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.

Glial fibrillary acidic protein levels are associated with global histone H4 acetylation after spinal cord injury in rats

Emerging evidence has suggested global histone H4 acetylation status plays an important role in neural plasticity. For instance, the imbalance of this epigenetic marker has been hypothesized as a key factor for the development and progression of several neurological diseases. Likewise, astrocytic reactivity-a wellknown process that markedly influences the tissue remodeling after a central nervous system injury-is crucial for tissue remodeling after spinal cord injury（SCI）. However, the linkage between the above-mentioned mechanisms after SCI remains poorly understood. We sought to investigate the relation between both glial fibrillary acidic protein（GFAP） and S100 calcium-binding protein B（S100B）（astrocytic reactivity classical markers） and global histone H4 acetylation levels. Sixty-one male Wistar rats（aged ~3 months） were divided into the following groups： sham; 6 hours post-SCI; 24 hours post-SCI; 48 hours post-SCI; 72 hours post-SCI; and 7 days post-SCI. The results suggested that GFAP, but not S100B was associated with global histone H4 acetylation levels. Moreover, global histone H4 acetylation levels exhibited a complex pattern after SCI, encompassing at least three clearly defined phases（first phase： no changes in the 6, 24 and 48 hours post-SCI groups; second phase： increased levels in the 72 hours post-SCI group; and a third phase： return to levels similar to control in the 7 days post-SCI group）. Overall, these findings suggest global H4 acetylation levels exhibit distinct patterns of expression during the first week post-SCI, which may be associated with GFAP levels in the perilesional tissue. Current data encourage studies using H4 acetylation as a possible biomarker for tissue remodeling after spinal cord injury.

Effect of Electroacupuncture Preconditioning on Serum S100 β and NSE in Patients undergoing Craniocerebral Tumor Resection

Objective：To investigate the effect of electroacupuncture preconditioning on the serum level of S100 calcium-binding protein beta（S100β）and neuron-specific enolase（NSE）in patients undergoing craniocerebral tumor operation.Methods：A total of 32 patients,who would go through craniocerebral tumor resection under general anesthesia,were randomly assigned to two groups,16 in each group.Patients in the electroacupuncture（EA）group received electroacupuncture on Fengfu acupoint（Du16）and Fengchi acupoint （GB20）for 30 min,2 h before operation.The stimulus is 1-4 mA with a density wave frequency of 2/15 Hz. Patients in the control group received no pretreatment.Anesthesia was maintained with remifentanil at the dose of 4-8 mg/kg per hour,pumped intravenous drip of vecuronium at 1.0-2.0μg/kg each hour,and discontinuous intravenous dripped with vecuronium bromide at 0.5-1 mg.The serum levels of S100βand NSE were measured with ELISA before operation,before skin incision,after tumor removal,at the end of operation,and at 24 h after operation.Results：The serum level of S100βand NSE did not change before skin incision.The serum level of NSE increased significantly and the level of S100βincreased insignificantly after the tumor resection. The serum levels of S100βand NSE in the EA group and the control group were 1.16±0.28μg/L vs 1.47±0.33μg/L,24.7±13.3μg/L vs 31.4±14.1μg/L at the end of the operation,respectively.Twenty-four h after operation,the correspondence indices were 1.18±0.31μg/L vs 1.55±0.26μg/L,and 25.5±12.4μg/L vs 32.4±11.7μg/L.The two indices at these two time points were significantly increased than those before operation, respectively（P〈0.05）.At the end of the operation and 24 h post-operation,the serum levels of S100βand NSE in the EA group were significantly lower than those in the control group（P〈0.05）.Conclusion：Electroacupuncture Fengchi and Fengfu for 30 min before craniocerbral tumor operation could decrease the serum level of S100βand NSE,thus may have potential protective effect on brain damage,which needs to befurther studied.

