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Shu-Jing Yu, Rong Jiang, Ying Z Mazzu, Cai-Bing Wei, Zong-Liang Sun, Yu-Zhen Zhang, Lian-Di Zhou, Qi-Hui Zhang
Drug-induced liver injury (DILI) is the most common cause of acute liver failure. Disruption of the Th17/Treg balance can lead to hepatic inflammation, which causes the main symptoms of DILI. Here we investigate the protective mechanisms of (-)-Epigallocatechin-3-gallate (EGCG) on triptolide (TP)-induced DILI that shows the Th17/Treg imbalance. Pretreatment with EGCG (5[Formula: see text]mg/kg) for 10 days before TP (0.5[Formula: see text]mg/kg) administration in mice significantly reduced the increased alanine aminotransferase (ALT) level ([Formula: see text]) induced by TP treatment...
2016: American Journal of Chinese Medicine
Nicole Niehoff, Alexandra J White, Lauren E McCullough, Susan E Steck, Jan Beyea, Irina Mordukhovich, Jing Shen, Alfred I Neugut, Kathleen Conway, Regina M Santella, Marilie D Gammon
BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) have been linked to breast cancer in many, but not all, previous studies. PAHs are lipophilic and stored in fat tissue, which we hypothesized may result in constant low-dose exposure to these carcinogens. No previous studies have evaluated whether obesity modifies associations between multiple measures of PAHs and breast cancer incidence. METHODS: This population-based study included 1,006 postmenopausal women with first primary in situ or invasive breast cancer and 990 age-frequency matched controls...
October 11, 2016: Environmental Research
Ruth Ruiz Esparza-Garrido, Juan Manuel Rodríguez-Corona, Javier Enrique López-Aguilar, Marco Antonio Rodríguez-Florido, Ana Claudia Velázquez-Wong, Rubí Viedma-Rodríguez, Fabio Salamanca-Gómez, Miguel Ángel Velázquez-Flores
Expression changes for long non-coding RNAs (lncRNAs) have been identified in adult glioblastoma multiforme (GBM) and in a mixture of adult and pediatric astrocytoma. Since adult and pediatric astrocytomas are molecularly different, the mixture of both could mask specific features in each. We determined the global expression patterns of lncRNAs and messenger RNA (mRNAs) in pediatric astrocytoma of different histological grades. Transcript expression changes were determined with an HTA 2.0 array. lncRNA interactions with microRNAs and mRNAs were predicted by using an algorithm and the LncTar tool, respectively...
October 13, 2016: Molecular Neurobiology
Sam Taylor, Ian Thomson, Jo Krysa
AIM: A ruptured abdominal aortic aneurysm (rAAA) remains a significant threat to life, with a 30-50% in-hospital mortality rate. The recent introduction of emergency endovascular aneurysm repair (rEVAR) in New Zealand presents an alternative to open repair for rAAAs. The aim of this paper is to review the current experience in New Zealand in the repair of rAAAs. METHODS: Data from the Australasian Vascular Audit (AVA) was reviewed, with data pertaining to rAAAs collected for the five-year period from January 2010 to December 2014...
October 14, 2016: New Zealand Medical Journal
Olivier Colin, Sylvie Favrelière, Alexandre Quillet, Jean-Philippe Neau, Jean-Luc Houeto, Claire Lafay-Chebassier, Marie-Christine Pérault-Pochat
Progressive multifocal leukoencephalopathy (PML) is an often fatal demyelinating disease of the central nervous system. As effective treatment is unavailable, identification of all drugs that could be associated with PML is essential. The objective of this study was to investigate the putative association of reports of PML and drugs. We used the case/noncase method in the French PharmacoVigilance Database (FPVD). Cases were reports of PML in the FPVD between January 2008 and December 2015. Noncases were all other reports during the same period...
October 13, 2016: Fundamental & Clinical Pharmacology
Jens Geginat, Moira Paroni, Ilko Kastirr, Paola Larghi, Massimiliano Pagani, Sergio Abrignani
Th17 cells are a heterogeneous population of pro-inflammatory T cells that have been shown to mediate immune responses against intestinal bacteria. Th17 cells are highly plastic and can transdifferentiate to Th1/17 cells or unconventional Th1 cells, which are highly pathogenic in animal models of immune-mediated diseases such as inflammatory bowel diseases. A recent European Journal of Immunology article by Liu et al. (Eur. J. Immunol. 2015. 45:1010-1018) showed, surprisingly, that Th1 cells have a similar plasticity, and could transdifferentiate to Th17 cells...
