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https://www.readbyqxmd.com/read/28551908/-involvement-of-epigenetic-regulation-in-cerebral-cell-death-following-traumatic-brain-injury-in-a-rat-model
#1
Mona Shehadeh, Moti Ben-Shabat, Jana Livshits, Eilam Palzur
INTRODUCTION: Traumatic brain injuries (TBI) are a major cause of mortality and disability among young adults. TBI are characterized by primary injury, the result of a mechanical impact to the cranium and a secondary injury, a series of molecular mechanism processes developing thereafter. Cerebral cells modify their gene and protein expression as a result of the injury. Epigenetic modifications have a key role as regulators of gene transcription and may simultaneously be involved in the regulation of the molecular pathways following TBI...
May 2017: Harefuah
https://www.readbyqxmd.com/read/28551849/long-non-coding-rna-malat1-promotes-proliferation-and-suppresses-apoptosis-of-glioma-cells-through-derepressing-rap1b-by-sponging-mir-101
#2
Zhenjiang Li, Chenyang Xu, Bingqian Ding, Ming Gao, Xinting Wei, Nan Ji
Long non-coding RNAs (lncRNAs) have been recently shown to be dysregulated and closely related to several cancers. Here, we aimed to elucidate the function and the possible molecular mechanisms of lncRNA Metastasis-associated lung Adenocarcinoma transcript-1 (MALAT1) in human glioma. Quantitative real-time PCR (qRT-PCR) was used to detect the expressions of MALAT1, miR-101 and Rap1B mRNA in U251 and U87 cells. The protein level of Rap1B was examined by western blot assays. Moreover, the proliferation and apoptosis of U251 and U87 cells were determined by CCK-8 assay and flow cytometry analysis, respectively...
May 27, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28551817/discovery-of-novel-inhibitors-for-leishmania-nucleoside-diphosphatase-kinase-ndk-based-on-its-structural-and-functional-characterization
#3
Arjun K Mishra, Nidhi Singh, Pragati Agnihotri, Shikha Mishra, Saurabh P Singh, Bala K Kolli, Kwang Poo Chang, Amogh A Sahasrabuddhe, M I Siddiqi, J Venkatesh Pratap
Nucleoside diphosphate kinases (NDKs) are ubiquitous enzymes that catalyze the transfer of the γ-phosphate moiety from an NTP donor to an NDP acceptor, crucial for maintaining the cellular level of nucleoside triphosphates (NTPs). The inability of trypanosomatids to synthesize purines de novo and their dependence on the salvage pathway makes NDK an attractive target to develop drugs for the diseases they cause. Here we report the discovery of novel inhibitors for Leishmania NDK based on the structural and functional characterization of purified recombinant NDK from Leishmania amazonensis...
May 27, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28551805/mitochondria-damage-and-kidney-disease
#4
Pu Duann, Pei-Hui Lin
The kidney is a vital organ that demands an extraordinary amount of energy to actively maintain the body's metabolism, plasma hemodynamics, electrolytes and water homeostasis, nutrients reabsorption, and hormone secretion. Kidney is only second to the heart in mitochondrial count and oxygen consumption. As such, the health and status of the energy power house, the mitochondria, is pivotal to the health and proper function of the kidney. Mitochondria are heterogeneous and highly dynamic organelles and their functions are subject to complex regulations through modulation of its biogenesis, bioenergetics, dynamics and clearance within cell...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28551794/functional-role-of-nox4-in-autophagy
#5
Maurizio Forte, Silvia Palmerio, Derek Yee, Giacomo Frati, Sebastiano Sciarretta
Accumulating lines of evidence suggest that reactive oxygen species (ROS) may act as intracellular signaling molecules under cellular stress conditions, activating several molecular pathways. Autophagy, the intracellular mechanism by which cells digest and recycle unfolded proteins and dysfunctional organelles, is emerging as a major target of ROS and NADPH oxidase (Nox) enzymes, the major generators of ROS. While autophagy represents an important self-defense mechanism in promoting cell survival, it may be maladaptive in some conditions...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28551788/functional-role-of-mitochondria-in-arrhythmogenesis
#6
