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https://www.readbyqxmd.com/read/27903228/synthesis-and-evaluation-of-the-hypoglycemic-and-hypolipidemic-activity-of-novel-sulfonamide-benzothiazole-derivatives-of-benzylidene-2-4-thiazolidnedione
#1
Abbas Ahmadi, Mohsen Khalili, Lida Sohrabi, Nazanin Delzendeh, Babak Nahri-Niknafs, Fariba Ansari
Thiazolidinediones (TZDs) and sulfonamides are important and highly consumption class of antidiabetic drugs having insulin sensitizing and stimulating properties in patients with type 2 diabetes, respectively. In this paper, some novel benzothiazole derivatives of TZD-sulfonamides were synthesized (I-IV) and evaluated for anti-hyperglycemic and anti-hyperlipidemic activities in the STZ-induced diabetic rat model. Results indicated that all new conjugated drugs showed significant hypoglycemic activities compared to the control animals that were better for I and IV than others...
November 29, 2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/27867269/platyphylloside-isolated-from-betula-platyphylla-inhibit-adipocyte-differentiation-and-induce-lipolysis-via-regulating-adipokines-including-ppar%C3%AE-in-3t3-l1-cells
#2
Mina Lee, Sang Hyun Sung
BACKGROUND: Obesity causes or aggravates many health problems, both independently and in association with several pathological disorders, including Type II diabetes, hypertension, atherosclerosis, and cancer. Therefore, we screened small compounds isolated from natural products for the development of anti-obesity drugs. OBJECTIVE: The purpose of this study was to investigate the anti-adipogenic activities of platyphylloside, diarylheptanoid isolated from Betula platyphylla, which was selected based on the screening using 3T3-L1 cells...
October 2016: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/27865894/activation-of-peroxisome-proliferator-activated-receptor-gamma-in-mammary-epithelial-cells-upregulates-the-expression-of-tumor-suppressor-cyld-to-mediate-growth-inhibition-and-anti-inflammatory-effects
#3
Athanasios Pseftogas, Christos Gonidas, George Mosialos
Several studies have implicated the downregulation of the tumor suppressor Cyld expression in breast cancer development. However, the mechanisms that regulate Cyld expression in mammary epithelial cells are largely unknown. In order to investigate them, a bioinformatic analysis of the promoter region of Cyld was performed and identified putative nuclear hormone receptor response elements that included peroxisome proliferator-activated receptor gamma (PPAR-γ)-responsive elements. In the present study, we showed that upon activation of the nuclear hormone receptor PPAR-γ by the agonist troglitazone (TZD), there was a significant increase in Cyld mRNA in human mammary epithelial cell lines...
November 16, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27759627/thiazolidinediones-for-nonalcoholic-steatohepatitis-a-meta-analysis-of-randomized-clinical-trials
#4
Lingling He, Xiaoli Liu, Lijia Wang, Zhiyun Yang
The findings regarding the effects of thiazolidinediones (TZDs) in nonalcoholic steatohepatitis (NASH) patients have been inconsistent, and the assessment of different clinical variables for evaluating the effects of TZDs confound a direct comparison of the results of different randomized clinical trials (RCTs), especially with regard to lifestyle changes. In this paper, we performed a meta-analysis of randomized controlled trials to clarify the effects of TZD treatment with and without lifestyle changes on histological markers of NASH and clinical variables related to insulin resistance (IR), hyperlipidemia, and obesity...
October 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27708617/increased-circulating-adiponectin-in-response-to-thiazolidinediones-investigating-the-role-of-bone-marrow-adipose-tissue
#5
Richard J Sulston, Brian S Learman, Bofeng Zhang, Erica L Scheller, Sebastian D Parlee, Becky R Simon, Hiroyuki Mori, Adam J Bree, Robert J Wallace, Venkatesh Krishnan, Ormond A MacDougald, William P Cawthorn
BACKGROUND: Bone marrow adipose tissue (MAT) contributes to increased circulating adiponectin, an insulin-sensitizing hormone, during caloric restriction (CR), but whether this occurs in other contexts remains unknown. The antidiabetic thiazolidinediones (TZDs) also promote MAT expansion and hyperadiponectinemia, even without increasing adiponectin expression in white adipose tissue (WAT). OBJECTIVES: To test the hypothesis that MAT expansion contributes to TZD-associated hyperadiponectinemia, we investigated the effects of rosiglitazone, a prototypical TZD, in wild-type (WT) or Ocn-Wnt10b mice...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27703271/pioglitazone-ameliorates-smooth-muscle-cell-proliferation-in-cuff-induced-neointimal-formation-by-both-adiponectin-dependent-and-independent-pathways
#6
Tetsuya Kubota, Naoto Kubota, Hiroyuki Sato, Mariko Inoue, Hiroki Kumagai, Tomokatsu Iwamura, Iseki Takamoto, Tsuneo Kobayashi, Masao Moroi, Yasuo Terauchi, Kazuyuki Tobe, Kohjiro Ueki, Takashi Kadowaki
The aim of this study is to elucidate to what degree adiponectin is involved in TZD-mediated amelioration of neointimal formation. We investigated the effect of 3- or 8-weeks' pioglitazone on cuff-induced neointimal formation in adiponectin-deficient (APN-KO) and wild-type (WT) mice. Pioglitazone for 3 weeks reduced neointimal formation in the WT mice with upregulation of the plasma adiponectin levels, but failed to reduce neointimal formation in the APN-KO mice, suggesting that pioglitazone suppressed neointimal formation by adiponectin-dependent mechanisms...
