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Junjie Li, Xiaochao Qu, Jie Tian, Jian-Ting Zhang, Ji-Xin Cheng
Recent advances have recognized metabolic reprogramming as an underlying mechanism for cancer drug resistance. However, the role of cholesterol metabolism in drug resistance remain elusive. Herein, we report an increased accumulation of cholesteryl ester in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) cells. A potent inhibitor of acyl-CoA cholesterol acyltransferase-1 (ACAT-1), avasimibe, effectively suppressed proliferation of gemcitabine-resistant PDAC cells. Combination of avasimibe and gemcitabine showed strong synergistic effect in suppressing PDAC cell viability in vitro and tumor growth in vivo...
2018: PloS One
Ángela Rojas, Paloma Gallego, Antonio Gil-Gómez, Rocío Muñoz-Hernández, Lourdes Rojas, Rosario Maldonado, Rocío Gallego, Marta García-Valdecasas, José A Del Campo, Juan D Bautista, Manuel Romero-Gómez
Background & aims. G-allele of PNPLA3 (rs738409) favours triglycerides accumulation and steatosis. In this study, we examined the effect of quercetin and natural extracts from mushroom and artichoke on reducing lipid accumulation in hepatic cells. MATERIAL AND METHODS: Huh7.5 cells were exposed to oleic acid (OA) and treated with quercetin and extracts to observe the lipid accumulation, the intracellular-TG concentration and the LD size. Sterol regulatory element binding proteins-1 (SREBP-1), peroxisome proliferator-activated receptor (PPARα-γ) and cholesterol acyltransferase (ACAT) gene expression levels were analysed...
March 1, 2018: Annals of Hepatology
Roger Clarnette, Ming Goh, Sneha Bharadwaj, Jillian Ryan, Suzanne Ellis, Anton Svendrovski, D William Molloy, Rónán O'Caoimh
Accurate detection of mild cognitive impairment (MCI) is important to stratify and address risk. Yet, few short cognitive screening instruments are validated for this. . In Australia, all clients referred to an Aged Care Assessment Team (ACAT) receive comprehensive geriatric assessment (CGA) including the Standardized Mini-Mental State Examination (SMMSE). We compared the accuracy of the quick mild cognitive impairment (Qmci) screen to the SMMSE in 283 participants: 195 with dementia, 47 with MCI, and 41 with subjective cognitive decline (SCD) in an Australian community-based ACAT...
February 15, 2018: Neuropsychology, Development, and Cognition. Section B, Aging, Neuropsychology and Cognition
Mehmet Akif Özgül, Elif Tanrıverdi, Şule Gül, Zehra Yaşar Asuk, Murat Acat, Kenan Abbaslı, Neslihan Akanıl Fener, Erdoğan Çetinkaya
Hemangiomas are benign tumors most frequently seen in childhood and are mostly associated with cutaneous and mucosal surfaces. Tracheal capillary hemangiomas are extremely rare. The most common presenting symptom is hemoptysis, ranging from minor to major and chronic cough. We present the case of a 12-year-old boy with recurrent hemoptysis due to tracheal capillary hemangioma, who was treated with interventional bronchoscopy.
October 2017: Turkish Thoracic Journal
Minal Mulye, Brianne Zapata, Stacey D Gilk
Coxiella burnetii is an obligate intracellular bacterial pathogen and a causative agent of culture-negative endocarditis. While C. burnetii initially infects alveolar macrophages, it has also been found in lipid droplet (LD)-containing foamy macrophages in the cardiac valves of endocarditis patients. In addition, transcriptional studies of C. burnetii-infected macrophages reported differential regulation of the LD coat protein-encoding gene perilipin 2 (plin-2). To further investigate the relationship between LDs and C...
2018: PloS One
Michael R Blaisse, Beverly Fu, Michelle C Y Chang
Thiolases are a class of carbon-carbon bond forming enzymes with important applications in biotechnology and metabolic engineering as they provide a general method for the condensation of two acyl coenzyme A (CoA) substrates. As such, developing a greater understanding of their substrate selectivity would expand our ability to engineer the enzymatic or microbial production of a broad range of small-molecule targets. Here, we report the crystal structures and biochemical characterization of Acat2 and Acat5, two biosynthetic thiolases from Ascaris suum with varying selectivity toward branched compared to linear compounds...
January 30, 2018: Biochemistry
Haiyan Xu, Shuai Zhou, Dechen Jiang, Hong-Yuan Chen
The classic electrochemical analysis of plasma membrane cholesterol at single cells utilizes cholesterol oxidase modified microelectrode that oxidizes local cholesterol efflux from plasma membrane to generate hydrogen peroxide for the electrochemical quantification. In this letter, a mixture of cholesterol oxidase and Triton X-100 was filled in the micro-capillary that could park at Pt layer coated tip due to slow hydrodynamic flow. During the contact of the tip with cellular membrane, Triton X-100 at the tip permeabilized the contacted membrane to release cholesterol for the reaction with cholesterol oxidase...
December 28, 2017: Analytical Chemistry
Silvia Castiglioni, Matteo Monti, Giuditta Ainis Buscherini, Lorenzo Arnaboldi, Monica Canavesi, Alberto Corsini, Stefano Bellosta
The data presented in this article is related to the research article entitled " ABCA1 and HDL3 are Required to Modulate Smooth Muscle Cells Phenotypic Switch after Cholesterol Loading " (Castiglioni et al., 2017) [1]. This data describes the characterization of the phenotypic changes induced by cholesterol loading in smooth muscle cells (SMCs) isolated from the aortae of C57BL/6 mice. Upon cholesterol loading, there is a significant and concentration-dependent decrease in the expression of Acta2 and a parallel increase in Mac-2, and ATP binding cassette (ABC) transporters Abca1 and Abcg1 ...
February 2018: Data in Brief
M Acat, U Toru Erbay, S Sahin, O Arik, C Ayada
OBJECTIVE: Asthma is known as a chronic inflammatory lung disease which has also systemic features. Insulin-like growth factor I (IGF-I) plays a role for asthma pathogenesis. Controversially, IGF-binding protein 3 (IGFBP3) blocks asthma development. That is why IGF-I and IGFBP3 are targeted for future therapeutic treatments of asthma. We aimed to investigate serum level of IGF-I and IGFBP3 in patients with asthma. This study was performed in 27 asthma and 23 healthy individuals. Serum levels of IGF-I and IGFBP3 were measured by human ELISA assay kits...
2017: Bratislavské Lekárske Listy
Yong-Tao Wang, Ying-Hong Wang, Yi-Tong Ma, Zhen-Yan Fu, Yi-Ning Yang, Xiang Ma, Xiao-Mei Li, Dilare Adi, Fen Liu, Bang-Dang Chen
Several studies suggest an important role of Acyl-CoA: cholesterol acyltransferase-1(ACAT-1) in the development of atherosclerosis. The aim of present study was to investigate whether there exists a possible correlation between genetic variations in ACAT-1 genes and coronary artery disease (CAD) risk. Four polymorphisms (rs1044925, rs11545566, rs12121758 and rs10913733) were finally selected and genotyped in 750 CAD patients and 580 health controls, using the improved multiplex ligation detection reaction (iMLDR) method...
October 24, 2017: Oncotarget
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...
December 15, 2017: Experimental Cell Research
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
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
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
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
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
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
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
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
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
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