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Hayato Akimoto, Akio Negishi, Shinji Oshima, Mitsuyoshi Okita, Sachihiko Numajiri, Naoko Inoue, Shigeru Ohshima, Daisuke Kobayashi
To evaluate the onset timing of musculoskeletal adverse events (MAEs) that develop during statin monotherapy and to determine whether concomitant drugs used concurrently with statin therapy shifts the onset timing of MAEs. Cases in which statins (atorvastatin, rosuvastatin, simvastatin, lovastatin, fluvastatin, pitavastatin, and pravastatin) were prescribed were extracted from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) Data Files. The onset timing of MAEs during statin monotherapy was evaluated by determining the difference between statin start date and MAE onset date...
December 2018: Pharmacology Research & Perspectives
Lu Lu, Huimei Yi, Chao Chen, Shichao Yan, Hui Yao, Guangchun He, Guifei Li, Yiqun Jiang, Tuo Deng, Xiyun Deng
The nucleolus is a dynamic structure that has roles in various physiological and pathophysiological processes. Perturbations on many aspects of the nucleolar functions are thought to cause "nucleolar stress", which occurs in response to a variety of chemotherapeutic drugs. The main characteristic changes of nucleolar stress include: 1) reduction of the size and volume of the nucleolus; 2) inhibition of RNA Pol I-mediated rRNA synthesis; and 3) nucleoplasmic translocation of nucleolar stress-related proteins...
2018: Journal of Cancer
Hiroya Itoh, Makoto Matsui, Yuki Miyamura, Itaru Takeda, Jun Ishii, Toshitaka Kumagai, Masayuki Machida, Takashi Shibata, Masanori Arita
For many secondary metabolites, heterologous synthesis is the definitive step to determine their required biosynthetic genes. Using a multivector expression system in Saccharomyces cerevisiae, we reconstituted not only two natural statins from two fungal species, i.e., lovastatin from Aspergillus terreus and FR901512 from Xylaria grammica, but also new statin structures by mixing their genes. Combinatorial gene exchange experiments revealed the functional promiscuity of two polyketide synthases in A. terreus, lovB, and lovF; they could synthesize FR901512 with Xylaria genes...
November 13, 2018: ACS Synthetic Biology
Yuan Yuan Pan, Gang Liu
More than half of the activity secondary metabolites from microorganisms are produced by filamentous fungi. The metabolites that are well known include penicillin, cyclosporine A, lovastatin, and so on. Due to their importance in agriculture, medicine and industry, biosynthesis and regulation of these fungal secondary metabolites have attracted much attention. The biosynthesis of fungal secondary metabolites is a complex process which generally includes multistep enzymatic reactions. Commonly, the process is controlled by elaborate regulations at different levels...
October 20, 2018: Yi Chuan, Hereditas
Jun-X Lu, Chao Guo, Wen-S Ou, Yun Jing, Hui-F Niu, Ping Song, Quan-Z Li, Zhan Liu, Jian Xu, Peng Li, Mo-L Zhu, Ya-L Yin
BACKGROUND: Atherosclerosis is a chronical inflammatory disease in arterial walls, which is involved in oxidative stress and endothelial dysfunction. Aromatherapy is one of the complementary therapies that use essential oils as the major therapeutic agents to treat several diseases. Citronellal (CT) is a monoterpene predominantly formed by the secondary metabolism of plants, producing antithrombotic, antiplatelet, and antihypertensive activities. AIM: The aim of the present study is to explore whether aromatherapy with CT improves endothelial function to prevent the formation of atherosclerotic plaque in vivo...
October 26, 2018: Journal of Cellular Biochemistry
Irene Ruiz-DeDiego, Stefania Fasano, Oscar Solís, José-Rubén Garcia-Montes, José Brea, María I Loza, Riccardo Brambilla, Rosario Moratalla
Increasing evidence supports a close relationship between Ras-ERK1/2 activation in the striatum and L-DOPA-induced dyskinesia (LID). ERK1/2 activation by L-DOPA takes place through the crosstalk between D1R/AC/PKA/DARPP-32 pathway and NMDA/Ras pathway. Compelling genetic and pharmacological evidence indicates that Ras-ERK1/2 inhibition prevents LID onset and may even revert already established dyskinetic symptoms. However, it is currently unclear whether exacerbation of Ras-ERK1/2 activity in the striatum may further aggravate dyskinesia in experimental animal models...
