Expression and clinical significance of serum SFRP5 and miR-124-3p in patients with hypertension during pregnancy / 中华内分泌外科杂志

Objective:To explore the expression levels and the clinical significance of serum secreted frizzled-related protein 5 (SFRP5) and miR-124-3p in patients with hypertension during pregnancy.Methods:Ninety-eight patients with hypertension during pregnancy diagnosed from Jan. 2019 to Feb. 2022 were selected as the observation group. According to the degree of the condition of patients, they were divided into 41 cases of pregnancy hypertension, 32 cases of mild preeclampsia, and 25 cases of severe preeclampsia, and 80 healthy subjects during the same period were selected as the control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression level of serum SFRP5 in patients, real-time fluorescence quantitative method (qRT-PCR) was used to detect the expression level of miR-124-3p. The relationship between SFRP5, miR-124-3p levels and clinicopathological indicators in patients with hypertension in pregnancy was analyzed, Pearson correlation analysis was used to analyze the correlation between SFRP5 and miR-124-3p. Multivariate Logistic regression was used to analyze the risk factors of hypertension in pregnancy.Results:Compared with the control group, the serum SFRP5 expression level of the observation group [ (33.78±5.21) ng/L vs (43.34±8.56) ng/L] was down-regulated, while the miR-124-3p level [ (2.16±0.41) vs (1.01±0.17) ] was up-regulated, and the serum SFRP5 level of the observation group decreased with the severity of the disease[ (38.43±6.37) ng/L (33.18±5.14) ng/L (26.94±3.38) ng/L], while the level of miR-124-3p increased with the severity of the disease[ (1.62±0.24) (2.19±0.43) (3.01±0.69) ], the difference was statistically significant ( P<0.05) . The expression levels of SFRP5 and miR-124-3p in the serum of patients with hypertension in pregnancy were related to the age, pregnancy, pre-pregnancy BMI, and fasting blood glucose level of patients ( P<0.05) , but not related to the gestational age of patients ( P>0.05) . Bioinformatics TargetScan website showed that SFRP5 and miR-124-3p had binding sites. Pearson correlation analysis showed that SFRP5 and miR-124-3p were negatively correlated ( r=-0.610, P<0.05) . Multivariate Logistic regression analysis showed that SFRP5 was a protective factor for pregnancy-induced hypertension in pregnant women, and miR-124-3p was a risk factor ( P<0.05) . Conclusion:The serum levels of SFRP5 and miR-124-3p are abnormally expressed in patients with hypertension during pregnancy, and there is a certain relationship with the degree of disease. Both are involved in the occurrence and development of hypertension during pregnancy.

Diagnostic prediction formula for diabetic nephropathy based on serum TFF3, SFRP5, Gal-3 and NES-1 / 国际生物医学工程杂志

Objective:To investigate the expression and correlation of serum trefoil factor 3 (TFF3), serum secreted frizzled-related protein 5 (SFRP5), galectin-3 (Gal-3), and nesfatin-1 (NES-1) in patients with type 2 diabetes(T2DM), diabetic nephropathy(DN), chronic kidney disease (CKD), and healthy controls. To explore the relationship between the above factors and the diagnosis of DN and to establish a diagnostic formula for the diagnosis of DN combined with the above four factors.Methods:In each group 36 patients hospitalized in Tianjin Third Central Hospital from April 2017 to June 2019 were enrolled. 36 healthy volunteers were also chosen as the healthy control group. After 8 to 10 hours of fasting, the venous blood of the subjects in each group was centrifuged, the serum was collected for detection, the serum levels of TFF3, SFRP5, Gal-3, and NES-1 were compared, and the Pearson correlation analysis was performed. According to whether the diagnosis of DN was repeated, the subjects were divided into the DN group and the non-DN group (including a healthy control group, T2DM group, and CKD group). The four datasets were analyzed by binary logistic regression, and the diagnostic prediction model of DN was established, which was further verified by receiver operating characteristic (ROC).Results:The serum levels of TFF3, Gal-3 and NES-1 in DN groups were significantly higher than those in healthy control group, T2DM group and CKD group (all P<0.05), but the serum level of SFRP5 in DN group was significantly lower than that in healthy control group, T2DM group and CKD group (all P<0.05). The differences between the four groups in the four aforementioned indicators were all statistically significant (all P<0.001). The Pearson correlation analysis showed that there was a significant correlation between the above four indicators (all P<0.01). The area under the ROC curve of TFF3, SFRP5, Gal-3, and NES-1 was 0.849, 0.807, 0.882, and 0.841 respectively. The area under the curve diagnosed by the combination of four indicators (0.986) was significantly higher than that of a single indicator, and the difference was statistically significant ( Z=3.75, 4.08, 3.63, 4.06, all P<0.05). Conclusions:The joint prediction model based on serum TFF3, SFRP5, Gal-3, and NES-1 can effectively improve the diagnostic accuracy of DN and provide an important basis for clinical diagnosis of DN.

