Insulin-like growth factor binding protein 3 promoter variant (rs2854744) is associated with nonalcoholic fatty liver disease

ABSTRACT Objective: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and a growing global epidemic. In NAFLD, liver fat surpasses 5% of hepatocytes without the secondary causes of lipid accumulation or excessive alcohol consumption. Given the link between NAFLD and insulin resistance, the possible association between the rs2854744 (−202 G>T) promoter polymorphism of insulin-like growth factor binding protein 3 (IGFBP3) gene and NAFLD was investigated in this study. Materials and methods: In this genetic case-control association study, the IGFBP3 rs2854744 genotypes of 315 unrelated individuals, including 156 patients with biopsy-proven NAFLD and 159 controls, were determined using polymerase chain reaction/restriction fragment length polymorphism analyses. Results: The "GT+TT" genotype of the IGFBP3 rs2854744 polymorphism, compared with the "GG" genotype, was associated with a 2.7-fold increased risk of NAFLD after adjustment for confounding factors (P = 0.009; odds ratio [OR] = 2.71; 95% confidence interval [CI] = 1.19-3.18). Additionally, the IGFBP3 rs2854744 "T" allele, in comparison with the "G" allele, was significantly overrepresented in NAFLD patients than the controls (P = 0.008; OR = 1.85; 95%CI = 1.23-2.94). Conclusion: Our findings first indicated that the IGFBP3 rs2854744 "GT+TT" genotype is a marker of increased NAFLD susceptibility; however, it needs to be supported by further investigations in other populations.

Single Value of NephroCheck� Performed at 4 Hours After Surgery Does Not Predict Acute Kidney Injury in Off?Pump Coronary Artery Bypass Surgery

Background: Quantification of urinary tissue inhibitor of metalloproteinase?2 (TIMP?2) and insulin?like growth factor binding protein (IFGBP?7), which is commercially known as NephroCheck�(NC) test have been suggested as promising tools for the early detection of acute kidney injury (AKI) after cardiac surgery involving cardio?pulmonary bypass (CPB). Objectives: The aim of the present study was to test the hypothesis that single value of postoperative NC test performed at 4 hours after surgery can predict AKI in off?pump coronary artery bypass grafting (OPCABG) surgery. Setting and Design: This prospective single?center study was conducted at the tertiary cardiac center in India from December 2017 to November 2018. Methods: Ninety adult patients of both sex undergoing elective OPCABG were included. Anesthesia was standardized to all patients. Urine samples were collected preoperatively and at 4 hours after surgery for NC test. Urine output, serum creatinine, estimated glomerular filtration rate (eGFR) were also measured. AKI staging was based on kidney disease improving global outcomes (KDIGO) guidelines. Statistical Analysis: To assess the predictability of NC test for the primary endpoint, area under the receiver operating characteristic curve (ROC), was calculated. Results: Thirteen patients developed AKI in the study cohort (14.4%) out of which 7 patients (7.8%) developed stage 2/3 AKI and the remaining stage 1 AKI. Baseline renal parameters were similar between AKI and non?AKI group. The area under curve (AUC) of NC test at 4 hours after surgery was 0.60 [95% confidence interval (CI): 0.42?0.77]. Postoperative NC test performed at 4 hours after surgery did not predict AKI in this study population (P = 0.24). There were no significant differences in duration of mechanical ventilation, length of intensive care stay and hospital stay between the two groups (P > 0.05). Conclusion: NephroCheck� test performed at 4 hours after surgery did not identify patients at risk for developing AKI following OPCABG surgery

The relationship between serum leptin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 levels and clinical parameters in primary fibromyalgia patients

