Epidermal Growth Factor Levels Research Articles

Transverse Tibial Bone Transport Enhances Distraction Osteogenesis and Vascularization in the Treatment of Diabetic Foot.

ObjectiveTo investigate the effect of transverse tibial bone transport on the treatment of Wagner Stage 4 diabetic foot.MethodsFrom January 2017 to October 2019, a total of 19 patients with Wagner Stage 4 diabetic foot ulcers were recruited. All patients were treated with transverse tibial bone transport. A detailed follow‐up was carried out at 1 week, 1 month, 3 months, 6 months, and 1 year after surgery. The wound healing rate and the limb salvage rate at 1 year after the surgery were evaluated. Preoperative and 3‐month postoperative digital subtraction angiography (DSA) were obtained. The level of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and platelet‐derived growth factor (PDGF) before surgery and on 1st, 4th, 11th, 18th, 28th, and 35th days after surgery were measured. Operation time, intraoperative blood loss, postoperative complications, visual analog scale (VAS) pain score, skin temperature, Semmes‐weinstein monofilament (SWM), and ankle brachial index (ABI) were also assessed.ResultsThe wound healing rate and the limb salvage rate were both 94.74% in the patients at 1 year after the surgery. DSA showed the thickening of the calf and foot arteries, clear visualization, and a rich vascular network. The levels of VEGF, bFGF, and PDGF on the 11th, 18th, 28th, and 35th days after surgery were significantly higher than those before surgery (p < 0.05). The EGF level on the 18th, 28th, and 35th days after surgery was significantly higher than that before surgery (p < 0.05). Superficial wound complications occurred in one patient during the hospitalization. There was no movement area infection, skin flap necrosis, tibial fracture, loosening of the external fixator, or rupture in study.ConclusionTransverse tibial bone transport can improve the blood circulation of the affected limbs, promote the healing of diabetic foot wounds, and reduce the amputation rate of the affected limbs. Transverse tibial bone transport can promote the healing of Wagner Stage 4 diabetic foot.

Curcumol Inhibits the Development of Prostate Cancer by miR-125a/STAT3 Axis

Aim This study aimed to learn the antineoplastic activity of curcumol (Cur) on prostate cancer (PCa) and elucidate its potential molecular mechanism. Methods The proliferation, invasion, and migration of PCa cells (PC3 and 22RV1) were detected by the cell counting kit 8 (CCK8), transwell, and wound healing assay, respectively. The expression of genes and proteins was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB), respectively. The protein expression in tissues and cells was tested through immunohistochemistry (IHC) and immunocytochemistry (ICC). Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the level of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF). The interaction between microRNA125a (miR-125a) and the signal transducer and activator of transcription 3 (STAT3) was confirmed via dual-luciferase reporter assay. Results Cur effectively restrained the proliferation, invasion, and migration of PC3 and 22RV1 cells. After Cur intervention, miR-125a, miR-375, miR-149, miR-183, and miR-106b were all upregulated in PC3 cells, among which miR-125a was the most significantly upregulated. Dual-luciferase reporter assay combined with qRT-PCR and WB experiments confirmed that miR-125a targeted STAT3. Both in vitro and in vivo, Cur enhanced miR-125a expression and suppressed the activation of the STAT3 pathway in PCa. Also, Cur effectively inhibited the growth of PCa. Conclusion Cur inhibited the development of PCa by miR-125a/STAT3 axis. This may provide a potential agent for treating PCa.

Investigation of EGF, IL1-α and IL-6 levels and selected hematological parameters (NLR, MPV) in patients with the chronic cholesteatomatous otitis media.

