Nasopharyngeal carcinoma (NPC) is a prevalent malignancy with a distinct geographical distribution. This study aimed to identify core glycolysis-related genes and investigate their functional roles in NPC pathogenesis. Integrated transcriptomic analysis was performed on multiple Gene Expression Omnibus datasets. Screening of core genes was performed computationally via machine learning algorithms on the pool of glycolysis-related differentially expressed genes (Gly-DEGs). The tumor-suppressive function of insulin-like growth factor 1 (IGF1) was demonstrated through a combination of in vitro assays, assessing proliferation, migration, invasion, apoptosis, and glycolysis, followed by validation in xenograft models. Co-immunoprecipitation (Co-IP) examined IGF1-PGM5 interaction; Western blotting measured IGF1R and p-IGF1R levels. PGM5 involvement was tested by knockdown rescue. IGF1 was identified as a significantly downregulated core gene in NPC. Its overexpression inhibited NPC cell proliferation, migration, invasion, and promoted apoptosis, while simultaneously suppressing glycolysis, evidenced by reduced glucose consumption, lactate production, and expression of key glycolytic enzymes hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA). These findings were corroborated in vivo. Co-IP revealed a direct physical interaction between IGF1 and PGM5. IGF1 overexpression did not alter total IGF1R or p-IGF1R levels, indicating IGF1R-independent action. IGF1 positively correlated with PGM5, and PGM5 knockdown attenuated IGF1's tumor-suppressive and glycolytic-inhibitory effects. In NPC, IGF1 serves to suppress tumor progression, inhibiting malignant phenotypes and aerobic glycolysis through the upregulation of PGM5. The IGF1-PGM5 axis represents a novel metabolic regulatory pathway that may warrant further investigation as a potential therapeutic target for NPC intervention.

Metabolic dysfunction-associated steatotic liver disease (MASLD) increases cardiovascular and kidney disease risk. Insulin-like growth factor 1 (IGF-1) regulates metabolic and vascular function, but its role in long-term cardio-kidney outcomes (CKO) in MASLD remains unclear. This study examined the association between MASLD, IGF-1 levels and CKO. In this prospective cohort study, we used data from 214 512 UK Biobank participants without baseline cardiovascular or chronic kidney disease (CKD). Participants were categorized into four groups: no-MASLD and MASLD stratified by age- and sex-specific tertiles of serum IGF-1 (T1-T3). The primary outcome was a composite CKO; secondary outcomes were incident CKD and 3-point major adverse cardiovascular events (3P-MACE). Over a median 13-year follow-up, 20 395 CKOs occurred. MASLD increased event rates across all IGF-1 tertiles (p < 0.001), with a significant interaction observed between MASLD and IGF-1 levels (P for interaction = 0.014). In multivariable Cox models, MASLD remained independently associated with CKO risk, strongest in the lowest IGF-1 tertile (T1: adjusted hazards ratio [aHR], 1.24 [95% CI: 1.18-1.30] vs. no-MASLD). Similar trends were observed for incident CKD (T1: aHR, 1.35 [95% CI: 1.22-1.49]) and 3P-MACE (T1: aHR, 1.26 [95% CI: 1.18-1.35]). Subgroup analyses indicated consistent associations across sex, BMI and diabetes, with stronger effects in participants < 65 years and markedly greater CKD risk among those with baseline albuminuria. MASLD independently predicted CKO, particularly among individuals with low IGF-1 levels. Incorporating IGF-1 into clinical evaluations may improve risk stratification beyond conventional metabolic factors.

