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https://www.readbyqxmd.com/read/29131265/metformin-reduces-satb2-mediated-osteosarcoma-stem-cell-like-phenotype-and-tumor-growth-via-inhibition-of-n-cadherin-nf-kb-signaling
#1
H Y Xu, W Fang, Z W Huang, J C Lu, Y Q Wang, Q L Tang, G H Song, Y Kang, X J Zhu, C Y Zou, H L Yang, J N Shen, J Wang
OBJECTIVE: To investigate the role of SATB2 in stem cell-like properties of osteosarcoma and identify new strategies to eliminate cancer stem cells of osteosarcoma. MATERIALS AND METHODS: Osteosarcoma cancer stem cells were derived by sarcosphere generation or chemo drug enrichment. SATB2 and pluripotency-associated gene expression in osteosarcoma CSCs were analyzed using qRT-PCR and Western blotting. The sphere formation assay, cell counting kit-8 assay and anti-chemotherapy proteins were used to measure the effects of altered SATB2, N-cadherin expression or metformin treatment in CSCs...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29128163/depsidone-and-xanthones-from-garcinia-xanthochymus-with-hypoglycemic-activity-and-the-mechanism-of-promoting-glucose-uptake-in-l6-myotubes
#2
Yunfang Li, Ping Zhao, Yu Chen, Yanze Fu, Kuan Shi, Liu Liu, Hui Liu, Mingrui Xiong, Qing-Hua Liu, Guangzhong Yang, Yuxiu Xiao
Garcinia xanthochymus is a widely used folk medicine in southwestern China. Previous studies indicated it possesses potential anti-diabetic activities both in vitro (Fu et al., 2014; Nguyen et al., 2017) and in vivo (Shivanand et al., 2017). To discover bioactive ingredients from it and unveil their mechanism of action against diabetes, the present study was designed to isolate constituents from extract of G. xanthochymus, determine their structures, screen their activities and investigate mechanism of action of the active substances...
November 8, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29125636/very-tight-versus-tight-control-which-should-be-the-criteria-for-pharmacologic-therapy-dose-adjustment-in-diabetes-in-pregnancy-evidence-from-randomized-controlled-trials
#3
Claudia Caissutti, Gabriele Saccone, Andrea Ciardulli, Vincenzo Berghella
INTRODUCTION: There is inconclusive evidence from randomized controlled trials (RCTs) to support any specific criteria for pharmacologic therapy dose adjustment in diabetes in pregnancy. Our objective was to analyze the criteria for dose adjustment of pharmacologic treatment for diabetes mellitus (DM) in pregnancy. MATERIAL AND METHODS: Data sources: MEDLINE, OVID and Cochrane Library were searched from their inception to September 2017. Selection criteria included all trials of DM in pregnancy managed by oral hypoglycemic agents or insulin reporting criteria for pharmacologic therapy dose adjustment...
November 10, 2017: Acta Obstetricia et Gynecologica Scandinavica
https://www.readbyqxmd.com/read/29122080/role-of-adenosine-monophosphate-activated-protein-kinase-on-cell-migration-matrix-contraction-and-matrix-metalloproteinase-1-and-matrix-metalloproteinase-2-production-in-nasal-polyp-derived-fibroblasts
#4
Ji-Young Um, Seoung-Ae Lee, Joo-Hoo Park, Jae-Min Shin, Il-Ho Park, Heung-Man Lee
PURPOSE: Activation of adenosine monophosphate-activated protein kinase (AMPK) by metformin, as a master regulator of metabolism, is involved in airway tissue remodeling. Here, we investigated the physical role of AMPK on cell migration, matrix contraction, and the production of matrix metalloproteinases (MMP) in nasal polyp-derived fibroblasts (NPDF). METHODS: Primary NPDFs from six patients with chronic rhinosinusitis and nasal polyps were isolated and cultured...
November 1, 2017: American Journal of Rhinology & Allergy
https://www.readbyqxmd.com/read/29113111/the-mxl-3-sbp-1-axis-is-responsible-for-glucose-dependent-fat-accumulation-in-c-elegans
#5
Fanny Mejia-Martinez, Berenice Franco-Juarez, Elizabeth Moreno-Arriola, Alain Hernández-Vázquez, Marco Martinez-Avila, Saul Gómez-Manzo, Jaime Marcial-Quino, Karla Carvajal, Antonio Velazquez-Arellano, Daniel Ortega-Cuellar
Chronic exposure to elevated glucose levels leads to fatty acid accumulation, which promotes the development of metabolic diseases such as obesity and type 2 diabetes. MXL-3 is a conserved transcriptional factor that modulates the inhibition of lipolysis in Caenorhabditis elegans. However, the role of MXL-3 in lipid metabolism during nutrient excess remains unknown. We hypothesized that inhibition of MXL-3 prevents glucose-dependent fat accumulation. Nematodes from wild-type N2, MXL-3::GFP and sbp-1 or mxl-3 null strains were grown on standard, high glucose or high glucose plus metformin plates for 24 h...
