褪黑素通过激活下丘脑室旁核SIRT1/炎症因子改善缺血性心力衰竭

目的探讨室旁核输注褪黑素通过激活下丘脑室旁核SIRT1信号通道并调控炎症因子改善缺血性心力衰竭的机制。方法在室旁核植入微型渗透胶囊泵并输注褪黑素,1周后建立大鼠缺血性心力衰竭模型。4周后行超声心动图监测心功能指标,采用免疫荧光法检测室旁核SIRT1活性,采用Western blot测定促炎因子IL-1β和抗炎因子IL-10的蛋白表达水平,采用ELISA试剂盒检测外周血中去甲肾上腺素(NE)的表达。结果室旁核输注褪黑素显著提高SIRT1活性,降低IL-1β蛋白表达水平,提高IL-10蛋白表达水平,降低NE的表达,显著改善大鼠心脏功能。结论室旁核输注褪黑素改善缺血性心力衰竭的作用是通过激活下丘脑室旁核SIRT1信号通道,调控炎症因子,并进一步降低外周交感神经活动来实现的。

A comparison of gene expression in mouse liver and kidney in obstructive cholestasis utilizing high-density oligonucleotide microarray technology

瞄准：用微数组技术在大量基因表示上估计妨碍的胆汁郁积的效果。方法：男 C57BL/6J 老鼠经历了胆总管结扎(BDL ) 并且与对美联储假冒操作控制被匹配。在 7 d 以后，动物被牺牲，全部的 RNA 从肝和肾被孤立。从每纸巾的 RNA 的相等的数量为每个组和 hybridized 被分享到包含 12488 个探针集合的一个总数的 Affymetrix GeneChip MG-U74Av2。数据分析用 GeneSpring 6.0 软件被执行。北分析和免疫荧光被用于确认。结果：在假冒操作和 BDL 老鼠，而 49 和 51% 分别地在肾被表示， 12488 中的 44 个和 50% 基因在肝被表示。在有 GeneOntology 注解的 BDL， 265 肝和 112 肾基因以后的七天是起来调整的， 113 肝和 36 肾基因与假冒操作控制比较是下面调整的。许多基因通常在代表的纸巾和新陈代谢相关的基因被调整最大的机能簇。结论：后面的 BDL，微数组分析在肝和肾揭示大量基因改变。

Fibrin glue-assisted for the treatment of corneal perforations using glycerin-cryopreserved corneal tissue

AIM: To evaluate the outcomes and safety of lamellar keratoplasty(LK) assisted by fibrin glue in corneal perforations. ·METHODS: Six eyes of 6 patients affected by different corneal pathologies(2 posttraumatic corneal scar and 3 bacterial keratitis) underwent LK procedures by using fibrin glue. The mean corneal perforation diameter was 1.35 ±0.64mm(range,0.7-2.5mm),and the greatest diameter of the ulcerative stromal defect was 2.47 ± 0.77mm in average(range,1.5-3.5mm). The donor corneal lamella diameters were 0.20-mm larger and thicker than the recipient to restore a physiologic corneal thickness and shape: mean donor diameter was 8.34 ± 0.28mm(range,8.2-8.7mm) and mean thickness was 352±40.27mm(range,220-400mm). Mean follow-up was 7.33±1.97 months(range,6-11 months). Postoperatively,the graft status,graft clarity,anterior chamber response,the visual prognosis,intraocular pressures,and postoperative complications were recorded. ·RESULTS:Allthecornealperforationsweresuccessfully healed after the procedure. The best-corrected visual acuity(BCVA) ranged from 20/1 000 to 20/50 in their initial presentation,and from 20/100 to 20/20 in their last visit,showed increase in all the patients. No major complications such as graft dislocation and graft failure were noted. Neovascularization developed in the superficial stroma of donor graft in 1 case. High intraocular pressure developed on day 2 after surgery,while was remained in normal range after application of anti-glaucomatous eyedrops for 1 week in 1 case. ·CONCLUSION: Fibrin glue-assisted sutureless LK is valuable for maintaining the ocular integrity in the treatment of corneal perforations.

Function of IgD on lymphocyte activation and effect of hIgD-Fc-Ig fusion protein on human PBMC proliferation

OBJECTIVE This study aimed to investigate the influence of IgD on T/B cell activation and construct h IgD-Fc-Igfusion protein to competitive inhibition IgD binding with IgDR.METHODS T/B cells were sorted by magnetic cell sorting.The differences of m IgD and IgD-R level between different T/B cell subtypes were detected by FCM.Serum IgD level was detected by ELISA.Human IgD-Fc-IgG1-Fc sequence was amplified by cross-PCR and then subcloned into PET28 a(+) empty vector.After prokaryotic expression through escherichia coli,we obtained the h IgD-Fc-Igfusion protein by affinity chromatograph.Western blot was used to identify the h IgD-Fc-Igfusion protein.Human peripheral blood monouclear cells(PBMC) and fibroblast like synoviocytes(FLS) proliferation were detected using a cell counting kit-8(CCK-8).RESULTS The percentage of CD3^+/CD4^+,CD3^+/IgD^+,CD3^+/CD4^+/IgD^+,CD3^+/IgD-R+and CD3^+/CD4^+/IgD-R+cells increased significantly in RA patients comparing to healthy people.IgD can stimulate PBMC proliferation.IgD(1,3,10,30 μg·mL^(-1)) stimulate PBMC proliferation significantly after 24 h.We obtained stable and active h IgD-Fc-Igfusion protein.The h IgD-Fc-Igfusion protein showed no effect on PBMC proliferation.But it could downregulate human IgD protein promoting proliferation effects in human PBMC.CONCLUSION This result suggests that IgD and IgDR play an important role on T/B cell activation in RA patients and the h IgD-Fc-Igfusion protein may competitively inhibit IgD′s function and may play an therapeutic role in autoimmune diseases.

