Search Results (1,166)

Insulin-like growth factor 1 (IGF-1) is an important endocrine and autocrine/paracrine factor that regulates various cellular responses in multiple biological systems. Its actions are mediated mainly via its binding to the type 1 IGF receptor (IGF-1R), while its bioactivity is also modulated by the IGF-binding proteins (IGFBPs). The IGF-1 system regulates cell growth, differentiation and energy metabolism and thus plays a crucial role in the modulation of key aspects of cancer biology, such as cancer cell growth, survival, transformation and invasion. The synthesis of IGF-1 is regulated, among other factors, by microRNAs (miRNAs), and it has been shown that the miRNA-induced regulation of IGF-1 is implicated in various stages of tumor development and/or progression in different types of cancer. The aim of this review was to identify and characterize the miRNA-induced regulation of the IGF-1 system in various types of cancer. It was revealed that many miRNAs can be used as potential biomarkers, while others may contribute to metastasis regulation, targeting components of the IGF-1 bioregulation system and being implicated in cancer staging and/or progression. Additional miRNAs and their role in IGF-1’s effects on other types of cancer have also been identified. Nevertheless, future studies are needed to expand the current knowledge on the role of miRNAs in the regulation of other components of the IGF-1 bioregulation system and in various types of cancer, contributing further to the characterization of the role of miRNAs and their target genes as pathogenic, therapeutic and diagnostic molecules for cancer in clinical practice. Full article

Background: Non-islet cell tumor hypoglycemia is increasingly reported with gastrointestinal stromal tumors (GIST), but population-level estimates of its clinical impact are limited. We evaluated associations between hypoglycemia and inpatient outcomes among GIST hospitalizations. Methods: We conducted a retrospective cross-sectional study of the National Inpatient Sample (NIS) 2018–2020. Adult GIST discharges were identified by ICD-10-CM codes and stratified by hypoglycemia. Primary outcomes were in-hospital mortality and resource utilization—length of stay (LOS) and total hospital charge. Secondary outcomes included malnutrition, sepsis, ascites, peritonitis, bowel perforation, intestinal obstruction, gastrointestinal bleeding, and iron deficiency anemia. Analyses used survey-weighted logistic regression for binary outcomes and generalized linear models for continuous outcomes. A propensity score-matched sensitivity analysis balanced sepsis and malnutrition. Results: Among 61,725 GIST hospitalizations, 0.72% had hypoglycemia. Mortality was 12.6% with hypoglycemia vs. 3.1% without; adjusted odds of death were higher (aOR 4.16, 95% CI 2.06–8.37; p < 0.001). Hypoglycemia was also associated with malnutrition (aOR 5.63, 3.37–9.40), sepsis (aOR 4.00, 2.24–7.14), ascites (aOR 3.43, 1.63–7.19), and peritonitis (aOR 2.91, 1.17–7.22). LOS was 4.61 days longer on average (not significant; p = 0.185), and total hospital charge was $5218 higher (β = 19,116.8; p = 0.95). In the matched cohort, the mortality association attenuated but persisted (aOR 1.38, 1.27–1.49; p < 0.001); peritonitis remained significant (aOR 1.10, 1.04–1.17), intestinal obstruction (aOR 4.91, 3.44–7.05) and iron deficiency anemia (aOR 3.54, 1.62–7.74) became significant, while ascites and gastrointestinal bleeding were not significant. Conclusions: Hypoglycemia in GIST, although uncommon, marks a higher-risk inpatient trajectory with increased mortality and several complications; these signals largely persist after balancing severity proxies. Resource-use differences were directionally higher but not statistically significant. Recognition of hypoglycemia may aid risk stratification and inpatient management in GIST. Full article

The intersection of type 2 diabetes mellitus (T2DM) and sarcopenia, often termed diabetic sarcopenia, represents a critical yet underrecognized comorbidity that significantly impacts the quality of life and functional capacity of older adults. This paper explores the complex interplay between T2DM and sarcopenia, focusing on the prevalence, risk factors, and underlying mechanisms driving muscle mass and strength decline in this population. Drawing from recent clinical studies, we highlight a prevalence of sarcopenia ranging from 15.36% to 30.2% among elderly T2DM patients, with notable gender disparities (41.3% in men versus 20.1% in women) and regional variations. Key risk factors identified include poor glycemic control (HbA1c ≥8%), longer diabetes duration (>5 years), low body mass index (BMI), and reduced levels of 25-hydroxyvitamin D and insulin-like growth factor-1 (IGF-1). We also recommend a practical screening algorithm for diabetic sarcopenia, integrating tools like the SARC-F questionnaire, dynamometry, and BMI-adjusted calf circumference to facilitate early diagnosis and staging in clinical settings. The review underscores the need for a multidisciplinary approach—encompassing pharmacological optimization, nutritional interventions with high-protein diets, and tailored physical exercise—to mitigate muscle loss and improve metabolic outcomes. Future research directions should focus on validating diagnostic protocols and diagnosis techniques and further exploring specific therapies to effectively address this dual burden. Full article

