PMID- 30872037 OWN - NLM STAT- In-Data-Review LR - 20190427 IS - 1095-8584 (Electronic) IS - 0022-2828 (Linking) VI - 129 DP - 2019 Apr TI - Bicuspid aortic valve, atherosclerosis and changes of lipid metabolism: Are there pathological molecular links? PG - 231-235 LID - S0022-2828(18)31091-5 [pii] LID - 10.1016/j.yjmcc.2019.03.004 [doi] AB - Bicuspid aortic valve (BAV) is recognized as a syndrome including aortic valve diseases and aortic wall alterations, such as aortic dilatation, dissection and rupture, but also coronary atherosclerosis. The current evidence, although partially controversial, suggests that several molecular mechanisms promoting atherosclerosis are activated in BAV patients and are involved in the progression of the related diseases, from aortic stenosis to aortopathies, along with altered hemodynamics. Among these factors, dyslipidemia (i.e., high LDL cholesterol, high lipoprotein (a)) and the activation of specific pro-inflammatory pathways (nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 inflammasome and Toll-like receptor 4) appear to play a pivotal role in the progression of BAV-associated diseases. The further elucidation of such molecular mechanisms may lead to a better and personalized prognosis and follow-up for BAV patients and suggest novel pharmacological approaches to prevent disease progression. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Magni, Paolo AU - Magni P AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita' degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy; IRCCS MultiMedica, via Milanese 300, 20099, Sesto S. Giovanni, Milano, Italy. Electronic address: paolo.magni@unimi.it. LA - eng PT - Journal Article PT - Review DEP - 20190311 PL - England TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 OTO - NOTNLM OT - Atherosclerosis OT - BAV OT - Cholesterol OT - Dyslipidemia OT - Inflammation OT - LDL cholesterol OT - Lipoprotein(a) EDAT- 2019/03/16 06:00 MHDA- 2019/03/16 06:00 CRDT- 2019/03/16 06:00 PHST- 2019/01/08 00:00 [received] PHST- 2019/03/03 00:00 [revised] PHST- 2019/03/07 00:00 [accepted] PHST- 2019/03/16 06:00 [pubmed] PHST- 2019/03/16 06:00 [medline] PHST- 2019/03/16 06:00 [entrez] AID - S0022-2828(18)31091-5 [pii] AID - 10.1016/j.yjmcc.2019.03.004 [doi] PST - ppublish SO - J Mol Cell Cardiol. 2019 Apr;129:231-235. doi: 10.1016/j.yjmcc.2019.03.004. Epub 2019 Mar 11. PMID- 30795775 OWN - NLM STAT- In-Data-Review LR - 20190305 IS - 1475-2891 (Electronic) IS - 1475-2891 (Linking) VI - 18 IP - 1 DP - 2019 Feb 22 TI - Nutraceutical approach for the management of cardiovascular risk - a combination containing the probiotic Bifidobacterium longum BB536 and red yeast rice extract: results from a randomized, double-blind, placebo-controlled study. PG - 13 LID - 10.1186/s12937-019-0438-2 [doi] AB - BACKGROUND: Probiotics incorporated into dairy products have been shown to reduce total (TC) and LDL cholesterolemia (LDL-C) in subjects with moderate hypercholesterolemia. More specifically, probiotics with high biliary salt hydrolase activity, e.g. Bifidobacterium longum BB536, may decrease TC and LDL-C by lowering intestinal cholesterol reabsorption and, combined with other nutraceuticals, may be useful to manage hypercholesterolemia in subjects with low cardiovascular (CV) risk. This study was conducted to evaluate the efficacy and safety of a nutraceutical combination containing Bifidobacterium longum BB536, red yeast rice (RYR) extract (10 mg/day monacolin K), niacin, coenzyme Q10 (Lactoflorene Colesterolo(R)). The end-points were changes of lipid CV risk markers (LDL-C, TC, non-HDL-cholesterol (HDL-C), triglycerides (TG), apolipoprotein B (ApoB), HDL-C, apolipoprotein AI (ApoAI), lipoprotein(a) (Lp(a), proprotein convertase subtilisin/kexin type 9 (PCSK9)), and of markers of cholesterol synthesis/absorption. METHODS: A 12-week randomized, parallel, double-blind, placebo-controlled study. Thirty-three subjects (18-70 years) in primary CV prevention and low CV risk (SCORE: 0-1% in 24 and 2-4% in 9 subjects; LDL-C: 130-200 mg/dL) were randomly allocated to either nutraceutical (N = 16) or placebo (N = 17). RESULTS: Twelve-week treatment with the nutraceutical combination, compared to placebo, significantly reduced TC (- 16.7%), LDL-C (- 25.7%), non-HDL-C (- 24%) (all p < 0.0001), apoB (- 17%, p = 0.003). TG, HDL-C, apoAI, Lp(a), PCSK9 were unchanged. Lathosterol:TC ratio was significantly reduced by the nutraceutical combination, while campesterol:TC ratio and sitosterol:TC ratio did not change, suggesting reduction of synthesis without increased absorption of cholesterol. No adverse effects and a 97% compliance were observed. CONCLUSIONS: A 12-week treatment with a nutraceutical combination containing the probiotic Bifidobacterium longum BB536 and RYR extract significantly improved the atherogenic lipid profile and was well tolerated by low CV risk subjects. TRIAL REGISTRATION: NCT02689934 . FAU - Ruscica, Massimiliano AU - Ruscica M AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy. FAU - Pavanello, Chiara AU - Pavanello C AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy. AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Centro E. Grossi Paoletti, Universita degli Studi di Milano, Milan, Italy. FAU - Gandini, Sara AU - Gandini S AD - Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. FAU - Macchi, Chiara AU - Macchi C AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy. FAU - Botta, Margherita AU - Botta M AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy. FAU - Dall'Orto, Daria AU - Dall'Orto D AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy. FAU - Del Puppo, Marina AU - Del Puppo M AD - Dipartimento di Medicina e Chirurgia, Universita degli Studi di Milano Bicocca, Monza, Italy. FAU - Bertolotti, Marco AU - Bertolotti M AD - Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Universita degli Studi di Modena e Reggio Emilia, Modena, Italy. FAU - Bosisio, Raffaella AU - Bosisio R AD - Centro Dislipidemie, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. FAU - Mombelli, Giuliana AU - Mombelli G AD - Centro Dislipidemie, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. FAU - Sirtori, Cesare R AU - Sirtori CR AD - Centro Dislipidemie, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. FAU - Calabresi, Laura AU - Calabresi L AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy. AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Centro E. Grossi Paoletti, Universita degli Studi di Milano, Milan, Italy. FAU - Magni, Paolo AU - Magni P AUID- ORCID: http://orcid.org/0000-0002-2254-8881 AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy. paolo.magni@unimi.it. AD - IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy. paolo.magni@unimi.it. LA - eng SI - ClinicalTrials.gov/NCT02689934 PT - Journal Article DEP - 20190222 PL - England TA - Nutr J JT - Nutrition journal JID - 101152213 PMC - PMC6387491 OTO - NOTNLM OT - Cardiovascular risk OT - Hypercholesterolemia OT - LDL-cholesterol OT - Monacolin K OT - Non-HDL cholesterol OT - Nutraceutical OT - Probiotic EDAT- 2019/02/24 06:00 MHDA- 2019/02/24 06:00 CRDT- 2019/02/24 06:00 PHST- 2018/09/11 00:00 [received] PHST- 2019/02/18 00:00 [accepted] PHST- 2019/02/24 06:00 [entrez] PHST- 2019/02/24 06:00 [pubmed] PHST- 2019/02/24 06:00 [medline] AID - 10.1186/s12937-019-0438-2 [doi] AID - 10.1186/s12937-019-0438-2 [pii] PST - epublish SO - Nutr J. 2019 Feb 22;18(1):13. doi: 10.1186/s12937-019-0438-2. PMID- 29948947 OWN - NLM STAT- In-Process LR - 20190308 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 56 IP - 2 DP - 2019 Feb TI - GABA-B1 Receptor-Null Schwann Cells Exhibit Compromised In Vitro Myelination. PG - 1461-1474 LID - 10.1007/s12035-018-1158-x [doi] AB - GABA-B receptors are important for Schwann cell (SC) commitment to a non-myelinating phenotype during development. However, the P0-GABA-B1(fl/fl) conditional knockout mice, lacking the GABA-B1 receptor specifically in SCs, also presented axon modifications, suggesting SC non-autonomous effects through the neuronal compartment. In this in vitro study, we evaluated whether the specific deletion of the GABA-B1 receptor in SCs may induce autonomous or non-autonomous cross-changes in sensory dorsal root ganglia (DRG) neurons. To this end, we performed an in vitro biomolecular and transcriptomic analysis of SC and DRG neuron primary cultures from P0-GABA-B1(fl/fl) mice. We found that cells from conditional P0-GABA-B1(fl/fl) mice exhibited proliferative, migratory and myelinating alterations. Moreover, we found transcriptomic changes in novel molecules that are involved in peripheral neuron-SC interaction. FAU - Faroni, Alessandro AU - Faroni A AD - Blond McIndoe Laboratories, Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK. FAU - Melfi, Simona AU - Melfi S AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via G. Balzaretti 9, 20133, Milan, Italy. FAU - Castelnovo, Luca Franco AU - Castelnovo LF AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via G. Balzaretti 9, 20133, Milan, Italy. FAU - Bonalume, Veronica AU - Bonalume V AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via G. Balzaretti 9, 20133, Milan, Italy. FAU - Colleoni, Deborah AU - Colleoni D AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via G. Balzaretti 9, 20133, Milan, Italy. FAU - Magni, Paolo AU - Magni P AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via G. Balzaretti 9, 20133, Milan, Italy. FAU - Arauzo-Bravo, Marcos J AU - Arauzo-Bravo MJ AD - Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastian, Spain. AD - Ikerbasque, Basque Foundation for Science, Bilbao, Spain. FAU - Reinbold, Rolland AU - Reinbold R AD - Institute of Biomedical Technologies, National Research Council, Milan, Italy. FAU - Magnaghi, Valerio AU - Magnaghi V AUID- ORCID: http://orcid.org/0000-0002-6903-7042 AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via G. Balzaretti 9, 20133, Milan, Italy. valerio.magnaghi@unimi.it. LA - eng GR - Progetto di Eccellenza/Ministry of Italian University and Research (MIUR) GR - MINECO BFU 2016-7798-P/Ministerio de Economia y Competitividad GR - DFG15/15; DFG 141/16/Diputacion Foral de Gipuzkoa Spain PT - Journal Article DEP - 20180612 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 OTO - NOTNLM OT - Conditional mice OT - GABA-A receptor OT - Gamma-aminobutyric acid OT - Peripheral nerve regeneration EDAT- 2018/06/28 06:00 MHDA- 2018/06/28 06:00 CRDT- 2018/06/28 06:00 PHST- 2018/02/15 00:00 [received] PHST- 2018/05/28 00:00 [accepted] PHST- 2018/06/28 06:00 [pubmed] PHST- 2018/06/28 06:00 [medline] PHST- 2018/06/28 06:00 [entrez] AID - 10.1007/s12035-018-1158-x [doi] AID - 10.1007/s12035-018-1158-x [pii] PST - ppublish SO - Mol Neurobiol. 2019 Feb;56(2):1461-1474. doi: 10.1007/s12035-018-1158-x. Epub 2018 Jun 12. PMID- 29852278 OWN - NLM STAT- MEDLINE DCOM- 20181126 LR - 20181126 IS - 1388-1981 (Print) IS - 1388-1981 (Linking) VI - 1863 IP - 9 DP - 2018 Sep TI - Plasma PCSK9 levels and lipoprotein distribution are preserved in carriers of genetic HDL disorders. PG - 991-997 LID - S1388-1981(18)30118-5 [pii] LID - 10.1016/j.bbalip.2018.05.015 [doi] AB - Proprotein convertase subtilisin/kexin 9 (PCSK9), a protein regulating the number of cell-surface LDL receptors (LDLR), circulates partially associated to plasma lipoproteins. How this interaction alters PCSK9 plasma levels is still unclear. In the present study, we took advantage of the availability of a large cohort of carriers of genetic HDL disorders to evaluate how HDL defects affect plasma PCSK9 levels and its distribution among lipoproteins. Plasma PCSK9 concentrations were determined by ELISA in carriers of mutations in LCAT, ABCA1, or APOAI genes, and lipoprotein distribution was analyzed by FPLC. Carriers of one or two mutations in the LCAT gene show plasma PCSK9 levels comparable to that of unaffected family controls (homozygotes, 159.4ng/mL (124.9;243.3); heterozygotes, 180.3ng/mL (127.6;251.5) and controls, 190.4ng/mL (146.7;264.4); P for trend=0.33). Measurement of PCSK9 in plasma of subjects carrying mutations in ABCA1 or APOAI genes confirmed normal values. When fractionated by FPLC, PCSK9 peaked in a region between LDL and HDL in control subjects. In carriers of all HDL defects, lipoprotein profile shows a strong reduction of HDL, but the distribution of PCSK9 was superimposable to that of controls. In conclusion, the present study demonstrates that in genetically determined low HDL states plasma PCSK9 concentrations and lipoprotein distribution are preserved, thus suggesting that HDL may not be involved in PCSK9 transport in plasma. