Search Results (396)

Background/Objectives: Central precocious puberty (CPP) is diagnosed via gonadotropin-releasing hormone (GnRH) stimulation testing, which can be burdensome in pediatric settings. This study evaluated the utility of baseline hormonal markers—particularly insulin-like growth fac-tor 1 (IGF-1) and IGF-binding protein 3 (IGFBP-3)—as auxiliary tools for CPP diagnosis in Korean children. Methods: We retrospectively analyzed patients who underwent GnRH stimulation testing. Baseline LH, FSH, IGF-1, and IGFBP-3 levels were assessed, along with standard deviation scores (SDS) calculated using two different reference intervals. Multivariable logistic regression was performed to improve diagnostic accuracy. Performance was evaluated using area under the curve (AUC) values from receiver operating characteristic (ROC) analyses, stratified by sex. Results: Among 2464 Korean children (2025 girls and 439 boys), CPP diagnosis rates were 54.2% in girls and 65.6% in boys. Among baseline markers, FSH showed the highest AUCs using raw values with sex-specific cutoffs (AUC = 0.767 in girls and 0.895 in boys). Although IGF-1 SDS and IGFBP-3 SDS showed AUCs < 0.7 when used alone, predictive models incorporating these SDS values yielded higher performance (AUC = 0.800 in girls and 0.920 in boys. Conclusions: SDS-based IGF-1 and IGFBP-3 enhance CPP diagnosis when used in predictive models, emphasizing the need for sex-specific interpretation and standardized reference intervals in real-world clinical practice. Full article

Background: Diabetic eye surface disease, including dry eye syndrome, corneal neuropathy, and diabetic retinopathy, is a common complication of diabetes. Tear fluid biomarkers may aid in early diagnosis and disease monitoring. The objective of this systematic review was to identify and evaluate tear fluid biomarkers in diabetic ocular surface disease according to PRISMA guidelines. Methods: PubMed, Scopus, and Embase databases were searched through June 2025. Eligible studies included clinical and observational studies measuring proteins, lipids, cytokines, trace elements, or nucleic acids in tear fluids in patients with diabetes. Results: The search identified 198 studies, and of those, 30 studies were included, comprising 14 original investigations with 871 participants (133 with type 1 diabetes, 453 with type 2 diabetes, 16 with pre-diabetes, and 269 healthy controls). The main biomarker categories were cytokines (IL-6, IL-8, TNF-α, and MMP-9), neuropeptides (substance P, NPY), proteins (IGFBP-3, progranulin), lipids, glycans, microRNAs, circRNAs, and trace elements. Conclusions: More than a dozen biomarkers in the tear fluid have been identified that may reflect diabetes-related changes in the ocular surface. Tear fluid analysis may be a valuable tool in personalizing the diagnosis and treatment of diabetic ocular surface diseases, but further studies are needed to confirm its clinical significance. Full article

Background and Objectives: The objectives of this review were as follows: to measure changes in renal biomarker levels before, immediately after, and 24 h post-marathon; to identify promising biomarkers for the diagnosis of acute kidney injury; and to describe the temporal patterns of biomarker dynamics in relation to the marathon. Materials and Methods: Studies of marathon runners reporting AKI-related biomarkers were included. Four databases (PubMed, EMBASE, Web of Science, and LILACS) were searched. Data on study design, participant characteristics, and biomarker values (pre-, post-, and 24 h post-race) were extracted, and a random effects meta-analysis was performed. Risk of bias was assessed with the National Heart, Lung, and Blood Institute pre–post tool. Results: The study showed significant increases in most biomarkers immediately after the marathon compared to baseline values. The largest increases were observed in Tissue Inhibitor of Metalloproteinases-2* Insulin-like Growth Factor Binding Protein-7 (TIMP-2*IGFBP), copeptin, urinary Liver-type Fatty Acid Binding Protein (L-FABP), urinary Monocyte Chemoattractant Protein-1 (MCP-1), IGFBP-7, urinary Chitinase 3-like Protein 1 (YKL-40), and TIMP-2, suggesting that these biomarkers are promising candidates for future research. Several patterns of biomarker evolution were observed: some increased without decreasing even at 24 h after the marathon; others increased post-marathon and decreased at 24 h while remaining above baseline; some increased after the marathon and then fell below baseline at 24 h. Conclusions: Marathon running causes significant increases in kidney injury biomarkers, with different patterns of evolution. Full article

