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https://www.readbyqxmd.com/read/29676229/viral-induced-oxidative-and-inflammatory-response-in-alzheimer-s-disease-pathogenesis-with-identification-of-potential-drug-candidates-a-systematic-review-using-systems-biology-approach
#1
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
https://www.readbyqxmd.com/read/29619072/a-network-pharmacology-approach-to-uncover-the-multiple-mechanisms-of-hedyotis-diffusa-willd-on-colorectal-cancer
#2
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
https://www.readbyqxmd.com/read/29522209/evidence-of-signaling-and-adhesion-roles-for-%C3%AE-catenin-in-the-sponge-ephydatia-muelleri
#3
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
https://www.readbyqxmd.com/read/29518019/network-based-identification-of-altered-stem-cell-pluripotency-and-calcium-signaling-pathways-in-metastatic-melanoma
#4
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
https://www.readbyqxmd.com/read/29493166/-establishment-pharmacological-research-platform-for-concurrent-treatment-of-the-brain-and-heart-and-its-application-on-dissecting-mechanism-of-danhong-injection
#5
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
https://www.readbyqxmd.com/read/29461205/pten-negatively-regulates-the-cell-lineage-progression-from-ng2-glial-progenitor-to-oligodendrocyte-via-mtor-independent-signaling
#6
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
https://www.readbyqxmd.com/read/29437498/association-of-wnt-pathway-genes-with-nonsyndromic-cleft-lip-with-or-without-cleft-palate
#7
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
https://www.readbyqxmd.com/read/29431119/hypermetabolic-macrophages-in-rheumatoid-arthritis-and-coronary-artery-disease-due-to-glycogen-synthase-kinase-3b-inactivation
#8
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
https://www.readbyqxmd.com/read/29393545/bu-shen-huo-xue-fang-bshxf-modulates-nucleus-pulposus-cell-proliferation-and-extracellular-matrix-ecm-remodeling-in-intervertebral-disc-degeneration-through-mir-483-regulation-of-wnt-pathway
#9
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
https://www.readbyqxmd.com/read/29381991/rna-sequencing-uncovers-the-key-micrornas-potentially-contributing-to-sudden-sensorineural-hearing-loss
#10
Qi Li, Xiaohong Peng, Haoran Huang, Jingjing Li, Fan Wang, Jie Wang
This study aimed to identify miRNAs that may contribute to the pathogenesis of sudden sensorineural hearing loss (SSNHL) by RNA-seq (RNA-sequencing).RNA was extracted from SSNHL patients and healthy volunteers, respectively. Sequencing was performed on HiSeq4000 platform. After filtering, clean reads were mapped to the human reference genome hg19. Differential expression analysis of miRNAs between the SSNHL samples and the normal samples was performed using DEseq to identify differentially expressed microRNAs (DEMs)...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29371955/a-comparative-global-phosphoproteomics-analysis-of-obinutuzumab-ga101-versus-rituximab-rtx-against-rtx-sensitive-and-resistant-burkitt-lymphoma-bl-demonstrates-differential-phosphorylation-of-signaling-pathway-proteins-after-treatment
#11
Aradhana Awasthi, Delphine C M Rolland, Janet Ayello, Carmella van de Ven, Venkatesha Basrur, Kevin Conlon, Damian Fermin, Matthew J Barth, Christian Klein, Kojo S J Elenitoba-Johnson, Megan S Lim, Mitchell S Cairo
We recently demonstrated that obinutuzumab (GA101), a novel glycoengineered type II CD20 Ab compared to rituximab (RTX) mediates significantly enhanced antibody-dependent cell cytotoxicity (ADCC) in vitro and increased overall survival in a Burkitt lymphoma (BL) xenograft non-obese diabetic severe combined immunodeficiency gamma (NSG) model. In this study we compared the phosphoproteomic changes by pathway analysis following obinutuzumab vs RTX against RTX-sensitive (Raji) and -resistant BL (Raji4RH). Phosphoproteomic analyses were performed by mass-spectrometry (MS)-based label-free quantitative phosphoproteomic profiling...
