Insulin-like Growth Factor-1 Levels Research Articles

Early detection of muscle wasting assessed by ultrasound and analysis of growth factor and systemic inflammation mediators in critically ill trauma patients: an observational study.

The present study aims to describe initial changes in muscle thickness and composition, muscle growth signaling mediators, and systemic inflammation in critically ill patients after major trauma. This observational study was carried out in a Level-I nonprofit trauma center. Thirty adults requiring mechanical ventilation were assessed within 24h post-admission. Skeletal muscle wasting was evaluated using ultrasound for muscle thickness and echogenicity along with circulating insulin-like growth factor 1 (IGF-1) and inflammatory cytokines over five consecutive days. Changes over time were assessed using ANOVA repeated-measures analysis with a Bonferroni post-hoc test. Bivariate correlations were evaluated using Pearson or Spearman coefficients. Over five days, a significant decrease (11%) in rectus femoris thickness (3.91 ± 0.86 to 3.47 ± 0.64, cm, p = 0.01) and an increase (29%) in echogenicity (62.1 ± 13.1 to 80.4 ± 17.3, AU, p < 0.01) were observed among the 30 patients included in this study. Circulating levels of IGF-1 exhibited a 38% reduction (68.8 ± 43.6 to 42.4 ± 29.4, ng/mL, p = 0.01). Furthermore, pro-inflammatory cytokine (IFN-y) increased by 17% (4.83 ± 1.39 to 5.66 ± 1.61, pg./mL, p = 0.02) from day 1 to day 5. These findings reveal substantial thickness and muscle composition alterations within 48h post-admission, worsening over five days. Despite standard rehabilitation care, changes in IGF-1 and IFN-y levels suggest early declines in muscle growth stimulus and increased inflammation.

Circulating insulin-like growth factor-1 and the risk of multiple sclerosis: a prospective cohort study.

Circulating insulin-like growth factor 1 (IGF-1) is positively associated with the risks of certain neurological disorders, including stroke, Alzheimer's disease, and Parkinson's disease. However, the association of IGF-1 with the risk of multiple sclerosis (MS) remains unclear. A total of 348,324 participants at baseline were included from the UK biobank in this prospective study. The association of circulating IGF-1 level with MS was analyzed by Cox proportional hazard models. Further, subgroup analyses were conducted to investigate the variables influencing these associations. Among 348,324 individuals, lower circulating IGF-1 concentrations were associated with a reduced risk of MS (95 % CI, 0.5930-0.9700; P value = 0.02763). The association between lower IGF-1 levels and reduced risk of MS remains robust in older and female participants. Moreover, risk of MS appeared to be lower in IGF-1-low individuals who never smoked, currently drinking alcohol, with higher body mass index, and higher glucose concentrations. Our findings indicate that a lower concentration of serum IGF-1 was associated with a reduced risk of MS. The results provide evidence that the circulating IGF-1 may play a significant role in the pathogenesis of MS.

Curcumin inhibits growth and triggers apoptosis in human castration-resistant prostate cancer cells via IGF-1/PI3K/Akt pathway.

This study aimed to investigate the possible mechanism by which curcumin inhibits human prostate cancer (PCa) and castration-resistant prostate cancer (CRPC). CRPC cells were treated with curcumin and their viability was assessed by MTT assay and apoptosis was detected by annexinV/propidium iodide double-staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays. Expression levels of insulin-like growth factor 1 receptor (IGF-1R) were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting. Phosphoinositide 3-kinase (PI3K), Akt, and forkhead box protein O1 (FOXO1) expression and phosphorylation were assessed by western blotting. The highly expressed PCa-related molecule IGF-1R was down-regulated in CRPC cells after curcumin treatment, as determined by RT-qPCR and western blotting. In addition, curcumin inhibited the tumor-related PI3K/Akt signaling pathway in CRPC cells. Moreover curcumin down-regulated the IGF-1/PI3K/Akt signaling pathway in tumors derived from CRPC cells. These results demonstrated that curcumin inhibits growth and triggers apoptosis of human CRPC cells via the IGF-1/PI3K/Akt pathway, thus providing potential new therapeutic strategies for PCa and CRPC.

RBM47 as a potential therapeutic target for thyroid-associated ophthalmopathy.

