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https://www.readbyqxmd.com/read/28411689/moutan-cortex-and-paeoniae-radix-rubra-reverse-high-fat-diet-induced-metabolic-disorder-and-restore-gut-microbiota-homeostasis
#1
Ling-Jun Zhong, Zhi-Sheng Xie, Hua Yang, Ping Li, Xiao-Jun Xu
The present study was designed to investigate the therapeutic effcts of Moutan Cortex (CM, root bark of Paeonia suffruticosa Andr) and Paeoniae Radix Rubra (PR, root of Paeonia veitchii Lynch) on metabolic disorders, focusing on the infuence of CM and PR on the obesity-related gut microbiota homeostasis. The diet-induced obese (DIO) mouse model was used to test the therapeutic effects of CM and PR. The mice were orally administered with CM and PR for 6 weeks, and oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed to evaluate the insulin sensitivity of the mice...
March 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28404659/early-glycemic-control-and-magnitude-of-hba1c-reduction-predict-cardiovascular-events-and-mortality-population-based-cohort-study-of-24-752-metformin-initiators
#2
Elisabeth Svensson, Lisbeth M Baggesen, Søren P Johnsen, Lars Pedersen, Helene Nørrelund, Esben S Buhl, Christiane L Haase, Reimar W Thomsen
OBJECTIVE: We investigated the association of early achieved HbA1c level and magnitude of HbA1c reduction with subsequent risk of cardiovascular events or death in patients with type 2 diabetes who initiate metformin. RESEARCH DESIGN AND METHODS: This was a population-based cohort study including all metformin initiators with HbA1c tests in Northern Denmark, 2000-2012. Six months after metformin initiation, we classified patients by HbA1c achieved (<6.5% or higher) and by magnitude of HbA1c change from the pretreatment baseline...
April 12, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28401767/expanded-target-chemical-analysis-reveals-extensive-mixed-organic-contaminant-exposure-in-u-s-streams
#3
Paul M Bradley, Celeste A Journey, Kristin M Romanok, Larry B Barber, Herbert T Buxton, William T Foreman, Edward T Furlong, Susan T Glassmeyer, Michelle L Hladik, Luke R Iwanowicz, Daniel K Jones, Dana W Kolpin, Kathryn M Kuivila, Keith A Loftin, Marc A Mills, Michael T Meyer, James L Orlando, Timothy J Reilly, Kelly L Smalling, Daniel L Villeneuve
Surface water from 38 streams nationwide was assessed using 14 target-organic methods (719 compounds). Designed-bioactive anthropogenic contaminants (biocides, pharmaceuticals) comprised 57% of 406 organics detected at least once. The 10 most-frequently detected anthropogenic-organics included eight pesticides (desulfinylfipronil, AMPA, chlorpyrifos, dieldrin, metolachlor, atrazine, CIAT, glyphosate) and two pharmaceuticals (caffeine, metformin) with detection frequencies ranging 66-84% of all sites. Detected contaminant concentrations varied from less than 1 ng L(-1) to greater than 10 μg L(-1), with 77 and 278 having median detected concentrations greater than 100 ng L(-1) and 10 ng L(-1), respectively...
April 12, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28393693/update-on-the-protective-renal-effects-of-metformin-in-diabetic-nephropathy
#4
Andreas Eisenreich, Ulrike Leppert
BACKGROUND: Diabetic nephropathy is one of the most important complications in patients with diabetes mellitus. Main steps crucial for the pathogenesis of diabetic nephropathy involve amongst others the modulation of cell signaling via AMP-activated kinase (AMPK) and mammalian target of rapamycin (mTOR), reactive oxygen generation, and endoplasmic reticulum stress under diabetic or hyperglycemic conditions. These processes mediate increased loss of renal cells, such as podocytes, which consequentially leads to renal damage and loss of renal functions, such as structural integrity and glomerular filtration in diabetic nephropathy...
April 4, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28393220/metformin-increases-sensitivity-of-osteosarcoma-stem-cells-to-cisplatin-by-inhibiting-expression-of-pkm2
#5
Depeng Shang, Ju Wu, Lianyi Guo, Yanju Xu, Lezi Liu, Jianmin Lu
Multiple drug resistance is reported to be a major obstacle in treatment of osteosarcoma (OS). Research has demonstrated that small subsets of cells called cancer stem cells (CSCs) are responsible for multiple drug resistance. CSCs are potential targets for reversing chemoresistance. In the present study, we compared cisplatin sensitivity between OS stem cells and OS non-stem cells. We confirmed that OS stem cells showed significant cisplatin-resistance compared with the OS non-CSCs. Mechanically, we proved that overexpression of the pyruvate kinase isoenzyme M2 (PKM2) was responsible for the resistance to cisplatin in OS stem cells...