November 6, 2017: Genes
https://www.readbyqxmd.com/read/29111280/akt-activation-a-potential-strategy-to-ameliorate-insulin-resistance
#6
REVIEW
Zhengyi Zhang, Huadong Liu, Jiankang Liu
Insulin resistance is a hallmark of type 2 diabetes and obesity while the mechanism remains unclear. Current therapy to treat type 2 diabetes is metformin, the 5'-monophosphate-activated protein kinase (AMPK) activator, owing to the ability to augment peripheral glucose uptake. However, metformin also displays limitations, as AMPK activation remains intact and regular in most type 2 diabetes and metformin does not seem to facilitate peripheral insulin resistance. Evidence has shown that PI3K-Akt/PKB pathway could be induced via insulin and act as an important effector...
October 27, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29110972/patient-reported-outcomes-in-patients-with-type-2-diabetes-treated-with-dulaglutide-added-to-titrated-insulin-glargine-award-9
#7
Maria Yu, Kate Van Brunt, Zvonko Milicevic, Oralee Varnado, Kristina S Boye
PURPOSE: This 28-week, randomized, double-blind study compared a once-weekly injection of dulaglutide 1.5 mg to placebo, both added to titrated once-daily insulin glargine (with or without metformin), in patients with type 2 diabetes mellitus and inadequate glycemia control (control defined as hemoglobin A1c, ≥7% and ≤10.5%). Patient-reported outcomes were assessed as an exploratory objective to further understand patients' physical, psychological, and social aspects of well-being and injection-device experience...
October 27, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/29110598/sirt1-as-a-therapeutic-target-in-diabetic-complications
#8
Justyna Strycharz, Żaneta Rygielska, Ewa Świderska, Józef Drzewoski, Janusz Szemraj, Leszek Szmigiero, Agnieszka Śliwińska
Background SIRT1 is an epigenetic enzyme involved in histone and non-histone protein deacetylation. It acts primarily as a metabolic sensor, which responses to changing energy status by deacetylating crucial transcription factors and cofactors. In this way, SIRT1 regulates mitochondrial function and biogenesis, oxidative stress, inflammation, apoptosis and cellular senescence. Disturbance of all of these phenomena promotes the pathogenesis of diabetic complications. These disorders are inseparably connected with chronic hyperglycemia, which possesses a strong epigenetic determinant...
November 6, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29106946/orodispersible-tablets-containing-taste-masked-solid-lipid-pellets-with-metformin-hydrochloride-influence-of-process-parameters-on-tablet-properties
#9
Gustavo Freire Petrovick, Peter Kleinebudde, Jörg Breitkreutz
Compaction of multiparticulates into tablets, particularly into orodispersible tablets (ODTs), is challenging. The compression of pellets, made by solid lipid extrusion/spheronization processes, presents peculiar difficulties since solid lipids usually soften or melt at relatively low temperature ranges and due to applied mechanical forces. Until now, there are no reports in literature about the development of ODTs based on solid lipid pellets. To investigate the feasibility of producing such tablets, a design of experiment (DoE) approach was performed to elucidate the influence of compression force and amount of two co-processed excipients (Ludiflash(®) and Parteck(®) ODT) on properties of the tablets (friability, tensile strength, and disintegration time)...
October 26, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/29106036/inhibition-of-mitochondrial-complex-i-improves-glucose-metabolism-independently-of-ampk-activation
#10
Wo-Lin Hou, Jun Yin, Miriayi Alimujiang, Xue-Ying Yu, Li-Gen Ai, Yu-Qian Bao, Fang Liu, Wei-Ping Jia
Accumulating evidences showed metformin and berberine, well-known glucose-lowering agents, were able to inhibit mitochondrial electron transport chain at complex I. In this study, we aimed to explore the antihyperglycaemic effect of complex I inhibition. Rotenone, amobarbital and gene silence of NDUFA13 were used to inhibit complex I. Intraperitoneal glucose tolerance test and insulin tolerance test were performed in db/db mice. Lactate release and glucose consumption were measured to investigate glucose metabolism in HepG2 hepatocytes and C2C12 myotubes...