October 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27693798/chronic-lpsf-gq-02-treatment-attenuates-inflammation-and-atherosclerosis-development-in-ldlr-mice
#7
Amanda Karolina Soares E Silva, Fabiana Oliveira Dos Santos Gomes, Bruna Dos Santos Silva, Edlene Lima Ribeiro, Amanda Costa Oliveira, Shyrlene Meyre da Rocha Araújo, Ingrid Tavares de Lima, Anne Gabrielle Vasconcelos Oliveira, Martina Rudnicki, Dulcineia S P Abdalla, Maria do Carmo Alves de Lima, Ivan da Rocha Pitta, Christina Alves Peixoto
BACKGROUND: Atherosclerosis is a complex disorder with a multifactorial pathogenesis. We previously indicated that the new TZD LPSF/GQ-02 inhibits hepatic steatosis and inflammation, which are reported as risk factors for atherosclerosis development. Here, we explored the effects of LPSF/GQ-02 on atherosclerosis in LDLr-/- mice comparing two treatment periods. METHODS AND RESULTS: LDLr(-/-) mice were fed a high-fat diet for 10 and 12 weeks and received oral treatment with LPSF/GQ-02 (30mg/kg/day) or pioglitazone (20mg/kg/day) for 15 and 30 days, respectively...
September 29, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27692066/macrophage-ppar%C3%AE-inhibits-gpr132-to-mediate-the-anti-tumor-effects-of-rosiglitazone
#8
Wing Yin Cheng, HoangDinh Huynh, Peiwen Chen, Samuel Peña-Llopis, Yihong Wan
Tumor-associated macrophage (TAM) significantly contributes to cancer progression. Human cancer is enhanced by PPARγ loss-of-function mutations, but inhibited by PPARγ agonists such as TZD diabetes drugs including rosiglitazone. However, it remains enigmatic whether and how macrophage contributes to PPARγ tumor-suppressive functions. Here we report that macrophage PPARγ deletion in mice not only exacerbates mammary tumor development but also impairs the anti-tumor effects of rosiglitazone. Mechanistically, we identify Gpr132 as a novel direct PPARγ target in macrophage whose expression is enhanced by PPARγ loss but repressed by PPARγ activation...
October 3, 2016: ELife
https://www.readbyqxmd.com/read/27687671/identification-of-small-molecules-that-bind-to-the-mitochondrial-protein-mitoneet
#9
Werner J Geldenhuys, Heather M Yonutas, Daniel L Morris, Patrick G Sullivan, Altaf S Darvesh, Thomas C Leeper
MitoNEET (CISD1) is a 2Fe-2S iron-sulfur cluster protein belonging to the zinc-finger protein family. Recently mitoNEET has been shown to be a major role player in the mitochondrial function associated with metabolic type diseases such as obesity and cancers. The anti-diabetic drug pioglitazone and rosiglitazone were the first identified ligands to mitoNEET. Since little is known about structural requirements for ligand binding to mitoNEET, we screened a small set of compounds to gain insight into these requirements...
September 6, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27622746/structure-activity-relationship-studies-of-non-carboxylic-acid-peroxisome-proliferator-activated-receptor-%C3%AE-%C3%AE-ppar%C3%AE-%C3%AE-dual-agonists
#10
Shogo Okazaki, Ryuta Shioi, Tomomi Noguchi-Yachide, Minoru Ishikawa, Makoto Makishima, Yuichi Hashimoto, Takao Yamaguchi
The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that contribute to the regulation of lipid, glucose and cholesterol homeostases. They are considered as therapeutic targets for metabolic diseases such as dyslipidemia and type 2 diabetes mellitus. Various PPAR agonists have been developed, but most of them contain a carboxylic acid (CA) or thiazolidinedione (TZD) moiety, which is essential for the activity. However, we recently discovered non-CA/non-TZD class PPARα/δ dual agonists having an acetamide structure...
