Growth factors最新文献

Fibroblast growth factor 2 (FGF-2) is a multifunctional protein that has major roles in wound healing, tissue repair, and regeneration. This therapeutic protein is widely used for burn treatment because it can stimulate cell proliferation and differentiation, angiogenesis, and extracellular matrix remodeling. In this study, we developed a simple method using a controlled heated brass rod to create a homogenous third-degree burn murine model and evaluated the treatment using recombinant human FGF-2 (rhFGF-2). The results indicated that the wound area was 0.83 ± 0.05 cm² and wound depth was 573.42 ± 147.82 μm. Mice treated with rhFGF-2 showed higher rates of wound closure, granulation tissue formation, angiogenesis, and re-epithelialization than that of phosphate-buffered saline (PBS)-treated group. In conclusion, our lab-made rhFGF-2 could be a potentially therapeutic protein for burn treatment as well as a bioequivalent drug for other commercial applications using FGF-2.

Gestational diabetes mellitus (GDM) constitutes an unfavorable intrauterine environment for embryonic and feto-placental development. Women with GDM are at higher risk for materno-fetal complications and placental abnormalities. The placenta acts as an interface between the maternal and fetal circulations and also plays an important role in protecting the fetus from adverse effects of maternal metabolic conditions. One of the earliest abnormalities observed in GDM pregnancies is increased oxidative stress in the placenta which affects fetal development. Imbalances in maternal nutrition particularly long-chain polyunsaturated fatty acid (LCPUFA) intake and/or metabolism lead to increased oxidative stress. Reports indicate that oxidative stress and LCPUFA such as docosahexaenoic acid affect the levels of neurotrophins. The present review aims to provide insights into a mechanistic link between oxidative stress, LCPUFA and neurotrophin in the placenta in women with GDM and its implications for neurodevelopmental outcomes in children.

Cell entry of influenza A virus (IAV) was reported to be promoted by epidermal growth factor receptor (EGFR). On the other hand, binding of heparin-binding EGF-like growth factor (HB-EGF) to EGFR leads to internalisation and degradation of the receptors. This study aimed to testify whether or not HB-EGF-induced downregulation of EGFR could attenuate IAV cell entry and subsequently diminish the infection. Immunoblotting and plaque assay revealed that HB-EGF-induced degradation of EGFR led to reduction of viral matrix 1 protein level and suppressed virion production. In addition, immunoblotting and imaging flow cytometric analysis demonstrated that IAV-induced phosphorylation of STAT1 and its localisation to nucleus in the early stage of infection were inhibited by HB-EGF treatment. This suggested the potential of HB-EGF in modulating uncontrolled and exaggerated inflammatory response caused by IAV infection. Together these findings attest the potential of HB-EGF mediated endocytosis and degradation of EGFR as a novel anti-IAV strategy.

Platelet-rich plasma (PRP) is a therapeutic option in different fields based on its growth factors. We investigated influence of PRP on islet survival, function, transplantation outcomes, and pancreatic genes expression in diabetic rats. In vitro: pancreatic isolated islets were incubated with/without PRP then viability, insulin secretion, and content were assessed. In vivo: Series 1 were designed to determine whether islet treatment with PRP improves transplantation outcome in diabetic rats by evaluating plasma glucose and insulin concentrations and oxidative parameters. Series 2, effects of PRP subcutaneous injection were evaluated on pancreatic genes expression and glucose tolerance test in diabetic rats. PRP enhanced viability and secretary function of islet. Reduced glucose and malondialdehyde levels as well as increased insulin levels, superoxide dismutase activity, and expressions of pdx1 and insulin were observed in diabetic rats. PRP treatment has positive effects on islet viability, function, transplantation outcome, and pancreatic genes expression in diabetic rats.

For patients with metastatic colorectal cancer (mCRC), epidermal growth factor receptor (EGFR) inhibitors are limited to patients with RAS wild-type tumours. Not all patients will benefit from treatment and better predictive biomarkers are needed. Here we investigated the prognostic and predictive impact of the EGFR ligands amphiregulin (AREG) and epiregulin (EREG). Expression levels were assessed by immunohistochemistry on 99 KRAS wild-type tumours. AREG and EREG positivity was seen in 49% and 50% of cases, respectively. No difference in expression was observed by primary tumour side. There was no significant difference in OS by AREG or EREG expression. In the subset of patients who received an EGFR inhibitor, EREG positivity was associated with longer OS (median 34.0 vs. 27.0 months, p = 0.033), driven by a difference in patients with a left-sided primary (HR 0.37, p = 0.015). Our study supports further investigation into EREG as a predictive biomarker in mCRC.

