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Trastuzumab therapy in HER2+ breast cancer patients has mixed success owing to acquired resistance to therapy. A detailed understanding of downstream molecular cascades resulting from trastuzumab resistance is yet to emerge. In this study, we investigate the cellular mechanisms underlying acquired resistance using trastuzumab-sensitive and -resistant cancer cells (BT474 and BT474R) treated with endogenous ligands EGF and HRG across time. We probe early receptor organization through microscopy and signaling events through multiomics measurements and assess the bioenergetic state through mitochondrial measurements. Integrative analyses of our measurements reveal significant alterations in EGF-treated BT474 HER2 membrane dynamics and robust downstream activation of PI3K/AKT/mTORC1 signaling. EGF-treated BT474R shows a sustained interferon-independent activation of the IRF1/STAT1 cascade, potentially contributing to trastuzumab resistance. Both cell lines exhibit temporally divergent metabolic demands and HIF1A-mediated stress responses. BT474R demonstrates inherently increased mitochondrial activity. HRG treatment in BT474R leads to a pronounced reduction in AR expression, affecting downstream lipid metabolism with implications for treatment response. Our results provide novel insights into mechanistic changes underlying ligand treatment in BT474 and BT474R and emphasize the pivotal role of endogenous ligands. These results can serve as a framework for furthering the understanding of trastuzumab resistance, with therapeutic implications for women with acquired resistance.

The scaffold protein PEAK1 acts downstream of integrin adhesion complexes and the epidermal growth factor receptor, orchestrating signaling events that control cell proliferation and cytoskeletal remodeling. In this study we investigated the role of PEAK1 in colorectal carcinoma (CRC) progression using various in vitro and in vivo models to replicate the stepwise pathogenesis of CRC. While we observed a cell-type specific role for PEAK1 in the proliferation and in human CRC cell lines in vitro, our in vivo experiments using different CRC mouse models driven by loss of Apc, with or without oncogenic Kras or Pten loss suggest that PEAK1 does not significantly contribute to tumor formation in vivo. However, the survival time of Peak1−/− mice in the Apcfl/+ model appeared to be slightly increased. Furthermore, PEAK1 promotes EGF-induced Caco-2 cell proliferation and regulates spheroid polarization and lumenization. Given that the Caco-2 cells harbor mutations in the tumor suppressors APC and β-CATENIN, but not in other tumor suppressors or in proto-oncogenes, we conclude that the PEAK1's impact on colon carcinogenesis is limited, potentially playing a role in the initial stage of the adenoma to carcinoma progression. [ABSTRACT FROM AUTHOR]

Generalized anxiety disorder (GAD) is a common and persistent mental illness accompanied by uncontrollable worries for daily staff. Physiological, environmental, genetic, and daily stress from surroundings is involved in developing GAD. Here, we aimed to assess the association of stromal cell-derived factor-1 (SDF-1) and epidermal growth factor (EGF) in the pathophysiology of GAD and their role as diagnostic tools. This case-control study recruited 50 GAD patients from the psychiatry department of a tertiary care teaching hospital in Dhaka city and 38 age-sex-matched healthy controls (HCs) from the surrounding areas. A qualified psychiatrist conducted standardized psychiatric interview to diagnose GAD patients and evaluate HCs by applying the diagnostic and statistical manual for mental disorders, 5th edition (DSM-5) and used the GAD-7 scale to assess the severity of the GAD symptoms. After confirming the inclusion and exclusion criteria, we collected 5 ml blood samples from each participant. We measured serum SDF-1 and EGF levels using ELISA techniques. We observed increased serum levels of EGF in GAD patients compared to HCs (5.91 ± 3.90 ng/ml vs. 1.59 ± 1.08 ng/ml; p < 0.001). Also, this increment is positively associated with the severity of GAD in patients (r = 0.479, p = 0.002). The receiver operating characteristic analysis showed good diagnostic performance (AUC 0.869, p < 0.001) with high sensitivity (82.5%), and specificity (81.1%) at cut off value of 2.31 ng/ml. However, we didn't find significant differences in serum SDF-1 levels between GAD patients and HCs (11.96 ± 4.50 ng/ml vs. 12.70 ± 11.76 ng/ml; p = 0.337). The present study suggests that GAD patients have increased serum EGF levels but not SDF-1 levels compared to HCs and that increased EGF levels are associated with increased GAD symptoms as well. Moreover, EGF levels could serve as a biomarker for GAD However, further interventional studies with larger and homogeneous samples are suggested to confirm and establish these findings. [ABSTRACT FROM AUTHOR]

The early expectations about growth factors' (GFs') discovery as an undisputed therapeutic solution for chronic wounds progressively eclipsed when they failed to accelerate acute wound closure and restore the healing trajectory of stagnant ulcers. Critical knowledge about chronic wound biology and GF pharmacology was a conundrum at that time. Diabetes undermines keratinocytes' and fibroblasts' physiology, impairing skin healing abilities. Diabetic ulcers, as other chronic wounds, are characterized by hyperinflammation, unbalanced proteolytic activity, catabolism, and free radical cytotoxicity. This hostile scenario for the chemical stability, integrity, and functionality of GFs led to the conclusion that topical administration may jeopardize GFs' clinical effectiveness. Epidermal growth factor (EGF) has a proximal position in tissues homeostasis by activating survival and mitogenic pathways from embryonic life to adulthood. Seminal experiments disclosed unprecedented pharmacological bounties of parenterally administered EGF. Accordingly, the experience accumulated for more than 20 years of EGF intralesional infiltration of diabetic wound bottoms and edges has translated into sustained healing responses, such as low recurrences and amputation rates. This delivery route, in addition to being safe and tolerated, has shown to restore a variety of circulating biochemical markers ordinarily disturbed in diabetic conditions. EGF infiltration triggers a cascade of local fibroblast reactions, supporting its molecular integrity, prolonged mean residence time, and ultimately eliciting its receptor trafficking and nuclear translocation. The intralesional delivery route seems to warrant that EGF reaches wound fibroblasts' epigenetic core, mitigating the consequences of metabolic memory imprinting. [ABSTRACT FROM AUTHOR]

The protein epidermal growth factor (EGF), which plays a crucial role in promoting cell proliferation and survival, has recently demonstrated potential in reducing inflammation. In this study, we examined the impact of EGF on the anti-inflammatory and anti-proliferative properties of pterygium, a prevalent hypervascular proliferative disease affecting the ocular surface. In surgically excised tissues, markers for fibrotic and inflammatory signals, including VIM, ACTA2, FAP, MMP2, VCAM1, ICAM1, CD86, IL6, and IL1B were upregulated in the pterygium body stroma compared to the normal conjunctival stroma. EGF exerted anti-inflammatory and anti-vasculogenic effects on pterygial fibroblasts when co-cultured with M1 macrophages. Moreover, exosomes derived from EGF-preconditioned M1 macrophages suppressed the heightened inflammatory and vasculogenic signals in pterygial fibroblasts induced by exosomes from M1 macrophages. Paradoxically, the proliferation of pterygial fibroblasts was inhibited by EGF in the in vitro microenvironment with M1 macrophages, despite EGF being known as a growth factor. EGF-preconditioning of M1 macrophages rescued the increased proliferation of pterygial fibroblasts induced by exosomes from M1 macrophages. In conclusion, our findings demonstrate that EGF effectively mitigates inflammation and proliferation in pterygial fibroblasts within a microenvironment containing M1 macrophages. [ABSTRACT FROM AUTHOR]

