Insulin-like growth factor 1 and sex hormones for assessment of anthropometric and pubertal growth of Egyptian children and adolescents with type 1 diabetes mellitus (single center study).

BACKGROUND: This study aimed to assess the anthropometric measures and pubertal growth of children and adolescents with Type 1 diabetes mellitus (T1DM) and to detect risk determinants affecting these measures and their link to glycemic control. PATIENTS AND METHODS: Two hundred children and adolescents were assessed using anthropometric measurements. Those with short stature were further evaluated using insulin-like growth factor 1 (IGF-1), bone age, and thyroid profile, while those with delayed puberty were evaluated using sex hormones and pituitary gonadotropins assay. RESULTS: We found that 12.5% of our patients were short (height SDS < -2) and IGF-1 was less than -2 SD in 72% of them. Patients with short stature had earlier age of onset of diabetes, longer duration of diabetes, higher HbA1C and urinary albumin/creatinine ratio compared to those with normal stature (p < 0.05). Additionally, patients with delayed puberty had higher HbA1c and dyslipidemia compared to those with normal puberty (p < 0.05). The regression analysis revealed that factors associated with short stature were; age at diagnosis, HbA1C > 8.2, and albumin/creatinine ratio > 8 (p < 0.05). CONCLUSION: Children with uncontrolled T1DM are at risk of short stature and delayed puberty. Diabetes duration and control seem to be independent risk factors for short stature.

Identification of potential mediators of the relationship between body mass index and colorectal cancer: a Mendelian randomization analysis.

BACKGROUND: Colorectal cancer (CRC) is the third-most-common cancer worldwide and its rates are increasing. Elevated body mass index (BMI) is an established risk factor for CRC, although the molecular mechanisms behind this association remain unclear. Using the Mendelian randomization (MR) framework, we aimed to investigate the mediating effects of putative biomarkers and other CRC risk factors in the association between BMI and CRC. METHODS: We selected as mediators biomarkers of established cancer-related mechanisms and other CRC risk factors for which a plausible association with obesity exists, such as inflammatory biomarkers, glucose homeostasis traits, lipids, adipokines, insulin-like growth factor 1 (IGF1), sex hormones, 25-hydroxy-vitamin D, smoking, physical activity (PA) and alcohol consumption. We used inverse-variance weighted MR in the main univariable analyses and performed sensitivity analyses (weighted-median, MR-Egger, Contamination Mixture). We used multivariable MR for the mediation analyses. RESULTS: Genetically predicted BMI was positively associated with CRC risk [odds ratio per SD (5 kg/m2) = 1.17, 95% CI: 1.08-1.24, P-value = 1.4 × 10-5] and robustly associated with nearly all potential mediators. Genetically predicted IGF1, fasting insulin, low-density lipoprotein cholesterol, smoking, PA and alcohol were associated with CRC risk. Evidence for attenuation was found for IGF1 [explained 7% (95% CI: 2-13%) of the association], smoking (31%, 4-57%) and PA (7%, 2-11%). There was little evidence for pleiotropy, although smoking was bidirectionally associated with BMI and instruments were weak for PA. CONCLUSIONS: The effect of BMI on CRC risk is possibly partly mediated through plasma IGF1, whereas the attenuation of the BMI-CRC association by smoking and PA may reflect confounding and shared underlying mechanisms rather than mediation.

Evolving growth hormone deficiency: proof of concept.

Introduction: We present the evolution of GHD in adolescent males with persistent growth failure, in whom the diagnosis was established after a second GH stimulation test (GST). Methods: We performed a retrospective chart review of children who presented for short stature (height less < 2SD for mean/mid-parental height) and/or growth failure (sustained growth velocity < 0 SD) to pediatric endocrinology at Mount Sinai Kravis Children's Hospital, New York and who had 2 GSTs. Data collected from electronic medical records were analyzed using SPSS v28.0. Results: Of 53 patients included, 42 were males. Average GH peak on initial GST was 15.48 ± 4.92 ng/ml, at 10.07 ± 2.65 years, mean height -1.68 ± 0.56SD(28% had <2SD), IGF-1 -1.00 ± 0.88SD. After 2.23 ± 1.22 years, at 12.04 ± 2.41years, height SDs decreased to -1.82 ± 0.63SD and IGF-1 was -1.08 ± 0.84SD. At repeat GST, average GH peak was 7.59 ± 2.12 ng/dL, with 36% ≤7 ng/dl and 32% in puberty. 12 males reached adult height of 0.08 ± 0.69 SD with a mean height gain of 1.83 ± 0.56SD(p<0.005), IGF-1 of -1.15 ± 0.81SD after 4.64 ± 1.4 years of GH. Conclusion: We offer evidence for Evolving Growth Hormone Deficiency (EGHD) through repeat GST in children with persistent growth slowdown, even with pubertal progression; emphasizing the need for careful longitudinal follow-up to make accurate diagnosis.

