Expression Of Insulin-like Growth Factor Research Articles

Effects of amitraz plus-Parapoxvirus ovis on EGF, VEGF, IGF-1 and IGF-2 in canine generalized demodicosis

Objective. The purpose of the study is to investigate the effect of treatment with amitraz plus-Parapoxvirus ovis (IPPVO) on serum concentrations and skin expressions of insulin-like growth factor (IGF)-1 and -2, epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), in dogs suffering from generalised demodicosis (GD). Materials and Methods. Generalised demodicosis affected dogs were injected 1 ml IPPVO on days 0, 2 and 9 subcutaneously in addition to amitraz (0.025 %) treatment twice weekly for 80 days. IGF-1, IGF-2, EGF and VEGF concentrations in blood serum were measured by canine-specific enzyme-linked immunosorbent assay kit.  EGF, VEGF, IGF-1, and IGF-2 expressions in skin biopsy specimens were examined immunohistochemically. Results. After the treatment of the dogs with amitraz plus-IPPVO in GD, we demonstrated a significant reduction in both circulating concentrations and skin expressions of EGF, VEGF, IGF-1, and IGF-2, which have a role in preserving skin integrity and wound healing. Conclusions. Results of this study suggest that IGF-1, IGF-2 EGF, and VEGF have a crucial role in the progression of GD in dogs. It is believed that the findings from this study will contribute to the development of new strategies for the treatment of GD, which is an important health problem for dogs.

Impact of Glyphosate on the Development of Type-2 Diabetes in Adipose Tissue: Role of Insulin-Like Growth Factor 1 and Tumor Necrosis Factor Alpha Expression

Glyphosate, a commonly used herbicide in agricultural and residential settings, has sparked concerns regarding its potential health impacts. Despite numerous studies exploring potential associations between glyphosate exposure and diabetes, the precise mechanisms remain unclear. Tumor Necrosis Factor-alpha (TNF-α) and Insulin-Like Growth Factor 1 (IGF-1) are implicated in insulin resistance and pancreatic beta cell dysfunction, playing crucial roles in diabetes pathogenesis, especially Type 2 diabetes. This study aimed to assess the effect of glyphosate on TNF-α and IGF-1 expression in male Wistar rats. The results revealed a dose-dependent increase (p<0.05) in TNF-α and IGF-1 expression in adipose tissue following glyphosate exposure compared to the control group. These findings suggest that glyphosate exposure may contribute to the development of diabetes by altering the expression of IGF-1 and TNF-α.

Antioxidant Vitamins (Vit C and E) Protect the Kidney from Glyphosate- Exposed Renal Damage in Experimental Rats - A Molecular Study

Glyphosate is a widely used herbicide and the active ingredient in Monsanto's Roundup, among other herbicide formulations. Vitamin C (ascorbic acid) and vitamin E (tocopherol) are both antioxidants that play important roles in reducing oxidative DNA damage and protecting cells from the harmful effects of free radicals. The study aimed to analyse the effect of antioxidant vitamins (vitamins C and E) on the expression of IGF-1 and KIM-1 molecules in the kidneys of glyphosate-exposed rats. Adult male Albino Wistar rats were grouped into 3. Group I: Control; Group II: Glyphosate treated (100mg); Group III: Glyphosate+ vitamin E & C treated. Serum, insulin, and mRNA expression of insulin-like growth factor (IGF-1) and kidney injury molecules (KIM-1) mRNA expression by RT-PCR. Serum insulin was measured by the ELISA method. Glyphosate-exposed rats developed hyperglycaemia and hyper compared to control but antioxidant vitamins (Vitamin C and E) supplementation, reduced the glyphosate mediate increased fasting blood glucose and insulin near to that of the control level. Similarly, mRNA expression of both IGF-1 and KIM-1 were also significantly altered due to glyphosate induction whose effects were found to be reduced when vitamins C and E were treated. It is concluded that glyphosate exposure causes renal damage and develops diabetic nephropathy by modulating the expression of IGF-1 and KIM-1 molecules in the kidney. Vitamin C and E potentially were able to reduce the detrimental changes caused by glyphosate. Hence, vitamin C and E supplements could be considered therapeutic drugs for diabetic nephropathy.

Effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor, interleukin-6, and insulin-like growth factor-1 in monocyte in pre-frail older adults: A randomized double-blind placebo-controlled trial.