Effects of 5-aza-2'-deoxycytidine on proliferation of SPC-Al cells and expression of SFRPl and MGMT methylated proteins in lung cancer / 中国药理学通报

Aim To observe the effect of methylation inhibitors of 5-aza-2'-deoxycytidine (5-Aza-CdR) on SPC-Al - lung cancer cell proliferation, cell scratches and apoptosis, to explore the influence of secretion curl associated protein 1 (SFRPl) and 06-methylguanine-DNA-methyltransferase (MGMT) gene promoter region in which DNA methylation mRNA and protein expression and meaning. Methods The effects of 5-Aza-CdR at different concentrations on the proliferation of human lung cancer SPC-A 1 cells were determined by CCK-8 assay. The effect of 5-Aza-CdR on the migration ability of SPC-A 1 cells was determined by scratch assay. The apoptosis of lung cancer SPC-A 1 cells was detected by Hoechst 33258 staining after treatment with 5-Aza-CdR for 24 h. mRNA and protein expressions of SFRPl and MGMT in SPC-Al cells were detected by RT-PCR and Western blot. Results 5-Aza-CdR could reduce the proliferation of SPC-A 1 cells by concentration gradient,and IC50 was 21.2 jjimol • L

Establishment and identification of secreted frizzled-related protein 4 transgenic mice and analysis of their biological properties / 西安交通大学学报(医学版)

【Objective】 To generate secreted frizzled-related protein 4 (SFRP4) transgenic mice and analyze their biological properties. 【Methods】 We generated SFRP4 transgenic mice by DNA microinjection and detected the expression of SFRP4 by qRT-PCR and Western blotting. 【Results】 SFRP4 transgenic mice were successfully generated by DNA microinjection. The expression of SFRP4 was dramatically increased in transgenic mice liver compared with that of wide type. 【Conclusion】 The transgenic mice model of SFRP4 was successfully established by DNA microinjection. It provides a good model for studying the function of SFRP4 and the mechanism of participating in metabolic diseases.

Insulin resistance is associated with Sfrp5 in obstructive sleep apnea / Resistência à insulina está associada à Sfrp5 na apneia obstrutiva do sono

Abstract Introduction: Obstructive sleep apnea, a common disease, is usually complicated by insulin resistance and type 2 diabetes mellitus. Adipokine is considered to play an important role in the development of insulin resistance and type 2 diabetes mellitus in obstructive sleep apnea. Objective: To assess whether secreted frizzled-related protein 5, a new adipokine, is involved in untreated obstructive sleep apnea patients. Methods: Seventy-six subjects with obstructive sleep apnea and thirty-three control subjects without obstructive sleep apnea were recruited and matched in terms of body mass index and age. The fasting secreted frizzled-related protein 5 plasma concentration was tested using ELISA. In addition, the correlation between secreted frizzled-related protein 5 and the homeostasis model assessment of insulin resistance was obtained. Multiple linear regression analysis models with stepwise selection were performed to determine the independent associations between various factors and secreted frizzled-related protein 5. Results: Plasma secreted frizzled-related protein 5 levels were significantly lower in the obstructive sleep apnea group than in the control group (obstructive sleep apnea group: 28.44 ± 13.25 ng/L; control group: 34.16 ± 13.51 ng/L; p = 0.023). In addition, secreted frizzled-related protein 5 was negatively correlated with homeostasis model assessment of insulin resistance but positively correlated with the mean and lowest oxygen saturation with or without adjusting for age, gender, body mass index, neck circumference, waist circumference and waist-to-hip ratio. The multiple linear regression analysis showed there was an independent negative association between secreted frizzled-related protein 5 and homeostasis model assessment of insulin resistance. Conclusion: Secreted frizzled-related protein 5 was involved in obstructive sleep apnea and the decrease in secreted frizzled-related protein 5 was directly proportional to the severity of obstructive sleep apnea. There was an independent negative correlation between homeostasis model assessment of insulin resistance and secreted frizzled-related protein 5 in the obstructive sleep apnea group. Secreted frizzled-related protein 5 might be a therapeutic target for insulin resistance in obstructive sleep apnea.

