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https://www.readbyqxmd.com/read/28440698/therapeutic-peg-ceramide-nanomicelles-synergize-with-salinomycin-to-target-both-liver-cancer-cells-and-cancer-stem-cells
#1
Meiping Wang, Fangyuan Xie, Xikai Wen, Han Chen, Hai Zhang, Junjie Liu, He Zhang, Hao Zou, Yuan Yu, Yan Chen, Zhiguo Sun, Xinxia Wang, Guoqing Zhang, Chuan Yin, Duxin Sun, Jie Gao, Beige Jiang, Yanqiang Zhong, Ying Lu
AIM: Salinomycin (SAL)-loaded PEG-ceramide nanomicelles (SCM) were prepared to target both liver cancer cells and cancer stem cells. MATERIALS & METHODS: The synergistic ratio of SAL/PEG-ceramide was evaluated to prepare SCM, and the antitumor activity of SCM was examined both in vitro and in vivo. RESULTS: SAL/PEG-ceramide molar ratio of 1:4 was chosen as the synergistic ratio, and SCM showed superior cytotoxic effect and increased apoptosis-inducing activity in both liver cancer cells and cancer stem cells...
April 25, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28439667/myricetin-induced-brown-adipose-tissue-activation-prevents-obesity-and-insulin-resistance-in-db-db-mice
#2
Tao Hu, Xiaoxue Yuan, Gang Wei, Haoshu Luo, Hyuek Jong Lee, Wanzhu Jin
PURPOSE: Myricetin, a dietary flavonoid, is effective in the treatment of obesity and insulin resistance by increasing glucose transport and lipogenesis in adipocyte and diminishing systemic inflammation in obesity. However, it has not been revealed yet whether myricetin is associated with brown adipose tissue (BAT) activation that tightly mediates systemic energy metabolism. Therefore, this study assessed whether myricetin activated brown adipose tissue in db/db mouse. METHODS: Myricetin (400 mg/kg) in distilled water was fed daily by oral gavage to leptin receptor-deficient db/db male mice at 4 weeks of age for 14 weeks...
April 24, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28431377/metabolic-regulation-and-the-anti-obesity-perspectives-of-human-brown-fat
#3
REVIEW
Camilla Scheele, Søren Nielsen
Activation of brown adipose tissue (BAT) in adult humans increase glucose and fatty acid clearance as well as resting metabolic rate, whereas a prolonged elevation of BAT activity improves insulin sensitivity. However, substantial reductions in body weight following BAT activation has not yet been shown in humans. This observation raise the possibility for feedback mechanisms in adult humans in terms of a brown fat-brain crosstalk, possibly mediated by batokines, factors produced by and secreted from brown fat...
April 11, 2017: Redox Biology
https://www.readbyqxmd.com/read/28427098/opa1-in-lipid-metabolism-function-of-opa1-in-lipolysis-and-thermogenesis-of-adipocytes
#4
Dinh-Toi Chu, Yang Tao, Kjetil Taskén
OPA1 (Optic Atrophy 1) is a mitochondrial GTPase known to regulate fission of mitochondria. It was recently also shown to locate on lipid droplets in adipocytes where it functions as an A-kinase anchoring protein (AKAP) that mediates adrenergic control of lipolysis by facilitating PKA phosphorylation of perilipin (Plin1). In brown adipocytes indirect evidence support the notion that OPA1 regulation of fission serves to increase thermogenesis, which thereby contributes to dissipation of energy. In white adipocytes, OPA1 located on lipid droplets serves as a gatekeeper to control lipolysis induced by adrenergic agonists...
April 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28422089/thermogenic-adipocytes-promote-hdl-turnover-and-reverse-cholesterol-transport
#5
Alexander Bartelt, Clara John, Nicola Schaltenberg, Jimmy F P Berbée, Anna Worthmann, M Lisa Cherradi, Christian Schlein, Julia Piepenburg, Mariëtte R Boon, Franz Rinninger, Markus Heine, Klaus Toedter, Andreas Niemeier, Stefan K Nilsson, Markus Fischer, Sander L Wijers, Wouter van Marken Lichtenbelt, Ludger Scheja, Patrick C N Rensen, Joerg Heeren
Brown and beige adipocytes combust nutrients for thermogenesis and through their metabolic activity decrease pro-atherogenic remnant lipoproteins in hyperlipidemic mice. However, whether the activation of thermogenic adipocytes affects the metabolism and anti-atherogenic properties of high-density lipoproteins (HDL) is unknown. Here, we report a reduction in atherosclerosis in response to pharmacological stimulation of thermogenesis linked to increased HDL levels in APOE*3-Leiden.CETP mice. Both cold-induced and pharmacological thermogenic activation enhances HDL remodelling, which is associated with specific lipidomic changes in mouse and human HDL...
