Expression Of Insulin-like Growth Factor Research Articles

Mechanisms of Low Temperature-Induced Growth Hormone Resistance via TRPA1 Channel Activation in Male Nile Tilapia.

Low temperatures significantly impact growth in ectothermic vertebrates, though the underlying mechanisms remain poorly understood. This study investigates the role of transient receptor potential ankyrin 1 (TRPA1) channels in mediating low temperature effects on growth performance and growth hormone (GH) resistance in Nile tilapia (Oreochromis niloticus). Prolonged exposure to low temperature (16°C for 35 days) impaired growth performance and induced GH resistance, characterized by elevated serum GH levels and decreased insulin-like growth factor-1 (IGF-1) levels. Molecular analysis revealed tissue-specific upregulation of TRPA1 expression in the pituitary and liver under low-temperature conditions, concurrent with alterations in GH/IGF-1 axis-related gene expression. Pharmacological modulation of TRPA1 using an agonist mimicked low temperature effects on the GH/IGF-1 axis, while an antagonist reversed cold-induced hormonal changes. In vitro experiments with tilapia hepatocytes demonstrated that TRPA1 activation decreased IGF-1 expression through Ca2+/calmodulin-dependent pathways and disrupted GH-induced JAK2/STAT5 signaling. Additionally, TRPA1 activation induced GH receptor degradation primarily through lysosomal pathways, with partial involvement of proteasomal mechanisms. This study is the first to reveal that TRPA1 channels play a crucial role in mediating the effects of low temperature on GH resistance in fish, providing new insights into temperature regulation of endocrine function. The evolutionary conservation of TRPA1 and the GH/IGF-1 axis suggests potential relevance to stress-induced endocrine dysfunction in other vertebrates, including mammals.

Targeting IGF1 to alleviate obesity through regulating energy expenditure and fat deposition.

Insulin-like growth factor 1 (IGF1) is a regulator of both cellular hypertrophy and lipogenesis, which are two key processes for pathogenesis of obesity. However, the in vivo role of IGF1 in the development of obesity remains unclear. Here, we show that IGF1 expression is increased in adipose tissue in obese human patients and animal models. Elevation of IGF1 is associated with increased lipogenic gene expression and decreased energy expenditure. Genetic down-regulation of IGF1 normalizes lipogenic gene expression, restores aberrant energy metabolism and alleviates obese phenotype of a genetic mouse model with IGF1-hypersecretion. Importantly, genetic down-regulation of IGF1 exerts similar effects on development of diet-induced obesity. Furthermore, berberine that is an AMP-activated protein kinase (AMPK) activator in medicinal herbs inhibits IGF1 secretion, decreases lipogenic gene expression and alleviates diet-induced adiposity. Collectively, our findings demonstrate that hypersecretion of IGF1 is a critical factor for the development of obesity and can be targeted using AMPK activators to alleviate obesity.

Effect of selenium on the dysfunction of rat salivary glands induced by 131I and expression of insulin-like growth factors and aquaporins.

To investigate the effects of selenium on functional and histopathological changes and mRNA expression levels of insulin-like growth factors 1 and 2 (IGF-1 and -2) and aquaporins 4 and 5 (AQP-4 and -5) in 131I-induced damaged rat parotid glands. Rats were divided into three groups: iodotherapy-with-selenium, iodotherapy-only, and control. Rats in the iodotherapy-with-selenium group were intragastrically administered 131I on the first day and selenomethionine through drinking water. Rats in the iodotherapy-only group were only administered 131I. Changes in parotid gland function were evaluated using the functional parameters of salivary gland dynamics imaging pre-experiment and on days 7, 30, and 90 post-treatment. Immunofluorescence and quantitative real-time PCR analyses detected IGF-1, IGF-2, AQP-4, and AQP-5 expression levels in tissues. The gland-to background ratio at a maximum count (G/BGmax), Tmax/Tmin, and Smax values were significantly impacted over time in the iodotherapy-with-selenium group; on day 30, the G/BGmax value was significantly higher than that in the iodotherapy-only group. Histopathological analysis revealed that on days 30 and 90, the iodotherapy-with-selenium group displayed greater parotid gland repair than the iodotherapy-only group. In the iodotherapy-with-selenium group, fluorescence intensity and mRNA levels of AQP-5 increased with the selenium supplementation period, reaching significantly higher levels on days 30 and 90 than in the iodotherapy-only group. Whereas the fluorescence intensity and mRNA levels of IGF-1 in the iodotherapy-with-selenium group were significantly higher on day 7 than on day 30 in the iodotherapy-only group. Selenium may repair 131I-induced tissue and functional damage in rat salivary glands by upregulating AQP-5 and IGF-1 expression.