Resumo Introdução: A apneia obstrutiva do sono, uma doença comum, é geralmente complicada com resistência à insulina e diabetes melito tipo 2. Acredita-se que a adipocina possa ter um papel importante no desenvolvimento de resistência à insulina e diabetes melito tipo 2 na apneia obstrutiva do sono. Objetivo: Avaliar se a proteína secretada relacionada ao receptor frizzled-5, uma nova adipocina, está envolvida em pacientes com apneia obstrutiva do sono não tratada. Método: Foram recrutados 76 indivíduos com apneia obstrutiva do sono e 33 indivíduos controle sem apneia obstrutiva do sono e pareados em relação a índice de massa corporal e idade. A concentração plasmática de proteína secretada relacionada ao receptor frizzled-5 foi testada em jejum com o teste Elisa. Além disso, obteve-se correlação entre a proteína secretada relacionada ao receptor frizzled-5 e o modelo de avaliação da homeostase de resistência à insulina. Modelos de análise de regressão linear múltipla com seleção stepwise foram feitos para determinar as associações independentes entre vários fatores e a proteína secretada relacionada ao receptor frizzled-5. Resultados: Os níveis plasmáticos de proteína secretada relacionada ao receptor frizzled-5 foram significativamente menores no grupo com apneia obstrutiva do sono do que no grupo controle (grupo com apneia obstrutiva do sono: 28,44 ± 13,25 ng/L; grupo controle: 34,16 ± 13,51 ng/L; p = 0,023). Além disso, a proteína secretada relacionada ao receptor frizzled-5 foi correlacionada negativamente com o modelo de avaliação da homeostase de resistência à insulina, mas se correlacionou positivamente com a média e a saturação mínima de oxigênio com ou sem ajuste para idade, gênero, índice de massa corporal, circunferência do pescoço, circunferência da cintura e relação cintura-quadril. A análise de regressão linear múltipla mostrou que houve uma associação negativa independente entre a proteína secretada relacionada ao receptor frizzled-5 e o modelo de avaliação da homeostase de resistência à insulina. Conclusões: A proteína secretada relacionada ao receptor frizzled-5 esteve envolvida na apneia obstrutiva do sono e sua diminuição foi diretamente proporcional à gravidade da apneia obstrutiva do sono. Houve uma correlação negativa independente entre o modelo de avaliação da homeostase de resistência à insulina e a proteína secretada relacionada ao receptor frizzled-5 no grupo da apneia obstrutiva do sono. A proteína secretada relacionada ao receptor frizzled-5 pode ser um alvo terapêutico para a resistência à insulina na apneia obstrutiva do sono.

MiR-1180 from bone marrow-derived mesenchymal stem cells induces glycolysis and chemoresistance in ovarian cancer cells by upregulating the Wnt signaling pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

BACKGROUND@#Bone marrow-derived mesenchymal stem cells (BM-MSCs) play an important role in cancer development and progression. However, the mechanism by which they enhance the chemoresistance of ovarian cancer is unknown.@*METHODS@#Conditioned media of BM-MSCs (BM-MSC-CM) were analyzed using a technique based on microRNA arrays. The most highly expressed microRNAs were selected for testing their effects on glycolysis and chemoresistance in SKOV3 and COC1 ovarian cancer cells. The targeted gene and related signaling pathway were investigated using in silico analysis and in vitro cancer cell models. Kaplan-Merier survival analysis was performed on a population of 59 patients enrolled to analyze the clinical significance of microRNA findings in the prognosis of ovarian cancer.@*RESULTS@#MiR-1180 was the most abundant microRNA detected in BM-MSC-CM, which simultaneously induces glycolysis and chemoresistance (against cisplatin) in ovarian cancer cells. The secreted frizzled-related protein 1 (SFRP1) gene was identified as a major target of miR-1180. The overexpression of miR-1180 led to the activation of Wnt signaling and its downstream components, namely Wnt5a, β-catenin, c-Myc, and CyclinD1, which are responsible for glycolysis-induced chemoresistance. The miR-1180 level was inversely correlated with SFRP1 mRNA expression in ovarian cancer tissue. The overexpressed miR-1180 was associated with a poor prognosis for the long-term (96-month) survival of ovarian cancer patients.@*CONCLUSIONS@#BM-MSCs enhance the chemoresistance of ovarian cancer by releasing miR-1180. The released miR-1180 activates the Wnt signaling pathway in cancer cells by targeting SFRP1. The enhanced Wnt signaling upregulates the glycolytic level (i.e. Warburg effect), which reinforces the chemoresistance property of ovarian cancer cells.

