Concentrations Of Epidermal Growth Factor Research Articles

Intraindividual variations of urinary biomarkers in hospitalized children with glomerular diseases: a prospective observational study

This study aimed to assess the intraindividual variations of urinary biomarkers in hospitalized children with glomerular diseases. Hospitalized children with glomerular diseases participated in the study. For each patient, an overnight (9:00 p.m.–7:00 a.m.) urine was collected, followed by a 24-h urine (classified into four distinct periods: morning 7:00 a.m.–12:00 p.m., afternoon 12:00 p.m.–4:00 p.m., evening 4:00 p.m.–9:00 p.m., and overnight 9:00 p.m.–7:00 a.m.). The concentrations of protein, albumin, N-acetyl-beta-D-glucosaminidase, and epidermal growth factor (EGF) were measured and normalized by three correction factors (creatinine, osmolality, or specific gravity, respectively). Additionally, the 2nd overnight urine sample was grouped into different aliquots according to centrifugation, additives, storage temperature, or delayed processing. Twenty (14 boys, 6 girls) children were enrolled, with an average age of 11.3 years. Among the three correction factors, creatinine-normalized biomarkers provided the best agreements among different periods over 24 h. There were significant diurnal variations during 24 h in the concentrations of urinary protein, albumin, N-acetyl-beta-D-glucosaminidase, and EGF (p = 0.001, p = 0.003, p = 0.003, and p = 0.003, respectively). Evening urine overestimated 24-h urinary protein and albumin, while overnight urine underestimated 24-h urinary albumin. Urinary EGF showed low variability within a day or between the 2 days (coefficients of variation 10.2% and 10.6%, respectively) and excellent agreements (intraclass correlation coefficients > 0.9) with 24-h urinary concentration. Furthermore, urinary EGF was not affected by centrifugation, additives, storage temperature, or delayed processing of urine samples (all p > 0.05). Conclusion: Given the diurnal variations of urinary biomarkers, urine samples should be collected during the same time period in clinical practice if possible. The results also extend the evidence for urinary EGF as a relatively stable biomarker applied in the future clinical practice.What is Known:• Urinary biomarkers have been widely used or discussed in making diagnoses and therapy regimens and estimating the prognosis of pediatric glomerular diseases. It remains unclear whether their levels would be affected by the time of sample collection, processing methods, and storage conditions in hospitalized children with glomerular diseases.What is New:• The levels of both commonly used biomarkers and novel biomarkers exhibited diurnal variations in hospitalized children with glomerular diseases.• Our results extend the evidence for urinary EGF as a relatively stable biomarker applied in the future clinical practice.

The determination of epidermal growth factor in Edible bird's nest by enzyme-linked immunosorbent assay

Edible bird's nest (EBN) is a traditional food which was nourishing and functional. Particularly, there is the epidermal growth factor (EGF) in EBN, which is thought to play an important role in promoting skin repair. However, the type and content of EGF in EBN were not determined yet. In this study, the type of EGF in EBN was identified as bird EGF by enzyme-linked immunosorbent assay and this method was validated to be accurate and precise. Moreover, it was found that the content of EGF in raw-unclean EBN, raw-clean EBN and stewed EBN was 3000 pg/g–4000 pg/g and there were no significant differences, which suggested that the batches, origins, forms, stewing temperatures and stewing times of EBN had no effect on the content of EGF in EBN. However, it was due to that enzyme destroyed the primary structure of EGF, the EGF content of neutral protease and trypsin hydrolysates of EBN was lower than that of flavor enzymes, alkaline protease and pepsin hydrolysates of EGF. This study was the first to determine the type and content of EGF in EBN, and provided a theoretical basis for the selection and processing of EBN and using EBN as a source of EGF.

Quantitative comparison of EGFR expression levels of optically trapped individual cells using a capacitance biosensor

Cellular endocytosis is an essential phenomenon which induces cellular reactions, such as waste removal, nutrient absorption, and drug delivery, in the process of cell growth, division, and proliferation. To observe capacitance responses upon endocytosis on a single-cell scale, this study combined an optical tweezer that can optically place a single cell on a desired location with a capacitance sensor and a cell incubation chamber. Single HeLa cancer cell was captured and moved to a desired location through optical trapping, and the single-cell capacitance change generated during the epidermal growth factor (EGF) molecule endocytosis was measured in real time. It was found that single HeLa cells showed a larger increase in capacitance values compared to that of the single NIH3T3 cells when exposed to varying EGF concentrations. In addition, the capacitance change was in proportion to the cell's EGF receptor (EGFR) level when cells of different levels of EGFR expression were tested. An equation derived from these results was able to estimate the EGFR expression level of a blind-tested cell. The biosensor developed in this research can not only quickly move a single cell to a desired location in a non-invasive manner but also distinguish specific responses between cancer and normal cells by continuous measurement of real-time interactions of a single cell in culture to the external ligands.

