Efficacy of recombinant human epidermal growth factor in pressure injury healing: evidence from Chinese randomized controlled trials.

OBJECTIVE: To evaluate the efficacy of recombinant human epidermal growth factor (rhEGF) in healing pressure injuries (PIs). METHODS: A meta-analysis was conducted of randomized controlled trials (RCTs) involving rhEGF in the treatment of PIs that were identified in PubMed, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure (CNKI). The population, intervention, comparison, outcomes, study design (PICOS) strategy was applied to determine analysis eligibility. The Cochrane risk of bias tool was used, and statistical analysis, including sensitivity analysis, was performed of 3 outcomes indicators: the primary outcome was total efficacy of rhEGF in treating PIs, and the secondary outcomes were the proportion of complete healing and the time to complete healing. Total efficacy refers to the proportion of cases that have been cured, obviously effective, or effective. Complete healing refers to cases where the wound has healed, scabbed, and the scab has sloughed off. RESULTS: Sixteen RCTs were included, comprising a total of 1,206 patients. Study and control group size varied by outcomes. The total effective healing rate in rhEGF group was 97.18%, which was significantly higher than 83.38% in control group (OR: 5.69, [95% CI: 3.61, 8.97], z=7.49, P < .001). The proportion of complete healing in the rhEGF group was 73.30%, which was higher than 39.52% in control group (OR: 3.88, [95% CI: 3.01, 5.01], z=10.39, P < .001). Furthermore, the healing time using rhEGF was shorter (SMD: -2.14 days, [95% CI: -2.60, -1.67], z=9.07, P < .001). Sensitivity analyses indicated that the results were robust. CONCLUSIONS: The meta-analysis indicated that rhEGF was effective in healing PIs with few negative effects. Further research beyond Chinese populations involving larger studies and studies that distinguish between results found in using rhEGF alone or in combination are recommended.

Evaluating the impact of recombinant human epidermal growth factor on scar formation in oral and maxillofacial traumatic wound healing.

Scarring following oral and maxillofacial trauma can have significant aesthetic and functional repercussions. Recombinant human epidermal growth factor (rhEGF) has emerged as a potential therapeutic agent to enhance wound healing and minimise scar formation. This retrospective study analysed data from March 2020 to June 2023 at a single institution. A total of 105 patients were divided into a control group (n = 70) receiving standard treatment and an observation group (n = 35) receiving standard treatment plus rhEGF. The primary outcomes were the incidence of scar hyperplasia and infection rates, with the secondary outcome being scar aesthetics measured by the visual analogue scale (VAS). No significant differences were found in baseline characteristics between the two groups. The observation group showed a significant reduction in scar hyperplasia (14.3% vs. 57.1%, χ2 = 20.98, p < 0.01) and infection rates (5.7% vs. 21.4%, χ2 = 4.246, p < 0.05) compared to the control group. VAS scores indicated a superior aesthetic outcome in the observation group at all post-treatment timepoints (p < 0.01). rhEGF treatment in oral and maxillofacial trauma patients resulted in favourable healing outcomes and reduced scar formation, improving aesthetic results. These findings highlight the therapeutic potential of rhEGF and underscore the need for larger-scale trials to further investigate its benefits.

The impact of chronic fentanyl administration on the cerebral cortex in mice: Molecular and histological effects.

PURPOSE: Fentanyl, a fully synthetic opioid, is widely used for severe pain management and has a huge abuse potential for its psychostimulant effects. Unlike other opioids, the neurotoxic effects of chronic fentanyl administration are still unclear. In particular, little is known about its effect on the cerebral cortex. The current study aims to test the chronic toxicity of fentanyl in the mice model. METHODS: Adult male Balb/c mice were chronically treated with low (0.05 mg/kg, i.p) and high (0.1 mg/kg, i.p) doses of fentanyl for 5 consecutive weeks, and various neurotoxic parameters, including apoptosis, oxidative stress, and neuroinflammatory response were assessed in the cortex. Potential histological as well as neurochemical changes were also evaluated. RESULTS: The results of this study show that chronic fentanyl administration induced intense levels of apoptosis, oxidative stress, and neuroinflammation in the cerebral cortex. These findings were found to be correlated with histopathological characteristics of neural degeneration and white matter injury. Moreover, fentanyl administration was found to reduce the expression of both NMDA receptor subunits and dopamine receptors and elevate the level of epidermal growth factor (EGF). CONCLUSION: Fentanyl administration induced neurotoxic effects in the mouse cerebral cortex that could be primarily mediated by the evoked oxidative-inflammatory response. The altered expression of NMDA receptors, dopamine receptors, and EGF suggests the pernicious effects of fentanyl addiction that may end in the development of toxic psychosis.

