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Mariana Angoa-Pérez, John H Anneken, Donald M Kuhn
The present review briefly explores the neurotoxic properties of methcathinone, mephedrone, methylone, and methylenedioxypyrovalerone (MDPV), four synthetic cathinones most commonly found in "bath salts." Cathinones are β-keto analogs of the commonly abused amphetamines and display pharmacological effects resembling cocaine and amphetamines, but despite their commonalities in chemical structures, synthetic cathinones possess distinct neuropharmacological profiles and produce unique effects. Among the similarities of synthetic cathinones with their non-keto analogs are their targeting of monoamine systems, the release of neurotransmitters, and their stimulant properties...
October 18, 2016: Current Topics in Behavioral Neurosciences
Zhen-Yao Chen, Xin Chen, Zhao-Xia Wang
MicroRNAs are a large group of non-coding RNAs that have emerged as regulators of various biological processes, especially carcinogenesis and cancer progression. Recent evidence has shown that microRNA-196a (miR-196a) is upregulated in most types of tumors and involved in multiple biological processes via translational inhibition and mRNA cleavage, such as cell proliferation, migration, and invasion, mostly functioning as an oncogene. Dysregulation of miR-196a promotes oncogenesis and tumor progression. In this review, we summarize the upstream regulators, target genes, signaling pathways, and single nucleotide polymorphisms of miR-196a, which collectively affect cell proliferation, migration, and invasion...
October 18, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Hye-Jin Park, Kang-Woo Lee, Eun S Park, Stephanie Oh, Run Yan, Jie Zhang, Thomas G Beach, Charles H Adler, Michael Voronkov, Steven P Braithwaite, Jeffry B Stock, M Maral Mouradian
OBJECTIVE: Protein phosphatase 2A (PP2A) is a heterotrimeric holoenzyme composed of a catalytic C subunit, a structural A subunit, and one of several regulatory B subunits that confer substrate specificity. The assembly and activity of PP2A are regulated by reversible methylation of the C subunit. α-Synuclein, which aggregates in Parkinson disease (PD) and dementia with Lewy bodies (DLB), is phosphorylated at Ser129, and PP2A containing a B55α subunit is a major phospho-Ser129 phosphatase...
October 2016: Annals of Clinical and Translational Neurology
Clare Parker Fischer, L Michael Romero
When wild animals are brought into captivity for the first time, they frequently develop chronic stress symptoms. Animals can develop glucocorticoid dysregulation or changes in the sympathetic nervous system over the course of the first week in captivity. By blocking the action of epinephrine and norepinephrine using α- or β-blockers, we hoped to reduce the degree of chronic stress symptoms exhibited by newly captured house sparrows. We measured corticosterone, heart rate and heart rate variability in 24 house sparrows (Passer domesticus) over the first week of captivity...
2016: Conservation Physiology
Xuehua Shao, Duo Lai, Ling Zhang, Hanhong Xu
Azadirachtin is one of the most effective botanical insecticides and has been widely used in pest control. Toxicological reports show that azadirachtin can induce apoptosis in various insect cell lines. However, studies of azadirachtin-induced autophagy in cultured insect cells are lacking. This study reports that azadirachtin A significantly inhibits cell proliferation by inducing autophagic and apoptotic cell death in Spodoptera litura cultured cell line (SL-1 cell). Characteristic autophagolysosome and Atg8-PE (phosphatidylethanolamine) accumulation were observed by electron microscopy and western blotting, indicating that azadirachtin triggered autophagy in SL-1 cell...
October 18, 2016: Scientific Reports
Norikazu Kiguchi, Huiping Ding, Christopher M Peters, Nancy D Kock, Shiroh Kishioka, J Mark Cline, Janice D Wagner, Mei-Chuan Ko
Neuroinflammation is a pathological condition that underlies diabetes and affects sensory processing. Given the high prevalence of pain in diabetic patients and crosstalk between chemokines and opioids, it is pivotal to know whether neuroinflammation-associated mediators are dysregulated in the central nervous system of diabetic primates. Therefore, the aim of this study was to investigate whether mRNA expression levels of glial markers, chemokines, and opioid receptors are altered in the spinal cord and thalamus of naturally occurring type 2 diabetic monkeys (n=7) compared with age-matched non-diabetic monkeys (n=6)...
October 14, 2016: Biochimica et Biophysica Acta
Juan Gea-Banacloche, Krishna Komanduri, Paul Carpenter, Sophie Paczesny, Stefanie Sarantopoulos, Jo-Anne Young, Nahed El Kassar, Robert Q Le, Kirk Schultz, Linda M Griffith, Bipin Savani, John R Wingard
Immune reconstitution following hematopoietic stem cell transplantation (HCT) beyond one year is not completely understood. Many transplant recipients who are free of graft versus host disease (GVHD) and not receiving any immunosuppression more than a year after transplant seem to be able to mount appropriate immune responses to common pathogens and respond adequately to immunizations. However, two large registry studies over the last two decades seem to indicate that infection is a significant cause of late mortality in some patients, even in the absence of concomitant GVHD...
