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We investigated circular RNA (circRNA) expression pattern from a rat intracerebral hemorrhage (ICH) model and tested therapeutic strategy. Hemorrhagic stroke was induced by stereotactic collagenase injection. Brain was harvested at 1, 3, and 7 days after ICH induction to study circRNA expression. Significantly altered circRNAs from microarray were examined by quantitative real-time polymerase chain reaction. Predicted target microRNA and nearby messenger RNA levels of significantly altered circRNAs were validated from previously published database. Therapeutic strategy based on potential target microRNA of significantly depressed circRNA was examined using in vitro and in vivo hemorrhagic model. Both significantly elevated/downregulated circRNA increased as time passed after ICH: 9, 159, and 704 circRNAs were significantly elevated, whereas 19, 276, and 656 circRNAs were significantly depressed at 1, 3 and 7 days after ICH induction, respectively, out of 13,298 studied circRNAs. The most elevated circRNAs were rno_circRNA_002714 and rno_circRNA_002715, which are located closely each other in chromosome 10, within exon sequence of glial fibrillary acidic protein. The most significantly downregulated circRNA was rno_circRNA_016465, which has several complementary sequences for miR-466b. The most commonly predicted microRNA response element of significantly depressed circRNAs was miR-466b. The antagonistic sequence against miR-466b significantly decreased neuronal cell death and improved neurological recovery in a hemorrhagic stroke model by upregulating insulin like growth factor receptors 1 and 2. This study illustrated dynamic circRNA expression pattern in a hemorrhagic stroke model, which correlated with microRNA and messenger RNA expression, suggesting the regulatory role of RNA dynamics in ICH. [ABSTRACT FROM AUTHOR]

The adverse effects of heat stress (HS) on the welfare and productivity of cattle are the result of the associated hyperthermia and the physiological and behavioral mechanisms performed by the animal to regulate body temperature. The negative effects of HS on in vitro oocyte maturation and in vitro bovine embryo production have been reported; being one of the major concerns due to economic and productive losses, and several mechanisms have been implemented to reduce its impact. These mechanisms include supplementation of the medium with hormones, adjuvants, identification of protective genes, among others. This review aims to explore the cellular and molecular mechanisms of insulin-like growth factor-1 (IGF-1) during in vitro and in vivo maturation of bovine oocytes and its thermoprotective effect under HS. Although the supplementation of the culture medium during oocyte maturation with IGF-1 has been implemented during the last years, there are still controversial results, however, supplementation with low concentration showed a positive effect on maturation and thermoprotection of oocytes exposed to higher temperatures. Additionally, IGF-1 is involved in multiple cellular pathways, and it may regulate cell apoptosis in cases of HS and protect oocyte competence under in vitro conditions.

Background: The total number of oocytes, oocyte maturation, and oocyte fertilization all significantly affect how successful in vitro fertilization (IVF) is. Additionally, it has been demonstrated that several chemicals in follicular fluid, including cytokines and growth factors, have a major impact on follicular maturation, ovulation, and follicular atresia. One of these molecules, Pregnancy Associated Plasma Protein-A (PAPP-A), a part of the Insulin like Growth Factor (IGF) pathway, has been demonstrated to be generated by granulosa cells and present in follicular fluid. Objective: The aim of this study is to measure the level of Pregnancy Associated Plasma Protein-A (PAPP-A) in Follicular Fluid (FF) of infertile women undergoing ICSI, and to looking into the connections of PAPP-A with some reproductive hormones level. Patients and Methods: The study included infertile women from Al-Wazyria Hospital, Infertility and IVF Center, Baghdad (Iraq), from December 2021 to April 2022. This study was conducted on 45 infertile women who are set to start their ICSI cycle. Results: FF PAPP-A was not significant with hormones level (FSH, LH, E2 and AMH) except PRO hormone was significant. Conclusion: Outcomes show that no relation between studied reproductive hormones and FF PAPP-A level except PRO levels; it was the main cause from the egg to mature and release from the ovary. [ABSTRACT FROM AUTHOR]

Objective: Basal metabolic rate (BMR) is an important factor in weight management and is influenced by fat-free mass (FFM), fat mass (FM) and age. Current knowledge of the influence of hormonal levels on BMR is based on studies with small populations, studies that investigate exogenous administration and studies frequently lacking correction for body composition., Design: Cross-sectional study., Patients: All men (n = 457) who were referred to our centre for a metabolic work-up were eligible for inclusion. Median age was 47 (18-78) years and the vast majority had obesity (BMI ≥ 30 kg/m², 90.9%)., Measurements: All men had a measurement of BMR, body composition and measurement of testosterone, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS), insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone (TSH) and free thyroxine (fT4). Men with low, normal and/or high levels of each of these hormones were compared. The association between hormone levels and BMR was assessed through linear regression models. All analyses were controlled for FFM, FM and age., Results: In men with obesity, testosterone (total or free) was not associated with BMR. Linear regression analysis showed that DHEAS was positively associated with BMR in a sample of men with obesity and normal endogenous DHEAS levels, with the following equation: BMR (adjusted R² = 0.72): (BMR [kcal/d] = 513.402 + 18.940 × FFM [kg] + 9.507 × FM [kg] - 3.362 × age [years] + 0.307 × DHEAS [µg/dL]) (p < 0.01). TSH, fT4 and IGF-1 were not associated with BMR., Conclusion: In men with obesity, endogenous DHEAS is positively associated with BMR. Testosterone, TSH, fT4 and IGF-1 were not associated with BMR in men with obesity. Since we examined the specific population of men with obesity and only examined endogenous hormone levels, no extrapolation of results to other populations or the overall population can be made., (© 2024 John Wiley & Sons Ltd.)

A woman's endocrine system plays a crucial role in orchestrating cellular interactions throughout her life. The growth hormone (GH) and insulin-like growth factor (IGF) system appears to impact crucial reproductive events and cell types of the ovary, such as granulosa cells, theca cells, and oocytes. Further, IGF1 is a cornerstone during embryonic development and influences predominantly developing and pre-antral follicles. In this commentary, we will emphasize the pleiotropic effects of IGF1 on physiological processes inside the egg. Herein, we will provide a brief overview on IGF1 related cell signal transduction pathways during the maturation and aging of oocytes. We aim to elucidate from a molecular and biochemical point of view if IGF1 in women with metabolic imbalances such as obesity or diabetes could be used in clinics as a novel, reliable estimator for the developmental competence of an oocyte. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus complicating pregnancy is one of the most common antenatal complications that are associated with significant perinatal mortality and morbidity. Insulin like growth factor-1 (IGF-1) has been implicated with micro-vascular complications during pregnancy. Glycosylated hemoglobin (HbA1c) is a reliable index, used to evaluate the glycemic control at the last 8 weeks. Aim: To find the relation between the level of insulin like growth factor and HbA1c at different gestational periods of pregnancy in diabetic pregnant women. Methods: The study was carried out on 190 pregnant women. They were 134 pregnant women with abnormal carbohydrate metabolism and 56 healthy pregnant women. Those of abnormal carbohydrate metabolism were also classified into two groups, those with gestational diabetes mellitus (70) and those with pregestational diabetes mellitus (64). IGF-1 and HbA1c levels were measured in the studied pregnant women at the second and third trimesters of pregnancy. Results: IGF-1 concentrations was found to be higher in patients with GDM when compared with those of PGDM and the control groups, in both 2nd and 3rd trimesters with a significant (P

A woman’s endocrine system plays a crucial role in orchestrating cellular interactions throughout her life. The growth hormone (GH) and insulin-like growth factor (IGF) system appears to impact crucial reproductive events and cell types of the ovary, such as granulosa cells, theca cells, and oocytes. Further, IGF1 is a cornerstone during embryonic development and influences predominantly developing and pre-antral follicles. In this commentary, we will emphasize the pleiotropic effects of IGF1 on physiological processes inside the egg. Herein, we will provide a brief overview on IGF1 related cell signal transduction pathways during the maturation and aging of oocytes. We aim to elucidate from a molecular and biochemical point of view if IGF1 in women with metabolic imbalances such as obesity or diabetes could be used in clinics as a novel, reliable estimator for the developmental competence of an oocyte.

