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Hilal Ahmad Parray, Jameel Lone, Jong Pil Park, Jang Won Choi, Jong Won Yun
OBJECTIVE: The aim of this study was to explore the browning and antioxidative effects of magnolol in 3T3-L1 adipocytes, as recruitment of beige-like adipocytes (browning) by natural compounds is being considered as a promising strategy to fight against obesity. METHODS: Magnolol-induced browning effect was evaluated by determining the expression levels of specific marker genes and proteins using real-time polymerase chain reaction and immunoblotting, respectively...
February 5, 2018: Nutrition
María Victoria Repetto, Matthew J Winters, Alan Bush, Wolfgang Reiter, David Maria Hollenstein, Gustav Ammerer, Peter M Pryciak, Alejandro Colman-Lerner
We report an unanticipated system of joint regulation by cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK), involving collaborative multi-site phosphorylation of a single substrate. In budding yeast, the protein Ste5 controls signaling through a G1 arrest pathway. Upon cell-cycle entry, CDK inhibits Ste5 via multiple phosphorylation sites, disrupting its membrane association. Using quantitative time-lapse microscopy, we examined Ste5 membrane recruitment dynamics at different cell-cycle stages...
March 15, 2018: Molecular Cell
Yun Bai, Chuan Liu, Lei Fu, Xiaoshan Gong, Ce Dou, Zhen Cao, Hongyu Quan, Jianmei Li, Fei Kang, Jingjin Dai, Chunrong Zhao, Shiwu Dong
Endochondral ossification is crucial for bone formation in both adult bone repair process and embryo long-bone development. In endochondral ossification, bone marrow-derived mesenchymal stem cells (BMSCs) first differentiate to chondrocyte, BMSC-derived chondrocyte then endure a hypertrophic process to generate new bone. Endochondral ossification-based bone repair is a promising strategy to cure massive bone defect, which is a major clinical issue in orthopedics. However, challenges still remain for this novel strategy...
March 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Jianjun Chang, Yan Ding, Zhiyu Zhou, Hong-Guang Nie, Hong-Long Ji
Transepithelial fluid and salt re-absorption in epithelial tissues play an important role in fluid and salt homeostasis. In absorptive epithelium, fluid and salt flux is controlled by machinery mainly composed of epithelial sodium channels (ENaC), cystic fibrosis transmembrane conductance regulator (CFTR), Na⁺/H⁺ exchanger (NHE), aquaporin, and sodium potassium adenosine triphosphatase (Na⁺/K⁺-ATPase). Dysregulation of fluid and salt transport across epithelium contributes to the pathogenesis of many diseases, such as pulmonary edema and cystic fibrosis...
March 16, 2018: International Journal of Molecular Sciences
Amjad M Husaini, Aafreen Sakina, Souliha R Cambay
Fusarium oxysporum, a ubiquitous soil-borne pathogen causes devastating vascular wilt in more than 100 plant species and ranks fifth among top ten fungal plant pathogens. It has emerged as a human pathogen too, causing infections in immune-compromised patients. It is, therefore, important to gain insight into the molecular processes involved in the pathogenesis of this trans-kingdom pathogen. A complex network comprising of interconnected and over lapping signal pathways; mitogen-activated protein kinase (MAPK) signaling pathways, Ras proteins, G-protein signaling components and their downstream pathways, components of the velvet (LaeA/VeA/VelB) complex and cAMP pathways, is involved in perceiving the host...
March 16, 2018: Molecular Plant-microbe Interactions: MPMI
Anna King, Anna Brain, Kelsey Hanson, Justin Dittmann, James Vickers, Carmen Fernandez-Martos
Disruption of leptin signalling has been implicated as playing a role in the development of Alzheimer's disease (AD). Leptin has previously been shown to be affected by amyloid-beta (Aβ)-related signalling; however, pathways that link leptin to the disease pathogenesis have not been determined. To characterize the association between increasing age-dependent Aβ levels with leptin signalling and the vulnerable brain regions in AD, we assessed the mRNA and protein expression profile of leptin and leptin receptor (Ob-Rb) at 9 and 18-month-age in APP/PS1 mice...
