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Mateusz Kucharczyk, Anna Kurek, Bartosz Pomierny, Jan Detka, Mariusz Papp, Katarzyna Tota, Bogusława Budziszewska
In the present study, we asked if the different types of stress alter neuronal plasticity markers distinctively in the frontal cortex (FCx) and in the hippocampus (Hp). To do so, we implemented various stress regimens to analyze changes evoked in these rat brain structures. We utilized several molecular techniques, including western blot, ELISA, quantitative RT-PCR, and various biochemical assays, to examine a range of proteins and subjected rats to behavioral tests to evaluate potential maladaptive alterations...
May 14, 2018: Psychoneuroendocrinology
Su Bin Park, Gwang Hun Park, Yurry Um, Ha Na Kim, Hun Min Song, Nahyun Kim, Hyun-Seok Kim, Jin Boo Jeong
Ginseng (Panax ginseng) has been reported to exert an anti-inflammatory activity in a variety of inflammatory condition. However, inflammation-regulatory activity of wood-cultivated ginseng has not been thoroughly evaluated. In this study, we evaluated the anti-inflammatory effect of wood-cultivated ginseng (WCG) and elucidated the potential mechanisms in LPS-stimulated RAW264.7 cells. WCG-O dose-dependently suppressed NO and PGE2 production in LPS-stimulated RAW264.7 cells. In addition, WCG-O attenuated LPS-mediated overexpression of iNOS and COX-2...
May 8, 2018: International Journal of Biological Macromolecules
Sajjad Sisakhtnezhad
Spermatogonial stem cells (SSCs), which are at the basis of spermatogenesis process, are valuable cells with different applications in biotechnology and regenerative medicine. Understanding the molecular basis of SSC self-renewal and differentiation at various developmental stages of the male organism is crucial to find key factors in the SSCs fate and function. Therefore, this study was aimed to use single-cell RNA-sequencing dataset analysis for identification of differentially expressed genes (DEGs) and their regulators in 3 and 7 days old mouse-derived single SSCs (mSSCs)...
May 11, 2018: Journal of Cellular Biochemistry
Jian-Ting Wang, Shang Wang, Song-Lin Liu, Yan-Chun Wang, Jia-Geng Li, Yu Chen
Xiaochaihu decoction is a classic prescription of traditional Chinese medicine. Modern research has proved its anti-depression effect. However, its pharmacological mechanism for anti-depression effect is difficult to be unveiled because of the complexity of compound Chinese medicines. Bupleuri Radix and Scutellariae Radix is the core drug pair of Xiaochaihu decoction. In this research, Bupleuri Radix and Scutellariae Radix were analyzed by the integrative pharmacology platform to study its molecular mechanism for anti-depression...
April 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Virginia Murillo-Garzón, Irantzu Gorroño-Etxebarria, Malin Åkerfelt, Mikael Christer Puustinen, Lea Sistonen, Matthias Nees, James Carton, Jonathan Waxman, Robert M Kypta
Wnt-11 promotes cancer cell migration and invasion independently of β-catenin but the receptors involved remain unknown. Here, we provide evidence that FZD8 is a major Wnt-11 receptor in prostate cancer that integrates Wnt-11 and TGF-β signals to promote EMT. FZD8 mRNA is upregulated in multiple prostate cancer datasets and in metastatic cancer cell lines in vitro and in vivo. Analysis of patient samples reveals increased levels of FZD8 in cancer, correlating with Wnt-11. FZD8 co-localizes and co-immunoprecipitates with Wnt-11 and potentiates Wnt-11 activation of ATF2-dependent transcription...
May 1, 2018: Nature Communications
Lifang Luo, Lijing Cai, Laibang Luo, Zhimou Tang, Xiaohui Meng
The present study aimed to investigate the anticancer effect of sorafenib combined with silencing of activating transcription factor 2 (ATF2) in hepatocellular carcinoma (HCC) cells and to assess the underlying molecular mechanisms. Huh‑7 HCC cell line was selected for the present study. Small interfering RNA (siRNA)‑ATF2 sequence was constructed to silence ATF2 expression. The experiment was divided into 6 groups: i) Control; ii) vector; iii) sorafenib (6.8 µM); iv) vector+sorafenib; v) siRNA‑ATF2; and vi) siRNA‑ATF2+sorafenib groups...
April 23, 2018: Molecular Medicine Reports
S Zhao, J Feng, C Li, H Gao, P Lv, J Li, Q Liu, Y He, H Wang, L Gong, D Li, Y Zhang
PURPOSE: Protein phosphorylation plays a key role in tumorigenesis and progression. However, little is known about the phosphoproteome profiles of growth hormone-secreting pituitary adenomas (GH-PAs). The aim of this study was to identify critical biomarkers and signaling pathways that might play important roles in GH-PAs and may, therefore, represent potential therapeutic targets. METHODS: The differential phosphoprotein expression patterns involved in GH-PAs were investigated by nano-LC-MS/MS in a group of samples...