Adrenomedullin 2 attenuates anxiety-like behaviors by increasing IGF-II in amygdala and re-establishing blood–brain barrier

Anxiety disorder, a prevalent mental health issue, is one of the leading causes of disability worldwide. Damage to the blood–brain barrier (BBB) is implicated in anxiety, but its regulatory mechanisms remain unclear. Herein, we show that adrenomedullin 2 (ADM2), a novel angiogenic growth factor, alleviates autistic and anxiety-like behaviors in mice. Based on transcriptome analysis and biochemical analyses, we found that ADM2 facilitates the expression of insulin-like growth factor 2 (IGF-II), which then triggers the activation of the AKT-GSK3β-mTOR signaling pathway via the IGF-II receptor (IGF-IIR), rather than the IGF-I receptor (IGF-IR). Furthermore, as evidenced by increased Evans blue staining and decreased VE-cadherin levels, the BBB exhibited dysfunction in ADM2 knockout mice with anxiety-like behaviors. In in vitro studies, ADM2 administration promoted the expression of VE-cadherin and decreased IGF-II leakage through the endothelial barrier in a BBB model. Taken together, ADM2 may alleviate anxiety-like behavior and social deficits by enhancing BBB integrity and increasing IGF-II levels in the brain. These findings highlight the potential of ADM2 as a therapeutic target for anxiety and related mental disorders.

Mir-483-5p-mediated activating of IGF2/H19 enhancer up-regulates IGF2/H19 expression via chromatin loops to promote the malignant progression of hepatocellular carcinoma

BackgroundThe insulin-like growth factor 2 (IGF2) and H19 are overexpressed in hepatocellular carcinoma (HCC). IGF2-derived miR-483-5p is implicated in the development of cancers. Here, we investigated the involvement of miR-483-5p in IGF2 and H19 overexpression regulation and its role in HCC.MethodsFirstly, the effect of miR-483-5p on the expression of IGF2 and H19, and the binding of miR-483-5p to IGF2/H19 enhancer were evaluated in HCC cells. Next, miR-483-5p-mediated IGF2/H19 enhancer activation and its mechanism were investigated in HCC cells. Then, the mechanism by which active IGF2/H19 enhancer mediated by miR-483-5p activate IGF2/H19 promoters was studied in HCC cells. Finally, the effect of MED1 on the expression of IGF2/H19 as well as the malignant phenotype of HCC cells in vitro and in vivo mediated by miR-483-5p was evaluated.ResultsMir-483-5p up-regulated IGF2 P2 mRNA-P4 mRNA and H19 expression by binding to IGF2/H19 enhancer resulting in IGF2/H19 enhancer activation in HCC cells. Mechanistically, miR-483-5p increased recruitment of Ago1 and Ago2 at IGF2/H19 enhancer and then activated transcription of IGF2/H19 eRNA by RNA polymerase II and p300, which further induced chromatin loops formation between IGF2/H19 enhancer and IGF2/H19 promoters to activate IGF2/H19 promoters via IGF2/H19 eRNA-MED1-IGF2/H19 promoters complex in HCC cells. In this process, MED1 promoted chromatin loops formation as well as the malignant phenotype of HCC cells in vitro and in vivo mediated by miR-483-5p.ConclusionsmiR-483-5p-mediated activating of IGF2/H19 enhancer up-regulates IGF2/H19 expression via DNA loops, thereby promoting the malignant progression of HCC.

Role of insulin-like growth factor-2 in Alzheimer's disease induced memory impairment and underlying mechanisms.

Alzheimer's disease (AD) is the most prevalent type of dementia. Treatments for AD do not reverse the loss of brain function; rather, they decrease the rate of cognitive deterioration. Current treatments are ineffective in part because they do not address neurotrophic mechanisms, which are believed to be critical for functional recovery. Given that structural losses are assumed to be the root cause of cognitive impairment in AD, strengthening neurotrophic pathways may be a useful preventative therapeutic approach. Insulin-like growth factor-2 (IGF2), which is widely expressed in the central nervous system (CNS), has emerged as a crucial mechanism of synaptic plasticity and learning and memory, and many studies have indicated that this neurotrophic peptide is a viable candidate for treating and preventing AD-induced cognitive decline. An increase in IGF2 levels improves memory in healthy animals and alleviates several symptoms associated with neurodegenerative disorders. These effects are primarily caused by the IGF2 receptor, which is widely expressed in neurons and controls protein trafficking, synthesis, and degradation. However, the use of IGF2 as a potential target for the development of novel pharmaceuticals to treat AD-induced memory impairment needs further investigation. We compiled recent studies on the role of IGF2 in AD-associated memory issues and summarized the current knowledge regarding IGF2 expression and function in the brain, specifically in AD-induced memory impairment.

Network Pharmacology Combined With Metabolomics Reveals the Mechanism of Yangxuerongjin Pill Against Type 2 Diabetic Peripheral Neuropathy in Rats.

