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Mariana Oliveira Mendes, Alexandra Isabel Rosa, Andreia Neves Carvalho, Maria João Nunes, Pedro Dionísio, Elsa Rodrigues, Daniela Costa, Sara Duarte-Silva, Patrícia Maciel, Cecília Maria Pereira Rodrigues, Maria João Gama, Margarida Castro-Caldas
Parkinson's disease (PD) is a progressive neurological disorder, mainly characterized by the progressive loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc) and by the presence of intracellular inclusions, known as Lewy bodies. Despite SNpc being considered the primary affected region in PD, the neuropathological features are confined solely to the nigro-striatal axis. With disease progression other brain regions are also affected, namely the cerebral cortex, although the spreading of the neurologic damage to this region is still not completely unraveled...
February 13, 2019: Molecular and Cellular Neurosciences
Federica Laudisi, Davide Di Fusco, Vincenzo Dinallo, Carmine Stolfi, Antonio Di Grazia, Irene Marafini, Alfredo Colantoni, Angela Ortenzi, Claudia Alteri, Francesca Guerrieri, Maria Mavilio, Francesca Ceccherini-Silberstein, Massimo Federici, Thomas Thornton MacDonald, Ivan Monteleone, Giovanni Monteleone
BACKGROUND & AIMS: Food additives, such as emulsifiers, stabilizers, or bulking agents, are present in the Western diet and their consumption is increasing. However, little is known about their potential effects on intestinal homeostasis. In this study we examined the effect of some of these food additives on gut inflammation. METHODS: Mice were given drinking water containing maltodextrin (MDX), propylene glycol, or animal gelatin, and then challenged with dextran sulfate sodium or indomethacin...
September 11, 2018: Cellular and Molecular Gastroenterology and Hepatology
Yingpeng Xu, Li Yang, Shujuan Zhao, Zhengtao Wang
BACKGROUND: Bear bile powder is a valuable medicinal material characterized by high content of tauroursodeoxycholic acid (TUDCA) at a certain ratio to taurochenodeoxycholic acid (TCDCA). We had created an engineered E. coli harboring two-step bidirectional oxidative and reductive enzyme-catalyzing pathway that could rapidly convert TCDCA to TUDCA at a specific percentage in shake flasks. RESULTS: We reported here the large-scale production of TUDCA containing products by balancing the bidirectional reactions through optimizing fermentation process of the engineered E...
February 8, 2019: Microbial Cell Factories
Jun Hee Lee, Yeo Min Yoon, Sang Hun Lee
Chronic kidney disease (CKD) leads to the loss of kidney function, as well as the dysfunction of several other organs due to the release of uremic toxins into the system. In a murine CKD model, reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress are increased in the hippocampus. Mesenchymal stem cells (MSCs) are one of the candidates for cell-based therapy for CKD; however severe pathophysiological conditions can decrease their therapeutic potential. To address these issues, we established tauroursodeoxycholic acid (TUDCA)-treated MSCs using MSCs isolated from patients with CKD (CKD-hMSCs) and assessed the survival and ROS generation of neural cell line SH-SY5Y cells by co-culturing with TUDCA-treated CKD-hMSCs...
January 31, 2019: International Journal of Molecular Sciences
Zhi Jian Chen, Jia Xing Chen, Li Kang Wu, Bi Yun Li, Ya Feng Tian, Min Xian, Zi Pei Huang, Ri An Yu
OBJECTIVE: This study was conducted to investigate the regulation of endoplasmic reticulum stress on Nrf2 signaling pathway in the kidneys of rats. METHODS: Rats were divided into twelve groups of six animals each. Some groups were pre-administered with bacitracin or tauroursodeoxycholic acid (TUDCA), and all of them were treated with 5-20 μmol/kg cadmium (Cd) for 48 h. The oxidative stress levels were analyzed using kits. The mRNA and protein expression levels of endoplasmic reticulum stress-related factors and Nrf2 signaling pathway-related factors were determined using RT-PCR and western blot...
