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Guang-Yang Yu, Xuan Wang, Su-Su Zheng, Xiao-Mei Gao, Qing-An Jia, Wen-Wei Zhu, Lu Lu, Hu-Liang Jia, Jin-Hong Chen, Qiong-Zhu Dong, Ming Lu, Lun-Xiu Qin
BACKGROUND/AIMS: Effective drug treatment for intrahepatic cholangiocarcinoma (ICC) is currently lacking. Therefore, there is an urgent need for new targets and new drugs that can prolong patient survival. Recently targeting the ubiquitin proteasome pathway has become an attractive anti-cancer strategy. In this study, we aimed to evaluate the therapeutic effect of and identify the potential mechanisms involved in targeting the proteasome subunit ADRM1 for ICC. METHODS: The expression of ADRM1 and its prognostic value in ICC was analyzed using GEO and TCGA datasets, tumor tissues, and tumor tissue arrays...
June 15, 2018: Cellular Physiology and Biochemistry
Wenya Ma, Fang He, Fengzhi Ding, Lai Zhang, Qi Huang, Chongwei Bi, Xiuxiu Wang, Bingjie Hua, Fan Yang, Ye Yuan, Zhenbo Han, Mengyu Jin, Tianyi Liu, Ying Yu, Benzhi Cai, Yanjie Lu, Zhimin Du
BACKGROUND/AIMS: Melatonin possesses many biological activities such as antioxidant and anti-aging. Cardiac progenitor cells (CPCs) have emerged as a promising therapeutic strategy for myocardial infarction (MI). However, the low survival of transplanted CPCs in infarcted myocardium limits the successful use in treating MI. In the present study, we aimed to investigate if melatonin protects against oxidative stress-induced CPCs damage and enhances its therapeutic efficacy for MI. METHODS: TUNEL assay and EdU assay were used to detect the effects of melatonin and miR-98 on H2O2-induced apoptosis and proliferation...
June 15, 2018: Cellular Physiology and Biochemistry
Le Geng, Zidun Wang, Chang Cui, Yue Zhu, Jiaojiao Shi, Jiaxian Wang, Minglong Chen
BACKGROUND/AIMS: Heart failure induced by tachycardia, the most common arrhythmia, is frequently observed in clinical practice. This study was designed to investigate the underlying mechanisms. METHODS: Rapid electrical stimulation (RES) at a frequency of 3 Hz was applied on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for 7 days, with 8 h/day and 24 h/day set to represent short-term and long-term tachycardia, respectively. Age-matched hiPSC-CMs without electrical stimulation or with slow electrical stimulation (1 Hz) were set as no electrical stimulation (NES) control or low-frequency electrical stimulation (LES) control...
June 15, 2018: Cellular Physiology and Biochemistry
Jiezhang Mo, Derun Lin, Jingzhen Wang, Ping Li, Wenhua Liu
Zinc pyrithione (ZPT) is widely used as a substitute booster biocide for tributyltin and is also an additive to antidandruff shampoos and medical cosmetic products. ZPT and pyrithione have been detected in different environmental matrices and biota, suggesting that it may pose health threats to aquatic organisms and even humans. The present study used HepG2 cells, a human hepatoma cell line, to study the hepatotoxicity of ZPT (0.1-5.0 μM). ZPT treatment caused marked viability reduction and induced apoptosis depending on its dose used...
June 15, 2018: Ecotoxicology and Environmental Safety
Ying Xiong, Yanlong Yan, Yuzhu Li
BACKGROUND: Corticosteroid-dependent dermatitis (CDD) is an inflammation caused by long-term repeated inappropriate external use of corticosteroids. Tripterine is a natural product from the root of Tripterygium wilfordii Hook.f. This study aimed to explore the effect and mechanism of tripterine on LPS-induced inflammatory injury in HaCaT cells. METHODS: In this study, different concentrations (0, 1, 2, 3 and 4 μM) of tripterine and 10 μM of LPS were used to treat HaCaT cells...
June 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Wen-Peng Zhao, Hong-Wei Wang, Jing Liu, Pan-Pan Tan, Lin Lin, Bian-Hua Zhou
Excessive fluoride (F) intake decreases the development of potential oocytes by inducing oxidative stress and apoptosis in female mice in our previous study. This study aims to investigate the underlying mechanisms of F-induced follicular developmental dysplasia. Pathomorphological changes in the ovary tissues were observed under light and transmission electron microscopes. DNA damage and proliferation in granulosa cells were analysed by TUNEL staining and BrdU measurement. The protein expression of cell proliferation related regulatory factors including JNK, STAT3, STAT5, CDK2, CDK4, PCNA and Ki67 in the ovary tissues was measured by immunohistochemistry and Western blot analyses...
