Search Results (1,264)

Prediabetes is increasingly recognized as a risk factor for sarcopenia, driven by chronic low-grade inflammation, insulin resistance, and impaired anabolic signaling. Nutritional interventions containing whey protein, hydroxymethylbutyrate (HMB), glucosamine, and micronutrients may offer a multi-target strategy to counteract muscle deterioration. This study aimed to evaluate the efficacy of HiLo Platinum™ supplementation in attenuating muscle strength decline in a prediabetic rat model, with integrated analysis of metabolic biomarkers and gut microbiome profiles. A randomized preclinical trial was conducted using male Sprague Dawley rats assigned to four groups: normal diet (ND), prediabetic control induced by cholesterol- and fat-enriched diet with fructose (CFEDF), and two treatment groups receiving low-dose (0.63 g/kg BW) or high-dose (1.26 g/kg BW) HiLo Platinum™. The intervention lasted six weeks. Muscle strength was assessed via a four-limb grip strength test (reverse hang time and holding impulse). Biomarkers related to inflammation, mitochondrial function, and anabolic signaling (TNF-α, IL-10, PGC-1α, IGF-1, SIRT-1, AMPK, mTOR, and myostatin), lipid profile, and blood glucose were analyzed. Gut microbiome composition and diversity were evaluated using taxonomic profiling and multivariate analyses. HiLo Platinum™ supplementation significantly improved muscle strength, evidenced by increased reverse hang time and holding impulse (p < 0.001). Both doses reduced blood glucose and improved lipid profiles, including increased HDL and decreased LDL, triglycerides, and total cholesterol. Anti-inflammatory effects were observed with reduced TNF-α and elevated IL-10 levels. Mitochondrial and metabolic regulators (PGC-1α, SIRT-1, AMPK) and anabolic mediators (IGF-1) were significantly upregulated, while mTOR levels decreased. Gut microbiome analysis revealed increased genus richness (Chao1 index) and distinct microbial shifts associated with improved metabolic and inflammatory markers. HiLo Platinum™ effectively mitigates prediabetes-induced muscle strength decline through integrated modulation of inflammatory pathways, mitochondrial function, metabolic homeostasis, and gut microbiome composition. These findings support its potential as a nutritional therapeutic strategy for preventing sarcopenia in prediabetic conditions, although further studies are needed to evaluate long-term effects and implications on muscle hypertrophy. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic disorder shaped by genetic variants and network-level interactions beyond obesity and insulin resistance. This study aimed to define the genetic and proteomic architecture of MASLD by integrating GWAS and plasma proteomic profiling from the UK Biobank. Genome-wide association analyses were conducted under additive and dominant models, with functional annotations performed using SIFT, PolyPhen-2, PROVEAN, REVEL, CADD, MutationTaster, and conservation metrics (GERP++, phyloP, phastCons, and B-statistic). Differential protein expression was assessed using the Olink^® platform, and STRING was applied for protein–protein interaction analysis. MASLD patients showed male predominance and significant differences in hepatic (AST, ALT, GGT, PDFF), metabolic (glucose, triglycerides, TyG index), and inflammatory markers (CRP, neutrophils, NLR, CAR). GWAS confirmed PNPLA3 (rs738409, I148M) and TM6SF2 (rs58542926, E167K) as major risk variants, while SAMM50 and NCAN showed weaker but conserved associations. Proteomics revealed downregulation of IGFBP2, IGFBP1, PON3, CKB, and APOF and upregulation of CPM, IGSF9, GUSB, ACY1, AFM, LEP, and GSTA1/3. PPI analysis identified ADIPOQ, LEP, FGF21, and ADH1B as central hubs in metabolic and inflammatory regulation. MASLD should be regarded as a network disease involving lipid metabolism, insulin/IGF signaling, mitochondrial function, and ECM–inflammatory pathways. These findings highlight PNPLA3 and TM6SF2 as major genetic drivers, while SAMM50, NCAN, and peripheral proteins contribute regulatory roles, suggesting novel biomarkers and therapeutic targets. Full article

