scholarly journals Effects of Zinc Ions Released from Ti-NW-Zn Surface on Osteogenesis and Angiogenesis in Vitro and in an in Vivo Zebrafish Model

2021 ◽  
Author(s):  
Wen-qing Zhu ◽  
Kang Li ◽  
Shan Su ◽  
Wei Chen ◽  
Yao Liu ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Signaling Pathway ◽  
Danio Rerio ◽  
Erk Signaling ◽  
Zinc Ions ◽  
Adult Fish ◽  
Zebrafish Model ◽  
Positive Effects

Abstract Objective: Zinc-modified titanium materials have been widely applied in oral implants, among them, our previous studies have also successfully prepared a novel acid-etched micro-structured titanium surface modified with zinc-containing nanowires (Ti-NW-Zn). However, there are very few reports concerned about the biological safeties of zinc ions released from material surface and the appropriate concentration range of released zinc ions which was more conducive to angiogenesis and bone regeneration. Danio rerio (Zebrafish) represents a powerful alternative in vivo model to study both angiogenesis and osteogenesis. Then, the aim of this study is to investigate the effects of zinc ions released from Ti-NW-Zn surfaces on angiogenesis and osteogenesis via zebrafish model, and further revealed the relationship between angiogenesis and osteogenesis via HUVECs and MC3T3-E1s in vitro models.Materials and methods: Tg (Fli‐1:EGFP)y1 zebrafish embryos were used to investigate the in vivo angiogenesis exposure to zinc ions, Wild-type Zebrafish (Danio rerio) adult fish and their embryos were used to investigate the in vivo bone regeneration and survival rate. Cell experiments including proliferation, adhesion, osteogenic differentiation and signaling pathway experiments were carried out by CCK-8, Laser scanning confocal microscope and Western blot, etc. Zinc ion release assay was detected by a Zinc assay kit.Results: The zinc ions released from Ti-NW-Zn surfaces were far lower than median lethal concentrations (LCs) of both embryos and adult fish, which was beneficial to osteogenesis and angiogenesis promotion of zebrafish model. Moreover, the appropriate concentration range of zinc ions was 1-2 ppm in vitro models, which could induce HUVECs proliferations, and the conditioned medium (CM) collected from the supernatant of 1-2 ppm zinc ions-induced HUVECs medium could obviously promote MC3T3-E1 osteoblasts behaviors via activated the MAPK/ERK signaling pathway.Conclusion: Zinc ions released from Ti-NW-Zn surfaces was at a biological safe and appropriate concentration, which could promote the angiogenesis and osteogenesis in vivo and vitro. The positive effects of the appropriate concentration of zinc ions on osteoblast behaviors might be regulated by activating the MAPK/ERK signaling pathway.

scholarly journals High-Pressure Supercritical CO2 Extracts of Ganoderma lucidum Fruiting Body and Their Anti-hepatoma Effect Associated With the Ras/Raf/MEK/ERK Signaling Pathway

2020 ◽  
Vol 11 ◽  
Author(s):  
Liping Zhu ◽  
Min Wu ◽  
Peng Li ◽  
Yanfei Zhou ◽  
Jinyi Zhong ◽  
...  
Keyword(s):  
High Pressure ◽  
Signaling Pathway ◽  
Fruiting Body ◽  
Ganoderma Lucidum ◽  
High Performance ◽  
Erk Signaling ◽  
Human Hepatoma ◽  
Mechanistic Investigation

As a noted medicinal mushroom, Ganoderma lucidum (G. lucidum) has been reported to have a number of pharmacological effects such as anti-tumor and liver protection. Compared with the common ethanol reflux method, supercritical CO2 extraction has obvious advantages in obtaining antitumor extracts from G. lucidum fruiting body such as short extraction time, low temperature and no solvent residue. However, Using high-pressure supercritical CO2 without entrainer to obtain the antitumor extracts from G. lucidum and studying their anti-hepatoma effect have not been reported. In this study, high-pressure supercritical CO2 extracts obtained under 65, 85, and 105 MPa pressure named as G65, G85, G105 respectively and ethanol reflux extract (GLE) were used to investigate their anti-hepatoma activity and the underlying molecular mechanism. The total triterpenoid content of G85 was significantly higher than that of G65 and GLE, but did not differ significantly from that of G105 by UV and high-performance liquid chromatography. GLE, G65, and G85 could inhibit cell proliferation, arrest cell cycle in G2/M phase, and induce apoptosis in two liver cancer cell lines (QGY7703 and SK-Hep1), of which G85 had the strongest effect. The results showed that the potency of their cytotoxicity of the high-pressure supercritical CO2 extracts on human hepatoma carcinoma cells in vitro was consistent with their total triterpenoid content. G85 exhibited significant anti-hepatoma effect with low toxicity In vivo. Further mechanistic investigation revealed that the anti-tumor effect of these extracts was associated with their inhibition of Ras/Raf/MEK/ERK signaling pathway. Our findings suggest that the high-pressure supercritical CO2 extraction of G. lucidum fruiting body can be used to obtain a triterpenoid-rich anti-tumor agent, which may have potential clinical significance for the treatment of human hepatoma.