MiR-1180 from bone marrow-derived mesenchymal stem cells induces glycolysis and chemoresistance in ovarian cancer cells by upregulating the Wnt signaling pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Background: Bone marrow-derived mesenchymal stem cells (BM-MSCs) play an important role in cancer development and progression. However, the mechanism by which they enhance the chemoresistance of ovarian cancer is unknown. Methods: Conditioned media of BM-MSCs (BM-MSC-CM) were analyzed using a technique based on microRNA arrays. The most highly expressed microRNAs were selected for testing their effects on glycolysis and chemoresistance in SKOV3 and COC1 ovarian cancer cells. The targeted gene and related signaling pathway were investigated using in silico analysis and in vitro cancer cell models. Kaplan-Merier survival analysis was performed on a population of 59 patients enrolled to analyze the clinical significance of microRNA findings in the prognosis of ovarian cancer. Results: MiR-1180 was the most abundant microRNA detected in BM-MSC-CM, which simultaneously induces glycolysis and chemoresistance (against cisplatin) in ovarian cancer cells. The secreted frizzled-related protein 1 (SFRP1) gene was identified as a major target of miR-1180. The overexpression of miR-1180 led to the activation of Wnt signaling and its downstream components, namely Wnt5a, β-catenin, c-Myc, and CyclinD1, which are responsible for glycolysis-induced chemoresistance. The miR-1180 level was inversely correlated with SFRP1 mRNA expression in ovarian cancer tissue. The overexpressed miR-1180 was associated with a poor prognosis for the long-term (96-month) survival of ovarian cancer patients. Conclusions: BM-MSCs enhance the chemoresistance of ovarian cancer by releasing miR-1180. The released miR-1180 activates the Wnt signaling pathway in cancer cells by targeting SFRP1. The enhanced Wnt signaling upregulates the glycolytic level (i.e. Warburg effect), which reinforces the chemoresistance property of ovarian cancer cells.

Effects of FRZB mRNA in adjusting WNT signal pathway for prognosis of non-small cell lung cancer / 临床检验杂志

Objective@#This study aimed to reveal the potential clinical and biological functions of frizzled related protein (FRZB) mRNA expression in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). @*Methods@#We used the keyword “lung cancer” to search the data through Gene Expression Omnibus (GEO) database attached to NCBI(National Center of Biotechnology) and download the data of LUAD and LUSC from TCGA (The Cancer Genome Atlas) Database. A total of eight LUAD and six LUSC datasets were incorporated in this analysis. We defined cutoff value of FRZB using Cutoff Finder into the two groups to calculate hazard ratio (HR). @*Results@#We found that high expression level of FRZB mRNA in tumor tissues was a positive prognostic factor for overall survival in LUAD [pooled HR（95%CI）=0.54（0.46-0.64）,P＜0.05 in univariate analysis; pooled HR（95%CI）=0.66（0.54-0.79）,P＜0.05 in multivariate analysis]. Interestingly, there was no similar results in LUSC [pooled HR（95%CI）=1.11（0.67-1.84）,P＞0.05 in univariate analysis; pooled HR（95%CI）=1.13（0.71-1.78）,P＞0.05 in multivariate analysis]. We also found that FRZB may inhibit WNT signal pathway by t-SNE and correlation analysis. By enrichment analysis, FRZB and its most correlated genes were involved in multiple immune-related pathways, such as complement and coagulation cascades, humoral immune response, etc. @*Conclusion@#High expression of FRZB mRNA in LUAD was associated with better prognosis of lung adenocarcinoma. These results suggest that FRZB may be used as a potential marker for favorable prognosis of lung adenocarcinoma.

