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https://www.readbyqxmd.com/read/28809398/precision-medicine-for-suicidality-from-universality-to-subtypes-and-personalization
#1
A B Niculescu, H Le-Niculescu, D F Levey, P L Phalen, H L Dainton, K Roseberry, E M Niculescu, J O Niezer, A Williams, D L Graham, T J Jones, V Venugopal, A Ballew, M Yard, T Gelbart, S M Kurian, A Shekhar, N J Schork, G E Sandusky, D R Salomon
Suicide remains a clear, present and increasing public health problem, despite being a potentially preventable tragedy. Its incidence is particularly high in people with overt or un(der)diagnosed psychiatric disorders. Objective and precise identification of individuals at risk, ways of monitoring response to treatments and novel preventive therapeutics need to be discovered, employed and widely deployed. We sought to investigate whether blood gene expression biomarkers for suicide (that is, a 'liquid biopsy' approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies...
August 15, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28801594/deficiency-in-catechol-o-methyltransferase-is-linked-to-a-disruption-of-glucose-homeostasis-in-mice
#2
Megumi Kanasaki, Swayam Prakash Srivastava, Fan Yang, Ling Xu, Sumiyo Kudoh, Munehiro Kitada, Norikazu Ueki, Hyoh Kim, Jinpeng Li, Satoru Takeda, Keizo Kanasaki, Daisuke Koya
2-methoxyestradiol (2-ME), an estrogen metabolite generated via catechol-o-methyltransferase (COMT), is multifunctional methoxy-catechol. Here, we report that COMT deficiency leads to glucose intolerance and 2-ME rescues COMT-deficient-associated metabolic defects. Liver COMT protein was suppressed in high fat diet (HFD)-fed or in pregnant mice. COMT suppression, by Ro41-0960 or siRNA, in HFD fed mice or in pregnant mice exacerbated glucose intolerance; 2-ME intervention ameliorated these defects. 2-ME effects on glucose tolerance were associated with AMPK phosphorylation in the liver and in islet cells...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801373/metformin-and-melatonin-in-adrenocortical-carcinoma-morphoproteomics-and-biomedical-analytics-provide-proof-of-concept-in-a-case-study
#3
Robert E Brown, Jamie Buryanek, Mary F McGuire
Metformin has been proposed as a novel anti-cancer drug for adrenocortical carcinoma (ACC) based upon Poli's recent preclinical studies that 1. "in vitro" metformin modulates the ACC cell model H295R and 2. "in vivo" metformin inhibits tumor growth in a xenograft model as confirmed by a significant reduction of Ki67 [1]. Here we report on our prior clinical case study that provides proof of concept for Poli's studies. We were requested to perform morphoproteomic analysis to further define the biology of, and raise targeted therapeutic options, for a case of post-treatment and chemoresistant ACC metastatic to the liver and the lung...
August 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28801099/immediate-reduction-of-serum-citrulline-but-no-change-of-steroid-profile-after-initiation-of-metformin-in-individuals-with-type-2-diabetes
#4
Michaela Breier, Simone Wahl, Cornelia Prehn, Uta Ferrari, Vanessa Sacco, Michaela Weise, Harald Grallert, Jerzy Adamski, Andreas Lechner
Metformin is the most important first-line treatment for type 2 diabetes mellitus (T2DM) but its exact mode of action remains unknown. In this study, we used targeted metabolomics to gain new insights into the metabolic effects of metformin in humans with T2DM. We also examined changes in the serum steroid hormone profile. We quantified 167 serum metabolites and 19 steroid hormones using liquid chromatography-tandem mass spectrometry at three time points in individuals with previously untreated T2DM: before the start of metformin therapy (time point A), after the first dose (B) and after short-term therapy for 4-6 weeks (C)...