Objective: To explore the clinical efficacy of adenosylmethionine combined with albumin in the treatment of neonatal jaundice and its effect on the levels of serum γ-glutamyltransferase and insulin-like growth factor in children. Methods: 203 cases of newborns with neonatal jaundice admitted to our hospital from March 2017 to March 2019 were selected, According to the method of random number table, they were divided into the observation group (n=105) and the control group (n=98). The control group was treated with albumin, while the observation group treated with adenosylmethionine combined with albumin. The therapeutic effect, jaundice regression time and jaundice index, changes of bilirubin indexes, γ-glutamyltransferase, insulin-like growth factor and transferrin level before and after treatment were observed and compared between two groups. Results: After treatment, the total effective rate of observation group was significantly higher than that of the control group [92.38％(97/105) vs. 80.61％(79/98)](P＜0.05). Jaundice regression time and jaundice index were significantly lower than the control group ［(4.15± 0.82) d vs. (5.31± 0.92) d，(56.02± 7.36) μmol/L vs. (82.86± 9.32) μmol/L］(P＜0.05). The levels of indirect bilirubin, conjugated bilirubin and total bilirubin were significantly lower than those of the control group ［(108.75± 6.21) d vs. (146.03± 7.32) d, (7.49± 0.85) μmol/L vs. (9.57± 1.02) μmol/L, (117.80± 6.52) μmol/L vs. (151.09± 8.34) μmol/L］(P＜0.05). γ-glutamyltransferase and insulin-like growth factor were significantly lower than those in the control group［(56.01± 6.45) U/L vs. (89.56± 10.73) U/L, (19.30± 2.17) ng/L vs 26.78± 3.67］ng/L)(P＜0.05). The level of transferrin was significantly higher than that of the control group[(1.96± 0.27)g/L vs. (1.60± 0.24)g/L](P＜0.05). Conclusions: The clinical effect of adenosylmethionine combined with albumin in the treatment of neonatal jaundice is significantly better than that of albumin alone. It can effectively improve the clinical symptoms of jaundice in children, and reduce the levels of serum bilirubin, γ-glutamyltransferase and insulin-like growth factor. [ABSTRACT FROM AUTHOR]

Introduction: Insulin like growth factor-1 (IGF-1) has been found to stimulate follicular development, estrogen and progesterone production and oocyte maturation. This study aims to detect the changes in the follicular fluid IGF-1 levels in normo-ovulatory women undergoing in vitro fertilization (IVF) cycle and evaluate the possibility of IGF-1 to be a predictive marker for IVF outcome in normo-ovulatory women. Materials and methods: This prospective cross-sectional study was performed among 88 IVF normo-ovulatory women who were categorized according to IVF pregnancy outcome (clinical pregnancy) into two groups: 55 pregnant women and 33 non-pregnant women. Follicular fluid IGF-1 levels have been measured at the time of oocyte retrieval by utilizing enzyme linked immune-sorbent assay (IGF-1 ELISA kit, Diametra, Inc, Italy). The relationship between follicular fluid IGF-1 (FF IGF-1) levels and the number of oocytes retrieved, number of mature oocytes, number of embryos, fertilization and clinical pregnancy rate were assessed. The demographic data were similar between two groups as regards age and BMI. Results: FF IGF-1 levels were significantly higher in pregnant women than in non-pregnant women (90.11 ± 44.31 ng/ml, 69.07 ± 30.55 ng/ml) respectively (p

Abstract Background Recent changes in nutrition and lifestyle have provoked an unprecedented increase in the prevalence of obesity and metabolic disorders. Recognition of the adverse effects on health has prompted intense efforts to understand the molecular determinants of insulin sensitivity and dysglycemia. In many respects, actions of insulin-like growth factors (IGFs) mirror those of insulin in metabolic regulation. Unlike insulin, however, the bioactivity of IGFs is regulated by a family of seven high-affinity binding proteins (IGFBPs) which confer temporospatial modulation with implications for metabolic homeostasis. In addition, evidence is accumulating that IGF-independent actions of certain of the IGFBPs can directly modulate insulin sensitivity. Scope of review In this review, we discuss the experimental data indicating a critical role for IGF/IGFBP axis in metabolic regulation. We highlight key discoveries through which IGFBPs have emerged as biomarkers or putative therapeutic targets in obesity and diabetes. Major conclusions Growing evidence suggests that several components of the IGF-IGFBP system could be explored for therapeutic potential in metabolic disorders. Both IGFBP-1 and IGFBP-2 have been favorably linked with insulin sensitivity in humans and preclinical data implicate direct involvement in the molecular regulation of insulin signaling and adiposity respectively. Further studies are warranted to evaluate clinical translation of these findings. [ABSTRACT FROM AUTHOR]

Bone marrow derived mesenchymal stem cells (BMSC) represent an attractive cell population for tissue engineering purpose. The objective of this study was to determine whether the addition of recombinant human bone morphogenetic protein (rhBMP-2) and insulin-like growth factor (IGF-1) to a silica-coated calcium hydroxyapatite (HASi) - rabbit bone marrow derived mesenchymal stem cell (rBMSC) construct promoted bone healing in a large segmental bone defect beyond standard critical -size radial defects (15mm) in rabbits. An extensively large 30mm long radial ostectomy was performed unilaterally in thirty rabbits divided equally in five groups. Defects were filled with a HASi scaffold only (group B); HASi scaffold seeded with rBMSC (group C); HASi scaffold seeded with rBMSC along with rhBMP-2 and IGF-1 in groups D and E respectively. The same number of rBMSC (five million cells) and concentration of growth factors rhBMP-2 (50µg) and IGF-1 (50µg) was again injected at the site of bone defect after 15 days of surgery in their respective groups. An empty defect served as the control group (group A). Radiographically, bone healing was evaluated at 7, 15, 30, 45, 60 and 90 days post implantation. Histological qualitative analysis with microCT (µ-CT), haematoxylin and eosin (H & E) and Masson’s trichrome staining were performed 90 days after implantation. All rhBMP-2-added constructs induced the formation of well-differentiated mineralized woven bone surrounding the HASi scaffolds and bridging bone/implant interfaces as early as eight weeks after surgery. Bone regeneration appeared to develop earlier with the rhBMP-2 constructs than with the IGF-1 added construct. Constructs without any rhBMP-2 or IGF-1 showed osteoconductive properties limited to the bone junctions without bone ingrowths within the implantation site. In conclusion, the addition of rhBMP-2 to a HASi scaffold could promote bone generation in a large critical-size-defect.

