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Yat Hei Leung, Francois Belanger, Jennifer Lu, Jacques Turgeon, Veronique Michaud
BACKGROUND: Drug-induced myopathy is a serious side effect that often requires removal of a medication from a drug regimen. For most drugs, the underlying mechanism of drug-induced myopathy remains unclear. Monocarboxylate transporters (MCTs) mediate L-lactic acid transport, and inhibition of MCTs may potentially lead to perturbation of L-lactic acid accumulation and muscular disorders. Therefore, we hypothesized that L-lactic acid transport may be involved in the development of drug-induced myopathy...
March 7, 2018: Current Pharmaceutical Biotechnology
Quan-Zhen Lv, Yu-Lin Qin, Lan Yan, Liang Wang, Chuyue Zhang, Yuan-Ying Jiang
Antifungal azole drugs inhibit the synthesis of ergosterol and cause the accumulation of sterols containing a 14α-methyl group, which is related to the properties of cell membrane. Due to the frequent recurrence of fungal infections and clinical long-term prophylaxis, azole resistance is increasing rapidly. In our research, Nsg2p, encoded by the ORF19.273 in Candida albicans , is found to be involved in the inhibition of 14α-methylated sterols and resistance to azoles. Under the action of fluconazole, nsg2 Δ/Δ mutants are seriously damaged in the integrity and functions of cell membranes with a decrease of ergosterol ratio and an increase of both obtusifoliol and 14α-methylfecosterol ratio...
2018: Frontiers in Microbiology
Chih-Yuan Wang, Hao-Ai Shui, Tien-Chun Chang
This study tested the hypothesis that the effects of lovastatin on anaplastic thyroid cancer cell growth are mediated by upregulation of transketolase (TKT) expression. The effects of lovastatin on TKT protein levels in ARO cells were determined using western blot and proteomic analyses. After treatment with lovastatin and oxythiamine, the in vitro and in vivo growth of ARO cells was determined using 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assays and tumor xenografts in nude mice...
March 2, 2018: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
Matheus de Castro Fonseca, Andressa França, Rodrigo Machado Florentino, Roberta Cristelli Fonseca, Antônio Carlos Melo, Paula Teixeira Vieira Vidigal, André G Oliveira, Laurent Dubuquoy, Michael H Nathanson, M Fátima Leite
Hepatocyte proliferation during liver regeneration is a well-coordinated process regulated by the activation of several growth factor receptors, including the insulin receptor (IR). The IR can be localized in part to cholesterol-enriched membrane microdomains, but the role of such domains in insulin-mediated events in hepatocytes is not known. We investigated whether partitioning of IRs into cholesterol-enriched membrane rafts is important for the mitogenic effects of insulin in the hepatic cells. IR and lipid rafts were labeled in HepG2 cells and primary rat hepatocytes...
February 22, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Hong Shen, Rui Li, Rong Yan, Xia Zhou, Xia Feng, Mengjie Zhao, Hong Xiao
There are some conflicting results regarding the benefit of adjunctive therapy with statins for severity of negative symptoms in schizophrenia. This study aimed to verify whether statins use for adjunctive therapy was indeed beneficial to improve psychiatric symptoms in schizophrenia. The data were from CENTRAL, PubMed, Embase and MEDLINE. The Boolean search term used for the electronic database search was (statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR mevastatin OR pitavastatin OR pravastatin OR rosuvastatin OR cerivastatin) and (schizophrenia OR schizoaffective disorder OR psychosis)...
February 5, 2018: Psychiatry Research
Beatrice A Golomb, Abril Verden, Alexis K Messner, Hayley J Koslik, Keith B Hoffman
INTRODUCTION: Apparent elevations in reporting of amyotrophic lateral sclerosis (ALS)-like conditions associated with statin use have been previously described from data obtained via US and European databases. OBJECTIVE: The aim of this study was to examine US FDA Adverse Event Reporting System (FAERS) data to compare reporting odds ratios (RORs) of ALS and ALS-like conditions between statins and other drugs, for each statin agent. METHODS: We assessed for disproportional rates of reported ALS and ALS-related conditions for each statin agent separately by using the ROR formula...
February 9, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
Yadunanda Budigi, Eugenia Z Ong, Luke N Robinson, Li Ching Ong, Kirk J Rowley, Alexander Winnett, Hwee Cheng Tan, Sven Hobbie, Zachary Shriver, Gregory J Babcock, Sylvie Alonso, Eng Eong Ooi
Dengue virus (DENV) infection imposes enormous health and economic burden worldwide with no approved treatment. Several small molecules, including lovastatin, celgosivir, balapiravir and chloroquine have been tested for potential anti-dengue activity in clinical trials; none of these have demonstrated a protective effect. Recently, based on identification and characterization of cross-serotype neutralizing antibodies, there is increasing attention on the potential for dengue immunotherapy. Here, we tested the ability of VIS513, an engineered cross-neutralizing humanized antibody targeting the DENV E protein domain III, to overcome antibody-enhanced infection and high but brief viremia, which are commonly encountered in dengue patients, in various in vitro and in vivo models...