Corticotropin-releasing hormone (CRH) induces an increase in growth hormone (GH) secretion in a subset of patients with acromegaly; however, the characteristics of these CRH responders remain poorly defined. 22 CRH responders were retrospectively compared with 43 nonresponders. CRH responders exhibited significantly larger tumors and more frequent visual field impairment than nonresponders, despite comparable baseline GH and insulin-like growth factor 1 (IGF-1) levels, and disease duration. Tumor volume and diameter were positively correlated with the GH increase ratio in CRH test, whereas GH and IGF-1 per tumor volume or diameter were significantly lower in CRH responders, indicating reduced GH secretory capacity relative to tumor size. Immunohistochemical analyses revealed higher corticotropin-releasing hormone receptor 1 (CRHR1) and lower CRHR2 expression in CRH responders. In addition, T-box transcription factor (TPIT) and adrenocorticotropic hormone (ACTH) expression were significantly more frequent in adenomas from CRH responders, suggesting a corticotroph-like phenotype. GH responses to CRH were significantly correlated with those to luteinizing hormone-releasing hormone but not thyrotropin-releasing hormone or oral glucose tolerance testing. GH responses to CRH tended to be inversely correlated with somatostatin receptor subtype 2 expression as a predictor of first-generation somatostatin receptor ligand efficacy but not with octreotide response or MRI signal intensity. These findings support that GH responsiveness to CRH identifies a biologically distinct subset of somatotroph adenomas characterized by corticotroph-like features, larger tumor size, and reduced GH secretory capacity. GH responsiveness to CRH may serve as a noninvasive indicator of intrinsic tumor biology and behavior.

Skeletal muscle undergoes progressive denervation-induced muscle atrophy (DIMA) after peripheral nerve injury that severely impairs the potential for motor functional recovery with reinnervation. There are currently no therapeutic strategies to reverse the deleterious effects of chronic DIMA, leaving affected patients with lifelong disability. Herein, we used a translational rodent forelimb nerve injury model to investigate whether targeted injection of syngeneic myoblasts to chronically atrophic muscle can reverse the histologic and functional consequences of DIMA. Male Lewis rats underwent median nerve transection followed by immediate (positive control) or delayed repair. Following a plateau of motor function, myoblasts were injected into the digital flexor muscles (n = 5-6 per group), delivered in either saline or a nanofiber hydrogel composite (NHC) loaded with agrin- and insulin-like growth factor 1 (IGF-1)-releasing nanoparticles (npNHC). Serial functional assessments of stimulated grip strength and terminal histological evaluation were used to measure recovery. Satellite cell-rich (Pax7 Hi ) myoblast therapy caused sustained improvement in stimulated grip strength from pretreatment baseline (p < 0.05). Histological evaluation demonstrated that myoblast therapy, when delivered in npNHC, reversed whole muscle atrophy compared to positive controls [p = 0.997 and 0.996] and restored mean myofiber cross-sectional area [p = 0.244]. Correlation analysis demonstrated functional improvements were associated with increased myofiber cross-sectional area [r = 0.900, p = 3.01E-09]. This data indicates that targeted injection of syngeneic myoblasts can reverse the functional and histologic effects of DIMA in skeletal muscles and is a promising strategy for improving recovery after peripheral nerve injuries.

A pilot study on the influence of early pregnancy interferon τ to the expression of IGF-binding proteins in primary bovine hepatocytes.

Bidirectional prospective relationship of endometriosis with major depressive disorder: the mediating role of metabolic biomarkers.

The weekly insulin-like growth factor I (IGF-I) profile for children and adolescents treated with long-acting growth hormone differs from that of daily growth hormone (GH). The objective of this study is to provide guidance on the use of once-weekly somapacitan and IGF-I monitoring in prepubertal short children and adolescents born small for gestational age (SGA) or with idiopathic short stature (ISS), Noonan syndrome (NS), or Turner syndrome (TS). Modeling, including population pharmacokinetic/pharmacodynamic (PK/PD) modeling, were utilized, analyzing IGF-I data from 4 clinical studies, including 2 phase 3 trials (REAL8: NCT05330325; REAL9: NCT05723835) involving children and adolescents born SGA (N = 80), ISS (N = 69), NS (N = 62), and TS (N = 79), along with additional data from phase 2 (REAL5: NCT03878446, N = 59) and phase 1 trials (NCT01973244, N = 24). Relationships between somapacitan dose, exposure, baseline IGF-I SD score (SDS), and height velocity (HV) were established in children born SGA, with similar responses anticipated for those with ISS, NS, or TS. A linear model enabled the estimation of average weekly IGF-I exposure from a single sample collected during the somapacitan dosing interval. IGF-I SDS simulations support flexible dosing changes while maintaining a minimum of 4 days between doses. Somapacitan 0.24 mg/kg/week produced similar IGF-I SDS changes and height velocity increases as daily GH in prepubertal short children and adolescents born SGA or with ISS, NS, or TS. The results support that the guidance already established for GHD regarding somapacitan initiation, dosing flexibility, and IGF-I monitoring remain appropriate for prepubertal short children and adolescents born SGA or with ISS, NS, or TS.