The Associations Between Serum Insulin-like Growth Factor-I, Brain White Matter Volumes, and Cognition in Mild Cognitive Impairment and Alzheimer's Disease.

Background: Insulin-like growth factor-I (IGF-I) regulates myelin, but little is known whether IGF-I associates with white matter functions in subjective and objective mild cognitive impairment (SCI/MCI) or Alzheimer's disease (AD). Objective: To explore whether serum IGF-I is associated with magnetic resonance imaging - estimated brain white matter volumes or cognitive functions. Methods: In a prospective study of SCI/MCI (n = 106) and AD (n = 59), we evaluated the volumes of the total white matter, corpus callosum (CC), and white matter hyperintensities (WMHs) as well as Mini-Mental State Examination (MMSE), Trail Making Test A and B (TMT-A/B), and Stroop tests I-III at baseline, and after 2 years. Results: IGF-I was comparable in SCI/MCI and AD (113 versus 118 ng/mL, p = 0.44). In SCI/MCI patients, the correlations between higher baseline IGF-I and greater baseline and 2-year volumes of the total white matter and total CC lost statistical significance after adjustment for intracranial volume and other covariates. However, after adjustment for covariates, higher baseline IGF-I correlated with better baseline scores of MMSE and Stroop test II in SCI/MCI and with better baseline results of TMT-B and Stroop test I in AD. IGF-I did not correlate with WMH volumes or changes in any of the variables. Conclusions: Both in SCI/MCI and AD, higher IGF-I was associated with better attention/executive functions at baseline after adjustment for covariates. Furthermore, the baseline associations between IGF-I and neuropsychological test results in AD may argue against significant IGF-I resistance in the AD brain.

IGF1 promotes human myotube differentiation toward a mature metabolic and contractile phenotype.

Skeletal muscle mediates the beneficial effects of exercise, thereby improving insulin sensitivity and reducing the risk for type 2 diabetes. Current human skeletal muscle models in vitro are incapable of fully recapitulating its physiological functions especially muscle contractility. By supplementation of insulin-like growth factor 1 (IGF1), a growth factor secreted by myofibers in vivo, we aimed to overcome these limitations. We monitored the differentiation process starting from primary human CD56-positive myoblasts in the presence/absence of IGF1 in serum-free medium in daily collected samples for 10 days. IGF1-supported differentiation formed thicker multinucleated myotubes showing physiological contraction upon electrical pulse stimulation (EPS) following day 6. Myotubes without IGF1 were almost incapable of contraction. IGF1 treatment shifted the proteome toward skeletal muscle-specific proteins that contribute to myofibril and sarcomere assembly, striated muscle contraction, and ATP production. Elevated PPARGC1A, MYH7, and reduced MYH1/2 suggest a more oxidative phenotype further demonstrated by higher abundance of proteins of the respiratory chain and elevated mitochondrial respiration. IGF1-treatment also upregulated glucose transporter (GLUT)4 and increased insulin-dependent glucose uptake compared with myotubes differentiated without IGF1. To conclude, addition of IGF1 to serum-free medium significantly improves the differentiation of human myotubes that showed enhanced myofibril formation, response to electrical pulse stimulation, oxidative respiratory capacity, and glucose metabolism overcoming limitations of previous standards. This novel protocol enables investigation of muscular exercise on a molecular level.NEW & NOTEWORTHY Human skeletal muscle models are highly valuable to study how exercise prevents type 2 diabetes without invasive biopsies. Current models did not fully recapitulate the function of skeletal muscle especially during exercise. By supplementing insulin-like growth factor 1 (IGF1), the authors developed a functional human skeletal muscle model characterized by inducible contractility and increased oxidative and insulin-sensitive metabolism. The novel protocol overcomes the limitations of previous standards and enables investigation of exercise on a molecular level.

