Predictive value of calprotectin for acute kidney injury in patients with sepsis / 中华急诊医学杂志

Objective:To explore the predictive value and prognosis effect of calprotectin on acute kidney injury (AKI) in patients with sepsis.Methods:A prospective observational study was conducted. From December 2018 to November 2020, patients with sepsis admitted to the Emergency Department of China Rehabilitation Research Center were enrolled. General clinical data of patients were collected continuously, and the acute physiology and chronic health evaluationⅡ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score and calprotectin were evaluated in 24 h after admission. The patients were divided into the AKI group and non-AKI group according to the occurrence of AKI within 7 days after admission. Calprotectin level and other clinical data were compared between the two groups. Logistic regression was used to analyze the risk factors for AKI in patients with sepsis, and receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of calprotectin for AKI in patients with sepsis. The patients with AKI were further divided into the survival group and death group according to the 28-day outcome, and the calprotectin levels between the two groups were compared.Results:A total of 207 patients with sepsis were enrolled, and the incidence of AKI was 68.12% (141/207). The level of calprotectin in patients with AKI was higher than that in patients without AKI [4.65 (3.25, 5.61) μg/mL vs. 3.42 (2.29, 4.09) μg/mL, P < 0.001]. Multivariable Logistic regression analysis showed that APACHEⅡ score ( OR=1.090, 95% CI: 1.043-1.139), C-reactive protein ( OR=1.004, 95% CI: 1.001-1.008) and calprotectin ( OR=1.590, 95% CI: 1.269-1.991) were independent risk factors for AKI in patients with sepsis. The area under ROC curve (AUC) of calprotectin for predicting AKI was 0.716 (95% CI: 0.643-0.788). The cutoff value of prediction was 4.63 μg/mL with the Yoden index of 0.405, which yielded a sensitivity of 0.511 and a specificity of 0.894. When calprotectin was combined with APACHE II score and SOFA score respectively, the predictive ability was significantly improved with the AUC of 0.768 (95% CI: 0.701-0.834) and 0.769 (95% CI: 0.701-0.837), respectively. We further divided patients with AKI into the survival group and non-survival group according to the 28-day outcome and there was no significant difference in calprotectin between the two groups [4.80 (3.40, 5.76) μg/mL vs. 4.19 (2.89, 5.29) μg/mL, P < 0.05]. Conclusions:The level of calprotectin in the AKI group is higher than that in the non-AKI group. Calprotectin can be regarded as an effective predictor of AKI in patients with sepsis, and the combination with APACHEⅡ score or SOFA score will improve its predictive efficacy. However, there is no significant difference in the concentration of calprotectin for patients with sepsis associated AKI with different prognosis.

MANF brakes TLR4 signaling by competitively binding S100A8 with S100A9 to regulate macrophage phenotypes in hepatic fibrosis

The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been recently identified as a neurotrophic factor, but its role in hepatic fibrosis is unknown. Here, we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl4. MANF deficiency in either hepatocytes or hepatic mono-macrophages, particularly in hepatic mono-macrophages, clearly exacerbated hepatic fibrosis. Myeloid-specific MANF knockout increased the population of hepatic Ly6Chigh macrophages and promoted HSCs activation. Furthermore, MANF-sufficient macrophages (from WT mice) transfusion ameliorated CCl4-induced hepatic fibrosis in myeloid cells-specific MANF knockout (MKO) mice. Mechanistically, MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation. Pharmacologically, systemic administration of recombinant human MANF significantly alleviated CCl4-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout (HKO) mice. This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a "brake" on the upstream of NF-κB pathway, which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.