IGF-1 (insulin-like growth factor 1) is a growth factor primarily secreted by dermal papilla cells on hair-bearing skin that stimulates hair follicle proliferation and vascularization, and promotes the transition to the anagen growth phase of the hair follicle by activating key pathways such as PI3K/Akt and MAPK/ERK. IGF-1 also inhibits apoptosis, prolongs the follicular growth phase, and boosts VEGF expression, which supports microcirculation and nutrient delivery to hair follicles. The combined effects of IGF-1 and other growth factors, including VEGF, KGF (FGF-7), and PDGF, further amplify its effects on follicular cell proliferation and tissue repair. IGF-1’s ability to regulate the hair growth cycle and its interactions with other signaling pathways make it a compelling therapeutic target for hair loss disorders. Both preclinical models and clinical evidence highlight IGF-1 as a promising therapeutic option for conditions like androgenetic alopecia (AGA), where IGF-1 levels are typically diminished. While topical IGF-1 treatments have shown efficacy and safety with minimal systemic absorption, additional research is needed to improve delivery methods, such as liposomal gels and exosome-based carriers, and to evaluate long-term effects. Full article

Background: Intermittent fasting (IF) is emerging as a promising non-pharmacological intervention in oncology, with the potential to modulate key biological processes including metabolic reprogramming, inflammation, autophagy, and immune function, particularly through the PI3K/AKT/mTOR pathway. However, translating IF into clinical practice requires robust tools to monitor its biological impact and therapeutic effectiveness. Objective: This narrative review aims to present and critically evaluate current diagnostic and monitoring strategies that can support the safe and effective integration of IF into oncological care. Methods: A comprehensive literature search was conducted across PubMed/Medline, Science Direct, Scopus, Wiley Online Library, and Google Scholar using a combination of free-text and MeSH terms related to intermittent fasting, oncology, biomarkers, immunophenotyping, metabolic pathways, gut microbiome, and diagnostic imaging. Results: Two principal categories of monitoring objectives were identified. The first—mechanistic monitoring—focuses on elucidating IF-induced biological effects, including modulation of insulin/IGF-1 signaling, oxidative stress reduction, autophagy activation, immune reprogramming, and microbiome alterations. Advanced research tools such as single-cell RNA sequencing, proteomics, metabolomics, and circulating tumor DNA (ctDNA) assays offer high-resolution insights but currently remain limited to preclinical or translational settings due to cost and complexity. The second—clinical response monitoring—assesses IF’s impact on treatment outcomes, including chemotherapy and immunotherapy response, toxicity reduction, tumor dynamics, and maintenance of nutritional and functional status. This requires clinically validated, accessible, and interpretable diagnostic tools. Conclusions: A dual-layered monitoring framework that integrates both mechanistic insights and clinical applicability is essential for the personalized implementation of IF in oncology. Although preliminary findings are promising, large-scale randomized trials with standardized protocols are necessary to confirm the efficacy, safety, and feasibility of IF in routine oncological care. The integration of IF with modern diagnostics may ultimately contribute to a more individualized, biologically informed cancer treatment paradigm. Full article

Background: Emerging evidence suggests that polyphenols may contribute to the attenuation of telomere attrition and the upregulation of insulin-like growth factor 1 (IGF-1), primarily in animal and cell studies, and to a lesser extent in humans. Pomegranate extract, known for its high antioxidant capacity, has shown promise in preventing telomere shortening and enhancing IGF-1 levels, but evidence in humans is lacking. Objective: To investigate the effects of pomegranate extract on telomere length and serum IGF-1 levels in older adults aged 55–70 years. Methods: Participants took part in a two-arm double-blind parallel trial, receiving either placebo capsules (maltodextrin) or pomegranate extract (740 mg) daily for 12 weeks. At baseline, week 6 and week 12, anthropometric measurements, blood pressure readings and blood samples were collected. Telomere length and serum IGF-1 levels were assessed. Results: A total of 72 participants completed the study. Analysis showed a significant effect of treatment and time on IGF-1 ((F_2,136 = 3.43, p = 0.04), with levels significantly increasing in the pomegranate extract group at week 12. No significant effects on telomere length were noted. Weight status, physical activity, age, gender and energy intake did not impact the outcomes. Conclusions: Pomegranate extract significantly increased IGF-1 levels and could exert a positive role on vascular ageing. Further research is needed to replicate these findings and confirm its long-term benefits. Extended studies are required to elucidate its potential to counteract telomere shortening. Full article