Effect of CO2 fractional laser combined with recombinant human epidermal growth factor gel on skin barrier.

To evaluate the impact of CO2 fractional laser combined with recombinant human epidermal growth factor (rhEGF) gel on skin barrier in acne scar patients. In a retrospective analysis, we examined 105 acne scar patients admitted between July 2018 and August 2021. Of these, 51 received only CO2 fractional laser (control group), while 54 underwent a combination of CO2 fractional laser and rhEGF gel (observation group). We assessed treatment efficacy, symptom relief, skin barrier parameters, pre- and posttreatment inflammatory factors, adverse reactions, posttreatment quality of life, and patient satisfaction. The observation group exhibited a higher overall response rate, significantly shorter wound healing, scab formation, and scab detachment times. Additionally, this group showed increased stratum corneum water content, decreased pH, and transdermal water loss (TEWL), and reduced hypersensitive C-reactive protein and interleukin-6 expression posttreatment. Quality of life scores were higher, with fewer adverse reactions and greater treatment satisfaction. Combining CO2 fractional laser with rhEGF gel markedly improves acne scar treatment efficacy, enhances skin barrier function, reduces inflammation, and elevates quality of life. Its safety profile supports its broader clinical adoption.

Roxithromycin and rhEGF Co-loaded Reactive Oxygen Species Responsive Nanoparticles for Accelerating Wound Healing.

BACKGROUND: Bacterial infection can delay wound healing and is therefore a major threat to public health. Although various strategies have been developed to treat bacterial infections, antibiotics remain the best option to combat infections. The inclusion of growth factors in the treatment approach can also accelerate wound healing. The co-delivery of antibiotics and growth factors for the combined treatment of wounds needs further investigation. OBJECTIVE: Here we aimed to develop antibiotic and growth factor co-loaded nanoparticles (NPs) to treat Staphylococcus aureus-infected wounds. METHODS: By using our previously prepared reactive oxygen species-responsive material (Oxi-αCD), roxithromycin (ROX)-loaded NPs (ROX/Oxi-αCD NPs) and recombinant human epidermal growth factor (rhEGF)/ROX co-loaded NPs (rhEGF/ROX/Oxi-αCD NPs) were successfully fabricated. The in vivo efficacy of this prepared nanomedicine was evaluated in mice with S. aureus-infected wounds. RESULTS: ROX/Oxi-αCD NPs and rhEGF/ROX/Oxi-αCD NPs had a spherical structure and their particle sizes were 164 ± 5 nm and 190 ± 8 nm, respectively. The in vitro antibacterial experiments showed that ROX/Oxi-αCD NPs had a lower minimum inhibitory concentration than ROX. The in vivo animal experiments demonstrated that rhEGF/ROX/Oxi-αCD NPs could significantly accelerate the healing of S. aureus-infected wounds as compared to the free ROX drug and ROX/Oxi-αCD NPs (P < 0.05). CONCLUSION: ROX and rhEGF co-loaded NPs can effectively eliminate bacteria in wounds and accelerate wound healing. Our present work could provide a new strategy to combat bacteria-infected wounds.

The role of epidermal growth factor-containing topical products on recovery and post-inflammatory hyperpigmentation prevention after laser surgeries: A systematic review and meta-analysis.

BACKGROUND: Post-inflammatory hyperpigmentation (PIH) is a common complication after laser surgeries. Recent studies applied epidermal growth factor (EGF) on the lasered area after laser surgery to decrease the incidence of PIH with controversial results. Therefore, a comprehensive literature review of randomized controlled trials (RCTs) was conducted to investigate the issue. METHODS: Two reviewers independently searched the literatures, extracted, and analyzed the data. A total of seven RCTs involving 169 patients were included to evaluate the efficacy of EGF on recovery and PIH prevention after laser surgery. RESULTS: The results show that the incidence of PIH in the EGF group was relatively lower than that in the control group, although the difference was not statistically significant (OR 0.64, 95% CI 0.33 ~ 1.25, p = 0.19). However, the EGF groups had a significant decrease in melanin index (MI) scores at the 1st month after the laser surgery when compared to the control groups (SMD -1.57, 95% CI -2.83 ~ -0.31, p = 0.01). In addition, the patients on the EGF side rated significantly higher satisfactory scores (SMD 0.49, 95% CI 0.22 ~ 0.76, p = 0.0004). There was no significant difference as regard to changes in MI at the 2nd week and 2nd month, erythema index (EI), and trans-epidermal water loss (TEWL) at days 3 and 7 after laser therapy, respectively. CONCLUSION: The current meta-analysis found a limited temporary inhibitory effect of EGF-containing topical products on PIH with no significant effect on reducing post-laser erythema or promoting epidermal barrier repair. More studies are needed in the future due to the small sample size and marked intergroup heterogeneities.