May 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28391030/metformin-triggers-autophagy-to-attenuate-drug-induced-apoptosis-in-nsclc-cells-with-minor-effects-on-tumors-of-diabetic-patients
#6
Zhiguang Xiao, Silvia Gaertner, Alicia Morresi-Hauf, Rebecca Genzel, Thomas Duell, Axel Ullrich, Pjotr G Knyazev
The biologic plausibility of an association between type 2 diabetes mellitus (T2D) and lung cancer has received increasing attention, but the results of investigations remain largely inconclusive. In the present study we investigated the influence of the anti-diabetic drug metformin on the cytotoxic effects of EGFR targeted therapy and chemotherapy in 7 non-small cell lung cancer (NSCLC) cell lines and a cohort of lung cancer patients with/without T2D. In vitro cell viability assays indicated that metformin didn't potentiate the growth inhibitory effects of erlotinib at different doses in cell lines that are of distinct genetic background...
April 6, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28390311/metformin-mitigates-carbon-tetrachloride-induced-tgf-%C3%AE-1-smad3-signaling-and-liver-fibrosis-in-mice
#7
Kerui Fan, Kejia Wu, Ling Lin, Pu Ge, Jie Dai, Xiaojiao He, Kai Hu, Li Zhang
Increasing evidence suggests that the widely used antidiabetic drug metformin have an extensive therapeutic range beyond hypoglycemic therapy. We previously found that metformin significantly attenuated acute hepatitis. The present study investigated the potential effects of metformin on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. The results indicated that treatment with metformin suppressed CCl4-induced elevation of liver index, formation of fibrotic septa, accumulation of connective tissue and upregulation of collagen I...
April 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28387573/metformin-inhibits-rankl-and-sensitizes-cancer-stem-cells-to-denosumab
#8
Elisabet Cuyàs, Begoña Martin-Castillo, Joaquim Bosch-Barrera, Javier A Menendez
The increased propensity of BRCA1 mutation carriers to develop aggressive breast tumors with stem-like properties begins to be understood in terms of osteoprotegerin (OPG)-unrestricted cross-talk between RANKL-overproducing progesterone-sensor cells and cancer-initiating RANK(+) responder cells that reside within pre-malignant BRCA1(mut/+) breast epithelial tissue. We recently proposed that, in the absence of hormone influence, cancer-initiating cells might remain responsive to RANKL stimulation, and hence to the therapeutic effects of the anti-RANKL antibody denosumab because genomic instability induced by BRCA1 haploinsufficiency might suffice to cell-autonomously hyperactivate RANKL gene expression...
April 7, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28386373/mechanism-of-progestin-resistance-in-endometrial-precancer-cancer-through-nrf2-survivin-pathway
#9
Rujia Fan, Yiying Wang, Yue Wang, Li Wei, Wenxin Zheng
Progestin is commonly used for young patients suffering from endometrial hyperplasia or cancer. However, there is approximately 30% failure rate with unclear mechanism. We investigated if Nrf2-survivin pathway contributes the progestin resistance (PR) in this setting. Current study detected Nrf2 and survivin protein expression in post progestin treated endometrial tissue samples by using immunohistochemistry. Transfection of Nrf2 and survivin into endometrial cancer cells in vitro was done to determine the roles of Nrf2 and survivin in progestin resistance...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28384260/denv-up-regulates-the-hmg-coa-reductase-activity-through-the-impairment-of-ampk-phosphorylation-a-potential-antiviral-target
#10
Rubén Soto-Acosta, Patricia Bautista-Carbajal, Margot Cervantes-Salazar, Antonio H Angel-Ambrocio, Rosa M Del Angel
Dengue is the most common mosquito-borne viral disease in humans. Changes of lipid-related metabolites in endoplasmic reticulum of dengue virus (DENV) infected cells have been associated with replicative complexes formation. Previously, we reported that DENV infection inhibits HMGCR phosphorylation generating a cholesterol-enriched cellular environment in order to favor viral replication. In this work, using enzymatic assays, ELISA, and WB we found a significant higher activity of HMGCR in DENV infected cells, associated with the inactivation of AMPK...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28383051/dual-inhibiting-oct4-and-akt-potently-suppresses-the-propagation-of-human-cancer-cells
#11
Wenxin Li, Yanwen Zhou, Xiaoqian Zhang, Ying Yang, Songsong Dan, Tong Su, Shiqi She, Weilai Dong, Qingwei Zhao, Jia Jia, Hangping Yao, Min Zheng, Bo Kang, Ying-Jie Wang