Expression of S100A8 and S100A9 in oviduct epithelial cells induced by estrogen and their possible role in oviduct / 中国药理学通报

Aim To study whether the genes S100A8 and S100A9 are related to the functional regulation of oviduct by estrogen, and to explore their possible effects on fallopian tubes. Methods The basic expression and distribution of S100A8 and S100A9 in ampullary oviduct tissues of healthy sheep in diestrum were verified by immunohistochemistry. The expressions of S100A8 and S100A9 (mRNA and protein) in oviduct epithelial cells were detected by q-PCR and immunofluorescence, the cells were treated by E2 at different time points and different concentrations. Results S100A8 and S100A9 were highly expressed in mucosal epithelium and glandular epithelium of sheep uterine tubes during the diestrum period, and in blood vessels as well. The expression of S100A8 and S100A9 in tubal epithelial cells changed dynamically at different time ponits under the action of high concentration of E2 in vitro, and reached the peak 6 hours after E2 treatment. At this time, different concentrations of E2 significantly induced the high expression of S100A8 and S100A9, but the expressions of S100A8 and S100A9 were the highest at the concentrations of 10-7 mol • L-1 and 10-8 mol • L-1 , and there was no significant difference between the two groups. Conclusions S100A8 and S100A9 in oviduct epithelial cells are regulated by estrogen. Under the regulation of high concentration estrogen, the high expression of SI00A8 and S100A9 may be related to the natural defense of reproductive tract during mating, and may be involved in the transport of eggs in fallopian tube.

Prognostic Role of S100A8 and S100A9 Protein Expressions in Non-small Cell Carcinoma of the Lung

BACKGROUND: S100A8 and S100A9 have been gaining recognition for modulating tumor growthand metastasis. This study aimed at evaluating the clinical significance of S100A8 and S100A9 innon-small cell lung cancer (NSCLC). METHODS: We analyzed the relationship between S100A8and S100A9 expressions, clinicopathological characteristics, and prognostic significance in tumorcells and peritumoral inflammatory cells. RESULTS: The positive staining of S100A8 in tumorcells was significantly increased in male (p < .001), smoker (p = .034), surgical method other thanlobectomy (p = .024), squamous cell carcinoma (SQCC) (p < .001) and higher TNM stage (p = .022)compared with female, non-smoker, lobectomy, adenocarcinoma (ADC), and lower stage. Theproportion of tumor cells stained for S100A8 was related to histologic type (p < .001) and patientsex (p = .027). The proportion of inflammatory cells stained for S100A8 was correlated with patientage (p = .022), whereas the proportion of inflammatory cells stained for S100A9 was correlatedwith patient sex (p < .001) and smoking history (p = .031). Moreover, positive staining in tumorcells, more than 50% of the tumor cells stained and less than 30% of the inflammatory cellsstained for S100A8 and S100A9 suggested a tendency towards increased survivability in SQCCbut towards decreased survivability in ADC. CONCLUSIONS: S100A8 and S100A9 expressions might be potential prognostic markers in patients with NSCLC.

The role and mechanism of TRAP1 in the development of esophageal cancer / 实用肿瘤学杂志

Objective The aim of this study was to investigate the role and mechanism of tumor necrosis factor receptor-re-lated protein 1(TRAP1)in the progression of human esophageal cancer. Methods Immunohistochemistry was used to detect the ex-pression of TRAP1 and S100A8 in human esophageal cancer tissues. A stably knocked-down TRAP1 cell line was established in the esophageal cancer KYSE150 cell line,the proliferation ability was detected by CCK-8,the transfer ability was detected by Transwell, and apoptosis was detected by flow cytometry. We conducted a gene profiling study to detect the expression of genes related to tumor progression. The expression of TRAP1 downstream genes-E-Cadherin,N-Cadherin and S100A8 was detected by Real-Time fluo-rescent quantitative PCR. Results The expression of TRAP1 in esophageal carcinoma was significantly higher than that in adjacent tissues and correlated with S100A8(χ2=4. 141,P<0. 001). The KYSE150 cell line with down-regulated of TRAP1(KYSE150-TRAP1)was established,and the expression of TRAP1 was down-regulated by 85% ,cell invaded ability was decreased by 46% ,no changes of cell proliferation and apoptosis were observed,when compared to the KYSE150 control cells. The expression level of E-cadherin was increased by 19% ,and the expression level of S100A8 was decreased by 39% in KYSE150-TRAP1 cells. Conclusion TRAP1 is overexpressed in esophageal carcinoma and promotes the metastasis of esophageal carcinoma by regulating S100A8 ex-pression.