Background: Disruption of insulin-like growth factor-I (IGF-I) increases health and life span in animal models, though this is unconfirmed in humans. If IGF-I stability indicates homeostasis, the absolute level of IGF-I may be less clinically relevant than maintaining an IGF-I setpoint.Methods: Participants were 945 U.S. community-dwelling individuals aged ≥65 years enrolled in the Cardiovascular Health Study with IGF-I levels at 3-6 timepoints. We examined the association of baseline IGF-I level, trajectory slope, and variability around the trajectory with mortality.Results: There were 633 deaths over median 11.3 years of follow-up. Lower IGF-I levels, declining or increasing slope, and increasing variability were each individually associated with higher mortality (all p < .001). In an adjusted model including all three trajectory parameters, baseline IGF-I levels <70 ng/mL (hazard ratio [HR] 1.58, 95% CI 1.28-1.96 relative to IGF-I levels of 170 ng/mL), steep declines and steep increases in trajectory slope (HR 2.22, 1.30-3.80 for a 15% decline; HR 1.40, 1.07-1.84 for a 10% decline; HR 1.80, 1.12-2.89 for a 15% increase; HR 1.31, 1.00-1.72 for a 10% increase, each vs no change), and variability ≥10% (HR 1.59, 1.09-2.32 for ≥ 30%; HR 1.36, 1.06-1.75 for 20%; and HR 1.17, 1.03-1.32 for 10% variability, each vs 0%) in IGF-I levels were independently associated with mortality.Conclusions: In contrast to data from animal models, low IGF-I levels are associated with higher mortality in older humans. Irrespective of the actual IGF-I level, older individuals with stability of IGF-I levels have lower mortality than those whose IGF-I levels fluctuate over time. [ABSTRACT FROM AUTHOR]

In today's digital age to feed this ever increasing population there is a high demand for more production of food. To meet this task, artificial hormones are being used to increase the production of milk and meat. In this review, we address the controversial issue of adverse effects of hormones being administered in cattle. Oestradiol, Progesterone, Testosterone, Zeranol, Trenbolone and Melengestrol hormones are approved by U.S. food and drug administration (FDA) for commercial use. These have been found to be used to increase the quantity of milk and meat in cattle but their adverse effects being observed on the consumers as they cause cancer and premature puberty in children. Similarly the utilization of recombinant bovine growth hormone (rBGH) in cattle is seen to be a burning issue as it causes cancer. Here, we present a deeper insight to above mentioned content. [ABSTRACT FROM AUTHOR]

A 60-day feeding trial was conducted to evaluate the effect of deoiled rice bran (DORB) on the growth performance and liver IGF-I and IGF-II mRNA expression in a freshwater fish, Labeo rohita . Six isonitrogenous (30%), isolipidic (6%) and iso-energetic (1.8 MJ/100 g) diets were prepared with different inclusion level of DORB viz., C (control, 0%) , T20 (20%), T30 (30%) , T40 (40%), T50 (50%) and T60 (60%). Three hundred and fifteen (315) fingerlings with 15 fish per tank having an average weight of 8.0 ± 0.5 g were randomly distributed in seven treatments in triplicates following a completely randomized design. At the end of the experiment, growth and nutrient utilization were evaluated in terms of weight gain% (WG %), SGR, FCR, PER, RNA/DNA ratio along with the gene expression of IGF-I and IGF-II. The weight gain % and specific growth rate were similar in 30, 40, 50 and 60% DORB fed groups, but higher ( p < 0.05) than the control and commercial diet fed groups. The PER (Protein Efficiency Ratio), LER (Lipid Efficiency Ratio) and FCR (Feed Conversion Ratio) were similar ( p > 0.05) in 30, 40, 50 and 60% DORB fed groups. The RNA-DNA ratio was significantly lower in T50 group, which was similar to T60 group. Based on second order polynomial regression analysis (y = − 0.008x 2 + 0.5227x + 1.3407, R 2 = 0.91), the expression of IGF-I was found to be maximum at 33% inclusion level. The hepatic IGF-I and IGF-II gene expression were checked using real time PCR normalised against the β-actin gene and found to be maximum at the dietary inclusion level of 33%. Hence, from these results it can be concluded that though growth rate was similar in all the groups fed with DORB at 30 to 60% of inclusion level, but an optimum inclusion level of DORB at 33% is best to support the nutrient utilization and growth performance of Labeo rohita fingerlings based on gene expression of IGFI and IGF II in liver. [ABSTRACT FROM AUTHOR]

This experiment investigated the association between SNP 5 UTR region of insulin -like growth factor-1 ( IGF-1 ) and phenotypic productive and physiological traits in cobb500 broiler breed .The study was conducted at poultry farm in Abu-Graib region during a period from 1Nov 2016-14Dec 2016 .Four hundred fifty broiler chicks one day old (cobb500) were wing -banded and divided to three treatment groups (three replicates each) according to gene polymorphisms .DNA was extracted from fresh blood samples .Restriction fragment length polymorphism was used in the 5 UTR region of IGF-1. Chicks were reared under conventional conditions according the guide and fed ad libitum at the end of experiment number of birds were killed to measure carcass cuts. Results showed a significant (P≤ 0.05) increase in live body weight of TT comparing with TC and CC in 1st week, whereas no significant differences was found between different polymorphisms in weight gain, blood traits and serum components in all weeks .on the other hand a significant (p≤ 0.05) increase was found in final body weight ,carcass weight and length of sternum and thigh bones for TT polymorphism in comparison with TC and CC. [ABSTRACT FROM AUTHOR]

The objectives of this study were 1. to determine the associations among circulating anti-Mullerian hormone (AMH), insulin like growth factor 1 (IGF1) and cadmium (Cd) concentrations of lactating Holstein cows at the time of superovulation and 2. to determine the effect of circulating AMH, IGF1 and Cd concentrations on the superovulatory response in Holstein dairy cows. Holstein cows (n = 30) were milked thrice daily and housed and fed in free stall barn as a separate group. All animals were synchronized for superovulation and flushed. Three blood samples for AMH, IGF1 and Cd analysis were collected prior to superovulation, at estrus and at the time of embryo collection. The concentrations of blood makers prior to superovulation were highly correlated to superovulatory response. Circulating concentrations of AMH, IGF1 prior to superovulation were negatively correlated to Cd concentrations (P < 0.05). There was no correlation between circulating concentrations of AMH and IGF1. The number of corpus luteum (r = 0.71), total embryo (r = 0.67), total transferable embryo (r = 0.51) and total grade 1 embryo (r = 0.5) were positively correlated to AMH concentrations (P < 0.05). There was a trend for negative correlation found between circulating cadmium concentrations and total grade 1 embryo yield (P < 0.1). When cows were classified into quartiles (Q) of circulating AMH concentration, number of corpus luteum, and total embryos, total transferable embryos and total grade 1 embryos yield was significantly different for AMH quartiles. The superovulatory response parameters evaluated were increased with increased AMH concentrations; particularly we observed a >2-fold difference between first and fourth AMH quartiles in total transferable embryo yield and total grade 1 embryo yield. In conclusion, circulating AMH concentration was strongly associated with superovulatory response. Measuring AMH before enrolling cows in superovulation programs will likely allow practitioners to improve numbers of embryos produced and, thereby, reduce costs per embryo produced. [ABSTRACT FROM AUTHOR]

