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https://www.readbyqxmd.com/read/29097185/serum-starvation-of-arpe-19-changes-the-cellular-distribution-of-cholesterol-and-fibulin3-in-patterns-reminiscent-of-age-related-macular-degeneration
#1
Dinusha Rajapakse, Katherine Peterson, Sanghamitra Mishra, Graeme Wistow
Retinal pigment epithelium (RPE) has been implicated as key source of cholesterol-rich deposits at Bruch's membrane (BrM) and in drusen in aging human eye. We have shown that serum-deprivation of confluent RPE cells is associated with upregulation of cholesterol synthesis and accumulation of unesterified cholesterol (UC). Here we investigate the cellular processes involved in this response. We compared the distribution and localization of UC and esterified cholesterol (EC); the age-related macular degeneration (AMD) associated EFEMP1/Fibulin3 (Fib3); and levels of acyl-coenzyme A (CoA): cholesterol acyltransferases (ACAT) ACAT1, ACAT2 and Apolipoprotein B (ApoB) in ARPE-19 cells cultured in serum-supplemented and serum-free media...
October 30, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29090229/ctla-4-gene-haplotypes-and-the-risk-of-chronic-hepatitis-c-infection-a-case-control-study
#2
Samaneh Sepahi, Alireza Pasdar, Sina Gerayli, Sina Rostami, Aida Gholoobi, Zahra Meshkat
BACKGROUND: The prevalence of hepatitis C virus (HCV) infection is increasing worldwide. Cytotoxic Tlymphocyte-associated protein 4 (CTLA-4) may play a role in the intensity of the disease. The aim of this study was to evaluate the association between genetic variants of the CTLA-4 and HCV infection. METHODS: Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was performed as the genotyping assay at four different positions (+49 A>G, -318 C>T, -1722 T>C, and - 1661 A>G)...
October 2017: Reports of Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29074218/avasimibe-a-novel-hepatitis-c-virus-inhibitor-that-targets-the-assembly-of-infectious-viral-particles
#3
Longbo Hu, Jinqian Li, Hua Cai, Wenxia Yao, Jing Xiao, Yi-Ping Li, Xiu Qiu, Huimin Xia, Tao Peng
Direct-acting antivirals (DAAs), which target hepatitis C virus (HCV) proteins, have exhibited impressive efficacy in the management of chronic hepatitis C. However, the concerns regarding high costs, drug resistance mutations and subsequent unexpected side effects still call for the development of host-targeting agents (HTAs) that target host factors involved in the viral life cycle and exhibit pan-genotypic antiviral activity. Given the close relationship between lipid metabolism and the HCV life cycle, we investigated the anti-HCV activity of a series of lipid-lowering drugs that have been approved by government administrations or proven safety in clinical trials...
October 23, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29031956/the-solubility-permeability-trade-off-of-progesterone-with-cyclodextrins-under-physiological-conditions-experimental-observations-and-computer-simulations
#4
Le Sun, Bing Zhang, Jin Sun
This study intended to evaluate the effect of cyclodextrins on the apparent solubility and permeability of lipophilic drugs under physiological conditions and establish in silico model to choose the optimal amount of cyclodextrins for cyclodextrin-containing oral formulations. In order to study the effect of cyclodextrins under physiological conditions, bile salts and lecithin were added into the rat intestinal perfusion solution to simulate the fasted intestinal fluid. In addition, the in vivo oral absorption performances of cyclodextrin-containing formulations were simulated by gastrointestinal simulation technology based on the advanced compartmental absorption and transit model (ACAT)...
October 12, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29028593/genetic-variations-in-the-p11-tpa-bdnf-pathway-are-associated-with-post-stroke-depression
#5
Jinfeng Liang, Yingying Yue, Haitang Jiang, Deqin Geng, Jun Wang, Jianxin Lu, Shenghua Li, Kezhong Zhang, Aiqin Wu, Yonggui Yuan
BACKGROUND: The effects of BDNF on post stroke depression (PSD) may be influenced by genetic variations in intracellular signal transduction pathways, such as the p11/tPA/BDNF pathway. In this study, we aimed to determine the association of polymorphisms in candidate genes of the gene transduction pathway with PSD, as well as the effects of the interactions between genes in our Chinese sample. METHODS: Two-hundred-fifty-four Chinese samples with acute ischaemic stroke included 122 PSD patients and 132 nonPSD patients...
