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https://www.readbyqxmd.com/read/28544624/pyrimidine-containing-epidermal-growth-factor-receptor-kinase-inhibitors-synthesis-and-biological-evaluation
#1
Gaurav Joshi, Himanshu Nayyar, Sourav Kalra, Praveen Sharma, Anjana Munshi, Sandeep Singh, Raj Kumar
Structure based design and synthesis of pyrimidine containing reversible epidermal growth factor receptor (EGFR) inhibitors 1a-d are reported. The compounds (1a-d) inhibited the EGFR kinase activity in vitro with IC50 range 740 nM to 3 μM. mRNA expression of EGFR downstream target genes i.e. twist, c-fos and aurora were found to be altered upon treatment with compounds 1a-d. The compounds 1a-d exhibited excellent anticancer activity at low micromolar level (3.2-9 μM) in lung, colon and breast cancer cell lines...
May 23, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28544557/lncrna-tcons_00026907-is-involved-in-the-progression-and-prognosis-of-cervical-cancer-through-inhibiting-mir-143-5p
#2
Xuejing Jin, Xiangjian Chen, Yan Hu, Furong Ying, Ruanmin Zou, Feng Lin, Zhengzheng Shi, Xuejie Zhu, Xiaojian Yan, Shi Li, Hua Zhu
Our previous long noncoding RNA (lncRNA) microarray revealed that lncRNA-TCONS_00026907 is aberrantly expressed between cervical cancer tissues and adjacent tissues. This study aims to explore the potential role of TCONS_00026907 in the development of cervical cancer. The expression levels of TCONS_00026907 in cervical cancer tissues and adjacent tissues from 83 patients of cervical cancer were detected by quantitative real-time polymerase chain reaction and the survival rate was analyzed. In vitro, HeLa and SiHa cells were transfected with small hairpin RNA (shRNA)-TCONS_00026907, then cell proliferation, cycle distribution, apoptosis, migration and invasion were measured...
May 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28539954/differential-histone-acetylation-in-sub-regions-of-bed-nucleus-of-the-stria-terminalis-underlies-fear-consolidation-and-extinction
#3
Vandana Ranjan, Sanjay Singh, Sarfraj Ahmad Siddiqui, Sukanya Tripathi, Mohd Yahiya Khan, Anand Prakash
OBJECTIVE: The hallmark of anxiety disorders is excessive fear. Previous studies have suggested that selective neural projections from Basal nucleus of stria terminalis (BNST) to amygdala and vice-versa precisely control the fear learning process. However the exact mechanism how the BNST controls fear consolidation and its extinction is largely unknown. In the present study we observed the changes in the BNST sub-regions following fear conditioning and its extinction. METHODS: The change in the number of positive neurons was determined by immunohistochemistry for Acetyl H3 (Histone 3), Acetyl H4 (Histone 4), cAMP response element binding Protein (CBP) and c-fos in three sub-regions of the BNST namely the anterio-lateral BNST (STLP) and anterio-medial BNST (STMA), and lateral-ventral BNST (STLV) of rats subjected to auditory fear conditioning and extinction...
May 2017: Psychiatry Investigation
https://www.readbyqxmd.com/read/28539261/g-protein-coupled-receptor-91-signaling-in-diabetic-retinopathy-and-hypoxic-retinal-diseases
#4
Jianyan Hu, Tingting Li, Xinhua Du, Qiang Wu, Yun-Zheng Le
G protein-coupled receptor 91 (GPR91) is a succinate-specific receptor and activation of GPR91 could initiate a complex signal transduction cascade and upregulate inflammatory and pro-angiogenic cytokines. In the retina, GPR91 is predominately expressed in ganglion cells, a major cellular entity involved in the pathogenesis of diabetic retinopathy (DR) and other hypoxic retinal diseases. During the development of DR and retinopathy of prematurity (ROP), chronic hypoxia causes an increase in the levels of local succinate...
May 21, 2017: Vision Research
https://www.readbyqxmd.com/read/28538192/hepatic-anti-inflammatory-effect-of-hexane-extracts-of-dioscorea-batatas-decne-possible-suppression-of-toll-like-receptor-4-mediated-signaling
#5
Hyun Jung Koo, SungRyul Lee, Kwang Jin Chang, Eunsoo Sohn, Eun-Hwa Sohn, Se Chan Kang, Suhkneung Pyo
The hepatic anti-inflammatory potential of hexane extracts of Dioscorea batatas Decne edible part (EDH-1e) and bark (EDH-2b) were investigated in Western-type diet-fed apolipoprotein E null [ApoE (-/-)] mice and HepG2 cells. EDH-1e and EDH-2b suppressed the increased levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, transforming growth factor beta 1 (TGF-β1), vascular cell adhesion protein 1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1), and reduced infiltration of monocytes into liver tissue...