This study aims to explore the mechanism of Yangxuerongjin pill (YXRJP) in the treatment of diabetic peripheral neuropathy (DPN) by network pharmacology and metabolomics technology combined with animal experiments, and to provide scientific basis for the treatment of DPN. In this study, network pharmacology analysis was applied to identify the active compounds, core targets and signal pathways, which might be responsible for the effect of DPN. The DPN model was established by high-fat diet combined with streptozotocin (STZ) injection, and the rats were given administration for 12weeks. The body weight, thermal withdrawal latency (TWL), sciatic motor nerve conduction velocity (MNCV), biochemical indexes, pathological sections of sciatic nerve, oxidative stress factors and the expression levels of neuroprotection-related proteins were detected. Metabolomics technology was used to analyze the potential biomarkers and potential metabolic pathways in DPN treated with YXRJP. The results of network pharmacology showed that YXRJP could treat DPN through baicalin, β-sitosterol, 7-methoxy-2-methylisoflavone, aloe-emodin and luteolin on insulin resistance, Toll-like receptor (TLR), tumor necrosis factor (TNF) and other signaling pathways. YXRJP can prolong the TWL, increase the MNCV of the sciatic nerve, alleviate the injury of the sciatic nerve, reduce the levels of triglyceride (TG), improve the expression of Insulin-like growth factor 1 (IGF-1) protein in the sciatic nerve, and reduce the expression of protein kinase B (AKT) protein. Metabolomics results showed that the potential metabolic pathways of YXRJP in the treatment of DPN mainly involved amino acid metabolism such as arginine, alanine, aspartic acid, lipid metabolism and nucleotide metabolism. YXRJP can effectively improve the symptoms of DPN rats and reduce nerve damage. The effects are mainly related to reducing oxidative stress injury, promoting the expression of neuroprotection-related proteins, reducing the expression of inflammation-related proteins, and affecting amino acid metabolism, lipid metabolism, and nucleotide metabolism pathways. Our findings revealed that YXRJP has a good therapeutic potential for DPN, which provides a reference for further studies on YXRJP.

Effects of sunflower seeds powder on insulin related genes in high Fat diets fed and streptozotocin induced prediabetes in Wistar Rats

Obesity and prediabetes are significant global health issues that may progress to diabetes mellitus and associated complications. High-fat diets and streptozotocin treatment are known to contribute to these conditions. Sunflower seeds (Helianthus annuus), even at high doses have demonstrated potential in lowering blood sugar levels. This study investigated the effects of sunflower seed powder on insulin-related gene expression in Wistar rats subjected to a high-fat diet (HFD) and streptozotocin-induced prediabetes. A total of 27 male Wistar rats (350–400 grams) were randomly assigned to 9 groups and fed for 6 weeks. Pancreatic tissue was analyzed for gene expression of insulin (INS), insulin-like growth factor 1 (IGF-1), glucose transporter 2 (GLUT2), and insulin receptor (INSR). The results revealed that HFD and streptozotocin treatment decreased expression of INSR, IGF-1, and GLUT2 while increasing INSR expression. However, sunflower seed powder dietary supplementation significantly enhanced messenger ribonucleic acid (mRNA) expression of INS, IGF-1, GLUT2, and INSR, suggesting a potential preventing of prediabetes and insulin resistance. This study highlights the beneficial effects of sunflower seed powder in modulating key genes involved in insulin signaling and glucose metabolism, providing a potential therapeutic strategy for managing prediabetes and obesity-related metabolic disorders.

Systematic Review of Sarcopenia Biomarkers in Hip Fracture Patients as a Potential Tool in Clinical Evaluation.

Hip fractures are associated with high morbidity and mortality. Sarcopenia is a significant factor contributing to poor prognosis; however, the clinical diagnosis of sarcopenia remains difficult in surgical patients. This systematic review aims to identify the biomarkers of sarcopenia as diagnostic and predictive tools in patients admitted for hip fracture surgery. A systematic search was conducted in the MEDLINE, EMBASE, and Google Scholar databases according to the PRISMA guidelines. Biomarker study quality was assessed using the BIOCROSS score. A total of 7 studies met the inclusion criteria and 515 patients were included, of whom 402 (78%) were female and 113 (22%) were male. The mean age of the participants was 83.1 years (SD: 5.9). Skeletal muscle biopsies were used for biomarker assessment in 14% (1/7) of studies and venous blood samples were used in the remaining 86% (6/7). The highlighted sarcopenia biomarkers included the low expression of insulin-like growth factor (IGF-I) and tumor necrosis factor-α (TNF-α), along with high serum myostatin and low serum vitamin D levels. Overall, the BIOCROSS score was satisfactory, with all studies obtaining at least a score of 13/20. The orthopedic literature is limited; however, the highlighted biomarkers in this review could be used as adjuncts in the diagnosis of sarcopenia in surgical patients.

