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Objective: To examine the correlation between serum insulin-like growth factor 1 (IGF-1) and osteoporosis (OP) in Parkinson's disease (PD). Methods: We retrospectively analyzed clinical data from 105 PD patients (PD group) and 78 individuals in the health examination group (HC group). We compared general clinical data and serum IGF-1 levels between the two groups. PD patients were further categorized into PD with OP (50 cases) and PD without OP (55 cases) based on dual-energy X-ray absorptiometry (DXA) results for bone density. We compared general clinical data and serum IGF-1 levels between these two subgroups. Pearson correlation coefficient analysis was conducted to assess the relationship between serum IGF-1 levels and bone density at the lumbar spine and left femoral neck. Multifactorial logistic regression analysis was performed to identify risk factors for PD with OP. Results: Serum IGF-1 levels were significantly lower in the PD group compared to the HC group (P < 0.05). Pearson correlation analysis revealed a positive association between serum IGF-1 levels and both lumbar spine and left femoral neck bone densities (r = 0.653, P < 0.001; r = 0.625, P < 0.001). Multivariate logistic regression analysis identified decreased serum IGF-1 levels, lower uric acid levels, and higher H-Y stage as risk factors for PD with OP (P < 0.05). Conclusion: Reduced levels of serum IGF-1, uric acid, and an increased H-Y stage are closely linked to osteoporosis in PD. Elevating serum levels of IGF-1 and uric acid may potentially offer therapeutic avenues for PD with osteoporosis. [ABSTRACT FROM AUTHOR]

Small extracellular vesicles (sEV) have emerged as a novel mode of intercellular material transport and information transmission. It has been suggested hormones may regulate the production and function of sEV. However, the specific impact of growth hormone-releasing hormone (GHRH) on pituitary sEV production and the role of sEV in the regulation of the GHRH-GH-IGF axis has not been previously reported. The results of the present study demonstrated that GHRH increased the production of pituitary sEV by promoting the expression of Rab27a. More importantly, GHRH induced alterations in protein and miRNA levels within GH3-sEV components. Notably, GH3-sEV with GHRH treatment exhibited the enhanced ability to impede BRL 3A cell proliferation and the expression of IGF-1. Conclusively, for the first time, we corroborate the influence of GHRH on pituitary sEV, thereby presenting novel evidence for how sEV participates in the balance of the GHRH-GH-IGF axis. Importantly, this study provides new insight into a novel balance mechanism mediated by sEV within the endocrine system. [ABSTRACT FROM AUTHOR]

Objectives: to estimate insulin-like growth factor-1 (IGF-1) levels in apparently healthy infants and prepubertal children and compare results among different nutritional statuses. Methods: Our cross-sectional work is a sub-study of a screening project for anemia and nutritional status. We included 252 apparently healthy infants and children with a mean age of 3.7 ± 1.3 years (1.1–6.6), with equal gender distribution. Data retrieved included breastfeeding and anthropometric measures. We tested the stored blood samples for IGF-1 levels. The sample size was reached when all kits were consumed. Results: abnormal anthropometric measures were detected in 32.9%, either a single or multiple, and 86.5% were breastfed. Girls had significantly higher serum IGF-1 levels than boys (P: <0.001), which was noticeable in girls with abnormal nutritional status detected with anthropometry. Breastfeeding showed no significant association with IGF-1 levels. No significant difference was observed between IGF-1 levels between children with normal versus those with abnormal growth measures. Children with overweight or obesity had significantly lower IGF-1 than children with other body mass index (BMI) categories. Serum IGF-1 levels correlated positively with arm muscle area Z scores in infants and toddlers and weight and BMI Z scores in children between three and four. Also, IGF-1 correlated positively with the triceps skinfold Z score and arm muscle area Z score between four and five. Conclusions: Among studied infants and prepubertal children, serum IGF-1 was significantly higher in girls than boys and was considerably lower in children with overweight or obesity. Breastfeeding showed no association with IGF-1 levels. [ABSTRACT FROM AUTHOR]

In humans' and experimental animals' components of the somatotropic axis, such as growth hormone (GH) and insulin-like growth factor 1 (IGF-1) concentrations, decrease with advancing age. Although there is evidence regarding IGF-1, the effect of age on GH in mares, as well as the relationships between both parameters, have not yet been elucidated. On the other hand, although GH and IGF-1 are related to follicular development, it is unknown if they could be correlated with the circulating concentrations of ovarian steroids in mares, as occurs in other species. The hypothesis of this study was that both GH and IGF-1 could experience physiological changes with advancing age also in mares, and that both GH/IGF-1 could be correlated with oestradiol-17β (E 2) and progesterone (P 4), as recorded for other species. Hence, the objective of this study was to evaluate the concentrations of GH, IGF-1, E 2 , and P 4 in mares, according to the different ages. Blood samples were drawn from 56 healthy cyclic Spanish Purebred mares belonging to four different age groups: 6–9 years, 10–13 years, 14–16 years and >16 years. Mares aged 6–9 years and 10–13 years showed higher GH concentrations (P < 0.05) than mares of 14–16 and >16 years; and mares aged 14–16 showed higher GH concentrations (P < 0.05) than >16 years (P < 0.05). Mares aged >16 years showed lower IGF-1 concentrations (P < 0.05) than mares of 6–9, 10–13 and 14–16 years (P < 0.05). The concentrations of E 2 and P 4 showed no significant differences among different age groups. Both GH and IGF-1 were not correlated with each other or with E 2 and P 4. The concentrations of E 2 and P4 did not change with age. Advancing age leads to a decrease in the activity of the somatotropic axis in physiological cyclic mares, represented by a significant GH reduction, which, however, was ascribed for IGF-1 exclusively to mares over 16 years of age, without alterations in steroid hormone patterns. • Age-related changes on GH, IGF-1, oestradiol-17β, and progesterone concentrations in mares were evaluated. • Mares aged 6–9 years and 10–13 years showed higher GH than mares of 14–16 and >16 years. • Mares aged 14–16 showed higher GH concentrations than >16 years. • Mares aged >16 years showed lower IGF-1 concentrations compared to all three age groups. • No correlations between GH, IGF-1, and ovarian steroids were observed. • Advancing age leads to a significant GH reduction which was ascribed for IGF-1 exclusively to mares >16 years [ABSTRACT FROM AUTHOR]

Introduction: Mammalian reproductive and somatic development is regulated by steroid hormones, growth hormone (GH), and insulin-like growth factor-1 (IGF-1). Based largely on information from humans, model organisms, and domesticated animals, testosterone (T) and the GH/IGF-1 system activate sexually differentiated development, promoting male-biased growth, often at a cost to health and survivorship. To test if augmented prenatal androgen exposure in females produces similar developmental patterns and trade-offs, we examine maternal effects in wild meerkats (Suricata suricatta), a non-model species in which adult females naturally, albeit differentially by status, express exceptionally high androgen concentrations, particularly during pregnancy. In this cooperative breeder, the early growth of daughters predicts future breeding status and reproductive success. Methods: We examine effects of normative and experimentally induced variation in maternal androgens on the ontogenetic patterns in offspring reproductive hormones (androstenedione, A4; T; estradiol, E2), IGF-1, growth from pup emergence at 1 month to puberty at 1 year, and survivorship. Specifically, we compare the male and female offspring of dominant control (DC or high-T), subordinate control (SC or lower-T), and dominant treated (DT or blocked-T) dams, the latter having experienced antiandrogen treatment in late gestation. Results: Meerkat offspring showed sex differences in absolute T and IGF-1 concentrations, developmental rates of A4 and E2 expression, and survivorship -- effects that were sometimes socially or environmentally modulated. Atypical for mammals were the early male bias in T that disappeared by puberty, the absence of sex differences in A4 and E2, and the female bias in IGF-1. Food availability was linked to steroid concentrations in females and to IGF-1, potentially growth, and survival in both sexes. Maternal treatment significantly affected rates of T, E2, and IGF-1 expression, and weight, with marginal effects on survivorship; offspring of DT dams showed peak IGF-1 concentrations and the best survivorship. Discussion: Maternal effects thus impact offspring development in meerkats, with associated trade-offs: Whereas prenatal androgens modify postnatal reproductive and somatic physiology, benefits associated with enhanced competitiveness in DC lineages may have initial costs of reduced IGF-1, delay in weight gain, and decreased survivorship. These novel data further confirm the different evolutionary and mechanistic pathways to cooperative breeding and call for greater consideration of natural endocrine variation in both sexes. [ABSTRACT FROM AUTHOR]