AKT serves as an epigenetic modulator that links epigenetic regulation to cell survival and proliferation while the epigenetic mediator OCT4 critically controls stem cell pluripotency and self-renewal. Emerging evidence indicated their complicated interplays in cancer cells and cancer stem cells (CSCs), and inhibiting either one may activate the other. Thus, in this study, we propose a strategy to targeting both factors simultaneously. Firstly, a combination of an OCT4-specific shRNA and the specific AKT inhibitor Akti-1/2 potently suppressed the propagation of human embryonal carcinoma cells, adherent cancer cells and stem-like cancer cells, establishing the proof-of-concept that dual inhibiting OCT4 and AKT can effectively target various cancer cells...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28382202/mitochondria-targeted-metformins-anti-tumour-and-redox-signalling-mechanisms
#12
REVIEW
Balaraman Kalyanaraman, Gang Cheng, Micael Hardy, Olivier Ouari, Adam Sikora, Jacek Zielonka, Michael Dwinell
Reports suggest that metformin exerts anti-cancer effects in diabetic individuals with pancreatic cancer. Thus, metformin is currently being repurposed as a potential drug in cancer treatment. Studies indicate that potent metformin analogues are required in cancer treatment because of the low bioavailability of metformin in humans at conventional antidiabetic doses. We proposed that improved mitochondrial targeting of metformin by attaching a positively charged lipophilic triphenylphosphonium group will result in a new class of mitochondria-targeted metformin analogues with significantly enhanced anti-tumour potential...
April 6, 2017: Interface Focus
https://www.readbyqxmd.com/read/28375658/empagliflozin-linagliptin-single-pill-combination-therapy-for-patients-with-type-2-diabetes-mellitus
#13
Rajeev Kumar Jain
Type 2 diabetes mellitus (T2DM) is typically progressive, with sequential addition of therapies often needed to address increasing hyperglycemia over the disease course. Using treatments in combination may be preferred to sequential addition, as a means of providing a more rapid clinical response and potentially avoiding clinical inertia. In such cases, a single-pill combination can help to reduce pill burden. Although various single-pill combinations of oral glucose-lowering agents are available, empagliflozin/linagliptin was the first approved combination of a sodium glucose co-transporter 2 (SGLT2) inhibitor with a dipeptidyl peptidase 4 (DPP-4) inhibitor in the United States...
April 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28373404/precancer-atlas-to-drive-precision-prevention-trials
#14
Avrum Spira, Matthew B Yurgelun, Ludmil Alexandrov, Anjana Rao, Rafael Bejar, Kornelia Polyak, Marios Giannakis, Ali Shilatifard, Olivera J Finn, Madhav Dhodapkar, Neil E Kay, Esteban Braggio, Eduardo Vilar, Sarah A Mazzilli, Timothy R Rebbeck, Judy E Garber, Victor E Velculescu, Mary L Disis, Douglas C Wallace, Scott M Lippman
Cancer development is a complex process driven by inherited and acquired molecular and cellular alterations. Prevention is the holy grail of cancer elimination, but making this a reality will take a fundamental rethinking and deep understanding of premalignant biology. In this Perspective, we propose a national concerted effort to create a Precancer Atlas (PCA), integrating multi-omics and immunity - basic tenets of the neoplastic process. The biology of neoplasia caused by germline mutations has led to paradigm-changing precision prevention efforts, including: tumor testing for mismatch repair (MMR) deficiency in Lynch syndrome establishing a new paradigm, combinatorial chemoprevention efficacy in familial adenomatous polyposis (FAP), signal of benefit from imaging-based early detection research in high-germline risk for pancreatic neoplasia, elucidating early ontogeny in BRCA1-mutation carriers leading to an international breast cancer prevention trial, and insights into the intricate germline-somatic-immunity interaction landscape...
April 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28373282/metformin-directly-binds-the-alarmin-hmgb1-and-inhibits-its-proinflammatory-activity
#15
Takahiro Horiuchi, Natsumi Sakata, Yoshihiro Narumi, Tomohiro Kimura, Takashi Hayashi, Keisuke Nagano, Keyue Liu, Masahiro Nishibori, Sohei Tsukita, Tetsuya Yamada, Hideki Katagiri, Ryutaro Shirakawa, Hisanori Horiuchi
Metformin is the first-line drug in the treatment of type 2 diabetes. In addition to its hypoglycemic effect, metformin has an anti-inflammatory function, but the precise mechanism promoting this activity remains unclear. High mobility group box 1 (HMGB1) is an alarmin that is released from necrotic cells and induces inflammatory responses by its cytokine-like activity and is therefore a target of anti-inflammatory therapies. Here we identified HMGB1 as a novel metformin binding protein by affinity purification using a biotinylated metformin analogue...