Metastasis in breast cancer is the first cause of death in patients. The epidermal growth factor (EGF) increases cancer cells' invasion, and migration. Melatonin's inhibitory effects on various types of cancer were confirmed. This study aimed to investigate whether melatonin could apply its impact through the EGF-related pathways or not. First, MDA-MB-231 and MCF7 cells were cultured, and then melatonin effects on cell viability were determined by MTT assay. Transwell invasion assay was applied to identify the invasiveness of these breast cancer cell lines under treatment of EGF and melatonin. Real-time RT-PCR then investigated the expression of MMP9 and MMP2 in determined groups. Cell proliferation was also assayed under EGF and melatonin treatment using Ki67 assessment by flow cytometry. The rate of invasion and migration of EGF-treated cells increased in both groups, in which melatonin caused increased invasion by EGF just in MCF7 cells. MMP9 and MMP2 expression increased significantly in both cell lines under EGF treatment, and melatonin increased these genes' expression in both cell lines (p<0.05). EGF increased the MMP9 and MMP2 gene expression, and melatonin increased EGF-induced expression (p<0.05). The EGF reduced the expression of the Ki67 protein in the MCF7 cell line, which was negatively affected by melatonin and EGF. In contrast, along with melatonin, EGF did not affect the proliferation of the MDA-MB-231 cell line. The results of this study show that melatonin in the presence of EGF does not show the anti-cancer properties previously described for this substance. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF) innovative preservative on hair follicle activity of rat vibrissae under low temperature conditions. Methods From January 2021 to December 2023, the upper of hair follicle (UHF) from male SD rat vibrissae was used in the experiment. These UHF were equally divided into NS, IGF-1, EGF, and IGF-1+EGF preservation solutions groups. At 3, 6 and 12 hours, the cultured UHF were analyzed by hematoxylin and eosin (HE) staining and alkaline phosphatase (ALP) activity. The UHF co-cultured with NS and IGF-1+EGF for 3 hours were further transplanted into the dorsum of nude mice. After 24 hours, the transplanted UHF was taken to observe by HE staining and ALP activity. Results In vitro preservation, HE staining results indicated that the cultured UHF at 3 hours, the follicle structure and cell arrangement were normal without obvious changes. At 12 hours, only the IGF-1+EGF group had intact follicle structure and clear organization. Moreover, ALP values showed that the IGF-1+EGF group at 3, 6 and 12 hours were significantly higher than the NS group (P＜0.001). Overall, ALP activity gradually decreased over time. In vivo transplantation, HE staining results showed that the IGF-1+EGF group were structurally distinct with orderly cell arrangements, compared to the NS group. ALP values were significantly higher than NS group (P＜0.05). Conclusion The innovative preservation solutions containing IGF-1 and EGF under low temperatures, can effectively enhance the activity of UHF, and promote the success of hair follicle transplantation. [ABSTRACT FROM AUTHOR]

Loss of osteogenic differentiation potential of osteoblasts has been associated with the pathogenesis of osteoporosis. Thus, stimulation of osteoblastic differentiation is a therapeutic strategy for osteoporosis. Relaxin‐2 is a peptide hormone with potent biological functions. However, the effects of Relaxin‐2 in osteoblastic differentiation and osteoporosis have not been reported before. Here, we report a novel physiological role of Relaxin‐2 in promoting osteoblastic differentiation and mineralization of MC3T3‐E1 cells. Our results indicate that exposure to Relaxin‐2 upregulated the expression, and elevated the activity of alkaline phosphatase (ALP) when MC3T3‐E1 cells were cultured in osteogenic differentiation medium (OM). Additionally, Relaxin‐2 upregulated the mRNA levels of osteocalcin (ocn), osteopontin (opn), and collagen type I alpha 1 (Col1a1). The alizarin red S staining assay revealed that Relaxin‐2 promoted the mineralization of MC3T3‐E1 cells. We also found that Relaxin‐2 increased the expression of Runx‐2 as well as the epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR). Importantly, silencing of EGF abolished the effects of Relaxin‐2 in osteoblastic differentiation and related gene expression. These findings suggest that Relaxin‐2 stimulates osteogenic differentiation through activating EGF/EGFR signaling. [ABSTRACT FROM AUTHOR]

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Abstract The scaffold protein PEAK1 acts downstream of integrin adhesion complexes and the epidermal growth factor receptor, orchestrating signaling events that control cell proliferation and cytoskeletal remodeling. In this study we investigated the role of PEAK1 in colorectal carcinoma (CRC) progression using various in vitro and in vivo models to replicate the stepwise pathogenesis of CRC. While we observed a cell-type specific role for PEAK1 in the proliferation and in human CRC cell lines in vitro, our in vivo experiments using different CRC mouse models driven by loss of Apc, with or without oncogenic Kras or Pten loss suggest that PEAK1 does not significantly contribute to tumor formation in vivo. However, the survival time of Peak1 −/− mice in the Apc fl/+ model appeared to be slightly increased. Furthermore, PEAK1 promotes EGF-induced Caco-2 cell proliferation and regulates spheroid polarization and lumenization. Given that the Caco-2 cells harbor mutations in the tumor suppressors APC and β-CATENIN, but not in other tumor suppressors or in proto-oncogenes, we conclude that the PEAK1’s impact on colon carcinogenesis is limited, potentially playing a role in the initial stage of the adenoma to carcinoma progression.

Abstract Generalized anxiety disorder (GAD) is a common and persistent mental illness accompanied by uncontrollable worries for daily staff. Physiological, environmental, genetic, and daily stress from surroundings is involved in developing GAD. Here, we aimed to assess the association of stromal cell-derived factor-1 (SDF-1) and epidermal growth factor (EGF) in the pathophysiology of GAD and their role as diagnostic tools. This case-control study recruited 50 GAD patients from the psychiatry department of a tertiary care teaching hospital in Dhaka city and 38 age-sex-matched healthy controls (HCs) from the surrounding areas. A qualified psychiatrist conducted standardized psychiatric interview to diagnose GAD patients and evaluate HCs by applying the diagnostic and statistical manual for mental disorders, 5th edition (DSM-5) and used the GAD-7 scale to assess the severity of the GAD symptoms. After confirming the inclusion and exclusion criteria, we collected 5 ml blood samples from each participant. We measured serum SDF-1 and EGF levels using ELISA techniques. We observed increased serum levels of EGF in GAD patients compared to HCs (5.91 ± 3.90 ng/ml vs. 1.59 ± 1.08 ng/ml; p

Tujuan: Untuk menganalisis ekspresi protein c-Fos pada cell line kanker payudara. Metode: Penelitian ini merupakan penelitian eksperimental murni menggunakan metode imunositofluoresens untuk melihat jumlah intensitas ekspresi protein c-Fos dengan sampel penelitian adalah cell line MCF-7 mewakili kanker payudara subtipe luminal A, cell line SKBR3 mewakili kanker payudara subtipe HER2+, dan cell line HaCat mewakili sel normal. Ekspresi protein c-Fos diinduksi dengan EGF 50 ng/mL, ATP 100µM dan gabungan ATP+EGF selama 45 menit. Perhitungan intensitas protein c-Fos menggunakan aplikasi imageJ. Hasil penelitian ekspresi c-Fos dianalisis menggunakan uji oneway anova apabila p0,05). Kesimpulan: Pemberian ATP, EGF dan kombinasi ATP+EGF meningkatkan intensitas protein c-Fos pada cell line kanker payudara tipe MCF-7 dan SKBR3.

Abstract The protein epidermal growth factor (EGF), which plays a crucial role in promoting cell proliferation and survival, has recently demonstrated potential in reducing inflammation. In this study, we examined the impact of EGF on the anti-inflammatory and anti-proliferative properties of pterygium, a prevalent hypervascular proliferative disease affecting the ocular surface. In surgically excised tissues, markers for fibrotic and inflammatory signals, including VIM, ACTA2, FAP, MMP2, VCAM1, ICAM1, CD86, IL6, and IL1B were upregulated in the pterygium body stroma compared to the normal conjunctival stroma. EGF exerted anti-inflammatory and anti-vasculogenic effects on pterygial fibroblasts when co-cultured with M1 macrophages. Moreover, exosomes derived from EGF-preconditioned M1 macrophages suppressed the heightened inflammatory and vasculogenic signals in pterygial fibroblasts induced by exosomes from M1 macrophages. Paradoxically, the proliferation of pterygial fibroblasts was inhibited by EGF in the in vitro microenvironment with M1 macrophages, despite EGF being known as a growth factor. EGF-preconditioning of M1 macrophages rescued the increased proliferation of pterygial fibroblasts induced by exosomes from M1 macrophages. In conclusion, our findings demonstrate that EGF effectively mitigates inflammation and proliferation in pterygial fibroblasts within a microenvironment containing M1 macrophages.