November 1, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27602497/modulation-of-glycogen-synthase-kinase-3%C3%AE-following-trail-combinatorial-treatment-in-cancer-cells
#11
Sreevidya Santha, Gantulga Davaakhuu, Aninda Basu, Rong Ke, Subhasis Das, Ajay Rana, Basabi Rana
Glycogen Synthase Kinase-3β (GSK3β) is a serine/threonine kinase, known to regulate various cellular processes including proliferation, differentiation, survival, apoptosis as well as TRAIL-resistance. Thus pathways that can modulate GSK3β axis are important targets for cancer drug development. Our earlier studies have shown that combinatorial treatment with Troglitazone (TZD) and TRAIL can induce apoptosis in TRAIL-resistant cancer cells. The current studies were undertaken to investigate whether GSK3β pathway was modulated during this apoptosis...
September 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27598860/does-thiazolidinedione-therapy-exacerbate-fluid-retention-in-congestive-heart-failure
#12
Ilia Goltsman, Emad E Khoury, Joseph Winaver, Zaid Abassi
The ever-growing global burden of congestive heart failure (CHF) and type 2 diabetes mellitus (T2DM) as well as their co-existence necessitate that anti-diabetic pharmacotherapy will modulate the cardiovascular risk inherent to T2DM while complying with the accompanying restrictions imposed by CHF. The thiazolidinedione (TZD) family of peroxisome proliferator-activated receptor γ (PPARγ) agonists initially provided a promising therapeutic option in T2DM owing to anti-diabetic efficacy combined with pleiotropic beneficial cardiovascular effects...
September 4, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27585542/association-between-use-of-oral-antidiabetic-drugs-and-the-risk-of-aortic-aneurysm-a-nested-case-control-analysis
#13
Chien-Yi Hsu, Yu-Wen Su, Yung-Tai Chen, Shih-Hung Tsai, Chun-Chin Chang, Szu-Yuan Li, Po-Hsun Huang, Jaw-Wen Chen, Shing-Jong Lin
BACKGROUND: Pleiotropic effects on cardiovascular protection have been suggested in several oral antidiabetic drugs (OAD). The impacts of OADs on aortic aneurysm (AA) growth have been found in animal studies, but the evidence of their beneficial effects for AA protection in human are lacking. We investigated the relationship between OAD therapy and the risk of developing AA. METHODS: We conducted a nested case-control analysis using the database extracted from Taiwan's National Health Insurance Research Database...
2016: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/27558352/characterization-of-alendronic-and-undecylenic-acid-coated-magnetic-nanoparticles-for-the-targeted-delivery-of-rosiglitazone-to-subcutaneous-adipose-tissue
#14
Katayoun Saatchi, Sarah E Tod, Donna Leung, Kenton E Nicholson, Irene Andreu, Christian Buchwalder, Veronika Schmitt, Urs O Häfeli, Sarah L Gray
Obesity is a state of positive energy balance where excess white adipose tissue accumulates to the detriment of metabolic health. Improving adipocyte function with systemic administration of thiazolidinediones (TZDs) improves metabolic outcomes in obesity, however TZD use is limited clinically due to undesirable side effects. Here we evaluate magnetic nanoparticles (MNPs) as a tool to target rosiglitazone (Rosi) specifically to adipose tissue. Results show Rosi can be adsorbed to MNPs (Rosi-MNPs) with hydrophobic coatings for which we present binding and release kinetics...
August 21, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27528232/ppar%C3%AE-agonists-promote-differentiation-of-cancer-stem-cells-by-restraining-yap-transcriptional-activity
#15
Upal Basu-Roy, Eugenia Han, Kirk Rattanakorn, Abhilash Gadi, Narendra Verma, Giulia Maurizi, Preethi H Gunaratne, Cristian Coarfa, Oran D Kennedy, Michael J Garabedian, Claudio Basilico, Alka Mansukhani
Osteosarcoma (OS) is a highly aggressive pediatric bone cancer in which most tumor cells remain immature and fail to differentiate into bone-forming osteoblasts. However, OS cells readily respond to adipogenic stimuli suggesting they retain mesenchymal stem cell-like properties. Here we demonstrate that nuclear receptor PPARγ agonists such as the anti-diabetic, thiazolidinedione (TZD) drugs induce growth arrest and cause adipogenic differentiation in human, mouse and canine OS cells as well as in tumors in mice...