October 2016: European Journal of Immunology
Sheketha R Hauser, Gerald A Deehan, Christopher P Knight, Jamie E Toalston, William J McBride, Zachary A Rodd
BACKGROUND: Drug-paired environments can act as stimuli that elicit drug craving. In humans, drug craving is influenced by the amount of time abstinent, number of past periods of abstinence, and inadvertent exposure to the previously abused drug. The current experiments were designed to determine the effects of (a) the duration of abstinence on expression of EtOH-seeking; (b) EtOH priming following a short and long abstinence period; and (c) repeated deprivation cycles on relapse drinking and EtOH-seeking...
October 2016: Alcoholism, Clinical and Experimental Research
Sayaka Sasaoka, Toshinobu Matsui, Yuuki Hane, Junko Abe, Natsumi Ueda, Yumi Motooka, Haruna Hatahira, Akiho Fukuda, Misa Naganuma, Shiori Hasegawa, Yasutomi Kinosada, Mitsuhiro Nakamura
Long QT syndrome (LQTS) is a disorder of the heart's electrical activity that infrequently causes severe ventricular arrhythmias such as a type of ventricular tachycardia called torsade de pointes (TdP) and ventricular fibrillation, which can be fatal. There have been no previous reports on the time-to-onset for LQTS based on data from spontaneous reporting systems. The aim of this study was to assess the time-to-onset of LQTS according to drug treatment. We analyzed the association between 113 drugs in 37 therapeutic categories and LQTS including TdP using data obtained from the Japanese Adverse Drug Event Report database...
2016: PloS One
Kaja Blagotinšek, Damjana Rozman
BACKGROUND: Hepatocellular carcinoma (HCC) represents the most common malignant liver tumor in humans, which incidence and mortality have increased in Europe and United States in the last years. Most patients are diagnosed at an advanced stage, when it is not amenable to curative therapies, so there is an urgent need for new, more effective therapeutic tools and strategies. The molecular mechanisms of hepatocarinogenesis and HCC progression have been increasingly understood with intense research in recent years...
October 6, 2016: Current Pharmaceutical Design
Naibin Yang, Shanshan Li, Guoxiang Li, Shengguo Zhang, Xinyue Tang, Shunlan Ni, Xiaomin Jian, Cunlai Xu, Jiayin Zhu, Mingqin Lu
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. As vectors for intercellular information exchange, the potential role of extracellular vesicles (EVs) in HCC formation, progression and therapy has been widely investigated. In this review, we explore the current status of the researches in this field. Altogether there is undeniable evidence that EVs play a crucial role in HCC development, metastasis. Moreover, EVs have shown great potential as drug delivery systems (DDSs) for the treatment of HCC...
October 4, 2016: Oncotarget
Jason Coult, Lawrence Sherman, Heemun Kwok, Jennifer Blackwood, Peter J Kudenchuk, Thomas D Rea
AIM: Quantitative waveform measures of the ventricular fibrillation (VF) electrocardiogram (ECG) predict defibrillation outcome. Calculation requires an ECG epoch without chest compression artifact. However, pauses in CPR can adversely affect survival. Thus the potential use of waveform measures is limited by the need to pause CPR. We sought to characterize the relationship between the length of the CPR-free epoch and the ability to predict outcome. METHODS: We conducted a retrospective investigation using the CPR-free ECG prior to first shock among out-of-hospital VF cardiac arrest patients in a large metropolitan region (n=442)...
October 1, 2016: Resuscitation
Wei-Wei Chen, Xia Zhang, Wen-Juan Huang
Pain and anxiety are the most common neurological responses to many harmful or noxious stimuli and their management clinically is often challenging. Many of the frequently used morphine-based drugs, non-steroid anti-inflammatory drugs and acetaminophen, while efficient for treating pain, lead to patients suffering from several unwanted side effects. Melatonin, produced from the pineal body is a hormone of darkness, is involved in the control of circadian rhythms, and exerts a number of pharmacological effects...
October 2016: Experimental and Therapeutic Medicine
Liqiong Zhu, Hui Chen, Meilan Liu, Yu Yuan, Zhaohua Wang, Ying Chen, Jing Wei, Fang Su, Jianping Zhang
Regulatory T cells (Treg) and T helper 17 cells (Th17) are 2 distinct subsets of CD4(+) T cells, which are mutually antagonistic in the immune response. Recently, dysregulation of these 2 cell subsets have been described in the pathogenesis of unexplained recurrent spontaneous abortion (URSA). The purpose of this study was to investigate whether the Treg/Th17 balance was perturbed in URSA patients and to explore contributing factors. We found that the proportion of Treg cells and expression of forkhead box P3 (Foxp3) messenger RNA (mRNA) were significantly lower in URSA patients than in healthy controls...
October 2, 2016: Reproductive Sciences
Sheketha R Hauser, Gerald A Deehan, Christopher P Knight, Jamie E Toalston, William J McBride, Zachary A Rodd
BACKGROUND: Drug-paired environments can act as stimuli that elicit drug craving. In humans, drug craving is influenced by the amount of time abstinent, number of past periods of abstinence, and inadvertent exposure to the previously abused drug. The current experiments were designed to determine the effects of (i) the duration of abstinence on expression of ethanol (EtOH)-seeking; (ii) EtOH priming following a short and long abstinence period; and (iii) repeated deprivation cycles on relapse drinking and EtOH-seeking...
