A novel Lyn‐protein kinase Cδ/ε‐protein kinase D axis is activated in B cells by signalosome‐independent alternate pathway BCR signaling

BCR signaling initiates multiple activities critical for B‐cell function. Recently, we identified an alternate BCR signaling pathway, induced by IL‐4, that is signalosome‐independent, unlike the classical signalosome‐dependent pathway, and that leads to activation of the MAP kinase, ERK. Here we questioned whether alternate pathway signaling extends to other key downstream events, especially protein kinase D (PKD) activation. We found that in murine spleen‐derived B cells the IL‐4‐induced alternate pathway for BCR signaling results in PKD and PKD substrate phosphorylation, and that alternate pathway phosphorylation of HDAC5/7 and other key substrates requires PKD. Furthermore, we found that tyrosine phosphorylation of PKCδ/ε occurs as a result of alternate but not classical pathway signaling and is required for phosphorylation of PKD and PKD substrates. This result identifies PKCδ/ε tyrosine phosphorylation as a unique outcome of the alternate pathway. The alternate pathway is mediated by Lyn that is not required for classical pathway signaling and we found that Lyn associates directly with PKCδ/ε and is required for phosphorylation of PKCδ/ε and of PKD. These findings indicate that IL‐4 influences B‐cell activation by inducing a novel signaling pathway from BCR to Lyn to PKCδ/ε to PKD.     

肝移植后炎症因子谱改变及ω-3鱼油脂肪乳的影响*

背景：ω-3鱼油脂肪乳可改变肝移植后机体的炎症状态。 目的：观察ω-3鱼油脂肪乳对肝移植后炎症因子谱及预后的影响。 方法：将36例同种异体原位肝移植患者前瞻性随机分为实验组和对照组。两组移植后给予等氮等热量的营养支持和相同的免疫抑制方案,实验组移植后第2天在中长链脂肪乳中添加ω-3鱼油脂肪乳,连用6 d;对照组中长链脂肪乳中未添加。 结果与结论：与对照组比较,实验组移植后第5,8天白细胞介素1β、白细胞介素2、白细胞介素6、肿瘤坏死因子α、前列腺素E2和白三烯B4等不同程度下调;白细胞介素4、白细胞介素10、转化生长因子β和白三烯B5等不同程度上调;移植后第8天白细胞介素6/白细胞介素10显著下降,白细胞介素10/肿瘤坏死因子α升高 (P < 0.01)。两组围手术期死亡率和急性排斥反应发生率差异无显著性意义,但实验组重症监护时间和住院时间显著短于对照组(P < 0.05)。说明肝移植后添加ω-3鱼油脂肪乳可调整促炎/抗炎因子平衡,纠正过度炎症反应,改善预后。     

Early neuroinflammation is associated with lower amyloid and tau levels in cognitively normal older adults

CNS inflammation is a key factor in Alzheimer’s Disease (AD), but its relation to pathological Aβ, tau, and APOE4 is poorly understood, particularly prior to the onset of cognitive symptoms. To better characterize early relationships between inflammation, APOE4, and AD pathology, we assessed correlations between cerebrospinal fluid (CSF) inflammatory markers and brain levels of Aβ and tau in cognitively normal older adults.Each participant received a lumbar puncture to collect and quantify CSF levels of TNFα, IL-6, IL-8, and IL-10, a T1-weighted MRI, and PET scanning with [¹⁸F]flortaucipir (FTP; n = 57), which binds to tau tangles and/or [¹⁸F]florbetapir (FBP; n = 58), which binds to Aβ. Parallel voxelwise regressions assessed relationships between each CSF inflammatory marker and FTP and FBP SUVR, as well as APOE4*CSF inflammation interactions.Unexpectedly, we detected significant negative associations between regional Aβ and tau PET uptake and CSF inflammatory markers. For Aβ PET, we detected negative associations with CSF IL-6 and IL-8 in regions known to show early accumulation of Aβ (i.e. lateral and medial frontal lobes). For tau PET, negative relationships were observed with CSF TNFα and IL-8, predominantly in regions known to exhibit early tau accumulation (i.e. medial temporal lobe). In subsequent analyses, significant interactions between APOE4 status and IL-8 on Aβ and tau PET levels were observed in spatially distinct regions from those showing CSF–Aβ/tau relationships.Results from the current cross-sectional study support previous findings that neuroinflammation may be protective against AD pathology at a given stage of the disease, and extend these findings to a cognitively normal aging population. This study provides new insight into a dynamic relationship between neuroinflammation and AD pathology and may have implications for whom and when neuroinflammatory therapies may be appropriate.     