To investigate the effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor (VDR), interleukine-6 (IL-6) and insulin-like growth factor-1 (IGF-1) in monocyte in pre-frail older adults. We conducted a randomized double-blinded placebo-controlled clinical trial for 12 weeks, involving 120 pre-frail older adults who were randomized to the cholecalciferol group (cholecalciferol 4000 IU/day) or the placebo group. All subjects were given calcium lactate 500 mg/day. Hand grip strength and walking speed, as primary outcomes, were analyzed using intention-to-treat analysis. The expression of VDR, IGF-1 and IL-6 in monocytes, as secondary outcomes, were analyzed using per-protocol analysis. After a 12-week intervention, there was a significant increase in serum 25(OH)D levels in both groups, with the increase being higher in the cholecalciferol group than in the placebo group (49.05 vs. 24.01 ng/mL; P < 0.001). No statistically significant differences were observed in hand grip strength (P = 0.228) and walking speed (P = 0.734) between the groups. There were no differences in the expression of VDR (P = 0.513), IL-6 (P = 0.509), and IGF-1 (P = 0.503) monocytes between the groups. Cholecalciferol supplementation for 12 weeks increased serum 25(OH)D levels among pre-frail older adults. However, it did not improve hand grip strength and walking speed, and nor did it change the expression of VDR, IL-6, and IGF-1 in monocytes. Geriatr Gerontol Int 2024; ••: ••-••.

IGF-1 rs6218 polymorphisms modulate the susceptibility to age-related cataract.

Single nucleotide polymorphisms (SNPs), as the most abundant form of DNA variation in the human genome, contribute to age-related cataracts (ARC) development. Apoptosis of lens epithelial cells (LECs) is closely related to ARC formation. Insulin-like growth factor 1 (IGF1) contributes to cell apoptosis regulation. Moreover, IGF1 was indicated to exhibit a close association with cataract formation. Afterward, an investigation was conducted to examine the correlation between polymorphisms in IGF1 and the susceptibility to ARC. The present investigation was a case-control study. Venous blood draws were collected from the participants for DNA genotyping. Lens capsule samples were collected to detect mRNA and apoptosis. TaqMan RT-PCR was used to detect IGF1 polymorphism genotypes and qRT PCR was used to detect IGF1 mRNA levels in LECs. LEC apoptosis was evaluated through flow cytometry. The chi-square test was used to compare differences between ARCs and controls of each SNP. We found that the G allele frequency in the IGF1-rs6218 was higher in the ARCs than in the controls. Furthermore, it was observed that the rs6218 GG genotype exhibited a positive correlation to elevated levels of IGF1 mRNA in LECs. The IGF1 mRNA in the LECs and the apoptosis of LECs in nuclear type of ARCs (ARNC) was higher than the controls. The susceptibility to ARC was related to IGF1-rs6218 polymorphism, and this polymorphism is associated with IGF1 expression at the mRNA level. Moreover, apoptosis in LECs of ARNCs was found to be increased.

Insulin-like growth factor 1 knockdown attenuates high glucose-induced podocyte injury by promoting the JAK2/STAT signalling-mediated autophagy.

Podocyte injury plays a crucial role in the development of diabetic nephropathy (DN). A high serum level of insulin-like growth factor 1 (IGF-1) has been observed in patients with DN. This paper is to study the role and mechanism of IGF-1 in high glucose (HG)-induced podocyte injury. Mouse podocytes MPC-5 were treated with HG to establish a DN model in vitro. db/db diabetic mice and db/m nondiabetic mice were used to evaluate the IGF-1 role in vivo. Western blotting was used for measuring protein levels of IGF-1 receptor, Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway-related markers, podocyte markers podocin and nephrin, apoptosis- and autophagy-related markers in MPC-5 cells. Immunofluorescence staining was implemented for measuring the expression of nephrin and the autophagy marker LC3. Flow cytometry was used for detecting podocyte apoptosis. IGF-1 expression was increased in HG-stimulated MPC-5 cells and the kidney of db/db diabetic mice compared with corresponding controls. Knocking down IGF-1 downregulated IGF-1R and inhibited JAK2/STAT signalling pathway in HG-treated MPC-5 cells and db/db diabetic mice. IGF-1 silencing attenuated HG-induced podocyte injury, apoptosis and reduction in autophagy. Activating the JAK2/STAT signalling pathway or inhibiting autophagy reversed the effects of IGF-1 silencing on HG-treated MPC-5 cells. Knocking down IGF-1 alleviates HG-induced podocyte injury and apoptosis by inactivating the JAK2/STAT signalling pathway and enhancing autophagy.

