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https://www.readbyqxmd.com/read/29156790/kaempferol-induces-autophagic-cell-death-of-hepatocellular-carcinoma-cells-via-activating-ampk-signaling
#1
Bing Han, Yi-Qun Yu, Qi-Lian Yang, Chun-Ying Shen, Xiao-Juan Wang
In the present study, we demonstrate that Kaempferol inhibited survival and proliferation of established human hepatocellular carcinoma (HCC) cell lines (HepG2, Huh-7, BEL7402, and SMMC) and primary human HCC cells. Kaempferol treatment in HCC cells induced profound AMP-activated protein kinase (AMPK) activation, which led to Ulk1 phosphorylation, mTOR complex 1 inhibition and cell autophagy. Autophagy induction was reflected by Beclin-1/autophagy gene 5 upregulation and p62 degradation as well as light chain 3B (LC3B)-I to LC3B-II conversion and LC3B puncta formation...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156787/natural-compound-bavachalcone-promotes-the-differentiation-of-endothelial-progenitor-cells-and-neovascularization-through-the-ror%C3%AE-erythropoietin-ampk-axis
#2
Shuang Ling, Rong-Zhen Ni, Yunyun Yuan, Yan-Qi Dang, Qian-Mei Zhou, Shuang Liang, Fujiang Guo, Wei Feng, Yuanyuan Chen, Katsumi Ikeda, Yukio Yamori, Jin-Wen Xu
In cardiovascular diseases, endothelial function is impaired and the level of circulating endothelial progenitor cells (EPCs) is low. This study investigated whether the natural bioactive component bavachalcone (BavaC) induces the differentiation of EPCs and neovascularization in vivo; the underlying mechanisms were also examined. We observed that the treatment of rat bone marrow-derived cells with a very low dose of BavaC significantly promoted EPC differentiation. In our hindlimb ischemia models, low-dose BavaC administered orally for 14 days stimulated the recovery of ischemic hindlimb blood flow, increased circulating EPCs, and promoted capillary angiogenesis...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156779/selecting-lncrnas-in-gastric-cancer-cells-for-directed-therapy-with-bioactive-peptides-and-chemotherapy-drugs
#3
Wenyan Han, Rui Xiao, Chuanling Zhang, Qimuge Suyila, Xian Li, Xiulan Su
Selecting lncRNAs for directed therapy with bioactive peptides and chemotherapy drugs may be an effective approach to treating gastric cancer (GC). We show genome-scale identification and characterization of differentially expressed lncRNAs in GC cells treated with a novel anti-cancer bioactive peptide (ACBP) and the chemotherapy drug oxaliplatin (ASLB). A total of 17,897 lncRNAs were identified through pairwise comparison, including 2,074 novel lncRNAs. Of those, 1,386 lncRNAs were differentially expressed (over 1...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156566/cgas-sting-pathway-in-cancer-jekyll-and-hyde-story-of-cancer-immune-response
#4
REVIEW
Debojit Bose
The last two decades have witnessed enormous growth in the field of cancer immunity. Mechanistic insights of cancer immunoediting have not only enhanced our understanding but also paved the way to target and/or harness the innate immune system to combat cancer, called cancer immunotherapy. Cyclic GMP-AMP synthase (cGAS)/Stimulator of interferon genes(STING) pathway has recently emerged as nodal player in cancer immunity and is currently being explored as potential therapeutic target. Although therapeutic activation of this pathway has shown promising anti-tumor effects in vivo, evidence also indicates the role of this pathway in inflammation mediated carcinogenesis...
November 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29156557/the-invasive-region-of-glioblastoma-defined-by-5ala-guided-surgery-has-an-altered-cancer-stem-cell-marker-profile-compared-to-central-tumour
#5
Stuart J Smith, Mohammed Diksin, Saachi Chhaya, Shwetha Sairam, Maria A Estevez-Cebrero, Ruman Rahman
Glioblastoma, a WHO grade IV astrocytoma, is a highly aggressive and heterogeneous tumour that infiltrates deeply into surrounding brain parenchyma, making complete surgical resection impossible. Despite chemo-radiotherapy, the residual cell population within brain parenchyma post-surgery causes inevitable recurrence. Previously, the tumour core has been the focus of research and the basis for targeted therapeutic regimes, which have failed to improve survival in clinical trials. Here, we focus on the invasive margin as defined by the region with 5-aminolevulinic acid (5ALA) (GliolanTM) fluorescence at surgery beyond the T1 enhancing region on magnetic resonance imaging (MRI)...