In this study we aimed to investigate epidermal growth factor (EGF), interleukin (IL1)-α and IL-6 levels, and hematological parameters in the serum samples of patients with chronic cholesteatomatous otitis media (CCOM). This prospective included 40 patients who underwent surgery due to CCOM between June 2020 and May 2021. The stage of middle ear cholesteatoma was determined on each chart using the EAONO/JOS system. The control group comprised of 30 adults who were scheduled for septoplasty over the same period in our hospital, had no otological complaints, and had normal otological findings. The demographic, clinical, and laboratory data of the patients were obtained from the electronic medical record system of our hospital. The serum EGF, IL1-α and IL-6 levels, and hematological parameters (neutrophil-lymphocyte ratio (NLR) and mean platelet volume (MPV)) were compared between the CCOM and control groups. Seven patients had Stage 1 and 33 patients had Stage 2 middle ear cholestatoma. There was no statistically significant difference between the CCOM and control groups in terms of age and gender (p=0.092 and p=0.616, respectively). The serum EGF and IL1-α levels of the CCOM group were statistically significantly higher than those of the control group (p=0.047 and p=0.013, respectively). No statistically significant difference was observed in the serum IL-6 levels of the CCOM and control groups (p=0.675). There was also no significant difference between the CCOM and control groups in terms of the mean NLR and MPV values ​​(p=0.887 and p=0.164, respectively). There was no significant difference between the Stage 1 and Stage 2 cholesteatoma subgroups in terms of the mean EGF, IL1-α, IL-6 levels (p=0.204, p=0.557 and p=0.613, respectively), and the mean NLR and MPV values (p=0.487, p=0.439, respectively). Increased serum EGF and IL1-α levels in patients with CCOM suggest that these cytokines may play a role in cholesteatomatous epithelial hyperproliferation.

Clinical Effect of Emergency Dermabrasion Combined with Biological Dressing A on Wound Microcirculation and Preventing Sepsis in Deep Degree-II Burns.

Objective The aim of this study is to explore the clinical effect of emergency dermabrasion combined with biological dressing A on wound microcirculation and preventing sepsis in deep degree-II burns. Methods A total of 90 patients with deep degree-II burns admitted to the hospital were retrospectively enrolled between January 2020 and January 2022. According to different treatment methods, they were divided into the control group (42 cases, biological dressing A) and the observation group (48 cases, emergency dermabrasion combined with biological dressing A). The clinical curative effect in both groups was observed. The wound repair rate and wound healing quality, and changes in levels of wound microcirculation-related indexes (serum epidermal growth factor (EGF), wound blood flow, and partial pressure of transcutaneous oxygen) and inflammatory cytokines (C-reactive protein (CPR), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), and procalcitonin (PCT)) before treatment, at 3d and 7d after treatment were compared between the two groups. The incidence of wound infection and sepsis in both groups was recorded. Results The wound healing time in the observation group was significantly shorter than that in the control group, and wound healing quality in the observation group was better than that in the control group (P < 0.05). At 3 d and 7d after treatment, the levels of serum EGF, wound blood flow and partial pressure of transcutaneous oxygen in both groups were all increased (P < 0.05), which were higher in the observation group than those in the control group (P < 0.05). The levels of CRP, IL-6, ESR, and PCT in both groups were all decreased (P < 0.05), which were lower in the observation group than those in the control group (P < 0.05). There was no significant difference in incidence of sepsis between observation group and control group (4.17% (2/48) vs. 7.14% (3/42)) (Fisher = 0.539). Conclusion Emergency dermabrasion combined with biological dressing A can effectively improve wound microcirculation in patients with deep degree-II burns, promote wound healing, shorten wound healing time, improve wound healing quality, effectively control inflammatory response, and prevent sepsis.

Evaluation of Postoperative Outcomes of Endoscopic Submucosal Dissection in Primary Gastric Cancer

Background: Few studies have investigated the changes in postoperative quality of life; serum Livin, epidermal growth factor (EGF), and interleukin (IL)-8 levels; and traumatic stress in patients with early gastric carcinoma after endoscopic submucosal dissection. Objectives: We aimed to determine the effect of endoscopic submucosal dissection on postoperative life satisfaction and serum Livin, EGF, and IL-8 levels in early gastric carcinoma patients. Methods: Seventy-three early gastric carcinoma patients were divided into the control (n = 35, traditional radical surgery) and case (n = 38, endoscopic submucosal dissection) groups based on surgical approaches. Results: The operative time, gastrointestinal recovery time, length of hospital stay, perioperative bleeding, EuroQol visual analog scale scores, gastrin, and motilin levels were significantly superior to those in the control group, whereas serum Livin, EGF, IL-8, and C-reactive protein levels, as well as the total incidence of postoperative complications, were significantly lower in the case group than in the control group (all P &lt; 0.05). Conclusion: Endoscopic submucosal dissection in early gastric carcinoma patients provides the advantages of a short operative time, less perioperative bleeding, rapid postoperative recovery, and less traumatic stress and postoperative complications, as well as reduced serum Livin, EGF, IL-8, and tumor marker levels.