PPARγ alleviates damage to chorionic trophoblast cells induced by high glucose and high lipids through regulation of IGF-1.

Overweight and obesity are the most common high-risk conditions that increase the risk of adverse outcomes during pregnancy, childbirth, and the postpartum period. Dysfunctions in trophoblastic peroxisome proliferator-activated receptor gamma (PPARγ) contribute to a variety of related pregnancy disorders. This study investigated whether PPARγ influences chorionic trophoblast cell damage induced by high glucose (HG) and high lipid (HL) by regulating insulin-like growth factor-1 (IGF-1). Human trophoblast HTR-8/SVneo cells were exposed to HG and HL conditions to simulate damaged trophoblasts during pregnancy in vitro. Cell Counting Kit-8 (CCK-8) was used to assess cell proliferation. The Scratch test was used to test cell migration. Cell invasion ability was assessed by Transwell assay. ELISA was used to assess the inflammatory factor levels. Glucose, lactic acid, and adenosine triphosphate (ATP) levels were measured using biochemical kits. High glucose/HL inhibited the proliferation, migration, and invasion of HTR-8/SVneo cells. High glucose and HL increased tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6 expression while decreasing IL-10 expression. High glucose and HL decreased glucose uptake and ATP levels. High glucose and HL reduced the expressiofns of PPARγ, IGF-1, insulin receptor substrate (IRS) 1, IRS2, GLUT1, and GLUT4. High PPARγ expression promoted cell proliferation, migration, and invasion induced by HG and HL, increased glucose uptake and ATP levels and inhibited inflammation. Low IGF-1 expression inhibited cell proliferation, migration, and invasion under HG and HL conditions, reduced glucose uptake and ATP levels, and increased inflammation. Low IGF-1 expression reversed the effects of PPARγ on HTR-8/SVneo cells under HG and HL conditions. Peroxisome proliferator-activated receptor gamma alleviated HTR-8/SVneo cell damage induced by HG and HL by regulating IGF-1, suggesting a potentially effective approach for treating gestational obesity.

Loss of Pigment Epithelium Derived Factor Sensitizes C57BL/6J Mice to Light-Induced Retinal Damage.

Pigment epithelium-derived factor (PEDF) is a neurotrophic glycoprotein secreted by the retinal pigment epithelium (RPE) that supports retinal photoreceptor health. Deficits in PEDF are associated with increased inflammation and retinal degeneration in aging and diabetic retinopathy. We hypothesized that light-induced stress in C57BL/6J mice deficient in PEDF would lead to increased retinal neuronal and RPE defects, impaired expression of neurotrophic factor Insulin-like growth factor 1 (IGF-1), and overactivation of Galectin-3-mediated inflammatory signaling. C57BL/6J mice expressing the RPE65 M450/M450 allele were crossed to PEDF KO/KO and wildtype (PEDF +/+) littermates. Mice were exposed to 50,000 lux light for 5 hours to initiate acute damage. Changes in visual function outcomes were tracked via electroretinogram (ERG), confocal scanning laser ophthalmoscopy(cSLO), and spectral domain optical coherence tomography (SD-OCT) on days 3, 5, and 7 post-light exposure. Gene and protein expression of Galectin-3 were measured by digital drop PCR (ddPCR) and western blot. To further investigate the role of galectin-3 on visual outcomes and PEDF expression after damage, we also used a small-molecule inhibitor to reduce its activity. Following light damage, PEDF KO/KO mice showed more severe retinal thinning, impaired visual function (reduced a-, b-, and c-wave amplitudes), and increased Galectin-3 expressing immune cell infiltration compared to PEDF +/+. PEDF KO/KO mice had suppressed damage-associated increases in IGF-1 expression. Additionally, baseline Galectin-3 mRNA and protein expression were reduced in PEDF KO/KO mice compared to PEDF +/+. However, after light damage, Galectin-3 expression decreases in PEDF +/+ mice but increases in PEDF KO/KO mice without reaching PEDF +/+ levels. Galectin-3 inhibition worsens retinal degeneration, reduces PEDF expression in PEDF +/+ mice, and mimics the effects seen in PEDF knockouts. Loss of PEDF alone does not elicit functional defects in C57BL/6J mice. However, under light stress, PEDF deficiency significantly increases severe retinal degeneration, visual deficits, Galectin-3 expression, and suppression of IGF-1 than PEDF +/+. PEDF deficiency reduced baseline expression of Galectin-3, and pharmacological inhibition of Galectin-3 worsens outcomes and suppresses PEDF expression in PEDF +/+, suggesting a novel co-regulatory relationship between the two proteins in mitigating light-induced retinal damage.

Effect of Different Regional Characteristics of Spawning and Growing Sites on Growth and Taste of Pacific Oyster, Crassostrea gigas.