RNA-binding motif 47 (RBM47) is a recently identified RNA-binding protein involved in early vertebrate development, immune homeostasis, and cancer development. This study examined the biological functions of RBM47 in thyroid-associated ophthalmopathy (TAO). Orbital fibroblasts (OFs) were obtained from the control (n=6) and TAO groups (n=6). Protein and gene expression in the obtained samples were investigated using immunohistochemistry, western blotting (WB), and RT-PCR. OFs with RBM47 knockdown were established using small interfering RNA. Subsequently, Oil Red O staining, WB, and RT-PCR were performed to assess adipogenesis in the OFs. The IL-1β-induced expression of proinflammatory molecules and hyaluronan (HA) was determined using enzyme-linked immunosorbent assay and RT-PCR. Moreover, TGF-β-induced fibrosis was evaluated using scratch assays, RT-PCR, and WB. RBM47 expression was markedly increased in orbital tissues and OFs obtained from individuals with TAO. RBM47 knockdown decreased adipogenesis and fibrosis in OFs, and downregulated the levels of insulin-like growth factor 1 receptor (IGF-1R), proinflammatory molecules, and HA. Furthermore, low RBM47 expression downregulated IGF-1R, which subsequently inhibited adipocyte differentiation by decreasing extracellular signal-regulated kinase signalling. These findings indicate that RBM47 may be involved in the regulation of adipogenesis, inflammation, HA production, and fibrosis, highlighting its potential of RBM47 as a therapeutic target for TAO.

Iron Chelation Prevents Age-Related Skeletal Muscle Sarcopenia in Klotho Gene Mutant Mice, a Genetic Model of Aging.

A decline in skeletal muscle mass and function known as skeletal muscle sarcopenia is an inevitable consequence of aging. Sarcopenia is a major cause of decreased muscle strength, physical frailty and increased muscle fatigability, contributing significantly to an increased risk of physical disability and functional dependence among the elderly. There remains a significant need for a novel therapy that can improve sarcopenia and related problems in aging. Iron accumulation, especially catalytic iron (labile iron) through increased oxidative stress, could be one of the contributing factors to sarcopenia. Our study aimed to examine the effect of an iron chelator on age-related sarcopenia in mice. We investigated the effect of iron chelation (deferiprone, DFP) in sarcopenia, using mice with klotho deficiency (kl/kl), an established mouse model for aging. Four weeks old Klotho -/- male mice were treated with 25 mg/kg body weight of iron chelator deferiprone in drinking water for 8-14 weeks (n = 12/group, treated and untreated). At the end of the study, gastrocnemius, quadriceps and bicep muscles were dissected and used for western blot and immunohistochemistry analysis, histopathology and iron staining. Serum total iron, catalytic iron and cytokine ELISAs were performed with established methods. Treatment with DFP significantly reduced loss of muscle mass in gastrocnemius and quadriceps muscles (p < 0.0001). Total and catalytic iron content of serum and iron in muscles were significantly (both p < 0.0001) lower in the treated animals. The inhibitory factor of myogenesis, the myostatin protein in gastrocnemius muscles (p = 0.019) and serum (p = 0.003) were downregulated after 8 weeks of therapy accompanied by an increased in muscle contractile protein myosin heavy chain (~2.9 folds, p = 0.0004). Treatment decreased inflammation (serum IL6 and TNFα) (p < 0.0001, p = 0.005), respectively, and elevated insulin-like growth factor levels (p = 0.472). This was associated with reduced DNA damage and reduced 8-hydroxy 2 deoxyguanosine in muscle and HO-1 protein (p < 0.001, p = 079), respectively. Significant weight loss (p < 0.001) and decreased water intake (p = 0.012) were observed in untreated mice compared to treatment group. Kaplan-Meier survival curves show the median life span of treated mice was 108 days as compared to 63 days for untreated mice (p = 0.0002). In summary, our research findings indicate that deferiprone reduced age-related sarcopenia in the muscles of Klotho-/- mice. Our finding suggests chelation of excess iron could be an effective therapy to counter sarcopenia. However, additional studies are needed to evaluate and determine the efficacy in humans.

