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Centrally mediated

Paula Perez-Pardo, Hemraj B Dodiya, Phillip A Engen, Christopher B Forsyth, Andrea M Huschens, Maliha Shaikh, Robin M Voigt, Ankur Naqib, Stefan J Green, Jeffrey H Kordower, Kathleen M Shannon, Johan Garssen, Aletta D Kraneveld, Ali Keshavarzian
OBJECTIVE: Recent evidence suggesting an important role of gut-derived inflammation in brain disorders has opened up new directions to explore the possible role of the gut-brain axis in neurodegenerative diseases. Given the prominence of dysbiosis and colonic dysfunction in patients with Parkinson's disease (PD), we propose that toll-like receptor 4 (TLR4)-mediated intestinal dysfunction could contribute to intestinal and central inflammation in PD-related neurodegeneration. DESIGN: To test this hypothesis we performed studies in both human tissue and a murine model of PD...
December 15, 2018: Gut
Géraldine Gazzo, Philippe Girard, Nisrine Kamoun, Marc Verleye, Pierrick Poisbeau
Inflammatory processes are critical promoting factors of chronic pain states, mostly by inducing peripheral and central sensitization of the nociceptive system. These processes are associated with a massive increase in glutamatergic transmission, sometimes facilitated by spinal disinhibition. In this study, we used etifoxine, a non-benzodiazepine anxiolytic known to amplify inhibition mediated by gamma-aminobutyric acid type A (GABAA ) receptors in pain processing regions, either directly (through allosteric modulation) or indirectly (through the synthesis of endogenous neurosteroids)...
December 12, 2018: European Journal of Pharmacology
Jim G Castellanos, Viola Woo, Monica Viladomiu, Gregory Putzel, Svetlana Lima, Gretchen E Diehl, Andrew R Marderstein, Jorge Gandara, Alexendar R Perez, David R Withers, Stephan R Targan, David Q Shih, Ellen J Scherl, Randy S Longman
Inflammatory bowel disease (IBD) results from a dysregulated interaction between the microbiota and a genetically susceptible host. Genetic studies have linked TNFSF15 polymorphisms and its protein TNF-like ligand 1A (TL1A) with IBD, but the functional role of TL1A is not known. Here, we found that adherent IBD-associated microbiota induced TL1A release from CX3CR1+ mononuclear phagocytes (MNPs). Using cell-specific genetic deletion models, we identified an essential role for CX3CR1+ MNP-derived TL1A in driving group 3 innate lymphoid cell (ILC3) production of interleukin-22 and mucosal healing during acute colitis...
December 5, 2018: Immunity
Meghan R Sullivan, Kara A Bernstein
The accurate repair of DNA is critical for genome stability and cancer prevention. DNA double-strand breaks are one of the most toxic lesions; however, they can be repaired using homologous recombination. Homologous recombination is a high-fidelity DNA repair pathway that uses a homologous template for repair. One central HR step is RAD51 nucleoprotein filament formation on the single-stranded DNA ends, which is a step required for the homology search and strand invasion steps of HR. RAD51 filament formation is tightly controlled by many positive and negative regulators, which are collectively termed the RAD51 mediators...
December 13, 2018: Genes
Yao-Wu Liu, Xiao-Li Liu, Li Kong, Meng-Ya Zhang, Ya-Jing Chen, Xia Zhu, Yun-Chao Hao
Although dietary flavonoid quercetin alleviates diabetes-associated cognitive decline in rodents, the mechanisms are not clearly clarified. This study was designed to investigate whether quercetin showed neuroprotection on central neurons against chronic high glucose through the enhancement of Nrf2/ARE/glyoxalase 1 (Glo-1) pathway. SH-SY5Y cells were divided into 8 groups: normal glucose, high glucose (HG), osmotic pressure control, solvent control, HG plus low, middle, high concentrations of quercetin, or Nrf2 activator (sulforaphane)...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Sandeep Kumar, Navneet Agnihotri
Colorectal cancer (CRC) is the most common carcinoma of the digestive tract. The slow growing nature of CRC offers a great opportunity for prevention strategies. The concept of chemoprevention of colorectal cancer using plant derived natural products is gaining substantial attention because it is an inherently safe and cost-effective alternative to conventional cancer therapies. Piperlongumine (PL), a natural alkaloid present in Piper longum Linn has been reported to exhibit notable anticancer effects in various in vitro studies...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Clara López-Serrano, Eva Santos-Nogueira, Isaac Francos-Quijorna, Marina Coll-Miro, Jerold Chun, Rubèn López-Vales
Lysophosphatidic acid (LPA) is an extracellular lipid mediator involved in many physiological functions by signaling through six known G-protein-coupled receptors (LPA1 -LPA6 ). In the central nervous system (CNS), LPA mediates a wide range of effects, including neural progenitor cell physiology, astrocyte and microglia activation, neuronal cell death, axonal retraction, and contributions to pain, schizophrenia and hydrocephalus. We recently reported that LPA-LPA1 signaling mediates functional deficits and myelin loss after spinal cord injury (SCI)...
