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lipid disorders

Andrea De Lorenzo, Juliana Duarte Lopes da Silva, Cinthia E James, Alexandre C Pereira, Annie Seixas Bello Moreira
BACKGROUND: Familial hypercholesterolemia (FH) is a common autosomal dominant disorder, characterized by a high level of low-density lipoprotein cholesterol (LDL-C) and a high risk of premature cardiovascular disease. OBJECTIVE: To evaluate clinical and anthropometric characteristics of patients with the familiar hypercholesterolemia (FH) phenotype, with or without genetic confirmation of FH. METHODS: Forty-five patients with LDL-C > 190 mg/dl were genotyped for six FH-related genes: LDLR, APOB, PCSK9, LDLRAP1, LIPA and APOE...
February 2018: Arquivos Brasileiros de Cardiologia
Shufang He, Weiwei Fan, Na Wu, Jingjing Zhu, Yunqiu Miao, Xiaran Miao, Feifei Li, Xinxin Zhang, Yong Gan
RNA interference (RNAi) technology has shown great promise for the treatment of cancer and other genetic disorders. Despite the efforts to increase the target tissue distribution, the safe and effective delivery of siRNA to the diseased cells with sufficient cytosolic transport is another critical factor for successful RNAi clinical application. Here, the constructed lipid-based liquid crystalline nanoparticles, called nano-Transformers, can transform the structure in the intracellular acidic environment, and perform high-efficient siRNA delivery for cancer treatment...
March 21, 2018: Nano Letters
Nabab Khan, Gaurav Datta, Jonathan D Geiger, Xuesong Chen
BACKGROUND: Apolipoprotein E (ApoE) is the major carrier protein that mediates the transport and delivery of cholesterol and other lipids in the brain. Three isoforms of ApoE (ApoE2, ApoE3, ApoE4) exist in humans, and their relative expression levels impact HIV-1 infection, HIV-1/AIDS disease progression, and cognitive decline associated with HIV-1-associated neurocognitive disorder. Because HIV-1 Tat, a viral protein essential for HIV-1 replication, can bind to low-density lipoprotein receptor-related protein 1 (LRP1) that controls ApoE uptake in the brain, we determined the extent to which different isoforms of ApoE affected Tat-mediated HIV-1 LTR transactivation...
March 20, 2018: Journal of Neuroinflammation
Soo-Min Lim, Eunju Kim, Jae-Ho Shin, Pu Reum Seok, Sangwon Jung, Sang-Ho Yoo, Yuri Kim
Obesity is a public concern and is responsible for various metabolic diseases. Xylobiose (XB), an alternative sweetener, is a major component of xylo-oligosaccharide. The purpose of this study was to investigate the effects of XB on obesity and its associated metabolic changes in related organs. For these studies, mice received a 60% high-fat diet supplemented with 15% d-xylose, 10% XB, or 15% XB as part of the total sucrose content of the diet for ten weeks. Body weight, fat and liver weights, fasting blood glucose, and blood lipids levels were significantly reduced with XB supplementation...
March 20, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Zhila Maghbooli, Leila Khorrami-Nezhad, Elham Adabi, Majid Ramezani, Effat Asadollahpour, Farideh Razi, Mohammadtaher Rezanezhad
OBJECTIVE: The aim of the study was to investigate the association between high-density lipoprotein (HDL) and bone status taking into account serum vitamin D levels in postmenopausal Iranian women. METHODS: During January 2015 and February 2016, a total of 488 postmenopausal Iranian women participated in this cross-sectional study, all of whom were not taking osteoporosis medication and were not suffering from any chronic disorder. Dual X-ray absorptiometry was used to assess bone mineral density (BMD) of the total hip, femoral neck, and lumbar vertebrae (L2-L4)...
March 19, 2018: Menopause: the Journal of the North American Menopause Society
Shihui Hao, Bishan Liang, Qiong Huang, Shumin Dong, Zhenzhen Wu, Wanming He, Min Shi
Ferroptosis is an iron-dependent and peroxidation-driven form of cell death associated with multiple metabolic disorders and disrupted homeostasis. A number of metabolic processes and homeostasis are affected by ferroptosis. The molecules that regulate ferroptosis are involved in metabolic pathways that regulate cysteine exploitation, glutathione state, nicotinamide adenine dinucleotide phosphate function, lipid peroxidation and iron homeostasis. The present review summarizes the metabolic networks involved in ferroptosis based on previous studies, and discusses the function of ferroptosis in pathological processes, including cancer...
