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https://www.readbyqxmd.com/read/28212985/nonsteroidal-anti-inflammatory-drugs-in-clinical-and-experimental-epilepsy
#1
REVIEW
Beatrice Mihaela Radu, Florin Bogdan Epureanu, Mihai Radu, Paolo Francesco Fabene, Giuseppe Bertini
Current antiepileptic drugs have limited efficacy and provide little or no benefits in 30% of the patients. Given that a role for brain inflammation in epilepsy has been repeatedly reported in recent years, the potential of anti-inflammatory drugs should be explored in depth, as they may provide new therapeutical approaches in preventing or reducing epileptogenesis. Here, we review preclinical (both in vivo and in vitro) and clinical epilepsy studies in which nonsteroidal antiinflammatory drugs (NSAIDs), i...
February 9, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28211326/evaluation-of-in%C3%A2-vivo-and-in%C3%A2-vitro-toxicological-and-genotoxic-potential-of-aluminum-chloride
#2
Letícia Nazareth Fernandes Paz, Laís Mesquita Moura, Danielle Cristinne A Feio, Mirella de Souza Gonçalves Cardoso, Wagner Luiz O Ximenes, Raquel C Montenegro, Ana Paula N Alves, Rommel R Burbano, Patrícia Danielle L Lima
Aluminum and its compounds are common contaminants of water and food, as well as medications and cosmetics. The wide distribution of the element facilitates the demand for detailed studies of its biological and toxicological effects. This work aimed to evaluate the possible genotoxic and toxic activity resulting from in vivo and in vitro exposure to Al. For in vivo analysis, 40 Swiss mice were used, various concentrations of hydrated aluminum chloride were administered orally. They were analyzed for possible genic activity and metal cytotoxicity using a micronucleus test (MN), and for toxicity through histopathological evaluation of the extracted organs...
February 3, 2017: Chemosphere
https://www.readbyqxmd.com/read/28210023/application-of-diode-laser-in-the-treatment-of-dentine-hypersensitivity
#3
Mirjana Gojkov-Vukelic, Sanja Hadzic, Amila Zukanovic, Enes Pasic, Veriva Pavlic
INTRODUCTION: Dentine hypersensitivity is characterized by acute, sharp pain arising from the exposed dentine, most commonly in response to thermal, tactile, or chemical stimuli, and which cannot be linked to any other pathological changes in the tooth or the environment. Therapy uses various impregnating agents in the form of solutions or gels and, in more recent times, laser. AIM: The aim of this research was to examine the effects of treatment of hypersensitive dental cervix with diode laser...
December 2016: Medical Archives
https://www.readbyqxmd.com/read/28202908/silencing-c-rel-in-macrophages-dampens-th1-and-th17-immune-responses-and-alleviates-experimental-autoimmune-encephalomyelitis-in-mice
#4
Hongling Zhang, Jiacheng Bi, Huqiang Yi, Tingting Fan, Qingguo Ruan, Lintao Cai, Youhai H Chen, Xiaochun Wan
Autoimmune Th1 and Th17 responses are critical for the development of central nervous system (CNS) pathology in experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. Although macrophages play important roles in the development of Th1 and Th17 responses, whether modulating macrophage gene transcription can diminish Th1- and Th17 cell-induced CNS pathology is unclear. In this study, we successfully silenced the expression of the transcription factor c-Rel in macrophages of mice with EAE (including those infiltrating the CNS) using chemically modified c-Rel-specific siRNAs delivered by nanoparticles...
February 16, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28202594/surface-microtopography-modulates-sealing-zone-development-in-osteoclasts-cultured-on-bone
#5
Michal Shemesh, Lia Addadi, Benjamin Geiger
Bone homeostasis is continuously regulated by the coordinated action of bone-resorbing osteoclasts and bone-forming osteoblasts. Imbalance between these two cell populations leads to pathological bone diseases such as osteoporosis and osteopetrosis. Osteoclast functionality relies on the formation of sealing zone (SZ) rings that define the resorption lacuna. It is commonly assumed that the structure and dynamic properties of the SZ depend on the physical and chemical properties of the substrate. Considering the unique complex structure of native bone, elucidation of the relevant parameters affecting SZ formation and stability is challenging...
