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Adrien Rougny, Pauline Gloaguen, Nathalie Langonné, Eric Reiter, Pascale Crépieux, Anne Poupon, Christine Froidevaux
With the dramatic increase of the diversity and the sheer quantity of biological data generated, the construction of comprehensive signaling networks that include precise mechanisms cannot be carried out manually anymore. In this context, we propose a logic-based method that allows building large signaling networks automatically. Our method is based on a set of expert rules that make explicit the reasoning made by biologists when interpreting experimental results coming from a wide variety of experiment types...
May 18, 2018: Scientific Reports
Rosa Bonaventura, Francesca Zito, Marco Chiaramonte, Caterina Costa, Roberta Russo
Many industrial activities release Nickel (Ni) in the environment with harmful effects for terrestrial and marine organisms. Despite many studies on the mechanisms of Ni toxicity are available, the understanding about its toxic effects on marine organisms is more limited. We used Paracentrotus lividus as a model to analyze the effects on the stress pathways in embryos continuously exposed to different Ni doses, ranging from 0.03 to 0.5 mM. We deeply examined the altered embryonic morphologies at 24 and 48 h after Ni exposure...
May 4, 2018: Marine Environmental Research
Jing-Si Zhou, Zhou Zhu, Feng Wu, Ying Zhou, Rui Sheng, Jun-Chao Wu, Zheng-Hong Qin
Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). Although the pathogenic mechanism underlying PD remains largely unknown, decreased nigral glutathione (GSH) in postmortem brains of PD patients supports the presence of oxidative stress in PD. We found that Nicotinamide adenine dinucleotide phosphate (NADPH), which is important for maintaining the level of GSH, protected dopaminergic (DA) neurons from neurotoxicity of MPTP/MPP+ ...
May 16, 2018: Acta Pharmacologica Sinica
Ao Wang, Qiwei Yang, Qiuju Li, Xiaonan Wang, Shuhong Hao, Jincheng Wang, Ming Ren
BACKGROUND The oxidative stress environment of pathological tissue has an adverse effect on the survival of bone marrow mesenchymal stem cells (BMSCs) transplantation. Ginkgo biloba L. extract (EGB) has a potent antioxidant effect. In this research, we assessed the protective effects of EGB and EGB-Containing Serum (EGB CS) on BMSCs against injury induced by hydrogen peroxide (H2O2). MATERIAL AND METHODS BMSCs were pretreated with EGB or EGB CS and treated with H2O2. The cell counting kit-8 (CCK-8) method was utilized to detect cell viability...
May 14, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Ammad Ahmad Farooqi, Sumbul Khalid, Fatima Tahir, Uteuliev Yerzhan Sabitaliyevich, Ilhan Yaylim, Rukset Attar, Baojun Xu
Research over decades has progressively explored pharmacological actions of bitter gourd (Momordica charantia). Biologically and pharmacologically active molecules isolated from M. charantia have shown significant anti-cancer activity in cancer cell lines and xenografted mice. In this review spotlight was set on the bioactive compounds isolated from M. charantia that effectively inhibited cancer development and progression via regulation of protein network in cancer cells. We summarize most recent high-quality research work in cancer cell lines and xenografted mice related to tumor suppressive role-play of M...
May 10, 2018: Food and Chemical Toxicology
Lorenzo Stramucci, Angelina Pranteda, Gianluca Bossi
TP53 is universally recognized as a pivotal protein in cell-cycle fate and apoptotic induction and, unsurprisingly, it is one of the most commonly hijacked control mechanisms in cancer. Recently, the kinase MKK3 emerged as a potential therapeutic target in different types of solid tumor being linked to mutant p53 gain-of-function. In this review, we summarize the delicate relationship among p53 mutational status, MKK3/MKK6 and the downstream activated master kinase p38MAPK, dissecting a finely-tuned crosstalk, in a potentially cell-context dependent scenario that urges towards a deeper characterization of the different molecular players involved in this signaling cascade and their interactions...
May 3, 2018: Cancers
Hong Zhou, Yonghong Sun, Lihui Zhang, Wenyuan Kang, Na Li, Yongjun Li
AIMS: To understand the roles of the RhoA/ROCK and MAPK pathways in high glucose (HG)-induced apoptosis and oxidative stress in cardiomyocytes. MATERIALS AND METHODS: Neonatal rat cardiomyocytes were cultured in DMEM, supplemented with 5.5 or 30 mmol/L D-glucose, in the presence or absence of fasudil (50 or 100 μM), SB203580, SP600125 or PD98059 (10 μM, respectively). The percentage of early apoptotic cardiomyocytes was evaluated using flow cytometry. The SOD activity and MDA contents in the cellular supernatants were measured...