Objectives: Cancer is a multifactorial disease determined by several factors. Metabolic disorders such as obesity and diabetes significantly contribute to cancer risk by promoting chronic inflammation, insulin resistance, and hormonal dysregulation. Obesity and hyperglycaemia elevate insulin-like growth factor-1 (IGF-1) levels, driving oncogenic pathways such as PI3K/Akt/mTOR, which promote tumour proliferation and survival. Furthermore, cancer cells undergo metabolic reprogramming, characterised by increased reliance on glycolysis (Warburg effect), facilitating tumour growth and therapy resistance. Hence, body weight reduction and glycaemic control may represent potential strategies for cancer prevention and treatment. Irisin, a myokine secreted by skeletal muscle, plays a critical role in cellular metabolism and energy homeostasis. Emerging evidence suggests that irisin may exert tumour-suppressive effects by modulating key metabolic and oncogenic pathways. Methods: A systematic literature search identified studies investigating irisin’s effects in various cancer models. Results: In vitro, irisin exerts dose- and time-dependent anti-proliferative effects in a variety of cancer cell lines, primarily via PI3K/Akt/mTOR inhibition and AMPK activation, leading to cell cycle arrest and apoptosis. Additionally, irisin inhibits epithelial–mesenchymal transition, which suppresses cancer cell migration and invasion. However, conflicting findings, particularly in hepatocellular carcinoma, suggest tissue-specific responses. Similarly, clinical data regarding systemic and tumoural irisin levels remain inconsistent and appear to vary based on cancer type and stage. Conclusions: Irisin represents a promising therapeutic target due to its ability to modulate metabolic and oncogenic pathways. However, further research is needed to elucidate its clinical relevance and optimise its application as an adjunct to existing cancer therapies. Full article

Cysteine-rich angiogenic inducer 61 (CYR61) promotes prostate cancer (PCa) cell growth, but its role in disease progression remains unclear. Given its insulin-like growth factor (IGF)-binding domain and the known involvement of insulin-like growth factor-1 (IGF1) in PCa, we investigated the molecular interplay between CYR61 and IGF1. CYR61 was silenced using small interfering RNA (siRNA) in prostate carcinoma 3 (PC3), lymph node carcinoma of the prostate (LNCaP), and androgen receptor (AR)-positive 22Rv1 cells, followed by assessments of their proliferation, viability, colony formation, migration, and signaling pathway activation. CYR61 knockdown significantly reduced cell growth, viability, prostasphere formation, and migration across all three cell lines. Mechanistically, CYR61 silencing inhibited PI3K/AKT signaling but had no effect on MAPK activation. In addition, treatment with recombinant IGF1 induced CYR61 expression in a time-dependent manner, and the inhibition of PI3K/AKT signaling suppressed both CYR61 expression and cell proliferation. These findings suggest that IGF1 promotes PCa progression through CYR61 and that CYR61 may serve as a potential therapeutic target for limiting tumor growth and metastasis. Full article

Breast cancer is the most prevalent solid tumor diagnosed in women worldwide, remaining a leading cause of cancer-related mortality. Among its subtypes, triple-negative breast cancer (TNBC) is characterized by high aggressiveness and heterogeneity, accounting for approximately 90% of breast cancer-related deaths. Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR) and the insulin-like growth factor I receptor (IGF-IR), are critical cell growth and survival regulators, with their dysregulation closely related to therapy resistance in breast cancer. Studies on RTK targeting have shown promise, and recently attention has shifted toward developing more physiologically relevant preclinical models. Unlike traditional two-dimensional (2D) cell cultures, 3D models such as spheroids better mimic the complex nature of the tumor microenvironment (TME), offering a more accurate representation of tumor behavior and progression. This study utilized both 2D and 3D culture models to assess the effects of EGFR and IGF-IR inhibition, individually and in combination, in two TNBC cell lines with distinct metastatic potential. The results demonstrate that both receptors play critical roles in regulating key cellular functions, including migration, expression of epithelial-to-mesenchymal transition (EMT) markers and matrix metalloproteinases (MMPs). The use of 3D spheroid models enabled the evaluation of additional functional properties, such as spheroid growth and dissemination, revealing treatment-dependent responses to combined receptor inhibition. Overall, this dual-model approach underscores the importance of incorporating 3D culture systems in preclinical cancer research and provides new insights into the regulatory roles of EGFR and IGF-IR in TNBC progression. Full article

