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PURPOSE: We aimed to investigate the relationship between the tri-ponderal mass index (TMI), a new indirect measure of fat mass, and insulin-like growth factor (IGF)-I/IGF binding protein (IGFBP)-3. METHODS: The study included 1,630 children and adolescents who visited Jeonbuk National University Children's Hospital. Each patient's medical record was retrospectively reviewed for age, sex, height, weight, body mass index (BMI), TMI, and IGF-1 and IGFBP-3 levels. Study participants were divided by sex and then categorized by age, BMI, and TMI. Finally, the correlations of TMI with IGF-1 level, IGF-1 standard deviation score (SDS), IGFBP-3 level, IGFBP-3 SDS, and IGF-1/IGFBP-3 ratio were investigated. RESULTS: All participants were <19 years of age. BMI correlated with IGF-1 and IGFBP-3 levels in both sexes; however, the relationship with TMI differed by sex. TMI correlated with IGF-1 and IGFBP-3 SDS in boys and with IGF-1, IGFBP-3, and IGFBP-3 SDS in girls across all ages. In boys, BMI and TMI significantly correlated with IGF-1, IGF-1 SDS, IGFBP-3, IGFBP-3 SDS, and the IGF-1/IGFBP-3 ratio in the normal-weight group. TMI also correlated with IGF-1, IGFBP-3, and IGFBP-3 SDS in the overweight group. In girls, BMI significantly correlated with IGF-1, IGF-1 SDS, IGFBP-3, IGFBP-3 SDS, and the IGF-1/IGFBP-3 ratio in the normal-weight group and with IGFBP-3 and IGFBP-3 SDS in the overweight group, while TMI correlated with IGF-1, IGF-1 SDS, and the IGF-1/IGFBP-3 ratio in the normal-weight group; with IGF-1, IGFBP-3, and IGFBP-3 SDS in the overweight group; and with IGFBP-3 SDS in the obese group. CONCLUSION: TMI may more strongly correlate with IGFBP-3 level than BMI in overweight boys and with IGFBP-3 SDS in overweight and obese girls. The correlation of IGFBP-3 SDS with TMI may be helpful for evaluating weight status in adolescent girls.

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Background and aim: Insulin-like growth factor-1 may be involved in the epithelial-to-mesenchymal transition process. It can mitigate adverse effects when interacting with insulin-like growth factor binding protein 3. This study aimed to explore alterations in the expression of these two factors in the colonic tissue of mice with ulcerative colitis. Method: This study utilized animal models. Mice were randomly allocated into three distinct groups. Disease activity index assessment was performed first, followed by histological grading of colitis. Protein and mRNA expression levels were determined using Western blotting and RT-qPCR. Immunohistochemical detection was used to determine histochemistry scores. Pearson correlation and SPSS 25.0 software were used for data analysis. Results: The findings indicated a reduction in the expression of the two investigated factors as well as in epithelial-to-mesenchymal transition epithelial markers during inflammation, while the expression of noninflammatory factors increased. These effects were notably amplified following treatment. Interestingly, the changes in epithelial-to-mesenchymal transition-inducing factors and mesenchymal markers contradicted this trend. Pearson correlation analysis revealed a correlation between molecular indicators of change and epithelial-to-mesenchymal transition. Conclusion: Insulin-like growth factor-1 and insulin-like growth factor binding protein 3 may play a protective role in the development and progression of ulcerative colitis, potentially through their inhibition of the epithelial-to-mesenchymal transition. These factors hold promise as targets for the clinical diagnosis and treatment of ulcerative colitis.