Objective: To study the effects of bailing capsules on levels of follicular fluid bone morphogenetic protein (BMP), growth differentiation factor -9 (GDF) and insulin like growth factor (IGF) ofpatients with polycystic ovary syndrome Methods: 90 patients with polycystic ovary syndrome who had received therapy from July 2013 to July 2016 in our hospital were selected and randomly divided into the observation group (n=45) and the control group (n=45). The patients in the control group were treated with Diane -35, while the patients in the observation group were treated with bailing capsules on the basis of the control group. Then the levels of glucose metabolism index, endocrine index, BMP-15, GDF-9 and IGF-1 and clinical curative effect between the two groups were observed and compared before and after the treatment. Results: After treatment, the levels of fasting blood glucose (FBG), fasting insulin (FINS) and insulin resistance (HOMA-IR) in the observation group were lower than those of the control group (P< 0.05); the levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) in the observation group were lower than those of the control group (P< 0.05); the levels ofBMP-15 and GDF-9 in the observation group were higher than those of the control group, and the levels ofIGF-1 was lower than that of the control group (P< 0.05); the total effective rate of the observation group was higher than that of the control group (P < 0.05) Conclusion: Bailing capsules was effective for polycystic ovary syndrome, which could effectively regulate the endocrine and improve the expression ofBMP-15, GDF-9 and IGF-1 in the follicular fluid. [ABSTRACT FROM AUTHOR]

Introduction: Insulin like growth factor-1 (IGF-1) has been found to stimulate follicular development, estrogen and progesterone production and oocyte maturation. This study aims to detect the changes in the follicular fluid IGF-1 levels in normo-ovulatory women undergoing in vitro fertilization (IVF) cycle and evaluate the possibility of IGF-1 to be a predictive marker for IVF outcome in normo-ovulatory women. Materials and methods: This prospective cross-sectional study was performed among 88 IVF normoovulatory women who were categorized according to IVF pregnancy outcome (clinical pregnancy) into two groups: 55 pregnant women and 33 non-pregnant women. Follicular fluid IGF-1 levels have been measured at the time of oocyte retrieval by utilizing enzyme linked immune-sorbent assay (IGF-1 ELISA kit, Diametra, Inc, Italy). The relationship between follicular fluid IGF-1 (FF IGF-1) levels and the number of oocytes retrieved, number of mature oocytes, number of embryos, fertilization and clinical pregnancy rate were assessed. The demographic data were similar between two groups as regards age and BMI. Results: FF IGF-1 levels were significantly higher in pregnant women than in non-pregnant women (90.11 ± 44.31 ng/ml, 69.07 ± 30.55 ng/ml) respectively (p < 0.05). There is no significantly correlation between FF IGF-1 levels and any IVF outcomes (retrieved oocyte number, mature oocyte number, fertilized oocyte number, embryos number, percent of mature oocytes, cleavage rate and fertilization rate). In addition to that there is no difference in terms of age and body mass index (BMI). Conclusion: Our study demonstrated that higher FF IGF-1 levels predict higher pregnancy rates in normoovulatory women undergoing IVF cycles. [ABSTRACT FROM AUTHOR]

Background Insulin and insulin like growth factor-1 (IGF-1) have growth promoting effects, while insulin like growth factor binding protein-3 (IGFBP-3) has growth inhibitory effects. The present study was designed to assess the concentrations of insulin, IGF-1, IGFBP-3 and their association with prostate size in patients with BPH. Methods Ninety 90 BPH cases and 90 controls were enrolled in the study. Insulin, IGF-1, IGFBP-3, PSA, testosterone and estradiol were estimated in both the groups. Results Insulin, IGF-1 and estradiol were increased and IGFBP-3/PSA was decreased in BPH cases when compared with controls. Insulin (r = 0.64, p = 0.001) and IGF-1 (r = 0.22, p = 0.03) were positively correlated and IGFBP-3/PSA (r = − 0.316, p = 0.002) were negatively correlated with prostate size in BPH. Multivariate analysis showed that insulin (p = 0.001) and IGFBP-3/PSA (p = 0.004) predicts the prostate size in patients with BPH. Insulin was increased and IGFBP-3/PSA was reduced in BPH patients with increased prostate size. At a cutoff concentration of 527.52, IGFBP-3/PSA ratio was found to differentiate benign growth of prostate from normal prostate with 96% sensitivity and 96% specificity. Conclusion Insulin is elevated and IGFBP-3/PSA is reduced with increase prostate size in BPH cases. [ABSTRACT FROM AUTHOR]

Background Alveolar epithelial cell injury has been proposed as a causative factor for the onset and progression of pulmonary fibrosis. However, the role of type II alveolar epithelial cells (AECs) in the epithelial mesenchymal transition (EMT) is controversial. Aims The present study performed in rats instilled with bleomycin investigated a) the expressions of the insulin growth factor (IGF-1) and insulin growth factor binding protein 5 (IGFBP-5) and transforming growth factor (TGF-β1) in the type II AECs, b) the role of type II AECs in EMT and extracellular matrix (ECM) formation and, c) the effect of pioglitazone on all the above parameters. Methods Male Wistar rats were divided into three Groups: Group I (saline control), Group II (Bleomycin, given as a single intratracheal instillation, 7 U/kg) and Group III (Bleomycin + Pioglitazone (40 mg/kg/day orally, starting 7 days post bleomycin instilled as in Group II). From lung tissues, the protein expressions of IGF-1, IGFBP-5, TGF-β1, surfactant protein C (SP-C, as a marker for type II AECs) and α-smooth muscle actin (α-SMA, as a marker for EMT), were determined on day 7 in Groups I and II and on days 14, 21 and 35 in all the three groups. Results IGFBP-5 and IGF-1 expressions were reduced significantly and TGF-β1 expression increased significantly in type II AECs in Group II from day 7 till day 35 as compared to Group I. An increase in SP-C and α-SMA expression and their co-localization were seen in the type II AECs undergoing EMT from day 7 till day 35. A concomitant remodeling and laying down of ECM was observed also. In Group III, with pioglitazone, there was a reversal with significant up-regulation in IGFBP-5 and IGF-1 expressions and down-regulation of TGF-β1 in the type II AECs along with a significant decrease in the solid area fraction, EMT and ECM in the lung tissue. Conclusions IGFBP-5, IGF-1 and TGF-β1 in the type II AECs play a key role in lung injury caused by bleomycin and pioglitazone attenuates the lung injury/fibrosis by restoring IGFBP-5 and IGF-1 and decreasing TGF-β1 expressions in the type II AECs. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus complicating pregnancy is one of the most common antenatal complications that are associated with significant perinatal mortality and morbidity. Insulin like growth factor-1 (IGF-1) has been implicated with micro-vascular complications during pregnancy. Glycosylated hemoglobin (HbA1c) is a reliable index, used to evaluate the glycemic control at the last 8 weeks. Aim: To find the relation between the level of insulin like growth factor and HbA1c at different gestational periods of pregnancy in diabetic pregnant women. Methods: The study was carried out on 190 pregnant women. They were 134 pregnant women with abnormal carbohydrate metabolism and 56 healthy pregnant women. Those of abnormal carbohydrate metabolism were also classified into two groups, those with gestational diabetes mellitus (70) and those with pregestational diabetes mellitus (64). IGF-1 and HbA1c levels were measured in the studied pregnant women at the second and third trimesters of pregnancy. Results: IGF-1 concentrations was found to be higher in patients with GDM when compared with those of PGDM and the control groups, in both 2nd and 3rd trimesters with a significant (P <0.001) difference among subgroups. HbA1c concentrations were found to be significantly (P< 0.001) higher in pregnant women with GDM and PGDM than in the control group. There was a significant (r=0.27, P<0.001) weak correlation between IGF-1 and HbA1c in both 2nd and 3rd trimesters. Conclusion: Both, IGF-1 and HbA1c levels elevate in pregnant women with GDM and PGDM, such rise is manifested by a weak positive correlation between the concentrations of the two parameters. Recommendation: It is useful to study the role of IGF-1 therapy in pregnant with diabetes mellitus especially those with vasculopathy. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the association between serum sex hormone levels and lower urinary tract symptoms in men. Material and Method: Forty-nine men with lower urinary tract symptoms aged 25-45 years (mean: 37.9±2.0 years) and 25 healthy men aged 25-45 years (mean: 35.9±2.0 years) as controls participated in this study. Estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone, dehydroepiandrosterone sulfate, insulin-like growth factor-binding protein 3 (IGFBP3), insulin-like growth factor -1 (IGF1), and sex hormone-binding globulin levels were measured using commercially available assay kits. All participants were asked to complete the International Prostate Symptom Score questionnaire. Results: Demographic data were similar belween patients and controls. Among the sex steroids studied, only FSH and E2 showed a statistically significant association with lower urinary tract symptoms (p<0.05). Besides, neither IGF1 nor IGFBP3 were associated with lower urinary tract symptoms. Discussion: Excess E2 may play an important role in the occurrence of lower urinary tract symptoms. E2 receptors located in the prostate tissue may take part in the development of benign prostatic hyperplasia. [ABSTRACT FROM AUTHOR]

