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Dependance mechanism

Nancy C Jao, Marcia M Tan, Phoenix A Matthews, Melissa A Simon, Robert Schnoll, Brian Hitsman
Introduction: Despite the overall decline in the prevalence of cigarette use in the United States, menthol cigarette use among smokers is rising, and evidence shows that it may lead to more detrimental effects on public health than regular cigarette use. One of the mechanisms by which nicotine sustains tobacco use and dependence is due to its cognitive enhancing properties, and basic science literature suggests that menthol may also enhance nicotine's acute effect on cognition. Aims and Methods: The purpose of this review is to suggest that the cognitive enhancing effects of menthol may be a potentially important neuropsychological mechanism that has yet to be examined...
December 14, 2018: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
Paolo Vercellini, Paola Viganò, Giussy Barbara, Laura Buggio, Edgardo Somigliana
Elagolix, an orally active non-peptidic GnRH antagonist, has been approved by the Food and Drug Administration for the management of moderate to severe pain associated with endometriosis. As the degree of ovarian suppression obtained with elagolix is dose-dependent, pain relief may be achieved by modulating the level of hypo-oestrogenism while limiting side effects. Elagolix may thus be considered a novelty in terms of its endocrine and pharmacological properties but not for its impact on the pathogenic mechanisms of endometriosis, as the target of this new drug is, yet again, alteration of the hormonal milieu...
December 14, 2018: Human Reproduction
Min Su, Xiaoliu Liang, Xiaoxiao Xu, Xinmou Wu, Bin Yang
Our previous studies show that vitamin C (VC) plays promising hepatoprotection in mice. Intrahepatic exposure of perfluorooctane sulfonate (PFOS) can induce dose-dependent cytotoxicity. However, pharmacology-based assessment of VC on PFOS remains uninvestigated. This study aimed to evaluate the therapeutic benefits of VC on inhibiting PFOS-induced liver steatosis in mice, followed by representative biochemical analysis and immunoassay. As results, VC was beneficial for reduced PFOS-induced liver damages, as showed in reductions of serological levels of transaminases (ALT and AST), lipids (TG and TC), fasting glucose and insulin, inflammatory cytokines (TNF-α and IL6), while content of fibroblast growth factor 21 (FGF21) in serum was increased...
December 5, 2018: Environmental Toxicology and Pharmacology
Anne-Sophie Voisin, Dietmar Kültz, Frédéric Silvestre
Early-life represents a critically sensitive window to endocrine disrupting chemicals, potentially leading to long-term repercussions on the phenotype later in life. The mechanisms underlying this phenomenon, referred to as the Developmental Origins of Health and Disease (DOHaD), are still poorly understood. To gain molecular understanding of these effects, we exposed mangrove rivulus (Kryptolebias marmoratus) for 28 days post hatching (dph) to 4 and 120 ng/L 17-α-ethinylestradiol, a model xenoestrogen...
December 11, 2018: Journal of Proteomics
Nai She, Yuan Zhao, Jingjing Hao, Songqiang Xie, Chaojie Wang
O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein. It plays an important role in many important cellular physiological catalytic reactions. Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations. The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues were identified to play a major role in the UDP stabilization in the active site of OGT, where hydrogen bonding and π-π interactions mainly occur...
December 11, 2018: Biochimica et biophysica acta. General subjects
Daniel Knowles, Kyle Brown, Silvio Aldrovandi
OBJECTIVE: One method of influencing an individual's food consumption involves placing unhealthy snacks further away from individuals, known as the "proximity effect". However, only one laboratory study has explored the effect while both an unhealthy and a healthy option are presented simultaneously. Further, little is known about the potential underpinning mechanisms of the effect. The current study aims to replicate the proximity effect in a competitive environment, and to explore the role of visual salience and effort in the proximity effect...
December 11, 2018: Appetite
Ming Li, Jianqiang Zhao, Liang Jia
Osteoarthritis (OA) is an inflammatory joint disease. USP14, a deubiquitinating enzyme critical for ubiquitin-mediated proteasomal protein degradation, is implicated in inflammation regulation. However, its role and mechanism in OA are poorly understood. Here, we report that USP14 is upregulated in OA articular cartilage as well as in chondrocytes treated with IL-1β in vitro. USP14 upregulation depends on NF-κB pathway activation, since inhibition of this pathway by ACHP, a selective inhibitor of IKK-β, abolishes USP14 upregulation...
December 11, 2018: Life Sciences
Ekaterina F Afanasyeva, Victoria N Syryamina, Marta De Zotti, Fernando Formaggio, Claudio Toniolo, Sergei A Dzuba
The antimicrobial action of peptides in bacterial membranes is commonly related to their mode of self-assembling which results in pore formation. To optimize peptide antibiotic use for therapeutic purposes, a study on the concentration dependence of self-assembling process is thus desirable. In this work, we investigate this dependence for peptaibol trichogin GA IV (Tric) in the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) model membrane in the range of peptide concentrations between 0.5 and 3.3 mol%...
