Qiming Gong, Yan Jiang, Junling Lu, Yanwu You
OBJECTIVE: To explore the mechanism by which fractalkine (CX3CL1; FKN) inhibits lipopolysaccharide (LPS)-induced immunological response in RAW264.7 cells. METHODS: A RAW264.7 cell model overexpressing FKN was established by transfection with the lentiviral vector CX3CL1. The effects of LPS, ICG-001 (a Wnt/β-catenin signaling pathway inhibitor), either alone or in combination, on M1 polarization of na?ve and FKN-overexpressing RAW264.7 cells were evaluated by detecting of intereukin-6 (IL-6) and tumor necrosis factor-α (TNF- α ) using ELISA...
December 30, 2020: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Jia Sun, Xiaozhong Huang, Chao Niu, Xuejiao Wang, Wanqian Li, Mengxue Liu, Ying Wang, Shuai Huang, Xixi Chen, Xiaokun Li, Yang Wang, Litai Jin, Jian Xiao, Weitao Cong
Vascular complications of diabetes are a serious challenge in clinical practice, and effective treatments are an unmet clinical need. Acidic fibroblast growth factor (aFGF) has potent anti-oxidative properties and therefore has become a research focus for the treatment of diabetic vascular complications. However, the specific mechanisms by which aFGF regulates these processes remain unclear. The purpose of this study was to investigate whether aFGF alleviates diabetic endothelial dysfunction by suppressing mitochondrial oxidative stress...
December 19, 2020: Redox Biology
Dongmei Yang, Qing Li, Renduo Shang, Liwen Yao, Lianlian Wu, Mengjiao Zhang, Lihui Zhang, Ming Xu, Zihua Lu, Jie Zhou, Li Huang, Xiaodong Huang, Du Cheng, Yanning Yang, Honggang Yu
BACKGROUND: Wingless and Int-related protein (Wnt) ligands are aberrantly expressed in patients with colorectal cancer (CRC). However, the aberrant level of Wnt ligands in serum have not been explored. Here, we aimed to identify the levels of WNT4 in serum and explored its oncogenic role in CRC. METHODS: The Oncomine database was used to analyze the relationship between WNT4 and the prognosis of CRC. ELISA was performed to measure WNT4 levels in serum and conditioned medium from fresh CRC tissues and adjacent normal tissues...
November 23, 2020: Journal of Experimental & Clinical Cancer Research: CR
Dingqing Feng, Keqin Yan, Haiyan Liang, Jing Liang, Wenhui Wang, Huan Yu, Ying Zhou, Weidong Zhao, Zhongjun Dong, Bin Ling
Our previous work demonstrated that Piwil2 reactivated by the human papillomavirus oncoproteins E6 and E7 may reprogram somatic cells into tumor-initiating cells (TICs), which contribute to cervical neoplasia lesions. Maintaining the stemness of TICs is critical for the progression of cervical lesions. Here, we determined that canonical Wnt signaling was aberrantly activated in HaCaT cells transfected with lentivirus expressing Piwil2 and in cervical lesion specimens of low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, and invasive carcinoma...
November 12, 2020: Neoplasia: An International Journal for Oncology Research
Arti Verma, Sandeep Artham, Payaningal R Somanath
Endothelial-to-mesenchymal transition (EndMT) indispensable in embryogenesis also occurs in several human pathologies. Although transforming growth factor-β (TGFβ) has been demonstrated to induce EndMT, the type-I receptors (ALK-1 and ALK-5) responsible for TGFβ-induced EndMT is unclear. In the current study, we investigated the role of the Akt1 pathway in ALK1 and ALK5 expression regulation in response to TGFβ1 and TGFβ2 in human microvascular endothelial cells (HMECs). Whereas treatment with TGFβ1 and TGFβ2 or Akt1 gene silencing promoted EndMT accompanied by increased ALK5 expression and reduced ALK1 expression accompanied by increased expression of N-cadherin and reduced expression of eNOS in HMECs, treatment with ALK-5 inhibitor (SB431542) blunted these effects...