Differential expression and clinical significance of IGF2BP3 in peritoneal dialysate of patients with varying duration of peritoneal dialysis.

This study aims to investigate the differential expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in the peritoneal dialysate among patients with different durations of peritoneal dialysis and its association with the angiogenic marker vascular* endothelial growth factor (VEGF), the fibronectin (FN), and various clinical indicators. A cohort of 122 peritoneal dialysis patients was categorized into short-term (≤1 year, n = 33), mid-term (>1 and ≤5 years, n = 55), and long-term (>5 years, n = 34) groups based on dialysis duration. We utilized enzyme-linked immunosorbent assay (ELISA) and western blot assays to quantify the levels of IGF2BP3, VEGF, and FN in the dialysate. Our findings showed a progressive increase in IGF2BP3 levels with the duration of PD, with the long-term group exhibiting significantly higher levels than both the short-term and mid-term groups (p < 0.001). A positive correlation between IGF2BP3 and VEGF (r = 0.386, p = 0.013), as well as between IGF2BP3 and FN (r = 0.340, p = 0.030), was observed. IGF2BP3 levels also correlated positively with serum creatinine, calcium, and phosphorus levels. Invitro analysis further confirmed that IGF2BP3 expression is enhanced in human peritoneal mesothelial cells under high-glucose conditions (p < 0.05). The study highlights the potential of IGF2BP3 in PD effluent as a biomarker for monitoring PF progression, with its expression significantly correlated with the duration of PD (Pearson r = 0.897, p < 0.001). In conclusion, our results underscore a correlation between elevated IGF2BP3 levels and PD duration, suggesting the clinical significance of IGF2BP3 as a biomarker for PF progression.

Aminophylline Improves Ventilator-Induced Diaphragmatic Dysfunction by Targeting IGF-1-FOXO1-MURF1 Pathway.

The usage of life-saving mechanical ventilation (MV) could cause ventilator-induced diaphragmatic dysfunction (VIDD), increasing both mortality and morbidity. Aminophylline (AP) has the potential to enhance the contractility of animal skeletal muscle fibers and improve the activity of human respiratory muscles, and the insulin-like growth factor-1 (IGF-1)- forkhead box protein O1 (FOXO1)-muscle RING finger-1 (MURF1) pathway plays a crucial role in skeletal muscle dysfunction. This study aimed to investigate the impact of AP on VIDD and to elucidate the role of the IGF-1-FOXO1-MURF1 pathway as an underlying mechanism. Rat models of VIDD were established through MV treatment. IGF-1 lentiviral (LV) interference (LV-IGF-1-shRNA; controlled by lentiviral negative control LV-NC) was employed to inhibit IGF-1 expression and thereby block the IGF-1-FOXO1-MURF1 pathway. Protein and mRNA levels of IGF-1, FOXO1, and MURF1 were assessed using western blot and real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), respectively. Diaphragm contractility and morphometry were examined through measurement of compound muscle action potentials (CMAPs) and hematoxylin and eosin (H&E) staining. Oxidative stress was evaluated by levels of hydrogen peroxide (H2O2), superoxide dismutase (SOD), antioxidant glutathione (GSH), and carbonylated protein. Mitochondrial stability was assessed by measuring the mitochondrial membrane potential (MMP), and mitochondrial fission and mitophagy were examined through protein levels of dynamin-related protein 1 (DRP1), mitofusin 2 protein (MFN2), phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1), and Parkin (western blot). Apoptosis was evaluated using the terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate (UTP) nick-end labeling (TUNEL) assay and levels of Bax, B-cell lymphoma 2 (BCL-2), and Caspase-3. Levels of Atrogin-1, neuronally expressed developmentally downregulated 4 (NEDD4), and muscle ubiquitin ligase of SCF complex in atrophy-1 (MUSA1) mRNA, as well as ubiquitinated protein, were utilized to determine protein degradation. Furthermore, the SUnSET (surface sensing of translation) method was employed to determine rates of protein synthesis. MV treatment upregulated IGF-1 while downregulated FOXO1 and MURF1 (p < 0.05). AP administration reversed IGF-1, FOXO1 and MURF1 (p < 0.05), which was suppressed again by IGF-1 inhibition (p < 0.05), demonstrating the blockage of the IGF-1-FOXO1-MURF1 pathway. MV treatment caused decreased CMAP and cross-sectional areas of diaphragm muscle fibers, and increased time course of CMAP (p < 0.05). Additionally, oxidative stress, cell apoptosis, and protein degradation were increased and mitochondrial stability was decreased by MV treatment (p < 0.05). Conversely, AP administration reversed all these changes induced by MV, but this reversal was disrupted by the blockage of the IGF-1-FOXO1-MURF1 pathway. In this study, MV treatment induced symptoms of VIDD in rats, which were all effectively reversed by AP regulating the IGF-1-FOXO1-MURF1 pathway, demonstrating the potential of AP in ameliorating VIDD.