Background: The causal relationship between gut microbiota and insulin-like growth factor 1 (IGF-1) remains unclear. The purpose of this study was to explore the causal relationship between gut microbiota and IGF-1 in men and women. Methods: Single-nucleotide polymorphisms (SNPs) related to gut microbiota were derived from pooled statistics from large genome-wide association studies (GWASs) published by the MiBioGen consortium. Pooled data for IGF-1 were obtained from a large published GWAS. We conducted Mendelian randomization (MR) analysis, primarily using the inverse variance weighted (IVW) method. Additionally, we performed sensitivity analyses to enhance the robustness of our results, focusing on assessing heterogeneity and pleiotropy. Results: In forward MR analysis, 11 bacterial taxa were found to have a causal effect on IGF-1 in men; 14 bacterial taxa were found to have a causal effect on IGF-1 in women (IVW, all P < 0.05). After false discovery rate (FDR) correction, all bacterial traits failed to pass the FDR correction. In reverse MR analysis, IGF-1 had a causal effect on nine bacterial taxa in men and two bacterial taxa in women respectively (IVW, all P < 0.05). After FDR correction, the causal effect of IGF-1 on order Actinomycetales (PFDR= 0.049) remains in men. The robustness of the IVW results was further confirmed after heterogeneity and pleiotropy analysis. Conclusion: Our study demonstrates a bidirectional causal link between the gut microbiota and IGF-1, in both men and women. [ABSTRACT FROM AUTHOR]

Background: The activation of the growth hormone receptor (GHR) is a major determinant of body growth. Defective GHR signaling, as seen in human Laron dwarfism, resulted in low plasma IGF-1 concentrations and limited growth, but also marked absence in the development of breast cancer and type 2 diabetes. In vitro, we identified a small molecule (C#1) that inhibits the translation of GHR mRNA to receptor protein. Methods: Before its application in humans as a potential anticancer drug, C#1 was tested in animals to evaluate whether it could be administered to achieve a plasma concentration in vivo that inhibits cell proliferation in vitro without causing unwanted toxicity. To evaluate the efficacy and toxicity of C#1, a group of six intact female Beagle dogs was treated daily each morning for 90 days with an oral solution of C#1 in Soiae oleum emulgatum at a dose of 0.1 mg/kg body weight. During treatment, dogs were closely monitored clinically, and blood samples were taken to measure plasma C#1 concentrations, complete blood counts (CBC), clinical chemistry, and endocrinology. At the end of the treatment, dogs were euthanized for gross and histopathological analysis. An additional group of six female Beagle dogs was included for statistical reasons and only evaluated for efficacy during treatment for 30 days. Results: Daily administration of C#1 resulted in a constant mean plasma concentration of approximately 50 nmol/L. In both groups, two out of six dogs developed decreased appetite and food refusal after 4–5 weeks, and occasionally diarrhea. No significant effects in CBC or routine clinical chemistry were seen. Plasma IGF-1 concentrations, used as biomarkers for defective GHR signaling, significantly decreased by 31% over time. As plasma growth hormone (GH) concentrations decreased by 51% as well, no proof of GHR dysfunction could be established. The measured 43% decrease in plasma acylated/non-acylated ghrelin ratios will also lower plasma GH concentrations by reducing activation of the GH secretagogue receptor (GHSR). C#1 did not directly inhibit the GHSR in vivo, as shown in vitro. There were no significant effects on glucose, lipid, or folate/homocysteine metabolism. Conclusions: It is concluded that with daily dosing of 0.1 mg C#1/kg body weight, the induction of toxic effects prevented further increases in dosage. Due to the concomitant decrease in both IGF-1 and GH, in vivo inhibition of GHR could not be confirmed. Since the concept of specific inhibition of GHR synthesis by small molecules remains a promising strategy, searching for compounds similar to C#1 with lower toxicity should be worthwhile. [ABSTRACT FROM AUTHOR]

Simple Summary: Age at puberty is a main factor affecting reproductive efficiency and, thus, livestock production. Besides species and breed, nutrition during growth plays a crucial role in the attainment of puberty. Controversial results are reported about the critical period during which heifers are more sensitive to the effects of nutrition on pubertal acceleration. Numerous papers are available about such topics, but they are characterized by very different experimental conditions (such as genetics, feeds, planes of nutrition, season and pasture quality, time windows, and parameters considered), making difficult the comparison among inconstant results by various trials. Several indicators during growth have been proposed as predictors of age at puberty, such as body weight gains, body fat reserves, and linear body measurements. Blood concentrations of hormones strictly linked to growth and reproduction have also been considered: higher Insulin-like Growth Factor-1 levels are reported to be related to earlier puberty, while leptin is not. More uniform experimental conditions should be encouraged for future research. Puberty onset and age at first calving have a critical impact on livestock production for good reproductive efficiency of the herd and to reduce the duration of the non-productive stage of the growing heifer. Besides genetic factors, sexual maturation is also affected by environmental factors, such as nutrition, which can account for up to 20% of the observed variability. The rate of body weight gain during growth is considered the main variable influencing the age at puberty, dependent on planes of nutrition in growing animals during the prepubertal-to-pregnancy stage. This paper reviews current knowledge concerning nutrition management and attainment of puberty in heifers, considering the relevance of some indicators such as body measurements and hormones strictly linked to the growth and puberty process. Puberty onset is dependent on the acquisition of adequate subcutaneous adipose tissue mass, as it is the main source of the hormone leptin. Until a certain level, body condition score and age at puberty are negatively correlated, but beyond that, for fatter animals, such correlation is gradually lost. Age at puberty in heifers was reported to be negatively related to IGF-1. Future research should be planned considering the need to standardize the experimental animals and conditions. [ABSTRACT FROM AUTHOR]

Somatrogon‐ghla is a long‐acting, recombinant human growth hormone approved for the treatment of pediatric patients with growth hormone deficiency. Forty‐nine healthy, adult males were enrolled in a randomized, crossover study to compare somatrogon exposure after subcutaneous doses administered using a frozen vial presentation or a prefilled, multiple dose pen. Somatrogon, insulin‐like growth factor‐I, and IGF‐1 binding protein‐3 concentrations were collected for up to 240 hours post dose to assess pharmacokinetic and pharmacodynamic responses. There was a 2‐week washout between administration of the doses. Seven participants did not complete the study due to withdrawal of consent (n = 2) or loss to follow‐up. Two treatment‐emergent adverse events, headaches, were judged by the investigator as possibly related to study drug administration. Both were mild. Injection site reactions were observed in 6/48 participants after administration with the pen and 12/46 after administration using the vial. Drug and biomarker concentrations were assessed using validated assays and noncompartmental methods were used to determine pharmacokinetic and pharmacodynamic parameters. Bioequivalence was demonstrated for somatrogon area under the concentration‐time curve, but not for the peak somatrogon concentration, where the lower limit of the 90% confidence interval for the ratio of pen/vial was 74.2%, which is less than the lower limit, 80.0%, dictated by bioequivalence criteria. The IGF‐1 responses were largely within bioequivalence limits. It was concluded that the 2 formulations are comparable. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the expression changes of H2S, IGF-1, and GH in traumatic brain injury (TBI) patients and to detect their neuroprotective functions after TBI. In this study, we first collected cerebrospinal fluid (CSF) and plasma from TBI patients at different times after injury and evaluated the concentrations of H2S, IGF-1, and GH. In vitro studies were using the scratch-induced injury model and cell–cell interaction model (HT22 hippocampal neurons co-cultured with LPS-induced BV2 microglia cells). In vivo studies were using the controlled cortical impact (CCI) model in mice. Cell viability was assessed by CCK-8 assay. Pro-inflammatory cytokines expression was determined by qRT-PCR, ELISA, and nitric oxide production. Western blot was performed to assess the expression of CBS, CSE, IGF-1, and GHRH. Moreover, the recovery of TBI mice was evaluated for behavioral function by applying the modified Neurological Severity Score (mNSS), the Rotarod test, and the Morris water maze. We discovered that serum H2S, CSF H2S, and serum IGF-1 concentrations were all adversely associated with the severity of the TBI, while the concentrations of IGF-1 and GH in CSF and GH in the serum were all positively related to TBI severity. Experiments in vitro and in vivo indicated that treatment with NaHS (H2S donor), IGF-1, and MR-409 (GHRH agonist) showed protective effects after TBI. This study gives novel information on the functions of H2S, IGF-1, and GH in TBI. [ABSTRACT FROM AUTHOR]

