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https://www.readbyqxmd.com/read/28637178/the-at04a-vaccine-against-proprotein-convertase-subtilisin-kexin-type-9-reduces-total-cholesterol-vascular-inflammation-and-atherosclerosis-in-apoe-3leiden-cetp-mice
#1
Christine Landlinger, Marianne G Pouwer, Claudia Juno, José W A van der Hoorn, Elsbet J Pieterman, J Wouter Jukema, Guenther Staffler, Hans M G Princen, Gergana Galabova
Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target for the treatment of hypercholesterolaemia and atherosclerosis. PCSK9 binds to the low density lipoprotein receptor and enhances its degradation, which leads to the reduced clearance of low density lipoprotein cholesterol (LDLc) and a higher risk of atherosclerosis. In this study, the AT04A anti-PCSK9 vaccine was evaluated for its therapeutic potential in ameliorating or even preventing coronary heart disease in the atherogenic APOE*3Leiden...
June 19, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28637103/-the-development-of-hepatocellular-carcinoma-in-non-alcoholic-fatty-liver-disease
#2
REVIEW
Oh Sang Kwon, Joon Hwan Kim, Ju Hyun Kim
Non-alcoholic fatty liver disease (NAFLD) may be one of the important causes of cryptogenic hepatocellular carcinoma (HCC). NAFLD-related HCCs (NAFLD-HCCs) have the following clinical features: high body mass index, deranged lipid profiles, diabetes mellitus, hypertension, and metabolic syndrome. Among them, obesity, diabetes mellitus, and high Fe contents in the liver are risk factors of developing HCC in patients with NAFLD. Inflammatory cytokines, adipokines, insulin like growth factor-I, and lipotoxicity are intermingled and may cross react with each other to develop HCC...
June 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28637010/local-application-of-bacteria-improves-safety-of-salmonella-mediated-tumor-therapy-and-retains-advantages-of-systemic-infection
#3
Dino Kocijancic, Sebastian Felgner, Tim Schauer, Michael Frahm, Ulrike Heise, Kurt Zimmermann, Marc Erhardt, Siegfried Weiss
Cancer is a devastating disease and a large socio-economic burden. Novel therapeutic solutions are on the rise, although a cure remains elusive. Application of microorganisms represents an ancient therapeutic strategy, lately revoked and refined via simultaneous attenuation and amelioration of pathogenic properties. Salmonella Typhimurium has prevailed in preclinical development. Yet, using virulent strains for systemic treatment might cause severe side effects. In the present study, we highlight a modified strain based on Salmonella Typhimurium UK-1 expressing hexa-acylated Lipid A...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636979/exosomes-in-diagnosis-and-therapy-of-prostate-cancer
#4
REVIEW
Jun Pan, Meng Ding, Kai Xu, Chunhua Yang, Li-Jun Mao
Exosomes are small vesicular bodies released by a variety of cells. Exosomes contain miRNAs, mRNAs and proteins with the potential to regulate signaling pathways in recipient cells. Exosomes deliver nucleic acids and proteins to mediate the communication between cancer cells and stroma cells. In this review, we summarize recent progress in our understanding of the role of exosomes in prostate cancer. The tumorigenesis, metastasis and drug resistance of prostate cancer are associated with the cargos of exosomes such as miRNAs, lncRNAs and proteins...