December 11, 2018: Biochimica et biophysica acta. Biomembranes
Kai-Ge Lu, Haiou Huang
Silica scaling of reverse osmosis membranes in brackish water desalination is less understood than hardness scaling due to the complex silica behaviors at the membrane/water interface. In this study, -COOH, -SO3 H, -NH2 and -OH functional groups were introduced onto polyamide membranes to create distinct surface physicochemical properties. The resulting membranes were further studied under similar scaling conditions to yield temporal flux loss data that were empirically interpreted by a logistic growth model...
November 30, 2018: Water Research
Yongliang Jiang, Yumin Zhou, Gongyong Peng, Heshen Tian, Dan Pan, Lei Liu, Xing Yang, Chao Li, Wen Li, Ling Chen, Pixin Ran, Aiguo Dai
The present study was designed to explore the role of transient receptor potential canonical 3 (TRPC3) in nicotine-induced chronic obstructive pulmonary disease (COPD) and its underlying mechanism. In this study, the expression and localization of α5 nicotinic acetylcholine receptor (α5-nAchR) in lung tissues were determined by western blotting and immunohistochemistry. The quantitative real-time PCR (qRT-PCR) analysis was performed to examine the mRNA expression levels of α5-nAchR and TRPC3 in human airway smooth muscle cells (HASMCs)...
December 11, 2018: Biochimie
Ezgi Oztas, Mahmoud Abudayyak, Muzeyyen Celiksoz, Gül Özhan
Synthetic cannabinoids were introduced into market in early 2000s; since these "legal highs" are dramatically popular among youth, it becomes a deadly problem. Synthetic cannabinoids have high affinity to cannabinoid receptors; leading to various clinical symptoms. AKB48 (Apinaca) has been classified as a third-generation synthetic cannabinoid for the first time in 2014. The toxicity profile of AKB48 is unclear due to little information that mainly obtained from clinical and forensic cases; however, it is believed to be similar with other psychoactive substances...
December 11, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Yan-Lai Tang, Xi Sun, Li-Bin Huang, Xiao-Jian Liu, Ge Qin, Li-Na Wang, Xiao-Li Zhang, Zhi-Yong Ke, Jie-Si Luo, Cong Liang, Chun-Jin Peng, Wen-Yan Tang, Yu Li, Wenlin Huang, Xue-Qun Luo, Wuguo Deng
MLL-rearranged leukemia is an aggressive malignancy associated with poor outcome, which is refractory to conventional treatment. Melatonin has been proven to exert anti-tumor activity, but the effect of melatonin on MLL-r leukemia and the underlying mechanism remain poorly understood. In this study, melatonin inhibited cell proliferation and induced apoptosis by activating the caspase-dependent apoptotic pathway in MLL-r leukemia cells. Mechanistic investigations revealed that melatonin suppressed the expression of hTERT by abrogating the binding activity of RBFOX3 to the hTERT promoter...
December 10, 2018: Cancer Letters
Xiaoling Wu, Jiamei Zhang, Chenjie Ma, Wu Li, Jin Zeng, Yujiong Wang, Guangcun Deng
Mycobacterium tuberculosis (Mtb)-induced autophagy of alveolar macrophages has been confirmed to play a central role in the pathogenesis of tuberculosis. Growing evidence indicates that excessive or uncontrolled autophagic activity, which results in type II programmed cell death, can be regulated by many factors, including Wnt/β-catenin signalling. Wnt/β-catenin signalling has been demonstrated to be involved in multiple diseases through the regulation of autophagy; however, its exact role in regulating autophagy induced by Mtb remains unclear...
December 11, 2018: Microbial Pathogenesis
Semil Selcen Gocmez, Tuğçe Demirtaş Şahin, Yusufhan Yazir, Gökhan Duruksu, Fatma Ceyla Eraldemir, Selen Polat, Tijen Utkan
Diabetes is one of the risk factors for the development of vascular dementia (VD), leading to endothelial dysfunction and cognitive impairment. Resveratrol has been shown to have antioxidant, antiinflammatory, and neuroprotective effects. The previous studies have also reported that resveratrol improves cognitive and vascular endothelial functions in several pathological conditions. In the present study we aimed to evaluate the effect of resveratrol on cognitive and vascular endothelial function and to explore the mechanisms of its effects in streptozotocin-induced diabetic rat model of VD...