Growing evidence suggests that insulin resistance (IR) might be a core, unifying mechanism linking various established risk factors for bladder cancer (BC). While factors like smoking, central obesity, sedentary lifestyle, and high-fat diets are known to increase BC risk, a common thread among them is their role in driving IR due to chronic hyperinsulinemia. Hyperinsulinemia promotes BC development in several ways. It acts as a potent growth factor, stimulating the proliferation and inhibiting the programmed cell death of malignant cells by activating the insulin/IGF signaling pathway. Furthermore, IR is closely associated with chronic low-grade inflammation and oxidative stress, both of which contribute to a pro-tumorigenic microenvironment. This convergence of growth-promoting and inflammatory signals highlights the central role of IR. While more research is needed to fully elucidate these complex interactions, the available data suggest that metabolic interventions aimed at improving insulin sensitivity could be a valuable, modifiable strategy for BC prevention. Full article

Background/Objectives: A blunted growth hormone (GH) response in stimulation tests (GHSTs) in obese patients is well documented, with less evidence for insulin-like growth factor-1 (IGF-1) concentrations. The aim of this study was to assess the relationships between nutritional status, GH peak in GHST, and IGF-1 concentrations, and to develop machine learning prediction models of GH deficiency (GHD) in children with short stature. Methods: A case–control study included 1592 children with short stature, whose height, weight, body mass index (BMI), GH peak in two GHSTs, IGF-1 concentration and bone age (BA) were assessed. The cut-off of GH peak in two GHSTs between GHD and idiopathic short stature (ISS) was 10.0 µg/L; additionally, a lower cut-off of 7.0 µg/L was used in repeated analysis. Univariate statistical analyses and classification models were used to identify variables related to the normal and subnormal results of GHST. Results: Depending on the cut-off of GH peak (10.0 vs. 7.0 µg/L), GHD was diagnosed in 604 vs. 279 patients (37.9% vs. 17.5%). Children with GHD had significantly lower (p < 0.001) BMI SDS and IGF-1 SDS than ones with ISS for both cut-offs of GH peak. Overnutrition was associated with the lowest GH peak but the highest IGF-1 SDS; the opposite results were observed in undernutrition. A decision tree predicted GHD in 156 patients, in 149 based on BMI SDS > 0.91. A Naïve Bayes classifier predicted GHD in 118 cases, with BMI SDS and IGF-1 SDS being the only significant variables. The best multilayer perceptron (MLP) neural network predicted GHD in 310 patients, while a logistic regression model did so in 269 patients.. Conclusions: Interpretation of GHST should include the patient’s nutritional status in order to avoid overdiagnosis of GHD in overweight and obese children. Full article

Background/Objectives: Clear cell renal cell carcinoma is the most common subtype of kidney cancer and exhibits marked biological heterogeneity, even among tumors of the same histological grade. Although tumor grade remains a key prognostic parameter, the molecular alterations associated with tumor differentiation are not fully understood. This study aimed to evaluate grade-dependent tissue-level expression patterns of proteins involved in cellular stress response, growth regulation, stemness, and apoptosis in clear cell renal cell carcinoma. Methods: Protein expression of heat shock protein 70, insulin-like growth factor 1, octamer-binding transcription factor 4, and apoptosis-inducing factor were analyzed in human clear cell renal cell carcinoma samples and normal renal cortex. Low-grade and high-grade tumors were compared using immunofluorescence staining combined with semi-quantitative and quantitative image analysis. The proportion of positive signals and the number of positive cells were assessed across tissue compartments. In addition, publicly available transcriptomic data from The Cancer Genome Atlas kidney renal clear cell carcinoma cohort were analyzed to explore associations between gene expression levels and overall survival. Results: Distinct grade-dependent expression patterns were observed for all investigated proteins. Heat shock protein 70, insulin-like growth factor 1, and octamer-binding transcription factor 4 showed a higher expression in normal renal tissue with a progressive reduction across tumor grades. In contrast, apoptosis-inducing factor exhibited increased expression in tumor tissue, particularly in low-grade tumors, with a relative decrease in high-grade carcinomas. Stromal compartments of tumor tissue showed minimal or no expression for most markers. Transcriptomic survival analysis did not reveal significant differences in overall survival between high- and low-expression groups for any of the investigated genes. Grade-stratified transcriptomic analysis of the TCGA KIRC cohort revealed consistent patterns for HSP70 family members and OCT4, with progressive grade-dependent mRNA reduction toward higher grades, while IGF1 showed an inverse mRNA trend and AIFM1 showed a uniform reduction across all tumor grades without a clear inter-grade pattern. Conclusions: The findings demonstrate that stress response, growth-related, stemness-associated, and apoptotic proteins display distinct grade-dependent tissue-level expression patterns in clear cell renal cell carcinoma, with the expression profiles of high-grade tumors being of particular translational interest given the aggressive clinical behavior and therapeutic resistance characteristic of this disease stage. These alterations appear to reflect tumor differentiation and biological behavior rather than independent prognostic value, highlighting the complexity of molecular regulation in renal tumorigenesis. Full article