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There is limited evidence regarding the effect of circuit-type low-intensity resistance exercise on physical fitness and blood parameters in breast cancer survivors (BCSs). Therefore, this study aimed to investigate the effect of low-intensity circuit resistance exercise on changes in physical fitness and blood parameters in BCSs. A total of 16 BCSs participated in a low-intensity circuit resistance exercise group (LCREG). The exercise program in the LCREG consisted of 50-60% of one repetition maximum, two to three times weekly, for 24 weeks. The control group (CG) did not receive any interventions. All participants were measured for physical fitness and blood parameters before and after the exercise intervention. The results showed that LCREG significantly improved body mass index (BMI) (p = 0.012), grip strength (p = 0.017), back strength (p = 0.042), plank (p = 0.036), balance (p = 0.030), low-density lipoproteins (LDL) (p = 0.050), total cholesterol (p = 0.017), and natural killer cell activity (NKCA) (p = 0.035) after exercise compared to before exercise. The LCREG also significantly improved BMI (p = 0.001), grip strength (p = 0.014), plank (p = 0.018), balance (p = 0.012), LDL (p = 0.024), total cholesterol (p = 0.012), and NKCA (p = 0.036) compared to the CG. These findings suggest that low-intensity circuit resistance exercise can increase physical fitness levels and improve the blood index in BCSs.

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(1) Colorectal cancer is a major cause of cancer-related death, with colorectal adenomas (CRAs) serving as precursors. Identifying risk factors such as vitamin D deficiency and the insulin-like growth factor (IGF) axis is crucial for prevention. (2) This case-control study included 85 participants (53 CRA patients and 32 controls) who underwent colonoscopy. We measured serum vitamin D3 (cholecalciferol), calcidiol (vitamin D metabolite), calcitriol (active vitamin D metabolite), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) to explore their associations with CRA risk. (3) Results: We found that lower cholecalciferol levels were a significant risk factor for CRA (OR = 4.63, p = 0.004). Although no significant differences in calcidiol and calcitriol levels were observed between CRA patients and controls, calcidiol deficiency was common in the study population. IGF-1 levels inversely correlated with age, calcitriol, and IGFBP-3 in CRA patients. (4) This study highlights the potential of lower cholecalciferol levels to detect patients at risk of CRA when calcidiol values cannot, suggesting the importance of evaluating different vitamin D metabolites in cancer prevention research. Our findings underscore the need to further investigate the interactions between calcitriol, the active form of vitamin D, and the IGF axis in colorectal cancer development.

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Insulin-like growth factor-binding proteins (IGFBPs) play important roles in regulating growth and development by binding to IGF, where IGFBP-3 and IGFBP-5 are the main binding carriers of IGF in the circulation system. In the present study, the gene sequences of igfbp-3, igfbp-5a, and igfbp-5b were cloned from the liver of yellowtail kingfish (Seriola lalandi). The ORF sequences of igfbp-3, igfbp-5a, and igfbp-5b were 888, 801, and 804 bp in length, which encoded 295, 266, and 267 amino acids, respectively. The above three genes were widely expressed in yellowtail kingfish tissues, with igfbp-3 being the most highly expressed in the heart, brain, and gonads, while igfbp-5a and igfbp-5b were both most highly expressed in the liver and kidney. The expression levels of igfbp-3, igfbp-5a, and igfbp-5b were detected throughout the embryonic and larval stages, suggesting their roles in early development and growth regulation of yellowtail kingfish. Besides, igfbp-3 and igfbp-5a were significantly up-regulated in the liver under food deprivation and high-density rearing conditions, which was exactly opposite to the growth performance of yellowtail kingfish, implying that they may serve as biomarkers of adverse culture conditions. Overall, the above results initially identified the molecular characteristics of igfbp-3/-5a/-5b in yellowtail kingfish and implied that they might play important roles in the growth and development, providing a basis for further research on underlying regulatory mechanisms.

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Nutrition and modulation of the hypermetabolic response to acute burns are reviewed in this article. Methods to determine caloric requirements are evaluated, including indirect calorimetry and predictive equations. Individual nutritional components of carbohydrates, fat, protein, vitamins, and trace elements are discussed specifically in relation to acute burn care. Selection of formula and route of administration are outlined, with an enteral high-carbohydrate, low-fat diet being preferable. Awareness and recognition of the signs and symptoms of malnutrition is critical in the management of variable caloric needs throughout hospitalization. Lastly, the catabolic state of acute burns is addressed through early excision and grafting and implementation of various pharmacologic agents, including growth hormone, insulin-like growth factor-1, insulin-like growth factor-binding protein-3, insulin, propranolol, and oxandrolone. Through a multipronged approach to nutrition, pediatric burn patients are provided the substrates for successful recovery and rehabilitation.