April 2018: Oncology Letters
Shingo Kishi, Rina Fujiwara-Tani, Yi Luo, Isao Kawahara, Kei Goto, Kiyomu Fujii, Hitoshi Ohmori, Chie Nakashima, Takamitsu Sasaki, Hiroki Kuniyasu
Trans fatty acids (TFAs) are risk factors for cardiovascular disorders, and the cancer-promoting effects of TFAs have been previously reported. The present study examined the effects and signaling of elaidic acid (EA), a TFA, in colorectal cancer (CRC) cells. Oral intake of EA was found to increase metastasis of HT29 human CRC cells. Results indicated that, in the plasma membrane, EA was integrated into cholesterol rafts, which contain epidermal growth factor receptors (EGFR). EA increased nanog and c-myc, and decreased PGC-1A through lipid raft-associated EGFR signaling in HT29 cells...
April 2018: Oncology Letters
Madhumitha Dhanasekaran, Maheshkumar Jaganathan, A Dhathathreyan
This study examines adsorption of Myoglobin (Mb) in solution and as colloid on supported lipid bilayers of neutral phospholipids and a mixture of neutral + cationic lipids formed on gold coated quartz in a Quartz crystal microbalance (QCM). Results indicate that thin adsorbed films of Mb in solution and as colloids, show atleast 3 steps in the interaction with the bilayers: i) An initial strain of a viscoelastic film ii) Entrained water that moves in and out of the adsorbed film and iii) The coupled load from the bulk liquid which increases the strain of the film...
March 16, 2018: International Journal of Biological Macromolecules
C Binot, C-H Chouard
The existence of an information vector common to very different pathologies is the hypothesis of one of us, the argumentation and discussion of which we present here. It is a mesomorphic state of material called liquid crystal. The liquid-ordered (Lo) phase, made up of membrane rafts mediated by cholesterol, lies at the center of our concept. This mesophase is either preexistent and then modified by the pathogenic process, or initiated by the latter. The most notable disorders involved are Alzheimer's, Parkinson's, Charcot and Creutzfeldt-Jakob diseases, flu-like illnesses and acquired immunodeficiency syndrome (AIDS), although this list may well be extended to include other anisotropic, birefringent amyloid proteinopathies, which have properties compatible with those of liquid crystals...
March 16, 2018: Revue Neurologique
Noelia Morales-Prieto, Julia Ruiz-Laguna, David Sheehan, Nieves Abril
The use of DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane) in some countries, although regulated, is contributing to an increased worldwide risk of exposure to this organochlorine pesticide or its derivative p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene]. Many studies have associated p,p'-DDE exposure to type 2 diabetes, obesity and alterations of the reproductive system, but their molecular mechanisms of toxicity remain poorly understood. We have addressed this issue by using commercial microarrays based on probes for the entire Mus musculus genome to determine the hepatic transcriptional signatures of p,p'-DDE in the phylogenetically close mouse species Mus spretus...
March 16, 2018: Environmental Pollution
Ariel Finkielsztein, Lorraine Mascarenhas, Veronika Butin-Israeli, Ronen Sumagin
Polymorphonuclear neutrophil-derived microparticles (PMN)-MPs) are lipid bilayer, spherical microvesicles with sizes ranging from 50-1,000 nm in diameter. MPs are a newly evolving, important part of cell-to-cell communication and signaling machinery. Because of their size and the nature of their release, until recently MP existence was overlooked. However, with improved technology and analytical methods their function in health and disease is now emerging. The protocols presented here are aimed at isolating and characterizing PMN-MPs by flow cytometry and immunoblotting...
March 2, 2018: Journal of Visualized Experiments: JoVE
Jun-Ichi Satoh, Yoshihiro Kino, Motoaki Yanaizu, Yuko Saito
Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder, characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by genetic mutations of either triggering receptor expressed on myeloid cells 2 ( TREM2 ) or TYRO protein tyrosine kinase binding protein ( TYROBP ), alternatively named DNAX-activation protein 12 ( DAP12 ), both of which are expressed on microglia in the brain and form the receptor-adaptor complex that chiefly recognizes anionic lipids. TREM2 transmits the signals involved in microglial survival, proliferation, chemotaxis, and phagocytosis...
February 2018: Intractable & Rare Diseases Research
Dan Wei, Ningning Zheng, Lanyan Zheng, Leting Wang, Liang Song, Luning Sun
Background: Metabolic syndrome (MS) is a global epidemic that has great socioeconomic and public health implications. This study reports observed effects of the Shexiang Baoxin Pill (SBP) in a rat model of MS and explores its underlying mechanisms of action. Methods: A diet-induced rat model of MS was established according to accepted methods, and the rats were randomly divided into two groups: a control group (0.9% NaCl, 100 mg/kg• d) and a SBP-treated group (SBP, 100 mg/kg• d). Systolic blood pressures, fasting blood glucose (FBS) levels, triglyceride (TG) levels, high-density lipoprotein cholesterol (HDL-C) levels, body weights, and abdominal perimeters were dynamically monitored and analyzed...