November 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29156518/linc00152-mir-139-5p-regulates-gastric-cancer-cell-aerobic-glycolysis-by-targeting-prkaa1
#6
Keke Sun, Pingping Hu, Feng Xu
Gastric cancer is one of the most common cancers in the world and glycolysis is a major feature of gastric cancer. MicroRNAs (miRNAs) involve in gastric cancer cell proliferation, glycolysis and other cellular processes. MiR-139-5p is reported as a tumor suppressor in cancers, however, the role of miR-139-5p including glycolytic metabolism is unclear in gastric cancer. So, the purpose of the present study is to elucidate the underlying mechanism in gastric cancer metabolism mediated by miR-139-5p. Our results revealed that miR-139-5p inhibited glycolysis by regulating AMP-activated, alpha 1 catalytic subunit (PRKAA1) expression in gastric cancer cells...
November 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29156421/impaired-mitochondrial-respiration-in-human-carotid-plaque-atherosclerosis-a-potential-role-for-pink1-in-vascular-smooth-muscle-cell-energetics
#7
Craig K Docherty, Andy Carswell, Elaine Friel, John R Mercer
BACKGROUND AND AIMS: DNA damage and mitochondrial dysfunction are thought to play an essential role in ageing and the energetic decline of vascular smooth muscle cells (VSMCs) essential for maintaining plaque integrity. We aimed to better understand VSMCs and identify potentially useful compensatory pathways that could extend their lifespan. Moreover, we wanted to assess if defects in mitochondrial respiration exist in human atherosclerotic plaques and to identify the appropriate markers that may reflect a switch in VSMC energy metabolism...
November 13, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29155778/a-detailed-protocol-for-physiological-parameters-acquisition-and-analysis-in-neurosurgical-critical-patients
#8
Xiang Wu, Guoyi Gao, Junfeng Feng, Qing Mao, Jiyao Jiang
Intracranial pressure (ICP) monitoring is now widely used in neurosurgical critical patients. Besides mean ICP value, the ICP derived parameters such as ICP waveform, amplitude of pulse (AMP), the correlation of ICP amplitude and ICP mean (RAP), pressure reactivity index (PRx), ICP and arterial blood pressure (ABP) wave amplitude correlation (IAAC), and so on, can reflect intracranial status, predict prognosis, and can also be used as guidance of proper treatment. However, most of the clinicians focus only on the mean ICP value while ignoring these parameters because of the limitations of the current devices...
October 17, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155580/a-unique-approach-to-design-potent-and-selective-cyclic-adenosine-monophosphate-response-element-binding-protein-binding-protein-cbp-inhibitors
#9
Sarah M Bronner, Jeremy M Murray, F Anthony Romero, Kwong Wah Lai, Vickie Tsui, Patrick Cyr, Maureen H Beresini, Gladys de Leon Boenig, Zhongguo Chen, Edna F Choo, Kevin R Clark, Terry D Crawford, Hariharan Jayaram, Susan Kaufman, Ruina Li, Yingjie Li, Jiangpeng Liao, Xiaorong Liang, Wenfeng Liu, Justin Q Ly, Jonathan Maher, John S Wai, Fei Wang, Aijun Zheng, Xiaoyu Zhu, Steven R Magnuson
The epigenetic regulator CBP/P300 presents a novel therapeutic target for oncology. Previously, we reported the development of potent and selective CBP bromodomain inhibitors by first identifying pharmacophores that bind the KAc region, and then building into the LPF shelf. Herein we report the "hybridization" of a variety of KAc-binding fragments with a tetrahydroquinoline scaffold that makes optimal interactions with the LPF shelf, imparting enhanced potency and selectivity to the hybridized ligand. To demonstrate the utility of our hybridization approach, two analogues containing unique Asn binders and the optimized tetrahydroquinoline moiety were rapidly optimized to yield single-digit nanomolar inhibitors of CBP with exquisite selectivity over BRD4(1) and the broader bromodomain family...
November 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29155261/the-phosphodiesterase-4-inhibitor-fcpr16-attenuates-ischemia-reperfusion-injury-in-rats-subjected-to-middle-cerebral-artery-occlusion-and-reperfusion
#10
Jiajia Chen, Hui Yu, Jiahong Zhong, Hongfang Feng, Haitao Wang, Yufang Cheng, Zhengqiang Zou, Chang Huang, Zhongzhen Zhou, Wenhua Zheng, Jiangping Xu
Current phosphodiesterase-4 (PDE4) inhibitors exert beneficial effects in central nervous system diseases via anti-inflammatory and anti-apoptotic properties, but many of them are plagued by side effects like nausea and emesis. FCPR16, a novel PDE4 inhibitor synthesized in our lab, has potential anti-inflammatory property. In the present study, we aimed to investigate the effects of FCPR16 in a rat model of ischemic stroke and evaluate its emetogenic potential. Our results showed that FCPR16 treatment improved neurological function, reduced cerebral infarct volume, and attenuated brain histological changes in rats subjected to middle cerebral artery occlusion and reperfusion (MCAO/R)...