Correlations between the levels of serum Wnt5a, Sfrp5, and glycemic control in elderly male patients with type 2 diabetes mellitus / 中华内分泌代谢杂志

Objective To investigate the levels of serum Wnt5a and Sfrp5 in elderly male patients with type 2 diabetes mellitus (T2DM), and identify associations between their levels and glycemic control. Methods A total of 67 elderly male T2DM patients and 65 nondiabetic subjects were studied. Participants were divided into four groups:normal control (NC group), T2DM patients were categorized by HbA1C quartile(Group Ⅰ: HbA1C<7％, Group Ⅱ:7％≤HbA1C < 9％, Group Ⅲ: HbA1C ≥9％). The serum Wnt5a and Sfrp5 concentrations were measured through ELISA. Influencing factors for Wnt5a and Sfrp5 were analyzed. Results Compared with the NC group, Wnt5a levels of elderly T2DM were decreased in groups Ⅱ and Ⅲ, in contrast, Sfrp5 levels were elevated in groups Ⅱ and Ⅲ than NC group(all P<0.05). Spearman correlation analysis suggested that Wnt5a levels were negatively correlated with HbA1C , GA, FPG, and 2hPG(r were -0.277, -0.298, -0.185, and -0.254 respectively, all P<0.05);Sfrp5 levels were positively correlated with HbA1C , GA, and FPG(r were 0.311, 0.247, and 0.200 respectively, all P<0.05) while negatively correlated with BMI and LDL-C( r were - 0.193 and - 0.190, both P< 0.05). Multivariate linear regression analysis showed that HbA1C was an independent association factor for Wnt5a, and FPG was an independent association factor for Sfrp5. Conclusions In the elderly male T2DM with worse glycemic control, Wnt5a levels were more decreased, and in contrast, Sfrp5 levels were elevated. This result indicated that Wnt5a and Sfrp5 may be associated with the level of glycemic control in elderly male T2DM patients.

Expression of secreted frizzled-related protein 4 in DNA mismatch repair-deficient and mismatch repair-proficient colorectal cancers / 南方医科大学学报

OBJECTIVE@#To investigate the expressions of secreted frizzled-related protein 4 (SFRP4) in stage Ⅱ DNA mismatch repair-deficient (dMMR) and mismatch repair- proficient (pMMR) colorectal cancers and explore their clinical significance.@*METHODS@#We collected fresh stage Ⅱ colon cancer tissues with different MMR status detected by immunohistochemistry (IHC). The differentially expressed mRNAs between dMMR and pMMR tumors were identified by Affymetrix Human oeLncRNA gene chip, and the expression of SFRP4 in these cancer tissues and in colorectal cancer cell lines were detected using Western blotting and real- time quantitative PCR. The apoptosis rates of HCT116 cells with and without siRNA- mediated transient SFRP4 knockdown were determined using flow cytometry. We further investigated the expression pattern of Ki-67 and its correlation with SFRP4 expression.@*RESULTS@#Compared with pMMR colon cancer tissues or cells, both dMMR colon cancer tissues (=0.014) and cells (=0.0079) showed significantly increased expression of SFRP4, which was in negative correlation with Ki-67 (=0.041). In HCT116 cells, transient SFRP4 knockdown resulted in decreased cell apoptosis, including both early apoptosis (=0.003) and late apoptosis (=0.024).@*CONCLUSIONS@#Up-regulation of SFRP4 in dMMR stage Ⅱ colon cancer promotes apoptosis and inhibits proliferation of the cancer cells, and may improve the prognosis of dMMR colon cancer.

Expression and significance of secreted frizzled-related protein 1 and β-catenin in gingival tissue of patients with chronic periodontitis / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study aimed to investigate the expression and correlation of secreted frizzled-related protein 1 (SFRP1) and β-catenin in gingival tissues of patients with chronic periodontitis (CP). The role of the classical Wnt/β-catenin signaling pathway in the development of periodontitis was also explored.</p><p><b>METHODS</b>Twenty-eight patients with CP (CP group) were enrolled in this study. Among them, 16 cases were moderate CP, and 12 demonstrated severe CP. Twelve healthy cases comprised the controls (normal group). Gingival tissue was collected, and the probing depth, bleeding index, and clinical attachment loss were recorded. The expression levels of SFRP1 and β-catenin were detected by immunohistochemistry, and staining intensity was evaluated by double scoring method. SPSS 19.0 was used for statistical analysis.</p><p><b>RESULTS</b>The staining strength scores of SFRP1 and β-catenin were 2.16±0.65 and 1.12±0.51 in the normal group, 3.57±0.45 and 2.36±0.49 in the CP group, 3.61±0.40 and 2.30±0.44 in the moderate CP group, and 3.52±0.52 and 2.45±0.55 in the severe CP group, respectively. The expression of SFRP1 and β-catenin in the CP group was higher than that in the normal group (P<0.01). A significant difference was noted between the normal group and the moderate and severe CP groups (P<0.01) but none between the moderate and severe CP groups (P>0.05). A positive correlation was found between the expression of SFRP1 and β-catenin (r=0.657, P<0.01). The expression levels of β-catenin and SFRP1 were related to periodontal indexes. The correlation between the expression of SFRP1 and probing depth was most significant (r=0.723, P<0.01), as well as that between β-catenin and bleeding index (r=0.697, P<0.01).</p><p><b>CONCLUSIONS</b>Patients with CP exhibit elevated expression of SFRP1 and β-catenin in gingival tissues, and this event is related to the degree of periodontal destruction. Abnormal expression of SFRP1 and β-catenin may promote the development of periodontitis.</p>

