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Valentina Siino, Antonella Amato, Francesca Di Salvo, Gaetano Felice Caldara, Marcello Filogamo, Peter James, Sonya Vasto
Obesity is closely associated to several diseases such as type 2 diabetes, cardiovascular disease, hepatic steatosis, airway disease, neurodegeneration, biliary diseases and certain cancers. It is, therefore, of importance to assess the role of nutrition in disease prevention as well as its effect in the course of such pathologies. In the present study, we addressed the impact of the exposure to different obesogenic diets in the mice brains phosphoproteome. To analyze if the obesity could be able to modify the protein pattern expression of brain neurons, obesity was induced in two different groups of mice...
May 1, 2018: Journal of Nutritional Biochemistry
Raquel Coronel, María Lachgar, Adela Bernabeu-Zornoza, Charlotte Palmer, Marta Domínguez-Alvaro, Ana Revilla, Inmaculada Ocaña, Andrés Fernández, Alberto Martínez-Serrano, Eva Cano, Isabel Liste
Amyloid precursor protein (APP) is implicated in neural development as well as in the pathology of Alzheimer's disease (AD); however, its biological function still remains unclear. It has been reported that APP stimulates the proliferation and neuronal differentiation of neural stem cells (NSCs), while other studies suggest an important effect enhancing gliogenesis in NSCs. As expected, APP protein/mRNA is detected in hNS1 cells, a model cell line of human NSCs, both under proliferation and throughout the differentiation period...
June 7, 2018: Molecular Neurobiology
Tongxing Wang, Lu Han, Xiaorui Zhang, Rongrong Wu, Xiaorui Cheng, Wenxia Zhou, Yongxiang Zhang
Growing evidence shows that the neuroendocrine immunomodulation (NIM) network plays an important role in maintaining and modulating body function and the homeostasis of the internal environment. The disequilibrium of NIM in the body is closely associated with many diseases. In the present study, we first collected a core dataset of NIM signaling molecules based on our knowledge and obtained 611 NIM signaling molecules. Then, we built a NIM molecular network based on the MetaCore database and analyzed the signaling transduction characteristics of the core network...
May 30, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Chaoying Jiang, Chao He, Zhiqiang Wu, Fengfeng Li, Jianru Xiao
SETD2 is a histone methyltransferase that catalyzes the trimethylation of lysine 36 on histone 3. SETD2 is frequently found to be mutated or deleted in a variety of human tumors, whereas the role of SETD2 in oncogenesis of osteosarcoma has never been defined. Here in our study, we uncovered that SETD2 regulates tumor growth and chemosensitivity of osteosarcoma. Overexpression of SETD2 significantly inhibited osteosarcoma cell growth in vitro and in vivo. Moreover, SETD2 significantly enhanced cisplatin-induced apoptosis in osteosarcoma cells and inhibited cancer stem cell properties in OS cells...
May 26, 2018: Biochemical and Biophysical Research Communications
Qi Ge, Liang Chen, Min Tang, Shu Zhang, Lu Gao, Shangshang Ma, Lanlan Liu, Ming Kong, Qin Yao, Keping Chen, Fan Feng
Mulberry leaves are one of the most commonly used medicinal and herbaceous traditional Chinese medicines that are currently considered for the treatment of diabetes mellitus and its complications. The alkaloids, flavonoids, and polysaccharides in mulberry leaves impart regulatory effects on blood sugar levels. To identify the hypoglycemia-related active components in mulberry leaves and their targets, the present study conducted gas chromatography-mass spectrometer (GC/MS), which identified 202 components of mulberry leaf, of which 22 components may have significant curative effects on diabetes mellitus and its complications and chronic inflammation...
May 18, 2018: European Journal of Pharmacology
Ye Hou, Liangliang Fu, Jingjin Li, Jingxuan Li, Yunxia Zhao, Yu Luan, An Liu, Huiying Liu, Xinyun Li, Shuhong Zhao, Changchun Li
>Emerging evidence indicates that microRNA (miRNA) plays an important role in adipogenesis and disease pathogenesis. To investigate the miRNA involved in regulating different periods of adipogenesis, we performed a comprehensive study on microRNAome during the stimulation of adipogenesis by an adipogenic differentiation cocktail in C2C12 myoblasts at 0, 2, 4, and 7 days using the Solexa sequencing technology. In this study, we identified 52 differentially expressed (DE) miRNA. Functional annotation indicated that the target genes of DE miRNA were mostly enriched in adipogenic transdifferentiation and fat metabolism-related pathways, including Wnt, mitogen-activated protein kinase (MAPK), and insulin signaling...
May 16, 2018: Lipids
Bin Xing, Lauren E Brink, Kelly Maers, Mara L Sullivan, Richard J Bodnar, Donna B Stolz, Franca Cambi
Apoptosis is recognized as the main mechanism of oligodendrocyte loss in Multiple Sclerosis caused either by immune mediated injury (Barnett & Prineas, ) or a direct degenerative process (oligodendrogliapathy; Lucchinetti et al., ). Cuprizone induced demyelination is the result of non-immune mediated apoptosis of oligodendrocytes (OL) and represents a model of oligodendrogliapathy (Simmons, Pierson, Lee, & Goverman, ). Glycogen Synthase Kinase (GSK) 3b has been shown to be pro-apoptotic for cells other than OL...