IGF2BP2 promotes cuproptosis of cardiomyocytes through m6A modification of MAP2K1 in sepsis-induced myocardial injury.

Paternal fenvalerate exposure causes autism-like behavior partly by altering epigenetic reprogramming of the imprinted gene IGF2 in fetal brain and paternal sperm.

A 28-day study was conducted to examine the effects of photoperiods with multiple light/dark cycles on growth performance and oxidative stress for largemouth bass (Micropterus salmoides) larvae in recirculating aquaculture systems (RAS). Larvae fish were exposed to four different photoperiods [light/dark (L:D), h] as follows: 6L:18D; 12L:12D; 18L:6D and 24L:0D. The feeding number was 8 times a day. The light duration of each treatment was 45min, 90min, 135min and 180min respectively in one light/dark cycle (feeding interval) of 180min. A total of six thousand fish (0.5229 ± 0.0180cm, 0.0021 ± 0.0002g) were randomly kept in the 12 cages (4 treatments × 3 replicates × 500 individuals). The results showed that the body weight, weight gain rate (WGR), specific growth rate (SGR), thermal growth coefficient (TGC), Fulton's condition factor (K) and mRNA expressions of growth hormone (gh) and insulin-like growth factor 1 (igf-1) generally increased with the extension of photoperiods, and they were highest in the 24L:0D treatment and were second in the 18L:6D treatment. The variation coefficients for body length (CVfl) and body weight (CVfw) were lowest in 18L:6D treatment. There was no significant difference in survival rate (SR) among four treatments. The levels of Malonaldehyde (MDA), total antioxidant capacity (T-AOC) and mRNA expressions of heat shock protein 70 (hsp70), corticotropin-releasing factor receptor 1 (crfr1) and caspase-3 (cas-3) were all significantly higher in 6L:18D and 24L:0D treatments than those of 18L:6D and 12L:12D treatments. This indicated the photoperiods of 6L:18D and 24L:0D regimes induced an oxidative stress response in the larvae when the photoperiods were excessively compressed and extended. Overall, 18L:6D treatment is the optimal light regime for largemouth bass larvae culture in RAS. However, experimental comparisons between cyclic light/dark and continuous regimes are warranted to further evaluate animal welfare implications and inform aquaculture practice.

CIMT combined with BoNT-A regenerates skeletal muscle and improves upper limb function through activating IGF-1/FGFR2 axis in hemiplegic cerebral palsy.

Impaired growth after immunization with a bivalent oil-adjuvanted vaccine occurs without detectable changes to aerobic capacity in juvenile rainbow trout.

