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https://www.readbyqxmd.com/read/27920819/co-administration-of-metformin-and-n-acetylcysteine-with-dietary-control-improves-the-biochemical-and-histological-manifestations-in-rats-with-non-alcoholic-fatty-liver
#1
Naglaa Mohamed El-Lakkany, Sayed Hassan Seif El-Din, Abdel-Nasser Abdel-Aal Sabra, Olfat Ali Hammam, Fatma Abdel-Latif Ebeid
Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem that affects 1/3 of the adult population and an increasing number of children in developed countries. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. This study was conceived in a NAFLD rat model to evaluate the efficacy of both metformin (MTF) and N-acetylcysteine (NAC) with dietary control on biochemical and histologic liver manifestations. Rats were classified into nine groups; normal (I), NAFLD-induced by feeding high-fat diet (HFD; II) for 12 weeks, NAFLD switched to regular diet (RD; III), NAFLD-HFD or -RD treated with MTF in a dose of 150 mg/kg (IV, V), NAC in a dose of 500 mg/kg (VI, VII) or MTF+NAC (VIII, IX) respectively for 8 weeks...
October 2016: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27919698/the-use-of-partially-hydrolysed-polyvinyl-alcohol-for-the-production-of-high-drug-loaded-sustained-release-pellets-via-extrusion-spheronisation-and-coating-in-vitro-and-in-vivo-evaluation
#2
G Verstraete, W De Jaeghere, J Vercruysse, W Grymonpré, V Vanhoorne, F Stauffer, T De Beer, A Bezuijen, J P Remon, C Vervaet
Partially hydrolysed polyvinyl alcohol (PVA) was evaluated as a pelletisation aid for the production of pellets with a high acetaminophen and metformin hydrochloride concentration (>70%, w/w). Mixtures with varying drug concentration and PVA/microcrystalline cellulose (MCC) ratios were processed via extrusion-spheronisation, either after addition of PVA as a dry powder or as an aqueous solution. Finally, high drug- loaded metformin pellets were coated with a methacrylic acid copolymer (Eudragit™ NM 30D) and evaluated for their sustained release potency in vitro and in vivo...
December 2, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27919027/phosphorylation-of-janus-kinase-1-jak1-by-amp-activated-protein-kinase-ampk-links-energy-sensing-to-anti-inflammatory-signaling
#3
Claire Rutherford, Claire Speirs, Jamie J L Williams, Marie-Ann Ewart, Sarah J Mancini, Simon A Hawley, Christian Delles, Benoit Viollet, Ana P Costa-Pereira, George S Baillie, Ian P Salt, Timothy M Palmer
Adenosine 5'-monophosphate-activated protein kinase (AMPK) is a pivotal regulator of metabolism at cellular and organismal levels. AMPK also suppresses inflammation. We found that pharmacological activation of AMPK rapidly inhibited the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in various cells. In vitro kinase assays revealed that AMPK directly phosphorylated two residues (Ser(515) and Ser(518)) within the Src homology 2 domain of JAK1. Activation of AMPK enhanced the interaction between JAK1 and 14-3-3 proteins in cultured vascular endothelial cells and fibroblasts, an effect that required the presence of Ser(515) and Ser(518) and was abolished in cells lacking AMPK catalytic subunits...
November 8, 2016: Science Signaling
https://www.readbyqxmd.com/read/27916907/metformin-inhibits-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-via-pkm2-relative-mtor-p70s6k-signaling-pathway-in-cervical-carcinoma-cells
#4
Keyan Cheng, Min Hao
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) plays a prominent role in tumorigenesis. Metformin exerts antitumorigenic effects in various cancers. This study investigated the mechanisms of metformin in TGF-β1-induced Epithelial-to-mesenchymal transition (EMT) in cervical carcinoma cells. METHODS: cells were cultured with 10 ng/mL TGF-β1 to induce EMT and treated with or without metformin. Cell viability was evaluated by CCK-8 (Cell Counting Kit 8, CCK-8) assay; apoptosis were analyzed by flow cytometry; cell migration was evaluated by wound-healing assay...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27914525/protective-effects-of-huanglian-wendan-decoction-aganist-cognitive-deficits-and-neuronal-damages-in-rats-with-diabetic-encephalopathy-by-inhibiting-the-release-of-inflammatory-cytokines-and-repairing-insulin-signaling-pathway-in-hippocampus
#5
Yue-Bi Li, Wei-Hua Zhang, Hua-Dong Liu, Zhou Liu, Shi-Ping Ma
Huanglian Wendan decoction (HLWDD) has been used for the treatment of symptom of "Re", one of major causes in diabetes and metabolic disorders, according to the theory of traditional Chinese medicine. The present study aimed at investigating the cerebral protective effects of HLWDD on diabetic encephalopathy (DE), one of the major diabetic complications. The effects of HLWDD and metformin were analyzed in the streptozocin (STZ) + high-glucose-fat (HGF) diet-induced DE rats by gastric intubation. In the present study, the effects of HLWDD on cognition deficits were investigated after 30-day intervention at two daily dose levels (3 and 6 g·kg(-1))...
