Growth factors最新文献

ABSTRACT/SUMMARYAnti-angiogenics, inhibitors of pathological blood vessel growth, are an important class of targeted agent for the treatment of common cancers and ocular conditions. However, efficacy is compromised by the absence of biomarkers to guide patient selection or inform the management of resistance. We describe an assay for modified endothelial cell (EC) responses to the VEGF-A-neutralizing monoclonal antibody bevacizumab as part of a biomarker discovery program. ECs are transduced by lentivector expressing an experimental or non-silencing shRNA, each co-expressed with a different fluorescent protein. A 1:1 mixed cell population is then cultured with bevacizumab or control antibody under VEGF-A-dependent conditions. A normalized ratio of surviving cells, obtained by flow cytometry analysis, reflects EC resistance or sensitization to bevacizumab mediated by the experimental shRNA. With reagents prepared, the protocol takes 10 days and rigorously quantifies the impact of gene perturbation on the EC response to bevacizumab or other targeted anti-angiogenics.

Oxaloacetate (OA) is a pivotal endogenous metabolite. Within our investigation, we ascertained that OA functions as an agonist for the epidermal growth factor receptor (EGFR), a key protagonist in the genesis of diverse tumours. We substantiated that escalating concentrations of OA initially enhanced the cellular viability of several cancer cells, followed by subsequent attenuation, which is similar to the effect of EGF. Furthermore, the protein phosphorylation profile in HepG2 cells exposed to OA closely paralleled that induced by epidermal growth factor (EGF). Additional findings underscored the capability of OA to induce the generation of EGFR dimers. Finally, our observations revealed that OA governs the activation of AKT and Erk, the typical downstream signalling proteins of EGFR. We postulate that the endogenous metabolite OA can function as either an agonist or inhibitor of EGFR at specific concentrations to modulate tumour proliferation, and provide new insights into the regulation of EGFR activation.

Pancreatic endocrine cells are categorized in to 5 types (alpha, beta, delta, pancreatic polypeptide cells and epsilon), which expresses glucagon, insulin, somatostatin, pancreatic polypeptide, and ghrelin, respectively. Several studies including lineage tracing in Ins2^Akita diabetic mice have been done to investigate the identities of pancreatic endocrine cells which concludes, alpha cells have enormous plasticity, which enables them to be reprogrammed by specific transcription factors into insulin secreting beta like cells. Gene therapy has provided the beneficial outcome. Pdx1, MaFA and PAX4 (the transcription factors) in alpha cells can be over expressed which results in reprogramming the targeted alpha cells into beta cells. This trans-differentiation may be induced by infusing an adeno-associated virus (AAV) loaded with distinct transcription factors in the duct of pancreas. Several researches have demonstrated the successful restoration of enhanced insulin secretion in diabetes induced mice. Additionally ductal neurogenin3 (Ngn3), Sglt2 inhibitors, Igfbp1, GLP1 and several clinical and non-clinical agents has been postulated as a basis of beta cell neogenesis. Alpha cell owing to its high plasticity, on prolonged exposure to GABA reprogrammed into beta-like cell due to downregulation of Arx expression by GABA. The various approaches for beta cell neogenesis open a new window towards the establishment of novel gene therapy accession to treat diabetes. However, broad studies are still needed to improve and optimize this treatment methodology. The potentiality of endogenous pancreatic alpha cell to beta cell conversion methods and its outcomes are invigorating. This accomplishment is presently being under trial in non-human primates.

The study was aimed to investigate the clinical effect and mechanism of Shugan-Jieyu-Jianpi (SGJYJP) formula for the treatment of irritable bowel syndrome (IBS) combined with non-alcoholic fatty liver disease (NAFLD). The clinical efficacy of SGJYJP was evaluated in 54 patients with IBS-NAFLD. The potential molecular mechanism of SGJYJP formula was investigated by network pharmacology. Animal models were constructed to explore the related mechanism. From clinical studies, the total effective rate of patients in SGJYJP group was significantly higher than that in pinaverium group. The protein expression of TGFB1 was declined in IBS-NAFLD rats, together with the increased expression of PTGS2 and TNF, which was abolished by SGJYJP treatment. SGJYJP significantly reduced the expression of TNF signalling related molecules of TRAF2, caspase-8, and elevated the expression of Bcl-xl in IBS-NAFLD animal models. SGJYJP may exert therapeutic effect on IBS-NAFLD by targeting PTGS2, TGFB1, and TNF genes and TNF signalling.

DEAD-box RNA helicase (DDX) is linked to the invasion, drug resistance, proliferation, and epithelial-mesenchymal transition of tumour cells. This study examined the potential mechanisms of DDX49 in breast cancer. The expression of DDX49 in breast cancer tissues and cells was evaluated. The effects of DDX49 on proliferation, invasion, migration and apoptosis of breast cancer cells were evaluated. The expression of proteins associated with the JAK/STAT pathway was examined. A xenograft tumour model was established. DDX49 expression is elevated in breast cancer tissues and cell lines. shDDX49 suppressed the ability of breast cancer cells to proliferate, invade, and migrate, but promoted apoptosis. Conversely, overexpression of DDX49 exerted an opposite effect. The activation of the JAK-STAT signalling pathway is inhibited by the shDDX49. shDDX49 efficiently inhibits tumour growth in mice with breast cancer. shDDX49 may hinder the growth and spread of breast cancer cells by inhibiting the JAK-STAT pathway.