February 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28195244/health-technology-assessment-introducing-a-vacuum-based-preservation-system-for-biological-materials-in-the-anatomic-pathology-workflow
#6
R Saliceti, E Nicodemo, A Giannini, A Cortese
INTRODUCTION: The objective of this work is to assess the implementation of a newly introduced medical equipment technology for the vacuum-based preservation of biological materials within an Anatomic Pathology service. METHODS: The approach selected for the analysis is the Health Technology Assessment (HTA ), a comprehensive evaluation method based on relevant scientific evidence and designed to support healthcare decision makers in purchasing, replacing or disposing of technologies...
March 2016: Pathologica
https://www.readbyqxmd.com/read/28194024/regnase-1-a-rapid-response-ribonuclease-regulating-inflammation-and-stress-responses
#7
REVIEW
Renfang Mao, Riyun Yang, Xia Chen, Edward W Harhaj, Xiaoying Wang, Yihui Fan
RNA-binding proteins (RBPs) are central players in post-transcriptional regulation and immune homeostasis. The ribonuclease and RBP Regnase-1 exerts critical roles in both immune cells and non-immune cells. Its expression is rapidly induced under diverse conditions including microbial infections, treatment with inflammatory cytokines and chemical or mechanical stimulation. Regnase-1 activation is transient and is subject to negative feedback mechanisms including proteasome-mediated degradation or mucosa-associated lymphoid tissue 1 (MALT1) mediated cleavage...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28193079/correlation-between-mmp-9-and-mmp-9-timps-complex-with-pulmonary-function-in-sulfur-mustard-exposed-civilians-sardasht-iran-cohort-study
#8
Sara Ghaffarpour, Tooba Ghazanfari, Sussan Kabudanian Ardestani, Shahryar Pourfarzam, Faramarz Fallahi, Jalaleddin Shams, Ensieh Sadat Mirsharif, Ali Mohammad Mohseni Majd, Soghrat Faghihzadeh
BACKGROUND: Matrix metalloproteinases (MMPs) are a family of proteinases and have the vigorous capacity to degrade all parts of the extracellular matrix. MMP enzymes strongly participate in physiological processes such as normal tissue remodeling and wound healing and in pathology of pulmonary diseases. They are released in response to environmental stimuli such as toxins and regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs). Sulfur mustard (SM) is a chemical toxic which can cause severe permanent damages to lung tissues...
February 2017: Archives of Iranian Medicine
https://www.readbyqxmd.com/read/28192917/simple-reagentless-quantification-of-total-bilirubin-in-blood-via-microfluidic-phototreatment-and-image-analysis
#9
Brandon L Thompson, Sarah L Wyckoff, Doris M Haverstick, James P Landers
Total bilirubin (T-Bil) is an important clinical diagnostic marker that is measured frequently by physicians to assist in the diagnosis, treatment, and monitoring of multiple medical conditions. The work demonstrated here utilizes the 48-year-old mechanism of phototherapy that is commonly implemented in the treatment of infants with exaggerated physiologic and pathologic jaundice but adapts it to the microfluidic level for the ultimate purpose of total bilirubin quantitation. After acquisition of a small volume of blood (<10 μL) and through subsequent separation (plasma + red blood cells), a 3 μL plasma sample was imaged by a portable scanner and analyzed through a custom algorithm for color intensity...