Study on the proliferation and the expression of S100A8 and S100A9 in Helicobacter pylor-infected human gastric epithelial cells GES-1 / 中华消化杂志

Objective@#To investigate the effects of Helicobacter pylori (H.pylori) on the proliferation of GES-1 cells and the expressions of S100A8 and S100A9 in human gastric epithelial cell line GES-1. @*Methods@#H. pylori were co-cultured with GES-1 cells at different infection plural (muhiplieity of infection (MOI) 50∶1, 100∶1, 200∶1), then the cells and cell culture supernatants were collected. The proliferative activity was detected by cell counting kit 8 (CCK-8) methods. The expression of S100A8 and S100A9 at mRNA level was determined by reverse transcription polymerase chain reaction (RT-PCR). The levels of S100A8 and S100A9 proteins and tumor necrosis factor-alpha (TNF-α) in cell culture supernatants were measured by enzyme linked immunosorbent assay (ELISA). T test and Pearson method were performed for statistical analysis. @*Results@#The negative control group was taken as the baseline, the proliferation rates of GES-1 cells of the H. pylori multiplicity 50∶1 group, 100∶1 group and 200∶1 group were (105.51±4.78)%, (168.97±11.29)% and (64.05±10.11)%, respectively. There was no statistically significant difference in the proliferation rate of GES-1 cells between H. pylori multiplicity 50∶1 group and negative control group (t=0.69, P=0.51). The proliferation rate of GES-1 cells of the H. pylori multiplicity 100∶1 group was higher than that of the negative control group, and the difference was statistically significant (t=10.63, P<0.01). The proliferation rate of GES-1 in the H. pylori multiplicity 200∶1 group was lower than that of the negative control group, and the difference was statistically significant (t=-5.54, P<0.01). The expression of S100A8 and S100A9 at the mRNA level in the H. pylori multiplicity 200∶1 group was 0.31±0.21 and 8.66±4.08, respectively, which were higher than those of the negative control group (0.06±0.05 and 0.08±0.08), and the differences were statistically significant (t=10.20 and 6.89, both P<0.05). The expressions of S100A8 at the protein level of H. pylori multiplicity 50∶1, 100∶1, and 200∶1 groups were (112.21±1.25) ng/mL, (120.39±1.61) ng/mL and (121.28±0.71) ng/mL, respectively; while the expression of S100A9 at the protein level were (179.43±2.44) ng/mL, (191.47±1.98) ng/mL and (201.80±2.06) ng/mL, respectively; and the expression of TNF-α levels were (285.52±3.64) ng/mL, (320.08±2.28) ng/mL and (350.97±2.90) ng/mL, respectively; which were all higher than those of the negative control group ((76.14±1.30) ng/mL, (161.35±1.31) ng/mL and (270.08±2.96) ng/mL, respectively), and the differences were statistically significant (tS100A8=35.09, 43.06, 43.92, tS100A9 = 11.13, 18.54, 24.90, tTNF-α= 6.34, 20.54, 33.23; all P<0.01). The expressions of S100A8 and S100A9 at the protein level were positively correlated with TNF-α (r=0.92 and 0.95, both P<0.01). @*Conclusion@#S100A8 and S100A9 may be involved in the process of H. pylori induced proliferation disorder and inflammation in GES-1 cells.

The expression and significance of S100A8 in Oral Squamous Cell Carcinoma / 实用口腔医学杂志

The expression of calcium binding protein S100A8 in 30 controls of normal oral tissue and 35 cases of OSCC was detected by immunohistochemical staining and Western blot respectively. The positive expression of S100A8 protein in OSCC and the controls was 68. 5％ and 36. 7％ respectively(P ＜ 0. 05). S100A8 may play a role in the development of OSCC.