Objective: This study aimed to investigate the effects of super-activated platelet lysate (sPL) on the proliferation, migration, and chondrogenic differentiation of human umbilical cord mesenchymal stem cells (hUCMSCs).

Methods: Cell proliferation and migration assay, enzyme-linked immunosorbent analysis, RT-qPCR, chondrogenic differentiation, and Western blot were performed on sPL-treated hUCMSCs.

Results: The extraction of sPL from PRP yielded a significant release of growth factors. The proliferation of hUCMSCs was significantly enhanced by both 5% and 10% sPL, and the 5% sPL showed the most promising results. Additionally, 10% sPL demonstrated the strongest positive effect on hUCMSC migration. The 20% sPL group showed a significant decrease in inflammatory factor levels compared to the 0% sPL group when hIL-1β was added to the differentiation system. Notably, hUCMSCs in the 5% sPL, 10% sPL and 20% sPL groups displayed excellent chondrogenic differentiation.

Conclusion: In summary, sPL demonstrates the ability to promote stem cell proliferation, migration, and chondrogenic differentiation, while also suppressing inflammation.

Tissue expressed human epidermal growth factor receptor 2 (HER2) is an established parameter of breast cancer, and it is determined in routine clinical practice by histology. This study aims to assess the prognostic value of serum HER2 protein quantified using ELISA in 66 primary breast cancer patients. The median follow-up period was 94 months. Prognostic performance was assessed through receiver operating characteristic (ROC), Cox proportional hazards regression, and Kaplan-Meier analyses. There was a significant difference between serum HER2 levels of patients with and without recurrence. Prognostic associations were significant for age, grade, nodal status, follicle-stimulating hormone, oestradiol, and serum HER2. The cut-off point for serum HER2 levels was 6.0 ng/mL. Recurrence incidence was 29% in the serum HER2^high subgroup, compared to only 10% in the serum HER2^low subgroup. Serum HER2 testing by ELISA holds promise as an additional tool alongside routine tissue HER2 analysis for primary breast cancer patients.

Activated Akt and loss of phosphatase and tensin homolog (PTEN) tumour suppression aid chemo- and radio-resistance in glioblastoma stem cells (GSC), contributing to treatment failure in glioblastoma. In this study, sixteen GSC lines were generated from 66 individual glioma samples, in gliomasphere culture conditions. Thirteen of 16 GSC lines expressed hyperphosphorylated Akt (Ser473); Akt phosphorylation did not correlated with EGFR expression. An LDH colorimetric assay was used to measure the in vitro cytotoxicity of eight of these lines. Akt X (20 µM) proved more effective at inducing in vitro GSC cytotoxicity (range: 22-73%) over 48 hours than triciribine (20 µM) (0-27%), although both agents inhibited Akt phosphorylation as detected by western blot analysis. A statistically significant correlation between PTEN loss (western blot) and the extent of Akt X-induced cytotoxicity was found (p = 0.03). Akt inhibition reduces in vitro proliferation of treatment-resistant GSC lines, especially in PTEN-deficient lines, warranting further translational investigation in glioblastoma.

Since its introduction in 2001, multiple platelet-rich fibrin (PRF) centrifugation protocols have emerged, but the variations in growth factor release that result from these protocols remain unclear. This review aimed to evaluate growth factor release across three PRF protocols: leukocyte-PRF (L-PRF), advanced-PRF (A-PRF/+), and injectable-PRF (i-PRF). A comprehensive search was conducted using the MEDLINE and Embase databases, identifying 14 studies that met the inclusion criteria. Due to significant heterogeneity in study designs and methodologies, a meta-analysis was not feasible. However, our findings suggest that lower-speed centrifugation protocols, such as A-PRF/+ and i-PRF, tend to provide a more uniform cell distribution and sustain higher growth factor release over time compared to the conventional L-PRF protocol. Despite these observations, the current evidence is insufficient to draw definitive conclusions about the growth factor release levels among L-PRF, A-PRF/+, and i-PRF. Further well-designed, comparative studies are required to clarify these differences and establish optimal protocols for clinical use.

Psoriasis pathogenisis remain unknown despite the fact that it is considered as the most common autoimmune skin disease. We raised the hypothesis whether the selected biomarkers in this study provide actual evidence of psoriasis presence and severity. We aim in a first level to study serum level of pro-angiogenic marker VEGF variation and its correlation with MMP-9 and its specific inhibitor TIMP-2 in psoriatic patients serum. The study included 115 psoriatic patients and 51 controls. The biological parameters were measured by ELISA methods. Logistic regression analysis showed that VEGF, MMP-9, and inflammation Z-score are associated with psoriasis. ROC analysis showed that VEGF has low discriminant power for PsVG, However TIMP-2 and inflammation Z-scorewell discriminate this variant of psoriasis. The combined analysis of VEGF-TIMP-2 resulted in a significant increase in discriminant power for PsVG. Increase inflammatory phase may be reflecting the tissue destruction byMMP-9, emphasizing the deleterious expanse and the architectural changes of the skin which are more severe in PsP.