Deposition of C3, C9 neoantigen and vitronectin (S-protein of complement) in lichen planus pemphigoides

We have compared the distribution of C3, C9 neoantigen (C9n) and vitronectin at the dermoepidermal junction in lichen planus pemphigoides with that in bullous pemphigoid. Eight out of 30 biopsies from patients with lichenoid lesions had linear C3 deposition at the basement membrane zone (BMZ); four of these patients had bullae and fulfilled the criteria for lichen planus pemphigoides. C9n immunoreactivity was detected as a linear or an intermittent linear/granular band at the BMZ only in these four patients, suggesting a role for the membrane attack complex of complement (MAC) in the pathogenesis of blister formation in lichen planus pemphigoides. Faint linear deposition of vitronectin, in addition to C9n, at the BMZ was seen in two of the four cases of lichen planus pemphigoides and three of six cases of bullous pemphigoid. This suggests that vitronectin may be deposited in association with C9n not only as part of the non-lytic SC5b-9 complex, but also as a regulatory step following the lytic action of MAC. A regulatory function for vitronectin in limiting tissue damage following activation of MAC is supported by our finding of a heavy deposition of vitronectin in association with C9n in a lichen planus pemphigoides patient in whom bulla formation had ceased.     

MicroRNA-29b Inhibits Diabetic Nephropathy in db/db Mice

Inflammation and its consequent fibrosis are two main features of diabetic nephropathy (DN), but target therapy on these processes for DN remains yet ineffective. We report here that miR-29b is a novel therapeutic agent capable of inhibiting progressive renal inflammation and fibrosis in type 2 diabetes in db/db mice. Under diabetic conditions, miR-29b was largely downregulated in response to advanced glycation end (AGE) product, which was associated with upregulation of collagen matrix in mesangial cells via the transforming growth factor-β (TGF-β)/Smad3-dependent mechanism. These pathological changes were reversed by overexpressing miR-29b, but enhanced by knocking-down miR-29b. Similarly, loss of renal miR-29b was associated with progressive diabetic kidney injury, including microalbuminuria, renal fibrosis, and inflammation. Restored renal miR-29b by the ultrasound-based gene therapy was capable of attenuating diabetic kidney disease. Further studies revealed that inhibition of Sp1 expression, TGF-β/Smad3-dependent renal fibrosis, NF-κB–driven renal inflammation, and T-bet/Th1-mediated immune response may be mechanisms associated with miR-29b treatment in db/db mice. In conclusion, miR-29b may play a protective role in diabetic kidney disease and may have therapeutic potential for diabetic kidney complication.     

Gas6 is complexed to the soluble tyrosine kinase receptor Axl in human blood

Summary. Background: The vitamin K‐dependent Gas6 protein (product of growth arrest specific gene 6) binds to, and activates the TAM receptor tyrosine kinases Tyro3, Axl and Mer. It has been suggested that Gas6 and the TAM receptors are important for primary platelet functions, but Gas6 cannot be found in human platelets. However, Gas6 is present in human plasma at a concentration of around 0.2 nM, which is a thousand‐fold lower than that of the homologous protein S. The Axl and Mer receptors can be cleaved close to the cell membrane, yielding soluble molecules consisting of the extracellular parts of the receptors. Objective: To investigate if soluble Axl (sAxl) is present in human serum and plasma and if Gas6 circulates in complex with sAxl. Methods: We expressed recombinant sAxl, raised antibodies and developed and validated an ELISA for Axl. Serum and plasma were analyzed using ELISAs for Gas6, Axl and sAxl–Gas6 complexes. Serum was gel filtered and fractions analyzed by the different ELISAs to determine if Gas6 in serum is free or complexed. Immunoprecipitation was used to investigate binding between Gas6 and sAxl in serum. Results: sAxl is present in serum and plasma at around 0.6 nM and all Gas6 is bound to sAxl. No complexes between Gas6 and the soluble forms of Mer and Tyro3 could be detected, indicating that sAxl is the physiological binder of Gas6 in human serum. Conclusions: Gas6 in circulation is bound to sAxl suggesting circulating Gas6 to be inhibited and incapable of stimulating the TAM receptors.     

保存12周的红细胞

现代液体红细胞保存体系运行良好,使一个国家供应的异体红细胞安全、廉价,并且有效率达到95％。现代红细胞保存系统在临床上用途广泛,如可为自身输血提供血液,可为战场上的手术输送血液,避免献血者接触新生儿,显然如果延长红细胞的保存期将会有更大的益处。然而,由于衰老的红细胞具有使血流不畅,细胞破裂后一些有毒性的脱出物可能使外伤病人的死亡率增加和导致输血相关急性肺损伤(TRALI),进一步研究建立更好的红细胞保存体系仍然很重要。     

实证医学与中医药研究和开发

临床疗效是衡量一切防治措施价值的最高准则,也是决定一个医疗卫生体系效益的最基本因素。实证医学的核心就是任何有关疾病防治的整体策略和具体措施的制定都应基于现有最严谨的关于其临床疗效的科学证据之一。使用无效甚至有害的防治措施在伦理上是不能接受的,更是对人类宝贵医疗资源的浪费。因此,中医药研究和开发应从临床疗效的验证开始。机理的研究、有效成份的探索和剂型的改进是重要的,但应以证实临床有效为前提。本文从 ４个方面进行了论证： １、一个防治措施若没有防治作用,就没有其相关的作用机理可被发现,也没有其相关的有效成份可被探索,更没有改进剂型的必要。２、中医药临床疗效评价,为从中医药中开发新药提供一个经济的、快捷的途径。因为它节省了用于无临床疗效的药物的临床前研究所需要的大量资源。同时也大大缩短了一个新药从开发到临床使用的时间。３、中医药临床疗效评价具有巨大的经济效益。临床上无效的防治措施被淘汰,而有效的被进一步推广。从而一个医疗体系会因减少使用无效的防治措施而提高效益。４、对中医药临床疗效的评价也是对其理论体系在实践上的检验。     

转换曲线分光光度法与其改良法的比较

目的：比较转换曲线分光光度法与6波长计算分光光度法的实用性。方法：分别用转换曲线分光光度法及 其改良法计算文献实例。结果：转换曲线分光光度法及其改良法对实例处理结果基本一致。结论：6波长计算分光 光度法在一定条件下比转换曲线分光光度法操作更简单,实用。