December 11, 2018: Physiology & Behavior
Priya S Shah, Nichole Link, Gwendolyn M Jang, Phillip P Sharp, Tongtong Zhu, Danielle L Swaney, Jeffrey R Johnson, John Von Dollen, Holly R Ramage, Laura Satkamp, Billy Newton, Ruth Hüttenhain, Marine J Petit, Tierney Baum, Amanda Everitt, Orly Laufman, Michel Tassetto, Michael Shales, Erica Stevenson, Gabriel N Iglesias, Leila Shokat, Shashank Tripathi, Vinod Balasubramaniam, Laurence G Webb, Sebastian Aguirre, A Jeremy Willsey, Adolfo Garcia-Sastre, Katherine S Pollard, Sara Cherry, Andrea V Gamarnik, Ivan Marazzi, Jack Taunton, Ana Fernandez-Sesma, Hugo J Bellen, Raul Andino, Nevan J Krogan
Mosquito-borne flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), are a growing public health concern. Systems-level analysis of how flaviviruses hijack cellular processes through virus-host protein-protein interactions (PPIs) provides information about their replication and pathogenic mechanisms. We used affinity purification-mass spectrometry (AP-MS) to compare flavivirus-host interactions for two viruses (DENV and ZIKV) in two hosts (human and mosquito). Conserved virus-host PPIs revealed that the flavivirus NS5 protein suppresses interferon stimulated genes by inhibiting recruitment of the transcription complex PAF1C and that chemical modulation of SEC61 inhibits DENV and ZIKV replication in human and mosquito cells...
December 13, 2018: Cell
Subrata Dutta, Thomas S Finn, Ariel J Kuhn, Benjamin Abrams, Jevgenij Raskatov
Amyloid β is an inherently disordered peptide that can form diverse neurotoxic aggregates, and its 42 amino acid long isoform is the believed culprit of Alzheimer's Disease. Cellular uptake of the peptide is a pivotal step for it to be able to exert many of its toxic actions. The cellular uptake process is complex, and numerous competing internalization pathways have been proposed. To date, it remains unclear, which of the uptake mechanisms are particularly important for the overall process, and improving this understanding is needed, so that better molecular therapeutics of Alzheimer's Disease can be designed...
December 14, 2018: Chembiochem: a European Journal of Chemical Biology
Vineeta Rustagi, D Gomika Udugamasooriya
The metal-chelated 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) has made a significant impact on the field of diagnostic imaging. This imaging mechanism is largely dependent on the four side arm functionalities around the DOTA scaffold. We previously demonstrated the effect of peptoid residue modification on these DOTA side arms, thereby conferring diverse physiochemical properties to the imaging mechanism. We generated two on-bead Eu(III)-DOTA libraries with three side arm modifications, where the remaining arm was used to attach DOTA onto the resin...
December 14, 2018: Biopolymers
Giuseppe Vanella, Livia Archibugi, Serena Stigliano, Gabriele Capurso
PURPOSE OF REVIEW: Alcohol is a type I carcinogen and the WHO stated that it caused 5% of all deaths in 2016, of which 13% because of cancers. Among digestive tract cancers, this association is clear for esophageal, liver and colorectal cancer, and more debated for gastric and pancreatic cancer. The present review will revise recent evidence on epidemiologic association and mechanisms linking alcohol with the risk of esophageal, gastric, colorectal and pancreatic cancers. RECENT FINDINGS: Moderate alcohol intake increases the risk of esophageal squamous cell carcinoma and colorectal cancer...
December 12, 2018: Current Opinion in Gastroenterology
Elena Stavenschi, David A Hoey
Macroscale loading of bone generates a complex local mechanical microenvironment that drives osteogenesis and bone mechanoadaptation. One such mechanical stimulus generated is hydrostatic pressure (HP); however, the effect of HP on mesenchymal stem cells (MSCs) and the mechanotransduction mechanisms utilized by these cells to sense this stimulus are yet to be fully elucidated. In this study, we demonstrate that cyclic HP is a potent mediator of cytoskeletal reorganization and increases in osteogenic responses in MSCs...
December 14, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Eva Gatineau, Dianne M Cohn, Marko Poglitsch, Analia S Loria, Ming Gong, Frederique Yiannikouris
The deletion of the prorenin receptor (PRR) in adipose tissue elevates systolic blood pressure (SBP) and circulating soluble form of PRR (sPRR) in male mice fed a high-fat diet (HF). However, sex differences in the contribution of adipose-PRR and sPRR to the regulation of the renin-angiotensin system (RAS) in key organs for blood pressure control are undefined. Therefore, we assessed blood pressure and the systemic and intrarenal RAS status in adipose-PRR KO female mice. Blockade of RAS with losartan blunted SBP elevation in HF-fed adipose-PRR KO mice...
December 14, 2018: American Journal of Physiology. Heart and Circulatory Physiology
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