1024-P: Identification of Sex-Specific Cytokine and Viral Infection Profiles in Type 1 Diabetes Patients

Type 1 Diabetes (T1D) is an autoimmune disease caused by the destruction of beta cells. Because both viral infections and cytokines are suggested to play a role in T1D pathogenesis, we analyzed the viral infection and cytokine profiles of T1D patients compared to age and sex-matched healthy controls. The median age in years of T1D patients was 16.9 ± 1.14 (mean ± SEM) and 17.88 ± 0.78 for the healthy subjects. The disease duration in years was 8 ± 1.1 (n=25, 13 females, 12 males) . We first assessed the viral infection history using a PepSeq-based highly multiplexed serological assay. This assay covers the full proteomes of human viruses and determines serum immunoglobulin-G (IgG) reactivity to 30mer viral peptides. We showed that enterovirus (EV) seropositivity were distinct between the two groups, with more EV-C and EV-D positives in the T1D samples and more EV-A and EV-B positives in the controls. The trends for the viruses showing higher seropositivity were primarily driven by the female patients. To determine the cytokine profiles, we measured the serum levels of 48 cytokines, chemokines and growth factors. Interestingly, we only observed significant sex-specific differences. For example, anti-inflammatory cytokines interleukin-4 (IL-4) , IL-13, IL-22, and pro-inflammatory cytokines IL-17E and tumor necrosis factor-β were significantly lower in female patients as compared to female controls. Male patients had increased levels of epidermal growth factor and platelet-derived growth factor compared to healthy males. IL-22 was unique, unlike the decrease in female patients, it increased in the male patients compared to healthy males. Altogether, we identified sex-dependent alterations in the cytokine profiles and observed a difference in EV exposure profiles between T1D patients and healthy subjects. Determining sex-specific cytokine profiles and the potential role of viral infections in T1D pathogenesis will help us to gain deeper insight into the pathogenesis of the disease. Disclosure K.Girdhar: n/a. A.Pina: None. J.Momirov: None. M.A.Atkinson: None. J.Ladner: None. E.Altindis: None. Funding NIH NIDDK 1K01DK117967-G. Harold &amp; Leila Y. Mathers Foundation grants to EA

Usefulness of urinary biomarkers to estimate the interstitial fibrosis surface in diabetic nephropathy with normal kidney function.

Kidney biopsies of patients with diabetic nephropathy (DN) and normal kidney function may exhibit interstitial fibrosis (IF) without reduction of glomerular filtration rate (GFR) because of hyperfiltration. The aim of our study was to analyse the performance of a set of biomarkers of tubular injury to estimate the extent of IF in patients with DN and normal kidney function. This cross-sectional study included 118 adults with DN diagnosed by kidney biopsy and GFR≥90mL/min/1.73 m2 and a control group of healthy subjects. We measured the urinary excretion of monocyte chemoattractant protein-1 (MCP-1) neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), β2-microglobulin and dickkopf-3 protein (DKK-3) at the time of kidney biopsy. GFR was measured by chromium-51 labeled ethylenediamine tetraacetic acid (Cr-EDTA) (measured GFR). IF was quantified using a quantitative morphometric procedure. Predictive multivariate models were developed to estimate the IF surface. Patients with DN showed significantly higher levels of DKK-3, MCP-1 and L-FABP and significantly lower levels of epidermal growth factor (EGF) than healthy controls. There were no significant between-group differences in the levels of β2-microglobulin, KIM-1 or NGAL. IF was negatively associated with EGF and positively with age, proteinuria, MCP-1, DKK-3 and L-FABP, but not with β2-microglobulin, KIM-1, NGAL or GFR. The best model to predict IF surface accounted for 59% of its variability and included age, proteinuria, EGF, DKK-3 and MCP-1. Our study provides a model to estimate the IF in DN that can be useful to assess the progression of IF in patients with normal kidney function.

Leveraging Bulk and Single-Cell RNA Sequencing Data of NSCLC Tumor Microenvironment and Therapeutic Potential of NLOC-15A, A Novel Multi-Target Small Molecule.

