Insulin Growth Factor-1 Expression Research Articles

Use of moringa protein hydrolysate as a fishmeal replacer in diet of Oreochromis niloticus: Effects on growth, digestive enzymes, protein transporters and immune status

In this study, we partially replaced fishmeal (FM) with moringa protein hydrolysate (MPH) in the diet of Nile tilapia, Oreochromis niloticus, in a ten-week feeding trial. We evaluated the consequences of this substitution on the growth, digestive enzyme activity, economic efficiency, immune status, and expression of immune genes, protein transporters, and insulin growth factor-1 (IGF-1). Fish (n = 225, 36.38 ± 0.06 g/fish) were randomly assigned to five groups with five replacement levels of MPH: 0, 15, 30, 45, and 60% (MPH0, MPH15, MPH30, MPH45, and MPH60). The results showed a linear increase in the growth parameters by replacing FM with MPH. A rise in the serum level of growth hormone and a reduction in the leptin hormone and glucose levels were observed with increasing the MPH replacement level. Higher amylase activity was detected with MPH replacement, with the highest activity noticed in the MPH45 group. The protease activity was linearly increased in the MPH45–60 groups. We reported significant up-regulation in the expression of IGF-1 and amino acid and peptide transporters in MPH groups. The immune indices (serum nitric oxide level, lysozyme activity, and phagocytic activity) and immune-related gene expression were linearly up-regulated by MPH replacement up to the 45% replacement level then decreased in the MPH60 group but still higher than the control group. FM replacement with MPH increased the Nile tilapia resistance to Aeromonas sobria challenge. In conclusion, MPH can replace FM up to 60% for good performance and immune status of fish.

Elevated insulin growth factor-1 in dentate gyrus induces cognitive deficits in pre-term newborns.

Prematurely born infants are deprived of maternal hormones and cared for in the stressful environment of Neonatal Intensive Care Units (NICUs). They suffer from long-lasting deficits in learning and memory. Here, we show that prematurity and associated neonatal stress disrupt dentate gyrus (DG) development and induce long-term cognitive deficits and that these effects are mediated by insulin growth factor-1 (IGF1). Nonmaternal care of premature rabbits increased the number of granule cells and interneurons and reduced neurogenesis, suggesting accelerated premature maturation of DG. However, the density of glutamatergic synapses, mature dendritic spines, and synaptic transmission were reduced in preterm kits compared with full-term controls, indicating that premature synaptic maturation was abnormal. These findings were consistent with cognitive deficits observed in premature rabbits and appeared to be driven by transcriptomic changes in the granule cells. Preterm kits displayed reduced weight, elevated serum cortisol and growth hormone, and higher IGF1 expression in the liver and DG relative to full-term controls. Importantly, blocking IGF-1 receptor in premature kits restored cognitive deficits, increased the density of glutamatergic puncta, and rescued NR2B and PSD95 levels in the DG. Hence, IGF1 inhibition alleviates prematurity-induced cognitive dysfunction and synaptic changes in the DG through modulation of NR2B and PSD95. The study identifies a novel strategy to potentially rescue DG maldevelopment and cognitive dysfunction in premature infants under stress in NICUs.

A variant rs6214 within IGF-1 confers risk for ulcerative colitis in Chinese Han populations.

Insulin growth factor-1 (IGF-1) has been found to correlate with various diseases such as cancer and cardiovascular diseases including ulcerative colitis (UC). The present study aimed to investigate the plausible association of rs6214 (C > T) within IGF-1 and UC susceptibility in Chinese Han populations. A total of 977 UC patients and 1029 healthy controls were enrolled, and rs6214 was genotyped with PCR and direct sequencing on the ABI 3730XL DNA analyzer platform. Logistic regression analysis was applied for the correlation of rs6214 and UC susceptibility via calculation of odds ratio (OR) with a 95% confidence interval (95% CI) adjusted for age and sex under different genetic models. The difference of clinical parameters between genotypes was measured by one-way analysis of variance (ANOVA). Additional functional assays were conducted to establish the probable relationship. The results indicated that the T allele of rs6214 showed roughly 37% greater risk for UC risk in the additive model (OR = 1.37, 95% CI = 1.21-1.55, P < 0.000001) when compared with C allele carriers, and the pattern was similar in other three genetic models. Further stratified analysis suggested that the association was particularly noteworthy in UC patients with extensive colitis and severe condition. Moreover, the blood level of IGF-1 was downregulated in UC patients, and the mRNA level was lower in T allele carriers in rectal tissues of UC cases. Additional luciferase assay demonstrated that rs6214 regulates IGF-1 expression via promoting miR-2053. Collectively, rs6214 increased UC susceptibility and suppresses IGF-1 expression by enhancing miR-2053 binding. The current findings provided evidence that rs6214 is a promising biomarker for UC prediction and prognosis.