2018: Frontiers in Pharmacology
Li-Qing Su, Yong-di Wang, Hai-Yan Chi
Objective: To investigate how curcumin affects the glucose and lipid metabolism in type 2 diabetes mellitus (DM) rat models, and to explore its effect on the free fatty acid (FFA) and tumor necrosis factor α (TNF-α) in serum. Methods: Successfully established type 2 DM rats were divided into three groups, i.e. the normal control group, model group and curcumin group, and received the medication for consecutive 8 weeks. Thereafter, we detected the level of fasting blood glucose (FBG), and the blood glucose at 30 min, 60 min and 120 min; besides, we also carried out the insulin tolerance tests to measure the levels of fasting serum insulin (FINS) and blood glucose at 40 min and 90 min; additionally, we also detected the levels of TC, TG, HDL-C, LDL-C, FFA and TNF-α in serum...
December 2017: Saudi Journal of Biological Sciences
Varda Shoshan-Barmatz, Edna Nahon-Crystal, Anna Shteinfer-Kuzmine, Rajeev Gupta
Alzheimer's disease (AD) is an age-related neurodegenerative disorder. Although an accumulation of brain amyloid-β (Aβ) peptide and hyperphosphorylated tau protein have been implicated in the pathogenesis of AD, the etiology of the disease remains unclear. Mitochondrial dysfunction has been identified as an early event in AD pathogenesis and is reflected by reduced metabolism, disruption of Ca2+ homeostasis, and increased levels of reactive oxygen species, lipid peroxidation, and apoptosis. The focus of this review is the involvement of mitochondrial dysfunction in AD, and specifically, the role of the voltage-dependent anion channel 1 (VDAC1), which has been linked to AD pathogenesis...
March 15, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Alec N Salt, Stefan K Plontke
Local drug delivery to the ear has gained wide clinical acceptance, with the choice of drug and application protocol in humans largely empirically-derived. Here, we review the pharmacokinetics underlying local therapy of the ear using the drugs commonly used in clinical practice as examples. Based on molecular properties and perilymph measurements interpreted through computer simulations we now better understand the principles underlying entry and distribution of these and other drugs in the ear. From our analysis, we have determined that dexamethasone-phosphate, a pro-drug widely-used clinically, has molecular and pharmacokinetic properties that make it ill-suited for use as a local therapy for hearing disorders...
March 11, 2018: Hearing Research
Sara Milanizadeh, Karrar Najm Najaf Zuwarali, Abbas Aliaghaei, Mohammad Reza Bigdeli
Brain ischemia is one of the most common causes of death and disability worldwide, which usually happens through diminished blood supply to the tissue. Cell therapy and treatments using trophic factors are some of the new methods to protect brain cells against damage. Specific properties of Sertoli cells (SCs) make them suitable for improving neurological disorders. This study is to evaluate possible neuroprotective effects of SCs transplantation on ischemic damage. Rats were divided into three experimental groups including sham, control, and SCs-treated group...
March 17, 2018: Journal of Molecular Neuroscience: MN
Alexander Kyrychenko, Nathan M Lim, Victor Vasquez-Montes, Mykola V Rodnin, J Alfredo Freites, Linh P Nguyen, Douglas J Tobias, David L Mobley, Alexey S Ladokhin
Dynamic disorder of the lipid bilayer presents a challenge for establishing structure-function relationships in membranous systems. The resulting structural heterogeneity is especially evident for peripheral and spontaneously inserting membrane proteins, which are not constrained by the well-defined transmembrane topology and exert their action in the context of intimate interaction with lipids. Here, we propose a concerted approach combining depth-dependent fluorescence quenching with Molecular Dynamics simulation to decipher dynamic interactions of membrane proteins with the lipid bilayers...
March 17, 2018: Journal of Membrane Biology
Kenichi Morigaki, Yasushi Tanimoto
One of the main questions in the membrane biology is the functional roles of membrane heterogeneity and molecular localization. Although segregation and local enrichment of protein/lipid components (rafts) have been extensively studied, the presence and functions of such membrane domains still remain elusive. Along with biochemical, cell observation, and simulation studies, model membranes are emerging as an important tool for understanding the biological membrane, providing quantitative information on the physicochemical properties of membrane proteins and lipids...
March 14, 2018: Biochimica et Biophysica Acta
Lulu Ning, Yuguang Mu
Prion diseases are neurodegenerative disorders characterized by the aggregation of an abnormal form of prion protein. The interaction of prion protein and cellular membrane is crucial to elucidate the occurrence and development of prion diseases. Its fragment, residues 106-126, has been proven to maintain the pathological properties of misfolded prion and was used as a model peptide. In this study, explicit solvent molecular dynamics (MD) simulations were carried out to investigate the adsorption, folding and aggregation of PrP106-126 with different sizes (2-peptides, 4-peptides and 6-peptides) on the surface of both pure neutral POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and negatively charged POPC/POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol) (3:1) lipids...
March 14, 2018: Biochimica et Biophysica Acta
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