The effect of dalargin on growth factors content in experimental ulcerative colitis

Introduction: The effectiveness of ulcerative colitis (UC) treatment is fairy moderate and it gives a rise to search for new ways of treating it. Considering the combination of dalargineffects, studying the dalargin influence on the UC development is of undoubted interest. The aim of the study was to evaluate the dalargin effect on the content of transforming growth factor-β (TGF-β) and epidermal growth factor (EGF) in the colonic wall in mice with experimental ulcerative colitis. Materials and methods: UC was simulated by replacing water with a 5% solution of dextran sodium sulfate in boiled water for 5 days. The mice were killed on the 5th, 7th and 28th days. The concentrations of TGF-β and EGF in the homogenate of the medial colon were determined by enzyme-linked immunosorbent assay using standard kits. Results and discussion: The dalargin daily subcutaneous administration (dose of 100 μg/kg) for 7 days led to a decrease in TGF-β levels on the 5th and 7th days compared to the control group. In chronic UC, the concentration of TGF-β was higher than in the control group. The EGF concentration was increased in mice with UC treated with dalargin throughout the experiment. There were no differences in dalargin and sulfasalazine effects on the content of TGF-β, and the concentration of EGF throughout the experiment was significantly higher in the animals treated with dalargin. Conclusion: Effect of dalargin on the TGF-β and EGF concentrations was explained by its stimulating action to opioid μ-receptors localized on immune cells of the colon.

Suspension culture strategies to enrich colon cancer stem cells.

How to efficiently obtain high-purity cancer stem cells (CSCs) has been the basis of CSC research, but the optimal conditions for serum-free suspension culture of CSCs are still unclear. The present study aimed to define the optimal culture medium composition and culture time for the enrichment of colon CSCs via suspension culture. Suspension cell cultures of colon cancer DLD-1 cells were prepared using serum-free medium (SFM) containing variable concentrations of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) to produce spheroids. Culture times were set at 10, 20 and 30 days. A total of nine different concentrations of EGF and bFGF were added to SFM to generate nine experimental groups. The proportions of CD44+, CD133+, and CD44+CD133+ double-positive spheroid cells were detected via flow cytometry. mRNA expression of stemness-, epithelial-mesenchymal transition- and Wnt/β-catenin pathway-associated genes was determined via reverse transcription-quantitative PCR. Self-renewal ability was evaluated by a sphere-forming assay. Tumorigenesis was studied in vitro using a colony formation assay and in vivo via subcutaneous cell injection in nude mice. It was found that the highest expression proportions of CD133+ and CD44+ spheroid cells were observed in group (G)9 (20 ng/ml EGF + 20 ng/ml bFGF) at 30 days (F=123.554 and 99.528, respectively, P<0.001), CD133+CD44+ cells were also observed in G9 at 30 days (and at 10 days in G3 and 20 days in G6; F=57.897, P<0.001). G9 at 30 days also displayed the highest expression of Krüppel-like factor 4, leucine-rich repeat-containing G protein-coupled receptor 5, CD44, CD133, Vimentin and Wnt-3a (F=22.682, 25.401, 3.272, 7.852, 13.331 and 17.445, respectively, P<0.001) and the lowest expression of E-cadherin (F=10.851, P<0.001). G9 at 30 days produced the highest yield of cell spheroids, as determined by a sphere forming assay (F=19.147, P<0.001); colony formation assays also exhibited the greatest number of colonies derived from G9 spheroids at 30 days (F=60.767, P<0.01), which also generated the largest mean tumor volume in the subcutaneous tumorigenesis xenograft model (F=12.539, P<0.01). In conclusion, 20 ng/ml EGF + 20 ng/ml bFGF effectively enriched colon CSCs when added to suspension culture for 30 days, and conferred the highest efficiency compared with other combinations.