October 14, 2016: Biology of Blood and Marrow Transplantation
Hao Li, Jizong Zhao, Wen Wang, Lu Zhang, Qing Lan, Jiangfei Wang, Yong Cao, Jizong Zhao
BACKGROUND: Intracranial aneurysm (IA) is a cerebrovascular disorder characterized by an abnormally bulged artery in the brain and subarachnoid hemorrhage caused by IA rupture with a high ratio of fatality and morbidity. However, the genetic etiology of IA remains largely unknown. MATERIALS AND METHODS: A dysregulated lncRNA-associated competing endogenous RNA (ceRNA) network was constructed by utilizing sample-matched microRNA (miRNA), long non-coding RNA (lncRNA) and mRNA expression profiles in 12 saccular IA samples and paired control arteries...
October 14, 2016: World Neurosurgery
Carrie J Finno, Matthew H Bordbari, Stephanie J Valberg, David Lee, Josi Herron, Kelly Hines, Tamer Monsour, Erica Scott, Danika L Bannasch, James Mickelson, Libin Xu
Specific spontaneous heritable neurodegenerative diseases have been associated with lower serum and cerebrospinal fluid α-tocopherol (α-TOH) concentrations. Equine neuroaxonal dystrophy (eNAD) has similar histologic lesions to human ataxia with vitamin E deficiency caused by mutations in the α-TOH transfer protein gene (TTPA). Mutations in TTPA are not present with eNAD and the molecular basis remains unknown. Given the neuropathologic phenotypic similarity of the conditions, we assessed the molecular basis of eNAD by global transcriptome sequencing of the cervical spinal cord...
October 14, 2016: Free Radical Biology & Medicine
Federica Parodi, Roberta Carosio, Marco Ragusa, Cinzia Di Pietro, Marco Maugeri, Davide Barbagallo, Fabio Sallustio, Giorgio Allemanni, Maria Pia Pistillo, Ida Casciano, Alessandra Forlani, Francesco P Schena, Michele Purrello, Massimo Romani, Barbara Banelli
In neuroblastoma, the epigenetic landscape is more profoundly altered in aggressive compared to lower grade tumors and the concomitant hypermethylation of many genes, defined as "methylator phenotype", has been associated with poor outcome. DNA methylation can interfere with gene expression acting at distance through the methylation or demethylation of the regulatory regions of miRNAs. The multiplicity of miRNA targets may result in the simultaneous alteration of many biological pathways like cell proliferation, apoptosis, migration and differentiation...
October 14, 2016: Biochimica et Biophysica Acta
Erika Yeh, Lauren A Weiss
Autism spectrum disorder (ASD) has been long known to have substantial genetic etiology. Much research has attempted to identify specific genes contributing to ASD risk with the goal of tying gene function to a molecular pathological explanation for ASD. A unifying molecular pathology would potentially increase understanding of what is going wrong during development, and could lead to diagnostic biomarkers or targeted preventative or therapeutic directions. We review past and current genetic mapping approaches and discuss major results, leading to the hypothesis that global dysregulation of gene or protein expression may be implicated in ASD rather than disturbance of brain-specific functions...
October 14, 2016: Molecular and Cellular Probes
Rong Lian, Baocai Lu, Lei Jiao, Shaomei Li, Huimin Wang, Wenjie Miao, Wenfa Yu
Increasing evidence indicates that the dysregulation of microRNAs is involved in tumor progression and development. The purpose of the present study was to explore the expression of microRNA-132 (miR-132) and its function in laryngeal squamous cell carcinoma (LSCC). The results showed that miR-132 expression was markedly upregulated in LSCC tissues and cell lines. Functional analyses indicated that overexpression of miR-132 enhanced cell proliferation and tumor growth, which resulted in the downregulation of p27 and p21 and the upregulation of cyclin D1...
October 14, 2016: European Journal of Pharmacology
Christina R Tyler, Matthew T Labrecque, Elizabeth R Solomon, Xun Guo, Andrea M Allan
Exposure to arsenic, a common environmental toxin found in drinking water, leads to a host of neurological pathologies. We have previously demonstrated that developmental exposure to a low level of arsenic (50ppb) alters epigenetic processes that underlie deficits in adult hippocampal neurogenesis leading to aberrant behavior. It is unclear if arsenic impacts the programming and regulation of embryonic neurogenesis during development when exposure occurs. The master negative regulator of neural-lineage, REST/NRSF, controls the precise timing of fate specification and differentiation of neural stem cells (NSCs)...
