Search Results (449)

The hallmark feature of empty follicle syndrome (EFS) is failure to retrieve oocytes from apparently mature follicles despite adequate ovarian stimulation and appropriate ovulation triggering. Although considered uncommon, with a reported prevalence ranging from 0.2% to 7%, EFS may have a profound clinical and psychological impact and can recur in assisted reproductive technology (ART) cycles. Modern classification systems divide EFS into genuine and false forms. Genuine EFS is potentially associated with intrinsic abnormalities involving luteinizing hormone/choriogonadotropin receptor (LHCGR) signaling, oocyte competence, and cumulus–oocyte interaction, whereas false EFS is primarily attributed to pharmacokinetic or pharmacodynamic factors resulting in inadequate trigger exposure. Borderline EFS represents a third phenotype characterized by incomplete or partial impairment of final oocyte maturation. This review examines the pharmacodynamics of ovulation-triggering agents, including human chorionic gonadotropin (hCG), gonadotropin-releasing hormone (GnRH) agonist protocols, and dual-trigger strategies, and their roles in regulating final oocyte maturation. The molecular aspects of periovulatory signal transduction and the mechanisms of LHCGR activation, epidermal growth factor (EGF)-like pathways, and meiotic resumption in relation to EFS etiopathogenesis will be described. The impact of patient-dependent conditions like obesity, poor ovarian reserve, polycystic ovary syndrome (PCOS), and pituitary response on trigger response will be assessed. New approaches like post-trigger monitoring of hormones and rescue treatment with gonadotropins represent a valuable method for avoiding cycle cancellation in patients at risk. Overall, EFS is increasingly regarded not as a single disorder but as a heterogeneous spectrum of periovulatory dysfunction arising from pharmacological, endocrine, and intrinsic ovarian factors that impair completion of final oocyte maturation. Full article

Deep wounds often lead to severe complications such as persistent infection, biofilm formation, and high patient morbidity. While skin injuries can usually be managed with functional dressings, wounds in deep layers without sufficient treatment may serve as primary entry points for bacterial infection, thereby posing a significant life-threatening risk to patients. With the rising prevalence of chronic diseases and an aging population, effective strategies for enhanced wound healing are still in high demand. In this study, an injectable and thermoresponsive hexamethylene diisocyanate–Pluronic F127 copolymer–hyaluronic acid composite hydrogel loaded with polyhexamethylene biguanide (PHMB) and epidermal growth factor (EGF), named PEHHPG, was developed for joint therapy of deep wounds. PEHHPG self-gels at 37 °C and stabilizes both agents in the gel matrix. Based on the results of microbial colony assay and analysis of fibroblast growth kinetics, PEHHPG with ≥200 ppm of PHMB and ≥0.15 μg/mL of EGF can eradicate bacteria and enhance cell proliferation in vitro, illustrating the functionalities of PEHHPG. Given the aforementioned effects, together with the recognized advantages of injectable hydrogels such as wound shape/depth adaptation, low adhesiveness, exudate absorptiveness, and moisture maintenance, the developed PEHHPG is anticipated to be a feasible dressing material for deep wound treatment after further in vivo examinations. Full article

Diabetic foot ulceration is a severe and common chronic complication of diabetes, accompanied by excessive reactive oxygen species (ROS) accumulation, persistent bacterial infection, prolonged inflammation, and insufficient angiogenesis. Traditional single-function wound dressings fail to simultaneously resolve these pathological barriers, leading to unsatisfactory healing outcomes. In this study, we developed a multifunctional composite hydrogel (E/MGel) by introducing mussel adhesive protein (MAP) into methacrylated hyaluronic acid (mHA) to construct an antibacterial and antioxidant delivery system, which was further loaded with epidermal growth factor (EGF) to promote angiogenesis. The as-prepared E/MGel exhibited a uniform porous structure, favorable rheology, high swelling ratio, and sustained protein release behavior. In vitro results demonstrated that E/MGel exerted potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E.coli), high ROS scavenging efficiency, good cytocompatibility, and remarkable pro-angiogenic effect on endothelial cells. In a mouse model of diabetic MRSA-infected full-thickness skin defect, E/MGel significantly accelerated wound closure, reduced bacterial burden, downregulated pro-inflammatory cytokines, promoted collagen deposition, and enhanced neovascularization. Meanwhile, no obvious systemic toxicity was observed. Taken together, this multifunctional hydrogel integrates antibacterial, antioxidant, and pro-angiogenic capacities to break the pathological vicious cycle of diabetic wounds, providing a promising and safe strategy for the clinical treatment of diabetic infected wounds. Full article