November 3, 2020: Gene
Lin Zhang, Yicong Wan, Zihan Zhang, Yi Jiang, Jinghe Lang, Wenjun Cheng, Lan Zhu
Although many studies have confirmed the relationship between obesity and endometrial cancer (EC), the molecular mechanism between obesity and EC progression has not been elucidated. Overexpression of fat mass and the obesity associated protein FTO leads to weight gain, although recently it has been discovered that FTO can serve as a demethylase which erases N6-methyladenosine (m6A) modification and regulates the metabolization of mRNAs. In this study, we found high expression of FTO in metastatic EC and that this action promote both metastasis and invasion in vivo and in vitro...
October 25, 2020: RNA Biology
Jian Fan, Yu-Wen Su, Mohammadhossein Hassanshahi, Chia-Ming Fan, Yaser Peymanfar, Alessandro Piergentili, Fabio Del Bello, Wilma Quaglia, Cory J Xian
Cancer chemotherapy can significantly impair the bone formation and cause myelosuppression; however, their recovery potentials and mechanisms remain unclear. This study investigated the roles of the β-catenin signaling pathway in bone and bone marrow recovery potentials in rats treated with antimetabolite methotrexate (MTX) (five once-daily injections, 0.75 mg/kg) with/without β-catenin inhibitor indocyanine green (ICG)-001 (oral, 200 mg/kg/day). ICG alone reduced trabecular bone volume and bone marrow cellularity...
October 20, 2020: Journal of Cellular Physiology
Maria Wiese, Feda H Hamdan, Klaudia Kubiak, Christopher Diederichs, Gerrit H Gielen, Gunther Nussbaumer, Angel M Carcaboso, Esther Hulleman, Steven A Johnsen, Christof M Kramm
Diffuse intrinsic pontine gliomas (DIPG) are the most aggressive brain tumors in children with 5-year survival rates of only 2%. About 85% of all DIPG are characterized by a lysine-to-methionine substitution in histone 3, which leads to global H3K27 hypomethylation accompanied by H3K27 hyperacetylation. Hyperacetylation in DIPG favors the action of the Bromodomain and Extra-Terminal (BET) protein BRD4, and leads to the reprogramming of the enhancer landscape contributing to the activation of DIPG super enhancer-driven oncogenes...
August 21, 2020: Cell Death & Disease
Haixing Feng, Hongling Hu, Ping Zheng, Tianrong Xun, Shulong Wu, Xixiao Yang, Liqian Mo
Advanced oxidative protein products (AOPPs) are novel uremic toxins whose concentrations continuously increases in patients with chronic kidney disease (CKD). Epithelial-to-mesenchymal transition (EMT) of tubular cells is the main mechanism underlying CKD pathogenesis. Studies have shown that AOPPs can induce EMT and promote renal fibrosis. However, the mechanism through which AOPPs induce tubular cell-EMT is poorly understood. In this study, we aimed to clarify the mechanisms underlying AOPP-induced EMT in human kidney proximal tubular (HKC-8) epithelial cells...
September 3, 2020: Biochemical and Biophysical Research Communications
Kaile Zhang, Xiaolan Fang, Jingjing Zhu, Ranxing Yang, Ying Wang, Weixin Zhao, Xiumei Mo, Qiang Fu
Hypospadias and urethral stricture are common urological diseases which seriously affect voiding function and life quality of the patients, yet current clinical treatments often result in unsatisfactory clinical outcome with frequent complications. In vitro experiments confirmed that ICG-001 (a well-established Wnt signaling inhibitor) could effectively suppress fibroblast proliferation and fibrotic protein expression. In this study, we applied a novel drug-delivering nanoyarn scaffold in urethroplasty in dog model, which continuously delivers ICG-001 during tissue reconstruction, and could effectively promote urethral recovery and resume fully functional urethra within 12 weeks...