Dietary omega-3 fatty acids are a type of polyunsaturated fat known to improve production and body health in animals and human as well. The current on-farm trial was to evaluate the effects of omega-3 fatty acids inclusion in the diets on milk production and fatty acid profiles and insulin growth factors-1 values in lactating dairy cattle. Three hundred Holstein lactating cows in a commercial farm were assorted to a control group fed basal control diet and two treated groups fed diets containing extruded flaxseed (7.0%) and salmate (25 g/head/day). The basal control, extruded flaxseed and salmate diets were formulated to be isonitrogenous and isoenergetic diets. The diets were given to each group from three weeks pre-parturition to week 23 of lactation. Feed intake, milk production and composition and fatty acid profiles were recorded during the study. Fat and energy corrected milk were calculated. Feed intake did not differ among groups. Flaxseed significantly (P<0.05) increased milk yield, fat corrected milk and energy corrected milk if compared to other groups. Milk fat (%) decreased significantly (P0.05), while saturated short-chain (C12:C15) and long-chain (C17:C20) fatty acids were higher (P0.05) in Salmate and extruded flaxseed groups. Moreover, the ratio of omega-6/omega-3 was the lowest in flaxseed group (3.76) compared to control (8.06) and salmate (8.31) groups. In conclusion, flaxseed diet improved (P < 0.05) milk production efficiency (kg milk/kg feed) and fatty acid profile compared to salmate and control diets. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a metabolic disease. Diabetes increases the risk of benign prostatic hyperplasia (BPH). Capsaicin is extracted from chili peppers and possesses many pharmacological properties, including anti-diabetic, pain-relieving, and anti-cancer properties. This study aimed to investigate the effects of capsaicin on glucose metabolism and prostate growth in T2DM mice and uncover the related mechanisms. Mice model of diabetes was established by administering a high-fat diet and streptozotocin. Oral administration of capsaicin for 2 weeks inhibited prostate growth in testosterone propionate (TP)-treated mice. Furthermore, oral administration of capsaicin (5 mg/kg) for 2 weeks decreased fasting blood glucose, prostate weight, and prostate index in diabetic and TP-DM mice. Histopathological alterations were measured using hematoxylin & eosin (H&E) staining. The protein expression of 5α-reductase type II, androgen receptor (AR), and prostate-specific antigen (PSA) were upregulated in diabetic and TP-DM mice, but capsaicin reversed these effects. Capsaicin decreased the protein expression of p-AKT, insulin-like growth factor-1 (IGF-1), IGF-1R, and the receptor for advanced glycation end products (RAGE) in diabetic and TP-DM mice. Capsaicin also regulated epithelial-mesenchymal transition (EMT) and modulated the expression of fibrosis-related proteins, including E-cadherin, N-cadherin, vimentin, fibronectin, α-SMA, TGFBR2, TGF-β1, and p-Smad in TP-DM mice. In this study, capsaicin alleviated diabetic prostate growth by attenuating EMT. Mechanistically, capsaicin affected EMT by regulating RAGE/IGF-1/AKT, AR, and TGF-β/Smad signalling pathways. These results provide with new therapeutic approach for treating T2DM or T2DM-induced prostate growth. [ABSTRACT FROM AUTHOR]

Purpose: Patients with obstructive sleep apnea syndrome (OSAS) frequently experience cognitive dysfunction, which may be connected to chronic intermittent hypoxia (CIH). Insulin-like growth factor-1 (IGF-1) is thought to be closely associated with cognitive function, but its role in cognitive impairment caused by OSAS is unclear. The purpose of this study was to investigate the potential protective effect of IGF-1 on cognitive impairment in OSAS rats. Methods: Healthy male SD rats (n = 40) were randomly assigned into four groups: control group, CIH group, NS + CIH group, and IGF-1 + CIH group. All experimental rats except for those in the control group were exposed to intermittent hypoxic (IH) environments for 8 h per day over 28 days. Prior to daily exposure to IH, rats in the IGF-1 + CIH group received subcutaneous injections of IGF-1. The Morris water maze test was conducted on all experimental rats. Brain tissue testing methods included Enzyme-Linked Immunosorbent Assay, Hematoxylin and eosin staining, Immunohistochemistry, and Western blotting. Results: The rat model of OSAS was successfully established following exposure to CIH and exhibited significant cognitive impairment. However, daily subcutaneous injections of IGF-1 partially restored the impaired cognitive function in OSAS rats. Compared with the control group, there was a significant decrease in the expression levels of IGF-1, p-IGF-IR, and SYP in the CIH group; however, these expression levels increased significantly in the IGF-I + CIH group. Conclusion: In OSAS rats, IGF-1 enhances learning memory; this effect may be linked to increased p-IGF-1R and SYP protein production in the hippocampus. [ABSTRACT FROM AUTHOR]

Background: Diabetes (primarily type 2) is linked to a higher risk of breast cancer. Insulin-like growth factor (IGF) is one of the most important factors that affects mitosis and thus inhibits apoptosis. The purpose of this study was to compare the pre-treatment insulin-like growth factor (IGF) levels in breast cancer against normal population. Methods: In this case-control study, 60 patients with breast cancer and 60 healthy controls were enrolled in 2017 and 2018 at Tehran's Shahid-Modarres Hospital. In this study, the blood sugar of the patients was examined before entering the study, and the age of the patients was also within the age limit of 18 to 70 years. They were studied to determine the relationship between insulin-like growth factor (ELISA method) and breast cancer. Results: Both groups have similar IGF-1 levels (Ctrl and Case) (P= 0.188). But, IGF-2 levels were significantly higher in breast cancer patients (373.4 vs. 317.3 ng/ml), (P=0.0001). Conclusion: According to our study, IGF-2 may serve as a prognostic biomarker and potential therapeutic target for breast cancer. However, further investigation is needed to validate this claim. [ABSTRACT FROM AUTHOR]

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Background: Malignant tumors of the breast are the most diagnosed cancers in females globally. Recent evidence suggests that carbohydrate restriction (CR), especially ketogenic diets, has become a potential treatment approach for many malignancies, including breast cancer. Tamoxifen (TAX) is a selective estrogen receptor modulator (ERM) that can reduce the risk of cancer recurrence. The current work was designed to assess the impact of CR on the proliferation of breast adenocarcinoma cells and to compare this impact with that of TAX. Study groups included: group 1: vehicle-treated mice; group 2: the Ehrlich group: injected Ehrlich ascites carcinoma (EAC) cells (2.5 × 106) in 0.25 ml isotonic saline; group 3: CR group: mice were supplied with a diet regimen of severe CR throughout the study and injected EAC at week 7; group 4: hormonal therapy (HT) group: mice in this group injected with EAC at week 7 and then received TAX at a dose of 20 mg/kg 3 times/week orally for 3 weeks; and lastly group 5: the group of combined intervention. The mice in the CR, HT, and the combined groups received Ehrlich cancer cells at the same dose and route as the Ehrlich group. Results: CR and HT groups demonstrated a significant decrease in levels of insulin-like growth factor (IGF-1), carbohydrate antigen (CA 15–3), hexokinase 2 (HK2), hypoxia-inducible factor-1 (HIF-1) α, and malondialdehyde (MDA) compared to the Ehrlich group. Additionally, the mean area % of caspase-3 was significantly increased, and the mean area % of Ki67 and estrogen receptor (ER)α was significantly decreased. Conclusions: The combined treatment demonstrated the most advantageous outcome, as evidenced by reduced CA 15–3 levels, tumor size, and the mean area % of Ki67. This suggests that the addition of severe CR to the conventional therapy of breast cancer has a beneficial effect. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression and clinical significance of serum Klotho, fibroblast growth factor 23 (FGF23) and insulin-like growth factor-1 (IGF-1) in patients with chronic periodontitis (CP). Methods: 108 patients with CP (CP group) who admitted to our hospital from January 2022 to June 2023 were selected, and 92 patients with oral health who underwent ultrasonic tooth cleaning in our hospital during the same period were selected (control group), CP patients were divided into mild group (55 cases) and moderate to severe group (53 cases) according to the severity of CP. The levels of serum Klotho, FGF23, IGF-1, inflammatory factors interleukin (IL) -6, IL-1ẞ and tumor necrosis factor-a (TNF-a) in CP group and control group were detected, and the periodontal clinical indicators of probing depth (PD), attachment loss (CAL) and bleeding index (BI) in CP group were examined. The correlation between serum Klotho, FGF23, IGF-1 and periodontal clinical indicators and inflammatory factors were analyzed by Pearson method. The value of serum Klotho, FGF23 and IGF-1 in the diagnosis of CP were analyzed by receiver operating characteristic (ROC) curve. Results: The levels of serum FGF23, IL-6, IL-1ẞ and TNF-a in CP group were higher than those in control group (P < 0.05) and the levels of serum Klotho and IGF-1 were lower than those in control group (P < 0.05) The levels of serum FGF23, IL-6, IL-1B, TNF-α, PD, CAL and BI in moderate to severe group were higher than those in mild group (P < 0.05) and the levels of serum Klotho and IGF-1 were lower than those in mild group (P < 0.05) The level of serum FGF23 of CP patients was positively correlated with IL-6, IL-1B, TNF-α, PD, CAL and BI (P < 0.05) and the serum Klotho and IGF-1 levels were negatively correlated with IL-6, IL-1B, TNF-α, PD, CAL and BI (P < 0.05) The area under the curve of serum Klotho, FGF23 and IGF-1 in the diagnosis of CP was 0.819, 0.816 and 0.861, respectively, the area under the curve of the combined diagnosis of the three indexes was 0.978, which was higher than that of the single diagnosis of each index. Conclusion: The increase of serum FGF23 level, and the decrease of Klotho and IGF-1 levels in CP patients are related to the occurrence of periodontal inflammation and tissue destruction, the combined detection of serum Klotho, FGF23 and IGF-1 has high value in the diagnosis of CP. [ABSTRACT FROM AUTHOR]

In the last three decades, gene therapy has demonstrated significant progress. Over 700 active investigational new drug (IND) applications have been reported. Research on in utero gene therapy has advanced, but ethical and safety concerns persist. A novel approach under investigation is placental gene therapy, which holds promise for targeting diseases associated with placental dysfunction, such as fetal growth restriction (FGR) and preeclampsia. One of the underlying causes of placental insufficiency in these conditions is reduced placental growth factor-driven angiogenesis and endothelial cell dysfunction during fetal development. Studies have explored the overexpression of growth factor transgenes like IGF-1 to address FGR, yielding promising outcomes in animal models. Furthermore, intra-placental gene transfer, instead of systemic delivery of gene therapy vectors, has the potential to treat and cure these disorders. However, challenges and limitations akin to in utero gene therapy persist, including the risk of in utero infection, potential impairment of the mother's future fertility, the risk of germline integration, and possible off-target effects of gene transfer in the fetus or the mother. Consequently, additional research and deliberation within the scientific and medical communities are warranted to fully comprehend the potential benefits and risks of placental gene therapy. [ABSTRACT FROM AUTHOR]