Scutellarin Attenuates Human-Neutrophil-Elastase-Induced Mucus Production by Inhibiting the PKC-ERK Signaling Pathway in Vitro and in Vivo

2011 ◽  
Vol 39 (06) ◽  
pp. 1193-1206 ◽  
Author(s):  
De-Peng Jiang ◽  
Qi Li ◽  
Jie Yang ◽  
Juliy M. Perelman ◽  
Victor P. Kolosov ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Erk Signaling ◽  
Control Group ◽  
Human Neutrophil Elastase ◽  
Dependent Manner ◽  
Mucus Production

The aim of this study was to investigate the influence of scutellarin on mucus production induced by human neutrophil elastase (HNE) and the possible in vitro and in vivo mechanisms. To this purpose, cells were incubated with saline, scutellarin or gefitinib for 60 min and exposed to 0.1 μM HNE for 24 h. After being pretreated respectively with saline, scutellarin or gefitinib, rats were challenged intratracheally with HNE by means of nebulization for 30 days. The expression of mucin (MUC) 5AC, protein kinase C (PKC), and extracellular signal-regulated kinase 1/2 (ERK1/2) was assessed by ELISA, RT-PCR or Western blotting. The results showed that scutellarin inhibited MUC5AC mRNA and protein expressions induced by HNE in a concentration-dependent manner in vitro. In the in vivo model, scutellarin significantly attenuated MUC5AC mRNA expression and goblet cell hyperplasia in rats treated with HNE for 30 days, as well as decreased the phosporylation of PKC and ERK1/2 compared to the HNE control group. Therefore, our study showed that scutellarin could prevent mucus hypersecretion by inhibiting the PKC-ERK signaling pathway. Inhalation scutellarin may be valuable in the treatment of chronic inflammatory lung disease.

scholarly journals Telocytes Promote the Metastasis of Hepatocellular Carcinoma by Activating ERK Signaling Pathway and Sponging miR-942-3p to Impact MMP9

2021 ◽  
Author(s):  
Ying Xu ◽  
Hu Tian ◽  
Chao Guang Luan ◽  
Kai Sun ◽  
peng Jin Bao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Signaling Pathway ◽  
Erk Signaling ◽  
Cancer Tissue ◽  
Proliferative Potential ◽  
Cancer Tissues ◽  
Hcc Cells

Abstract Background: Hepatocellular carcinoma(HCC) in China is considered as a familiar malignant tumor with poor prognosis, high metastasis and disease relapse. Telocytes(TCs) have been verified to participate in progresses of tumorigenesis, invasions and migrations by secreting functional proteins and transmitting cell-to-cell information. Extracellular signal-regulared protein kinase(ERK) signal pathway is a vital mechanism driving cell proliferation, metastasis and apoptosis, but whether this molecular signaling mechanism contributes to matrix metalloproteinase-9(MMP) expression of TCs remains unclear. Methods: Telocytes and MMP9 expression in the liver cancer tissues are measured by immunohistochemistry assay, Westen blot assay and RT-PCR technique, meanwhile primary telocytes from liver para-cancer tissues are cultured in vitro. To demonstrate the function of telocytes for hepatocellular carcinoma, the metastatic cancer animal model is established by three typs of liver cancer cell-lines in vivo. Results: In our study, we elucidate that TCs in the para-cancer tissue can promote the metastasis of HCC cells by MMP-9 expression, in vitro and in vivo. PDGF derived from HCC cells has a capacity to activate Ras/ERK signaling pathway of TC as a result of accelerating MMP-9 expression, but it’s no significant for proliferative potential and apoptotic rate of TCs. While tyrosine kinase inhibitors and miR-942-3p suppress MMP-9 expression to make loss functions of TCs. Various mutations of TCs are also tested and single nucleotide polymorphisms of MMP-9 may be the potentially molecular mechanism of increasing protein expression in the invasive process of HCC. Conclusion: Our results demonstrate two potential mechanisms between HCC cells and TCs, suggesting that TC is a novel marker and target on deciphering reasons of cancer metastasis.

scholarly journals Schisantherin A Inhibits Pulmonary Fibrosis via Regulating ERK Signaling Pathway

2020 ◽  
Vol 15 (8) ◽  
pp. 1934578X2094835
Author(s):  
Wenyue Zhuang ◽  
Na Zhao ◽  
Di Li ◽  
Xiaoming Su ◽  
Yueyang Wang ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Western Blot ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Erk Signaling ◽  
Mesenchymal Transition ◽  
Tgf Β1 ◽  
Schisantherin A