Objective: To illustrate an unusual mechanism causing hypoglycaemia. Material and methods: A 76-year-old man presented with episodes of agitation and confusion and was resuscitated with oral glucose gel when found to be hypoglycaemic. Results: A CT scan for an abdominal mass confirmed a solitary fibrous tumour (SFT). The sarcoma multidisciplinary team suggested conservative management. The patient's episodic hypoglycaemia was managed with diet modification including corn-based starch, scheduled snacks and dexamethasone. Glucose levels were within normal range at discharge from hospital. The patient was referred to the palliative care team for follow-up. Conclusion: SFTs causing non-islet cell tumour hypoglycaemia are difficult to treat.

The adverse effects of heat stress (HS) on the welfare and productivity of cattle are the result of the associated hyperthermia and the physiological and behavioral mechanisms performed by the animal to regulate body temperature. The negative effects of HS on in vitro oocyte maturation and in vitro bovine embryo production have been reported; being one of the major concerns due to economic and productive losses, and several mechanisms have been implemented to reduce its impact. These mechanisms include supplementation of the medium with hormones, adjuvants, identification of protective genes, among others. This review aims to explore the cellular and molecular mechanisms of insulin-like growth factor-1 (IGF-1) during in vitro and in vivo maturation of bovine oocytes and its thermoprotective effect under HS. Although the supplementation of the culture medium during oocyte maturation with IGF-1 has been implemented during the last years, there are still controversial results, however, supplementation with low concentration showed a positive effect on maturation and thermoprotection of oocytes exposed to higher temperatures. Additionally, IGF-1 is involved in multiple cellular pathways, and it may regulate cell apoptosis in cases of HS and protect oocyte competence under in vitro conditions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

IGFBP-6 binds IGF-II with higher affinity than IGF-I and it is a relatively specific inhibitor of IGF-II actions. More recently, IGFBP-6 has also been reported to have IGF-independent effects on cell proliferation, survival, differentiation and migration. IGFBP-6 binds to several ligands in the extracellular space, cytoplasm and nucleus. These interactions, together with activation of distinct intracellular signaling pathways, may contribute to its IGF-independent actions; for example, IGF-independent migration induced by IGFBP-6 involves interaction with prohibitin-2 and activation of MAP kinase pathways. A major challenge for the future is delineating the relative roles of the IGF-dependent and –independent actions of IGFBP-6, which may lead to the development of therapeutic approaches for diseases including cancer. [ABSTRACT FROM AUTHOR]

A growth hormone (GH) dependent substance responsible for sulfate uptake by costal cartilage of hypophysectomized rats, labeled sulfation factor, was reported in 1957. In 1962 the radioimmunoassay for GH was described. The clinical picture of severe GH deficiency but with high serum concentrations of GH was reported in 3 siblings in 1966 and followed by a 1968 report of 22 patients belonging to 14 consanguineous oriental Jewish families in Israel. Defective sulfation factor generation was demonstrated in 15 of these individuals and in a 1971 report; FFA response to IV GH and growth response to GH injections suggested competitive saturation of peripheral tissue receptors by an abnormal GH. However, studies published in 1973 demonstrated normal fractionation of their circulating GH, and normal binding of GH from 22 patients to various antisera used for radioimmunoassay. In 1976, the Israeli investigators reported that circulating GH from 7 patients reacted normally in the recently developed radioreceptor assay for GH. In 1984, using hepatic microsome pellets, they demonstrated that the defect was a failure of GH binding to receptors. Characterization of the human GH receptor (GHR) gene, reported in 1989, included the initial description of a genetic defect of the GHR in 2 of 9 Israeli patients. At about the same time began the identification in Ecuador of what was to become the largest population of GH insensitivity in the world, ~ 100 individuals, and the only substantial population with a common mutation of the GH receptor. Treatment studies with recombinant IGF-I began in 1990. Growth response was modest compared to that of GH treated GH deficient subjects. The spectrum of GH insensitivity has expanded beyond GH receptor deficiency to include postreceptor abnormalities: IGF-I gene mutation (1996); IGF-I receptor mutation (2003); signal transducer and activator of transcription 5b mutation (2003); and mutation of the GH-dependent acid labile subunit (2004). Conclusion Rare conditions of GH insensitivity caused by GH receptor and postreceptor abnormalities have provided insights into the processes of growth, body composition, and metabolism. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to assess retinal vascular characteristics of patients with Laron syndrome (LS) as a genetic model of IGF-I deficiency before and after rhIGF1/IGFBP3 treatment and to compare them with healthy controls. Methods: A total of 28 subjects (11 LS, and 17 controls) were enrolled. Patients with LS received combined rhIGF1/rhIGFBP3 1–2 mg/kg/d in a single dose and digital fundus imaging was performed. The number of branching points and tortuosity of retinal vessels were studied. Pre- and post-treatment findings were compared with each other and with controls. Results: The number of branching points was significantly lower in patients with LS in comparison to controls (12.73 ± 3.41, and 17.47 ± 5.82 respectively,p = 0.012). This difference persisted after treatment (12.09 ± 2.66 post-treatment LS versus controls,p = 0.017). Tortuosity indices of nasal arteries (NA) were significantly less in LS than that of controls (upper NA 1.07 ± 0.04 and 1.12 ± 0.06 respectivelyp = 0.022; lower NA 1.07 ± 0.03 and 1.13 ± 0.07 respectively,p = 0.004). This difference also persisted following treatment (p < 0.05). Remaining vessels did not differ in tortuosity index. There was no significant difference of tortuosity index and number of branching points before and after treatment in patients with LS. Conclusion: Retinal vascular development may be adversely affected in the setting of severe IGF-I deficiency confirming a major role for GH/IGF-I axis during retinal vascular development in humans antenatally. Resolution of IGF-I deficiency following birth using rhIGF1, however, may not reverse these changes, suggesting that IGF-I may be necessary but insufficient by itself for postnatal angiogenesis. [ABSTRACT FROM PUBLISHER]