Polydeoxyribonucleotide (PDRN) activates the adenosine A2A receptor (A2AR), triggering anti-inflammatory signaling and providing essential nucleotides for the salvage pathway, thereby helping bypass metabolic bottlenecks and promoting tissue repair. Combining PDRN with biochemical agents and physical stimuli represents a significant shift in medical treatment, moving from monotherapy to an integrated, multi-target regenerative approach. These combinatorial strategies effectively address the limitations of PDRN, such as its rapid degradation and diffusion, by simultaneously meeting the structural, metabolic, and signaling needs of injured tissues. The mechanism of action for PDRN involves a synergistic effect with hyaluronic acid, amplification of growth factors (e.g., Platelet-Rich Plasma (PRP), Epidermal Growth Factor (EGF), Platelet-Derived Growth Factor (PDGF)), and enhancements from extracorporeal shockwave therapy (ESWT) and lasers. This results in a notable acceleration of the repair process for chronic wounds, musculoskeletal disorders, and neurological injuries. As intelligent delivery systems like responsive hydrogels and sustainable L-PDRN production continue to advance, these synergistic protocols are poised to redefine global standards of care in regenerative medicine and esthetic dermatology. Future clinical success will hinge on the standardization of sequence-specific protocols and large-scale validation to ensure long-term safety and efficacy. Full article

Introduction: Gastric cancer is a prevalent and aggressive malignancy driven by complex signaling networks. Estrogen receptor-α36 (ER-α36), a membrane-localized receptor, mediates non-genomic signaling and promotes tumor progression. ER-α36 can interact with epidermal growth factor receptor (EGFR) to activate downstream mitogen-activated protein kinase (MAPK) signaling, but the detailed mechanism in gastric cancer remains unclear. This study aimed to explore whether ER-α36 promotes gastric cancer progression by regulating serum and glucocorticoid-regulated kinase 1 (SGK1)-mediated Erk1/2 activation.Methods:We collected 53 human gastric adenocarcinoma specimens and detected ER-α36 expression by immunohistochemistry. Bioinformatics analysis was used to identify ER-α36-related kinases. Gastric cancer cell lines (SGC7901, HGC27, NCI-N87, and MFC) were used for in vitro studies. Western blotting, qRT-PCR, immunofluorescence, co-immunoprecipitation (Co-IP), wound healing, MTT, and Transwell invasion analyses, and nude mouse orthotopic tumor models were applied to investigate the function and mechanism of the ER-α36/SGK1/Erk1/2 axis. Results: ER-α36 was positively expressed in 62.3% of gastric adenocarcinoma tissues and was associated with poor differentiation and prognosis. SGK1 was identified as a key kinase downstream of ER-α36. ER-α36, SGK1, and p-Erk1/2 were co-upregulated in gastric cancer tissues and cells. ER-α36 regulated Raf/MEK1/2/Erk1/2 phosphorylation in an SGK1-dependent manner. EGF-induced Erk1/2 activation required both ER-α36 and SGK1. Overexpression of ER-α36 promoted the proliferation, migration, and invasion of gastric cancer cells, while SGK1 knockdown abolished these oncogenic effects. In vivo experiments confirmed that ER-α36 promoted gastric tumor growth and EGFR/Erk signaling, which was attenuated by SGK1 knockdown. Conclusions: ER-α36 contributes to the malignant progression of gastric adenocarcinoma by activating the Erk1/2 pathway through SGK1. The ER-α36–SGK1–Erk1/2 axis may serve as a novel therapeutic target for gastric cancer. Full article