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OBJECTIVE: To explore the relationship between Growth Hormone Insulin-like Growth Factors (GH-IGFs) and growth retardation in children with bronchial asthma. METHODS: 112 children with bronchial asthma and 50 healthy children were studied. Serum GH, IGF-1, and Insulin-like Growth Factor Binding Protein 3 (IGFBP3) were assessed by ELISA. GH-IGFs-related parameters were compared, and the correlation between the parameters and bronchial asthma severity was analyzed. The bronchial asthma group was divided into the growth retardation group and non-growth retardation group to analyze the diagnostic value of GH-IGFs in growth retardation and the relationship between GH-IGFs and growth retardation. RESULTS: GH, IGF-1, and IGFBP3 in the bronchial asthma group were lower. GH, IGF-1, and IGFBP3 levels were decreased with the severity of bronchial asthma. GH, IGF-1, and IGFBP3 in the growth retardation group were lower than those in the non-growth retardation group. The AUC of GH-IGFs combined detection was higher than that of GH and IGFBP3 alone detection. GH < 9.27 µg/L and IGF-1 < 179.53 mmoL/L were risk factors for growth retardation in patients with bronchial asthma. CONCLUSION: GH-IGFs-related parameters have diagnostic value for growth retardation in children, and decreased levels of GH and IGF-1 are risk factors for growth retardation in children.

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Microvascular invasion (MVI) has been widely valued in the field of liver surgery because MVI positivity indicates poor prognosis in hepatocellular carcinoma (HCC) patients. However, the potential molecular mechanism underlying the poor prognosis of MVI-positive HCC patients is unclear. Therefore, this study focused on identifying the key genes leading to poor prognosis in patients with a high degree of malignancy of HCC by examining the molecular signaling pathways in MVI-positive HCC patients. Through RNA sequencing, TOX high mobility group box family member 3 (TOX3) was demonstrated to be significantly highly expressed in MVI-positive HCC tissues, which was associated with poor prognosis. The results of in vivo and in vitro showed that TOX3 can promote the oncogenesis and development of HCC by targeting key molecules of the MAPK and EMT signaling pathways. The IP-MS results indicated that proteasome degradation of TOX3 in HCC cells is potentially mediated by a tripartite motif containing 56 (TRIM56, an E3 ligase) in HCC cells. Inhibiting TRIM56 enhances TOX3 protein levels. Overall, our study identified TOX3 as a key gene in the MAPK and EMT signaling pathways in HCC, and its overexpression confers significant proliferation and invasiveness to tumor cells.

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Prostate cancer (PCa) is a prevalent malignancy among men, with a majority of patients presenting with distant metastases at the time of initial diagnosis. These patients are at a heightened risk of developing more aggressive castration­resistant PCa following androgen deprivation therapy, which poses a greater challenge for treatment. Notably, the inhibition of tumor angiogenesis should not be considered an ineffective treatment strategy. The regulatory role of CDK12 in transcriptional and post­transcriptional processes is essential for the proper functioning of various cellular processes. In the present study, the expression of CDK12 was first knocked down in cells using CRISPR or siRNA technology. Subsequently, RNA­seq analysis, co­immunoprecipitation, western blotting, reverse transcription­quantitative polymerase chain reaction and the LinkedOmics database were employed to reveal that CDK12 inhibits insulin like growth factor binding protein 3 (IGFBP3). Western blot analysis also demonstrated that CDK12 promoted VEGFA expression by inhibiting IGFBP3, which involves the Akt signaling pathway. Then, CDK12 was found to promote PCa cell proliferation, cell migration and angiogenesis by inhibiting IGFBP3 through cell proliferation assays, cell migration assays and tube formation assays, respectively. Finally, animal experiments were performed for in vivo validation. It was concluded that CDK12 promoted PCa and its angiogenesis by inhibiting IGFBP3.