Extremely elevated IL-18 levels may help distinguish systemic-onset juvenile idiopathic arthritis from other febrile diseases

The aim of this research was to explore whether IL-18 can be a serological marker for the diagnosis of systemic-onset juvenile idiopathic arthritis (sJIA). A total of 23 sJIA patients (13 males, median age 8.2), 20 acute lymphoblastic leukemia (ALL) patients, 18 patients with severe infections (SIF), 26 Kawasaki disease (KD) patients, 18 juvenile idiopathic arthritis (JIA) patients, and 25 healthy control patients were selected for this study. Enzyme-linked immunosorbent assays (ELISAs) were used to determine the serum concentrations of the S100A8, S100A9, and IL-6 proteins. The serum IL-18 levels were detected by a cytometric bead array (CBA). The serum IL-6 concentrations in various disease groups were significantly higher than that in the healthy control group. The IL-6 concentrations exhibited no significant difference between disease groups. The S100A8 level in the sJIA group was significantly higher than those of the ALL, JIA, and healthy control groups but showed no significant difference compared to the SIF and KD groups. The S100A9 serum concentration in the sJIA group was significantly higher than those in the ALL and healthy control groups and exhibited no significant difference from the SIF, KD, and JIA groups. The IL-18 level of the sJIA group was significantly higher than that of the other febrile disease groups. The IL-18 serum concentration may be used as a biological serum marker to distinguish sJIA from other febrile diseases.

S100A8 inhibits PDGF-induced proliferation of airway smooth muscle cells dependent on the receptor for advanced glycation end-products

BACKGROUND: Airway remodeling is a key feature of asthma, characterized by increased proliferation of airway smooth muscle cells (ASMCs). S100A8 is a calcium-binding protein with a potential to regulate cell proliferation. Here, the effect of exogenous S100A8 protein on the proliferation of ASMCs induced by platelet-derived growth factor (PDGF) and the underlying molecular mechanism was investigated. METHODS: Rat ASMCs were cultured with or without a neutralizing antibody to the receptor for advanced glycation end-products (RAGE), a potential receptor for S100A8 protein. Purified recombinant rat S100A8 protein was then added into the cultured cells, and the proliferation of ASMCs induced by PDGF was detected by colorimetric-based WST-8 assay and ampedance-based xCELLigence proliferation assay. The expression levels of RAGE in ASMCs were analyzed using western blotting assay. RESULTS: Results showed that exogenous S100A8 inhibited the PDGF-induced proliferation of rat ASMCs in a dose- dependent manner with the maximal effect at 1 µg/ml in vitro. Furthermore, when ASMCs was pre-treated with anti-RAGE neutralizing antibody, the inhibitory effect of S100A8 on PDGF-induced proliferation was significantly suppressed. In addition, neither the treatment with S100A8 or PDGF alone nor the pre-treatment with rS100A8 followed by PDGF stimulation affected the expression levels of RAGE. CONCLUSIONS: Our study demonstrated that S100A8 inhibits PDGF-induced ASMCs proliferation in a manner dependent on membrane receptor RAGE.

Relationship of serum S100A8/A9 complex and retinal inflammation in patients with diabetic retinopathy / 中华实验眼科杂志