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are emerging as potent cell-free mediators of tissue repair, whose composition and function can be tuned by the cellular microenvironment. Although inflammatory cues modulate mesenchymal stromal cell (MSC) behavior, how defined preconditioning strategies program extracellular vesicle (EV) functional outputs remains incompletely understood. Here, we systematically evaluated how priming bone marrow-derived MSCs with interferon-gamma/tumor necrosis factor-alpha (I/T) or lipopolysaccharide (LPS) generates EV populations with distinct immunomodulatory and regenerative properties. Using a murine full-thickness wound model, we performed an integrative analysis of biodistribution, immune response, and extracellular matrix (ECM) remodeling, complemented by single-cell, transcriptomic, and proteomic profiling. All EV populations were retained at the wound site following subcutaneous delivery and supported wound contraction; however, they drove distinct, treatment-specific repair trajectories. I/T-EVs promoted a coordinated regenerative response characterized by balanced macrophage (MΦ) activation, controlled immune modulation, and efficient resolution of inflammation, resulting in organized ECM remodeling. In contrast, LPS-EVs induced a more pro-inflammatory response, accelerating wound contraction and promoting compensatory matrix stiffening with reduced structural coordination. Control EVs primarily facilitated early immune resolution with limited induction of regenerative remodeling pathways. Proteomic profiling of EVs identified enrichment of proteins associated with insulin-like growth factor signaling, MΦ recruitment, and ECM remodeling, consistent with invivo protein expression patterns and linking EV cargo to functional outcomes. These findings demonstrate that preconditioning does not uniformly enhance EV efficacy but instead selectively programs distinct MSC-EV functional states, establishing EV preconditioning as a tunable strategy for engineering cell-free therapeutics with predictable and context-specific therapeutic outcomes.

High-intensity interval exercise (HIIE) induces transient increases in reactive oxygen species (ROS) and inflammatory mediators that drive skeletal muscle adaptations. Sex influences oxidative stress and inflammation, yet the interplay between sex and exercise-induced signaling remains incompletely understood. The purpose of this study was to investigate sex differences in markers of inflammation, oxidative stress, and antioxidant status at rest and following acute HIIE in young, healthy males and females matched for aerobic fitness. Twenty-four participants (12/sex) underwent muscle biopsies and blood sampling at rest and immediately postexercise (10 × 1 min at 90% HRmax). Skeletal muscle was analyzed for oxidative stress [NADPH oxidase 2 (NOX2), 4-hydroxynonenal (4HNE), total protein carbonylation via oxyblot, p38 MAPK], antioxidant enzymes [thioredoxin 1 (TRX1), glutathione reductase (GR), and glutathione peroxidase 1 (GPX1)], and cytokine content (array), and plasma was analyzed for inflammatory markers (IL-6 and TNFα) and antioxidant status. Acute HIIE increased plasma IL-6 and TNFα and decreased total antioxidant status with no differences between sexes. Basally, females had higher phosphorylation of p38 MAPK and elevated growth- and repair-associated cytokines [insulin-like growth factor binding protein 1 and 3 (IGFBP-1/3), tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1/2), transforming growth factor- β2/3 (TGF-β2/3), FGF-7/9, macrophage colony-stimulating factor (M-CSF), and stromal cell derived factor (SDF)-1], whereas males had higher basal proinflammatory cytokines (IL-1α, IL-13, IP-10, and oncostatin M). Following exercise, males showed a greater upregulation of growth and repair mediators, whereas females had broader suppression of inflammatory and chemotactic factors. No sex differences were observed in muscle oxidative stress markers or antioxidant content. These findings indicate that although acute HIIE elicits comparable plasma inflammatory responses in males and females, underlying skeletal muscle cytokine signaling and adaptive potential are sex-specific, emphasizing the need to consider sex in exercise physiology studies. NEW & NOTEWORTHY We investigated whether sex influenced the inflammatory or oxidative stress response to acute exercise. Although no differences were observed in plasma markers, in skeletal muscle, females had elevated growth- and repair-associated cytokines, whereas males had higher proinflammatory cytokines at rest. Following exercise, males had greater upregulation of growth and repair mediators, whereas inflammatory and chemotactic factors were suppressed in females. The sex divergence in skeletal muscle cytokines may have implications postexercise signaling and chronic adaptations.

Molecular mechanisms of skeletal muscle atrophy: clinical challenges and future therapeutic strategies.