Ang Ⅱinduces up-expression of secreted frizzled-related protein 5 in cardiomyocyte hypertrophy of rats / 基础医学与临床

Obj ective To investigate the mechanism of secreted frizzled-related Protein 5 ( sFRP5) expression in cardiomyocyte hypertrophy.Methods In vivo experiment, neonatal rat ventricular myocytes were exposed to Ang Ⅱ(10-6 mmol/L, 48 h).Telmisartan, Y27632, PD98059,SB203580 and SP600125 were used to block angiotensin type 1 receptor( AT1R) , Rho/ROCK, p38 MAPK, ERK1/2 and JNK pathway, respective-ly.Western blot was applied to determine the expressions of sFRP5, ROCK1, ROCK2, total MYPT1, p-MYPT1.RT-PCR was used to determine sFRP5 expression.Results There was significant inhibition of sFRP5 expression when treated with Y37632 and SP699125, but less with SB203580 and PD98059 in AngⅡ-induced cardiomyocytes.Moreover, telmisartan down-regulated the expression of ROCK1, but no effect on the expression of ROCK2.Conclusions The expression of sFRP5 is up-regulated mainly by Rho/ROCK1/JNK pathway in cardiomyocyte hypertrophy induced by Ang Ⅱ.

Relationship between plasma secreted frizzled-related protein 5 with type 2 diabetes mellitus and carotid atherosclerosis / 中国糖尿病杂志

Objective To investigate the relationships between plasma secreted frizzled-related protein (SFRP) 5 level with type 2 diabetes (T2DM ) and carotid atherosclerosis (CAS). Methods According to the results of carotid color Doppler ultrasound ,56 T2DM patients were divided into 28 with carotid atherosclerosis (CAS group) and 28 without carotid atherosclerosis (NAS group). 28 healthy volunteers served as normal control (NC group). Serum SFRP5 was measured by ELISA. Results The level of serum SFRP5 in T2DM patients was lower than NC group (114.36 ± 25.48) vs (48.19 ± 11.82) , (43.88 ± 8.19)pg/ml ,(P 0.05 ]. Pearson correlation analysis showed that serum SFRP5 was negatively correlated with age ,TG ,hsC-RP ,FPG ,FIns , HOMA-IR ,HbA1c ,TC ,LDL-C and BMI (P0.05). Multiple linear regression results showed that age ,FIns and HbA1 c were independent influencing factors of serum SFRP5. Conclusion SFRP5 may be a protective factor for T2DM by ameliorating insulin resistance which may provide a new clue for the prevention and treatment of T 2DM.

Expression and clinical significance of SFRP4 in pancreatic ductal adenocarcinoma / 临床与实验病理学杂志

Purpose To investigate the expression of secreted frizzled-related protein 4 (SFRP4) and to evaluate its clinical significance in pancreatic ductal adenocarcinoma (PDAC).Methods RT-PCR was performed to analyze SFRP4 mRNA expression level in 30 paired PDAC lesion and matched adjacent non-tuimor tissue.Immunohistochemistry staining detection of 205 matched cases tissue microarray was conducted to explore SFRP4 protein expression pattern.The correlation between SFRP4 and clinical characteristics was also analyzed,including overall survival.Results SFRP4 expression pattern both at mRNA and protein level in PDAC lesion was higher than that in matched adjacent non-tumor tissue.At mRNA level,to found that expression of SFRP4 was elevated in 90％ (27/30) of PDAC tissues (P =0.007 2).To found that high expression of SFRP4 was detected in 56.5％ (116/205) of PDAC tissue,while only 28.8％ (59/205) in the adjacent non-tumor tissue.Moreover,no significant association was observed between SFRP4 expression and clinical characteristics.Kaplan-Meier survival analysis showed high level of SFRP4 expression was correlated with poor overall survival (x2 =3.467,P =0.024).Conclusion SFRP4 can be a novel prognostic biomarker in PDAC.