April 24, 2018: Journal of Endocrinological Investigation
Mansi Srivastava, Mirza S Baig
A hallmark of the AP1 functioning is its nuclear translocation, which induces proinflammatory cytokine expression and hence the inflammatory response. After endotoxin shock AP1 transcription factor, which comprises Jun, ATF2, and Fos family of proteins, translocates into the nucleus and induces proinflammatory cytokine expression. In the current study, we found, NOS1 inhibition prevents nuclear translocation of the AP1 transcription factor subunits. Pharmacological inhibition of NOS1 impedes translocation of subunits into the nucleus, suppressing the transcription of inflammatory genes causing a diminished inflammatory response...
March 29, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Bingrui Li, Nianyu Li, Le Zhang, Kai Li, Yingtian Xie, Meilan Xue, Zheng Zheng
Background: circRNAs are part of the competitive endogenous RNA network, which putatively function as miRNA sponges and play a crucial role in the development of numerous diseases. However, studies of circRNAs in rheumatoid arthritis (RA) disease are limited. This work aims to identify the expression pattern of circRNAs in synovial tissues and their inflammatory regulation mechanism. Methods: We first compared the mRNA expression in rheumatoid arthritis patients with that in healthy volunteers by GEO database mining to identify gene loci specifically expressed in synovial tissues...
2018: Journal of Immunology Research
Pedro M Miranda, Giada De Palma, Viktoria Serkis, Jun Lu, Marc P Louis-Auguste, Justin L McCarville, Elena F Verdu, Stephen M Collins, Premysl Bercik
BACKGROUND: Changes in hygiene and dietary habits, including increased consumption of foods high in fat, simple sugars, and salt that are known to impact the composition and function of the intestinal microbiota, may explain the increase in prevalence of chronic inflammatory diseases. High salt consumption has been shown to worsen autoimmune encephalomyelitis and colitis in mouse models through p38/MAPK signaling pathway. However, the effect of high salt diet (HSD) on gut microbiota and on intestinal immune homeostasis, and their roles in determining vulnerability to intestinal inflammatory stimuli are unknown...
March 22, 2018: Microbiome
Chun Wang, Susan Hockerman, E Jon Jacobsen, Yael Alippe, Shaun R Selness, Heidi R Hope, Jeffrey L Hirsch, Stephen J Mnich, Matthew J Saabye, William F Hood, Sheri L Bonar, Yousef Abu-Amer, Ariela Haimovich, Hal M Hoffman, Joseph B Monahan, Gabriel Mbalaviele
p38α activation of multiple effectors may underlie the failure of global p38α inhibitors in clinical trials. A unique inhibitor (CDD-450) was developed that selectively blocked p38α activation of the proinflammatory kinase MK2 while sparing p38α activation of PRAK and ATF2. Next, the hypothesis that the p38α-MK2 complex mediates inflammasome priming cues was tested. CDD-450 had no effect on NLRP3 expression, but it decreased IL-1β expression by promoting IL-1β mRNA degradation. Thus, IL-1β is regulated not only transcriptionally by NF-κB and posttranslationally by the inflammasomes but also posttranscriptionally by p38α-MK2...
March 16, 2018: Journal of Experimental Medicine
Heather N Carter, Marion Pauly, Liam D Tryon, David A Hood
Mitochondrial impairments are often noted in aged skeletal muscle. The transcriptional coactivator PGC-1α is integral to maintaining mitochondria, and its expression declines in aged muscle. It remains unknown whether this is due to a transcriptional deficit during aging. Our study examined PGC-1α transcription in muscle from young and old F344BN rats. Using a rat PGC-1α promoter-reporter construct, we found that PGC-1α transcription was reduced by ~65% in aged TA muscle, accompanied by decreases in PGC-1α mRNA and transcript stability...
March 15, 2018: Journal of Applied Physiology
Robert James Shute, Matthew William Heesch, Roksana Barbara Zak, Jodi L Kreiling, Dustin R Slivka
PGC-1α mRNA is increased with both exercise and exposure to cold temperature. However, transcriptional control has yet to be examined during exercise in the cold. Additionally, the need for environmental cold exposure after exercise may not be a practical recovery modality. The purpose of this study was to determine mitochondrial-related gene expression and transcriptional control of PGC-1α following exercise in a cold compared to room temperature environment. Eleven recreationally trained males completed two 1-h cycling bouts in a cold (7 {degree sign}C) or room temperature (20 {degree sign}C) environment followed by 3 h of supine recovery in standard room conditions...
March 14, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Melanie Tingler, Sabrina Kurz, Markus Maerker, Tim Ott, Franziska Fuhl, Axel Schweickert, Janine M LeBlanc-Straceski, Stéphane Noselli, Martin Blum
Anatomical and functional asymmetries are widespread in the animal kingdom [1, 2]. In vertebrates, many visceral organs are asymmetrically placed [3]. In snails, shells and inner organs coil asymmetrically, and in Drosophila, genitalia and hindgut undergo a chiral rotation during development. The evolutionary origin of these asymmetries remains an open question [1]. Nodal signaling is widely used [4], and many, but not all, vertebrates use cilia for symmetry breaking [5]. In Drosophila, which lacks both cilia and Nodal, the unconventional myosin ID (myo1d) gene controls dextral rotation of chiral organs [6, 7]...
