Like the ovaries and prostate, the thyroid exhibits characteristic hormone secretion and regulation. Thyroid cancer (TC), especially differentiated thyroid carcinoma, has typical sex-specific and age-specific hormone-driven clinical features. Previous research has primarily focused on the effects of thyroid stimulating hormone, thyroid hormones, and estrogens on the onset and progression of TC, while the roles of growth hormone (GH), androgens, and glucocorticoids have largely been overlooked. Similarly, few studies have investigated the interactions between hormones and hormone systems. In fact, numerous studies of patients with acromegaly have shown that serum levels of GH and insulin-like growth factor-1 (IGF-1) may be associated with the onset and progression of TC, although the influences of age, sex, and other risk factors, such as obesity and stress, remain unclear. Sex hormones, the GH/IGF axis, and glucocorticoids are likely involved in the onset and progression of TC by regulating the tumor microenvironment and metabolism. The aim of this review was to clarify the roles of hormones and hormone systems in TC, especially papillary thyroid carcinoma, as references for further investigations.

Insulin-like growth factor binding protein 7 (IGFBP7) serves as a crucial extracellular matrix protein, exerting pivotal roles in both physiological and pathological processes. This comprehensive review meticulously delineates the structural attributes of IGFBP7, juxtaposing them with other members within the IGFBP families, and delves into the expression patterns across various tissues. Furthermore, the review thoroughly examines the multifaceted functions of IGFBP7, encompassing its regulatory effects on cell proliferation, apoptosis, and migration, elucidating the underlying mechanistic pathways. Moreover, it underscores the compelling roles in tumor progression, acute kidney injury, and reproductive processes. By rigorously elucidating the diverse functionalities and regulatory networks of IGFBP7 across various physiological and pathological contexts, this review aims to furnish a robust theoretical framework and delineate future research trajectories for leveraging IGFBP7 in disease diagnosis, therapeutic interventions, and pharmaceutical innovations.

UNASSIGNED: Uterine fibroids (UFs) are benign tumors of the female reproductive system originating from the smooth muscle of the uterus. Currently, progesterone is known to play a key role in the differentiation of the myometrial tissue to form UFs and their abnormal growth. The mechanism of action of progesterone in UF tumorigenesis involves its effect on increasing the concentrations and dysregulation of selected growth factors.
UNASSIGNED: A retrospective cohort study was performed to evaluate and compare tumor necrosis factor α (TNF-α), insulin-like growth factor 1 (IGF-1), plasminogen activator inhibitor-1 (PAI-1) serum concentrations in patients with UFs without prior hormonal treatment, patients with UFs treated with a 3-month standard ulipristal acetate (UPA - a type of selective progesterone receptor modulator) scheme (5 mg/day) and in control patients without UFs. A total of 120 patients were divided into 3 groups (controls, UFs with UPA treatment, UFs without UPA treatment).
UNASSIGNED: There were no significant differences in TNF-α serum concentrations between patients with UFs who underwent UPA treatment and patients who did not. Serum concentrations of IGF-1 and PAI-1 did not show significant intergroup differences.
UNASSIGNED: No significant differences were found between TNF-α concentrations in the serum of patients with UFs treated with UPA, and patients without UPA treatment. In addition, our data analysis did not show significant differences in the concentrations of IGF-1 and PAI-1 between patients with UFs and the control group. Further studies on the dependence of specific symptoms on selected growth factors are mandatory.

UNASSIGNED: The aim of the study was to evaluate the ability of cultivated odontoblast to form dentin-like tissue using fibroblast growth factor (FGF) and insulin-like growth factor (IGF).
UNASSIGNED: Dental pulp stem cells (DPSCs) were extracted from 10 human teeth. They were isolated and cultivated in vitro with the use of stem cell markers. The human DPSCs were characterized for trilineage differentiation. They were then differentiated into odontoblasts. The ability of cultivated odontoblasts to form dentin-like tissue was evaluated using FGF and IGF.
UNASSIGNED: IGF showed superior ability to form dentin-like tissue as compared to FGF. The addition of FGF showed no significant difference in the formation of dentin-like tissue. A combination of FGF and IGF in odontoblast showed an enhanced ability to form dentin-like tissue.
UNASSIGNED: The use of growth factors IGF and FGF with dental stem cells showed a greater potential to form dentin-like tissue. This can profoundly alter the paradigms of conservative vital pulp therapy, which may eventually make it possible to treat dental diseases by regeneration of lost dentine.