Sprayable and self-healing chitosan-based hydrogels for promoting healing of infected wound via anti-bacteria, anti-inflammation and angiogenesis.

Treatment of infected wound by simultaneously eliminating bacteria and inducing angiogenesis to promote wound tissue regeneration remains a clinical challenge. Dynamic and reversable hydrogels can adapt to irregular wound beds, which have raised great attention as wound dressings. Herein, a sprayable chitosan-based hydrogel (HPC/CCS/ODex-IGF1) was developed using hydroxypropyl chitosan (HPC), caffeic acid functionalized chitosan (CCS), oxidized dextran (ODex) to crosslink through the dynamic imine bond, which was pH-responsive to the acidic microenvironment and could controllably release insulin growth factor-1 (IGF1). The HPC/CCS/ODex-IGF1 hydrogels not only showed self-healing, self-adaptable and sprayable properties, but also exhibited excellent antibacterial ability, antioxidant property, low-cytotoxicity and angiogenetic activity. In vivo experiments demonstrated that hydrogels promoted tissue regeneration and healing of bacteria-infected wound with a rate of approximately 98.4 % on day 11 by eliminating bacteria, reducing inflammatory and facilitating angiogenesis, demonstrating its great potential for wound dressing.

Comparison of growth factor levels in injectable platelet-rich fibrin obtained from healthy individuals and patients with chronic periodontitis: a pilot study.

BACKGROUND: This study aimed to assess and compare the concentrations of growth factors, white blood cells (WBCs), and platelets in injectable platelet-rich fibrin (i-PRF) derived from people with healthy periodontal conditions and those with chronic periodontitis. METHODS: Venous blood samples were obtained from 30 patients diagnosed with chronic periodontitis (test group) and 30 participants with healthy periodontal conditions (control group). The i-PRF was then acquired from centrifuged blood. The growth factors (VEGF, IGF-1, TGF-ß1, PDGF-BB and EGF) released from the i-PRF samples were compared between groups with ELISA testing. The amounts of WBCs and platelets were also compared. RESULTS: No significant differences in the concentrations of growth factors were found between the groups (the mean values for the control and test groups were, respectively: IGF: 38.82, 42.46; PDGF: 414.25, 466.28; VEGF: 375.69, 412.18; TGF-ß1: 21.50, 26.21; EGF: 138.62, 154.82). The test group exhibited a significantly higher WBC count than the control group (8.80 vs. 6.60, respectively). However, the platelet count did not show a statistically significant difference between the groups (control group 242.0 vs. test group 262.50). No significant correlation was observed between WBC count and growth factor level in either group. CONCLUSIONS: The growth factor levels in i-PRFs did not exhibit significant difference between the two groups. This suggests that the levels of these growth factors may be unaffected by the periodontal disease.

Promotion of hair growth by a conditioned medium from human umbilical cord mesenchymal stem cells cultivated in a 3D scaffold of gelatin sponge.

BACKGROUND: This study aims to investigate the effects of a conditioned medium (CM) from human umbilical cord mesenchymal stem cells (HuMSCs) cultivated in gelatin sponge (GS-HuMSCs-CM) on hair growth in a mouse model. METHODS: CM was collected from the HuMSCs cultivated in a monolayer or in a gelatin sponge. Vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), keratinocyte growth factor (KGF), and hepatocyte growth factor (HGF) levels in CMs were measured by enzyme-linked immunosorbent assays (ELISAs). A hair loss model by a C57 BL/6J mouse was prepared. The effects of GS-HuMSCs-CM and HuMSCs on hair regrowth in mice were investigated by intradermal injection in the depilated back skin with normal saline (NS) as the control. The time for hair regrowth and full covering in depilated areas was observed, and the hair growth was evaluated histologically and by grossly measuring hair length and diameter. RESULTS: Compared with monolayer cultured cells, the three-dimensional (3D) culture of HuMSCs in gelatin sponge drastically increased VEGF, IGF-1, KGF, and HGF production. GS-HuMSCs-CM and HuMSCs injection both promoted hair regeneration in mice, while GS-HuMSCs-CM presented more enhanced effects in hair length, hair diameter, and growth rate. GS-HuMSCs-CM significantly promoted angiogenesis in injected skin areas, which might also contribute to faster hair regrowth. CONCLUSION: GS-HuMSCs-CM exerted significant effects on inducing hair growth and promoted skin angiogenesis in C57BL/6J mice.