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy worldwide, with molecular heterogeneity complicating early detection and treatment stratification. The insulin-like growth factor (IGF) axis interacts bidirectionally with immune regulatory mechanisms in ways that shape tumor phenotype and therapeutic vulnerability. This review synthesizes evidence on how IGF signaling orchestrates immunosuppression through effects on tumor-associated macrophages, regulatory T cells, and myeloid-derived suppressor cells, while inflammatory cytokines reciprocally modulate IGF bioavailability. Three mechanistic principles emerge: IGF binding protein 2 (IGFBP-2) functions as a central coordinator linking growth factor signaling to immune evasion through STAT3-dependent pathways driving M2 macrophage polarization and regulatory T cell differentiation; IGF–immune crosstalk varies considerably across molecular subtypes, with microsatellite-stable tumors exhibiting high reliance on IGF-I receptor-mediated immune silencing; and local paracrine IGF production increasingly dominates over systemic regulation as disease progresses. These bidirectional connections establish self-reinforcing circuits that determine whether tumors remain immunologically responsive or develop immune exclusion. Multi-marker panels incorporating IGFBP-2 alongside complementary biomarkers have shown improved diagnostic performances for early CRC detection, underscoring the need for the large-scale prospective clinical evaluation of IGF network components as biomarkers for CRC in diverse populations. The convergence of IGF signaling with checkpoint regulation suggests that combined targeting warrants investigation for resistance in tumors lacking effective immunotherapy options. Full article

Background: The immunologically cold nature and immunosuppressive tumor microenvironment (TME) of intrahepatic cholangiocarcinoma (ICC) contribute to its poor prognosis. This study aims to identify novel biomarkers related to prognosis and TME in ICC. Methods: We first identified the high expression of m6A reader insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) in ICC through bioinformatics screening. Subsequently, a retrospective study was conducted on 224 ICC patients who had undergone radical resection. The expression levels of IGF2BP2 and programmed death ligand 1 (PD-L1) were detected in a tissue microarray (TMA) using immunohistochemistry (IHC). The co-localization of IGF2BP2, PD-L1, programmed cell death protein 1 (PD-1), and CD8⁺T cells was evaluated by multiple immunofluorescence techniques. Results: IHC confirmed a significant upregulation of IGF2BP2 in tumor tissues compared with normal bile duct epithelia (p < 0.05). IGF2BP2 expression was positively correlated with PD-L1 expression (TPS R = 0.215, p = 0.016; CPS R = 0.295, p = 0.008). High IGF2BP2 expression was associated with increased PD-L1/PD-1 positivity and reduced CD8⁺T cell infiltration. Kaplan–Meier analysis revealed significantly worse 3-year overall survival (OS: 20.56% vs. 29.91%, p = 0.0291) and recurrence-free survival (RFS: 9.72% vs. 18.56%, p = 0.0372) in the IGF2BP2-high group. Multivariate analysis identified IGF2BP2 as an independent risk factor for both OS (HR = 1.683, p = 0.044) and RFS (HR = 1.946, p = 0.042). Conclusions: IGF2BP2, as a potential biomarker and independent prognostic factor for ICC, is associated with increased PD-L1 expression. Full article