Various etiologies, including diabetic keratopathy (DK), dry eye disease (DED), and neurotrophic keratopathy (NK), can disrupt corneal homeostasis, exacerbating corneal epithelial defects. Topical insulin has emerged as a promising therapy for promoting corneal wound healing and addressing underlying pathologies. This review systematically evaluates the efficacy of topical insulin across different corneal disorders. A literature review was conducted across the PubMed, Google Scholar, and Scopus research databases. The search resulted in a total of 19 articles, consisting of clinical trials, retrospective studies, and case reports. In DK, topical insulin accelerates corneal wound healing post-vitreoretinal surgery with lower concentrations showing higher outcomes when compared to conventional therapy, possibly due to improved epithelial stem cell migration. In comparison, the dry-eye disease results are inconclusive regarding patient-reported outcomes and corneal staining. For NK, topical insulin accelerates corneal wound healing and restores corneal nerve sensation. Other persistent epithelial defect (PED) etiologies that have been treated with topical insulin are infection, immune-mediated, mechanical and chemical trauma, and chronic ocular surface alterations. Although individual mechanisms for the benefits of topical insulin for each of these etiologies have not been studied, the literature demonstrates that topical insulin is efficacious for PEDs regardless of etiology. Future clinical trials need to be conducted to further evaluate optimal dosing, duration, and use of topical insulin for the restoration of the corneal surface.

UNASSIGNED: Gut microbiota influences energy homeostasis in part through circulating hormones. Insulin-like growth factor-binding protein (IGFBP)-2 is a biomarker whose increase in systemic circulation is associated with positive effects on body weight and metabolism. In a recent clinical trial, probiotic Lacticaseibacillus rhamnosus HA-114 supplementation showed positive effects on eating behaviors and insulin resistance in overweight participants undergoing a weight-loss intervention. In this context, this ancillary study aimed at assessing the impact of L. rhamnosus HA-114 supplementation on plasma IGFBP-2 levels in these individuals, and whether this modulation correlated with changes in fat mass, energy metabolism, and eating behaviors.
UNASSIGNED: Fasting plasma IGFBP-2 concentrations were quantified in 100 overweight or obese men and women enrolled in a 12-week diet-based weight reduction program (-500 kcal/day), in combination with probiotic L. rhamnosus HA-114 or placebo supplementation. Baseline and changes in circulating IGFBP-2 concentrations were correlated with anthropometric parameter, glucose and lipid metabolism, cardiorespiratory function and eating behaviors.
UNASSIGNED: On average, the intervention reduced BMI by 4.6 % and increased IGFBP-2 by 13 %, regardless of supplementation group. Individuals who presented an increase in IGFBP-2 levels had significantly greater reductions in BMI. Changes in IGFBP-2 levels were correlated with loss in fat mass (r = 0.2, p < 0.001) in the probiotic-supplemented group, but not with other metabolic parameters or eating behaviors. Baseline IGFBP-2 levels were not associated with weight loss or improvements in cardiometabolic parameters.
UNASSIGNED: Probiotic supplementation with L. rhamnosus HA-114 did not modulate plasma IGFBP-2 levels. Changes in IGFBP-2 levels were correlated with greater reductions in BMI, but not with other metabolic parameters or eating behaviors, indicating that the benefits of HA-114 on eating behaviors are likely independent of IGFBP-2. Additional changes in microbiota might be required to modulate IGFBP-2 and observe its associations with eating behaviors and cardiometabolic improvements.

Aim: Azithromycin (AZM) is widely used to treat mycoplasma infection in pregnancy. However, there is no adequate evaluation of its side effect on the placenta. In this study, using human placental syncytiotrophoblasts and a mouse model, we investigated whether AZM use in pregnancy might adversely affect placental function and pregnancy outcome. Results: Transcriptomic analysis of AZM-treated human placental syncytiotrophoblasts showed increased expression of endoplasmic reticulum (ER) stress-related genes and decreased expression of genes for hormone production and growth factor processing. Verification studies showed that AZM increased the abundance of ER stress mediators (phosphorylated eIF2α, activating transcription factor 4 [ATF4], and C/EBP Homologous Protein [CHOP]) and decreased the abundance of enzymes involved in progesterone and estradiol synthesis (STS, CYP11A1, and CYP19A1) and insulin-like growth factor binding protein (IGFBP) cleavage (PAPPA and ADAM12) in human placental syncytiotrophoblasts. Inhibition of ER stress blocked AZM-induced decreases in the expression of CYP19A1, CYP11A1, PAPPA, and ADAM12, suggesting that the inhibition of AZM on those genes\' expression was secondary to AZM-induced ER stress. Further mechanism study showed that increased ATF4 in ER stress might repressively interact with C/EBPα to suppress the expression of those genes, including CEBPA itself. Mouse studies showed that AZM administration decreased fetal weights along with increased ER stress mediators and decreased levels of insulin-like growth factor, estrogen, and progesterone in the maternal blood, which could be alleviated by inhibition of ER stress. Innovation and Conclusion: These findings first support the fact that AZM, often used during pregnancy, may affect fetal growth by inhibiting crucial enzymes for estrogen and progesterone synthesis and disrupting crucial proteases for IGFBP cleavage via inducing ER stress in placental syncytiotrophoblasts.

