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https://www.readbyqxmd.com/read/28231521/therapeutic-journey-of-2-4-thiazolidinediones-as-a-versatile-scaffold-an-insight-into-structure-activity-relationship
#1
REVIEW
Mohd Javed Naim, Md Jahangir Alam, Shujauddin Ahmad, Farah Nawaz, Neelima Shrivastava, Meeta Sahu, Ozair Alam
Thiazolidinedione is an important heterocyclic ring system, a pharmacophore and a privileged scaffold in medicinal chemistry; is a derivative of thiazolidine ring which came into existence for its role as antihyperglycemic agent and a specific ligand of PPAR's (Peroxisome proliferator activated receptor). Exhaustive research has led to determination of its vast biological profile with wide range of therapeutic applications. This review covers recent pharmacological advancements of thiazolidinedione moiety along with structure activity relationship so as to provide better correlation among different structures and their receptor interactions...
February 20, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28231489/moving-and-positioning-the-endolysosomal-system
#2
REVIEW
Juan S Bonifacino, Jacques Neefjes
The endolysosomal system is extremely dynamic, yet highly organized. The spatio-temporal distribution of endolysosomal organelles depends on transport driven by microtubule motors such as kinesins and dynein, and by actin-based myosin motors. It has recently become appreciated that interactions with motors are controlled by contacts with other organelles, particularly the endoplasmic reticulum (ER). The ER also controls the concentration of endolysosomal organelles in the perinuclear area, as well as their fission and fusion, through a complex system of tethering proteins...
February 20, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28231052/review-the-role-of-peroxisome-proliferator-activated-receptor-in-the-treatment-of-non-alcoholic-fatty-liver-disease
#3
Xin Sun, Yan Zhang, Meilin Xie
Non-alcoholic fatty liver disease (NAFLD) has been defined as a spectrum of histological abnormalities and is characterized by significant and excessive accumulation of triglycerides in the hepatocytes in patients without alcohol consumption or other diseases. Current studies are targeting new molecular mechanisms that underlie NAFLD and associated metabolic disorders. Many therapeutic targets have been found and used in clinical studies. Peroxisome proliferator-activated receptors (PPARs) are among the potential targets and have been demonstrated to exert a pivotal role in modulation of NAFLD...
March 1, 2017: Acta Pharmaceutica
https://www.readbyqxmd.com/read/28225824/caloric-restriction-reduces-the-systemic-progression-of-mouse-aapoaii-amyloidosis
#4
Lin Li, Jinko Sawashita, Xin Ding, Mu Yang, Zhe Xu, Hiroki Miyahara, Masayuki Mori, Keiichi Higuchi
In mouse senile amyloidosis, apolipoprotein (Apo) A-II is deposited extracellularly in many organs in the form of amyloid fibrils (AApoAII). Reduction of caloric intake, known as caloric restriction (CR), slows the progress of senescence and age-related disorders in mice. In this study, we intravenously injected 1 μg of isolated AApoAII fibrils into R1.P1-Apoa2c mice to induce experimental amyloidosis and investigated the effects of CR for the next 16 weeks. In the CR group, AApoAII amyloid deposits in the liver, tongue, small intestine and skin were significantly reduced compared to those of the ad libitum feeding group...
2017: PloS One
https://www.readbyqxmd.com/read/28225792/the-adamts9-gene-is-associated-with-cognitive-aging-in-the-elderly-in-a-taiwanese-population
#5
Eugene Lin, Shih-Jen Tsai, Po-Hsiu Kuo, Yu-Li Liu, Albert C Yang, Chung-Feng Kao, Cheng-Hung Yang
Evidence indicates that the pathophysiologic mechanisms associated with insulin resistance may contribute to cognitive aging and Alzheimer's diseases. In this study, we hypothesize that single nucleotide polymorphisms (SNPs) within insulin resistance-associated genes, such as the ADAM metallopeptidase with thrombospondin type 1 motif 9 (ADAMTS9), glucokinase regulator (GCKR), and peroxisome proliferator activated receptor gamma (PPARG) genes, may be linked with cognitive aging independently and/or through complex interactions in an older Taiwanese population...