Urinary epidermal growth factor (uEGF) and clusterin (uCLU) are emerging biomarkers in chronic kidney disease (CKD), but rigorous analytical validation is required before clinical implementation. We evaluated intra-individual variability and long-term storage stability of uEGF and uCLU in CKD. In the prospective, multicenter UVALID study, 60 adults with CKD stages 2–4 underwent urine sampling at three visits over 8 weeks. First-morning and 24-h urine samples were collected to assess intra-individual variability over 24 h, 3 days and 8 weeks. Biomarkers were measured in duplicate by ELISA and normalized to urinary creatinine (/Cr). Inter-laboratory performance was assessed using quality control samples. Stability after 12 and 15 months of storage at −20 °C and −80 °C and the influence of pH were evaluated. Over 24 h, 3 days, and 8 weeks, uEGF/Cr demonstrated low variability and remained stable after long-term storage at both temperatures. In contrast, uCLU/Cr showed greater variability and pronounced instability at −20 °C, whereas stability was preserved at −80 °C. Samples with pH > 6 partially preserved uCLU stability at −20 °C. Inter-laboratory reproducibility was acceptable for uEGF but suboptimal for uCLU at low concentrations. Thus, uEGF showed robust analytical performance, supporting its potential clinical applicability in CKD, whereas uCLU exhibited important analytical and pre-analytical limitations, warranting further assay optimization. These findings underscore the need for rigorous validation to facilitate biomarker implementation in clinical practice. Full article

Epidermal Growth Factor (EGF) plays an important role in skin regeneration and repair by promoting cell proliferation and collagen synthesis. However, its topical application is limited by low stability, susceptibility to degradation, and poor penetration through the stratum corneum due to its hydrophilic nature and relatively large molecular size. Microencapsulation offers a strategy to protect sensitive bioactives and improve their delivery in cosmetic formulations. In this study, EGF was encapsulated in Arabic gum/gelatine A (AG/GE) coacervate microcapsules and incorporated into a hydrating cream. The work extends previous studies using the same microcapsule composition for lipophilic compounds, demonstrating its applicability for a hydrophilic bioactive and highlighting the versatility of the encapsulation platform. The resulting microcapsules exhibited spherical, multinucleated morphology with an encapsulation efficiency of 78.8 + 1.0%. Although diffusion of microencapsulated EGF in the cream could not be directly determined, the formulation showed trends towards improvement in several skin parameters during the volunteer evaluation, including reduction in surface spots (31%), brown spots (21%) and pore visibility (10%), and improved texture (22%). A 25% decrease in transepidermal water loss and a 33% increase in elasticity suggested improved skin barrier function. Volunteers reported high acceptance regarding non-irritancy, texture, and sensory experience. Full article

Background: This study evaluates short-term skin compatibility and biophysical changes in new cosmetic preparations containing PRF and EGF, conducted through in vivo studies. Material and Methods: The study involved 20 healthy volunteers (aged 20–40) who received three identically packaged creams to be applied for a period of four weeks to specific facial areas: formulation 1: base formulation (control); formulation 2: base formulation human epidermal growth factor (EGF) loaded; and formulation 3: base formulation platelet-rich fibrin (PRF) loaded. Skin assessments were conducted at baseline (week 0) and at weeks 1, 2, and 4. Transepidermal water loss (TEWL), skin hydration using corneometry to determine the moisture content of the stratum corneum, skin elasticity using a cutometer to measure the skin’s ability to return to its original state after deformation, and dermal bioavailability were measured. EGF concentration in the stratum corneum will be measured using the tape-stripping method followed by HPLC (high-performance liquid chromatography) analysis. Results: A significant decrease in TEWL was observed for all tested formulations (24%, 37%, and 34%, for formulations 1, 2, and 3, respectively), indicating improved skin barrier function. Formulation 3 showed the highest increase in skin hydration (by 95%), followed by formulation 2. Both formulations 2 and 3 demonstrated improvements in skin elasticity, with formulation 3 showing the greatest enhancement. EGF concentration in the stratum corneum increased over the four-week period, reaching equilibrium with the product concentration by week four. Conclusions: The in vivo instrumental compatibility studies confirmed that the new cosmetic formulations were well tolerated and associated with short-term improvement in selected skin parameters. Full article

