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https://www.readbyqxmd.com/read/29334602/high-dose-metformin-plus-temozolomide-shows-increased-anti-tumor-effects-in-glioblastoma-in-vitro-and-in-vivo-compared-with-monotherapy
#1
Jung Eun Lee, Ji Hee Lim, Yong Kil Hong, Seung Ho Yang
Purpose: The purpose of the study is to investigate the efficacy of combined treatment with temozolomide (TMZ) and metformin for glioblastoma (GBM) in vitro and in vivo. Materials and Methods: We investigated the efficacy of combined treatment with TMZ and metformin using cell viability and apoptosis assays. A GBM orthotopic mice model was established by inoculation of 5x105 U87 cells and treated with metformin, TMZ, and the combination for 4 weeks. Western blotting and immunofluorescence of tumor specimens were analyzed to investigate AMP-activated protein kinase (AMPK) and AKT pathway...
January 10, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29333720/degree-of-sglt1-phosphorylation-is-associated-with-but-does-not-determine-segment-specific-glucose-transport-features-in-the-porcine-small-intestines
#2
Stefanie Klinger, Patrick Lange, Elisabeth Brandt, Karin Hustedt, Bernd Schröder, Gerhard Breves, Jens Herrmann
Glucose-induced electrogenic ion transport is higher in the porcine ileum compared with the jejunum despite equal apical abundance of SGLT1. The objective of this study was a detailed determination of SGLT1 and GLUT2 expressions at mRNA and protein levels along the porcine small intestinal axis. Phosphorylation of SGLT1 at serine 418 was assessed as a potential modulator of activity. Porcine intestinal tissues taken along the intestinal axis 1 h or 3 h after feeding were analyzed for relative mRNA (RT-PCR) and protein levels (immunoblot) of SGLT1, pSGLT1, GLUT2, (p)AMPK, β2 -receptor, and PKA substrates...
January 2018: Physiological Reports
https://www.readbyqxmd.com/read/29333122/metformin-enhanced-in-vitro-radiosensitivity-associates-with-g2-m-cell-cycle-arrest-and-elevated-adenosine-5-monophosphate-activated-protein-kinase-levels-in-glioblastoma
#3
Sebastian Adeberg, Denise Bernhardt, Semi B Harrabi, Nils H Nicolay, Juliane Hörner-Rieber, Laila König, Michael Repka, Angela Mohr, Amir Abdollahi, Klaus-Josef Weber, Juergen Debus, Stefan Rieken
Background: It is hypothesized that metabolism plays a strong role in cancer cell regulation. We have recently demonstrated improved progression-free survival in patients with glioblastoma who received metformin as an antidiabetic substance during chemoradiation. Although metformin is well-established in clinical use the influence of metformin in glioblastoma is far from being understood especially in combination with other treatment modalities such as radiation and temozolomide. Materials and Methods: In this study, we examined the influence of metformin in combinations with radiation and temozolomide on cell survival (clonogenic survival), cell cycle (routine flow cytometric analysis, FACScan), and phosphorylated Adenosine-5'-monophosphate-activated protein kinase (AMPK) (Phopho-AMPKalpha1 - ELISA) levels in glioblastoma cell lines LN18 and LN229...
December 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/29331700/effects-of-macrophage-migration-inhibitory-factor-on-cardiac-reperfusion-injury-in-mice-with-depression-induced-by-constant-darkness
#4
Lu-Yuan Tao, Ming-Yuan Huang, Saroj-Thapa, Jiao-Ni Wang, Shao-Ze Wu, Fei He, Kai-Yu Huang, Yang-Jing Xue, Lingwei-Jin, Lian-Ming Liao, Ji-Fei Tang, Kang-Ting Ji
RATIONALE: Depression is associated with coronary artery disease and increases adverse outcomes and mortality in patients with acute myocardial infarction, but the underlying pathophysiological mechanisms remain unclear. OBJECTIVE: To evaluate the effect of macrophage migration inhibitory factor (MIF) on cardiac ischemia-reperfusion (I/R) injury in mice with constant darkness-induced depression. METHODS AND RESULTS: Twenty C57BL/6 mice (8 weeks old, male) were randomly divided into 2 groups: one group was housed in a 12h light/dark cycle environment (LD) and the other in a constant darkness environment (DD)...
December 27, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29331689/baicalin-inhibits-pressure-overload-induced-cardiac-fibrosis-through-regulating-ampk-tgf-%C3%AE-smads-signaling-pathway
#5
Yichuan Xiao, Jiantao Ye, Ying Zhou, Junjun Huang, Xiawen Liu, Biyun Huang, Liu Zhu, Bo Wu, Genshui Zhang, Yi Cai
AMP-activated protein kinase (AMPK) is a central regulator of multiple metabolic pathways. It has been shown that activation of AMPK could inhibit fibroblast proliferation and extracellular matrix (ECM) accumulation, thereby suppressing cardiac fibrosis. Baicalin, the major component found in skullcap, possesses multiple protective effects on the cardiovascular system. However, little is known about the effect of baicalin on cardiac fibrosis and the molecular mechanism by which baicalin exerts its anti-fibrotic effects has not been investigated...