Role of enkephalin derivative in promoting wound healing and scar remodeling via increased epidermal growth factor in a mouse model

Background Enkephalin, an endogenous neuropeptide, binds to the delta (δ) opioid receptor and exerts an antinociceptive effect. Recent studies have suggested that neuropeptides might effectuate cutaneous wound healing. Therefore, we investigated the effects of an enkephalin derivative on wound healing and scar formation in vivo.Methods Enkephalin derivatives (leucine-enkephalin) were synthesized using the alanine scan method, and the most promising derivative (E10) was selected for further testing. In 15 C57BL/6N mice, two full-thickness skin defects (10 mm in diameter) were made on both sides of the back (left side, enkephalin group; right side, control group). The enkephalin group was administered 100 μL of E10 (AGGFL, 200 μg/mL), and the control group received phosphate-buffered saline. The wound size was digitally analyzed on days 2, 4, 7, and 10. After 21 days, the scar tissues were histologically evaluated for the scar depression index (SDI), and the epidermal growth factor (EGF) concentration was assessed using an enzyme-linked immunosorbent assay.Results The skin defect percentages were 98.4%±17.9% (day 2), 83.2%±24.0% (day 4), 39.7%±17.4% (day 7), and 16.2%±10.0% (day 10) in the control group and 86.1%±15.0% (day 2), 61.4%±11.6% (day 4), 26.6%±8.8% (day 7), and 16.4%±8.8% (day 10) in the enkephalin group. The SDI values were significantly lower in the enkephalin group (0.06±0.19) than in the control group (0.22±0.13, P&lt;0.001). The EGF level was significantly higher in the enkephalin group (102.2±22.6 pg/mL) than in the control group (42.1±20.5 pg/mL, P&lt;0.001).Conclusions An enkephalin derivative promoted wound healing and reduced depressed scar formation in a mouse model.

Epidermal growth factor regulates autophagy activity and endocytosis of yak cumulus cells in a concentration-dependent manner.

Autophagy and endocytosis are crucial biological activities in mammalian follicle development and oocyte maturation, which are easily affected by external environmental factors. Epidermal growth factor (EGF), as an important component of follicular fluid, regulates the growth and apoptosis of follicular cells. However, its regulatory mechanism of autophagy and endocytosis in mammals, especially in large domestic animals such as plateau yak, remains unclear. This study aimed to investigate the regulatory mechanism of EGF on autophagy and endocytosis in yak cumulus cells. Yak cumulus cells were treated with different concentrations of EGF and appropriate concentrations of EGFR inhibitor gefitinib (10 μM). The dynamic expression levels of Atg5, Beclin1, LC3, Cav1 and Cav2 were detected by immunofluorescence staining, qRT-PCR and Western-blot. EGF inhibited autophagy in yak cumulus cells by down-regulating the expression of Atg5, Beclin1, and LC3. The level of autophagy varied with the concentration of ligands, and the inhibition was most significant at 100 ng/mL. Noteworthy, EGF can promote endocytosis by regulating the expression of Cav1 and Cav2, but the EGFR-mediated signaling pathway is not the main way to regulate the expression of these proteins. These results provide a reference for further exploring the effects of growth factors on livestock germ cells and the regulatory role of autophagy-endocytosis crosstalk mechanism in follicle development and oocyte maturation, to improve the fecundity of yaks.

Patching Retinal Breaks with Chitosan for Retinal Detachment in Rabbits.