October 2016: Alcoholism, Clinical and Experimental Research
Pengxiang Yang, Yue Yang, Weiwei An, Jianyu Xu, Gan Zhang, Jing Jie, Qingyuan Zhang
BACKGROUND AND AIM: LincRNAs have critical roles in elevating efficacy of anticancer therapy and tumor progression. Recent studies show that long intergenic noncoding RNA-ROR (lincRNA-ROR) is aberrantly expressed in several types of cancer, including colorectal cancer (CRC). Radiotherapy is considered as a standard preoperative treatment. However, a considerable number of CRCs are resistant to radiotherapy. In this study, we evaluated the role of lincRNA-ROR in radiotherapy for CRC and detected the underlying molecular mechanism...
October 3, 2016: Journal of Gastroenterology and Hepatology
Andrzej T Slominski, Tae-Kang Kim, Judith V Hobrath, Allen S W Oak, Edith K Y Tang, Elaine W Tieu, Wei Li, Robert C Tuckey, Anton M Jetten
The classical pathway of vitamin D activation follows the sequence D3→25(OH)D3→1,25(OH)2D3 with the final product acting on the receptor for vitamin D (VDR). An alternative pathway can be started by the action of CYP11A1 on the side chain of D3, primarily producing 20(OH)D3, 22(OH)D3, 20,23(OH)2D3, 20,22(OH)2D3 and 17,20,23(OH)3D3. Some of these metabolites are hydroxylated by CYP27B1 at C1α, by CYP24A1 at C24 and C25, and by CYP27A1 at C25 and C26. The products of these pathways are biologically active...
September 28, 2016: Journal of Steroid Biochemistry and Molecular Biology
Cyrielle Billon, Sadichha Sitaula, Thomas P Burris
OBJECTIVE: Cardiovascular diseases (CVDs) are the leading cause of mortality in Western countries. Atherosclerosis is a multi-step inflammatory disease characterized at early stages by accumulation of cholesterol in the arterial wall followed by recruitment of immune cells. We sought to determine if pharmacological suppression of RORα/γ activity is beneficial in treatment of atherosclerosis. METHODS: To identify the role of RORα and RORγ in atherosclerosis, we used the LDL-R(-/-) mouse model of atherosclerosis placed on a high cholesterol diet treated with SR1001, a RORα/γ inverse agonist, for four weeks...
October 2016: Molecular Metabolism
Valentin Mutemberezi, Owein Guillemot-Legris, Giulio G Muccioli
Oxysterols are cholesterol metabolites that can be produced through enzymatic or radical processes. They constitute a large family of lipids (i.e. the oxysterome) involved in a plethora of physiological processes. They can act through GPCR (e.g. EBI2, SMO, CXCR2), nuclear receptors (LXR, ROR, ERα) and through transporters or regulatory proteins. Their physiological effects encompass cholesterol, lipid and glucose homeostasis. Additionally, they were shown to be involved in other processes such as immune regulatory functions and brain homeostasis...
September 26, 2016: Progress in Lipid Research
Thi Thu Ha Nguyen, Antoine Pariente, Jean-Louis Montastruc, Maryse Lapeyre-Mestre, Vanessa Rousseau, Olivier Rascol, Bernard Bégaud, François Montastruc
AIMS: Pharmacovigilance databases are usually used to detect new potential signals relevant for drug safety. They are seldom used for explanatory purposes, e.g. to understand the mechanisms of adverse drug reactions (ADRs). The aim of the present study was to combine pharmacovigilance and pharmacodynamic data to investigate the association between D2, 5HT2A, and M1 receptor occupancy and the risks of antipsychotic (AP)-induced movement disorders. METHODS: First, we performed a case non-case analysis using spontaneous reports from the World Health Organization (WHO) Global Individual Case Safety Report (ICSR) database, VigiBase®...
September 30, 2016: British Journal of Clinical Pharmacology
Joep H G Scholl, Eugène P van Puijenbroek
PURPOSE: In pharmacovigilance, the commonly used disproportionality analysis (DPA) in statistical signal detection is known to have its limitations. The aim of this study was to investigate the value of the time to onset (TTO) of ADRs in addition to DPA. METHODS: We performed a pilot study using individual case safety reports (ICSRs) for three drugs (Cervarix®, nitrofurantoin and simvastatin) from the Lareb spontaneous reporting database. TTO distributions for drug - ADR associations were compared to other ADRs for the same drug and to other drugs for the same ADR using two-sample Anderson-Darling testing...
September 30, 2016: Pharmacoepidemiology and Drug Safety
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