Background Inflammation is one of the most popular aspects in the studies of diabetic retinopathy (DR) mechanisms.Researches showed that S100A8/A9 participate in the inflammatory procedure of many diseases,however,the relationship between S100A8/A9 complex and retinal inflammation of DR needs to be researched.Objective This study was to detect the serum S100A8/A9 level of diabetes mellitus (DM) and DR patients,and explore its role in DM an DR development.Methods A cases-controlled study was carried out.The DR patients,type 2 DM patients without retinal change and heathy controls were enrolled in Shanghai Xuhui Central Hospital from January to June 2014,and 30 patients for each group.The DR patients were subgrouped to non-proliferative DR (NPDR) group and proliferative DR (PDR) group.The periphery blood was collected to isolate the serum,and serum S100A8/A9 complex level was detected by ELISA.Serum high-sensitivity C-reactive protein (hsCRP) and glycosylated hemoglobin A1C (HbAlc) level was assayed by immunity turbidimetry and immune agglutination respectively.Results Serum S100A8/A9 complex levels in the DR group,DM group and normal control group were (9.74±0.59),(11.41 ±0.64) and (6.46 ±0.62) μg/L,respectively,and the serum S100A8/A9 complex level in the DM group and DR group was significantly higher than that in the normal control group,and the serum S100A8/A9 complex level in the DM group raised in compared with the DR group (all at P＜0.01).Serum hsCRP levels in the DR group,DM group and normal control group were (1.40±0.34),(1.27±0.13) and (1.11 ± 0.12)mg/L,respectively,with the highest value in the DR group and the lowest value in the normal control group (all at P=0.00).The serum HbAlc levels were higher in the DR group and DM group than those in the normal control group (both at P =0.00),while no significant difference was found in the serum HbAlc level between DR group and DM group (P =0.12).There was no significant differece in the serum S100A8/A9,hsCRP and HbAlc levels between NPDR group and PDR group (t=-0.10,P =0.92;t =-0.17,P =0.87;t =0.66,P =0.51).A weak positive correlation was seen between serum S100A8/A9 level and serum hsCRP level (r =0.36,P =0.00).Conclusions As an inflammatory marker,S100A8/A9 complex might play an important role in the pathogenesis and development of DR.Intensive control of glycemia can alleviate retinal inflammation in DM patients.

Expression and clinical significance of induced sputum neutrophil S100 A8/A9 in children with bronchial asthma / 天津医药

Objective To investigate the expression and clinical significance of neutrophil S100A8/A9 in induced sputum in children with bronchial asthma. Methods A total of 108 cases of bronchial asthma patients in the FourthAffiliated Hospital of Nanchang University were involved in the study form October 2014 to October 2015. According to the severity of the disease, the patients were divided into mild group (n=40), moderate group (n=36) and severe group (n=32). Twenty health children were taken as control group at the same period. All the patients were treated with budesonide aerosol for three months, and the control group was received aerosol inhalation for normal saline (NS). The ratio of forced expiratory volume in one second and forced vital capacity (FEV1/FVC, FEV1%) were used to evaluate the pulmonary function in two groups. The asthma control questionnaire (AcQ-5) score was used to estimate the asthma control effects. The expression level of neutrophil S100A8/A9 mRNA in induced sputum was detected by real-time PCR. The correlation of S100A8/A9 mRNA, AcQ-5 score and FEV1%was analyzed. Results Before the treatment, the FEV1%decreased, while the AcQ-5 score and express level of S100A8/A9 mRNA significantly increased with the severity of disease (all P<0.01). Three months after treatment, asthma was completely controlled in 60 patients, partial controlled in 31 cases and uncontrolled in 17 cases. With the improvement of the therapeutic efficacy, the FEV1%significantly decreased, while the express level of S100A8/A9 mRNA significantly increased (all P < 0.01). The express level of S100A8/A9 mRNA in induced sputum neutrophils was negatively correlated with FEV1%(r=-0.327 and-0.406 respectively, P<0.05), which was positively correlated with ACQ-5 score (r=0.704 and 0.817, P<0.05). Conclusion The level of S100A8/A9 expression in induced sputum neutrophil is positively correlated with the severity of asthma, which can be used as clinical indicators of the severity and the efficacy of asthma.

Construction and anti-tumor efficacy of a pentameric peptide vaccine that targets S100A8 / 药学学报

Myeloid-derived suppressor cells (MDSC) play critical roles in immune escape of tumor. We hypothesized that elimination of tumor-induced MDSCs might help to block tumor growth. Therefore, we constructed a cholera toxin B based peptide vaccine that targets a MDSC surface marker S100A8. Immunized BALB/c mice with CTB-S100A8 plus aluminum hydroxide induced high titers of anti-S100A8 antibodies and reduced tumor burden significantly in 4T1 mice model. We also found the vaccination led to significant reduction of tumor-induced monocytic MDSC (M-MDSC), with no effect on innate MDSCs, dendritic cell (DC) and macrophage (Mφ), demonstrating that targeting tumor-induced MDSC may be a promising approach in cancer immunotherapy.