Objective: Matrix metalloproteinase (MMP-1 and −9), Epidermal Growth Factor (EGF), and Transforming Growth factor (TGF)-β are expressed in the oral ulcer wound-healing process. The Adipose mesenchymal stem cell metabolites (AdMSCMs) may accelerate wound-healing. This study aimed to investigate the expression of MMP-1, MMP-9, EGF, and TGF-β in the oral mucosa ulcer rat model treated with topical AdMSCMs. Materials and Methods: Oral ulcer models were created in twenty healthy male Wistar rats (Rattus novergicus) divided into AdMSCMs and control groups. The oral ulcer model was treated topically using AdMSCMs oral gel three times daily for 3 and 7 days. The expression of MMP-1, MMP-9, EGF, TGF-β was evaluated through histological examination using the immunohistochemistry method. Independent t-test was used to compare the mean of expression of MMP-1, MMP-9, EGF, TGF-β between control and treatment groups (AdMSCMs), and paired t-test was used to analyze the mean between day 3 and day 7 of each group. Results: A lower expression of MMP-1, MMP-9 in AdMSCMs group and higher expression EGF and TGF-β in AdMSCMs group compared to the control group in day 3 and day 7. Independent t-test results showed a significant difference in the expression of MMP-1, MMP-9, EGF between the control and AdMSCMs group in day 3 and day 7. Only TGF-β expression mean difference between day 3 and day 7 showed a significant difference compared to the control groups (p

Epidermal growth factor (EGF) is known to be a critical stimulant for inducing the proliferation of glioma cancer cells. In our study, we observed that GST‐RhoA binds to pyruvate kinase M2 (PKM2) in vitro. While EGF reduced the levels of RhoA protein, it significantly increased p‐Y42 RhoA, as well as PKM1 and PKM2 in LN18 glioma cell line. We determined that RhoA undergoes degradation through ubiquitination involving SCF1 and Smurf1. Interestingly, we observed that p‐Y42 RhoA binds to PKM2, while the dephosphomimetic form, RhoA Y42F, did not. Additionally, our observation revealed that PKM2 stabilized both RhoA and p‐Y42 RhoA. Importantly, RhoA, p‐Y42 RhoA, and PKM2, but not RhoA‐GTP, were localized in the nucleus upon EGF stimulation. Knockdown of RhoA with siRNA resulted in the reduced levels of phosphoglycerate kinase1 (PGK1) and microtubule affinity‐regulating kinase 4 (MARK). Furthermore, we found that the promoter of PGK1 was associated with β‐catenin and YAP. Notably, p‐Y42 RhoA and PKM2 co‐immunoprecipitated with β‐catenin and YAP. Based on these findings, we proposed a novel mechanism by which p‐Y42 RhoA and PKM2, in conjunction with β‐catenin and YAP, regulate PGK1 expression, contributing to the progression of glioma upon EGF. [ABSTRACT FROM AUTHOR]

Background/Objectives: Various biological response modifiers play important roles in the immunopathogenesis of chronic hepatitis C (CHC). While serum levels of cytokines and growth factors change with the disease severity and treatment responses, the impact of concomitant liver steatosis on systemic inflammatory response is largely unknown. The aim of this study was to analyze the characteristics and kinetics of serum profiles of interleukins and growth factors in CHC patients with steatotic liver disease (SLD). Methods: Serum concentrations of 12 cytokines (IL-5, IL-13, IL-2, IL-6, IL-9, IL-10, IFN-γ, TNF-α, IL-17A, IL-17F, IL-4 and IL-22) and 6 growth factors (Angiopoietin-2, EGF, EPO, HGF, SCF, VEGF) were analyzed in 56 CHC patients at four time points (baseline, week 4, week 8 and SVR12) with bead-based flow cytometry assay. Results: At baseline, patients with SLD had significantly lower IL-9, IL-10, IL-13 and IL-22 and higher serum concentrations of EGF, VEGF and ANG. In a subgroup of patients with advanced liver fibrosis, SLD was linked with lower serum concentrations of IL-4, IL-5, IL-9, IL-10, IL-13 and IL-22 and higher concentrations of HGH and VEGF. Distinct cytokine kinetics during DAA treatment was observed, and SLD was identified as the main source of variation for IL-5, IL-9, IL-10, IL-13, IL-17A, IL-22, EGF, VEGF and ANG. Patients with SLD at SVR12 had significantly higher VEGF and HGF serum concentrations. Conclusions: SLD is associated with distinct cytokine and growth factor profiles and kinetics during CHC treatment, which might be associated with disease severity and the capacity for liver regeneration and contribute to fibrosis persistence. [ABSTRACT FROM AUTHOR]

Immortalized keratinocytes can offer a low‐cost experimental platform for human skin research, with increased cell yield compared to primary cultures. However, the usefulness of these surrogate cell models is highly dependent on their ability to retain the phenotypic attributes of the parent cells. Keratins K14 and K5 are the hallmarks of undifferentiated, mitotically active basal keratinocytes. We observed occasional progressive loss of K14 expression in growing keratinocyte cell lines, with persistent retention of K5 and an epithelial phenotype, and investigated possible reasons for this. We show that K14 repression occurs by DNA promoter methylation of KRT14 gene and is compounded by histone deacetylation and by the presence of EGF. In vivo, keratinocytes shut down K14 synthesis as they commit to terminal differentiation and move from the basal to spinous layer, but by laser‐capture microdissection of human epidermis we could detect no evidence of increased selective KRT14 methylation in this normal process. Loss of K14 expression suggests that epidermal identity of cultured keratinocytes can be compromised in certain tissue culture situations, possibly due to the immortalization method and persistent EGF supplementation. [ABSTRACT FROM AUTHOR]

The March 20, 2014, magnitude Mw3.9 earthquake near Arzew, Algeria, instigated a study to deepen comprehension of seismic activity and hazard in the region. Analyzing data from Algerian and Spanish seismic networks, we explored earthquake characteristics and rupture mechanisms. The earthquake's epicenter was located at 35.825° latitude and -0.366° longitude, with a depth of 7 km, exhibiting intensity IV-V in the Arzew-Oran area. Preceding this event, a magnitude MD3.1 foreshock occurred on February 1, 2014, at the same location. The waveforms of the foreshock and mainshock exhibited striking similarities, validating the effectiveness of the Empirical Green's Function method employed for deconvolution. Through waveform inversion and P-wave polarities, we estimated the focal mechanism, revealing a near-pure strike-slip mechanism with nodal planes oriented ~E-W and ~N-S. The rupture process, characterized by multiple episodes, propagated predominantly from the south towards the N5°-15°E direction at a velocity around 2.7 km/s along an 870 m fault length in 0.32 seconds. The mainshock's fault plane was identified as the N-S plane, indicating the direction of rupture propagation. Source parameter estimation utilizing the EGF method revealed larger corner frequencies and stress drops compared to individual spectra estimation, attributed to the method's improved correction for attenuation and site effects, without the need for simplified a priori models. Despite its low magnitude, the 2014 Arzew earthquake provided valuable insights into the region's seismic behavior, contributing significantly to ground motion predictions. In particular, the study highlights the necessity of accounting for rupture directivity in seismic hazard assessments and mitigation strategies. [ABSTRACT FROM AUTHOR]

