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Lipid new treatments

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https://www.readbyqxmd.com/read/29467937/temozolomide-sirolimus-and-chloroquine-is-a-new-therapeutic-combination-that-synergizes-to-disrupt-lysosomal-function-and-cholesterol-homeostasis-in-gbm-cells
#1
Sanford P C Hsu, John S Kuo, Hsin-Chien Chiang, Hsin-Ell Wang, Yu-Shan Wang, Cheng-Chung Huang, Yi-Chun Huang, Mau-Shin Chi, Minesh P Mehta, Kwan-Hwa Chi
Glioblastoma (GBM) cells are characterized by high phagocytosis, lipogenesis, exocytosis activities, low autophagy capacity and high lysosomal demand are necessary for survival and invasion. The lysosome stands at the cross roads of lipid biosynthesis, transporting, sorting between exogenous and endogenous cholesterol. We hypothesized that three already approved drugs, the autophagy inducer, sirolimus (rapamycin, Rapa), the autophagy inhibitor, chloroquine (CQ), and DNA alkylating chemotherapy, temozolomide (TMZ) could synergize against GBM...
January 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29467300/high-throughput-metabolomic-analysis-predicts-mode-of-action-of-uncharacterized-antimicrobial-compounds
#2
Mattia Zampieri, Balazs Szappanos, Maria Virginia Buchieri, Andrej Trauner, Ilaria Piazza, Paola Picotti, Sébastien Gagneux, Sonia Borrell, Brigitte Gicquel, Joel Lelievre, Balazs Papp, Uwe Sauer
Rapidly spreading antibiotic resistance and the low discovery rate of new antimicrobial compounds demand more effective strategies for early drug discovery. One bottleneck in the drug discovery pipeline is the identification of the modes of action (MoAs) of new compounds. We have developed a rapid systematic metabolome profiling strategy to classify the MoAs of bioactive compounds. The method predicted MoA-specific metabolic responses in the nonpathogenic bacterium Mycobacterium smegmatis after treatment with 62 reference compounds with known MoAs and different metabolic and nonmetabolic targets...
February 21, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29466714/cell-wall-enrichment-unveils-proteomic-changes-in-the-cell-wall-during-treatment-of-mycobacterium-smegmatis-with-sub-lethal-concentrations-of-rifampicin
#3
Clemens Hermann, Alexander D Giddey, Andrew J M Nel, Nelson C Soares, Jonathan M Blackburn
Understanding the cell wall of mycobacteria is crucial for improving drug design or identifying new antigens suitable to vaccination. Yet this remains problematic due to the complexity of the cell wall composition. In this study, we successfully developed gel-free approaches to study cell wall proteins in Mycobacterium smegmatis. The cell wall was subjected to differential centrifugation, differential detergent solubilisation and phase separation to yield the genuine cell wall proteome. Next, protein extracts were digested by filter-assisted sample preparation for LC-MS/MS analysis on a Q Exactive mass spectrometer, and identified proteins filtered through a stringent bioinformatics pipeline...
February 18, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29464937/vascular-dysfunction-elicited-by-a-crosstalk-between-periaortic-adipose-tissue-and-the-vascular-wall-is-reversed-by-pioglitazone
#4
Isabel Quesada, Jimena Cejas, Rodrigo García, Beatriz Cannizzo, Analía Redondo, Claudia Castro
AIM: Perivascular adipose tissue (PVAT) is in intimate contact with the vessel wall and extravascular PVAT-derived inflammatory mediators may adversely influence atherosclerotic plaque formation and stability through outside-to-inside signalling. We sought to investigate the role of PVAT on the atheroma development in an experimental animal model of Metabolic Syndrome (MS) associated with oxidative stress and low-grade inflammatory state. We also studied the effect of Pioglitazone an insulin sensitizer, on the aortic wall and its surrounding PVAT, considering a bi-directional communication between both layers...
February 21, 2018: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/29464513/lipids-in-ra-is-less-not-necessarily-more
#5
REVIEW
Jorge Plutzky, Katherine P Liao
PURPOSE OF REVIEW: In rheumatoid arthritis (RA), lipid levels are dynamic and can fluctuate along with changes in inflammation. A reduction in inflammation, most commonly as a result of disease-modifying anti-rheumatic drug (DMARD) therapy, is associated with increases in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). In this review, we discuss new evidence shedding light on the potential mechanism underlying changes in lipid levels observed with changes in inflammation...