Investigation of the efficacy of epidermal growth factor, boric acid and their combination in cartilage injury in rats: An experimental study.

OBJECTIVES: In this study, we aimed to determine the bioefficacy of epidermal growth factor (EGF), boric acid (BA), and their combination on cartilage injury in rats. MATERIALS AND METHODS: In in vitro setting, the cytotoxic effects of BA, EGF, and their combinations using mouse fibroblast cell (L929), human bone osteosarcoma cell (Saos-2), and human adipose derived mesenchymal stem cells (hAD-MSCs) were determined by applying MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] test. In in vivo setting, 72 rats were randomly divided into four groups. A standard chondral defect was created and microfracture was performed in all groups. Group A was determined as the control group. In addition to the standard procedure, Group B received 100 ng/mL of EGF, Group C received a combination of 100 ng/mL of EGF and 10 µg/mL of BA combination, and Group D 20 µg/mL of BA. RESULTS: The cytotoxic effect of the combinations of EGF dilutions (1, 5, 10, 25, 50, 100, 200 ng/mL) with BA (100, 300, 500 µg/mL) was observed only in the 72-h application period and in Saos-2. The cytotoxic effect of BA was reduced when combined with EGF. There was no significant difference in the histopathological scores among the groups (p=0.13). CONCLUSION: Our study showed that EGF and low-dose BA application had a positive effect on cartilage healing in rats. Significant decreases in recovery scores were observed in the other groups. The combination of EGF and BA promoted osteoblast growth. Detection of lytic lesions in the group treated with 20 µg/mL of BA indicates that BA may have a cytotoxic effect.

MIG6 loss confers resistance to ALK/ROS1 inhibitors in NSCLC through EGFR activation by low-dose EGF.

Although tyrosine kinase inhibitor (TKI) therapy shows marked clinical efficacy in patients with anaplastic lymphoma kinase-positive (ALK+) and ROS proto-oncogene 1-positive (ROS1+) non-small cell lung cancer (NSCLC), most of these patients eventually relapse with acquired resistance. Therefore, genome-wide CRISPR/Cas9 knockout screening was performed using an ALK+ NSCLC cell line established from pleural effusion without ALK-TKI treatment. After 9 days of ALK-TKI therapy, sequencing analysis was performed, which identified several tumor suppressor genes, such as NF2 or MED12, and multiple candidate genes. Among them, this study focused on ERRFI1, which is known as MIG6 and negatively regulates EGFR signaling. Interestingly, MIG6 loss induced resistance to ALK-TKIs by treatment with quite a low dose of EGF, which is equivalent to plasma concentration, through the upregulation of MAPK and PI3K/AKT/mTOR pathways. Combination therapy with ALK-TKIs and anti-EGFR antibodies could overcome the acquired resistance in both in vivo and in vitro models. In addition, this verified that MIG6 loss induces resistance to ROS1-TKIs in ROS1+ cell lines. This study found a potentially novel factor that plays a role in ALK and ROS1-TKI resistance by activating the EGFR pathway with low-dose ligands.

Effects of 1-year tofacitinib therapy on angiogenic biomarkers in rheumatoid arthritis.