SUMMARY OBJECTIVE: The aim of this study was to investigate the levels of leptin, growth hormone, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 and their relations with clinical parameters in patients with primary fibromyalgia and healthy controls. METHODS: Our study was performed on 30 female patients with primary fibromyalgia and 30 healthy controls. The levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 were measured by a two-site immunoradiometric assay. The serum level of leptin was measured by the ELISA kit. RESULTS: The serum level of leptin was significantly higher, but the serum levels of insulin-like growth factor-1 were significantly lower in patients with fibromyalgia syndrome than healthy controls (p<0.001). The leptin level was positively correlated with the Visual Analog Scale, Fibromyalgia Impact Questionnaire score, Beck Depression Inventory score, tender point count, age, and duration of disease (p<0.001), but it was negatively correlated with insulin-like growth factor-1 (p<0.001). The insulin-like growth factor-1 level was negatively correlated with age, Visual Analog Scale, Fibromyalgia Impact Questionnaire and Beck Depression Inventory scores, duration of disease, and tender point count (p<0.001). CONCLUSION: Our results indicate that high levels of serum leptin and low levels of serum insulin-like growth factor-1 may play a role in the physiopathogenesis of fibromyalgia and may be related to some symptoms.

Expression of miR-4783-3p in hepatocellular carcinoma tissue and its effect on the proliferation and migration of hepatocellular carcinoma cells / 国际外科学杂志

Objective:To study the expression of microRNA (miRNA)-4783-3p in liver cancer tissue and its effect on the proliferation and migration of liver cancer Huh-7 cells.Methods:The cBioPortal database was used to analyze the expression of miR-4783-3p in liver cancer tissues and adjacent tissues. In strict accordance with the instructions of Lipofectamine? 2000 transfection kit, miR-4783-3p overexpression mimics or overexpression control mimics were transfected into Huh-7 cells respectively, namely overexpression group and control group. The proliferation of Huh-7 cells was analyzed by CCK-8 assay, and the migration of Huh-7 cells was analyzed by cell scratch method. The targeting relationship between miR-4783-3p and insulin-like growth factor binding protein 2 ( IGFBP2) mRNA was detected by dual-luciferase reporter gene assay. RT-qPCR was used to detect the expression of IGFBP2 mRNA. Western-blotting was used to detect the expression of IGFBP2 protein and EGFR-STAT3 molecular pathway proteins. Results:The expression of miR-4783-3p in liver cancer tissues was significantly lower than that in adjacent tissues ( P<0.01). Compared with the control group, the proliferation ability of Huh-7 cells in the overexpression group was significantly decreased ( P<0.05). The scratch healing rates of Huh-7 cells in the control group and the overexpression group were (67.71±9.04)% and (29.58±10.51)%, respectively, and the scratch healing rate in the overexpression group was significantly lower ( P<0.01). miR-4783-3p targeted and bound to IGFBP2 mRNA ( P<0.01). The expression of IGFBP2 mRNA in the control and overexpression groups was 5.76±1.44 and 0.99±0.47, respectively, and miR-4783-3p negatively regulated the expression of IGFBP2 mRNA ( P<0.01). Compared with the control group, the expressions of IGFBP2 protein and EGFR-STAT3 molecular pathway protein were decreased in the overexpression group. Conclusions:miR-4783-3p is lowly expressed in liver cancer tissues. miR-4783-3p can attenuate the proliferation and invasion ability of liver cancer Huh-7 cells by inducing the low expression of IGFBP2 gene.

The predictive value of TIMP-2 and IGFBP7 in delayed renal function recovery after DCD renal transplantation / 中华泌尿外科杂志