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Ruscica, Massimiliano AU - Ruscica M AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Italy. FAU - Simonelli, Sara AU - Simonelli S AD - Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Italy. FAU - Botta, Margherita AU - Botta M AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Italy. FAU - Ossoli, Alice AU - Ossoli A AD - Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Italy. FAU - Lupo, Maria Giovanna AU - Lupo MG AD - Department of Pharmaceutical and Pharmacological Sciences, Universita degli Studi Padova, Italy. FAU - Magni, Paolo AU - Magni P AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Italy. FAU - Corsini, Alberto AU - Corsini A AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Italy; Multimedica IRCCS, Milano, Italy. FAU - Arca, Marcello AU - Arca M AD - Atherosclerosis Center, Department of Internal Medicine and Allied Sciences, Sapienza University of Rome, Italy. FAU - Pisciotta, Livia AU - Pisciotta L AD - Department of Internal Medicine, University of Genova, Italy. FAU - Veglia, Fabrizio AU - Veglia F AD - IRCCS Centro Cardiologico Monzino, Milano, Italy. FAU - Franceschini, Guido AU - Franceschini G AD - Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Italy. FAU - Ferri, Nicola AU - Ferri N AD - Department of Pharmaceutical and Pharmacological Sciences, Universita degli Studi Padova, Italy. FAU - Calabresi, Laura AU - Calabresi L AD - Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Italy. Electronic address: laura.calabresi@unimi.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180529 PL - Netherlands TA - Biochim Biophys Acta Mol Cell Biol Lipids JT - Biochimica et biophysica acta. Molecular and cell biology of lipids JID - 101731727 RN - 0 (ABCA1 protein, human) RN - 0 (ATP Binding Cassette Transporter 1) RN - 0 (Apolipoprotein A-I) RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, LDL) RN - 0 (apolipoprotein A-I Paris) RN - EC 2.3.1.43 (LCAT protein, human) RN - EC 2.3.1.43 (Phosphatidylcholine-Sterol O-Acyltransferase) RN - EC 3.4.21.- (PCSK9 protein, human) RN - EC 3.4.21.- (Proprotein Convertase 9) SB - IM MH - ATP Binding Cassette Transporter 1/*blood/deficiency/genetics MH - Adult MH - Aged MH - Apolipoprotein A-I/*blood/deficiency/genetics MH - Case-Control Studies MH - Female MH - Gene Expression Regulation MH - Heterozygote MH - Homozygote MH - Humans MH - Hypolipoproteinemias/*blood/genetics/pathology MH - Lipoproteins, HDL/blood/genetics MH - Lipoproteins, LDL/blood/genetics MH - Male MH - Middle Aged MH - Phosphatidylcholine-Sterol O-Acyltransferase/*blood/genetics MH - Proprotein Convertase 9/*blood/genetics OTO - NOTNLM OT - *Genetic HDL disorders OT - *High-density lipoproteins OT - *Lecithin:cholesterol acyltransferase OT - *Proprotein convertase subtilisin/kexin 9 EDAT- 2018/06/01 06:00 MHDA- 2018/11/27 06:00 CRDT- 2018/06/01 06:00 PHST- 2017/10/10 00:00 [received] PHST- 2018/04/18 00:00 [revised] PHST- 2018/05/27 00:00 [accepted] PHST- 2018/06/01 06:00 [pubmed] PHST- 2018/11/27 06:00 [medline] PHST- 2018/06/01 06:00 [entrez] AID - S1388-1981(18)30118-5 [pii] AID - 10.1016/j.bbalip.2018.05.015 [doi] PST - ppublish SO - Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Sep;1863(9):991-997. doi: 10.1016/j.bbalip.2018.05.015. Epub 2018 May 29. PMID- 27757595 OWN - NLM STAT- MEDLINE DCOM- 20180904 LR - 20181113 IS - 1436-6215 (Electronic) IS - 1436-6207 (Linking) VI - 57 IP - 2 DP - 2018 Mar TI - Effect of soy on metabolic syndrome and cardiovascular risk factors: a randomized controlled trial. PG - 499-511 LID - 10.1007/s00394-016-1333-7 [doi] AB - BACKGROUND: Cardiovascular diseases are currently the commonest cause of death worldwide. Different strategies for their primary prevention have been planned, taking into account the main known risk factors, which include an atherogenic lipid profile and visceral fat excess. METHODS: The study was designed as a randomized, parallel, single-center study with a nutritional intervention duration of 12 weeks. Whole soy foods corresponding to 30 g/day soy protein were given in substitution of animal foods containing the same protein amount. RESULTS: Soy nutritional intervention resulted in a reduction in the number of MetS features in 13/26 subjects. Moreover, in the soy group we observed a significant improvement of median percentage changes for body weight (-1.5 %) and BMI (-1.5 %), as well as for atherogenic lipid markers, namely TC (-4.85 %), LDL-C (-5.25 %), non-HDL-C (-7.14 %) and apoB (-14.8 %). Since the majority of the studied variables were strongly correlated, three factors were identified which explained the majority (52 %) of the total variance in the whole data set. Among them, factor 1, which loaded lipid and adipose variables, explained the 22 % of total variance, showing a statistically significant difference between treatment arms (p = 0.002). CONCLUSIONS: The inclusion of whole soy foods (corresponding to 30 g/day protein) in a lipid-lowering diet significantly improved a relevant set of biomarkers associated with cardiovascular risk. FAU - Ruscica, Massimiliano AU - Ruscica M AUID- ORCID: http://orcid.org/0000-0002-0195-7061 AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. massimiliano.ruscica@unimi.it. FAU - Pavanello, Chiara AU - Pavanello C AD - Centro Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Gandini, Sara AU - Gandini S AD - Division of Epidemiology and Biostatistics, European Institute of Oncology, 20146, Milan, Italy. FAU - Gomaraschi, Monica AU - Gomaraschi M AD - Centro Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Vitali, Cecilia AU - Vitali C AD - Centro Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Macchi, Chiara AU - Macchi C AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Morlotti, Beatrice AU - Morlotti B AD - Centro Dislipidemie, A.S.S.T. Grande Ospedale Metropolitano Niguarda, Milan, Italy. FAU - Aiello, Gilda AU - Aiello G AD - Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Milano, Milan, Italy. FAU - Bosisio, Raffaella AU - Bosisio R AD - Centro Dislipidemie, A.S.S.T. Grande Ospedale Metropolitano Niguarda, Milan, Italy. FAU - Calabresi, Laura AU - Calabresi L AD - Centro Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Arnoldi, Anna AU - Arnoldi A AD - Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Milano, Milan, Italy. FAU - Sirtori, Cesare R AU - Sirtori CR AD - Centro Dislipidemie, A.S.S.T. Grande Ospedale Metropolitano Niguarda, Milan, Italy. FAU - Magni, Paolo AU - Magni P AD - Centro Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. paolo.magni@unimi.it. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20161018 PL - Germany TA - Eur J Nutr JT - European journal of nutrition JID - 100888704 RN - 0 (Biomarkers) RN - 0 (Cholesterol, LDL) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Adiposity MH - Aged MH - Biomarkers/blood MH - Body Mass Index MH - Cardiovascular Diseases/epidemiology/etiology/*prevention & control MH - Cholesterol/blood MH - Cholesterol, LDL/blood MH - Cohort Studies MH - *Diet, Fat-Restricted MH - Dyslipidemias/blood/complications/*diet therapy/physiopathology MH - Female MH - *Functional Food MH - Humans MH - Italy/epidemiology MH - Male MH - Metabolic Syndrome/epidemiology/etiology/*prevention & control MH - Middle Aged MH - Overweight/blood/complications/*diet therapy/physiopathology MH - Risk Factors MH - *Soy Foods MH - Waist Circumference MH - Weight Loss OTO - NOTNLM OT - Lipids OT - Metabolic syndrome and obesity OT - Soy protein EDAT- 2016/10/21 06:00 MHDA- 2018/09/05 06:00 CRDT- 2016/10/21 06:00 PHST- 2016/06/23 00:00 [received] PHST- 2016/10/12 00:00 [accepted] PHST- 2016/10/21 06:00 [pubmed] PHST- 2018/09/05 06:00 [medline] PHST- 2016/10/21 06:00 [entrez] AID - 10.1007/s00394-016-1333-7 [doi] AID - 10.1007/s00394-016-1333-7 [pii] PST - ppublish SO - Eur J Nutr. 2018 Mar;57(2):499-511. doi: 10.1007/s00394-016-1333-7. Epub 2016 Oct 18. PMID- 29396407 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20190202 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 8 IP - 1 DP - 2018 Feb 2 TI - High Density Lipoproteins Inhibit Oxidative Stress-Induced Prostate Cancer Cell Proliferation. PG - 2236 LID - 10.1038/s41598-018-19568-8 [doi] AB - Recent evidence suggests that oxidative stress can play a role in the pathogenesis and the progression of prostate cancer (PCa). Reactive oxygen species (ROS) generation is higher in PCa cells compared to normal prostate epithelial cells and this increase is proportional to the aggressiveness of the phenotype. Since high density lipoproteins (HDL) are known to exert antioxidant activities, their ability to reduce ROS levels and the consequent impact on cell proliferation was tested in normal and PCa cell lines. HDL significantly reduced basal and H2O2-induced oxidative stress in normal, androgen receptor (AR)-positive and AR-null PCa cell lines. AR, scavenger receptor BI and ATP binding cassette G1 transporter were not involved. In addition, HDL completely blunted H2O2-induced increase of cell proliferation, through their capacity to prevent the H2O2-induced shift of cell cycle distribution from G0/G1 towards G2/M phase. Synthetic HDL, made of the two main components of plasma-derived HDL (apoA-I and phosphatidylcholine) and which are under clinical development as anti-atherosclerotic agents, retained the ability of HDL to inhibit ROS production in PCa cells. Collectively, HDL antioxidant activity limits cell proliferation induced by ROS in AR-positive and AR-null PCa cell lines, thus supporting a possible role of HDL against PCa progression. FAU - Ruscica, Massimiliano AU - Ruscica M AUID- ORCID: http://orcid.org/0000-0002-0195-7061 AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milano, Italy. FAU - Botta, Margherita AU - Botta M AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milano, Italy. FAU - Ferri, Nicola AU - Ferri N AD - Dipartimento di Scienze del Farmaco, Universita degli Studi di Padova, Padova, Italy. FAU - Giorgio, Eleonora AU - Giorgio E AD - Centro Enrica Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milano, Italy. FAU - Macchi, Chiara AU - Macchi C AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milano, Italy. FAU - Franceschini, Guido AU - Franceschini G AD - Centro Enrica Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milano, Italy. FAU - Magni, Paolo AU - Magni P AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milano, Italy. paolo.magni@unimi.it. FAU - Calabresi, Laura AU - Calabresi L AD - Centro Enrica Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milano, Italy. FAU - Gomaraschi, Monica AU - Gomaraschi M AD - Centro Enrica Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milano, Italy. monica.gomaraschi@unimi.