OBJECTIVES: Cardiovascular (CV) morbidity and mortality, and perpetuated synovial angiogenesis have been associated with RA. In our study we evaluated angiogenic factors in relation to vascular inflammation and function, and clinical markers in RA patients undergoing 1-year tofacitinib therapy. METHODS: Thirty RA patients treated with either 5 mg or 10 mg twice daily tofacitinib were included in a 12-month follow-up study. Eventually, 26 patients completed the study and were included in data analysis. Levels of various angiogenic cytokines (TNF-α, IL-6), growth factors [VEGF, basic fibroblast (bFGF), epidermal (EGF), placental (PlGF)], cathepsin K (CathK), CXC chemokine ligand 8 (CXCL8), galectin-3 (Gal-3) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) were determined at baseline, and at 6 and 12 months after initiating tofacitinib treatment. In order to assess flow-mediated vasodilation, common carotid intima-media thickness (ccIMT) and carotid-femoral pulse-wave velocity, ultrasonography was performed. Synovial and aortic inflammation was also assessed by 18F-fluorodeoxyglucose-PET/CT. RESULTS: One-year tofacitinib therapy significantly decreased IL-6, VEGF, bFGF, EGF, PlGF and CathK, while it increased Gal-3 production (P < 0.05). bFGF, PlGF and NT-proBNP levels were higher, while platelet-endothelial cell adhesion molecule 1 (PECAM-1) levels were lower in RF-seropositive patients (P < 0.05). TNF-α, bFGF and PlGF correlated with post-treatment synovial inflammation, while aortic inflammation was rather dependent on IL-6 and PECAM-1 as determined by PET/CT (P < 0.05). In the correlation analyses, NT-proBNP, CXCL8 and Cath variables correlated with ccIMT (P < 0.05). CONCLUSIONS: Decreasing production of bFGF, PlGF or IL-6 by 1-year tofacitinib therapy potentially inhibits synovial and aortic inflammation. Although NT-proBNP, CXCL8 and CathK were associated with ccIMT, their role in RA-associated atherosclerosis needs to be further evaluated.

Does locally applied epidermal growth factor stop anastomotic leak in the colon?

AIM: Anastomosis leakage is one of the most common complications after colorectal surgery. Studies have shown that the incidence of anastomotic leakage is between 0.5-30%. The aim of our study was to investigate the efficacy of local application of of epidermal growth factor (EGF) on colon anastomosis healing. MATERIAL AND METHODS: 28 Wistar rats were randomly divided into 4 groups. Sham group, control group, saline injection group, EGF injection group. Anastomosis line was determined as 3 cm distal to ilealcecal junction. The rats were reoperated on the 7th postoperative day. The colon segment was cut out 3 cm proximal and distal to the anastomotic line.The bursting pressure of each removed colon segment was measured and the segments were fixed with 10% formaldehyde for pathology examination. Anastomosis line was stained with hematoxylin eosin and histopathological evaluation was performed. Evaluation parameters were inflammatory cells, fibroblast, angiogenesis (neovascularization) and collagen amounts. RESULTS: Bursting pressure was higher in the EGF group than in the control group and saline injection group. There was statistically significant difference between EGF and positive control group. (p<0,05) Histopathological examination revealed that the inflammatory cell density was higher in the positive control group than in the other groups. Fibroblast cell density, neovascularization and collagen content were higher in EGF group than the others. However, no statistically significant difference was found between the control group,saline injection group and EGF injection group. CONCLUSION: As result of our study,we think that local application of EGF may have a positive effect on healing of colon anastomosis. KEY WORDS: Colonic Anastomosis, Egf, Experimental, Healing.

Novel Insights about Synergistic Effect of Zamzam Water with SGL2 Inhibitors on Wound Healing in STZ-Induced Diabetic Rats: The Role of anti-Inflammatory and Proangiogenic Effects.

Background: Hyperglycemia usually impairs wound healing by dysregulating the inflammatory response and angiogenesis. This study aimed to examine the synergistic effect of dapagliflozin and Zamzam water (ZW) on the healing of diabetic wounds and to explore their anti-inflammatory and proangiogenic effects.Materials and methods: A full-thickness excisional wound was made on the backs of all groups after two weeks of diabetes induction. Forty rats were divided into five groups, with eight rats per group; Group 1: Control non-diabetic rats; Group II: Untreated diabetic rats; Group III: Diabetic rats drinking ZW; Group IV: Diabetic rats receiving an oral dose of 1 mg/kg dapagliflozin; and Group V: Received both dapagliflozin and ZW. The healing of diabetic wounds was assessed by measuring wound closure, oxidative stress markers, immunohistochemical staining of NF-ßB, VEGF, CD34, CD45, Ki-67, and eNOS, gene expression of MMP-9, TGF-ß1, EGF-b1, FGF, and Col1A1, protein levels of TNFα, IL-1ß, IL6, Ang II, and HIF-1α by ELISA assay, and histological examination with H & E and Masson's trichrome. Combined treatment with dapagliflozin and ZW significantly (p < 0.05) enhanced the wound closure and antioxidant enzyme level, with apparent histological improvement, and shortened the inflammatory stage of the diabetic wound by decreasing the level of inflammatory markers NF-κB, TNF-α, IL-1ß, IL6, and CD45. Therefore, it improved angiogenesis markers VEGF, CD34, eNOS, EGF-ß1, FGF, Ang II, and HIF-1α, increasing Ki-67 cellular proliferation. Moreover, it enhanced the remodeling stage by increasing MMP-2, TGF-ß1, and Col1A1 levels compared to diabetic rats.

