Activation of Paraventricular Melatonin Receptor 2 Mediates Melatonin-Conferred Cardioprotection Against Myocardial Ischemia/Reperfusion Injury.

Previous studies have shown that melatonin (Mel) can effectively ameliorate myocardial ischemia/reperfusion (MI/R) injury, but the mechanism is yet to be fully elucidated. Mel receptors are expressed in the paraventricular nucleus (PVN), which is also involved in regulating cardiac sympathetic nerve activity. The aim of this study was to examine whether Mel receptors in the PVN are involved in the protective effects of Mel against MI/R injury. The results of quantitative polymerase chain reaction, western blot, and immunofluorescence assays indicated that Mel receptor 2 (MT2) expression in the PVN was upregulated after MI/R. Intraperitoneal administration of Mel significantly improved post-MI/R cardiac function and reduced the infarct size, whereas shRNA silencing of MT2 in the PVN partially blocked this effect. Intraperitoneal administration of Mel reduced sympathetic nerve overexcitation caused by MI/R, whereas shRNA silencing of MT2 in the PVN partially diminished this effect. Furthermore, enzyme-linked immunosorbent assay and western blot results indicated that intraperitoneal administration of Mel lowered the levels of inflammatory cytokines in the PVN after MI/R injury, whereas the application of sh-MT2 in the PVN reduced this effect of Mel. Mel significantly reduced the levels of NF-κB after astrocyte oxygen and glucose deprivation/reoxygenation injury, and this effect was offset when MT2 was silenced. The above experimental results suggest that MT2 in the PVN partially mediated the protective effects of Mel against MI/R injury, and its underlying mechanisms may be related to postactivation amelioration of PVN inflammation and reduction of cardiac sympathetic nerve overexcitation.

Icariin protects cardiomyocytes against ischaemia/reperfusion injury by attenuating sirtuin 1-dependent mitochondrial oxidative damage.

BACKGROUND AND PURPOSE: Icariin, a major active ingredient in traditional Chinese medicines, is attracting increasing attention because of its unique pharmacological effects against ischaemic heart disease. The histone deacetylase, sirtuin-1, plays a protective role in ischaemia/reperfusion (I/R) injury, and this study was designed to investigate the protective role of icariin in models of cardiac I/R injury and to elucidate the potential involvement of sirtuin-1. EXPERIMENTAL APPROACH: I/R injury was simulated in vivo (mouse hearts), ex vivo (isolated rat hearts) and in vitro (neonatal rat cardiomyocytes and H9c2 cells). Prior to I/R injury, animals or cells were exposed to icariin, with or without inhibitors of sirtuin-1 (sirtinol and SIRT1 siRNA). KEY RESULTS: In vivo and in vitro, icariin given before I/R significantly improved post-I/R heart contraction and limited the infarct size and leakage of creatine kinase-MB and LDH from the damaged myocardium. Icariin also attenuated I/R-induced mitochondrial oxidative damage, decreasing malondialdehyde content and increasing superoxide dismutase activity and expression of Mn-superoxide dismutase. Icariin significantly improved mitochondrial membrane homeostasis by increasing mitochondrial membrane potential and cytochrome C stabilization, which further inhibited cell apoptosis. Sirtuin-1 was significantly up-regulated in hearts treated with icariin, whereas Ac-FOXO1 was simultaneously down-regulated. Importantly, sirtinol and SIRT1 siRNA either blocked icariin-induced cardioprotection or disrupted icariin-mediated mitochondrial homeostasis. CONCLUSIONS AND IMPLICATIONS: Pretreatment with icariin protected cardiomyocytes from I/R-induced oxidative stress through activation of sirtuin-1 /FOXO1 signalling.

Chloroform fraction of Scutellaria barbata D. Don inhibits the growth of colorectal cancer cells by activating miR­34a.