Maternal high-fat diet during pregnancy and lactation affects factors that regulate cell proliferation and apoptosis in the testis of adult progeny.

Context A maternal high-fat diet is thought to pose a risk to spermatogenesis in the progeny. Aims We tested whether a maternal high-fat diet would affect Sertoli cell expression of transcription factors (insulin-like growth factor I (IGF-I); glial-cell line-derived neurotrophic factor (GDNF); Ets variant 5 (ETV5)) and cell proliferation and apoptotic proteins, in the testis of adult offspring. Methods Pregnant rats were fed ad libitum with a standard diet (Control) or a high-fat diet (HFat) throughout pregnancy and lactation. After weaning, male pups were fed the standard diet until postnatal day 160. Males were monitored daily from postnatal day 34 to determine onset of puberty. On postnatal day 160, their testes were processed for morphometry and immunohistochemistry. Key results The HFat diet increased seminiferous-tubule diameter (P P P P P P P P Conclusions A maternal high-fat diet alters the balance between spermatogonia proliferation and spermatid apoptosis. Implications A maternal high-fat diet seems to 'program' adult male fertility.

Extravascular administration of IGF1R antagonists protects against aortic aneurysm in rodent and porcine models.

An abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease. We identified plasma insulin-like growth factor 1 (IGF1) as an independent risk factor in patients with AAA by correlating plasma IGF1 with risk. Smooth muscle cell- or fibroblast-specific knockout of Igf1r, the gene encoding the IGF1 receptor (IGF1R), attenuated AAA formation in two mouse models of AAA induced by angiotensin II infusion or CaCl2 treatment. IGF1R was activated in aortic aneurysm samples from human patients and mice with AAA. Systemic administration of IGF1C, a peptide fragment of IGF1, 2 weeks after disease development inhibited AAA progression in mice. Decreased AAA formation was linked to competitive inhibition of IGF1 binding to its receptor by IGF1C and modulation of downstream alpha serine/threonine protein kinase (AKT)/mammalian target of rapamycin signaling. Localized application of an IGF1C-loaded hydrogel was developed to reduce the side effects observed after systemic administration of IGF1C or IGF1R antagonists in the CaCl2-induced AAA mouse model. The inhibitory effect of the IGF1C-loaded hydrogel administered at disease onset on AAA formation was further evaluated in a guinea pig-to-rat xenograft model and in a sheep-to-minipig xenograft model of AAA formation. The therapeutic efficacy of IGF1C for treating AAA was tested through extravascular delivery in the sheep-to-minipig model with AAA established for 2 weeks. Percutaneous injection of the IGF1C-loaded hydrogel around the AAA resulted in improved vessel flow dynamics in the minipig aorta. These findings suggest that extravascular administration of IGF1R antagonists may have translational potential for treating AAA.

Association of lncRNA MEG3 rs941576 polymorphism, expression profile, and its related targets with the risk of obesity-related colorectal cancer: potential clinical insights.