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180202 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Antioxidants) RN - 0 (Apolipoprotein A-I) RN - 0 (Lipoproteins, HDL) RN - 0 (Phosphatidylcholines) RN - 0 (RNA, Small Interfering) RN - BBX060AN9V (Hydrogen Peroxide) SB - IM MH - Antioxidants/chemical synthesis/*pharmacology MH - Apolipoprotein A-I/chemical synthesis/*pharmacology MH - Cell Cycle/drug effects MH - Cell Line, Tumor MH - Cell Proliferation/*drug effects MH - Healthy Volunteers MH - Humans MH - Hydrogen Peroxide/metabolism MH - Lipoproteins, HDL/*metabolism MH - Male MH - Oxidative Stress/*drug effects MH - PC-3 Cells MH - Phosphatidylcholines/chemical synthesis/*pharmacology MH - Prostatic Neoplasms/*pathology MH - RNA Interference MH - RNA, Small Interfering/genetics PMC - PMC5797231 EDAT- 2018/02/06 06:00 MHDA- 2018/12/12 06:00 CRDT- 2018/02/04 06:00 PHST- 2017/07/24 00:00 [received] PHST- 2018/01/04 00:00 [accepted] PHST- 2018/02/04 06:00 [entrez] PHST- 2018/02/06 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] AID - 10.1038/s41598-018-19568-8 [doi] AID - 10.1038/s41598-018-19568-8 [pii] PST - epublish SO - Sci Rep. 2018 Feb 2;8(1):2236. doi: 10.1038/s41598-018-19568-8. PMID- 28648620 OWN - NLM STAT- MEDLINE DCOM- 20180423 LR - 20181105 IS - 1872-8057 (Electronic) IS - 0303-7207 (Linking) VI - 454 DP - 2017 Oct 15 TI - Iron overload induces hypogonadism in male mice via extrahypothalamic mechanisms. PG - 135-145 LID - S0303-7207(17)30346-5 [pii] LID - 10.1016/j.mce.2017.06.019 [doi] AB - INTRODUCTION: Iron overload leads to multiple organ damage including endocrine organ dysfunctions. Hypogonadism is the most common non-diabetic endocrinopathy in primary and secondary iron overload syndromes. AIM: To explore the molecular determinants of iron overload-induced hypogonadism with specific focus on hypothalamic derangements. A dysmetabolic male murine model fed iron-enriched diet (IED) and cell-based models of gonadotropin-releasing hormone (GnRH) neurons were used. RESULTS: Mice fed IED showed severe hypogonadism with a significant reduction of serum levels of testosterone (-83%) and of luteinizing hormone (-86%), as well as reduced body weight gain, body fat and plasma leptin. IED mice had a significant increment in iron concentration in testes and in the pituitary. Even if iron challenge of in vitro neuronal models (GN-11 and GT1-7 GnRH cells) resulted in 10- and 5-fold iron content increments, respectively, no iron content changes were found in vivo in hypothalamus of IED mice. Conversely, mice placed on IED showed a significant increment in hypothalamic GnRH gene expression (+34%) and in the intensity of GnRH-neuron innervation of the median eminence (+1.5-fold); similar changes were found in the murine model HFE(-/-), resembling human hemochromatosis. CONCLUSIONS: IED-fed adult male mice show severe impairment of hypothalamus-pituitary-gonadal axis without a relevant contribution of the hypothalamic compartment, which thus appears sufficiently protected from systemic iron overload. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Macchi, Chiara AU - Macchi C AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, 20133 Milan, Italy. FAU - Steffani, Liliana AU - Steffani L AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, 20133 Milan, Italy. FAU - Oleari, Roberto AU - Oleari R AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, 20133 Milan, Italy. FAU - Lettieri, Antonella AU - Lettieri A AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, 20133 Milan, Italy. FAU - Valenti, Luca AU - Valenti L AD - Pathophysiology and Transplantation, Universita degli Studi Milano, UO Medicina Interna 1B, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20100 Milan, Italy. FAU - Dongiovanni, Paola AU - Dongiovanni P AD - Pathophysiology and Transplantation, Universita degli Studi Milano, UO Medicina Interna 1B, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20100 Milan, Italy. FAU - Romero-Ruiz, Antonio AU - Romero-Ruiz A AD - Department of Cell Biology, Physiology and Immunology, University of Cordoba, Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Hospital Universitario Reina Sofia, 14004 Cordoba, Spain. FAU - Tena-Sempere, Manuel AU - Tena-Sempere M AD - Department of Cell Biology, Physiology and Immunology, University of Cordoba, Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Hospital Universitario Reina Sofia, 14004 Cordoba, Spain; CIBER Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos III, 14004 Cordoba, Spain. FAU - Cariboni, Anna AU - Cariboni A AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, 20133 Milan, Italy. Electronic address: anna.cariboni@unimi.it. FAU - Magni, Paolo AU - Magni P AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, 20133 Milan, Italy. Electronic address: paolo.magni@unimi.it. FAU - Ruscica, Massimiliano AU - Ruscica M AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, 20133 Milan, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170623 PL - Ireland TA - Mol Cell Endocrinol JT - Molecular and cellular endocrinology JID - 7500844 RN - 0 (Ferric Compounds) RN - 0 (Quaternary Ammonium Compounds) RN - 33515-09-2 (Gonadotropin-Releasing Hormone) RN - E1UOL152H7 (Iron) RN - UVP74NG1C5 (ferric ammonium citrate) SB - IM MH - Animals MH - Cell Line MH - Diet MH - Ferric Compounds/pharmacology MH - Gonadotropin-Releasing Hormone/metabolism MH - Homeostasis/drug effects MH - Hypogonadism/*etiology MH - Hypothalamo-Hypophyseal System/metabolism MH - Hypothalamus/drug effects/*metabolism MH - Iron/pharmacology MH - Iron Overload/*complications MH - Male MH - Mice, Inbred C57BL MH - Phenotype MH - Quaternary Ammonium Compounds/pharmacology MH - Testis/metabolism OTO - NOTNLM OT - *GnRH OT - *Hypogonadism OT - *Iron overload OT - *Median eminence OT - *Testes EDAT- 2017/06/27 06:00 MHDA- 2018/04/24 06:00 CRDT- 2017/06/27 06:00 PHST- 2017/02/02 00:00 [received] PHST- 2017/06/08 00:00 [revised] PHST- 2017/06/17 00:00 [accepted] PHST- 2017/06/27 06:00 [pubmed] PHST- 2018/04/24 06:00 [medline] PHST- 2017/06/27 06:00 [entrez] AID - S0303-7207(17)30346-5 [pii] AID - 10.1016/j.mce.2017.06.019 [doi] PST - ppublish SO - Mol Cell Endocrinol. 2017 Oct 15;454:135-145. doi: 10.1016/j.mce.2017.06.019. Epub 2017 Jun 23. PMID- 28710141 OWN - NLM STAT- MEDLINE DCOM- 20180423 LR - 20181113 IS - 2156-5376 (Electronic) IS - 2161-8313 (Linking) VI - 8 IP - 4 DP - 2017 Jul TI - Perspective: Improving Nutritional Guidelines for Sustainable Health Policies: Current Status and Perspectives. PG - 532-545 LID - 10.3945/an.116.014738 [doi] AB - A large body of evidence supports the notion that incorrect or insufficient nutrition contributes to disease development. A pivotal goal is thus to understand what exactly is appropriate and what is inappropriate in food ingestion and the consequent nutritional status and health. The effective application of these concepts requires the translation of scientific information into practical approaches that have a tangible and measurable impact at both individual and population levels. The agenda for the future is expected to support available methodology in nutrition research to personalize guideline recommendations, properly grading the quality of the available evidence, promoting adherence to the well-established evidence hierarchy in nutrition, and enhancing strategies for appropriate vetting and transparent reporting that will solidify the recommendations for health promotion. The final goal is to build a constructive coalition among scientists, policy makers, and communication professionals for sustainable health and nutritional policies. Currently, a strong rationale and available data support a personalized dietary approach according to personal variables, including sex and age, circulating metabolic biomarkers, food quality and intake frequency, lifestyle variables such as physical activity, and environmental variables including one's microbiome profile. There is a strong and urgent need to develop a successful commitment among all the stakeholders to define novel and sustainable approaches toward the management of the health value of nutrition at individual and population levels. Moving forward requires adherence to well-established principles of evidence evaluation as well as identification of effective tools to obtain better quality evidence. Much remains to be done in the near future. CI - (c) 2017 American Society for Nutrition. FAU - Magni, Paolo AU - Magni P AUID- ORCID: http://orcid.org/0000-0002-2254-8881 AD - Department of Pharmacological and Biomolecular Sciences, and paolo.magni@unimi.it andrea.peracino@lorenzinifoundation.org. FAU - Bier, Dennis M AU - Bier DM AD - Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX. FAU - Pecorelli, Sergio AU - Pecorelli S AD - Giovanni Lorenzini Medical Science Foundation, Houston, TX. FAU - Agostoni, Carlo AU - Agostoni C AD - Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, DISCCO, Universita degli Studi di Milano, Milan, Italy. FAU - Astrup, Arne AU - Astrup A AD - Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark. FAU - Brighenti, Furio AU - Brighenti F AD - Department of Food Sciences, University of Parma, Parma, Italy. FAU - Cook, Robert AU - Cook R AD - Bazian, Economist Intelligence Unit Healthcare, London, United Kingdom. FAU - Folco, Emanuela AU - Folco E AD - Giovanni Lorenzini Medical Science Foundation, Milan, Italy. FAU - Fontana, Luigi AU - Fontana L AD - Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. AD - Department of Medicine, Washington University, St. Louis, MO. FAU - Gibson, Robert A AU - Gibson RA AD - School of Agriculture, Food and Wine, FOODplus Research Centre, University of Adelaide, Adelaide, Australia. FAU - Guerra, Ranieri AU - Guerra R AD - Department of Preventive Health, Ministry of Health, Rome, Italy. FAU - Guyatt, Gordon H AU - Guyatt GH AD - Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada. FAU - Ioannidis, John Pa AU - Ioannidis JP AD - Department of Health Policy and Research, Stanford University, Stanford, CA. FAU - Jackson, Ann S AU - Jackson AS AD - Giovanni Lorenzini Medical Science Foundation, Houston, TX. FAU - Klurfeld, David M AU - Klurfeld DM AD - Human Nutrition Program, USDA Agricultural Research Service, Beltsville, MD. FAU - Makrides, Maria AU - Makrides M AD - Healthy Mothers, Babies and Children, South Australian Health and Medical Research Institute, Adelaide, Australia. FAU - Mathioudakis, Basil AU - Mathioudakis B AD - Consulting sprl, Food Legislation and Nutrition, Brussels, Belgium. FAU - Monaco, Alessandro AU - Monaco A AD - Giovanni Lorenzini Medical Science Foundation, Milan, Italy. FAU - Patel, Chirag J AU - Patel CJ AD - Department of Biomedical Informatics, Harvard Medical School, Boston, MA. FAU - Racagni, Giorgio AU - Racagni G AD - Department of Pharmacological and Biomolecular Sciences, and. FAU - Schunemann, Holger J AU - Schunemann HJ AD - Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada. FAU - Shamir, Raanan AU - Shamir R AD - Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine, University of Tel Aviv, Tel Aviv, Israel; and. FAU - Zmora, Niv AU - Zmora N AD - Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. FAU - Peracino, Andrea AU - Peracino A AD - Giovanni Lorenzini Medical Science Foundation, Milan, Italy; paolo.magni@unimi.it andrea.peracino@lorenzinifoundation.org. LA - eng GR - R00 ES023504/ES/NIEHS NIH HHS/United States PT - Journal Article DEP - 20170714 PL - United States TA - Adv Nutr JT - Advances in nutrition (Bethesda, Md.) JID - 101540874 SB - IM MH - Databases, Factual MH - Health Promotion/*legislation & jurisprudence/*standards MH - Healthy Diet/*standards MH - Humans MH - Life Style MH - Nutrition Policy/*legislation & jurisprudence MH - Nutritional Status PMC - PMC5502870 OTO - NOTNLM OT - food OT - genetics OT - microbiome OT - nutritional status OT - personalized nutrition COIS- Author disclosures: PM, DMB, SP, CA, AA, FB, RC, EF, LF, RAG, RG, GHG, JPAI, ASJ, DMK, MM, BM, AM, CJP, GR, HJS, RS, NZ, and AP, no conflicts of