January 10, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29331024/combination-therapy-of-lovastatin-and-ampk-activator-improves-mitochondrial-and-peroxisomal-functions-and-clinical-disease-in-eae-model
#6
Inderjit Singh, Devadoss J Samuvel, Seungho Choi, Nishant Saxena, Avtar K Singh, Jeseong Won
Recent studies report that loss and dysfunction of mitochondria and peroxisomes contribute to the myelin and axonal damage in multiple sclerosis (MS). In this study, we investigated the efficacy of lovastatin and AMPK activator (AICAR) combination on the loss and dysfunction of mitochondria and peroxisomes and myelin and axonal damage in the spinal cords, relative to the clinical disease symptoms, using a mouse model of experimental autoimmune encephalomyelitis (EAE, a model for MS). We observed that lovastatin and AICAR treatments individually provided partial protection of mitochondria/peroxisomes, myelin/axons, and thus partial attenuation of clinical disease in EAE mice...
January 13, 2018: Immunology
https://www.readbyqxmd.com/read/29330340/the-adiponectin-receptor-agonist-adiporon-ameliorates-diabetic-nephropathy-in-a-model-of-type-2-diabetes
#7
Yaeni Kim, Ji Hee Lim, Min Young Kim, Eun Nim Kim, Hye Eun Yoon, Seok Joon Shin, Bum Soon Choi, Yong-Soo Kim, Yoon Sik Chang, Cheol Whee Park
Adiponectin exerts renoprotective effects against diabetic nephropathy (DN) by activating the AMP-activated protein kinase (AMPK)/peroxisome proliferative-activated receptor-α (PPARα) pathway through adiponectin receptors (AdipoRs). AdipoRon is an orally active synthetic adiponectin receptor agonist. We investigated the expression of AdipoRs and the associated intracellular pathways in 27 patients with type 2 diabetes and examined the effects of AdipoRon on DN development in male C57BLKS/J db/db mice, glomerular endothelial cells (GECs), and podocytes...
January 12, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29330052/esco2-knockdown-inhibits-cell-proliferation-and-induces-apoptosis-in-human-gastric-cancer-cells
#8
Hongmei Chen, Lei Zhang, Wenting He, Liu Tao, Yang Zhao, Hao Chen, Yumin Li
Establishment of cohesion 1 homolog 2 (ESCO2), an essential gene for cohesion regulation and genomic stability, has not been studied in human gastric cancer (GC). We found that ESCO2 knockdown in human GC cell lines dramatically inhibited cell proliferation and induced cell apoptosis in vitro and suppressed tumor xenograft development in vivo. Furthermore, adenosine monophosphate-activated protein kinase (AMPK) was activated following the suppression of its downstream targets, including mammalian target of rapamycin (mTOR) and p70 ribosomal S6 kinase 1 (p70S6K1), and this result was consistent with p53 activation...
January 9, 2018: Biochemical and Biophysical Research Communications
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
#9
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/29328363/support-vector-machine-classifier-for-prediction-of-the-metastasis-of-colorectal-cancer
#10
Jiajun Zhi, Jiwei Sun, Zhongchuan Wang, Wenjun Ding
Colorectal cancer (CRC) is one of the most common cancers and a major cause of mortality. The present study aimed to identify potential biomarkers for CRC metastasis and uncover the mechanisms underlying the etiology of the disease. The five datasets GSE68468, GSE62321, GSE22834, GSE14297 and GSE6988 were utilized in the study, all of which contained metastatic and non-metastatic CRC samples. Among them, three datasets were integrated via meta-analysis to identify the differentially expressed genes (DEGs) between the two types of samples...
January 2, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29327584/gama-aminobutyric-acid-enriched-rice-bran-diet-attenuates-insulin-resistance-and-balances-energy-expenditure-via-modification-of-gut-microbiota-and-scfas
#11
Xu Si, Wenting Shang, Zhongkai Zhou, Guanghou Shui, Sin Man Lam, Christopher L Blanchard, Padraig Strappe
In this study, gama-aminobutyric acid (GABA) enriched rice bran (ERB) was supplemented to obese rats to investigate the attenuation of metabolic syndromes induced by high-fat diet. ERB-containing diet stimulated butyrate and propionate production by promoting Anaerostipes, Anaerostipes sp. and associated synthesizing enzymes. This altered SCFA distribution further enhanced circulatory levels of leptin and glucagon-like peptide-1, controlling food intake by down-regulating orexigenic factors. Together with the enhanced fatty acid β-oxidation highlighted by Prkaa2, Ppara, Scd1 expression via AMPK signaling pathway and Non-alcoholic fatty liver disease pathway, energy expenditure was positively modulated...