Association of ultra-processed food-related metabolites with selected biochemical markers in the UK Biobank

BackgroundUltra-processed food (UPF) intake is positively associated with multiple adverse health outcomes. However, the underlying biological mechanisms remain unclear. Serum metabolites may elucidate these mechanisms. We investigated serum metabolites correlated with UPF and un/minimally processed food (UNPF) intake and evaluated their association with selected biochemical markers.MethodsCross-sectional study within the UK biobank, including a total of 72,817 participants with 24-hour recall dietary data and 134 nuclear magnetic resonance metabolites. UPF and UNPF intakes were evaluated using the NOVA classification, and related metabolites were identified using elastic net penalized regression. A UPF metabolomic signature was computed as a weighted sum of UPF-related metabolites, using elastic net coefficients as weights. Associations between UPF and UNPF-related metabolites, and serum C-reactive protein (CRP), insulin-like growth factor-1(IGF-1), sex hormone-binding globulin (SHBG), and testosterone were examined using multiple quantile regression.ResultsElastic net model identified 17 and 15 metabolites uniquely related to UPF and UNPF intake, respectively. Acetoacetate, acetone, high-density lipoprotein (HDL) diameter, docosahexaenoic acid, linoleic acid, ω-3 fatty acids (FA), total lipids in large HDL cholesterol, and valine levels were decreased, but free cholesterol in extremely small very low-density lipoproteins (LDL), glutamine, glycine, glycoprotein acetyls, lactate, saturated FA, sphingomyelins, triglycerides in large LDL, and triglycerides in medium HDL levels were increased with high UPF intake. Opposite relationships were observed for UNPF intake. Heterogeneous associations were observed between UPF-related metabolites and CRP, IGF-1, SHBG, and testosterone levels. A UPF metabolomic signature was positively associated with CRP (regression coefficient per standard deviation, 1.45, 95% confidence interval, 1.385, 1.515) and negatively associated with IGF-1 (-3.16, -4.493, -1.827) and SHBG (-13.878, -15.291, -12.465).ConclusionA UPF metabolomic profile, including VLDL free cholesterol, saturated FA, triglycerides, glutamine, glycine, and glycoprotein acetyl was associated with inflammatory, insulin signalling, and reproductive biomarkers. This metabolomic profile should be explored as a potential mediators of UPF-disease associations, and as an objective marker of UPF intake.

Differences in VEGF (Vascular Endothelial Growth Factor) Levels AND IGF-1 (Insulin like Growth Factor-1) in Controlled and Uncontrolled Diabetes Mellites TIP 2 Patients at Puskesmas Padang Bulan Medan City

Diabetes mellitus is a metabolic disorder characterized by an increase in blood sugar due to decreased insulin secretion by pancreatic beta cells or impaired insulin function (insulin resistance) that can lead to microvascular and macrovascular complications. The results of previous studies state that plasma levels of VEGF and IGF-1 are associated with the incidence of diabetic retinopathy and diabetic nephropathy. The examinations carried out include HbA1C using the HPLC method, measurement of VEGF and IGF-1 levels using Bioassay Technology Laboratory ELISA Human IGF-1 and VEGF. Of the 52 patients examined, it was found that 10 type 2 DM were controlled and 42 type 2 DM were uncontrolled. Uncontrolled type 2 DM had a higher VEGF level of 409 (ng/ml) than controlled 391.8 (ng/ml). IGF-1 levels of uncontrolled type 2 DM were higher at 8.8 (ng/ml) than controlled 6.6 (ng/ml). The conclusion obtained from this study is that there is no significant difference in VEGF and IGF-1 levels in controlled and uncontrolled type 2 DM. Controlled type 2 DM VEGF levels are lower than uncontrolled, while controlled IGF-1 levels are lower than uncontrolled. There was no significant difference in IGF- 1 levels with obese and non-obese patients based on Body Mass Index (BMI). IGF-1 levels of obese type 2 DM are lower than those who are not obese.