2017: PloS One
https://www.readbyqxmd.com/read/28224418/dietary-restriction-reduces-blood-lipids-and-ameliorates-liver-function-of-mice-with-hyperlipidemia
#6
Hai-Tao Gao, Wen-Zhao Cheng, Qian Xu, Lin-Xiang Shao
Dietary restriction (DR) can delay senescence, prolong lifespan of mammals and improve their learning-memory activity. The purpose of the study was to explore the effects of DR on hypolipidemic action and liver function of mice with hyperlipidemia. To investigate these effects, hyperlipidemia mouse models were established with high-fat diet (HFD) (34% of energy), then randomly divided into HFD group, DR30% group and DR50% group. Mice in DR30% and DR50% group were respectively supplied with HFD as much as about 70% and 50% of the consumption of HFD in the mice of HFD group...
February 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28223925/effects-of-intermittent-alcohol-exposure-on-emotion-and-cognition-a-potential-role-for-the-endogenous-cannabinoid-system-and-neuroinflammation
#7
Laura Sanchez-Marin, Francisco J Pavon, Juan Decara, Juan Suarez, Ana Gavito, Estela Castilla-Ortega, Fernando Rodriguez de Fonseca, Antonia Serrano
Intermittent alcohol exposure is a common pattern of adolescent alcohol use that can lead to binge drinking episodes. Alcohol use is known to modulate the endocannabinoid system (ECS), which is involved in neuronal communication, neuroplasticity, neuroinflammation and behavior. Adolescent male Wistar rats were exposed to 4-week intermittent alcohol intoxication (3 g/kg injections for 4 days/week) or saline (N = 12 per group). After alcohol deprivation, adult rats were assessed for emotionality and cognition and the gene expression of the ECS and other factors related to behavior and neuroinflammation was examined in the brain...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28223870/bioactivity-and-chemical-characterization-of-acalypha-fruticosa-forssk-growing-in-saudi-arabia
#8
Ghada Ahmed Fawzy, Areej Mohammad Al-Taweel, Shagufta Perveen, Shabana Iqrar Khan, Fatma Abdulaziz Al-Omary
Acalypha is an important genus of the Euphorbiaceae family. The genus is represented by five species in Saudi Arabia. Acalypha fruticosa Forssk. Fl. Aeg is traditionally used as a cure for stomachache, dyspepsia, rheumatism, dermatitis, and swellings of the body. The present study endeavors to provide a phytochemical and biological evaluation of the plant, with the aim of relating activity to constituting secondary metabolites in the plant. Column chromatographic separation of the methanol extract led to the isolation of four compounds namely 2-methyl-5,7-dihydroxychromone 5-O-β-d-glucopyranoside 1, acalyphin 2, apigenin 3 and kaempferol 3-O-rutinoside 4...
January 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28223292/muscle-pgc-1%C3%AE-is-required-for-long-term-systemic-and-local-adaptations-to-a-ketogenic-diet-in-mice
#9
Svenia Schnyder, Kristoffer Svensson, Bettina Cardel, Christoph Handschin
Low carbohydrate/high-fat (LCHF) diets are increasingly popular dietary interventions for body weight control and as treatment for different pathological conditions. However, the mechanisms of action are still poorly understood, in particular in long-term administration. Besides liver, brain and heart, skeletal muscle is one of the major organs involved in the regulation of physiological and pathophysiological ketosis. We now assessed the role of the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in skeletal muscle of male wild type control (CTRL) and PGC-1α muscle-specific knockout (PGC-1α mKO) mice upon 12 weeks of LCHF diet feeding...
February 21, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28222744/herpes-simplex-virus-1-infection-dampens-the-immediate-early-antiviral-innate-immunity-signaling-from-peroxisomes-by-tegument-protein-vp16
#10
Chunfu Zheng, Chenhe Su
BACKGROUND: Herpes simplex virus 1 (HSV-1) is an archetypal member of the alphaherpesvirus subfamily with a large genome encoding over 80 proteins, many of which play a critical role in virus-host interactions and immune modulation. Upon viral infections, the host cells activate innate immune responses to restrict their replications. Peroxisomes, which have long been defined to regulate metabolic activities, are reported to be important signaling platforms for antiviral innate immunity...