Abstract 13062: In vivo Knockdown of Proapoptotic Mir-320 Restores Cardiac Function and Angiogenesis in a Mouse Model of Type 2 Diabetes

Background: Non-ischemic diabetic heart disease (NiDHD) is characterised by diastolic dysfunction and decreased or preserved systolic function, eventually resulting in heart failure. The fundamental mechanisms leading to NiDHD are still not known. microRNAs (miRNAs) plays a significant role in the development of NiDHD. Objective: To investigate the pathological role of cardiomyocyte enriched pro-apoptotic miR-320 in the development of NiDHD and to determine if therapeutic knockdown of miR-320 can restore impaired cardiac function and angiogenesis in the diabetic heart. Methods and Results: Cardiac tissue were collected from type-2 diabetic individuals undergoing cardiac surgery showed marked upregulation of miR-320, which was associated with downregulation of its direct target pro-survival insulin growth factor-1 (IGF-1) and anti-apoptotic protein Bcl-2. Analysis of cardiac tissue samples collected from type 2 diabetic mice (BKS.Cg-m+/+Leprdb/J) every 4wks, from 8 to 32wks of age showed activation of miR-320 and downregulation of IGF-1 at the later stages of diabetes. To determine if therapeutic knockdown of miR-320 is beneficial, high glucose cultured adult cardiomyocytes were treated with either locked nucleic acid (LNA) anti-precursor (pre)-miR-320 or scrambled (Scr) sequence. Results showed that LNA-anti-pre-320 significantly restored IGF-1 expression and reduced apoptotic cells death (3.1±05 in Scr vs 1.3±0.6 in LNA-anti-pre-320, P&lt;0.01). Finally, to confirm if the effect can be translated in vivo , 24 weeks old type 2 diabetic mice with established systolic dysfunction were injected with LNA-anti-pre-320 once a week for 4wks. Echocardiography confirmed significant restoration of diastolic function and partial restoration of systolic function. Molecular analysis showed marked reduction in miR-320 expression, which was associated with recovery of IGF-1 and Bcl-2. Further, histological analysis confirmed improved angiogenesis and reduced fibrosis in the LNA-anti-pre-320 treated group. Conclusion: miR-320 is a late responding miRNA that aggravates apoptosis and cardiac dysfunction in diabetic heart, and that therapeutic knockdown of miR-320 is beneficial in partially restoring the deteriorated cardiac function.

Expression of caspase-3, caspase-9, GDF-9 and IGF-1 genes in ovine oocytes cultured with optimum and elevated doses of Amphiregulin, Neuregulin-1 and Tumour necrosis factor-α in-vitro

The present study was conducted to evaluate the expression of caspase-3, caspase-9, growth differentiation factor-9 (GDF-9) and insulin growth factor-1 (IGF-1) genes in oocytes cultured in vitro with optimum and elevated doses of amphiregulin (50 ng and 150 ng), neuregulin-1 (25 ng and 150 ng) and tumor necrosis factor-α (25 ng and 150 ng) during in vitro maturation of oocytes based on the results of effects of AREG or NRG-1 or TNF-α concentration on maturation of oocytes which caused significant effect, were selected for gene expression studies along with the basal/control level. Total RNA was extracted from in vitro matured oocytes using Trizol method and Real-time reverse transcription polymerase chain reaction was used to evaluate the expression of genes. There was an upregulation of caspase-3 at 150 ng of TNF-α, caspase-9 at 50 ng of AREG, GDF-9 at 150 ng of AREG and IGF-1 at 150 ng of AREG and 25 ng of TNF-α. These results suggested that AREG at elevated dose and TNF-α at optimum dose enhanced the expression of GDF-9 and IGF-1, while the presence of elevated dose of TNF-α and optimum dose of AREG activated caspase-3 and caspase-9, respectively in oocytes cultured in vitro.

