Search Results (413)

Although epidermal growth factor (EGF) has potential wide applications in the cosmetic industry, it still has limitations, such as a costly purification process and low stability in the surrounding environment. To overcome these limitations, we developed genetically modified Pediococcus pentosaceus CBT SL4, which can secrete EGF protein in growth media, thereby producing probiotic-derived PP-EGF culture medium supernatant (PP-EGF-SUP). Even at low EGF concentrations, PP-EGF-SUP exhibited EGF activities, such as cell scratch wound healing, tyrosinase inhibition, and improvements in anti-wrinkle factors, similar to or stronger than those of recombinant human EGF (rhEGF), which was used as a positive control. PP-EGF-SUP exhibited strong additional biological activities, such as antioxidant, anti-inflammatory, and anti-microbial activities, even though rhEGF did not have such properties. PP-EGF-SUP could be easily transformed to PP-EGF-SUP dried powder (PP-EGF-DP) using the freeze-drying method, and it could also be well resolved in water up to 20 mg/mL; furthermore, it still maintained its bioactivity after the manufacturing process. To determine melasma improvement efficacy, a human application test was performed using melasma ampoules containing 1% or 5% PP-EGF-DP formulations for four weeks. When comparing the melasma values before and after treatment, it was found that the light melasma value statistically decreased by 3.38% and 3.79% and that the dark melasma value statistically decreased by 1.74% and 2.93% in the test groups applying the 1% and 5% PP-EGF-DP melasma ampoules, respectively. In addition, the melasma area also decreased by 21.21% and 29.1%, while the control group showed no statistical difference. During the study period, no significant adverse skin reactions were observed due to the application of the PP-EGF-DP melasma ampoule. In conclusion, PP-EGF-DP may offer unique advantages in the cosmetic ingredient market, such as safety (as a probiotic derivative), stability (postbiotics protect EGF activity), and diverse bioactivities (activity potentiation and postbiotic-derived biological activities). Full article

Background: Epigenetic mechanisms and RNA signalling profoundly impact body growth during the early stages of embryonic development. RNA molecules, like microRNAs, play a vital role in early embryonic development, laying the groundwork for future growth and function. miR-124-3p microinjected into mouse fertilised eggs (miR-124-3p*) exhibited a significantly overgrowth phenotype. Behavioural test results showed that miR-124-3p mice were more physically active, as indicated by total distance and movement velocity. However, the molecular mechanism leading to these phenotypic changes mediated by miR-124-3p remains a mystery. This study aimed to investigate the role of epidermal growth factor (EGF) in developing an overgrowth phenotype in miR-124-3p* mice. Results: In this research, we preferred to work with neurospheres (NSs) due to the challenges of handling a single embryo, as NSs exhibit similar features, especially regarding cell growth, differentiation, and capacity for self-renewal. We examined the mRNA expression levels of Sox8, Sox9, Sox10, Doublecortin (Dcx), and Neurod1 genes, which are linked to a tiny phenotype in knockout mice, in total embryos at E7.5 and hippocampal cells isolated from E19.5-day fetus and neurospheres aged 12 and 21 days, which were derived from these hippocampal cells through primary cell culture. These genes are significantly overexpressed in miR-124-3p* NSs, but not in the E7.5 total embryos or the hippocampus of the E19.5 fetus. Conclusions: These findings suggest a possible link between miR-124-3p microinjection and EGF activation, which may be associated with early neurogenesis and neuronal differentiation in embryos. This molecular shift might contribute to the development of mice exhibiting increased physical activity and enlarged body size, although these observations remain correlative and require further validation. Full article

The successful application of assisted reproductive technologies (ARTs), such as in vitro maturation (IVM) and artificial oocyte activation, requires species-specific adaptations. Although these methods are routinely used in laboratory rodents, their use in wild or non-model species remains limited, such as the Spix’s yellow-toothed cavy, a Neotropical species of ecological and reproductive interest. This study evaluated the effects of different concentrations of epidermal growth factor (EGF; 10 or 50 ng/mL) on IVM (Experiment 1) and of 6-dimethylaminopurine (6-DMAP) on artificial oocyte activation (Experiment 2). EGF at 10 ng/mL (93.8% ± 1.6; 84.9% ± 0.7) promoted greater viability and less apoptosis in cumulus cells, compared to 50 ng/mL (83.0% ± 1.6; 78.9% ± 2.7), maintaining cumulus expansion, ultrastructural integrity, and better morphometric quality of oocytes. Thus, this concentration was used in the next step, where oocytes were activated with or without 6-DMAP. After five days, the presence of 6-DMAP increased cleavage rates (69.3% ± 5.0) compared to activation without the compound (53.5% ± 3.5), without significantly affecting morula formation (13.2% ± 3.1 to 17.3% ± 2.9). It is concluded that EGF improves the oocyte microenvironment, while 6-DMAP enhances cleavage, with these being the initial steps in the development of ARTs for Spix’s yellow-toothed cavy. Full article

Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds. Full article

Phosphoinositide-binding pleckstrin homology (PH) domains interact with both phospholipids and proteins, often complicating their use as specific lipid biosensors. In this study, we introduced specific mutations into the phosphatidylinositol 3,4,5-trisphosphate (PIP₃)-specific PH domains of protein kinase B (Akt) and general receptor for phosphoinositides 1 (GRP1) that disrupt protein-mediated interactions while preserving lipid binding, in order to enhance biosensor specificity for PIP₃, and evaluated their impact on plasma membrane (PM) localization and lipid-tracking ability. Using bioluminescence resonance energy transfer (BRET) and confocal microscopy, we assessed the localization of PH domains in HEK293A cells under different conditions. While Akt-PH mutants showed minimal deviations from the wild type, GRP1-PH mutants exhibited significantly reduced PM localization both at baseline and after stimulation with epidermal growth factor (EGF), insulin, or vanadate. We further developed tandem mutant GRP1-PH domain constructs to enhance PM PIP₃ avidity. Additionally, our investigation into the influence of ADP ribosylation factor 6 (Arf6) activity on GRP1-PH-based biosensors revealed that while the wild-type sensors were Arf6- dependent, the mutants operated independently of Arf6 activity level. These optimized GRP1-PH constructs provide a refined biosensor system for accurate and selective detection of dynamic PIP₃ signaling, expanding the toolkit for dissecting phosphoinositide-mediated pathways. Full article

Endometriosis is the extrauterine engraftment of endometrium-like tissue, causing chronic pain. Complex sensory–vascular–immune interactions, including growth factors, cytokines, and neuropeptides, are implicated in its pathophysiology, but the mechanisms remain unknown. Here, epidermal growth factor (EGF), vascular endothelial growth factor, interleukins (IL-1β, IL-6, IL-8), macrophage migration inhibitory factor (MIF), calcitonin gene-related peptide, and somatostatin were measured in the serum of endometriosis patients with different disease severities, menstruation cycle- and pharmacotherapy-related hormonal status compared with controls. Mediator levels in deep-infiltrating rectosigmoid nodules were also compared with those in non-endometriotic colon tissues. Pain was assessed by the visual analogue scale. Serum EGF was significantly lower in mild endometriosis and in the secretory phase. MIF and IL-6 were higher in stage I–IV endometriosis, with MIF also higher in the secretory phase and in patients not receiving oral contraceptives. Somatostatin was lower in mild endometriosis than that in healthy individuals and the severe endometriosis group. No tissue-level differences were found. A strong positive correlation between serum EGF and somatostatin levels and dysmenorrhea and dysuria was detected in mild cases. It is concluded that certain serum alterations may be related to severity- and hormone status-dependent endometriosis mechanisms, but their diagnostic/prognostic value seems to be limited due to variability and lack of specificity. Full article

Exploring the neurogenic potential of extraneural stem cells under the actions of proneurogenic biomolecules may enhance the success of autologous cell therapy for neurodegenerative diseases such as Parkinson’s. Neural stem and progenitor cells (NSPCs) from extraneural tissues have emerged as potential sources of functional dopaminergic (DA) neurons. Background/Objectives: This study aimed to generate DA neurons from ovarian cortical cells (OCC)-derived NSPCs to elucidate whether follicle-stimulating hormone (FSH) can enhance this process and to evaluate the electrophysiological functionality of differentiated neural cells using the patch-clamp technique. Methods: OCC-NSPCs were differentiated towards the DA pathway during the neurosphere (NS) assay after two culture periods for cell expansion (CEP-1, CEP-2) with one of these media: M1 (positive control with epidermal growth factor, EGF, and fibroblast growth factor2, FGF2), M2 (control), and M3 (M2 with FSH, 50 ng/mL). Image analysis, morphometric evaluation, cell proliferation assays, and gene expression analysis of NSPC-specific transcripts were performed. After CEP-2, NS cells were cultured for 30 days in a serum-free medium containing Sonic-Hedgehog, FGF2, FGF8, and brain-derived neurotrophic factor (BDNF) for differentiation. At the end of culture, expression, and immunolocalization of GFAP, Olig2, NeuN, and tyrosine hydroxylase (TH) were analyzed in cells, along with patch-clamp recordings in differentiated neurons. Results: Cell proliferation and NS development were larger in OCC-NSPCs from groups M1 and M3 than in M2. Expression of NSPC-related transcripts was higher in M2; however, M1 and M3 cultures showed greater expression of differentiation markers NeuN, GFAP, Olig2, and TH. NeuN, GFAP, and TH were immunolocalized in differentiated cells and NS that were generated during differentiation. TH was localized in neural precursor cells, some neurons, core cells of small-, medium-, and large-sized NS, and in cells close to the outer cell layer of large NS, with greatest immunolocalization percentages in NS primed with FSH during CEP-1/2 (M3). Electrophysiological recordings revealed a major incidence of plateau potentials and a significant proportion of complete action potentials, reflecting successful functional neuronal differentiation. Conclusions: DA precursors and functional neurons can be successfully obtained after OCC-NSPCs-directed differentiation. FSH priming during the expansion period enhances the neurogenic potential of these cells towards the DA pathway. Future research will explore the eventual therapeutic use of these findings for neurodegenerative diseases. Full article