Progression of secreted frizzled-related protein family in cancer / 国际肿瘤学杂志

Secreted frizzled-related protein (SFRP) can inhibit the expression of Wnt signaling pathway through Frizzled protein.The silencing of SFRP gene promoter methylation is associated with the occurrence and metastasis of many cancers such as colorectal cancer,gastric cancer,liver carcinoma,lung cancer and ovarian cancer.Several studies have found that SFRP gene has latent clinical value,which is expected to become the novel target for the gene diagnosis and treatment of cancer.

Expression of SFRP5 mRNA in Rat Skeletal Muscle after Contusion / 法医学杂志

Objective T o investigate the relationship betw een the expression of secreted frizzled-related protein 5 (SFR P5) m RNA and the tim e interval after skeletal m uscle injury in rats by real-tim e PC R . Methods A total of ninety SD rats w ere random ly divided into the contusion groups at different tim es including 4 h, 8 h, 12 h, 16 h, 20 h, 24 h, 28 h, 32 h, 36 h, 40 h, 44 h, 48 h after contusion, incision groups at different tim es including 4h and 8h after incision and the control group. T he sam ples w ere taken from the contused zone at different tim e points. T he total RNA w as isolated from the sam ples and re-versely transcribed to analyze the expression levels of SFRP5 m RNA . Results C om pared to the control group, the expression of SFRP5 m RNA in contusion groups w ere dow n-regulated w ithin 48 h after con-tusion and reached the low est level at 20 h, and the expression of SFRP5 m RNA gradually increased from 20 h to 48 h after contusion. T he expression of SFRP5 m RNA in the incised groups w ere signifi-cantly low er than that of the contusion groups at 4 h after injury. A t the tim e of 8 h, the expression levels betw een the contusion and incision groups show ed no statistically significant difference. Conclusion It is suggested that SFRP5 m RNA analysis m ay show regular expression and can be a m arker for estim ation of skeletal m uscle injury age.

Relationship between serum secreted Frizzled-related protein 4 and the pancreaticβcell function / 中华内分泌代谢杂志

Objective To investigate the relationship between serum secreted frizzled-related protein 4 (SFRP4) and the first-phase of glucose-stimulated insulin secretion from pancreatic β cell under different glucose tolerance statuses. Methods Fifty-six patients with newly diagnosed type 2 diabetes mellitus ( T2DM group), 52 patients with impaired glucose tolerance (IGT group), and 42 subjects with normal glucose tolerance (NGT group) underwent intravenous glucose tolerance test. Fasting serum SFRP4 and interleukin ( IL)-1β were assayed by ELISA. Acute insulin response ( AIR), the area under the curve of the first-phase (0-10 min) insulin secretion (AUC), glucose disposition index(GDI), homeostasis model assessment for β cell function index(HOMA-β), and insulin resistance index(HOMA-IR) were calculated. Results (1) The levels of SFRP4 and IL-1β in T2DM group and IGT group were significantly higher than that in NGT group [(184. 38 ± 61. 34 or 141. 64 ± 40. 46 or 95. 46 ± 20. 13)ng/ ml, P<0. 01]. AIR, AUC, and GDI in T2DM group and IGT group were significantly lower than those in NGT group(P<0. 01), and these results were more significantly reduced in T2DM group compared with those in IGT group. (2) SFRP4 was negatively correlated with AIR, AUC, GDI, HOMA-β (P<0. 01), and positively correlated with fasting plasma glucose, 2 h plasma glucose after glucose loading, HbA1C , IL-1β, and high sensitive C-reactive protein(P<0. 01). (3) Multiple stepwise regression analysis showed that AUC, HOMA-IR, and serum IL-1β level were independently associated with SFRP4. Conclusion The concentration of serum SFRP4 is closely correlated with the glycolipid metabolic disorder, the first-phase of glucose-stimulated insulin secretion, and chronic low-grade inflammation. SFRP4 may be involved in the mechanism of β cell dysfunction in type 2 diabetes mellitus.

