HMGB1, IL-1α, IL-33 and S100 proteins： dual-function alarmins

Our immune system is based on the close collaboration of the innate and adaptive immune systems for the rapid detection of any threats to the host. Recognition of pathogen-derived molecules is entrusted to specific germline- encoded signaling receptors. The same receptors have now also emerged as efficient detectors of misplaced or altered self-molecules that signal tissue damage and cell death following, for example, disruption of the blood supply and subsequent hypoxia. Many types of endogenous molecules have been shown to provoke such sterile inflammatory states when released from dying cells. However, a group of proteins referred to as alarmins have both intracellular and extracellular functions which have been the subject of intense research. Indeed, alarmins can either exert beneficial cell housekeeping functions, leading to tissue repair, or provoke deleterious uncontrolled inflammation. This group of proteins includes the high-mobility group box 1 protein （HMGB1）, interleukin （IL）-1α, IL-33 and the Ca^2＋-binding S100 proteins. These dual-function proteins share conserved regulatory mechanisms, such as secretory routes, post-translational modifications and enzymatic processing, that govern their extracellular functions in time and space. Release of alarmins from mesenchymal cells is a highly relevant mechanism by which immune cells can be alerted of tissue damage, and alarmins play a key role in the development of acute or chronic inflammatory diseases and in cancer development.

Binding of transition metals to S100 proteins

The S100 proteins are a unique class of EF-hand Ca^(2+) binding proteins distributed in a cell-specific, tissue-specific, and cell cycle-specific manner in humans and other vertebrates. These proteins are distinguished by their distinctive homodimeric structure, both intracellular and extracellular functions, and the ability to bind transition metals at the dimer interface. Here we summarize current knowledge of S100 protein binding of Zn^(2+), Cu^(2+) and Mn^(2+) ions, focusing on binding affinities, conformational changes that arise from metal binding, and the roles of transition metal binding in S100 protein function.

The S100 protein family and its application in cardiac diseases

The S100 protein family is the largest group of EF-hand signaling proteins in humans. The members of the S100 protein family are expressed in many tissues and play different functions. Many diseases are related to S100 proteins, which function as new biochemical markers especially in cardiac diseases. The most studied members, protein S100Β and protein S100A1, exhibit activities in cardiac diseases, and these immunohistochemical expressions or serum levels have been used in predicting neurologic outcome after resuscitation of cardiac arrest or recovery of cardioprotective function.

S100 protein expression during induced Schwann cell-like cell differentiation of rat bone marrow mesenchymal cells in vitro

BACKGROUND： S100 protein can promote axonal growth. Therefore, transplantation of induced bone marrow-derived mesenchymal stem cells （MSCs） that can secrete S100 may provide a beneficial microenvironment for neural regeneration. OBJECTIVE： To explore the changes in S100 expression during rat MSCs differentiation into Schwann ceils in vitro. DESIGN, TIME AND SETTING： This cytology experiment was performed at the Jiangsu Key Laboratory of Neuroregeneration, Nantong University in China, from January 2006 to May 2007. MATERIALS： The rabbit anti-S100 polyclonal antibody was purchased from Dako, Denmark; the mouse anti-rat S100 monoclonal antibody was purchased from Sigma, USA. METHODS： MSCs were cultured from adult Sprague-Dawley rat femur and tibia. Cell proliferation was determined by the MTT method and CD markers, and cell cycle was measured by flow cytometry. MSCs were induced to differentiate into SC cells. SC cells were stained for S100 protein, glial fibrillary acidic protein, and low-affinity nerve growth factor receptor. S100 protein and mRNA levels were evaluated by flow cytometry, Western blot, and reverse transcription-polymerase chain reaction. MAIN OUTCOME MEASURES： S100 protein and mRNA expression. RESULTS： MSCs exhibited high amplification potential over eight passages. Prior to induction, the majority of MSCs were at the G0/G1 phase of the cell cycle. After induction, MSCs displayed morphology changes similar to Schwann cells. Moreover, induction increased S100 mRNA levels. Immunofluorescence showed that MSCs expressed S100 protein, glial fibrillary acidic protein, and low-affinity nerve growth factor receptor at 7 days of induction. Induction also increased S100 protein levels compared with untreated MSCs. CONCLUSION： MSCs are capable of differentiating into Schwann cells-like cells under conditional induction in vitro, with increasing S100 mRNA and protein expression.