Phytochemicals targeting epidermal growth factor receptor (EGFR) for the prevention and treatment of HNSCC: A review.

Head and neck squamous cell carcinoma (HNSCC) develops from the mucosal epithelium of the oral cavity, pharynx, and larynx, and is the most common malignancy of the head and neck, the incidence of which continues to rise. The epidermal growth factor receptor is thought to play a key role in the pathogenesis of HNSCC. Inhibition of epidermal growth factor receptor has been identified as an effective target for the treatment of HNSCC. Many phytochemicals have emerged as potential new drugs for the treatment of HNSCC. A systematic search was conducted for research articles published in PubMed, and Medline on relevant aspects. This review provides an overview of the available literature and reports highlighting the in vitro effects of phytochemicals on epidermal growth factor in various HNSCC cell models and in vivo in animal models and emphasizes the importance of epidermal growth factor as a current therapeutic target for HNSCC. Based on our review, we conclude that phytochemicals targeting the epidermal growth factor receptor are potentially effective candidates for the development of new drugs for the treatment of HNSCC. It provides an idea for further development and application of herbal medicines for cancer treatment.

Modulation of Viability, Proliferation, and Stemness by Rosmarinic Acid in Medulloblastoma Cells: Involvement of HDACs and EGFR.

Medulloblastoma (MB) is a heterogeneous group of malignant pediatric brain tumors, divided into molecular groups with distinct biological features and prognoses. Currently available therapy often results in poor long-term quality of life for patients, which will be afflicted by neurological, neuropsychiatric, and emotional sequelae. Identifying novel therapeutic agents capable of targeting the tumors without jeopardizing patients' quality of life is imperative. Rosmarinic acid (RA) is a plant-derived compound whose action against a series of diseases including cancer has been investigated, with no side effects reported so far. Previous studies have not examined whether RA has effects in MB. Here, we show RA is cytotoxic against human Daoy (IC50 = 168 µM) and D283 (IC50 = 334 µM) MB cells. Exposure to RA for 48 h reduced histone deacetylase 1 (HDAC1) expression while increasing H3K9 hyperacetylation, reduced epidermal growth factor (EGFR) expression, and inhibited EGFR downstream targets extracellular-regulated kinase (ERK)1/2 and AKT in Daoy cells. These modifications were accompanied by increased expression of CDKN1A/p21, reduced expression of SOX2, and a decrease in proliferative rate. Treatment with RA also reduced cancer stem cell markers expression and neurosphere size. Taken together, our findings indicate that RA can reduce cell proliferation and stemness and induce cell cycle arrest in MB cells. Mechanisms mediating these effects may include targeting HDAC1, EGFR, and ERK signaling, and promoting p21 expression, possibly through an increase in H3K9ac and AKT deactivation. RA should be further investigated as a potential anticancer agent in experimental MB.

Phase II, Open-Label Clinical Trial of Urinary-Derived Human Chorionic Gonadotropin/Epidermal Growth Factor for Life-Threatening Acute Graft-versus-Host Disease.