Scutellaria barbata D. Don (SB) is a well known formula in traditional Chinese medicine, which exhibits potent anticancer effects on various cancers. Many miRNAs play crucial roles in the regulation of cancer, for instance, miR­34a functions as a tumor suppressor, and is often downregulated during cancer. In this study, we investigated the role of ECSB in suppressing the growth of human colon cancer HCT­8 cells, and whether this is mediated by regulation of miR­34a and its downstream target genes, using real-time PCR and western blot analysis. ECSB treatment significantly inhibited the proliferation of HCT­8 cells and promoted apoptosis in a dose-dependent manner. In addition, ECSB treatment significantly increased the level of miR­34a expression and decreased the levels of Bcl-2, Notch1/2 and Jagged1 expression. Furthermore, knockdown of miR­34a expression through transfection of anti-miR­34a oligonucleotide was significantly reversed by ECSB treatment. Likewise, knockdown of miR­34a resulted in significant upregulation of Bcl-2, Notch1/2 and Jagged1 expression, which was reversed following ECSB treatment. Therefore, this study reveals that ECSB inhibited cancer cell growth via promoting apoptosis and inhibiting proliferation, through regulation of miR­34a. These findings further support the use of ECSB as an effective therapeutic agent against colon cancer.

[Study on Spectral Characteristics of Filaments in Three Layers Gas Gap in Dielectric Barrier Discharge].

By optical emission spectrum, we report on the first investigation on the spectral characteristics of filaments in three layers gas gap in dielectric barrier discharge, which filled with gas-mixture of argon and air. The filaments are generated in 1 mm gas gap, 4 mm gas gap and 2 mm gas gap, respectively. With previous single layers gas gap or double layers gas gap of the filaments are very different in terms of spectral characteristics. The emission spectra of the N2 second positive band (C(3)Π(u)→B(3)Π(g))are measured, from which the molecule vibrational temperature of the filaments which generated in different gas gap are calculated. Based on the relative intensity of the line at 391.4 nm and the N2 line at 394.1 nm, the electron average energy of the filaments which generated in different gas gap are investigated. Increasing the content of argon, the change of the molecule vibrational temperature and the electron average energy of the filaments are investigated. It is found the ascending order of the molecule vibrational temperature in the same argon content is: 2 mm gas gap, 1 mm gas gap and 4 mm gas gap. However the ascending order of the electron average energy in the same argon content is: 4 mm gas gap, 2 mm gas gap and 1 mm gas gap. The molecule vibrational temperature and the electron average energy of the filaments decrease with the argon content increasing.

Changes of serum Krebs von den Lungen-6 levels in interstitial lung disease associated with dermatomyositis and secondary Sj(o)gren's syndrome: a case report / 北京大学学报(医学版)

Interstitial lung diseases (ILDs) are a diverse group of pulmonary disorders characterized by various patterns of inflammation and fibrosis in the interstitium of the lung.The underlying pathogene sis of ILDs is complex and associated with multiple rheumatologic conditions,such as systemic sclerosis,rheumatoid arthritis,pollymyositis and dermatomyositis,Sjt(o)gren's syndrome,and systemic lupus erythematosus.As the disease progresses,excessive pulmonary fibrosis impairs alveolar gas exchange and damages pulmonary function.The common methods to diagnose ILDs,such as clinical manifestations,pulmonary function test,and radiological examinations are not specific for ILDs and not able to diagnose ILDs at the early stage due to their low sensitivity.So,the easy way is important to diagnose ILDs.One important biomarker for ILDs is the high-molecular-weight glycoprotein,Krebs von den Lungen-6 (KL-6).KL-6 encoded by the MUC1 gene is a mucin-like glycoprotein with high molecular weight and expressed predominantly on the cell surface of type Ⅱ alveolar epithelial cells,and is detectable in the serum of patients with ILDs.We here report a case of ILDs associated with dermatomyositis and secondary Sj(o)gren's syndrome.A 60-year-old woman was admitted to our hospital with the chief complaints of debilitation,dry mouth,dyspnea and astasia.ILDs associated with dermatomyositis and secondary Sj(o)gren's syndrome was diagnosed clinically when the following criteria were satisfied:(1) development of dyspnea within 2 months of presentation,(2) pulmonary dispersion dysfunction,(3) bilateral infiltrative shadows on chest high resolution computed tomography (HRCT).She was treated with prednisone 50 mg/d prior to admission,but the result of therapy was not good.In our hospital she was treated with intravenous methylprednisolone and cyclophosphamide and oral hydroxychloroquine sulfate.Subsequently,her serum KL-6 levels gradually decreased after treatment,pulmonary diffuse function improved,and the improvement in the clinical manifestation and HRCT findings were observed.Nevertheless,the combination treatment of glucocorticoid and cyclophosphamide had contributed to the favourable outcomes.In conclusion,detection of serum KL-6 levels in ILDs associated with connective tissue diseases may be beneficial to making a definitive diagnosis,predicting the prognosis and monitoring the disease activity,which would be of great help in clinical practice.However,a well-designed clinical study with more patients and a longer follow-up period are required to arrive at a more conclusive judgment on the role of serum KL-6 in patients with ILDs.