The history of stromal-derived factor-1 (SDF-1), alias CXCL12, started serendipitously and relatively late in the cytokine cDNA cloning era (1975–2000) and evolved at the biological level from progenitor cell-specific chemokine in the bone marrow to multifunctional cytokine with growth factor-like and tissue-regenerative activities. This evolution was parallelled by the integration of SDF-1/CXCL12 within the protein families of chemokines, cytokines and cell growth-promoting recombinant products having the potential for clinical applications. Here, we use this central position of CXCL12 as small signaling protein as an example for future developments in regenerative medicine. We provide context about SDF-1 biology within the field of skin wound healing research and how this compares with studies of other cytokines and growth factors. We also discuss whether SDF-1 formulations may be exemplary for other cytokines used for tissue regeneration. Normal skin wound healing is fraught with delays and complications in patients with specific underlying diseases, such as diabetes, hypertension and other elderly-related comorbidities, skin infections and accidental physical insults. Except for platelet-derived growth factor (PDGF), many cytokines, including vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), have failed so far in clinical studies of skin wound healing. This is in part due to the fact that (i) the biology of tissue regeneration is complex and insufficiently studied, (ii) in vitro approaches hardly mimic in vivo situations and (iii) commonly used animal models of acute and chronic wounding do not perfectly match human skin wound regeneration. A review of critical cells and molecules in normal skin and their actions in wounded tissue and a balanced comparison of the recent literature are preambles for progress in wound repair. We define advantages and limitations of recent approaches and appeal for more research. In particular, the possibilities of cellular immunomodulation mediated by endogenous and exogenous SDF-1/CXCL12 as a key molecule for skin regeneration are reviewed. Furthermore, biomaterials and scaffolds for the delivery and use of cytokines in precision medicine and aspects of their biofabrication are outlined with SDF-1 as an example. Finally, we indicate how applications of dermatological SDF-1 formulations for skin wound healing may be tailored for applications in other acute and chronic inflammatory conditions and regenerative medicine. Thereby, SDF-1/CXCL12 is placed at the crossroads between recombinant products, cytokines, chemokines and growth factors and occupies a central position between regenerative biology and medicine. Full article

Objectives: The epidermal growth factor receptor (EGFR) is a clinically relevant membrane receptor that is frequently overexpressed or dysregulated in multiple types of cancer, making it an important target for antibody-based strategies. Nanobodies, derived from camelid heavy-chain antibodies, possess favorable properties such as small size, high stability, and strong antigen-binding capacity. This study aimed to generate EGFR-specific nanobodies and to systematically characterize their binding properties and initial functional activity. Methodology: Bactrian camels were immunized with a whole-cell antigen prepared from 293F cells transiently transfected to express full-length human EGFR. A high-diversity phage display nanobody library was constructed from peripheral blood lymphocytes. After two rounds of biopanning against EGFR, positive clones were screened and selected. The identified nanobodies were recombinantly expressed in Escherichia coli and purified. Binding specificity, epitope relationships, and kinetic parameters were evaluated using high-performance liquid chromatography (HPLC), bio-layer interferometry (Octet), and flow cytometry. The effect of selected nanobodies on EGF-induced cell proliferation was evaluated using a CCK-8 assay. Results: Two EGFR-specific nanobodies, Nb2H4 and Nb2B6, were successfully isolated. Both nanobodies exhibited specific binding to EGFR and recognized distinct, non-competing epitopes. Kinetic analyses revealed favorable binding affinities, and flow cytometry confirmed their ability to recognize EGFR in its native cellular context. In addition, Nb2H4 significantly suppressed EGF-induced proliferation in an EGFR-overexpression cell model, indicating preliminary functional activity. Conclusions: This study reports on the successful generation and in vitro characterization of EGFR-targeting nanobodies based on the extracellular domain of EGFR. The identified nanobodies provide useful molecular tools for epitope mapping, structural studies, and the further exploration of EGFR-directed antibody engineering strategies. Full article