December 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/29331582/inositol-polyphosphates-contribute-to-cellular-circadian-rhythms-implications-for-understanding-lithium-s-molecular-mechanism
#12
Heather Wei, Dominic Landgraf, George Wang, Michael J McCarthy
Most living organisms maintain cell autonomous circadian clocks that synchronize critical biological functions with daily environmental cycles. In mammals, the circadian clock is regulated by inputs from signaling pathways including glycogen synthase kinase 3 (GSK3). The drug lithium has actions on GSK3, and also on inositol metabolism. While it is suspected that lithium's inhibition of GSK3 causes rhythm changes, it is not known if inositol polyphosphates can also affect the circadian clock. We examined whether the signaling molecule inositol hexaphosphate (IP6 ) has effects on circadian rhythms...
April 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29301979/increased-rounds-of-gonadotropin-stimulation-have-side-effects-on-mouse-fallopian-tubes-and-oocytes
#13
Valentina Di Nisio, Gianna Rossi, Maria Grazia Palmerini, Guido Macchiarelli, Gian Mario Tiboni, Sandra Cecconi
In this study, it was evaluated if increased rounds of gonadotropin stimulation could affect in mice: (i) expression levels of proteins regulating cell cycle and DNA repair in fallopian tubes and (ii) meiotic spindle morphology of ovulated oocytes. To this end, adult female mice were subjected or not (Control) to 6 or 8 rounds of gonadotropin stimulation. Ovulated oocytes were incubated with anti A/B tubulin to evaluate spindle morphology. Fallopian tubes were analyzed to detect Cyclin D1, phospho-p53/p53, phospho-AKT/AKT, phospho-GSK3B/GSK3B, SOX2, OCT3/4, phospho-B-catenin/B-catenin, phospho-CHK1 and phospho-H2A...
March 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29234702/high-frequency-electrical-stimulation-hfes-data-lean-and-obese-zucker-rat-tibialis-anterior-muscle-regulation-of-glycogen-synthase-kinase-3-beta-gsk3b-associated-proteins
#14
Gautam K Ginjupalli, Kevin M Rice, Anjaiah Katta, Nandini D P K Manne, Ravikumar Arvapalli, Miaozong Wu, Shinichi Asano, Eric R Blough
Anaerobic exercise has been advocated as a prescribed treatment for the management of diabetes: however, alterations in exercise-induced signaling remain largely unexplored in the diabetic muscle. Here, we compare the basal and the in situ contraction-induced phosphorylation of the AMPK, GSK3beta, and Shp2 in the lean and obese (fa/fa) Zucker rat tibialis anterior (TA) muscle following a single bout of contractile stimuli. This article represents data associated with prior publications from our lab (Katta et al...
February 2018: Data in Brief
https://www.readbyqxmd.com/read/29191219/neurons-derived-from-sporadic-alzheimer-s-disease-ipscs-reveal-elevated-tau-hyperphosphorylation-increased-amyloid-levels-and-gsk3b-activation
#15
Anna Ochalek, Balázs Mihalik, Hasan X Avci, Abinaya Chandrasekaran, Annamária Téglási, István Bock, Maria Lo Giudice, Zsuzsanna Táncos, Kinga Molnár, Lajos László, Jørgen E Nielsen, Bjørn Holst, Kristine Freude, Poul Hyttel, Julianna Kobolák, András Dinnyés
BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia, affecting one in eight adults over 65 years of age. The majority of AD cases are sporadic, with unknown etiology, and only 5% of all patients with AD present the familial monogenic form of the disease. In the present study, our aim was to establish an in vitro cell model based on patient-specific human neurons to study the pathomechanism of sporadic AD. METHODS: We compared neurons derived from induced pluripotent stem cell (iPSC) lines of patients with early-onset familial Alzheimer's disease (fAD), all caused by mutations in the PSEN1 gene; patients with late-onset sporadic Alzheimer's disease (sAD); and three control individuals without dementia...
December 1, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29164477/genetic-variants-within-molecular-targets-of-antipsychotic-treatment-effects-on-treatment-response-schizophrenia-risk-and-psychopathological-features
#16
Marco Calabrò, Stefano Porcelli, Concetta Crisafulli, Sheng-Min Wang, Soo-Jung Lee, Changsu Han, Ashwin A Patkar, Prakash S Masand, Diego Albani, Ilaria Raimondi, Gianluigi Forloni, Sofia Bin, Carlotta Cristalli, Vilma Mantovani, Chi-Un Pae, Alessandro Serretti
Schizophrenia (SCZ) is a common and severe mental disorder. Genetic factors likely play a role in its pathophysiology as well as in treatment response. In the present study, we investigated the effects of several single nucleotide polymorphisms (SNPs) within 9 genes involved with antipsychotic (AP) mechanisms of action. Two independent samples were recruited. The Korean sample included 176 subjects diagnosed with SCZ and 326 healthy controls, while the Italian sample included 83 subjects and 194 controls. AP response as measured by the positive and negative syndrome scale (PANSS) was the primary outcome, while the secondary outcome was the SCZ risk...
