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https://www.readbyqxmd.com/read/29334584/in-vitro-and-in-vivo-metabolite-identification-of-a-novel-benzimidazole-compound-zln005-by-lc-ms-ms
#1
Wenchao Sun, Khoa Dinh Nguyen, William L Fitch, Samuel D Banister, Hongxiang Tang, Xiaolan Zhang, Lewis Yu, Edgar G Engleman, Jayakumar Rajadas
RATIONALE: A novel benzimidazole compound ZLN005 was previously identified as a transcriptional activator of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in certain metabolic tissues. Upregulation of PGC-1α by ZLN005 has been shown to have beneficial effect in a diabetic mouse model and in a coronary artery disease model in vitro. ZLN005 could also have therapeutic potential in neurodegenerative diseases involving down-regulation of PGC-1α. Given the phenotypic efficacy of ZLN005 in several animal models of human disease, its metabolic profile was investigated to guide the development of novel therapeutics using ZLN005 as the lead compound...
January 15, 2018: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/29329611/early-intervention-with-didang-decoction-delays-macrovascular-lesions-in-diabetic-rats-through-regulating-amp-activated-protein-kinase-signaling-pathway
#2
Dan-Dan Ren, Jing Li, Bai Chang, Chun-Shen Li, Ju-Hong Yang
The study aimed to investigate the intervening role of Didang decoction (DDD) at different times in macrovascular endothelial defense function, focusing on its effects on the AMP-activated protein kinase (AMPK) signaling pathway. The effects of DDD on mitochondrial energy metabolism were also investigated in rat aortic endothelial cells (RAECs). Type 2 diabetes were induced in rats by streptozotocin (STZ) combined with high fat diet. Rats were randomly divided into non-intervention group, metformin group, simvastatin group, and early-, middle-, late-stage DDD groups...
November 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29326403/resveratrol-an-nrf2-activator-ameliorates-aging-related-progressive-renal-injury
#3
Eun Nim Kim, Ji Hee Lim, Min Young Kim, Tae Hyun Ban, In-Ae Jang, Hye Eun Yoon, Cheol Whee Park, Yoon Sik Chang, Bum Soon Choi
BACKGROUND: Two important issues in the aging kidney are mitochondrial dysfunction and oxidative stress. An Nrf2 activator, resveratrol, is known to have various effects. Resveratrol may prevent inflammation and oxidative stress by activating Nrf2 and SIRT1 signaling. We examined whether resveratrol could potentially ameliorate the cellular condition, such as renal injury due to cellular oxidative stress and mitochondrial dysfunction caused by aging. METHODS: Male 18-month-old C57BL/6 mice were used...
January 11, 2018: Aging
https://www.readbyqxmd.com/read/29325933/sestrin2-prevents-age-related-intolerance-to-post-myocardial-infarction-via-ampk-pgc-1%C3%AE-pathway
#4
Nanhu Quan, Lin Wang, Xu Chen, Chelsea Luckett, Courtney Cates, Thomas Rousselle, Yang Zheng, Ji Li
We have revealed that a novel stress-inducible protein, Sestrin2, declines in the heart with aging. Moreover, there is an interaction between Sestrin2 and energy sensor AMPK in the heart in response to ischemic stress. The objective of this study is to determine whether Sestrin2-AMPK complex modulates PGC-1α in the heart and protects the heart from ischemic insults. In order to characterize the role of cardiac Sestrin2-AMPK signaling cascade in aging, C57BL/6 wild type young mice (3-4months), aged mice (24-26months) and young Sestrin2 KO mice were subjected to left anterior descending coronary artery occlusion for in vivo regional ischemia...
January 8, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29324783/sirt3-activator-honokiol-attenuates-%C3%AE-amyloid-by-modulating-amyloidogenic-pathway
#5
Sindhu Ramesh, Manoj Govindarajulu, Tyler Lynd, Gwyneth Briggs, Danielle Adamek, Ellery Jones, Jake Heiner, Mohammed Majrashi, Timothy Moore, Rajesh Amin, Vishnu Suppiramaniam, Muralikrishnan Dhanasekaran
Honokiol (poly-phenolic lignan from Magnolia grandiflora) is a Sirtuin-3 (SIRT3) activator which exhibit antioxidant activity and augment mitochondrial functions in several experimental models. Modern evidence suggests the critical role of SIRT3 in the progression of several metabolic and neurodegenerative diseases. Amyloid beta (Aβ), the precursor to extracellular senile plaques, accumulates in the brains of patients with Alzheimer's disease (AD) and is related to the development of cognitive impairment and neuronal cell death...