Background: The process of healing skin wounds frequently faces obstacles due to inadequate repair. Even though recombinant Epidermal Growth Factor (EGF) is a significant therapeutic agent, its short half-life and instability limit its clinical application. The study’s objective was to establish a lipid nanoparticle (LNP) delivery method for efficiently transporting EGF mRNA, with the goal of achieving sustained local protein expression to aid in wound healing. Methods: EGF mRNA was produced through in vitro transcription and enclosed in pH-sensitive LNPs using microfluidic techniques. The LNP-mRNAEGF’s physicochemical attributes, stability, and biocompatibility were assessed. Its effects on the proliferation and migration of HaCaT cells and on EGF expression were assessed in vitro. The therapeutic effectiveness was assessed using a mouse model with full-thickness skin defects and compared to control groups (saline, empty LNP, recombinant EGF). The study analyzed wound closure rate, histology, immunofluorescence, and systemic safety. Results: The LNP-mRNA_EGF formulation showed a spherical shape and demonstrated good stability. In vitro, it showed excellent biocompatibility, facilitated prolonged EGF expression in HaCaT cells depending on the dose for more than 72 h, and greatly enhanced cell proliferation and migration. In vivo, a single dose of LNP-mRNA_EGF greatly sped up wound healing, almost completely closing the wound by day 10, and was much more effective than all control groups. Histological and immunofluorescence analyses revealed enhanced re-epithelialization, significantly increased and optimized collagen I/III deposition, and an upregulated expression of EGF and E-cadherin. Moreover, no significant toxicity was found in the systemic safety assessment. Conclusions: The LNP-based EGF mRNA delivery platform enables efficient and sustained local protein expression via a single administration. It offers a promising translational strategy for protein replacement therapy in skin repair by significantly accelerating wound healing through enhanced re-epithelialization and optimized collagen remodeling. Full article

Background: Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase that is frequently post-translationally modified by glycosylation. In cancer, EGFR amplifications and hotspot mutations such as L858R that promote proliferation have been detected in a significant fraction of non-small cell lung carcinomas and breast adenocarcinomas. Analyses of disruptions to glycosylation pathways in cancer cells identified EGFR glycosylation at residue N361 as one of the most heavily impacted sites. Methods: We stably expressed a glycosylation-deficient mutant EGFR, N361A, with or without the oncogenic EGFR mutation L858R in cells. Proximity ligation assays were employed to study the effects of the glycosylation mutant on the co-localization of EGFR and HER2. The effects of the glycosylation-deficient mutant on the efficacy of agonists, such as EGF and amphiregulin, or antagonists, such as osimertinib and necitumumab, were defined using cell viability assays and immunoblots. Results: N361A increased the membrane localization and co-localization of EGFR with its binding partner HER2. The glycosylation-deficient mutation decreased cell proliferation, including proliferative responses to EGFR ligands. The mutant cells demonstrated reduced sensitivity to inhibition using the antibody inhibitor necitumumab, which inhibits EGFR by binding the extracellular domain. Conclusions: Disruption of glycosylation at N361, located near the ligand binding and dimerization regions, created a dominant negative form of EGFR, which non-productively co-localized with HER2, resulting in a blockage in proliferation. These findings underline the critical relevance of post-translational glycosylation modifications on EGFR function. Full article