Objective:This study is to investigate the predictive value of serum levels of TIMP-2 and insulin-like growth factor-binding protein 7(IGFBP7) in patients with DCD(donation after cardiac death) kidney transplantation.Methods:A prospective research design was used to select DCD kidney transplant patients admitted to the Li Huili Hospital of Ningbo University from January 2018 to October 2020.Inclusion criteria: ①Complete data; ②There were no serious complications affecting the function of the transplanted kidney in the early postoperative period.Exclusion criteria: ①Incomplete data; ②Patients were unable or unwilling to cooperate with the study; ③Severe complications affecting the function of the transplanted kidney occurred early after the operation.The ELASE method was used to quantitatively detect the serum TIMP-2 and IGFBP7 levels at 6, 12, 24, 48, 72 hours and 7 days after renal transplantation, and monitor the serum creatinine values during the same period and 21 days after the operation. According to the occurrence of DGF, the measured values of TIMP-2 and IGFBP7 at different time points and their product's ability to predict the occurrence of DGF after kidney transplantation were analyzed. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic efficacy of TIMP-2 and IGFBP7 for DGF.Results:A total of 33 patients were enrolled, 7 patients (21.2%) in the DGF group and 26 patients (78.8%) in the non-DGF group. Between the two groups, the donor glomerular filtration rate were [98.5(15.8-132.5)ml/(min·1.73m 2) and 79.1(60.6-102.5)ml/(min·1.73m 2)], recipient gender (male/female: 3/4 cases and 10/16 cases), recipient age [48(34-56) Years old and 45(23-61) years old], the recipient's preoperative creatinine [1114.0(731.4-1293.0)μmol/L and 858.4(657.6-1051.9)μmol/L], the recipient's preoperative urea nitrogen [15.0(13.2-19.6)mmol/L and 17.3(13.6-20.9)mmol/L], receptor preoperative albumin [43.5(38.5-45.3)mmol/L and 41.2(37.5-46.1) mmol/L], recipient dialysis method [hemodialysis/peritoneal dialysis: 3/4 cases and 9/17 cases], warm ischemia time [6(5-7) and 5(4-6) min, there was no statistically significant difference] ( P>0.05). The values of serum IGFBP7 and TIMP-2×IGFBP7 in the DGF group were higher than those in the non-DGF group at all time points ( F=15.753, P=0.040; F=13.000, P=0.024), while serum TIMP-2 was not significant between the two groups difference ( F=1.157, P=0.075). For the diagnostic value of DGF, the AUC of serum IGFBP7 at 48 h after surgery was 0.863 (95% CI 0.696-1.000, P=0.004). When 5.97 ng/ml was used as the cut-off value, the sensitivity was 85.7% and the specificity was 80.8 %. The AUC of TIMP-2×IGFBP7 at 48 hours after surgery was 0.819 (95% CI 0.641-0.996, P=0.011). When 62.06(ng/ml) 2 was used as the cutoff value, the sensitivity was 71.4% and the specificity was 80.8%.There was no statistical difference in the area under the curve between the two ( P>0.05). There were differences in the dynamic trend of serum IGFBP7 and creatinine in the DGF group. Serum IGFBP7 at 7 days after surgery was positively correlated with creatinine at 21 days after surgery. Conclusion:Serum IGFBP7 and TIMP-2×IGFBP7 could predict the occurrence of DGF after DCD donor kidney surgery. The predictive value changes with time. Among them, 48h and 7d after surgery are the most valuable. However, serum TIMP-2 has not been found to have predictive value in this study.

Gallbladder cancer-associated fibroblasts promote the migration of lymphatic endothelial cells via releasing IGFBP3 / 西安交通大学学报(医学版)

【Objective】 To investigate the effects of gallbladder cancer-associated fibroblasts (CAFs) on the migration of lymphatic endothelial cells (LECs) so as to elucidate the molecular mechanisms involved. 【Methods】 The CAFs and normal fibroblasts (NFs) were extracted by enzymatic digestion, and the supernatant (CM) of CAFs and NFs was collected. The levels of IL-6, IGFBP3 and other related cytokines were detected by semi-quantitative protein factor microarray and ELISA. The expressions of α-SMA (CAFs maker) and IGFBP3 in gallbladder cancer and para-cancer tissues were detected by immunohistochemistry, and the correlation of α-SMA and IGFBP3 expressions with clinicopathological characteristics were analyzed. LECs were cultured and divided into serum-free medium group (control group), CAF-CM co-culture group, NF-CM co-culture group, IGFBP3 group, and CAF-CM+IGFBP3 inhibitor (2-Deoxy-D-glucose, 2-DG) group according to different treatment. Transwell migration assays and wound healing assays were applied to analyze the migration ability of LECs under different treatment. The expressions of E-cadherin, N-cadherin and Vimentin were detected by Western blotting. 【Results】 Protein factor microarray and ELISA showed that the concentration of IGFBP3 in CAF-CM was significantly increased, and the expression of α-SMA was significantly related to lymph node metastasis, advanced TNM stage and expression of IGFBP3. IGFBP3 secreted from CAF-CM significantly promoted LECs migration, up-regulated the expression of N-cadherin and Vimentin, and down-regulated the expression of E-cadherin. Treatment with IGFBP3 inhibitor 2-DG could reverse the effect of CAF-CM on migration of LECs and related protein expressions. 【Conclusion】 Gallbladder CAFs promote the migration of LECs via releasing IGFBP3, which affects EMT transformation.