April 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28418009/effect-of-umod-genotype-on-long-term-graft-survival-after-kidney-transplantation-in-patients-treated-with-cyclosporine-based-therapy
#6
E Abdel-Hady Algharably, J Beige, R Kreutz, J Bolbrinker
The genetic rs12917707-G>T variant in uromodulin (UMOD) has been associated with renal function, chronic kidney disease and hypertension with the minor T-allele showing a protective effect. Hypertension and nephrotoxicity are adverse effects of chronic cyclosporine treatment. We tested whether UMOD rs12917707-T in donor kidneys associates with long-term graft survival in 393 Caucasian patients with stable graft function for more than 10 weeks after kidney transplantation treated with a cyclosporine-based maintenance therapy (mean graft survival 9 years)...
April 18, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28414311/a-self-sustained-loop-of-inflammation-driven-inhibition-of-beige-adipogenesis-in-obesity
#7
Kyoung-Jin Chung, Antonios Chatzigeorgiou, Matina Economopoulou, Ruben Garcia-Martin, Vasileia I Alexaki, Ioannis Mitroulis, Marina Nati, Janine Gebler, Tjalf Ziemssen, Susan E Goelz, Julia Phieler, Jong-Hyung Lim, Katia P Karalis, Thalia Papayannopoulou, Matthias Blüher, George Hajishengallis, Triantafyllos Chavakis
In obesity, inflammation of white adipose tissue (AT) is associated with diminished generation of beige adipocytes ('beige adipogenesis'), a thermogenic and energy-dissipating function mediated by beige adipocytes that express the uncoupling protein UCP1. Here we delineated an inflammation-driven inhibitory mechanism of beige adipogenesis in obesity that required direct adhesive interactions between macrophages and adipocytes mediated by the integrin α4 and its counter-receptor VCAM-1, respectively; expression of the latter was upregulated in obesity...
April 17, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28414146/tissue-distribution-of-a-therapeutic-monoclonal-antibody-determined-by-large-pore-microdialysis
#8
Satyawan B Jadhav, Vipada Khaowroongrueng, Matthias Fueth, Michael B Otteneder, Wolfgang Richter, Hartmut Derendorf
Therapeutic monoclonal antibodies (mAbs) exhibit limited distribution to the target tissues. Determination of target tissue interstitial concentration of mAbs is an important aspect in the assessment of their pharmacokinetic/pharmacodynamics (PK/PD) relationship especially for mAbs targeting membrane bound receptors. The pharmacokinetics of R7072, a full length mAb (IgG) targeting human insulin like growth factor-1 receptor (IGF-1R) was evaluated following a single intravenous (IV) dose at 1, 6.25 and 25 mg/kg in healthy female SCID-beige mice...
April 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28408241/maternal-retinoids-increase-pdgfr%C3%AE-progenitor-population-and-beige-adipogenesis-in-progeny-by-stimulating-vascular-development
#9
Bo Wang, Xing Fu, Xingwei Liang, Zhixiu Wang, Qiyuan Yang, Tiande Zou, Wei Nie, Junxing Zhao, Pengfei Gao, Mei-Jun Zhu, Jeanene M de Avila, Joseph Maricelli, Buel D Rodgers, Min Du
Maternal vitamin A intake varies but its impact on offspring metabolic health is unknown. Here we found that maternal vitamin A or retinoic acid (RA) administration expanded PDGFRα(+) adipose progenitor population in progeny, accompanied by increased blood vessel density and enhanced brown-like (beige) phenotype in adipose tissue, protecting offspring from obesity. Blockage of retinoic acid signaling by either BMS493 or negative RA receptor (RARαDN) over-expression abolished the increase in blood vessel density, adipose progenitor population, and beige adipogenesis stimulated by RA...
April 4, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28404643/the-beach-containing-protein-wdr81-coordinates-p62-and-lc3c-to-promote-aggrephagy
#10
Xuezhao Liu, Yang Li, Xin Wang, Ruxiao Xing, Kai Liu, Qiwen Gan, Changyong Tang, Zhiyang Gao, Youli Jian, Shouqing Luo, Weixiang Guo, Chonglin Yang
Autophagy-dependent clearance of ubiquitinated and aggregated proteins is critical to protein quality control, but the underlying mechanisms are not well understood. Here, we report the essential role of the BEACH (beige and Chediak-Higashi) and WD40 repeat-containing protein WDR81 in eliminating ubiquitinated proteins through autophagy. WDR81 associates with ubiquitin (Ub)-positive protein foci, and its loss causes accumulation of Ub proteins and the autophagy cargo receptor p62. WDR81 interacts with p62, facilitating recognition of Ub proteins by p62...