June 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636916/structural-behavior-of-the-peptaibol-harzianin-hk-vi-in-a-dmpc-bilayer-insights-from-md-simulations
#5
Marina Putzu, Sezgin Kara, Sergii Afonin, Stephan L Grage, Andrea Bordessa, Grégory Chaume, Thierry Brigaud, Anne S Ulrich, Tomáš Kubař
Microsecond molecular dynamics simulations of harzianin HK VI (HZ) interacting with a dimyristoylphosphatidylcholine bilayer were performed at the condition of low peptide-to-lipid ratio. Two orientations of HZ molecule in the bilayer were found and characterized. In the orientation perpendicular to the bilayer surface, HZ induces a local thinning of the bilayer. When inserted into the bilayer parallel to its surface, HZ is located nearly completely within the hydrophobic region of the bilayer. A combination of solid-state NMR and circular dichroism experiments found the latter orientation to be dominant...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28636889/complications-of-hematopoietic-stem-transplantation-fungal-infections
#6
REVIEW
Ali S Omrani, Reem S Almaghrabi
Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk of invasive fungal infections, especially during the early neutropenic phase and severe graft-versus-host disease. Mold-active prophylaxis should be limited to the highest risk groups. Empiric antifungal therapy for HSCT with persistent febrile neutropenia is associated with unacceptable response rates, unnecessary antifungal therapy, increased risk of toxicity, and inflated costs. Empiric therapy should not be a substitute for detailed work up to identify the cause of fever in such patients...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28636885/differential-changes-in-the-pharmacokinetics-of-statins-in-collagen-induced-arthritis-rats
#7
Chun-Han Lin, Ke-Wei Hsu, Chia-Hao Chen, Yow-Shieng Uang, Chun-Jung Lin
The elevated systemic levels of cytokines in rheumatoid arthritis (RA) can change the expression of metabolic enzymes and transporters. Given that statins are lipid-lowering agents frequently used in RA patients with concurrent cardiovascular diseases, the objective of the present study was to investigate the impacts of RA on the pharmacokinetics of statins of different disposition properties in rats with collagen-induced arthritis (CIA). The expression of metabolic enzymes and transporters in tissues of CIA rats were analyzed by RT-qPCR...
June 18, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28636837/microrna-101-2-5p-targets-the-apob-gene-in-liver-of-chicken-gallus-gallus
#8
Zheng Ma, Hong Li, Hang Zheng, Keren Jiang, Lijuan Jia, Fengbin Yan, Yadong Tian, Xiangtao Kang, Yanbin Wang, Xiaojun Liu
Apolipoprotein B (ApoB) is a major protein component of plasma lipoproteins, which have been involved in many important biological processes such as lipid transportation, enzyme activity regulation and receptor recognition. Extensive studies have showed that the expression of the ApoB was regulated at multiple levels. However, the regulation of ApoB expression by microRNAs (miRNAs) still remains unknown. In present studies, miRNAs that interact with ApoB have been predicted in chicken. The targeted relationship between the predicated miRNAs and ApoB was verified through dual luciferase reporter assay in chicken DF1 cells, and the effect of miRNAs on ApoB expression was analyzed in chicken embryo hepatocytes stimulated by 17β-estradiol...
June 21, 2017: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28636818/critical-temperature-of-1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine-monolayers-and-its-possible-biological-relevance
#9
Jordi Hernandez Borrell, Oscar Domenech
Since transmembrane proteins (TMPs) can be obtained with sufficient purity for x-ray diffraction studies more frequently than decades ago, their mechanisms of action may now be elucidated. One of the pending issues is the actual interplay between transmembrane proteins and membrane lipids. There is strong evidence of the involvement of specific lipids with some membrane proteins, such as the potassium crystallographically sited activation channel (KcsA) of Streptomyces lividans and the secondary transporter of lactose LacY of Escherichia coli, the activities of which are associated with the presence of anionic phospholipids such as the phosphatidylglycerol (PG) and phosphatidyethanolamine (PE), respectively...
June 21, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28636657/novel-sirna-formulation-to-effectively-knockdown-mutant-p53-in-osteosarcoma
#10
Anup K Kundu, Swathi V Iyer, Sruti Chandra, Amit S Adhikari, Tomoo Iwakuma, Tarun K Mandal
OBJECTIVES: The tumor suppressor p53 plays a crucial role in the development of osteosarcoma. The primary objective of this study is to develop and optimize lipid based nanoparticle formulations that can carry siRNA and effectively silence mutant p53 in 318-1, a murine osteosarcoma cell line. METHODS: The nanoparticles were composed of a mixture of two lipids (cholesterol and DOTAP) and either PLGA or PLGA-PEG and prepared by using an EmulsiFlex-B3 high pressure homogenizer...