February 21, 2017: Virology Journal
https://www.readbyqxmd.com/read/28220896/mitochondrial-dysregulation-secondary-to-endoplasmic-reticulum-stress-in-autosomal-dominant-tubulointerstitial-kidney-disease-umod-adtkd-umod
#11
Elisabeth Kemter, Thomas Fröhlich, Georg J Arnold, Eckhard Wolf, Rüdiger Wanke
'Autosomal dominant tubulointerstitial kidney disease - UMOD' (ADTKD-UMOD) is caused by impaired maturation and secretion of mutant uromodulin (UMOD) in thick ascending limb of Henle loop (TAL) cells, resulting in endoplasmic reticulum (ER) stress and unfolded protein response (UPR). To gain insight into pathophysiology, we analysed proteome profiles of TAL-enriched outer renal medulla samples from ADTKD-UMOD and control mice by quantitative LC-MS/MS. In total, 212 differentially abundant proteins were identified...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220855/extending-calibration-free-force-measurements-to-optically-trapped-rod-shaped-samples
#12
Frederic Català, Ferran Marsà, Mario Montes-Usategui, Arnau Farré, Estela Martín-Badosa
Optical trapping has become an optimal choice for biological research at the microscale due to its non-invasive performance and accessibility for quantitative studies, especially on the forces involved in biological processes. However, reliable force measurements depend on the calibration of the optical traps, which is different for each experiment and hence requires high control of the local variables, especially of the trapped object geometry. Many biological samples have an elongated, rod-like shape, such as chromosomes, intracellular organelles (e...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220655/ppars-in-the-central-nervous-system-roles-in-neurodegeneration-and-neuroinflammation
#13
Juan M Zolezzi, Manuel J Santos, Sussy Bastías-Candia, Claudio Pinto, Juan A Godoy, Nibaldo C Inestrosa
Over 25 years have passed since peroxisome proliferators-activated receptors (PPARs), were first described. Like other members of the nuclear receptors superfamily, PPARs have been defined as critical sensors and master regulators of cellular metabolism. Recognized as ligand-activated transcription factors, they are involved in lipid, glucose and amino acid metabolism, taking part in different cellular processes, including cellular differentiation and apoptosis, inflammatory modulation and attenuation of acute and chronic neurological damage in vivo and in vitro...
February 20, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28220523/inflammation-is-independent-of-steatosis-in-a-murine-model-of-steatohepatitis
#14
Wei Wang, Ming-Jiang Xu, Yan Cai, Zhou Zhou, Haixia Cao, Partha Mukhopadhyay, Pal Pacher, Shusen Zheng, Frank J Gonzalez, Bin Gao
Obesity and alcohol consumption synergistically promote steatohepatitis, and neutrophil infiltration is believed to be associated with steatosis. However, the underlying mechanisms remain obscure. Peroxisome proliferator-activated receptor-gamma (PPARγ) plays a complex role in lipid metabolism and inflammation, therefore, the purpose of this study was to dissect its role in regulating steatosis and neutrophil infiltration in a clinically relevant mouse steatohepatitis model of 3-month high-fat diet (HFD) feeding plus a binge of ethanol (HFD -plus-binge ethanol)...
February 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28219837/chronic-maternal-calcium-and-25-hydroxyvitamin-d-deficiency-in-wistar-rats-programs-abnormal-hepatic-gene-expression-leading-to-hepatic-steatosis-in-female-offspring
#15
Sona S Sharma, Nivedita M Jangale, Abhay M Harsulkar, Medha K Gokhale, Bimba N Joshi
Importance of calcium and vitamin D deficiency is well established in adult dyslipidemia. We hypothesized that maternal calcium and vitamin D deficiency could alter offspring's lipid metabolism. Our objective was to investigate the effect of maternal dietary calcium and vitamin D deficiency on lipid metabolism and liver function of the F1 generation offspring. intergenerational calcium-deficient (CaD) and vitamin D-deficient (VDD) models were developed by mating normal male rats with deficient females and continuing maternal-deficient diets through pregnancy and lactation...