The association study of rs5498 (A/G K469E) and rs1799969 (G/A R241G) in intercellular adhesion molecule 1 gene polymorphism with diabetic peripheral neuropathy in Han population / 天津医药

Objective To investigate the association of genetic polymorphisms of intercellular adhesion molecule 1 (ICAM-1) with diabetic peripheral neuropathy (DPN). Methods A total of 607 type 2 diabetes patients from the Affiliated Hospital of Weifang Medical University were enrolled in this study between June 2013 and December 2014. Rs5498 (A/G K469E) and rs1799969 (G/A R241G) in the ICAM-1 gene were genotyped by using TaqMan allelic discrimination in 295 patients with DPN and 312 subjects without DPN. The distribution of these two SNPs and the genetic influence of ICAM-1 gene polymorphisms on the development of DPN were conducted. Results Genotype distributions of both SNPs were coincided with Hardy-Weinberg equilibrium in the two groups. SNP rs1799969 (G/A R241G) in the ICAM-1 gene showed a high GG genotypic frequency at 96.8%(non DPN) and 99.0%(DPN) respectively. SNP rs5498 (A/G K469E) represented AA and AG genotypes. The values were AA 48.7%/AG 39.4%in non DPN group and AA 51.5%/AG 41.7%in DPN group. There were no significant differences in genotypic distributions and allele frequencies of SNPs rs1799969 (G/A R241G) and rs5498 (A/G K469E) between the patients with DPN group and patients without DPN group (P>0.05). The dominant(AA+AG)/GG and additive (GG/AA) models of rs5498 (A/G K469E) were associated with higher risk of DPN (ORadjusted=1.585, 1.575 respectively, P<0.05). To carry A allele was related to the susceptibility of DPN. There was no such association in genetic models of rs1799969 (G/A R241G) and DPN pathogenesis. Conclusion The present study provides evidence that SNP rs5498 E469K (A/G) in the ICAM-1 gene is associated with susceptibility of DPN, and the carrying A allele appears to be a risk of DPN.

[Study on Square Super-Lattice Pattern with Surface Discharge in Dielectric Barrier Discharge by Optical Emission Spectra].