The American cockroach (Periplaneta americana) serves as an exemplary model for regeneration research due to its exceptional regenerative capabilities, particularly in appendage regeneration. In this study, regenerated coxa tissue underwent histological analysis through H & E straining. Microscopic examination revealed the progression of regeneration. To elucidate the underlying mechanisms, a comparative transcriptomic analysis was conducted between regenerating legs and non-amputated control legs. This analysis identified 2343 differentially expressed genes (DEGs) between 0 days post-amputation (0 dpa) and 7 dpa, 2963 DEGs between 14 dpa and 0 dpa, and 3135 DEGs between 14 dpa and 7 dpa. Significantly, several DEGs are associated with growth- or regeneration-related processes, including extracellular matrix (different collagen, Pro-resilin isoforms, integrin beta (itgb) and matrix metalloproteinase (mmp)), immune-related genes (Toll-like receptor 13 (tlr13), defensin (def), drosomycin-like defensin (dld), Polyphenoloxidases2 (ppo2), cytochrome P450 (p450), peptidoglycan recognition protein (pgrp) and secreted C-type lectin (sClec)), insulin-like growth factor (IGF) and Epidermal Growth Factor Receptor (EGFR). Functional validation through RNA interference (RNAi) further suggested that EGFR and a specific C-type lectin (Regenectin) regulate leg regeneration in Periplaneta americana. These findings enhance our understanding of the molecular mechanisms governing regeneration in this species. Full article

Traumatic brain injury (TBI), a leading cause of mortality and disability, recognizes a primary, immediate injury due to external forces, and a secondary phase that includes inflammation that can lead to complications such as the post-traumatic confusional state (PTCS), potentially impacting long-term neurological recovery. An earlier identification of these complications, including PTCS, upon admission to intensive rehabilitation units (IRU) could possibly allow the design of personalized rehabilitation protocols in the immediate post-acute phase of moderate-to-severe TBI. The present study aims to identify potential biomarkers to distinguish between TBI patients with and without PTCS. We analyzed cellular and molecular mechanisms involved in neuroinflammation (IL-6, IL-1β, IL-10 cytokines), neuroendocrine function (norepinephrine, NE, epinephrine, E, dopamine), and neurogenesis (glial cell line-derived neurotrophic factor, GDNF, insuline-like growth factor 1, IGF-1, nerve growth factor, NGF, brain-derived growth factor, BDNF) using enzyme-linked immunosorbent assay (ELISA), comparing results between 29 TBI patients (17 with PTCS and 12 non-confused) and 34 healthy controls (HC), and correlating results with an actigraphy-derived sleep efficiency parameter. In TBI patients compared to HC, serum concentration of (1) pro-inflammatory IL-1β cytokine was significantly increased while that of anti-inflammatory IL-10 cytokine was significantly decreased; (2) NE, E and DA were significantly increased; (3) GDNF, NGF and IGF-1 were significantly increased while that of BDNF was significantly decreased. Importantly, IL-10 serum concentration was significantly lower in PTCS than in non-confused patients, correlating positively with an improved actigraphy-derived sleep efficiency parameter. An anti-inflammatory environment may be associated with better prognosis after TBI. Full article

Gestational diabetes mellitus (GDM) increases the risk of fetal overgrowth and macrosomia, yet the molecular mechanisms remain unclear. Emerging evidence implicates primate-specific placental microRNAs (miRNAs) from the C19MC cluster in modulating fetal growth via the insulin-like growth factor (IGF) axis. This study aimed to investigate the expression of circulating C19MC miRNAs in GDM pregnancies and their association with IGF axis biomarkers and birthweight outcomes. In this cross-sectional study, 158 pregnant women were stratified into normoglycemic pregnancies (n = 52), GDM with normal birthweight (n = 56), and GDM with large-for-gestational-age (LGA) newborns (n = 50). Plasma levels of 19 C19MC miRNAs and IGF-related proteins were measured. Associations between miRNAs, IGF axis components, and birthweight were analyzed using linear regression and correlation models adjusted for relevant covariates. Several miRNAs, including miR-516a-5p, miR-518d-3p, miR-521, and miR-525-3p, were differentially expressed in GDM, particularly in LGA cases. Strong correlations were observed, such as that of miR-516a-5p with IGFBP-5 (r = 0.705; p < 0.001). Inverse associations with birthweight were found for miR-519b-3p, miR-518d-5p, and miR-520a-5p. Circulating C19MC miRNAs are dysregulated in GDM and correlate with IGF signaling and fetal growth, supporting their potential as early biomarkers for macrosomia risk in GDM. Full article