Objective: To study the correlation between serum C-reactive protein (CRP), melatonin (MT), insulin-like growth factor-1 (IGF-1) and oxidative stress indexes and cognitive function in patients with first-episode untreated schizophrenia (SP). Methods: 140 patients with first-episode untreated SP who were treated in Xuzhou Oriental Hospital Affiliated to Xuzhou Medical University from January 2021 to June 2023 were selected as observation group, the patients were divided into high score group (≥70 points) with 57 cases and low score group (<70 points) with 83 cases according to the positive and negative symptom scale (PANSS) score. Another 140 volunteers who received physical examination in our hospital during the same period were selected as control group. Serum oxidative stress indexes, CRP, MT and IGF-1 levels were detected, and patients' cognitive dysfunction was evaluated by MATRICS cognitive assessment system (MCCB) score. The correlation between serum CRP, MT, IGF-1 and PANSS score, serum oxidative stress index, MCCB score and total score was analyzed. Results: Serum CRP in observation group was higher than that in control group, and MT and IGF-1 were lower than those in control group (P<0.05). The serum CRP in high score group was higher than that in low score group, and the MT and IGF-1 were lower than those in low score group (P<0.05). Serum SOD and GSH-Px in high score group were lower than those in low score group, while NO was higher than that in low score group (P<0.05). The MCCB scores and total scores in high score group were lower than those in low score group, and the PANSS score was higher than that in low score group (P<0.05). Pearson correlation showed that, serum CRP was positively correlated with PANSS score and NO, and negatively correlated with SOD, GSH-Px and MCCB scores and total scores (P<0.05). Serum MT and IGF-1 were negatively correlated with PANSS score and NO, and positively correlated with SOD, GSH-Px and MCCB scores and total score (P<0.05). Conclusion: The level of serum CRP in patients with first-episode untreated SP increase, and the levels of MT and IGF-1 decrease, there is a significant correlation between the three and oxidative stress indicators and cognitive function. [ABSTRACT FROM AUTHOR]

Objective: To investigate the difference of serum vitamin A, IGF-1 and SOCS1 mRNA levels and prognostic factors in children with different types of respiratory tract infection. Methods: 80 children with respiratory tract infections who came to our hospital from January 2021 to December 2023 were selected and divided into pneumonia group (38 cases) and upper respiratory tract infection group (42 cases) according to the types of infection. The general data, laboratory test results of blood routine, serum vitamin A, IGF-1 and SOCSImRNA levels in two groups were compared, and the prognosis in two groups were analyzed. The influencing factors of good prognosis and poor prognosis were compared, and the predictive value of serum vitamin A, IGF-1 and SOCS1mRNA levels on the prognosis of children with pneumonia was analyzed. Results: The age and serum lymphocytes of pneumonia group were significantly lower than those of upper respiratory tract infection group, the proportion of fever and cough was higher than that of upper respiratory tract infection group, and the proportion of sore throat was lower than that of upper respiratory tract infection group (P<0.05). The levels of vitamin A and IGF-1 in the pneumonia group were lower than those in the upper respiratory tract infection group, and SOCS1 mRNA was higher than those in the upper respiratory tract infection group (P<0.05). All 42 cases of upper respiratory tract infection were cured. Among the 38 children with pneumonia, 22 cases were cured, 8 cases were effective, and 8 cases were ineffective. The cured + effective group was regarded as the good prognosis group, with a total of 30 cases, accounting for 78.95% (30/38), and 8 cases with poor prognosis, accounting for 21.95% (8/38). Multivariate Logsitic regression analysis showed that age 1-6 years old, decreased vitamin A level, decreased IGF-1 level, and increased SOCS1 mRNA level were risk factors for poor prognosis in children with pneumonia (P<0. 05). Vitamin A and IGF-1 can be used to predict the prognosis of pediatric pneumonia, with AUC>0.80, P<0.05. SOCS1 mRNA has poor diagnostic efficacy for the prognosis of pediatric pneumonia, P>0.05. Conclusion: Compared with children with upper respiratory tract infection, the serum vitamin A and IGF-1 are significantly reduced, and the SOCS1 mRNA level is significantly increased. Vitamin A and IGF-1 can be used to judge the prognosis of pediatric pneumonia. Age 1-6 years, vitamin A, IGF-1 and SOCS1 mRNA levels are risk factors for poor prognosis of children with pneumonia. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF) innovative preservative on hair follicle activity of rat vibrissae under low temperature conditions. Methods From January 2021 to December 2023, the upper of hair follicle (UHF) from male SD rat vibrissae was used in the experiment. These UHF were equally divided into NS, IGF-1, EGF, and IGF-1+EGF preservation solutions groups. At 3, 6 and 12 hours, the cultured UHF were analyzed by hematoxylin and eosin (HE) staining and alkaline phosphatase (ALP) activity. The UHF co-cultured with NS and IGF-1+EGF for 3 hours were further transplanted into the dorsum of nude mice. After 24 hours, the transplanted UHF was taken to observe by HE staining and ALP activity. Results In vitro preservation, HE staining results indicated that the cultured UHF at 3 hours, the follicle structure and cell arrangement were normal without obvious changes. At 12 hours, only the IGF-1+EGF group had intact follicle structure and clear organization. Moreover, ALP values showed that the IGF-1+EGF group at 3, 6 and 12 hours were significantly higher than the NS group (P＜0.001). Overall, ALP activity gradually decreased over time. In vivo transplantation, HE staining results showed that the IGF-1+EGF group were structurally distinct with orderly cell arrangements, compared to the NS group. ALP values were significantly higher than NS group (P＜0.05). Conclusion The innovative preservation solutions containing IGF-1 and EGF under low temperatures, can effectively enhance the activity of UHF, and promote the success of hair follicle transplantation. [ABSTRACT FROM AUTHOR]

Massage therapy increases muscle blood flow and heat, relieving pain, improving immune function, and increasing vagal activity. The mechanisms are unclear. Muscles release cytokines and other peptides called myokines. These myokines exert their effects on different tissues and organs in para-, auto-, and endocrine fashion. The aim of this intervention study was to investigate if massage therapy affects circulating myokine levels. A total of 46 healthy, normal-weight subjects (15 men) aged 18–35 were recruited. Forty-five minutes of massage Swedish therapy was applied to the back and hamstrings. Blood samples via cannula were taken at the baseline, during the massage (30 min), end of the massage (45 min), and 30 min and 1 h after the massage. Interleukin 6 (IL-6) and insulin-like growth factor 1 (IGF-1) were measured as surrogate markers by ELISAs. There was a significant increase in IL-6 from 1.09 pg/mL to 1.85 pg/mL over time (Wilks' Lambda Value 0.545, p < 0.000; repeated measures ANOVA). Pair-wise comparisons showed a significant increase after 1 h of massage. No significant increase was observed in IGF-1 levels. The change in myokine levels was not correlated with muscle mass (p = 0.16, 0.74). The increase in IL-6 suggests that there might be anti-inflammatory effects, affecting glucose and lipid metabolism pathways via IL-6 signaling to muscles, fat tissue, and the liver. [ABSTRACT FROM AUTHOR]

Aim: To test the hypothesis that liver‐expressed antimicrobial peptide 2 (LEAP2) genetic variants might influence the susceptibility to human obesity. Methods: Using data from the UK Biobank, we identified independent LEAP2 gene single nucleotide polymorphisms (SNPs) and examined their associations with obesity traits and serum insulin‐like growth factor‐1 (IGF‐1) concentration. These associations were evaluated for both individual SNPs and after combining them into a genetic risk score (GRSLEAP2) using linear and logistic regression models. Sex‐stratified analyses were also conducted. Results: Five SNPs showed positive associations with obesity‐related traits. rs57880964 was associated with body mass index (BMI) and waist‐to‐hip ratio adjusted for BMI (WHRadjBMI), in the total population and among women. Four independent SNPs were positively associated with higher serum IGF‐1 concentrations in both men and women. GRSLEAP2 was associated with BMI and WHRadjBMI only in women and with serum IGF‐1 concentration in both sexes. Conclusions: These findings reveal sex‐specific associations between key LEAP2 gene variants and several obesity traits, while also indicating a strong independent association of LEAP2 variants with serum IGF‐1 concentration. [ABSTRACT FROM AUTHOR]