Abstract 2136: Genetic ancestry dependent variability in stromal cells: An unexplored player in breast cancer disparity

Abstract Genetic ancestry dependent variability in cancer incidence, mutation patterns, response to chemotherapy, and outcome has been documented. While an association between social determinants of health and breast cancer disparity has already been established, there is emerging evidence for genetic ancestry dependent variability in normal breast biology impacting breast cancer biology and potentially outcome. Tumor biology studies in the context of genetic ancestry and disparity have often focused on intrinsic properties of tumor cells or tumor infiltrating immune cells. However, other stromal cell types have received very little attention. Through immunohistochemistry of breast tissues from healthy women of African and European ancestry and primary cell culturing system, we had previously demonstrated enrichment of a stromal cell population called PZP cells (PROCR+/ZEB1+/PDGFRA+) with mesenchymal stem-like and fibroadipogenic properties in the normal breast tissues of women of African ancestry. In this study, we used single nuclei ATAC-seq and/or RNA-seq to further characterize stromal fibroblasts in the breast tissues of women of Ashkenazi Jewish-European, European, Indigenous American, Hispanic-European, African, and Asian ancestry. Among eight fibroblast cell clusters generated from women of African and European ancestry, only three cell clusters overlapped between two groups. While Complement Factor D (CFD, also called adipsin) expression was observed in unique fibroblast clusters of African ancestry, the expression of Insulin-like Growth Factor 1 (IGF1) was enriched in clusters unique to European ancestry. Interestingly, previous studies have demonstrated African ancestry-specific genomic variants for CFD linked to cardiometabolic disorders. Additional genes that showed genetic ancestry dependent variability in expression within fibroblasts include ABCA10, ABCA9, ABCA8, NEGR1 (enriched in African ancestry), MMP16, MAGI1, KIAA1217, PTPRK and SEMA5A (enriched in European ancestry). NEGR1 (Neuronal Growth Regulator 1) is a trans-neural growth promoting factor, whereas PTPRK (Protein Tyrosine Phosphatase Receptor Type K) is a negative regulator of EGFR signaling. These results suggest genetic ancestry dependent variability in stromal-epithelial cell communications under normal and cancerous conditions. These genetic ancestry dependent differences could impact intracellular signaling networks in epithelial cells with consequential effects on cancer incidence, mutation patterns, drug sensitivity, and outcome. Citation Format: Poornima Bhat-Nakshatri, Hongyu Gao, Cihat Erdogan, Yunlong Liu, Harikrishna Nakshatri. Genetic ancestry dependent variability in stromal cells: An unexplored player in breast cancer disparity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2136.

The effects of nano-curcumin on growth performance, feed utilization, blood biochemistry, disease resistance, and gene expression in European seabass (Dicentrarchus labrax) fingerlings