Expression of IGFBP-rP1 in ovarian and breast cancers in association with diabetes mellitus status

@#Introduction: Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is an important component of the IGF system that regulates insulin resistance-related to tumour development. The aim of this study is to investigate the expression of IGFBP-rP1 among female cancer patients who are known or not known to have Type 2 Diabetes Mellitus (T2DM). Materials and Methods: Using a cross-sectional design, cases of ovarian and breast cancer with clinical status of T2DM were selected over a 10-year period in Hospital Universiti Sains Malaysia. Immunohistochemical staining for IGFBP-rP1 was performed on paraffin-embedded tissues and the results were correlated with the patient’s demographic and clinicopathological data. Results: A total of 152 breast cancer patients were recruited into the current study with 33.5% (51/152) patients were positive T2DM. Most of the breast cancer patients with T2DM were IGFBP-rP1-negative (66.7%, 34/51). The IGFBP-rP1 expression was significantly difference between breast cancer subjects with and without T2DM (p<0.001). There was no significant association of IGFBP-rP1 expression with data on the demographic and clinicopathological profiles of patients with breast cancer. Meanwhile, positive IGFBP-rP1 expression was evident in 44 out of 108 (40.74%) ovarian cancer cases. Among these cases, 36 were T2DM. In contrast to breast cancer cases, IGFBP-rP1 was mostly expressed among ovarian cancer patients with T2DM (66.7%, 24/36, p < 0.001). However, the -positive expression was not significantly associated with any sociodemographic and clinicopathological features of ovarian cancers. Conclusions: Majority of breast cancer patients with T2DM did not express IGFBP-rP1. In contrast, majority of the ovarian cancer patients with T2DM expressed IGFBP-rP1.

Study on Genetic Polymorphism of IGFBP-3 Gene in Egyptian Buffalo

Aim: The present work was carried out to study the genetic characteristics of the IGFBP-3 gene in buffaloes reared in Egypt, where it is considered as one of the important molecular markers for productivity traits like growth and immunity in livestock species. One-hundred animals were used in this research work. Methods: The studied gene was amplified through polymerase chain reaction technique. Afterwards, the amplified fragment at 651-bp was digested with three different endonucleases; HaeIII, MspI, and TaqI. The genetic character of the IGFBP-3 gene was studied by using PCR-RFLP and nucleotide sequencing. Results: The PCR products after the digestion with those restriction enzymes revealed that the presence of the following fragments: two fragments at 506- and 145-bp with MspI two fragments at 240- and 411-bp with TaqI; and eight fragments at 199-, 164-, 154-, 56-, 36-, 18-, 16- and 8-bp with HaeIII. The restriction digestion of the amplified fragments of the IGFBP-3 gene did not show a genetic polymorphism or nucleotide substitution where all restricted fragments yielded from the digestion with three restriction enzymes were of the same sizes. Conclusion: Our findings indicated that the absence of the genetic polymorphism of the IGFBP-3 gene in Egyptian buffalo. Based on our results in addition to the significant effect of this gene on different productivity traits, the crossing between Egyptian buffalo with other breeds, particularly the Italian breed, is needed for more improvements of Egyptian buffalo's productivity where the Italian buffaloes characterized by high growth and fertility phenomena.