Background: Organic anion transporter 3 (OAT3) in the kidney proximal tubule cells plays a critical role in renal clearance of numerous endogenous metabolites and exogenous drugs and toxins. In this study, we discovered that epidermal growth factor (EGF) regulates the expression and activity of OAT3 through palmitoylation, a novel mechanism that has never been described in the OAT field. Methods/Results: Our results showed that treatment of OAT3-expressing cells with EGF led to a ~40% increase in OAT3 expression and OAT3-mediated transport of estrone sulfate, a prototypical substrate for OAT3. EGF-stimulated OAT3 transport activity was abrogated by H-89, a protein kinase A (PKA) inhibitor, indicating that an EGF-PKA signaling pathway is involved in the regulation of OAT3. We also showed that treatment of OAT3-expressing cells with EGF resulted in an enhancement of OAT3 palmitoylation, a novel type of post-translational modification for OATs, and such an enhancement was blocked by H-89, suggesting that the EGF-PKA signaling pathway participated in the modulation of OAT3 palmitoylation. Palmitoylation was catalyzed by a group of palmitoyltransfereases, and we showed that OAT3 palmitoylation and expression were inhibited by 2-BP, a general inhibitor for palmitoyltransfereases. We also explored the relationship among EGF/PKA signaling, OAT palmitoylation, and OAT transport activity. We treated OAT3-expressing cells with EGF or Bt2-cAMP, a PKA activator, in the presence and absence of 2-BP, followed by the measurement of OAT3-mediated transport of estrone sulfate. We showed that both EGF- and Bt2-cAMP-stimulated OAT3 transport activity were abolished by 2-BP, suggesting that palmitoylation mediates the regulation of EGF/PKA on OAT3. Finally, we showed that osimertinib, an anti-cancer drug/EGFR inhibitor, blocked EGF-stimulated OAT3 transport activity. Conclusions: In summary, we provided the first evidence that palmitoylation transduces the EGF/PKA signaling pathway to the modulation of OAT3 expression and function. Our study also provided an important implication that during comorbidity therapies, EGFR inhibitor drugs could potentially decrease the transport activity of renal OAT3, which would subsequently alter the therapeutic efficacy and toxicity of many co-medications that are OAT3 substrates. Full article