May 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28536511/aripiprazole-facilitates-extinction-of-conditioned-fear-in-adolescent-rats
#6
Despina E Ganella, Liubov Lee-Kardashyan, Sophia J Luikinga, Danny L D Nguyen, Heather B Madsen, Isabel C Zbukvic, Russell Coulthard, Andrew J Lawrence, Jee Hyun Kim
Anxiety disorders are the most common type of mental disorder during adolescence, which is at least partly due to the resistance to extinction exhibited at this age. The dopaminergic system is known to be dysregulated during adolescence; therefore, we aimed to facilitate extinction in adolescent rats using the dopamine receptor 2 partial agonist aripiprazole (Abilify™), and examine the behavioral and neural outcomes. Adolescent rats were conditioned to fear a tone. The next day, rats received extinction 30 min after a systemic injection of either 5 mg/kg aripiprazole or vehicle, and then were tested the following day...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28536510/influence-of-pre-reproductive-maternal-enrichment-on-coping-response-to-stress-and-expression-of-c-fos-and-glucocorticoid-receptors-in-adolescent-offspring
#7
Debora Cutuli, Erica Berretta, Greta Pasqualini, Paola De Bartolo, Paola Caporali, Daniela Laricchiuta, Patricia Sampedro-Piquero, Francesca Gelfo, Matteo Pesoli, Francesca Foti, Azucena Begega, Laura Petrosini
Environmental enrichment (EE) is an experimental setting broadly used for investigating the effects of complex social, cognitive, and sensorimotor stimulations on brain structure and function. Recent studies point out that parental EE experience, even occurring in the pre-reproductive phase, affects neural development and behavioral trajectories of the offspring. In the present study we investigated the influences of pre-reproductive EE of female rats on maternal behavior and adolescent male offspring's coping response to an inescapable stressful situation after chronic social isolation...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28527956/comparison-of-the-induction-of-c-fos-egfp-and-fos-protein-in-the-rat-spinal-cord-and-hypothalamus-resulting-from-subcutaneous-capsaicin-or-formalin-injection
#8
Yasuhito Motojima, Takanori Matsuura, Mitsuhiro Yoshimura, Hirofumi Hashimoto, Reiko Saito, Hiromichi Ueno, Takashi Maruyama, Satomi Sonoda, Hitoshi Suzuki, Makoto Kawasaki, Hideo Ohnishi, Akinori Sakai, Yoichi Ueta
We evaluated whether a c-fos-enhanced green fluorescent protein (eGFP) transgenic rat line, which expresses the c-fos and eGFP fusion gene, can be useful for the study of nociceptive pathways and processing. Capsaicin solution (15%) or formalin (5%) was subcutaneously injected bilaterally into the hind paws (100 μL per each paw) of adult male c-fos-eGFP transgenic or wild type rats. Control rats were injected with ethanol or physiological saline respectively. Transgenic and wild type rats were perfused at 1...
May 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28527849/role-of-piezo-channels-in-ultrasound-stimulated-dental-stem-cells
#9
Qianhua Gao, Paul R Cooper, A Damien Walmsley, Ben A Scheven
INTRODUCTION: Piezo1 and Piezo2 are mechanosensitive membrane ion channels. We hypothesized that Piezo proteins may play a role in transducing ultrasound-associated mechanical signals and activate downstream mitogen-activated protein kinase (MAPK) signaling processes in dental cells. In this study, the expression and role of Piezo channels were investigated in dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) after treatment with low-intensity pulsed ultrasound (LIPUS)...
May 17, 2017: Journal of Endodontics
https://www.readbyqxmd.com/read/28527681/decreased-food-anticipatory-activity-of-obese-mice-relates-to-hypothalamic-c-fos-expression
#10
C Luna-Illades, T Morales, M Miranda-Anaya
During daily Food Restriction (FR), obese Neotomodon alstoni mice present decreased Food Anticipatory Activity (FAA) compared to lean mice. Here, we investigated whether FOS expression in hypothalamic nuclei involved in food synchronization and anticipation parallels decreased FAA during daily FR of obese N. alstoni. Locomotor activity of lean and obese mice in ad libitum feeding conditions was monitored for at least two weeks. Then, a gradual restriction of food access was followed to establish a 5h period of daily food access...