January 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29138341/long-noncoding-rna-neat1-regulated-by-the-egfr-pathway-contributes-to-glioblastoma-progression-through-the-wnt-%C3%AE-catenin-pathway-by-scaffolding-ezh2
#17
Qun Chen, Jinquan Cai, Qixue Wang, Yunfei Wang, Mingyang Liu, Jingxuan Yang, Junhu Zhou, Chunsheng Kang, Min Li, Chuanlu Jiang
Purpose: Long noncoding RNAs have been implicated in gliomagenesis, but their mechanisms of action are mainly undocumented. Through public glioma mRNA expression data sets, we found that NEAT1 was a potential oncogene. We systematically analyzed the clinical significance and mechanism of NEAT1 in glioblastoma. Experimental Design: Initially, we evaluated whether NEAT1 expression levels could be regulated by EGFR pathway activity. We subsequently evaluated the effect of NEAT1 on the WNT/β-catenin pathway and its target binding gene...
February 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29136244/a-molecular-cascade-modulates-map1b-and-confers-resistance-to-mtor-inhibition-in-human-glioblastoma
#18
Dan R Laks, Juan A Oses-Prieto, Alvaro G Alvarado, Jonathan Nakashima, Shreya Chand, Daniel B Azzam, Ankur A Gholkar, Jantzen Sperry, Kirsten Ludwig, Michael C Condro, Serli Nazarian, Anjelica Cardenas, Michelle Y S Shih, Robert Damoiseaux, Bryan France, Nicholas Orozco, Koppany Visnyei, Thomas J Crisman, Fuying Gao, Jorge Z Torres, Giovanni Coppola, Alma L Burlingame, Harley I Kornblum
Background: Clinical trials of therapies directed against nodes of the PI3K/AKT/mTOR signaling axis in Glioblastoma (GBM) have had disappointing results. Resistance to mTOR inhibitors limits their efficacy. Methods: To determine mechanisms of resistance to chronic mTOR inhibition, we performed tandem screens on patient-derived GBM cultures. Results: An unbiased phosphoproteomic screen quantified phosphorylation changes associated with chronic exposure to the mTOR inhibitor rapamycin and our analysis implicated a role for GSK3B attenuation in mediating resistance that was confirmed by functional studies...
November 9, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29117336/clinical-and-genetic-predictors-of-paclitaxel-neurotoxicity-based-on-patient-versus-clinician-reported-incidence-and-severity-of-neurotoxicity-in-the-icon7-trial
#19
S B Park, J B Kwok, R Asher, C K Lee, P Beale, F Selle, M Friedlander
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of paclitaxel, with no reliable method to identify at-risk patients. We investigated the incidence and risk factors including genetic polymorphisms associated with the development of CIPN based on clinician and patient reporting of neuropathic symptoms. Patients and methods: Risk factors for the development of CIPN were examined in 454 patients treated with paclitaxel/carboplatin from the International Collaboration on Ovarian Neoplasms 7 (ICON7) trial...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29110225/a-deregulated-pi3k-akt-signaling-pathway-in-patients-with-colorectal-cancer
#20
Tao Zhang, Yuanping Ma, Jiansong Fang, Chang Liu, Liangrong Chen
BACKGROUND: Molecular switches in phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway may serve as potential targets for the treatment of colorectal cancer (CRC). This study aims to profile the gene alterations involved in PI3K-AKT signaling pathway in patients with CRC. METHODS: Tumoral and matched peritumoral tissues were collected from 15 CRC patients who went routine surgery. A human PI3K-AKT signaling pathway polymerase chain reaction (PCR) array, which profiled the transcriptional changes of a total number of 84 genes involved in the PI3K-AKT pathway, was then applied to determine the gene alterations in CRC tumoral tissue with matched peritumoral tissue as a healthy control...
November 7, 2017: Journal of Gastrointestinal Cancer
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