Uncovering the intricacies of IGF-1 in Alzheimer's disease: new insights from regulation to therapeutic targeting.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β plaques and tau tangles, leading to cognitive decline and dementia. Insulin-like Growth Factor-1 (IGF-1) is similar in structure to insulin and is crucial for cell growth, differentiation, and regulating oxidative stress, synaptic plasticity, and mitochondrial function. IGF-1 exerts its physiological effects by binding to the IGF-1 receptor (IGF-1R) and activating PI3K/Akt pathway. In addition to the physiological activities in the brain, numerous studies point to a potential protective role of the IGF-1 pathway in the pathogenesis of neurodegenerative diseases, such as AD. Interestingly, patients with AD often exhibit altered insulin and IGF-1 levels, along with an inadequate insulin response. Dysregulation of IGF-1 signaling contributes to hyperphosphorylation of tau, NFT accumulation, increased β- and γ-secretase activity, elevated Aβ production, and impaired Aβ clearance, highlighting the need to explore the role of this signaling for potential therapeutic targets of AD. This review explores the role of IGF signaling in AD pathology, highlighting IGF-1 as a promising therapeutic target due to its significant involvement in disease mechanisms. Modulating IGF-1 activity could help mitigate neurodegeneration and preserve cognitive function in AD. A comprehensive understanding of the mechanisms underlying IGF-1 dysregulation is crucial for developing targeted therapeutic strategies to address the complex and multifaceted nature of AD.

Unlocking the full potential of resistance training: a comparative analysis of low- and high-intensity effects on neurotrophic growth factors and homocysteine

ObjectiveResistance training has been demonstrated an effective approach for preventing the cognitive function decline through physiological mechanisms; however, the effect of acute resistance training at different intensities on growth factor and homocysteine levels remains unclear. This study aimed to compare the impact of resistance training at varying intensities on peripheral neurobiological factors and homocysteine levels in young adults.MethodsTwelve young male adults, predominantly engaged in various sports activities but without prior strength training experience, were recruited to participate in a randomized controlled cross-over trial. They implemented two different resistance training protocols: high intensity (HIRT, 12 repetitions at 80% 1RM) and low intensity (LIRT, 24 repetitions at 40% 1RM). Blood samples were collected at three time points: pre-training, post training, and after 30 min of rest to measure changes in serum lactate, serum brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), irisin, and plasma homocysteine (Hcy) levels.ResultsBoth resistance training protocols significantly increased blood lactate and perceived exertion compared to pre-training (HIRT, p < 0.01; LIRT, p < 0.01), with higher levels observed in HIRT. Acute HIRT significantly elevated serum BDNF, IGF-1, and VEGF levels post training compared to LIRT (p < 0.05), while no difference was observed in irisin levels between the two protocols at any time point. Both training protocols significantly reduced plasma Hcy levels post training (p < 0.01) and maintained lower levels than pre-training and after 30 min of rest (p < 0.05), with no significant differences between the two protocols.ConclusionsThis study demonstrates that high intensity training appears to have a greater impact on specific neurobiological factors; however, regardless of intensity, resistance training can significantly decrease plasma homocysteine.Trial registration ClinicalTrials.gov ID: NCT06114550. Date of registration 01/30/2024. https://clinicaltrials.gov/study/NCT06114550.

The Essential Role of Right Amount and Quality of Protein for Ensuring Child Growth and Maintenance of Bone and Muscle Mass

Protein is a vital macronutrient, essential for growth, tissue repair, and immune function. However, the impact of elevated protein intake during childhood and adolescence remains controversial. While high protein intake in older adults is often recommended for maintaining muscle mass and preventing frailty, excessive intake in younger populations has raised concerns about potential health risks, particularly related to obesity. This review aims to update current literature on the long-term effects of protein consumption in children and adolescents (ages 4-18) and to explore emerging methods for evaluating protein metabolism in this age group. The RDA for protein varies based on age, sex, and activity level. Generally, it is suggested that children consume about 0.95-1.3 grams of protein per kilogram of body weight per day, depending on age and specific requirements. In many developed countries, children and adolescents often consume protein at levels 2-3 times higher than the RDA, potentially leading to both positive and negative health outcomes. Protein is critical for normal growth and development during childhood and adolescence. Adequate intake supports muscle development, immune function, and the production of hormones. Studies suggest that elevated protein intake may be linked to increased Fat-Free Mass Index (FFMI), which is beneficial for muscle development and overall body composition. High protein diets have been associated with increased satiety, which can help in managing appetite and potentially reducing overall caloric intake, thus contributing to healthier weight maintenance. Some evidence suggests a correlation between high protein intake in infancy and childhood and increased risk of obesity later in life. This association may be due to the overactivation of growth pathways and increased insulin-like growth factor-1 (IGF-1) levels. Excessive protein intake has been hypothesized to strain kidney function, especially in individuals with pre-existing kidney conditions. However, current evidence in healthy children and adolescents is inconclusive. This narrative review emphasizes the need for a nuanced understanding of protein intake in children and adolescents, considering both the benefits and potential risks associated with high protein consumption. As research evolves, dietary guidelines may need to be adjusted to reflect the latest findings.

