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Centrally mediated

Chao-Zhi Tang, Jun-Tang Yang, Qing-Hui Liu, Ya-Ru Wang, Wen-Sheng Wang
Depression represents a condition characterized by cognitive deficits and neural dysfunction and has recently been correlated with microRNAs (miRs) and their respective target genes. The present study was conducted with the goal of investigating the expression of miR-192-5p and its target gene fibulin (Fbln)-2 in an attempt to evaluate their roles in the occurrence and progression of cognitive impairment and neural function in mice with chronic unpredictable mild stress (CUMS)-induced depression through regulation of the TGF-β1 signal transduction pathway...
August 17, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Samuel S Pappas, Jay Li, Tessa M LeWitt, Jeong-Ki Kim, Umrao R Monani, William T Dauer
Cholinergic dysfunction is strongly implicated in dystonia pathophysiology. Previously (Pappas et al., eLife 2015;4:e08352), we reported that Dlx5/6-Cre mediated forebrain deletion of the DYT1 dystonia protein torsinA (Dlx-CKO) causes abnormal twisting and selective degeneration of dorsal striatal cholinergic interneurons (ChI) (1). A central question raised by that work is whether the ChI loss is cell autonomous or requires torsinA loss from neurons synaptically connected to ChIs. Here, we addressed this question by using ChAT-Cre mice to conditionally delete torsinA from cholinergic neurons ('ChAT-CKO')...
August 17, 2018: ELife
Zhen Xu, Wei-Hua Shi, Longbiao Xu, Min-Feng Shao, Zu-Peng Chen, Guo-Chong Zhu, Qun Hou
Early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (SAH) contributes to high morbidity and mortality. Although it is well recognized that acute neuroinflammation reaction is one of the most important triggers of EBI, pharmacotherapy proved to be clinically effective against the initiating of neuroinflammation after SAH is lacking. The resident microglia and infiltrated peripheral monocyte are two main types of immune cells in central nervous system (CNS) and control the inflammation process in brain after SAH...
August 17, 2018: ACS Chemical Neuroscience
Basant K Puri, Anne Derham, Jean A Monro
Background The use of indwelling central venous access devices (CVADs) is associated with the development of bloodstream infections. When CVADs are used to administer systemic antibiotics, particularly second- or higher-generation cephalosporins, there is a particular risk of developing Clostridium difficile infection. The overall bloodstream infection rate is estimated to be around 1.74 per 1000 central venous catheter (CVC)-days. Objective We hypothesised that daily oral administration of the anion-binding resin colestyramine (cholestyramine) would help prevent infections in those receiving intravenous antibiotic treatment via CVADs...
August 17, 2018: Reviews on Recent Clinical Trials
Laura J den Hartigh, Leela Goodspeed, Shari A Wang, Heidi L Kenerson, Mohamed Omer, Kevin D O'Brien, Warren Ladiges, Raymond Yeung, Savitha Subramanian
NEW FINDINGS: What is the central question of this study? Whether chronic oral rapamycin promotes beneficial effects on glucose/lipid metabolism and energy balance when administered to mice with an obesogenic diet rich in saturated fat and sucrose has not been explored. What is the main finding and its importance? Chronic oral rapamycin reduces body weight and fat gain, improves insulin sensitivity, and reduces hepatic steatosis when administered to mice with a high fat high sucrose diet...
August 16, 2018: Experimental Physiology
Woojin M Han, Shannon E Anderson, Mahir Mohiuddin, Daniela Barros, Shadi A Nakhai, Eunjung Shin, Isabel Freitas Amaral, Ana Paula Pêgo, Andrés J García, Young C Jang
Muscle satellite cells (MuSCs) play a central role in muscle regeneration, but their quantity and function decline with comorbidity of trauma, aging, and muscle diseases. Although transplantation of MuSCs in traumatically injured muscle in the comorbid context of aging or pathology is a strategy to boost muscle regeneration, an effective cell delivery strategy in these contexts has not been developed. We engineered a synthetic hydrogel-based matrix with optimal mechanical, cell-adhesive, and protease-degradable properties that promotes MuSC survival, proliferation, and differentiation...
August 2018: Science Advances
Patrícia Ferreira Boasquívis, Giovanna Melo Martins Silva, Franciny Aparecida Paiva, Rodrigo Marinho Cavalcanti, Cecília Verônica Nunez, Riva de Paula Oliveira
Guarana ( Paullinia cupana ) is largely consumed in Brazil in high energy drinks and dietary supplements because of its stimulant activity on the central nervous system. Although previous studies have indicated that guarana has some protective effects in Parkinson's (PD), Alzheimer's (AD), and Huntington's (HD) disease models, the underlying mechanisms are unknown. Here, we investigated the protective effects of guarana hydroalcoholic extract (GHE) in Caenorhabditis elegans models of HD and AD. GHE reduced polyglutamine (polyQ) protein aggregation in the muscle and also reduced polyQ-mediated neuronal death in ASH sensory neurons and delayed β -amyloid-induced paralysis in a caffeine-independent manner...