2017: PloS One
https://www.readbyqxmd.com/read/28636650/the-formation-of-lipid-droplets-favors-intracellular-mycobacterium-leprae-survival-in-sw-10-non-myelinating-schwann-cells
#11
Song-Hyo Jin, Sung-Kwan An, Seong-Beom Lee
Leprosy is a chronic infectious disease that is caused by the obligate intracellular pathogen Mycobacterium leprae (M.leprae), which is the leading cause of all non-traumatic peripheral neuropathies worldwide. Although both myelinating and non-myelinating Schwann cells are infected by M.leprae in patients with lepromatous leprosy, M.leprae preferentially invades the non-myelinating Schwann cells. However, the effect of M.leprae infection on non-myelinating Schwann cells has not been elucidated. Lipid droplets (LDs) are found in M...
June 21, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28636532/a-novel-pan-nox-inhibitor-apx-115-protects-kidney-injury-in-streptozotocin-induced-diabetic-mice-possible-role-of-peroxisomal-and-mitochondrial-biogenesis
#12
Guideock Kwon, Md Jamal Uddin, Gayoung Lee, Songling Jiang, Ahreum Cho, Jung Hwa Lee, Sae Rom Lee, Yun Soo Bae, Sung Hwan Moon, Soo Jin Lee, Dae Ryong Cha, Hunjoo Ha
NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are increasingly recognized as a key factor in inflammation and extracellular matrix accumulation in diabetic kidney disease. APX-115 (3-phenyl-1-(pyridin-2-yl)-4-propyl-1-5-hydroxypyrazol HCl) is a novel orally active pan-Nox inhibitor. The objective of this study was to compare the protective effect of APX-115 with a renin-angiotensin system inhibitor (losartan), the standard treatment against kidney injury in diabetic patients, on streptozotocin (STZ)-induced diabetic kidney injury...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636510/the-balance-of-omega-3-polyunsaturated-fatty-acids-for-reducing-residual-risks-in-patients-with-coronary-artery-disease
#13
Yuji Nishizaki, Kazunori Shimada, Hiroyuki Daida
Residual risk, which cannot be prevented by statins alone, must be controlled for inhibiting the onset of coronary events. Omega-3 polyunsaturated fatty acids (PUFAs) play an important role in controlling residual risk. The Japan eicosapentaenoic acid (EPA) Lipid Intervention Study demonstrated the inhibitory effect of high-purity EPA preparations on the residual risk of cardiovascular events. Omega-3 PUFAs inhibit coronary artery disease (CAD) through various actions, including triglyceride-lowering action...
March 21, 2017: Acta Cardiologica
https://www.readbyqxmd.com/read/28636491/atherosclerosis-induced-by-a-high-cholesterol-and-high-fat-diet-in-the-inbred-strain-of-the-wuzhishan-miniature-pig
#14
Yuqiong Zhao, Lei Xiang, Yaqian Liu, Miaomiao Niu, Jifang Yuan, Hua Chen
Coronary artery disease has a significant genetic predisposition, which mainly results from atherosclerosis. Miniature pig is an excellent model to investigate atherosclerosis. This study investigated whether the occurrence and development of atherosclerosis in the Wuzhishan miniature pigs (WZSPs) that were closely bred 12 generations had better consistency. The WZSPs (n = 9) were fed a high-cholesterol and high-fat diet (HCFD). After continuous feeding, 3 WZSPs each were sacrificed at 6, 8, and 12 months, respectively, and the general clinical manifestations and serological indexes were detected...
June 21, 2017: Animal Biotechnology
https://www.readbyqxmd.com/read/28636483/lumping-kinetics-of-abe-fermentation-wastewater-treatment-by-oleaginous-yeast-trichosporon-cutaneum
#15
Can Wang, Chao Huang, Xue-Fang Chen, Hai-Rong Zhang, Lian Xiong, Xiao-Mei Li, Hai-Jun Guo, Gao-Xiang Qi, Xiao-Qing Lin, Xin-De Chen
Lumping kinetics models were built for the biological treatment of ABE (acetone-butanol-ethanol) fermentation wastewater by oleaginous yeast Trichosporon cutaneum with different fermentation temperatures. Compared with high temperature (33°C, 306 K) and low temperature (23°C, 296 K), medium temperature (28°C, 301 K) was beneficial for the cell growth and COD degradation during the early stage of fermentation but the final yeast biomass and COD removal were influenced little. By lumping method, the materials in the bioconversion network were divided into five lumps (COD, lipid, polysaccharide, other intracellular products, other extracellular products), and the nine rate constants (k1-k9) for the models can well explain the bioconversion laws...