Diagnostic value of fasting insulin and insulin-like growth factor-1 levels in girls with central precocious puberty.

The gonadotropin-releasing hormone (GnRH) provocation test is crucial for diagnosing central precocious puberty (CPP). However, due to its invasion and high cost, it is essential to find a simpler biomarker. This study aimed to investigate the feasibility of fasting insulin (FINS) and insulin-like growth factor-1 (IGF-1) as potential biomarkers for diagnosing girls with CPP and to analyze their effects on puberty development. From May 2023 to June 2024, we retrospectively analyzed 145 girls in the growth clinic of the Third Affiliated Hospital of Zhengzhou University, including 80 CPP girls as the case group and 65 normal growth and development girls as the control group. Collect their growth and development parameters and blood samples. The levels of FINS, IGF-1, and sex hormones were detected and compared between the two groups. Compared with the control group, girls in the CPP group showed higher levels of FINS, IGF-1, and IGF-1 standard deviation score (IGF-1 SDS) (p<0.001). Multivariate logistic regression analysis showed that the risk of CPP increased with the increase of FINS, IGF-1, and IGF-1SDS levels [OR=1.141, 95 % CI=(1.029-1.265), p<0.05; OR=1.062, 95 % CI=(1.011-1.116), p<0.05; OR=1.610, 95 % CI=(1.029-2.520), p<0.05]. The areas under the curve of FINS, IGF-1, IGF-1SDS, and their combination in the diagnosis of CPP were 0.759, 0.716, 0.707, and 0.777, respectively. Elevated FINS and IGF-1 levels in girls with CPP indicate their potential as effective biomarkers for early screening and diagnosis of CPP.

Clinical outcomes of switching to lonapegsomatropin from somatropin for treatment of pediatric growth hormone deficiency.

This study aimed to assess differences in insulin-like growth factor 1 (IGF-1) levels following the transition from somatropin to lonapegsomatropin in patients with pediatric growth hormone deficiency (GHD). Secondary objectives included the evaluation of dose titrations based on IGF-1 levels, changes in annualized height velocity (AHV) and body mass index (BMI), and assessing reported adverse effects associated with lonapegsomatropin therapy. A single-center, retrospective review was conducted including patients diagnosed with pediatric GHD initially treated with somatropin who transitioned to lonapegsomatropin between January 1, 2022, and December 31, 2023. Fourteen patients (median age: 9 years) were included. The median somatropin dose was 0.18 mg/kg/week (range, 0.09 to 0.29) at the time of transition and patients were initiated on a median lonapegsomatropin dose of 0.23 mg/kg/week (range, 0.15 to 0.26). This resulted in an IGF-1 increase of 2.3 SDS post-switch. Dose adjustments were made based on IGF-1 levels. Five patients required immediate dose reductions; four of these required further adjustments due to persistent elevation. There were no serious adverse effects reported. Lonapegsomatropin may be a favorable option to reduce injection burden for those with pediatric GHD, though the manufacturer's recommended starting dose of 0.24 mg/kg/week may require individualization. Careful monitoring and dose adjustment based on IGF-1 levels are necessary to maintain safety and efficacy.

Effect of Ozonated Water on Periodontitis: A Clinical Study

ABSTRACT This study aims to evaluate the effects of subgingival ozonated water irrigation as an adjunct to non-surgical periodontal treatment on clinical and biochemical parameters of patients with moderate and severe periodontitis. A total of 72 Stage II and III periodontitis patients were included in the study. The 72 systemically healthy patients were treated non-surgically. Finally of each visit concerning periodontal treatment, the pocket of each tooth was irrigated with a sterile plastic syringe (10 mL per quadrant) with a blunt tip containing ozonated water (OW; ozone groups), 0.12% chlorhexidine (CHX groups) or saline (C; control groups) for 30-60s. Periodontal clinical parameters, gingival crevicular fluid (GCF), vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) levels were evaluated at baseline and 8 weeks after therapy. GI and PPD values of Stage II periodontitis patients and the PPD values of Stage III periodontitis patients were lower in the OW group compared with the CHX and C groups, showing statistical difference (p < 0.05). The beneficial impact of subgingival OW applications VEGF and IGF levels, which are thought to play a role in the pathogenesis of periodontal disease and periodontal regeneration, should be taken into consideration.