Epidermal melanin unit integrity is crucial for skin homeostasis and pigmentation. Epidermal growth factor (EGF) receptor (EGFR) is a pivotal player in cell growth, wound healing, and maintaining skin homeostasis. However, its influence on skin pigmentation is relatively unexplored. This study investigates the impact and underlying mechanisms of EGFR inhibitors on skin pigmentation. We evaluated EGF and EGFR expression in various skin cells using quantitative real‐time PCR, Western blot, and immunofluorescence. EGF and EGFR were predominantly expressed in epidermal keratinocytes, and treatment with the EGFR tyrosine kinase inhibitors (EGFR‐TKIs) gefitinib and PD153035 significantly increased stem cell factor (SCF) and endothelin‐1 (ET‐1) expression in cultured keratinocytes. Enhanced melanocyte migration and proliferation were observed in co‐culture, as evidenced by time‐lapse live imaging and single‐cell tracking assays. Furthermore, topical application of gefitinib to guinea pig dorsal skin induced increased pigmentation and demonstrated efficacy in mitigating rhododendrol‐induced leukoderma. Suppression of EGF signaling indirectly enhanced skin pigmentation by upregulating SCF and ET‐1 in epidermal keratinocytes. This novel mechanism highlights the pivotal role of EGF signaling in regulating skin pigmentation, and topical EGFR‐TKI therapy at an appropriate dose may be a promising approach for depigmentation disorder management. [ABSTRACT FROM AUTHOR]

The Cucurbitaceae family includes several edible species that are consumed globally as fruits and vegetables. These species produce high volumes of seeds that are often discarded as waste. In this study, we investigate the chemical composition and biological activity of three seed oils from Cucurbitaceae plants, namely, cantaloupe, honeydew, and zucchini, in comparison to the widely used pumpkin seed oil for their ability to enhance and accelerate wound healing in rats. Our results showed that honeydew seed oil (HSO) was effective in accelerating wound closure and enhancing tissue repair, as indicated by macroscopic, histological, and biochemical analyses, as compared with pumpkin seed oil (PSO). This effect was mediated by down-regulation of the advanced glycation end products (AGE) and its receptor (RAGE) cue, activating the cytoprotective enzymes nuclear factor erythroid 2 (Nrf2) and heme oxygenase-1 (HO-1), suppressing the inflammatory mediators tumor necrosis factor (TNF)-α, nuclear factor kappa B (NF-κB), and nod-like receptor protein 3 (NLRP3), and reducing the levels of the skin integral signaling protein connexin (CX)-43. Furthermore, immunohistochemical staining for epidermal growth factor (EGF) showed the lowest expression in the skin after treatment with HSO, indicating a well-organized and complete healing process. Other seed oils from cantaloupe and zucchini exhibited favorable activity when compared with untreated rats; however, their efficacy was comparatively lower than that of PSO and HSO. Gas chromatographic analysis of the derivatized oils warranted the superior activity of HSO to its high nutraceutical content of linoleic acid, which represented 65.9% of the fatty acid content. This study's findings validate the use of honeydew seeds as a wound-healing fixed oil and encourage further investigation into the potential of Cucurbitaceae seeds as sources of medicinally valuable plant oils. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase (MMP-1 and −9), Epidermal Growth Factor (EGF), and Transforming Growth factor (TGF)-β are expressed in the oral ulcer wound-healing process. The Adipose mesenchymal stem cell metabolites (AdMSCMs) may accelerate wound-healing. This study aimed to investigate the expression of MMP-1, MMP-9, EGF, and TGF-β in the oral mucosa ulcer rat model treated with topical AdMSCMs. Oral ulcer models were created in twenty healthy male Wistar rats (Rattus novergicus) divided into AdMSCMs and control groups. The oral ulcer model was treated topically using AdMSCMs oral gel three times daily for 3 and 7 days. The expression of MMP-1, MMP-9, EGF, TGF-β was evaluated through histological examination using the immunohistochemistry method. Independent t -test was used to compare the mean of expression of MMP-1, MMP-9, EGF, TGF-β between control and treatment groups (AdMSCMs), and paired t -test was used to analyze the mean between day 3 and day 7 of each group. A lower expression of MMP-1, MMP-9 in AdMSCMs group and higher expression EGF and TGF-β in AdMSCMs group compared to the control group in day 3 and day 7. Independent t -test results showed a significant difference in the expression of MMP-1, MMP-9, EGF between the control and AdMSCMs group in day 3 and day 7. Only TGF-β expression mean difference between day 3 and day 7 showed a significant difference compared to the control groups (p < 0.05) AdMSCMs oral gel may accelerate oral ulcer healing models by reducing the expression MMP-1, MMP-9, and increasing EGF and TGF-β expressions during the wound-healing process. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common dermatological disease affecting both children and adults. No drug-free emulgel has been developed and studied in vitro and in vivo for the treatment of AD. The aim of this study was to develop and assess the efficacy of a topical emulgel containing hyaluronic acid, glycerol, Calendula officinalis, Aloe vera, polyphenols and EGF for the concomitant treatment in patients with AD aged over 14. Objective skin barrier function parameters were included, such as transepidermal water loss (TEWL), skin temperature, pH, stratum corneum hydration, skin elasticity and erythema. The subjective opinion of the patients was determined including acceptability, absorption, comfort of use and tolerability, as well as the degree of improvement in patients' quality of life. We observed an improvement in the subjective parameters studied and statistically significant differences in the objective parameters. Specifically, we found an improvement in TEWL (p = 0.006), erythema (p = 0.008) and hydration (p < 0.001), parameters indicating an improvement in the epidermal barrier. One hundred per cent of patients were satisfied with the product. Therefore, these results suggest that the product may contribute to the treatment of AD. [ABSTRACT FROM AUTHOR]

Hui Zhang, Wei Jiang Department of Orthopedics, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of ChinaCorrespondence: Wei Jiang, Email jiangweicz@tom.comBackground: Epidermal growth factor (EGF) is a potent pro-angiogenic molecule promoting the angiogenic phenotype of ankylosing spondylitis (AS). Studies demonstrated that EGF rs3756261 polymorphism was associated with the risk of inflammatory diseases, but not including AS.Methods: To investigate the association between EGF rs3756261 polymorphism and the risk of AS, we genotyped the EGF rs3756261 polymorphism in 208 patients with AS and 412 controls in a Chinese Han population using a custom-by-design 48-Plex SNP scanTM Kit. The serum EGF levels were measured using an enzyme-linked immunosorbent assay in 208 AS patients and 412 controls.Results: Our data indicated that EGF rs3756261 polymorphism was associated with an increased risk of AS in the Chinese Han population. Stratified analyses indicated that the EGF rs3756261 polymorphism elevated the risk of AS among the males, smokers, drinkers and those aged < 30 years. In addition, the EGF rs3756261 polymorphism was related to increased CRP and HLA-B27 levels in AS patients. Next, we found that the average serum levels of EGF were significantly higher in AS patients compared with controls. Meanwhile, EGF serum levels were significantly higher in AG genotype carriers when compared with AA genotype carriers in AS patients.Conclusion: In conclusion, this study indicated that EGF rs3756261 polymorphism was associated with the risk of AS and EGF serum levels in a Chinese Han population.Keywords: EGF, rs3756261 polymorphism, serum levels, ankylosing spondylitis, case–control study

Chronic atrophic gastritis (AG) is initiated mainly by Helicobacter pylori infection, which may progress to stomach cancer following the Correa's cascade. The current treatment regimen is H. pylori eradication, yet evidence is lacking that this treatment is effective on later stages of AG especially gastric gland atrophy. Here, using AG mouse model, patient samples, gastric organoids, and lineage tracing, this study unraveled gastric stem cell (GSC) defect as a crucial pathogenic factor in AG in mouse and human. Moreover, a natural peptide is isolated from a traditional Chinese medicine that activated GSCs to regenerate gastric epithelia in experimental AG models and revitalized the atrophic gastric organoids derived from patients. It is further shown that the peptide exerts its functions by stabilizing the EGF‐EGFR complex and specifically activating the downstream ERK and Stat1 signaling. Overall, these findings advance the understanding of AG pathogenesis and open a new avenue for AG treatment. [ABSTRACT FROM AUTHOR]