2020: Frontiers in Bioengineering and Biotechnology
Lai-Sheung Chan, Hong-Lok Lung, Roger Kai-Cheong Ngan, Anne Wing-Mui Lee, Sai Wah Tsao, Kwok-Wai Lo, Michael Kahn, Maria Li Lung, Rotraud Wieser, Nai-Ki Mak
The Wnt signaling pathway is one of the major signaling pathways used by cancer stem cells (CSC). Ecotropic Viral Integration Site 1 (EVI1) has recently been shown to regulate oncogenic development of tumor cells by interacting with multiple signaling pathways, including the Wnt signaling. In the present study, we found that the Wnt modulator ICG-001 could inhibit the expression of EVI1 in nasopharyngeal carcinoma (NPC) cells. Results from loss-of-function and gain-of-function studies revealed that EVI1 expression positively regulated both NPC cell migration and growth of CSC-enriched tumor spheres...
July 31, 2020: International Journal of Molecular Sciences
Jiaojiao Deng, Lingyang Hua, Tao Han, Mi Tian, Daijun Wang, Hailiang Tang, Shuchen Sun, Hong Chen, Haixia Cheng, Tao Zhang, Qing Xie, Lixin Wan, Hongda Zhu, Ye Gong
Background: Meningiomas with Neurofibromin 2 gene mutations ( NF2 -mutant meningiomas) account for ~40% of the sporadic meningiomas. However, there is still no effective drug treatment for the disease. Methods: Expression profile of Merlin protein was explored through immunohistochemistry in a meningioma patient cohort ( n = 346). A 20-agent library covering a wide range of meningioma relevant targets was tested using meningioma cell lines IOMM-Lee ( NF2 wildtype) and CH157-MN ( NF2 deficient)...
January 2020: Neuro-oncology advances
Mingtian Che, Soo-Mi Kweon, Jia-Ling Teo, Yate-Ching Yuan, Laleh G Melstrom, Richard T Waldron, Aurelia Lugea, Raul A Urrutia, Stephen J Pandol, Keane K Y Lai
BACKGROUND: Although cyclic AMP-response element binding protein-binding protein (CBP)/β-catenin signaling is known to promote proliferation and fibrosis in various organ systems, its role in the activation of pancreatic stellate cells (PSCs), the key effector cells of desmoplasia in pancreatic cancer and fibrosis in chronic pancreatitis, is largely unknown. METHODS: To investigate the role of the CBP/β-catenin signaling pathway in the activation of PSCs, we have treated mouse and human PSCs with the small molecule specific CBP/β-catenin antagonist ICG-001 and examined the effects of treatment on parameters of activation...
June 5, 2020: Cancers
Fen Long, Qing Wang, Di Yang, Menglin Zhu, Jinghuan Wang, YiZhun Zhu, Xinhua Liu
Myocardial fibrosis is the pathological consequence of injury-induced fibroblastto-myofibroblast transition, resulting in increased stiffness and diminished cardiac function. Histone modification has been shown to play an important role in the pathogenesis of cardiac fibrosis. Here, we identified H3K27me3 demethylase JMJD3/KDM6B promotes cardiac fibrosis via regulation of fibrogenic pathways. Using neonatal rat cardiac fibroblasts (NRCF), we show that the expression of endogenous JMJD3 is induced by angiotensin II (Ang II), while the principle extracellular matrix (ECM) such as fibronectin, CTGF, collagen I and III are increased...