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.

Interpreting IGF-1 in children treated with recombinant growth hormone: challenges during early puberty.

It can be challenging to determine the correct dosage of recombinant growth hormone (GH) in children with GH deficiency, leading to highly variable treatment responses. Insulin-like growth factor-1 (IGF-1) is a tool for monitoring GH treatment and dosing. However, IGF-1 levels depend on sex, age, and pubertal stage, amongst other factors, making its interpretation somewhat difficult. This study aimed to evaluate descriptively a group of 93 children treated per protocol with GH to assess the influence of pubertal signs and sex steroid levels on the interpretation of IGF-1. 93 (67 boys and 26 girls) prepubertal children who participated in a previous GH treatment trial were included. Age, pubertal stage, weight, height, GH dose, and IGF-1 plasma concentrations were collected at least yearly from 2 years before pubertal start and 3 years after pubertal start. Levels of estradiol in girls and testosterone in boys were analyzed from previously collected frozen samples. Nine of 58 (15.5%) estradiol samples in girls with Tanner breast stage 1 had pubertal levels of estradiol ≥25 pmol/L. For boys with testes size <4 mL, 24 out of the 153 (15.7%) testosterone samples were above the pubertal cut-off, ≥0.47 nmol/L. All the IGF-1 samples were divided into two groups based on an IGF-1 standard deviation score (SDS) of ≥2 or <2 SDS. The IGF-1 ≥2 SDS samples had a higher median (range) GH dose, 0.042 (0.02-0.10) mg/kg/day, compared with the IGF-1 <2 SDS samples, 0.038 (0.01-0.10) mg/kg/day, p<0.001. In the IGF-1 ≥2 SDS samples vs the IGF <2 SDS samples, estradiol levels were lower among girls, 13 (3-214) vs 102 (1-1070) pmol/L p<0.001, and testosterone levels were lower among boys, 0.35 (0.11-27.2) vs 6.9 (0.04-31.2) nmol/L p<0.001. Interpretation of IGF-1 near puberty is challenging due to the influence of sex steroids. Variations in sex steroid levels and pubertal status can lead to misleading interpretations and an overestimation of IGF-1 SDS. Establishing an IGF-1 reference range that includes sex steroid levels can improve its clinical use to monitor GH treatment.

METTL14 knockdown attenuates neuron injury and improves function recovery after spinal cord injury via regulating FGF21 in a m6A-IGF2BP1 dependent mechanism.

Fibroblast growth factor 21 (FGF21) and Methyltransferase-like 14 (METTL14) have been identified to be involved in spinal cord injury (SCI). However, whether FGF21 functioned in SCI via METTL14-induced N6-methyladenosine (m6A) modification remains unclear. PC12 cells were exposed to lipopolysaccharide (LPS) in vitro. qRT-PCR and western blotting analyses were applied to detect the mRNA and protein levels of METTL14, FGF21 and Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1). The CCK-8 assay, EdU assay, flow cytometry and ELISA analysis were used to conduct in vitro functional analyses. Cell ferroptosis was assessed by measuring the levels of Fe2+, reactive oxygen species, glutathione and related regulators. The N6-methyladenosine (m6A) modification profile was analyzed by methylated RNA immunoprecipitation (MeRIP) assay. The interaction between IGF2BP1 and FGF21 was validated using RIP assay. SCI animal models were constructed for in vivo analysis. Levels of FGF21 were decreased in LPS-induced PC12 cells. Functionally, FGF21 overexpression reversed LPS-induced proliferation inhibition, apoptosis, ferroptosis and inflammation in PC12 cells. Mechanistically, METTL14 induced FGF21 m6A modification in SCI cell models, and m6A-binding protein IGF2BP1 was involved in regulating FGF21 expression by METTL14. METTL14 silencing abolished LPS-induced neuronal apoptosis, inflammation and ferroptosis via regulating FGF21. Moreover, METTL14 silencing improved neuronal injury in SCI rat models by modulating FGF21 expression. METTL14 knockdown attenuates neuron injury and improves function recovery after SCI via up-regulating FGF21 in an m6A-IGF2BP1 dependent mechanism, suggesting a useful target for SCI recovery.