Jessica Gambardella, Daniela Sorriento, Michele Ciccarelli, Carmine Del Giudice, Antonella Fiordelisi, Luigi Napolitano, Bruno Trimarco, Guido Iaccarino, Gaetano Santulli
Growing evidence indicate that mitochondria play a functional role in arrhythmogenesis. We report here the molecular mechanisms underlying the action of these highly dynamic organelles in the regulation of cell metabolism, action potential and, overall, heart excitability. In particular, we examine the role of cardiac mitochondria in linking metabolism and cell excitability. The importance of the main mitochondrial channels is evaluated as well, including the recently identified calcium uniporter. Promises and pitfalls of potential therapeutic strategies targeting mitochondrial pathways are also assessed...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28551771/synergistic-effects-of-chuanxiong-chishao-herb-pair-on-promoting-angiogenesis-at-network-pharmacological-and-pharmacodynamic-levels
#7
Yan Wang, Gang Guo, Bin-Rui Yang, Qi-Qi Xin, Qi-Wen Liao, Simon Ming-Yuen Lee, Yuan-Jia Hu, Ke-Ji Chen, Wei-Hong Cong
OBJECTIVE: To investigate the synergistic effects of Chuanxiong-Chishao herb-pair (CCHP) on promoting angiogenesis in silico and in vivo. METHODS: The mechanisms of action of an herb-pair, Chuanxiong- Chishao, were investigated using the network pharmacological and pharmacodynamic strategies involving computational drug target prediction and network analysis, and experimental validation. A set of network pharmacology methods were created to study the herbs in the context of targets and diseases networks, including prediction of target profiles and pharmacological actions of main active compounds in Chuanxiong and Chishao...
May 27, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28551748/anatomy-and-cell-biology-of-autism-spectrum-disorder-lessons-from-human-genetics
#8
Kristel T E Kleijer, Guillaume Huguet, Julie Tastet, Thomas Bourgeron, J P H Burbach
Until recently autism spectrum disorder (ASD) was regarded as a neurodevelopmental condition with unknown causes and pathogenesis. In the footsteps of the revolution of genome technologies and genetics, and with its high degree of heritability, ASD became the first neuropsychiatric disorder for which clues towards molecular and cellular pathogenesis were uncovered by genetic identification of susceptibility genes. Currently several hundreds of risk genes have been assigned, with a recurrence below 1% in the ASD population...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28551692/when-do-paediatric-patients-with-familial-hypercholesterolemia-need-statin-therapy
#9
Matylda Hennig, Agnieszka Brandt, Joanna Bautembach-Minkowska, Dominik Świętoń, Agnieszka Mickiewicz, Magdalenia Chmara, Bartosz Wasąg, Ewa Kamińska, Anna Balcerska, Janusz Limon, Andrzej Rynkiewicz, Marcin Gruchała, Małgorzata Myśliwiec
INTRODUCTION: Familial hypercholesterolemia (FH) is one of the most common autosomal dominant disorders. It is characterized by elevated LDL cholesterol levels occurring already by early childhood. Awareness of health risks in FH patients should incite health professionals to actively seek and treat children with lipid disorders to reduce their risk of myocardial infarction and stroke. OBJECTIVE: The aim of the study was to evaluate the suitability of taking into account the following parameters: ApoB/ApoA index, IMT and e-tracking examination, when initiating statin therapy in FH patients...
2017: Developmental Period Medicine
https://www.readbyqxmd.com/read/28551639/a-novel-near-infrared-fluorescent-protein-irfp720-facilitates-transcriptional-profiling-of-prostate-cancer-bone-metastasis-in-mice
#10
Mariko Honda, Satomi Yogosawa, Minori Kamada, Yuko Kamata, Takahiro Kimura, Yusuke Koike, Toru Harada, Hiroyuki Takahashi, Shin Egawa, Kiyotsugu Yoshida
BACKGROUND: Bone represents a frequent site of prostate cancer metastasis. As the molecular mechanism remains unclear, an accessible animal model is required. MATERIALS AND METHODS: We established a novel murine metastasis model using near-infrared fluorescent protein iRFP720-labelled prostate cancer (PC3) cells. To clarify transcriptional alterations during metastasis, iRFP720-PC3 cells were intracardially injected into male mice. mRNA expression profiles of metastasis in bone using marrow cancer cells extracted by centrifugal separation and cell sorting were compared with those of parental cells by microarray...