S100 calcium binding protein A6 and associated long noncoding ribonucleic acids as biomarkers in the diagnosis and staging of primary biliary cholangitis

BACKGROUND Primary biliary cholangitis(PBC)is a chronic and slowly progressing cholestatic disease,which causes damage to the small intrahepatic bile duct by immunoregulation,and may lead to cholestasis,liver fibrosis,cirrhosis and,eventually,liver failure.AIM To explore the potential diagnosis and staging value of plasma S100 calcium binding protein A6(S100A6)messenger ribonucleic acid(mRNA),LINC00312,LINC00472,and LINC01257 in primary biliary cholangitis.METHODS A total of 145 PBC patients and 110 healthy controls(HCs)were enrolled.Among them,80 PBC patients and 60 HCs were used as the training set,and 65 PBC patients and 50 HCs were used as the validation set.The relative expression levels of plasma S100A6 mRNA,long noncoding ribonucleic acids LINC00312,LINC00472 and LINC01257 were analyzed using quantitative reverse transcription-polymerase chain reaction.The bile duct ligation(BDL)mouse model was used to simulate PBC.Then double immunofluorescence was conducted to verify the overexpression of S100A6 protein in intrahepatic bile duct cells of BDL mice.Human intrahepatic biliary epithelial cells were treated with glycochenodeoxycholate to simulate the cholestatic environment of intrahepatic biliary epithelial cells in PBC.RESULTS The expression of S100A6 protein in intrahepatic bile duct cells was up-regulated in the BDL mouse model compared with sham mice.The relative expression levels of plasma S100A6 mRNA,log10 LINC00472 and LINC01257 were upregulated while LINC00312 was down-regulated in plasma of PBC patients compared with HCs(3.01±1.04 vs 2.09±0.87,P<0.0001;2.46±1.03 vs 1.77±0.84,P<0.0001;3.49±1.64 vs 2.37±0.96,P<0.0001;1.70±0.33 vs 2.07±0.53,P<0.0001,respectively).The relative expression levels of S100A6 mRNA,LINC00472 and LINC01257 were up-regulated and LINC00312 was down-regulated in human intrahepatic biliary epithelial cells treated with glycochenodeoxycholate compared with control(2.97±0.43 vs 1.09±0.08,P=0.0018;2.70±0.26 vs 1.10±0.10,P=0.0006;2.23±0.21 vs 1.10±0.10,P=0.0011;1.20±0.04 vs 3.03±0.15,P<0.0001,respectively).The mean expression of S100A6 in the advanced stage(III and IV)of PBC was up-regulated compared to that in HCs and the early stage(II)(3.38±0.71 vs 2.09±0.87,P<0.0001;3.38±0.71 vs 2.57±1.21,P=0.0003,respectively);and in the early stage(II),it was higher than that in HCs(2.57±1.21 vs 2.09±0.87,P=0.03).The mean expression of LINC00312 in the advanced stage was lower than that in the early stage and HCs(1.39±0.29 vs 1.56±0.33,P=0.01;1.39±0.29 vs 2.07±0.53,P<0.0001,respectively);in addition,the mean expression of LINC00312 in the early stage was lower than that in HCs(1.56±0.33 vs 2.07±0.53,P<0.0001).The mean expression of log10 LINC00472 in the advanced stage was higher than those in the early stage and HCs(2.99±0.87 vs 1.81±0.83,P<0.0001;2.99±0.87 vs 1.77±0.84,P<0.0001,respectively).The mean expression of LINC01257 in both the early stage and advanced stage were up-regulated compared with HCs(3.88±1.55 vs 2.37±0.96,P<0.0001;3.57±1.79 vs 2.37±0.96,P<0.0001,respectively).The areas under the curves(AUC)for S100A6,LINC00312,log10 LINC00472 and LINC01257 in PBC diagnosis were 0.759,0.7292,0.6942 and 0.7158,respectively.Furthermore,the AUC for these four genes in PBC staging were 0.666,0.661,0.839 and 0.5549,respectively.The expression levels of S100A6 mRNA,log10 LINC00472,and LINC01257 in plasma of PBC patients were decreased(2.35±1.02 vs 3.06±1.04,P=0.0018;1.99±0.83 vs 2.33±0.96,P=0.036;2.84±0.92 vs 3.69±1.54,P=0.0006),and the expression level of LINC00312 was increased(1.95±0.35 vs 1.73±0.32,P=0.0007)after treatment compared with before treatment using the paired t-test.Relative expression of S100A6 mRNA was positively correlated with log10 LINC00472(r=0.683,P<0.0001);serum level of collagen type IV was positively correlated with the relative expression of log10 LINC00472(r=0.482,P<0.0001);relative expression of S100A6 mRNA was positively correlated with the serum level of collagen type IV(r=0.732,P<0.0001).The AUC for the four biomarkers obtained in the validation set were close to the training set.CONCLUSION These four genes may potentially act as novel biomarkers for the diagnosis of PBC.Moreover,LINC00472 acts as a potential biomarker for staging in PBC.