May 9, 2018: Diabetes/metabolism Research and Reviews
Bicheng Zhang, Zhimin Zhang, Jun Wang, Bo Yang, Yong Zhao, Zhiguo Rao, Jianfei Gao
Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin isolated from the traditional Chinese herb Artemisia annua , is an effective novel antimalarial agent. Studies have suggested that it also exhibits anticancer effects when administered alone or in combination with conventional chemotherapeutic agents. The present study investigated the therapeutic effect of DHA combined with carboplatin (CBP) on Lewis lung carcinoma (LLC) cells and the possible underlying molecular mechanisms. MTT and clonogenic assays demonstrated that the proliferation activity of LLC cells was inhibited in a dose-dependent manner by DHA combined with CBP...
May 2018: Oncology Letters
Barbara Michalak, Agnieszka Filipek, Piotr Chomicki, Małgorzata Pyza, Marta Woźniak, Barbara Żyżyńska-Granica, Jakub P Piwowarski, Agnieszka Kicel, Monika A Olszewska, Anna K Kiss
Aim of the study: Taking into account that overactivated leukocytes are an important factor in the development of many chronic diseases, we investigated the activity of phytochemically characterized (HPLC-DAD-MSn ) extracts from forsythia leaves and flowers on the pro- and anti-inflammatory functions of leukocytes (effects on IL-1β, IL-8, TNF-α, and TGFβ release) and their adherence to endothelial cells. Using bio-guided fractionation, we isolated the active compounds and determined their biological activity, and we included the positive control quercetin...
2018: Frontiers in Pharmacology
Priyanshu Bhargava, Vidhi Malik, Ye Liu, Jihoon Ryu, Sunil C Kaul, Durai Sundar, Renu Wadhwa
Withaferin-A (Wi-A) has been shown to possess anticancer activity. Molecular mechanism(s) of its action have not been fully resolved. We recruited low dose of Wi-A that caused slow growth arrest in cancer cells, and was relatively safe for normal cells. Consistently, we detected nuclear translocation of NFκB and activation of p38MAPK selectively in cancer cells. Bioinformatics analyses revealed that Wi-A did not disrupt IKK/IKKβ-Nemo complex that regulates NFκB activity. However, it caused moderate change in the conformation of IKKβ-Nemo interacting domain...
April 28, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Chunfeng Ren, Zhiyuan Liang
BACKGROUND: This study aimed to investigate whether piperine has anti-inflammatory activities in lipopolysaccharide (LPS)-induced inflammatory injury of murine chondrogenic ATDC5 cells and to explore the potential mechanisms. METHODS: ATDC5 cells were pretreated with piperine and then stimulated by LPS for 12 h. Cell Counting Kit-8 (CCK-8) and flow cytometry were used to assess cell viability and apoptosis, respectively. qRT-PCR, enzyme-linked immuno sorbent assay (ELISA) and western blotting were used to detect the expression levels of inflammatory cytokines, microRNA-127 (miR-127) and MyD88, as well as key factors involved in nuclear factor kappa B (NF-κB) and p38-mitogen activated protein kinase (p38MAPK) signaling pathways, respectively...
April 23, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Lei Zhang, Peng Zhang, Guangfu Wang, Huaye Zhang, Yajun Zhang, Yilin Yu, Mingxu Zhang, Jian Xiao, Piero Crespo, Johannes W Hell, Li Lin, Richard L Huganir, J Julius Zhu
How signaling molecules achieve signal diversity and specificity is a long-standing cell biology question. Here we report the development of a targeted delivery method that permits specific expression of homologous Ras-family small GTPases (i.e., Ras, Rap2, and Rap1) in different subcellular microdomains, including the endoplasmic reticulum, lipid rafts, bulk membrane, lysosomes, and Golgi complex, in rodent hippocampal CA1 neurons. The microdomain-targeted delivery, combined with multicolor fluorescence protein tagging and high-resolution dual-quintuple simultaneous patch-clamp recordings, allows systematic analysis of microdomain-specific signaling...
April 24, 2018: Neuron
Marta Woźniak, Barbara Michalak, Joanna Wyszomierska, Marta K Dudek, Anna K Kiss
Aim of the study: The aim of the present study was to investigate the effects of phytochemically characterized extracts connected with the traditional use (infusions and ethanolic extracts) of different parts of Syringa vulgaris (common lilac) on the pro-inflammatory functions of neutrophils. Active compounds were isolated from the most promising extract(s) using bioassay-guided fractionation, and their activity and molecular mechanisms of action were determined. Methods: The extracts were characterized using a HPLC-DAD- MSn method...
2018: Frontiers in Pharmacology
N Cong, W Huang, J-P Yuan, G-Z Li, G-S Zhai, B-S Li
OBJECTIVE: Peroxiredoxin1 (PRDX1), a class of thiol peroxidases, is a multifunctional protein. We aimed at analyzing the effect of PRDX1 on proliferation, apoptosis, migration and invasion of colorectal cancer and to investigate the potential mechanism. MATERIALS AND METHODS: Western blot and PCR were used to validate the silencing efficiency in SW480 cell by transfection of PRDX1-siRNA. The cell proliferation was detected by Cell Counting Kit-8 (CCK-8) test. Flow cytometry Annexin V/PI double staining was used to analyze cell apoptosis...