Lung cancer poses a serious threat to human health and has recently been tagged the most common malignant disease with the highest incidence and mortality rate. Although epidermal growth factor (EGFR)-tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations, patients often develop resistance to these drugs. There is therefore a need to identify new drug candidates with multitarget potential for treating NSCLC. We hereby provide preclinical evidence of the therapeutic efficacy of NLOC-015A a multitarget small-molecule inhibitor of EGFR/mitogen-activated protein (MAP) kinase kinase 1 (MAP2K1)/mammalian target of rapamycin (mTOR)/yes-associated protein 1 (YAP1) for the treatment NSCLC. Our multi-omics analysis of clinical data from cohorts of NSCLC revealed that dysregulation of EGFR/MAP2K1/mTOR/YAP1 signaling pathways was associated with the progression, therapeutic resistance, immune-invasive phenotypes, and worse prognoses of NSCLC patients. Analysis of single-cell RNA sequencing datasets revealed that MAP2K1, mTOR, YAP1 and EGFR were predominantly located on monocytes/macrophages, Treg and exhaustive CD8 T cell, and are involved in M2 polarization within the TME of patients with primary and metastatic NSCLC which further implied gene’s role in remodeling the tumor immune microenvironment. A molecular-docking analysis revealed that NLOC-015A bound to YAP1, EGFR, MAP kinase/extracellular signal-related kinase kinase 1 (MEK1), and mTOR with strong binding efficacies ranging –8.4 to –9.50 kcal/mol. Interestingly, compared to osimertinib, NLOC-015 bound with higher efficacy to the tyrosine kinase (TK) domains of both T790M and T790M/C797S mutant-bearing EGFR. Our in vitro studies and sequencing analysis revealed that NLOC-015A inhibited the proliferation and oncogenic phenotypes of NSCLC cell lines with concomitant downregulation of expression levels of mTOR, EGFR, YAP1, and MEK1 signaling network. We, therefore, suggest that NLOC-015A might represent a new candidate for treating NSCLC via acting as a multitarget inhibitor of EGFR, mTOR/NF-κB, YAP1, MEK1 in NSCLC.

Low serum epidermal growth factor level is associated with lack of diabetic control in type 2 diabetes mellitus in diabetic patients in Jordan

Low serum epidermal growth factor level is associated with lack of diabetic control in type 2 diabetes mellitus in diabetic patients in Jordan

A Comparative Study on Inhibition of Breast Cancer Cells and Tumors in Mice by Carotenoid Extract and Nanoemulsion Prepared from Sweet Potato (Ipomoea batatas L.) Peel.

The objectives of this study were to determine carotenoid composition in sweet potato (TNG66) peel and prepare carotenoid nanoemulsion to study its inhibition effect on breast cancer cells MCF-7 and tumors in mice. Results showed that a total of 10 carotenoids were separated within 30 min by employing a YMC C30 column and a gradient mobile phase of methanol/acetonitrile/water (74:14:12, v/v/v) and dichloromethane (B) with a flow rate of 1 mL/min, column temperature of 25 °C, and detection wavelength of 450 nm. Following quantitation, all-trans-β-carotene was present in the highest amount (663.8 μg/g). The method validation data demonstrated a high accuracy and precision of this method. The carotenoid nanoemulsion was prepared by mixing an appropriate proportion of carotenoid extract, Tween 80, PEG 400, soybean oil and deionized water with the mean particle size being 15.7 nm (transmission electron microscope (TEM)), polydispersity index 0.238, encapsulation efficiency 97% and zeta potential −69.8 mV. A high stability of carotenoid nanoemulsion was shown over a 90-day storage period at 25 °C and during heating at 100 °C for 2 h. The release percentage of total carotenoids from carotenoid nanoemulsion under gastric and intestinal condition was 18.3% and 49.1%, respectively. An antiproliferation study revealed that carotenoid nanoemulsion was more effective than carotenoid extract in inhibiting the growth of human breast cancer cells MCF-7. Following treatments of paclitaxel (10 μg/mL), carotenoid nanoemulsion (20 and 10 μg/mL) and carotenoid extract (20 and 10 μg/mL), the tumor weight of mice respectively decreased by 77.4, 56.2, 40.3, 36.1 and 18.7%, as well as tumor volume of mice by 75.4, 65.0, 49.7, 46.7 and 26.5%. Also, both carotenoid extract and nanoemulsion could reduce the levels of epidermal growth factor (EGF) and (vascular endothelial growth factor (VEGF) in serum, with the latter being more effective. This finding suggested that carotenoid nanoemulsion was more effective than carotenoid extract in inhibiting tumor growth in mice.

Impact of obstructive sleep apnea on the expression of inflammatory mediators in diabetic macular edema.