Rhegmatogenous retinal detachment (RRD) is caused by one or more full-thickness retinal breaks. The current RRD treatments have several drawbacks. Chitosan is one of the most commonly used natural polymers for wound healing and has been demonstrated to be biodegradable, biocompatible, non-toxic, bioadhesive, and bioactive. This study aimed to determine the reliability and effectiveness of chitosan for sealing retinal breaks in rabbits. Eighteen blue purple rabbits were randomly divided into three groups: chitosan (n = 6), RRD (n = 6), and control (n = 6). The RRD model was established using vitrectomy, making retinal holes, and subretinal fluid injection in the RRD and chitosan groups. One week after the establishment of the model, chitosan was applied within the range of the holes in the chitosan group, and the vitreous body was filled with perfusion fluid. Except the chitosan treatment, the RRD group underwent the same procedure. Intraocular pressure (IOP) measurement, fundus photography, B-mode ultrasound, optical coherence tomography (OCT), histology, and enzyme linked immunosorbent assay (ELISA) were performed. Retinas of all eyes in the RRD group were detached, whereas those of all eyes in the chitosan group remained attached. The concentrations of epidermal growth factor (EGF), fibroblast growth factor (FGF)-2, transforming growth factor β (TGF-β), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and IL-8 in the vitreous fluid of the RRD group were significantly higher than those of the control group (p < 0.05). Furthermore, the concentrations of EGF, FGF-2, TGF-β, and VEGF in the vitreous fluid of the chitosan group were higher compared to those of the RRD group (p < 0.05), whereas the concentrations of IL-6 and IL-8 were lower (p < 0.05). Chitosan may be a reliable method for sealing retinal breaks. Moreover, chitosan can maintain high levels of growth factors and reduce inflammatory factors in the vitreous, which may reduce and delay the death of retinal cells and help restore visual function after retinal repositioning.

The effect of olsalazine of chinese generic drugs on ulcerative colitis induced by dextran sulfate sodium salt in BALB/c mice.

To explore effect and mechanism of olsalazine of Chinese generic drugs on ulcerative colitis induced by dextran sulfate sodium salt (DSS) in BALB/c mice. The mouse model of ulcerative colitis was induced by free drinking of 3% (w/v) DSS aqueous solution for seven days. The mice were treated with olsalazine (0.6 g·kg-1) of Chinese generic drugs. The therapeutic effect of olsalazine on ulcerative colitis mice was evaluated by measuring disease activity index (DAI), colonic mucosal injury index (CMDI), histopathological score (HS), and detected the expression levels of interleukin (IL)-2, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-1β in serum and IL-7, IL-17, IL-22, epidermal growth factor (EGF), transforming growth factor β1 (TGF-β1) in colonic homogenate of mice. Olsalazine significantly increased the contents of IL-2, IL-10, IL-22, TGF and EGF in ulcerative colitis rats, and significantly decreased the scores of DAI, CMDI, HS and the contents in IL-7, IL-17, TNF-α, IL-1β and IFN-γ when compared with the model group. It improved the degree of colonic lesion in ulcerative colitis mice. It was suggested that olsalazine has a therapeutic effect on ulcerative colitis induced by DSS in mice, and the mechanism may be related to the increase of IL-2, IL-10, IL-22, TGF, and EGF and the decrease of the expression of IL-7, IL-17, TNF-α, IL-1β, and IFN-γ.

The effect of the reparative action drug in treatment of pediatric duodenal ulcer

Background. Digestive tract diseases occupy one of the first places in the structure of childhood pathology, including duodenal ulcers (DU), the development of which in 70-100% of cases is associated with H.pylori infection. It is found that the important role in the development of inflammatory process in digestive tract have toll-like receptors 4 (TLR4), due to reactiveness to H.pylori. It is proved that growth factors, in particular epidermal growth factor (EGF), are able to influence on the healing processes in the mucous membrane. It is advisable to include drugs of reparative action in complex treatment of pediatric DU. Purpose - to evaluate the effect of the reparative action drug in the treatment of pediatric DU, taking into account the dynamics of TLR4 and EGF in blood serum. Materials and methods. The total clinical group consisted of 39 children aged 7-18 years with H.pylori-associated duodenal ulcer. In 20 patients of the group 1 with DU a standard triple regimen was used. In 19 patients of the group 2 a drug of reparative action was included. The content of TLR4 and EGF in serum were determined by ELISA. Results. It was found that the level of TLR 4 decreased by 15.1% and 27.5% after a course of treatment in patients of the group 1 and in the group 2, respectively сompared to a level before treatment. It is showed that in patients of the group 1 and the group 2 after 3 weeks from the start of treatment there were changes in the content of EGF manifested by a decrease by 19.81% and 23.3%, сompared to a level before treatment. Сonclusions. Our results indicated that after the course of treatment the content of TLR4 and EGF in the group 1 of patients was lower by 12.37% and 3.49% respectively, than in the group 2. 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 interests was declared by the authors.

Desquamated Epithelial Cells of Unstimulated Human Whole Saliva Express Both EGF Transcript and Protein.