April 2018: European Review for Medical and Pharmacological Sciences
Leandra C Constantino, Luisa B Binder, Samuel Vandresen-Filho, Giordano G Viola, Fabiana K Ludka, Mark W Lopes, Rodrigo B Leal, Carla I Tasca
N-methyl D-aspartate (NMDA) preconditioning is evoked by the administration of a subtoxic dose of NMDA and is protective against neuronal excitotoxicity. This effect may involve a diversity of targets and cell signaling cascades associated to neuroprotection. Phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinases (MAPKs) such as extracellular regulated protein kinase 1/2 (ERK1/2) and p38MAPK pathways play a major role in neuroprotective mechanisms. However, their involvement in NMDA preconditioning was not yet fully investigated...
April 20, 2018: Neurotoxicity Research
Li Su, Zeng Wang, Fei Huang, Ruilong Lan, Xiuying Chen, Deping Han, Lurong Zhang, Weijian Zhang, Jinsheng Hong
Radiation-induced inflammation plays an important role in radiation-induced tissue injury. 18β-glycyrrhetinic acid (18β-GA) has shown an anti-inflammatory activity. This study aimed to assess the activity of 18β-GA against radiation-induced skin damage, and explore the underlying mechanisms. In vitro assay revealed 18β-GA treatment decreased the production of IL-1β, IL-6, PGE2 and decreased p38MAPK phosphorylation, DNA-binding activity of AP-1, and NF-κB activation in irradiated RAW264.7 macrophages. Additionally, 18β-GA suppressed NF-κB activation by inhibiting NF-κB/p65 and IκB-α phosphorylation and alleviated ROS overproduction in irradiated RAW264...
April 13, 2018: Environmental Toxicology and Pharmacology
Hai-Xia Du, Hui-Fen Zhou, Yu He, Jie-Hong Yang, Yi-Yu Lu, Yi-Chen Fan, Hai-Tong Wan
This paper aimed to investigate the effect of Yinhua Pinggan granule and San-ao decoction on the immunologic mechanisms of influenza viral pneumonia mice in vivo , in order to study the activity of the combined administration of different formulas on influenza A/H1N1 virus. The model of pneumonia was established in mice through nasal dropping influenza virus, and then divided randomly into five groups: normal control group, influenza virus model group, oseltamivir control group, Yinhua Pinggan granule group, and San-ao decoction group...
March 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Jiao Xu, Shu Tang, Bin Yin, Jiarui Sun, Endong Bao
In this report, we investigate the protective mechanism of co-enzyme Q10 on chicken primary myocardial cells during heat stress. Morphological observations indicate that addition of co-enzyme Q10 protects myocardial cells from heat stress, reduces the damage of mitochondria and nucleus, and decreases the mean number of vacuolated mitochondria. We have previously shown that co-enzyme Q10 can protect myocardial cells by upregulating the expression of Hsp70. Therefore, signaling pathways involved in this process were explored...
April 18, 2018: Molecular and Cellular Biochemistry
Dayanira Alsina-Beauchamp, Alejandra Escós, Pilar Fajardo, Diego González-Romero, Ester Díaz-Mora, Ana Risco, Miguel A Martín-Serrano, Carlos Del Fresno, Jorge Dominguez-Andrés, Noelia Aparicio, Rafal Zur, Natalia Shpiro, Gordon D Brown, Carlos Ardavín, Mihai G Netea, Susana Alemany, Juan J Sanz-Ezquerro, Ana Cuenda
Candida albicans is a frequent aetiologic agent of sepsis associated with high mortality in immunocompromised patients. Developing new antifungal therapies is a medical need due to the low efficiency and resistance to current antifungal drugs. Here, we show that p38γ and p38δ regulate the innate immune response to C. albicans We describe a new TAK1-TPL2-MKK1-ERK1/2 pathway in macrophages, which is activated by Dectin-1 engagement and positively regulated by p38γ/p38δ. In mice, p38γ/p38δ deficiency protects against C...
April 16, 2018: EMBO Molecular Medicine
Guanlin Yang, Dongyu Min, Junwei Yan, Ming Yang, Guijun Lin
BACKGROUND: Injection of snakegourd peel (SP), an herb used in traditional Chinese medicine, is used to treat coronary artery disease and stable angina in China. However, its therapeutic role and mechanism of action for the treatment of myocardial infarction (MI) is not fully understood. PURPOSE: The present study was designed to investigate the effect of SP on MI-induced cardiac injury and elucidate its underlying molecular mechanisms. METHODS: To create an in vivo model of MI, we ligated the left coronary artery of Wistar rats...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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