Renal fibrosis represents the final common pathway in the progression of chronic kidney disease (CKD), characterized by excessive deposition of extracellular matrix (ECM) and progressive disruption of renal architecture. To date, no approved therapy can fully reverse established or advanced fibrosis. This review comprehensively summarizes the molecular mechanisms through which epidermal growth factor receptor (EGFR) signaling contributes to renal fibrosis and critically evaluates the therapeutic potential of EGFR-targeted interventions. Accumulating evidence reveals a context-dependent dual role for EGFR in kidney pathophysiology: transient EGFR activation supports epithelial repair following acute kidney injury, whereas sustained or dysregulated EGFR signaling promotes maladaptive repair and fibrogenesis. Mechanistically, persistent EGFR activation potentiates TGF-β/Smad signaling, activates mitogen-activated protein kinase (MAPK) cascades, promotes G2/M cell-cycle arrest and partial epithelial–mesenchymal transition (p-EMT) in tubular epithelial cells, and exacerbates inflammatory and oxidative responses involving nuclear factor kappa B (NF-κB), the NLRP3 inflammasome, and reactive oxygen species (ROS). Importantly, p-EMT in renal fibrosis is increasingly viewed as a profibrotic epithelial reprogramming state that impairs regenerative capacity and enhances paracrine signaling to interstitial fibroblasts rather than necessarily reflecting complete conversion of tubular epithelial cells into matrix-producing myofibroblasts. Together with metabolic dysfunction, these interconnected processes sustain fibroblast activation and pathological ECM accumulation. Current therapeutic strategies targeting EGFR include synthetic small-molecule inhibitors, natural bioactive compounds, and biological approaches. Although pharmacological EGFR inhibition demonstrates antifibrotic efficacy in preclinical models, clinical translation remains limited by systemic toxicity, insufficient renal specificity, and the absence of direct clinical validation in renal fibrosis. Overall, EGFR functions as a context-dependent molecular switch linking adaptive renal repair to maladaptive fibrotic remodeling. Future therapeutic development should therefore prioritize selective modulation of pathological EGFR activity and kidney-targeted delivery strategies that preserve beneficial repair-associated signaling while minimizing systemic toxicity.
Early detection is a hallmark of lung cancer management. Despite extensive investigation into blood-based biomarkers for this purpose, their widespread implementation in clinical practice remains limited. The low molecular weight (LMW) peptide signatures employed by MALDI-TOF MS have been extensively employed for early lung cancer detection. However, the majority of reported discriminatory peaks have exhibited variations among different studies. To address the key question of reproducibility across studies, we performed a systematic review of published reports evaluating mass spectrometry-based peptide profiling in blood as a diagnostic tool for lung cancer. The PubMed, Embase, and Scopus databases were systematically searched for original studies reporting the discriminatory peaks retrieved from lung cancer classification models after MALDI-TOF MS analysis. A total of 14 profile studies were qualified for inclusion in the review. A high degree of methodological heterogeneity was observed among these reports, particularly in pre-analytical factors and the lung cancer classification model. Despite this variability, we revealed evidence of certain reproducible discriminatory peaks among studies that consistently correlated with the presence of lung cancer. Furthermore, we present the peptide that might potentially be a biomarker for lung cancer. Our combined analysis and recent findings suggest that this blood-based peptide profiling has considerable potential to enhance lung cancer management, especially in terms of early detection. However, we need additional prospective studies that employ standardized protocols and involve larger, independent cohorts to move this technology toward clinical implementation.
Ocular diseases involving both the anterior and posterior segments—such as dry eye disease, keratitis, glaucoma, cataracts, diabetic retinopathy, retinal vein occlusion, and ocular tumors—remain major contributors to global visual impairment. Conventional topical and systemic therapies are limited by rapid clearance, restricted penetration across ocular barriers, and poor bioavailability, particularly for posterior-segment targets. Nanotechnology has introduced a transformative therapeutic paradigm by enabling controlled pharmacokinetics, enhanced tissue penetration, and site-specific delivery. A wide range of engineered nanomaterials—including polymeric nanoparticles, lipid-based carriers, dendrimers, metallic and metal-oxide nanoparticles, mesoporous silica systems, cerium oxide nanozymes, carbon quantum dots, nanogels, and electrospun nanofibers—has demonstrated improved drug loading, sustained release, ocular surface retention, and compatibility with biologics and gene-based agents. Emerging minimally invasive platforms, such as 4D printed smart scaffolds, dissolving microneedles and magnetically driven microrobots, further enable precise transscleral or intravitreal delivery, active navigation through the vitreous, and targeted interaction with retinal lesions. Parallel clinical advances, including FDA-approved nanoformulations and ongoing trials, confirm the translational potential of these technologies. Plus, artificial intelligence now accelerates both ophthalmic diagnosis and nanocarrier design, enabling predictive modeling of nano–bio interactions, personalized delivery strategies, and real-time disease assessment. This review integrates current advances in nanomaterial engineering and AI-guided innovation, outlining their convergent roles in shaping next-generation precision therapeutics for vision preservation and restoration.