The aim of this study was to investigate if desquamated oral epithelial cells (DOECs) express the epidermal growth factor (EGF) and if these cells thereby may contribute to salivary EGF contents. DOECs have recently been shown to harbor the antimicrobial peptide LL-37, proposing that they may also store other biologically important salivary peptides/proteins. The EGF peptide is a growth factor which plays a critical role to maintain epithelial integrity and promote epithelial healing. The EGF is produced by salivary glands, but it is not known whether DOECs contain the EGF and thereby contribute to salivary EGF levels. DOECs were isolated from unstimulated whole saliva collected from four healthy volunteers. EGF protein expression was determined in cell lysates by dot blot and ELISA. Cellular distribution of cytokeratin, the proliferation marker Ki67, and EGF immunoreactivity were assessed by immunocytochemistry. EGF gene expression was investigated by qPCR. Expression of EGF transcript and protein in DOECs was compared to that in the human cultured keratinocyte cell line (HaCaT) cells. EGF protein expression was detected in DOEC cell lysates by both dot blot and ELISA. Strong cytoplasmic EGF immunoreactivity was observed in DOECs, although some cells showed only a weak immunoreactive signal for EGF. Moreover, DOECs, besides containing EGF protein, also expressed transcript for EGF. Interestingly, ELISA analysis revealed that EGF protein contents were higher in DOECs than in HaCaT cells. ELISA analysis also disclosed that EGF concentration was about 10 times higher in whole saliva compared to DOECs. EGF transcript expression was about 50% lower in HaCaT cells stimulated with high (10%) compared to low (0.1%) concentration of fetal bovine serum, representing growth-stimulated and growth-restricted conditions, respectively, implying that growth-stimulus exerts negative feedback on EGF gene activity in HaCaT cells. Here, we show for the first time that DOECs express the EGF, arguing that these cells contribute to salivary EGF contents and hence may play a role in gingival epithelial repair and wound healing.

126 Effect of oestrus synchronisation protocol with a high dose of oestradiol and an intravaginal progesterone-releasing device on the endometrial epidermal growth factor concentrations and fertility in recipient cows

Reproduction, Fertility and Development is an international journal publishing original research , review and comment in the fields of reproduction and developmental biology in humans, domestic animals and wildlife

Differences in salivary secretion and epidermal growth factor concentrations in mild reflux esophagitis and non-erosive reflux disease.

Sex differences in salivary secretion have been reported among healthy subjects. In the present study, salivary secretion and salivary epidermal growth factor (EGF) concentrations were investigated in mild reflux esophagitis patients, non-erosive reflux disease (NERD) patients, and healthy controls by matching the sex ratio. Thirty-three (male:female = 11:22) patients with NERD, 33 (11:22) with mild reflux esophagitis, and 33 (11:22) healthy controls were recruited for this case-control study. Salivary secretion was assessed as follows: each patient chewed sugar-free gum for 3min prior to endoscopy, and the amount of saliva secretion, salivary pH, and salivary pH after acid loading as an index of the acid-buffering capacity were measured. Salivary EGF concentrations were measured by ELISA. No significant differences were observed in the amount of saliva secretion, salivary pH, or the acid-buffering capacity between the mild reflux esophagitis and NERD groups. However, the amount of saliva secretion and the acid-buffering capacity in the mild reflux esophagitis group and the amount of saliva secretion, salivary pH, and the acid-buffering capacity in the NERD group were significantly lower than those in the healthy control group. No significant differences were noted in salivary EGF concentrations between the mild reflux esophagitis and NERD groups. After matching the sex ratio, the saliva secretion was significantly lower in patients with mild reflux esophagitis and NERD than in healthy controls. However, no significant differences were observed in the amount of saliva secretion or salivary EGF concentrations between both groups.

Effect of Epidermal Growth Factor in Human Milk and Maternal Diet on Late-Onset Breast Milk Jaundice: A Case-Control Study in Beijing.