To determine differences in inflammatory markers expressed in diabetic macular edema (DME) patients with and without obstructive sleep apnea (OSA). This was a prospective, cross-sectional study. Patients with treatment naive DME were enrolled in the study. They were stratified into 2 groups based on Apnea Hypopnea Index (AHI) from overnight polysomnography: OSA + (AHI ≥ 15) and OSA - (AHI<15). Multiplex immunoassay was performed for aqueous and serum cytokines including VEGF, placental growth factor (PGF), ICAM, IL2, IL3, IL6, IL8, IL10, IL17, vascular cell adhesion molecule-1 (VCAM1), monocyte attractant protein-1 (MCP1), epidermal growth factor (EGF) and platelet derived growth factor (PDGF). Statistical significance was defined as p < 0.004 using Bonferroni correction. 32 DME positive patients were enrolled in the study; of which 17 patients were OSA + and 15 OSA-. The OSA + cohort had significantly higher levels of serum EGF (p = 0.003), and trended towards higher levels of most serum cytokines including ICAM and IL6. OSA- cohort had significantly higher levels of aqueous IL17 compared to the OSA + cohort (2.97 ± 1.7 vs. 1.4 ± 0.46 pg/mL, p = 0.004). There were no significant differences in other aqueous cytokines. OSA + group trended towards higher levels of most serum inflammatory markers, suggesting a greater pro-inflammatory state. However, they did not have significantly greater level of aqueous cytokines.

Upregulated iRhom2 in the Hypothalamic Paraventricular Nucleus is Associated with TACE‐Mediated Shedding of Transforming Growth Factor‐α and Sympathetic Excitation in Heart Failure Rats

Tumor necrosis factor (TNF)‐α converting enzyme (TACE), also known as a disintegrin and metalloprotease (ADAM)17, is a key mediator of cell signaling by proteolytically cleaving extracellular domains of various cytokines and growth factors. TACE‐mediated shedding of transforming growth factor (TGF)‐α, has been shown to transactivate epidermal growth factor receptor (EGFR) to activate the mitogen‐activated protein kinase signaling pathway in the pathophysiological conditions. We previously reported that both TACE and TGF‐α are upregulated in the hypothalamic paraventricular nucleus (PVN, a critical cardiovascular and autonomic center) and contribute to the sympathetic excitation in heart failure (HF). However, the mechanisms by which TACE and TGF‐α are upregulated in the PVN in HF remain unclear. Recent evidence reveals that inactive Rhomboid proteins (iRhoms) including iRhom1 and iRhom2 are essential upstream regulators of TACE/ADAM17. The present study sought to determine the expression of iRhoms and its relationship with TACE‐mediated shedding of TGF‐α in the PVN in HF. Male rats underwent coronary artery ligation to induce HF or sham surgery (Sham). The left ventricular function and infarction size were assessed by echocardiography. Four weeks later, these animals were euthanized to collect cerebrospinal fluid (CSF), PVN tissues and blood for molecular and biochemical measurements. All values are expressed as the mean ± SD. Real‐time PCR showed abundant mRNA expression of both iRhom1 and iRhom2 in the PVN and brain cortex in Sham or HF rats. Compared with Sham rats, HF rats had significantly (*P&lt;0.05) increased mRNA expression of iRhom2 (2.00 ± 0.57* vs 1.03 ± 0.28, HF vs Sham) but not iRhom1 (1.32 ± 0.41 vs 1.02 ± 0.21) in the PVN. Additionally, HF rats exhibited marked increases in mRNA expression of TACE (2.25 ± 1.15* vs 1.04 ± 0.36) in the PVN and the plasma level of norepinephrine (NE, a marker of sympathetic excitation, 12.39 ± 4.96* vs 5.82 ± 2.76 ng/mL), along with elevated levels of TGF‐α (23.54 ± 6.25* vs 10.08 ± 4.38 pg/mL) in CSF. The levels of epidermal growth factor (9.88 ± 3.59 vs 8.15 ± 4.24 pg/mL) in the CSF did not alter significantly in HF compared with Sham rats. Moreover, the linear regression analysis indicated that the mRNA expression of iRhom2 in the PVN was positively correlated with TACE level in the PVN (R2 = 0.62, P &lt;0.01), TGF‐α level in the CSF (R2 = 0.64, P &lt;0.01) and NE level in the plasma (R2 = 0.63, P &lt;0.01). These results suggest that the upregulated expression of iRhom2 in the PVN may promote ectodomain shedding of TGF‐α by enhancing TACE expression to drive sympathetic activation in HF. Brain iRhom2 is a potential target for therapeutic intervention in HF.