May 17, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28524179/a-fkbp5-mutation-is-associated-with-paget-s-disease-of-bone-and-enhances-osteoclastogenesis
#11
Bingru Lu, Yulian Jiao, Yinchang Wang, Jing Dong, Muyun Wei, Bin Cui, Yafang Sun, Laicheng Wang, Bingchang Zhang, Zijiang Chen, Yueran Zhao
Paget's disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. Herein, we report a case of Chinese familial PDB without mutations in known genes and identify a novel c...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28522214/p2-purinergic-receptor-antagonists-disrupt-maternal-behavior-in-lactating-rats
#12
Luciana C Teodoro, Layla D M Cabral, Fabiana C Vilela, Alexandre Giusti-Paiva
The involvement of purinergic signaling in several brain functions has been recognized, but the modulation on maternal behavior by the purinergic system is not established, even though there are functional interactions between the purinergic and oxytocinergic systems. Therefore, the aim of our study was to investigate whether central administration of P2 receptor antagonists affected the maternal behavior of lactating rats and c-Fos immunoreactivity in the forebrain. On day 7 of lactation, female rats were treated with vehicle (5μL; i...
May 15, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28516430/ramelteon-improves-post-traumatic-stress-disorder-like-behaviors-exhibited-by-fatty-acid-binding-protein-3-null-mice
#13
Yasushi Yabuki, Ibuki Takahata, Kazuya Matsuo, Yuji Owada, Kohji Fukunaga
We previously reported that fatty acid-binding protein 3 (FABP3) knockout (Fabp3 (-/-)) mice exhibit abnormal dopamine-related behaviors such as enhanced dopamine D2 receptor antagonist-induced catalepsy behaviors. Here, we report that Fabp3 null mice exhibit cognitive deficits, hyperlocomotion and impaired fear extinction, and thus show post-traumatic stress disorder (PTSD)-like behaviors. Notably, chronic administration of ramelteon (1.0 mg/kg, p.o.), a melatonin receptor agonist, improved all PTSD-like behaviors tested in Fabp3 (-/-) mice...
May 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28514446/identification-of-preoptic-sleep-neurons-using-retrograde-labelling-and-gene-profiling
#14
Shinjae Chung, Franz Weber, Peng Zhong, Chan Lek Tan, Thuc Nghi Nguyen, Kevin T Beier, Nikolai Hörmann, Wei-Cheng Chang, Zhe Zhang, Johnny Phong Do, Shenqin Yao, Michael J Krashes, Bosiljka Tasic, Ali Cetin, Hongkui Zeng, Zachary A Knight, Liqun Luo, Yang Dan
In humans and other mammalian species, lesions in the preoptic area of the hypothalamus cause profound sleep impairment, indicating a crucial role of the preoptic area in sleep generation. However, the underlying circuit mechanism remains poorly understood. Electrophysiological recordings and c-Fos immunohistochemistry have shown the existence of sleep-active neurons in the preoptic area, especially in the ventrolateral preoptic area and median preoptic nucleus. Pharmacogenetic activation of c-Fos-labelled sleep-active neurons has been shown to induce sleep...
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28513573/nrf2-inhibits-periodontal-ligament-stem-cell-apoptosis-under-excessive-oxidative-stress
#15
Yanli Liu, Hongxu Yang, Yi Wen, Bingyi Li, Yinhua Zhao, Jing Xing, Min Zhang, Yongjin Chen
The present study aimed to analyze novel mechanisms underlying Nrf2-mediated anti-apoptosis in periodontal ligament stem cells (PDLSCs) in the periodontitis oxidative microenvironment. We created an oxidative stress model with H₂O₂-treated PDLSCs. We used real-time PCR, Western blotting, TUNEL staining, fluorogenic assay and transfer genetics to confirm the degree of oxidative stress and apoptosis as well as the function of nuclear factor-erythroid 2-related factor 2 (Nrf2). We demonstrated that with upregulated levels of reactive oxygen species (ROS) and malondialdehyde (MDA), the effect of oxidative stress was obvious under H₂O₂ treatment...