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Rationale: Platinum-based chemotherapy is commonly used for treating solid tumors, but drug resistance often limits its effectiveness. Cancer-associated fibroblast (CAF)-derived extracellular vesicle (EV), which carry various miRNAs, have been implicated in chemotherapy resistance. However, the molecular mechanism through which CAFs modulate cisplatin resistance in oral squamous cell carcinoma (OSCC) is not well understood. We employed two distinct primary CAF types with differential impacts on cancer progression: CAF-P, representing a more aggressive cancer-promoting category, and CAF-D, characterized by properties that moderately delay cancer progression. Consequently, we sought to investigate whether the two CAF types differentially affect cisplatin sensitivity and the underlying molecular mechanism. Methods: The secretion profile was examined by utilizing an antibody microarray with conditioned medium obtained from the co-culture of OSCC cells and two types of primary CAFs. The effect of CAF-dependent factors on cisplatin resistance was investigated by utilizing conditioned media (CM) and extracellular vesicle (EVs) derived from CAFs. The impacts of candidate genes were confirmed using gain- and loss-of-function analyses in spheroids and organoids, and a mouse xenograft. Lastly, we compared the expression pattern of the candidate genes in tissues from OSCC patients exhibiting different responses to cisplatin. Results: When OSCC cells were cultured with conditioned media (CM) from the two different CAF groups, cisplatin resistance increased only under CAF-P CM. OSCC cells specifically expressed insulin-like growth factor binding protein 3 (IGFBP3) after co-culture with CAF-D. Meanwhile, IGFBP3-knockdown OSCC cells acquired cisplatin resistance in CAF-D CM. IGFBP3 expression was promoted by GATA-binding protein 1 (GATA1), a transcription factor targeted by miR-876-3p, which was enriched only in CAF-P-derived EV. Treatment with CAF-P EV carrying miR-876-3p antagomir decreased cisplatin resistance compared to control miRNA-carrying CAF-P EV. On comparing the staining intensity between cisplatin-sensitive and -insensitive tissues from OSCC patients, there was a positive correlation between IGFBP3 and GATA1 expression and cisplatin sensitivity in OSCC tissues from patients. Conclusion: These results provide insights for overcoming cisplatin resistance, especially concerning EVs within the tumor microenvironment. Furthermore, it is anticipated that the expression levels of GATA1 and miR-876-3p, along with IGFBP3, could aid in the prediction of cisplatin resistance.

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Objective To investigate the relationship between vitamin K2,insulin-like growth factor bind-ing protein 3(IGFBP-3),Omentin-1 and the therapeutic effect on children with idiopathic short stature(ISS),and to build a prediction model.Methods A total of 242 ISS children in Jinan Second Maternal and Child Health Hospital from 2019 to 2021 were selected.All of them received recombinant human growth hormone(rhGH)treatment and were divided into effective group and ineffective group according to the therapeutic effect after 12 months of treatment.The general data,vitamin K2,IGFBP-3 and Omentin-1 in the two groups were analyzed.The influencing factors of ISS children's therapeutic effect were analyzed by Logistic regression model and decision tree model.The predictive performance of two models was analyzed by using receiver oper-ating characteristic(ROC)curve.Results There were statistically significant differences in 25-hydroxy vita-min D[25(OH)D],parathyroid hormone(PTH),thyroid stimulating hormone(TSH),vitamin K2,IGFBP-3,Omentin-1,rhGH dosage and weekly outdoor exercise time between the two groups(P＜0.05).Logistic re-gression showed that PTH(OR=7.011,95％CI:2.456-20.014),vitamin K2(OR=0.605,95％CI:.0.465-0.788),IGFBP-3(OR=0.458,95％CI:0.321-0.654),Omentin-1(OR=0.514,95％CI:0.389-0.679)and rhGH dose(OR=0.563,95％CI:0.445-0.712)]were the influential factors for treatment ineffectiveness in ISS children(P＜0.05).The decision tree model showed that vitamin K2,IGFBP-3 and Omentin-1 were the factors influencing the therapeutic effect of ISS,and IGFBP-3 had the most significant impact.ROC curve re-sults showed that the area under the curve of decision tree model and Logistic regression model were 0.922 and 0.908,respectively,with good classification effect.Conclusion The therapeutic effect of ISS children is in-fluenced by factors such as vitamin K2,IGFBP-3,Omentin-1,and so on,and IGFBP-3 has the most significant impact.Logistic regression model and decision tree model could complement each other so as to provide refer-ence for improving the therapeutic effect of ISS children from different aspects.