Platelets contain most of the potent mitogenic factors present in serum and follicular fluid and intraovarian injection of autologous platelet rich plasma (PRP) was shown to improve ovarian function and development of preantral follicles. This study evaluated the effect of PRP on caprine oocyte maturation in vitro and subsequent fertilization and embryonic development. Cumulus oocyte complexes were cultured in a maturation medium supplemented with (1) fetal bovine serum (FBS, control), (2) PRP, extracted from healthy female goats, (3) polyvinyl alcohol (PVA), and (4) PVA plus PRP (PVA-PRP). The degree of cumulus expansion was scored, and denuded oocytes were used for assessment of nuclear maturation, mitochondrial activity, lipid content, redox status, yield and quality of in vitro embryo development, and cryosurvival of the resulting blastocysts. PRP supported the same beneficial effects of FBS on cumulus expansion, nuclear maturation, in vitro developmental competence of oocytes, and survival of vitrified-warmed blastocysts. Moreover, PRP protected oocytes from undesirable effects FBS exerted on the mitochondrial activity and intracytoplasmic lipid content of maturing oocyte. Although PVA could support the same beneficial effects of neither FBS nor PRP on oocyte maturation, its combined addition with PRP improved the yield and quality of oocyte maturation at rates closely similar to PRP. PRP efficiently substitutes beneficial effects of serum during in vitro oocyte maturation and helps maintain the mitochondrial activity of maturing oocytes.

Fibroblast growth factor 10 functions as a paracrine mesenchymal molecule to initiate signalling pathways regarding to cellular development and health. However, the low thermal stability restricts it's functionality in the human body and the shelf-life of FGF10-based formulations. The current study aimed to employ rational design and bioinformatics approaches to identify some point mutations which may improve the thermal stability of FGF10. Bioinformatics analyses resulted in N105D, C106F, K144R, K153M and I156R as the potential stability conferring mutations. The identified mutants were subjected to MD simulation indicating that all mutations are both structurally and energetically favoured. Finally, the effects of the identified mutations on receptor binding of FGF10 were predicted and the results showed that K144R and K153M mutations may increase the binding affinity relative to the wild type. The findings of the current study propose potentially improved FGF10 analogues for further experimental investigations.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is highly expressed in the brain. It influences neuronal survival, growth and acts as a control centre for neurotransmitters. It also plays a crucial role in learning and memory. Current evidence indicates that BDNF may be a possible neurotrophic factor that controls cognitive functions under normal and neuropathological conditions. Recent findings indicate a reduction in cognitive performance in individuals with Alzheimer's disease (AD). This relationship between cognitive performance and AD is important for investigating both the time they overlap and the pathophysiological mechanism in each case. Therefore, this study reviewed the existing knowledge about BDNF and cognitive performance in the AD population. The findings support the idea that this tropic factor may be a potential biomarker for evaluating the changes in cognitive performance in AD.

Growth hormone (GH), in addition to its classic actions on growth and metabolism in the body, exerts pleiotropic effects on the immune system, particularly on the thymus. The aim of this study was to evaluate the influence of GH on the interactions between mature thymocytes and the thymic endothelium involved in the migratory process. To this end, fresh thymocytes (C57BL/6 mice) and the thymic endothelial cell line (tEnd.1) were used. In the cell adhesion assay, the GH-treated thymocytes adhered more to tEnd.1 cells. Additionally, there was an improvement in the deposition of fibronectin by tEnd.1 cells when co-cultured with GH-pre-treated thymocytes. Furthermore, GH induced thymocyte F-actin polymerization. In the transendothelial migration assay, a large number of GH-treated thymocytes, mainly the CD4^-CD8⁺ subset, migrated towards the endothelium under the stimulus of insulin-like growth factor 1. In conclusion, we demonstrated the positive actions of GH in thymocyte/thymic endothelium interactions, including transendothelial migration.

Individuals suffering from cancer, including hematological malignancies, are at increased risk of cardiovascular disease (CVD). Elevated levels of several biomarkers in blood are associated with an increased risk of CVD. The aim of this study was to investigate whether a subset of such CVD risk biomarkers was elevated in patients with untreated chronic lymphocytic leukemia (CLL). Blood plasma and serum from 139 CLL patients and 71 healthy age-matched controls were analyzed for 11 proposed CVD risk biomarkers. The CLL cohort displayed a more heterogeneous pattern of biomarker expression compared to controls. The majority, eight out of 11, analyzed CVD risk biomarkers differed significantly in concentrations between CLL patients and controls. Increased levels of the biomarkers GDF15 and myostatin have not previously been reported in CLL. Further prospective studies are warranted to investigate whether these biomarkers predict future cardiovascular events in patients with CLL.