Growth factors最新文献

Human epidermal growth factor (hEGF) is an important therapeutic compound with multiple applications particularly in pharmaceutical industry. Human EGF has already been expressed in different expression systems, however, the production of hEGF with bioactivity in chloroplasts has not been successful so far. In this study, we expressed a 6 × His-tagged hEGF in tobacco chloroplasts in its native conformation for the potential of large-scale production of hEGF for industrial applications. Several transplastomic plant lines were obtained, which were screened by PCR (polymerase chain reaction) using primers specific to selectable gene aadA, hEGF- and GFP-coding sequences that were included in the chloroplast expression vector. The selected lines were confirmed to be homoplasmic by PCR verification and Southern blot analysis. Immunoblotting assays of homoplasmic lines using antibodies raised against hEGF confirmed the accumulation of hEGF in transplastomic plants and the ELISA results demonstrated the expression levels of hEGF were between 0.124% and 0.165% of the total soluble proteins (TSP), namely, 23.16-25.77 ng/g of the fresh weight. In terms of activity, the data from cell proliferation and elongation assays showed that the tobacco-derived recombinant hEGF was as bioactive as its commercial counterpart. To our knowledge, this is the first report of recombinant production of hEGF with native bioactivity form in the chloroplast stroma. Overall, our results demonstrate the potential of higher plant chloroplasts for the production of a human therapeutic, hEGF, in an active conformation.

Propofol is an important and widely used anaesthetic drug in the clinic. Many works have shown that propofol has important biological functions except as an anaesthetic. In the current study, we mainly explored the effect of propofol on the biological activity of IGF-1, which is an important growth factor involved in regulating the growth and development of the stomach. Here, we explored the effect of propofol on the biological activity of IGF-1 in a GES-1-cell model. We found that propofol affected the biological activity of IGF-1. It not only reduces IGF-1/IGF-1R signalling but also changes IGF-1R cell characteristics. We further explored the mechanism by which propofol affected IGF-1 activity. Through a series of experiments, we found that propofol affected the stability of membrane-localised IGF-1R. It also affects the recycling of the IGF-1R receptor Propofol can affect the degradation of IGF-1R by changing the endocytosis of IGF-1R. In short, the current study found that propofol affected the biological activity of IGF-1, which laid the foundation for related research.

Acute myeloid leukemia (AML) is a common malignancy worldwide. Human immune deficiency virus type 1 enhancer-binding protein 3 (HIVEP3) was verified to play a vital role in types of cancers. However, the functional role of HIVEP3 in AML was rarely reported. In this study, CCK-8, colony formation assay, flow cytometry, and Trans-well chamber experiments were applied for detecting cell proliferation, apoptosis, and invasion in AML cells. The expression of proteins related to TGF-β/Smad signaling pathway was determined by western blot. Our data showed that the expression level of HIVEP3 was closely related to the risk classification and prognosis of AML patients. Moreover, HIVEP3 was highly expressed in AML patients and cells. Knockdown of HIVEP3 significantly repressed cell proliferation invasion, and enhanced cell apoptosis in HL-60 and THP-1 cells. In addition, HIVEP3 donwreglation could inhibit the TGF-β/Smad signaling pathway. TGF-β overexpression could reverse the inhibition effects of HIVEP3 knockdown on AML development and the TGF-β/Smad signaling pathway. These findings indicated that HIVEP3 contributed to the progression of AML via regulating the TGF-β/Smad signaling pathway and had a prognostic value for AML.

Platelet-rich blood derivatives are being nowadays increasingly used in the treatment of tendon-related pathologies as a rich source of growth factors. We sought to ascertain if local application of platelet lysate (PL) to augment rotator cuff repair ameliorates patient outcomes compared to ketorolac tromethamine treated group. A total of forty patients, with clinical diagnosis of Rotator Cuff Tendinopathy were randomized to receive sub acromial injections of PL every week for a total of 3 injections and two injection of ketorolac tromethamine once every two weeks. Subjective assessments included VAS, SPADI and shoulder range of motion were assessed at baseline and at 1 and 6 months after injection. Taking both control and PL groups, it was vividly seen that the outcomes were identical at the initial state, as well as the short-term one; whereas, when considering the 6-month period, there is a seemingly remarkable superiority in PL group in all parameters.

This study aimed to explore the specific effect of miR-200c in anaplastic thyroid cancer (ATC). Hth74 and ARO cell lines were used. Proliferation, invasion, and colony formation activities of Hth74 and ARO cell lines affected by miR-200c were studied. Expression of epithelial-to-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, Slug, and Snail) in the Hth74 and ARO cell lines were validated by western blot and qRT-PCR. In addition, the regulation of the parathyroid hormone-like hormone (PTHLH) by miR-200c was assessed. Overexpression of miR-200c inhibited the invasion, proliferation, and colony formation of the ATC cell lines, whereas its downregulation achieved the opposite results. PTHLH was found to be regulated negatively by miR-200c through a miR-200c binding site within the 3'-UTR of PTHLH. miR-200c repressed the proliferation, invasion, and EMT process of cells in ATC cell lines by targeting PTHLH post-transcriptionally, which indicates that miR-200c may be a potential target for the treatment of ATC.