化瘀温胆汤对代谢综合征大鼠血脂、血压及脂肪细胞因子的干预作用

目的：探讨化瘀温胆汤对代谢综合征大鼠血压、血脂异常的治疗作用及部分机制。方法：健康雄性SD大鼠高温高湿环境下喂饲高脂高糖高盐饮食12周,复制大鼠代谢综合征模型。通过检测血压、血清胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL-C）、高密度脂蛋白（HDL-C）,探讨化瘀温胆汤灌胃给药4周后对模型大鼠血压、血脂异常的改善作用。检测脂联素、瘦素、肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）变化情况,探讨该方治疗代谢综合征的部分机制。结果：化瘀温胆汤可明显降低模型大鼠的血清TC、TG、LDL-C水平,升高HDL-C,与模型对照组比较有显著性差异（P〈0.01）;可降低模型大鼠血压,与模型对照组比较有显著性差异（P〈0.01）。化瘀温胆汤可使脂联素水平明显升高,与模型对照组比较有显著性差异（P〈0.01）;瘦素水平、TNF-α、IL-6水平均有不同程度的降低,与模型对照组比较均具有显著性差异（P〈0.01）。结论：化瘀温胆汤对代谢综合征模型大鼠血压、血脂异常有较好的疗效,其机制可能与其调节脂联素、瘦素、TNF-α、IL-6水平有关。     

芪明颗粒治疗非增殖期糖尿病性视网膜病变患者脉络膜循环及干眼症的疗效观察

目的:观察芪明颗粒对非增殖期糖尿病性视网膜病变(NPDR)的脉络膜循环的作用及其对干眼症的改善情况,并分析芪明颗粒部分作用机制。方法:选取2013年4月至2015年11月河北省人民医院眼科收治确诊的NPDR患者100例,根据治疗方法不同分为对照组(单纯使用羟苯磺酸钙治疗)和观察组(芪明颗粒联合羟苯磺酸钙治疗),每组50例。治疗2个月后,测量2组患者的组织因子(TF)、色素上皮衍生因子(PEDG)、胰岛素样生长因子-1(IGF-1)、血管内皮生长因子(VEGF)的浓度变化以及血清支链氨基酸的含量进行比较和分析。结果:1)对照组血清内TF、IGF-1,VEGF含量均显著高于观察组,而PEDF含量明显低于观察组,差异有统计学意义(P 0. 05)。2)对照组血清缬氨酸、异亮氨酸、亮氨酸的含量均显著高于观察组,差异有统计学意义(P 0. 05)。3)观察组临床总有效率92%,与对照组78%比较,差异有统计学意义(P 0. 05)。结论:芪明颗粒能够抑制视网膜内形成新生血管以及改善脉络膜循环,对患者的干眼症提供有效的治疗帮助。     

不明原因复发性流产免疫学发病机制的研究进展

复发性流产发生率为1%~5%,其中40%~60%原因不明,称为不明原因复发性流产(unexplained recurrent spontaneous abortion,URSA)。近年研究表明,URSA的发生与免疫失衡关系密切,又称为同种免疫型复发性流产。本文论述URSA免疫学的发病机制、诊断、治疗的最新研究进展,重点论述了发病机制中免疫失衡方面的研究进展。     

过敏性紫癜患儿血、尿标本中IL-13受体α2水平及其他细胞因子的检测分析

目的：探讨过敏性紫癜（HSP）患儿血清和尿中IL-13受体α2（IL-13Rα2）与白细胞介素（IL）-4,-6,-8,肿瘤坏死因子α(TNF-α)的关系及其临床意义。方法：采用ELISA法检测了52例HSP患儿(其中29例有肾脏损害)以及45例正常健康儿童的血清和尿IL-13Rα2及IL-4,-6,-8,TNF-α水平,比较上述各组患儿的IL-13Rα2与各细胞因子水平的关系。结果：①HSP患儿的血清中IL-4,IL-6,IL-8,IL-13Rα2及TNF-α水平高于健康对照组(P<0.01或0.05);HSP患儿尿液中IL-6,TNF-α水平高于正常对照组(P<0.01)。②有肾损害（HSPN）组血清IL-4,-6,-8,IL-13Rα2及TNF-α水平均高于健康对照组;有肾损害（HSPN）组尿液中IL-6,IL-13Rα2及TNF-α水平高于健康对照组。结论：IL-13Rα2,IL-4,-6,-8,TNF-α均可能参与HSP/HSPN的发病过程。［中国当代儿科杂志,2009,11（1）：37-40］     