January 2019: Biomedical and Environmental Sciences: BES
Hangqi Luo, Changzuan Zhou, Jufang Chi, Sunlei Pan, Hui Lin, Feidan Gao, Tingjuan Ni, Liping Meng, Jie Zhang, Chengjian Jiang, Zheng Ji, Haitao Lv, Hangyuan Guo
PURPOSE: The role of endoplasmic reticulum (ER) stress in cardiovascular disease is now recognized. Tauroursodeoxycholic acid (TUDCA) is known to have cardiovascular protective effects by decreasing ER stress. This study aimed to assess the ability of TUDCA to decrease ER stress, inhibit dedifferentiation of vascular smooth muscle cells (VSMCs), and reduce in-stent restenosis. METHODS: The effect of TUDCA on dedifferentiation of VSMCs and ER stress was investigated in vitro using wound-healing assays, MTT assays, and western blotting...
January 21, 2019: Cardiovascular Drugs and Therapy
K-Y Bian, H-F Jin, W Sun, Y-J Sun
OBJECTIVE: To investigate the effect of tauroursodeoxycholic acid (TUDCA) on neurological impairment induced by acute cerebral infarction (ACI) and its relevant mechanism of action. PATIENTS AND METHODS: A total of 60 male Sprague-Dawley (SD) rats were randomly divided into Sham group (n = 20), ACI group (n = 20), and TUDCA group (n = 20). The rat model of ACI in middle cerebral artery was established. TUDCA was intravenously injected into rats in the TUDCA group, while an equal amount of sodium bicarbonate solution was intravenously injected into the other two groups...
January 2019: European Review for Medical and Pharmacological Sciences
Márcio Cardoso Pinto, Danilo Chorfi Berton, Alexandre Cavenatti de Oliveira, Carolina Martins Lazaro, Silvana Aparecida Calafatti Carandina
Background: Ursodeoxycholic acid (UDCA) and its metabolites tauroursodeoxycholic acid (TUDCA) and glycoursodeoxycholic acid (GUDCA) have been the subject of several pharmacological studies. The objective of this study was to develop an innovative method of quantification by HPL-tandem mass spectrometry (LC-MS/MS), with a lower cost and suitable, for application in bioequivalence studies. Methods: The procedure involved liquid-liquid extraction for quantification of UDCA/GUDCA and precipitation extraction for TUDCA, using deuterated substances as internal standards (ISs) and Phenomenex Luna 250×4...
2019: Clinical Pharmacology: Advances and Applications
Yi Zheng, Hua Qu, Xin Xiong, Yuren Wang, Xiufei Liu, Linlin Zhang, Xiaoyu Liao, Qian Liao, Zheng Sun, Qin Ouyang, Gangyi Yang, Zhiming Zhu, Jing Xu, Hongting Zheng
Mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) is an integral component of the respiratory chain, and recent studies have suggested that it plays an important role in hepatic glucose homeostasis. However, its function in hepatic lipid metabolism is unclear. Here, we identified a novel role for mGPDH in nonalcoholic fatty liver disease (NAFLD). Specifically, mGPDH expression and activity were lower in fatty livers from NAFLD patients and mice (ob/ob, HFD and db/db). Liver-specific depletion of mGPDH in mice or mGPDH knockdown in cultured hepatocytes exacerbated diet-induced triglyceride accumulation and steatosis through enhanced lipogenesis...
January 17, 2019: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Yuta Kitamura, Guzel Bikbova, Takayuki Baba, Shuichi Yamamoto, Toshiyuki Oshitari
To determine the effectiveness of a single or a combination of topical neurotrophic factors (NFs) in protecting retinal ganglion cells (RGCs) in the rat optic nerve crush (ONC) model, the left ONC was performed to induce the death of the RGCs in adult Sprague-Dawley rats. The NFs studied were tauroursodeoxycholic acid (TUDCA), citicoline, neurotrophin-4 (NT-4), combined TUDCA/citicoline (Doublet-1), combined TUDCA/NT-4 (Doublet-2), combined TUDCA/citicoline/NT-4 (Triplet), and PBS. After 2 weeks, the number of RGCs was determined by Brn3a immunostaining...