Potential Role of S100A8 in Cutaneous Squamous Cell Carcinoma Differentiation

BACKGROUND: S100A8 is differentially expressed in various cell types and is associated with a number of malignant disorders. S100A8 may affect tumor biology. However, its role in cutaneous squamous cell carcinoma (SCC) is not well established. OBJECTIVE: This study aims to investigate the relationship between S100A8 and cutaneous SCC development. METHODS: We performed immunohistochemical staining to detect S100A8 expression in facial skin specimens of premalignant actinic keratosis (AK), malignant SCC, and normal tissues. In addition, we utilized postconfluence and high calcium-induced differentiation in a culture system model. Furthermore, we constructed a recombinant adenovirus expressing GFP-tagged S100A8 to investigate the role of S100A8 in SCC cell differentiation. RESULTS: S100A8 was significantly overexpressed in human cutaneous SCC compared to that in normal and AK tissues. S100A8 was gradually upregulated in SCC cells in a post-confluence-induced differentiation model. Overexpression of S100A8 in SCC cells induced by adenoviral transduction led to increased expression levels of differentiation markers, such as loricrin, involucrin, and filaggrin. S100A8 overexpression also increased loricrin and involucrin luciferase activity. CONCLUSION: S100A8 regulates cutaneous SCC differentiation and induces well-differentiated SCC formation in skin.

S100A8/A9 as a biomarker for synovial inflammation and joint damage in patients with rheumatoid arthritis

S100A8 and S100A9 are major leukocyte proteins, known as damage-associated molecular patterns, found at high concentrations in the synovial fluid of patients with rheumatoid arthritis (RA). A heterodimeric complex of S100A8/A9 is secreted by activated leukocytes and binds to Toll-like receptor 4, which mediates downstream signaling and promotes inflammation and autoimmunity. Serum and synovial fluid levels of S100A8/A9 are markedly higher in patients with RA than in patients with osteoarthritis or miscellaneous inflammatory arthritis. Serum levels of S100A8/A9 are significantly correlated with clinical and laboratory markers of inflammation, such as C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and the Disease Activity Score for 28 joints. Significant correlations have also been found between S100A8/A9 and radiographic and clinical assessments of joint damage, such as hand radiographs and the Rheumatoid Arthritis Articular Damage score. In addition, among known inflammatory markers, S100A8/A9 has the strongest correlation with total sum scores of ultrasonography assessment. Furthermore, baseline levels of S100A8/A9 are independently associated with progression of joint destruction in longitudinal studies and are responsive to change during conventional and biologic treatments. These findings suggest S100A8/A9 to be a valuable diagnostic and prognostic biomarker for RA.

Upregulated expression of S100A8 in mice brain after focal cerebral ischemia reperfusion / 世界急诊医学杂志（英文）

BACKGROUND:Recent studies have showed that S100A8 has been implicated in the pathobiology of inflammatory disorders, and that cerebral ischemia reperfusion (I/R) rapidly activates inflammation responses via Toll-like receptor 4 (TLR4). This study aimed to explore the expression of S100A8 and the relationship between S100A8 and TLR4 in focal cerebral ischemia reperfusion injury.METHODS:C3H/HeJ mice (n=30) and C3H/HeN mice (n=30) were divided randomly into a C3H/HeJ model group (n=18), a C3H/HeJ control group (n=12), a C3H/HeN model group (n=18), and a C3H/HeN control group (n=12). Middle cerebral artery I/R model in mice was produced using a thread embolism method. The brains of the mice were collected after ischemia for 1 hour and reperfusion for 12 hours. Stroke outcome was evaluated by determination of infarct volume and assessment of neurological impairment scores. Brain injury after cerebral I/R was observed by an optical microscope after TTC and HE dyeing. The immunofluorescence technique and real time PCR were used to test the expression level of S100A8 in brain damage.RESULTS:Compared with C3H/HeN mice, TLR4-deficient mice (C3H/HeJ) had lower infarct volumes and better outcomes in neurological tests. The levels of S100A8 increased sharply in the brains of mice after I/R injury. In addition, mice that lacked TLR4 (C3H/HeJ) had lower expression of I/R-induced S100A8 than C3H/HeN mice in the model group, indicating that a close relationship might exist between the levels of S100A8 and TLR4.CONCLUSION:S100A8 interaction with TLR4 might be involved in brain damage and in inflammation triggered by I/R injury.