February 13, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28191280/macrophage-migration-inhibitory-factor-as-an-emerging-drug-target-to-regulate-antioxidant-response-element-system
#10
REVIEW
Hiroshi Yukitake, Masayuki Takizawa, Haruhide Kimura
Oxidative stress is involved in pathophysiology and pathological conditions of numerous human diseases. Thus, understanding the mechanisms underlying the redox homeostasis in cells and organs is valuable for discovery of therapeutic drugs for oxidative stress-related diseases. Recently, by applying chemical biology approach with an ARE activator, BTZO-1, we found macrophage migration inhibitory factor (MIF) as a new regulator of antioxidant response element- (ARE-) mediated gene transcription. BTZO-1 and its active derivatives bound to MIF and protected cells and organs from oxidative insults via ARE activation in animal models with oxidative stress such as ischemia/reperfusion injury, inflammatory bowel diseases, and septic shock...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28188297/alternative-splicing-in-the-cytochrome-p450-superfamily-expands-protein-diversity-to-augment-gene-function-and-redirect-human-drug-metabolism
#11
Andrew J Annalora, Craig B Marcus, Patrick L Iversen
The human genome encodes 57 cytochrome P450 (CYP) genes whose enzyme products metabolize hundreds of drugs, thousands of xenobiotics and unknown numbers of endogenous compounds including steroids, retinoids and icosinoids. Indeed, CYP genes are the first line of defense against daily environmental chemical challenges in a manner that parallels the immune system. Several databases, including PubMed, AceView, and Ensembl, were queried to establish a comprehensive analysis of the full human CYP transcriptome. This review describes a remarkable diversification of the 57 human CYP genes, which may be alternatively processed into nearly 1000 distinct mRNA transcripts to shape an individual's CYP proteome...
February 10, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28187433/doxycycline-directly-targets-par1-to-suppress-tumor-progression
#12
Weilong Zhong, Shuang Chen, Qiang Zhang, Ting Xiao, Yuan Qin, Ju Gu, Bo Sun, Yanrong Liu, Xiangyan Jing, Xuejiao Hu, Peng Zhang, Honggang Zhou, Tao Sun, Cheng Yang
Doxycycline have been reported to exert anti-cancer activity and have been assessed as anti-cancer agents in clinical trials. However, the direct targets of doxycycline in cancer cells remain unclear. In this study, we used a chemical proteomics approach to identify the Protease-activated receptor 1 (PAR1) as a specific target of inhibition of doxycycline. Binding assays and single-molecule imaging assays were performed to confirm the inhibition of doxycycline to PAR1. The effect of doxycycline on multi-omics and cell functions were assessed based on a PAR1/thrombin model...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185915/targeting-kinase-signaling-pathways-with-constrained-peptide-scaffolds
#13
REVIEW
Laura E Hanold, Melody D Fulton, Eileen J Kennedy
Kinases are amongst the largest families in the human proteome and serve as critical mediators of a myriad of cell signaling pathways. Since altered kinase activity is implicated in a variety of pathological diseases, kinases have become a prominent class of proteins for targeted inhibition. Although numerous small molecule and antibody-based inhibitors have already received clinical approval, several challenges may still exist with these strategies including resistance, target selection, inhibitor potency and in vivo activity profiles...
February 6, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28185804/7-cyclopentyl-5-4-phenoxyphenyl-7h-pyrrolo-2-3-d-pyrimidin-4-ylamine-inhibits-the-proliferation-and-migration-of-vascular-smooth-muscle-cells-by-suppressing-erk-and-akt-pathways
#14
Hyang-Hee Seo, Sang Woo Kim, Chang Youn Lee, Kyu Hee Lim, Jiyun Lee, Soyeon Lim, Seahyoung Lee, Ki-Chul Hwang
Excessive vascular smooth muscle cell (VSMC) proliferation and migration after vascular injury significantly contributes to the development of occlusive vascular disease. Therefore, inhibiting the proliferation and migration of VSMCs is a validated therapeutic modality for occlusive vascular disease such as atherosclerosis and restenosis. In the present study, we screened chemical compounds for their anti-proliferative effects on VSMCs using multiple approaches, such as MTT assays, wound healing assays, and trans-well migration assays...
February 6, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28185763/bariatric-surgery-attenuates-colitis-in-an-obese-murine-model
#15
Shiri Li, Alessio Vinci, Judith Behnsen, Chunmei Cheng, Stefan Jellbauer, Manuela Raffatellu, Kyle M Sousa, Robert Edwards, Ninh T Nguyen, Michael J Stamos, Alessio Pigazzi
BACKGROUND: Obesity and inflammatory bowel disease (IBD) represent chronic inflammatory conditions. Bariatric surgery improves some obesity-related co-morbidities, but the effects of bariatric surgery on IBD have not been well studied. OBJECTIVES: To examine if bariatric surgery may attenuate colitis in an obese murine model of IBD and study the mechanisms underlying the postsurgical amelioration of intestinal inflammation. SETTING: University of California Irvine, Department of Surgery and Microbiology laboratories...