Breast milk is crucial in the development of late-onset breast milk jaundice (BMJ), possibly due to the composition of breast milk and the lactating mother's diet. To explore the possible nutritional pathogenesis of late-onset BMJ, we investigated the lactation diet and collected breast milk by following the 42-day postpartum mother-infants pairs in Beijing and a total of 94 pairs were enrolled. The macronutrient content of breast milk was measured, and the epidermal growth factor (EGF) content in breast milk was determined by ELISA. Data on in-hospital and out-of-hospital breastfeeding, infant growth, jaundice-related vaccination, and puerperium diet were collected. The BMJ group received the second dose of hepatitis B vaccine later than the control group, and the difference was statistically significant (p &lt; 0.001). The EGF concentration in breast milk was lower in the BMJ group than in the control group (p = 0.03). When EGF increased by 1 ng/mL, the transcutaneous bilirubin (TcB) value decreased by 0.33 ng/mL and 0.27 ng/mL before and after the adjustment, respectively. A 1 g increase in oil intake led to a 0.38 ng/mL increase in EGF concentration before the adjustment. With a 1 g increase in oil intake, the TcB value decreased by 0.27 ng/mL before the adjustment, and with a 1 g increase in soybean and soybean product intake, the TcB value decreased by 0.34 ng/mL after the adjustment. Collectively, EGF in breast milk may inhibit the occurrence of late-onset BMJ, and the dietary intake of oil in lactating mothers may affect the level of EGF in breast milk, thus affecting the occurrence of late-onset BMJ. Finally, dietary oil intake may be a protective factor for the occurrence of late-onset BMJ by increasing EGF levels in breast milk.

Plasma human growth cytokines in children with vasovagal syncope.

PurposeThe study was designed to investigate the profile of plasma human growth cytokines in pediatric vasovagal syncope (VVS).Materials and methodsIn the discovery set of the study, plasma human growth cytokines were measured using a Quantiboby Human Growth Factor Array in 24 VVS children and 12 healthy controls. Scatter and principal component analysis (PCA) diagrams were used to describe the samples, an unsupervised hierarchical clustering analysis was used to categorize the samples. Subsequently, the cytokines obtained from the screening assays were verified with a suspension cytokine array in the validation set of the study including 53 VVS children and 24 controls. Finally, the factors associated with pediatric VVS and the predictive value for the diagnosis of VVS were determined.ResultsIn the discovery study, the differential protein screening revealed that the plasma hepatocyte growth factor (HGF), transforming growth factor b1 (TGF-b1), insulin-like growth factor binding protein (IGFBP)-4, and IGFBP-1 in children suffering from VVS were higher than those of the controls (all adjust P- value < 0.05). However, the plasma IGFBP-6, epidermal growth factor (EGF), and IGFBP-3 in pediatric VVS were lower than those of the controls (all adjust P- value < 0.01). Meanwhile, the changes of 7 differential proteins were analyzed by volcano plot. Unsupervised hierarchical cluster analysis demonstrated that patients in the VVS group could be successfully distinguished from controls based on the plasma level of seven differential proteins. Further validation experiments showed that VVS patients had significantly higher plasma concentrations of HGF, IGFBP-1, and IGFBP-6, but lower plasma concentrations of EGF and IGFBP-3 than controls. The logistics regression model showed that increased plasma concentration of HGF and IGFBP-1 and decreased plasma concentration of EGF were correlated with the development of pediatric VVS. ROC curve analysis showed that the abovementioned 3 proteins were useful for assisting the diagnosis of VVS.ConclusionPlasma human growth cytokine profiling changed in pediatric VVS. Elevated plasma concentrations of HGF and IGFBP-1, and decreased EGF were associated factors in the development of pediatric VVS. The abovementioned three proteins are helpful for the diagnosis of pediatric VVS.

Integrated analysis of clinical, bioelectrical and functional variables in newly diagnosed lung cancer adult patients: pilot study

BackgroundMany variables have been studied in cancer patients. Nevertheless, an study that analyzes simultaneously physical, functional and biological variables in they from clinical, physical and statistical points of views is not reported in the literature. The aim of this study is to propose an integrated analysis of clinical, bioelectrical and functional variables in newly diagnosed lung cancer adult patients for the integral evaluation and possible prognostic of them.MethodsThis Pilot study was retrospective and cross-sectional and 23 patients aged 53–82 years participated in it. The electrical resistance and capacitive electrical reactance were measured with the Bodystat Quadscan® 4000 analyzer. The electrical impedance modulus and the phase angle were calculated. The serum concentrations of epidermal growth factor, CYFRA21-1 and CA 72–4 were quantified. Correlations/associations among variables and the principal component analysis were suggested.ResultsThe majority of patients had tumor markers, electrical resistance and the phase angle in their respective normal ranges. The capacitive electrical resistance was below its normal range. Minimum, low and moderate grades of linear correlation/association prevailed among studied variables. The principal components I and II were interpreted as prognosis and body energetic reserve of the patient, respectively.ConclusionsIt is concluded that the clinical, bioelectrical and functional variables allow the integral analysis and possible prognosis of newly diagnosed lung cancer adult patients. The decrease of the capacitive electrical reactance is the most influence to the loss of the body energetic reserve that leads to alterations of the overall health, tiredness and decrease of weight and body mass index of these patients.