interest. EDAT- 2017/07/16 06:00 MHDA- 2018/04/24 06:00 CRDT- 2017/07/16 06:00 PHST- 2017/07/16 06:00 [entrez] PHST- 2017/07/16 06:00 [pubmed] PHST- 2018/04/24 06:00 [medline] AID - 8/4/532 [pii] AID - 10.3945/an.116.014738 [doi] PST - epublish SO - Adv Nutr. 2017 Jul 14;8(4):532-545. doi: 10.3945/an.116.014738. Print 2017 Jul. PMID- 26548330 OWN - NLM STAT- MEDLINE DCOM- 20170626 LR - 20180313 IS - 1878-1810 (Electronic) IS - 1878-1810 (Linking) VI - 173 DP - 2016 Jul TI - Proprotein convertase subtilisin kexin type 9 and high-density lipoprotein metabolism: experimental animal models and clinical evidence. PG - 19-29 LID - S1931-5244(15)00345-X [pii] LID - 10.1016/j.trsl.2015.10.004 [doi] AB - Proprotein convertase subtilisin kexin type 9 (PCSK9) belongs to the proprotein convertase family. Several studies have demonstrated its involvement in the regulation of low-density lipoprotein (LDL) cholesterol levels by inducing the degradation of the LDL receptor (LDLR). However, experimental, epidemiologic, and pharmacologic data provide important evidence on the role of PCSK9 also on high-density lipoproteins (HDLs). In mice, PCSK9 regulates the HDL cholesterol (HDL-C) levels by the degradation of hepatic LDLR, thus inhibiting the uptake of apolipoprotein (Apo)E-containing HDLs. Several epidemiologic and genetic studies reported positive relationship between PCSK9 and HDL-C levels, likely by reducing the uptake of the ApoE-containing HDL particles. PCSK9 enhances also the degradation of LDLR's closest family members, ApoE receptor 2, very low-density lipoprotein receptor, and LDLR-related protein 1. This feature provides a molecular mechanism by which PCSK9 may affect HDL metabolism. Experimental studies demonstrated that PCSK9 directly interacts with HDL by modulating PCSK9 self-assembly and its binding to the LDLR. Finally, the inhibition of PCSK9 by means of monoclonal antibodies directed to PCSK9 (ie, evolocumab and alirocumab) determines an increase of HDL-C fraction by 7% and 4.2%, respectively. Thus, the understanding of the role of PCSK9 on HDL metabolism needs to be elucidated with a particular focus on the effect of PCSK9 on HDL-mediated reverse cholesterol transport. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Ferri, Nicola AU - Ferri N AD - Dipartimento di Scienze del Farmaco, Universita di Padova, Padua, Italy. Electronic address: nicola.ferri@unipd.it. FAU - Corsini, Alberto AU - Corsini A AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy; Multimedica IRCCS, Milan, Italy. FAU - Macchi, Chiara AU - Macchi C AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. FAU - Magni, Paolo AU - Magni P AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy; Centro per lo Studio delle Malattie Dismetaboliche e delle Iperlipemie-Enrica Grossi Paoletti, Universita degli Studi di Milano, Milan, Italy. FAU - Ruscica, Massimiliano AU - Ruscica M AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Milan, Italy. Electronic address: massimiliano.ruscica@unimi.it. LA - eng PT - Journal Article PT - Review PT - Research Support, Non-U.S. Gov't DEP - 20151020 PL - United States TA - Transl Res JT - Translational research : the journal of laboratory and clinical medicine JID - 101280339 RN - 0 (Lipoproteins, HDL) RN - 0 (Receptors, LDL) RN - EC 3.4.21.- (Proprotein Convertase 9) SB - AIM SB - IM MH - Animals MH - *Clinical Trials as Topic MH - Humans MH - *Lipid Metabolism MH - Lipoproteins, HDL/*metabolism MH - Models, Animal MH - Proprotein Convertase 9/chemistry/*metabolism MH - Receptors, LDL/metabolism EDAT- 2015/11/10 06:00 MHDA- 2017/06/27 06:00 CRDT- 2015/11/10 06:00 PHST- 2015/08/18 00:00 [received] PHST- 2015/10/03 00:00 [revised] PHST- 2015/10/12 00:00 [accepted] PHST- 2015/11/10 06:00 [entrez] PHST- 2015/11/10 06:00 [pubmed] PHST- 2017/06/27 06:00 [medline] AID - S1931-5244(15)00345-X [pii] AID - 10.1016/j.trsl.2015.10.004 [doi] PST - ppublish SO - Transl Res. 2016 Jul;173:19-29. doi: 10.1016/j.trsl.2015.10.004. Epub 2015 Oct 20. PMID- 25863491 OWN - NLM STAT- MEDLINE DCOM- 20161104 LR - 20181113 IS - 1559-0100 (Electronic) IS - 1355-008X (Linking) VI - 51 IP - 2 DP - 2016 Feb TI - Free and bound plasma leptin in anorexia nervosa patients during a refeeding program. PG - 380-3 LID - 10.1007/s12020-015-0598-6 [doi] FAU - Ruscica, Massimiliano AU - Ruscica M AD - Department of Pharmacological and Biomolecular Sciences; Centro per lo Studio delle Malattie Dismetaboliche e delle Iperlipemie - Enrica Grossi Paoletti, Universita degli Studi di Milano, Milan, Italy. FAU - Macchi, Chiara AU - Macchi C AD - Department of Pharmacological and Biomolecular Sciences; Centro per lo Studio delle Malattie Dismetaboliche e delle Iperlipemie - Enrica Grossi Paoletti, Universita degli Studi di Milano, Milan, Italy. FAU - Gandini, Sara AU - Gandini S AD - Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy. FAU - Morlotti, Beatrice AU - Morlotti B AD - Centro Dislipidemie, A.O., Ospedale Niguarda Ca Granda, Milan, Italy. FAU - Erzegovesi, Stefano AU - Erzegovesi S AD - Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele, Milan, Italy. FAU - Bellodi, Laura AU - Bellodi L AD - Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele, Milan, Italy. FAU - Magni, Paolo AU - Magni P AD - Department of Pharmacological and Biomolecular Sciences; Centro per lo Studio delle Malattie Dismetaboliche e delle Iperlipemie - Enrica Grossi Paoletti, Universita degli Studi di Milano, Milan, Italy. paolo.magni@unimi.it. AD - Centro Dislipidemie, A.O., Ospedale Niguarda Ca Granda, Milan, Italy. paolo.magni@unimi.it. LA - eng PT - Letter DEP - 20150412 PL - United States TA - Endocrine JT - Endocrine JID - 9434444 RN - 0 (Leptin) SB - IM MH - Adolescent MH - Adult MH - Anorexia Nervosa/*blood/psychology/therapy MH - Behavior Therapy MH - *Body Mass Index MH - Feeding Behavior MH - Female MH - Humans MH - Leptin/*blood MH - Young Adult EDAT- 2015/04/13 06:00 MHDA- 2016/11/05 06:00 CRDT- 2015/04/13 06:00 PHST- 2015/01/09 00:00 [received] PHST- 2015/04/05 00:00 [accepted] PHST- 2015/04/13 06:00 [entrez] PHST- 2015/04/13 06:00 [pubmed] PHST- 2016/11/05 06:00 [medline] AID - 10.1007/s12020-015-0598-6 [doi] AID - 10.1007/s12020-015-0598-6 [pii] PST - ppublish SO - Endocrine. 2016 Feb;51(2):380-3. doi: 10.1007/s12020-015-0598-6. Epub 2015 Apr 12. PMID- 26293833 OWN - NLM STAT- MEDLINE DCOM- 20160804 LR - 20151012 IS - 1879-0828 (Electronic) IS - 0953-6205 (Linking) VI - 26 IP - 8 DP - 2015 Oct TI - Increased circulating adiponectin in males with chronic HCV hepatitis. PG - 635-9 LID - 10.1016/j.ejim.2015.08.001 [doi] LID - S0953-6205(15)00248-4 [pii] AB - BACKGROUND: Increased levels of adiponectin, a major adipokine with insulin sensitizing properties showing a strong sexual dimorphism, have been reported in individuals with chronic HCV infection (CHC), but data are limited by small samples and lack of control for the genetic background and hepatic fibrosis. The aim of this study was to compare adiponectin levels between CHC patients and accurately matched controls. METHODS: We considered 184 CHC patients, matched (1:1) for age, gender, body mass index, and Adiponectin genotype (ADIPOQ) with healthy individuals. To control for the severity of liver disease, a second control group consisting of 95 patients with histological nonalcoholic fatty liver disease (NAFLD) further matched (1:1) for severe fibrosis was exploited. ADIPOQ genotype was evaluated by Taqman assays, serum adiponectin measured by ELISA. RESULTS: Serum adiponectin was higher in CHC patients than in healthy individuals (9.0+/-5.0 mug/ml vs. 7.3+/-4.0 mug/ml; p=0.001; adjusted estimate +1.8, 1.7-2.9; p=0.001), and than in NAFLD patients (8.3+/-4.5 mug/ml vs. 6.0+/-4.2 mug/ml; p<0.001; adjusted estimate +0.8, 0.2-1.4, p=0.006). After stratification for sex, serum adiponectin was higher in males with CHC than in healthy individuals and NAFLD patients (p<0.005 for both), whereas the difference was not significant in females. CONCLUSIONS: CHC is associated with increased serum adiponectin independently of age, body mass, diabetes, ADIPOQ genotype, and of severe liver fibrosis, particularly in men. CI - Copyright (c) 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. FAU - Canavesi, Elena AU - Canavesi E AD - Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Department of Pathophysiology and Transplantation, Centro Malattie Metaboliche del Fegato, Universita degli Studi di Milano, Milano, Italy. Electronic address: elena.canavesi@unimi.it. FAU - Porzio, Marianna AU - Porzio M AD - Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Department of Pathophysiology and Transplantation, Centro Malattie Metaboliche del Fegato, Universita degli Studi di Milano, Milano, Italy. Electronic address: marianna.porzio@unimi.it. FAU - Ruscica, Massimiliano AU - Ruscica M AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milano, Italy. Electronic address: massimiliano.ruscica@unimi.it. FAU - Rametta, Raffaela AU - Rametta R AD - Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Department of Pathophysiology and Transplantation, Centro Malattie Metaboliche del Fegato, Universita degli Studi di Milano, Milano, Italy. Electronic address: raffaela.rametta@unimi.it. FAU - Macchi, Chiara AU - Macchi C AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milano, Italy. Electronic address: chiara.macchi@unimi.it. FAU - Pelusi, Serena AU - Pelusi S AD - Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Department of Pathophysiology and Transplantation, Centro Malattie Metaboliche del Fegato, Universita degli Studi di Milano, Milano, Italy. Electronic address: serena.pelusi@unimi.it. FAU - Fracanzani, Anna Ludovica AU - Fracanzani AL AD - Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Department of Pathophysiology and Transplantation, Centro Malattie Metaboliche del Fegato, Universita degli Studi di Milano, Milano, Italy. Electronic address: anna.fracanzani@unimi.it. FAU - Dongiovanni, Paola AU - Dongiovanni P AD - Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Department of Pathophysiology and Transplantation, Centro Malattie Metaboliche del Fegato, Universita degli Studi di Milano, Milano, Italy. Electronic address: paola.dongiovanni@policlinico.mi.it. FAU - Fargion, Silvia AU - Fargion S AD - Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Department of Pathophysiology and Transplantation, Centro Malattie Metaboliche del Fegato, Universita degli Studi di Milano, Milano, Italy. Electronic address: silvia.fargion@unimi.it. FAU - Magni, Paolo AU - Magni P AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milano, Italy. Electronic address: paolo.magni@unimi.it. FAU - Valenti, Luca AU - Valenti L AD - Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Department of Pathophysiology and Transplantation, Centro Malattie Metaboliche del Fegato, Universita degli Studi di Milano, Milano, Italy. Electronic address: luca.valenti@unimi.