Objective: The neuroprotective effect of insulin like growth factor (IGF-1) and its positive efficacy at prognosis of patients with acute cerebrovascular diseases (CVD) have been defined recently. Therefore, in our study, we aimed to investigate the relationship between IGF-1 and the severity of CVD, subgroups of CVD, and risk factors of CVD. Material and Method: One hundred and five consecutive ischemic CVD patients were enrolled to the study. National Institute of Health Stroke (NIHS) Scale were performed to the patients at their T' and 15th days of hospitalizations. Risk factors of patients were recorded. Patients were grouped according to CVD subgroups. The relationship between IGF-1 levels and the NIHS scale, subgroups of CVD, and risk factors of CVD were investigated. Results: There was a weak reverse correlation between IGF-1 level and NIHS scale. Amongs risk factors; atrial fibrillation (AF) group had the lowest level of IGF-1. Conclusion: Patients withAF had the lowest level of IGF- 1 when compared to the levels of IGF-1 of other risk factors. [ABSTRACT FROM AUTHOR]

IGFBP-6 is an O-linked glycoprotein that preferentially binds IGF-II over IGF-I. It is a relatively selective inhibitor of IGF-II actions including proliferation, survival and differentiation of a wide range of cells. IGFBP-6 has recently been shown to have a number of IGF-independent actions, including promotion of apoptosis in some cells and inhibition of angiogenesis. IGFBP-6 also induces migration of tumour cells including rhabdomyosarcomas by an IGF-independent mechanism. This chemotactic effect is mediated by MAP kinases. IGFBP-6 binds to prohibitin-2 on the cell surface and the latter is required for IGFBP-6-induced migration by a mechanism that is independent of MAP kinases. IGFBP-6 may enter the nucleus and modulate cell survival and differentiation. IGFBP-6 expression is decreased in a number of cancer cells and it has been postulated to act as a tumour suppressor. IGFBP-6 expression is increased in a smaller number of cancers, which may reflect a compensatory mechanism to control IGF-II actions or IGF-independent actions. The relative balance of IGF-dependent and IGF-independent actions of IGFBP-6 in vivo together with the related question regarding the roles of IGFBP-6 binding to IGF and non-IGF ligands are keys to understanding the physiological role of this protein. [ABSTRACT FROM AUTHOR]

Growth hormone (GH) deficiency in children manifests as short stature but is also associated with metabolic disturbances. Paucity of GH is also likely to be associated with increased intima media thickness. Data on body composition (BC) and carotid intima media thickness (cIMT) in children with growth hormone deficiency (GHD) from developing countries are very scarce. Therefore, objectives of present study were to assess effect of 1 year of rhGH therapy on (i) BC and lipid profile (LP) in a cohort of Indian GHD children and (ii) effect on atherosclerotic markers - cIMT in subsample. Anthropometry, BC [% body fat (BF), % lean body mass (LBM), bone mineral content (BMC)] (DXA) and LP were measured in 49 pre-pubertal GHD-children (9.3 ± 3.1 years) at baseline and after 1 year of rhGH therapy. On subset of 20 children, cIMT of right common carotid artery was also measured. Baseline BC parameters were compared with age-gender matched healthy controls ( n = 49). At baseline % BF was 23 ± 9 %, LBM was 9 ± 3 kg and BMC was 0.306 ± 0.15 kg in GHD- children; BF was comparable, while lean and bone were less than controls ( p < 0.05). Post therapy, significant reduction in fat (15%), and cIMT (7%) and increase in LBM and BMC by 40% and 44%, respectively ( p < 0.05) was seen. Our cohort of untreated GHD children had abnormal BC and cIMT as compared to controls. rhGH therapy for 1 year had beneficial effect on BC and cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Birth size has been associated with adult life diseases, but the endocrine factors that are likely involved are not established. We evaluated the associations of maternal and cord blood hormones with birth size in normal pregnancies, and examined possible effect modification by maternal height, on the basis of prior suggestive evidence. In a prospective study of normal singleton pregnancies in Boston, USA and Shanghai, China, maternal hormone levels at the 27th gestational week were available for 225 pregnancies in Boston and 281 in Shanghai and cord blood measurements for 92 pregnancies in Boston and 110 in Shanghai. Pearson partial correlation coefficients of log-transformed hormone levels with birth weight and length were calculated. Overall, positive correlations with birth weight were found for maternal estriol (r = 0.19; p < 0.001) and progesterone (r = 0.15; p < 0.001) and these associations were more evident among taller mothers. There was an inverse association of cord blood progesterone (r = −0.16; p < 0.03) with birth weight. In Boston, cord blood IGF-1 was positively associated with birth weight (r = 0.22; p < 0.04) and length (r = 0.25; p < 0.02), particularly among taller mothers (r = 0.43 and 0.38, respectively; p < 0.02), whereas among taller mothers in Shanghai the associations of IGF-2 with birth size appeared to be at least as strong as those of IGF-1. In conclusion, maternal estriol and progesterone, and cord blood IGF-1 were positively correlated with birth size. All correlations tended to be more pronounced among offspring of taller mothers. Among taller mothers in Shanghai, IGF-2 appeared to be at least as strongly associated with birth size as IGF-1. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) assigns high priority to the prevention of non-communicable age-related diseases such as heart disease, cancer, diabetes, stroke and chronic lower respiratory diseases. They are now the leading causes of death, in both industrialised and developing countries, mostly due to increased life expectancy and urbanisation with associated changes in lifestyle and environment. Tobacco smoking, physical inactivity and resulting obesity are established risk factors for many chronic diseases. Yet, the aetiology of age-related diseases is complex and varies between individuals. This often makes it difficult to identify causal risk factors, especially if their relative effects are weak. For example, the associations of both obesity and air pollution with several age-related diseases remain poorly understood with regard to causality and biological mechanisms. Exposure to both, excess body fat and particulate matter, is accompanied by systemic low-grade inflammation as well as alterations in insulin/insulin-like growth factor signalling and cell cycle control. These mechanisms have also been associated in animal and some human studies with longevity and ageing in more general terms. In this paper, it is therefore hypothesised that they may, at least in part, be responsible for the adverse health effects of obesity and air pollution. It is argued that molecular and genetic epidemiology now offer novel instruments to improve the understanding of these pathophysiological pathways and their link to disease aetiology. Understanding the causality of exposure disease associations and differences in susceptibilities to environment and lifestyle is an important aspect for effective prevention.