Epidermal growth factor deficiency predisposes to progressive renal disease.

Epidermal growth factor (EGF) is produced in the kidney by thick ascending limbs of the loop of Henle and by distal convoluted tubules (DCTs). Reduced urinary EGF levels have been associated with chronic kidney disease but it is not known whether physiological levels of EGF protect the kidney from progressive renal disease. Here, we show that EGF-deficient mice on a mixed genetic background had increased urinary microalbumin, and a subset of these mice developed severe progressive renal disease with azotemia that was not seen in WT or TGFα-deficient littermates with this mixed genetic background. These azotemic EGF-deficient mice developed crescentic glomerulonephritis linked to HB-EGF/EGFR hyperactivation in glomeruli, as well as attenuation of the proximal tubule brush border, distal convoluted tubule (DCT) dilatation, and kidney fibrosis associated with renal β-catenin/mTOR hyperactivation. The observation of these severe renal pathologies only in a subset of EGF-deficient mice suggests that independent segregation of strain-specific modifier alleles contributes to the severity of the renal abnormalities that only manifest when EGF is lacking. These findings link the lack of EGF to renal pathologies in the adult mammalian kidney, in support of a role of physiological levels of EGF for maintaining the function of glomeruli, proximal tubules, and DCTs. These observations suggest that diminished EGF levels predispose kidneys to progressive renal disease.

GALNT12 is associated with the malignancy of glioma and promotes glioblastoma multiforme in vitro by activating Akt signaling

Abnormal expression of mucin-type O-glycosylation has been reported to be associated with a variety of human cancers including gliomas. However, little is known about its contribution to the malignancy of Glioblastoma Multiforme (GBM), the deadliest form of brain tumors. Here, we conducted a detailed analysis of the expression profiles of GALNT gene family, which encode polypeptide-N-acetyl-galactosaminyltransferases (GalNAc-Ts) and are responsible for initiating O-glycans, both in the Cancer Genome Atlas (TCGA) and in the Chinese Glioma Genome Atlas (CGGA) databases. We discovered that GALNT12 is the only member within the GALNT family, whose expression demonstrated significant correlation with a worse prognosis of GBM. Genetic knockdown (KD) and knockout (KO) of GALNT12 in U87 MG, a representative GBM cell line with high GALNT12 expression, confirmed that GALNT12 deficiency leads to decreased cell proliferation, migration and invasion. Mechanism study revealed that GALNT12 KD and KO decreased the level of epidermal growth factor (EGF) and consequently attenuated Akt signaling within the cell. In summary, our results indicated that GALNT12 facilitates the malignant characteristics of GBM by influencing the PI3K/Akt/mTOR axis and may serve as a novel prognosis biomarker and a potential therapeutic target of GBM.

Multi-Omics Signatures Link to Ticagrelor Effects on Vascular Function in Patients With Acute Coronary Syndrome.

Long-term antiplatelet agents including the potent P2Y12 antagonist ticagrelor are indicated in patients with a previous history of acute coronary syndrome. We sought to compare the effect of ticagrelor with that of aspirin monotherapy on vascular endothelial function in patients with prior acute coronary syndrome. This was a prospective, single center, parallel group, investigator-blinded randomized controlled trial. We randomized 200 patients on long-term aspirin monotherapy with prior acute coronary syndrome in a 1:1 fashion to receive ticagrelor 60 mg BD (n=100) or aspirin 100 mg OD (n=100). The primary end point was change from baseline in brachial artery flow-mediated dilation at 12 weeks. Secondary end points were changes to platelet activation marker (CD41_62p) and endothelial progenitor cell (CD34/133) count measured by flow cytometry, plasma level of adenosine, IL-6 (interleukin-6) and EGF (epidermal growth factor), and multi-omics profiling at 12 weeks. After 12 weeks, brachial flow-mediated dilation was significantly increased in the ticagrelor group compared with the aspirin group (ticagrelor: 3.48±3.48% versus aspirin: -1.26±2.85%, treatment effect 4.73 [95% CI, 3.85-5.62], P<0.001). Nevertheless ticagrelor treatment for 12 weeks had no significant effect on platelet activation markers, circulating endothelial progenitor cell count or plasma level of adenosine, IL-6, and EGF (all P>0.05). Multi-omics pathway assessment revealed that changes in the metabolism and biosynthesis of amino acids (cysteine and methionine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis) and phospholipids (glycerophosphoethanolamines and glycerophosphoserines) were associated with improved brachial artery flow-mediated dilation in the ticagrelor group. In patients with prior acute coronary syndrome, ticagrelor 60 mg BD monotherapy significantly improved brachial flow-mediated dilation compared with aspirin monotherapy and was associated with significant changes in metabolomic and lipidomic signatures. URL: https://www. gov; Unique identifier: NCT03881943.