January 12, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29326403/resveratrol-an-nrf2-activator-ameliorates-aging-related-progressive-renal-injury
#12
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
#13
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/29325930/integrated-study-on-comparative-transcriptome-and-skeletal-muscle-function-in-aged-rats
#14
Jing Zhou, Zhiyin Liao, Jinliang Chen, Kexiang Zhao, Qian Xiao
The present study aimed to reveal aging-related changes in the skeletal muscle of SD rats by comparing transcriptome analysis, integrated with muscle physiological parameters. Ten rats aged 25 months were set as the old group (OG) and ten rats aged 6 months were set as the young group (YG). After 6 weeks of feeding, the body mass, grip strength, and gastrocnemius muscle mass were determined, and the differentially expressed genes were analyzed by transcriptome sequencing, followed by GO enrichment analysis and KEGG analysis...
January 8, 2018: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29325290/-effect-of-hepatitis-c-virus-nonstructural-protein-5a-and-its-domains-ii-on-hepatocyte-gluconeogenesis-in-mice
#15
J J Zhang, Q Liu, L Qiao
Objective: To investigate the role of hepatitis C virus nonstructural protein 5A (NS5A) and its domains I, II, and III in regulating gluconeogenesis in mice and the underlying mechanism. Methods: A total of 60 male C57BL/6J mice were randomly divided into six groups. Recombinant lentiviral particles with specific expression of full-length NS5A, NS5A domain I, NS5A domain II, or NS5A domain III were injected via the caudal vein to establish a mouse model, and the group without injection and the group with the injection of the lentiviral particles containing enhanced green fluorescent protein (EGFP) were established as negative control...
December 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29324976/ginsenoside-rg1-inhibits-apoptosis-by-increasing-autophagy-via-the-ampk-mtor-signaling-in-serum-deprivation-macrophages
#16
Ping Yang, Lu Ling, Wenjing Sun, Junquan Yang, Ling Zhang, Guoji Chang, Jiazhi Guo, Jun Sun, Lin Sun, Di Lu
Ginsenoside Rg1 (Rg1) has been widely used in a broad range of cardiovascular and cerebral-vascular diseases because of its unique therapeutic properties. However, the underlying mechanisms of Rg1 in the treatment of atherosclerosis have not been fully explored. This study sought to determine the precise molecular mechanisms on how Rg1 might be involved in regulating apoptosis in serum deprivation-induced Raw264.7 macrophages and primary bone marrow-derived macrophages. Results demonstrated that Rg1 treatment effectively suppressed apoptosis and the expression of phosphorylation level of mTOR induced by serum deprivation in Raw264...
January 9, 2018: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29324783/sirt3-activator-honokiol-attenuates-%C3%AE-amyloid-by-modulating-amyloidogenic-pathway
#17
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/29323154/effects-of-metformin-on-colorectal-cancer-stem-cells-depend-on-alterations-in-glutamine-metabolism
#18
Jae Hyun Kim, Kyoung Jin Lee, Yoojeong Seo, Ji-Hee Kwon, Jae Pil Yoon, Jo Yeon Kang, Hyun Jung Lee, Soo Jung Park, Sung Pil Hong, Jae Hee Cheon, Won Ho Kim, Tae Ii Kim
Metformin has been known to suppress cancer stem cells (CSCs) in some cancers. However, the differential effects of metformin on CSCs and their mechanisms have not been reported. Herein, metformin induced pAMPK activation and pS6 suppression in metformin-sensitive (HT29) cells, but not in metformin-resistant (SW620) cells. The oxygen consumption rate was higher in HT29 cells than in SW620 cells and showed a prominent decrease after metformin treatment in HT29 cells. In glutamine-depleted medium, but not in low-glucose medium, SW620 cells became sensitive to the CSC-suppressing effect of metformin...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29322792/krasg12d-loh-promotes-malignant-biological-behavior-and-energy-metabolism-of-pancreatic-ductal-adenocarcinoma-cells-through-the-mtor-signaling-pathway
#19
X Shen, L G Chang, M Y Hu, D Yan, L N Zhou, Y Ma, S K Ling, Y Q Fu, S Y Zhang, B Kong, P L Huang
Oncogenic Kras with loss of heterozygosity (LOH) is frequently detected in various tumours. However, the exact function and mechanism by which KrasG12D-LOH operates remain unclear. Therefore, the current study investigated the effect of KrasG12D-LOH on the malignant phenotype of pancreatic ductal adenocarcinoma (PDAC) cells. Our investigation revealed that KrasG12D-LOH is associated with increased proliferation, invasion and reduced apoptosis in PDAC cells. The results also exhibited enhanced glycolytic phenotype of KrasG12D-LOH PDAC cells...
2018: Neoplasma
https://www.readbyqxmd.com/read/29322691/raspberry-supplementation-improves-insulin-signaling-and-promotes-brown-like-adipocyte-development-in-white-adipose-tissue-of-obese-mice
#20
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
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