March 15, 2018: Metabolic Brain Disease
Sven Persoon, Michael Paulus, Stephan Hirt, Carsten Jungbauer, Alexander Dietl, Andreas Luchner, Christof Schmid, Lars S Maier, Christoph Birner
Implantation of left ventricular assist devices (LVADs) as bridge to transplant in end-stage heart failure allows for analyzing reverse remodeling processes of the supported heart. Whether this therapy influences the cGMP-PKG signaling pathway, which is currently under thorough investigation for developing new heart failure therapeutics, is unknown. In fourteen end-stage heart failure patients (8 with dilated cardiomyopathy, DCM; 6 with ischemic cardiomyopathy, ICM) tissue specimens of left ventricles were collected at LVAD implantation and afterwards at receiver heart explantation, respectively...
March 15, 2018: Heart and Vessels
Matheus D Baldissera, Carine F Souza, Carla Cristina Zeppenfeld, Sharine Descovi, Aleksandro S da Silva, Bernardo Baldisserotto
The phosphotransfer network system, through the enzymes creatine kinase (CK), adenylate kinase (AK), and pyruvate kinase (PK), contributes to efficient intracellular energetic communication between cellular adenosine triphosphate (ATP) consumption and production in tissues with high energetic demand, such as cerebral tissue. Thus, the aim of this study was to evaluate whether aflatoxin B1 (AFB1 ) intoxication in diet negatively affects the cerebral phosphotransfer network related to impairment of cerebral ATP levels in silver catfish (Rhamdia quelen)...
March 15, 2018: Fish Physiology and Biochemistry
Anat Elmann, Alona Telerman, Rivka Ofir, Yoel Kashman, Orly Lazarov
Alzheimer's disease (AD) is the most prevalent cause of dementia in adults. Current available drugs for AD transiently alleviate some of the symptoms, but do not modify the disease mechanism or cure it. Therefore, new drugs are desperately needed. Key contributors to AD are amyloid beta (Aβ)- and reactive oxygen species (ROS)-induced cytotoxicities. Plant-derived substances have been shown to affect various potential targets in various diseases including AD. Therefore, phytochemicals which can protect neuronal cells against these insults might help in preventing and treating this disease...
March 15, 2018: Journal of Natural Medicines
Yang Chen, Youyou Wang, Lujun Zhao, Ping Wang, Jifeng Sun, Rudi Bao, Chenghai Li, Ningbo Liu
Objective: To investigate the potential of HS-10182, a second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), as a radiosensitizer in non-small cell lung cancer (NSCLC). Methods: Two cell lines of NSCLCs, A549 that possesses wild-type (WT) EGFRs and H1975 that possesses EGFR L858R/T790M double mutations, were treated with HS-10182 at various concentrations, and cell viabilities were determined using the MTS assay. The cells were tested by clonogenic survival assays to identify the radiosensitivity of both groups...
February 2018: Cancer Biology & Medicine
Muhammad Khairi Ahmad, Nur Ainina Abdollah, Nurul Husna Shafie, Narazah Mohd Yusof, Siti Razila Abdul Razak
Mitogen-activated protein kinases (MAPKs) are the main regulators of cellular proliferation, growth, and survival in physiological or pathological conditions. Aberrant MAPK signaling plays a pivotal role in carcinogenesis, which leads to development and progression of human cancer. Dual-specificity phosphatase 6 (DUSP6), a member of the MAPK phosphatase family, interacts with specifically targeted extracellular signal-regulated kinase 1/2 via negative feedback regulation in the MAPK pathway of mammalian cells...
February 2018: Cancer Biology & Medicine
Katarzyna Morawska, Françoise Goirand, Laurine Marceau, Madeline Devaux, Adèle Cueff, Aurélie Bertaut, Julie Vincent, Leila Bengrine-Lefevre, François Ghiringhelli, Antonin Schmitt
Aims: 5-FU is used as the main backbone of chemotherapy regimens for patients with colorectal and other gastrointestinal cancers. Despite development of new strategies that allowed enhancing clinical effectiveness and tolerability of 5-FU, 10-30% of patients treated with 5-FU-based regimens experience severe treatment-related toxicity. In our study, we evaluated the 5-FU exposure-toxicity relationship and investigated the efficacy of PK-guided dosing in increasing tolerability of 5-FU-based chemotherapy...
February 20, 2018: Oncotarget
Qiujun Liu, Xianyao Zhou, Chuan Li, Xuemei Zhang, Chang Long Li
There is limited knowledge regarding the influence of autophagy on the anticancer effect of dihydroartemisinin (DHA). The present study aimed to investigate this influence within human breast cancer cells. Changes in cell viability, cell cycle distribution, apoptosis and associated genes were analyzed in MDA-MB-231 cells subjected to DHA following alteration in autophagy levels; the autophagy level was decreased following autophagy-related 7 (Atg7) knockdown or increased using rapamycin. The data indicated that rapamycin had the ability to notably enhance the anticancer effect of DHA on MDA-MB-231 cells...