November 6, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29103210/insulin-for-the-treatment-of-women-with-gestational-diabetes
#11
REVIEW
Julie Brown, Luke Grzeskowiak, Kathryn Williamson, Michelle R Downie, Caroline A Crowther
BACKGROUND: Gestational diabetes mellitus (GDM) is associated with short- and long-term complications for the mother and her infant. Women who are unable to maintain their blood glucose concentration within pre-specified treatment targets with diet and lifestyle interventions will require anti-diabetic pharmacological therapies. This review explores the safety and effectiveness of insulin compared with oral anti-diabetic pharmacological therapies, non-pharmacological interventions and insulin regimens...
November 5, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29100387/metabolic-modulation-of-ewing-sarcoma-cells-inhibits-tumor-growth-and-stem-cell-properties
#12
Atreyi Dasgupta, Matteo Trucco, Nino Rainusso, Ronald J Bernardi, Ryan Shuck, Lyazat Kurenbekova, David M Loeb, Jason T Yustein
Ewing sarcoma (EWS) is a highly aggressive and metabolically active malignant tumor. Metabolic activity can broadly be characterized by features of glycolytic activity and oxidative phosphorylation. We have further characterized metabolic features of EWS cells to identify potential therapeutic targets. EWS cells had significantly more glycolytic activity compared to their non-malignant counterparts. Thus, metabolic inhibitors of glycolysis such as 2-deoxy-D-glucose (2DG) and of the mitochondrial respiratory pathway, such as metformin, were evaluated as potential therapeutic agents against a panel of EWS cell lines in vitro...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29094287/targeting-ampk-mtor-and-%C3%AE-catenin-by-combined-metformin-and-aspirin-therapy-in-hcc-an-appraisal-in-egyptian-hcc-patients
#13
Doaa Ali Abdelmonsif, Ahmed S Sultan, Wessam F El-Hadidy, Dina Mohamed Abdallah
BACKGROUND: Hepatocellular carcinoma (HCC) is an expanding health problem with a great impact on morbidity and mortality, both in Egypt and worldwide. Recently, metformin and aspirin showed a potential anticancer effect on HCC, although the mechanism of this effect is not fully elucidated. OBJECTIVE: The current work aimed to investigate the possibility of targeting AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and β-catenin proteins through combined metformin/aspirin treatment in the HepG2 cell line, and to explore such molecular targets in Egyptian HCC patients...
November 1, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/29093681/quantitative-and-systems-pharmacology-3-network-based-identification-of-new-targets-for-natural-products-enables-potential-uses-in-aging-associated-disorders
#14
Jiansong Fang, Li Gao, Huili Ma, Qihui Wu, Tian Wu, Jun Wu, Qi Wang, Feixiong Cheng
Aging that refers the accumulation of genetic and physiology changes in cells and tissues over a lifetime has been shown a high risk of developing various complex diseases, such as neurodegenerative disease, cardiovascular disease and cancer. Over the past several decades, natural products have been demonstrated as anti-aging interveners via extending lifespan and preventing aging-associated disorders. In this study, we developed an integrated systems pharmacology infrastructure to uncover new indications for aging-associated disorders by natural products...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29082640/achieving-ada-ispad-clinical-guideline-goals-is-associated-with-higher-insulin-sensitivity-and-cardiopulmonary-fitness-in-adolescents-with-type-1-diabetes-results-from-resistance-to-insulin-in-type-1-and-type-2-diabetes-resistant-and-effects-of-metformin-on
#15
Petter Bjornstad, Melanie Cree-Green, Amy Baumgartner, Gregory Coe, Yesenia Garcia Reyes, Michal Schäfer, Laura Pyle, Judith G Regensteiner, Jane Eb Reusch, Kristen J Nadeau
OBJECTIVE: Most youth with type 1 diabetes do not meet the American Diabetes Association (ADA) and International Society for Pediatric and Adolescent Diabetes (ISPAD) targets for hemoglobin A1c (HbA1c), blood pressure (BP), lipids, and body mass index (BMI). We hypothesized that ISPAD/ADA goal achievement would be associated with better insulin sensitivity (IS) and cardiopulmonary fitness. METHODS: IS was quantified as glucose infusion rate (GIR) from a hyperinsulinemic-euglycemic clamp in youth with type 1 diabetes from the RESistance to InSulin in Type 1 ANd Type 2 diabetes (RESISTANT) (n = 86) and Effects of MEtformin on CardiovasculaR Function in AdoLescents with Type 1 Diabetes (EMERALD) (n = 41) cohorts (n = 127; age 15...