Transforming growth factor beta (TGF-β) plays a complex role in carcinogenesis. In 30 melanoma patients and 20 healthy controls (HC) we analysed functional and phenotypic characteristics of NK cells by Flow cytometry, gene expression of TGF-β1 in peripheral blood mononuclear cells by qPCR and serum and supernatant level of free TGF-β1 by ELISA. Melanoma patients had significantly higher serum level of circulatingTGF-β1 compared to HC, especially those with metastasis into the central nervous system (subclass M1d) and high LDH serum values. Melanoma patients compared to HC had significantly higher level of TGF-β1 gene in PBMC. TGF-β1 serum values negatively correlate with NK cell activity analysed by CD107a (degranulation marker), IFN-γ, NKG2D, and NKp46 in patients. Study shows the association of high level of TGF-β1 with NK cell inhibition in patients represents the main mechanism of tumour immune evasion. Targeting TGF-β may become an important cancer treatment for improving antitumor immunity.

This study was to probe the role of penehyclidine hydrochloride (PHC) mediating the impact of toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) signalling pathway on myocardial ischaemia-reperfusion injury (MI/RI) in rats through miR-199a-3p. The rat MI/RI model was established through ligating left anterior descending (LAD) coronary artery. PHC was injected preoperatively into the model rats, and injected with miR-199a-3p lentiviral vector or TLR4 antagonist (TAK-242). Next, cardiac function of rats was examined by echocardiography, and rat serum indicators, oxidative stress levels and inflammatory factors were detected. HE staining was applied to detect pathological tissue structure, TUNEL staining to detect apoptosis rate, qRCR and western blot to detect miR-199a-3p and TLR4/MyD88/NF-κB expressions in rat myocardial tissues. Dual luciferase reporter experiment was conducted to confirm the relationship between miR-199a-3p and TLR4. In conclusion, PHC suppresses TLR4/MyD88/NF-κB signalling pathway through miR-199a-3p, thereby improving MI/RI in rats.

Type 2 diabetes mellitus (T2DM) is associated with increased atherogenicity and inflammatory responses, which may be related to high mobility group box 1 (HMGB1) and Dickkopf-related protein 1 (DKK1). The role of HMGB1 and DKK1 in T2DM is examined in association with lipid and insulin profiles. Serum HMGB1 and DKK1 were measured in T2DM with and without hypertension and compared with controls. The results showed that HMGB1 and DKK1 are higher in T2DM irrespective of hypertension. A large part of the variance in the β-cell index and glucose toxicity was explained by the combined effects of HMGB1 and DKK1. In conclusion, both HMGB1 and DKK1 may contribute to increased atherogenicity in T2DM. Moreover, both biomarkers may cause more deficits in β-cell function and increase glucose toxicity leading to the development of more inflammation and diabetic complications. HMGB1 and the Wnt pathways are other drug targets in treating T2DM.

This study explored the impacts of matrine on hepatocellular carcinoma (HCC) cell growth, metastasis, epithelial-mesenchymal transition (EMT), and stemness through regulating the microRNA (miR)-299-3p/phosphoglycerate mutase 1 (PGAM1) axis. The association between miR-299-3p expression with the prognosis of HCC patients was studied. miR-299-3p and PGAM1 sequences were transfected into matrine-treated HCC cells, and cell proliferation, invasion, apoptosis, and stemness were detected, as well as protein expression of EMT- and stemness-related makers. The targeting relationship between miR-299-3p and PGAM1 was identified. Matrine elevated miR-299-3p expression, repressed proliferation, invasion, and anti-apoptosis of HCC cells, and constrained EMT and stemness in vitro. PGAM1 was a target of miR-299-3p. Repression of PGAM1 rescued the effects of miR-299-3p downregulation on HCC cells. Matrine stimulates HCC cell apoptosis and represses the process of EMT and stemness through the miR-299-3p/PGAM1 axis.

The present study aimed to explore the effects of antifibrotic agent halofuginone on uterine leiomyomas (ULs) cells. The survival of the uterine smooth muscle (UtSMC) cells and UL ELT3 cells were measured. Flow cytometry was used to assess the cell cycle distribution and apoptosis. Effects of halofuginone on the state of AKT/mTOR pathway were evaluated. Xenograft animal model was applied to explore the effects of halofuginone in vivo. Halofuginone inhibited the proliferation of ELT3 cells dose-dependently without obvious influence on UtSMC cells. Halofuginone suppressed cell cycle progression and promoted apoptosis of ELT3 cells dose-dependently. Also, p-AKT/AKT and p-p70S6/p70S6 were significantly lowered after treatment with 20 nM halofuginone. Additionally, halofuginone reduced ELT3 tumor growth in xenograft tumor animal model. The present study illustrates that halofuginone inhibits cell proliferation of ULs with low side effects on normal smooth muscle cells, and AKT/mTOR signaling pathway was inactivated meanwhile.