While Pacific oysters are important commercial aquaculture species worldwide, the effect of hormonal regulation and environmental conditions on growth and taste profile have not been fully known. Insulin-like growth factor (IGF) systems are known to play a major role in regulating neuroendocrine functions across various physiological processes and are particularly involved in growth. IGFs expression also is directly related to the nutritional status of vertebrates, however, full mechanism has not been clearly identified in bivalves. In this study, differences in growth, IGFs expression, and taste according to cultivation site of Pacific oysters were investigated. Oysters were collected in three different spawning sites located on the south coast of Korea in July 2022 and hardened until June 2023. Then, the oysters were cultured in two different growing sites (Tongyeong site, TS; Geoje site, GS) for six months. The total weight of oysters, along with their condition index and tissue weight rate, was significantly higher in TS. Additionally, IGF expression was higher in TS during most of the sampled months. However, oysters from the GS scored higher in taste evaluations. The IGFs system in oysters shows a similar trend to previous studies, with higher levels in faster-growing individuals, suggesting oysters in TS were more adequately nourished by the surrounding environment in this research. However, in taste evaluation, oysters from the GS showed better results than those from the TS. Despite these results, determining whether one site is superior in certain aspects is still not fully possible, which warrants further investigations.

A011: Effects of Aerobic Exercise on Microbiota

Background/Objective: Gut flora plays an important role in host stress response, anxiety, depression and cognitive function through the gut-brain axis. Microbial diversity decreases with age, which in turn affects the function of the nervous system. The role of exercise in the prevention and treatment of age-related diseases and neurodegenerative diseases has received increasing attention. The purpose of this study was to elucidate the regulatory role of intestinal flora, gut-brain axis and nervous system function in the prevention of nervous system function decline in the elderly. Methods: The sample consisted of 16, 52-week-old SPF C57BL/6 male mice that were randomly divided into two groups: a old control group (OC) and an old treadmill exercise group (OE). The mice underwent 16 W moderate intensity incremental load exercise. ELISA was used to detect 5-Hydroxytryptamine (5-HT), gamma-aminobutyric acid (GABA) and Dopamine (DA) in the hippocampus. Serum and hippocampal glutamate and serum Acetylcholine (ACH) were determined by ultraviolet colorimetry. The expression of insulin-like growth factors 1 (IGF1) and brain-derived neurotrophic factor (BDNF) in hippocampus and vascular epithelial growth factor (VEGF) were measured by Western blot. Fecal samples were collected and analyzed by 16S rDNA sequencing. Results: (1) 5-HT and Glu in the hippocampus (P < 0.01), and DA and GABA in the hippocampus were significantly increased (P < 0.05) after aerobic exercise. Serum Glu and serum Ach in aerobic exercise group were significantly higher than those in the control group (P < 0.01). (2) The expression of BDNF, VEGF and IGF1 in the hippocampus of naturally aged mice were significantly increased after aerobic exercise (P < 0.01). (3) The results of Alpha diversity analysis showed that Shannon index, Simpson index and Chao1 in OE group were significantly increased compared with those in OC group (P < 0.01). The relative abundances of Bacteroidetes and Parasicutes were significantly increased, while the relative abundances of Proteobacteria in naturally aged mice were significantly decreased (P < 0.01) after aerobic exercise. Conclusions: The composition of intestinal flora and the expression of central neurotransmitters in elderly mice were significantly improved after 16 weeks of moderate-intensity aerobic exercise with incremental load. The expression of adult hippocampal neurogenesis (AHN)-related proteins in hippocampus: VEGF, IGF1 and BDNF were significantly improved, and neurogenesis was promoted. Intestinal microbiota - gut - brain axis plays an important role in the improvement of hippocampal neurogenesis in elderly mice.

Investigation the impact of turmeric supplementation on mRNA expression of growth-related peptides and gut health in broilers

Antibiotic resistance has prohibited its use for non-therapeutic purposes in livestock. Recent studies have suggested that turmeric, a natural compound, could serve as a potential alternative to antibiotics in promoting growth in chickens. Therefore, this study aimed to determine the effects of turmeric supplementation on the gene expression of growth-related peptide and mucin2, an indicator of intestinal health, in broilers. We added two percentages of turmeric (0.5% and 1%) to the standard diet, categorizing them as turmeric 0.5% and turmeric 1%, and compared the results with the control group (turmeric 0.0%). Gene expression analysis was conducted anterior pituitary (APit), liver, and intestine. The results showed that body weight gain was higher in the turmeric-treated groups, and feed conversion ratio was improved significantly, indicating that turmeric is more efficient in converting feed into body mass. Analysis of gene expression by RT-qPCR revealed an increase in mucin2 gene expression in the turmeric-treated groups, suggesting an enhancement of gut health. Furthermore, the study found overexpression of the growth hormone (GH) and thyroid-stimulating hormone mRNA expression in the APit. In the liver, an increase in the mRNA expression of the GH receptor in the turmeric-treated groups could facilitate GH action on hepatocytes, leading to an increase in the gene expression of insulin-like growth factors and their binding proteins, which supports muscle cell differentiation and proliferation. Data suggested that turmeric might stimulate myoblast differentiation and satellite cell proliferation to increase muscular growth. In summary, turmeric addition promoted body growth by activating certain genes and inhibiting others. This effect could be due to an increase in the expression of genes that drive muscle cell proliferation. Finally, turmeric enhances gut health through the mucin2 gene.