Epidermal growth factor (EGF), an essential factor for the proliferation and survival of renal tubular cells, is expressed by distal tubules and normally excreted via urine. Previous studies in rats demonstrated that acute tubular injury reduces urinary EGF levels. However, it is unclear whether urinary EGF is a suitable monitoring marker of tubular repair status after acute kidney injury (AKI) in humans. To address this question, we measured serum and urinary EGF in patients with AKI (n = 99) using ELISA and investigated whether urinary EGF levels were associated with the severity of tubular injury and renal prognosis. Urinary EGF was abundant in healthy controls but showed a significant decrease in AKI patients (14,522 ± 2190 pg/mL vs. 3201 ± 459.7 pg/mL, p < 0.05). The urinary EGF level in patients with renal AKI was notably lower than that in patients with pre-renal AKI. Furthermore, the urinary EGF level in patients with AKI stage 3 was significantly lower than that in patients with AKI stage 1. Urinary EGF levels were negatively correlated with urinary β-2MG and serum creatinine levels but positively correlated with hemoglobin levels and eGFR. Urinary EGF was not significantly correlated with urinary NAG, α-1MG, L-FABP, NGAL, KIM-1, or urinary protein concentrations. No significant correlation was observed between serum and urinary EGF levels, suggesting that urinary EGF is derived from the renal tubules rather than the blood. In living renal transplantation donors, the urinary EGF/Cr ratio was approximately half the preoperative urinary EGF/Cr ratio after unilateral nephrectomy. Collectively, these data suggest that urinary EGF is a suitable noninvasive indicator of not only the volume of functional normal renal tubules but also the status of tubular repair after AKI. [ABSTRACT FROM AUTHOR]

The evolutionary conserved Notch signaling pathway functions as a mediator of direct cell–cell communication between neighboring cells during development. Notch plays a crucial role in various fundamental biological processes in a wide range of tissues. Accordingly, the aberrant signaling of this pathway underlies multiple genetic pathologies such as developmental syndromes, congenital disorders, neurodegenerative diseases, and cancer. Over the last two decades, significant data have shown that the Notch signaling pathway displays a significant function in the mature brains of vertebrates and invertebrates beyond neuronal development and specification during embryonic development. Neuronal connection, synaptic plasticity, learning, and memory appear to be regulated by this pathway. Specific mutations in human Notch family proteins have been linked to several neurodegenerative diseases including Alzheimer's disease, CADASIL, and ischemic injury. Neurodegenerative diseases are incurable disorders of the central nervous system that cause the progressive degeneration and/or death of brain nerve cells, affecting both mental function and movement (ataxia). There is currently a lot of study being conducted to better understand the molecular mechanisms by which Notch plays an essential role in the mature brain. In this study, an in silico analysis of polymorphisms and mutations in human Notch family members that lead to neurodegenerative diseases was performed in order to investigate the correlations among Notch family proteins and neurodegenerative diseases. Particular emphasis was placed on the study of mutations in the Notch3 protein and the structure analysis of the mutant Notch3 protein that leads to the manifestation of the CADASIL syndrome in order to spot possible conserved mutations and interpret the effect of these mutations in the Notch3 protein structure. Conserved mutations of cysteine residues may be candidate pharmacological targets for the potential therapy of CADASIL syndrome. [ABSTRACT FROM AUTHOR]

BACKGROUND: The process of wound healing is complex, and expediting it remains a challenge. The advantages of extremely low frequency electric and magnetic fields (ELF-EMF) are its non-invasive treatment, promotes healing and promotes myogenesis of C2C12 cells. Epidermal growth factor (EGF) is known to play a vital role in promoting wound healing, so a combination of ELF-EMF and EGF can have far-reaching significance. OBJECTIVE: To study the effect of recombinant murine epidermal growth factor (rmEGF) combined with ELF-EMF on wound healing. METHODS: Thirty-six rats were randomly divided into three groups: normal control group, EGF group, and ELF-EMF + EGF group, and a 20 mm × 20 mm dorsal wound was made. The wound healing rate of rats was calculated on the 3rd, 7th, 11th and 15th day. HE staining was used to observe the micro-morphological changes during the wound healing process. RESULTS: The wound healing rate of EGF + ELF-EMF group was better than other groups. On the 15th day of wound healing, the wounds of each group were completely healed. On the 3rd, 7th, 11th and 15th day of HE staining, the early inflammatory cell infiltration, the arrangement of fibroblasts and the number of new capillaries in the wounds of EGF + ELF-EMF group were better than those of the other groups. CONCLUSIONS: rmEGF combined with ELF-EMF significantly promotes wound healing in SD rats. [ABSTRACT FROM AUTHOR]

The handshake between the complex networks of matrix components in the tumor micro-environment (TME) is considered as a crucial event in the progression of several cancers including cervical carcinoma (CC). A number of studies report a connection between epidermal growth factor (EGF) and matrix component production. Studies demonstrate that the mechano-transduction trigger by collagen, influences the tumor cells to undergo epithelial–mesenchymal transition (EMT) and block the entry of drugs. We hypothesize that the intervention to prevent EGF triggered deposition of matrix components could sensitize several therapies for CC cells. We utilized morphological assessment, MTT assay, mitored tracking, acridine orange (AO)/ ethidium bromide (EtBr) staining and bromodeoxyuridine (BrdU) assay to measure the cell viability, mitochondrial activity, cellular apoptosis, and DNA synthesis. Clonogenic assay and scratch healing assay were executed to address the stemness and migratory potential. Detection of glycosaminoglycan’s (GAGs), collagen, matrix metalloproteinase (MMP)-2/9 secretion and calcium (Ca2+) ions were performed to assess the production of matrix components. Finally, the interaction between EGFR and plumbagin was evaluated by employing molecular dynamics (MD) simulation. Pre-treating the cells with plumbagin inhibited the EGF-induced EMT along with reduction in cell proliferation, migration, clonogenesis and depletion of matrix components. The actions of EGF and plumbagin were more pronounced in HPV-positive CC cells than HPV-negative CC cells. This study identified that increased matrix production triggered by EGF-rich milieu is inhibited by plumbagin in human papilloma viral (HPV) 68 positive ME180, HPV 16 positive SiHa and HPV-negative C33A cell lines. Delivery of plumbagin directly to TME would effectively accelerate the clearance of CC cells, reduce metastasis and matrix abundance by employing targeted delivery to minimize the undesired effects of plumbagin. [ABSTRACT FROM AUTHOR]

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Our goal was to investigate the effects of epidermal growth factor (EGF) and interferons (IFNs) on signal transducer and activator of transcription STAT1 and STAT4 mRNA and active phosphorylated protein expression in Sjögren's syndrome cell culture models. iSGECs (immortalized salivary gland epithelial cells) and A253 cells were treated with EGF, IFN-alpha, -beta, -gamma, or mitogen-activated protein kinase p38 alpha (p38-MAPK) inhibitor for 0–24–48–72 h. STAT1 and STAT4 mRNA expression was quantified by qRT-PCR. Untreated and treated cells were compared using the delta-delta-CT method based on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) normalized relative fold changes. phospho-tyrosine-701-STAT1 and phospho-serine-721-STAT4 were detected by Western blot analysis. STAT4 mRNA expression decreased 48 h after EGF treatment in A253 cells, immortalized salivary gland epithelial cells iSGECs nSS2 (sicca patient origin), and iSGECs pSS1 (anti-SSA negative Sjögren's Syndrome patient origin). EGF and p38-MAPK inhibitor decreased A253 STAT4 mRNA levels. EGF combined with IFN-gamma increased phospho-STAT4 and phospho-STAT1 after 72 h in all cell lines, suggesting additive effects for phospho-STAT4 and a major effect from IFN-gamma for phospho-STAT1. pSS1 and nSS2 cells responded differently to type I and type II interferons, confirming unique functional characteristics between iSGEC cell lines. EGF/Interferon related pathways might be targeted to regulate STAT1 and STAT4 expression in salivary gland epithelial cells. Further investigation is required learn how to better target the Janus kinases/signal transducer and activator of transcription proteins (JAK/STAT) pathway-mediated inflammatory response in Sjögren's syndrome. [ABSTRACT FROM AUTHOR]