The identification of novel screening tools is imperative to empower the early detection of colorectal cancer (CRC). The influence of the long non-coding RNA maternally expressed gene 3 (MEG3) rs941576 single nucleotide polymorphism on CRC susceptibility remains uninvestigated. This research appraised MEG3 rs941576 association with the risk and clinical features of CRC and obesity-related CRC and its impact on serum MEG3 expression and its targets miR-27a/insulin-like growth factor 1 (IGF1)/IGF binding protein 3 (IGFBP3) and miR-181a/sirtuin 1 (SIRT1), along with the potential of these markers in obesity-related CRC diagnosis. 130 CRC patients (60 non-obese and 70 obese) and 120 cancer-free controls (64 non-obese and 56 obese) were enrolled. MEG3 targets were selected using bioinformatics analysis. MEG3 rs941576 was associated with magnified CRC risk in overall (OR (95% CI) 4.69(1.51-14.57), P = 0.0018) and stratified age and gender groups, but not with obesity-related CRC risk or MEG3/downstream targets' expression. Escalated miR-27a and IGFBP3 and reduced IGF1 serum levels were concomitant with MEG3 downregulation in overall CRC patients versus controls and obese versus non-obese CRC patients. Serum miR-181a and SIRT1 were upregulated in CRC patients versus controls but weren't altered in the obese versus non-obese comparison. Serum miR-181a and miR-27a were superior in overall and obesity-related CRC diagnosis, respectively; meanwhile, IGF1 was superior in distinguishing obese from non-obese CRC patients. Only serum miR-27a was associated with obesity-related CRC risk in multivariate logistic analysis. Among overall CRC patients, MEG3 rs941576 was associated with lymph node (LN) metastasis and tumor stage, serum MEG3 was negatively correlated with tumor stage, while SIRT1 was correlated with the anatomical site. Significant correlations were recorded between MEG3 and anatomical site, SIRT1 and tumor stage, and miR-27a/IGFBP3 and LN metastasis among obese CRC patients, while IGF1 was correlated with tumor stage and LN metastasis among non-obese CRC patients. Conclusively, this study advocates MEG3 rs941576 as a novel genetic marker of CRC susceptibility and prognosis. Our findings accentuate circulating MEG3/miR-27a/IGF1/IGFBP3, especially miR-27a as valuable markers for the early detection of obesity-related CRC. This axis along with SIRT1 could benefit obesity-related CRC prognosis.

Presence of single nucleotide polymorphisms in transforming growth factor ß and insulin-like growth factor 1 in class II malocclusions due to retrognathic mandible.

AIM: The aim of this study was to evaluate specific single nucleotide polymorphisms (SNP) of transforming growth factor-beta (TGF-ß) (rs1800469) and insulin-like growth factor-1 (IGF-1) (rs17032362) genes in Class II individuals with a normal maxilla and retrognathic (short) mandible.

Low-Protein Infant Formula Enriched with Alpha-Lactalbumin during Early Infancy May Reduce Insulin Resistance at 12 Months: A Follow-Up of a Randomized Controlled Trial.

High protein intake during infancy results in accelerated early weight gain and potentially later obesity. The aim of this follow-up study at 12 months was to evaluate if modified low-protein formulas fed during early infancy have long-term effects on growth and metabolism. In a double-blinded RCT, the ALFoNS study, 245 healthy-term infants received low-protein formulas with either alpha-lactalbumin-enriched whey (α-lac-EW; 1.75 g protein/100 kcal), casein glycomacropeptide-reduced whey (CGMP-RW; 1.76 g protein/100 kcal), or standard infant formula (SF; 2.2 g protein/100 kcal) between 2 and 6 months of age. Breastfed (BF) infants served as a reference. At 12 months, anthropometrics and dietary intake were assessed, and serum was analyzed for insulin, C-peptide, and insulin-like growth factor 1 (IGF-1). Weight gain between 6 and 12 months and BMI at 12 months were higher in the SF than in the BF infants (p = 0.019; p < 0.001, respectively), but were not significantly different between the low-protein formula groups and the BF group. S-insulin and C-peptide were higher in the SF than in the BF group (p < 0.001; p = 0.003, respectively), but more alike in the low-protein formula groups and the BF group. Serum IGF-1 at 12 months was similar in all study groups. Conclusion: Feeding modified low-protein formula during early infancy seems to reduce insulin resistance, resulting in more similar growth, serum insulin, and C-peptide concentrations to BF infants at 6-months post intervention. Feeding modified low-protein formula during early infancy results in more similar growth, serum insulin, and C-peptide concentrations to BF infants 6-months post intervention, probably due to reduced insulin resistance in the low-protein groups.

Associations Between Hypertension, Angiotensin-Converting Enzyme Inhibitors, and Physical Performance in Very Old Adults: Results from the ilSIRENTE Study.