Treatments that aid inflammation resolution, immune tolerance, and epithelial repair may improve outcomes beyond high-dose corticosteroids and other broad immunosuppressants for life-threatening acute graft-versus-host disease (aGVHD). We studied the addition of urinary-derived human chorionic gonadotropin/epidermal growth factor (uhCG/EGF; Pregnyl; Organon, Jersey City, NJ) to standard aGVHD therapy in a prospective Phase II clinical trial (ClinicalTrials.gov identifier NCT02525029). Twenty-two patients with Minnesota (MN) high-risk aGVHD received methylprednisolone 48 mg/m2/day plus 2000 units/m2 of uhCG/EGF s.c. every other day for 1 week. Patients requiring second-line aGVHD therapy received uhCG/EGF 2000 to 5000 units/m2 s.c. every other day for 2 weeks plus standard of care immunosuppression (physician's choice). Responding patients were eligible to receive maintenance doses twice weekly for 5 weeks. Immune cell subsets in peripheral blood were evaluated by mass cytometry and correlated with plasma amphiregulin (AREG) level and response to therapy. Most patients had stage 3-4 lower gastrointestinal tract GVHD (52%) and overall grade III-IV aGVHD (75%) at time of enrollment. The overall proportion of patients with a response at day 28 (primary endpoint) was 68% (57% with complete response, 11% with partial response). Nonresponders had higher baseline counts of KLRG1+ CD8 cells and T cell subsets expressing TIM-3. Plasma AREG levels remained persistently elevated in nonresponders and correlated with AREG expression on peripheral blood T cells and plasmablasts. The addition of uhCG/EGF to standard therapy is a feasible supportive care measure for patients with life-threatening aGVHD. As a commercially available, safe, and inexpensive drug, uhCG/EGF added to standard therapy may reduce morbidity and mortality from severe aGVHD and merits further study.

Evaluation of Acetic Acid-Induced Chronic Gastric Ulcer Healing by Propionyl-L-Carnitine Administration.

The aim of our study was to investigate the healing effect of propionyl-L-carnitine (PLC) on chronic gastric ulcers and its underlying mechanisms. This study included rats with gastric ulcers induced by applying serosal glacial acetic acid. These rats were then given either saline (vehicle) or PLC at doses of 60 and 120 mg/kg, administered orally 3 days after ulcer induction for 14 consecutive days. Our study found that treatment with PLC resulted in a reduction of the gastric ulcer area, a faster rate of ulcer healing, and stimulated mucosal restoration. Additionally, the treatment with PLC reduced the number of Iba-1+ M1 macrophages while increasing the number of galectin-3+ M2 macrophages, as well as desmin+ microvessels, and α-SMA+ myofibroblasts in the gastric ulcer bed. The mRNA expression of COX-2, eNOS, TGF-ß1, VEGFA, and EGF in the ulcerated gastric mucosa was greater in the PLC-treated groups compared with the vehicle-treated rats. In conclusion, these findings suggest that PLC treatment may accelerate gastric ulcer healing by stimulating mucosal reconstruction, macrophage polarization, angiogenesis, and fibroblast proliferation, as well as fibroblast-myofibroblast transition. This process is associated with the upregulation of TGF-ß1, VEGFA, and EGF, as well as modulation of the cyclooxygenase/nitric oxide synthase systems.

Effect of ascorbic acid and epidermal growth factor in a rat tibia defect.

PURPOSE: Bone repair aims to restore the anatomical, biomechanical, and functional integrity of the affected structure. Here we study the effects of ascorbic acid (AA) and epidermal growth factor (EGF) applied in a single dose and in combination on the repair of a noncritical bone defect model. METHODS: Twenty-four rats were divided into four groups: an intact G-1 control group, and three groups that underwent a noncritical bone defect in the right tibia: G-2 treated with AA, G-3 treated with EGF, and G-4 treated with AA in combination with EGF. After 21 days of treatment, rats were sacrificed, the tibias were dissected and a destructive biomechanical analysis of three-point flexion test was performed in a universal testing machine; the values of stiffness, resistance, maximum energy, and energy at maximum load were statistically compared. RESULTS: G-3 and G-4 recovered the biomechanical properties of strength and stiffness of an intact tibia 3 weeks after their application. Not so the energy and energy at maximum load. For G-2, only the stiffness of an intact tibia was recovered. CONCLUSIONS: EGF and AA-EGF applied to a noncritical bone defect in the rat tibia favors the recovery of bone resistance and stiffness.

Intralesional epidermal growth factor therapy in recalcitrant diabetic foot ulcers.