February 9, 2018: PLoS Neglected Tropical Diseases
Ming Tan, Guofang Li, Siyan Qi, Xiaojie Liu, Xilong Chen, Juanjuan Ma, Dong Zhang, Mingyu Han
Cytokinins (CKs) play a crucial role in promoting axillary bud outgrowth and targeting the control of CK metabolism can be used to enhance branching in plants. CK levels are maintained mainly by CK biosynthesis (isopentenyl transferase, IPT) and degradation (dehydrogenase, CKX) genes in plants. A systematic study of the IPT and CKX gene families in apple, however, has not been conducted. In the present study, 12 MdIPTs and 12 MdCKXs were identified in the apple genome. Systematic phylogenetic, structural, and synteny analyses were performed...
January 31, 2018: Gene
Fan Yang, Xiao Feng, Arndt Rolfs, Jiankai Luo
Niemann-Pick Type C (NPC) disease is a rare neurovisceral disorder caused by mutations of either NPC1 or NPC2 gene and characterized by defective intracellular transport of cholesterol and glycosphingolipids, leading to neuron loss and myelin aberration in the central nervous system. In this study, by comparing protein expression in the cortical white matter tracts from mice at different postnatal days, we identified that in the NPC1 mutant (NPC1-/-) mice, the onset of myelination is delayed and the amount of the major myelin protein MBP and PLP, and oligodendrocyte regulatory factor Olig1 and Olig2, but not NG2 and Sox10, decreased significantly, suggesting a disruption of oligodendrocyte differentiation...
March 15, 2018: Journal of the Neurological Sciences
Liujiang Song, Xiaojun Tao, Li Lin, Chao Chen, Hui Yao, Guangchun He, Guangyang Zou, Zhong Cao, Shichao Yan, Lu Lu, Huimei Yi, Di Wu, Siyuan Tan, Wanxin Ouyang, Zhifei Dai, Xiyun Deng
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a higher risk in younger women and a poorer prognosis and without targeted therapies available currently. Cancer stem cells (CSCs) are increasingly recognized as the main cause of treatment failure and tumor recurrence. The present paper reported the encapsulation of lovastatin (LV) into cerasomes incorporating distearoyl phosphatidylcholine (DSPC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N -polyethylene glycol 2000 (DSPE-PEG2000) through thin film hydration method in combination with sol-gel reaction and self-assembly process...
February 6, 2018: ACS Applied Materials & Interfaces
Tsung-Kun Lin, Yi-Sheng Liou, Ching-Heng Lin, Pesus Chou, Gwo-Ping Jong
Background: Statins have been linked to new-onset osteoporotic fractures (NOFs), and different statins may alter the risk for the development of NOFs. Aim: In this study, we investigated the association between different statins and the development of NOFs. Patients and methods: This was a longitudinal cohort study performed using data from claim forms submitted to the Taiwan Bureau of National Health Insurance, including case patients with NOFs from January 2004 to December 2013 and non-NOF subjects...
2018: Clinical Epidemiology
Eun Suk Song, David W Rodgers, Louis B Hersh
Insulin-degrading enzyme (IDE) functions in the catabolism of bioactive peptides. Established roles include degrading insulin and the amyloid beta peptide (Aβ), linking it to diabetes and Alzheimer's disease. IDE is primarily located in the cytosol, and a longstanding question is how it gains access to its peptide substrates. Reports suggest that IDE secreted by an unconventional pathway participates in extracellular hydrolysis of insulin and Aβ. We find that IDE release from cultured HEK-293 or BV-2 cells represents only ~1% of total cellular IDE, far less than has been reported previously...
February 5, 2018: Scientific Reports
Kathryn P Trogden, Rachel A Battaglia, Parijat Kabiraj, Victoria J Madden, Harald Herrmann, Natasha T Snider
Vimentin is a cytoskeletal intermediate filament protein that is expressed in mesenchymal cells and cancer cells during the epithelial-mesenchymal transition. The goal of this study was to identify vimentin-targeting small molecules by using the Tocriscreen library of 1120 biochemically active compounds. We monitored vimentin filament reorganization and bundling in adrenal carcinoma SW13 vimentin-positive (SW13-vim+) cells via indirect immunofluorescence. The screen identified 18 pharmacologically diverse hits that included 2 statins-simvastatin and mevastatin...