January 14, 2019: Scientific Reports
Zichao Li, Luying Zhang, Mingquan Gao, Mei Han, Kaili Liu, Zhuang Zhang, Zhi Gong, Lifei Xing, Xianzhou Shi, Kui Lu, Hui Gao
BACKGROUND: Xanthoangelol (XAG) was reported to exhibit antitumor properties in several cancer. However, the specific anti-tumor activity of XAG in human hepatocellular carcinoma (HCC) and the relevant mechanisms are not known. METHODS: The effects of XAG on HCC cell proliferation and apoptosis were respectively examined by CCK-8 assay and Annexin V-FITC/PI apoptosis kit. Western blotting was conducted to detect the expression of proteins. The effect of XAG on the development of acidic vesicle organelles was assessed using acridine orange staining...
January 8, 2019: Journal of Experimental & Clinical Cancer Research: CR
Pablo Binder, Shunyao Wang, Maria Radu, Min Zi, Lucy Collins, Saba Khan, Yatong Li, Karolina Sekeres, Neil E Humphreys, Eileithyia Swanton, Adam Reid, Fay Pu, Delvac Oceandy, Kaomei Guan, Susanne Hille, Norbert Frey, Oliver J Müller, Elizabeth J Cartwright, Jonathan Chernoff, Wei Liu, Xin Wang
RATIONALE: Secreted and membrane-bound proteins, which account for 1/3 of all proteins, play critical roles in heart health and disease. The endoplasmic reticulum (ER) is the site for synthesis, folding and quality control of these proteins. Loss of ER homeostasis and function underlies the pathogenesis of many forms of heart disease. OBJECTIVE: To investigate mechanisms responsible for regulating cardiac ER function, and to explore therapeutic potentials of strengthening ER function in order to treat heart disease...
January 8, 2019: Circulation Research
Luping Wang, Lu Yun, Xiaojun Wang, Liying Sha, Luning Wang, Yingying Sui, Hui Zhang
AIM: Colorectal cancer (CRC) is a common human malignancy which accounts for 600,000 deaths annually at the global level. Soyasapogenol B (Soy B), an ingredient of soybean, has been found to exert anti-proliferative activities in vitro in human breast cancer cells. The current study aimed to evaluate the efficacy of Soy B in suppressing CRC. METHODS AND MATERIALS: The effect of Soy B on cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. The effect of Soy B on cell proliferation was determined using colony formation assay...
December 13, 2018: Life Sciences
Stefano Carli, Giulia Fioravanti, Andrea Armirotti, Francesca Ciarpella, Mirko Prato, Giuliana Ottonello, Marco Salerno, Alice Scarpellini, Daniela Perrone, Elena Marchesi, Davide Ricci, Luciano Fadiga
Localized drug delivery represents one of the most challenging uses of systems based on conductive polymer films. Typically, anionic drugs are incorporated within conductive polymers through the electrostatic interaction with the positively charged polymer. Following this approach, the synthetic glucocorticoid Dexamethasone-phosphate is often delivered from neural probes to reduce the inflammation of the surrounding tissue. Encouraged by recent literature on the neuroprotective and anti-inflammatory properties of Tauroursodeoxycholic acid (TUDCA), we incorporated for the first time this natural bile acid within Poly(3,4-ethylenedioxythiophene) (PEDOT)...
December 11, 2018: Chemistry: a European Journal
Won Ho Kim, Chi-Ho Lee, Jung-Hwa Han, Sujin Kim, Seong Yong Kim, Jae Hyang Lim, Kwon Moo Park, Duk Seop Shin, Chang-Hoon Woo
It has been well established that HMG-CoA reductase inhibitors (statins) cause adverse side effects in skeletal muscle ranging from mild to fatal myotoxicity upon dose, drug interaction, and exercise. However, the underlying mechanisms by which statins induce myotoxicity have not been fully addressed. Recent reports showed that statins induce endoplasmic reticulum (ER) stress and cell death in immune cells and myoblasts in vitro. Therefore, the goal of study is to investigate the molecular mechanism by which statins induce skeletal muscle cell death and myopathy via the regulation of ER stress...