December 20, 2016: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/28179188/diacetyl-and-related-flavorant-%C3%AE-diketones-biotransformation-cellular-interactions-and-respiratory-tract-toxicity
#16
M W Anders
Exposure to diacetyl and related α-diketones causes respiratory-tract damage in humans and experimental animals. Chemical toxicity is often associated with covalent modification of cellular nucleophiles by electrophilic chemicals. Electrophilic α-diketones may covalently modify nucleophilic arginine residues in critical proteins and, thereby, produce the observed respiratory-tract pathology. The major pathway for the biotransformation of α-diketones is reduction to α-hydroxyketones (acyloins), which is catalyzed by NAD(P)H-dependent enzymes of the short-chain dehydrogenase/reductase (SDR) and the aldo-keto reductase (AKR) superfamilies...
February 5, 2017: Toxicology
https://www.readbyqxmd.com/read/28178198/zinc-transporter-3-znt3-in-the-enteric-nervous-system-of-the-porcine-ileum-in-physiological-conditions-and-during-experimental-inflammation
#17
Sławomir Gonkowski, Maciej Rowniak, Joanna Wojtkiewicz
Zinc transporter 3 (ZnT3) is a member of the solute-linked carrier 30 (SLC 30) zinc transporter family. It is closely linked to the nervous system, where it takes part in the transport of zinc ions from the cytoplasm to the synaptic vesicles. ZnT3 has also been observed in the enteric nervous system (ENS), but its reactions in response to pathological factors remain unknown. This study, based on the triple immunofluorescence technique, describes changes in ZnT3-like immunoreactive (ZnT3-LI) enteric neurons in the porcine ileum, caused by chemically-induced inflammation...
February 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28174120/xenobiotics-and-the-glucocorticoid-receptor
#18
REVIEW
Linda S M Gulliver
Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes...
February 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28168870/annotation-of-functional-impact-of-voltage-gated-sodium-channel-mutations
#19
Valérie Hinard, Aurore Britan, Mathieu Schaeffer, Monique Zahn-Zabal, Urs Thomet, Jean-Sébastien Rougier, Amos Bairoch, Hugues Abriel, Pascale Gaudet
Voltage-gated sodium channels are pore-forming transmembrane proteins that selectively allow sodium ions to flow across the plasma membrane according to the electro-chemical gradient thus mediating the rising phase of action potentials in excitable cells and playing key roles in physiological processes such as neurotransmission, skeletal muscle contraction, heart rhythm and pain sensation. Genetic variations in the nine human genes encoding these channels are known to cause a large range of diseases affecting the nervous and cardiac systems...
February 7, 2017: Human Mutation
https://www.readbyqxmd.com/read/28166796/coenzyme-q10-partially-restores-pathological-alterations-in-a-macrophage-model-of-gaucher-disease
#20
Mario de la Mata, David Cotán, Manuel Oropesa-Ávila, Marina Villanueva-Paz, Isabel de Lavera, Mónica Álvarez-Córdoba, Raquel Luzón-Hidalgo, Juan M Suárez-Rivero, Gustavo Tiscornia, José A Sánchez-Alcázar
BACKGROUND: Gaucher disease (GD) is caused by mutations in the GBA1 gene which encodes lysosomal β-glucocerebrosidase (GCase). In GD, partial or complete loss of GCase activity causes the accumulation of the glycolipids glucosylceramide (GlcCer) and glucosylsphingosine in the lysosomes of macrophages. In this manuscript, we investigated the effects of glycolipids accumulation on lysosomal and mitochondrial function, inflammasome activation and efferocytosis capacity in a THP-1 macrophage model of Gaucher disease...
February 6, 2017: Orphanet Journal of Rare Diseases
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