Improved growth and immunity in Nile tilapia Oreochromis niloticus fed a fermented rice bran supplement

Improvement of growth performance and disease resistance of cultured species is an important objective of the aquaculture industry. In this study, solid-state fermentation (SSF) was applied for increasing the nutritional value of rice bran with baker's yeast (Saccharomyces cerevisiae). Four diets containing different levels of fermented rice bran (FRB) at 0, 100, 200 and 300 g/kg (FRB0, FRB10, FRB20 and FRB30, respectively) were tested using juvenile Nile tilapia Oreochromis niloticus (average body weight = 5.22±0.02 g) for 56 days. Compared to FRB0, all diets improved growth performance of the experimental fish (P<0.05). Intestinal amylase and protease amounts were significantly increased (P<0.05). The experimental fish were intraperitoneally injected with Streptococcus agalactiae and the cumulative mortality rate was monitored for 10 days. All FRB-supplemented diets resulted in greater survival rates in challenge fish. The FRB20 and FRB30 diets promoted expression of insulin-like growth factor I (IGF-I) transcripts and enhanced non-specific immunity; lysozyme and antioxidant enzyme activities; myeloperoxidase (MPO), catalase (CAT), and superoxide dismutase (SOD) (P<0.05). The expression level of interleukin 8 (IL-8) was down-regulated in fish fed FRB20 and FRB30 (P<0.05) but IL-10 was up-regulated in fish fed FRB10 and FRB30 (P<0.05) while IL-1β was up-regulated in fish fed FRB20 (P<0.05). The expression of complementary 3 (C3) transcripts was significantly increased while nuclear factor-kappa B (NF-κB) was decreased in fish fed all FRB-supplemented diets (P<0.05). Conventional histology revealed increased villus height following FRB30 treatment (P<0.05). These results suggest the beneficial use of FRB supplementation on growth, immune defense and stress tolerance for juvenile O. niloticus.

Late-gestation maternal undernutrition induces circulatory redistribution while preserving uteroplacental function independent of fetal glycaemic state.

Programming effects of maternal undernutrition on fetal metabolic and cardiovascular systems are well elucidated, yet a detailed characterization of maternal haemodynamics is not available. This study used comprehensive cardiovascular magnetic resonance (CMR) imaging to quantify maternal haemodynamics after 29days (111-140 days) of late-gestation undernutrition (LGUN) in pregnant sheep. Control ewes received 100% of metabolizable energy requirements (MERs, n=15), whereas LGUN ewes were globally nutrient restricted to 50% MER (n=18), with a subset of fetuses undergoing continuous glucose infusion (LGUN+G, n=6/18). Ewes underwent CMR (138-140 days' gestation), and placental tissue was collected the next day. Ewes in both LGUN groups had reduced body weight and mean blood glucose concentration across gestation. Ventricular dimensions were lower in both LGUN groups. Uterine artery blood flow (QUtA) was elevated in the LGUN group compared with controls, whereas peripheral blood flow was reduced and further diminished in LGUN+G. Maternal weight change correlated with all haemodynamic parameters across all groups. Uteroplacental oxygen and glucose delivery were increased in LGUN compared to control ewes, whereas uteroplacental oxygen consumption was preserved. LGUN did not impact placental or fetal weight, and markers of brain-sparing physiology were absent. Placental expression of insulin-like growth factors (IGF-1 and IGF-2) and their receptors, glucose, fatty acid (FA) or amino acid transporters and markers of angiogenesis was not impacted. FA transporter expression was positively correlated with QUtA, and FA binding protein correlated negatively with maternal weight change. Maternal cardiovascular adaptations in response to LGUN manifest as preservation of placental growth and function, thereby preserving fetal growth. KEY POINTS: Maternal undernutrition during pregnancy alters fetal metabolic and cardiovascular physiology, but little is known about alterations in maternal haemodynamics. Late-gestation undernutrition (LGUN) and LGUN+G redirected maternal blood flow from the periphery to the uteroplacental unit, concomitantly increasing the delivery of glucose and oxygen to the uteroplacental unit. Substrate transporter expression and uteroplacental oxygen consumption were preserved in LGUN and LGUN+G, suggesting prioritization of the placenta. This study is the first to report detailed maternal haemodynamics in the setting of maternal undernutrition, where placental growth and function were maintained, ultimately preserving fetal oxygen metabolism and growth.