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150817 PL - Netherlands TA - Eur J Intern Med JT - European journal of internal medicine JID - 9003220 RN - 0 (Adiponectin) SB - IM MH - Adiponectin/*blood/genetics MH - Case-Control Studies MH - Female MH - Genotype MH - Hepatitis C, Chronic/*blood MH - Humans MH - Male MH - Middle Aged MH - Non-alcoholic Fatty Liver Disease/blood MH - Severity of Illness Index MH - Sex Factors OTO - NOTNLM OT - Adipokines OT - Adiponectin OT - Gender OT - Hepatic fibrosis OT - Hepatitis C virus OT - Nonalcoholic fatty liver disease EDAT- 2015/08/22 06:00 MHDA- 2016/08/05 06:00 CRDT- 2015/08/22 06:00 PHST- 2014/12/23 00:00 [received] PHST- 2015/05/04 00:00 [revised] PHST- 2015/08/03 00:00 [accepted] PHST- 2015/08/22 06:00 [entrez] PHST- 2015/08/22 06:00 [pubmed] PHST- 2016/08/05 06:00 [medline] AID - S0953-6205(15)00248-4 [pii] AID - 10.1016/j.ejim.2015.08.001 [doi] PST - ppublish SO - Eur J Intern Med. 2015 Oct;26(8):635-9. doi: 10.1016/j.ejim.2015.08.001. Epub 2015 Aug 17. PMID- 25640999 OWN - NLM STAT- MEDLINE DCOM- 20151130 LR - 20181202 IS - 1879-0828 (Electronic) IS - 0953-6205 (Linking) VI - 26 IP - 2 DP - 2015 Mar TI - Risk identification and possible countermeasures for muscle adverse effects during statin therapy. PG - 82-8 LID - 10.1016/j.ejim.2015.01.002 [doi] LID - S0953-6205(15)00003-5 [pii] AB - The use of statins for cardiovascular disease prevention is clearly supported by clinical evidence. However, in January 2014 the U.S. Food and Drug Administration released an advice on statin risk reporting that "statin benefit is indisputable, but they need to be taken with care and knowledge of their side effects". Among them the by far most common complication is myopathy, ranging from common but clinically benign myalgia to rare but life-threatening rhabdomyolysis. This class side effect appears to be dose dependent, with more lipophilic statin (i.e., simvastatin) carrying a higher overall risk. Hence, to minimize statin-associated myopathy, clinicians should take into consideration a series of factors that potentially increase this risk (i.e., drug-drug interactions, female gender, advanced age, diabetes mellitus, hypothyroidism and vitamin D deficiency). Whenever it is appropriate to stop statin treatment, the recommendations are to stay off statin until resolution of symptoms or normalization of creatine kinase values. Afterwards, clinicians have several options to treat dyslipidemia, including the use of a lower dose of the same statin, intermittent non-daily dosing of statin, initiation of a different statin, alone or in combination with nonstatin lipid-lowering agents, and substitution with red yeast rice. CI - Copyright (c) 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. FAU - Magni, Paolo AU - Magni P AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Italy; Centro Dislipidemie, Ospedale Niguarda Ca Granda, Milan, Italy. Electronic address: paolo.magni@unimi.it. FAU - Macchi, Chiara AU - Macchi C AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Italy. FAU - Morlotti, Beatrice AU - Morlotti B AD - Centro Dislipidemie, Ospedale Niguarda Ca Granda, Milan, Italy. FAU - Sirtori, Cesare R AU - Sirtori CR AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Italy; Centro Dislipidemie, Ospedale Niguarda Ca Granda, Milan, Italy. FAU - Ruscica, Massimiliano AU - Ruscica M AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Italy; Centro Dislipidemie, Ospedale Niguarda Ca Granda, Milan, Italy. LA - eng PT - Journal Article PT - Review DEP - 20150129 PL - Netherlands TA - Eur J Intern Med JT - European journal of internal medicine JID - 9003220 RN - 0 (Anticholesteremic Agents) RN - 0 (Fatty Acids, Monounsaturated) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Indoles) RN - 4L066368AS (Fluvastatin) RN - 83MVU38M7Q (Rosuvastatin Calcium) RN - EC 2.7.3.2 (Creatine Kinase) RN - EOR26LQQ24 (Ezetimibe) RN - P4SG24WI5Q (Colesevelam Hydrochloride) SB - IM MH - Age Factors MH - Aged MH - Aged, 80 and over MH - Anticholesteremic Agents/*therapeutic use MH - Colesevelam Hydrochloride/therapeutic use MH - Creatine Kinase/blood MH - Drug Interactions MH - Drug Therapy, Combination MH - Dyslipidemias/*drug therapy/epidemiology MH - Ezetimibe/therapeutic use MH - Fatty Acids, Monounsaturated/adverse effects MH - Female MH - Fluvastatin MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects MH - Indoles/adverse effects MH - Male MH - Muscular Diseases/chemically induced/metabolism MH - Myalgia/blood/*chemically induced MH - Rhabdomyolysis/blood/*chemically induced MH - Risk Assessment MH - Risk Factors MH - Rosuvastatin Calcium/adverse effects MH - Sex Factors MH - Vitamin D Deficiency/epidemiology OTO - NOTNLM OT - Cardiovascular risk OT - Creatine kinase OT - Skeletal muscle toxicity OT - Statin-related myopathy EDAT- 2015/02/03 06:00 MHDA- 2015/12/15 06:00 CRDT- 2015/02/03 06:00 PHST- 2014/12/12 00:00 [received] PHST- 2014/12/28 00:00 [revised] PHST- 2015/01/05 00:00 [accepted] PHST- 2015/02/03 06:00 [entrez] PHST- 2015/02/03 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] AID - S0953-6205(15)00003-5 [pii] AID - 10.1016/j.ejim.2015.01.002 [doi] PST - ppublish SO - Eur J Intern Med. 2015 Mar;26(2):82-8. doi: 10.1016/j.ejim.2015.01.002. Epub 2015 Jan 29. PMID- 24685426 OWN - NLM STAT- MEDLINE DCOM- 20150109 LR - 20140529 IS - 1879-0828 (Electronic) IS - 0953-6205 (Linking) VI - 25 IP - 5 DP - 2014 Jun TI - Statin therapy and related risk of new-onset type 2 diabetes mellitus. PG - 401-6 LID - 10.1016/j.ejim.2014.03.003 [doi] LID - S0953-6205(14)00078-8 [pii] AB - The use of statins for cardiovascular disease (CVD) prevention is clearly supported by clinical evidence. Although statin therapy is rather well tolerated, recent data from prospective and retrospective clinical trials and related meta-analyses suggest an increased incidence of new-onset type 2 diabetes mellitus (T2DM) in association with such treatment. The incidence of this adverse effect is not negligible, especially for specific subsets of patients, such as women, elderly, presence of familial history of T2DM and Asian ethnicity. Statin-driven T2DM appears to be a medication class-effect, mostly not related to potency nor to individual statin, as well as to be independent of previous history of CVD. Therefore, implementation of strategies for identification of patients using statins and at specific risk of incident T2DM, as well as of different therapeutic options is important and is discussed in this article. As most authors emphasized that benefits of CVD reduction by statin therapy seem to far exceed the risk of T2DM development itself, these medications remain the cornerstone for primary and secondary CVD prevention, although a specific attention to glucose metabolism and metabolic syndrome features should be payed before and during statin treatment, especially in cohorts at greater risk. CI - Copyright (c) 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. FAU - Ruscica, Massimiliano AU - Ruscica M AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Italy; Centro Dislipidemie, Ospedale Niguarda Ca Granda, Milan, Italy. FAU - Macchi, Chiara AU - Macchi C AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Italy; Centro Dislipidemie, Ospedale Niguarda Ca Granda, Milan, Italy. FAU - Morlotti, Beatrice AU - Morlotti B AD - Centro Dislipidemie, Ospedale Niguarda Ca Granda, Milan, Italy. FAU - Sirtori, Cesare R AU - Sirtori CR AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Italy; Centro Dislipidemie, Ospedale Niguarda Ca Granda, Milan, Italy. FAU - Magni, Paolo AU - Magni P AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Italy; Centro Dislipidemie, Ospedale Niguarda Ca Granda, Milan, Italy. Electronic address: paolo.magni@unimi.it. LA - eng PT - Journal Article PT - Review DEP - 20140327 PL - Netherlands TA - Eur J Intern Med JT - European journal of internal medicine JID - 9003220 RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - KXO2KT9N0G (Pravastatin) SB - IM MH - Cardiovascular Diseases/*prevention & control MH - Diabetes Mellitus, Type 2/*chemically induced MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage/*adverse effects/therapeutic use MH - Pravastatin/therapeutic use MH - Primary Prevention MH - Risk Assessment MH - Risk Factors MH - Secondary Prevention OTO - NOTNLM OT - Cardiovascular risk OT - New-onset diabetes risk OT - Statins EDAT- 2014/04/02 06:00 MHDA- 2015/01/13 06:00 CRDT- 2014/04/02 06:00 PHST- 2013/12/23 00:00 [received] PHST- 2014/03/03 00:00 [revised] PHST- 2014/03/07 00:00 [accepted] PHST- 2014/04/02 06:00 [entrez] PHST- 2014/04/02 06:00 [pubmed] PHST- 2015/01/13 06:00 [medline] AID - S0953-6205(14)00078-8 [pii] AID - 10.1016/j.ejim.2014.03.003 [doi] PST - ppublish SO - Eur J Intern Med. 2014 Jun;25(5):401-6. doi: 10.1016/j.ejim.2014.03.003. Epub 2014 Mar 27. PMID- 24528686 OWN - NLM STAT- MEDLINE DCOM- 20141021 LR - 20151119 IS - 1933-2874 (Print) IS - 1876-4789 (Linking) VI - 8 IP - 1 DP - 2014 Jan-Feb TI - Nutraceutical approach to moderate cardiometabolic risk: results of a randomized, double-blind and crossover study with Armolipid Plus. PG - 61-8 LID - 10.1016/j.jacl.2013.11.003 [doi] LID - S1933-2874(13)00338-3 [pii] AB - BACKGROUND: Primary cardiovascular prevention may be achieved by lifestyle/nutrition improvements and specific drugs, although a relevant role is now emerging for specific functional foods and nutraceuticals. OBJECTIVES: The aim of this study was to evaluate the usefulness of a nutraceutical multitarget approach in subjects with moderate cardiovascular risk and to compare it with pravastatin treatment. SUBJECTS: Thirty patients with moderate dyslipidemia and metabolic syndrome (according to the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults) were included in an 8-week randomized, double-blind crossover study and took either placebo or a nutraceutical combination that contained red yeast rice extract, berberine, policosanol, astaxanthin, coenzyme Q10, and folic acid (Armolipid Plus). Subsequently, they were subjected to another 8-week treatment with pravastatin 10 mg/d. This dosage was selected on the basis of its expected -20% efficacy in reducing low-density lipoprotein-cholesterol. RESULTS: Treatment with Armolipid Plus led to a significant reduction of total cholesterol (-12.8%) and low-density lipoprotein-cholesterol (-21.1%), similar to pravastatin (-16% and -22.6%, respectively), and an increase of high-density lipoprotein-cholesterol (4.8%). Armolipid Plus improved the leptin-to-adiponectin ratio, whereas adiponectin levels were unchanged. CONCLUSIONS: These results indicate that this nutraceutical approach shows a lipid-lowering activity comparable to pravastatin treatment. Hence, it may be a safe and useful option, especially in conditions of moderate cardiovascular risk, in which a pharmacologic intervention may not be appropriate. CI - Copyright (c) 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved. FAU - Ruscica, Massimiliano AU - Ruscica M AD - Centro Dislipidemie, A. O. Ospedale Niguarda Ca Granda, Milano, Italy; Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy. FAU - Gomaraschi, Monica AU - Gomaraschi M AD - Centro Dislipidemie, A. O. Ospedale Niguarda Ca Granda, Milano, Italy; Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy. FAU - Mombelli, Giuliana AU - Mombelli G AD - Centro Dislipidemie, A. O. Ospedale Niguarda Ca Granda, Milano, Italy. FAU - Macchi, Chiara AU - Macchi C AD - Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy. FAU - Bosisio, Raffaella AU - Bosisio R AD - Centro Dislipidemie, A. O. Ospedale Niguarda Ca Granda, Milano, Italy. FAU - Pazzucconi, Franco AU - Pazzucconi F AD - Centro Dislipidemie, A. O. Ospedale Niguarda Ca Granda, Milano, Italy; Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy. FAU - Pavanello, Chiara AU - Pavanello C AD - Centro Dislipidemie, A. O. Ospedale Niguarda Ca Granda, Milano, Italy. FAU - Calabresi, Laura AU - Calabresi L AD - Centro Dislipidemie, A. O. Ospedale Niguarda Ca Granda, Milano, Italy; Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy. FAU - Arnoldi, Anna AU - Arnoldi A AD - Centro Dislipidemie, A. O. Ospedale Niguarda Ca Granda, Milano, Italy; Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Milano, Milano, Italy. FAU - Sirtori, Cesare R AU - Sirtori CR AD - Centro Dislipidemie, A. O. Ospedale Niguarda Ca Granda, Milano, Italy; Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy. Electronic address: cesare.sirtori@unimi.it. FAU - Magni, Paolo AU - Magni P AD - Centro Dislipidemie, A. O. Ospedale Niguarda Ca Granda, Milano, Italy; Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20131111 PL - United States TA - J Clin Lipidol JT - Journal of clinical lipidology JID - 101300157 RN - 0 (Biological Products) RN - 0 (Biomarkers) RN - 0 (Cholesterol, LDL) RN - 0 (Fatty Alcohols) RN - 0 (Inflammation Mediators) RN - 0 (Xanthophylls) RN - 0 (red yeast rice) RN - 0I8Y3P32UF (Berberine) RN - 1339-63-5 (Ubiquinone) RN - 142583-61-7 (policosanol) RN - 8XPW32PR7I (astaxanthine) RN - 935E97BOY8 (Folic Acid) RN - EJ27X76M46 (coenzyme Q10) RN - KXO2KT9N0G (Pravastatin) SB - IM MH - Berberine/therapeutic use MH - Biological Products/therapeutic use MH - Biomarkers/blood MH - Cardiovascular Diseases/*drug therapy/*metabolism MH - Cholesterol, LDL/blood MH - Cross-Over Studies MH - *Dietary Supplements MH - Double-Blind Method MH - Endpoint Determination MH - Fatty Alcohols/therapeutic use MH - Female MH - Folic Acid/therapeutic use MH - Humans MH - Inflammation Mediators/blood MH - Male MH - Middle Aged MH - Pravastatin/therapeutic use MH - Time Factors MH - Ubiquinone/analogs & derivatives/therapeutic use MH - Xanthophylls/therapeutic use OTO - NOTNLM OT - Berberine OT - Cardiovascular risk OT - HDL-cholesterol OT - LDL-cholesterol OT - Monacolin K EDAT- 2014/02/18 06:00 MHDA- 2014/10/22 06:00 CRDT- 2014/02/18 06:00 PHST- 2013/07/08 00:00 [received] PHST- 2013/10/07 00:00 [revised] PHST- 2013/11/04 00:00 [accepted] PHST- 2014/02/18 06:00 [entrez] PHST- 2014/02/18 06:00 [pubmed] PHST- 2014/10/22 06:00 [medline] AID - S1933-2874(13)00338-3 [pii] AID - 10.1016/j.jacl.2013.11.003 [doi] PST - ppublish SO - J Clin Lipidol. 