The reproductive caste of higher termites exhibits remarkable longevity, but the mechanisms by which they manage age-related oxidative stress during lifespan extension remain insufficiently understood. This study investigated the dynamic regulation of the insulin/IGF (IIS)–FOXO axis, a key anti-aging regulatory pathway that integrates insulin signaling with downstream processes, including antioxidant defense and DNA repair, as well as the superoxide dismutase (SOD) system in female Odontotermes formosanus reproductives at various life stages (Swarming Queen (SQ), 1-Year Queen (1YQ), 8-Year Queen (8YQ)) through transcriptomic, qRT-PCR, and enzyme activity analyses. Age-dependent upregulation of IIS pathway components (InR, chico, PDK1, Akt, Sirt1, FOXO) was observed, alongside the identification of six SOD transcripts, including two SOD1, two SOD2, and two SOD3 isoforms. Notably, mitochondrial SOD2 (particularly SOD2_b) showed a progressive increase with age, exhibiting the highest enzymatic activity and being associated with reduced mitochondrial oxidative stress and the disruption of reactive oxygen species (ROS) amplification cycles. These findings suggest that O. formosanus reproductives counteract the potential lifespan-reducing effects of chronic IIS activation by maintaining or enhancing FOXO activity, thereby supporting DNA repair, antioxidant defenses, and cellular homeostasis. The IIS–FOXO–SOD2 axis is identified as a key regulator of reproductive longevity in higher termites, offering new insights into the molecular mechanisms behind lifespan extension in social insects. Full article

Acute liver failure is often accompanied by neurological disturbances collectively referred to as hepatic encephalopathy (HE), characterized by neuroinflammation and subsequent cognitive decline. Insulin-like growth factor 1 (IGF1) is a neuroprotective peptide with anti-inflammatory properties in the brain. The role of IGF1 in cognitive deficits and neuroinflammation during HE remains largely unexplored. In C57Bl/6 mice, HE was established through an intraperitoneal injection of azoxymethane (AOM), and tissues were collected at defined time points during disease development. IGF1 expression in the cortex was downregulated following AOM administration. Central infusion of recombinant mouse IGF1 (rmIGF1) before AOM injection resulted in delayed neurological impairment, reduced microglial activation, and decreased proinflammatory cytokine and chemokine production in AOM mice. In vitro, rmIGF1 and conditioned media derived from rmIGF1-treated primary neurons attenuated phagocytic activity and C–C motif chemokine ligand 2 (CCL2) production in the microglial cell line EOC-20. Collectively, our results show that IGF1, whose levels decline during HE, alleviates neuroinflammation and improves the pathological state of AOM-treated mice through the suppression of microglial activation and the regulation of neuron–microglia paracrine communication. Full article

Background/Objectives: Aging is associated with declines in cognitive function and neurotrophic support. Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) are peripheral biomarkers discussed in relation to brain health and aging. This study investigated changes in serum BDNF, IGF-1, and cognitive screening scores after a 16-week Hatha Yoga program performed twice or four times per week in older women. Methods: Fifty-one community-dwelling women aged 70–79 years were allocated to a twice-per-week yoga group (2YG; n = 17), a four-times-per-week yoga group (4YG; n = 17), or a non-exercise control group (CON; n = 17) based on availability and participant preference; forty-three participants completed the study. Serum BDNF and IGF-1 were analyzed using enzyme-linked immunosorbent assay and chemiluminescent immunoassay, and cognitive status was evaluated using the Cognitive Impairment Screening Test (CIST). Outcomes were analyzed using two-way repeated-measures ANOVA and additional ANCOVA models adjusting for corresponding baseline values. Exploratory correlations were examined between biomarker changes and CIST changes. Effect sizes and 95% confidence intervals were reported. Results: BDNF showed a significant main effect of time (p < 0.05) without a significant group × time interaction; ANCOVA adjusting for baseline BDNF showed no significant group effect (p = 0.270). IGF-1 showed a significant group × time interaction (p < 0.01) with increases in both yoga groups; ANCOVA adjusting for baseline IGF-1 showed a significant group effect (p = 0.001). CIST showed a significant main effect of time (p < 0.01), but changes were small and the group × time interaction was not significant; ANCOVA adjusting for baseline CIST showed no significant group effect (p = 0.114). Biomarker changes were not clearly correlated with CIST changes (ΔBDNF–ΔCIST: r = −0.244, p = 0.115; ΔIGF-1–ΔCIST: r = −0.050, p = 0.750). Conclusions: In this quasi-experimental study with non-random allocation and limited covariate information, changes in peripheral neurotrophic factors and only small changes in cognitive screening scores were observed after participation in a 16-week Hatha Yoga program. However, frequency-dependent conclusions are limited, and findings should be interpreted cautiously as screening-level, hypothesis-generating reference data. Nevertheless, the program is considered a feasible, low-risk health promotion activity for older women and may inform future randomized or well-controlled studies. Full article