Fibroblast growth factors and their receptors (FGFR) have major roles in both human growth and oncogenesis. In adults, therapeutic FGFR inhibitors have been successful against tumors that carry somatic FGFR mutations. In pediatric patients, trials testing these anti-tumor FGFR inhibitor therapeutics are underway, with several recent reports suggesting modest positive responses. Herein, we report an unforeseen outcome in a pre-pubescent child with an FGFR1-mutated glioma who was successfully treated with FDA-approved erdafitinib, a pan-FGFR inhibitor approved for treatment of Bladder tumors. While on treatment with erdafitinib, the patient experienced rapid skeletal and long bone overgrowth resulting in kyphoscoliosis, reminiscent of patients with congenital loss-of-function FGFR3 mutations. We utilized normal dermal fibroblast cells established from the patient as a surrogate model to demonstrate that insulin-like growth factor 1 (IGF-1), a factor important for developmental growth of bones and tissues, can activate the PI3K/AKT pathway in erdafitinib-treated cells but not the MAPK/ERK pathway. The IGF-I-activated PI3K/AKT signaling rescued normal fibroblasts from the cytotoxic effects of erdafitinib by promoting cell survival. We, therefore, postulate that IGF-I-activated P13K/AKT signaling likely continues to promote bone elongation in the growing child, but not in adults, treated with therapeutic pan-FGFR inhibitors. Importantly, since activated MAPK signaling counters bone elongation, we further postulate that prolonged blockage of the MAPK pathway with pan-FGFR inhibitors, together with actions of growth-promoting factors including IGF-1, could explain the abnormal skeletal and axial growth suffered by our pre-pubertal patient during systemic therapeutic use of pan-FGFR inhibitors. Further studies to find more targeted, and/or appropriate dosing, of pan-FGFR inhibitor therapeutics for children are essential to avoid unexpected off-target effects as was observed in our young patient.

BACKGROUND: Optimal size at birth dictates perinatal survival and long-term risk of developing common disorders such as obesity, type 2 diabetes and cardiovascular disease. The imprinted Grb10 gene encodes a signalling adaptor protein capable of inhibiting receptor tyrosine kinases, including the insulin receptor (Insr) and insulin-like growth factor type 1 receptor (Igf1r). Grb10 restricts fetal growth such that Grb10 knockout (KO) mice are at birth some 25-35% larger than wild type. Using a mouse genetic approach, we test the widely held assumption that Grb10 influences growth through interaction with Igf1r, which has a highly conserved growth promoting role.
RESULTS: Should Grb10 interact with Igf1r to regulate growth Grb10:Igf1r double mutant mice should be indistinguishable from Igf1r KO single mutants, which are around half normal size at birth. Instead, Grb10:Igf1r double mutants were intermediate in size between Grb10 KO and Igf1r KO single mutants, indicating additive effects of the two signalling proteins having opposite actions in separate pathways. Some organs examined followed a similar pattern, though Grb10 KO neonates exhibited sparing of the brain and kidneys, whereas the influence of Igf1r extended to all organs. An interaction between Grb10 and Insr was similarly investigated. While there was no general evidence for a major interaction for fetal growth regulation, the liver was an exception. The liver in Grb10 KO mutants was disproportionately overgrown with evidence of excess lipid storage in hepatocytes, whereas Grb10:Insr double mutants were indistinguishable from Insr single mutants or wild types.
CONCLUSIONS: Grb10 acts largely independently of Igf1r or Insr to control fetal growth and has a more variable influence on individual organs. Only the disproportionate overgrowth and excess lipid storage seen in the Grb10 KO neonatal liver can be explained through an interaction between Grb10 and the Insr. Our findings are important for understanding how positive and negative influences on fetal growth dictate size and tissue proportions at birth.

Insulin serves multiple functions as a growth-promoting hormone in peripheral tissues. It manages glucose metabolism by promoting glucose uptake into cells and curbing the production of glucose in the liver. Beyond this, insulin fosters cell growth, drives differentiation, aids protein synthesis, and deters degradative processes like glycolysis, lipolysis, and proteolysis. Receptors for insulin and insulin-like growth factor-1 are widely expressed in the central nervous system. Their widespread presence in the brain underscores the varied and critical functions of insulin signaling there. Insulin aids in bolstering cognition, promoting neuron extension, adjusting the release and absorption of catecholamines, and controlling the expression and positioning of gamma-aminobutyric acid (GABA). Importantly, insulin can effortlessly traverse the blood-brain barrier. Furthermore, insulin resistance (IR)-induced alterations in insulin signaling might hasten brain aging, impacting its plasticity and potentially leading to neurodegeneration. Two primary pathways are responsible for insulin signal transmission: the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, which oversees metabolic responses, and the mitogen-activated protein kinase (MAPK) pathway, which guides cell growth, survival, and gene transcription. This review aimed to explore the potential shared metabolic traits between Alzheimer\'s disease (AD) and IR disorders. It delves into the relationship between AD and IR disorders, their overlapping genetic markers, and shared metabolic indicators. Additionally, it addresses existing therapeutic interventions targeting these intersecting pathways.