Preparation of Polyclonal Antisera of Dairy Cow S100A12 Protein

[Objective] This study aimed to prepare dairy cow anti-S100A12 antisem and develop a highly effective and sensitive immunological detection reagent for further investigation of the functions of dairy cow S100A12. [Method] Purified S100A12 protein was respectively emulsified with Freund＇s complete adjuvant and Freund＇s incomplete adjuvant as the antigen for immunizing New Zealand white rabbits to prepare the polyclonal antisera. The titer was detected using agar double diffusion assay and indirect enzyme-linked immunoserbent assay （ELISA） and the specificity was determined with Western Blot. [ Result ] The titer of anti- S100A12 antisera was 1： 8 as determined by agar double diffusion assay and over 1：409 600 by ELISA. Western Blot result showed that the polyclonal antisera could be specifically combined with S100A12 protein. [ Conclusion] The results indicated that anti-S100A12 polyclonal antibody with high fiter and high specificity was successfully obtained, which provided a novel tool for further investigation of the functions of S100A12 gene.

Effect of sevoflurane inhalation and general anesthesia on serum IL-6 and S100β levels and coagulation function in elderly patients undergoing total hip replacement

Objective:To investigate the effects of sevoflurane inhalation general anesthesia on serum IL-6,brain injury protein S100βand coagulation function in elderly patients undergoing total hip arthroplasty.Method:From May 2017 to May 2019,84 patients,age 60-75 underwent total hip arthroplasty in our hospital.were randomly divided into two groups:group A(n=42)and group B(n=42).Group A was maintained with sevoflurane inhalation by general anesthesia and group B with propofol by intravenous anesthesia.The surgical related indexes and postoperative complications in the two groups were compared.The level of serum IL-6,S100β,Coagulation function index[platelet count(PLT),Fibrinogen(FIB),plasma D-dimer(D-D),activated partial enzyme activity time(APTT),prothrombin time(PT)],MMSE score and MoCA score were compared between two groups before and after operation.Results:There was no significant difference in anesthesia time,operation time,intraoperative bleeding and postoperative drainage(P>0.05).1h,1d and 7d after operation,the level of PLT,D-D and FIB in group A were significantly lower than that in group B(P<0.05),PT and APTT were significantly higher than that in group B(P<0.05).1h,1d and 7d after operation,the level of IL-6,S100βin group A were significantly lower than that in group B(P<0.05).1d after operation,the MMSE and MoCA scores in group B were significantly lower than those in group A(P<0.05).The incidence of lower extremity deep venous thrombosis(2.38%)and cognitive impairment(2.38%)in group A was lower than that in group B(14.29%,16.67%)(t1=3.896,P1=0.048;t2=4.974,P2=0.026).Conclusion:sevoflurane anesthesia can reduce the incidence of deep venous thrombosis and cognitive impairment of the lower extremity after operation in elderly patients with thr,stabilize the coagulation index of patients,and downregulate the expression of il-6 and S100β.

Immunoexpression of Cathepsin D and S100A4 Protein and Their Molecular Subtyptes in Canine Mammary Carcinomas

Cathepsin D (CD), a lysosomal protease, and S100A4 protein, a calcium binding motif, are considered to be involved in metastasis in various human cancers. No data regarding such proteins are available for canine mammary carcinomas (CMCs). Accordingly, their expression in association with known factors of prognosis was investigated in this study. For that, 66 surgically resected CMCs were submitted to an immunohistochemical evaluation using anti CD, S100A4 protein, HER2, estrogen receptor α, cytokeratin 5, and p63 antibodies, further characterizing the tumors' molecular subtype. An increase in S100A4 immunoexpression by neoplastic luminal mammary cells was associated with an infiltrative tumor mode of growth, consequently leading us to conclude that S100A4 protein could be related to progression in CMCs. Additionally, the occurrence of the luminal A molecular subtype was associated with the complex histotype in CMCs. Although we have demonstrated that changes in S100A4 protein immunoexpression occurs in CMCs, further studies are needed to determine whether this represents important independent biomarkers for CMCs.