April 12, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28401363/characterization-of-marinovum-faecis-sp-nov-an-alphaproteobacterium-isolated-from-marine-sediment
#11
Jaewoo Yoon, So Young Kim, Songhee Park, Hyukjae Choi
A Gram-negative, strictly aerobic, chemoheterotrophic, beige-pigmented, ovoid bacterium, designated YP194(T), was isolated from marine sediment in the Republic of Korea. A phylogenetic analysis based on the 16S rRNA gene sequence indicated that the novel marine strain belongs to the family Rhodobacteraceae of the class Alphaproteobacteria, with high sequence similarity (98.4%) to Marinovum algicola FF3(T). The DNA-DNA relatedness values between strains YP194(T) and M. algicola FF3(T) were 34.1 ± 2.7%. The DNA G+C content of strain YP194(T) was 63...
April 11, 2017: Antonie Van Leeuwenhoek
https://www.readbyqxmd.com/read/28385602/svct-2-determines-the-sensitivity-to-ascorbate-induced-cell-death-in-cholangiocarcinoma-cell-lines-and-patient-derived-xenografts
#12
Changzheng Wang, Hongwei Lv, Wen Yang, Ting Li, Tian Fang, Guishuai Lv, Qin Han, Liwei Dong, Tianyi Jiang, Beige Jiang, Guangshun Yang, Hongyang Wang
Cholangiocarcinoma (CC) is a devastating malignancy with late diagnosis and poor response to conventional chemotherapy. Recent studies have revealed anti-cancer effect of vitamin C (l-ascorbic acid, ascorbate) in several types of cancer. However, the effect of l-ascorbic acid (AA) in CC remains elusive. Herein, we demonstrated that AA induced cytotoxicity in CC cells by generating intracellular reactive oxygen species (ROS), and subsequently DNA damage, ATP depletion, mTOR pathway inhibition. Moreover, AA worked synergistically with chemotherapeutic agent cisplatin to impair CC cells growth both in vitro and in vivo...
April 4, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28380386/untargeted-metabolite-analysis-based-uhplc-q-tof-ms-reveals-significant-enrichment-of-p-hydroxybenzyl-dimers-of-citric-acids-in-fresh-beige-scape-gastrodia-elata-wutianma
#13
Chang-Jiang-Sheng Lai, Yuan Yuan, Da-Hui Liu, Chuan-Zhi Kang, Yu Zhang, Liangping Zha, Liping Kang, Tong Chen, Tie-Gui Nan, Qing-Xiu Hao, Lu-Qi Huang
In order to comprehensively elucidate the chemical biosynthesis process of the beige-scape Gastrodia elata Blume (Wutianma) as a traditional herbal medicines, the untargeted analysis-based UHPLC-PDA-ESI-Q-TOF-MS reveals the metabolites ranging from the skeletons to novel dimers of citric acids in fresh and dried immature/mature stem tubers. Interestingly, two novel types of dimers for citric acids with the anhydride groups at sn-1 and/or sn-5 were discovered in fresh samples. Moreover, the classical mono- versus novel di-mers, and the aglycons versus the glycosides could be easily discriminated by signature fragmentation patterns and some novel adduct ions...
June 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28380374/mitochondrial-patch-clamp-of-beige-adipocytes-reveals-ucp1-positive-and-ucp1-negative-cells-both-exhibiting-futile-creatine-cycling
#14
Ambre M Bertholet, Lawrence Kazak, Edward T Chouchani, Marta G Bogaczyńska, Ishan Paranjpe, Gabrielle L Wainwright, Alexandre Bétourné, Shingo Kajimura, Bruce M Spiegelman, Yuriy Kirichok
Cold and other environmental factors induce "browning" of white fat depots-development of beige adipocytes with morphological and functional resemblance to brown fat. Similar to brown fat, beige adipocytes are assumed to express mitochondrial uncoupling protein 1 (UCP1) and are thermogenic due to the UCP1-mediated H(+) leak across the inner mitochondrial membrane. However, this assumption has never been tested directly. Herein we patch clamped the inner mitochondrial membrane of beige and brown fat to provide a direct comparison of their thermogenic H(+) leak (IH)...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380369/now-ucp-rotein-now-you-don-t-ucp1-is-not-mandatory-for-thermogenesis
#15
Ildiko Szabo, Mario Zoratti
Adipocyte-targeted therapies could potentially combat obesity and metabolic disorders; however, our understanding of adipogenesis and the characterization of the various adipose tissues are incomplete. In this issue, Bertholet et al. (2017) report the existence of two types of heat-producing beige-like adipocytes, those with and those without the mitochondrial uncoupling protein 1 (UCP1).