June 5, 2020: Biochemical and Biophysical Research Communications
Vivek P Singh, Jaya Pratap Pinnamaneni, Aarthi Pugazenthi, Deepthi Sanagasetti, Megumi Mathison, Kai Wang, Jianchang Yang, Todd K Rosengart
Background Given known inefficiencies in reprogramming of fibroblasts into mature induced cardiomyocytes (iCMs), we sought to identify small molecules that would overcome these barriers to cardiac cell transdifferentiation. Methods and Results We screened alternative combinations of compounds known to impact cell reprogramming using morphologic and functional cell differentiation assays in vitro. After screening 6 putative reprogramming factors, we found that a combination of the histone deacetylase inhibitor sodium butyrate, the WNT inhibitor ICG-001, and the cardiac growth regulator retinoic acid (RA) maximally enhanced iCM generation from primary rat cardiac fibroblasts when combined with administration of the cardiodifferentiating transcription factors Gata4, Mef2C, and Tbx5 (GMT) compared with GMT administration alone (23±1...
June 5, 2020: Journal of the American Heart Association
A Kuckhahn, M Ramsperger-Gleixner, J Distler, B Spriewald, S Ensminger, M Weyand, C Heim
PURPOSE: The canonical wnt pathway with its central signaling molecule β-catenin is important for tissue development and homeostasis and its dysregulation leads to many diseases including pathologies of the cardiovascular system. Inhibition of the wnt pathway has the potential to protect against cardiac allograft vasculopathy (CAV), because it reduces the proliferation of smooth muscle cells (SMCs), which is a main pathomechanism of CAV and causes neointima formation and vessel occlusion...
April 2020: Journal of Heart and Lung Transplantation
Xin-Rong Xiong, Xin-Li Tian, Ru-Jie Huo, Yan-Ting Dong, Dai Liu, Jing-Cui Bai, Yun-Feng Qi, Xin-Rui Tian
BACKGROUND: The transforming growth factor β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) has been proven associated with the pathogenesis of asthmatic airway remodeling, in which the Wnt/β-catenin pathway plays an important role, notably with regard to TGF-β1. Recent studies have shown that 1α, 25-dihydroxyvitamin D3(1α, 25(OH)2D3) inhibits TGF-β1-induced EMT, although the underlying mechanism have not yet been fully elucidated. METHODS: Alveolar epithelial cells were exposed to 1α, 25(OH)2D3, ICG-001, or a combination of both, followed by stimulation with TGF-β1...
May 14, 2020: Chinese Medical Journal
Xiumin Lin, Shutao Tan, Lin Fu, Qianze Dong
Introduction: Dysregulation of BCAT1 has been implicated in carcinogenesis. However, its clinical significance and biological roles in human non-small cell lung cancer (NSCLC) are not clear. Methods: Immunohistochemistry was used to examine the protein expression of BCAT1 in 107 cases of lung cancer tissues. Biological roles and potential mechanisms of BCAT1 were examined using MTT, colony formation assay, Matrigel invasion assay, Western blot, RNA-sequencing, and luciferase reporter assay...
2020: OncoTargets and Therapy
Chen Zhao, Jin-Yang Chen, Wen-Ming Peng, Bo Yuan, Qing Bi, You-Jia Xu
Osteoarthritis (OA) is one of the most prevalent joint disorders globally. Patients suffering from OA are often obese and adiposity is linked to chronic inflammation. In the present study, the potential of using exosomes isolated from adipose‑derived stem cells (ADSCs) as a therapeutic tool for reducing chronic inflammation and promoting chondrogenesis was investigated using patient‑derived primary cells. First, it was tested whether patient‑derived ADSCs could differentiate into chondrogenic and osteogenic lineages...
February 7, 2020: Molecular Medicine Reports
Chengze Wang, Yongzheng Li, Ke Yu, Zhiwei Jiang, Ying Wang, Guoli Yang
INTRODUCTION: Human periodontal ligament stem cells (hPDLSCs) are stem cells found near the tooth periodontal ligament. These cels are involved in the regeneration of the periodontal ligament and alveolar bone during orthodontic treatment and chronic periodontitis. OBJECTIVES: The Homeobox gene HOXA10 regulates the osteogenic differentiation of stem cells. However, the role of HOXA10 in hPDLSCs remains unclear. Therefore, we studied the effects of HOXA10 on human PDLSC osteogenic differentiation in vitro ...
April 16, 2020: Connective Tissue Research
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