Urine acute kidney injury biomarkers in extremely low gestational age neonates: a nested case control study of 21 candidate urine biomarkers.

Acute kidney injury (AKI) is common and is associated with poor clinical outcomes in premature neonates. Urine biomarkers hold the promise to improve our understanding and care of patients with kidney disease. Because kidney maturation and gender can impact urine biomarker values in extremely low gestational age neonates (ELGANs), careful control of gestational age (GA) and time is critical to any urine biomarker studies in neonates. To improve our understanding of the potential use of urine biomarkers to detect AKI during the first postnatal weeks, we performed a nested case-control study to evaluate 21 candidate urine AKI biomarkers. Cases include 20 ELGANs with severe AKI. Each case was matched with 2 controls for the same GA week (rounded down to the nearest week), gender, and birth weight (BW) (± 50g). Urine cystatin C, creatinine, ghrelin, fibroblast growth factor-23 (FGF23), tissue metalloproteinase 2 (TIMP2) and vascular endothelial growth factor A (VEGFa) concentrations were higher in ELGANs with early severe AKI compared to matchedcontrol subjects without AKI. Urine epidermal growth factor (EGF) and uromodulin (UMOD) concentrations are lower in cases than controls. Interleukin (IL)-15 was lower on day 1, but higher on day 8 in cases than controls; while VEGFa was lower on day 1, but higher on day 5 in cases than controls. Urine biomarkers hold the promise to improve our ability to reliably detect kidney injury. Interventional studies are needed to determine the biomarkers' ability to predict outcomes, enhance AKI phenotypes, and improve timely interventions which can prevent the sequalae of AKI in ELGANs. A higher resolution version of the Graphical abstract is available as Supplementary information.

Effectiveness of Lateral Elbow Tendinopathy Treatment Depends on the Content of Biologically Active Compounds in Autologous Platelet-Rich Plasma.

Autologous platelet-rich plasma (PRP) injection is an alternative treatment option for patients with lateral elbow tendinopathy. The treatment is supposed to accelerate tissue regeneration by providing high concentrations of growth factors derived from platelets. The aim of the study was to assess the relationship between the content of biologically active compounds in PRP and the clinical effect of the treatment. Thirty patients with lateral elbow tendinopathy treated with a single PRP injection, were evaluated. The pain intensity (measured by a visual analogue scale (VAS)), the pressure pain threshold (PPT), the grip strength and strength of the main arm and forearm muscle groups, and the functional outcome (measured by the Disability of Arm, Shoulder and Hand (DASH) and Patient-Rated Tennis Elbow Evaluation (PRTEE) questionnaires), were assessed before PRP injection and at one- and three-months follow-up. Flow cytometry measurements of the growth factors and inflammatory cytokines in PRP were performed, and the results were used to establish the relationship between those molecules and the clinical outcome. After three months from the intervention, the minimal clinically important difference in pain reduction and functional improvement was observed in 67% and 83% of patients, respectively. Positive correlations were found between the extent of pain reduction after three months and concentrations in the PRP of platelets, epidermal growth factor (EGF), vascular endothelial growth factor, and platelet-derived growth factors. The concentration of EGF in the PRP significantly correlated with an improvement in grip strength, strength of wrist extensors, and the size of functional improvement measured by the PRTEE. The local injection of PRP is a safe and effective treatment option for lateral elbow tendinopathy, and the clinical outcome is correlated with concentrations of its biologically active compounds.

Maternally derived epidermal growth factor mediates protection in neonates from opportunistic intestinal pathogens.