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Objective To investigate the role of Smad signaling pathway in rat model of cerebral in-farction and explore the expression of insulin-like growth factor binding protein 3(IGFBP-3)in brain tissue and its relationship with neural function.Methods Sixty healthy adult male SD rats were randomly and equally divided into model group,sham-operation group,and normal control group.The model of cerebral infarction was established by using intraluminal thread occlusion,and the rats of the sham-operation group were only given exposure of the internal carotid artery and direct suture of the incision.In 1 week after successful modeling,Modified Neurological Seve-rity Score(mNSS)was used to evaluate the neurological function.HE staining was employed to observe the histopathological changes in the brain tissues.Western blotting and RT-PCR were adopted to detect the brain expression of IGFBP-3,Smad2 and Smad4 at protein and mRNA le-vels.Spearman correlation analysis was conducted to analyze the correlation among the expression levels of IGFBP-3,Smad2,Smad4 and P21.Results HE staining displayed that obvious brain ede-ma,characterized by disordered arrangement of brain cells,increased microglia,and blurred nucleo-lus of brain cells were observed in the rats of the model group,with the area of cerebral infarct of 20.55％.The mNSS score and the protein and mRNA levels of IGFBP-3,Smad2 and Smad4 were significantly higher,but the P21 protein and mRNA levels were obviously reduced in the model group than the sham-operation group and normal control group(P＜0.05,P＜0.01).Spearman correlation analysis showed that the mRNA level of IGFBP-3 in cerebral infarction rats was posi-tively correlated with the mNSS score and mRNA expression levels of Smad2 and Smad4(r=0.568,r=0.623,r=0.597;P＜0.01),and negatively with P21 mRNA level in the brain tissue(r=-0.573;P＜0.01).Conclusion The level of IGFBP-3 is significantly increased in brain tissue of rats with cerebral infarction,and it is closely associated with neural function of these rats,which may be related to Smad signaling pathway.

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Abstract Objective To explore the relationship between Growth Hormone Insulin-like Growth Factors (GH-IGFs) and growth retardation in children with bronchial asthma. Methods 112 children with bronchial asthma and 50 healthy children were studied. Serum GH, IGF-1, and Insulin-like Growth Factor Binding Protein 3 (IGFBP3) were assessed by ELISA. GH-IGFs-related parameters were compared, and the correlation between the parameters and bronchial asthma severity was analyzed. The bronchial asthma group was divided into the growth retardation group and non-growth retardation group to analyze the diagnostic value of GH-IGFs in growth retardation and the relationship between GH-IGFs and growth retardation. Results GH, IGF-1, and IGFBP3 in the bronchial asthma group were lower. GH, IGF-1, and IGFBP3 levels were decreased with the severity of bronchial asthma. GH, IGF-1, and IGFBP3 in the growth retardation group were lower than those in the non-growth retardation group. The AUC of GH-IGFs combined detection was higher than that of GH and IGFBP3 alone detection. GH < 9.27 μg/L and IGF-1 < 179.53 mmoL/L were risk factors for growth retardation in patients with bronchial asthma. Conclusion GH-IGFs-related parameters have diagnostic value for growth retardation in children, and decreased levels of GH and IGF-1 are risk factors for growth retardation in children.