2018: PloS One
https://www.readbyqxmd.com/read/29324398/epilepsy-in-patients-with-pineal-gland-cyst
#6
Jelena Bosnjak, Silva Soldo Butkovic, Snjezana Miskov, Lejla Coric, Ana Jadrijevic-Tomas, Vlatka Mejaski-Bosnjak
OBJECTIVE: The aim of the study is to describe types of epileptic seizures in patients with pineal gland cyst (PGC) and their outcome during follow up period (6-10 years). We wanted to determine whether patients with epilepsy differ in PGC volume and compression of the PGC on surrounding brain structures compared to patients with PGC, without epilepsy. PATIENTS AND METHODS: We analyzed prospectivelly 92 patients with PGC detected on magnetic resonance (MR) of the brain due to various neurological symptoms during the period 2006-2010...
January 4, 2018: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/29324254/prdm14-is-expressed-in-germ-cell-tumors-with-constitutive-overexpression-altering-human-germline-differentiation-and-proliferation
#7
Joanna J Gell, Jasmine Zhao, Di Chen, Timothy J Hunt, Amander T Clark
Germ cell tumors (GCTs) are a heterogeneous group of tumors occurring in gonadal and extragonadal locations. GCTs are hypothesized to arise from primordial germ cells (PGCs), which fail to differentiate. One recently identified susceptibility loci for human GCT is PR (PRDI-BF1 and RIZ) domain proteins 14 (PRDM14). PRDM14 is expressed in early primate PGCs and is repressed as PGCs differentiate. To examine PRDM14 in human GCTs we profiled human GCT cell lines and patient samples and discovered that PRDM14 is expressed in embryonal carcinoma cell lines, embryonal carcinomas, seminomas, intracranial germinomas and yolk sac tumors, but is not expressed in teratomas...
January 4, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29322691/raspberry-supplementation-improves-insulin-signaling-and-promotes-brown-like-adipocyte-development-in-white-adipose-tissue-of-obese-mice
#8
Tong Xing, Yifei Kang, Xinglian Xu, Bo Wang, Min Du, Mei-Jun Zhu
SCOPE: Excessive lipid accumulation in white adipose tissue (WAT) leads to chronic inflammation and metabolic dysfunction. Raspberry (RB) contains high amount of polyphenolics and dietary fibers. The objective of the study is to evaluate effects of RB supplementation on WAT morphology, inflammation and insulin signaling in high fat diet (HFD)-induced obese mice, and further explore the underlying mechanisms. METHODS AND RESULTS: C57BL/6J mice were fed with a control diet or a HFD supplemented with 0 or 5% freeze dried RB for 12 weeks...
January 10, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29320730/esrrb-complementation-rescues-development-of-nanog-null-germ-cells
#9
Man Zhang, Harry G Leitch, Walfred W C Tang, Nicola Festuccia, Elisa Hall-Ponsele, Jennifer Nichols, M Azim Surani, Austin Smith, Ian Chambers
The transcription factors (TFs) Nanog and Esrrb play important roles in embryonic stem cells (ESCs) and during primordial germ-cell (PGC) development. Esrrb is a positively regulated direct target of NANOG in ESCs that can substitute qualitatively for Nanog function in ESCs. Whether this functional substitution extends to the germline is unknown. Here, we show that germline deletion of Nanog reduces PGC numbers 5-fold at midgestation. Despite this quantitative depletion, Nanog-null PGCs can complete germline development in contrast to previous findings...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29319388/woohwangcheongsimwon-prevents-high-fat-diet-induced-memory-deficits-and-induces-sirt1-in-mice
#10
Hyunwoo Park, Mia Kim, Im-Joon Shin, Jonghee Park, Soo Yong Bang, Chunsik Yi, Myoung-Ae Kim, Jae-Hwan Lew, Joo Won Suh, Sungho Maeng
Woohwangcheongsimwon (WHC) is a mixture of herbal medicines that is widely prescribed in Korean traditional medicine. SIRT1 is known for its regulatory roles in energy metabolism, oxidative stress, and circadian rhythms. This study was designed to determine whether WHC can increase and mimic the biological reactions of SIRT1 activation. Ten-month-old male mice were divided into four groups: nontreated normal diet (ND), nontreated high-fat diet (HFD), WHC-treated ND, and WHC-treated HFD. Body weight and cognitive functions were evaluated after treatment...