Abstract 1631: Anti-cancer effects of vorinostat on 3D cultured pancreatic cancer cells

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, often having a low survival rate mainly due to late diagnosis and limited therapies because of drug resistance. Treatment results shown in cell models used in studying various drugs often fail in clinical trials. The lack of translation of the effects observed in vitro to patients continues to halt progress. Genetic mutations are known in PDAC; however, recent studies have suggested the role of epigenetics in its initiation and progression to a malignant phenotype. Histone deacetylase (HDAC) proteins are highly expressed in a variety of cancers, including pancreatic cancer. Recent studies have shown that targeting these proteins through the use of HDAC inhibitors may be an effective therapy for pancreatic cancer. Using a 3D cultured pancreatic cell model, anti-cancer effects by vorinostat, a HDAC inhibitor, were investigated. Although both pancreatic cell lines, PANC-1 and Mia, contain mutated K-ras and P53, a differential effect in response to vorinostat was observed in expression of cancer genes using a Human Pancreatic Adenocarcinoma TagMan Array 96 (Applied Biosystems). In the PANC-1 cell model, vorinostat decreased expression of STAT6, which is known to play a role in migration and invasion. It also decreased significantly expression of insulin growth factor 1 (IGF1), IL-6, EGF, VEGFA and TGFB1. CCND2 and CCND2 were also downregulated. In contrast, Mia cell model showed decreased expression of EGF and IGF1, but no change with the other genes. These data suggest that vorinostat has effects on several potential pathways in pancreatic cancer possibly through epigenetic mechanisms that affect certain genes involved in progression and invasion. Currently, this drug in combination with other drugs is being investigated for pancreatic cancer. Citation Format: Fatemeh Nouri Emamzaden, Beverly Word, George Hammons, Beverly D. Lyn-Cook. Anti-cancer effects of vorinostat on 3D cultured pancreatic cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1631.

Evaluation of IGF-1, TNF-α, and TGF-β Gene Expression after Oral Vitamin D Supplementation in School-Aged Children with Chronic Bronchial Asthma

BACKGROUND: Airway remodeling in children with bronchial asthma is due to the effect of inflammatory mediators and growth factors on the bronchial epithelium. Vitamin D (VitD) has immunomodulatory effect in many inflammatory diseases as bronchial asthma. The ant-inflammatory and anti-fibrotic role of VitD could prevent or improve air way remodeling in asthmatic patients. AIM: The study investigated the effect of VitD supplementation on the expression of transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α), and insulin growth factor 1(IGF-1) and to correlate them with asthma severity and level of control. METHODS: The serum level of VitD and the mRNA expression of IGF-1, TGF-β, and TNF-α were estimated in 50 patients and 20 healthy controls control subjects using quantitative PCR in real-time. Asthmatic patients with VitD deficiency received VitD supplementation for 2 months followed by remeasurement of serum VitD and the genes expression TGF-β, TNF-α, and IGF-1. RESULT: Pre-intake of VitD and serum level of VitD were lower in all patients than control subjects (p = 0.005). VitD level was directly correlated with IGF-1 mRNA expression, which was indirectly correlated with TGF-β, r = 0.5 and −0.57; p = 0.0001 and 0.002, respectively. After VitD supplementation, the expression of the TGF-β mRNA gene was the only gene that decreased significantly (p = 0.04) together with improved asthma control and spirometric parameters. CONCLUSIONS: VitD supplementation down regulated the gene expression of TGF-β and improved asthma control level, but it did not significantly affect the gene expression of TNF-α and IGF-1.