November 16, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29153408/ampk-sensing-glucose-as-well-as-cellular-energy-status
#11
REVIEW
Sheng-Cai Lin, D Grahame Hardie
Mammalian AMPK is known to be activated by falling cellular energy status, signaled by rising AMP/ATP and ADP/ATP ratios. We review recent information about how this occurs but also discuss new studies suggesting that AMPK is able to sense glucose availability independently of changes in adenine nucleotides. The glycolytic intermediate fructose-1,6-bisphosphate (FBP) is sensed by aldolase, which binds to the v-ATPase on the lysosomal surface. In the absence of FBP, interactions between aldolase and the v-ATPase are altered, allowing formation of an AXIN-based AMPK-activation complex containing the v-ATPase, Ragulator, AXIN, LKB1, and AMPK, causing increased Thr172 phosphorylation and AMPK activation...
November 15, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29153167/a-100-year-review-reproductive-technologies-in-dairy-science
#12
S G Moore, J F Hasler
Reproductive technology revolutionized dairy production during the past century. Artificial insemination was first successfully applied to cattle in the early 1900s. The next major developments involved semen extenders, invention of the electroejaculator, progeny testing, addition of antibiotics to semen during the 1930s and 1940s, and the major discovery of sperm cryopreservation with glycerol in 1949. The 1950s and 1960s were particularly productive with the development of protocols for the superovulation of cattle with both pregnant mare serum gonadotrophin/equine chorionic gonadotrophin and FSH, the first successful bovine embryo transfer, the discovery of sperm capacitation, the birth of rabbits after in vitro fertilization, and the development of insulated liquid nitrogen tanks...
December 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/29151645/management-of-staphylococcus-mediated-systemic-infection-by-enhancing-the-resurging-activity-of-co-trimoxazole-in-presence-of-cryptdin-2
#13
Amrita Kaur, Shiv Kumar Chabba, Ujjwal Jit Kaur, Arashdeep Kaur, Simran Preet, Praveen Rishi
Resurgence of sensitivity of the antibiotics, to which the pathogen had developed resistance in the past, requires special attention for strengthening the reservoir of antimicrobial compounds. Reports in the recent past have suggested that co-trimoxazole (COT) has regained its activity against methicillin resistant Staphylococcus aureus (MRSA). The present study exploited the use of COT in the presence of an antimicrobial peptide (AMP), cryptdin-2 (a murine Paneth cell alpha defensin), in order to reduce the selective pressure of the antibiotic on the pathogen...
December 2017: Indian Journal of Microbiology
https://www.readbyqxmd.com/read/29151267/impaired-permeability-and-antimicrobial-barriers-in-type-2-diabetes-skin-are-linked-to-increased-serum-levels-of-advanced-glycation-end-product
#14
Jae-Hong Kim, Na Young Yoon, Dong Hye Kim, Minyoung Jung, Myungsoo Jun, Hwa-Young Park, Choon Hee Chung, Kyohoon Lee, Sunki Kim, Chang Seo Park, Kwang-Hyeon Liu, Eung Ho Choi
BACKGROUND: The incidence of type 2 diabetes mellitus (DM) has been increasing rapidly, and the disease has become a serious sociomedical problem. Many skin problems, such as xerosis, pruritus, skin infections, and delayed wound healing, that might be related to chronic impairment of skin barrier function decrease the quality of life in DM patients. However, the status of the permeability and antimicrobial barrier of the skin in DM remains unknown. OBJECTIVE: This study aimed to elucidate skin barrier impairment in type 2 DM patients and its patho-mechanisms using classic animal models of type 2 DM...
November 19, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/29151105/eryptosis-the-neglected-cause-of-anemia-in-end-stage-renal-disease
#15
Florian Lang, Rosi Bissinger, Majed Abed, Ferruh Artunc
End stage renal disease (ESRD) invariably leads to anemia which has been mainly attributed to compromised release of erythropoietin from the defective kidneys with subsequent impairment of erythropoiesis. However, erythropoietin replacement only partially reverses anemia pointing to the involvement of additional mechanisms. As shown more recently, anemia of ESRD is indeed in large part a result of accelerated erythrocyte loss due to suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the cell surface...