Epithelial differentiation and function are tightly coupled to the keratin intermediate filament cytoskeleton. Keratin filaments are unique among the cytoskeletal filament systems in terms of biochemical properties, diversity and turnover mechanisms supporting epithelial plasticity in response to a multitude of environmental cues. Epidermal growth factor (EGF) is such a cue. It is not only intricately intertwined with epithelial physiology but also modulates keratin filament network organization by increasing keratin filament turnover. The involved EGF receptor (EGFR)-dependent intracellular signaling cascades, however, have not been identified to date. We therefore tested the effect of selective inhibitors of downstream effectors of the EGFR on keratin filament turnover using quantitative fluorescence recovery after photobleaching experiments as readouts. We find that SRC and ERK kinases are involved in the regulation of keratin filament turnover, whereas PI3K/AKT and FAK have little or no effect. The identification of SRC and ERK as major keratin filament regulators extends beyond EGF signaling since they are also activated by other signals and stresses. Our data unveil a mechanism that allows modification of the properties of keratin filaments at very high temporal and spatial acuity. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with unmet therapeutic needs. This study investigates the therapeutic potential of Periplaneta americana L. extract (PAE) and its molecular mechanisms, integrating network pharmacology and experimental validation. Liquid chromatography–mass spectrometry identified 1355 compounds in PAE. Network pharmacology analysis revealed that inosine, vidarabine, and adenosine 5′-monophosphate (AMP) were core components and the core components synergistically regulated key targets and acted on inflammation-related pathways, thereby establishing a multi-target anti-inflammatory regulatory network. In vivo experiments demonstrated that these compounds significantly alleviated colitis symptoms in dextran sulfate sodium-induced mice, as evidenced by reduced disease activity index scores, preserved colonic mucosal architecture, and decreased inflammatory infiltration. Mechanistically, core compounds down-regulated granulocyte-macrophage colony-stimulating factor (GM-CSF), inducible nitric oxide synthase (iNOS)/NOS2, monocyte chemoattractant protein 1 (MCP-1), and transforming growth factor beta 1 (TGF-β1), while they up-regulated interleukin-10 (IL-10) and epidermal growth factor (EGF). Additionally, they activated epidermal growth factor receptor (EGFR)-mediated pathways. Molecular docking analysis revealed that adenosine analogs preferentially bound to A1/A2a receptors, triggering signaling cascades essential for epithelial repair and inflammation resolution. This study established the multi-component, multi-pathway mechanism of PAE in UC, highlighting its dual role in suppressing inflammation and promoting mucosal healing. By bridging traditional herbal use with modern molecular insights, these findings provided a translational foundation for developing PAE-based therapies for UC. Full article

Lafora progressive myoclonus epilepsy (LD, OMIM#254780, ORPHA:501) is an ultra-rare and severe autosomal recessive neurological disorder that typically manifests in early adolescence. It is characterized by the accumulation of insoluble forms of aberrant glycogen in the brain and peripheral tissues. Given the urgent need for reliable tools to monitor disease progression, we aimed to identify reliable biomarkers in minimally invasive fluids, which could also provide valuable insights into the natural history of the disease. Plasma-EDTA samples from eleven LD patients and healthy controls were analyzed to identify potential biomarkers of LD using a high-throughput assay. The findings were subsequently validated using specific enzyme-linked immunosorbent assays (ELISAs). Eleven cytokines and growth factors were identified to be significantly reduced in LD patient samples compared to healthy controls. Among these, four mediators [platelet-derived growth factor subunit B (PDGF-BB), epidermal growth factor (EGF), brain derived growth factor (BDNF), and macrophage migration inhibitory factor (MIF)] exhibited the greatest fold change between the groups and were further validated. Given the minimally invasive nature of plasma sampling and the straightforward quantification via ELISA assays, these biomarkers hold strong promise for rapid translation to the clinic, potentially enhancing early diagnosis and longitudinal disease monitoring in LD patients. Full article

Salivary gland cancers (SGCs) pose a therapeutic challenge due to their aggressive nature and limited treatment options. Ion transporters, particularly the sodium/iodide symporter (SLC5A5), which transport iodine in the form of iodide anion (I⁻) into cells, have emerged as potential therapeutic targets in tumors of glandular origin. Our research indicates that SLC5A5 is expressed predominantly in ductal cells of human and murine SGC cells. We assessed the effects of potassium iodide (KI), a source of iodide ions. KI treatment reduced SGC cell proliferation and viability without impacting migration. KI increased ROS levels and triggered caspase-dependent apoptosis, as indicated by the upregulation of the pro-apoptotic protein BAX, downregulation of the anti-apoptotic protein Bcl-2, and induction of SGC cell shrinkage. KI did not affect NF-κB or TNF-α and SLC5A5 expression. Adding the antioxidant N-acetylcysteine reversed KI-induced growth inhibition, underscoring ROS-induced oxidative stress’s crucial role in growth inhibition. While KI administered in drinking water to mice increased epidermal growth factor (EGF) expression in non-malignant salivary gland tissues, KI decreased EGF receptor (EGFR) expression in malignant SGC cell cultures, where EGFR signaling is frequently dysregulated in SGCs but promoted AKT phosphorylation. Combining KI and anti-EGFR treatment did not yield synergistic anti-SGC cell effects. The study underscores the therapeutic potential of KI as a standalone treatment in vitro for SGC cells. However, the upregulation of EGF in non-malignant tissues and, therefore, the possibility to enhance EGFR-driven signals and AKT phosphorylation after KI treatment in cancer patients could indicate a risk of rendering SGC cells more drug resistant, warranting further investigation to optimize its clinical application. Full article