February 21, 2018: Current Rheumatology Reports
https://www.readbyqxmd.com/read/29463911/disruption-of-lipid-raft-localized-g%C3%AE-s-tubulin-complexes-by-antidepressants-a-unique-feature-of-hdac6-inhibitors-ssri-and-tricyclic-compounds
#6
Harinder Singh, Nathan Wray, Jeffrey M Schappi, Mark M Rasenick
Current antidepressant therapies meet with variable therapeutic success and there is increasing interest in therapeutic approaches not based on monoamine signaling. Histone deacetylase 6 (HDAC6), which also deacetylates α-tubulin shows altered expression in mood disorders and HDAC6 knockout mice mimic traditional antidepressant treatments. Nonetheless, a mechanistic understanding for HDAC6 inhibitors in the treatment of depression remains elusive. Previously, we have shown that sustained treatment of rats or glioma cells with several antidepressants translocates Gαs from lipid rafts toward increased association with adenylyl cyclase (AC)...
February 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29463801/compensatory-increases-in-tear-volume-and-mucin-levels-associated-with-meibomian-gland-dysfunction-caused-by-stearoyl-coa-desaturase-1-deficiency
#7
Takaaki Inaba, Yasuhisa Tanaka, Shusaku Tamaki, Tomotaka Ito, James M Ntambi, Kazuo Tsubota
The stearoyl-CoA desaturase (SCD) family of enzymes catalyzes monounsaturated fatty acid synthesis by inserting a cis double bond at the Δ9 position of saturated fatty acids. Disruption of these enzymes has been reported to induce a severe dry skin phenotype. Since lipid abnormalities in the meibomian glands have been associated with dry eye, we analyzed selected eye tissues contributing to tear volume and composition in genetically SCD-1-deficient mice (SCD-1 KO), including the lacrimal glands and conjunctiva...
February 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29462928/omega-3-pufa-loaded-in-resveratrol-based-solid-lipid-nanoparticles-physicochemical-properties-and-antineoplastic-activities-in-human-colorectal-cancer-cells-in-vitro
#8
Simona Serini, Roberta Cassano, Paola Antonia Corsetto, Angela Maria Rizzo, Gabriella Calviello, Sonia Trombino
New strategies are being investigated to ameliorate the efficacy and reduce the toxicity of the drugs currently used in colorectal cancer (CRC), one of the most common malignancies in the Western world. Data have been accumulated demonstrating that the antineoplastic therapies with either conventional or single-targeted drugs could take advantage from a combined treatment with omega-3 polyunsaturated fatty acids (omega-3 PUFA). These nutrients, shown to be safe at the dosage generally used in human trials, are able to modulate molecules involved in colon cancer cell growth and survival...
February 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29462565/pycnogenol-r-protects-against-diet-induced-hepatic-steatosis-in-apolipoprotein-e-deficient-mice
#9
Difei Wang, Huiying Cong, Xiaoli Wang, Yanli Cao, Shoichiro Ikuyama, Bin Fan, Jianqiu Gu
Pycnogenol (PYC), a combination of active flavonoids derived from French maritime pine bark, is a natural antioxidant that has various pharmacological activities. Here, we investigated the beneficial effect of PYC on diet-induced hepatic steatosis. Apolipoprotein E (ApoE)-deficient male mice were administered PYC at oral doses of 30 or 100 mg•kg-1 •day-1 for two weeks in advance and were then fed a high cholesterol and fat diet (HCD) for eight weeks. Biochemical, immunohistochemical, and gene expression analyses were conducted to explore the effect of PYC on lipid metabolism in ApoE-deficient mice on a HCD...
February 20, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29460176/marrow-fat-a-new-target-to-treat-bone-diseases
#10
REVIEW
Beata Lecka-Czernik, Sudipta Baroi, Lance A Stechschulte, Amit Sopan Chougule
PURPOSE OF REVIEW: The goal of this review is to summarize recent findings on marrow adipose tissue (MAT) function and to discuss the possibility of targeting MAT for therapeutic purposes. RECENT FINDINGS: MAT is characterized with high heterogeneity which may suggest both that marrow adipocytes originate from multiple different progenitors and/or their phenotype is determined by skeletal location and environmental cues. Close relationship to osteoblasts and heterogeneity suggests that MAT consists of cells representing spectrum of phenotypes ranging from lipid-filled adipocytes to pre-osteoblasts...