October 23, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29150763/heat-stress-in-cows-at-pasture-and-benefit-of-shade-in-a-temperate-climate-region
#16
Isabelle Veissier, Eva Van Laer, Rupert Palme, Christel P H Moons, Bart Ampe, Bart Sonck, Stéphane Andanson, Frank A M Tuyttens
Under temperate climates, cattle are often at pasture in summer and are not necessarily provided with shade. We aimed at evaluating in a temperate region (Belgium) to what extent cattle may suffer from heat stress (measured through body temperature, respiration rate and panting score, cortisol or its metabolites in milk, and feces on hot days) and at assessing the potential benefits of shade. During the summer of 2012, 20 cows were kept on pasture without access to shade. During the summer of 2011, ten cows had access to shade (young trees with shade cloth hung between them), whereas ten cows had no access...
November 17, 2017: International Journal of Biometeorology
https://www.readbyqxmd.com/read/29150696/impact-of-prolonged-overfeeding-on-skeletal-muscle-mitochondria-in-healthy-individuals
#17
Frederico G S Toledo, Darcy L Johannsen, Jeffrey D Covington, Sudip Bajpeyi, Bret Goodpaster, Kevin E Conley, Eric Ravussin
AIMS/HYPOTHESES: Reduced mitochondrial capacity in skeletal muscle has been observed in obesity and type 2 diabetes. In humans, the aetiology of this abnormality is not well understood but the possibility that it is secondary to the stress of nutrient overload has been suggested. To test this hypothesis, we examined whether sustained overfeeding decreases skeletal muscle mitochondrial content or impairs function. METHODS: Twenty-six healthy volunteers (21 men, 5 women, age 25...
November 17, 2017: Diabetologia
https://www.readbyqxmd.com/read/29150317/amp-activated-protein-kinase-regulation-of-the-nlrp3-inflammasome-during-aging
#18
REVIEW
Mario D Cordero, Matthew R Williams, Bernhard Ryffel
The NLRP3 inflammasome has recently emerged as an unexpected marker of stress and metabolic risk and has also been implicated in the development of major aging-related diseases such as gout, type 2 diabetes, obesity, cancer, and neurodegenerative and cardiovascular disorders. Several pathways regulating the NLRP3 inflammasome are currently being studied, but how the NLRP3 inflammasome is regulated remains unknown. AMP-activated protein kinase (AMPK), a central regulator of multiple metabolic pathways involved in the pathophysiology of aging and age-related diseases, has emerged as an important integrator of signals controlling inflammation including the inflammasome...
November 14, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29150224/reduced-gene-expression-of-sirtuins-and-active-ampk-levels-in-children-and-adolescents-with-obesity-and-insulin-resistance
#19
Zahra Arab Sadeghabadi, Mitra Nourbakhsh, Parvin Pasalar, Solaleh Emamgholipour, Abolfazl Golestani, Bagher Larijani, Maryam Razzaghy-Azar
BACKGROUND: Sirtuins, including SIRT1 and SIRT2, are longevity-associated deacetylase enzymes that modulate metabolic homeostasis in response to the cellular energy state. Adenosine monophosphate activated protein kinase (AMPK) and SIRT1 are interrelated and share several common target pathways. This study aimed to evaluate the SIRT1 and SIRT2 gene expression in peripheral blood mononuclear cells (PBMCs) as well as plasma levels of AMPK, in obese children and adolescents. MATERIALS AND METHODS: Participants included 60 children and adolescents (30 obese and 30 age- and gender-matched control subjects)...
November 14, 2017: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/29149500/ep-radiofrequency-generators-significant-offsets-between-selected-and-delivered-power
#20
Felix Bourier, Bernhard Schwarz, Amir Brkic, Lara Wolf, Verena Semmler, Marc Kottmaier, Elena Risse, Marta Telishevska, Stephanie Brooks, Sarah Lengauer, Marielouise Kornmayer, Katharina Koch-Büttner, Florian Berger, Gabriele Hessling, Isabel Deisenhofer, Tilko Reents
INTRODUCTION: For radiofrequency ablation, the EP Shuttle®, Ampere®, and SmartAblate® generator models are most frequently used in clinical practice. The aim of this study was to assess the correlation between selected and delivered RF power for different generators. METHODS AND RESULTS: In an experimental setup, ablation catheters were connected to the EP Shuttle®, Ampere®, and SmartAblate® generators. The power delivered by the generators was measured using a current converter and an oscilloscope...
November 17, 2017: Journal of Cardiovascular Electrophysiology
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