August 8, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28794822/overview-of-glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-patients-with-type-2-diabetes
#5
Kelvin Lingjet Tran, Young In Park, Shalin Pandya, Navin John Muliyil, Brandon David Jensen, Kovin Huynh, Quang T Nguyen
BACKGROUND: It is estimated that 29.1 million people or 9.3% of the US population have diabetes, which contributes to considerable medical and financial burden. Type 2 diabetes mellitus is characterized by insulin resistance and insulin secretion impairment leading to hyperglycemia. The presence of insulin resistance is strongly correlated with obesity. OBJECTIVE: This article reviews the available glucagon-like peptide-1 (GLP-1) receptor agonists and their role in the management of patients with diabetes, to help guide the selection of the most suitable agent for the individualized treatment of patients with type 2 diabetes...
June 2017: American Health & Drug Benefits
https://www.readbyqxmd.com/read/28792171/glycemic-pentad
#6
Glycemic Pentad Forum
BACKGROUND: Conventionally, diabetes management involved targeting the triad of FPG, PPG, and HbA1c. However, several studies have suggested the quintessential need for a paradigm shift to incorporate glycemic variability and quality of life in the holistic diabetes control regimen. AIM: To generate a consensus and ratify the position of Glycemic Variability (GV) and Quality of Life (QOL), along with the traditional triad, in diabetes management in India. To evaluate whether the triple fixed dose combination of metformin, glimepiride, and voglibose can accomplish the goals of glycemic pentad...
July 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28791253/potential-role-of-metabolic-intervention-in-the-management-of-advanced-differentiated-thyroid-cancer
#7
Sri Harsha Tella, Anuhya Kommalapati, Mary Angelynne Esquivel, Ricardo Correa
Well-differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy that has an excellent prognosis with a 5-year survival rate of about 98%. However, approximately 50% of the patients with DTC who present with distant metastases (advanced DTC) die from the disease within 5 years of initial diagnosis even after getting the appropriate therapy. Apart from recent advancements in chemotherapy agents, the potential role of metabolic interventions, including the use of metformin, ketogenic diet, and high-dose vitamin C in the management of advanced cancers have been investigated as a less toxic co-adjuvant therapies...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28776086/the-mechanisms-of-action-of-metformin
#8
REVIEW
Graham Rena, D Grahame Hardie, Ewan R Pearson
Metformin is a widely-used drug that results in clear benefits in relation to glucose metabolism and diabetes-related complications. The mechanisms underlying these benefits are complex and still not fully understood. Physiologically, metformin has been shown to reduce hepatic glucose production, yet not all of its effects can be explained by this mechanism and there is increasing evidence of a key role for the gut. At the molecular level the findings vary depending on the doses of metformin used and duration of treatment, with clear differences between acute and chronic administration...
August 3, 2017: Diabetologia
https://www.readbyqxmd.com/read/28774208/moving-beyond-subcutaneous-insulin-the-application-of-adjunctive-therapies-to-the-treatment-of-type-1-diabetes
#9
Kathleen H Ang, Jennifer L Sherr
With the discovery of insulin nearly a century ago, the diagnosis of Type 1 Diabetes (T1D) transformed from a death sentence to a chronic medical condition. Despite the advances that have been made, the vast majority of those living with T1D still struggle to achieve targeted control. Yet, a plethora of agents have been developed to treat those with Type 2 Diabetes. Exploration of how these agents may benefit those with T1D has been an area of intense investigation, especially due to the overweight/obesity epidemic, which now afflicts more than 60% of those living with T1D...
August 3, 2017: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/28770331/the-pharmacogenetics-of-metformin
#10
REVIEW
Jose C Florez
Despite its widespread use as the first-line agent for the treatment of type 2 diabetes, it has become clear that metformin does not work optimally for everyone. Elucidating who are the likely metformin responders and non-responders is hampered by our limited knowledge of its precise molecular mechanism of action. One approach to achieve the related goals of stratifying patients into response subgroups and identifying the molecular targets of metformin involves the deployment of agnostic genome-wide approaches in cohorts of appropriate size to attain sufficient statistical power...