October 30, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/29080400/aging-and-stem-cell-therapy-ampk-as-an-applicable-pharmacological-target-for-rejuvenation-of-aged-stem-cells-and-achieving-higher-efficacy-in-stem-cell-therapy
#16
REVIEW
Mohammadhossein Khorraminejad-Shirazi, Mohammad Farahmandnia, Bahareh Kardeh, Alireza Estedlal, Sina Kardeh, Ahmad Monabati
In recent years, tissue regeneration has become a promising field for developing stem cell-based transplantation therapies for human patients. Adult stem cells are affected by the same aging mechanisms that involve somatic cells. One of the mechanisms involved in cellular aging is hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) and disruption of 5' adenosine monophosphate-activated protein kinase (AMPK). Aging of stem cells results in their impaired regenerative capacity and depletion of stem cell pools in adult tissue, which results in lower efficacy of stem cell therapy...
October 19, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/29080083/evaluation-of-metformin-effects-in-the-chronic-phase-of-spontaneous-seizures-in-pilocarpine-model-of-temporal-lobe-epilepsy
#17
Soraya Mehrabi, Nima Sanadgol, Mahmood Barati, Ali Shahbazi, Gelareh Vahabzadeh, Mitra Barzroudi, Morteza Seifi, Mazaher Gholipourmalekabadi, Fereshteh Golab
Temporal lobe epilepsy (TLE) is a common form of drug-resistant epilepsy that sometimes responds to dietary manipulation such as the 'ketogenic diet'. Here we have investigated the effects of metformin in the rat pilocaroin model of TLE. Male rats were treated with intra peritoneal injection of pilocarpine hydrochloride, in dose of 360 mg/kg to induce status epilepticus (SE). At 45 day after induction of SE, metformin was injected intraperitoneally in dose of 250 mg/kg/day for 5 days. We show that metformin potently reduces the progression of seizures and blocks seizure-induced over-expression of brain-derived neurotropic factor (BDNF) and its receptor, Tropomyosin receptor kinase B (TrkB)...
October 27, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29080075/current-therapies-that-modify-glucagon-secretion-what-is-the-therapeutic-effect-of-such-modifications
#18
REVIEW
Magnus F Grøndahl, Damien J Keating, Tina Vilsbøll, Filip K Knop
PURPOSE OF REVIEW: Hyperglucagonemia contributes significantly to hyperglycemia in type 2 diabetes and suppressed glucagon levels may increase the risk of hypoglycemia. Here, we give a brief overview of glucagon physiology and the role of glucagon in the pathophysiology of type 2 diabetes and provide insights into how antidiabetic drugs influence glucagon secretion as well as a perspective on the future of glucagon-targeting drugs. RECENT FINDINGS: Several older as well as recent investigations have evaluated the effect of antidiabetic agents on glucagon secretion to understand how glucagon may be involved in the drugs' efficacy and safety profiles...
October 28, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/29079305/kras-yap-and-obesity-in-pancreatic-cancer-a-signaling-network-with-multiple-loops
#19
REVIEW
Guido Eibl, Enrique Rozengurt
Pancreatic ductal adenocarcinoma (PDAC) continues to be a lethal disease with no efficacious treatment modalities. The incidence of PDAC is expected to increase, at least partially because of the obesity epidemic. Increased efforts to prevent or intercept this disease are clearly needed. Mutations in KRAS are initiating events in pancreatic carcinogenesis supported by genetically engineered mouse models of the disease. However, oncogenic KRAS is not entirely sufficient for the development of fully invasive PDAC...
October 24, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29070511/metformin-in-gestational-diabetes-mellitus-predictors-of-poor-response
#20
Inês Gante, Luís Melo, Jorge Dores, Luísa Ruas, Maria do Céu Almeida
OBJECTIVE: Metformin can be regarded as a first-line treatment in Gestational Diabetes Mellitus (GDM) due to its safety and effectiveness. However, a proportion of women do not achieve adequate glycemic control with metformin alone. We aim to identify predictors of this poor response to metformin. DESIGN AND METHODS: Retrospective multicentre cohort study of women with GDM who started metformin as first-line treatment. The assessed cohort was divided into a metformin group and metformin plus insulin group...
October 25, 2017: European Journal of Endocrinology
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