November 2016: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/27903154/type-2-diabetes-mellitus-and-cancer-the-role-of-pharmacotherapy
#6
Gadi Shlomai, Brian Neel, Derek LeRoith, Emily Jane Gallagher
Purpose Type 2 diabetes mellitus (T2DM) is becoming increasingly prevalent worldwide. Epidemiologic data suggest that T2DM is associated with an increased incidence and mortality from many cancers. The purpose of this review is to discuss the links between diabetes and cancer, the effects of various antidiabetic medications on cancer incidence and mortality, and the effects of anticancer therapies on diabetes. Design This study is a review of preclinical and clinical data regarding the effects of antidiabetic medications on cancer incidence and mortality and the effects of anticancer therapies on glucose homeostasis...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27903152/obesity-and-cancer-mechanisms-cancer-metabolism
#7
Benjamin D Hopkins, Marcus D Goncalves, Lewis C Cantley
Obesity is a risk factor for cancer development and is associated with poor prognosis in multiple tumor types. The positive energy balance linked with obesity induces a variety of systemic changes including altered levels of insulin, insulin-like growth factor-1, leptin, adiponectin, steroid hormones, and cytokines. Each of these factors alters the nutritional milieu and has the potential to create an environment that favors tumor initiation and progression. Although the complete ramifications of obesity as it relates to cancer are still unclear, there is convincing evidence that reducing the magnitude of the systemic hormonal and inflammatory changes has significant clinical benefits...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27903149/obesity-and-breast-cancer-prognosis-evidence-challenges-and-opportunities
#8
Sao Jiralerspong, Pamela J Goodwin
Purpose To summarize the evidence of an association between obesity and breast cancer prognosis. Methods We reviewed the literature regarding overweight and obesity and breast cancer survival outcomes, overall and with regard to breast cancer subtypes, breast cancer therapies, biologic mechanisms, and possible interventions. We summarize our findings and provide clinical management recommendations. Results Obesity is associated with a 35% to 40% increased risk of breast cancer recurrence and death and therefore poorer survival outcomes...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27902686/genomic-characterization-of-metformin-hepatic-response
#9
Marcelo R Luizon, Walter L Eckalbar, Yao Wang, Stacy L Jones, Robin P Smith, Megan Laurance, Lawrence Lin, Paul J Gallins, Amy S Etheridge, Fred Wright, Yihui Zhou, Cliona Molony, Federico Innocenti, Sook Wah Yee, Kathleen M Giacomini, Nadav Ahituv
Metformin is used as a first-line therapy for type 2 diabetes (T2D) and prescribed for numerous other diseases. However, its mechanism of action in the liver has yet to be characterized in a systematic manner. To comprehensively identify genes and regulatory elements associated with metformin treatment, we carried out RNA-seq and ChIP-seq (H3K27ac, H3K27me3) on primary human hepatocytes from the same donor treated with vehicle control, metformin or metformin and compound C, an AMP-activated protein kinase (AMPK) inhibitor (allowing to identify AMPK-independent pathways)...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27902459/anti-tumor-activity-of-metformin-from-metabolic-and-epigenetic-perspectives
#10
REVIEW
Xilan Yu, Wuxiang Mao, Yansheng Zhai, Chong Tong, Min Liu, Lixin Ma, Xiaolan Yu, Shanshan Li
Metformin has been used to treat type 2 diabetes for over 50 years. Epidemiological, preclinical and clinical studies suggest that metformin treatment reduces cancer incidence in diabetes patients. Due to its potential as an anti-cancer agent and its low cost, metformin has gained intense research interest. Its traditional anti-cancer mechanisms involve both indirect and direct insulin-dependent pathways. Here, we discussed the anti-tumor mechanism of metformin from the aspects of cell metabolism and epigenetic modifications...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27898267/combining-treatment-with-myo-inositol-and-d-chiro-inositol-40-1-is-effective-in-restoring-ovary-function-and-metabolic-balance-in-pcos-patients
#11
Giovanni Monastra, Vittorio Unfer, Abdel Halim Harrath, Mariano Bizzarri
Polycystic ovary syndrome (PCOS), a relevant cause of infertility, is a heterogeneous, endocrine disorder affecting up to 10-15% of women in reproductive age. Besides hyperandrogenism, insulin resistance (IR) plays a key role in such syndrome. Insulin-sensitizing drugs, such as Metformin, are effective in treating hyper-insulinemic PCOS patients. Recently, inositols - myo-inositol (MI) and D-chiro-inositol (DCI) - have shown to be an efficient and safe alternative in PCOS management, as both inositol isoforms are able to counteract downstream consequences of insulin resistance...