Icariin, the principal active compound of Epimedium species used in traditional East Asian medicine, exhibits anti-inflammatory and lipid-regulating effects. However, its effects on human sebocytes and dermal fibroblasts, which could be implicated in the management of acne and atrophic scarring, remain unexplored. This study aimed to evaluate the effects of icariin on human sebocytes, keratinocytes and dermal fibroblasts. Icariin's effects on cell viability, lipid synthesis, inflammation, abnormal keratinization and extracellular matrix (ECM) synthesis were assessed using human SEB-1 sebocytes, HaCaT keratinocytes and Detroit 551 fibroblasts. Icariin modestly promoted the proliferation of SEB-1 sebocytes, HaCaT keratinocytes and Detroit 551 fibroblasts. It reduced mRNA levels of lipogenic and proinflammatory markers in SEB-1 sebocytes and HaCaT keratinocytes. Icariin counteracted arachidonic acid-induced lipogenesis in SEB-1 sebocytes in parallel with modulation of the insulin-like growth factor 1 receptor/Akt signalling pathway. In Detroit 551 fibroblasts, it enhanced ECM protein expression and reduced the expression of ECM-degrading enzymes, accompanied by upregulation of platelet-derived growth factor receptor and latent transforming growth factor β binding protein 4. In conclusion, this study demonstrates that icariin modulates key pathophysiological processes of acne and promotes ECM synthesis, suggesting its potential as a novel therapeutic agent for managing both acne and atrophic acne scars.

Cancer-associated thrombosis (CAT) and cancer-associated cachexia (CAC) are the most common comorbidities in patients with malignant diseases. Their development is modulated by several factors related to the patient, tumour and antineoplastic treatments. Intriguingly, they share a pro-inflammatory setting induced by cytokines released by cancer and host cells in the tumour microenvironment, which leads to metabolic and endocrine derangements across organ systems. The insulin-like growth factor 1 (IGF-1) axis, implicated in metabolism, tissue homeostasis, and tumourigenesis, may play a key role in this interface. Specifically, the dysregulation of the IGF1R-PI3K-Akt-mTOR pathway, which governs protein synthesis (anabolism) and degradation (catabolism), has been involved in muscle wasting associated with CAC. Concerning CAT, while less explored, the roles of the IGF-1 axis in angiogenesis and endothelial stability suggest a potential connection. To address knowledge gaps, this comprehensive narrative review examined the current literature on the IGF-1 pathway's involvement in CAT and CAC, including the implications of genetic markers. As the IGF-1 axis may serve as a signalling bond between these paraneoplastic syndromes, further investigation may lead to the identification of disease predictors, supporting risk stratification and early intervention.

Thyrotropin (TSH) and insulin-like growth factor 1 (IGF-1) signals have been shown to be additive in their action on thyroid cells and fibroblasts, and this coordination emphasizes the role of TSH receptor (TSHR) and IGF-1 receptor (IGF-1R) signaling exerted by stimulating TSHR antibodies in patients with thyroid eye disease (TED). Here, we have reanalyzed the influence of TSHR autoantibodies on TSHR and IGF-1R expression in a fibroblast model. We developed a new method to assess TSHR expression using a hinge-region monoclonal antibody (MC-1) that does not interfere with TSH or TSHR antibodies. Using molecular dynamic simulations, we first assessed access to the binding sites for TSH and TSHR antibodies within the leucine-rich repeat region of the TSHR ectodomain in the presence of MC-1 binding. 3T3-L1 fibroblasts and human orbital fibroblasts were treated with increasing doses of TSH or the stimulating TSHR antibody M22. TSHR and IGF-1R expressions were measured by flow cytometry and real-time quantitative polymerase chain reaction (RT-qPCR), with 3T3-L1 cell differentiation confirmed by Oil Red O staining. To explore mechanisms of TSH- and M22-induced receptor upregulation, we assessed the effects of inhibiting protein synthesis and endocytosis. TSH ligand induced a dose-dependent increase in detectable expression of the TSHR as measured using MC-1 binding. Furthermore, parallel assessment of IGF-1R expression showed a similar dose-dependent increase in expression induced by TSH. Studies with stimulating TSHR antibody (M22) also demonstrated a similar increase in TSHR and IGF-1R expression peaking at 48 hours. These data could not be explained by transcriptional changes as measured by RT-qPCR. In addition, analysis of the effect of protein synthesis inhibition failed to reduce TSHR and IGF-1R induction. However, inhibition of endocytosis markedly reduced enhancement of TSHR and IGF-1R expression. These data strengthen the role of TSHR antibodies in TED by showing that they enhance TSHR and IGF-1R expression in fibroblasts, helping to explain their additive retroorbital signaling. This enhancement is largely driven by receptor recycling, which can be blocked by inhibiting endocytosis and may be therapeutically targeted. The dual increase in both receptors also supports prior evidence of TSHR/IGF-1R complex formation.