OBJECTIVES: Diabetic foot ulcers (DFUs) cause high morbidity and mortality despite best treatment. Thus, new products are urgently needed to treat DFUs. Intralesional epidermal growth factor (EGF) (Heberprot-p) is considered to be an adjuvant therapy to standard of care (SOC) in DFUs. In the present study, the effect of Heberprot-p treatment on wound healing is compared to standard treatment. METHODS: The data of patients with DFUs were retrospectively analysed. The patients who had had DFUs of at least four weeks' duration and who had been treated in the wound clinic between January 2014 and 2017 were included in the study. The patients were divided into study and control groups. The study group consisted of patients in whom intralesional recombinant human EGF, Heberprot-p 75µg, was applied; the control group consisted of the remaining patients in whom EGF was not applied. The efficacy of Heberprot-p treatment in Wagner 2 and 3 DFUs were retrospectively investigated. RESULTS: The study group (n=29 patients) who received Heberprot-p treatment was found to have shorter treatment times and higher rates of wound healing than the control group (n=22 patients). Although the amputation rate in the study group was less than the control group, the difference was not statistically significant. CONCLUSION: Heberprot-p therapy is a promising treatment in DFUs, which can be routinely used as an adjunct to standard care.

Associations of Urine Biomarkers of Kidney Tubule Health With Incident Hypertension and Longitudinal Blood Pressure Change in Middle-Aged Adults: The CARDIA Study.

BACKGROUND: Urine biomarkers of kidney tubule injury associate with incident hypertension in older adults with comorbidities, but less is known about these associations in younger adults. METHODS: In 1170 participants of the CARDIA study (Coronary Artery Risk Development in Young Adults; mean age, 45 years; 40% Black people; 56% women) without hypertension, cardiovascular disease, or kidney disease at baseline, we examined associations of urine MCP-1 (monocyte chemoattractant protein-1), α1m (alpha-1-microglobulin), KIM-1 (kidney injury molecule-1), EGF (epidermal growth factor), IL (interleukin)-18, YKL-40 (chitinase-3-like protein 1), and UMOD (uromodulin) with incident hypertension (onset of systolic blood pressure [BP] ≥130 mm Hg or diastolic BP ≥80 mm Hg or initiation of hypertension medications) and longitudinal BP change in models adjusted for hypertension risk factors, estimated glomerular filtration rate, and albuminuria. RESULTS: After a median 9.9 (interquartile range, 5.9-10.2) years, 376 participants developed incident hypertension. In demographic-adjusted analyses, higher tertiles of EGF associated with lower risk of incident hypertension in both Black and White participants. After multivariable adjustment, the risk of incident hypertension remained lower in tertile 2 (hazard ratio, 0.70 [95% CI, 0.50-0.97]) and tertile 3 (hazard ratio, 0.58 [0.39-0.85]) of EGF versus tertile 1. In fully adjusted models, participants in EGF tertile 3 had smaller 10-year increases in systolic (-3.4 [95% CI, -6.1 to -0.7] mm Hg) and diastolic BP (-2.6 [95% CI, -4.6 to -0.6] mm Hg) than tertile 1. Other biomarkers showed inconsistent associations with incident hypertension and BP change. CONCLUSIONS: In middle-aged adults without hypertension, cardiovascular disease, or kidney disease, higher urine EGF associated with lower risk of incident hypertension and lower 10-year BP elevations.

EGF, a veteran of wound healing: highlights on its mode of action, clinical applications with focus on wound treatment, and recent drug delivery strategies.

Epidermal growth factor (EGF) has been used in wound management and regenerative medicine since the late 1980s. It has been widely utilized for a long time and still is because of its excellent tolerability and efficacy. EGF has many applications in tissue engineering, cancer therapy, lung diseases, gastric ulcers, and wound healing. Nevertheless, its in vivo and during storage stability is a primary concern. This review focuses on the topical use of EGF, especially in chronic wound healing, the emerging use of biomaterials to deliver it, and future research possibilities. To successfully deliver EGF to wounds, a delivery system that is proteolytically resistant and stable over the long term is required. Biomaterials are an area of interest for the development of such systems. These systems may be used in non-healing wounds such as diabetic foot ulcers, pressure ulcers, and burns. In these pathologies, EGF can reduce the risk of amputation of the lower extremities, as it accelerates the wound healing process. Furthermore, appropriate delivery system would also stabilize and control the EGF release profile in a wound. Several in vitro and in vivo studies have already proven the efficacy of such systems in the above-mentioned types of wounds. Moreover, several formulations such as ointments and intralesional injections are already available on the market. However, these products are still problematic in terms of inadequate diffusion of EGF, low bioavailability storage conditions, and shelf-life. This review discusses the nano formulations comprising biomaterials infused with EGF which could be a promising delivery system for chronic wound healing in the future.