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Metabolic modulation

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https://www.readbyqxmd.com/read/28454423/the-nutritional-herb-epimedium-grandiflorum-inhibits-the-growth-in-a-model-for-the-luminal-a-molecular-subtype-of-breast-cancer
#1
Nitin T Telang, Gou Li, Meena Katdare, Daniel W Sepkovic, H Leon Bradlow, George Y C Wong
The Luminal A subtype of breast cancer expresses the estrogen receptor (ER)-α and progesterone receptor (PR), but not the human epidermal growth factor receptor (HER)-2 oncogene. This subtype of breast cancer responds to endocrine therapy involving the use of selective estrogen receptor modulators and/or inhibitors of estrogen biosynthesis. However, these therapeutic agents are frequently associated with long-term systemic toxicity and acquired tumor resistance, emphasizing the need to identify non-toxic alternative treatments for chemo-endocrine therapy responsive breast cancer...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454210/statins-and-pancreatic-cancer
#2
Jun Gong, Esha Sachdev, Lori A Robbins, Emily Lin, Andrew E Hendifar, Monica M Mita
Pancreatic cancer remains among the most lethal cancers, despite ongoing advances in treatment for all stages of the disease. Disease prevention represents another opportunity to improve patient outcome, with metabolic syndrome and its components, such as diabetes, obesity and dyslipidemia, having been recognized as modifiable risk factors for pancreatic cancer. In addition, statins have been shown to potentially reduce pancreatic cancer risk and to improve survival in patients with a combination of metabolic syndrome and pancreatic cancer...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453831/sortilin-1-loss-of-function-protects-against-cholestatic-liver-injury-by-attenuating-hepatic-bile-acid-accumulation-in-bile-duct-ligated-mice
#3
Jibiao Li, Benjamin L Woolbright, Wen Zhao, Yifeng Wang, David Matye, Bruno Hagenbuch, Hartmut Jaeschke, Tiangang Li
Sortilin 1 (Sort1) is an intracellular trafficking receptor that mediates protein sorting in the endocytic or secretory pathways. Recent studies revealed a role of Sort1 in the regulation of cholesterol and bile acid metabolism. This study further investigated the role of Sort1 in modulating bile acid detoxification and cholestatic liver injury in bile duct ligated mice. We found that Sort1 KO mice had attenuated liver injury 24 h after BDL, which was mainly attributed to less bile infarct formation. Sham-operated Sort1 KO mice had about 20% larger bile acid pool size than sham-operated WT mice, but 24 h after BDL Sort1 KO mice had significantly attenuated hepatic bile acid accumulation and smaller bile acid pool size...
April 26, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28453493/s-adenosylmethionine-attenuates-oxidative-stress-and-neuroinflammation-induced-by-amyloid-%C3%AE-through-modulation-of-glutathione-metabolism
#4
Qian Li, Jing Cui, Chen Fang, Min Liu, Guowen Min, Liang Li
Oxidative stress and neuroinflammation are mainly involved in the pathogenic mechanisms of Alzheimer's disease (AD). Amyloid-β (Aβ), the main component of senile plaques, is a kind of strong inducer of oxidative stress. Glutathione is an endogenous antioxidant protecting cells from oxidative injury. S-adenosylmethionine (SAM) produced in the methionine cycle is the primary methyl donor and the precursor of glutathione. In this study, the Aβ intrahippocampal injection rat model and cultured SH-SY5Y cells were used to explore the neuroprotective effect of SAM...
April 28, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28449106/microbiomeanalyst-a-web-based-tool-for-comprehensive-statistical-visual-and-meta-analysis-of-microbiome-data
#5
Achal Dhariwal, Jasmine Chong, Salam Habib, Irah L King, Luis B Agellon, Jianguo Xia
The widespread application of next-generation sequencing technologies has revolutionized microbiome research by enabling high-throughput profiling of the genetic contents of microbial communities. How to analyze the resulting large complex datasets remains a key challenge in current microbiome studies. Over the past decade, powerful computational pipelines and robust protocols have been established to enable efficient raw data processing and annotation. The focus has shifted toward downstream statistical analysis and functional interpretation...