2018: Oxidative Medicine and Cellular Longevity
Jubao Duan, Harald H H Göring, Alan R Sanders, Winton Moy, Jessica Freda, Eugene I Drigalenko, Mark Kos, Deli He, Pablo V Gejman
The dopaminergic hypothesis of schizophrenia (SZ) postulates that dopaminergic over activity causes psychosis, a central feature of SZ, based on the observation that blocking dopamine (DA) improves psychotic symptoms. DA is known to have both receptor- and non-receptor-mediated effects, including oxidative mechanisms that lead to apoptosis. The role of DA-mediated oxidative processes in SZ has been little studied. Here, we have used a cell perturbation approach and measured transcriptomic profiles by RNAseq to study the effect of DA exposure on transcription in B-cell transformed lymphoblastoid cell lines (LCLs) from 514 SZ cases and 690 controls...
August 16, 2018: Translational Psychiatry
Shreyas Lingadahalli, Sudhir Jadhao, Ying Ying Sung, Mi Chen, Lingling Hu, Xin Chen, Edwin Cheung
The human genome is mostly transcribed, yielding a rich repository of non-coding transcripts that are involved in a myriad of biological processes including cancer. However, how many non-coding transcripts such as long non-coding RNAs (lncRNAs) function in cancer is still unclear. This study, identified a novel set of clinically relevant androgen-regulated lncRNAs in prostate cancer. Among this group, LINC00844 was demonstrated to be a direct androgen-regulated target that is actively transcribed in androgen receptor (AR)-dependent prostate cancer cells...
August 16, 2018: Molecular Cancer Research: MCR
Anthony J Hayes, James Melrose
The aim of the present study was to examine the roles of l-fucose and the glycosaminoglycans (GAGs) keratan sulfate (KS) and chondroitin sulfate/dermatan sulfate (CS/DS) with selected functional molecules in neural tissues. Cell surface glycans and GAGs have evolved over millions of years to become cellular mediators which regulate fundamental aspects of cellular survival. The glycocalyx, which surrounds all cells, actuates responses to growth factors, cytokines and morphogens at the cellular boundary, silencing or activating downstream signaling pathways and gene expression...
August 16, 2018: Biochemical Journal
Gregory L Beatty, Safi Shahda, Thaddeus Beck, Nikhil Uppal, Steven J Cohen, Ross Donehower, Afshin Eli Gabayan, Albert Assad, Julie Switzky, Huiling Zhen, Daniel D Von Hoff
LESSONS LEARNED: Itacitinib in combination with nab -paclitaxel plus gemcitabine demonstrated an acceptable safety profile with clinical activity in patients with advanced solid tumors including pancreatic cancer.The results support future studies of itacitinib as a component of combination regimens with other immunologic and targeted small molecule anticancer agents. BACKGROUND: Cytokine-mediated signaling via JAK/STAT is central to tumor growth, survival, and systemic inflammation, which is associated with cancer cachexia, particularly in pancreatic cancer...
August 16, 2018: Oncologist
Saurav De, Fawziya Karim, Ezechielle Kiessu, Leah Cushing, Lih-Ling Lin, Jean-Laurent Casanova, Anne Puel, Cyrille Hoarau, Pegah Ghandil, Vikram R Rao
Interleukin-1 receptor (IL1R)-associated kinase 4 (IRAK4) is a central regulator of innate immune signaling, controlling IL-1R and Toll-like receptor (TLR)-mediated responses and containing both scaffolding and kinase activities. Humans deficient in IRAK4 activity have autosomal recessive primary immune deficiency (PID). Here, we characterized the molecular mechanism of dysfunction of two IRAK4 PID variants, G298D and the compound variant R12C (R12C/R391H/T458I). Using these variants and the kinase-inactive D329A variant to delineate the contributions of IRAK4's scaffolding and kinase activities to IL1R signaling, we found that the G298D variant is kinase-inactive and expressed at extremely low levels, acting functionally as a null mutation...
August 16, 2018: Journal of Biological Chemistry
Tokiko Suzuki, Kimimasa Sakata, Natsumi Mizuno, Sailesh Palikhe, Shigeyuki Yamashita, Kohshi Hattori, Naoyuki Matsuda, Yuichi Hattori
Pulmonary endothelial injury is central in the pathogenesis of acute lung injury (ALI). The MAPK signaling cascades are generally thought to be involved in the molecular mechanism underlying the ALI development, but their roles in pulmonary endothelial injury is poorly understood. We thus examined the involvement of the MAPK family member in inflammatory responses of human pulmonary microvascular endothelial cells (HPMVECs) stimulated with LPS and IFN-γ. HPMVECs were found to exhibit the upregulation of expression of Toll-like receptor 4 by IFN-γ, resulting in potentiation of inflammatory cytokine release by LPS stimulation...