May 15, 2018: Glia
Ji-Eun Kim, Ah-Reum Ko, Hye-Won Hyun, Su-Ji Min, Tae-Cheon Kang
Recently, we have reported that heat shock protein B1 (HSPB1) and purinergic receptor P2X7 (P2RX7) are involved in astroglial autophagy (clasmatodendrosis), following status epilepticus (SE). However, the underlying mechanisms of astroglial autophagy have not been completely established. In the present study, we found that the lacking of P2rx7 led to prolonged astroglial HSPB1 induction due to impaired mitogen-activated protein kinase 1/2 (MAPK1/2)-mediated specificity protein 1 (SP1) phosphorylation, following kainic acid-induced SE...
May 10, 2018: Cell Death & Disease
Olga C Jorge-Torres, Karolina Szczesna, Laura Roa, Carme Casal, Louisa Gonzalez-Somermeyer, Marta Soler, Cecilia D Velasco, Pablo Martínez-San Segundo, Paolo Petazzi, Mauricio A Sáez, Raúl Delgado-Morales, Stephane Fourcade, Aurora Pujol, Dori Huertas, Artur Llobet, Sonia Guil, Manel Esteller
Rett syndrome (RTT) is the second leading cause of mental impairment in girls and is currently untreatable. RTT is caused, in more than 95% of cases, by loss-of-function mutations in the methyl CpG-binding protein 2 gene (MeCP2). We propose here a molecular target involved in RTT: the glycogen synthase kinase-3b (Gsk3b) pathway. Gsk3b activity is deregulated in Mecp2-knockout (KO) mice models, and SB216763, a specific inhibitor, is able to alleviate the clinical symptoms with consequences at the molecular and cellular levels...
May 8, 2018: Cell Reports
Chung-Feng Kao, Yu-Li Liu, Younger W-Y Yu, Albert C Yang, Eugene Lin, Po-Hsiu Kuo, Shih-Jen Tsai
It is well established that brain-derived neurotrophic factor (BDNF) signaling pathway plays a key role in the pathophysiology of major depressive disorder (MDD) and in therapeutic mechanisms of antidepressants. We aim to identify genetic vairiants related to MDD susceptibility and antidepressant therapeutic response by using gene-based association analysis with genes related to the neurotrophic pathway. The present study investigated the role of genetic variants in the 10 neurotrophic-related genes (BDNF, NGFR, NTRK2, MTOR, VEGFA, S100A10, SERPINE1, ARHGAP33, GSK3B, CREB1) in MDD susceptibility through a case-control (455 MDD patients and 2,998 healthy controls) study and in antidepressant efficacy (n = 455)...
May 3, 2018: Scientific Reports
Jivan Khlghatyan, Alesya Evstratova, Simon Chamberland, Aleksandra Marakhovskaia, Arash Bahremand, Katalin Toth, Jean-Martin Beaulieu
Genetic variants of the fragile X mental retardation syndrome-related protein 1 ( FXR1) have been associated to mood regulation, schizophrenia, and bipolar disorders. Nonetheless, genetic association does not indicate a functional link of a given gene to neuronal activity and associated behaviors. In addition, interaction between multiple genes is often needed to sculpt complex traits such as behavior. Thus, modulation of neuronal functions by a given gene product, such as Fxr1, has to be thoroughly studied in the context of its interactions with other gene products...
2018: Frontiers in Molecular Neuroscience
Puneet Talwar, Renu Gupta, Suman Kushwaha, Rachna Agarwal, Luciano Saso, Shrikant Kukreti, Ritushree Kukreti
Alzheimer's disease (AD) is genetically complex with multifactorial etiology. Here, we aim to identify the potential viral pathogens leading to aberrant inflammatory and oxidative stress response in AD along with potential drug candidates using systems biology approach. We retrieved protein interactions of amyloid precursor protein (APP) and tau protein (MAPT) from NCBI and genes for oxidative stress from NetAge, for inflammation from NetAge and InnateDB databases. Genes implicated in aging were retrieved from GenAge database and two GEO expression datasets...
April 19, 2018: Current Neuropharmacology
Xinkui Liu, Jiarui Wu, Dan Zhang, Kaihuan Wang, Xiaojiao Duan, Xiaomeng Zhang
Background: As one of the most frequently diagnosed cancer diseases globally, colorectal cancer (CRC) remains an important cause of cancer-related death. Although the traditional Chinese herb Hedyotis diffusa Willd. (HDW) has been proven to be effective for treating CRC in clinical practice, its definite mechanisms have not been completely deciphered. Objective: The aim of our research is to systematically explore the multiple mechanisms of HDW on CRC. Methods: This study adopted the network pharmacology approach, which was mainly composed of active component gathering, target prediction, CRC gene collection, network analysis, and gene enrichment analysis...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Klaske J Schippers, Scott A Nichols
β-catenin acts as a transcriptional co-activator in the Wnt/β-catenin signaling pathway and a cytoplasmic effector in cadherin-based cell adhesion. These functions are ancient within animals, but the earliest steps in β-catenin evolution remain unresolved due to limited data from key lineages - sponges, ctenophores and placozoans. Previous studies in sponges have characterized β-catenin expression dynamics and used GSK3B antagonists to ectopically activate the Wnt/β-catenin pathway; both approaches rely upon untested assumptions about the conservation of β-catenin function and regulation in sponges...