Three cases of retroperitoneal schwannoma diagnosed by EUS-FNA

Schwannomas are peripheral nerve tumors that are typically solitary and benign.Their diagnosis is largely based on surgically resected specimens.Recently,a number of case reports have indicated that retroperitoneal schwannomas could be diagnosed with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA).We report the diagnosis of three cases of schwannoma using EUS-FNA.Subjects were two males and one female,ages 22,40,and 46 years,respectively,all of whom were symptom-free.Imaging findings showed well-circumscribed round tumors.However,as the tumors could not be diagnosed using these findings alone,EUS-FNA was performed.Hematoxylin-eosin staining of the resulting tissue fragments revealed bland spindle cells with nuclear palisading.There was no disparity in nuclear sizes.Immunostaining revealed S-100 protein positivity and all cases were diagnosed as schwannomas.Ki-67 indexes were 3%-15%,2%-3%,and 3%,respectively.No case showed any signs of malignancy.As most schwannomas are benign tumors and seldom become malignant,we observed these patients without therapy.All tumors demonstrated no enlargement and no change in characteristics.Schwannomas are almost always benign and can be observed following diagnosis by EUS-FNA.

双表型鼻腔鼻窦肉瘤1例

1 临床资料 患者,男,75岁,因反复左鼻出血半月余,于2021-09-16入院。患者半月余前无明显诱因下突然出现左鼻出血,出血量中,不能自止,无全身性出血,无紫癜、瘀斑、呕血等症状。行鼻腔填塞后出血明显缓解,但仍有间断渗血;随后出现嗅觉减退及左侧面部胀痛,持续1周。查体:鼻腔黏膜稍充血,左侧鼻腔嗅区及中鼻道充满灰褐色新生物,表面光滑,触之易出血。

Benign intratesticular schwannoma:a rare finding

Schwannoma is a peripheral nerve tumour, occasionally located in the genitourinary tract. We described an extremely rare case of intratesticular neurinoma in a 79-year-old patient. （Asian JAndrol 2006 Jan; 8： 101-103）

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.

Brazilein intervention for sciatic nerve injury in BALB/c mice

Brazilein has been shown to exert an immune regulation effect on regeneration in the central nervous system, but there is currently no consensus regarding its effect on sciatic nerve injury. In the current study, western blot and real-time PCR detection revealed that, after 16 and 8 g/kg of brazilein intervention, the amount of S100 protein and mRNA at L4-6 spinal segments of sciatic nerve injured mice was significantly greater than after 4 g/kg brazilein administration, and in an untreated model group. Luxol Fast Blue myelin staining revealed that neural regeneration after 16 and 8 g/kg of brazilein intervention was significantly better than after 4 g/kg brazilein administration, and in the model group. In addition, electrophysiological and immunohistochemical examinations further confirmed the effect of brazilein in repairing sciatic nerve injury in BALB/c mice. These results indicated that brazilein was able to activate the S100 in anterior horn cells of the spinal cord, promoting sciatic nerve regeneration and repair. Both moderate and high doses were found to exert significant effects.

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.

Association of Serum Antioxidant Enzymes and Nervous Tissue Markers in Hypertensive Patients

Background and Purpose: Hypertension has serious effects on cerebral blood vessels. Oxidative stress seems to be implicated in blood pressure elevation, through increased reactive oxygen species and/or decreased antioxidant capacity. Recently blood markers indicating damage to the central nervous system were reported to be increased in hypertensive patients. However, it is unknown whether antioxidant capacity is related to these changes. This study was designed to explore if the concentration of blood markers for nervous tissue damage was associated to antioxidant capacity in hypertensive patients. Methods: Twenty hypertensive patients and 23 healthy controls were studied. They were paired by age, sex, ethnicity, or risk factors. Serum neuron specific enolase (NSE) and S100 calcium binding protein B (S100B) were measured as nervous tissue damage markers, as well as the activity of antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase and gamma-glutamyltransferase). Results: Serum neuronal specific enolase (NSE) and S100 calcium binding protein B (S100B) concentrations determined by immunoassay were significantly increased in patients vs. controls. The activities of antioxidant enzymes measured by spectrophotometry showed that plasmatic catalase and erythrocytic glutathione peroxidase were significantly increased in patients, but erythocytic catalase was decreased. Gamma-glutamyltransferase activity was significantly correlated with S100B in hypertensive patients, while erythrocytic catalase activity was decreased in subjects with higher NSE levels. Conclusion: This preliminary investigation suggested that antioxidant status might be modulated through changes in antioxidant enzymatic activity in hypertensive patients. The association of some of these changes with peripheral markers of damage to the central nervous system could indicate that the increased levels of these proteins in hypertension are partly related to oxidative stress.