Core microbe Bifidobacterium in the hindgut of calves improves the growth phenotype of young hosts by regulating microbial functions and host metabolism

BackgroundThe growth and health of young ruminants are regulated by their gut microbiome, which can have lifelong consequences. Compared with subjective grouping, phenotypic clustering might be a more comprehensive approach to revealing the relationship between calf growth state and core gut microbes. However, the identification of beneficial gut bacteria and its internal mechanisms of shaping host phenotype differentiation remains unclear.ResultsIn this study, calves were divided into two clusters, cluster1 and cluster2, based on 29 phenotypic indicators using cluster analysis. Calves in cluster2 showed better growth performance, including higher body weight (BW), average daily gain (ADG), and dry matter intake (DMI), as well as better serum indicators with a high level of total superoxide dismutase (T-SOD), interleukin-6 (IL-6), and insulin-like growth factor-1 (IGF-1) compared to those in cluster1. Multi-omics was used to detect microbial features among calves in different phenotypic clusters. Distinct differences were observed between the two clustered gut microbiomes, including microbial diversity and composition. The close relationships between growth performance, blood metabolites, and microbiome were also confirmed. In cluster2, Bifidobacterium members were the dominant contributors to microbial metabolic functions with a higher abundance. Furthermore, pathways involved in carbohydrate degradation, glycolysis, and biosynthesis of propionate and proteins were active, while methane production was inhibited. In addition, the diversity and richness of hindgut resistome in cluster2 were lower than those in cluster1. The isolation and culture of Bifidobacterium strain, as well as the mice experiment, indicated that B. longum 1109 from calf feces in cluster2 could promote the growth of young hosts, enhance their blood immunity and antioxidation, and improve the development of hindgut.ConclusionsIn summary, cluster analysis has proved to be a feasible and reliable approach for identifying phenotypic subgroups of calves, prompting further exploration of host-microbiome interactions. Bifidobacterium as a core microbe in the hindgut of calves may play a crucial probiotic role in host phenotypic differentiation. This study enhances our comprehension of how gut core microbe shapes the host phenotype and provides new insights into the manipulation of beneficial gut colonizers to improve the growth performance and productivity of young ruminants.EbRLLe7F-yvVZ5Dd-FAxmeVideo

Effects of Tesamorelin on Neurocognitive Impairment in Abdominally Obese Persons with HIV.

In people with HIV (PWH) who are virally suppressed (VS) on antiretroviral therapy (ART), abdominal obesity (AO) is linked to neurocognitive impairment (NCI), potentially due to visceral adiposity, inflammation, and reduced insulin-like growth factor 1 (IGF-1). Tesamorelin, a growth hormone-releasing hormone, reduces AO and increases IGF-1, suggesting it might mitigate NCI in VS PWH. This 6-month, Phase II randomized, open-label clinical trial compared Tesamorelin versus standard-of-care (SOC) for NCI in abdominally obese PWH. Participants had VS, NCI, and AO (elevated waist circumference [WC]). Exclusions included conditions other than HIV causing NCI, active substance use disorder, and malignancy. Seventy-three participants were randomized 3:2 to Tesamorelin or SOC (2mg subcutaneously daily). The primary outcome was the change in neurocognitive performance at 6 months, with secondary outcomes including WC, mood, and daily functioning. The groups were well-matched at baseline. The Tesamorelin group showed a trend toward improved neurocognitive performance after 6 months (mean change: 0.146, 95% CI: -0.002 to 0.294, p=0.060), while the SOC group did not (0.103, 95% CI: -0.095 to 0.301, p=0.295), but the between-group difference was not significant (p=0.673). IGF-1 levels increased, but changes did not correlate with sRCS or WC. The Tesamorelin group had a greater reduction in WC than the SOC group (median difference -2.7 cm, p=0.015). While tesamorelin reduced WC, the cognitive benefits did not significantly differ between groups. Recognizing the limitations of insufficient power and no placebo arm, this study suggests no clear benefit of short-term AO reduction with tesamorelin on NCI.