Assessment of the nutritional impact of substituting fishmeal with enzymatically hydrolyzed jojoba meal (Simmondsia chinensis) in the diets of Nile tilapia, Oreochromis niloticus

Enzymatic hydrolysis is a technology that is widely used to enhance the biological and functional characteristics of plant proteins and deactivate anti-nutritious components. In order to tackle this pressing issue, considerable research has been conducted on plant-based proteins as a potential substitute. This study sought to comprehensively examine the impacts of replacing fish meal with enzymatically hydrolyzed jojoba meal (EHJM) in the Nile tilapia, Oreochromis niloticus diets. After the enzymatic hydrolysis process for jojoba meal, hydrolyzed amino acid content increased in enzymatically hydrolyzed jojoba meal (EHJM), while fiber content, phytic acid, saponins, and trypsin inhibitors dramatically decreased. A thorough evaluation of key parameters included growth, gene expression, digestive enzyme activity, digestibility, intestinal histomorphometry, biochemical indicators, and antioxidant enzyme activity. Fish (n = 360, 6.41 ± 0.05 g fish−1) were allocated at random to four groups consisting of four replacement levels of fishmeal protein content with EHJM: 0 % (control diet), 25 % (EHJM25), 50 % (EHJM50) and 75 % (EHJM75) for 74 days. The results showed both the control diet and the EHJM25 groups showed remarkable improvements in performance metrics such as final body weight, specific growth rate, weight gain, feed conversion ratio, and protein efficiency ratio, with no discernible variations between them. The inclusion of EHJM up to 50 % produced a noteworthy (P < 0.05) rise in the intestinal lipase and amylase activities. Furthermore, a high apparent digestibility coefficient for crude lipid and protein values was observed in EHJM25% and EHJM50%. The presence of EHJM up to 25 % in tilapia diets, as a substitute for FM, had a significant impact (P < 0.05) on various parameters in the intestine, including goblet cells, muscularis mucosa, villi height, villi width, absorption area, and height muscularis. Moreover, the inclusion of EHJM with different levels in tilapia diets resulted in a noticeable reduction (P < 0.05) in alkaline phosphatase (ALP) and serum alanine aminotransferase (ALT) levels, with fish given the EHJM75% diet showing the lowest amounts in their plasma. In addition, the amount of plasma total protein, albumin, and globulin were found to rise sharply with the escalating replacement of EHJM in fish diet, reaching the highest values in the EHJM25% and EHJM50% diets. Interestingly, the catalase (CAT) and superoxide dismutase (SOD) levels in fish that were given the control diet and EHJM25% showed a remarkable increase compared to the other treatments (P < 0.05). Fish fed EHJM50% diet had the highest glutathione peroxidase and the lowest malondialdehyde levels. In addition, the fish that were fed the control diet exhibited the highest expression of insulin-like growth factor and growth hormone genes, compared to those fed the EHJM25% diet. Based on the results, the EHJM25% and EHJM50% diets were more effective than the EHJM75% diet in improving the efficiency of Nile tilapia. The inclusion of EHJM in Nile tilapia diets had a neutral effect on growth indices compared to a fishmeal diet (control diet). The optimal replacement level is 55.3 %.

Characterization of a novel IGFBP-2 transcript in the ovarian granulosa cells of chicken follicles: mRNA expression, function and effect of reproductive hormones and IGF1

Insulin-like growth factor binding protein-2 (IGFBP-2), a binding protein of insulin-like growth factor (IGF) system, regulates the activity of IGFs and also influences cellular function with endogenous activity. In mammals, IGFBP-2 is reported to affect ovarian follicle development and steroidogenesis; however, its role in the chicken ovary is unknown. In this study, we investigated the mRNA expression and function of a novel IGFBP-2 transcript and the effect of reproductive hormones and insulin-like growth factor 1 (IGF1) on its expression in the ovarian granulosa cells of chicken follicles. The mRNA expression of IGFBP-2 was significantly increased in granulosa cells after follicle selection and was higher in hierarchical granulosa cells (Post-GCs) than in pre-hierarchical granulosa cells (Pre-GCs). IGFBP-2 promoted the proliferation and inhibited the apoptosis of both Pre-GCs and Post-GCs, enhanced the mRNA expression of genes involved in progesterone (P4) synthesis in Pre-GCs. However, in Post-GCs, IGFBP-2 inhibited the mRNA expression of these genes and suppressed P4 secretion. The mRNA expression of IGFBP-2 was inhibited by estradiol (E2) and follicle-stimulating hormone (FSH), but enhanced by P4 in Pre-GCs. In Post-GCs, FSH and IGF1 stimulated the mRNA expression of IGFBP-2 synergistically. Knockdown of IGFBP-2 attenuated the stimulatory effect of IGF1 on the mRNA expression of the side chain cleavage enzyme cytochrome P450 family 11 subfamily A member 1 (CYP11A1). These findings indicate that IGFBP-2 is regulated by FSH and IGF1, exerts different functions in Pre-GCs and Post-GCs in regulating IGF1 and plays an important role in chicken follicle development by affecting granulosa cell proliferation and P4 synthesis.