Phytochemicals are used in fish farming to reduce stress and combat diseases during intensification. Recently, nanotechnology has represented a paradigm shift in the aquatic feed industry to improve the solubility, availability, and efficacy of phytochemicals. The purpose of this research was to investigate the effects of dietary supplementation with nano-curcumin (CUNE) on the growth, feed utilization, body composition, blood biochemistry, antioxidant status, disease resistance to Vibrio parahaemolyticus (V. parahaemolyticus), and the expression of insulin-like growth factor 1 (IGF-1), growth hormone (GH), interleukin-10 (IL-10), and interlukin-1β (IL-1β) genes in European Seabass (Dicentrarchus labrax) fingerlings. Fish (6.02±0.01) were randomly divided into four equal groups and fed varying levels of CUNE: 0 (CUNE0), 50 (CUNE1), 60 (CUNE2), and 70 mg/kg (CUNE3) of nano-curcumin for 56 days, respectively. The inclusion of dietary CUNE significantly improved the growth indices (final body weight and weight gain, and specific growth rate) and feed utilization (improved feed intake and lower FCR) of European seabass fingerlings (p<0.05). However, CUNE inclusion had no significant effect on body composition including the percentages of dry mater, crude protein, crude lipid, and ash (p>0.05). All CUNE groups established an enhancement in blood hematology in a dose-dependent manner, with CUNE3 demonstrating the highest values. CUNE supplementation (70 mg/kg diet) produced the highest levels of total protein, albumin, globulin, and triglycerides, as well as the lowest levels of glucose, and hepatic enzymes (ALT, AST, and ALP; p<0.05) compared to other groups. Furthermore, the CUNE-supplemented groups showed significant improvements in superoxide dismutase, catalase, and glutathione peroxidase, while reducing malondialdehyde (p<0.05). Additionally, the consumption of CUNE increased the expression of IGF-1, GH, and IL-10 genes in a dose-dependent manner (p<0.05). Interestingly, fish fed 70 mg of CUNE in their diets had lower expression of the IL-1β gene compared to the other groups (p<0.05). When the fish were challenged with V. parahaemolyticus, the addition of CUNE in their diets resulted in reduced mortality rates. Therefore, nano-curcumin could be considered as a natural feed additive to promote growth, feed utilization, and bacteria resistance via supporting antioxidant status, serum metabolites, and the regulation of GH, IL-10, and IGF-1 in the hepatic tissues of European seabass fingerlings.

Dietary feed nanozeolite, Pediococcus, and medium-chain fatty acid enhanced growth performance and transcription of growth-related gene of Nile tilapia (Oreochromis niloticus)

AbstractThe current trial was designed to evaluate the positive impacts of different feed additives singly or in combination on the growth performance, nutritional parameters, intestinal histology, and gene expression of some growth and fat metabolism-related genes in the liver tissue of Nile tilapia. The experimented fish were allocated into eight groups in a glass aquarium (10 fish/aquarium in triplicate) with Pediococcus acidilactici, nanozeolites, and/or medium-chain fatty acid additives. The studied treatments were control (T0), nanozeolite (T1), Pediococcus (T2), medium-chain fatty acid (T3), nanozeolite + Pediococcus (T4), nanozeolite + medium-chain fatty acid (T5), Pediococcus + medium-chain fatty acid (T6), and nanozeolite + Pediococcus + medium-chain fatty acid (T7). The results of the growth and nutritional parameters (i.e., final body weight, total weight gain, feed intake, specific growth rate, feed conversion ratio, and protein efficiency ratio) of tilapia-fed diets supplemented with Pediococcus, nanozeolites, and medium-chain fatty acids improved, but the combination of these additives was significantly more effective. Moreover, expression of growth hormone receptor 1 gene was upregulated (P ≤ 0.05) in T7 fish when compared with T0, other groups showing intermediate values. Expression of insulin-like growth factor-1 was upregulated (P ≤ 0.05) in T5, T6, and T7 fish when compared with the other groups. The expression of the fatty acid-binding protein was higher in T6 and T7 fish (P ≤ 0.05) when compared with T0, T1, and T3 fish. In conclusion, combined additives had significant effects on improving growth and regulating growth-related genes.

Ostarine blunts the effect of endurance training on submaximal endurance in rats.

The purpose of this study is to study the effects of ostarine alone and in combination with endurance training in sexually mature, male Wistar rats. The rats were divided into a treadmill-trained group and a sedentary group. Half of each group received either ostarine or vehicle for 8weeks (n = 10 each, in total n = 40). We examined some functional, hormonal, and anthropometric parameters and the myogenic gene expression of myostatin, insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor-A (VEGF-A) in m. gastrocnemius. Ostarine decreased submaximal endurance and increased myogenic gene expression of myostatin but had no effect on maximal time to exhaustion and grip strength. Training increased submaximal endurance, maximal time to exhaustion, and grip strength. Our results indicate that both exercise and ostarine treatment had no significant effects on serum levels of luteinizing hormone, follicle-stimulating hormone, and testosterone, or on the myogenic gene expression of IGF-1 and VEGF-A. Neither ostarine nor the training had a significant effect on the testis, liver, and heart weights. In conclusion,ostarine had no effect on anthropometric and hormonal parameters but increased the myostatin gene expression in muscle. The SARM treatment decreased submaximal endurance without affecting maximal time to exhaustion, and training increased both metrics.