S100A8 promotes epithelial-mesenchymal transition and metastasis under TGF-β/USF2 axis in colorectal cancer

Background:The transforming growth factor-β(TGF-β)pathway plays a pivotal role in inducing epithelial-mesenchymal transition(EMT),which is a key step in cancer invasion and metastasis.However,the regulatory mechanism of TGF-βin inducing EMT in colorectal cancer(CRC)has not been fully elucidated.In previous studies,it was found that S100A8 may regulate EMT.This study aimed to clarify the role of S100A8 in TGF-β-induced EMT and explore the underlying mechanism in CRC.Methods:S100A8 and upstream transcription factor 2(USF2)expression was detected by immunohistochemistry in 412 CRC tissues.Kaplan-Meier survival analysis was performed.In vitro,Western blot,and migration and invasion assays were performed to investigate the effects of S100A8 and USF2 on TGF-β-induced EMT.Mouse metastasis models were used to determine in vivo metastasis ability.Luciferase reporter and chromatin immunoprecipitation assay were used to explore the role of USF2 on S100A8 transcription.Results:During TGF-β-induced EMT in CRC cells,S100A8 and the transcription factor USF2 were upregulated.S100A8 promoted cell migration and invasion and EMT.USF2 transcriptionally regulated S100A8 expression by directly binding to its promoter region.Furthermore,TGF-βenhanced the USF2/S100A8 signaling axis of CRC cells whereas extracellular S100A8 inhibited the USF2/S100A8 axis of CRC cells.S100A8 expression in tumor cells was associated with poor overall survival in CRC.USF2 expression was positively related to S100A8 expression in tumor cells but negatively related to S100A8-positive stromal cells.Conclusions:TGF-βwas found to promote EMT and metastasis through the USF2/S100A8 axis in CRC while extracellular S100A8 suppressed the USF2/S100A8 axis.USF2 was identified as an important switch on the intracellular and extracellular S100A8 feedback loop.

人脐血单个核细胞输注对血管性痴呆大鼠的行为改善作用

目的观察颈内动脉输注人脐血单个核细胞(human cord blood mononuclear cells,HCMNCs)对血管性痴呆(vascular dementia,VD)大鼠的行为学改善的作用以及对VD大鼠血清脑特异性蛋白神经元特异性烯醇化酶(neuron spcific enolase,NSE)和S-100蛋白的影响。方法大鼠随机分为模型组、治疗组、对照组;各组大鼠又分为2、4、8周3个时相点。以穿梭箱对大鼠行为学进行检测。用ELISA法对大鼠血清中NSE和S-100蛋白进行检测。结果穿梭箱结果显示HCMNCs治疗组大鼠术后各时相点主动回避反应(active avoidance response,AAR)比例均显著高于模型组。治疗组大鼠术后各时相点血清NSE和S-100蛋白含量与模型组有显著性差异,与对照组比较无显著性差异。结论采用HCMNCs治疗对VD大鼠的行为学有一定的改善作用,说明HCMNCs治疗对脑组织细胞有一定的保护作用。

七叶皂苷钠联合头孢曲松治疗细菌性脑膜炎的效果分析

目的 探究七叶皂苷钠联合头孢曲松治疗细菌性脑膜炎(bacterial meningitis,BM)的临床效果。方法 收集 2019 年 4月至2021年4月宁国市人民医院急诊科收治的BM患者共80例,依照随机抽签法按1∶1比例分为观察组和对照组,每组各40例。对照组采用头孢曲松治疗,观察组采用七叶皂苷钠联合头孢曲松治疗。比较两组临床疗效、症状消失时间、治疗前后炎症因子[降钙素原(procalcitonin,PCT)、白介素-6(interleukin-6,IL-6)、C-反应蛋白(C-reactive protein,CRP)、可溶性血管细胞黏附分子1(soluble vascular cell adhesion molecule 1,sVCAM-1)]水平、氧化应激指标[超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、丙二醛(malondialdehyde,MDA)]、脑水肿指标[水通道蛋白4(aquaporin 4,AQP4)、S-100钙结合蛋白(S-100 calcium binding protein,S-100B)]及治疗期间不良反应发生率。结果 观察组总有效率(92.50%)高于对照组(75.00%)(P<0.05);观察组发热消退、颅高压消失、意识恢复、惊厥消失时间短于对照组(P<0.05);治疗后观察组血清PCT、IL-6、CRP、sVCAM-1、AQP4、S-100B水平低于对照组(P<0.05);治疗后观察组血清SOD、GSH-Px水平高于对照组,MDA水平低于对照组(P<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论 七叶皂苷钠联合头孢曲松治疗BM患者效果显著,可有效改善症状,减轻机体炎症及氧化应激反应,缓解脑水肿,且安全性高。