Chronic bone loss is an under-recognized complication of malaria, the underlying mechanism of which remains incompletely understood. We have previously shown that persistent accumulation of Plasmodium products in the bone marrow leads to chronic inflammation in osteoblast (OB) and osteoclast (OC) precursors causing bone loss through MyD88, an adaptor molecule for diverse inflammatory signals. However, the specific contribution of MyD88 signaling in OB or OC precursors in malaria-induced bone loss remains elusive. To assess the direct cell-intrinsic role of MyD88 signaling in adult bone metabolism under physiological and infection conditions, we used the Lox-Cre system to specifically deplete MyD88 in the OB or OC lineages. Mice lacking MyD88 primarily in the maturing OBs showed a comparable decrease in trabecular bone density by microcomputed tomography to that of controls after Plasmodium yoelii non-lethal infection. In contrast, mice lacking MyD88 in OC precursors showed significantly less trabecular bone loss than controls, suggesting that malaria-mediated inflammatory mediators are primarily controlled by MyD88 in the OC lineage. Surprisingly, however, depletion of MyD88 in OB, but not in OC, precursors resulted in reduced bone mass with decreased bone formation rates in the trabecular areas of femurs under physiological conditions. Notably, insulin-like growth factor-1, a key molecule for OB differentiation, was significantly lower locally and systemically when MyD88 was depleted in OBs. Thus, our data demonstrate an indispensable intrinsic role for MyD88 signaling in OB differentiation and bone formation, while MyD88 signaling in OC lineages plays a partial role in controlling malaria-induced inflammatory mediators and following bone pathology. These findings may lead to the identification of novel targets for specific intervention of bone pathologies, particularly in malaria-endemic regions. [ABSTRACT FROM AUTHOR]

Prematurity has physical consequences, such as lower birth weight, decreased muscle mass and increased risk of adult‐onset metabolic disease. Insulin‐like growth factor 1 (IGF‐1) has therapeutic potential to improve the growth and quality of muscle and tendon in premature births, and thus attenuate some of these sequalae. We investigated the effect of IGF‐1 on extensor carpi radialis muscle and biceps brachii tendon of preterm piglets. The preterm group consisted of 19‐day‐old preterm (10 days early) piglets, treated with either IGF‐1 or vehicle. Term controls consisted of groups of 9‐day‐old piglets (D9) and 19‐day‐old piglets (D19). Muscle samples were analysed by immunofluorescence to determine the cross‐sectional area (CSA) of muscle fibres, fibre type composition, satellite cell content and central nuclei‐containing fibres in the muscle. Tendon samples were analysed for CSA, collagen content and maturation, and vascularization. Gene expression of the tendon was measured by RT‐qPCR. Across all endpoints, we found no significant effect of IGF‐1 treatment on preterm piglets. Preterm piglets had smaller muscle fibre CSA compared to D9 and D19 control group. Satellite cell content was similar across all groups. For tendon, we found an effect of age on tendon CSA, and mRNA levels of COL1A1, tenomodulin and scleraxis. Immunoreactivity for elastin and CD31, and several markers of tendon maturation, were increased in D9 compared to the preterm piglets. Collagen content was similar across groups. IGF‐1 treatment of preterm‐born piglets does not influence the growth and maturation of skeletal muscle and tendon. What is the central question of this study?Does infusion of insulin‐like growth factor‐1 in preterm piglets stimulate growth parameters of muscle and tendon?What is the main finding and its importance?IGF‐1 treatment of preterm born piglets does not influence growth and maturation of skeletal muscle and tendon. This adds to the current knowledge on the effect of IGF‐1 on muscle and tendon growth, and is relevant for future research in potential therapies for premature infants. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-1 (IGF-1) signaling has multiple physiological roles in cellular growth, metabolism, and aging. Myocardial hypertrophy, cell death, senescence, fibrosis, and electrical remodeling are hallmarks of various heart diseases and contribute to the progression of heart failure. This review highlights the critical role of IGF-1 and its cognate receptor in cardiac hypertrophy, aging, and remodeling. [ABSTRACT FROM AUTHOR]

Abstract Small extracellular vesicles (sEV) have emerged as a novel mode of intercellular material transport and information transmission. It has been suggested hormones may regulate the production and function of sEV. However, the specific impact of growth hormone-releasing hormone (GHRH) on pituitary sEV production and the role of sEV in the regulation of the GHRH-GH-IGF axis has not been previously reported. The results of the present study demonstrated that GHRH increased the production of pituitary sEV by promoting the expression of Rab27a. More importantly, GHRH induced alterations in protein and miRNA levels within GH3-sEV components. Notably, GH3-sEV with GHRH treatment exhibited the enhanced ability to impede BRL 3A cell proliferation and the expression of IGF-1. Conclusively, for the first time, we corroborate the influence of GHRH on pituitary sEV, thereby presenting novel evidence for how sEV participates in the balance of the GHRH-GH-IGF axis. Importantly, this study provides new insight into a novel balance mechanism mediated by sEV within the endocrine system. Graphical Abstract

Abstract Objectives to estimate insulin-like growth factor-1 (IGF-1) levels in apparently healthy infants and prepubertal children and compare results among different nutritional statuses. Methods Our cross-sectional work is a sub-study of a screening project for anemia and nutritional status. We included 252 apparently healthy infants and children with a mean age of 3.7 ± 1.3 years (1.1–6.6), with equal gender distribution. Data retrieved included breastfeeding and anthropometric measures. We tested the stored blood samples for IGF-1 levels. The sample size was reached when all kits were consumed. Results abnormal anthropometric measures were detected in 32.9%, either a single or multiple, and 86.5% were breastfed. Girls had significantly higher serum IGF-1 levels than boys (P:

Abstract Background Malignant tumors of the breast are the most diagnosed cancers in females globally. Recent evidence suggests that carbohydrate restriction (CR), especially ketogenic diets, has become a potential treatment approach for many malignancies, including breast cancer. Tamoxifen (TAX) is a selective estrogen receptor modulator (ERM) that can reduce the risk of cancer recurrence. The current work was designed to assess the impact of CR on the proliferation of breast adenocarcinoma cells and to compare this impact with that of TAX. Study groups included: group 1: vehicle-treated mice; group 2: the Ehrlich group: injected Ehrlich ascites carcinoma (EAC) cells (2.5 × 106) in 0.25 ml isotonic saline; group 3: CR group: mice were supplied with a diet regimen of severe CR throughout the study and injected EAC at week 7; group 4: hormonal therapy (HT) group: mice in this group injected with EAC at week 7 and then received TAX at a dose of 20 mg/kg 3 times/week orally for 3 weeks; and lastly group 5: the group of combined intervention. The mice in the CR, HT, and the combined groups received Ehrlich cancer cells at the same dose and route as the Ehrlich group. Results CR and HT groups demonstrated a significant decrease in levels of insulin-like growth factor (IGF-1), carbohydrate antigen (CA 15–3), hexokinase 2 (HK2), hypoxia-inducible factor-1 (HIF-1) α, and malondialdehyde (MDA) compared to the Ehrlich group. Additionally, the mean area % of caspase-3 was significantly increased, and the mean area % of Ki67 and estrogen receptor (ER)α was significantly decreased. Conclusions The combined treatment demonstrated the most advantageous outcome, as evidenced by reduced CA 15–3 levels, tumor size, and the mean area % of Ki67. This suggests that the addition of severe CR to the conventional therapy of breast cancer has a beneficial effect.

Abstract Prematurity has physical consequences, such as lower birth weight, decreased muscle mass and increased risk of adult‐onset metabolic disease. Insulin‐like growth factor 1 (IGF‐1) has therapeutic potential to improve the growth and quality of muscle and tendon in premature births, and thus attenuate some of these sequalae. We investigated the effect of IGF‐1 on extensor carpi radialis muscle and biceps brachii tendon of preterm piglets. The preterm group consisted of 19‐day‐old preterm (10 days early) piglets, treated with either IGF‐1 or vehicle. Term controls consisted of groups of 9‐day‐old piglets (D9) and 19‐day‐old piglets (D19). Muscle samples were analysed by immunofluorescence to determine the cross‐sectional area (CSA) of muscle fibres, fibre type composition, satellite cell content and central nuclei‐containing fibres in the muscle. Tendon samples were analysed for CSA, collagen content and maturation, and vascularization. Gene expression of the tendon was measured by RT‐qPCR. Across all endpoints, we found no significant effect of IGF‐1 treatment on preterm piglets. Preterm piglets had smaller muscle fibre CSA compared to D9 and D19 control group. Satellite cell content was similar across all groups. For tendon, we found an effect of age on tendon CSA, and mRNA levels of COL1A1, tenomodulin and scleraxis. Immunoreactivity for elastin and CD31, and several markers of tendon maturation, were increased in D9 compared to the preterm piglets. Collagen content was similar across groups. IGF‐1 treatment of preterm‐born piglets does not influence the growth and maturation of skeletal muscle and tendon.

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Background: Diabetes (primarily type 2) is linked to a higher risk of breast cancer. Insulin-like growth factor (IGF) is one of the most important factors that affects mitosis and thus inhibits apoptosis. The purpose of this study was to compare the pre-treatment insulin-like growth factor (IGF) levels in breast cancer against normal population. Methods: In this case-control study, 60 patients with breast cancer and 60 healthy controls were enrolled in 2017 and 2018 at Tehran's Shahid-Modarres Hospital. In this study, the blood sugar of the patients was examined before entering the study, and the age of the patients was also within the age limit of 18 to 70 years. They were studied to determine the relationship between insulin-like growth factor (ELISA method) and breast cancer. Results: Both groups have similar IGF-1 levels (Ctrl and Case) (P= 0.188). But, IGF-2 levels were significantly higher in breast cancer patients (373.4 vs. 317.3 ng/ml), (P=0.0001). Conclusion: According to our study, IGF-2 may serve as a prognostic biomarker and potential therapeutic target for breast cancer. However, further investigation is needed to validate this claim.