January 10, 2018: Journal of Medicinal Food
https://www.readbyqxmd.com/read/29317208/zinc-alpha2-glycoprotein-promotes-browning-in-adipocytes
#11
Xin-Hua Xiao, Xiao-Yan Qi, Ya-Di Wang, Li Ran, Jing Yang, Huan-Li Zhang, Can-Xin Xu, Ge-Bo Wen, Jiang-Hua Liu
Recent studies have highlighted recruiting and activating brite adipocytes in WAT (so-called "browning") would be an attractive anti-obesity strategy. Zinc alpha2 glycoprotein (ZAG) is reported to ameliorate glycolipid metabolism and lose body weight in obese mice. However whether the body reducing effect mediated by browning programme remains unclear. Here, we show that overexpression of ZAG in 3T3-L1 adipocytes enhanced expression of brown fat-specific markers (UCP-1, PRDM16 and CIDEA), mitochondrial biogenesis genes (PGC-1α, NRF-1/2 and mtTFA) and the key lipid metabolism lipases (ATGL, HSL, CPT1-A and p-acyl-CoA carboxylase)...
January 6, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29316934/physiological-mitochondrial-and-oxidative-stress-differences-in-the-presence-or-absence-of-lactation-in-rats
#12
Hayden W Hyatt, Yufeng Zhang, Wendy R Hood, Andreas N Kavazis
BACKGROUND: Human epidemiological data show that breastfeeding reduces the mother's probability of developing several disease conditions, including obesity and type II diabetes compared to mothers that give birth but do not breastfeed. The goal of this investigation was to characterize how lactation changes a rat's body composition, metabolism, mitochondrial function, and oxidative stress. METHODS: Ten-week old female Sprague-Dawley rats were divided into three groups (n = 8 per group): 1) non-reproductive (NR), 2) those that were allowed to mate and give birth, but were not allowed to suckle their pups (PP), and 3) those that were allowed to mate and give birth, and suckled their young until weaning at 21 days (PL)...
January 9, 2018: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/29315416/human-induced-pluripotent-stem-cells-and-male-infertility-an-overview-of-current-progress-and-perspectives
#13
Fang Fang, Zili Li, Qian Zhao, Honggang Li, Chengliang Xiong
Recently, significant progress has been made in ART for the treatment of male infertility. However, current ART has failed to help infertile patients with non-obstructive azoospermia, unless donor sperm is used. In fact, most couples wish to have their own genetically related child. Human induced pluripotent stem cells (hiPSCs) can be generated from patients' somatic cells and in vitro derivation of functional germ cells from patient-specific iPSCs may provide new therapeutic strategies for infertile couples...
January 5, 2018: Human Reproduction
https://www.readbyqxmd.com/read/29315328/pgc-1%C3%AE-regulates-alanine-metabolism-in-muscle-cells
#14
Yukino Hatazawa, Kun Qian, Da-Wei Gong, Yasutomi Kamei
The skeletal muscle is the largest organ in the human body, depositing energy as protein/amino acids, which are degraded in catabolic conditions such as fasting. Alanine is synthesized and secreted from the skeletal muscle that is used as substrates of gluconeogenesis in the liver. During fasting, the expression of PGC-1α, a transcriptional coactivator of nuclear receptors, is increased in the liver and regulates gluconeogenesis. In the present study, we observed increased mRNA expression of PGC-1α and alanine aminotransferase 2 (ALT2) in the skeletal muscle during fasting...
