Growth factors最新文献

Background: "Quantile-dependent expressivity" occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g. growth factor concentration) is high or low relative to its distribution.

Methods: Quantile-regression analysis was applied to family sets from the Framingham Heart Study to determine whether the heritability (h²) of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), angiopoietin-2, and angiopoietin-2 (sTie-2) and VEGFR1 (sFlt-1) receptor concentrations were quantile-specific.

Results: Quantile-specific h² (±SE) increased with increasing percentiles of the age- and sex-adjusted VEGF (P_trend<10^-16), HGF (P_trend=0.0004), angiopoietin-2 (P_trend=0.0002), sTie-2 (P_trend=1.2 × 10^-5), and sFlt-1 distributions (P_trend=0.04).

Conclusion: Heritabilities of VEGF, HGF, angiopoitein-2, sTie-2 and sFlt-1 concentrations are quantile dependent. This may explain reported interactions of genetic loci (rs10738760, rs9472159, rs833061, rs3025039, rs2280789, rs1570360, rs2010963) with metabolic syndrome, diet, recurrent miscarriage, hepatocellular carcinoma, erysipelas, diabetic retinopathy, and bevacizumab treatment in their effect on VEGF concentrations.

The BMP6 protein (Bone Morphogenetic Protein 6) is part of the superfamily of transforming growth factor-beta (TGF-β) ligands, participates in iron homeostasis, inhibits invasion by increasing adhesions and cell-cell type interactions and induces angiogenesis directly on vascular endothelial cells. BMP6 is coded by a tumor suppressor gene whose subexpression is related to the development and cancer progression; during neoplastic processes, methylation is the main mechanism by which gene silencing occurs. This work presents a review on the role of BMP6 protein in breast cancer (BC) and other types of cancer. The studies carried out to date suggest the participation of the BMP6 protein in the epithelial-mesenchymal transition (EMT) phenotype, cell growth and proliferation; however, these processes are affected in a variable way in the different types of cancer, the methylated CpG sites in BMP6 gene promoter, as well as the interaction with other proteins could be the cause of such variation.

Vasomotor tone-associated factors play important roles in normal pregnancy, but their roles in the pregnancy outcome of women who undergo in vitro fertilization and embryo transfer (IVF-ET) remain unclear. A total of 82 infertile women who underwent successful IVF-ET were enrolled, including 18 pregnancy losses, 11 complications, and 53 normal deliveries. The serum NO and iNOS levels were significantly higher in the pregnancy loss group and significantly lower in the complication group than in the normal delivery group (p < 0.05). Significantly increased ET-1 and decreased PGI2 were found in both the pregnancy loss and complication groups compared with those in the normal delivery group (p < 0.05). NO, iNOS, and ET-1 are risk factors and PGI2 is a protective factor for pregnancy loss. ET-1 + PGI2 (AUC, 0.897; sensitivity, 90.6%; specificity, 83.3%) showed a relatively good predictive value for pregnancy loss following IVF-ET.

Utilising rabbit corneal endothelial cells (CEC) in three different paradigms, two human FGF1 derivatives (TTHX1001 and TTHX1114), engineered to exhibit greater stability, were tested as proliferative agents. Primary CECs and mouse NIH 3T3 cells treated with the two FGF1 derivatives showed equivalent EC₅₀ ranges (3.3-24 vs.1.9-16. ng/mL) and, in organ culture, chemically lesioned corneas regained half of the lost endothelial layer in three days after treatment with the FGF1 derivatives as compared to controls. In vivo, following cryolesioning, the CEC monolayer, as judged by specular microscopy, regenerated 10-11 days faster when treated with TTHX1001. Over two weeks, all treated eyes showed clearing of opacity about twice that of untreated controls. In all three rabbit models, both FGF1 derivatives were effective in inducing CEC proliferation over control conditions, supporting the prediction that these stabilised FGF1 derivatives can potentially regenerate corneal endothelial deficits in humans.

Meterorin-like hormone (Metrnl), as a novel secreted factor, has been shown to be involved in physiological and pathophysiological processes. The behaviour of Metrnl in metabolic conditions like type 2 diabetes is conflicting. Metrnl-mediated (treatment with Metrnl) auto/paracrine actions in skeletal muscle are glucose uptake, fat oxidation and muscle regeneration. Exercise-induced Metrnl actions are increased fat oxidation in both skeletal muscle and adipose tissue, the control of inflammation in adipose tissue (metainflammation), and the regulation of muscle regeneration. Based on the current knowledge, Metrnl as a myokine can establish the muscle-fat crosstalk; however, the ability of Metrnl as a myokine to create other crosstalks remains unclear yet. Additionally, given the considerable anti-inflammatory roles of Metrnl in muscle regeneration, it could be a potential therapeutic candidate for muscle-related inflammatory diseases and ageing skeletal muscle which need to be addressed in the future studies.

Fibroblast growth factor (FGF) family has a wide range of metabolic processes. FGF21 exerts critical physiological functions in clinical application. This study aimed to explore a convenient and highly efficient approach for rhFGF21 expression using TMV-TES. Firstly, the vector pTTEV-GFP was constructed, followed by optimisation of the expression parameters in Nicotiana benthamiana. Then, the rhFGF21 encoding gene harbouring vector pTTEV-rhFGF21 was constructed. Agrobacterium-mediated vacuum infiltration was performed with the optimised parameters and the expression of rhFGF21 was confirmed by the immunoblotting analysis. ELISA revealed that the protein accumulation of rhFGF21 accounts for 0.11% of total soluble proteins. The biological activity was evaluated and the results suggested that tobacco-expressed rhFGF21 could stimulate the glucose uptake in swiss 3T3-L1 adipocytes, which was similar to the activity of commercial products, suggesting its native biological activity. Therefore, using TMV-TES to express rhFGF21 will be a feasible approach for the mass production of rhFGF21.

Autologous conditioned serum (ACS) is a blood-derived product that is prepared by the incubation of whole blood with medical-grade glass beads, resulting in serum enrichment in interleukin-1 receptor antagonist (IL-1Ra), anti-inflammatory cytokines (IL-4, IL-10, and IL-13), and high concentrations of growth factors. ACS has shown qualitatively and quantitatively better therapeutic effects than most established pharmacological treatments and surgery for joint diseases given its ability to both target the inflammatory cascade to decrease cartilage destruction as well as improve endogenous repair mechanisms. ACS application is simple and safe with limited adverse effects. This article reviews the role of ACS in degenerative joint disease, in addition to other inflammatory and autoimmune diseases, given its regenerative and immune-modulating properties.