October 14, 2016: Neurotoxicology and Teratology
Mohammad Reza Safari, Soudeh Ghafouri-Fard, Rezvan Noroozi, Arezou Sayad, Mir Davood Omrani, Alireza Komaki, Mohammad Mahdi Eftekharian, Mohammad Taheri
Autism Spectrum Disorders (ASD) are a group of heterogeneous neurodevelopmental disorders associated with immune system dysregulation. There are supporting evidences for the role of Forkhead Box P3 (FOXP3) gene as a lineage specification factor of regulatory T cells in the pathogenesis of ASD. The aim of this study was to explore possible relationship between genetic variants rs2232365 and rs3761548 of FOXP3 and ASD in 523 ASD patients versus 472 control individuals. Allele frequency analyses showed significant overpresentation of rs2232365-G allele in cases versus controls...
October 14, 2016: Gene
Maureen O'Sullivan
Since its foundation by remarkably talented and insightful individuals, prominently including Pepper Dehner, pediatric soft tissue tumor pathology has developed at an immense rate. The morphologic classification of tumoral entities has extensively been corroborated, but has also evolved with refinement or realignment of these classifications, through accruing molecular data, with many derivative ancillary diagnostic assays now already well-established. Tumors of unclear histogenesis, classically morphologically undifferentiated, are prominent amongst pediatric sarcomas, however, the classes of undifferentiated round- or spindle-cell-tumors-not-otherwise-specified are being dismantled gradually with the identification of their molecular underpinnings...
September 5, 2016: Seminars in Diagnostic Pathology
A Mekinian, J Cohen, G Kayem, L Carbillon, P Nicaise-Roland, B Gaugler, E Darai, M Bornes, O Fain
About 1-3% of women experience early recurrent miscarriages, defined by ≥3 fetal loss before 14 weeks of gestation. About half of these recurrent early miscarriages could be related to a genetic cause. Pre-implantation genetic diagnosis is used in several European countries, but it is still prohibited in France except for couples at risk for transmission of severe genetic diseases. The immune dysregulation, and in particular allo-immune excessive response, could be responsible for fetal loss in remaining cases, although currently we lack biomarker to confirm the immune-mediated fetal loss...
October 14, 2016: La Revue de Médecine Interne
Petrus R de Jong, José M González-Navajas, Nicolaas J G Jansen
Failure of gut homeostasis is an important factor in the pathogenesis and progression of systemic inflammation, which can culminate in multiple organ failure and fatality. Pathogenic events in critically ill patients include mesenteric hypoperfusion, dysregulation of gut motility, and failure of the gut barrier with resultant translocation of luminal substrates. This is followed by the exacerbation of local and systemic immune responses. All these events can contribute to pathogenic crosstalk between the gut, circulating cells, and other organs like the liver, pancreas, and lungs...
October 18, 2016: Critical Care: the Official Journal of the Critical Care Forum
Joshua J Joseph, Sherita H Golden
Controversy exists over the role of stress and depression in the pathophysiology of type 2 diabetes mellitus. Depression has been shown to increase the risk for progressive insulin resistance and incident type 2 diabetes mellitus in multiple studies, whereas the association of stress with diabetes is less clear, owing to differences in study designs and in forms and ascertainment of stress. The biological systems involved in adaptation that mediate the link between stress and physiological functions include the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous and immune systems...
October 17, 2016: Annals of the New York Academy of Sciences
Naoshi Nishida, Masatoshi Kudo
Accumulation of genetic and epigenetic alterations is a hallmark of cancer genomes, including those in hepatocellular carcinoma (HCC). Particularly, in human HCC, epigenetic changes are more frequently observed than genetic changes in a variety of cancer-related genes, suggesting a potential role for epigenetic alterations during hepatocarcinogenesis. Several environmental factors, such as inflammation, obesity, and steatosis, are reported to affect the epigenetic status in hepatocytes, which could play a role in HCC development...
2016: Digestive Diseases
Daniel Konstantinou, Nina Bertaux-Skeirik, Yana Zavros
The Hedgehog (Hh) signaling pathway not only plays a key part in controlling embryonic development, but in the adult stomach governs important cellular events such as epithelial cell differentiation, proliferation, gastric disease, and regeneration. In particular, Sonic Hedgehog (Shh) signaling has been well studied for its role in gastric physiology and pathophysiology. Shh is secreted from the gastric parietal cells and contributes to the regeneration of the epithelium in response to injury, or the development of gastritis during Helicobacter pylori infection...
October 14, 2016: Current Opinion in Pharmacology
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