August 3, 2017: Diabetologia
https://www.readbyqxmd.com/read/28770326/the-effects-of-metformin-on-gut-microbiota-and-the-immune-system-as-research-frontiers
#11
REVIEW
Michael Pollak
Recent studies have revealed that metformin influences gut microbiota and the immune system although neither is a classic target of the drug. This research has revealed complexity not previously appreciated, and opened new research directions. The extent to which immunomodulatory effects and actions on the microbiota are related to each other and account for effects on host energy metabolism remains to be determined. These sites of action may be relevant not only to the efficacy of metformin for its established use in type 2 diabetes, but also to proposed novel indications in oncology and other diseases...
August 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/28766170/aegle-marmelos-differentially-affects-hepatic-markers-of-glycolysis-insulin-signalling-pathway-hypoxia-and-inflammation-in-hepg2-cells-grown-in-fructose-versus-glucose-rich-environment
#12
H Aggarwal, J Nair, P Sharma, R Sehgal, U Naeem, P Rajora, R Mathur
Fructose consumption is responsible for the onset of insulin resistance (IR), and metabolic syndrome. It possesses no functional utility in body and its detrimental effects on hepatic metabolic milieu are beyond those produced by glucose. The need of the hour is to identify fructose-induced IR as an unique pathological state to be managed differentially. The effect of aqueous leaf extract of Aegle marmelos (AM) on hepatic markers of insulin resistance using HepG2 cells cultured in either fructose or glucose-rich environment is investigated...
August 1, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28760223/clinical-profile-of-patients-with-type-2-diabetes-mellitus-treated-with-sodium-glucose-cotransporter-2-inhibitors-and-experience-in-real-world-clinical-practice-in-spain
#13
Gabriel Cuatrecasas, Fernando Goñi-Goicoechea
The main aim of the treatment of type 2 diabetes is overall control of cardiovascular risk factors. Almost 50% of patients with type 2 diabetes do not achieve glycaemic targets, and a much higher percentage do not achieve weight and blood pressure targets, despite the therapeutic arsenal that has appeared in the last decade for the treatment of this disease. In addition, antidiabetic secretatogues and insulin are associated with weight gain and an increased risk of hyperglycaemic episodes. Clinical practice guidelines recommend sodium-glucose cotransporter-2 inhibitors (SGLT2i) as an alternative in the same therapeutic step as the other options after initiation of metformin therapy...
November 2016: Medicina Clínica
https://www.readbyqxmd.com/read/28755883/metformin-insights-into-its-anticancer-potential-with-special-reference-to-ampk-dependent-and-independent-pathways
#14
REVIEW
Shoeb Ikhlas, Masood Ahmad
Metformin has been known for its antidiabetic effects for decades and is used as a first line therapy in type 2 diabetes. But recently its anticancer potential has also been discovered. Metformin targets many pathways that play an important role in cancer cell proliferation and angiogenesis, mTORC1 signaling is a crucial pathway among them. Metformin inhibits mTORC1 via AMPK dependent and AMPK independent pathways, thereby inhibiting cancer cell growth and development. Encouraged by positive results of numerous preclinical studies on various types of cancer, many clinical trials are underway to study metformin's effect in chemoprevention and treatment of cancers in humans...
July 26, 2017: Life Sciences
https://www.readbyqxmd.com/read/28754674/adipose-progenitor-cell-secretion-of-gm-csf-and-mmp9-promotes-a-stromal-and-immunological-microenvironment-that-supports-breast-cancer-progression
#15
Francesca Reggiani, Valentina Labanca, Patrizia Mancuso, Cristina Rabascio, Giovanna Talarico, Stefania Orecchioni, Andrea Manconi, Francesco Bertolini
A cell population with progenitor-like phenotype (CD45-CD34+) resident in human white adipose tissue (WAT) is known to promote the progression of local and metastatic breast cancer and angiogenesis. However, the molecular mechanisms of the interaction have not been elucidated. In this study, we identified two proteins that were significantly up-regulated in WAT-derived progenitors after co-culture with breast cancer: granulocyte-macrophage colony-stimulating factor (GM-CSF) and matrix metallopeptidase 9 (MMP9)...