Abstract This study aimed to elucidate the influence of miR-483-3p on human renal tubular epithelial cells (HK-2) under high glucose conditions and to understand its mechanism. Human proximal tubular epithelial cells (HK-2) were exposed to 50 mmol/L glucose for 48 h to establish a renal tubular epithelial cell injury model, denoted as the high glucose group (HG group). Cells were also cultured for 48 h in a medium containing 5.5 mmol/L glucose, serving as the low glucose group. Transfection was performed in various groups: HK-2 + low glucose (control group), high glucose (50 mM) (HG group), high glucose + miR-483-3p mimics (HG + mimics group), high glucose +miR-483-3p inhibitor (HG + inhibitor group), and corresponding negative controls. Real-time quantitative polymerase chain reaction (qPCR) assessed the mRNA expression of miR-483-3p, bax, bcl-2, and caspase-3. Western blot determined the corresponding protein levels. Proliferation was assessed using the CCK-8 assay, and cell apoptosis was analyzed using the fluorescence TUNEL method. Western blot and Masson’s staining were conducted to observe alterations in cell fibrosis post miR-483-3p transfection. Furthermore, a dual-luciferase assay investigated the targeting relationship between miR-483-3p and IGF-1. The CCK8 assay demonstrated that the HG + mimics group inhibited HK-2 cell proliferation, while the fluorescent TUNEL method revealed induced cell apoptosis in this group. Conversely, the HG + inhibitor group promoted cell proliferation and suppressed cell apoptosis. The HG + mimics group upregulated mRNA and protein expression of pro-apoptotic markers (bax and caspase-3), while downregulating anti-apoptotic marker (bcl-2) expression. In contrast, the HG + inhibitor group showed opposite effects. Collagen I and FN protein levels were significantly elevated in the HG + mimics group compared to controls (P

Abstract Background Aging results in many changes in health status, body composition, muscle strength, and, ultimately, functional capacity. These changes coincide with significant alterations in the endocrine system, such as insulin-like growth factor-1 (IGF-1) and IGF-binding proteins (IGFBPs), and may be associated with many symptoms of aging. The objectives of this study is to investigate the potential influence of different types of exercise, such as resistance training and aerobic training, on IGF-1 and IGFBP-3 levels in postmenopausal women. Methods Medline, Scopus, and Google Scholar databases were systematically searched up to November 2023. The Cochrane Collaboration tool was used to assess the risk of bias and the quality of the studies. The random-effects model, weighted mean difference (WMD), and 95% confidence interval (CI) were used to estimate the overall effect. Between-study heterogeneity was assessed using the chi-squared and I2 tests. Results Seventeen studies were included in the present systematic review and 16 studies were included in the meta-analysis. The pooled results from 16 studies (21 trials) with 1170 participants examining the impact of exercise on IGF-1 concentration showed a significant increase in IGF-1, and the pooled results among six studies (trials) showed a significant decrease in IGFBP-3 concentration (730 participants). In addition, resistance training and aerobic training had a significant effect on increasing IGF-1 concentration post-exercise compared with placebo. Conclusion Based on this meta-analysis, Women who have completed menopause and followed an exercise routine showed changes in IGF-1 and IGFBP-3 levels that can indirectly be associated with risk of chronic age-related conditions.

Abstract Purpose An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary reduction or withdrawal of DA, which are needed to maintain normal prolactin levels. This study was aimed to measure IGF-1 levels, at baseline and during follow-up, in a cohort of patients with prolactinoma, treated with cabergoline, stratified by body mass index. Methods We retrospectively enrolled 35 patients (15 F/20 M; age m ± SD, years: 43.4 ± 13.7) with prolactinoma (21 microadenomas and 14 macroadenomas) who were followed-up at the Endocrinology Unit, in Siena, and with available pituitary hormone assessment at baseline and during follow-up (m ± SD, years: 2.74 ± 0.55). Results IGF-1 increased in the whole cohort, but remaining within normal range, except two patients, in whom acromegaly was ruled out with oral glucose tolerance test. After dividing patients by weight, this trend was confirmed only in subjects with overweight and obesity (OV/OB) (p = 0.04). Interestingly, the reduction of prolactin levels was significantly greater in the OV/OB compared to normal-weight patients (median decrease of 97.5% versus 88.2%, p = 0.04). Conclusions Since DA and normalization of prolactin are known to improve insulin sensitivity, we speculated they have favored the increase of IGF-1 in OV/OB. Our results should be confirmed and the hypothesis proven by further studies.

• Dapagliflozin enhances the Nrf2 pathway and increases IGF-1, IGFBP-3, and BDNF levels in a rat ASD model. • Treatment reduces TNF-α, IL-17, and MDA levels, demonstrating anti-inflammatory properties. • Dapagliflozin improves cognitive and memory functions in PPA-induced ASD. • Modulates apoptotic mechanisms, suggesting therapeutic potential for oxidative stress and inflammation-related ASD. • Further studies needed to explore additional pathways and validate clinical potential. The biological effects of dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, reveal its antioxidant and anti-inflammatory properties, suggesting therapeutic benefits beyond glycemic control. This study explores the neuroprotective effects of dapagliflozin in a rat model of autism spectrum disorder (ASD) induced by propionic acid (PPA), characterized by social interaction deficits, communication challenges, repetitive behaviors, cognitive impairments, and oxidative stress. Our research aims to find effective treatments for ASD, a condition with limited therapeutic options and significant impacts on individuals and families. PPA induces ASD-like symptoms in rodents, mimicking biochemical and behavioral features of human ASD. This study explores dapagliflozin's potential to mitigate these symptoms, providing insights into novel therapeutic avenues. The findings demonstrate that dapagliflozin enhances the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway and increases levels of neurotrophic and growth factors such as brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-binding protein-3 (IGFBP-3). Additionally, dapagliflozin reduces pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17), and decreases the oxidative stress marker malondialdehyde (MDA). Dapagliflozin's antioxidant properties support cognitive functions by modulating apoptotic mechanisms and enhancing antioxidant capacity. These combined effects contribute to reducing learning and memory impairments in PPA-induced ASD, highlighting dapagliflozin's potential as an adjunctive therapy for oxidative stress and inflammation-related cognitive decline in ASD. This study underscores the importance of exploring new therapeutic strategies targeting molecular pathways involved in the pathophysiology of ASD, potentially improving the quality of life for individuals affected by this disorder. [ABSTRACT FROM AUTHOR]

Simple Summary: In dairy cows, a hormone called insulin-like growth factor 1 (IGF-1) helps to control growth and reproduction. It affects how oocytes develop in the ovaries. IGF-1 is usually attached to binding proteins (IGFBPs), which can limit its effects. This study looked at how IGF-1 transfers between blood and the fluid around the oocyte. We checked IGF-1 and protein levels in both places and also measured energy levels using ketones. We examined gene activity in ovary cells too to look for local regulation. We found that IGF-1 levels in blood and ovarian fluid are related. High ketone levels, which indicate low energy, were linked to lower IGF-1 and some of the IGFBP. Some gene activity is also related to IGF-1 levels. In summary, while additional research is necessary to fully understand the local regulatory mechanisms, our findings suggest that the transfer of IGF-1 between systems may link metabolic issues to fertility challenges in dairy cows. Insulin-like growth factor 1 (IGF-1) regulates dairy cow reproduction, while the paracrine IGF system locally influences fertility. In both systems, IGF-1 bioactivity is regulated through binding proteins (IGFBPs) inhibiting IGF-1 binding to its receptor (IGF1R). This study aimed to investigate a possible transfer between this endocrine and paracrine system. Therefore, blood and follicular fluid (FF) from postpartum dairy cows were analysed for ß-hydroxybutyrate (BHB), IGF-1, IGFBP-2, -3, -4, -5, and an IGFBP fragment in two study parts. The mRNA expression of IGFBP-2, IGFBP-4, IGF1R, and the pregnancy-associated plasma protein A (PAPP-A) in granulosa cells was measured. The results showed correlations between plasma and FF for IGF-1 (r = 0.57, p < 0.001) and IGFBP-2 (r = −0.57, p < 0.05). Blood BHB negatively correlated with IGF-1 in blood and FF and IGFBP-3, -5 and total IGFBP in blood (IGF-1 plasma: r = −0.26, p < 0.05; FF: r = −0.35, p < 0.05; IGFBP-3: r = −0.64, p = 0.006; IGFBP-5: r = −0.49, p < 0.05; total IGFBP: r = −0.52, p < 0.05). A negative correlation was found between IGFBP-2 expression and IGF-1 concentration in FF (r = −0.97, p = 0.001), while an IGFBP fragment positively correlated with IGF1R-mRNA in FF (r = 0.82, p = 0.042). These findings suggest a transfer and local regulation between the somatotropic axis and the follicular IGF system, linking the metabolic status with local effects on dairy cow fertility. [ABSTRACT FROM AUTHOR]