September 29, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28851737/cholesterol-metabolism-and-cx43-cx46-cx50-gap-junction-protein-expression-and-localisation-in-normal-and-diabetic-and-obese-ob-ob-and-db-db-mouse-testes
#6
R-Marc Pelletier, Casimir D Akpovi, Li Chen, Maria Leiza Vitale
Decreased fertility and birth rates are afflictions arising from metabolic disorders. This study assesses cholesterol metabolism and Cx46, Cx50, Cx43 expression in interstitium- and seminiferous tubule-enriched fractions of leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice, two type 2 diabetes and obesity models associated with infertility. Testosterone decreased, glucose, free and esterified cholesterol increased in serum whereas in interstitium, free and esterified cholesterol decreased in ob/ob and db/db...
August 29, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28770489/in-silico-absorption-analysis-of-valacyclovir-in-wildtype-and-pept1-knockout-mice-following-oral-dose-escalation
#7
Bei Yang, David E Smith
PURPOSE: We developed simulation and modeling methods to predict the in vivo pharmacokinetic profiles of acyclovir, following escalating oral doses of valacyclovir, in wildtype and Pept1 knockout mice. We also quantitated the contribution of specific intestinal segments in the absorption of valacyclovir in these mice. METHODS: Simulations were conducted using a mechanistic advanced compartmental absorption and transit (ACAT) model implemented in GastroPlus™. Simulations were performed for 3 h post-dose in wildtype and Pept1 knockout mice following single oral doses of 10, 25, 50 and 100 nmol/g valacyclovir, and compared to experimentally observed plasma concentration-time profiles of acyclovir...
November 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28719608/cholesterol-esterification-inhibition-and-imatinib-treatment-synergistically-inhibit-growth-of-bcr-abl-mutation-independent-resistant-chronic-myelogenous-leukemia
#8
Shovik Bandyopadhyay, Junjie Li, Elie Traer, Jeffrey W Tyner, Amy Zhou, Stephen T Oh, Ji-Xin Cheng
Since the advent of tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib, and dasatinib, chronic myelogenous leukemia (CML) prognosis has improved greatly. However, ~30-40% of patients develop resistance to imatinib therapy. Although most resistance is caused by mutations in the BCR-ABL kinase domain, 50-85% of these patients develop resistance in the absence of new mutations. In these cases, targeting other pathways may be needed to regain clinical response. Using label-free Raman spectromicroscopy, we evaluated a number of leukemia cell lines and discovered an aberrant accumulation of cholesteryl ester (CE) in CML, which was found to be a result of BCR-ABL kinase activity...
2017: PloS One
https://www.readbyqxmd.com/read/28690119/cholesterol-lowering-effect-of-aralia-elata-miq-seem-via-the-activation-of-srebp-2-and-the-ldl-receptor
#9
Kyung-A Hwang, Yu-Jin Hwang, Jin Song
BACKGROUND: Hyperlipidemia causes arteriosclerosis, a risk factor for coronary heart disease. Prevention of hyperlipidemia by improving dietary habits has recently attracted attention. In this regard, we investigated whether Aralia elata (Miq.) Seem (AE) extract inhibits hepatic cholesterol accumulation and modulate the cellular signaling pathway. METHODS: To determine AE's cholesterol regulating mechanism, we measured cholesterol level, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity and cholesterol regulating-related gene expression in HepG2 cells and in high-fat diet (HFD)-induced mice using ELISA and RT-PCR assay...
July 6, 2017: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/28484475/de-novo-sequencing-and-transcriptome-analysis-reveal-key-genes-regulating-steroid-metabolism-in-leaves-roots-adventitious-roots-and-calli-of-periploca-sepium-bunge
#10
Jian Zhang, Xinglin Li, Fuping Lu, Shanying Wang, Yunhe An, Xiaoxing Su, Xiankuan Li, Lin Ma, Guangjian Han
Periploca sepium Bunge is a traditional medicinal plant, whose root bark is important for Chinese herbal medicine. Its major bioactive compounds are C21 steroids and periplocin, a kind of cardiac glycoside, which are derived from the steroid synthesis pathway. However, research on P. sepium genome or transcriptomes and their related genes has been lacking for a long time. In this study we estimated this species nuclear genome size at 170 Mb (using flow cytometry). Then, RNA sequencing of four different tissue samples of P...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28482635/the-anti-amyloid-%C3%AE-and-neuroprotective-properties-of-a-novel-tricyclic-pyrone-molecule
#11
Izumi Maezawa, Bende Zou, Jacopo Di Lucente, William S Cao, Conrado Pascual, Sahani Weerasekara, Man Zhang, Xinmin Simon Xie, Duy H Hua, Lee-Way Jin