May 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28512295/camp-dependent-cell-differentiation-triggered-by-activated-crhr1-in-hippocampal-neuronal-cells
#16
Carolina Inda, Juan José Bonfiglio, Paula A Dos Santos Claro, Sergio A Senin, Natalia G Armando, Jan M Deussing, Susana Silberstein
Corticotropin-releasing hormone receptor 1 (CRHR1) activates the atypical soluble adenylyl cyclase (sAC) in addition to transmembrane adenylyl cyclases (tmACs). Both cAMP sources were shown to be required for the phosphorylation of ERK1/2 triggered by activated G protein coupled receptor (GPCR) CRHR1 in neuronal and neuroendocrine contexts. Here, we show that activated CRHR1 promotes growth arrest and neurite elongation in neuronal hippocampal cells (HT22-CRHR1 cells). By characterising CRHR1 signalling mechanisms involved in the neuritogenic effect, we demonstrate that neurite outgrowth in HT22-CRHR1 cells takes place by a sAC-dependent, ERK1/2-independent signalling cascade...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28511913/the-non-peptide-crh1-antagonist-cp-154-526-elicits-a-paradoxical-route-dependent-activation-of-the-hpa-axis
#17
Dmitry V Zaretsky, Maria V Zaretskaia, Sumit Sarkar, Daniel E Rusyniak, Joseph A DiMicco
The corticotropin-releasing hormone (CRH) plays an important role in mediating physiological response to stress and is thought to be involved in the development of various psychiatric disorders. In this paper, we compare the differences between the effect of intraperitoneal (i.p.) and intraarterial (i.a.) administration of the non-peptide CRH1 antagonist CP-154,526 (CP) (10 and 20mg/kg) on plasma adrenocorticotropic hormone levels (ACTH), heart rate, MAP, and c-Fos expression in the paraventricular nucleus of the hypothalamus...
May 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28509372/differential-expression-of-micrornas-related-to-irritable-bowel-syndrome-in-a-rabbit-model
#18
Qinqin Yang, Xiaoping Xu, Hongshu Zhao, Yueqin Cai, Yongming Pan, Jianqin Xu, Quanxin Ma, Minli Chen
AIM: In the study we evaluated differential expression of miRNAs in the white hair and black eyes(WHBE) rabbit model of irritable bowel syndrome(IBS). METHODS: WHBE IBS rabbits were exposed to moist heat, stress, and stimulation with a low-dose laxative. Intestional propulsion rate(IPR) was measured. Blood samples were taken to detect changes in serum 5-hydroxytryptamine(5-HT) and dopamine(DA) levels, and colon tissues were to detect c-fos by immunohistochemistry...
May 16, 2017: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28506618/the-ptz-kindling-mouse-model-of-epilepsy-exhibits-exploratory-drive-deficits-and-aberrant-vta-dopamine-neuron-activity-in-both-familiar-and-novel-space
#19
Mahboubeh Ahmadi, Jean-Philippe Dufour, Erich Seifritz, Javad Mirnajafi-Zadeh, Bechara J Saab
Recurrent seizures that define epilepsy are often accompanied by psychosocial problems and cognitive deficits with incompletely understood aetiology. We therefore used the pentylenetetrazol (PTZ) kindling model of epilepsy in mice to examine potential seizure-associated neuropathologies, focusing on motivation, memory and novel-environment-induced activation of midbrain dopaminergic neurons. In addition to recurrent seizures, we found that PTZ kindling led to a strong suppression of novelty-driven exploration while largely sparing fear-driven exploration...
May 12, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28502165/grape-seed-proanthocyanidin-inhibits-mucin-synthesis-and-viral-replication-by-suppression-of-ap-1-and-nf-%C3%AE%C2%BAb-via-p38-mapks-jnk-signaling-pathways-in-respiratory-syncytial-virus-infected-a549-cells
#20
Jin-Woo Lee, Young Il Kim, Chang-Nim Im, Sung Wan Kim, Su Jin Kim, Seoyeon Min, Yong Hoon Joo, Sung-Vin Yim, Namhyun Chung
Airway epithelial cells are often infected by respiratory syncytial virus (RSV), one of the most common causes of asthma, bronchiolitis, chronic obstructive pulmonary disease (COPD), and pneumonia. During the infection process, excessive mucins aggravate airway inflammation. However, the mechanism underlying RSV-induced airway hyperresponsiveness and inflammation is poorly understood. Furthermore, no reliable vaccines or drugs for antiviral therapy are available. In this study, the effect of the natural compound grape seed proanthocyanidin (GSP) on RSV-infected human airway epithelial cells A549 was evaluated...
May 15, 2017: Journal of Agricultural and Food Chemistry
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