2018: PloS One
https://www.readbyqxmd.com/read/29312638/coregulator-profiling-of-the-glucocorticoid-receptor-in-lymphoid-malignancies
#15
Dorien Clarisse, Jonathan Thommis, Karlien Van Wesemael, René Houtman, Dariusz Ratman, Jan Tavernier, Fritz Offner, Ilse Beck, Karolien De Bosscher
Coregulators cooperate with nuclear receptors, such as the glucocorticoid receptor (GR), to enhance or repress transcription. These regulatory proteins are implicated in cancer, yet, their role in lymphoid malignancies, including multiple myeloma (MM) and acute lymphoblastic leukemia (ALL), is largely unknown. Here, we report the use and extension of the microarray assay for real-time nuclear receptor coregulator interactions (MARCoNI) technology to detect coregulator associations with endogenous GR in cell lysates...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29309922/pyridostigmine-protects-against-cardiomyopathy-associated-with-adipose-tissue-browning-and-improvement-of-vagal-activity-in-high-fat-diet-rats
#16
Yi Lu, Qing Wu, Long-Zhu Liu, Xiao-Jiang Yu, Jin-Jun Liu, Man-Xiang Li, Wei-Jin Zang
Obesity, a major contributor to the development of cardiovascular diseases, is associated with an autonomic imbalance characterized by sympathetic hyperactivity and diminished vagal activity. Vagal activation plays important roles in weight loss and improvement of cardiac function. Pyridostigmine is a reversible acetylcholinesterase inhibitor, but whether it ameliorates cardiac lipid accumulation and cardiac remodeling in rats fed a high-fat diet has not been determined. This study investigated the effects of pyridostigmine on high-fat diet-induced cardiac dysfunction and explored the potential mechanisms...
January 5, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29309801/moderate-treadmill-exercise-ameliorates-amyloid-%C3%AE-induced-learning-and-memory-impairment-possibly-via-increasing-ampk-activity-and-up-regulation-of-the-pgc-1%C3%AE-fndc5-bdnf-pathway
#17
Mohammad Azimi, Reza Gharakhanlou, Nasser Naghdi, Davar Khodadadi, Soomaayeh Heysieattalab
Alzheimer's disease (AD) is a neurodegenerative disorder associated with loss of memory and cognitive abilities. Previous evidence suggested that exercise ameliorates learning and memory deficits by increasing brain derived neurotrophic factor (BDNF) and activating downstream pathways in AD animal models. However, upstream pathways related to increase BDNF induced by exercise in AD animal models are not well known. We investigated the effects of moderate treadmill exercise on Aβ-induced learning and memory impairment as well as the upstream pathway responsible for increasing hippocampal BDNF in an animal model of AD...
January 5, 2018: Peptides
https://www.readbyqxmd.com/read/29306019/sirt1-and-hif1%C3%AE-signaling-in-metabolism-and-immune-responses
#18
Qing Yu, Lin Dong, Yan Li, Gaungwei Liu
SIRT1 and HIF1α are regarded as two key metabolic sensors in cellular metabolism pathways and play vital roles in influencing immune responses. SIRT1 and HIF1α regulate immune responses in metabolism-dependent and -independent ways. Here, we summarized the recent knowledge of SIRT1 and HIF1α signaling in metabolism and immune responses. HIF1α is a direct target of SIRT1. Sometimes, SIRT1 and HIF1α cooperate or act separately to mediate immune responses. In innate immune responses, SIRT1 can regulate the glycolytic activity of myeloid-derived suppressor cells (MDSCs) and influence MDSC functional differentiation...
January 3, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29298131/a-systematic-review-of-p53-regulation-of-oxidative-stress-in-skeletal-muscle
#19
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
January 3, 2018: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/29296613/mglur2-3-activation-of-the-sirt1-axis-preserves-mitochondrial-function-in-diabetic-neuropathy
#20
Krish Chandrasekaran, Anjaneyulu Muragundla, Tyler G Demarest, Joungil Choi, Avinash R Sagi, Neda Najimi, Pranith Kumar, Anmol Singh, Cheng-Ying Ho, Gary Fiskum, Lauren G Koch, Steven L Britton, James W Russell
Objectives: There is a critical need to develop effective treatments for diabetic neuropathy. This study determined if a selective mGluR2/3 receptor agonist prevented or treated experimental diabetic peripheral neuropathy (DPN) through glutamate recycling and improved mitochondrial function. Methods: Adult male streptozotocin treated Sprague-Dawley rats with features of type 1 diabetes mellitus (T1DM) or Low Capacity Running (LCR) rats with insulin resistance or glucose intolerance were treated with 3 or 10 mg/kg/day LY379268...
December 2017: Annals of Clinical and Translational Neurology
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