Abdominal paracentesis drainage ameliorates severe acute pancreatitis in rats by regulating the polarization of peritoneal macrophages

AIM To investigate the role of peritoneal macrophage(PM) polarization in the therapeutic effect of abdominal paracentesis drainage(APD) on severe acute pancreatitis(SAP).METHODS SAP was induced by 5% Na-taurocholate retrograde injection in Sprague-Dawley rats. APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after the induction of SAP. To verify the effect of APD on macrophages, PMs were isolated and cultured in an environment, with the peritoneal inflammatory environment simulated by the addition of peritoneal lavage in complete RPMI 1640 medium. Hematoxylin and eosin staining was performed. The levels of pancreatitis biomarkers amylase and lipase as well as the levels of inflammatory mediators in the blood and peritoneal lavage were determined. The polarization phenotypes of the PMs were identified by detecting the marker expression of M1/M2 macrophages via flow cytometry, qPCR and immunohistochemical staining. The protein expression in macrophages that had infiltrated the pancreas was determined by Western blot.RESULTS APD treatment significantly reduced the histopathological scores and levels of amylase, lipase, tumor necrosis factor-α and interleukin(IL)-1β, indicating that APD ameliorates the severity of SAP. Importantly, we found that APD treatment polarized PMs towards the M2 phenotype, as evidenced by the reduced number of M1 macrophages and the reduced levels of proinflammatory mediators, such as IL-1β and L-selectin, as well as the increased number of M2 macrophages and increased levels of anti-inflammatory mediators, such as IL-4 and IL-10. Furthermore, in an in vitro study wherein peritoneal lavage from the APD group was added to the cultured PMs to simulate the peritoneal inflammatory environment, PMs also exhibited a dominant M2 phenotype, resulting in a significantly lower level of inflammation. Finally, APD treatment increased the proportion of M2 macrophages and upregulated the expression of the anti-inflammatory protein Arg-1 in the pancreas of SAP model rats.CONCLUSION These findings suggest that APD treatment exerts antiinflammatory effects by regulating the M2 polarization of PMs, providing novel insights into the mechanism underlying its therapeutic effect.     

高同型半胱氨酸血症对高海拔地区阿尔茨海默病影响的观察

目的：探讨高同型半胱氨酸（Hey）水平对高原地区阿尔茨海默病（AD）的影响以及干预治疗。方法：选取30例高海拔地区（西宁海拔2260m）AD患者,28例同龄同一地区健康老年人为对照组。测定血清Hcy、叶酸、维生素B12水平,并对AD患者进行了12周叶酸5mg及维生素B12 500μg干预治疗。主要疗效指标为神经量表MMSE、ADAS—cog和ADL。结果：AD患者血清Hcy水平高于对照组（P〈0．01）,血清叶酸水平低于对照组（P〈0．05）,VitB12在2组间变化不大。AD组有18例（60．0％）患者有高同型半胱氨酸血症,而对照组6例（21．0％）,P〈0．01。治疗12周后AD患者MMSE、ADAS—00g和ADL差别有统计学意义（P〈0．01和P〈0．05）,血清Hcy水平较治疗前明显下降（P〈0．01）。结论：高海拔AD患者血清Hcy水平明显增高,而高Hcy与高海拔AD患者饮食中叶酸摄入不足有密切关系。经干预治疗可降低AD患者血清Hcy水平,有效地改善AD患者认知功能、社会活动以及日常生活能力。     

镧、钙、氟对釉质脱矿影响的比较

目的：用化学致龋法对比镧、钙、氟对釉质脱矿的影响。方法：１５０个离体前磨牙分成６组,用酸性凝胶化学致龋,偏光显微镜观察龋形态及深度。结果：各实验组龋深度均浅于对照组,镧处理组龋深度浅于钙、氟及镧氟、氟镧先后处理组。结论：推测镧可从改善釉质结构及增加釉质外环境中钙饱和度两方面增强釉质的抗酸能力。     

Polarized light and oviposition site selection in the yellow fever mosquito: no evidence for positive polarotaxis in Aedes aegypti

Aquatic insects and insects associated with water use horizontally polarized light (i.e., positive polarotaxis) to detect potential aquatic or moist oviposition sites. Mosquitoes lay their eggs onto wet substrata, in water, water-filled tree/rock holes, or man-made small containers/bottles/old tyres containing water. Until now it has remained unknown whether mosquitoes are polarotactic or not. The knowledge how mosquitoes locate water would be important to develop new control measures against them. Thus, we studied in dual-choice laboratory experiments the role of horizontally polarized light in the selection of oviposition sites in blood-fed, gravid females of the yellow fever mosquito, Aedes aegypti. On the basis of our results we propose that Ae. aegypti is not polarotactic. Thus the yellow fever mosquito is the first known water-associated insect species that does not detect water by means of the horizontally polarized water-reflected light. This can be explained by the reflection-polarization characteristics of small-volume water-filled cavities/containers preferred by Ae. aegypti as oviposition sites.     