Lactococcus cremoris subsp. cremoris FC-fermented milk activates protein synthesis and increases skeletal muscle mass in middle-aged mice

Age-related muscle atrophy is associated with decreased protein anabolic capacity. Dietary intervention is an important strategy for the treatment of age-related muscle atrophy. This study examined the effect of Lactococcus cremoris subsp. cremoris FC-fermented milk on muscle mass and protein anabolic signaling in middle-aged mice. Male C57BL/6J mice (18-month-old) were divided into the control and Lactococcus cremoris subsp. cremoris FC-fermented milk supplementation groups. Mice were administered unfermented or fermented milk (300 μL/day) by gavage every alternate day for 8 weeks; thereafter, muscle weight, protein metabolic signaling factors, and inflammatory factors were investigated. Soleus muscle weight was higher in the fermented milk group than in the control group. Expression of insulin growth factor-1, a typical anabolic factor, and phosphorylation levels of anabolic signaling factors (mTOR and p70S6K) were higher after fermented milk supplementation. Levels of tumor necrosis factor-α, an inhibitor of protein anabolism, were lower in the fermented milk group. These data suggest that the daily intake of Lactococcus cremoris subsp. cremoris FC-fermented milk increased skeletal muscle mass as well as protein synthesis in the middle-aged mice, which may be mediated by reduction in the levels of inflammatory factors. Therefore, accelerated protein synthesis, induced by the consumption of fermented milk, has a potential role in counteracting muscle atrophy.

Beneficial impact of dietary methyl methionine sulfonium chloride and/or L-carnitine supplementation on growth performance, feed efficiency, and serum biochemical parameters in broiler chicken: role of IGF-1 and MSTN genes.

The purpose of this study was to examine the effect of dietary supplementation with methyl methionine sulfonium chloride (MMSC), and L-carnitine (L-CAR) alone or in combination on the growth performance of broilers through their impact on the expression of IGF-1 and MSTN genes associated with growth in broilers. One-day-old female Ross 308 broiler chicks were allocated into four groups, each of which received a broiler starter diet and water daily ad libitum. The control group (group 1) was given drinking water without any additives. Group 2 received 0.25g L-carnitine per liter of drinking water, group 3 received 0.25g MMSC per liter of drinking water, and group 4 received 0.25g of both L-carnitine and MMSC per liter of drinking water. Birds were given a starter diet to 21days after which they received a broiler grower diet to 35days when the experiment ended. There were five replicate groups of 12 birds per treatment. Body weights and feed intake were recorded weekly. Compared to the control group of birds, supplementation with MMSC either alone or in combination with L-carnitine resulted in an increase in growth rate or feed utilization efficiency; L-carnitine by itself had no effect. MMSC supplementation, again either alone or in combination with L-carnitine, increased jejunal and ileal villi height, increased serum total proteins and globulins, downregulated myostatin (MSTN) mRNA, and upregulated insulin growth factor-1 (IGF-1) mRNA expression. Supplementation with L-carnitine alone showed none of these effects. We conclude that MMSC supplementation improved growth performance through the upregulation of IGF-1 mRNA expression and downregulation of MSTN mRNA expression.

Muscle adaptation to sleeve gastrectomy: Potential role of nutritional supplementation and physical exercise.

Skeletal muscle is metabolically and functionally flexible and contractile under normal conditions. Obesity is a risk factor that causes metabolic disorders and reduces muscle contractility. Sleeve gastrectomy (SG) has been used for surgical correction of obesity. This work aimed to investigate how obesity and its surgical correction affects skeletal muscle and the possible role of nutritional supplementation and physical exercise. Adult male albino rats were randomly divided into five groups, 8 rats per group: group Ia (control non-obese), group Ib (control obese), group II (post-operative, SG), group III (post SG + nutritional supplementation) and group IV (post SG + nutritional supplementation + physical exercise). SG resulted in cellular and metabolic degenerative disorders in the muscle including wasting, weakness and fibrosis with elevated inflammatory, oxidative and injury markers. Nutritional supplementation induced the post SG muscle regeneration indicated by high expression of insulin growth factor-1 (IGF-1) and myogenin and low expression of transforming growth factor beta 1 (TGF-β1). Interestingly, it improved the metabolic state of the muscle by reducing the oxidative stress, inflammatory and muscle injury markers and delaying the onset of fatigue. What is more, physical exercise along with nutritional supplementation resulted in further improvement of the muscle metabolic state and function. In conclusion, nutritional supplementations together with physical exercise after SG are essential for preserving muscle mass and contractility and improving its metabolic and functional status.

