Amyloid precursor-like protein 2 C-terminal fragments upregulate S100A9 gene and protein expression in BV2 cells

The murine microglial cell line BV2 has neuroprotective effects, but is toxic to neurons by secret-ing inlfammatory cytokines, and is an important target in the treatment of nerve inlfammation and neurodegenerative diseases. In the present study, we observed the effects of transfecting three amyloid precursor-like protein 2 （APLP2） C-terminal fragments （CTFs; C57, C50 and C31） in the pEGFP-N1 vector on S100A9 expression in BV2 cells. Reverse transcription-PCR, western blot assay and immunocytochemistry revealed that S100A9 protein and mRNA expression was greater in BV2 cells after CTF transfection than after mock transfection with an empty vector. Furthermore, transfection of full-length APLP2-751 resulted in low levels of S100A9 protein ex-pression. Our results show that APLP2-CTFs upregulate S100A9 protein and mRNA expression in BV2 cells, and identify a novel pathway involved in neuronal injury and apoptosis, and repair and protection in Alzheimer’s disease.

S100 calcium-binding protein A9 promotes skin regeneration through toll-like receptor 4 during tissue expansion

Background:In plastic surgery,tissue expansion is widely used for repairing skin defects.However,low expansion efficiency and skin rupture caused by thin,expanded skin remain significant challenges in promoting skin regeneration during expansion.S100 calcium-binding protein A9(S100A9)is essential in promoting wound healing;however,its effects on skin regeneration during tissue expansion remain unclear.The aim of the present study was to explore the role of S100A9 in skin regeneration,particularly collagen production to investigate its importance in skin regeneration during tissue expansion.Methods:The expression and distribution of S100A9 and its receptors-toll-like receptor 4(TLR-4)and receptor for advanced glycation end products were studied in expanded skin.These character-istics were investigated in skin samples of rats and patients.Moreover,the expression of S100A9 was investigated in stretched keratinocytes in vitro.The effects of S100A9 on the proliferation and migration of skin fibroblasts were also observed.TAK-242 was used to inhibit the binding of S100A9 to TLR-4;the levels of collagen I(COL I),transforming growth factor beta(TGF-β),TLR-4 and phospho-extracellular signal-related kinase 1/2(p-ERK1/2)in fibroblasts were determined.Furthermore,fibroblasts were co-cultured with stretched S100A9-knockout keratinocytes by siRNA transfection and the levels of COL I,TGF-β,TLR-4 and p-ERK1/2 in fibroblasts were investigated.Additionally,the area of expanded skin,thickness of the dermis,and synthesis of COL I,TGF-β,TLR-4 and p-ERK1/2 were analysed to determine the effects of S100A9 on expanded skin.Results:Increased expression of S100A9 and TLR-4 was associated with decreased extracellular matrix(ECM)in the expanded dermis.Furthermore,S100A9 facilitated the proliferation and migration of human skin fibroblasts as well as the expression of COL I and TGF-βin fibroblasts via the TLR-4/ERK1/2 pathway.We found that mechanical stretch-induced S100A9 expression and secretion of keratinocytes stimulated COL I,TGF-β,TLR-4 and p-ERK1/2 expression in skin fibroblasts.Recombined S100A9 protein aided expanded skin regeneration and rescued dermal thinning in rats in vivo as well as increasing ECM deposition during expansion.Conclusions:These findings demonstrate that mechanical stretch promoted expanded skin regeneration by upregulating S100A9 expression.Our study laid the foundation for clinically improving tissue expansion using S100A9.

人胚胎结肠肠神经系统发育的观察

目的 研究人胚胎结肠肠神经系统的发育过程 ,为进一步研究先天性巨结肠的发病机制提供参考。 方法 采用一抗为蛋白基因产物 (protein gene product9.5 ,PGP9.5 )和 S- 10 0蛋白抗体的免疫组织化学 PAP法 ,显示结肠肠神经系统中的神经元和神经胶质。 结果 人胚胎结肠肠神经系统发育有明显的阶段性。在胚胎发育早期 (胎龄 2～ 3月 ) ,肠管壁发育差 ,以后出现菲薄的平滑肌层和低平的肠粘膜 ,此期偶在原始肌间神经丛位置见S- 10 0蛋白免疫反应性神经 ;至发育中期 (胎龄 4～ 5月 ) ,肠壁分化出 4层结构 ,出现相当发达的绒毛 ,肌间神经丛中细胞明显增多 ,呈弥散分布于整个肌层间并逐渐迁移到粘膜下层和粘膜层 ,由初级和次级突起构成复杂的神经网络 ;至晚期 (6～ 9月 ) ,肠壁各层均增厚 ,肌间神经丛成簇分布 ,神经纤维构成的网络出现更为细小的 3级突起 ,粘膜下神经丛分化形成浅丛和深丛。 结论 结肠神经系的发育具有明显的阶段性。发育早期神经开始在肠壁肌间丛位置出现 ,发育中期神经成分在肠壁各层中出现并发育增生 ,晚期肠壁各层神经已分化和成熟 ,而在不同的发育阶段 。

亚低温环境下盐酸纳洛酮注射液治疗重症颅脑损伤的临床研究

目的观察亚低温环境下盐酸纳洛酮注射液治疗重症颅脑损伤的临床疗效及安全性。方法 162例重症颅脑损伤患者随机分为对照组及试验组,各81例。对照组给予常规治疗+亚低温治疗,试验组在对照组治疗的基础上,给予盐酸纳洛酮注射液0.3 mg·kg^(^(-1))·d^(^(-1))持续静脉滴注,qd。2组均持续治疗7 d。比较2组患者治疗前后血清基质金属蛋白酶-9(MMP-9)、S100蛋白(S100-B)水平,及治疗的有效率和安全性。结果治疗后,试验组和对照组的总有效率分别为82.72%(67/81例)和67.91%(55/81例),差异有统计学意义(P<0.05)。治疗后,对照组和试验组患者血清MMP-9分别为(38.64±5.42),(24.48±3.41)μg·mL^(^(-1));S100-B水平分别为(0.98±0.14),(0.15±0.05)μg·L^(^(-1)),差异均有统计学意义(均P<0.05)。对照组的药物不良反应有胃肠道反应、肝肾功能异常,药物不良反应的发生率为11.11%(9/81例);试验组的药物不良反应有胃肠道反应、肝肾功能异常,药物不良反应的发生率为7.41%(6/81例)。2组患者药物不良反应发生率比较,差异无统计学意义(P>0.05)。结论低温环境下盐酸纳洛酮治疗能够显著降低重症颅脑损伤患者的血清MMP-9及S100-B水平,提高临床疗效,且安全性较高。