD, which was not observed in the L-carnitine group. Before treatment, the L-carnitine group and the fructose group had significantly higher indices of myocardial zymogram and levels of MDA, sFas, and sFasL and a significantly lower level of SOD than the control group (P<0.05), while there were no significant differences in these indices between the L-carnitine group and the fructose group (P>0.05). After treatment, the L-carnitine group and the fructose group had significant reductions in the indices of myocardial zymogram and levels of MDA, sFas, and sFasL and a significant increase in the level of SOD (P<0.05); the fructose group had a significantly higher level of creatine kinase (CK) than the control group and the L-carnitine group, and there were no significant differences in other myocardial enzyme indices, MDA, sFas, and sFasL between the L-carnitine group and the fructose group, as well as between the L-carnitine and fructose groups and the control group (P>0.05). SOD level was negatively correlated with aspartate aminotransferase, lactate dehydrogenase (LDH), CK, and creatine kinase-MB (CK-MB) (r=-0.437, -0.364, -0.397, and -0.519 respectively; P<0.05), and MDA level was positively correlated with LDH and CK-MB (r=0.382 and 0.411 respectively; P<0.05).

CONCLUSIONSL-carnitine exerts a good myocardial protective effect in children with HFMD caused by Coxsackie A16 virus, possibly by clearing oxygen radicals and inhibiting cardiomyocyte apoptosis.

Carnitine ; therapeutic use ; Child, Preschool ; Coxsackievirus Infections ; complications ; Female ; Hand, Foot and Mouth Disease ; drug therapy ; etiology ; metabolism ; Heart ; drug effects ; Humans ; Infant ; Male ; Malondialdehyde ; analysis ; Myocardium ; metabolism ; pathology ; Superoxide Dismutase ; metabolism

OBJECTIVETo study the effect of leptin on the expression of calcium-activated neutral protease 1 (calpain-1) and B cell lymphoma-2 (Bcl-2) and apoptosis in the myocardial tissue of neonatal rats after asphyxia.

METHODSA total of 48 neonatal rats were randomly and equally divided into normal control group, asphyxia group, leptin treatment groups, and calpain-1 inhibitor (CAI-1) group. The neonatal rat model of asphyxia under normal atmospheric condition was established in all groups except the control group. For the leptin treatment groups, rats received 20, 80, and 160 μg/kg leptin by intraperitoneal injection immediately after model establishment, respectively. For the CAI-1 group, rats received 10 mg/kg CAI-1 by intraperitoneal injection immediately after model establishment. For all the groups, the myocardial tissue was collected at 2 hours after model establishment. Immunohistochemistry was used to measure the expression of calpain-1 and Bcl-2. The TUNEL method was used to evaluate apoptosis of myocardial cells.

RESULTSThe expression of calpain-1 and Bcl-2 and apoptosis index (AI) were significantly higher in the asphyxia group than in the normal control group (P˂0.05). The leptin treatment groups and the CAI-1 group had significantly lower expression of calpain-1, significantly lower AI, and significantly higher expression of Bcl-2 than the asphyxia group (P˂0.05). The CAI-1 group had the largest changes in all the indices compared with the asphyxia group. However, there were no significant differences in all indices between the 160 μg/kg leptin treatment group and the CAI-1 group. After asphyxia, the expression of calpain-1 was positively correlated with AI, while the expression of Bcl-2 was negatively correlated with AI and the expression of calpain-1 (P˂0.05).

CONCLUSIONSLeptin reduces apoptosis of myocardial cells in asphyxiated neonatal rats by the inhibition of calpain-1 activation and upregulation of Bcl-2 expression.

Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Asphyxia Neonatorum ; metabolism ; pathology ; Calpain ; analysis ; antagonists & inhibitors ; Leptin ; pharmacology ; Myocardium ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Rats ; Rats, Sprague-Dawley