January 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Christina Bergqvist, Bilal Abdallah, Divina-Justina Hasbani, Ossama Abbas, Abdul Ghani Kibbi, Lamiaa Hamie, Mazen Kurban, Nelly Rubeiz
Congenital Hemidysplasia with Ichthyosiform nevus and Limb Defects (CHILD syndrome) is a rare X-linked dominant genodermatosis caused by mutations in the NAD(P) dependent steroid dehydrogenase-like protein gene. Its defect leads to accumulation of toxic metabolic intermediates upstream from the pathway block and to the deficiency of bulk cholesterol, probably leading to altered keratinocyte membrane function, resulting in the phenotype seen in CHILD syndrome. Symptomatic treatment using emollients and retinoids to reduce scaling has long been used until recently, whereby new therapeutic means based on the pathogenesis-targeted therapy have been developed...
February 2, 2018: American Journal of Medical Genetics. Part A
Bilal Khokhar, Linda Simoni-Wastila, Julia F Slejko, Eleanor Perfetto, Min Zhan, Gordon S Smith
OBJECTIVE: To assess the relationship between posttraumatic brain injury statin use and (1) mortality and (2) the incidence of associated morbidities, including stroke, depression, and Alzheimer's disease and related dementias following injury. SETTING AND PARTICIPANTS: Nested cohort of all Medicare beneficiaries 65 years of age and older who survived a traumatic brain injury (TBI) hospitalization during 2006 through 2010. The final sample comprised 100 515 beneficiaries...
January 30, 2018: Journal of Head Trauma Rehabilitation
Cuiping Jiang, Yi Zhao, Yun Yang, Jian Hua He, Wenli Zhang, Jianping Liu
Recombinant high-density lipoprotein (rHDL) displays similar anti-atherosclerotic effect with native HDL and could also be served as a carrier of cardiovascular drug for atherosclerotic plaque targeting. In our previous studies, rHDL has shown more potent anti-atherosclerotic efficacy as compared to other conventional nanoparticles with a payload of lovastatin (LS). Therefore, we hypothesized that a synergistic anti-atherosclerotic effect of rHDL carrier and the encapsulated LS might exist. In this study, the dose-effect relationships and combined effect of rHDL and LS were quantitatively evaluated in RAW 264...
January 30, 2018: Molecular Pharmaceutics
Mostafa Shahrezaee, Ahmad Oryan, Farshid Bastami, Sepanta Hosseinpour, Mohammad Hossein Shahrezaee, Amir Kamali
PURPOSE: In addition to lipid-lowering properties, statins have been suggested to affect bone turnover by increasing the osteoblastic bone formation and blocking the osteoclastogenesis. However, there are many controversial reports regarding the beneficial effect of statins on osteoporosis. In this study, we investigated the therapeutic effects of the most important lipophilic statins administered orally for 60 days to the ovariectomized (OVX) female Sprague-Dawley rats and compared the effects on different harvested trabecular and compact bones...
January 25, 2018: Endocrine
Amit Kumar Verma, Bhakti Laha, Monika Pandey, Uttariya Pal, Monidipa Ghosh
Leishmania establishes a successful parasitism by evading both oxidative and non-oxidative killing pathways, and its drug resistance against the currently available therapeutics demands for a safe and cheap drug. Since the parasite synthesizes ergosterol instead of cholesterol, using the same biochemical pathway and enzymes, an inhibitor of HMG-CoA-Reductase, Lovastatin, has been tried for its anti-Leishmanial effect. Lovastatin, being an inhibitor of HMG-CoA-Reductase, inhibits infection by cholesterol depletion, while chromium chloride complexes, at their higher concentrations, are reported to exhibit cytotoxicity...
September 2017: Journal of Biosciences
Wu-Wen Feng, Shuang-Yu Kuang, Can Tu, Zhi-Jie Ma, Jing-Yao Pang, Yan-Hui Wang, Qing-Ce Zang, Ta-Si Liu, Yan-Ling Zhao, Xiao-He Xiao, Jia-Bo Wang
Studies have shown that satins and herbal products have potential to treat non-alcohol fatty liver disease (NAFLD) in clinic. However, no study has compared their effects, and their mechanisms remain unresolved. Here, we choose lovastatin and two herbal products including berberine and curcumin to compare their effects in treating NAFLD. NAFLD model was established by high fat food, and rats were administrated with lovastatin, berberine, curcumin, berberine + curcumin at the dosage of 100, 100, 100, 50 + 50 mg/kg bw, respectively...
January 17, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Liang Zhao, Yan Xiao, Jin Xiu, Long-Chun Tan, Zhi-Zhong Guan
The treatment of neurodegenerative diseases with statins has drawn increasing attention, but the related molecular mechanisms remain elusive. To examine the pleiotropic cholesterol-independent effects of statins in connection with the treatment of Alzheimer disease, we probed the influence of lovastatin on the metabolism of amyloid precursor protein (APP) , expression of nicotinic acetylcholine receptors (nAChRs), and activity of mitogen-activated protein kinase in primary cultured neurons and SH-SY5Y cells over-expressing human APP670/671...
January 13, 2018: American Journal of Pathology
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