November 29, 2016: Gynecological Endocrinology
https://www.readbyqxmd.com/read/27889750/metformin-protects-neurons-against-oxygen-glucose-deprivation-reoxygenation-induced-injury-by-down-regulating-mad2b
#12
Xianfang Meng, Guangpin Chu, Zhihua Yang, Ping Qiu, Yue Hu, Xiaohe Chen, Wenpeng Peng, Chen Ye, Fang-Fang He, Chun Zhang
BACKGROUND/AIMS: Metformin, the common medication for type II diabetes, has protective effects on cerebral ischemia. However, the molecular mechanisms are far from clear. Mitotic arrest deficient 2-like protein 2 (MAD2B), an inhibitor of the anaphase-promoting complex (APC), is widely expressed in hippocampal and cortical neurons and plays an important role in mediating high glucose-induced neurotoxicity. The present study investigated whether metformin modifies the expression of MAD2B and to exert its neuroprotective effects in primary cultured cortical neurons during oxygen-glucose deprivation/reoxygenation (OGD/R), a widely used in vitro model of ischemia/reperfusion...
November 11, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27875520/the-cell-autonomous-mechanisms-underlying-the-activity-of-metformin-as-an-anticancer-drug
#13
Francesca Sacco, Alberto Calderone, Luisa Castagnoli, Gianni Cesareni
The biguanide drug metformin profoundly affects cell metabolism, causing an impairment of the cell energy balance and triggering a plethora of pleiotropic effects that vary depending on the cellular or environmental context. Interestingly, a decade ago, it was observed that metformin-treated diabetic patients have a significantly lower cancer risk. Although a variety of in vivo and in vitro observations emphasising the role of metformin as anticancer drug have been reported, the underlying mechanisms are still poorly understood...
November 22, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27865164/metformin-improves-lipid-metabolism-disorders-through-reducing-the-expression-of-microsomal-triglyceride-transfer-protein-in-oletf-rats
#14
Nianhong Wang, Junqing Zhang, Yiming Wu, Jia Liu, Lin Liu, Xiaohui Guo
OBJECTIVE: This study aimed to investigate the role of MTP on lipid metabolism disorders in insulin-resistant rats and the potential mechanism through which metformin can improve lipid metabolism disorders. METHODS: 30 OLETF rats served as research subjects and 18 LETO rats of the same strain served as the control group (LETO group). After the first oral glucose tolerance test (at 8-week-old), 6 rats were randomly killed from each group. The remaining 24 OLETF rats were randomly divided into untreated group (OLETF group) and treated group (OLETF/M group, cured with metformin)...
October 15, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/27863704/cardiovascular-effects-of-glucose-lowering-therapies-for-type-2-diabetes-new-drugs-in-perspective
#15
REVIEW
Peter L Thompson, Timothy M E Davis
PURPOSE: The purpose of this study was to review the results of clinical trials assessing the cardiovascular effects of drugs for type 2 diabetes and the cardiovascular effects of newer available drugs. METHODS: We performed a detailed search of PubMed-listed publications, reports from international meetings, and ongoing studies from clinical trials.gov. FINDINGS: Currently available drugs have neutral or, in some cases, negative effects on cardiovascular outcomes...