流体剪切力作用下鼠极化破骨细胞的形态变化

目的探讨流体剪切力作用下大鼠极化破骨细胞的形态变化。方法机械分离培养大鼠极化破骨细胞,对破骨细胞鉴定后,采用本课题组白行研制的流体剪切力装置在0．29Pa条件下,观察流体剪切力作用0、15、30、45、60、75、90、105、120min时破骨细胞的形态变化。结果大鼠极化破骨细胞抗泊石酸酸性磷酸酶（TRAP）染色阳性,吸收试验阳性,细胞形态较大,直径约30μm,形状不规则以类圆形多见,核3～20个,可见空泡,周边大量细胞丝。随流体剪切力作用时间的延长,极化破骨细胞面积、直径均有增大趋势,30min组、105min组与0min组（对照组）间差异有统计学意义（P〈0．05）。结论在本试验条件下,随流体剪切力作用时间的增加,SD-大鼠极化破骨细胞的形态呈波动性变化,直径和面积均有增大的趋势。     

Impedance changes in chronically implanted and stimulated cochlear implant electrodes

Abstract

Objectives

Electrode impedance increases following implantation and undergoes transitory reduction with onset of electrical stimulation. The studies in this paper measured the changes in access resistance and polarization impedance in vivo before and following electrical stimulation, and recorded the time course of these changes.

Design

Impedance measures recorded in (a) four cats following 6 months of cochlear implant use, and (b) three cochlear implant recipients with 1.5–5 years cochlear implant experience.

Results

Both the experimental and clinical data exhibited a reduction in electrode impedance, 20 and 5% respectively, within 15–30 minutes of stimulation onset. The majority of these changes occurred through reduction in polarization impedance. Cessation of stimulation was followed by an equivalent rise in impedance measures within 6–12 hours.

Conclusions

Stimulus-induced reductions in impedance exhibit a rapid onset and are evident in both chronic in vivo models tested, even several years after implantation. Given the impedance changes were dominated by the polarization component, these findings suggest that the electrical stimulation altered the electrode surface rather than the bulk tissue and fluid in the cochlea.     

基于TLR4/MyD88/NF-κB信号通路研究黄连素对小鼠巨噬细胞极化的干预作用

目的:基于Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核因子κB(NF-κB)信号通路研究黄连素对小鼠巨噬细胞极化的影响。方法:以小鼠巨噬细胞RAW264.7为对象,以阿托伐他汀钙为阳性对照,经脂多糖(LPS)诱导以复制炎症细胞模型,采用酶联免疫吸附测定法检测低、中、高剂量黄连素(5、10、20μmol/L)作用24 h后细胞培养液中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、NF-κB含量,采用实时荧光定量聚合酶链反应法检测细胞中TLR4、MyD88 mRNA的表达水平,采用Western blotting法检测细胞中TLR4、MyD88、诱导型一氧化氮合酶(iNOS)、CD206蛋白的表达水平。结果:与空白对照组比较,LPS诱导组细胞培养液中TNF-α、IL-6、NF-κB含量,细胞中TLR4、MyD88 mRNA的相对表达量以及TLR4、MyD88、iNOS蛋白相对表达量均显著升高(P<0.05)。与LPS诱导组比较,阿托伐他汀钙组和黄连素中、高剂量组TNF-α、IL-6含量,TRL4、MyD88 mRNA及其蛋白的相对表达量以及各给药组NF-...     

2-Hexyl-4-Pentylenic Acid (HPTA) Stimulates the Radiotherapy-induced Abscopal Effect on Distal Tumor through Polarization of Tumor-associated Macrophages

Objective The aim of this study was to explore the effects of 2-hexyl-4-pentylenic acid (HPTA) in combination with radiotherapy (RT) on distant unirradiated breast tumors.Methods Using a rat model of chemical carcinogen (7,12-dimethylbenz[a]anthracene,DMBA)-induced breast cancer, tumor volume was monitored and treatment response was evaluated by performing HE staining, immunohistochemistry, immunofluorescence, qRT-PCR, and western blot analyses.Results The results demonstrated that HPTA in combination with RT significantly delayed the growth of distant, unirradiated breast tumors. The mechanism of action included tumor-associated macrophage (TAM) infiltration into distant tumor tissues, M1 polarization, and inhibition of tumor angiogenesis by IFN-γ.Conclusion The results suggest that the combination of HPTA with RT has an abscopal effect on distant tumors via M1-polarized TAMs, and HPTA may be considered as a new therapeutic for amplifying the efficacy of local RT for non-targeted breast tumors.     

Xanthotoxol alleviates secondary brain injury after intracerebral hemorrhage by inhibiting microglia-mediated neuroinflammation and oxidative stress

BackgroundOxidative damage and inflammation are two critical mechanisms underlying secondary brain injury (SBI) following intracerebral hemorrhage (ICH). Xanthotoxol is reported to alleviate brain edema and inhibit inflammatory responses. Herein, we investigated the effects of xanthotoxol and its related mechanisms in SBI post-ICH.MethodsTo explore the clinical effects of xanthotoxol an animal model of ICH was established. Neurological scores, survival rates and brain water content were measured. Inflammatory responses and oxidative damage in the peri-hemorrhagic areas were determined by measuring pro-inflammatory cytokines and oxidative related factors. The activation of the M1/M2 phenotype was detected by western blotting and immunofluorescence.ResultsXanthotoxol improved the neurological functions and reduced cerebral edema in ICH mice. Additionally, xanthotoxol inhibited microglia activation and promotes microglial phagocytosis. Simultaneously, xanthotoxol promoted the transformation of BV2 cells from M1 phenotype to M2 phenotype, and protected BV2 cells against hemin-induced inflammation and oxidative stress. Mechanistically, xanthotoxol inactivated the NF-κB p65 signaling pathway in the hemin-challenged BV2 cells.ConclusionXanthotoxol ameliorates SBI post-ICH by suppressing microglia-mediated neuroinflammation and oxidative stress and enhancing microglial phagocytosis through inhibition of NF-κB signaling.