Background: The precise role of RNA modification in post-traumatic stress disorder (PTSD) remains incompletely understood. This study aims to elucidate the effects of five common RNA modifications in PTSD, specifically m⁶A, m⁵C, m¹A, m⁷G, and ψ. Methods: We extracted data from the GEO repository to conduct a series of bioinformatics analyses. These included differential analysis to identify key regulators of five common RNA modifications, model construction using random forest (RF), least absolute shrinkage and selection operator (LASSO), and nomogram techniques, as well as consensus clustering of RNA modification subtypes. Furthermore, GO enrichment analysis was performed on DEGs associated with various RNA modification patterns. Immune cell infiltration was assessed using PCA and ssGSEA. RT-qPCR was performed to validate RNA modification-related genes (RMGs). Results: Twenty-one differentially expressed RMGs were identified. LASSO and RF intersection yielded eight signature genes (YTHDC1, IGFBP1, IGF2BP1, ALKBH5, NSUN4, TET2, TET3, WDR4) that robustly diagnosed PTSD (AUC = 0.804). Furthermore, these feature genes were validated using RT-qPCR, which was basically consistent with the results of bioinformatics analysis. Consensus clustering analysis may reveal two distinguishable subtypes: clusterA marked by high immunoinflammation, and clusterB characterized by high-neuroendocrine dysregulation. Conclusions: RMGs may play a crucial role in the pathogenesis of PTSD. Analyzing RNA modification patterns could offer potential diagnostic markers and help to guide immunotherapeutic approaches or neurotransmitter system interventions for PTSD in the future. Full article

Cardiorenal syndrome (CRS) reflects the intricate and bidirectional interplay between cardiac and renal dysfunction, commonly resulting in diagnostic uncertainty, therapeutic dilemmas and poor outcomes. While traditional biomarkers like serum creatinine (Cr) and natriuretic peptides remain widely used, their limitations in specificity, timing and contextual interpretation often hinder optimal management. This narrative review synthesizes the current evidence on established and emerging biomarkers in CRS, with emphasis on their clinical relevance, integration into real-world practice, and potential to inform precision therapy. Markers of glomerular filtration rate beyond creatinine—such as cystatin C—offer more accurate assessment in frail or sarcopenic patients, while tubular injury markers such as NGAL, KIM-1, and urinary L-FABP (uL-FABP) provide early signals of structural renal damage. The FDA-approved NephroCheck^® test—based on TIMP-2 and IGFBP7— enables risk stratification for imminent AKI up to 24 h before functional decline. Congestion-related markers such as CA125 and bio-adrenomedullin outperform natriuretic peptides in certain CRS phenotypes, particularly in right-sided heart failure or renally impaired patients. Fibrosis and inflammation markers (galectin-3, sST2, GDF-15) add prognostic insights, especially when combined with NT-proBNP or troponin. Rather than presenting biomarkers in isolation, this review proposes a framework that links them to specific clinical contexts—such as suspected decongestion-related renal worsening or persistent congestion despite therapy—to support actionable interpretation. A tailored, scenario-based, multi-marker strategy may enhance diagnostic precision and treatment safety in CRS. Future research should prioritize prospective biomarker-guided trials and standardized pathways for clinical integration. Full article