Is there a role of taurine bromamine in inflammation? Interactive effects with nitrite and hydrogen peroxide

Objective and Design: The myeloperoxidase system of neutrophils generates chlorinating and brominating oxidants in vivo. The major haloamines of the system are taurine chloramine (TauCl) and taurine bromamine (TauBr). It has been demonstrated in vitro that TauCl exerts both antiinflammatory and anti-bacterial properties. Much less is known about TauBr. The present study was conducted to compare bactericidal and immunoregulatory capacity of TauBr with that of the major chlorinating oxidants: HOCl and TauCl. Moreover, the effect of nitrites and H₂O₂ on TauBr activity was investigated.Materials: TauBr was prepared by reaction of HOBr with taurine. The reaction was monitored by UV absorption spectra.Methods: Bactericidal activity of TauBr, TauCl and HOCl was tested by incubation of E. coli with the compounds and determined by the pour-plate method. To test the anti-inflammatory activity the compounds were incubated with LPS and IFN- stimulated murine peritoneal macrophages. The production of following mediators was measured: nitrites by Griess reaction; TNF-, IL-6, IL-10, IL-12p40 using capture ELISA. In some experiments the compounds were incubated with either nitrites or H₂O₂.Results: In our experimental set-up TauBr and HOCl exerted strong bactericidal effects on E. coli (MBC = 110 M and 8 M, respectively), while TauCl (< 1000 M) did not kill test bacteria. However, both, TauBr and TauCl, at noncytotoxic concentrations (< 300 M) inhibited the cytokine and nitric oxide production by macrophages. H₂O₂ completely abolished the biological activities of TauBr but not those of TauCl. Nitrites did not affect any activity of TauBr or TauCl while they diminished the HOCl^– mediated bacterial killing.Conclusion: TauBr, despite very low concentration of Br^– in body fluids, may support TauCl and HOCl in the regulation of inflammatory response and in killing of bacteria by neutrophils. However, TauBr activity in vivo will depend on the presence of H₂O₂ and possible other mediators of inflammation which can compete with target molecules for TauBr.Received 16 August 2004; returned for revision 16 September 2004; accepted by A. Falus 13 October 2004     

Tenascin C levels in patients with mild and severe preeclampsia

Objective: To determine the serum tenascin-C (TN-C) levels in cases with mild and severe preeclampsia.

Methods: Pregnant women were divided into three groups, namely healthy pregnants (Group 1, n?=?20), pregnants with mild preeclampsia (Group 2, n?=?20) and pregnants with severe preeclampsia (Group 3, n?=?20). The groups were formed so as to match each other in terms of gestational week. From each pregnant woman, pre- and post-delivery blood samples were obtained to measure serum TN-C levels. The data were evaluated using the Kruskall–Wallis variance analysis. For the obtained values of p?<?0.05, the groups were compared in pairs. A p value of <?0.017 was accepted as significant.

Results: In Groups 1, 2 and 3, the prepartum TN-C levels were 5.02?±?0.4?µg/ml, 12.8?±?2.9?µg/ml and 33.8?±?11.7?µg/ml, and in the postpartum TN-C levels were 4.7?±?0.1?µg/ml, 11.7?±?1.8?µg/ml and 50.6?±?33.8?µg/ml, respectively. There was a significant difference between the groups in terms of the prepartum and postpartum TN-C levels (p?<?0.017, Mann–Whitney U [MWU] test). There was also a significant difference in the prepartum TN-C levels between Groups 2 and 3 (p?<?0.017, MWU test).

Conclusions: The prepartum and postpartum TN-C levels were significantly higher in mild and severe preeclampsia than those in healthy pregnants.