Achieving optimal skin penetration with bioactive cosmetic ingredients, such as epidermal growth factor (EGF), presents ongoing challenges. This study introduces a novel elastosome-based EGF delivery system co-loading dexpanthenol, which achieves superior skin penetration and multifunctional cosmetic efficacy compared with a conventional liposome formulation. The EGF FLEXIR-SOME formulation was characterized to determine its physicochemical properties measured for comparison against a conventional liposome control. Efficacy and safety were confirmed through in vitro and in vivo evaluations, including clinical trials of the formulation and primary skin irritation tests. The formulated EGF FLEXIR-SOME particles exhibited an average diameter of 124.8 nm and a zeta potential of −57.53 mV, demonstrating enhanced stability and skin penetration relative to the control. The results of clinical trials confirmed significant efficacy in anti-aging, moisture, skin barrier improvement, and hyperpigmentation reduction. Additionally, primary skin irritation tests classified the product as a non-irritant. In conclusion, an elastosome-based EGF formulation significantly enhances skin penetration and bioavailability. The formulation effectively improves skin elasticity, hydration, and barrier function while simultaneously reducing visible signs of aging and pigmentation. This study successfully developed an innovative formulation utilizing elastosome technology, maximizing the transdermal efficiency and stability of EGF, thereby offering a novel strategy for functional cosmeceutical development. Full article

Breast cancer and lung adenocarcinoma share common features, including female predominance and the expression of estrogen receptor (ER) and epidermal growth factor receptor (EGFR) during carcinogenesis. Patients with breast cancer have a significantly higher risk of developing second primary lung cancer than those without breast cancer. ER beta expression is associated with resistance to EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutant lung adenocarcinoma, indicating a potentially important interaction between ER and EGFR. However, the mechanisms underlying this crosstalk remain poorly understood. Our clinical data showed a significant correlation between antiestrogen treatment for breast cancer and mutant EGFR expression (p = 0.021) in lung adenocarcinoma patients. In vitro, tamoxifen upregulated phosphorylated EGFR (p-EGFR) in EGFR-mutant lung adenocarcinoma cell lines. Heparin-binding EGF-like growth factor was identified as a key mediator from the ER pathway that stimulates p-EGFR. Tamoxifen counteracts estrogen’s effect and restores p-EGFR upregulation. Furthermore, coadministration of tamoxifen and the EGFR TKI gefitinib potentially inhibited p-EGFR expression in EGFR-mutant lung adenocarcinoma. Regular follow-up with chest computed tomography is recommended for patients with breast cancer. For those diagnosed with both ER-positive breast cancer and EGFR-mutant lung adenocarcinoma, combined tamoxifen and EGFR TKI therapy may offer an effective targeted treatment strategy. Full article

The transcription factor SOX11 is implicated in tumor progression across multiple types of cancers, including head and neck squamous cell carcinoma (HNSCC). However, its mechanistic role in HNSCC remains elusive. In this study, we found that the expression of SOX11 was induced by epidermal growth factor (EGF) but suppressed by an epidermal growth factor receptor (EGFR) inhibitor in HNSCC cells. The signal transducer and activator of transcription 3 (STAT3) bound to the Sox11 gene promoter and transcriptionally upregulated the expression of Sox11 in HNSCC cells. Meanwhile, analyses of The Cancer Genome Atlas (TCGA) gene expression datasets indicated that Sox11 gene expression was significantly overexpressed in HNSCC versus adjacent normal tissues and correlated with those of most epithelial–mesenchymal transition transcription factors (EMT-TFs) and marker genes. Knockdown of SOX11 significantly downregulated the expression of EMT-related genes, including EMT-TFs, vimentin, fibronectin, and N-cadherin, but significantly upregulated E-cadherin and vice versa when SOX11 was overexpressed. Collectively, our studies demonstrated that SOX11 was regulated by EGF-EGFR-STAT3 signals, promoting EMT in HNSCC. Full article