scholarly journals The impact of epidermal growth factor supernatant on pig performance and ileal microbiota1

2018 ◽  
Vol 2 (2) ◽  
pp. 184-194 ◽  
Author(s):  
Crystal L Levesque ◽  
Nadeem Akhtar ◽  
Evanna Huynh ◽  
Carrie Walk ◽  
Pete Wilcock ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Performance ◽  
Intestinal Microbiota ◽  
Feed Additives ◽  
Gut Health ◽  
Epidermal Growth ◽  
Relative Abundances ◽  
Pig Performance ◽  
The Impact

Abstract Weaning of pigs can lead to low-feed intake resulting in a lag in growth performance, reduced gut health, and diarrheal diseases. Epidermal growth factor (EGF), the most abundant growth factor in milk, increased weaned pig BW gain and feed efficiency in our previous work. It is believed that intestinal microbiota plays an important role in gut health and pig growth, but limited data are available on the impact of feed additives, such as EGF, on the microbial communities of the intestines. The objective of the study was to investigate if the positive influence of EGF supplementation on weight gain and gut health was related to differences in intestinal microbiota. To examine the efficacy of EGF, a 21-d animal trial was performed using 72 pigs (two equal blocks of 36 pigs with three barrows and three gilts/pen). Pigs were assigned to one of two dietary treatments at weaning (20 ± 2 d of age; n = 6 pens/treatment) balancing across treatment for litter, gender, and initial BW. Recombinant yeast supernatant containing EGF at 120 μg/kg BW/d and without EGF (control) was added to the feed for 21 d, followed by a common diet for 7 d. Pig performance was measured weekly and ileal digesta was collected at day 21 from six pigs/treatment for microbiome analysis. Pigs fed diets containing EGF fermentation supernatant had greater (P = 0.01) daily gain in week 3 and overall resulting in heavier (P = 0.029) BW at day 28, which was consistent to our previous finding. No difference in alpha-diversity (Chao1, Shanon, and Simpson indices) and beta-diversity (weighted and unweighted UniFrac distances) of ileal digesta microbiota between EGF supplemented and control pigs were observed. The relative abundances of bacterial taxa did not differ among treatment groups at the phylum level. The relative abundances of Corynebacterium (0.0 vs. 0.9%), Blautia (0.003 vs. 0.26%), and Coprococcus (0.0 vs. 0.05%) genera, and Rumminococcaceae family (0.001 vs. 0.08%) were decreased (P < 0.05) in EGF group compared to control and were negatively correlated (P < 0.05, r > 0.60) with growth performance. Pathways related to detoxification and carbohydrate metabolism were differentially represented in the luminal bacterial populations. The improved growth of pigs supplemented with EGF supernatant produced by Pichia pastoris may be related to changes in functional capacity of the gut microbial populations. However, the impact on mucosa-associated or large intestinal communities is still unknown.

scholarly journals Biallelic MADD variants cause a phenotypic spectrum ranging from developmental delay to a multisystem disorder

Brain ◽  
2020 ◽  
Vol 143 (8) ◽  
pp. 2437-2453
Author(s):  
Pauline E Schneeberger ◽  
Fanny Kortüm ◽  
Georg Christoph Korenke ◽  
Malik Alawi ◽  
René Santer ◽  
...  
Keyword(s):  
Nervous System ◽  
Autonomic Nervous System ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Developmental Delay ◽  
Autonomic Nervous ◽  
Organ Systems ◽  
Tnf Α ◽  
Epidermal Growth ◽  
The Impact

Abstract In pleiotropic diseases, multiple organ systems are affected causing a variety of clinical manifestations. Here, we report a pleiotropic disorder with a unique constellation of neurological, endocrine, exocrine, and haematological findings that is caused by biallelic MADD variants. MADD, the mitogen-activated protein kinase (MAPK) activating death domain protein, regulates various cellular functions, such as vesicle trafficking, activity of the Rab3 and Rab27 small GTPases, tumour necrosis factor-α (TNF-α)-induced signalling and prevention of cell death. Through national collaboration and GeneMatcher, we collected 23 patients with 21 different pathogenic MADD variants identified by next-generation sequencing. We clinically evaluated the series of patients and categorized the phenotypes in two groups. Group 1 consists of 14 patients with severe developmental delay, endo- and exocrine dysfunction, impairment of the sensory and autonomic nervous system, and haematological anomalies. The clinical course during the first years of life can be potentially fatal. The nine patients in Group 2 have a predominant neurological phenotype comprising mild-to-severe developmental delay, hypotonia, speech impairment, and seizures. Analysis of mRNA revealed multiple aberrant MADD transcripts in two patient-derived fibroblast cell lines. Relative quantification of MADD mRNA and protein in fibroblasts of five affected individuals showed a drastic reduction or loss of MADD. We conducted functional tests to determine the impact of the variants on different pathways. Treatment of patient-derived fibroblasts with TNF-α resulted in reduced phosphorylation of the extracellular signal-regulated kinases 1 and 2, enhanced activation of the pro-apoptotic enzymes caspase-3 and -7 and increased apoptosis compared to control cells. We analysed internalization of epidermal growth factor in patient cells and identified a defect in endocytosis of epidermal growth factor. We conclude that MADD deficiency underlies multiple cellular defects that can be attributed to alterations of TNF-α-dependent signalling pathways and defects in vesicular trafficking. Our data highlight the multifaceted role of MADD as a signalling molecule in different organs and reveal its physiological role in regulating the function of the sensory and autonomic nervous system and endo- and exocrine glands.