Dynamic criticality—the balance between order and chaos—is fundamental to genome regulation and cellular transitions. In this study, we investigate the distinct behaviors of gene expression dynamics in MCF-7 breast cancer cells under two stimuli: heregulin (HRG), which promotes cell fate transitions, and epidermal growth factor (EGF), which binds to the same receptor but fails to induce cell-fate changes. We model the system as an open, nonequilibrium thermodynamic system and introduce a convergence-based approach for the robust estimation of information-thermodynamic metrics. Our analysis reveals that the Shannon entropy of the critical point (CP) dynamically synchronizes with the entropy of the rest of the whole expression system (WES), reflecting coordinated transitions between ordered and disordered phases. This phase synchronization is driven by net mutual information scaling with CP entropy dynamics, demonstrating how the CP governs genome-wide coherence. Furthermore, higher-order mutual information emerges as a defining feature of the nonlinear gene expression network, capturing collective effects beyond simple pairwise interactions. By achieving thermodynamic phase synchronization, the CP orchestrates the entire expression system. Under HRG stimulation, the CP becomes active, functioning as a Maxwell’s demon with dynamic, rewritable chromatin memory to guide a critical transition in cell fate. In contrast, under EGF stimulation, the CP remains inactive in this strategic role, passively facilitating a non-critical transition. These findings establish a biophysical framework for cell fate determination, paving the way for innovative approaches in cancer research and stem cell therapy. Full article

Receptor-mediated endocytosis (RME) is a commonly recognized receptor internalization process of receptor degradation or recycling. However, recent studies have supported that RME is closely related to signal propagation and amplification from the plasma membrane to the cytosol. Few studies have elucidated the role of H₂O₂, a mild oxidant among reactive oxygen species (ROS) in RME and second messenger of signal propagation. In the present study, we investigated the regulatory function of H₂O₂ in early endosomes during signaling throughout receptor-mediated endocytosis. In mammalian cells with a physiological amount of H₂O₂ generated during epidermal growth factor (EGF) activation, fluorescence imaging showed that the levels of two activating phosphorylations on Ser⁴⁷³ and Thr³⁰⁸ of Akt were transiently increased in the plasma membrane, but the predominant p-Akt on Ser⁴⁷³ appeared in early endosomes. To examine the role of endosomal H₂O₂ molecules as signaling mediators of Akt activation in endosomes, we modulated endosomal H₂O₂ through the ectopic expression of an endosomal-targeting catalase (Cat-Endo). The forced removal of endosomal H₂O₂ inhibited the Akt phosphorylation on Ser⁴⁷³ but not on Thr³⁰⁸. The levels of mSIN and rictor, two components of mTORC2 that work as a kinase in Akt phosphorylation on Ser⁴⁷³, were also selectively diminished in the early endosomes of Cat-Endo-expressing cells. We also observed a decrease in the endosomal level of the adaptor protein containing the PH domain, the PTB domain, and the Leucine zipper motif 1 (APPL1) protein, which is an effector of Rab5 and key player in the assembly of signaling complexes regulating the Akt pathway in Cat-Endo-expressing cells compared with those in normal cells. Therefore, the H₂O₂-dependent recruitment of the APPL1 adaptor protein into endosomes was required for full Akt activation. We proposed that endosomal H₂O₂ is a promoter of Akt signaling. Full article

Background: Breast milk is the most important nutrition for newborns. Growth factors such as insulin-like growth factor 1 (IGF-1), epidermal growth factor (EGF), transforming growth factor-β (TGF-β), and nerve growth factor (NGF) are among its components that play pivotal roles in neonatal development, immune system priming, and gastrointestinal maturation. This study examined the effects of gestational diabetes mellitus (GDM), maternal hypothyroidism, and method of delivery on the concentrations of these factors in colostrum collected at three distinct postpartum time points. Methods: A group of 39 women was included, 20 of whom gave birth vaginally, whereas caesarean section was performed in 19 patients. A total of 18 volunteers were diagnosed with GDM, and 17 suffered from hypothyroidism. Colostrum samples were collected from the volunteers in the first 3 days after birth under hospital conditions. Growth factors like IGF-1, EGF, NGF, and TGF-β were measured in the samples using commercial immunoenzymatic assays. Results: No significant differences were observed in the values of these parameters between the groups of women (with GDM or hypothyroidism and healthy, as well as giving birth naturally and by caesarean section). In addition, the growth factors exhibited good stability within the first few postpartum days (CVs for all studied parameters: in the range of 0.7–5.0%). Conclusions: The pregnancy disorders that were properly controlled and treated by specialists appeared not to affect the levels of the analyzed growth factors—just like the type of delivery and the day of colostrum collection. Full article