Exposure interval to ambient fine particulate matter (PM2.5) collected in Southwest China induced pulmonary damage through the Janus tyrosine protein kinase‐2/signal transducer and activator of transcription‐3 signaling pathway both in vivo and in vitro

Astaxanthin (AXT), a xanthophyll carotenoid compound, has potent antioxidant, anti-inflammatory and neuroprotective properties. Neuroinflammation and oxidative stress are significant in the pathogenesis and development of Alzheimer’s disease (AD). Here, we studied whether AXT could alleviate neuroinflammation, oxidative stress and memory loss in lipopolysaccharide (LPS) administered mice model. Additionally, we investigated the anti-oxidant activity and the anti-neuroinflammatory response of AXT in LPS-treated BV-2 microglial cells. The AXT administration ameliorated LPS-induced memory loss. This effect was associated with the reduction of LPS-induced expression of inflammatory proteins, as well as the production of reactive oxygen species (ROS), nitric oxide (NO), cytokines and chemokines both in vivo and in vitro. AXT also reduced LPS-induced β-secretase and Aβ1–42 generation through the down-regulation of amyloidogenic proteins both in vivo and in vitro. Furthermore, AXT suppressed the DNA binding activities of the signal transducer and activator of transcription 3 (STAT3). We found that AXT directly bound to the DNA- binding domain (DBD) and linker domain (LD) domains of STAT3 using docking studies. The oxidative stress and inflammatory responses were not downregulated in BV-2 cells transfected with DBD-null STAT3 and LD-null STAT3. These results indicated AXT inhibits LPS-induced oxidant activity, neuroinflammatory response and amyloidogenesis via the blocking of STAT3 activity through direct binding.

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In vivo and in vitro inflammatory responses to fine particulate matter (PM2.5) from China and California

Toxicology Letters ◽

10.1016/j.toxlet.2020.04.010 ◽

2020 ◽

Vol 328 ◽

pp. 52-60 ◽

Cited By ~ 1

Author(s):

Wanjun Yuan ◽

Ciara C. Fulgar ◽

Xiaolin Sun ◽

Christoph F.A. Vogel ◽

Ching-Wen Wu ◽

...

Keyword(s):

Particulate Matter ◽

Inflammatory Responses ◽

Fine Particulate Matter ◽

Fine Particulate

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Splicing factor hnRNPA2B1 contributes to tumorigenic potential of breast cancer cells through STAT3 and ERK1/2 signaling pathway

Tumor Biology ◽

10.1177/1010428317694318 ◽

2017 ◽

Vol 39 (3) ◽

pp. 101042831769431 ◽

Cited By ~ 22

Author(s):

Ying Hu ◽

Zihan Sun ◽

Jinmu Deng ◽

Baoquan Hu ◽

Wenting Yan ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Signal Transducer ◽

Extracellular Signal Regulated Kinase ◽

Extracellular Signal ◽

Tumorigenic Potential ◽

Transcription 3

Increasing evidence has indicated that the splicing factor hnRNPA2B1 plays a direct role in cancer development, progression, gene expression, and signal transduction. Previous studies have shown that knocking down hnRNPA2B1 in breast cancer cells induces apoptosis, but the mechanism and other functions of hnRNPA2B1 in breast cancer are unknown. The goal of this study was to investigate the biological function, clinical significance, and mechanism of hnRNPA2B1 in breast cancer. The expression of hnRNPA2B1 in 92 breast cancer and adjacent normal tissue pairs was analyzed by immunohistochemical staining. Stable clones exhibiting knockdown of hnRNPA2B1 via small hairpin RNA expression were generated using RNA interference technology in breast cancer cell lines. The effects of hnRNPA2B1 on cell proliferation were examined by MTT and EdU assay, and cellular apoptosis and the cell cycle were examined by flow cytometry. A nude mouse xenograft model was established to elucidate the function of hnRNPA2B1 in tumorigenesis in vivo. The role of hnRNPA2B1 in signaling pathways was investigated in vitro. Our data revealed that hnRNPA2B1 was overexpressed in breast cancer tissue specimens and cell lines. Knockdown of hnRNPA2B1 reduced breast cancer cell proliferation, induced apoptosis, and prolonged the S phase of the cell cycle in vitro. In addition, hnRNPA2B1 knockdown suppressed subcutaneous tumorigenicity in vivo. On a molecular level, hnRNPA2B1 knockdown decreased signal transducer and activator of transcription 3 and extracellular-signal-regulated kinase 1/2 phosphorylation. We concluded that hnRNPA2B1 promotes the tumorigenic potential of breast cancer cells, MCF-7 and MDA-MB-231, through the extracellular-signal-regulated kinase 1/2 or signal transducer and activator of transcription 3 pathway, which may serve as a target for future therapies.