The significance of S100A8 expression to cerebral ischemia reperfusion injury / 中华急诊医学杂志

Objective To study the expression of S100A8 and the relationship between S100A8 and Toll-like receptor 4 (TLR4) in focal cerebral ischemia reperfusion (I/R) injury.Methods C3H/HeJ mice with TLR4 gene mutation (n =30) and C3H/HeN with normal TLR4 gene mice (n =30) were divided into 4 groups at random (random number),namely C3H/HeJ model group (n =18),C3H/HeJ control group (n =12),and C3H/HeN model group (n =18).C3H/HeN control group (n =12).Middle cerebral artery was occluded to make I/R model in mice by using thread embolism method.Brain tissues were collected after ischemia for one hour and reperfusion for 12 hours.Stroke outcome was evaluated by determination of infarct volume of brain tissue and assessment of neurological scores.And brain injury after cerebral I/R was observed by optical microscope after TTC and HE staining.The immunofluorescence technique and RT-PCR were used to determine the protein level and expression of S100A8 mRNA in damaged brain tissues.Results Compared with C3H/HeN model mice,TLR4-deficient model mice (C3H/ He J) had lower infarct volumes and better outcomes of neurological function after resuscitation for 12 hours.Compared with control groups,the expression of S100A8 mRNA and level of S100A8 protein increased greatly in damaged brain tissues of model mice after I/R injury.In addition,model mice with lacked TLR4 (C3H/HeJ) had lower expression of I/R-induced S100A8 mRNA than C3H/HeN mice in model group,indicating that the close relationship between the levels of S100A8 and TLR4.Conclusions S100A8 interaction with TLR4 might be involved in brain damage and in inflammation triggered by I/R injury.

mRNA Expression of S100A8 as a Prognostic Marker for Progression of Non-Muscle-Invasive Bladder Cancer

PURPOSE: S100A8 is a member of the S100 protein family containing 2EF-hand calcium-binding motifs. S100 proteins are involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. Altered expression of this protein is associated with various diseases and cancers. The present study aimed to evaluate whether S100A8 has prognostic value for non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: A total of 103 primary NMIBC samples obtained by transurethral resection were evaluated. mRNA levels were examined by real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis. The results were compared with clinico-pathological parameters. The Kaplan-Meier method was applied to plot the curves for progression-free survival. The multivariate Cox regression model was used to identify the independent prognostic factors for progression. RESULTS: mRNA expression levels of S100A8 were significantly related to the progression of NMIBC. Kaplan-Meier estimates demonstrated significant differences in tumor progression according to the level of S100A8 expression (log-rank test, p<0.001). The multivariate Cox regression model revealed that the S100A8 mRNA expression level (hazard ratio: 12.538; 95% confidence interval: 2.245-70.023, p=0.004) was an independent predictor for disease progression of NMIBC. CONCLUSIONS: Expression levels of S100A8 might be a useful prognostic marker for disease progression of NMIBC.