Approximately 10,000 children in France with growth hormone deficiency (GHD) are being administered daily recombinant human growth hormone (rhGH). Although this treatment has long proved efficient for restoring children's growth and metabolism, daily injections of rhGH have a few limitations, such as difficulties in terms of adherence to treatment, which may compromise growth during childhood but also metabolism in adulthood. In addition to the disease burden and besides the adherence hurdles, the obligations related to daily injection have a negative impact on the quality of life of patients and their families. The hypothesis that injections administered at intervals of 1 week, or even 1 month, could improve compliance, reduce treatment discontinuations, and optimize quality of life and therapeutic effectiveness has led to the emergence of new long-acting growth hormone (LAGH). Recent access to LAGHs (somatrogon MA) on the European and French market will likely be followed by a high demand from the families concerned and may raise questions on their effectiveness, safety, and practical use. Numerous practical and practice-related points are needed to guide prescribing physicians while many concerns are still left unresolved (treatment effectiveness or ineffectiveness endpoints, long-term effectiveness, etc.). These issues can only be addressed in the future by compiling registries and conducting long-term real-world studies. [ABSTRACT FROM AUTHOR]

The insulin-like growth factor 1 (IGF-1) is a pleiotropic hormone that regulates essential life-history traits and is known for its major contribution to determining individual ageing processes. High levels of IGF-1 have been linked to increased mortality and are hypothesised to cause oxidative stress. This effect has been observed in laboratory animals, but whether it pertains to wild vertebrates has not been tested. This is surprising because studying the mechanisms that shape individual differences in lifespan is important to understanding mortality patterns in populations of free-living animals. We tested this hypothesis under semi-natural conditions by simulating elevated IGF-1 levels in captive bearded reedlings, a songbird species with an exceptionally fast pace of life. We subcutaneously injected slow-release biodegradable microspheres loaded with IGF-1 and achieved a systemic 3.7-fold increase of the hormone within the natural range for at least 24 h. Oxidative damage to lipids showed marked sexual differences: it significantly increased the day after the manipulation in treated males and returned to baseline levels four days post-treatment, while no treatment effect was apparent in females. Although there was no overall difference in survival between the treatment groups, high initial (pre-treatment) IGF-1 and low post-treatment plasma malondialdehyde levels were associated with enhanced survival prospects in males. These results suggest that males may be more susceptible to IGF-1-induced oxidative stress than females and quickly restoring oxidative balance may be related to fitness. IGF-1 levels evolve under opposing selection forces, and natural variation in this hormone's level may reflect the outcome of individual optimization. [ABSTRACT FROM AUTHOR]

Blood flow restriction (BFR) has been incorporated in resistance training for over 20 years. We aimed to investigate the impact of low‐intensity suspension training with BFR (LIST+BFR) on GH, IGF‐1, and their association with physical fitness in young women. Thirty‐six active women participated and were randomly assigned to either the high‐intensity suspension training (HIST), LIST+BFR, or control (CON) groups. Training groups exercised three sessions weekly for 8 weeks. The CON only engaged in regular physical activity. Fasting serum hormones and physical fitness were assessed 48 h before and after the training intervention. GH and IGF‐1 levels significantly higher in the LIST+BFR compared to the HIST and CON. These hormones were significantly higher by HIST, compared to CON. LIST+BFR led to significant enhancements in muscular strength and endurance compared to HIST and CON. Additionally, HIST significantly higher than compared to CON. Sprinting and agility time lower in both suspension training groups rather than the CON. No significant between‐groups differences were found in weight. There was a large or moderate correlation between GH and IGF‐1 and muscular strength, endurance, sprint, and agility performance. LIST+BFR could more enhanced GH, IGF‐1, and muscular strength and endurance in females than HIST. [ABSTRACT FROM AUTHOR]

Simple Summary: Early-stage hepatocellular carcinoma (HCC) is notorious for its high recurrence rate even after curative treatment. Several studies have suggested the association between diabetes mellitus (DM) and the risk of HCC. However, current evidence regarding the impact of glycemic burden on the outcomes of HCC is still limited. The present study provides an important insight into the relationship between glycemic burden and outcomes of early-stage HCC. Lower glycemic burden was an independent factor associated with better overall survival as well as lower recurrence in early-stage HCC. Moreover, there was a dose–response relationship between recurrence/overall survival and glycemic burden. Good glycemic control should be considered as a significant part of HCC management. Early-stage hepatocellular carcinoma (HCC) is still difficult to cure for its high recurrence rate. This study aimed to examine whether glycemic burden management could be one way to improve outcomes of early-stage HCC. A total of 137 very early or early-stage HCC patients who underwent resection or ablation at Samsung Medical Center and had glycemic burden assessment were analyzed. Glycemic burden was assessed using hemoglobin A1c (HbA1c) level. Outcomes were recurrence and overall survival. Risks of recurrence and overall survival were compared according to glycemic burden using a cut-off point of 6.5% or two cut-off points of 6.0% and 7.5%. Overall, 51 (37.2%) patients experienced HCC recurrence. The adjusted hazard ratio (aHR) for recurrence comparing patients with HbA1c > 6.5% to those with HbA1c ≤ 6.5% was 2.66 (95% CI: 1.26–5.78). The risk of recurrence increased in a dose-dependent manner by glycemic burden; aHR for 6.0 < HbA1c ≤ 7.5%: 2.00 (95% CI: 0.78–5.55); aHR for HbA1c > 7.5%: 6.05 (95% CI: 2.31–17.5). Mortality was observed in 16 (11.7%) patients. The risk of mortality was higher for HbA1c > 6.5% than for HbA1c ≤ 6.5% (aHR: 2.33; 95% CI: 1.10–5.08). There was also a dose–response relationship between overall survival and glycemic burden. Glycemic burden assessed using HbA1c level was significantly associated with outcomes of early-stage HCC patients. Good glycemic control could be a therapeutic goal to improve clinical outcomes in these populations. [ABSTRACT FROM AUTHOR]

Purpose: Studies on intestinal microbiota in acromegaly are scant. This study aimed to characterize the gut microbiome in patients with acromegaly. Method: Stool samples were collected from 11 patients newly diagnosed with acromegaly and 12 healthy controls matched for body mass index (BMI) and age after three days on a standard diet. Clinical and gut microbial composition assessments were performed for the two participant groups using 16S rRNA gene amplicon sequencing. Results: There was no difference in the alpha diversity of the microbiota between the samples from patients with acromegaly and those from the healthy controls. Based on beta diversity measurements, differences in microbial community structures were found to be significant only when compared using the Jaccard similarity index. The corresponding Firmicutes/Bacteroidota ratio tended to be higher in individuals with acromegaly than in healthy controls. The mean relative abundance of Actinobacteriota was 2.3 times higher in the acromegaly patient group than in the control group. Eggerthellaceae, Christensenellaceae, and Bacteroidaceae were among the significantly abundant bacterial families in the samples from the acromegaly patient group, while Butyricicoccaceae and Tannerellaceae were decreased. At the level of the genus, the most discriminative features were the abundance of Prevotella 7, Bacteroides, Senegalimassilia, Enterohabdus, the Family XIII AD3011 group, Howardella, and Hungatella in the samples from the acromegaly patient group. In contrast, the Butyrivibrio and the Eubacterium eligens group were the most discriminative genera for the healthy controls and were significantly less abundant in patients with acromegaly. While there were no significantly differentiated taxa between the diabetic and non-diabetic subgroups, Prevotella_7 was significantly enriched in the osteoarthritis (OA) subgroup. No significant association was found between individual genera and growth hormone (GH) levels and insulin-like growth factor-1 (IGF-1) levels as well as the upper limit of normal (ULN). Conclusion: Although alpha and beta diversity were mainly similar between the two groups, significant differences were observed between the acromegaly group and the control group at the family and genus levels. These results suggest that the differences between the microbial communities in patients with acromegaly and those in healthy individuals consist primarily of compositional differences independent of abundance. Prospective studies are needed to further explore the clinical implications of gut microbiome dysbiosis in patients with acromegaly. [ABSTRACT FROM AUTHOR]

Hereditary neurodegenerative diseases (hNDDs) such as Alzheimer's, Parkinson's, Huntington's disease, and others are primarily characterized by their progressive nature, severely compromising both the cognitive and motor abilities of patients. The underlying genetic component in hNDDs contributes to disease risk, creating a complex genetic landscape. Considering the fact that growth factors play crucial roles in regulating cellular processes, such as proliferation, differentiation, and survival, they could have therapeutic potential for hNDDs, provided appropriate dosing and safe delivery approaches are ensured. This article presents a detailed overview of growth factors, and explores their therapeutic potential in treating hNDDs, emphasizing their roles in neuronal survival, growth, and synaptic plasticity. However, challenges such as proper dosing, delivery methods, and patient variability can hinder their clinical application. [ABSTRACT FROM AUTHOR]