Effect of Morphologically Transformed Acellular Dermal Matrix on Chronic Diabetic Wounds: An Experimental Study in a Calvarial Bone Exposure Diabetic Rat Model.

The use of acellular dermal matrix on chronic diabetic wounds in clinical practice is hindered by its high cost and difficulty in application. We aimed to acquire experimental evidence on the effect of morphologically transformed acellular dermal matrix on chronic diabetic wounds and investigate how this transformation affects the wound healing mechanism. We developed a new chronic wound model that resembles a diabetic chronic wound as it involves an open wound with partial calvarial bone exposure in diabetic rats. According to treatment materials, rats were assigned into the CONTROL, ADM, and PASTE groups. The wound healing period was subdivided into T1 and T2 (postoperative days 14 and 30, respectively). Three-staged analyses were performed using 3D camera, histological analysis, and real-time quantitative polymerase chain reaction. The morphologically transformed acellular dermal matrix showed a compatible treatment rate in the total wound and more rapidly reduced the initial bone exposure area. In the PASTE group, collagen scaffold appeared at a later period and expression levels of epidermal growth factor and epidermal growth factor receptor increased. The transformation of acellular dermal matrix into the pulverized form is thought to contribute to its non-inferior therapeutic effect compared with normal acellular dermal matrix. With respect to the mechanism, the pulverized form reduced the bone exposure area in the early stage and provided a collagen scaffold at a later period. An increase in epithelial growth factors through mechanochemical transformations along with increased contact area contribute to the enhanced healing capacity of the morphologically transformed acellular dermal matrix.

Ендогенні поліпептидні фактори росту в дітей, хворих на виразку дванадцятипалої кишки

Currently, the attention of many researchers is drawn to determine the features of the regeneration of the mucous membrane of the gastrointestinal tract in ulcers, as one of the most important protective factors in this pathology. Purpose - to investigate the indicators of endogenous polypeptides (epidermal growth factor - EGF and transforming growth factor α-TGF-α) in the serum of children with duodenal ulcers. Materials and methods. The study included 56 children aged 7-18 years (36 children with duodenal ulcer - the main group and 20 healthy children (comparison group). The content of endogenous polypeptides in serum was determined by enzyme-linked immunosorbent assay (ELISA) using the Human EGF ELISA Kit (Invitrogen, USA) for EGF and R&amp;D system (USA) for TGF-α according to the manufacturer’s instructions. Statistical processing of the obtained results was carried out using parametric and non-parametric methods of evaluation of the obtained results. Results. Slightly higher levels of EGF and TGF-α were found in boys of both subgroups of the main group (EGF: 561.45 [391.81-699.34] pg/ml and 544.67 [411.23-569.77] pg/ml, p&gt;0.05; TGF-α: 47.91 [21.41-29.69] and 42.56 [35.45-49.21] pg/ml, p&gt;0.05). Concentrations of endogenous factors in exacerbation of ulcerative process are higher than in remission (p&lt;0.001) and in remission does not reach that in healthy children, p&lt;0.01). In patients with severe duodenal ulcers, EGF and TGF-α concentrations are higher (p&lt;0.01), which may be due to the maximum degree of inflammatory-destructive process. Conclusions. The course of duodenal ulcer leads to disorders in the regulation of proliferative processes in the mucous membrane, which is manifested by increased levels of EGF and TGF-α in the serum of sick children, the more severe the course, the higher process. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local ethics committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: children, duodenal ulcer, epidermal growth factor (EGF), transforming growth factor α (TGF-α).