Exosomal miR-223 promotes ARDS by targeting insulin-like growth factor 1 receptor: A cell communication study

Background Acute respiratory distress syndrome (ARDS) is a respiratory failure syndrome characterized by hypoxemia and changes in the respiratory system. ARDS is the most common cause of death in COVID-19 deaths was ARDS. In this study, we explored the role of miR-223 in exosomes in ARDS. Methods Exosomes were purified from the supernatants of macrophages. qPCR was used to detect relative mRNA levels. A luciferase reporter assay was performed to verify the miRNA target genes. Western blotting was used to detect the activation of inflammatory pathways. Flow cytometry was performed to assess apoptosis. An LPS-induced ARDS mouse model was used to assess the function of miR-223 in ARDS. Results Exosomes secreted by macrophages promoted apoptosis in A549 cells. Macrophages and exosomes contain high levels of miR-223. Exogenous miR-223 can decrease the expression of insulin-like growth factor 1 receptor (IGF-1R) in A549 and promote the apoptosis of A549.Transfection of anti-miR223 antisense nucleotides effectively reduced the level of miR-223 in macrophages and exosomes and eliminated the pro-apoptotic effect of A549. In vivo, LPS stimulation increased inflammatory cell infiltration in the lungs of mice, whereas knockdown of miR-223 in mice resulted in significantly reduced eosinophil infiltration. Conclusions Macrophages can secrete exosomes containing miR-223 and promote apoptosis by targeting the IGF-1R/Akt/mTOR signaling pathway in A549 cells and mouse models, suggesting that miR-223 is a potential target for treating COVID-19 induced ARDS.

Hsa_circ_0005320 affects cell proliferation and the cell cycle via the IGF2BP3/CDK2 axis in bladder cancer

BackgroundCircular RNAs (circRNAs), which are covalently closed non-coding RNAs, are frequently dysregulated in cancer. However, their precise role in bladder cancer (BCa) remains largely unknown. MethodsExpression of hsa_circ_0005320 in tissues and cell lines was detected using quantitative real-time PCR. Proliferation and colony forming capacity of BCa cells were assessed using Cell Counting Kit-8, ethynyl-labeled deoxyuridine, and colony formation assays. The cell cycle was analyzed using flow cytometry. Protein expression of insulin-like growth factor II mRNA-binding protein 3 (IGF2BP3) and cyclin dependent kinase 2 (CDK2) was examined using western blots. The binding of RNA and protein was validated using RNA immunoprecipitation. Additionally, xenograft tumor models were established to validate the function of hsa_circ_0005320 in vivo. ResultsWe screened hsa_circ_0005320 from previous high-throughput sequencing and found that it was highly expressed in BCa tissues and associated with tumor differentiation and depth of invasion in BCa patients. Through functional experiments, we demonstrated that hsa_circ_0005320 promoted cell proliferation and regulated the cell cycle. Mechanistically, hsa_circ_0005320 interacted with and upregulated the expression of IGF2BP3, which binds to and enhances the stability of CDK2 mRNA. Furthermore, knockdown of hsa_circ_0005320 resulted in a reduction in tumor burden in vivo. ConclusionsCollectively, these findings highlight the pro-oncogenic role of hsa_circ_0005320 in BCa through the IGF2BP3/CDK2 axis, providing valuable insights into the mechanism of circRNAs in tumor progression.

Association between Expression of Insulin-like Growth Factor-1 (IGF-1), IGF-1 Receptor (IGF-1R), and Hypertension-Mediated Organ Damage (HMOD) Parameters in Leukocytes and Plasma of Children/Adolescents with Primary Hypertension.