Protein-carbohydrate interaction effects on energy balance, FGF21, IGF-1, and hypothalamic gene expression in rats.

Amino acids are involved in energy homeostasis, just as are carbohydrates and lipids. Therefore, mechanisms controlling protein intake should operate independently and in combination with systems controlling overall energy intake to coordinate appropriate metabolic and behavioral responses. The objective of this study was to quantify the respective roles of dietary protein and carbohydrate levels on energy balance, plasma fibroblast growth factor 21 (FGF21) and insulin growth factor 1 (IGF-1) concentrations, and hypothalamic neurotransmitters (POMC, NPY, AgRP, and CART). In a simplified geometric framework, 7-wk-old male Wistar rats were fed 12 diets containing 3%-30% protein for 3 wk, in which carbohydrates accounted for 30%-75% of the carbohydrate and fat part of the diet. As a result of this study, most of the studied parameters (body composition, energy expenditure, plasma FGF21 and IGF-1 concentrations, and Pomc/Agrp ratio) responded mainly to the protein content and to a lesser extent to the carbohydrate content in the diet.NEW & NOTEWORTHY As mechanisms controlling protein intake can operate independently and in combination with those controlling energy intakes, we investigated the metabolic and behavioral effects of the protein-carbohydrate interaction. With a simplified geometric framework, we showed that body composition, energy balance, plasma FGF21 and IGF-1 concentrations, and hypothalamic Pomc/Agrp ratio were primarily responsive to protein content and, to a lesser extent, to carbohydrate content of the diet.

Protective effect of swimming and genistein on the expression of microRNA 132, insulin growth factor 1, and brain-derived neurotrophic factor genes, as well as spatial memory, in the hippocampus of diabetic ovariectomized rats

Background and Objective: The present study aimed to assess the effects of the combined use of exercise and genistein on the hippocampal expression of microRNA-132, IGF-1, and BDNF in type 2 diabetic ovariectomized rats. Materials and Methods: Wistar female rats in the weight range of 180-220 gr (n=10) were assigned to six groups: sham, ovariectomy, ovariectomized diabetic, ovariectomized diabetic treated with genistein for eight weeks, diabetic ovariectomized treated with swimming for eight weeks, and a group that was treated with both genistein and swimming for eight weeks. The effect of those treatments was assessed by the determination of microRNA-132, insulin growth factor 1 (IGF-1), and brain-derived neurotrophic factor (BDNF) expression levels within the hippocampus. These genes were evaluated by real-time-polymerase chain reaction (RT-PCR) and spatial memory was assessed by the Morris water maze. Results: Ovariectomy demonstrated a decrease in the expression of microRNA-132, IGF-1, and BDNF in the hippocampus, as well as spatial memory, in diabetic ovariectomized rats, which showed a greater reduction in the expression of those genes in rats (P&lt;0.05). Nevertheless, genistein administration, swimming training, and a combination of them significantly up-regulated microRNA-132, BDNF, and IGF-1 expression, as well as spatial memory (P&lt;0.05). Conclusions: As evidenced by the obtained results, the combined use of genistein and swimming could prevent estrogen deficiency effects in the hippocampus of ovariectomized diabetic rats

Bone regeneration in a mouse model of type 1 diabetes: Influence of sex, vitamin D3, and insulin