There is an urgent unmet need for new therapeutics for Alzheimer's disease (AD), the most common cause of dementia in the elderly. Therapeutic approaches targeting amyloid-β (Aβ) and its downstream toxicities have become major strategies in AD drug development. We have taken a rational design approach and synthesized a class of tricyclic pyrone (TP) compounds that show anti-Aβ and other neuroprotective actions. The in vivo efficacy of a lead TP named CP2 to ameliorate AD-like pathologies has been shown in mouse models...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28413489/retrospective-review-of-epidemic-viral-pneumonia-cases-in-turkey-a-multicenter-study
#12
Mustafa Çörtük, Murat Acat, Onur Yazici, Zehra Yasar, Kemal Kiraz, Sena Yapicioglu Ataman, Elif Tanriverdi, Burcak Zitouni, Cenk Kirakli, Ozlem Ediboglu, Fevziye Tuksavul, Adem Dirican, Hale Kefeli Celik, Sevket Ozkaya, Erdogan Cetinkaya
Influenza A (H1N1) caused its first pandemic in 2009 in USA and Mexico. Since then, clinicians have exercised great care in order to make an early diagnosis of viral pneumonias. This is due in part to pandemic influenza A infection having greater impact on populations <65 years old than other viral strains, including seasonal influenza. Chest radiographies of those affected displayed a rapid progression of patchy infiltrates, and a large proportion of individuals required admission to intensive care units (ICU)...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28393731/moxifloxacin-related-thrombocytopeniae-a-case-report
#13
Mustafa Çörtük, Ali Ramazan Benli, Mustafa Köroğlu, Onur Yazıcı, Murat Acat, Hasan Casim, Erdoğan Çetinkaya
Drug-induced thrombocytopenia can be caused by various medications, most frequently, antibiotics. There have been reports of thrombocytopenia cases due to the usage of quinolone antibiotics, although moxifloxacin-related thrombocytopenia has been reported very rarely. The case is here presented of a 60-year old male with chronic obstructive pulmonary disease who presented with complaints of progressively worsening dyspnea. After hospitalization, progressive thrombocytopenia was detected which had started on the 3rd day of moxifloxacin treatment...
September 2016: Tüberküloz Ve Toraks
https://www.readbyqxmd.com/read/28386186/mechanistic-prediction-of-food-effects-for-compound-a-tablet-using-pbpk-model
#14
Xueqing Li, Lei Shi, Xiuling Tang, Qinghui Wang, Lun Zhou, Wei Song, Zhijun Feng, Jie Ge, Jian Kang Li, Lin Yang, Aidong Wen, Yan Zhang
Physiologically based pharmacokinetic (PBPK) modeling has been extensively used to study the factors of effect drug absorption, distribution, metabolize and extraction progress in human. In this study, Compound A(CPD A) is a BCS Class II drug, which has been extensive applied in clinical as lipid-lowering drug, administered orally after food, they displayed positive food effects in human, A PBPK model was built to mechanistic investigate the food effect of CPD A tablet in our study. By using gastroplus™ software, the PBPK models accurately predicted the results of food effects and predicted data were within 2-fold error of the observed results...
March 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/28366160/-moxifloxacin-related-thrombocytopeniae-a-case-report
#15
Mustafa Çörtük, Ali Ramazan Benli, Mustafa Köroğlu, Onur Yazıcı, Murat Acat, Hasan Casim, Erdoğan Çetinkaya
Drug-induced thrombocytopenia can be caused by various medications, most frequently, antibiotics. There have been reports of thrombocytopenia cases due to the usage of quinolone antibiotics, although moxifloxacin-related thrombocytopenia has been reported very rarely. The case is here presented of a 60-year old male with chronic obstructive pulmonary disease who presented with complaints of progressively worsening dyspnea. After hospitalization, progressive thrombocytopenia was detected which had started on the 3rd day of moxifloxacin treatment...
September 2016: Tüberküloz Ve Toraks
https://www.readbyqxmd.com/read/28265181/comparison-of-the-fractional-exhaled-nitric-oxide-levels-in-adolescents-at-three-schools-located-three-different-distances-from-a-large-steel-mill
#16
MULTICENTER STUDY
Murat Acat, Yusuf Aydemir, Onur Yazıcı, Mahmut Turğut, Mustafa Çörtük, Murat Çakar, Zehra Yaşar, Sami Deniz, Erdoğan Çetinkaya
Objectives. Exposure to ambient metals and air pollutants in urban environments has been associated with impaired lung health and inflammation in the lungs. Fractional exhaled nitric oxide (FeNO) is a reliable marker of airway inflammation. In this study, we aimed to compare the FeNO levels of three schools that have different distances from iron and steel industry zone for assessing the effects of heavy metals and air pollution on their respiratory health. Methods. Pulmonary function test and FeNO measurements were evaluated in 387 adolescents in three schools which have different distance from plant...