August 9, 2018: Immunobiology
Simone Corrêa-Silva, Aline P Alencar, Jusciele B Moreli, Alexandre U Borbely, Larissa de S Lima, Cristóforo Scavone, Débora C Damasceno, Marilza V C Rudge, Estela Bevilacqua, Iracema M P Calderon
This study was based on the hypothesis that IL-1β and its central regulator, the inflammasome, may play a role in the inflammatory condition exhibited by placental tissues from mothers with different gestational hyperglycemia levels. Pregnant women were classified according to the glycemic reference as non-diabetic (n = 15), mild gestational hyperglycemia (n = 15), gestational diabetes mellitus (n = 15) and type 2 diabetes mellitus (n = 15). We investigated levels of pro-inflammatory factors in maternal plasma and placental tissues (by ELISA or immunohistochemistry) and, NFKB activity (by electrophoretic mobility shift assay) and inflammasome protein expression (by Western blot) in chorionic villous...
August 13, 2018: Cytokine
Andrew H Cooper, Jennifer J Brightwell, Naomi S Hedden, Bradley K Taylor
The left and right central nucleus of the amygdala (CeA) exert asymmetric pronociceptive functions. In the setting of a transient noxious stimulus or persistent inflammatory pain, neuronal activity increases in the right but not left CeA, regardless of side of injury. Much less is known regarding this lateralization with respect to the behavioral manifestations of persistent neuropathic pain. To address this question, we conducted spared nerve injury (SNI) to the left or right hindlimb and then inactivated the left and/or right CeA with local microinjection of lidocaine...
August 13, 2018: Neuroscience Letters
Jihoon Shin, Junghoon Kim, Sung Ha Park, Tai Hwan Ha
The central dogma of molecular biology is the principal framework for understanding how nucleic acid information is propagated and used by living systems to create complex biomolecules. Here, by integrating the structural and dynamic paradigms of DNA nanotechnology, we present a rationally designed synthetic platform which functions in an analogous manner to create complex DNA nanostructures. Starting from one type of DNA nanostructure, DNA strand displacement circuits were designed to interact and pass along the information encoded in the initial structure to mediate the self-assembly of a different type of structure, the final output structure depending on the type of circuit triggered...
August 16, 2018: ACS Nano
Georgia Kalozoumi, Olga Kel-Margoulis, Elizabeth Vafiadaki, David Greenberg, Hélène Bernard, Hermona Soreq, Antoine Depaulis, Despina Sanoudou
The Mesio-Temporal Lobe Epilepsy syndrome is the most common form of intractable epilepsy. It is characterized by recurrence of focal seizures and is often associated with hippocampal sclerosis and drug resistance. We aimed to characterize the molecular changes occurring during the initial stages of epileptogenesis in search of new therapeutic targets for Mesio-Temporal Lobe Epilepsy. We used a mouse model obtained by intra-hippocampal microinjection of kainate and performed hippocampal whole genome expression analysis at 6h, 12h and 24h post-injection, followed by multilevel bioinformatics analysis...
2018: PloS One
Zuotian Wu, Gaohua Wang, Yanyan Wei, Ling Xiao, Huiling Wang
Early neurodevelopmental dysplasia or disorder is an important stimulus for depression, but early stress can easily damage nerve development and lead to decreased neural plasticity. Because of the characteristics of nerve cell, nerve loop, structure instability and so on, stress can often lead to the occurrence and recurrence of depression. Stress is often associated with the release of inflammatory factors in the central nervous system. Recent studies suggest that neuroinflammatory factors are most likely involved in the occurrence and development of stress-induced depression, attacking neuronal cells through central inflammatory factors...
August 15, 2018: Neuroreport
Ming Gao, Ye-Cheng Wang, Kai-Rui Yang, Wei He, Xiao-Liang Yang, Z-J Yao
The first and enantioselective total synthesis of (+)-plumisclerin A, a novel unique complex cytotoxic marine diterpenoid, has been accomplished. Around the central cyclopentane anchorage, a sequential ring-formation protocol was adopted to generate the characteristic tricycle[,5]decane and trans-fused dihyrdopyran moiety. Scalable enantioselective La(III)-catalyzed Michael reaction, palladium(0)-catalyzed carbonylation and SmI2-mediated radical conjugate addition were successfully applied in the synthesis, affording multiple grams of the complex and rigid B/C/D-ring system having six continuous stereogenic centers and two all-carbon quaternary centers...
August 15, 2018: Angewandte Chemie
Zhilin Hu, Qiang Zou, Bing Su
T cells are an important adaptive immune response arm that mediates cell-mediated immunity. T cell metabolism plays a central role in T cell activation, proliferation, differentiation, and effector function. Specific metabolic programs are tightly controlled to mediate Tcell immune responses, and alterations in Tcell metabolism may result in many immunological disorders. In this review, we will summarize the main Tcell metabolic pathways and the important factors participating in Tcell metabolic programming during Tcell homeostasis, differentiation, and function...
August 16, 2018: Frontiers of Medicine
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