October 18, 2018: Scientific Reports
Guofang Li, Ming Tan, Fang Cheng, Xiaojie Liu, Siyan Qi, Hongfei Chen, Dong Zhang, Caiping Zhao, Mingyu Han, Juanjuan Ma
Axillary bud activation and outgrowth were dependent on local cytokinin, and that bud activation preceded the activation of cell cycle and cell growth genes in apple branching. Cytokinin is often applied to apple trees to produce more shoot branches in apple seedlings. The molecular response of apple to the application of cytokinin, and the relationship between bud activation and cell cycle in apple branching, however, are poorly understood. In this study, RNA sequencing was used to characterize differential expression genes in axillary buds of 1-year grafted "Fuji" apple at 4 and 96 h after cytokinin application...
October 2018: Plant Molecular Biology
Vineet Kumar Gupta, Nikita S Sharma, Kousik Kesh, Patricia Dauer, Alice Nomura, Bhuwan Giri, Vikas Dudeja, Santanu Banerjee, Sanjoy Bhattacharya, Ashok Saluja, Sulagna Banerjee
Metabolic rewiring is an integral part of tumor growth. Among metabolic pathways, the Mevalonic-Acid-Pathway (MVAP) plays a key role in maintaining membrane architecture through cholesterol synthesis, thereby affecting invasiveness. In the current study, we show for the first time that CD133Hi pancreatic tumor initiating cells (TIC) have increased expression of MVAP enzymes, cholesterol-content and Caveolin expression. Further, we show that CD133 in these cells is localized in the lipid-rafts (characterized by Cav-1-cholesterol association)...
October 2, 2018: Cancer Letters
Li Zhang, Wenquan Kang, Xiaolan Lu, Shiyang Ma, Lei Dong, Baicang Zou
OBJECTIVE: This study aimed to identifying and validating therapeutic compounds which might have positive effects on patients with gastric cancer (GC) based on weighted gene co-expression network analysis (WGCNA) and connectivity map (CMap). METHODS: We performed WGCNA to gain insights into the molecular aspects of GC. Raw microarray datasets (including 132 samples) were downloaded from the Gene Expression Omnibus (GEO) website. We utilized the WGCNA to identify the coexpressed genes (modules) and modular hub genes after non-specific filtering...
January 10, 2019: Gene
Neda Shakour, Vanessa Bianconi, Matteo Pirro, George E Barreto, Farzin Hadizadeh, Amirhossein Sahebkar
INTRODUCTION: Aggregation of amyloid-β (Aβ) peptides represents a crucial step in the pathogenesis of Alzheimer disease (AD). Compelling evidence from preclinical studies has established that statins may reduce amyloidogenesis and Aβ-mediated neurodegeneration, supporting a potential role of statin treatment in the prevention of AD. Different statins have been shown to interfere indirectly with Aβ production and clearance through either cholesterol-dependent or cholesterol-independent mechanisms...
September 27, 2018: Journal of Cellular Biochemistry
Yi-Bing Hu, En-De Hu, Rong-Quan Fu
Background: Type 2 diabetes mellitus (T2DM) patients are involved closely with cancer. This work aims to conduct a systematic review and network meta-analysis (NMA) to examine the effect of different types of statins on cancer incidence in patients with T2DM. Methods: We systematically searched the Cochrane Library, PubMed, Embase, and Wanfang databases from January 1999 to March 2017. We performed a pairwise meta-analysis to estimate the pooled ratios (ORs) and 95% confidence intervals (CIs)...
2018: Gastroenterology Research and Practice
Beth A Taylor, Paul D Thompson
Since the first approval of lovastatin in 1987, hydroxy-methyl-glutaryl CoA (HMG CoA) reductase inhibitors, or statins, have been effective and widely popular cholesterol-lowering agents with substantial benefits for the prevention and treatment of cardiovascular disease. Not all patients can tolerate these drugs, however, and statin intolerance is most frequently associated with a range of side effects directed toward skeletal muscle, termed statin-associated muscle symptoms or SAMS. SAMS are particularly difficult to treat because there are no validated biomarkers or tests that can be used to confirm patient self-reports of SAMS, and a number of patients who report SAMS have non-specific muscle pain not attributable to statin therapy...
September 24, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Richard Pentz, Christoph Kaun, Barbara Thaler, Stefan Stojkovic, Max Lenz, Konstantin A Krychtiuk, Andreas Zuckermann, Kurt Huber, Johann Wojta, Philipp J Hohensinner, Svitlana Demyanets
Interleukin (IL)-33 is a member of the IL-1 family and is able to act cardioprotective. The aim of this study was to investigate the regulation of IL-33 by 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitors (statins) and bisphosphonates (BPs) in human cardiac tissue. The lipophilic fluvastatin, simvastatin, atorvastatin, and lovastatin as well as the nitrogenous BPs alendronate and ibandronate, but not hydrophilic pravastatin increased IL-33 mRNA and intracellular IL-33 protein levels in both human adult cardiac myocytes (HACM) and fibroblasts (HACF)...