March 7, 2018: Molecular Biology and Evolution
Ben-Hur Neves de Oliveira, Carla Dalmaz, Fares Zeidán-Chuliá
Malignancy of cancer has been linked to distinct subsets of stem-like cells, the so-called cancer stem cells (CSCs), which persist during treatment and seem to lead to drug-resistant recurrence. Metastatic spread of cancer cells is one of the hallmarks of malignancy and contributes to most human melanoma-related deaths. Recently, overlapping groups of proteins and pathways were shown to regulate stem cell migration and cancer metastasis, raising the question of whether genes/proteins involved in stem cell pluripotency may have important implications when applied to the biology of cancer metastasis...
March 8, 2018: Medical Sciences: Open Access Journal
Xiao-Ping Zhao, Yun-Ru Yu, Xue Li, Qing Shao, Yi-Min Wang, Tao Zhao, Chao Zhao, Bu-Chang Zhao, Yue-Fei Wang, Yi Wang
The Concurrent treatment of the brain and heart (CTBH) theory is proposed based on traditional Chinese medical theory and clinical practice. In this study, a framework for the pharmacological research platform was established to investigate the principles of concurrent treatment of the brain and heart. The platform for CTBH includes several key techniques for network modeling, discovery of active substances, dissecting mechanism of action and investigation of pharmacokinetic property of TCM. Taking network modeling of CTBH as an example, using database search, literature mining, network construction and module analysis, the that network modules closely associated with the pathological progress of cardiovascular and cerebrovascular diseases were identified, while further functional enrichment analysis of these modules indicated that the key biological processes included oxidative stress, metabolism and inflammation...
December 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Estibaliz González-Fernández, Hey-Kyeong Jeong, Masahiro Fukaya, Hyukmin Kim, Rabia R Khawaja, Isha N Srivastava, Ari Waisman, Young-Jin Son, Shin H Kang
Oligodendrocytes (OLs), the myelin-forming CNS glia, are highly vulnerable to cellular stresses, and a severe myelin loss underlies numerous CNS disorders. Expedited OL regeneration may prevent further axonal damage and facilitate functional CNS repair. Although adult OL progenitors (OPCs) are the primary players for OL regeneration, targetable OPC-specific intracellular signaling mechanisms for facilitated OL regeneration remain elusive. Here, we report that OPC-targeted PTEN inactivation in the mouse, in contrast to OL-specific manipulations, markedly promotes OL differentiation and regeneration in the mature CNS...
February 20, 2018: ELife
V Vijayan, R Ummer, R Weber, R Silva, A Letra
OBJECTIVE: Nonsyndromic cleft lip with or without cleft palate (NSCL±P) is a common craniofacial anomaly with multifactorial etiology. Evidence suggests that variations in WNT pathway genes contribute to an increased susceptibility to NSCL±P. The aim of this study was to investigate the association of AXIN1, APC, CTNNB1, DVL2, and GSK3β gene variants with NSCL±P in a case-control data set from Brazil. PATIENTS: 471 individuals with NSCL±P and 504 unrelated control individuals of Caucasian ethnicity...
March 2018: Cleft Palate-craniofacial Journal
Markus Zeisbrich, Rolando E Yanes, Hui Zhang, Ryu Watanabe, Yinyin Li, Lukas Brosig, Jison Hong, Barbara B Wallis, John C Giacomini, Themistocles L Assimes, Jörg J Goronzy, Cornelia M Weyand
OBJECTIVES: Accelerated atherosclerotic disease typically complicates rheumatoid arthritis (RA), leading to premature cardiovascular death. Inflammatory macrophages are key effector cells in both rheumatoid synovitis and the plaques of coronary artery disease (CAD). Whether both diseases share macrophage-dependent pathogenic mechanisms is unknown. METHODS: Patients with RA or CAD (at least one myocardial infarction) and healthy age-matched controls were recruited into the study...
February 3, 2018: Annals of the Rheumatic Diseases
Shaofeng Yang, Linghui Li, Liguo Zhu, Chao Zhang, Zhaoyong Li, Yantao Guo, Ying Nie, Zhenhua Luo
Intervertebral disc degeneration (IDD) has been widely considered as one of the main causes for low back pain (LBP) which can cause severe impact to human health and huge economic burden to worldwide society. IDD pathogenesis can be affected by extensive degradation of extracellular matrix (ECM) and the hyperproliferation of nucleus pulposus (NP) cell. During IDD process, ECM degradation enzymes MMP and ADAMTS expression increases, while ECM synthesis-related Aggrecan and COL2A1 expression decreases. In addition, Wnt signaling pathway is reportedly involved in the process of IDD...
February 2, 2018: Journal of Cellular Biochemistry
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