August 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27513562/anti-hyperglycemic-agents-and-new-onset-acute-myocardial-infarction-in-diabetic-patients-with-end-stage-renal-disease-undergoing-dialysis
#16
Ting-Tse Lin, Chih-Chen Wu, Yao-Hsu Yang, Lian-Yu Lin, Jiunn-Lee Lin, Pau-Chung Chen, Juey-Jen Hwang
BACKGROUND: Diabetes and chronic kidney disease (CKD) are a high-stakes combination for cardiovascular disease. Patients with decreased kidney function and end-stage renal disease (ESRD) have increased risk of hypoglycemia when attaining better glycemic control, leading to higher risk of myocardial infarction (MI). For these patients, which kinds of anti-hyperglycemic agents would be associated with higher risk of MI is not clear. METHODS: We identified patients from a nation-wide database called Registry for Catastrophic Illness, which encompassed almost 100% of the patients receiving dialysis therapy in Taiwan from 1995 to 2008...
2016: PloS One
https://www.readbyqxmd.com/read/27512874/comparative-efficacy-of-interventions-on-nonalcoholic-fatty-liver-disease-nafld-a-prisma-compliant-systematic-review-and-network-meta-analysis
#17
Ratree Sawangjit, Bunchai Chongmelaxme, Pochamana Phisalprapa, Surasak Saokaew, Ammarin Thakkinstian, Kris V Kowdley, Nathorn Chaiyakunapruk
BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) has significantly increased over the last decades. Despite existence of several interventions, there remains unclear which interventions work the best. METHODS: A systematic review and network meta-analysis of randomized trials comparing efficacy of all treatment options in NAFLD were performed to determine comparative efficacy and safety of interventions in the management of NAFLD. Several electronic databases were searched up to Nov 15, 2015...
August 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27506737/adiponectin-as-a-target-for-the-treatment-of-nonalcoholic-steatohepatitis-with-thiazolidinediones-a-systematic-review
#18
REVIEW
Stergios A Polyzos, Christos S Mantzoros
Thiazolidinediones (TZDs; pioglitazone and rosiglitazone) have provided promising results in clinical trials for nonalcoholic steatohepatitis (NASH). The main purpose of this systematic review was to summarize evidence on circulating adiponectin levels in relation to histological changes following TZD treatment in patients with histologically confirmed NASH. We performed a systematic search in PubMed, Scopus and Cochrane Library. We included four studies, published between 2006 and 2012, providing data for 187 histologically confirmed NASH adult patients (105 on TZD and 82 controls) treated for 6-12months...
September 2016: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/27403152/pioglitazone-attenuates-drug-eluting-stent-induced-proinflammatory-state-in-patients-by-blocking-ubiquitination-of-ppar
#19
Zhongxia Wang, Tao Zhang, Lizhe Sun, Ruifeng Li, Yuanyuan Wei, Xiaojuan Fan, Zuyi Yuan, Junhui Liu, Tao Chen
The inflammatory response after polymer-based drug-eluting stent (DES) placement has recently emerged as a major concern. The biologic roles of peroxisome proliferator-activated receptor-γ (PPAR-γ) activators thiazolidinedione (TZD) remain controversial in cardiovascular disease. Herein, we investigated the antiinflammatory effects of pioglitazone (PIO) on circulating peripheral blood mononuclear cells (MNCs) in patients after coronary DES implantation. Methods and Results. Twenty-eight patients with coronary artery disease and who underwent DES implantations were randomly assigned to pioglitazone (30 mg/d; PIO) or placebo (control; Con) treatment in addition to optimal standard therapy...
2016: PPAR Research
https://www.readbyqxmd.com/read/27397605/molecular-remodeling-of-the-insulin-receptor-pathway-by-thiazolidinediones-in-type-2-diabetes-mellitus-a-brief-review
#20
Nikhil S Sahajpal, Subheet K Jain
Type 2 diabetes mellitus (T2DM) is characterized by abnormalities in carbohydrate, lipoprotein and lipid metabolism, leading to hyperglycemia and several other complications. Insulin is the major hormone regulating these facets by eliciting various biological responses through its receptor. Insulin exerts diverse effects on cells by targeting distinct functions such as gene expression, fatty acid synthesis, glucose transport and receptor translocation. Insulin mediates these effects through signaling pathways utilizing adapter molecules like small Gproteins, lipid and tyrosine kinases...
2016: Protein and Peptide Letters
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