December 2018: Journal of Cellular and Molecular Medicine
Huajing Teng, Fengbiao Mao, Jialong Liang, Meiying Xue, Wenqing Wei, Xianfeng Li, Kun Zhang, Dongdong Feng, Baoguo Liu, Zhongsheng Sun
Papillary thyroid carcinoma (PTC) is the fastest-growing disease caused by numerous molecular alterations in addition to previously reported DNA mutations. There is a compelling need to identify novel transcriptomic alterations that are associated with the pathogenesis of PTC with potential diagnostic and prognostic implications. Methods: We gathered and compared 242 expression profiles between paired PTC and adjacent normal tissues and identified and validated the coding and long non-coding RNAs (lncRNAs) associated with the extrathyroidal extension (ETE) of 655 PTC patients in two independent cohorts, followed by predicting their interactions with drugs...
2018: Theranostics
Carly M Bond, Yi Tang
Simvastatin is a semisynthetic cholesterol-lowering medication and one of the top-selling statins in the world. Currently, industrial production of simvastatin acid (SVA) is a multistep process starting from the natural product lovastatin. For this reason, there is significant interest in direct production of simvastatin from a microbial host. In this study, six heterologous biosynthetic genes were introduced into Saccharomyces cerevisiae and the acyl-donor dimethylbutyryl-S-methyl mercaptopropionate (DMB-SMMP) was added, resulting in initial production of 0...
September 10, 2018: Metabolic Engineering
Soheila Koohestanimobarhan, Siamak Salami, Vahideh Imeni, Zeinab Mohammadi, Omid Bayat
Resistance to therapies, recurrence, and metastasis remain challenging issues for breast cancer patients, particularly for triple-negative and breast cancer stem cells. The activation of the epithelial-to-mesenchymal transition (EMT) plays an indispensable role in the poor prognosis of those types. The accumulating proofs indicated that the mevalonate pathway crucially mediates a poor prognosis. Here, the effects of lipophilic 3-hydroxy-3-methyl-glutaryl-coenzyme A inhibitors, atorvastatin, lovastatin, and simvastatin, were investigated on expression and function of a selected profile of EMT-related genes in breast cancer stem-like cells...
September 6, 2018: Journal of Cellular Biochemistry
Hsien-Tsung Chiu, Li-Jiuan Shen, Yee-Chun Chen, Jung-Hsin Lin, Chi-Chuan Wang
OBJECTIVES: The immunomodulatory effects of statins may reduce the immune response induced by influenza vaccines. However, evidence regarding the effect of statin use on the effectiveness of seasonal influenza vaccines against medically attended acute respiratory illness (MAARI) in the elderly remains scarce. METHODS: We conducted a retrospective cohort study using data from Taiwan's National Health Insurance Research Database. Elderly adults aged ≧ 66 years who were vaccinated with seasonal influenza vaccines during the 2007-2008 to 2012-2013 influenza seasons were enrolled for this analysis...
October 1, 2018: Vaccine
Li Yu, Hua Liu
BACKGROUNDS: Nitric oxide (NO) produced by endothelial NO synthase (eNOS) is essential for cardiovascular homeostasis owing to its anti-inflammatory, antithrombotic, antiproliferative, and antioxidant effects. Perillaldehyde (PAH), one of the major oil components in Perilla frutescens, has anti-inflammatory effects. AIM: This study was designed to explore whether PAH prevents atherosclerosis through normalizing eNOS functions. METHODS: The model of atherosclerosis was induced by feeding rats and mice with high-fat diet or plus balloon injury...
September 1, 2018: Journal of Cellular Biochemistry
K Eljaaly, S Alshehri, S Bhattacharjee, J A Al-Tawfiq, A E Patanwala
OBJECTIVES: Antimicrobial agents are commonly used in ambulatory care settings. Our objective was to examine national-level patterns of contraindications between oral antibacterial or antifungal agents and patients' other oral medications in the US ambulatory care setting. METHODS: This cross-sectional study included multiple year pooled data (2003-2011) from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey (NHAMCS Outpatient Department)...
August 11, 2018: Clinical Microbiology and Infection
Janani Balraj, Karunyadevi Jairaman, Vidhya Kalieswaran, Angayarkanni Jayaraman
Beside anti-cholesterol activity, lovastatin garners worldwide attention for therapeutical application against various diseases especially cancer. A total of 36 filamentous fungi from soil samples were isolated and screened for lovastatin production by yeast growth bioassay method. C9 strain (later identified as Cunninghamella blakesleeana) was screened as potential strain of lovastatin production. Further confirmation of the compound was made using TLC, HPTLC and HPLC in which similar Rf value, densitogram peak and chromatogram peak against the standard lovastatin were observed, respectively...
August 2018: 3 Biotech
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