Square super-lattice pattern with surface discharge consisting of central spots and dim spots is firstly observed in the mixture of argon and air by using a dielectric barrier discharge device with water electrodes. By observing the image, it is found that the central spot is located at the centriod of its surrounding four dim spots. The short-exposure image recorded by a high speed video camera shows that the dim spot results from the surface discharges (SDs). The brightness of the central spot and is quite different from that of the dim spot, which indicates that the plasma states of the central spot and the dim spot may be differentiated. The optical emission spectrum method is used to further study the several plasma parameters of the central spot and the dim spot in different argon content. The emission spectra of the N2 second positive band (C³IIu --> B³ IIg) are measured, from which the molecule vibration temperatures of the central spot and the dim spot are calculated respectively. The broadening of spectral line 696.57 nm (2P2-->1S5) is used to study the electron densities of the central spot and the dim spot. It is found that the molecule vibration temperature and electron density of the dim spot are higher than those of the central spot in the same argon content The molecule vibration temperature and electron density of the central spot and the dim spot increase with the argon content increasing from 90% to 99.9%. The surface discharge induced by the volume discharge (VD) has the determinative effect on the formation of the dim spot The experimental results above play an important role in studying the formation mechanism of surface discharg&of square super-lattice pattern with surface discharge. In addition, the studies exert an influence on the application of surface discharge and volume discharge in different fields.

[Study on the Plasma Parameters of the Spot-Halo Hexagon Pattern with Optical Emission Spectrum].

The spot-halo hexagon pattern consisted of the center spot and hexagon halo in dielectric barrier discharge is researched, which filled with gas-mixture of argon and air. The pictures taken from the experiment shows that there is an obvious difference on brightness between the center spot and hexagon halo. All of these phenomena suggest that the center spot and hexagon halo are probably in different plasma state. The plasma parameters of the center spot and hexagon halo in the spot-halo hexagon pattern as a function of gas pressure are studied in details by using optical emission spectra. The emission spectra of the N2 second positive band(C3Πu→B3Πg)are measured, from which the molecule vibrational temperature of the center spot and hexagon halo are calculated. Based on the relative intensity of the line at 391.4 nm and the N2 line at 394.1 nm, the change of the electron average energy of the center spot and hexagon halo as a function of gas pressure is investigated. The electron density is studied by using the broadening of the spectral line 696.5 nm. It is found that the main chart of the spot-halo hexagon pattern is the argon content from 60% to 75% and the pressure from 30 to 46 kPa. The molecule vibrational temperature and electron average energy of the hexagon halo are higher than those of the center spot at the same pressure. As the pressure gradually increased from 30 to 46 kPa, the molecule vibrational temperature and electron average energy of the center spot and hexagon halo are increased, too. The broadening of the spectral line of the hexagon halo is bigger than the center spot at the same pressure, which increases with the gas pressure increasing. It indicates that the electron density increases with gas pressure increasing. The different plasma state of the center spot and hexagon halo show that the different formations mechanism of them. It is found that there are volume discharges firstly and then comes surface discharges with e high speed camera.

[Clinical study of argon laser photocoagulation for central serous chorioretinopathy].

OBJECTIVE: To evaluate the clinical effect of argon laser photocoagulation for central serous chorioretinopthy. METHODS: This study included 102 consecutive cases of central serous chorioretinopathy (102 eyes) with fluorescein dye leakage located 500 microm away from the central fovea of the macula lutea as defined by fundus fluorescein angiography (FFA). Argon laser photocoagulation of the leakage spots was performed once (98 eyes) or twice (4 eyes) with the spot diameter for exposure ranging from 100 to 200 microm and exposure time of 0.2 s that delivered energy of 80 to 150 mW. RESULTS: The visual acuity was improved in 95 cases by one row on the standard vision chart within 2 or 3 d after the laser treatment, while in the other 7 cases, the visual acuity remained unchanged. The symptoms of micropsia, metamorphopsia and blurred vision disappeared in 87 cases. Serous detachment of the sensory retina and the fovea light reflex recovered in 80 cases within two weeks after the treatment and no fovea injuries due to photocoagulation were recorded. During the follow-up lasting for 6 to 12 months no recurrence or long-term complications in relation with photocoagulation treatment were observed in these cases. CONCLUSION: Argon laser photocoagulation is effective for central serous choiroretinopathy, and strict control of the photocoagulation conditions is crucial for preventing complications in relation to laser coagulation.