A decrease in IGF-1 is often linked to inflammation. Low systemic and local IGF-1 production and downregulation of IGF-1R expression may precede and predict PH development in children/adolescents. Leukocyte mRNA expression of IGF-1 and its receptor (IGF-1R) and plasma IGF-1 were measured in a group of 39 PH children/adolescents (29 boys and 10 girls) and 35 age-matched normotensive children (19 boys and 16 girls) using the RT-PCR and ELISA tests. The expression of the IGF-1R protein was assessed by flow cytometry. Plasma IGF-1 concentration was evaluated with ELISA. The expression of IGF-1 and IGF-1R and plasma concentrations of IGF-1 did not differ between groups. However, the PH children had a decreased percentage in IGF-1R-bearing lymphocytes (p = 0.02) and monocytes (p = 0.0003), as well as a low density of IGF-R in monocytes (p = 0.02). The IGF-1 expression was negatively correlated with pulse-wave velocity (PWV) (r = -0.49), systolic blood pressure (SBP) (-0.44), and carotid intima-media thickness (cIMT) (-0.43). The IGF-1R expression was negatively correlated with PWV (r = -0.42) and SBP (r = -0.41). Our results suggest that early subclinical hypertensive arterial injury is associated with lower activity of IGF-1-IGF-1R expression and loss of protective actions.

Identification of Insulin-like Growth Factor (IGF) Family Genes in the Golden Pompano, Trachinotus ovatus: Molecular Cloning, Characterization and Gene Expression.

Insulin-like growth factors (IGFs) are hormones that primarily stimulate and regulate animal physiological processes. In this study, we cloned and identified the open reading frame (ORF) cDNA sequences of IGF family genes: the insulin-like growth factor 1 (IGF1), insulin-like growth factor 2 (IGF2), and insulin-like growth factor 3 (IGF3). We found that IGF1, IGF2, and IGF3 have a total length of 558, 648, and 585 base pairs (bp), which encoded a predicted protein with 185, 215, and 194 amino acids (aa), respectively. Multiple sequences and phylogenetic tree analysis showed that the mature golden pompano IGFs had been conserved and showed high similarities with other teleosts. The tissue distribution experiment showed that IGF1 and IGF2 mRNA levels were highly expressed in the liver of female and male fish. In contrast, IGF3 was highly expressed in the gonads and livers of male and female fish, suggesting a high influence on fish reproduction. The effect of fasting showed that IGF1 and mRNA expression had no significant difference in the liver but significantly decreased after long-term (7 days) fasting in the muscles and started to recover after refeeding. IGF2 mRNA expression showed no significant difference in the liver but had a significant difference in muscles for short-term (2 days) and long-term fasting, which started to recover after refeeding, suggesting muscles are more susceptible to both short-term and long-term fasting. In vitro incubation of 17β-estradiol (E2) was observed to decrease the IGF1 and IGF3 mRNA expression level in a dose- (0.1, 1, and 10 μM) and time- (3, 6, and 12 h) dependent manner. In addition, E2 had no effect on IGF2 mRNA expression levels in a time- and dose-dependent manner. The effect of 17α-methyltestosterone (MT) in vitro incubation was observed to significantly increase the IGF3 mRNA expression level in a time- and dose-dependent manner. MT had no effect on IGF2 mRNA but was observed to decrease the IGF1 mRNA expression in the liver. Taken together, these data indicate that E2 and MT may either increase or decrease IGF expression in fish; this study provides basic knowledge and understanding of the expression and regulation of IGF family genes in relation to the nutritional status, somatic growth, and reproductive endocrinology of golden pompano for aquaculture development.

Impact of Growth Hormone on Microglial and Astrocytic Function.

The role of growth hormone (GH) in the central nervous system (CNS) involves neuroprotection, neuroregeneration, formation of axonal projections, control of cognition, and regulation of metabolism. As GH induces insulin-like growth factor-1 (IGF-1) expression in many tissues, differentiating the specific functions of GH and IGF-1 in the organism is a significant challenge. The actions of GH and IGF-1 in neurons have been more extensively studied than their functions in nonneuronal cells (e.g., microglial cells). Glial cells are fundamentally important to CNS function. Microglia, astrocytes, oligodendrocytes, and tanycytes are essential to the survival, differentiation, and proliferation of neurons. As the interaction of the GH/IGF-1 axis with glial cells merits further exploration, our objective for this review was to summarize and discuss the available literature regarding the genuine effects of GH on glial cells, seeking to differentiate them from the role played by IGF-1 action whenever possible.