Abstract: The normal on and off switching of the PI3-K (phosphoinositide 3-kinase)/Akt pathway, particularly by its major activators insulin and IGF-1 (insulin-like growth factor-1), is a powerful integrator of physiological responses rudimentary to successful aging. This is highlighted by extensive studies showing that reducing, but not obliterating, activation of the PI3-K/Akt/mTOR signal, at several levels, can extend healthy lifespan in organisms from yeast to mammals. Moreover, aberrant control of the PI3-K/Akt axis is emerging to be a primary causative node in all major diseases of aging: cancer, type 2 diabetes mellitus (T2DM), heart disease and neurodegeneration. Aging is the major risk factor for AD, the most common dementia disorder. The integrated coordination of neuronal responses through the PI3-K/Akt pathway has significant functional impact on key events that go awry in Alzheimer's disease (AD), including: synaptic plasticity, neuronal polarity, neurotransmission, proteostasis, use-dependent translation, metabolic control and stress responses including DNA repair. Investigation of the status of the PI3-K/Akt system in brains of individuals who have had AD shows aberrant and sustained activation of neuronal PI3-K/Akt/mTOR signaling to be an early feature of the disease. This is mechanistically linked to progressive desensitization of normal brain insulin and IGF-1 responses, aberrant proteostasis of Aβ and tau, synaptic loss and cognitive decline in the disease. Notably, concomitantly with feedback inhibition of insulin and IGF-1 responses, increased activation of the neuronal PI3-K/Akt/mTOR axis is a major candidate effector system for transmission of pathophysiological signals from Aβ to tau in the context of defects in synaptic transmission that lead to cognitive decline. Therapeutic approaches targeted at normalizing signaling through either the neuronal PI3-kinase/Akt/mTOR pathway or its activation by insulin and IGF-1 have been shown to be protective against the development of AD pathology and cognitive decline in animal models of AD and some of these therapies are entering clinical trials in patients with the disease. [Copyright &y& Elsevier]

Prostate specific antigen (PSA) has long been used as a biological marker for prostatic cancer. Recent studies have demonstrated that PSA synthesis can be induced by steroid hormones in several tissues of women. Menstrual cycle is regulated by the cyclic variation of estradiol and progesterone. This study was undertaken in order to study the correlation of serum PSA to both these corpus luteal hormones. 110 serum samples and 10 saliva samples were collected from healthy women aged 18-45 years of age having normal menstrual cycles. Active PSA DSL-9700 ultrasensitive kit with detection limit 0.001 ng/ml was used to analyze PSA. 38.2 % of all serum samples and 10 % of saliva samples had detectable concentrations of PSA. The serum PSA was highest during mid follicular phase (between 4th and 8th days of cycle). Variation in PSA levels seemed to follow the variations in progesterone with a lag period of 12-14 days, but did not appear to bear any relationship with the estradiol levels. [ABSTRACT FROM AUTHOR]

Background: The effects of curcumin on the activities and gene expression of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-Stransferase (G-ST), B-cell CLL/lymphoma 2 (Bcl-2) and insulin like growth factor-1 (IGF-1) in diabetic rats were studied. Methods: Twenty four rats were assigned to three groups (8 rats for each). Rats of first group were non diabetic and rats of the second group were rendered diabetic by streptozotocin (STZ). Both groups received vehicle, corn oil only (5 ml/kg body weight) and served as negative and positive controls, respectively. Rats of the third group were rendered diabetic and received oral curcumin dissolved in corn oil at a dose of 15 mg/5 ml/kg body weight for 6 weeks. Results: Diabetic rats showed significant increase of blood glucose, thiobarbituric acid reactive substances (TBARS) and activities of all antioxidant enzymes with significant reduction of reduced glutathione (GSH) compare to the control non diabetic group. Gene expression of Bcl2, SOD, CAT, GPX and GST was increased significantly in diabetic untreated rats compare to the control non diabetic group. The administration of curcumin to diabetic rats normalized significantly their blood sugar level and TBARS values and increased the activities of all antioxidant enzymes and reduced glutathione concentration. In addition, curcumin treated rats showed significant increase in gene expression of IGF-1, Bcl2, SOD and GST compare to non diabetic and diabetic untreated rats. Conclusion: Curcumin was antidiabetic therapy, induced hypoglycemia by up-regulation of IGF-1 gene and ameliorate the diabetes induced oxidative stress via increasing the availability of GSH, increasing the activities and gene expression of antioxidant enzymes and Bcl2. Further studies are required to investigate the actual mechanism of action of curcumin regarding the up regulation of gene expression of examined parameters. [ABSTRACT FROM AUTHOR]

Abstract: The insulin like growth factor receptor subtype 1(IGF-1R) plays an important role in cancers transformation and progression. The aim is to investigate the effects of sunitinib on IGF-1R cell signaling transduction, especially on receptor phosphorylation and ubiquitination. In HEK293 cells, IGF-1R signaling pathways are activated in response to IGF-1, which induces obvious phosphorylations of receptor tyrosine and Akt, ERK. However, the phosphorylations of receptor tyrosine, Akt and ERK were significant inhibited by sunitinib. We found that both IGF-1 and sunitinib obviously down regulated the IGF-1R expression. For analysis the ubiquitination, HEK293 cells were simulated with 100ng/ml IGF-1 or 10nM sunitinib for 10min after serum starvation for 24h. Both IGF-1 and sunitinib could obviously induce the IGF-1R ubiquitination at 10min compared with control (only serum free, no stimulation), indicating IGF-1 and sunitinib down-regulate the IGF-1R by increasing the receptor degradation through ubiquitination dependent proteasome pathway. We also found that MDM2 combined to IGF-1R in response to sunitinib stimulation. To confirm it, HEK293 cells were transfected with human HA-MDM2 (+MDM2) or siRNA to MDM2 (−MDM2). Following 24h serum starvation, cells were stimulated with 10nM sunitinib for 10min. In over-expressed MDM2 cells, IGF-1R was more ubiquitinated than that in mock-transfected cells (control), and no ubiquitination in −MDM2 cells. These results mean that sunitinib mediates ubiquitination of IGF-1R dependent on MDM2. In summary, sunitinib could block signaling transduction and mediate degradation of IGF-1R. [Copyright &y& Elsevier]

Abstract: Alzheimer''s disease (AD) is the most common chronic neurodegenerative disorder associated with aging. This study aimed to explore new markers for AD as total homocysteine (tHcy), insulin, insulin like growth factor-1 (IGF-1), interlukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α); to determine the modulatory effects of vitamin E (VE), acetyl-l-carnitine (ALC) and α-lipoic acid (LA) on the investigated parameters and to evaluate the possible therapeutic role of these nutraceutical in AD-induced in rats. Our results revealed that brain acetylcholine esterase (AChE) activity and tHcy levels were significantly increased in AD model. Folic acid, vitamin B12 levels and Na+/K+ ATPase activity were markedly reduced. Plasma insulin and IGF-1 levels were noticeably decreased but plasma TNF-α and IL-1β concentrations were significantly increased, confirming that abnormal inflammatory response is associated with AD. Treatment by VE, ALC and LA restored the above mentioned parameters to about normal levels comparable to those of donepezil, indicating that tHcy, insulin, IGF-1, IL-1β and TNF-α may be considered as new biomarkers for AD. The study points to the potential restoring effects of VE, ALC and LA in AD model. Our study provides evidence for the importance of dietary supplementation in delaying the progression of age-related neurodegenerative diseases. [Copyright &y& Elsevier]