A comparative study of the genetically improved Abbassa Nile tilapia strain (GIANT-G9) and a commercial strain in Egypt: growth vs. stress response

Selective breeding is a potent method for developing strains with enhanced traits. This study compared the growth performance and stress responses of the genetically improved Abbassa Nile tilapia strain (G9; GIANT-G9) with a local commercial strain over 12 weeks, followed by exposure to stressors including high ammonia (10 mg TAN/L), elevated temperature (37 °C), and both for three days. The GIANT-G9 showed superior growth, including greater weight gain, final weight, length gain, specific growth rate, and protein efficiency ratio, as well as a lower feed conversion ratio and condition factor compared to the commercial strain. The expression of growth hormone in the brain of the GIANT‐G9 increased significantly after 6 weeks, although it slightly decreased after 12 weeks. Growth hormone receptor 1 expression also increased significantly after 6 weeks. Muscle insulin-like growth factors (igf1 and igf2) levels up-regulated significantly only after 12 weeks in the GIANT‐G9. Under stress, serum enzymes (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase (ALP)) were significantly higher in the GIANT‐G9, while the commercial strain had lower levels. No significant changes were observed in liver ALP activity among stressed strains. Under stress, the GIANT‐G9 exhibited marked upregulation of splenic Toll-like receptors (tlr2, tlr9, tlr21), myeloid differentiation primary response protein 88 (myd88), nuclear factor kappa B (nf-κB), interleukin (il) 1β, and il6. Notably, il6 expression was higher than il1β in the spleen, with the opposite pattern in the head kidney. In response to immune stimulation, globulin levels significantly increased in the GIANT‐G9 but with similar values to the stressed commercial strain. Myostatin expression increased in the spleen of the stressed GIANT‐G9. The commercial strain exhibited the best liver catalase and superoxide dismutase activities under stress, while the GIANT‐G9 showed increased liver glutathione-S-transferase (GST) activity after exposure to ammonia and temperature stress. Serum lysozyme activity increased in the stressed commercial strain and under temperature stress in the GIANT‐G9 but decreased under other stress conditions. Overall, the stressed commercial strain demonstrated higher survivability than the stressed GIANT‐G9. The study revealed significant interactions between strains and stress factors. The GIANT‐G9 exhibited higher growth rates but lower antioxidant and immune capacities compared to the commercial strain at the juvenile stage of life and production cycle.

Prevalence of neoplasms in acromegaly: a Turkish single-center retrospective study

Aims: This study aimed to investigate the prevalence of benign and malignant neoplasms and to assess associated clinical conditions in patients with acromegaly. Methods: In this single center, retrospective and observational study, data from 71 patients with acromegaly followed at an endocrinology and metabolism diseases outpatient clinic between January 2010 and December 2023 were reviewed through the hospital's electronic database. Patients' medical histories, demographic data, blood examinations, medications, pituitary MRI scans, thyroid ultrasound, mammography, colonoscopy, endoscopy, and pathology reports were evaluated. Acromegaly diagnosis was based on elevated insulin-like growth factor-1 (IGF-1) levels and unsuppressed growth hormone (GH) levels after oral glucose tolerance testing. The chi-square test and Mann-Whitney U test were used to compare patients with malignancy to other patients in terms of demographic and clinical characteristics. Results: The study included predominantly female patients (60.6%) with an average age of 55.6 years. The mean age at diagnosis was 44.3±11.3 years, and the mean disease duration was 11.3±8.4 years. Malignancies, including breast, thyroid, and colorectal cancers, were detected in 9.9% of patients. Additionally, thyroid nodules were present in 62% of patients, and colon polyps in 14.1%. No significant differences were observed in clinical features including age, gender, disease duration, GH levels, IGF-1 levels, adenoma size, or remission frequency between patients with and without malignancy (p&gt;0.05 for all). Conclusion: This study reveals an increased prevalence of breast, colon, and thyroid cancers in patients with acromegaly. Performing cancer screenings in patients with acromegaly more comprehensively and at an earlier stage compared to the normal population may be beneficial.