Effects of aerobic exercise plus diet control on serum levels of total IGF-1 and IGF-1 binding protein-3 in female obese youths and adolescents / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects of 4-week moderate aerobic exercise plus diet control on serum levels of total insulin-like growth factor 1(IGF-1) and IGF-1 binding protein-3 (IGFBP-3) as well as IGF-1 activity (reflected by molar ratio of IGF-1/IGFBP-3) in female obese adolescents and youths, and their possible role on fat loss, and improvement of glucose and lipid metabolism.@*METHODS@#Nine female obese youths (age:18~19 y) and 30 female obese adolescents (age:14~16 y) were recruited and undertook 4-week aerobic exercise such as swimming and jogging (6 days/week, twice a day, 2 h/time with 5 min rest per 30 min exercise) with gradual increase of intensity from low (heart rate immediately post-exercise of 1st week:100~120 beats/min) to moderate (heart rate immediately post-exercise of 2-4 weeks:120~140 beats/min) level, combined with a diet intervention (total daily energy intake of 1 400 or 1 600 kcal according to basal metabolism rate) in Shanghai Dianfeng weight loss enclosed camp. Nine normal weight young women and 9 female children matched at age and nationality were recruited as the normal control. Before and after the experimental period, anthropometric index (body weight, body mass index(BMI) and waist circumference), glucose and lipid metabolism parameters including fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride (TG); total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein (HDL), and serum levels of total IGF-1 and IGFBP-3 were measured, and IGF-1 activity was calculated in the obese and normal control female adolescents.@*RESULTS@#①Compared with normal control, the serum levels of total IGF-1 and IGFBP-3 were decreased in the female obese youths and adolescents, and IGF-1 activity was reduced only in the obese female adolescents. ②The serum level of IGFBP-3 was down-regulated and IGF-1 activity was up-regulated while no change of serum total IGF-1 was induced by 4-week moderate aerobic exercise plus diet control, accompanied with significant decreases of body weight, BMI and waist circumference as well as improvement of glucose and lipid metabolism in the female obese youths and adolescents. Except for a positive association between the increased IGF-1 activity and the decreased waist circumference was found in the female obese youths by Pearson's correlation analysis, there was no relation of the decreased IGFBP-3, the increased IGF-1 activity with the improvements of anthropometric index and glucose and lipid metabolism in female obese youths and adolescents.@*CONCLUSIONS@#The serum level of IGFBP-3 was down-regulated and the IGF-1 activity was up-regulated by 4-week moderate aerobic exercise plus diet control in female obese youths and adolescents. The increase of IGF-1 activity might be associated with the exercise-plus-diet-induced decrease of waist circumstance in female obese youths.

Study on relationship between IGFBP-5/p53 axis and anti-proliferation effect of tetrandrine in MCF-7 cells / 中国药理学通报

Aim To study the effect of tetrandrine ( Tet ) on proliferation of MCF-7 breast cancer cells and the possible mechanism underlying this biological process. Methods CCK-8, flow cytometric and Western blot were introduced to analyze the effect of Tet on proliferation and apoptosis in MCF-7 cells.Re-al-time PCR and/or Western blot assay were employed to detect the effect of Tet on expression of IGFBP-5 , p53 and MDM2.CCK-8 and recombinant adenovirus were utilized to determine the effect of IGFBP-5 on the proliferation inhibitory effect of Tet .Western blot assay was introduced to evaluate the effect of IGFBP-5 on p53 which was induced by Tet .Results Tet inhibited the proliferation , arrested cell cycle at G 1 phase and decreased the expression of PCNA concentration dependently in MCF-7 cells.Meanwhile, Tet increased the percentage of apoptotic cells , the level of Bad and reduced the level of Bcl-2.Tet increased the expres-sion of IGFBP-5 either mRNA or protein , over-expres-sion of IGFBP-5 enhanced the anti-proliferation activity of Tet in MCF-7 cells, but knockdown of IGFBP-5 at-tenuated this effect of Tet .Tet increased the level of p53 and decreased that of MDM2, and exogenous IG-FBP-5 enhanced the effect of Tet on p53 and MDM2, respectively .Conclusion Tet can inhibit the prolifer-ation of MCF-7 cells, and this activity is partly media-ted by increasing the function of p 53 signal , which may be triggered by the Tet-induced IGFBP-5.