June 21, 2017: Preparative Biochemistry & Biotechnology
https://www.readbyqxmd.com/read/28636346/halogenated-flame-retardants-in-predator-and-prey-fish-from-the-laurentian-great-lakes-age-dependent-accumulation-and-trophic-transfer
#16
Guanyong Su, Robert J Letcher, Daryl McGoldrick, Sean M Backus
The identification, persistence, accumulation and trophic transfer of 25 polybrominated diphenyl ether (PBDE) congeners, 23 non-PBDE halogenated flame retardants (NPHFRs), 4 polybrominated-diphenoxybenzenes (PB-DiPhOBzs) and 6 methoxylated (MeO-) PB-DiPhOBzs were investigated in predator and prey fish collected in 2010 from sites in the North American Great Lakes of Ontario (n=26) and Erie (n=39). Regardless of locations or species, 20 PBDEs and 12 NPHFRs were quantifiable in at least one of the 65 analyzed samples, and polybrominated-1,4-diphenoxybenzenes (PB-DiPhOBzs) and MeO-PB-DiPhOBzs were not detectable in any of analyzed samples...
June 21, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28636345/levels-of-organochlorine-pesticides-are-associated-with-amyloid-aggregation-in-apex-avian-brains
#17
Kelly A Heys, Richard F Shore, M Gloria Pereira, Francis Luke Martin
Organochlorine (OC) pesticides pose a significant environmental risk to wildlife and humans and have been associated with Alzheimer's disease (AD). This study aims to spectroscopically analyse brains from free-flying birds and link the results to OC exposure and consequent amyloid aggregation. As long-lived apex predators, predatory birds represent a sentinel species similar to humans. Therefore, the results have implications for both species and may also add to our understanding of the role OC pesticides play in the development of AD...
June 21, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28636327/maldi-ms-guided-liquid-microjunction-extraction-for-ce-esi-ms-analysis-of-single-pancreatic-islet-cells
#18
Troy J Comi, Monika A Makurath, Marina C Philip, Stanislav S Rubakhin, Jonathan V Sweedler
The ability to characterize chemical heterogeneity in biological structures is essential to understanding cellular level function in both healthy and diseased states, but these variations remain difficult to assess using a single analytical technique. While mass spectrometry (MS) provides sufficient sensitivity to measure many analytes from volume-limited samples, each type of mass spectrometric analysis uncovers only a portion of the complete chemical profile of a single cell. Matrix-assisted laser desorp-tion/ionization (MALDI) MS and capillary electrophoresis electrospray ionization (CE-ESI)-MS are complementary analytical platforms frequently utilized for single cell analysis...
June 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28636311/insights-into-integrated-lead-generation-and-target-identification-in-malaria-and-tuberculosis-drug-discovery
#19
John Okombo, Kelly Chibale
New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery...
June 21, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28636309/quantitative-chemical-proteomic-profiling-of-the-in-vivo-targets-of-reactive-drug-metabolites
#20
Landon R Whitby, R Scott Obach, Gabriel M Simon, Matthew M Hayward, Benjamin F Cravatt
Idiosyncratic liver toxicity represents an important problem in drug research and pharmacotherapy. Reactive drug metabolites that modify proteins are thought to be a principal factor in drug-induced liver injury. Here, we describe a quantitative chemical proteomic method to identify the targets of reactive drug metabolites in vivo. Treating mice with clickable analogues of four representative hepatotoxic drugs, we demonstrate extensive covalent binding that is confined primarily to the liver. Each drug exhibited a distinct target profile that, in certain cases, showed strong enrichment for specific metabolic pathways (e...
June 21, 2017: ACS Chemical Biology
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