June 2017: Anticancer Research
https://www.readbyqxmd.com/read/28551620/impact-of-small-molecules-on-%C3%AE-catenin-and-e-cadherin-expression-in-hpv16-positive-and-negative-squamous-cell-carcinomas
#11
Benedikt Kramer, Clemens Hock, Johannes David Schultz, Anne Lammert, Beatrice Kuhlin, Richard Birk, Karl Hörmann, Christoph Aderhold
BACKGROUND: The validation of potential molecular targets in head and neck squamous cell carcinoma (SCC) is mandatory. β-Catenin and E-cadherin are crucial for cancer progression through epithelial-mesenchymal transition. We analyzed the effect of the tyrosine kinase inhibitors nilotinib, dasatinib, erlotinib and gefitinib on β-catenin and E-cadherin expression in SCC with respect to human papillomavirus (HPV) status. MATERIALS AND METHODS: Expression of β-catenin and E-cadherin in cell lines UMSCC 11A, UMSCC 14C and CERV196 under the influence of tyrosine kinase inhibitors were analyzed by enzyme-linked immunosorbent assay...
June 2017: Anticancer Research
https://www.readbyqxmd.com/read/28551613/erdheim-chester-disease-comprehensive-review-of-molecular-profiling-and-therapeutic-advances
#12
REVIEW
Faysal Haroun, Kristen Millado, Imad Tabbara
The revised 2016 World Health Organization classification introduced Erdheim-Chester disease (ECD) as a provisional entity within the histiocytic and dendritic cell neoplasms separate from the juvenile xanthogranuloma family based on distinct molecular features. However, evolving knowledge regarding the molecular and genetic aberrations in addition to common clinical features of ECD support the classification of ECD together with Langerhans cell histiocytosis (LCH). Accordingly, ECD can be thought of as an inflammatory myeloid clonal disorder based on the detection of various activating mutations along the mitogen activated protein kinase-extracellular signal regulated kinase (MAPK-ERK) pathway with most notable variant being a valine to a glutamic acid substitution at amino acid 600 in the B-rapidly accelerated fibrosarcoma protein (BRAFV600E)...
June 2017: Anticancer Research
https://www.readbyqxmd.com/read/28551612/pancreatic-cancer-stem-cells-and-therapeutic-approaches
#13
REVIEW
Gulinnaz Ercan, Ayfer Karlitepe, Bulent Ozpolat
Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest human cancers, with 1-5% 5-year survival rates (~6-month median survival duration) despite therapy; thus, PDAC represents an unmet therapeutic challenge. PDAC is the major histological subtype, comprising 90% of all pancreatic cancers. It is a highly complex and aggressive malignancy, presenting with early local invasion and metastasis, and is resistant to most therapies, all of which are believed to contribute to its extremely poor prognosis...
June 2017: Anticancer Research
https://www.readbyqxmd.com/read/28551544/molecular-assessment-of-protective-effect-of-vitex-negundo-in-iso-induced-myocardial-infarction-in-rats
#14
Maruthi Prasad E, Ramgopal Mopuri, Madhusudana Pulaganti, Mohammed Abdul Kareem, Md Shahidul Islam, Dase Gowda K R, Mackraj Irene, Yingli Lu, Lakshmi Devi Kodidhela
Myocardial infarction (MI) is the one of the major causes of death worldwide, however the molecular mechanisms hidden under this disease conditions remain unknown. This demands serious attention to unravel the molecular mechanisms to identify the therapeutic strategies either to prevent or to control MI. Ayurveda is becoming one of the best alternatives for the modern medicines. On the other hand, Vitex negundo is one of the medicinally important plants used for various diseases and to date, its cardioprotective role is not fully elucidated...
May 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28551502/promiscuity-and-selectivity-of-small-molecule-inhibitors-across-tam-receptor-tyrosine-kinases-in-pediatric-leukemia
#15
Mao-Hua Liu, Shi-Bing Chen, Juan Yu, Cheng-Jun Liu, Xiao-Jing Zhang
The TAM receptor tyrosine kinase family member Mer has been recognized as an attractive therapeutic target for pediatric leukemia. Beside Mer the family contains other two kinases, namely, Tyro3 and Axl, which are highly homologues with Mer and thus most existing small-molecule inhibitors show moderate or high promiscuity across the three kinases. Here, the structural basis and energetic property of selective binding of small-molecule inhibitors to the three kinases were investigated at molecular level. It is found that the selectivity is primarily determined by the size, shape and configuration of kinase's ATP-binding site; the Mer and Axl possess a small, closed active pocket as compared to the bulky, open pocket of Tyro3...