Insulin-like growth factor 2 (IGF2) plays a pivotal role in regulating growth and development; however, its functional involvement in skeletal muscle satellite cells (SMSCs) remains incompletely understood. To elucidate the regulatory role of IGF2, goose SMSCs were engineered to overexpress IGF2 via lentiviral transduction, followed by comprehensive transcriptomic profiling. Comparative analysis revealed 2802 differentially expressed genes (DEGs) in IGF2-overexpressing cells relative to controls, comprising 1202 upregulated and 1600 downregulated genes. IGF2 overexpression markedly activated fibrogenic programs, as evidenced by the upregulation of AP-1 complex components (FOS, JUN), extracellular matrix-related genes (COL1A1, COL5A3), and Wnt signaling receptors (FZD1, FZD7). In contrast, genes involved in myogenic differentiation and contractile function were broadly suppressed, including key myogenic transcription factors (MEF2C, MEF2D), sarcomeric structural proteins (MYBPC1, ACTN2, MYOM3), and metabolic enzymes. Through the construction of protein–protein interaction networks coupled with functional enrichment analysis, we observed a concerted suppression of myogenic regulatory networks critical for myofiber formation. Quantitative real-time PCR validation further confirmed the reliability of the transcriptomic data. Collectively, these findings suggest that overexpression of IGF2 induces a phenotypic shift from myoblasts toward a fibroblast-like state, uncoupling proliferation from differentiation while enhancing fibrogenic identity. This study provides novel insights into IGF2-mediated regulatory mechanisms underlying skeletal muscle development and fibrotic processes. Full article

Modern genetic selection for high productivity has created a physiological conflict in ruminants, where the metabolic demands of lactation compete directly with the energy requirements of reproduction. This review provides a mechanistic synthesis of how key nutritional factors modulate the endocrine and cellular pathways governing reproductive success in cattle and sheep. Negative energy balance (NEB), characteristic of the early postpartum period, suppresses the hypothalamic–pituitary–gonadal (HPG) axis by impairing the pulsatile secretion of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH), mediated through reduced kisspeptin signaling, growth hormone (GH) resistance, and decreased circulating insulin, insulin-like growth factor-1 (IGF-1), and leptin. At the macronutrient level, excess rumen-degradable protein elevates blood urea nitrogen and impairs the uterine environment, while omega-3 polyunsaturated fatty acids inhibit prostaglandin F2α synthesis to support corpus luteum maintenance. At the micronutrient level, selenium, copper, and zinc are essential antioxidant cofactors protecting gametes and embryos from oxidative stress, while vitamins A, D, and E regulate gene expression in reproductive tissues. Furthermore, maternal nutrition during critical gestational windows programs the reproductive capacity of offspring through epigenetic modifications, with profound implications for long-term herd fertility. Understanding these nutritional–reproductive interactions is crucial for developing precision feeding strategies that optimize herd fertility, improve animal welfare, and ensure the economic sustainability of livestock management. A thorough understanding of these nutritional–reproductive interactions is essential for developing precision feeding strategies that optimize fertility in high-producing ruminants. Full article