AimThis study set forth a question: are there any differences in bone responses to insulin and/or vitamin D3 treatment in female and male type 1 diabetic (T1D) mice? Main methodsTo address this issue, a non-critical sized femur defect was created in streptozotocin (STZ)-T1D mice. Control non-diabetic and T1D female and male mice received: saline; vitamin D3; insulin; or vitamin D3 plus insulin, for 21 days. Key findingsFemale and male T1D mice showed impaired bone healing, as indicated by histological and micro-computed tomography (micro-CT) analysis. Vitamin D3 or insulin improved the bone regeneration in T1D mice, irrespective of sex. Vitamin D3 plus insulin did not exhibit any additional effects. There were no differences regarding the numbers of TRAP-stained osteoclasts in either evaluated groups. The osteoblast-related gene osterix was upregulated in vitamin D3-treated male T1D mice, as revealed by RT-qPCR. Female T1D mice treated with vitamin D3, insulin, or vitamin D3 plus insulin presented an increased expression of insulin growth factor-1 (IGF-1) mRNA. Conversely, IGF-1 mRNA levels were reduced by the same treatments in male TD1 mice. SignificanceAltogether, the results suggested that T1D similarly delayed the osseous healing in female and male mice, with beneficial effects for either vitamin D3 or insulin in T1D mice of both sexes. However, data indicated marked sex differences regarding the expression of genes implicated in bone formation, in T1D mice treated with vitamin D3 and/or insulin.

The expression and significance of miR-29b and IGF-1 in type 2 diabetes mellitus patients with depression

Objective To detect the levels of serum micro RNA (miRNA) -29b and insulin growth factor-1 (IGF-1) in patients with type 2 diabetes mellitus (T2DM) and depression, and to analyze their clinical significance. Methods 504 patients with T2DM admitted to our hospital from February 2016 to February 2018 were selected, among them, 264 patients without depression, the other 240 patients with depression were selected as the study group, and 200 patients with physical examination were selected as the control group. Serum triglyceride (TG), cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), glycosylated hemoglobin (HbA1c), fasting blood glucose (FPG) were measured by automatic biochemical analyzer. Levels of serum IGF-1 were measured by automatic chemiluminescence instrument in all subjects. The expression of miR-29b in serum was detected by quantitative real-time polymerase chain reaction (qRT-PCR). All subjects were scored with 24 Hamilton Scales (HAMD). Results The serum TC, TG, LDL, FPG, HbA1c, and HAMD scores of patients with depression in T2DM were significantly higher than those of control group and patients with T2DM (P<0.05); the serum TC, TG, FPG, HbA1c of patients with T2DM were significantly higher than those of the control group (P<0.05). The levels of serum miR-29b in patients with T2DM and depression were significantly lower than those in patients with T2DM and control group (P<0.05), while the level of IGF-1 was significantly higher than that in patients with T2DM and in control group (P<0.05); the level of serum miR-29b in patients with T2DM was significantly lower than that in control group (P<0.05), while the level of IGF-1 was significantly higher than that in control group (P<0.05). The levels of serum miR-29b in patients with severe depression and T2DM were significantly lower than those in patients with mild or moderate depression (P<0.05), while the level of IGF-1 showed the opposite (P<0.05). There was a significant negative correlation between serum miR-29b and IGF-1 level in patients with T2DM and depression (P<0.05). Logistic regression analysis showed that high levels of serum HbA1c (≥11.06%) and IGF-1 (≥25.74 ng/ml) were risk factors for depression in patients with T2DM, and high level of serum miR-29b (≥0.39) was protective (P<0.05). Conclusions The serum levels of IGF-1 increased and miR-29b decreased in patients with type 2 diabetes mellitus and depression. Serum levels of miR-29b were negatively correlated with the levels of IGF-1. High levels of IGF-1 were risk factors for depression in patients with type 2 diabetes mellitus, and high levels of miR-29b were protective factors. Key words: MicroRNAs; Insulin-like growth factor I; Diabetes mellitus, type 2; Depressive disorder

Human Induced Pluripotent Stem Cell–Derived Cardiomyocyte Patch in Rats With Heart Failure