BACKGROUND: Results regarding the associations between hypertension-related parameters and physical performance in older adults are conflicting. A possible explanation for these divergent results is that investigations may not have adjusted their analyses according to the use of angiotensin-converting enzyme inhibitors (ACEIs). OBJECTIVES: To examine the associations between hypertension-related parameters, ACEI use, and a set of physical performance tests in very old adults. DESIGN: Cross-sectional study from the ilSIRENTE database. SETTING: Mountain community of the Sirente geographic area (L'Aquila, Abruzzo, Italy). PARTICIPANTS: All persons born in the Sirente area (13 municipalities) before 1 January 1924 and living in that region at the time of study were identified and invited to participate. The final sample included 364 older adults (mean age: 85.8 ± standard deviation [SD] 4.8). MEASUREMENTS: Physical performance was assessed using isometric handgrip strength (IHG), walking speed (WS) at normal and fast pace, 5-time sit-to-stand test (5STS), and muscle power measures. Blood pressure (BP) was measured after 20 to 40 min of rest, while participants sat in an upright position. Drugs were coded according to the Anatomical Therapeutic and Chemical codes. ACEIs were categorized in centrally (ACEI-c) and peripherally (ACEI-p) acting. Blood inflammatory markers, free insulin-like growth factor 1 (IGF-1), and IGF-binding protein 3 (IGFBP-3) were assayed. RESULTS: Results indicated that 5STS test was significantly and negatively associated with diastolic BP values. However, significance was lost when results were adjusted for ACEI use. Participants on ACEIs were more likely to have greater specific muscle power and higher blood levels of IGFBP-3 than non-ACEI users. When participants were categorized according to ACEI subtypes, those on ACEI-p had higher blood IGF-1 levels compared with ACEI-c users. CONCLUSIONS: The main findings of the present study indicate that ACEI use might influence the association between hypertension-related parameters and neuromuscular parameters in very old adults. Such results may possibly be linked to the effects of ACEI-p on the IGF-1 pathway.

The Effect of a Rotating Magnetic Field on the Regenerative Potential of Platelets.

Platelets are actively involved in tissue injury site regeneration by producing a wide spectrum of platelet-derived growth factors such as PDGF (platelet-derived growth factor), IGF-1 (insulin-like growth factor), TGF-ß1 (transforming growth factor ß), FGF (fibroblast growth factor), etc. A rotating magnetic field (RMF) can regulate biological functions, including reduction or induction regarding inflammatory processes, cell differentiation, and gene expression, to determine the effect of an RMF on the regenerative potential of platelets. The study group consisted of 30 healthy female and male volunteers (n = 15), from which plasma was collected. A portion of the plasma was extracted and treated as an internal control group. Subsequent doses of plasma were exposed to RMF at different frequencies (25 and 50 Hz) for 1 and 3 h. Then, the concentrations of growth factors (IGF-1, PDGF-BB, TGF-ß1, and FGF-1) were determined in the obtained material by the ELISA method. There were statistically significant differences in the PDGF-BB, TGF-ß1, IGF-1, and FGF-1 concentrations between the analyzed groups. The highest concentration of PDGF-BB was observed in the samples placed in RMF for 1 h at 25 Hz. For TGF-ß1, the highest concentrations were obtained in the samples exposed to RMF for 3 h at 25 Hz and 1 h at 50 Hz. The highest concentrations of IGF-1 and FGF-1 were shown in plasma placed in RMF for 3 h at 25 Hz. An RMF may increase the regenerative potential of platelets. It was noted that female platelets may respond more strongly to RMF than male platelets.

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

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

The involvement of Akt, mTOR, and S6K in the in vivo effect of IGF-1 on the regulation of rat cardiac Na+/K+-ATPase.