December 11, 2018: Brain, Behavior, and Immunity
Xuemei Chen, Yuan Hu, Wenlu Zhang, Ke Chen, Jie Hu, Xiaosong Li, Li Liang, Xuefei Cai, Jieli Hu, Kai Wang, Ailong Huang, Ni Tang
Chronic hepatitis B virus (HBV) infection remains a serious global health concern. Cisplatin is a chemotherapeutic agent commonly used to treat various cancers. However, HBV-infected patients receiving chemotherapy are at risk of HBV reactivation via unknown mechanisms, which we aimed to elucidate in this study. We found that autophagy plays a central role in cisplatin-induced HBV replication. Cisplatin treatment induced autophagy in both HBV-replicating cells and an HBV-transgenic mouse model as evident from marked upregulation of microtubule-associated protein 1 light chain 3 (LC3)-II and the accumulation of red fluorescent protein (RFP)-LC3 puncta...
December 11, 2018: Free Radical Biology & Medicine
A U Joshi, A E Ebert, B Haileselassie, D Mochly-Rosen
Huntington's disease (HD) is a fatal hereditary neurodegenerative disorder, best known for its clinical triad of progressive motor impairment, cognitive deficits and psychiatric disturbances, is caused by CAG-repeat expansion in exon 1 of Huntingtin (HTT). However, in addition to the neurological disease, mutant HTT (mHTT), which is ubiquitously expressed in all tissues, impairs other organ systems. Not surprisingly, cardiovascular dysautonomia as well as the deterioration of circadian rhythms are among the earliest detectable pathophysiological changes in individuals with HD...
December 11, 2018: Journal of Molecular and Cellular Cardiology
Deepali Singhal, Pranita Sahay, Prafulla K Maharana, Nimmy Raj, Namrata Sharma, Jeewan S Titiyal
Vernal keratoconjunctivitis, a chronic, bilateral, seasonal allergic inflammatory disease of the eye, is an important cause of visual debilitation and impairment of quality of life in children and young adults in certain parts of the world such as the Mediterranean areas, Central and West Africa, the Middle East, Japan, the Indian subcontinent, and South America. It usually has a self-limiting course; however, in a few cases the disease is recurrent and leads to long-term visual disabling complications like keratoconus and limbal stem cell deficiency...
December 11, 2018: Survey of Ophthalmology
Ludovica Montanucci, Hafid Laayouni, Begoña Dobon, Kevin L Keys, Jaume Bertranpetit, Juli Peretó
Metabolic networks comprise thousands of enzymatic reactions functioning in a controlled manner and have been shaped by natural selection. Thanks to the genome data, the footprints of adaptive (positive) selection are detectable, and the strength of purifying selection can be measured. This has made possible to know where, in the metabolic network, adaptive selection has acted and where purifying selection is more or less strong and efficient. We have carried out a comprehensive molecular evolutionary study of all the genes involved in the human metabolism...
2018: PloS One
Di Wu, Litao Wu, Huanping An, Hongcun Bao, Pengfei Guo, Bei Zhang, Huimei Zheng, Fan Zhang, Wanzhong Ge, Yu Cai, Yongmei Xi, Xiaohang Yang
By the end of neurogenesis in Drosophila pupal brain neuroblasts (NBs), nuclear Prospero (Pros) triggers cell cycle exit and terminates NB lifespan. Here, we reveal that in larval brain NBs, an intrinsic mechanism facilitates import and export of Pros across the nuclear envelope via a Ran-mediated nucleocytoplasmic transport system. In rangap mutants, the export of Pros from the nucleus to cytoplasm is impaired and the nucleocytoplasmic transport of Pros becomes one-way traffic, causing an early accumulation of Pros in the nuclei of the larval central brain NBs...
December 13, 2018: Aging Cell
Puja Agrawal, Katelyn E Heimbruch, Sridhar Rao
Gene expression is regulated by numerous elements including enhancers, insulators, transcription factors, and architectural proteins. Regions of DNA distal to the transcriptional start site, called enhancers, play a central role in the temporal and tissue-specific regulation of gene expression through RNA polymerase II. The identification of enhancers and other cis regulatory elements has largely been possible due to advances in next generation sequencing technologies. Enhancers regulate gene expression through chromatin loops mediated by architectural proteins such as YY1, CTCF, the cohesin complex, and LDB1...