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

Acute kidney injury (AKI) is a frequent and severe complication in trauma patients, affecting up to 28% of intensive care unit (ICU) admissions and contributing significantly to morbidity, mortality, and long-term renal impairment. Trauma-related AKI (TRAKI) arises from diverse mechanisms, including hemorrhagic shock, ischemia–reperfusion injury, systemic inflammation, rhabdomyolysis, nephrotoxicity, and complex organ crosstalk involving the brain, lungs, and abdomen. Pathophysiologically, TRAKI involves early disruption of the glomerular filtration barrier, tubular epithelial injury, and renal microvascular dysfunction. Inflammatory cascades, oxidative stress, immune thrombosis, and maladaptive repair mechanisms mediate these injuries. Trauma-related rhabdomyolysis and exposure to contrast agents or nephrotoxic drugs further exacerbate renal stress, particularly in patients with pre-existing comorbidities. Traditional markers such as serum creatinine (sCr) are late indicators of kidney damage and lack specificity. Emerging structural and stress response biomarkers—such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), interleukin-18 (IL-18), C-C motif chemokine ligand 14 (CCL14), Dickkopf-3 (DKK3), and the U.S. Food and Drug Administration (FDA)-approved tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein 7 (TIMP-2 × IGFBP-7)—allow earlier detection of subclinical AKI and better predict progression and the need for renal replacement therapy. Together, functional indices like urinary sodium and fractional potassium excretion reflect early microcirculatory stress and add clinical value. In parallel, risk stratification tools, including the Renal Angina Index (RAI), the McMahon score, and the Haines model, enable the early identification of high-risk patients and help tailor nephroprotective strategies. Together, these biomarkers and risk models shift from passive AKI recognition to proactive, personalized management. A new paradigm that integrates biomarker-guided diagnostics and dynamic clinical scoring into trauma care promises to reduce AKI burden and improve renal outcomes in this critically ill population. Full article

Endocrine-disrupting chemicals such as benzophenone-3 (BP-3) can have severe consequences for human reproduction by affecting critical processes during pregnancy. To shed further light on potential harmful BP-3 actions, our current study addressed the impact of BP-3 on decidualization and trophoblast invasion. Decidualization was initiated in human endometrial stromal cells (THESC) upon treatment with a mixture of cAMP, progesterone, and estradiol. In parallel to hormonal treatment, the cells were exposed to different BP-3 concentrations ranging from 0.001 µM to 10 µM. The expression of decidualization and invasion markers was determined. Moreover, trophoblastic spheroids derived from JEG-3 cells were transferred to decidualized THESC after BP-3 exposure, and spheroid attachment and invasion were analyzed. Hormonal treatment successfully initiated decidualization in THESC, which was confirmed by increased prolactin levels and IGFBP1 and NCOA-3 mRNA expression. Notably, BP-3 exposure did not affect these markers. Furthermore, BP-3 changed neither THESC proliferation nor viability nor the frequency of cells expressing MMP2/9 or TIMP1/3. Trophoblastic spheroid attachment and outgrowth into THESC were not altered through any of the BP-3 concentrations applied. Our results do not provide evidence for an influence of BP-3 on the decidualization process and the capability of trophoblast cells to adhere and invade into endometrial stromal cells. Full article

Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive cartilage disorder caused by biallelic variants in CCN6, which encodes the matricellular protein WISP3. Although WISP3 is thought to contribute to extracellular matrix (ECM) homeostasis, its precise molecular role in PPD remains unclear. To elucidate how disease-associated CCN6 variants affect chondrocyte function, we overexpressed four variants—p.Cys52*, p.Tyr109*, p.Gly83Glu, and p.Cys114Trp—all located within the IGFBP domain, and evaluated their impact on parameters including redox balance, ER stress, ECM remodeling, gene expression, and protein–protein interactions. The p.Cys52* variant resulted in rapid degradation of WISP3, indicating a complete loss-of-function. The p.Tyr109* variant disrupted ECM regulation, markedly reducing protein interaction capacity, which was correlated with elevated mitochondrial ROS (mtROS) levels and triggered a strong response that led to programmed cell death. Although both missense variants yielded full-length proteins, their effects diverged significantly: p.Gly83Glu induced minor cellular alterations, whereas p.Cys114Trp caused severe protein destabilization, increased ROS accumulation, and high levels of ER stress. Proteomic analysis revealed that p.Cys114Trp acquired novel interaction partners, suggesting a potential gain-of-function mechanism. Collectively, these findings demonstrate that the functional consequences of CCN6 variants depend not only on variant type or domain location but also on their positional and structural context. The distinct cellular responses elicited by each variant underscore the importance of functional validation in modeling PPD pathogenesis and offer valuable biological and therapeutic perspectives. Full article