2014 Jan-Feb;8(1):61-8. doi: 10.1016/j.jacl.2013.11.003. Epub 2013 Nov 11. PMID- 23816043 OWN - NLM STAT- MEDLINE DCOM- 20140318 LR - 20130809 IS - 1464-3391 (Electronic) IS - 0968-0896 (Linking) VI - 21 IP - 17 DP - 2013 Sep 1 TI - Antiproliferative activity on human prostate carcinoma cell lines of new peptidomimetics containing the spiroazepinoindolinone scaffold. PG - 5470-9 LID - 10.1016/j.bmc.2013.06.006 [doi] LID - S0968-0896(13)00537-3 [pii] AB - Peptidomimetics containing the spiroazepinoindolinone scaffold were designed and synthesized in order to ascertain their antiproliferative activity on the DU-145 human prostatic carcinoma cell line. Ethyl 2'-oxa-1,2,3,5,6,7-hexahydrospiro[4H-azepine-4,3'-3H-indole]-1'-carboxylate scaffold was functionalized at nitrogen azepino ring with Aib-(l/d)Trp-OH dipeptides. Combining the different stereochemistries of the scaffold and the tryptophan, diastereoisomeric peptidomimetics were prepared and tested. Their biological activity was evaluated by proliferation studies proving that the isomer containing S spiroazepino-indolinone scaffold and l tryptophan is the most active compound. Docking studies confirmed that the active peptidomimetic could bind the GHSR-1a receptor with docking scores comparable with those of well-known agonists even though with a somewhat different binding mode. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. FAU - Pellegrino, Sara AU - Pellegrino S AD - DISFARM, sezione di Chimica Generale e Organica A. Marchesini, Universita degli Studi di Milano, via Venezian 21, Milano 20133, Italy. sara.pellegrino@unimi.it FAU - Ruscica, Massimiliano AU - Ruscica M FAU - Magni, Paolo AU - Magni P FAU - Vistoli, Giulio AU - Vistoli G FAU - Gelmi, Maria Luisa AU - Gelmi ML LA - eng PT - Journal Article DEP - 20130613 PL - England TA - Bioorg Med Chem JT - Bioorganic & medicinal chemistry JID - 9413298 RN - 0 (Azepines) RN - 0 (Dipeptides) RN - 0 (Indoles) RN - 0 (Peptidomimetics) RN - 0 (Receptors, Ghrelin) RN - 0 (Spiro Compounds) RN - 8724FJW4M5 (indole) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) SB - IM MH - Azepines/chemistry MH - Binding Sites MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Dipeptides/chemistry MH - Humans MH - Indoles/chemical synthesis/*chemistry/pharmacology MH - Male MH - Mitogen-Activated Protein Kinase 1/metabolism MH - Mitogen-Activated Protein Kinase 3/metabolism MH - Molecular Docking Simulation MH - Peptidomimetics MH - Phosphorylation/drug effects MH - Prostatic Neoplasms/metabolism/pathology MH - Protein Structure, Tertiary MH - Receptors, Ghrelin/chemistry/metabolism MH - Spiro Compounds/chemistry MH - Stereoisomerism OTO - NOTNLM OT - Docking OT - Ghrelin OT - Peptidomimetics OT - Prostate cancer EDAT- 2013/07/03 06:00 MHDA- 2014/03/19 06:00 CRDT- 2013/07/03 06:00 PHST- 2012/11/21 00:00 [received] PHST- 2013/05/30 00:00 [revised] PHST- 2013/06/04 00:00 [accepted] PHST- 2013/07/03 06:00 [entrez] PHST- 2013/07/03 06:00 [pubmed] PHST- 2014/03/19 06:00 [medline] AID - S0968-0896(13)00537-3 [pii] AID - 10.1016/j.bmc.2013.06.006 [doi] PST - ppublish SO - Bioorg Med Chem. 2013 Sep 1;21(17):5470-9. doi: 10.1016/j.bmc.2013.06.006. Epub 2013 Jun 13. PMID- 23046862 OWN - NLM STAT- MEDLINE DCOM- 20130711 LR - 20130513 IS - 1475-2662 (Electronic) IS - 0007-1145 (Linking) VI - 109 IP - 10 DP - 2013 May 28 TI - Phaseolus vulgaris extract affects glycometabolic and appetite control in healthy human subjects. PG - 1789-95 LID - 10.1017/S0007114512003741 [doi] AB - Extracts of Phaseolus vulgaris (beans) are known to reduce glycaemia and food intake in rodents and humans. The present study evaluated the effects of a new, standardised and purified P. vulgaris extract (PVE), when employed as a supplement in a mixed balanced meal (60 % carbohydrates, 25 % lipids and 15 % protein), on glycometabolic and appetite control. To this end, a randomised, double-blind, placebo-controlled study was performed in twelve volunteers. Plasma glucose, insulin, C-peptide, ghrelin and satiety sensation ratings were assessed at baseline and during 3 h after meal consumption associated with PVE (100 mg) or placebo. Compared with placebo, PVE consumption resulted in lower increments in glucose (+15.4 (sem 5.4) v. 26.1 (SEM 7.3) %, P= 0.04 at 30 min), insulin (+981 (SEM 115) v. 1325 (SEM 240) %, P= 0.04 between 45 and 120 min) and C-peptide (+350 (SEM 27) v. 439 (SEM 30) %, P= 0.04 between 30 and 90 min). In the first 2 h, plasma ghrelin decreased similarly in both groups but did not rebound as in placebo thereafter (P= 0.04). Correspondingly, satiety sensation in the third hour was significantly reduced in the placebo but not in the PVE condition. PVE induced a lower desire to eat than placebo (P= 0.02) over the 3 h. In conclusion, PVE supplementation reduced postprandial glucose, insulin and C-peptide excursions, suppressed ghrelin secretion and affected satiety sensations, inducing a lower desire to eat. These results support that further studies are needed to prove the concept of employing PVE as a supplement in mixed balanced meals in obese, glucose-intolerant and diabetic subjects. FAU - Spadafranca, Angela AU - Spadafranca A AD - Department of Food, Environmental and Nutritional Sciences, International Center for the Assessment of Nutritional Status, Universita degli Studi di Milano, Via Celoria 2, 20133 Milan, Italy. angela.spadafranca@unimi.it FAU - Rinelli, Samuele AU - Rinelli S FAU - Riva, Antonella AU - Riva A FAU - Morazzoni, Paolo AU - Morazzoni P FAU - Magni, Paolo AU - Magni P FAU - Bertoli, Simona AU - Bertoli S FAU - Battezzati, Alberto AU - Battezzati A LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20121009 PL - England TA - Br J Nutr JT - The British journal of nutrition JID - 0372547 RN - 0 (Blood Glucose) RN - 0 (Ghrelin) RN - 0 (Insulin) RN - 0 (Plant Extracts) RN - 9007-41-4 (C-Reactive Protein) SB - IM MH - Adult MH - Appetite Regulation/*drug effects MH - Blood Glucose/*metabolism MH - C-Reactive Protein/*metabolism MH - Diabetes Mellitus/blood/drug therapy MH - Diet MH - Dietary Supplements MH - Double-Blind Method MH - Female MH - Ghrelin/*blood MH - Humans MH - Insulin/*blood MH - Male MH - Obesity/blood/drug therapy MH - *Phaseolus MH - Phytotherapy MH - Plant Extracts/*pharmacology/therapeutic use MH - Postprandial Period MH - Reference Values MH - Satiation/drug effects MH - Young Adult EDAT- 2012/10/11 06:00 MHDA- 2013/07/13 06:00 CRDT- 2012/10/11 06:00 PHST- 2012/10/11 06:00 [entrez] PHST- 2012/10/11 06:00 [pubmed] PHST- 2013/07/13 06:00 [medline] AID - S0007114512003741 [pii] AID - 10.1017/S0007114512003741 [doi] PST - ppublish SO - Br J Nutr. 2013 May 28;109(10):1789-95. doi: 10.1017/S0007114512003741. Epub 2012 Oct 9. PMID- 22898488 OWN - NLM STAT- MEDLINE DCOM- 20130411 LR - 20181113 IS - 1471-230X (Electronic) IS - 1471-230X (Linking) VI - 12 DP - 2012 Aug 16 TI - The I148M PNPLA3 polymorphism influences serum adiponectin in patients with fatty liver and healthy controls. PG - 111 AB - BACKGROUND: Reduced adiponectin is implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), and the I148M Patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism predisposes to NAFLD and liver damage progression in NASH and chronic hepatitis C (CHC) by still undefined mechanisms, possibly involving regulation of adipose tissue function. Aim of this study was to evaluate whether the I148M PNPLA3 polymorphism influences serum adiponectin in liver diseases and healthy controls. METHODS: To this end, we considered 144 consecutive Italian patients with NAFLD, 261 with CHC, 35 severely obese subjects, and 257 healthy controls with very low probability of steatosis, all with complete clinical and genetic characterization, including adiponectin (ADIPOQ) genotype. PNPLA3 rs738409 (I148M) and ADIPOQ genotypes were evaluated by Taqman assays, serum adiponectin by ELISA. Adiponectin mRNA levels were evaluated by quantitative real-time PCR in the visceral adipose tissue (VAT) of 35 obese subjects undergoing bariatric surgery. RESULTS: Adiponectin levels were independently associated with the risk of NAFLD and with the histological severity of the disease. Adiponectin levels decreased with the number of 148 M PNPLA3 alleles at risk of NASH both in patients with NAFLD (p = 0.03), and in healthy subjects (p = 0.04). At multivariate analysis, PNPLA3 148 M alleles were associated with low adiponectin levels (<6 mg/ml, median value) independently of NAFLD diagnosis, age, gender, BMI, and ADIPOQ genotype (OR 1.67, 95% c.i. 1.07-2.1 for each 148 M allele). The p.148 M PNPLA3 variant was associated with decreased adiponectin mRNA levels in the VAT of obese patients (p < 0.05) even in the absence of NASH. In contrast, in CHC, characterized by adiponectin resistance, low adiponectin was associated with male gender and steatosis, but not with PNPLA3 and ADIPOQ genotypes and viral features. CONCLUSIONS: The I148M PNPLA3 variant is associated with adiponectin levels in patients with NAFLD and in healthy subjects, but in the presence of adiponectin resistance not in CHC patients. The I148M PNPLA3 genotype may represent a genetic determinant of serum adiponectin levels. Modulation of serum adiponectin might be involved in mediating the susceptibility to steatosis, NASH, and hepatocellular carcinoma in carriers of the 148 M PNPLA3 variant without CHC, with potential therapeutic implications. FAU - Valenti, Luca AU - Valenti L AD - Department of Internal Medicine, Universita degli Studi Milano, UO Medicina Interna 1B, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. luca.valenti@unimi.it FAU - Rametta, Raffaela AU - Rametta R FAU - Ruscica, Massimiliano AU - Ruscica M FAU - Dongiovanni, Paola AU - Dongiovanni P FAU - Steffani, Liliana AU - Steffani L FAU - Motta, Benedetta Maria AU - Motta BM FAU - Canavesi, Elena AU - Canavesi E FAU - Fracanzani, Anna Ludovica AU - Fracanzani AL FAU - Mozzi, Enrico AU - Mozzi E FAU - Roviaro, Giancarlo AU - Roviaro G FAU - Magni, Paolo AU - Magni P FAU - Fargion, Silvia AU - Fargion S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120816 PL - England TA - BMC Gastroenterol JT - BMC gastroenterology JID - 100968547 RN - 0 (Adiponectin) RN - 0 (Membrane Proteins) RN - EC 3.1.1.3 (Lipase) RN - EC 3.1.1.3 (adiponutrin, human) SB - IM MH - Adiponectin/*blood MH - Adult MH - Aged MH - Alleles MH - Case-Control Studies MH - Fatty Liver/*blood/epidemiology/*genetics MH - Female MH - Genetic Predisposition to Disease/genetics MH - Genotype MH - Hepatitis C, Chronic/blood/genetics MH - Humans MH - Lipase/*genetics MH - Male MH - Membrane Proteins/*genetics MH - Middle Aged MH - Multivariate Analysis MH - Obesity/blood/genetics MH - Polymorphism, Genetic/*genetics MH - Risk Factors PMC - PMC3444917 EDAT- 2012/08/18 06:00 MHDA- 2013/04/12 06:00 CRDT- 2012/08/18 06:00 PHST- 2012/03/05 00:00 [received] PHST- 2012/08/07 00:00 [accepted] PHST- 2012/08/18 06:00 [entrez] PHST- 2012/08/18 06:00 [pubmed] PHST- 2013/04/12 06:00 [medline] AID - 1471-230X-12-111 [pii] AID - 10.1186/1471-230X-12-111 [doi] PST - epublish SO - BMC Gastroenterol. 