Human umbilical cord blood mesenchymal stem cells engineered to overexpress growth factors accelerate outcomes in hair growth

Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) are used in tissue repair and regeneration; however, the mechanisms involved are not well understood. We investigated the hair growth-promoting effects of hUCB-MSCs treatment to determine whether hUCB-MSCs enhance the promotion of hair growth. Furthermore, we attempted to identify the factors responsible for hair growth. The effects of hUCB-MSCs on hair growth were investigated in vivo, and hUCB-MSCs advanced anagen onset and hair follicle neogeneration. We found that hUCB-MSCs co-culture increased the viability and up-regulated hair induction-related proteins of human dermal papilla cells (hDPCs) in vitro. A growth factor antibody array revealed that secretory factors from hUCB-MSCs are related to hair growth. Insulin-like growth factor binding protein-1 (IGFBP-1) and vascular endothelial growth factor (VEGF) were increased in co-culture medium. Finally, we found that IGFBP-1, through the co-localization of an IGF-1 and IGFBP-1, had positive effects on cell viability; VEGF secretion; expression of alkaline phosphatase (ALP), CD133, and β-catenin; and formation of hDPCs 3D spheroids. Taken together, these data suggest that hUCB-MSCs promote hair growth via a paracrine mechanism.

Reduction of venous pressure during the resection of liver metastases compromises enteric blood flow: IGFBP-1 as a novel biomarker of intestinal barrier injury

OBJECTIVES: Disruption of the intestinal barrier and bacterial translocation commonly occur when intestinal blood flow is compromised. The aim of this study was to determine whether liver resection induces intestinal damage. METHODS: We investigated intestinal fatty-acid binding protein and insulin-like growth factor binding protein levels in the plasma of patients who underwent liver resection. RESULTS: We show that liver resection is associated with significant intestinal barrier injury, even if the Pringle maneuver is not performed. CONCLUSION: We propose the use of insulin-like growth factor binding protein-1 as a novel biomarker of intestinal damage in such situations.

The expression and significance of IGFBP-3 in salivary gland pleomorphic adenoma / 实用口腔医学杂志

Objective:To investigate the expression of insulin-like growth factor binding protein 3 (IGFBP-3) in salivary pleomorphic adenoma(SPA).Methods:The expression of IGFBP-3 protein in 40 cases of SPA(group SPA),40 of normal glandular tissue(group N) and 10 of salivary gland malignant tumor(group CA) was detected by Western blot.The expression of IGFBP-3 mRNA in 50 cases of SPA,50 of salivary gland normal tissue and 10 of CA was detected by qRT-PCR.Results:The expression(A value) of IGFBP-3 protein in group N,SPA and CA was 8.54 ± 3.95,4.78 ± 2.07,3.63 ± 2.27 respectively.The expression ration of IGFBP-3 mRNA of group N vs SPA or CA,P ＜ 0.05;SPA vs CA,P ＞ 0.05 (SPA/N was 0.654 ± 0.387,CA/N:0.452 ± 0.229) respectively,but showed no significance difference between SPA and the CA groups(P ＞ 0.05).Difference of IGFBP-3 mRNA expression was observed with different envelope infiltration of SPA (P ＜ 0.05),no significant difference was observed in different age,gender or relapse groups.Conclusion:IGFBP-3 Low expression of IGFBP-3 in pleomorphic adenomas may reduce the antagonism of IGF-1R,causing the proliferation of tumor cells and promote tumor formation.

Effects of IGFBP2 and IGFBP3 expression in ovarian tumors on migration, invasion of ovarian cancer / 中国比较医学杂志

Objective To study the effect on ovarian tumor migration invasion after inhibition the expression of IGFBP2, IGFBP3.Methods siRAN interference IGFBP2, IGFBP3 expression in ovarian cancer cell lines SKOV3, SKOV3 proliferation detected by CCK-8 kits,SKOV3 apoptosis detected by flow cytometry ,SKOV3 migration and invasion detected by transwell experiment and scratched cell healing detection; CCK-8 method detected survival after treated different concentrations of cisplatin (5, 10, 15, 20 ug/mL).Results The proliferation ability of SKOV3 dropped and apoptosis increased after treated siRAN IGFBP 2, IGFBP3 compared with the control group , migration and invasion function decline, resistance level to improve greatly.Conclusions The expression of IGFBP2, IGFBP3 in ovarian cancer affected migration and invasion .