2017: Canadian Respiratory Journal: Journal of the Canadian Thoracic Society
https://www.readbyqxmd.com/read/28192948/c3n4-nanosheet-modified-microwell-array-with-enhanced-electrochemiluminescence-for-total-analysis-of-cholesterol-at-single-cells
#17
Jingjing Xu, Depeng Jiang, Yanling Qin, Juan Xia, Dechen Jiang, Hong-Yuan Chen
Here, a g-C3N4 nanosheet modified microwell array providing enhanced electrochemiluminescence (ECL) and better visible sensitivity was prepared to simultaneously analyze total (membrane and intracellular) cholesterol at single cells. The detection limit for ECL visualization of hydrogen peroxide at microwell array was improved to be 500 nM that guaranteed the detection of low concentration cholesterol at single cells in parallel. To achieve single cell cholesterol analysis, the individual cells cultured at the microwell array were exposed to cholesterol oxidase generating hydrogen peroxide for luminescence analysis of membrane cholesterol, and then treated with triton X-100, cholesterol esterase, and cholesterol oxidase to produce hydrogen peroxide from intracellular cholesterol for luminescence determination...
February 9, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28045498/spectroscopic-studies-of-the-eutt-adenosyltransferase-from-salmonella-enterica-evidence-of-a-tetrahedrally-coordinated-divalent-transition-metal-cofactor-with-cysteine-ligation
#18
Ivan G Pallares, Theodore C Moore, Jorge C Escalante-Semerena, Thomas C Brunold
The EutT enzyme from Salmonella enterica, a member of the family of ATP:cobalt(I) corrinoid adenosyltransferase (ACAT) enzymes, requires a divalent transition metal ion for catalysis, with Fe(II) yielding the highest activity. EutT contains a unique cysteine-rich HX11CCX2C(83) motif (where H and the last C occupy the 67th and 83rd positions, respectively, in the amino acid sequence) not found in other ACATs and employs an unprecedented mechanism for the formation of adenosylcobalamin. Recent kinetic and spectroscopic studies of this enzyme revealed that residues in the HX11CCX2C(83) motif are required for the tight binding of the divalent metal ion and are critical for the formation of a four-coordinate (4c) cob(II)alamin [Co(II)Cbl] intermediate in the catalytic cycle...
January 17, 2017: Biochemistry
https://www.readbyqxmd.com/read/27780164/assessment-of-palliative-care-in-lung-cancer-in-turkey
#19
Y Bülbül, T Ozlu, S Arinc, B A Ozyurek, H Gunbatar, A Senturk, A Bahadir, M Ozcelik, U Yilmaz, M O Akbay, L Saglam, T Kilic, G Kirkil, N Ozcelik, D Tatar, S A Baris, D M Yavsan, H S Sen, S Berk, M Acat, G Cakmak, P F Yumuk, Y S Intepe, U Toru, S O Ayik, I Basyigit, S Ozkurt, L C Mutlu, Z A Yasar, H Esme, M M Erol, O Oruc, Y Erdoğan, S Asker, A Ulas, S Erol, B Kerget, A E Erbaycu, T Teke, M Beşiroğlu, H Can, A Dalli, F Talay
OBJECTIVE: To investigate the symptoms of lung cancer in Turkey and to evaluate approaches to alleviate these symptoms. SUBJECTS AND METHODS: This study included 1,245 lung cancer patients from 26 centers in Turkey. Demographic characteristics as well as information regarding the disease and treatments were obtained from medical records and patient interviews. Symptoms were evaluated using the Edmonton Symptom Assessment Scale (ESAS) and were graded on a scale between 0 and 10 points...
2017: Medical Principles and Practice: International Journal of the Kuwait University, Health Science Centre
https://www.readbyqxmd.com/read/27714478/clinically-applied-procedures-for-human-ovarian-tissue-cryopreservation-result-in-different-levels-of-efficacy-and-efficiency
#20
Lobke Bastings, Johan R Westphal, Catharina C M Beerendonk, Ruud L M Bekkers, Petra L M Zusterzeel, Jan C M Hendriks, Didi D M Braat, Ronald Peek
PURPOSE: Different protocols are being used worldwide for the cryopreservation of human ovarian tissue for fertility preservation purposes. The efficiency and efficacy of the majority of these protocols has not been extensively evaluated, possibly resulting in sub-optimally cryopreserved ovarian tissue. To address the impact of this issue, we assessed the effects of two clinically successful human ovarian tissue slow-freezing cryopreservation procedures on the quality of the cryopreserved tissue...
December 2016: Journal of Assisted Reproduction and Genetics
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