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OBJECTIVE: To investigate the expression of insulin-like growth factor binding protein-3(IGFBP-3) in HELLP syndrome and its possible role in the pathogenesis of this disease. METHODS: 1) 87 subjects were enrolled, including 29 patients with HELLP syndrome, 29 patients with pre-eclampsia (PE), and 29 healthy gravidae as control. The levels of IGFBP-3, IGF-1, TGF-ß1, and VEGF in maternal and umbilical blood of them were detected using ELISA. Correlation analysis was used to observe the correlation between IGFBP-3 and IGF-1/TGF-ß1/VEGF in maternal and umbilical blood, as well as that between maternal serum IGFBP-3 and clinical diagnostic indicators of HELLP syndrome. 2) Human hepatic sinusoid endothelial cells (HLSEC) and human umbilical vein endothelial cells (HUVEC) were cultured with different concentrations of IGFBP-3. After 72 h of culture, cell apoptosis and the normal living cells rate were detected and compared. RESULTS: 1) In both maternal and umbilical blood of HELLP group, levels of IGFBP-3 and TGF-ß1 were higher than control and PE group, IGF-1was lower than control group, VEGF was lower than control and PE group. IGFBP-3 in maternal blood was correlated with IGF-1/TGF-ß1/ VEGF, while IGFBP-3 in umbilical blood was linked to IGF-1/TGF-ß1. In maternal blood, there was a negative correlation between PLT and IGFBP-3, and a positive correlation between ALT/AST/LDH and IGFBP-3. 2) After cultured with IGFBP-3, the total apoptosis rate of either HLSEC or HUVEC was considerably elevated, while the normal living rate was decreased. CONCLUSION: The expression of IGFBP-3 is elevated in HELLP syndrome, which may subsequently promote cell apoptosis by affecting the expression and function of IGF-1, VEGF, and TGFß1 in the IGF/PI3K/Akt, TGF-ß1/Smad3, and VEGF/eNOS/NO pathways. IGFBP-3 aggravates inflammatory reactions of the vascular endothelium and liver under hypoxia, affects the normal function of cells, and plays a role in the pathogenesis of diseases.

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The Insulin-like growth factor 2 (IGF-2) has been recently proven to alleviate depressive-like behaviors in both rats and mice models. However, its potential role as a peripheral biomarker has not been evaluated in depression. To do this, we measured plasma IGF-2 and other members of the IGF family such as Binding Proteins (IGFBP-1, IGFBP-3, IGFBP-5 and IGFBP-7) in a depressed group of patients (n = 51) and in a healthy control group (n = 48). In some of these patients (n = 15), we measured these proteins after a period (19 ± 6 days) of treatment with antidepressants. The Hamilton Depressive Rating Scale (HDRS) and the Self-Assessment Anhedonia Scale (SAAS) were used to measure depression severity and anhedonia, respectively. The general cognition state was assessed by the Mini-Mental State Examination (MMSE) test and memory with the Free and Cued Selective Reminding Test (FCSRT). The levels of both IGF-2 and IGFBP-7 were found to be significantly increased in the depressed group; however, only IGF-2 remained significantly elevated after correction by age and sex. On the other hand, the levels of IGF-2, IGFBP-3 and IGFBP-5 were significantly decreased after treatment, whereas only IGFBP-7 was significantly increased. Therefore, peripheral changes in the IGF family and their response to antidepressants might represent alterations at the brain level in depression.

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OBJECTIVES: To investigate the therapeutic effect of recombinant human growth hormone (rhGH) on children with growth hormone deficiency (GHD) and different pituitary developmental conditions. METHODS: A prospective study was performed on 90 children with GHD who were admitted to Xuchang Maternity and Child Health Hospital from June 2020 to December 2021. According to pituitary height on the median sagittal plane, they were divided into three groups: pituitary dysplasia group (n=45), normal pituitary group (n=31), and enlarged pituitary growth group (n=14). The changes in body height, growth velocity, height standard deviation score and serum levels of insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) were examined after treatment in the above three groups, and the differences of the above indices before and after treatment were compared among the three groups. RESULTS: After treatment, all three groups had significant increases in body height, growth velocity, height standard deviation score, and the serum levels of IGFBP-3 and IGF-1 (P<0.05). Compared with the normal pituitary group, the pituitary dysplasia group and the enlarged pituitary growth group had significantly higher values in terms of the differences in body height, growth velocity, height standard deviation score, IGF-1, and IGFBP-3 before and after treatment (P<0.05). There was no significant difference in the incidence rate of adverse reactions among the three groups (P>0.05). CONCLUSIONS: In GHD children with different pituitary developmental conditions, rhGH can promote bone growth and increase body height, especially in children with pituitary dysplasia and pituitary hyperplasia, with good safety.