Insulin-like Growth Factor Binding Protein-1/ alpha-fetoprotein versus Placental alpha microglobulin-1 for diagnosis of premature fetal membranes rupture.

Objectives: To compare insulin-like growth factor binding protein-1/alpha-fetoprotein (IGFBP-1/AFP) to placental alpha microglobulin-1 (PAMG-1) for diagnosis of premature fetal membranes rupture (PROM). Methods: 220 pregnant women ≥ 37 and < 39 weeks` gestation studied and classified into two groups; study group (PROM) and control group (no PROM). Examination of the studied women followed by abdominal ultrasound (TAS) and sterile vaginal speculum examination to visualize amniotic fluid leaking and for collection of samples for fern, nitrazine, AmniSure® and AmnioQuick® Duo+ tests on admission. Results: The sensitivity and specificity of AmnioQuick® Duo+ test to detect PROM was 93.6% and 86.4%; respectively compared to 95.5% and 89.1%; respectively for AmniSure® test, 72.7% and 80.9%; respectively for fern test and 76.4% and 83.6%; respectively for nitrazine test. PPV, NPV and accuracy of AmnioQuick® Duo+ test to detect PROM were 87.3%, 93.1% and 90%; respectively compared to 89.7, 95.1% and 92.3%; respectively for AmniSure® test, 79.2%, 74.8% and 76.8%; respectively for fern test and 82.4%, 77.97% and 80%; respectively for nitrazine test. AmnioQuick® Duo+ and AmniSure® tests had higher sensitivity, specificity, predictive values and accuracy to detect PROM compared to conventional diagnostic tests. Conclusion: AmnioQuick® Duo+ test for detection of IGFBP-1/AFP was rapid, accurate bedside test better than the individual conventional diagnostic tests and has same accuracy and performance like AmniSure® test.

Study on IGF-1 and IGFBP-3 gene expression in liver of young rats with intermittent hypoxia / 临床耳鼻咽喉头颈外科杂志

Objective:Using the model of young rats with intermittent hypoxia, to study the expression of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in liver, and to provide objective evidence for the possible existence of growth retardation in children with OSAHS. Method:Divided 24 rats randomly into three groups, as control group and the mild and severe hypoxia group. Normally fed control group, without treatment, the other two groups were kept in the cabin has been simulated mild and severe intermittent hypoxia conditions of OSAHS in children. 8-hour day cycle of intermittent hypoxia, a total of 35 days. To the last day, animals were sacrificed and fresh liver tissues were fixed in liquid nitrogen, stored in the -80°C refrigerator, then took the molecular biology experiment of IGF-1 and IGFBP-3 in the liver. Result:The expression of IGF-1 mRNA in liver, semi-quantitative analysis showed that the difference of mRNA expression of IGF-1 among the three groups was statistically significant (P<0.05), pairwise comparison, mild hypoxia group was higher than control and severe group, there were significant differences (P<0.05), the control group and severe hypoxia had no significant difference (P>0.05). The expression of IGFBP-3 mRNA in liver showed that, differences between the three groups was not significant (P>0.05). IGF-1 expression in liver tissue analysis showed that, differences between the three groups was statistically significant (P<0.05), pairwise comparisons, its expression in the control group was lower than mild hypoxia group and severe group, there were significant differences (P<0.05), mild hypoxia and severe hypoxia group had no significant difference (P>0.05). IGFBP-3 expression in liver tissue analysis showed that, differences between the three groups was statistically significant (P<0.05), pairwise comparisons, the control group was higher than mild and severe hypoxic group, there were significant differences (P<0.05), mild hypoxia and severe hypoxia group had no significant difference (P>0.05). Conclusion:IGF-1 and IGFBP-3 in the liver of mild hypoxia group, severe hypoxic group and control group showed that their transcription levels and the severity of hypoxia had no significant correlation.