Tubular and glomerular biomarkers of renal tissue function in the urine of fetuses with posterior urethral valves

Posterior urethral valve (PUV) is a congenital malformation characterized by a membranous structure located in the prostatic portion of the male posterior urethra that obstructs the urinary flow. Efforts have been made to determine the degree of impairment of fetal kidney function in this condition. This study aimed to measure the levels of urinary biomarkers of glomerular and tubular functions in fetuses with PUV and to compare with the levels of the same molecules in healthy male premature newborns. Urine samples from 43 fetuses with PUVs were collected and compared with urine samples from 40 healthy male newborns of the same gestational age (controls). Tubular and glomerular biomarkers levels were measured in urine samples by MILLIPLEX® assay kits. Levels of the molecules were related to creatinine (Cr) measurements at same urine samples and expressed as pg/mg Cr. Results were analysed with Graphpad Prism version 7.0 and SPSS version 20.0. Fetuses with PUV showed a significant reduction in urine levels of Epidermal Growth Factor (EGF), Calbindin, Osteoactivin, Molecule Renal Injury 1 (KIM-1 and Factor of trefoil 3 (TFF-3) when compared to controls. On the other hand, urine levels of cystatin C and renin were higher in PUV fetuses. The levels of molecules also differed according to urine osmolality and grade of hydronephrosis. Some urinary excreted molecules may indicate kidney damage in several segments along the nephron, while others may exert important functions. Mechanical and immunological mechanisms related to PUV might significantly modulate the synthesis of cytokines related to glomerular and tubular physiology, leading to alterations in urinary concentrations of those molecules. These biomarkers can be used as future diagnostic and prognostic markers in clinical practice. Early kidney structural and functional impairment influenced the synthesis of glomerular and tubular molecules related to kidney physiological processes in fetuses with PUV.

Effects of Cream Containing Three-Dimensional Human Adipose-Derived Mesenchymal Stem Cell Conditioned Medium Secreting Growth Factors on Skin Elasticity

Purpose: In this study, the effect on skin elasticity of a cream containing three-dimensional human adipose tissue derived mesenchymal stem cell conditioned medium (3D ADMSC-CM) was examined.Methods: The clinical efficacy of the cream was evaluated by examining the skin for skin lifting, elasticity, and resilience after examining the cell proliferative capacity, expression levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) in 3D ADMSC-CM, and collagen expression in skin cells due to the 3D ADMSC-CM cream.Results: Skin cell viability was well maintained, with no cytotoxicity from the 3D ADMSC-CM. The amount of EGF and VEGF contained in the 3D ADMSC-CM was 2.692 pg/mL and 27.89 pg/mL, respectively. In addition, skin cells treated with the 3D ADMSC-CM cream experienced a collagen expression increase of 183%. In clinical evaluation of the 3D ADMSC-CM cream, skin lifting and skin elasticity improvement showed significant effects at both two and four weeks. After the 3D ADMSC-CM cream was used, the improved skin elasticity and resilience was analyzed by variables, and an improvement was observed in both after two and four weeks of use.Conclusion: A cream containing 3D ADMSC-CM derived from a 3D culture environment, similar to that of an in vivo environment, is highly effective in enhancing skin elasticity, and 3D ADMSC-CM is expected to lead the field of cosmeceuticals.

Renal and Inflammatory Proteins as Biomarkers of Diabetic Kidney Disease and Lupus Nephritis.

Current methods for differentiation of kidney disease types are unspecific and may be invasive. Thus, there is a need for development of new biomarkers of kidney disorders that are specific and less invasive. In this study, we analyzed serum samples of diabetic kidney disease (DKD) and lupus nephritis (LN) patients to identify biomarkers of these two disorders. Serum samples were analyzed by Simple Plex assays. We calculated the area under the curve (AUC) as well as receiver operating characteristics (ROC) to obtain the sensitivity and specificity and other biomarker-related variables of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin- (IL-) 18, Lipocalin-2/NGAL, epidermal growth factor (EGF), u-Plasminogen Activator (uPA), and C-reactive protein (CRP) as potential biomarkers. Protein levels of ASC, IL-18, EGF, and Lipocalin-2/NGAL were higher in DKD and LN patients when compared to controls, whereas only uPA was elevated in DKD patients and CRP in LN patients. As determined by the AUC, of the six analytes studied, EGF (AUC = 0.9935), Lipocalin-2/NGAL (0.9554), ASC (0.7666), and uPA (0.7522) are reliable biomarkers of DKD, whereas EGF (1.000), Lipocalin-2/NGAL (0.9412), uPA (0.7443), and IL-18 (0.7384) are more reliable for LN. The biomarkers analyzed can differentiate between healthy and affected individuals. However, there was no difference between the levels of these biomarkers in DKD vs LN. Thus, although these biomarkers cannot be used to categorize patients between DKD and LN, they are useful as biomarkers of renal pathology.