February 19, 2018: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/29459241/the-atherogenic-dyslipidemia-complex-and-novel-approaches-to-cardiovascular-disease-prevention-in-diabetes
#11
REVIEW
Priska Stahel, Changting Xiao, Robert A Hegele, Gary F Lewis
Despite the effectiveness of low-density lipoprotein (LDL)-lowering strategies for the treatment of diabetic dyslipidemia, significant residual risk of atherosclerotic cardiovascular disease remains. Residual risk might in part be explained by lipid abnormalities that go beyond LDL cholesterol elevation, collectively termed the "atherogenic dyslipidemia complex (ADC)," consisting of hypertriglyceridemia, elevated small dense LDL particles, reduced high-density lipoprotein cholesterol, and high-density lipoprotein particle numbers, increased remnant lipoproteins, and postprandial hyperlipidemia...
December 15, 2017: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/29457839/brincidofovir-as-salvage-therapy-for-adenovirus-disease-in-intestinal-transplant-recipients
#12
Nimisha Sulejmani, Shunji Nagai, Mohamed Safwan, Michael D Rizzari, Mohammad Raoufi, Marwan S Abouljoud, Mayur Ramesh
Adenoviruses are double-stranded DNA viruses that typically cause mild self-limiting respiratory, ocular, and gastrointestinal infections. In immunocompromised patients, especially transplant recipients, the infection can be severe, with dissemination and multiorgan failure. In intestinal transplant recipients, the incidence is as high as 57%. To our knowledge, no standardized guidelines or United States Food and Drug Administration-approved medications exist for the treatment of adenovirus disease. We describe two isolated intestinal transplant recipients who developed adenovirus disease (viremia with viral enteritis) that was managed with a new experimental drug, brincidofovir (an oral lipid conjugate prodrug of cidofovir), as salvage therapy...
February 19, 2018: Pharmacotherapy
https://www.readbyqxmd.com/read/29454969/jip3-knockout-protects-mice-against-high-fat-diet-induced-liver-injury
#13
Xiao-Jun Ma, Hai-Zhou Xing, Gao-Fei Ren, Xiao-Juan Rao, Zhi-Zhen Li
Multiple pathways contribute to nonalcoholic fatty liver disease (NAFLD) in response to high fat diets (HFD). A homolog of mammalian JNK-interacting protein 3 (JIP3), also known as JSAP-1, activates different components in various signaling pathways to modulate cellular processes. The purpose of this study was to examine the role of JIP3 in obesity-related pathologies pathway. Wild-type (WT) C57BL/6 and JIP3-knockout (JIP3-/- ) mice were randomized to chow or HFD. HFD-fed WT mice increased hepatic JIP3 expression...
February 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29453982/glucagon-like-peptide-1-contributes-to-increases-abca1-expression-by-downregulating-mir-758-to-regulate-cholesterol-homeostasis
#14
Yue Yao, Qiang Li, Ping Gao, Wei Wang, Lili Chen, Jinchao Zhang, Yi Xu
Abnormal regulation of lipid metabolism is associated with type 2 diabetes mellitus (T2DM). GLP-1 as a new treatment for T2DM, has unique effects in modulating cholesterol homeostasis. However, the mechanism of this effect is largely missing. The aim of this study was to determine the effects of GLP-1 on cholesterol-induced lipotoxicity in hepatocytes and examine the underlying mechanisms. The cell viability was determined, and caspase-3 was used to detect the effects of GLP-1 on cholesterol-induced apoptosis...
February 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29453462/gq-11-a-new-ppar-agonist-improves-obesity-induced-metabolic-alterations-in-ldlr-mice
#15
Jacqueline C Silva, Edson M de Oliveira, Walter M Turato, Gustavo H G Trossini, Vinícius G Maltarollo, Marina G R Pitta, Ivan R Pitta, Beatriz de Las Heras, Lisardo Boscá, Martina Rudnicki, Dulcineia S P Abdalla
BACKGROUND: Obesity and insulin resistance/diabetes are important risk factors for cardiovascular diseases and demand safe and efficacious therapeutics. OBJECTIVE: To assess the effects of a new thiazolidine compound-GQ-11-on obesity and insulin resistance induced by a diabetogenic diet in LDL receptor-deficient (LDLr -/- ) mice. METHODS: Molecular docking simulations of GQ-11, PPARα and PPARγ structures were performed. Male C57BL/6J LDLr -/- mice fed a diabetogenic diet for 24 weeks were treated with vehicle, GQ-11 or pioglitazone or (20 mg/kg/day) for 28 days by oral gavage...