Effects of magnolol in combination with 5-FU on cell proliferation and SFRP-4 expression of human colon cancer HCT-8 cells / 肿瘤

Objective: To investigate the effects of magnolol in combination with 5-fluorouracil (5-FU) on the proliferation of human colon cancer HCT-8 cells and the expression of secreted frizzled-related protein-4 (SFRP-4). Methods: After treatment with magnolol and 5-FU alone or magnolol in combination with 5-FU, the proliferation of colon cancer HCT-8 cells was detected by MTT method, and the cell cycle distribution and the apoptosis of HCT-8 cells were examined by flow cytometry (FCM) and Hoechst 33258 nucleic acid staining, respectively. The expression levels of SFRP-4 and p-catenin proteins in HCT-8 cells were examined by Western blotting. Results: The proliferation of HCT-8 cells was inhibited by magnolol and 5-FU alone or mamgnolol in combination with 5-FU (all P 2/M phases were decreased in 5-FU alone group and the combination treatment group (both P < 0.05). The expression levels of SFRP-4 in HCT-8 cells in all three treatment groups were higher than that in the blank control group (without any treatment) (P < 0.05), while the expression level of p-catenin in HCT-8 cells in combination treatment group was lower than those in 5-FU and magnolol alone groups (P < 0.05). Conclusion: Magnolol in combination with 5-FU can enhance the inhibition effect on proliferation of human colon cancer HCT-8 cells, and arrest the cells at G0/G1 phase. This mechanism may be related to regulating the expressions of SFRP-4 and p-catenin proteins.

Effect of metformin on SFRP5 release and insulin resistance in diabetic rat / 中华内分泌代谢杂志

Diabetic rat model accompanied by insulin resistance was established by intraperitoneal injection of streptozocin.Following metformin treatment for 5 weeks,ELISA was used to detect the level of plasma secreted frizzled-related protein (SFRP) 5,and immunohistochemistry was used to detect the expression of p-JNK in the liver.insulin resistance(IR) and p-JNK were significantly increased in diabetic group compared with the control group (P＜0.05),while plasma SFRP5 level was reduced (P＜0.01).After metformin treatment,the plasma SFRP5 levels were significantly increased (P＜0.05),while IR and p-JNK was decreased (P＜O.05).Metformin may ameliorate insulin resistance via upregulating the SFRP5 expression of diabetic rats.

Relation of plasma secreted frizzled-related protein 5 to obesity and type 2 diabetes mellitus / 中华内分泌代谢杂志

To investigate the relationships among plasma secreted frizzled-related protein ( sfrp) 5 level and body fat parameters, glucolipid metabolism, insulin resistance index, and inflammation. 89 subjects with normal glucose tolerance(NGT) and 87 patients with type 2 diabetes mellitus (T2DM) were enrolled and each group was divided into no-obese and obese subgroups. Obesity was defined as body mass index ( BMI)≥25 kg/m2 according to the World Health Organization -Western Pacific Region diagnostic criteria ( 2000 ) . Body fat parameters were measured and BMI, waist-hip ratio were evaluated, meanwhile, the levels of blood glucose-lipid parameters and fasting insulin were also determined. Insulin resistance index ( IR) was assessed by homeostasis model assessment ( HOMA) . The concentrations of plasma sfrp5 and interleukin 6 were detected by enzyme-linked immunosorbent assay. Plasma sfrp5 level in T2DM group was significantly lower than that in NGT group [(8. 35±3. 38 vs 11. 35±3. 69)ng/ml, P<0. 01]. The levels of plasma sfrp5 in subjects with obesity were also lower than those in subjects with no-obesity in both NGT and T2DM groups [(9. 46±2. 70 vs 13. 12±3. 62)ng/ml and(6. 70±2. 34 vs 10. 12±3. 45) ng/ml, both P<0. 01]. Plasma concentrations of sfrp5 in T2DM-obese group were significantly lower than that in NGT-obese group(P<0. 01). Correlation analysis showed that plasma sfrp5 levels were negatively correlated with waist-hip ratio, HbA1C, fasting insulin, triglycerides, waist circumference, fasting plasma glucose, interleukin 6, natural logarithm of HOMA-IR [ln(HOMA-IR)], and BMI(P<0. 01 or P<0. 05). Multiple linear regression showed that ln(HOMA-IR), BMI, triglycerides were independent related factors in influencing the levels of plasma sfrp5 (r2=0. 216, 0. 177, 0. 113, all P<0. 05). Plasma sfrp5 levels were decreased in obesity and T2DM subjects and were correlated with body fat disposition, glucose-lipid metabolism, insulin resistance and inflammation. Lack of sfrp5 may contribute to the pathophysiology of obesity and T2DM.