There is no effective method for treating pulmonary fibrosis (PF) until now. This study investigated the anti-fibrotic effect of schisantherin A (SCA) extracted from Schisandra chinensis and its potential molecular mechanism in PF. A bleomycin-induced PF mouse model in vivo and transforming growth factor (TGF)-β1-induced A549 epithelial-mesenchymal transition (EMT) cell model in vitro were used for assessing the anti-fibrotic effect of SCA. Histopathological examination was conducted after hematoxylin and eosin and Masson staining. The level of TGF-β1 was tested by ELISA. The expression levels of α-smooth muscle actin, E-cadherin, and inflammatory cytokines (COX2, IL-1β, IL-6, and TNF-α) were determined by quantitative reverse transcription polymerase chain reaction and Western blot. The expression of extracellular signal-regulated kinase (ERK) was tested in lung tissues and cells by Western blot. The in vivo experiments revealed that SCA treatment markedly improved body weight and pulmonary index and reformed the destruction of the lung tissue structure. We observed that SCA inhibited the process of TGF-β1-induced EMT in the in vitro experiments. Inflammatory cytokines were reduced greatly in lung tissues and cells by SCA. Our study also indicated that SCA decreased phosphorylated ERK. It was concluded that SCA can attenuate PF by regulating the ERK signaling pathway, which suggests that SCA may be used as a potential therapeutic drug for PF.

scholarly journals REG3A/REG3B promotes acinar to ductal metaplasia through binding to EXTL3 and activating the RAS-RAF-MEK-ERK signaling pathway

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Huairong Zhang ◽  
Andrea Liliam Gomez Corredor ◽  
Julia Messina-Pacheco ◽  
Qing Li ◽  
George Zogopoulos ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Signaling Pathway ◽  
3D Culture ◽  
Intraepithelial Neoplasia ◽  
Erk Signaling ◽  
Ductal Adenocarcinoma ◽  
Human Pancreas ◽  
Acinar To Ductal Metaplasia

AbstractPersistent acinar to ductal metaplasia (ADM) is a recently recognized precursor of pancreatic ductal adenocarcinoma (PDAC). Here we show that the ADM area of human pancreas tissue adjacent to PDAC expresses significantly higher levels of regenerating protein 3A (REG3A). Exogenous REG3A and its mouse homolog REG3B induce ADM in the 3D culture of primary human and murine acinar cells, respectively. Both Reg3b transgenic mice and REG3B-treated mice with caerulein-induced pancreatitis develop and sustain ADM. Two out of five Reg3b transgenic mice with caerulein-induced pancreatitis show progression from ADM to pancreatic intraepithelial neoplasia (PanIN). Both in vitro and in vivo ADM models demonstrate activation of the RAS-RAF-MEK-ERK signaling pathway. Exostosin-like glycosyltransferase 3 (EXTL3) functions as the receptor for REG3B and mediates the activation of downstream signaling proteins. Our data indicates that REG3A/REG3B promotes persistent ADM through binding to EXTL3 and activating the RAS-RAF-MEK-ERK signaling pathway. Targeting REG3A/REG3B, its receptor EXTL3, or other downstream molecules could interrupt the ADM process and prevent early PDAC carcinogenesis.

scholarly journals pERK-mediated IL8 secretion can enhance the migration, invasion, and cisplatin resistance of CD10-positive oral cancer cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yinfei Pu ◽  
Qingxiang Li ◽  
Yifei Wang ◽  
Le Xu ◽  
Qiao Qiao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Oral Cancer ◽  
Cancer Stem Cells ◽  
Signaling Pathway ◽  
Cisplatin Resistance ◽  
Erk Signaling ◽  
Spheroid Formation ◽  
Oral Cancer Cells

Abstract Background Cancer stem cells (CSCs) drive tumor initiation and progression and participate in tumor chemoresistance. We recently discovered that oral squamous cell carcinoma (OSCC) cells that highly express CD10 (CD10H cells) present cancer stem cells (CSC)-associated characteristics, which, in turn, affect the tumor growth, epithelial-mesenchymal transition (EMT), and resistance to cisplatin. In this study, we further investigated this mechanism in vitro and in vivo. We hypothesized that IL8 might regulate migration, invasion, and cisplatin resistance of CD10-positive oral cancer cells through the ERK pathway. Methods CD10 MicroBead Kit was used to select HN6 cells with high and low expression of CD10. The target protein IL8 was screened via protein chip assay. Lentiviral transduction and specific inhibitor were applied to investigate the signaling pathway. Real-time PCR, Western blot, and immunohistochemistry were used to analyze the mRNA and protein expression; transwell assay, spheroid formation assay, and cell viability assay were used to study the cell biological behavior in vitro; xenograft animal model was used to evaluate the tumor formation rate in vivo. Results Overexpression of CD10 promoted CSC-related genes expression and enhanced migration, invasion, spheroid formation, and chemoresistance in HN6 cells. Moreover, the overexpression of IL8 was detected in OSCC tumor tissue and cell lines (HN6 and CAL27) overexpressing CD10. IL8 secreted by CD10H HN6 promoted migration and invasion and restored tumor chemosensitivity via the p-ERK signaling pathway, while the inhibition of IL8 increased the chemosensitivity to cisplatin. Conclusions IL8 secretion by CD10 positive cells promotes migration, invasion, and cisplatin resistance of OSCC via the p-ERK signaling pathway.

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