Traditional Pediatric Massage Enhanced Hippocampal GR, BDNF and IGF-1 Expressions and Exerted an Anti-depressant Effect in an Adolescent Rat Model of CUMS-induced Depression

This study aimed to investigate the anti-depressant effect of traditional pediatric massage (TPM) in adolescent rats and its possible mechanism. The adolescent depression model in rats was established by using chronic unpredictable mild stress (CUMS). All rats were randomly divided into five groups (seven per group), including the groups of control (CON), CUMS, CUMS with TPM, CUMS with back stroking massage (BSM) and CUMS with fluoxetine (FLX). The tests of sucrose preference, Morris water maze and elevated plus maze were used to evaluate depression-related behaviors. Plasma corticosterone (CORT) level was measured by ELISA. The gene and protein expressions of glucocorticoid receptor (GR), brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) were measured by RT-qPCR and IHC respectively. The results showed that CUMS induced depression-related behaviors in the adolescent rats, along with decreased weight gain and reduced hippocampal expressions of GR, IGF-1 and BDNF. TPM could effectively prevent depression-related behaviors in CUMS-exposed adolescent rats, manifested as increasing weight gain, sucrose consumption, ratio of open-arm entry, times of crossing the specific quadrant and shortening escape latency. TPM also decreased CORT level in plasma, together with enhancing expressions of GR, IGF-1 and BDNF in the hippocampus. These results may support the clinical application of TPM to prevent and treat adolescent depression.

Novel insights into heat tolerance: the impact of dwarf and frizzled feather traits on crossbreed chicken performance under thermal stress

Heat stress (HS) poses significant challenges to broiler production, negatively influencing growth performance and meat quality. This study explores the resilience and the meat quality of hybrid chickens with dwarf size and frizzled feather traits to HS. We investigated F1 progeny derived from a crossbreed of dwarf yellow chickens (DYCs) with Yuexi frizzled feather chickens. Following a rearing period of 12 weeks, we randomly assigned 72 chickens into two distinct environmental conditions: a HS group subjected to 35 ± 1 °C for 8 h per day, and a control group (CN) maintained at 26 ± 1 °C. Seven days post-HS, multiple tissue samples were collected to assess meat quality attributes and measure expression levels of heat shock proteins (HSPs), muscle growth-related genes and cytokines. The results demonstrated a substantial reduction in weight gain of the F1 chickens exposed to HS, along with decreased expression of insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) in the liver. Furthermore, HS exposure significantly increased muscle shear force and the expression of HSP70 in both liver and pectoral muscle tissues (p < .05). Despite these changes, there were no significant alterations in the other meat quality indices, or indicators of splenic and hepatic tissue injury. Likewise, expression levels of growth hormone receptor (GHR) and cytokines remained stable, implying a lack of heightened inflammation. These observations suggest an inherent thermotolerance in the chickens possessing dwarf size and frizzled feather traits, warranting further exploration for their potential in heat-stress-prone poultry production environments. Highlights Dwarf and frizzled feather traits in crossbreed chickens show potential for improved heat tolerance in poultry production. Heat stress had limited impact on meat quality parameters, suggesting resilience of these local chicken traits. Understanding the genetic basis of thermotolerance can inform breeding strategies for climate-resilient chickens.

Phospholysine phosphohistidine inorganic pyrophosphate phosphatase suppresses insulin-like growth factor 1 receptor expression to inhibit cell adhesion and proliferation in gastric cancer.

Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has recently emerged as a novel tumor suppressor. Researchers have observed that LHPP plays a crucial role in inhibiting proliferation, growth, migration, invasion, and cell metabolism across various cancers. Nevertheless, the specific functions and underlying mechanisms of LHPP as a tumor suppressor in gastric cancer (GC) require further exploration. The expression of LHPP was assessed in human GC specimens and cell lines. Various assays were employed to evaluate the impact of LHPP on GC cells. RNA sequencing and Gene Set Enrichment Analysis were conducted to unravel the mechanism through which LHPP regulates GC cell behavior. Additionally, xenograft nude mouse models were utilized to investigate the in vivo effects of LHPP. The findings indicate that LHPP, functioning as a tumor suppressor, is downregulated in both GC tissues and cells. LHPP emerges as an independent risk factor for GC patients, and its expression level exhibits a positive correlation with patient prognosis. LHPP exerts inhibitory effects on the adhesion and proliferation of GC cells by suppressing the expression of insulin-like growth factor 1 receptor (IGF1R) and modulating downstream signaling pathways. Consequently, LHPP holds potential as a biomarker for targeted therapy involving IGF1R inhibition in GC patients.