April 2018: Oncology Letters
Ji Wang, Chunying Wang, Gaofeng Bu
Cancer stem cells are considered as a main cause of cancer recurrence. In the present study, the effects of curcumin on the growth of liver cancer stem cells (LCSCs) were investigated. The proliferation and apoptosis of LCSCs were assessed by MTT assays and flow cytometry. Changes in the expression of apoptosis-related proteins were identified by western blotting. The results of the study demonstrated that curcumin treatment inhibited the growth of LCSCs, induced cell apoptosis, as well as regulated the expression of apoptosis-associated proteins and the release of cytochrome c...
April 2018: Experimental and Therapeutic Medicine
Peng You, Ning Chen, Lin Su, Tao Peng, Guodong Chen, Yulan Liu
Transforming growth factor β1 (TGF-β1) has a crucial role in regulating the balance of type 17 T-helper cells (Th17) and T regulatory cells (Tregs) that are involved in the pathogenesis of inflammatory bowel disease, while the function of local TGF-β1 in this process has remained to be fully elucidated. The present study investigated the effects of different local TGF-β1 levels on the Treg/Th17 balance and on the dexamethasone efficacy in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis...
April 2018: Experimental and Therapeutic Medicine
Jun Bian, Dan Cao, Jie Shen, Bo Jiang, Dan Chen, Lanzheng Bian
N-methyl pyrrolidone (NMP), a small bioactive molecule, has the potential to stimulate bone formation and inhibit osteoclast differentiation. The aim of the present study was to investigate the effect of NMP on the inflammatory response and underlying molecular mechanisms in MG-63 cells. The mRNA and protein expression of cytokines from peripheral blood in children with or without ankle fracture were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and ELISA, respectively...
April 2018: Experimental and Therapeutic Medicine
Haitao Luo, Caixia Liang
Non-small cell lung cancer (NSCLC) accounts for ~80% of all types of lung cancer, which has the highest morbidity and mortality of all types of cancer worldwide. It is important to identify novel biomarkers and the molecular mechanism of NSCLC to improve current treatments of NSCLC. The present study aimed to investigate the effect of miR-148b expression on the proliferation, epithelial-mesenchymal transition (EMT) and radiosensitivity of NSCLC cells. It was demonstrated that miR-148b expression was significantly decreased in NSCLC tissues and cell lines...
April 2018: Experimental and Therapeutic Medicine
Chengzhi Fang, Lili Xie, Chunmei Liu, Chunhua Fu, Wei Ye, Hong Liu, Binghong Zhang
Neonatal necrotizing enterocolitis (NEC) is a severe acquired disease that predominantly affects the small intestine of neonates. NEC is caused by a combination of metabolic products, dysfunctions of the blood vessels, mucus and other unknown factors. Berberine may induce beneficial effects on necrotic and cardiovascular diseases due to its anti-inflammatory and anti-apoptotic effects on epithelial cells. In the present study, the therapeutic effects of berberine were investigated and the potential mechanisms by which it functions within a neonatal NEC mouse model were analyzed...
April 2018: Experimental and Therapeutic Medicine
Huan Gao, Yue Zhang, Lei Dong, Xiao-Yu Qu, Li-Na Tao, Yue-Ming Zhang, Jing-Hui Zhai, Yan-Qing Song
To investigate the effects of triptolide (TPI) on proliferation, autophagy and death in human breast cancer MCF-7 cells, and to elucidate the associated molecular mechanisms, intracellular alterations were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays. The results of the MTT assay revealed that TPI significantly reduced the MCF-7 cell survival rate when the concentration was >10 nmol/l. TPI activated a caspase cascade reaction by regulating Bcl-2-associated X protein (Bax), caspase-3 and B-cell lymphoma 2 expression, and promoted programmed cell death via the mitochondrial pathway...
April 2018: Experimental and Therapeutic Medicine
Jian-Song Sun, Xiu-Hai Yang
The aim of the present study was to explore the expression and distribution of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in tumor tissues and adjacent normal mucosa tissues of patients with laryngeal squamous cell carcinoma (LSCC), and further analyze the association between the expression and the clinicopathological parameters of patients with LSCC. Clinical data of tumor tissues and corresponding adjacent normal mucosa tissues of pathologically diagnosed LSCC in 96 cases were collected in the present study...
April 2018: Experimental and Therapeutic Medicine
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