scholarly journals EGFRAmplification and Glioblastoma Stem-Like Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Katrin Liffers ◽  
Katrin Lamszus ◽  
Alexander Schulte
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Current Knowledge ◽  
Growth Factor Receptor ◽  
Model Systems ◽  
Preclinical Research ◽  
Epidermal Growth ◽  
Methodological Approaches ◽  
The Impact

Glioblastoma (GBM), the most common malignant brain tumor in adults, contains a subpopulation of cells with a stem-like phenotype (GS-cells). GS-cells can be maintainedin vitrousing serum-free medium supplemented with epidermal growth factor, basic fibroblast growth factor-2, and heparin. However, this method does not conserve amplification of the Epidermal Growth Factor Receptor (EGFR) gene, which is present in over 50% of all newly diagnosed GBM cases. GS-cells with retainedEGFRamplification could overcome the limitations of currentin vitromodel systems and contribute significantly to preclinical research on EGFR-targeted therapy. This review recapitulates recent methodological approaches to expand stem-like cells from GBM with differentEGFRstatus in order to maintain EGFR-dependent intratumoral heterogeneityin vitro. Further, it will summarize the current knowledge about the impact ofEGFRamplification and overexpression on the stem-like phenotype of GBM-derived GS-cells and different approaches to target the EGFR-dependent GS-cell compartment of GBM.

scholarly journals Epidermal growth factor receptor pathway as therapeutic development in head and neck cancers: present and future

2011 ◽  
Vol 2 (2) ◽  
pp. 137
Author(s):  
Chancellor E. Donald ◽  
Luis E. Raez ◽  
Edgardo S. Santos
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Head And Neck ◽  
Intracellular Signaling ◽  
Therapeutic Option ◽  
Locally Advanced ◽  
Tyrosine Kinase Domain ◽  
Epidermal Growth ◽  
The Impact ◽  
Human Epidermal Receptor

The understanding of the epidermal growth factor pathway in terms of intracellular signaling and its role in proliferation and cell survival has impacted the therapeutic management of many solid tumor malignancies in which this pathway has been dysregulated. Once the receptor is targeted at its cellular membrane level or tyrosine kinase domain, its blockage induces downregulation of oncogenic and tumorigenesis mechanisms which were in place, and thus inhibits proliferation and induces apoptosis of the malignant cell. Nowadays, we have several monoclonal antibodies as well as small molecules which target the receptor of epidermal growth factor. Although several receptors have been described within the human epidermal receptor family, our discussion will be focused on the impact of human epidermal receptor-1 as a therapeutic option for locally advanced squamous cell carcinoma of the head and neck.

scholarly journals The combination of nutraceuticals and functional feeds as additives modulates gut microbiota and blood markers associated with immune response and health in weanling piglets

2020 ◽  
Vol 98 (8) ◽  
Author(s):  
Luca Lo Verso ◽  
Guylaine Talbot ◽  
Bruno Morissette ◽  
Frédéric Guay ◽  
J Jacques Matte ◽  
...  
Keyword(s):  
Immune Response ◽  
Birth Weight ◽  
Growth Performance ◽  
Intestinal Microbiota ◽  
Mononuclear Cells ◽  
Lactobacillus Reuteri ◽  
Bovine Colostrum ◽  
Feed Additives ◽  
Weanling Piglets ◽  
The Impact

Abstract This study aimed to evaluate the effects of a combination of feed additives with complementary functional properties on the intestinal microbiota, homocysteine, and vitamins E and B status as well as systemic immune response of weanling piglets. At weaning, 32 litters were assigned to one of the following dietary treatments (DT): 1) conventional diet (CTRL); 2) CTRL diet supplemented with antibiotics (ATB); 3) a cocktail of feed additives containing cranberry extract, encapsulated carvacrol, yeast-derived products, and extra vitamins A, D, E, and B complex (CKTL); or 4) CKTL diet with bovine colostrum in replacement of plasma proteins (CKTL + COL). Within each litter, the piglets with lowest and highest birth weights (LBW and HBW, respectively) and two piglets of medium birth weight (MBW) were identified. The MBW piglets were euthanized at 42 d of age in order to characterize the ileal and colonic microbiota. Blood samples were also collected at weaning and at 42 d of age from LBW and HBW piglets to measure insulin-like growth factor-1 (IGF-1), cysteine, homocysteine, and vitamins E, B6, and B12, and to characterize the leukocyte populations. At 42 d of age, cytokine production by stimulated peripheral blood mononuclear cells was also measured. In a second experiment, piglets were reared under commercial conditions to evaluate the effects of the DT on the growth performance. At the indicator species analysis, the highest indicator value (IV) for Succinivibrio dextrinosolvens was found in the CKTL group, whereas the highest IV for Lactobacillus reuteri and Faecalibacterium prausnitzii was evidenced in the CKTL + COL group (P < 0.05). Compared with the other DT, CTRL piglets had higher concentrations of homocysteine, whereas the CKTL and CKTL + COL supplementations increased the concentrations of vitamins E and B12 (P < 0.05). DT had no effect on IGF-1 concentration and on blood leukocytes populations; however, compared with HBW piglets, LBW animals had lower values of IGF-1, whereas the percentages of γδ T lymphocytes and T helper were decreased and increased, respectively (P < 0.05). CKTL + COL also improved the growth performance of piglets reared under commercial conditions (P < 0.05). This study highlights the impact of birth weight on piglet systemic immune defenses and the potential of weaning diet supplemented with feed additives and bovine colostrum to modulate the homocysteine metabolism and the intestinal microbiota.

Sign in / Sign up

Export Citation Format

Share Document