IGF-1 impacts neocortical interneuron connectivity in epileptic spasm generation and resolution

Little is known about the mechanisms that generate epileptic spasms following perinatal brain injury. Recent studies have implicated reduced levels of Insulin-like Growth Factor 1 (IGF-1) in these patients’ brains. Other studies have reported low levels of the inhibitory neurotransmitter, GABA. In the TTX brain injury model of epileptic spasms, we undertook experiments to evaluate the impact of IGF-1 deficiencies on neocortical interneurons and their role in spasms. Quantitative immunohistochemical analyses revealed that neocortical interneurons that express glutamic acid decarboxylase, parvalbumin, or synaptotagmin 2 co-express IGF-1. In epileptic rats, expression of these three interneuron markers were reduced in the neocortex. IGF-1 expression was also reduced, but surprisingly this loss was confined to interneurons. Interneuron connectivity was reduced in tandem with IGF-1 deficiencies. Similar changes were observed in surgically resected neocortex from infantile epileptic spasms syndrome (IESS) patients. To evaluate the impact of IGF-1 deficiencies on interneuron development, IGF-1R levels were reduced in the neocortex of neonatal conditional IGF-1R knock out mice by viral injections. Four weeks later, this experimental maneuver resulted in similar reductions in interneuron connectivity. Treatment with the IGF-1 derived tripeptide, (1–3)IGF-1, abolished epileptic spasms in most animals, rescued interneuron connectivity, and restored neocortical levels of IGF-1. Our results implicate interneuron IGF-1 deficiencies, possibly impaired autocrine IGF-1 signaling and a resultant interneuron dysmaturation in epileptic spasm generation. By restoring IGF-1 levels, (1–3)IGF-1 likely suppresses spasms by rescuing interneuron connectivity. Results point to (1–3)IGF-1 and its analogues as potential novel disease-modifying therapies for this neurodevelopmental disorder.

IGF2BP3/CTCF Axis-Dependent NT5DC2 Promotes M2 Macrophage Polarization to Enhance the Malignant Progression of Lung Squamous Cell Carcinomas.

Lung squamous cell carcinoma (LUSC) is a type of lung cancer that develops in the squamous cells. It is known to be promoted by the activation of various signaling pathways and the dysregulation of key regulatory molecules. One such molecule, 5'-nucleotidase domain containing 2 (NT5DC2), has been identified as a critical regulator in various cancers including lung cancer. However, there are no data regarding its role in LUSC. The mRNA expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), CCCTC-binding factor (CTCF), and NT5DC2 was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR), whereas their protein expression was assessed using a western blotting assay. Cell proliferation was determined using a cell counting kit-8 (CCK-8) assay. Cell apoptosis, CD11b expression, and CD206 expression were analyzed using flow cytometry. Tube formation was assessed through a tube formation assay. Glucose consumption, lactate production, and ATP levels were measured using colorimetric methods. The effect of NT5DC2 on the malignant progression of LUSC cells was analyzed using a xenograft mouse model assay. The levels of transforming growth factor-beta 1 (TGF-β1) and interleukin-10 (IL-10) were detected using enzyme-linked immunosorbent assays. The associations among IGF2BP3, CTCF and NT5DC2 were identified using dual-luciferase reporter assay, RNA immunoprecipitation assay and m6A RNA immunoprecipitation assay. The expression of NT5DC2 was found to be upregulated in LUSC tissues and cells when compared with normal lung tissues and normal human bronchial epithelial cells. Silencing of NT5DC2 inhibited LUSC cell proliferation, tube formation, glycolysis, M2 macrophage polarization, and tumor formation while inducing cell apoptosis. In addition, CTCF was found to transcriptionally activate NT5DC2 in LUSC cells. IGF2BP3 stabilized the mRNA expression of CTCF through m6A methylation. Further, overexpression of CTCF or NT5DC2 attenuated the effects of IGF2BP3 silencing in both NCI-520 and SK-MES-1 cells. The IGF2BP3/CTCF axis-dependent NT5DC2 promotes M2 macrophage polarization, thereby enhancing the malignant progression of LUSC. This study was the first to reveal the role of NT5DC2 in LUSC and the underlying mechanism. The result suggests that targeting the IGF2BP3/CTCF/NT5DC2 axis may have clinical significance in the treatment of LUSC.