To treat chronic heart failure (CHF), we developed a robust, easy to handle bioabsorbable tissue-engineered patch embedded with human neonatal fibroblasts and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). This patch was implanted on the epicardial surface of the heart covering the previously infarcted tissue. Sprague-Dawley rats (6-8 weeks old) underwent sham surgery (n= 12) or left coronary artery ligation (n= 45). CHF rats were randomized 3 weeks after ligation to CHF control with sham thoracotomy (n= 21), or a fibroblasts/hiPSC-CMs patch (n= 24) was implanted. All sham surgery rats also underwent a sham thoracotomy. At 3 weeks after randomization, hemodynamics, echocardiography, electrophysiologic, and cell survival studies were performed. Patch-treated rats had decreased (P < .05) left ventricular-end diastolic pressure and the time constant of left ventricular relaxation (Tau), increased anterior wall thickness in diastole, and improved echocardiography-derived indices of diastolic function (E/e' [ratio of early peak flow velocity to early peak LV velocity] and e'/a' [ratio of early to late peak left ventricular velocity]). All rats remained in normal sinus rhythm, with no dysrhythmias. Rats treated with the patch showed improved electrical activity. Transplanted hiPSC-CMs were present at 7 days but not detected at 21 days after implantation. The patch increased (P < .05) gene expression of vascular endothelial growth factor, angiopoietin 1, gap junction α-1 protein (connexin 43), β-myosin heavy 7, and insulin growth factor-1 expression in the infarcted heart. Epicardial implantation of a fibroblasts/hiPSC-CMs patch electrically enhanced conduction, lowered left ventricular end-diastolic pressure, and improved diastolic function in rats with CHF. These changes were associated with increases in cytokine expression.

Feed additives can differentially modulate NF-κB (RelA/p65), IGF-1, GLUT2, and SGLT1 gene expression in porcine jejunal explants

ABSTRACT The intestinal gene expression of RelA/p65 (NF-κB), insulin growth factor 1 (IGF-1), glucose transporter 2 (GLUT2), and Na+/dependent glucose transporter 1 (SGLT1) were evaluated in response to benzoic acid, yeast culture, L-glutamine, and oregano essential oil, using an ex vivo model. Six piglets weighing approximately 20 kg each were sacrificed, and their jejunum was collected and segmented into five 2-cm explants. Each explant was immersed in cell culture medium according to one of the following treatments: control (without additive), [...]

Challenge with fumonisins B1 and B2 changes IGF-1 and GHR mRNA expression in liver of Nile tilapia fingerlings

Although fumonisins are identified as responsible for alterations in weight gain, little information is available on their effects on expression of growth-related genes, especially for Nile tilapia (Oreochromis niloticus) fingerlings. In this study, Nile tilapia fingerlings were treated with increasing levels of fumonisin B1 (FB1) and fumonisin B2 (FB2) (diets of 0, 20, 40, and 60 mg/kg) to evaluate their effects on weight gain (WG), feed intake (FI), feed efficiency (FE), growth hormone receptor (GHR) and insulin growth factor 1 (IGF-1) mRNA expression in liver of this fish. All variables were evaluated at 15 and 30 days of treatment. Diet containing 0 mg fumonisin/kg was used as control treatment. Treatment with 20, 40, and 60 mg fumonisin/kg of diet significantly reduced WG (P&lt;0.0001) and FE (P&lt;0.0001), while GHR and IGF-1 mRNA expression was reduced both at 15 and 30 days of treatment. Feed intake was not affected by diets in any of the evaluated periods. These results indicate that fumonisins (FB1 + FB2) affect the growth of Nile tilapia fingerlings through mechanisms that involve reduction of GHR and IGF-1 expression.

JiangTang XiaoKe granule attenuates cathepsin K expression and improves IGF-1 expression in the bone of high fat diet induced KK-Ay diabetic mice

AimTo assess the beneficial effects of JiangTang XiaoKe (JTXK) granule on the bone metabolism in high fat diet (HFD) fed KK-Ay diabetic mice. Materials and methodsThe KK-Ay mice were used as a diabetic model, while C57BL/6 mice were utilized as the non-diabetic control. The left tibia was used for determining bone mineral density (BMD) and bone ash coefficient. The HE and alizarin red S staining of femur were employed to evaluate bone pathology and calcium deposition. The expressions of alkaline phosphatase (ALP), insulin growth factor 1 (IGF-1) and cathepsin K were assessed by western blotting and immunohistochemical staining. Key findingsJTXK granule significantly improved the bone ash coefficient, the distribution of trabecular bone and the calcification nodules deposition in KK-Ay mice with diabetes. IGF-1 and ALP expressions were significantly decreased, and cathepsin K expression was dramatically increased in the HFD fed KK-Ay diabetic model mice, which can be reversed by JTXK granule treatment. JTXK granule at medium or high dosage was more efficient in improving diabetic bone quality when compared with that in mice with a low dosage. However, the BMD values in each group of KK-Ay diabetic mice were not significantly different. SignificanceWe demonstrate that cathepsin K expression is increased in KK-Ay diabetic mouse model. JTXK granule treatment inhibits osteoclastic bone resorption and promotes the new bone formation by decreasing cathepsin K activity and increasing IGF-1 and ALP levels. These changes may contribute to the increase of bone strength and thus reducing the risk of bone fractures.