Effect of IGFBP7 overexpression on proliferation of human hepatocellular carcinoma HepG2 cells / 中国医师杂志

Objective To present study was to investigate the effects of insulin-like growth factor binding protein 7 (IGFBP7)on the proliferation of human hepatocellular carcinoma HepG2 cells.Methods Human hepatocellular carcinoma HepG2 cells was cultured,and plasmid pIRES2-ZsGreen1-IGFBP7 or empty plasmid was transfected into HepG2 cells and the cell transfection efficiency was examined by fluores-cence microscopy;MTT was performed to evaluate the effect of IGFBP7 on proliferation and apoptosis of HepG2 cells in 48 hours after transfection.Results IGFBP7 transfected group decreased cell proliferation noticeably.Conclusions Overexpression of IGFBP7 can down-regulte the proliferation of human hepatocel-lular carcinoma HepG2 cells.

A 20-week program of resistance or concurrent exercise improves symptoms of schizophrenia: results of a blind, randomized controlled trial

Objective: To evaluate the effects of 20 weeks of resistance and concurrent training on psychotic and depressive symptoms, quality of life outcomes, and serum IGF-1, IGFBP-3, and brain-derived neurotrophic factor (BDNF) concentrations in patients with schizophrenia. Methods: In this blind, randomized controlled clinical trial, 34 patients with schizophrenia were assigned to one of three groups: control (CTRL, n=13), resistance exercise (RESEX, n=12), or concurrent exercise (CONCEX, n=9). Symptoms, quality of life, strength, and other variables were assessed. Results: A significant time-by-group interaction was found for the RESEX and CONCEX groups on the Positive and Negative Syndrome Scale (PANSS) total score for disease symptoms (p = 0.007), positive symptoms (p = 0.003), and on the arm extension one-repetition maximum (1RM) test (p = 0.016). In addition, significant improvements on negative symptoms (p = 0.027), on the role-physical domain of the Short Form-36 Health Survey (p = 0.019), and on the chest press 1RM test (p = 0.040) were observed in the RESEX group. No changes were observed for the other variables investigated. Conclusions: In this sample of patients with schizophrenia, 20 weeks of resistance or concurrent exercise program improved disease symptoms, strength, and quality of life. ClinicalTrials.gov: NCT01674543.

PPARγ induces growth inhibition and apoptosis through upregulation of insulin-like growth factor-binding protein-3 in gastric cancer cells

Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.

Relationship between cisplatin resistance of primary lung cancer and expression levels of ERCC1 and IGFBP5 in patient-derived tumor xenograft models / 中国肿瘤临床

Objective:To establish a lung cancer model of patient-derived tumor xenografts (PDTX) and to explore the relation-ship between primary cisplatin resistance and ERCC1 and IGFBP5 expression levels. Methods:Lung cancer tissues from 84 patients who underwent surgery were collected and implanted into nude mice. Patient characteristics for the first generation xenografts that were and were not engrafted were compared. Passage 3 xenografts were treated with cisplatin. The expression levels of ERCC1 and IGFBP5 in cisplatin-resistant and cisplatin-sensitive groups were detected using immunohistochemistry assay. Results:The model success rates were 32.14%(27/84) in first-generation xenografts, 88.89%(24/27) in second-generation xenografts, and 95.83%(23/24) in third-gener-ation xenografts. The tumorigenicity of first-generation xenografts was correlated with size, differentiation, clinical stage, and histologi-cal type. PDTX tumors maintain the histological type of parental tumors through serial passage in nude mice. ERCC1 expression level was significantly higher in the cisplatin-resistant group than in the cisplatin-sensitive group, whereas the IGFBP5 expression level was lower in the cisplatin-resistant group than in the cisplatin-sensitive group. Conclusion:Lung cancer PDTX models were successfully es-tablished, and histological characteristics of the primary cancers were retained. Therefore, the models may serve a function in preclini-cal research of lung tumor biology and for exploring the drug resistance mechanism of tumors. The cisplatin resistance of primary lung cancer may be correlated with the expression level of ERCC1 and IGFBP5 in lung carcinoma.