December 13, 2018: Comprehensive Physiology
Samuel W Flake, Peter J Weisberg
Severe drought has resulted in widespread tree die-off events in forests and woodlands globally and is forecast to become more frequent in coming decades. Tree mortality is a complex process influenced by climate, soils, characteristics of individual trees, interactions between trees, and the dynamics of pests and pathogens. The role of stand structure and stand density in mediating the resistance of trees to drought remains poorly understood, especially in semiarid woodlands, which are expected to be highly susceptible to future severe drought...
December 13, 2018: Ecological Applications: a Publication of the Ecological Society of America
Kelvin Kai-Wan Hui, Chesarahmia Dojo Soeandy, Stephano Chang, Frederick S Vizeacoumar, Thomas Sun, Alessandro Datti, Jeffrey T Henderson
Aberrant regulation of programmed cell death (PCD) has been tied to an array of human pathologies ranging from cancers to autoimmune disorders to diverse forms of neurodegeneration. Pharmacologic modulation of PCD signalling is therefore of central interest to a number of clinical and biomedical applications. A key component of PCD signalling involves the modulation of pro- and anti-apoptotic Bcl-2 family members. Among these, Bax translocation represents a critical regulatory phase in PCD. In the present study, we have employed a high-content high-throughput screen to identify small molecules which inhibit the cellular process of Bax re-distribution to the mitochondria following commitment of the cell to die...
December 13, 2018: Journal of Cellular and Molecular Medicine
Heli P Siltala, Juha M Holma, Maria Hallman
BACKGROUND: Family violence (FV) is a prevalent health issue around the world and health care services have an important role in both recognizing and treating the consequences of violence. However, FV experiences among health care professionals themselves have not been investigated much. We also lack specific knowledge on the associations between FV and mental health. AIM: The purpose of the study was to investigate the prevalence and effects of FV in a sample of Finnish health care professionals...
December 12, 2018: Scandinavian Journal of Caring Sciences
Mireia Recasens, Kalpana Shrivastava, Beatriz Almolda, Berta González, Bernardo Castellano
When central nervous system (CNS) homeostasis is altered, microglial cells become rapidly activated, proliferate and release a broad range of molecules. Among the plethora of molecules involved in the regulation of microglial activation, cytokines are considered crucial. Although production of interleukin-10 (IL-10) has been demonstrated after different types of CNS injuries and associated with protective functions, the specific role played by IL-10 modulating microglial cells remains unclear. Hence, the objective of this study was to evaluate the effects of transgenic astrocyte IL-10 production on microglial activation associated with axonal anterograde degeneration...
December 11, 2018: Glia
Stephen Hughes, Girish S Agarwal
We describe how magnetic fields can be exploited to control dipole-induced transparency in quantum dot cavity systems. Coupling a linearly-polarized microcavity mode to two spin charged exciton states of a single quantum dot, we demonstrate how cavity-mediated interference and magnetic-field resonance shifts can be utilized to control the transmission of light and on-chip photons, in both magnitude and phase. In particular, we show a triple resonance feature, which also survives with weakly coupled cavities, as long as one operates in the good cooperativity regime...
December 15, 2018: Optics Letters
Sriram Gubbi, Fady Hannah-Shmouni, Constantine A Stratakis, Christian A Koch
The pituitary gland and the hypothalamus can be affected by autoimmune-mediated structural and functional disruption. These autoimmune-mediated diseases occur more commonly in females and are often found during pregnancy or in the post-partum period. Autoimmune diseases can either affect parts of the pituitary or hypothalamus, or can involve both sellar and suprasellar structures. Most of these cases comprise primary hypophysitis (PRH). Over the years, there has been a tremendous increase in the number of reported PRH cases and related disorders, including hypophysitis induced by immune checkpoint inhibitors...
December 13, 2018: Reviews in Endocrine & Metabolic Disorders
Mohamed Dawood Shamout, Malek Bakheet Elayan
This data article provides numeric values about one of the most important sectors in Dubai, Dubai Central Fruit and Vegetable Market (DCM), which attracted world attention through its solid infrastructure and outstanding business environment. The dataset has been collected using a questionnaire obtained from the operational managers in the selected market, and several ethical considerations during the data collection process have been applied to assure the quality and credibility of the obtained data. A structural equation modeling (SEM) was applied using IBM SPSS AMOS...
December 2018: Data in Brief
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