Pretreatments with injured microenvironmental signals altered the characteristics of human umbilical cord mesenchymal stem cells.

Human umbilical cord mesenchymal stem cells (hUCMSCs) have renoprotective effects but the influence of the microenvironment on characteristics of hUCMSCs has not been well studied. Here, we investigate the effects of injury conditions on properties of hUCMSCs. hUCMSCs were treated in vitro under conditions mimicking the injury microenvironment of acute kidney injury. Cells stimulated with factor-treated medium proliferated slowly at first but quickly afterwards their morphology subsequently changed from spindle to stellate shape. Increased number of cells with strong expression of thymine-1 (Thy-1) or α-smooth muscle actin (α-SMA) was detected at 1 or 2 weeks after stimulation. Hepatocyte growth factor (HGF) level markedly increased after culture for 6 h under hypoxia condition. The expressions of HGF and insulin growth factor-1 (IGF-1) were significantly up-regulated from 0.22 ± 0.03 to 0.9 ± 0.02 and 0.07 ± 0.03 to 0.19 ± 0.01 in H/R-treated hUCMSCs respectively. Co-culture with injured renal tubular epithelial cells significantly promoted the expression of HGF (1.19 ± 0.21) and IGF-1 (0.24 ± 0.03) in hUCMSCs. The characteristics of hUCMSCs change in response to inured conditions, which may enhance the efficacy of stem cell therapy and provide novel strategies in maximizing biological and functional properties of hUCMSCs.

Protective Effects of Clenbuterol against Dexamethasone-Induced Masseter Muscle Atrophy and Myosin Heavy Chain Transition

BackgroundGlucocorticoid has a direct catabolic effect on skeletal muscle, leading to muscle atrophy, but no effective pharmacotherapy is available. We reported that clenbuterol (CB) induced masseter muscle hypertrophy and slow-to-fast myosin heavy chain (MHC) isoform transition through direct muscle β2-adrenergic receptor stimulation. Thus, we hypothesized that CB would antagonize glucocorticoid (dexamethasone; DEX)-induced muscle atrophy and fast-to-slow MHC isoform transition.MethodologyWe examined the effect of CB on DEX-induced masseter muscle atrophy by measuring masseter muscle weight, fiber diameter, cross-sectional area, and myosin heavy chain (MHC) composition. To elucidate the mechanisms involved, we used immunoblotting to study the effects of CB on muscle hypertrophic signaling (insulin growth factor 1 (IGF1) expression, Akt/mammalian target of rapamycin (mTOR) pathway, and calcineurin pathway) and atrophic signaling (Akt/Forkhead box-O (FOXO) pathway and myostatin expression) in masseter muscle of rats treated with DEX and/or CB.Results and ConclusionMasseter muscle weight in the DEX-treated group was significantly lower than that in the Control group, as expected, but co-treatment with CB suppressed the DEX-induced masseter muscle atrophy, concomitantly with inhibition of fast-to-slow MHC isoforms transition. Activation of the Akt/mTOR pathway in masseter muscle of the DEX-treated group was significantly inhibited compared to that of the Control group, and CB suppressed this inhibition. DEX also suppressed expression of IGF1 (positive regulator of muscle growth), and CB attenuated this inhibition. Myostatin protein expression was unchanged. CB had no effect on activation of the Akt/FOXO pathway. These results indicate that CB antagonizes DEX-induced muscle atrophy and fast-to-slow MHC isoform transition via modulation of Akt/mTOR activity and IGF1 expression. CB might be a useful pharmacological agent for treatment of glucocorticoid-induced muscle atrophy.