CD93 is a highly glycosylated transmembrane glycoprotein with key functional domains, including a C-type lectin-like domain (CTLD) and epidermal growth factor (EGF)-like domains. Primarily expressed in endothelial cells (ECs), CD93 regulates critical physiological processes such as angiogenesis, cell adhesion, migration, and apoptotic cell clearance through interactions with ligands like multimerin-2 (MMRN2) and insulin-like growth factor-binding protein 7 (IGFBP7). Aberrant CD93 expression has been observed in various pathological conditions, including inflammation, cardiovascular diseases, autoimmune disorders, and cancer. Notably, CD93 is overexpressed in tumor-associated blood vessels, which is associated with poor prognosis and advanced disease stages. Targeting the CD93 signaling pathway has the potential to improve tumor vascular function and enhance the efficacy of immunotherapy, making it a promising therapeutic target. This review summarizes the current understanding of CD93’s structure, function, and disease mechanisms, providing a framework for further research and clinical translation in related fields. 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

Nile tilapia (Oreochromis niloticus) is a key species due to its rapid growth, high nutritional value, and adaptability to diverse environments. However, changes in water salinity pose significant challenges to tilapia farming. Elucidating the adaptive strategies of tilapia to fluctuating salinity environments is crucial for improving aquaculture efficiency. This study investigated the transcriptional signature of growth-hormone-releasing hormone, somatostatin, growth hormone, and insulin-like growth factor (grhr-sst-gh-igf) axis in Nile tilapia under different salinity conditions (0 g/L, 16 g/L, and 30 g/L). The results showed that in brackish or seawater, Nile tilapia rapidly upregulate brain igfbp5 paralogues and their regulators (sst5, sstr2) to sustain growth-active IGF-1 signaling, while in the liver and gut, they downregulate sstr2b, igfbp1/7, and ghrh to reallocate energy toward osmoregulation. Physiological regulation, such as the use of ligand analogs, or genetic enhancement targeting these genes might hold promise for improving salt acclimation, which would enable profitable farming in brackish or coastal ponds and offer a simple tool for more resilient and efficient tilapia production. Full article

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Despite significant advances in screening and treatment, the prognosis for advanced-stage disease continues to be poor. One thriving area of research focuses on the use of epigenetic alterations for the diagnosis, prediction of treatment response, and prognosis of CRC. In this study, we evaluated original studies and meta-analyses published within the past five years to identify the most clinically relevant epigenetic biomarkers. DNA methylation-based assays, particularly those targeting SDC2 and SEPT9 in stool and plasma, exhibit superior diagnostic accuracy compared to other epigenetic modalities. Circulating microRNAs (miRNAs), including miR-211, miR-197, and miR-21, as well as specific long non-coding RNAs (lncRNAs) such as SNHG14, LINC01485, and ASB16-AS1, also show promising diagnostic potential. Furthermore, panels combining multiple epigenetic markers, especially those incorporating DNA methylation targets, have demonstrated improved sensitivity and specificity for early-stage CRC detection. In the context of therapeutic prediction, microRNAs such as miR-140, miR-21, and miR-4442 have been associated with chemotherapy resistance and recurrence risk. DNA methylation markers like LINE-1, mSEPT9 and ERCC1 have also shown predictive value, while lncRNAs including MALAT1 and GAS6-AS1 remain less validated. Regarding prognosis, miRNAs appear to be the most promising biomarkers, with miR-675-5p and miR-150 being associated with poor survival, while miR-767-5p and miR-215 predict favorable outcomes. Methylation of NKX6.1, IGFBP3, and LMX1A has been identified as an independent negative prognostic factor, while SFRP2 hypermethylation is linked to better prognosis. Selected lncRNAs, including THOR and LINC01094, have also demonstrated significant prognostic value. Despite these advances, challenges persist, including inconsistent reporting, limited external validation, and a lack of replication by independent research groups. Full article