Abstract The intestinal epithelial barrier is vital in preventing translocating bacteria and subsequent systemic infections. This protection is provided by host factors, by the intestinal microbiota, and, during early life, by breast milk. While the beneficial functions of breast milk are numerous to the nursing infant, it has been observed that proteins such as antibodies and growth factors are secreted in higher concentrations early during lactation and decrease as the milk matures. One such growth factor, epidermal growth factor (EGF), regulates the development of colonic goblet cell-associated antigen passages (GAPs). Decrease of EGF through disruption of synchronous breastfeeding or deletion of the epidermal growth factor receptor from goblet cells alters the kinetics of GAP formation, which can serve as a passage for pathogenic bacteria. In a murine model of early GAP formation utilizing an inhibitor of EGF receptor, we observed a variety of gut-resident pathogens were able to utilize GAPs to disseminate systemically and cause disease, including Escherichia coli, Enterococcus faecalis, Enterobacter cloacae, and Pseudomonas aeruginosa. In human studies, we found a strong correlation between concentrations of EGF in the diet and stool of very low birth weight infants. Notably, formula-fed infants contained significantly less EGF in both diet and stool. Future work will assess EGF in donor milk, which we find has highly variable EGF concentration. This work has strong implications for how diet influences risk of developing infections from gut-resident pathogens and how maternal EGF present in breastmilk is synchronized to the newborn infant to provide appropriate protection in early life. Supported by grants from NIH (AI144721, DK122187)

Diminished Pulmonary Arterial Smooth Muscle Cell Membrane Cholesterol Unmasks EGFR‐dependent Vasoconstriction

IntroductionChronic hypoxia (CH) leads to increased pulmonary vascular resistance and resultant pulmonary hypertension (PH) in patients with chronic obstructive pulmonary disease, sleep apnea, or in residents at high altitude. Recent studies from our laboratory have demonstrated that CH augments vasoconstrictor reactivity to a variety of stimuli, including pulmonary arterial smooth muscle cell (PASMC) stretch, membrane depolarization, and stimulation of G protein‐coupled receptors. This effect of CH is mediated by a switch in PASMC signaling from Ca2+‐dependent mechanisms towards a novel epidermal growth factor receptor (EGFR)‐NADPH oxidase 2 (NOX2)‐Rho kinase (ROK) Ca2+ sensitization pathway. The overall objective of this study is to understand the mechanism by which CH mediates this switch in signaling. We have recently demonstrated that CH decreases membrane cholesterol, a component of lipid membrane domains that can regulate both EGFR and NOX2 activity in other cell types. Therefore, we hypothesized that this EGFR‐NOX2‐ROK signaling pathway is intact in PASMC from control animals but quiescent due to inhibition by membrane cholesterol.MethodsWe first validated our ability to manipulate membrane cholesterol levels by treating primary cultures of PASMCs from Sprague Dawley rats with either cholesterol (2 mM), epicholesterol (an epimeric form of cholesterol; 2 mM), or MβCD (cholesterol chelator; 10 mM). Membrane cholesterol content was quantified by filipin (50 mg/ml) fluorescence using confocal microscopy. Subsequently, we examined vasoconstrictor responses to increasing concentrations of epidermal growth factor (EGF) (10‐10 – 10‐6 M) in pressurized, endothelium‐disrupted rat pulmonary arteries (~150 mm diameter). The effect of diminished membrane cholesterol on vasomotor responses was tested by substituting native cholesterol with epicholesterol (2 mM), which lacks the ability participate in protein‐sterol interactions while maintaining normal membrane fluidity. Vessels were additionally treated with the selective NOX2 inhibitor gp91ds‐tat (50 mM), the selective Rho kinase inhibitor fasudil (10 mM), or their respective vehicles.ResultsCholesterol supplementation significantly increased PASMC membrane cholesterol as indicated by filipin fluorescence. Conversely, treatment with either MβCD or epicholesterol significantly decreased membrane cholesterol compared to vehicle‐treated cells (Figure 1). In agreement with our hypothesis, epicholesterol‐dependent substitution of cholesterol revealed concentration‐dependent vasoconstriction to EGF in pulmonary arteries (Figure 2A). Treatment with either fasudil (Figure 2A) or gp91ds‐tat (Figure 2B) attenuated this effect.ConclusionsThe EGFR‐NOX2‐RhoA signaling cascade is present in arteries from normoxic animals but is normally inhibited by membrane cholesterol. The results of this study will allow for improved mechanistic analysis of how cholesterol regulates this pathway that is central to enhanced vasoconstrictor reactivity in PH.