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The Neurofibromatosis Type 1 Tumor Suppressor Controls Cell Growth by Regulating Signal Transducer and Activator of Transcription-3 Activity In vitro and In vivo

Yearbook of Oncology ◽

10.1016/s1040-1741(10)79527-0 ◽

2010 ◽

Vol 2010 ◽

pp. 175-176

Author(s):

R.J. Arceci

Keyword(s):

Cell Growth ◽

Tumor Suppressor ◽

Neurofibromatosis Type 1 ◽

Neurofibromatosis Type ◽

Signal Transducer ◽

Transcription 3

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A Preclinical Investigation of GBM-N019 as a Potential Inhibitor of Glioblastoma via Exosomal mTOR/CDK6/STAT3 Signaling

Cells ◽

10.3390/cells10092391 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2391

Author(s):

Alexander T. H. Wu ◽

Hsu-Shan Huang ◽

Ya-Ting Wen ◽

Bashir Lawal ◽

Ntlotlang Mokgautsi ◽

...

Keyword(s):

Mammalian Target Of Rapamycin ◽

Treatment Resistance ◽

Signaling Networks ◽

Drug Candidate ◽

Signal Transducer ◽

Cyclin Dependent Kinase ◽

Stat3 Signaling ◽

Transcription 3

Glioblastoma (GBM) is one of the most aggressive brain malignancies with high incidences of developing treatment resistance, resulting in poor prognoses. Glioma stem cell (GSC)-derived exosomes are important players that contribute to GBM tumorigenesis and aggressive properties. Herein, we investigated the inhibitory roles of GBM-N019, a novel small molecule on the transfer of aggressive and invasive properties through the delivery of oncogene-loaded exosomes from GSCs to naïve and non-GSCs. Our results indicated that GBM-N019 significantly downregulated the expressions of the mammalian target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3), and cyclin-dependent kinase 6 (CDK6) signaling networks with concomitant inhibitory activities against viability, clonogenicity, and migratory abilities of U251 and U87MG cells. Treatments with GBM-N019 halted the exosomal transfer of protein kinase B (Akt), mTOR, p-mTOR, and Ras-related protein RAB27A to the naïve U251 and U87MG cells, and rescued the cells from invasive and stemness properties that were associated with activation of these oncogenes. GBM-N019 also synergized with and enhanced the anti-GBM activities of palbociclib in vitro and in vivo. In conclusion, our results suggested that GBM-N019 possesses good translational relevance as a potential anti-glioblastoma drug candidate worthy of consideration for clinical trials against recurrent glioblastomas.

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The Neurofibromatosis Type 1 Tumor Suppressor Controls Cell Growth by Regulating Signal Transducer and Activator of Transcription-3 Activity In vitro and In vivo

Cancer Research ◽

10.1158/0008-5472.can-09-2178 ◽

2010 ◽

Vol 70 (4) ◽

pp. 1356-1366 ◽

Cited By ~ 47

Author(s):

S. Banerjee ◽

J. N. Byrd ◽

S. M. Gianino ◽

S. E. Harpstrite ◽

F. J. Rodriguez ◽

...

Keyword(s):

Cell Growth ◽

Tumor Suppressor ◽

Neurofibromatosis Type 1 ◽

Neurofibromatosis Type ◽

Signal Transducer ◽

Transcription 3

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Interleukin-11 Promotes Migration, But Not Proliferation, of Human Trophoblast Cells, Implying a Role in Placentation

Endocrinology ◽

10.1210/en.2007-0517 ◽

2007 ◽

Vol 148 (11) ◽

pp. 5566-5572 ◽

Cited By ~ 53

Author(s):

Premila Paiva ◽

Lois A. Salamonsen ◽

Ursula Manuelpillai ◽

Claire Walker ◽

Alejandro Tapia ◽

...