Lapatinib is a targeted therapeutic inhibiting HER2 and EGFR proteins. It is used for the therapy of HER2-positive breast cancer, although not all the patients respond to it. Using human blood serum samples from 14 female donors (separately taken or combined), we found that human blood serum dramatically abolishes the lapatinib-mediated inhibition of growth of the human breast squamous carcinoma SK-BR-3 cell line. This antagonism between lapatinib and human serum was associated with cancelation of the drug induced G1/S cell cycle transition arrest. RNA sequencing revealed 308 differentially expressed genes in the presence of lapatinib. Remarkably, when combined with lapatinib, human blood serum showed the capacity of restoring both the rate of cell growth, and the expression of 96.1% of the genes expression of which were altered by the lapatinib treatment alone. Co-administration of EGF with lapatinib also restores the cell growth and cancels alteration of expression of 95.8% of the genes specific to lapatinib treatment of SK-BR-3 cells. Differential gene expression analysis also showed that in the presence of human serum or EGF, lapatinib was unable to inhibit the Toll-Like Receptor signaling pathway and alter expression of genes linked to the Gene Ontology term of Focal adhesion. [ABSTRACT FROM AUTHOR]

The NF-κB pathway plays a pivotal role in impeding the diabetic wound healing process, contributing to prolonged inflammation, diminished angiogenesis, and reduced proliferation. In contrast to modern synthetic therapies, naturally occurring phytoconstituents are well-studied inhibitors of the NF-κB pathway that are now attracting increased attention in the context of diabetic wound healing because of lower toxicity, better safety and efficacy, and cost-effectiveness. This study explores recent research on phytoconstituent-based therapies and delve into their action mechanisms targeting the NF-κB pathway and potential for assisting effective healing of diabetic wounds. For this purpose, we have carried out surveys of recent literature and analyzed studies from prominent databases such as Science Direct, Scopus, PubMed, Google Scholar, EMBASE, and Web of Science. The classification of phytoconstituents into various categorie such as: alkaloids, triterpenoids, phenolics, polyphenols, flavonoids, monoterpene glycosides, naphthoquinones and tocopherols. Noteworthy phytoconstituents, including Neferine, Plumbagin, Boswellic acid, Genistein, Luteolin, Kirenol, Rutin, Vicenin-2, Gamma-tocopherol, Icariin, Resveratrol, Mangiferin, Betulinic acid, Berberine, Syringic acid, Gallocatechin, Curcumin, Loureirin-A, Loureirin-B, Lupeol, Paeoniflorin, and Puerarin emerge from these studies as promising agents for diabetic wound healing through the inhibition of the NF-κB pathway. Extensive research on various phytoconstituents has revealed how they modulate signalling pathways, including NF-κB, studies that demonstrate the potential for development of therapeutic phytoconstituents to assist healing of chronic diabetic wounds.

The adenopituitary secretes follicle‐stimulating hormone (FSH), which plays a crucial role in regulating the growth, development, and reproductive functions of organisms. Investigating the process of FSH synthesis and secretion can offer valuable insights into potential areas of focus for reproductive research. Epidermal growth factor (EGF) is a significant paracrine/autocrine factor within the body, and studies have demonstrated its ability to stimulate FSH secretion in animals. However, the precise mechanisms that regulate this action are still poorly understood. In this research, in vivo and in vitro experiments showed that the activation of epidermal growth factor receptor (EGFR) by EGF induces the upregulation of miR‐27b‐3p and that miR‐27b‐3p targets and inhibits Foxo1 mRNA expression, resulting in increased FSH synthesis and secretion. In summary, this study elucidates the precise molecular mechanism through which EGF governs the synthesis and secretion of FSH via the EGFR/miR‐27b‐3p/FOXO1 pathway. [ABSTRACT FROM AUTHOR]

Angiogenesis is fundamental for tumor growth and metastasis across many solid malignancies. Considerable interest has focused on the molecular regulation of tumor angiogenesis as a means to predict disease outcomes and guide therapeutic decisions. In the present study, we investigated the prognostic value of transforming growth factor beta (TGF-β), epidermal growth factor (EGF), fibroblast growth factor (FGF), delta-like ligand 4 (DLL4), and vascular endothelial growth factor (VEGF) in the serum of 120 women diagnosed with breast cancer using ELISA as well as examined their associations with clinical parameters and the outcome of the disease. Our results demonstrated that the serum concentration of TGF-β and EGF were remarkably higher in patients with higher tumor size, end stages of the disease, and positive lymph node involvement compared to patients with lower tumor size, early stages of the disease, and negative lymph node involvement. In addition, we found a significant correlation between the serum concentration of VEGF and the level of EGF, FGF, and DLL4 in patients with breast cancer. Furthermore, both univariate and multivariate analyses showed that TGF-β and EGF can be used as end-stage predictors. Based on our findings, increasing the level of angiogenesis factors is significantly associated with higher tumor size and late stages of the disease in patients with breast cancer. Moreover, measuring the level of angiogenesis factors could lead to better prediction of disease outcomes and choosing the best treatments for patients. [ABSTRACT FROM AUTHOR]

In vitro maturation (IVM) system is an alternative method to superovulation protocols to obtain mature oocytes. Epidermal Growth Factor (EGF) and Insulin-like Growth Factor I (IGF-I) have been widely used in IVM medium in different species. Although the guinea pig is a valuable animal model for reproductive studies, IVM is rarely used. We aimed to establish a suitable in vitro production system using EGF and/or IGF-I during IVM to improve oocyte competence. Firstly, immunolocalization of EGF and IGF-I receptors in the ovary was assessed. An IVM dose-response experiment was performed with cumulus-oocyte complexes (COCs) supplemented with: 1) EGF [0, 10, 50, 100 ng/mL or 10% fetal calf serum (FCS)]; 2) IGF-I [0, 50, 100, 200 ng/mL or 10% FCS]; or 3) the concentrations of EGF and IGF-I which showed the best IVM index in the previous experiments, with or without Fetal Calf Serum (FCS). Cortical granule and mitochondria distribution patterns were determined in in vivo and in vitro -matured oocytes for the first time in this species. Apoptotic rate after IVM and oocyte competence by in vitro embryo development were evaluated. Immunohistochemistry results showed positive immunostaining of EGF and IGF receptors in corpus luteum, oocytes, granulosa and theca cells in follicles in all stages of development. Supplementation of IVM medium with 50 ng/mL EGF or 100 ng/mL IGF-I or their combination with FCS successfully led to oocyte nuclear and cytoplasmic maturation and reduced the apoptotic rate. Both growth factors improved oocyte competence during IVM in this species since early embryos were in vitro developed, showing better results when FCS was used in the IVM medium. • EGF and IGF-I receptors were identified in all guinea pig follicle stages and corpus luteum. • Cortical granule and mitochondria migration patterns were first studied in guinea pig oocytes. • EGF, IGF-I, or their combination improve in vitro nuclear and cytoplasmic oocyte maturation. • EGF and IGF-I enhance oocyte competence during IVM, enabling in vitro embryo development. [ABSTRACT FROM AUTHOR]