July 28, 2017: Cancer Research
https://www.readbyqxmd.com/read/28751004/polyphenols-activate-energy-sensing-network-in-insulin-resistant-models
#16
Radika Mutlur Krishnamoorthy, Anuradha Carani Venkatraman
Unhealthy diet deficient in fruits and vegetables but rich in calories is considered to be one factor responsible for the increased prevalence of insulin resistance and type 2 diabetes (T2D). The consumption of fast foods and soft drinks increases fructose consumption per se and this is of major concern since prolonged fructose intake induces insulin resistance and thereby T2D. The energy homeostasis is regulated by a network consisting of "fuel gauze" called AMP-activated protein kinase (AMPK), the NAD(+) dependent type III deacetylase (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) which is disrupted in T2D...
July 24, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28750219/continuous-glucose-monitoring-detected-hypoglycaemia-in-the-treating-to-target-in-type-2-diabetes-trial-4-t
#17
J C Levy, M J Davies, R R Holman
AIMS: Hypoglycaemia is a significant risk in insulin treated type 2 diabetes and has been associated with future risk of cardiovascular events. We compared the frequency of low-glucose events using continuous glucose monitoring (CGM) with that of self-reported hypoglycemic events at the end of the first and third years of the Treating to Target in Type 2 Diabetes Trial (4-T), which compared biphasic, prandial and basal insulin regimens added to sulfonylurea and metformin. METHODS: CGM using a Medtronic Gold system was performed in a subgroup of 4-T participants...
March 21, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28747113/developing-a-metformin-prescribing-tool-for-use-in-adults-with-mental-illness-to-reduce-medication-related-weight-gain-and-cardiovascular-risk
#18
Cassie Smith, Hannah Myles, Cherrie Galletly
OBJECTIVES: There is considerable evidence that metformin reduces weight gain associated with antipsychotic medication. The aim of this study was to develop an easy-to-use metformin prescribing tool in order to enable clinicians to prescribe metformin safely and confidently. METHODS: The authors undertook a survey of clinicians and reviewed the published literature and existing guidelines concerning the use of metformin to reduce weight gain in adults with mental illness...
August 2017: Australasian Psychiatry: Bulletin of Royal Australian and New Zealand College of Psychiatrists
https://www.readbyqxmd.com/read/28744157/the-abc7-regimen-a-new-approach-to-metastatic-breast-cancer-using-seven-common-drugs-to-inhibit-epithelial-to-mesenchymal-transition-and-augment-capecitabine-efficacy
#19
Richard E Kast, Nicolas Skuli, Samuel Cos, Georg Karpel-Massler, Yusuke Shiozawa, Ran Goshen, Marc-Eric Halatsch
Breast cancer metastatic to bone has a poor prognosis despite recent advances in our understanding of the biology of both bone and breast cancer. This article presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat aspects of epithelial-to-mesenchymal transition (EMT) that lead to dissemination of breast cancer to bone. As add-on to current standard treatment with capecitabine, ABC7 uses ancillary attributes of seven already-marketed noncancer treatment drugs to stop both the natural EMT process inherent to breast cancer and the added EMT occurring as a response to current treatment modalities...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28742368/borapetoside-e-a-clerodane-diterpenoid-extracted-from-tinospora-crispa-improves-hyperglycemia-and-hyperlipidemia-in-high-fat-diet-induced-type-2-diabetes-mice
#20
Yuhui Xu, Yanfen Niu, Yuan Gao, Fang Wang, Wanying Qin, Yanting Lu, Jing Hu, Li Peng, Jikai Liu, Wenyong Xiong
An insidious increase in the incidence of obesity, insulin resistance, and hyperlipidemia has led to an epidemic of type 2 diabetes worldwide. Tinospora crispa (T. crispa) is a familiar plant traditionally used in herbal medicine for diabetes; however, the major active ingredients of this plant are still unclear. In this study, we identified the therapeutic effects of borapetoside E, a small molecule extracted from T. crispa, in high-fat-diet (HFD)-induced obesity in mice. The therapeutic effects of borapetoside E in HFD-induced obese mice were assessed physiologically, histologically, and biochemically following intraperitoneal injection...
July 25, 2017: Journal of Natural Products
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