February 8, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28219733/meibocyte-differentiation-and-renewal-insights-into-novel-mechanisms-of-meibomian-gland-dysfunction-mgd
#16
REVIEW
Ho Sik Hwang, Geraint J Parfitt, Donald J Brown, James V Jester
This paper reviews our current understanding of age-related meibomian gland dysfunction (MGD) and the role of the nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARγ), in the regulation of meibomian gland function, meibocyte differentiation and lipid synthesis. The studies suggest that PPARγ is a master regulator of meibocyte differentiation and function, whose expression and nuclear signaling coupled with meibocyte renewal is altered during aging, potentially leading to atrophy of the meibomian gland as seen in clinical MGD...
February 17, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28219719/cysteine-deprivation-prevents-induction-of-peroxisome-proliferator-activated-receptor-gamma-2-and-adipose-differentiation-of-3t3-l1-cells
#17
Nadia Nabil Haj-Yasein, Ole Berg, Fredrik Jernerén, Helga Refsum, Hilde I Nebb, Knut Tomas Dalen
Plasma cysteine is strongly associated with body fat mass in human cohorts and diets low in cysteine prevents fat accumulation in mice. It is unclear if plasma cysteine affects fat development or if fat accumulation raises plasma cysteine. To determine if cysteine affects adipogenesis, we differentiated 3T3-L1 preadipocytes in medium with reduced cysteine. Cells incubated in media with 10-20μM cysteine exhibited reduced capacity to differentiate into triacylglycerol-storing mature adipocytes compared with cells incubated with 50μM cysteine...
February 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28219679/thiazolidinediones-abrogate-cervical-cancer-growth
#18
Beverly R Wuertz, Lindsay Darrah, Justin Wudel, Frank G Ondrey
Peroxisome proliferator-activated receptor gamma (PPAR γ) is activated by thiazolidinedione drugs (TZDs) and can promote anti-cancer properties. We used three TZDs (pioglitazone, rosiglitazone, and ciglitazone) to target cervical cancer cell lines and a nude mouse animal model. Each agent increased activation of PPAR γ, as judged by a luciferase reporter gene assay in three HPV-associated cell lines (CaSki, SiHa, and HeLa cells) while decreasing cellular proliferation in a dose-dependent manner. They also promoted Oil Red O accumulation in treated cell lines and upregulated the lipid differentiation marker adipsin...
February 17, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28218036/chemopreventive-effect-of-omega-3-polyunsaturated-fatty-acids-and-atorvastatin-in-rats-with-bladder-cancer
#19
Nahla E El-Ashmawy, Eman G Khedr, Hoda A El-Bahrawy, Samar M Al-Tantawy
Bladder cancer remains a huge concern for the medical community because of its incidence and prevalence rates, as well as high percentage of recurrence and progression. Omega-3 polyunsaturated fatty acids and atorvastatin proved anti-inflammatory effects through peroxisome proliferator-activated receptor gamma mechanism. However, their chemopreventive effect still remained to be examined and clarified. In this study, bladder cancer was induced in rats by the chemical carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28216505/-effect-of-hypoxia-on-expression-of-multidrug-resistance-protein-2-and-its-regulation-mechanism
#20
Bingfeng Luo, Wenbin Li, Rong Wang, Hui Lu, Tao Yang, Zhengping Jia
Drug efflux transporters plays a key role in pharmacokinetics parameters changes. In recent years, in addition to P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), MRP2 has become an advanced research hotspot. Several signaling pathways andtranscription factors have been reported to be involved in regulation of MRP2 expression in hypoxic microenvironment of tumor, such as peroxisome proliferators-activated receptors (PPARα), nuclear factor κB (NF-κB), pregnane X receptor (PXR), farnesoid X receptor (FXR), constitutive androstane receptor (CAR) and microRNA...
January 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
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