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Objective@#To analyze the alterations and clinical significance of serum calcium binding protein S100A8/A9 and soluble receptor for advanced glycation end products (sRAGE) levels in patients with chronic obstructive pulmonary disease(COPD).@*Methods@#Enzyme-linked immonosorbent assay was established to detect serum levels of S100A8/A9 and sRAGE in 203 patients with COPD[male166, female 37, aged 52-92 years, average years(69.72±9.079)] and in 41 smoking elderly non-COPD patients[male 35,female 6, aged 55-89 years, average years(68.66±8.74)], and 167 non-smoking healthy subjects as the control group[male 132, female 35, aged 57-92 years, average years(69.13±7.21)] from April 2018 to January 2019. The relationship between the S100A8/A9, sRAGE and clinical biomarkers [the percentage of fored expiratory volume in one second(FEV1) in the predicted value, FEV1/fored vital capacity(FVC), neutrophile granulocyte(NEU)%, pack-year] were investigated. The diagnostic value of S100A8/A9, sRAGE and their combined detection for COPD was analyzed using the subject operating characteristic curve.@*Results@#The serum S100A8/A9 level [(2.70±1.11)μg/ml] in COPD patients was significantly higher than that in the smoking control group [(1.65±0.63) μg/ml] and the non-smoking control group[(0.99±0.48)μg/ml], t=5.807, P<0.000 1; t=18.45, P<0.000 1. The serum S100A8/A9 levels in patients with COPD[GOLD Ⅰ(2.08±1.08) μg/ml, GOLDⅡ (2.58±1.06) μg/ml, GOLD Ⅲ (2.69±1.12) μg/ml, GOLDⅣ (2.95±1.10)μg/ml] were significantly higher than the non-smoking control group(0.99±0.48)μg/ml, t=6.616, P<0.000 1; t=14.56, P<0.000 1; t=17.10, P<0.000 1; t=18.09, P<0.000 1.The serum sRAGE level [(0.29±0.25)ng/ml] in COPD patients was significantly higher than that in the smoking control group[(0.60±0.24)ng/ml] and the non-smoking control group[(0.85±0.35)ng/ml], t=7.367, P<0.000 1; t=18.14, P<0.000 1. The serum sRAGE levels in patients with COPD[GOLD Ⅰ(0.46±0.40),GOLDⅡ (0.28±0.25),GOLD Ⅲ (0.29±0.25),GOLD Ⅳ (0.25±0.19)ng/ml] were significantly lower compared with non-smoking control group[(0.85±0.35)ng/ml], t=3.459, P=0.000 5; t=10.23, P<0.000 1; t=13.95, P<0.000 1; t=11.70, P<0.000 1. Serum S100A8/A9 levels were positively correlated with smoking amount and NEU% (r=0.458 5, P<0.000 1; r=0.228 3, P=0.001 1), negatively correlated with FEV1/FVC, the percentage of FEV1 in the predicted value, and sRAGE(r=-0.190 6, P=0.006 4; r=-0.186 3, P=0.007 8; r=-0.201 7, P=0.003 9). sRAGE levels were negatively correlated with NEU% (r=-0.155 9, P=0.026 4). In the ROC curve, the area under the curve of S100A8/A9, sRAGE and combined detection were 0.922[95%CI(0.897-0.947)], 0.926[95%CI(0.899-0.952)]and 0.966 [95%CI(0.950-0.983)], respectively.@*Conclusion@#S100A8/A9 and sRAGE are closely correlated with the degree of airflow constrains and the levels of serum inflammatory mediators, which are expected to be as potential biomarkers of COPD.
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Objective@#To investigate the expression levels of S100A6, Notch1 in multiple myeloma (MM) patients and its clinical significance.@*Mathods@#The expression levels of S100A6, Notch1 in 28 MM cases and 20 healthy controls were determined by real time quantitative PCR (RQ-PCR) , and their relationships with clinical features and outcomes were analyzed. Immunohistochemical was used to analysis the levels of S100A6 and Notch1 in bone marrow biopsy samples and intramedullary metastases soft tissues. RQ-PCR and Western blot were used to test the changes of Notch1 mRNA and Notch1 protein in U266 MM cells after S100A6 silenced by siRNA.@*Results@#①The expression levels of S100A6, Notch1 in primary MM patients was 2.19±1.25, 2.98±0.64, significantly higher than those in controls (0.71±0.20, 0.58±0.39, P<0.05) and patients in platform status (0.85±0.26, 0.72±0.40, P<0.05) . 8 cases with intramedullary metastasis had significantly higher levels of S100A6 (3.36±1.23) and Notch1 (5.71±3.96) , as compared to those without extra medullary metastases. ②S100A6 expression was positive correlation with Notch1 (r=0.505, P=0.007) . ③S100A6 and Notch1 proteins were positive in plasma cells of bone marrow biopsy samples and intramedullary metastases soft tissues. ④The Notch1 mRNA and Notch1 expression decreased significantly after 48 hours treatment by S100A6 siRNA in U266 cells.@*Conclusion@#S100A6 and Notch1 were closely associated with MM progress and intramedullary metastasis. They have significant correlation and might be as two prognostic molecular markers in MM.
ABSTRACT
Objective To investigate the inhibitory effects and related mechanism of S100A4 gene silencing on oxygen-induced retinal neovascularization.Methods 7-day-old C57BL/6J mice were randomly divided into 5 groups including normal group,normal-S100A4 group,oxygen induced retinopathy (OIR) group,OIR-S100A4 group,OIR-green fluorescent protein (GFP) group.To establish the OIR model,mice from all groups except normal one were exposed to (75±2) ％ oxygen for 5 days and then to room air.In the OIR-S100A4 group and OIR-GFP group,the OIR mice were given an intravitreal injection of 1 μl of 1.0 × 109 PFU/ml adenovirus of Ad-S100A4-RNAi or Ad-GFP at P12,and then returned to normoxia for the next 5 days.In the OIR group,OIR was induced in C57bl/6J mice from P7 to P17.In the normal-S100A4 group,the normal P12 mice were give an intravitreal injection of 1 μl of Ad-S100A4-RNAi adenovirus,and maintained in room air from P12 to P17.In normal group,newborn mouse litters were maintained in room air from P0 to P17 without any treatment.Mice in all five groups were euthanized at P17,and retinas were collected for biochemical assays and morphological study.Retinal neovascularization (RNV) was evaluated by counting the number of pre-retinal neovascular cells and the whole mount immunofluorescent staining of the mouse retina.Protein and mRNA expression levels of S100A4,cAMP responsive element binding protein (CREB),B cell lymphoma-2 (bcl-2),Caspase-3 were determined with western blot and real-time PCR.Results The number of pre-retinal neovascular cell nuclei in retinas from OIR-S100A4 group were obviously lower than those in the retinas from OIR group and OIR-GFP group (t=13.61,14.64;P＜0.05).In OIR-S100A4 group,the retinal neovascular tufts area and the vaso-oblitertion area were both significantly smaller than those in OIR group and OIR-GFP group (P＜0.05).Protein level of CREB and bcl-2 were significantly down-regulated in OIR-S100A4 group than those in OIR and OIR-GFP group (P＜0.05).On the contrary,protein levels of Caspase-3 were up-regulated in OIR-S100A4 group than those in OIR and OIR-GFP group (P＜0.05).Conclusion Ad-S100A4-RNAi transfer ameliorates RNV in mouse model of OIR maybe through down-regulating the expression of bcl-2 and CREB,and up-regulating the Caspase-3.
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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.