Background: Acromegaly occurs due to overproduction of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Galectin-3 (Gal-3) has recently emerged as a novel biomarker, related to IGF-1. This study aimed to assess Gal-3 in patients with acromegaly and compare its effectiveness with traditional biomarker tests. Materials and methods: A randomized case control study conducted in a single center included 50 acromegaly patients and 40 apparently healthy subjects (HS) serve as control group matched both age and BMI. Laboratory test was measured by routine assay used in center. Gal-3, GH, and IGF-1 were measured by enzyme-linked immunosorbent assay (ELISA). Result: There were 50 patients with an average age of 50.40 ± 12.229 (50% of males). Compared with HS, patients' serum GAL-3 levels have increased significantly. The serum GAL-3 exceeds 14.363 ng/ml, with a sensitivity of 100.0 and a specificity of 100.0. Furthermore, serum Gal-3 levels in combination with traditional tests (GH and IGF-1) by DeLoongs test had a significant difference in discriminating acromegaly more accurately than traditional tests. Conclusion: In a summary, this study recommended clinicians measure serum Gal-3 as biomarkers for patients with acromegaly. In addition, the result above shed light on role of Gal-3 on acromegaly pathogenesis and might provide a therapeutic target of acromegaly patients. [ABSTRACT FROM AUTHOR]

The review discusses the relationship between acromegaly and uterine fibroids. It highlights variations in research methodologies and inconsistent findings, emphasizing the complex nature of fibroid development and the role of the somatotropic axis. Additionally, it addresses demographic factors and examines the potential impact of therapies on the risk and prevalence of uterine fibroids in individuals with acromegaly. We conducted an analysis of previously published literature that examined the repercussions of acromegaly on gynecological health in female cohorts, with specific attention directed towards elucidating the prevalence of uterine fibroids. We suggest that larger, more focused studies are needed to understand the specific impact of different treatments on the occurrence of gynecological issues in acromegaly patients. Additionally, our study emphasizes the importance of factors such as disease duration and treatment effectiveness. We hypothesize that a relationship between acromegaly and uterine fibroids may occur. However, it remains an area of ongoing research, with the need for larger, multi-center studies to draw more definitive conclusions. [ABSTRACT FROM AUTHOR]

Background: Aging results in many changes in health status, body composition, muscle strength, and, ultimately, functional capacity. These changes coincide with significant alterations in the endocrine system, such as insulin-like growth factor-1 (IGF-1) and IGF-binding proteins (IGFBPs), and may be associated with many symptoms of aging. The objectives of this study is to investigate the potential influence of different types of exercise, such as resistance training and aerobic training, on IGF-1 and IGFBP-3 levels in postmenopausal women. Methods: Medline, Scopus, and Google Scholar databases were systematically searched up to November 2023. The Cochrane Collaboration tool was used to assess the risk of bias and the quality of the studies. The random-effects model, weighted mean difference (WMD), and 95% confidence interval (CI) were used to estimate the overall effect. Between-study heterogeneity was assessed using the chi-squared and I2 tests. Results: Seventeen studies were included in the present systematic review and 16 studies were included in the meta-analysis. The pooled results from 16 studies (21 trials) with 1170 participants examining the impact of exercise on IGF-1 concentration showed a significant increase in IGF-1, and the pooled results among six studies (trials) showed a significant decrease in IGFBP-3 concentration (730 participants). In addition, resistance training and aerobic training had a significant effect on increasing IGF-1 concentration post-exercise compared with placebo. Conclusion: Based on this meta-analysis, Women who have completed menopause and followed an exercise routine showed changes in IGF-1 and IGFBP-3 levels that can indirectly be associated with risk of chronic age-related conditions. [ABSTRACT FROM AUTHOR]

This study aimed to elucidate the influence of miR-483-3p on human renal tubular epithelial cells (HK-2) under high glucose conditions and to understand its mechanism. Human proximal tubular epithelial cells (HK-2) were exposed to 50 mmol/L glucose for 48 h to establish a renal tubular epithelial cell injury model, denoted as the high glucose group (HG group). Cells were also cultured for 48 h in a medium containing 5.5 mmol/L glucose, serving as the low glucose group. Transfection was performed in various groups: HK-2 + low glucose (control group), high glucose (50 mM) (HG group), high glucose + miR-483-3p mimics (HG + mimics group), high glucose +miR-483-3p inhibitor (HG + inhibitor group), and corresponding negative controls. Real-time quantitative polymerase chain reaction (qPCR) assessed the mRNA expression of miR-483-3p, bax, bcl-2, and caspase-3. Western blot determined the corresponding protein levels. Proliferation was assessed using the CCK-8 assay, and cell apoptosis was analyzed using the fluorescence TUNEL method. Western blot and Masson's staining were conducted to observe alterations in cell fibrosis post miR-483-3p transfection. Furthermore, a dual-luciferase assay investigated the targeting relationship between miR-483-3p and IGF-1. The CCK8 assay demonstrated that the HG + mimics group inhibited HK-2 cell proliferation, while the fluorescent TUNEL method revealed induced cell apoptosis in this group. Conversely, the HG + inhibitor group promoted cell proliferation and suppressed cell apoptosis. The HG + mimics group upregulated mRNA and protein expression of pro-apoptotic markers (bax and caspase-3), while downregulating anti-apoptotic marker (bcl-2) expression. In contrast, the HG + inhibitor group showed opposite effects. Collagen I and FN protein levels were significantly elevated in the HG + mimics group compared to controls (P < 0.05). Conversely, in the HG + inhibitor group, the protein expression of Collagen I and FN was notably reduced compared to the HG group (P < 0.05). The dual luciferase reporter assay confirmed that miR-483-3p could inhibit the luciferase activity of IGF-1's 3′-UTR region (P < 0.05). miR-483-3p exerts targeted regulation on IGF-1, promoting apoptosis and fibrosis in renal tubular epithelial cells induced by high glucose conditions. [ABSTRACT FROM AUTHOR]

Background: A common complication of thalassemia is secondary osteoporosis. This study aimed to assess the prevalence and factors associated with low BMD in thalassemic patients. Method: This is a cross-sectional study. Eligible patients were males aged within 18-49 years or premenopausal women diagnosed with thalassemia in Chiang Mai University Hospital between July 2021 and July 2022. The diagnosis of low BMD by dual-energy x-ray absorptiometry (DXA) was defined as a Z-score of -2.0 SD or lower in either the lumbar spine or femoral neck. Clinical factors associated with low BMD were analyzed using a logistic regression model. Results: Prevalence of low BMDwas 62.4% from 210 patientswith a mean age of 29.7 ± 7.6 years. The predominant clinical characteristics of low BMD thalassemia patients were being female, transfusion-dependent (TDT) and a history of splenectomy. From multivariable analysis, the independent variables associated with low BMD were transfusion dependency (odds ratio, OR 2.36; 95%CI 1.28 to 4.38; p=0.006) and body mass index (BMI) (OR 0.71; 95%CI 0.61 to 0.82; p<0.001). Among patients with low BMD, we observed a correlation between a Z-score with low IGF-1 levels (b=-0.42; 95% CI -0.83 to -0.01; p=0.040), serum phosphate levels (b=0.40; 95% CI 0.07 to 0.73; p=0.016) and hypogonadism (b=-0.48, 95% CI -0.91 to -0.04, p=0.031). Conclusion: This study found a prevalence of low BMD in 62.4% of subjects. Factors associated with low BMD were TDT and BMI. Within the low BMD subgroup, hypogonadism, serum phosphate and low serum IGF-1 levels were associated with a lower Z-score. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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. Results: 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. Conclusion: Knocking down IGF‐1 alleviates HG‐induced podocyte injury and apoptosis by inactivating the JAK2/STAT signalling pathway and enhancing autophagy. [ABSTRACT FROM AUTHOR]

Growth hormone (GH) receptor (GHR) is abundantly expressed in neurons that co‐release the agouti‐related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARH). Since ARHAgRP/NPY neurons regulate several hypothalamic–pituitary‐endocrine axes, this neuronal population possibly modulates GH secretion via a negative feedback loop, particularly during food restriction, when ARHAgRP/NPY neurons are highly active. The present study aims to determine the importance of GHR signaling in ARHAgRP/NPY neurons on the pattern of GH secretion in fed and food‐deprived male mice. Additionally, we compared the effect of two distinct situations of food deprivation: 16 h of fasting or four days of food restriction (40% of usual food intake). Overnight fasting strongly suppressed both basal and pulsatile GH secretion. Animals lacking GHR in ARHAgRP/NPY neurons (AgRP∆GHR mice) did not exhibit differences in GH secretion either in the fed or fasted state, compared to control mice. In contrast, four days of food restriction increased GH pulse frequency, basal GH secretion, and pulse irregularity/complexity (measured by sample entropy), whereas pulsatile GH secretion was not affected in both control and AgRP∆GHR mice. Hypothalamic Ghrh mRNA levels were unaffected by fasting or food restriction, but Sst expression increased in acutely fasted mice, but decreased after prolonged food restriction in both control and AgRP∆GHR mice. Our findings indicate that short‐term fasting and prolonged food restriction differentially affect the pattern of GH secretion, independently of GHR signaling in ARHAgRP/NPY neurons. [ABSTRACT FROM AUTHOR]