The insulin-like growth factor 1 (IGF-1) gene plays a key role in growth and production traits in livestock. Limited information is available regarding its genetic polymorphisms in Saudi camel breeds. This study aimed to investigate genetic variation in the IGF-1 gene among Saudi camel breeds to provide baseline genetic information for future association studies. A total of 176 camels representing six Saudi breeds were sampled. DNA was extracted and Polymerase chain reaction (PCR) amplification and Sanger sequencing were applied to detect IGF-1 polymorphisms. Genotype and allele frequencies were calculated across breeds, and statistical comparisons were performed based on proportional distributions to account for unequal sample sizes. Two single-nucleotide polymorphisms (SNPs) were identified: c.365G>A in exon 3 and c.435C>T in exon 5. The exon 3 variant resulted in a missense mutation (p. Arg122His) but was detected in heterozygous form in only one camel, and subsequent screening of 109 additional samples confirmed its rarity. The exon 5 variant was synonymous in isoform X1 and located in the 3′ untranslated region of isoform X2. Sequencing of 176 camels revealed that c.435C>T was highly polymorphic across the examined breeds. Significant differences in genotype frequencies were observed within and among breeds (p < 0.001). The CT genotype predominated in Waddah (60%), Shageh (48%), and Sofor (60%), significantly exceeding CC and TT frequencies (p < 0.001). In Majaheem and Saheli, CT (47%) and TT (45%) were nearly equal and both significantly higher than CC (p < 0.001). Shaele exhibited a distinct pattern, with TT being most frequent (57%), significantly higher than CC (7%, p < 0.001) and CT (36%, p < 0.01). These findings indicate directional selection favoring the C allele in the Waddah and Shageh breeds, whereas the T allele is favored in the remaining breeds. This study provides the first baseline characterization of IGF-1 polymorphisms among Saudi camel breeds. Although no phenotypic associations were assessed, the results offer a foundation for future research examining relationships between IGF-1 variants and economically important traits. Full article

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness characterized by disrupted physiologic vascularization followed by pathologic neovascularization, classically organized around the insulin-like growth factor-1 (IGF-1)–vascular endothelial growth factor (VEGF) axis in the retina. Increasing evidence suggests that early-life gut dysbiosis may act as an upstream modifier of this biphasic process. In this review, we synthesize human cohort studies, multi-omics analyses, and experimental animal models examining associations between the neonatal gut microbiome and ROP. Preterm infants who develop severe ROP demonstrate enrichment of facultative anaerobes and reduced acquisition of obligate anaerobes, alongside altered predicted metabolic capacity. Microbiome-derived metabolites, including short-chain fatty acids, bile acid derivatives, and lipid mediators, have been shown in experimental systems to influence systemic IGF-1 production, hypoxia-inducible factor-1α stabilization, and VEGF signaling. Rodent oxygen-induced retinopathy models offer a translation framework to assess the functional link between microbial perturbation and retinal angiogenic responses. Collectively, these findings support a conceptual microbiome–IGF-1–VEGF–retina axis in which early intestinal dysbiosis may modulate inflammatory tone, metabolic signaling, and retinal vascular development. Although current evidence remains largely associative, integrating microbiome profiling with mechanistic and longitudinal studies may clarify potential causal pathways and identify novel biomarkers or preventive strategies for severe ROP. Full article

Atherosclerosis is a complex, multifactorial disease that progresses through distinct stages: initiation, progression, and complication, ultimately leading to acute coronary syndromes (ACS). Endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages are central players in this process, influencing plaque stability and vulnerability. Insulin-Like Growth Factor 1 (IGF-1), soluble-Klotho (S-Klotho), and the Growth Hormone Receptor exon 3 deletion polymorphism (GHRd3) have emerged as key modulators of vascular health, impacting these cellular components through various mechanisms. IGF-1 supports endothelial function, enhances VSMC survival and migration, and mitigates inflammation by inhibiting macrophage recruitment and activation, ultimately reducing the risk of plaque destabilization. S-Klotho, an anti-aging protein with potent anti-inflammatory and antioxidant properties, has been linked to vascular protection, with its deficiency associated with endothelial dysfunction, vascular calcification, and impaired VSMC survival. Evidence suggests that IGF-1 may enhance Klotho shedding, indicating a potential synergistic role in maintaining vascular integrity. This narrative review aims to outline the fundamental stages of atherosclerosis progression, consolidate current evidence on the roles of IGF-1 and S-Klotho in modulating key cellular components of atherosclerosis, and shed light on their potential involvement in plaque healing—an area that remains largely unexplored. By integrating established molecular mechanisms, we explore how these factors may contribute to endothelial integrity, VSMC survival, and macrophage activation and polarization, potentially shaping a more stable plaque phenotype and influencing future therapeutic strategies in cardiovascular disease. Full article