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BACKGROUND: Currently, there are no effective markers to diagnose and monitor patients with neuroendocrine tumors (NETs). The aim of this study was to assess bone metabolism based on selected markers of bone turnover: OST, OPG, and IGFBP-3, in both the group of patients with NETs and the control group. Associations with selected sociodemographic, biochemical, and clinicopathological characteristics were examined. We also evaluated any potential associations between these markers and selected biochemical markers of NETs commonly used in clinical practice. METHODS: The study group included 60 patients with GEP-NETs and BP-NETs, while the control group comprised 62 healthy individuals. The serum concentrations of OST, OPG and IGFBP-3 were assessed using ELISA. RESULTS: OST and OPG levels were significantly higher in the study group compared to the control group. In the study group, we observed a significant correlation between OPG and the clinical stage and chromogranin A. Additionally, an association was found between OPG and histological grade, Ki-67, and metastasis in GEP-NET cases. CONCLUSIONS: Markers of bone turnover cannot be used in the routine diagnostics of neuroendocrine tumors. Nonetheless, these markers may help evaluate the skeletal system in patients with NETs. Further research is needed to determine the utility of osteocalcin (OST) and osteoprotegerin (OPG) as potential biomarkers for neuroendocrine tumors.

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BACKGROUND: Tooth development, as one of the major mineralized tissues in the body, require fine-tuning of mineralization micro-environment. The interaction between dental epithelium and mesenchyme plays a decisive role in this process. With epithelium-mesenchyme dissociation study, we found interesting expression pattern of insulin-like growth factor binding protein 3 (IGFBP3) in response to disruption of dental epithelium-mesenchyme interaction. Its action and related mechanisms as regulator of mineralization micro-environment during tooth development are investigated. RESULTS: Expressions of osteogenic markers at early stage of tooth development are significantly lower than those at later stage. BMP2 treatment further confirmed a high mineralization micro-environment is disruptive at early stage, but beneficial at later stage of tooth development. In contrast, IGFBP3's expression increased gradually from E14.5, peaked at P5, and decreased afterwards, demonstrating an inverse correlation with osteogenic markers. RNA-Seq and Co-immunoprecipitation showed that IGFBP3 regulates the Wnt/beta-catenin signaling pathway activity by enhancing DKK1 expression and direct protein-protein interaction. The suppression of the mineralization microenvironment effectuated by IGFBP3 could be reversed by the DKK1 inhibitor WAY-262611, further demonstrating that IGFBP3 exerted its influence via DKK1. CONCLUSION: A deeper understanding of tooth development mechanisms is essential for tooth regeneration, which have great implications for dental care. The current study demonstrated that the IGFBP3 expression is regulated in accordance with the needs of the mineralization microenvironment during tooth development, and IGFBP3 exerts its modulating action on osteogenic/odontogenic differentiation of hDPSCs by DKK1-Wnt/ beta-catenin axis.