At present, high environmental temperature is the main factor endangering animal production, growth and development. Therefore, the harmful effects of heat stress led by hot environment on livestock have attracted much attention. In this work, the cellar property and signaling property of epidermal growth factor (EGF) below heat stress remains unclear in swine testicular cells. Here, the effect of heat stress on EGF-induced intracellular signaling and cell behavior was explored in the ST (a porcine testis cell line). A series of experiments were done to study the cellular behavior and signaling properties of EGF under heat stress. It can be discovered which high ambient temperature changed the cellular characteristics of EGF/EGFR. The eventuates displayed when cells were exposed to thermal environment, EGF/EGFR basically did not internalize, mainly gathered on the cell membrane. Our group also researched the effect of EGF's signaling properties, and the results showed that the ability of EGF to activate EGFR-mediated intracellular signaling decreased significantly under heat stress. Finally, this study illustrated that EGF's cell behavior and signaling profile are obviously altered, indicating that heat stress seriously affected the biological activity of EGF/EGFR, which establish a solid foundation for studying the effect of the EGF on testicular tissue under heat environment. [ABSTRACT FROM AUTHOR]

Cancer is an important health problem nowadays. One of these problems is esophageal cancer (EC). The 7th most common cancer is EC worldwide. Rhomboid-related biomarkers play an important role in EC. Analysis of such biomarkers can yield important insights into the role of rhomboid 5 Homolog 2 (RHBDF2) in cancer pathology. The characterization of genes was made in silico tools such as STRING, SWISS-MODEL, UCSF Chimera ver 1.15, ProtParam, and GeneCards. The protein interactions string of the rhomboid 5 homologs 2 (RHBDF2) gene was obtained from STRING. Epidermal growth factor (EGF), and ADAM Metallopeptidase Domain 17 (ADAM17) genes were detected as related genes. Amino acid sequences of these genes were obtained from NCBI. Homology models, and Ramachandran graphic of RHBDF2, ADAM17, and EGF genes were created by the SWISS-MODEL database and UCSF Chimera ver 1.15 program. Physicochemical properties of RHBDF2, ADAM17, and EGF genes were calculated by the ProtParam database. Subcellular localizations were detected by the GeneCards server. As a result of this study, genomic and subcellular localization of RHBDF2, ADAM17, and EGF genes were obtained. Amino acid sequences, 3D-protein structures, and physicochemical properties were detected. [ABSTRACT FROM AUTHOR]

Epithelial tissue regeneration may be favored if the tissue receives both therapeutic agents such as recombinant human epidermal growth factor (rhEGF) and, simultaneously, antibacterial materials capable of reducing the risk of infections. Herein, we synthesized silver nanoparticles (AgNPs), which are well-known antibacterial materials, and impregnate them with rhEGF in order to study a bio-nanomaterial of potential interest for epithelial tissue regeneration. A suspension of Ag NPs is prepared by the chemical reduction method, employing sodium citrate as both a reducer and capping agent. The AgNPs suspension is mixed with a saline solution containing rhEGF, producing rhEGF-coated Ag NPs with rhEGF loadings between 0.1 and 0.4% w/w. ELISA assays of supernatants demonstrate that, in all studied cases, over 90% of the added rhEGF forms part of the coating, evidencing a high efficiency in impregnation. During the preparation of rhEGF-coated Ag NPs, no significant changes are observed on the nanoparticles, which are characterized by UV-Vis spectroscopy, transmission electron microscopy (TEM) and infrared spectroscopy. The liberation of rhEGF in vitro was followed for 72 h, finding that approximately 1% of rhEGF that is present is released. The rhEGF-coated AgNPs shows antibacterial activity against E. coli, although such activity is decreased with respect to that observed from naked AgNPs. Having confirmed the possibility of simultaneously liberating rhEGF and reducing the proliferation of bacteria, this work helps to support the use of rhEGF-loaded metallic nanoparticles for tissue regeneration. [ABSTRACT FROM AUTHOR]

Abstract Chronic atrophic gastritis (AG) is initiated mainly by Helicobacter pylori infection, which may progress to stomach cancer following the Correa's cascade. The current treatment regimen is H. pylori eradication, yet evidence is lacking that this treatment is effective on later stages of AG especially gastric gland atrophy. Here, using AG mouse model, patient samples, gastric organoids, and lineage tracing, this study unraveled gastric stem cell (GSC) defect as a crucial pathogenic factor in AG in mouse and human. Moreover, a natural peptide is isolated from a traditional Chinese medicine that activated GSCs to regenerate gastric epithelia in experimental AG models and revitalized the atrophic gastric organoids derived from patients. It is further shown that the peptide exerts its functions by stabilizing the EGF‐EGFR complex and specifically activating the downstream ERK and Stat1 signaling. Overall, these findings advance the understanding of AG pathogenesis and open a new avenue for AG treatment.

Epithelial tissue regeneration may be favored if the tissue receives both therapeutic agents such as recombinant human epidermal growth factor (rhEGF) and, simultaneously, antibacterial materials capable of reducing the risk of infections. Herein, we synthesized silver nanoparticles (AgNPs), which are well-known antibacterial materials, and impregnate them with rhEGF in order to study a bio-nanomaterial of potential interest for epithelial tissue regeneration. A suspension of Ag NPs is prepared by the chemical reduction method, employing sodium citrate as both a reducer and capping agent. The AgNPs suspension is mixed with a saline solution containing rhEGF, producing rhEGF-coated Ag NPs with rhEGF loadings between 0.1 and 0.4% w/w. ELISA assays of supernatants demonstrate that, in all studied cases, over 90% of the added rhEGF forms part of the coating, evidencing a high efficiency in impregnation. During the preparation of rhEGF-coated Ag NPs, no significant changes are observed on the nanoparticles, which are characterized by UV-Vis spectroscopy, transmission electron microscopy (TEM) and infrared spectroscopy. The liberation of rhEGF in vitro was followed for 72 h, finding that approximately 1% of rhEGF that is present is released. The rhEGF-coated AgNPs shows antibacterial activity against E. coli, although such activity is decreased with respect to that observed from naked AgNPs. Having confirmed the possibility of simultaneously liberating rhEGF and reducing the proliferation of bacteria, this work helps to support the use of rhEGF-loaded metallic nanoparticles for tissue regeneration.

The Cucurbitaceae family includes several edible species that are consumed globally as fruits and vegetables. These species produce high volumes of seeds that are often discarded as waste. In this study, we investigate the chemical composition and biological activity of three seed oils from Cucurbitaceae plants, namely, cantaloupe, honeydew, and zucchini, in comparison to the widely used pumpkin seed oil for their ability to enhance and accelerate wound healing in rats. Our results showed that honeydew seed oil (HSO) was effective in accelerating wound closure and enhancing tissue repair, as indicated by macroscopic, histological, and biochemical analyses, as compared with pumpkin seed oil (PSO). This effect was mediated by down-regulation of the advanced glycation end products (AGE) and its receptor (RAGE) cue, activating the cytoprotective enzymes nuclear factor erythroid 2 (Nrf2) and heme oxygenase-1 (HO-1), suppressing the inflammatory mediators tumor necrosis factor (TNF)-α, nuclear factor kappa B (NF-κB), and nod-like receptor protein 3 (NLRP3), and reducing the levels of the skin integral signaling protein connexin (CX)-43. Furthermore, immunohistochemical staining for epidermal growth factor (EGF) showed the lowest expression in the skin after treatment with HSO, indicating a well-organized and complete healing process. Other seed oils from cantaloupe and zucchini exhibited favorable activity when compared with untreated rats; however, their efficacy was comparatively lower than that of PSO and HSO. Gas chromatographic analysis of the derivatized oils warranted the superior activity of HSO to its high nutraceutical content of linoleic acid, which represented 65.9% of the fatty acid content. This study’s findings validate the use of honeydew seeds as a wound-healing fixed oil and encourage further investigation into the potential of Cucurbitaceae seeds as sources of medicinally valuable plant oils.