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28370281/new-insights-into-the-local-and-systemic-functions-of-sclerostin-regulation-of-quiescent-bone-lining-cells-and-beige-adipogenesis-in-peripheral-fat-depots
#16
Jesus Delgado-Calle, Teresita Bellido
No abstract text is available yet for this article.
March 29, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28368209/enhanced-cytotoxic-effect-of-camptothecin-nanosponges-in-anaplastic-thyroid-cancer-cells-in-vitro-and-in-vivo-on-orthotopic-xenograft-tumors
#17
Casimiro Luca Gigliotti, Benedetta Ferrara, Sergio Occhipinti, Elena Boggio, Giuseppina Barrera, Stefania Pizzimenti, Mirella Giovarelli, Roberto Fantozzi, Annalisa Chiocchetti, Monica Argenziano, Nausicaa Clemente, Francesco Trotta, Caterina Marchiò, Laura Annaratone, Renzo Boldorini, Umberto Dianzani, Roberta Cavalli, Chiara Dianzani
Anaplastic carcinoma of the thyroid (ATC) is a lethal human malignant cancer with median survival of 6 months. To date, no treatment has substantially changed its course, which makes urgent need for the development of novel drugs or novel formulations for drug delivery. Nanomedicine has enormous potential to improve the accuracy of cancer therapy by enhancing availability and stability, decreasing effective doses and reducing side effects of drugs. Camptothecin (CPT) is an inhibitor of DNA topoisomerase-I with several anticancer properties but has poor solubility and a high degradation rate...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28355132/angiopoietin-2-in-white-adipose-tissue-improves-metabolic-homeostasis-through-enhanced-angiogenesis
#18
Yu A An, Kai Sun, Nolwenn Joffin, Fang Zhang, Yingfeng Deng, Olivier Donzé, Christine M Kusminski, Philipp E Scherer
Despite many angiogenic factors playing crucial roles in metabolic homeostasis, effects of angiopoietin-2 (ANG-2) in adipose tissue (AT) remain unclear. Utilizing a doxycycline-inducible AT-specific ANG-2 overexpression mouse model, we assessed the effects of ANG-2 in AT expansion upon a high-fat diet (HFD) challenge. ANG-2 is significantly induced, with subcutaneous white AT (sWAT) displaying the highest ANG-2 expression. ANG-2 overexpressing mice show increased sWAT vascularization and are resistant to HFD-induced obesity...
March 29, 2017: ELife
https://www.readbyqxmd.com/read/28347739/targeting-white-brown-and-perivascular-adipose-tissue-in-atherosclerosis-development
#19
Andrea D van Dam, Mariëtte R Boon, Jimmy F P Berbée, Patrick C N Rensen, Vanessa van Harmelen
Obesity is a well-established risk factor for atherosclerosis. However, the mechanistic link between accumulation of adipose tissue and development of atherosclerosis is not clear. Adipose tissue comprises various depots including white adipose tissue (WAT), brown adipose tissue (BAT) and thoracic and abdominal perivascular adipose tissue (PVAT). The phenotype of thoracic PVAT resembles BAT, whereas abdominal PVAT is more like WAT. Here, we review the distinct roles of the adipose tissue depots in the development of atherosclerosis with the ultimate aim to understand how these can be targeted to reduce atherosclerosis...
March 24, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28347611/ambient-particulate-matter-and-carbon-monoxide-at-an-urban-site-of-india-influence-of-anthropogenic-emissions-and-dust-storms
#20
Ravi Yadav, L K Sahu, G Beig, Nidhi Tripathi, S N A Jaaffrey
Continuous measurements of PM2.5, PM10 and CO were conducted at an urban site of Udaipur in India from April 2011 to March 2012. The annual mean concentrations of PM2.5, PM10 and CO were 42 ± 17 μg m(-3), 114 ± 31 μg m(-3) and 343 ± 136 ppbv, respectively. Concentrations of both particulate and CO showed high values during winter/pre-monsoon (dry) period and lowest in the monsoon season (wet). Local anthropogenic emission and long-range transport from open biomass burning sources along with favourable synoptic meteorology led to elevated levels of pollutants in the dry season...
March 24, 2017: Environmental Pollution
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