Cytokine storm (CS) is associated with poor prognosis in COVID-19 patients. Hypoxic signaling has been proposed to influence proinflammatory pathways and to be involved in the development of CS. Here, for the first time, the role of hypoxia in coronavirus-mediated inflammation has been investigated, using transcriptomic and proteomic approaches. Analysis of the transcriptome of A549 lung epithelial cells using RNA sequencing revealed 191 mRNAs which were synergistically upregulated and 43 mRNAs which were synergistically downregulated by the combination of human Betacoronavirus OC43 (HCoV-OC43) infection and hypoxia. Synergistically upregulated mRNAs were strongly associated with inflammatory pathway activation. Analysis of the expression of 105 cytokines and immune-related proteins using antibody arrays identified five proteins (IGFBP-3, VEGF, CCL20, CD30, and myeloperoxidase) which were markedly upregulated in HCoV-OC43 infection in hypoxia compared to HCoV-OC43 infection in normal oxygen conditions. Our findings show that COVID-19 patients with lung hypoxia may face increased risk of inflammatory complications. Two of the proteins we have identified as synergistically upregulated, the cytokines VEGF and CCL20, represent potential future therapeutic targets. These could be targeted directly or, based on the novel findings described here by inhibiting hypoxia signaling pathways, to reduce excessive inflammatory cytokine responses in patients with severe infections. Full article

The insulin-like growth factor (IGF) system regulates implantation, placental development, and angiogenesis in eutherian mammals. However, little is known about the changes in this system in equine placenta (chorioallantois; CA) and the endometrium (EN) during pregnancy, or the relationship to vascular endothelial growth factor (VEGF) expression. The current study investigated the expression of the IGF system components, namely the ligands (IGF1 and IGF2), their receptors (IGF1R, IGF2R, and INSR), and their binding proteins (IGFBPs and IGF2BPs) in equine CA at 45 days, 4, 6, 10, and 11 months of gestational age (GA) and immediately postpartum (PP), and in equine EN at 4, 6, 10, and 11 months GA. IGF1 immunolocalization and serum concentrations were also evaluated across gestation. IGF1 mRNA expression in CA increased from day 45 to peak at 6 months and then gradually declined to reach a nadir in PP samples. This profile correlated positively with the VEGF expression profile (r = 0.62, p = 0.001). In contrast, IGF2 expression in CA was not correlated with VEGF (p = 0.14). Interestingly, IGF2 mRNA was more abundant in equine CA than IGF1 (p < 0.05) throughout gestation. Among the IGFBPs investigated in CA, the expression of IGFBP2 and IGF2BP2 was highly abundant (p < 0.05) at day 45 compared to other GAs. Conversely, mRNA expression for IGFBP3 and IGFBP5 was more abundant (p < 0.05) in PP than at all investigated GAs. Immunohistochemistry revealed that IGF1 is localized in the equine chorionic epithelium (cytoplasm and nucleus). IGF1 serum concentrations peaked at 9 months and declined to their lowest levels PP. In conclusion, this study demonstrates a positive correlation between IGF1 and VEGF expression in equine CA during gestation, suggesting that the IGF system plays a crucial role in placental angiogenesis by regulating VEGF. Full article