Comparison of the Expression Profile of JunB, c-Jun, and S100A8 (Calgranulin A) in Psoriasis Vulgaris and Guttate Psoriasis

BACKGROUND: Psoriasis is a chronic, inflammatory, immune- mediated skin disease. Recently, several psoriasis-linked genetic loci have been reported; PSORS4 contains S100A8 (calgranulin A), and PSOR6 (19p13) locus harbors JunB (19p13.2). S100A8 is considered to be a marker of inflammation in a variety of diseases. The expression of JunB and c-Jun have been reported to be reduced in psoriatic lesions. OBJECTIVE: We attempted to assess the role and correlation of S100A8, JunB, and c-Jun in the pathogenesis of guttate psoriasis and psoriasis vulgaris by studying whether any difference of immunohistochemical expression existed. METHODS: Skin biopsy specimens from patients with psoriasis vulgaris (n=37) and guttate psoriasis (n=17), and a normal skin controls (n=9) were utilized in the study. Formalin-fixed and paraffin-embedded tissue sections were prepared and JunB, c-Jun, and calgranulin A were immunohistochemically stained in order to compare the expression of those three proteins in each group. RESULTS: Reduced JunB expression was observed in patients with psoriasis vulgaris and guttate psoriasis, as compared to patients in the control group; however, c-Jun expression was reduced only in the psoriasis vulgaris group. The expression of S100A8 increased in the psoriasis groups as compared to the control group. In addition, the expression of S100A8 was different between the psoriasis vulgaris and guttate psoriasis groups; S100A8 was expressed more profoundly in the guttate psoriasis group (p<0.05). CONCLUSION: Our results indicate that S100A8 contributes to the pathogenesis of guttate psoriasis, and it may be a good target for therapy for guttate psoriasis provoked by microorganisms.

The Expression of Interleukin-22 and S100A7, A8, A9 mRNA in Patients with Psoriasis Vulgaris / 华中科技大学学报（医学）（英德文版）

In order to study the expression of intedeukin-22 (IL-22) and S100A7, A8, A9 mRNA in the skin lesions of patients with psoriasis vulgaris and their relationship, the biopsies were taken from skin lesions in 35 patients with psoriasis vulgaris and the skin of 16 normal controls, and the expres- sion levels of IL-22 and S 100A7, A8 and A9 mRNA were detected by semi-quantitative RT-PCR. The results showed that (1) IL-22 and SI00A8, A9 mRNA were positively expressed in the psoriatic skin lesions but negatively expressed in the normal controls; The expression level of S100A7 was (1.133±0.040) in the psoriatic skin lesions, significantly higher than that in the normal controls (0.744±0.037, P<0.01). (2) There were significantly positive correlations between the expression of IL-22/S100A7 mRNA, IL-22/S100A8 mRNA, IL-22/S100A9 mRNA in the psoriasis vulgaris (r1=0.543, r2=0.774, r3=0.621, P<0.01). It was concluded that IL-22 and S100A7, A8, A9 might play important roles in the occurrence and progression of psoriasis.

Effect of S100A8/A9 Protein Complex on F-actin Network in Human Cervical Carcinoma Cell Line,CasKi Cells / 中国微创外科杂志

Objective To investigate the effect of S100A8/A9 protein complex on the surface morphology and the F-actin network in human cervical carcinoma cell line,CasKi cells.Methods After being cultured with 20 ?g/ml S100A8/A9 protein complex,the cell skeleton of the CasKi cells were observed under a confocal scanning fluorescence microscope by staining the F-actin network.Atomic force microscopy(AFM) was employed to reveal the change of ultrastructure of the cell surface in vivo.ResultsAfter being cultured with the S100A8/A9 protein complex for 24 hours,the F-actin network disorder was revealed.Most of the F-actins distributed peripherally.The OD value of the F-actin decreased significantly from 92.42?5.16 to 57.67?3.70 after been treated with the S100A8/A9(t=5.268,P=0.000).The AFM showed a withdrawing morphology with reduced pseudopodia and destruction of stress fibers. Conclusion S100A8/A9 protein complex can change the ultrastructure of the surface of CasKi cells and its stress fibers by re-distributing of the F-actin in the cells.