七氟烷麻醉对新生7d大鼠学习记忆功能及S100β蛋白的影响

目的 探讨新生7dSD大鼠接受七氟烷麻醉后对其发育期学习记忆功能及S100β蛋白含量的影响.方法 出生7d龄SD大鼠48只,体质量12 ～ 16 g,雌雄各半,采用随机数字表法将其分为三组（n=16）：A组和B组分别吸入3％七氟烷6h和2h,C组为空白对照组.待大鼠生长至16～ 24 d时先后利用Morris水迷宫实验和Y型迷宫实验测试其学习记忆能力;分别于8d和25 d时每组随机取8只大鼠采用快速断头法处死取血,利用ELISA法检测S100β蛋白含量的变化.结果 （1）Morris水迷宫实验中：与C组比较,A组及B组17 ～20d时平均逃避潜伏期均延长（P＜0.05或0.01）,A组19～20 d平均逃避潜伏期较B组延长（P＜0.01）;21 d时,各组大鼠原平台象限活动时间及穿越原平台次数差异均无统计学意义（均P＞0.05）.（2）Y型迷宫实验中：22 d时,与C组比较：A组及B组全天总反应时间均延长（P＜0.05或0.01）、错误次数均增加（P＜0.01）;23～24 d时各组学习成绩差异均无统计学意义（P＞0.05）.（3）血清指标检测结果：8 d时,A组和B组S100β蛋白含量均较C组增加（P＜0.01）,且A组较B组S100β蛋白含量增加（P＜0.05）;25 d时各组间差异均无统计学意义（P＞0.05）.结论 新生7d大鼠接受3％七氟烷麻醉后,可一过性降低其发育期学习记忆功能,且这种影响与吸入七氟烷的时间长短呈正相关,其机制可能与七氟烷能短暂性增加大脑S100β蛋白表达有关.

Research progress on the correlation between S100protein family and Kawasaki disease with coronary artery aneurysm

Background Kawasaki disease(KD)is the systemic vasculitis with unknown cause.The S100 protein outside cells have an important effect on congenital and adaptive immunity,chemotaxis,white blood cell(WBC)and tumor cell invasion,tissue growth and repair.Recently,multiple works have investigated the value of S100 proteins as the predictive biomarker of KD.The most serious complication of KD is coronary artery aneurysm(CAA).KD is the most common cause of acquired heart disease among children within developed countries and a risk factor for myocardial infarction in early adulthood.Early treatment with intravenous immunoglobulin(IVIG)has been shown to reduce the risk of CAA in KD from 15%-25%to about 4%.S100 family proteins are calcium-binding proteins,some of which have been shown to have intracellular and extracellular functions associated with inflammation.Persistent elevation of S100 protein level(S100A8/A9 and S100A12)after IVIG therapy was reported in patients suffering CAA.In this paper,the role and mechanism of S100 protein family in CAA development in patients with KD were briefly reviewed.

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.

Dynamic change of serum protein S100b and its clinical significance in patients with traumatic brain injury

Objective: To analyze the dynamic change of serum protein S100b in patients with traumatic brain injury and its clinical value in assessing brain damage. Methods: According to Glasgow coma scale (GCS), 102 cases of traumatic brain injury were divided into mild brain injury group (GCS≥13, n=31, Group A), moderate brain injury group (8<GCS<13, n=37, Group B) and severe brain injury group (GCS≤8, n=34, Group C). Serial S100b concentrations were analyzed by enzyme-linked immunosorbent assay (ELISA) in blood samples taken on admission, 12 h, 24 h, 48 h, 72 h and 7 days after traumatic brain injury. Results: The severe brain injury group showed significantly higher concentration of serum S100b, with earlier increase and longer duration, than the mild and moderate brain injury groups. The patients with higher S100b exhibited lower GCS scores and poor clinical prognosis. The increase in S100b could emerge before clinical image evidence indicated so. Conclusions: Serum S100b can be used as a sensitive index for assessment and prediction of traumatic brain injury severity and prognosis.

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.