May 15, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28551457/a-multiplex-pcr-assay-for-molecular-capsular-serotyping-of-mannheimia-haemolytica-serotypes-1-2-and-6
#16
Cassidy L Klima, Rahat Zaheer, Robert E Briggs, Tim A McAllister
Mannheimia haemolytica is an important respiratory pathogen of ruminants. Of the 12 capsular serovars identified, 1 and 6 are most frequently associated with disease in cattle, while 2 is largely a commensal. Comparative analysis of 24 M. haemolytica genomes was used to identify unique genes associated with capsular polysaccharide synthesis as amplification targets in a multiplex PCR assay to discriminate between serotype 1, 2 and 6 strains. The specificity of serotype specific gene targets was evaluated against 47 reference strains representing 12 known serovars of M...
May 24, 2017: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/28551412/heterogeneity-in-renal-cell-carcinoma
#17
REVIEW
Alp Tuna Beksac, David J Paulucci, Kyle A Blum, Shalini Singh Yadav, John P Sfakianos, Ketan K Badani
INTRODUCTION: In recent years, molecular characterization of renal cell carcinoma has facilitated the identification of driver genes, specific molecular pathways, and characterization of the tumor microenvironment, which has led to a better understanding of the disease. This comprehension has revolutionized the treatment for patients with metastatic disease, but despite these advancements many patients will develop resistance leading to treatment failure. A primary cause of this resistance and subsequent treatment failure is tumor heterogeneity...
May 24, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28551389/mutation-analysis-of-ctnnb1-gene-and-the-ras-pathway-genes-kras-nras-braf-and-pik3ca-in-eyelid-sebaceous-carcinomas
#18
Mi Jung Kwon, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Ji-Young Choe
Sebaceous carcinoma (SC) represents a rare, aggressive eyelid malignancy with poor prognosis and is a possible component of Muir-Torre syndrome. However, genetic features as driver mutations or potential therapeutic targets are not fully elucidated. Recent a few studies have shown that SCs have concurrently multiple mutations including RAS/RAF/MAPK and PI3K/Akt pathways via next-generation sequencing in western population. Because we recently demonstrated absence of KRAS mutations in Korean eyelid SCs, we extended our previous study to the analysis of NRAS, BRAF, PIK3CA, and CTNNB1 mutations, and the examination of related protein expressions in 15 eyelid SCs...
March 1, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28551028/bidirectional-interactions-between-diabetes-and-alzheimer-s-disease
#19
REVIEW
Mitsuru Shinohara, Naoyuki Sato
Clinical studies have indicated that diabetes is associated with Alzheimer's disease (AD) and neurodegeneration. However, the mechanisms underlying this association have not been fully elucidated. Diabetes causes neurodegeneration by inducing changes in vascular function and structure, glucose metabolism, and insulin signaling, as well as by modifying β-amyloid (Aβ)/tau metabolisms. In turn, AD influences systemic glucose metabolism by inducing behavioral changes, memory disturbances, hypothalamic dysfunction, frailty and possibly plasma/peripheral Aβ level changes...
May 24, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28550959/coexistence-of-egfr-kras-braf-and-pik3ca-mutations-and-alk-rearrangement-in-a%C3%A2-comprehensive-cohort-of-326-consecutive-spanish-nonsquamous-nsclc-patients
#20
Paloma Martín Martorell, Marisol Huerta, Amparo Compañ Quilis, Rosario Abellán, Enrique Seda, Sebastián Blesa, Felipe J Chaves, Diego Dualde Beltrán, Susana Roselló Keränen, José Franco, Amelia Insa
INTRODUCTION: Molecular screening is crucial for the care of nonsquamous non-small-cell lung cancer (NSCLC) patients. The coexistence of mutations could have important consequences regarding treatment. We described the mutational patterns and coexistence among patients and their outcomes after targeted treatment. MATERIALS AND METHODS: Data from consecutive patients with newly diagnosed nonsquamous NSCLC were prospectively collected. Next-generation sequencing analysis of mutational hotspots in the EGFR, KRAS, PIK3CA, and BRAF genes and analysis of anaplastic lymphoma kinase (ALK) rearrangement were performed...
April 27, 2017: Clinical Lung Cancer
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