June 12, 2018: Chemosphere
Chen Cheng, Shen Yu-Feng, Hu Yang, Liu Lei, Chen Wei-Chao, Wang Gao-Xue, Zhu Bin
As one of nine piscine viruses recognized by the International Office of Epizootics, spring viraemia of carp virus (SVCV) is an important pathogen bringing high mortality to cyprinids. Up to now, there is no approved therapy on SVCV, making them strong public health threat in aquaculture. In this study, the anti-SVCV activities of 12 plant crude extracts were investigated by using epithelioma papulosum cyprini (EPC) cells. Among these plants, Psoralea corylifolia Linn. showed the highest inhibition on SVCV replication, with an inhibitory percentage of 67...
June 15, 2018: Virus Research
Zili He, Wen Deng, Bo Jiang, Sulai Liu, Mingchun Tang, Yi Liu, Jian Zhang
Previous studies have shown that high levels of PLK1 are expressed in HCC, and PLK1 inhibitors are being tested in clinical trials. However, the mechanisms, which regulate PLK1 expression in HCC, have not been clarified. Here, we show that induction of let-7b over-expression inhibits the PLK1-regulated luciferase activity in HEK-293T cells, and decreases the levels of PLK1 expression in HCC cells. Furthermore, the levels of let-7b expression were negatively correlated with PLK1 expression in HCC tissues. Let-7b over-expression inhibited the proliferation of HCC cells and promoted their apoptosis, which were partially rescued by increased PLK1 expression...
June 15, 2018: Gene
Roberto Marques Damiani, Dinara Jaqueline Moura, Cassiana Macagnan Viau, Verônica Brito, Ana Moira Morás, João Antonio Pêgas Henriques, Jenifer Saffi
Doxorubicin (DOX) and Mitoxantrone (MTX) are very effective drugs for a range of tumors despite being highly cardiotoxic. DNA topoisomerase 2 beta (Top2ß) was revealed as key mediator of DOX-induced cardiotoxicity, although ROS generation is also an important mechanism. Oxidative stress is also an important issue in MTX-induced cardiotoxicity that is manifested by mitochondrial dysfunction. Studies have demonstrated the relationship between PARP-1 overactivation and cell viability in DOX-treated cardiomyocytes...
June 15, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Kang Qi, Xiangdong Li, Yongjian Geng, Hehe Cui, Chen Jin, Peihe Wang, Yue Li, Yuejin Yang
OBJECTIVE: Endothelial barrier function in the onset and Tongxinluo (TXL) protection of myocardial ischemia/reperfusion (I/R) injury, and TXL can induce the secretion of Angiopoietin-like 4 (Angptl4) in human cardiac microvascular endothelial cells during hypoxia/reoxygenation. We intend to demonstrate whether TXL can attenuate myocardial I/R injury in diabetes, characterized with microvascular endothelial barrier disruption, by induction of Angptl4-mediated protection of endothelial barrier integrity...
2018: PloS One
Xianli Chen, Xiaoguang Li, Wei Zhao, Tiejun Li, Qi Ouyang
Understanding how gene alterations induce oncogenesis plays an important role in cancer research and may be instructive for cancer prevention and treatment. We conducted a parameter sensitivity analysis to the mitochondrial apoptosis model. Both a nonlinear bifurcation analysis of the deterministic dynamics and energy barrier analysis of the corresponding stochastic models were performed. We found that the parameter sensitivity ranking according to the change of the bifurcation-point locations in deterministic models and the change of the barrier heights from a living to death state of the cell in stochastic models are highly correlated...
2018: PloS One
Qian Zhao, Xinyue Tang, Junhua Huang, Jiajia Li, Qinfen Chen, Yangjie Sun, Jiansheng Wu
OBJECTIVES: The objective of this study is to explore the effect of melatonin on endoplasmic reticulum stress in acute pancreatitis (AP) and the molecular mechanism. METHODS: Acute pancreatitis was induced in vivo in Sprague-Dawley rats by the retrograde injection of 5% taurocholate into the biliopancreatic duct and in vitro by treating AR42J cells with cerulein (10 nmol/L) plus lipopolysaccharide (LPS) (10 mg/L). The rats and cells were treated with melatonin (50 mg/kg in rats and 0...
June 16, 2018: Pancreas
Jian Chen, Qian Wang, Wei Zhou, Zheng Zhou, Peng-Yu Tang, Tao Xu, Wei Liu, Lin-Wei Li, Lin Cheng, Zhi-Min Zhou, Jin Fan, Guo-Yong Yin
GPCR kinase 2-interacting protein-1 (GIT1) is a scaffold protein that plays an important role in cell adaptation, proliferation, migration, and differentiation; however, the role of GIT1 in the regulation of neuronal death after spinal cord injury remains obscure. Here, we demonstrate that GIT1 deficiency remarkably increased neuronal apoptosis and enhanced JNK/p38 signaling, which resulted in stronger motor deficits by ischemia-reperfusion in vivo, consistent with the finding of oxygen-glucose deprivation/reoxygenation-induced neuronal injury in vitro...