Osteoporosis is a systemic skeletal disorder characterized by impaired bone microarchitecture and reduced bone strength arising from dysregulated coupling between osteoclast-mediated resorption and osteoblast-driven formation. Estrogen deficiency, chronic inflammation, oxidative stress, and altered RANKL/OPG signaling amplify osteoclastogenesis while suppressing Wnt/β-catenin-dependent osteoblast differentiation, resulting in progressive trabecular thinning and cortical porosity. Although antiresorptive agents and anabolic therapies reduce fracture risk, they do not fully restore bone quality, microvascular integrity, or osteoimmune balance. Platelet-derived biomaterials (PDBs), including platelet-rich plasma, platelet-rich fibrin, platelet lysates, and platelet-based hydrogels, represent autologous bioactive systems enriched with platelet-derived growth factor, transforming growth factor-β, vascular endothelial growth factor, insulin-like growth factor-1, and bioactive lipid mediators. Upon activation, PDBs provide an early burst and sustained release of growth factors within a fibrin matrix that supports mesenchymal stem cell recruitment, RUNX2- and Osterix-mediated osteogenic differentiation, extracellular matrix deposition, and angiogenic coupling through VEGF-driven neovascularization. Concurrently, PDBs modulate osteoclast activity by influencing the RANKL/OPG axis, promoting macrophage polarization toward an M2 reparative phenotype, and attenuating inflammatory cytokine signaling. Integration of PDBs with osteoconductive scaffolds and nanostructured delivery platforms further enhances mechanical stability, local retention, and spatiotemporal biofactor presentation in osteoporotic bone defects. Preclinical evidence demonstrates improvements in bone mineral density, trabecular architecture, and fracture repair; emerging clinical applications in spinal fusion and fracture management suggest translational promise. However, variability in platelet concentration, activation protocols, and dosing standardization remains a barrier to widespread clinical adoption. PDB-based regenerative strategies therefore offer a mechanistically targeted and clinically adaptable approach to restoring skeletal integrity in osteoporosis.

Human insulin-like growth factor-1 (hIGF-1) is a non-glycosylated polypeptide hormone that plays a crucial role in prenatal and postnatal growth. Recently, various engineered variants of hIGF-1 have been created to enhance protein stability and activity. However, challenges persist in the production process, including yield, purification, and production costs. In this study, we simultaneously expressed active TEV protease and His-tagged hIGF-1 fused with the TrxA solubility tag in SHuffle T7 Express and Rosetta-gami 2(DE3) strains to assess expression yield and in vivo digestion of the soluble TrxA-free His-tagged hIGF-1 fusion protein. Our findings revealed efficient expression of recombinant TrxA-TEVs-His.hIGF-1, with successful digestion by TEV protease to release TrxA-free His-tagged hIGF-1 in both strains. However, the SHuffle strain exhibited higher expression levels and TEV protease functionality under optimized conditions. Furthermore, bioactivity assays of the purified TrxA-free His-tagged hIGF-1 demonstrated comparable activity to a commercial hIGF-1. This study developed a simple and feasible method for producing and purifying soluble, active recombinant hIGF-1 without any solubility tag through effective in vivo cleavage. By maintaining protein activity, this method is expected to simplify downstream processing and reduce both the time and cost of protein production.