November 15, 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27857021/effects-and-mechanisms-of-metformin-on-the-proliferation-of-esophageal-cancer-cells-in-vitro-and-in-vivo
#16
Jian-Cai Tang, Rui An, Yi-Qing Jiang, Jian Yang
Purpose: To observe the effects of metformin on human esophageal cancer cell, and to investigate its possible mechanisms. Materials and Methods: Cell viability was detected by using a cell counting kit-8(CCK-8), while cell cycle and apoptosis were assessed by flow cytometry and western blot was used to measure the expression of the related proteins. RNAi was used to knockout pyruvate kinase muscle isozyme 2 (PKM2). An Eca109 tumor model was established to evaluate the antitumor effect in vivo...
November 11, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/27856330/metformin-suppresses-adipogenesis-through-both-amp-activated-protein-kinase-ampk-dependent-and-ampk-independent-mechanisms
#17
Suet Ching Chen, Rebecca Brooks, Jessica Houskeeper, Shaun K Bremner, Julia Dunlop, Benoit Viollet, Pamela J Logan, Ian P Salt, S Faisal Ahmed, Stephen J Yarwood
People with Type 2 diabetes mellitus (T2DM) have reduced bone mineral density and an increased risk of fractures due to altered mesenchymal stem cell (MSC) differentiation in the bone marrow. This leads to a shift in the balance of differentiation away from bone formation (osteogenesis) in favour of fat cell development (adipogenesis). The commonly used anti-diabetic drug, metformin, activates the osteogenic transcription factor Runt-related transcription factor 2 (Runx2), which may suppress adipogenesis, leading to improved bone health...
November 14, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27856287/the-inhibition-of-spinal-synaptic-plasticity-mediated-by-activation-of-amp-activated-protein-kinase-signaling-alleviates-the-acute-pain-induced-by-oxaliplatin
#18
Yun-Zhi Ling, Zhen-Yu Li, Han-Dong Ou-Yang, Chao Ma, Shao-Ling Wu, Jia-You Wei, Huan-Huan Ding, Xiao-Long Zhang, Meng Liu, Cui-Cui Liu, Zhen-Zhen Huang, Wen-Jun Xin
Our recent findings demonstrated that oxaliplatin entering CNS may directly induce spinal central sensitization, and contribute to the rapid development of CNS-related side effects including acute pain during chemotherapy. However, the mechanism is largely unclear. In the current study, we found that the amplitude of C-fiber-evoked field potentials was significantly increased and the expression of phosphorylated mammalian AMP-activated protein kinase α (AMPKα) was markedly decreased following high frequency stimulation (HFS) or single intraperitoneal injection of oxaliplatin (4mg/kg)...
November 14, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27855689/metformin-reduces-morphine-tolerance-by-inhibiting-microglial-mediated-neuroinflammation
#19
Yinbing Pan, Xiaodi Sun, Lai Jiang, Liang Hu, Hong Kong, Yuan Han, Cheng Qian, Chao Song, Yanning Qian, Wentao Liu
BACKGROUND: Tolerance seriously impedes the application of morphine in clinical medicine. Thus, it is necessary to investigate the exact mechanisms and efficient treatment. Microglial activation and neuroinflammation in the spinal cord are thought to play pivotal roles on the genesis and maintaining of morphine tolerance. Activation of adenosine monophosphate-activated kinase (AMPK) has been associated with the inhibition of inflammatory nociception. Metformin, a biguanide class of antidiabetic drugs and activator of AMPK, has a potential anti-inflammatory effect...
November 17, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27854055/fixed-dose-combination-of-canagliflozin-and-metformin-for-the-treatment-of-type-2-diabetes-an-overview
#20
REVIEW
Jaime A Davidson, Lance Sloan
: Metformin is recommended as a first-line therapy for patients with type 2 diabetes mellitus (T2DM). However, many patients do not achieve glycemic goals with metformin monotherapy and require subsequent combination therapy with other antihyperglycemic agents (AHAs). For newly diagnosed patients with high blood glucose, initial combination therapy may be required to achieve glycemic control. The American Association for Clinical Endocrinologists algorithm for the treatment of T2DM recommends metformin plus a sodium glucose co-transporter 2 (SGLT2) inhibitor as the first oral combination in patients who present with HbA1c ≥7...
November 16, 2016: Advances in Therapy
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