BACKGROUND: We previously demonstrated that insulin-like growth factor-1 (IGF-1) regulates sodium/potassium adenosine triphosphatase (Na+/K+-ATPase) in vascular smooth muscle cells (VSMC) via phosphatidylinositol-3 kinase (PI3K). Taking into account that others' work show that IGF-1 activates the PI3K/protein kinase B (Akt) signaling pathway in many different cells, we here further questioned if the Akt/mammalian target of rapamycin (mTOR)/ribosomal protein p70 S6 kinase (S6K) pathway stimulates Na+/K+-ATPase, an essential protein for maintaining normal heart function. METHODS AND RESULTS: There were 14 adult male Wistar rats, half of whom received bolus injections of IGF-1 (50 µg/kg) for 24 h. We evaluated cardiac Na+/K+-ATPase expression, activity, and serum IGF-1 levels. Additionally, we examined the phosphorylated forms of the following proteins: insulin receptor substrate (IRS), phosphoinositide-dependent kinase-1 (PDK-1), Akt, mTOR, S6K, and α subunit of Na+/K+-ATPase. Additionally, the mRNA expression of the Na+/K+-ATPase α1 subunit was evaluated. Treatment with IGF-1 increases levels of serum IGF-1 and stimulates Na+/K+-ATPase activity, phosphorylation of α subunit of Na+/K+-ATPase on Ser23, and protein expression of α2 subunit. Furthermore, IGF-1 treatment increased phosphorylation of IRS-1 on Tyr1222, Akt on Ser473, PDK-1 on Ser241, mTOR on Ser2481 and Ser2448, and S6K on Thr421/Ser424. The concentration of IGF-1 in serum positively correlates with Na+/K+-ATPase activity and the phosphorylated form of mTOR (Ser2448), while Na+/K+-ATPase activity positively correlates with the phosphorylated form of IRS-1 (Tyr1222) and mTOR (Ser2448). CONCLUSION: These results indicate that the Akt/mTOR/S6K signalling pathway may be involved in the IGF-1 regulating cardiac Na+/K+-ATPase expression and activity.

MiR-18 regulates lipid metabolism of non-alcoholic fatty liver disease via IGF1.

We aimed to illustrate the regulatory effect of miR-18 on the onset of non-alcoholic fatty liver disease (NAFLD). MiR-18 level in liver tissues collected from NAFLD patients and mice was detected. In vivo and in vitro influences of miR-18 on biochemical indexes, glucose tolerance and insulin resistance (IR) in NAFLD were determined. H&E staining was conducted to observe hepatic steatosis in NAFLD mice. The downstream target of miR-18 was finally detected by luciferase assay. MiR-18 was upregulated in liver tissues collected from NAFLD patients and mice. Knockdown of miR-18 reduced levels of AST, ALT, TG and TC in NAFLD mice and culture medium of FFA-induced LO2 cells. Meanwhile, knockdown of miR-18 alleviated hepatic steatosis and IR in NAFLD mice. IGF1 was the target of miR-18, and it was negatively regulated by miR-18. MiR-18 is upregulated in NAFLD patients and mice. Knockdown of miR-18 alleviates HFD-induced hepatic steatosis and IR through interacting with IGF1 to regulate to lipid metabolism and insulin signals.

The effect of tamoxifen on estradiol, SHBG, IGF-1, and CRP in women with breast cancer or at risk of developing breast cancer: a meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: The effects of tamoxifen on the serum levels of hormones and acute phase reactants have been studied previously, but study results have been inconsistent, especially in women with breast cancer. Hence, we conducted this meta-analysis of randomized controlled trials (RCTs) to try to clarify the effects of tamoxifen on estradiol, insulin-like growth factor 1 (IGF-1), sex hormone binding globulin (SHBG), and C-reactive protein (CRP) serum levels in women with breast cancer or at risk of developing breast cancer. METHODS: Databases were systematically searched up to December 2023. The meta-analysis was generated through a random-effects model and is presented as the weighted mean difference (WMD) and 95 % confidence intervals (CI). RESULTS: Nine publications were included in the present meta-analysis. The comprehensive findings from the random-effects model revealed an elevation in estradiol (WMD: 13.04 pg/mL, 95 % CI: 0.79, 25.30, p = 0.037) and SHBG levels (WMD: 21.26 nmol/l, 95 % CI: 14.85, 27.68, p = 0.000), as well as a reduction in IGF-1 (WMD: -14.41 µg/L, 95 % CI: -24.23, -4.60, p = 0.004) and CRP concentrations (WMD: -1.17 mg/dL, 95 % CI: -2.29, -0.05, p = 0.039) following treatment with tamoxifen in women with breast cancer or at risk of developing breast cancer, with no impact on IGFBP-3 levels (WMD: 0.11 µg/mL, 95 % CI: -0.07, 0.30, p = 0.240). CONCLUSION: Tamoxifen administration seems to increase estradiol and SHBG levels and reduce CRP and IGF-1 levels in women with breast cancer or at risk of developing breast cancer. Further studies are needed to determine whether these changes have any clinical relevance.