March 5, 2018: Current Biology: CB
Adrian J Giovannone, Christine Winterstein, Pallavi Bhattaram, Elena Reales, Seng Hui Low, Julie E Baggs, Mimi Xu, Matthew A Lalli, John B Hogenesch, Thomas Weimbs
Syntaxins are a conserved family of SNARE proteins and contain C-terminal transmembrane anchors required for their membrane fusion activity. Here we show that Stx3 (syntaxin 3) unexpectedly also functions as a nuclear regulator of gene expression. We found that alternative splicing creates a soluble isoform that we termed Stx3S, lacking the transmembrane anchor. Soluble Stx3S binds to the nuclear import factor RanBP5 (RAN-binding protein 5), targets to the nucleus, and interacts physically and functionally with several transcription factors, including ETV4 (ETS variant 4) and ATF2 (activating transcription factor 2)...
April 13, 2018: Journal of Biological Chemistry
Oksana Voloshanenko, Uwe Schwartz, Dominique Kranz, Benedikt Rauscher, Michael Linnebacher, Iris Augustin, Michael Boutros
Wnt signaling is an evolutionarily conserved signaling route required for development and homeostasis. While canonical, β-catenin-dependent Wnt signaling is well studied and has been linked to many forms of cancer, much less is known about the role of non-canonical, β-catenin-independent Wnt signaling. Here, we aimed at identifying a β-catenin-independent Wnt target gene signature in order to understand the functional significance of non-canonical signaling in colon cancer cells. Gene expression profiling was performed after silencing of key components of Wnt signaling pathway and an iterative signature algorithm was applied to predict pathway-dependent gene signatures...
February 16, 2018: Scientific Reports
Daniel Vázquez-Ramírez, Yvonne Genzel, Ingo Jordan, Volker Sandig, Udo Reichl
Increasing the yield and the productivity in cell culture-based vaccine manufacturing using high-cell-density (HCD) cultivations faces a number of challenges. For example, medium consumption should be low to obtain a very high concentration of viable host cells in an economical way but must be balanced against the requirement that accumulation of toxic metabolites and limitation of nutrients have to be avoided. HCD cultivations should also be optimized to avoid unwanted induction of apoptosis or autophagy during the early phase of virus infection...
February 9, 2018: Vaccine
Haijing Zhou, Lin Cai, Xiupeng Zhang, Ailin Li, Yuan Miao, Qingchang Li, Xueshan Qiu, Enhua Wang
Rho guanine nucleotide exchange factor 39 (ARHGEF39), also called C9orf100, is a new member of the Dbl-family of guanine nucleotide exchange factors. Although ARHGEF39 has been proven to regulate tumor progression in hepatocellular carcinoma, the downstream signaling pathway of ARHGEF39 and its clinical associations in non-small cell lung cancer (NSCLC) are currently unknown. In the present study, using MTT, colony formation, flow cytometry, mice xenografts, wound healing, and transwell assays, we showed that ARHGEF39 promoted tumor proliferation, migration, and invasion...
January 30, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Hongkai Shang, Liping Sun, Thorsten Braun, Qi Si, Jinyi Tong
Dexamethasone (DEX) could induce low birth weight of infant, and low birth weight has close associations with glucocorticoid levels, insulin resistance, hypertension, and metabolic syndrome in adulthood. This study was designed to reveal the action mechanisms of DEX on the birth weight of infant.Using quantitative real-time polymerase chain reaction (qRT-PCR), trophoblast cells of human placenta were identified and the optimum treatment time of DEX were determined. Trophoblast cells were treated by DEX (DEX group) or ethanol (control group) (each group had 3 samples), and then were performed with RNA-sequencing...
January 2018: Medicine (Baltimore)
Xianlong Gao, Xiaomin Wu, Jiajie Yan, Jingqun Zhang, Weiwei Zhao, Dominic DeMarco, Yongguo Zhang, Mamdouh Bakhos, Gregory Mignery, Jun Sun, Zhenyu Li, Michael Fill, Xun Ai
Aims: c-jun N-terminal kinase (JNK) is a critical stress response kinase that activates in a wide range of physiological and pathological cellular processes. We recently discovered a pivotal role of JNK in the development of atrial arrhythmias in the aged heart, while cardiac CaMKIIδ, another pro-arrhythmic molecule, was also known to enhance atrial arrhythmogenicity. Here, we aimed to reveal a regulatory role of the stress kinase JNK2 isoform on CaMKIIδ expression. Methods and results: Activated JNK2 leads to increased CaMKIIδ protein expression in aged human and mouse atria, evidenced from the reversal of CaMKIIδ up-regulation in JNK2 inhibitor treated wild-type aged mice...
April 1, 2018: Cardiovascular Research
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