2012 Aug 16;12:111. doi: 10.1186/1471-230X-12-111. PMID- 20580704 OWN - NLM STAT- MEDLINE DCOM- 20101028 LR - 20131121 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 641 IP - 1 DP - 2010 Sep 1 TI - The natural antioxidant alpha-lipoic acid induces p27(Kip1)-dependent cell cycle arrest and apoptosis in MCF-7 human breast cancer cells. PG - 29-34 LID - 10.1016/j.ejphar.2010.05.009 [doi] AB - Unlike normal cells, tumor cells survive in a specific redox environment where the elevated reactive oxygen species contribute to enhance cell proliferation and to suppress apoptosis. Alpha-lipoic acid, a naturally occurring reactive oxygen species scavenger, has been shown to possess anticancer activity, due to its ability to suppress proliferation and to induce apoptosis in different cancer cell lines. Since at the moment little information is available regarding the potential effects of alpha-lipoic acid on breast cancer, in the present study we addressed the question whether alpha-lipoic acid induces cell cycle arrest and apoptosis in the human breast cancer cell line MCF-7. Moreover, we investigated some molecular mechanisms which mediate alpha-lipoic acid actions, focusing on the role of the PI3-K/Akt signalling pathway. We observed that alpha-lipoic acid is able to scavenge reactive oxygen species in MCF-7 cells and that the reduction of reactive oxygen species is followed by cell growth arrest in the G1 phase of the cell cycle, via the specific inhibition of Akt pathway and the up-regulation of the cyclin-dependent kinase inhibitor p27(kip1), and by apoptosis, via changes of the ratio of the apoptotic-related protein Bax/Bcl-2. Thus, the anti-tumor activity of alpha-lipoic acid observed in MCF-7 cells further stresses the role of redox state in regulating cancer initiation and progression. CI - Copyright (c) 2010 Elsevier B.V. All rights reserved. FAU - Dozio, Elena AU - Dozio E AD - Department of Human Morphology and Biomedical Sciences Citta Studi, via L. Mangiagalli 31, Universita degli Studi di Milano, Milan, Italy. elena.dozio@unimi.it FAU - Ruscica, Massimiliano AU - Ruscica M FAU - Passafaro, Luca AU - Passafaro L FAU - Dogliotti, Giada AU - Dogliotti G FAU - Steffani, Liliana AU - Steffani L FAU - Marthyn, Paola AU - Marthyn P FAU - Pagani, Alessandra AU - Pagani A FAU - Demartini, Germana AU - Demartini G FAU - Esposti, Daniele AU - Esposti D FAU - Fraschini, Franco AU - Fraschini F FAU - Magni, Paolo AU - Magni P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100524 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Antioxidants) RN - 0 (Biological Products) RN - 0 (Reactive Oxygen Species) RN - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27) RN - 73Y7P0K73Y (Thioctic Acid) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM EIN - Eur J Pharmacol. 2011 Jan 10;650(1):486. Marthyn, Paola [added] MH - Antioxidants/*pharmacology MH - Apoptosis/*drug effects MH - Biological Products/*pharmacology MH - Breast Neoplasms/*pathology MH - Cell Cycle/*drug effects MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Cyclin-Dependent Kinase Inhibitor p27/*metabolism MH - Down-Regulation/drug effects MH - Gene Expression Regulation, Neoplastic/drug effects MH - Humans MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Reactive Oxygen Species/metabolism MH - Signal Transduction/drug effects MH - Thioctic Acid/*pharmacology EDAT- 2010/06/29 06:00 MHDA- 2010/10/29 06:00 CRDT- 2010/06/29 06:00 PHST- 2010/01/08 00:00 [received] PHST- 2010/04/13 00:00 [revised] PHST- 2010/05/06 00:00 [accepted] PHST- 2010/06/29 06:00 [entrez] PHST- 2010/06/29 06:00 [pubmed] PHST- 2010/10/29 06:00 [medline] AID - S0014-2999(10)00425-5 [pii] AID - 10.1016/j.ejphar.2010.05.009 [doi] PST - ppublish SO - Eur J Pharmacol. 2010 Sep 1;641(1):29-34. doi: 10.1016/j.ejphar.2010.05.009. Epub 2010 May 24. PMID- 20070489 OWN - NLM STAT- MEDLINE DCOM- 20100726 LR - 20131121 IS - 1600-079X (Electronic) IS - 0742-3098 (Linking) VI - 48 IP - 2 DP - 2010 Mar TI - Pharmacokinetics of orally administered melatonin in critically ill patients. PG - 142-7 LID - 10.1111/j.1600-079X.2009.00737.x [doi] AB - Critically ill patients exhibit reduced melatonin secretion, both in nocturnal peaks and basal daytime levels. Oral melatonin supplementation may be useful for known sedative and antioxidant properties. Its early enteral absorption and daily pharmacokinetics were determined in two cohorts of six high-risk patients in this prospective trial. During their third and fourth Intensive Care Unit (ICU) day, they underwent two different sets of repeated blood samples to detect serum melatonin levels through radio-immuno-assay. Cohort 1: samples taken at 20:00, 20:45, 21:30, 24:00, 03:00, 06:00, 14:00, 20:00 to describe the daily pharmacokinetics. Cohort 2: 20:00, 20:05, 20:10, 20:20, 20:30, 20:45 to study the early absorption. On ICU day 3, endogenous levels were measured, while the absorption of exogenous melatonin was determined on ICU day 4 after administration, at 20:00, of 3 mg melatonin. All basal levels were below the expected values. Following enteral administration, pharmacological levels were already reached in 5 min, with a serum peak after 16 min (half-absorption time: 3 min 17 s). The maximum serum level observed was 11040 pg/mL and the disappearance rate indicated a half-elimination time of 1 hr 34 min. Serum melatonin levels decreased significantly after midnight; pharmacological levels were maintained up to 10 hr following administration. No excessive sleepiness was reported in this patient group. Critically ill patients exhibited reduced melatonin secretion, as reported in the literature. Despite the critical illness, the oral bioavailability was satisfactory: serum levels after oral administration showed basically unchanged intestinal absorption, while disappearance rate was slower than reported elsewhere in healthy volunteers. FAU - Mistraletti, Giovanni AU - Mistraletti G AD - Dipartimento di Anestesiologia, Terapia Intensiva e Scienze Dermatologiche, Universita degli Studi di Milano, Milano, Italy. giovanni.mistraletti@unimi.it FAU - Sabbatini, Giovanni AU - Sabbatini G FAU - Taverna, Martina AU - Taverna M FAU - Figini, Maria Adele AU - Figini MA FAU - Umbrello, Michele AU - Umbrello M FAU - Magni, Paolo AU - Magni P FAU - Ruscica, Massimiliano AU - Ruscica M FAU - Dozio, Elena AU - Dozio E FAU - Esposti, Roberto AU - Esposti R FAU - DeMartini, Germana AU - DeMartini G FAU - Fraschini, Franco AU - Fraschini F FAU - Rezzani, Rita AU - Rezzani R FAU - Reiter, Russel J AU - Reiter RJ FAU - Iapichino, Gaetano AU - Iapichino G LA - eng PT - Journal Article DEP - 20100108 PL - England TA - J Pineal Res JT - Journal of pineal research JID - 8504412 RN - 0 (Hypnotics and Sedatives) RN - JL5DK93RCL (Melatonin) SB - IM MH - Administration, Oral MH - Aged MH - Aged, 80 and over MH - Biological Availability MH - Circadian Rhythm MH - *Critical Illness MH - Female MH - Humans MH - Hypnotics and Sedatives MH - Male MH - Melatonin/administration & dosage/blood/*pharmacokinetics MH - Middle Aged MH - Prospective Studies EDAT- 2010/01/15 06:00 MHDA- 2010/07/27 06:00 CRDT- 2010/01/15 06:00 PHST- 2010/01/15 06:00 [entrez] PHST- 2010/01/15 06:00 [pubmed] PHST- 2010/07/27 06:00 [medline] AID - JPI737 [pii] AID - 10.1111/j.1600-079X.2009.00737.x [doi] PST - ppublish SO - J Pineal Res. 2010 Mar;48(2):142-7. doi: 10.1111/j.1600-079X.2009.00737.x. Epub 2010 Jan 8. PMID- 17299136 OWN - NLM STAT- MEDLINE DCOM- 20070723 LR - 20101118 IS - 0888-8809 (Print) IS - 0888-8809 (Linking) VI - 21 IP - 5 DP - 2007 May TI - Leukemia inhibitory factor induces the chemomigration of immortalized gonadotropin-releasing hormone neurons through the independent activation of the Janus kinase/signal transducer and activator of transcription 3, mitogen-activated protein kinase/extracellularly regulated kinase 1/2, and phosphatidylinositol 3-kinase/Akt signaling pathways. PG - 1163-74 AB - Leukemia inhibitory factor (LIF) is a pleiotropic cytokine of the IL-6 superfamily. LIF acts through a cell-surface receptor complex formed by two subunits, the specific LIF receptor beta (LIFRbeta) and the glycoprotein 130. Little is known about LIF involvement in modulating the neuroendocrine circuitry governing the reproductive function and, specifically, the development of GnRH-secreting neurons. In the present study, we evaluated the effect of LIF on the in vitro migration of GN11 cells, a model of immature and migratory GnRH neurons, and the signaling pathways involved in this process. GN11 cells expressed both LIFRbeta and glycoprotein 130 subunits. Exposure of GN11 cells to 100 ng/ml LIF resulted in activation of the Janus kinases (Jaks)/signal transducer and activator of transcription 3, MAPK/ERK1/2, and phosphatidylinositol 3-kinase/protein kinase B/Akt pathways. The selective inhibition of Jaks, MAPK kinase, and phosphatidylinositol 3-kinase indicated that these signaling pathways were activated independently by LIF and that Jak2 is not the main kinase involved in LIF signaling. Exposure of GN11 cells to LIF for 3 h induced a concentration-dependent chemotactic response, with a plateau at 100 ng/ml LIF. LIF was also found to induce chemokinesis of GN11 cells. Furthermore, LIF-promoted GN11 migration was the result of the partial and independent contribution of all the three signaling pathways activated by LIF. The present data, together with the observation that LIF and LIFRbeta are expressed prenatally in the mouse nasal compartment, would suggest that LIF might participate in the migration of GnRH neurons. FAU - Magni, Paolo AU - Magni P AD - Department of Endocrinology, Center of Excellence on Neurodegenerative Diseases, University of Milan, via G. Balzaretti, 9, 20133 Milano, Italy. paolo.magni@unimi.it FAU - Dozio, Elena AU - Dozio E FAU - Ruscica, Massimiliano AU - Ruscica M FAU - Watanobe, Hajime AU - Watanobe H FAU - Cariboni, Anna AU - Cariboni A FAU - Zaninetti, Roberta AU - Zaninetti R FAU - Motta, Marcella AU - Motta M FAU - Maggi, Roberto AU - Maggi R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070213 PL - United States TA - Mol Endocrinol JT - Molecular endocrinology (Baltimore, Md.) JID - 8801431 RN - 0 (DNA Primers) RN - 0 (Leukemia Inhibitory Factor) RN - 0 (Recombinant Proteins) RN - 33515-09-2 (Gonadotropin-Releasing Hormone) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.10.2 (Janus Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) SB - IM MH - Animals MH - Cell Line MH - Cell Line, Tumor MH - Cell Movement/*drug effects MH - DNA Primers MH - Enzyme Activation MH - Extracellular Signal-Regulated MAP Kinases/*metabolism MH - Gonadotropin-Releasing Hormone/*physiology MH - Humans MH - Janus Kinases/*metabolism MH - Leukemia Inhibitory Factor/*pharmacology MH - Mitogen-Activated Protein Kinase 3/*metabolism MH - Neurons/drug effects/*physiology MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Recombinant Proteins/pharmacology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction EDAT- 2007/02/15 09:00 MHDA- 2007/07/24 09:00 CRDT- 2007/02/15 09:00 PHST- 2007/02/15 09:00 [pubmed] PHST- 2007/07/24 09:00 [medline] PHST- 2007/02/15 09:00 [entrez] AID - me.2006-0270 [pii] AID - 10.1210/me.2006-0270 [doi] PST - ppublish SO - Mol Endocrinol. 