Effects of immunoglobulin D on expression of IgD receptor and protein tyrosine kinase signaling in human CD4^+ T cells

OBJECTIVE To observe whether human CD4^+T cells could be activated by immuno-globulin D(IgD) via IgD receptor(IgDR)-Lck.METHODS Human CD4^+T cells were purified from peripheral blood mononuclear cells(PBMCs) with microbeads.The viability of T cells were detected by CCK-8.The binding affinity and expression of IgDR on T cells were detected by flow cytometry.The protein expression of IgDR,Lck and P-Lck were analyzed by western blot.RESULTS IgD could concentration-dependent bind to IgDR on CD4^+T cells.The expression of IgDR was increased in response to treatment with IgD in a time-dependent and concentration-dependent manner.Stimulating by IgD resulted in enhanced phosphorylation of Lck compared with that in the medium control sample.The expression of Lck was not changed.As inhibitor of PTK,Herbimycin A or A770041,which combined with IgD could significantly inhibit phosphorylation of Lck(Tyr^(394)).The proliferation promoting effect of IgD was blocked by Herbimycin A or A770041.IgD could stimulate CD4^+T cell activation and proliferation through upregulating activating tyrosine residue of Lck(Tyr^(394)) phosphorylation.CONCLUSION These results demonstrate that IgD exaggerates CD4^+T cell activities,which may be through promoting Lck phosphorylation.

Chronic Intracerebroventricular Infusion of Metformin Inhibits Salt-Sensitive Hypertension via Attenuation of Oxidative Stress and Neurohormonal Excitation in Rat Paraventricular Nucleus

Metformin(MET), an antidiabetic agent, also has antioxidative effects in metabolic-related hypertension.This study was designed to determine whether MET has anti-hypertensive effects in salt-sensitive hypertensive rats by inhibiting oxidative stress in the hypothalamic paraventricular nucleus(PVN). Salt-sensitive rats received a highsalt(HS) diet to induce hypertension, or a normal-salt(NS)diet as control. At the same time, they received intracerebroventricular(ICV) infusion of MET or vehicle for 6 weeks. We found that HS rats had higher oxidative stress levels and mean arterial pressure(MAP) than NS rats. ICV infusion of MET attenuated MAP and reduced plasma norepinephrine levels in HS rats. It also decreased reactive oxygen species and the expression of subunits of NAD(P)H oxidase, improved the superoxide dismutase activity,reduced components of the renin-angiotensin system, and altered neurotransmitters in the PVN. Our findings suggest that central MET administration lowers MAP in saltsensitive hypertension via attenuating oxidative stress,inhibiting the renin-angiotensin system, and restoring the balance between excitatory and inhibitory neurotransmitters in the PVN.

Blockade of Endogenous Angiotensin-(1–7) in Hypothalamic Paraventricular Nucleus Attenuates High Salt-Induced Sympathoexcitation and Hypertension

Angiotensin(Ang)-(1–7) is an important biologically-active peptide of the renin-angiotensin system. This study was designed to determine whether inhibition of Ang-(1–7) in the hypothalamic paraventricular nucleus(PVN) attenuates sympathetic activity and elevates blood pressure by modulating pro-inflammatory cytokines(PICs)and oxidative stress in the PVN in salt-induced hypertension. Rats were fed either a high-salt(8% NaCl) or a normal salt diet(0.3% NaCl) for 10 weeks, followed by bilateral microinjections of the Ang-(1–7) antagonist A-779 or vehicle into the PVN. We found that the mean arterial pressure(MAP), renal sympathetic nerve activity(RSNA), and plasma norepinephrine(NE) were significantly increased in salt-induced hypertensive rats. The high-salt diet also resulted in higher levels of the PICs interleukin-6, interleukin-1 beta, tumor necrosis factor alpha, and monocyte chemotactic protein-1, as well as higher gp91 phoxexpression and superoxide production in the PVN. Microinjection of A-779(3 nmol/50 nL) into the bilateral PVN of hypertensive rats not only attenuated MAP, RSNA, and NE, but also decreased the PICs and oxidative stress in the PVN. These results suggest that the increased MAP and sympathetic activity in salt-induced hypertension can be suppressed by blockade of endogenous Ang-(1–7) in the PVN, through modulation of PICs and oxidative stress.

SPECTRAL APPROXIMATION ORDERS OF MULTIDIMENSIONAL NONSTATIONARY BIORTHOGONAL SEMI-MULTIRESOLUTION ANALYSIS IN SOBOLEV SPACE

分算法(静止或非静止) 是在小浪的最活跃、令人激动的研究话题之一分析和应用数学理论。处于多维的非静止的状况，它的限制功能简洁地两个都被支持并且无穷地可辨。另外，这些限制功能能用作可伸缩的功能产生多维非静止直角或 biorthogonal semi-multiresolution 分析(Semi-MRAs ) 。光谱多维的 nonstationary biorthogonal Semi-MRAs 的近似性质在这篇论文被考虑。基于放大函数的 nonstationary 分计划和它的限制，多维的 nonstationary biorthogonal Semi-MRAs 有，这被显示出光谱在 Sobolev 空格 H 的近似顺序 r [s ](R [d ]) ，为所有 r s 0。[从作者抽象]