April 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28351720/estradiol-effects-on-hypothalamic-ampk-and-bat-thermogenesis-a-gateway-for-obesity-treatment
#16
REVIEW
Miguel López, Manuel Tena-Sempere
In addition to their prominent roles in the control of reproduction, estrogens are important modulators of energy balance, as evident in conditions of deficiency of estrogens, which are characterized by increased feeding and decreased energy expenditure, leading to obesity. AMP-activated protein kinase (AMPK) is a ubiquitous cellular energy gauge that is activated under conditions of low energy, increasing energy production and reducing energy wasting. Centrally, the AMPK pathway is a canonical route regulating energy homeostasis, by integrating peripheral signals, such as hormones and metabolites, with neuronal networks...
March 25, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28350075/co-treatment-of-breast-cancer-cells-with-pharmacologic-doses-of-2-deoxy-d-glucose-and-metformin-starving-tumors
#17
Ulrike Wokoun, Martin Hellriegel, Günter Emons, Carsten Gründker
A characteristic of tumor cells is the increased aerobic glycolysis for energy production. Thus, inhibition of glycolysis represents a selective therapeutic option. It has been shown that glycolysis inhibitor 2-deoxy-D-glucose (2DG) induces apoptotic cell death in different tumor entities. In addition, the antitumor activity of the anti-diabetic drug metformin has been demonstrated. In the present study, we aimed to ascertain whether the combination of pharmacologic doses of 2DG with metformin increases the antitumor efficacy...
April 2017: Oncology Reports
https://www.readbyqxmd.com/read/28344112/efficacy-and-safety-of-once-weekly-semaglutide-versus-once-daily-insulin-glargine-as-add-on-to-metformin-with-or-without-sulfonylureas-in-insulin-naive-patients-with-type-2-diabetes-sustain-4-a-randomised-open-label-parallel-group-multicentre-multinational
#18
Vanita R Aroda, Stephen C Bain, Bertrand Cariou, Milivoj Piletič, Ludger Rose, Mads Axelsen, Everton Rowe, J Hans DeVries
BACKGROUND: Several pharmacological treatment options are available for type 2 diabetes; however, many patients do not achieve optimum glycaemic control and therefore new therapies are necessary. We assessed the efficacy and safety of semaglutide, a glucagon-like peptide-1 (GLP-1) analogue in clinical development, compared with insulin glargine in patients with type 2 diabetes who were inadequately controlled with metformin (with or without sulfonylureas). METHODS: We did a randomised, open-label, non-inferiority, parallel-group, multicentre, multinational, phase 3a trial (SUSTAIN 4) at 196 sites in 14 countries...
March 23, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28337263/receptor-for-advanced-glycation-end-as-drug-targets-in-diabetes-induced-skin-lesion
#19
Xiang-Fang Chen, Wei Tang, Wei-Dong Lin, Zi-Yu Liu, Xiao-Xiao Lu, Bei Zhang, Fei Ye, Zhi-Min Liu, Jun-Jie Zou, Wan-Qing Liao
The involvement of the receptor for advanced glycation end (RAGE) in different diseases has been reviewed in great detail, previously, but the effects of diabetic drugs on RAGE-induced skin lesion during long course diabetes remains poorly understood. In the present study, we have shown that RAGE was overexpressed in both diabetic rats and human keratinocytes (HaCaT cells). Cell cycle arrest and apoptosis as well as alternations of relative protein levels were also found in diabetic rats and HaCaT cells with overexpression of RAGE that were rectified by metformin (Met) treatment...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28324049/piloting-a-remission-strategy-in-type-2-diabetes-results-of-a-randomized-controlled-trial
#20
Natalia McInnes, Ada Smith, Rose Otto, Jeffrey Vandermey, Zubin Punthakee, Diana Sherifali, Kumar Balasubramanian, Stephanie Hall, Hertzel C Gerstein
Context: Medical strategies targeting remission of type 2 diabetes have not been systematically studied. Objective: This trial assessed the feasibility, safety and potential to induce remission of a short-term intensive metabolic strategy. Design: A randomized, parallel, open-label pilot trial in 83 participants followed for 52 weeks. Setting: Ambulatory care. Participants: Patients with type 2 diabetes of up to 3 years in duration...
March 15, 2017: Journal of Clinical Endocrinology and Metabolism
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