December 7, 2018: Biochemical and Biophysical Research Communications
Li Chen, Chao Huang, Zhuo Chen
Depression is a mental disease that causes severe economic and social burdens. The mechanism for the onset of depression remains largely unknown. Recently, more and more attention is being given to the role of neuroinflammation and oxidative stress in depression. Tauroursodeoxycholic acid (TUDCA), a clinically available agent used to treat cholesterol gallstone and protect neurons against neurodegeneration, has been reported to prevent neuroinflammation and oxidative stress. In this study, we investigated the effect of TUDCA on lipopolysaccharide (LPS)-induced depression-like behavior, neuroinflammation, and oxido-nitrosative stress in mice...
December 5, 2018: Pharmacology
C De Miguel, R Sedaka, M Kasztan, J M Lever, M Sonnenberger, A Abad, C Jin, P K Carmines, D M Pollock, J S Pollock
AIM: Chronic high salt intake exaggerates renal injury and inflammation, especially with the loss of functional ETB receptors. Tauroursodeoxycholic acid (TUDCA) is a chemical chaperone and bile salt that is approved for the treatment of hepatic diseases. Our aim was to determine whether TUDCA is reno-protective in a model of ETB receptor deficiency with chronic high salt-induced renal injury and inflammation. METHODS: ETB -deficient and transgenic control rats were placed on normal (0...
November 30, 2018: Acta Physiologica
David Peter Obert, Alexander Karl Wolpert, Sebastian Korff
BACKGROUND: Impaired function of the endoplasmic reticulum (ER) results in ER stress, an accumulation of proteins in the ER lumen. ER stress is a major contributor to inflammatory diseases and is part of the pathomechanism of ischemia-reperfusion injury (IRI). Since severe traumatic injury is often accompanied by remote organ damage and immune cell dysfunction, we investigated the influence of ER stress modulation on the systemic inflammatory response and liver damage after hemorrhagic shock and reperfusion (HS/R)...
November 28, 2018: Shock
Sevtap Han, Nur Banu Bal, Gökhan Sadi, Suzan Emel Usanmaz, Merve Matilda Tuglu, Mecit Orhan Uludag, Emine Demirel-Yilmaz
Hypertension has complex vascular pathogenesis and therefore the molecular etiology remains poorly elucidated. Endoplasmic reticulum stress (ERS), which is a condition of the unfolded/misfolded protein accumulation in the endoplasmic reticulum, has been defined as a potential target for cardiovascular disease. In the present study, the effects of ERS inhibition on hypertension-induced alterations in the vessels were investigated. In male Wistar albino rats, hypertension was induced through unilateral nephrectomy, deoxycorticosterone-acetate (DOCA) injection (20 mg/kg, twice a week) and 1% NaCl with 0...
November 17, 2018: Vascular Pharmacology
Sebastian Thams, Emily Rhodes Lowry, Marie-Hélène Larraufie, Krista J Spiller, Hai Li, Damian J Williams, Phuong Hoang, Elise Jiang, Luis A Williams, Jackson Sandoe, Kevin Eggan, Ivo Lieberam, Kevin C Kanning, Brent R Stockwell, Christopher E Henderson, Hynek Wichterle
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease selectively targeting motor neurons in the brain and spinal cord. The reasons for differential motor neuron susceptibility remain elusive. We developed a stem cell-based motor neuron assay to study cell-autonomous mechanisms causing motor neuron degeneration, with implications for ALS. A small-molecule screen identified cyclopiazonic acid (CPA) as a stressor to which stem cell-derived motor neurons were more sensitive than interneurons. CPA induced endoplasmic reticulum stress and the unfolded protein response...
October 19, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
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