Living cells communicate with their microenvironment and exchange information through signaling pathways in order to carry out most biological processes. The CCN family of proteins has the ability to coordinate the extracellular and intracellular signaling pathways and epithelial-stromal cross-talks. CCN proteins have been shown to play roles in multiple processes including cancer, either as tumor suppressors or oncogenes. Particularly, loss of CCN6 expression has been reported in highly aggressive breast cancer types, especially in inflammatory breast cancer and breast cancer with axillary lymph node metastasis. Recent findings can better explain the biological relevance of CCN6 as a tumor suppressor protein in breast tumorigenesis. CCN6 loss triggers the process of epithelial to mesenchymal transition (EMT), which converts epithelial cells into migratory and invasive mesenchymal-like cells at least in part through modulation of IGF-1 receptor signaling pathway. Emerging data support the hypothesis that CCN6 also exerts growth factor independent functions, especially related to cell survival and anoikis resistance. Thus, our work provides new insights into the functions and mechanisms of tumor suppression exerted by CCN6 in the breast. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To evaluate the relationship between endometriosis and polymorphisms in insulin-like growth factors (IGFs) and IGF-I receptor genes. Study design: In a case–control study, 128 women with endometriosis and 108 control women were recruited at the Department of Obstetrics and Gynecology in Seoul National University Hospital. Determinations of −969(CA) block, −603A>T, and −553T>C single nucleotide polymorphism (SNP)s in the IGF-I gene, c.517C>T, c.540G>T and 820G>A SNPs in the IGF-II gene, and c.3129G>A SNP in the IGF-I receptor gene were performed to evaluate the prevalence of IGFs and IGF-I receptor genotypes or alleles. Results: Among studied SNPs, the IGF-II 820G>A polymorphism was associated with endometriosis. Women with endometriosis were observed 1.99 times more frequently in the GG genotype of the IGF-II 820G>A polymorphism compared with non-GG genotype (95% confidence level: 1.18–3.35). The similar finding was observed only in early stage endometriosis (stages I and II). Conclusions: The IGF-II 820G>A polymorphism is a genetic factor which may be associated with the development of endometriosis in Korean women. [Copyright &y& Elsevier]

Abstract: The klotho gene is highly expressed in the distal convoluted tubule of the kidney, while its encoded protein has many physiological and pathophysiological renal roles. We investigated the effect of klotho protein on physiological compensatory renal hypertrophy after nephrectomy in klotho transgenic (KLTG) mice. Renal hypertrophy was suppressed in KLTG mice compared with wild-type mice, and this was associated with suppression of insulin growth factor-1 (IGF-1) signaling by klotho protein. In vitro, IGF-1 signaling was suppressed in human proximal tubular cells transfected with the klotho plasmid. Our data suggest that klotho modulates compensatory renal hypertrophy after nephrectomy via suppression of the IGF-1 signaling pathway, indicating a novel physiological role for klotho protein in the kidney. [Copyright &y& Elsevier]

The article presents a study of insulin-like growth factor-I and -II (IGF-I and IGF-II) found in the follicles, granulosa cells, corpus luteum (CL), and corpus albicans (CA) of buffalo ovary. The reverse transcription-polymerase chain reaction (RT-PCR) was utilized to determine the existence of IGF-I and IGF-II. It discusses the effects of follicle stimulating hormone (FSH) and leutinizing hormone (LH) and their applications on IGF-I and IGF-II. Results reveal the significance of IGF-I and IGF-II on buffalo ovary's FSH and LH phases.

Testicular cancer is a disease with elusive pathogenesis. Recent studies demonstrated a relationship between insulin- like growth factor (IGF) signaling pathway and the pathogenesis of various types of cancer. On the other hand inconclusive data correlate increasing height, a trait depending on IGF signaling pathway, with increasing incidence of testicular cancer. Thus, it is possible that IGF system may be implicated in the pathogenesis of germ cell tumors. The purpose of the study was to identify the role of IGF signaling pathway in the pathogenesis of testicular germ cell tumors (GCTs). 50 patients with GCTs prior to the onset of chemotherapy and 16 male age matched controls were enrolled. Three blood samples were drawn from the patients, the first at baseline, the second 20-30 days after completion of the second cycle of chemotherapy and the third 9-14 months after the completion of chemotherapy; and one blood sample was drawn from the controls. We measured serum IGF-1 and IGFBP-3 and calculated their molar ratio using quantitative sandwich enzyme immunoassay technique. Patients and controls had similar demographic characteristics. Mean IGF-1/IGFBP-3 molar ratio was higher in patients than controls (0.27±0.07 vs. 0.11±0.03; p=0.02'7). IGF-1 decreased significantly between the baseline and 1 year after chemotherapy was completed (261.2±483 vs. 96.4±23.1 ng/mL, respectively; p<0.001) and between the second sample and the third sample (205.7±41.7 vs. 96.4±23.1 ng/mL; p<0.001 IGFBP-3 was increased after chemotherapy (mean values of first and second samples were 3545±687.3 vs. 4714±827.1 ng/mL; p=0.045, and mean values between first and third samples were 3591±697.6 vs. 5145±1073.2 ng/mL; p=0.005 IGF1/IGFBP3 molar ratio was found to decrease after initiation and completion of chemotherapy (mean values were: 0.269±0.05 vs. 0.211±0.04; between the first and third samples, p=0.035; 0.308±0.07 vs. 0.083±0.02 between the second and third samples, p<0.001and 0.211±0.04 vs. 0.084±0.02 between the first and second samples, p<0.00). The concept that IGF signaling system has a role in germ cell cancer pathogenesis is an appealing idea and our study seems to provide further evidence in favor of our initial hypothesis, although larger prospective studies are needed to further elucidate it. [ABSTRACT FROM AUTHOR]

Background: A high percentage of preterm neonates are born small for gestational age (SGA). These children show a high morbidity and mortality after birth and often develop insulin resistance with ensuing impaired glucose metabolism in adulthood. Since insulin is important for intrauterine growth, fetal insulin resistance might also influence birth weight of preterm neonates. Objectives: A common polymorphism in the promoter region of the human hepatic glucokinase (-258) is associated with a decreased promoter activity, an enhanced insulin secretion, and hypertension and hepatic insulin resistance in adults. In this pilot study we wanted to investigate whether the G/A polymorphism at -258 of the hepatic glucokinase promoter has an effect on birth weight of preterm neonates and therefore might constitute a genotype leading to low birth weight and metabolic defects. Methods: We enrolled 106 preterm neonates in our study. 44 of them were SGA and 62 AGA neonates. We extracted DNA from a buccal swab and identified the polymorphism by PCR-ARMS. Results: We found no difference in the prevalence of the polymorphism in either groups. Conclusion: The polymorphism at -258 of the fetal hepatic glucokinase promoter is most probably not of a major relevance in the pathophysiology of low birth weight in preterm neonates. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article offers information on insulin-like growth factor (IGF) binding proteins and their role in the growth, differentiation, and proliferation of breast cancer cells. It states that IGF interact to influence cell-signalling pathways that controls cancer cell growth, differentiation and proliferation. It discusses IGF binding protein-3 (IGFBP-3) and IGFBP-rP1 as important members of the IGF superfamily the modulates the anti-apoptotic effects of IGF-1 on breast cancer.