Abstract Background To investigate the role of neutrophils in corneal nerve regeneration. Methods A mouse model simulating corneal nerve injury was established and samples from corneal scraping with and without neutrophil closure were collected. These samples were used for corneal nerve staining, ribonucleic acid sequencing, and bioinformatics. Differential expression analysis was used to perform enrichment analysis to identify any significant differences between these two groups. The differential genes were then intersected with neutrophil-associated genes and a protein-protein interaction network was constructed using the intersected genes. The immune infiltration between the two groups was examined along with the immune cell variation between the high and low gene expression groups. Results Neutrophil removal delays corneal epithelial and nerve regeneration. A total of 546 differential genes and 980 neutrophil-associated genes, with 27 genes common to both sets were obtained. Molecular Complex Detection analysis yielded five key genes, namely integrin subunit beta 2 (ITGB2), matrix metallopeptidase 9 (MMP9), epidermal growth factor (EGF), serpin family E member 1 (SERPINE1), and plasminogen activator urokinase receptor (PLAUR). Among these genes, ITGB2, SERPINE1, and PLAUR exhibited increased expression in the neutrophil-confined group, while MMP9 and EGF showed decreased expression, with MMP9 and EGF displaying a more significant difference. Immune infiltration was also observed between the two groups, revealing significant differences in the infiltration of M0 macrophages, activated mast cells, and neutrophils. Moreover, the neutrophil levels were lower in the groups with low MMP9 and EGF expressions and higher in the high-expression group. Conclusion Neutrophil confinement might significantly affect the MMP9 and EGF expression levels. Strategies to inhibit MMP9 could potentially yield therapeutic benefits.

Abstract Background Lymphocyte antigen 6 complex locus K (LY6K), a glycosylphosphatidylinositol‐anchored protein, plays a dynamic role in cancer metastasis. In the current study, we deciphered the effects of LY6K on transforming growth factor‐β (TGF‐β) and epidermal growth factor (EGF) signaling through clathrin‐ and caveolin‐1 (CAV‐1)‐mediated endocytosis. Methods Analysis of the TCGA and GTEx dataset were performed to explore the expression and survival of LY6K in cancer patients. Short interfering RNA (siRNA) was used to knockdown the expression of LY6K in human cervical cancer patients. The effect of lack of LY6K on cell proliferation, migration, and invasion was performed, and RT‐qPCR and immunoblotting were performed to identify LY6K‐affected TGF‐β and EGF signaling pathways. Additionally, Immunofluorescence (IF) and transmission electron microscope (TEM) were performed to identify the role of LY6K in CAV‐1‐ and Clathrin‐mediated endocytosis. Results Lymphocyte antigen 6 complex locus K expression level is elevated in higher grade cervical cancer patients correlating with poor overall survival, progression‐free survival, and disease‐free survival. LY6K‐depletion in HeLa and SiHa cancer cells suppressed EGF‐induced proliferation and TGF‐β‐enhanced migration and invasion. Both TGF‐β receptor‐I (TβRI) and EGF receptor (EGFR) localized at the plasma membrane regardless of LY6K expression, and LY6K bound TβRI irrespective of the presence of TGF‐β; however, LY6K did not bind EGFR. LY6K‐depleted cells showed impaired Smad2 phosphorylation upon TGF‐β treatment and lower proliferation rates following long‐term treatment with EGF. We revealed the atypical movement of TβRI and EGFR from plasma membrane upon ligand stimulation in LY6K‐depleted cells and an impaired movement of the endocytic proteins clathrin and CAV‐1. Conclusions Our study demonstrates the key role of LY6K in both clathrin‐ and CAV‐1‐mediated endocytic pathways regulated by TGF‐β and EGF, and it suggests a correlation between LY6K overexpression in cervical cancer cells and poor overall survival.

Abstract Microneedle patches have been extensively employed for wound healing, while the lack of rapid hemostasis efficiency and multiple tissue-repair properties restrict their values in hemorrhagic wound applications. Herein, we propose a Yunnan Baiyao-loaded multifunctional microneedle patch, namely (BY + EGF)@MN, with deep tissue penetration, hemostasis efficiency and regenerative properties for hemorrhagic wound healing. The (BY + EGF)@MNs are designed with a BY-loaded Bletilla striata polysaccharide (BSP) base for rapid hemostasis and epidermal growth factor (EGF)-loaded GelMA tips for subsequent wound healing. As the BSP base can be fastly dissolved and completely release BY in 6 min to promote platelet adhesion and activate coagulation system, while the EGF can achieve a controlled and sustained release behavior in 7 days with the gradual degradation of the GelMA tips, the (BY + EGF)@MNs exhibit strong pro-coagulability and satisfactory hemostatic effect in a rat hepatic hemorrhage wound model. Based on the multifunctional characteristics, we have verified that when applied in rat cutaneous wounds, the proposed MNs can accelerate the wound healing process by enhancing neovascularization, fibroblast density, and collagen deposition. Thus, we believe that such (BY + EGF)@MNs are promising candidates for rapid hemostasis and diverse wound healing applications. Graphical Abstract

Background: The EGFR pathway is involved in intrinsic and acquired resistance to a wide variety of targeted therapies in cancer. Vaccination represents an alternative to the administration of anti-EGFR monoclonal antibodies, such as cetuximab or panitumumab. Here, we tested if anti-EGF antibodies generated by vaccination (anti-EGF VacAbs) could potentiate the activity of drugs targeting the ERK/MAPK and PI3K/Akt pathways. Methods: Non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and melanoma cell lines harboring KRAS, NRAS, BRAF and PIK3CA mutations were used. Anti-EGF VacAbs were obtained by immunizing rabbits with a fusion protein containing a synthetic, highly mutated variant of human EGF. Cell viability was determined by MTT, total and phosphorylated proteins by Western blotting, cell cycle distribution and cell death by flow cytometry and emergence of resistance by microscopic examination in low density cultures. Results: Anti-EGF VacAbs potentiated the antiproliferative effects of MEK, KRAS G12C, BRAF, PI3K and Akt inhibitors in KRAS, NRAS, BRAF and PIK3CA mutant cells and delayed the appearance of resistant clones in vitro. The effects of anti-EGF VacAbs were comparable or superior to those of panitumumab and cetuximab. The combination of anti-EGF VacAbs with the targeted inhibitors effectively suppressed EGFR downstream pathways and sera from patients immunized with an anti-EGF vaccine also blocked activation of EGFR effectors. Conclusions: Anti-EGF VacAbs enhance the antiproliferative effects of drugs targeting the ERK/MAPK and PIK3CA/Akt pathways. Our data provide a rationale for clinical trials testing anti-EGF vaccination combined with inhibitors selected according to the patient's genetic profile.

Sarcosine (N-methylglycine), a glutamatergic modulator, reduces the primary negative symptoms of schizophrenia. These beneficial changes might be mediated by trophic factors such as epidermal growth factor (EGF). We assessed associations between initial serum EGF levels or changes in serum EGF levels and symptom severity during the addition of sarcosine to stable antipsychotic treatment and thereby evaluated the associations between glutamatergic modulation, clinical changes and peripheral EGF concentrations. Fifty-eight subjects with a diagnosis of chronic schizophrenia with dominant negative symptoms, stably treated with antipsychotics, completed a prospective 6-month, randomized, double-blind, placebo-controlled study. Subjects received orally 2 g of sarcosine (n = 28) or placebo (n = 30) daily. Serum EGF levels and symptom severity (using the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS)) were assessed at baseline, 6-week and 6-month follow-up. Augmentation antipsychotic treatment with sarcosine had no effect on EGF serum levels at any time points. Only the sarcosine group showed a significant improvement in negative symptoms, general psychopathology subscales and the overall PANSS score. We found a reduction in serum EGF levels in the placebo group, but levels in the sarcosine remained stable during the study. Our data indicate that improvement in negative symptoms due to sarcosine augmentation is not directly mediated by EGF, but effective treatment may induce the production or block the decrease in EGF concentrations, which indicates the neuroprotective effect of treatment and confirms the relationship between neuroprotection and EGF levels. [ABSTRACT FROM AUTHOR]