Background Prostate cancer (PC) is a global major health concern, and radiotherapy is part of the standard treatment for locally advanced disease. Despite medical advances, the effectiveness of this therapy is often compromised by radiation resistance, a complex and adaptive process that allows tumor recurrence and progression. MicroRNAs (miRNAs) have emerged as key regulators of radiation response, influencing DNA repair, apoptosis, and survival signaling. These molecules actively contribute to radiation resistance acquisition and mediate dynamic interactions within the tumor ecosystem. Methods This review analyzes the molecular basis of radiation resistance in PC, focusing on miRNAs with experimental evidence of involvement in PC radiation response. A structured literature search was performed to identify original studies investigating the role of miRNAs in PC radioresistance. Results Radiation resistance is mediated by the coordination of various mechanisms, including DNA damage repair, pro-survival signaling, adaptation to oxidative stress, metabolic reprogramming, and phenotypic plasticity, such as epithelial-mesenchymal transition and cancer stem cell-like states. Through a structured analysis of 17 studies, we identified the main miRNAs associated with radioresistance, and their experimentally validated targets showed convergence in shared signaling pathways, including the FOXO pathways. Conclusions miRNAs represent candidate biomarkers and therapeutic targets for PC radioresponse; however, their predictive value for radiotherapy response requires prospective clinical validation. miRNAs are key regulators of PC radioresistance, while their validated targets converge within shared molecular networks, supporting their potential as candidate biomarkers and therapeutic targets for future precision radiotherapy strategies. Emerging evidence also suggests that extracellular vesicle-derived miRNAs may contribute to intercellular communication of resistance phenotypes, warranting future investigation.
Background Polyendocrine metabolic ovarian syndrome (PMOS), formerly named polycystic ovary syndrome (PCOS), is a common endocrine–metabolic disorder with limited treatments. Chiglitazar, a novel pan-PPAR agonist, shows multitarget potential, but its systemic mechanisms in PMOS remain unclear. Objective To compare chiglitazar with metformin and pioglitazone in a PMOS-like mouse model and elucidate its multiorgan mechanisms via integrated omics. Methods A letrozole-induced PMOS-like mouse model was established. Mice were divided into five groups: normal control, PMOS model, and PMOS treated with metformin, pioglitazone, or chiglitazar. Phenotypic assessments included glucose tolerance, hormone levels, ovarian morphology, and estrous cycle. Multiomics analyses comprised DIA proteomics of liver, skeletal muscle, and visceral adipose tissue (VAT); ovarian transcriptomics; and 16S rRNA gut microbiota sequencing. Results Chiglitazar significantly improved insulin resistance (IR), reduced testosterone, restored estrous cyclicity, and ameliorated polycystic ovarian morphology. Proteomics revealed tissue-specific remodeling, with the VAT showing the most extensive proteomic remodeling. In the liver, chiglitazar downregulated mitochondrial OXPHOS proteins (Uqcrb, Ndufs4, Cox6a1) and upregulated insulin-degrading enzymes (Ide, Apeh). In adipose tissue, it inhibited OXPHOS pathways. In skeletal muscle, it modulated ubiquitin-mediated proteolysis. Ovarian transcriptomics indicated regulation of MAPK/GnRH signaling. Gut microbiota diversity was restored with enriched metabolic pathways. Conclusions Chiglitazar induces metabolic reprogramming across multiple organs in PMOS-like mice, targeting IR, hyperandrogenism, ovarian dysfunction, and gut dysbiosis through distinct yet convergent pathways. These integrated mechanisms support its potential as a novel multitarget therapy for PMOS.