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Introducción: La subunidad ácido-lábil (ALS) tiene un papel importante en los efectos endocrinos de los factores de crecimiento similares a la insulina (IGF) en tejidos diana. Históricamente ha recibido una atención limitada. El objetivo de nuestro estudio fue describir el rango normal de ALS en niños sanos y su relación con otros factores de crecimiento. Pacientes y métodos: Se diseñó un estudio descriptivo transversal. Se recopilaron datos sobre edad, altura, índice de masa corporal, edad gestacional, antropometría al nacer y niveles séricos de ALS, IGF1 e IGFBP3 de niños sanos de 2 a 15años con estatura estándar. Los niveles de ALS, IGF1 e IGFBP3 se midieron mediante ELISA. Se utilizaron modelos de normalización GAMLSS para la estandarización de variables. Resultados: Se recogieron muestras de 446 niños. En niños prepúberes, los niveles de ALS, IGF1 e IGFBP3 se correlacionaron de manera positiva en ambos sexos y con la edad (p<0,01). Los niveles de ALS, IGF1 e IGFBP3 y la relación molar IGF1/IGFBP3 fueron significativamente diferentes entre ambos sexos y más altos en los niños puberales (p<0,01). Se realizaron gráficas de normalidad por género para cada uno de los componentes del complejo ternario y para las relaciones molares IGF1/IGFBP3 e IGFBP3/ALS. Además, se construyeron fórmulas modelo para calcular el Z Score según la edad y el sexo. ConclusionesEste estudio podría determinar valores de referencia específicos por edad y sexo para IGF1, IGFBP3, ALS, IGF1/IGFBP3 e IGFBP3/ALS en niños españoles y parece establecer la relación entre edad, sexo y estadio puberal. (AU)

Introduction: The acid-labile subunit (ALS) plays an important role in the endocrine effects of insulin-like growth factors (IGFs) on target tissues. Historically, it has attracted limited attention. The aim of our study was to describe the normal range of ALS in healthy children and its association with other growth factors. Patients and methods: We designed a cross-sectional descriptive study. We collected data on age, height, body mass index, gestational age, anthropometry at birth and serum levels of ALS, IGF1 and IGFBP3 in healthy children aged 2-15years with a normal height. The levels of ALS, IGF1 and IGFBP3 were measured by ELISA. We fitted GAMLSS normalization models to standardize the variables. Results: Samples were collected from 446 children. In prepubertal children, the levels of ALS, IGF1 and IGFBP3 were positively correlated in both sexes and with age (P<.01). We found significant differences in the levels of ALS, IGF1 and IGFBP3 and the IGF1/IGFBP3 molar ratio between the sexes and higher levels in pubertal boys (P<.01). We generated normal probability plots for each sex for each of the components of the ternary complex and for the IGF1/IGFBP3 and IGFBP3/ALS molar ratios. In addition, we extracted equations from the models for the calculation of z-scores for age and sex. Conclusions: This study may contribute to age- and sex-specific reference values for IGF1, IGFBP3 and ALS levels and IGF1/IGFBP3 and IGFBP3/ALS ratios in Spanish children and suggests an association between age, sex and pubertal stage. (AU)

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INTRODUCTION: The acid-labile subunit (ALS) plays an important role in the endocrine effects of insulin-like growth factors (IGFs) on target tissues. Historically, it has attracted limited attention. The aim of our study was to describe the normal range of ALS in healthy children and its association with other growth factors. PATIENTS AND METHODS: We designed a cross-sectional descriptive study. We collected data on age, height, body mass index, gestational age, anthropometry at birth and serum levels of ALS, IGF1 and IGFBP3 in healthy children aged 2-15 years with a normal height. The levels of ALS, IGF1 and IGFBP3 were measured by ELISA. We fitted GAMLSS normalization models to standardize the variables. RESULTS: Samples were collected from 446 children. In prepubertal children, the levels of ALS, IGF1 and IGFBP3 were positively correlated in both sexes and with age (P < .01). We found significant differences in the levels of ALS, IGF1 and IGFBP3 and the IGF1/IGFBP3 molar ratio between the sexes and higher levels in pubertal boys (P < .01). We generated normal probability plots for each sex for each of the components of the ternary complex and for the IGF1/IGFBP3 and IGFBP3/ALS molar ratios. In addition, we extracted equations from the models for the calculation of z-scores for age and sex. CONCLUSIONS: This study may contribute age- and sex-specific reference values for IGF1, IGFBP3 and ALS levels and IGF1/IGFBP3 and IGFBP3/ALS ratios in Spanish children and suggests an association between age, sex, and pubertal stage.

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