Background: Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by variants in the SMN1 gene. This study investigates the functional and biochemical effects of moderate-intensity aerobic exercise in SMA Type III patients. Methods: Twenty-three patients aged 18–57 years were included in this study. The training group underwent a 12-week aerobic exercise program using a bicycle ergometer at 60–70% of their maximum heart rate three times per week for 30 min per session. The training continued for an additional four months. The primary outcome measures were the six-minute walk distance and oxygen uptake, both reflecting exercise capacity. Secondary outcome measures included muscle strength with dynamometer, functional performance, and fatigue with different scales. Furthermore, serum survival motor neuron (SMN) protein and insulin-like growth factor-1 (IGF-1) hormone levels were measured at baseline, post-training first measurement (after 12 weeks), and post-training second measurement (after 28 weeks). Results: The exercise group showed a significant increase in exercise capacity (p < 0.001) and 6MWT walking distance (p = 0.003). Furthermore, reduction in walking time in the 10-m walk test (p = 0.019) and improvements in strength of the right and left quadriceps (p = 0.004, p = 0.031) and right gastrocnemius (p = 0.034) muscles were identified. Furthermore, an improvement in the Fatigue Severity Scale (FSS) (p = 0.037) was found. SMN protein and IGF-1 levels were increased in the second measurement in the training group (p = 0.022 and p = 0.016, respectively). Conclusions: An aerobic exercise program improved physical function and muscle strength and reduced fatigue in SMA Type III patients, with sustained biochemical improvements. Aerobic exercise may serve as a beneficial adjunct therapy for this population. Full article

Insulin-like growth factor I (IGF-I) is a neurotrophic factor that regulates neurogenesis, synaptogenesis, and neuronal survival. It also enhances neuronal activity and facilitates synaptic plasticity. Additionally, IGF-I plays a critical role in the regulation of metabolism in mammals. Emerging evidence indicates that IGF-I modulates sleep architecture. The circadian integration of metabolic and neuronal systems serves to optimize energy utilization across the light/dark cycle. Current data suggest that IGF-I may be a key mediator of this integration, promoting brain activity during wakefulness, a state that coincides with increased metabolic demand. In this review, we summarize recent findings on the interplay between metabolism, IGF-I, and brain activity. Full article

Background: Breast cancer, particularly the luminal subtype, often responds to endocrine therapies. However, 20–30% of patients develop resistance, resulting in more aggressive disease. Long non-coding RNAs (lncRNAs) are implicated in cancer progression and treatment resistance. Objective: This study aimed to evaluate the role of the lncRNA insulin-like growth factor 2 antisense (IGF2-AS) in tamoxifen-resistant breast cancer and assess its potential as a therapeutic target. Methods: Two tamoxifen-resistant breast cancer cell lines (TAMR-V and TAMR-H) were used to assess IGF2-AS expression via qPCR. Knockdown experiments with siRNA evaluated the role of IGF2-AS in cell proliferation, invasion, and migration. Next-generation sequencing (NGS) analyzed gene expression differences between the cell lines. Kaplan–Meier survival analysis determined the clinical significance of IGF2-AS expression in breast cancer patients. Results: IGF2-AS expression was significantly upregulated in TAMR-V and TAMR-H cell lines compared to control MCF-7 cells. Knockdown of IGF2-AS reduced cell proliferation and invasion in TAMR-V cells but did not significantly affect TAMR-H cells, indicating a cell line-specific role in tamoxifen resistance. NGS revealed differential gene expression profiles between TAMR-V and TAMR-H cells, suggesting variability in resistance mechanisms. Survival analysis demonstrated that higher IGF2-AS expression was associated with poorer prognosis in breast cancer patients, including those with hormone-positive and triple-negative subtypes. Conclusions: IGF2-AS is upregulated in tamoxifen-resistant breast cancer and promotes cell proliferation and invasion in a cell line-specific manner. Its differential expression in TAMR-V and TAMR-H cells highlights the complexity of resistance mechanisms, suggesting IGF2-AS as a potential therapeutic target for overcoming tamoxifen resistance. Full article