Keyword(s):

First Trimester ◽

Extravillous Trophoblast ◽

Hybridoma Cells ◽

Adult Health ◽

Signal Transducer ◽

Human Trophoblast ◽

And Migration ◽

Transcription 3

Trophoblast growth and invasion of the uterine endometrium are critical events during placentation and are tightly regulated by factors produced within the trophoblast-endometrial microenvironment. Deficiencies in placentation can result in early miscarriage or preeclampsia and intrauterine growth restriction, leading to impaired fetal health. The latter has been linked to major adult health disorders. IL-11 is essential for blastocyst implantation in mice. In humans, IL-11 and its receptor IL-11 receptor α (IL-11Rα) are maximally expressed in the decidua and chorionic villi during early pregnancy; however, the role of IL-11 in trophoblast function is unknown. Therefore, we examined whether IL-11Rα is expressed in human first trimester implantation sites, and whether IL-11 influences proliferation and migration of a human extravillous trophoblast (EVT)-hybridoma cell line and primary EVT cells, used as models for EVT. Immunoreactive IL-11Rα localized to subpopulations of interstitial and endovascular EVT cells in vivo. In EVT cells in vitro, IL-11: 1) stimulated phosphorylation of signal transducer and activator of transcription-3; 2) was without effect on EVT cell proliferation; and 3) stimulated significant migration of EVT-hybridoma cells (no endogenous IL-11), whereas in primary EVT, blocking endogenous IL-11 inhibited EVT migration by 30–40%. These data demonstrate that IL-11 stimulates human EVT migration, but not proliferation, likely via signal transducer and activator of transcription-3, indicating an important role for IL-11 in placentation.

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Loss of Signal Transducer and Activator of Transcription 3 Impaired the Osteogenesis of Mesenchymal Progenitor Cells in Vivo and in Vitro

10.21203/rs.3.rs-530012/v1 ◽

2021 ◽

Author(s):

ZIJING HUANG ◽

Jingyi Feng ◽

Xin Feng ◽

Laiting Chan ◽

Jiarui Lu ◽

...

Keyword(s):

Critical Role ◽

Micro Ct ◽

Signal Transducer ◽

Alizarin Red ◽

Mesenchymal Progenitors ◽

Osteogenic Markers ◽

Osteogenic Induction ◽

Transcription 3

Abstract Background: Signal transducer and activator of transcription 3 (Stat3) is a cytoplasmic transcription factor that participates in various biologic processes. Loss of Stat3 causes hyperimmunoglobulin E syndrome, presenting with skeletal disorders including osteoporosis, recurrent fractures, scoliosis, and craniosynostosis. The objective of this study is to explore the effect and mechanism of Stat3 on osteogenesis of mesenchymal progenitors.Methods: Stat3 was conditionally knockout (CKO) in mesenchymal progenitors by crossing the pair-related homeobox gene 1-cre (Prx1-Cre) with Stat3-floxed strain mice. Whole-mount-skeletal staining, histology, and Micro-CT were used to assess the differences between Stat3 CKO and control mice. Further, in vitro experiments were conducted to evaluate the osteogenesis potential of primary isolated bone marrow mesenchymal stem cells (BMSCs) from both control and Stat3 CKO mice. After osteogenic induction for 14d, alizarin red staining was used to show the calcium deposit, while the western blotting was applied to detect the expression of osteogenic markers.Results: Compared with the control, Stat3 CKO mice were present with shortened limbs, multiple fractures of long bone, and open calvarial fontanels. The abnormal growth plate structure and reduced collagen fiber were found in Stat3 CKO limbs. According to micro-CT analysis, the reduced cortical bone thickness and bone volume were found on Stat3 CKO mice. The in vitro osteogenic differentiation of BMSCs was inhibited in Stat3 CKO samples. After osteogenic induction for 14d, the significantly diminished calcium deposits were found in Stat3 CKO BMSCs. The decreased expression of osteogenic markers (OPN and COL1A1) was observed in Stat3 CKO BMSCs, compared with the control. Conclusions: Stat3 played a critical role in bone development and osteogenesis. Loss of Stat3 impaired the osteogenesis of mesenchymal progenitors in vivo and in vitro.

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