January 30, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29451090/study-of-changes-in-lipid-profile-and-insulin-resistance-in-egyptian-patients-with-chronic-hepatitis-c-genotype-4-in-the-era-of-daas
#16
Ghada El Sagheer, Elwy Soliman, Asmaa Ahmad, Lamiaa Hamdy
Chronic hepatitis C virus (HCV) infection is associated with altered metabolism, including dyslipidemia and insulin resistance. These contribute to disease progression and influences the response to therapy. To investigate the relationships of new direct-acting antiviral drugs, simeprevir/sofosbuvir, with lipid profile and insulin resistance (IR). Eighty chronic hepatitis C genotype 4 patients were included; they were divided into four groups according to the severity of fibrosis as detected by fibroscan. Forty healthy persons volunteered as a control group...
December 2018: Libyan Journal of Medicine
https://www.readbyqxmd.com/read/29448116/immunoliposomes-in-clinical-oncology-state-of-the-art-and-future-perspectives
#17
REVIEW
María Merino, Sara Zalba, María J Garrido
Liposomal formulations entrapping a vast number of molecules have improved cancer therapies overcoming certain pharmacokinetic (PK) and pharmacodynamic limitations, many of which are associated with tumor characteristics. In this context, immunoliposomes represent a new strategy that has been widely investigated in preclinical cancer models with promising results, although few have reached the stage of clinical trials. This contrasts with the emerging clinical application of monoclonal antibodies (mAbs). This formulation allows the conjugation of different mAbs or antibody derivatives, such as monovalent variable fragments Fab', to the polymers covering the surface of liposomes...
February 12, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29447742/a-comparative-analysis-of-current-lipid-treatment-guidelines-nothing-stands-still
#18
REVIEW
Anjan Tibrewala, Arif Jivan, William J Oetgen, Neil J Stone
Lipid treatment guidelines have continued to evolve as new evidence emerges. We sought to review similarities and differences of 5 lipid treatment guidelines from the American College of Cardiology/American Heart Association, Canadian Cardiovascular Society, European Society for Cardiology/European Atherosclerosis Society, U.S. Preventive Services Task Force, and U.S. Veterans Affairs/Department of Defense. All guidelines utilize rigorous evidentiary review, highlight statin therapy for primary and secondary prevention of atherosclerotic cardiovascular disease, and emphasize a clinician-patient risk discussion...
February 20, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29447191/euglena-extract-suppresses-adipocyte-differentiation-in-human-adipose-derived-stem-cells
#19
Ryota Sugimoto, Naoko Ishibashi-Ohgo, Kohei Atsuji, Yuko Miwa, Osamu Iwata, Ayaka Nakashima, Kengo Suzuki
Euglena gracilis Z (Euglena) is a unicellular, photosynthesizing, microscopic green alga. It contains several nutrients such as vitamins, minerals, and unsaturated fatty acids. In this study, to verify the potential role of Euglena consumption on human health and obesity, we evaluated the effect of Euglena on human adipose-derived stem cells. We prepared a Euglena extract and evaluated its effect on cell growth and lipid accumulation, and found that cell growth was promoted by the addition of the Euglena extract...
2018: PloS One
https://www.readbyqxmd.com/read/29444239/therapeutic-efficacy-of-microtube-embedded-chondroitinase-abc-in-a-canine-clinical-model-of-spinal-cord-injury
#20
Hilary Z Hu, Nicolas Granger, S Balakrishna Pai, Ravi V Bellamkonda, Nick D Jeffery
Many hundreds of thousands of people around the world are living with the long-term consequences of spinal cord injury and they need effective new therapies. Laboratory research in experimental animals has identified a large number of potentially translatable interventions but transition to the clinic is not straightforward. Further evidence of efficacy in more clinically-relevant lesions is required to gain sufficient confidence to commence human clinical trials. Of the many therapeutic candidates currently available, intraspinally applied chondroitinase ABC has particularly well documented efficacy in experimental animals...
February 9, 2018: Brain: a Journal of Neurology
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