2007 May;21(5):1163-74. doi: 10.1210/me.2006-0270. Epub 2007 Feb 13. PMID- 17187019 OWN - NLM STAT- MEDLINE DCOM- 20070215 LR - 20070101 IS - 0172-780X (Print) IS - 0172-780X (Linking) VI - 27 IP - 6 DP - 2006 Dec TI - Plasma nerve growth factor (NGF) and inflammatory cytokines (IL-6 and MCP-1) in young and adult subjects with Down syndrome: an interesting pathway. PG - 773-8 AB - OBJECTIVES: Down's syndrome (DS) is the most frequent chromosomal aberration in men and it is invariably associated with mental retardation. MATERIAL AND METHODS: Plasma levels of nerve growth factor (NGF), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) from non demented DS subjects of three different age-cohorts (2-14 years; 20-50 yrs; >60 yrs) and healthy controls were measured. No clinical and sub-clinical inflammation was apparent in DS patients. RESULTS: Plasma levels of NGF were higher in children, adult and old DS subjects than in controls. However, a significant age-related decrease of NGF levels was present in DS subjects. Serum levels of IL-6 and MCP-1 were also increased in DS children and adults, but not in older DS patients. CONCLUSIONS: High levels of circulating NGF might protect DS from clinical complications of atherosclerosis. However, the striking decrement of peripheral NGF levels with advancing age may predispose DS to clinical manifestation of dementia after adulthood. FAU - Corsi, Massimiliano M AU - Corsi MM AD - Institute of General Pathology, Laboratory of Clinical Pathology, Medical Faculty, University of Milan, Italy. mmcorsi@unimi.it FAU - Dogliotti, Giada AU - Dogliotti G FAU - Pedroni, Francesca AU - Pedroni F FAU - Palazzi, Elisa AU - Palazzi E FAU - Magni, Paolo AU - Magni P FAU - Chiappelli, Martina AU - Chiappelli M FAU - Licastro, Federico AU - Licastro F LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Sweden TA - Neuro Endocrinol Lett JT - Neuro endocrinology letters JID - 8008373 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-6) RN - 9061-61-4 (Nerve Growth Factor) SB - IM MH - Adolescent MH - Adult MH - Age Factors MH - Aged MH - Aging/*blood MH - Atherosclerosis/blood/complications MH - Case-Control Studies MH - Chemokine CCL2/*blood MH - Child MH - Child, Preschool MH - Down Syndrome/*blood/complications MH - Female MH - Humans MH - Interleukin-6/*blood MH - Male MH - Middle Aged MH - Nerve Growth Factor/*blood MH - Statistics, Nonparametric EDAT- 2006/12/26 09:00 MHDA- 2007/02/16 09:00 CRDT- 2006/12/26 09:00 PHST- 2006/09/08 00:00 [received] PHST- 2006/10/23 00:00 [accepted] PHST- 2006/12/26 09:00 [pubmed] PHST- 2007/02/16 09:00 [medline] PHST- 2006/12/26 09:00 [entrez] AID - NEL270606A12 [pii] PST - ppublish SO - Neuro Endocrinol Lett. 2006 Dec;27(6):773-8. PMID- 15913496 OWN - NLM STAT- MEDLINE DCOM- 20060110 LR - 20181113 IS - 1522-6417 (Print) IS - 1522-6417 (Linking) VI - 7 IP - 3 DP - 2005 Jun TI - Aldosterone receptor antagonists: biology and novel therapeutic applications. PG - 206-11 AB - A dysregulation of the aldosterone system has been involved in the pathophysiology of cardiovascular diseases, including myocardial failure and, partially, essential hypertension. In humans and in rat models, aldosterone action induces heart remodeling and interstitial and perivascular myocardial fibrosis. Therefore, a rationale for using aldosterone antagonists (ARAs) of the spironolactone family, which have been available for decades for the treatment of aldosterone excess syndromes, has now emerged. The development of compounds such as eplerenone, with a greater selectivity for mineralocorticoid receptors, is promising also in terms of reduction of endocrine side effects. The use of ARAs for the treatment of myocardial failure and selected cases of hypertension, in combination with the current therapy, has been strongly supported by trials such as the Randomized Aldactone Evaluation Study (RALES) and the Eplerenone Neurohormonal Efficacy and Survival Study (EPHESUS). Thus, the addition of ARAs to the conventional therapy appears beneficial, leading to an improved survival rate and a reduced incidence of cardiac complications. FAU - Magni, Paolo AU - Magni P AD - Istituto di Endocrinologia, University of Milan, via G. Balzaretti, 9, 20133 Milano, Italy. paolo.magni@unimi.it FAU - Motta, Marcella AU - Motta M LA - eng PT - Journal Article PT - Review PL - United States TA - Curr Hypertens Rep JT - Current hypertension reports JID - 100888982 RN - 0 (Mineralocorticoid Receptor Antagonists) RN - 4964P6T9RB (Aldosterone) SB - IM MH - Aldosterone/physiology MH - Heart Failure/drug therapy/metabolism/physiopathology MH - Humans MH - Hyperaldosteronism/drug therapy/metabolism MH - Hypertension/drug therapy/metabolism MH - *Mineralocorticoid Receptor Antagonists/chemistry/*pharmacology MH - Molecular Structure RF - 45 EDAT- 2005/05/26 09:00 MHDA- 2006/01/13 09:00 CRDT- 2005/05/26 09:00 PHST- 2005/05/26 09:00 [pubmed] PHST- 2006/01/13 09:00 [medline] PHST- 2005/05/26 09:00 [entrez] PST - ppublish SO - Curr Hypertens Rep. 2005 Jun;7(3):206-11. PMID- 15670195 OWN - NLM STAT- MEDLINE DCOM- 20050420 LR - 20061115 IS - 0300-0664 (Print) IS - 0300-0664 (Linking) VI - 62 IP - 2 DP - 2005 Feb TI - Free and bound plasma leptin in normal weight and obese men and women: relationship with body composition, resting energy expenditure, insulin-sensitivity, lipid profile and macronutrient preference. PG - 189-96 AB - OBJECTIVE: The adipose-borne hormone leptin circulates in free and protein-bound forms but little information is available about their biological significance. Free leptin (FL) levels are related to changes in fat mass, whereas bound leptin (BL) appears to be associated with resting energy expenditure (REE). Our aim was to assess FL and BL levels in normal weight and obese subjects and correlate them with metabolic and nutritional variables. DESIGN AND PATIENTS: The partitioning of plasma leptin between FL and BL was evaluated in a population (n = 44) including both genders and different degrees of adiposity [body mass index (BMI) range 18.6-79.6 kg/m2]. MEASUREMENTS: Total leptin and FL and BL concentrations were measured by fast protein liquid chromatography (FPLC) followed by radioimmunoassay (RIA). Body composition, REE, insulin sensitivity, lipid parameters associated with cardiovascular risk and macronutrient preference were also assessed. RESULTS: The BL/FL ratio was significantly reduced in obese subjects due to a major increase in FL compared with BL. Consequently, the gender difference of the %BL/%FL ratio present in lean subjects (35/65 in women; 65/35 in men) was lost in obese subjects. REE was negatively correlated with total leptin (P < 0.0001) and %FL (P < 0.0001), and positively with %BL (P < 0.001). Total leptin and FL were correlated with the diet carbohydrate content in all subjects. CONCLUSIONS: FL increases with the amount of fat mass; the prevalence of FL in normal weight women in comparison to men suggests that this fraction is particularly linked to the amount of subcutaneous fat. Moreover, the correlation of BL with REE and the relationship of FL with food intake favours the view of different biological activities for the two circulating forms of leptin. FAU - Magni, Paolo AU - Magni P AD - Istituto di Endocrinologia, Universita degli Studi di Milano, Milan, Italy. paolo.magni@unimi.it FAU - Liuzzi, Antonio AU - Liuzzi A FAU - Ruscica, Massimiliano AU - Ruscica M FAU - Dozio, Elena AU - Dozio E FAU - Ferrario, Silvia AU - Ferrario S FAU - Bussi, Isabella AU - Bussi I FAU - Minocci, Alessandro AU - Minocci A FAU - Castagna, Alessandra AU - Castagna A FAU - Motta, Marcella AU - Motta M FAU - Savia, Giulio AU - Savia G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Clin Endocrinol (Oxf) JT - Clinical endocrinology JID - 0346653 RN - 0 (Blood Proteins) RN - 0 (Cholesterol, HDL) RN - 0 (Cholesterol, LDL) RN - 0 (Dietary Carbohydrates) RN - 0 (Leptin) RN - 0 (Triglycerides) SB - IM MH - Adipose Tissue/metabolism MH - Adolescent MH - Adult MH - *Basal Metabolism MH - Blood Proteins/metabolism MH - *Body Composition MH - Cardiovascular Diseases/metabolism MH - Case-Control Studies MH - Cholesterol, HDL/blood MH - Cholesterol, LDL/blood MH - Dietary Carbohydrates/adverse effects MH - Energy Intake MH - Female MH - Humans MH - Insulin Resistance MH - Leptin/*blood MH - Male MH - Middle Aged MH - Obesity/blood/*metabolism MH - Risk Factors MH - Triglycerides/blood EDAT- 2005/01/27 09:00 MHDA- 2005/04/21 09:00 CRDT- 2005/01/27 09:00 PHST- 2005/01/27 09:00 [pubmed] PHST- 2005/04/21 09:00 [medline] PHST- 2005/01/27 09:00 [entrez] AID - CEN2195 [pii] AID - 10.1111/j.1365-2265.2005.02195.x [doi] PST - ppublish SO - Clin Endocrinol (Oxf). 2005 Feb;62(2):189-96. doi: 10.1111/j.1365-2265.2005.02195.x. PMID- 12570784 OWN - NLM STAT- MEDLINE DCOM- 20030801 LR - 20180605 IS - 1389-2037 (Print) IS - 1389-2037 (Linking) VI - 4 IP - 1 DP - 2003 Feb TI - Hormonal control of the neuropeptide Y system. PG - 45-57 AB - Neuropeptide Y (NPY) and the related receptors represent a widely diffused system that is involved in the regulation of multiple biological functions. NPY, a 36-aminoacid peptide expressed in several areas of the nervous system, is a pleiotropic factor participating to the control of some physiological processes, such as cognitive functions, eating behavior, circadian rhythms, neuroendocrine mechanisms, reproductive and cardiovascular functions. NPY acts through a series of G-protein-associated membrane receptors (NPY-Rs), characterized by different tissue distribution and affinity for the ligand. The expression and secretion of NPY and the expression of NPY-R isoforms are controlled by a very wide range of agents, acting in an endocrine and/or paracrine fashion. NPY and NPY-Rs appear to be strongly involved in the control of eating behavior; their expression is modulated by changes of food intake and energy balance and is disrupted in several animal models of obesity and diabetes. Moreover, the hypothalamic NPY system appears to integrate signals of energy balance in the modulation of the reproductive axis. Agents that stimulate their expression include activators of intracellular signalling pathways (protein kinase A and C), classical neurotransmitters, steroid and peptide hormones and growth factors, while other agents (leptin, insulin and retinoic acid) have been shown to be inhibitory. Interestingly, some agents, like retinoic acid, have been shown to modulate the expression of both NPY and NPY-Rs in the same direction, thus providing a fine mechanism for the tuning of the system. The regulation of NPY/NPY-R expression and function appears to be part of a complex system controlling multiple physiological functions, and its disruption might be relevant in the pathophysiology of disease states such as obesity. FAU - Magni, Paolo AU - Magni P AD - Istituto di Endocrinologia, Universita degli Studi di Milano, Milan, Italy. paolo.magni@unimi.it LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United Arab Emirates TA - Curr Protein Pept Sci JT - Current protein & peptide science JID - 100960529 RN - 0 (Hormones) RN - 0 (Neuropeptide Y) SB - IM MH - Amino Acid Sequence MH - Animals MH - Body Weight MH - Gene Expression Regulation MH - Hormones/*metabolism MH - Humans MH - Molecular Sequence Data MH - Neuropeptide Y/genetics/*metabolism MH - Reproduction MH - Signal Transduction RF - 178 EDAT- 2003/02/07 04:00 MHDA- 2003/08/02 05:00 CRDT- 2003/02/07 04:00 PHST- 2003/02/07 04:00 [pubmed] PHST- 2003/08/02 05:00 [medline] PHST- 2003/02/07 04:00 [entrez] PST - ppublish SO - Curr Protein Pept Sci. 2003 Feb;4(1):45-57.