June 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Amir Saeid Mohammadi, Xianchan Li, Andrew G Ewing
We used time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging to investigate the effect of cisplatin, the first member of the platinum-based anti-cancer drugs, on the membrane lipid composition of model cells to see if lipid changes might be involved in the changes in exocytosis observed. Platinum-based anti-cancer drugs have been reported to affect neurotransmitter release resulting in what is called the "chemobrain"; however, the mechanism for the influence is not yet understood. TOF-SIMS imaging was carried out using a high energy 40 keV (CO2)6000+ gas cluster ion beam with improved sensitivity for intact lipids in biological samples...
June 18, 2018: Analytical Chemistry
Minhao Yu, Yang Luo, Zhijie Cong, Yifei Mu, Yier Qiu, Ming Zhong
Background/Aims: Hippo signaling is an evolutionarily conserved pathway that controls organ size by regulating cell proliferation, survival, apoptosis, and stem cell self-renewal. In addition, Hippo signaling is profoundly implicated in intestinal regeneration and cancer. However, its roles in the pathogenesis of Crohn's disease (CD) remain largely unexplored. Methods: Quantitative real-time PCR was performed to identify the deregulated molecules in Hippo signaling...
April 18, 2018: Journal of Crohn's & Colitis
Kyle Crassini, Tahni Pyke, Yandong Shen, William S Stevenson, Richard I Christopherson, Stephen P Mulligan, Oliver Giles Best
The Raf-1 kinase inhibitory protein (RKIP) is an important regulatory element in multiple signaling pathways, including MAPK-ERK1/2. We investigated whether targeted disruption of RKIP is a therapeutic option for chronic lymphocytic leukemia (CLL). The RKIP inhibitor locostatin-induced apoptosis of CLL cells, irrespective of poor prognostic indications or treatment history. Locostatin down-regulated MAPK-ERK1/2 and AKT phosphorylation, decreased expression of the chemokine receptor CXCR4 (p = .04) and reduced the migratory capacity of CLL cells toward stroma-derived factor 1α (SDF-1α, p = ...
June 18, 2018: Leukemia & Lymphoma
Karthik M Kodigepalli, Serena Bonifati, Nagaraja Tirumuru, Li Wu
Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) is a mammalian dNTP hydrolase that acts as a negative regulator in the efficacy of cytarabine treatment against acute myeloid leukemia (AML). However, the role of SAMHD1 in AML development and progression remains unknown. We have reported that SAMHD1 knockout (KO) in the AML-derived THP-1 cells results in enhanced proliferation and reduced apoptosis, but the underlying mechanisms are unclear. Here we show that SAMHD1 KO in THP-1 cells increased PI3K activity and reduced expression of the tumor suppressor PTEN...
June 18, 2018: Cell Cycle
Nadav Shinhar, Dana Marcoviciu, Dror Dicker
BACKGROUND: Type 2 diabetes mellitus is a multifactorial disease in which genetic susceptibility and environmental factors induce pancreatic β-cell dysfunction and insulin resistance. Additional factors such as hyperglycemia and hyperlipidemia have roles in β-cell dysfunction and disease progression. The phenomenon of lipid-induced pancreatic β-dysfunction, designated as lipotoxicity, has been observed in several in vitro and in vivo experiments; however, there is still no solid evidence for the occurrence of this event in humans...
June 2018: Israel Medical Association Journal: IMAJ
Mohammadreza Sharifi, Mahdi Fasihi-Ramandi, Abdolkarim Sheikhi, Abbas Moridnia, Maryam Saneipour
MicroRNAs (miRNAs) involved in regulation of the genes. The CCAAT/enhancer-binding protein-α ( CEBPα ) is a crucial transcription factor for normal hematopoiesis and cell cycle that frequently disrupted in human acute myeloid leukemia (AML). The miR-182 up-regulation in several malignant diseases such as AML was reported, in the other hand bioinformatics analysis revealed CEBPα targeted by miR-182.miR-182-5p inhibition in human acute promyelocytic leukemia (APL) cell line was performed by using locked nucleic acid (LNA) and subsequently miR-182-5p and CEBPα expression, apoptosis, necrosis and cell proliferation were measured...
March 2018: Molecular Biology Research Communications
Cong Wang, Weisheng Cheng, Qian Yu, Tian Xing, Shoubin Chen, Lei Liu, Li Yu, Jian Du, Qingli Luo, Jilong Shen, Yuanhong Xu
Toxoplasma gondii infection evokes a strong Th1-type response with interleukin (IL)-12 and interferon (IFN)-γ secretion. Recent studies suggest that the infection of pregnant mice with T. gondii may lead to adverse pregnancy results caused by subversion of physiological immune tolerance at maternofetal interface rather than direct invasion of the parasite. Genotype-associated dense granule protein GRA15II tends to induce classically activated macrophage (M1) differentiation and subsequently activating NK, Th1, and Th17 cells whereas rhoptry protein ROP16I/III drives macrophages to alternatively activated macrophage (M2) polarization and elicits Th2 immune response...
2018: Frontiers in Immunology
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