April 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28448568/inhibitory-effects-of-fenretinide-metabolites-n-4-methoxyphenyl-retinamide-mpr-and-4-oxo-n-4-hydroxyphenyl-retinamide-3-keto-hpr-on-fenretinide-molecular-targets-%C3%AE-carotene-oxygenase-1-stearoyl-coa-desaturase-1-and-dihydroceramide-%C3%AE-4-desaturase-1
#6
Eugenia Poliakov, William Samuel, Todd Duncan, Danielle B Gutierrez, Nathan L Mata, T Michael Redmond
The therapeutic capacity of fenretinide (N-[4-hydroxyphenyl] retinamide; 4-HPR) has been demonstrated for several conditions, including cancer, obesity, diabetes, and ocular disease. Yet, the mechanisms of action for its pleiotropic effects are still undefined. We hypothesized that investigation of two of the major physiological metabolites of fenretinide, N-[4-methoxyphenyl]retinamide (MPR) and 4-oxo-N-(4-hydroxyphenyl)retinamide (3-keto-HPR), might begin to resolve the multifaceted effects of this synthetic retinoid...
2017: PloS One
https://www.readbyqxmd.com/read/28447868/doxorubicin-loaded-liposomes-enhancing-the-oral-bioavailability-by-modulation-of-physicochemical-characteristics
#7
Marjan Daeihamed, Azadeh Haeri, Seyed Nasser Ostad, Masoud Faghih Akhlaghi, Simin Dadashzadeh
AIM: In this study, the effects of liposome characteristics on oral absorption of doxorubicin, as a hydrophilic low-permeability drug, were investigated. MATERIALS & METHODS: Different doxorubicin-loaded liposomes were prepared, characterized and orally administered to 18 groups of rats. Plasma concentrations of doxorubicin and its aglycone metabolite were measured, and Caco-2 uptake and transport of optimum liposomes were investigated. RESULTS: After studying different factors, a fourfold increase in oral bioavailability was achieved with the non-PEGylated, 120-nm-sized positively charged rigid liposomes (lipid to drug ratio = 10)...
April 27, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28447763/berberine-protects-against-diet-induced-obesity-through-regulating-metabolic-endotoxemia-and-gut-hormone-levels
#8
Jian Hui Xu, Xing Zhen Liu, Wei Pan, Da Jin Zou
Systemic inflammation, which can be induced by metabolic endotoxemia, and corresponding high‑fat diet‑mediated metabolic disorders are associated with gut microbiota. In the present study reverse transcription-polymerase chain reaction, immunofluorescence, pyrosequencing, ELISA and Oil Red O staining were performed to assess whether berberine can protect against diet-induced obesity, through modulating the gut microbiota and consequently improving metabolic endotoxemia and gastrointestinal hormone levels...
March 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28446906/stratified-bacterial-diversity-along-physico-chemical-gradients-in-high-altitude-modern-stromatolites
#9
Diego M Toneatti, Virginia H Albarracín, Maria R Flores, Lubos Polerecky, María E Farías
At an altitude of 3,570 m, the volcanic lake Socompa in the Argentinean Andes is presently the highest site where actively forming stromatolite-like structures have been reported. Interestingly, pigment and microsensor analyses performed through the different layers of the stromatolites (50 mm-deep) showed steep vertical gradients of light and oxygen, hydrogen sulfide and pH in the porewater. Given the relatively good characterization of these physico-chemical gradients, the aim of this follow-up work was to specifically address how the bacterial diversity stratified along the top six layers of the stromatolites which seems the most metabolically important and diversified zone of the whole microbial community...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28446878/computational-model-predicts-the-effects-of-targeting-cellular-metabolism-in-pancreatic-cancer
#10
Mahua Roy, Stacey D Finley
Reprogramming of energy metabolism is a hallmark of cancer that enables the cancer cells to meet the increased energetic requirements due to uncontrolled proliferation. One prominent example is pancreatic ductal adenocarcinoma, an aggressive form of cancer with an overall 5-year survival rate of 5%. The reprogramming mechanism in pancreatic cancer involves deregulated uptake of glucose and glutamine and other opportunistic modes of satisfying energetic demands in a hypoxic and nutrient-poor environment. In the current study, we apply systems biology approaches to enable a better understanding of the dynamics of the distinct metabolic alterations in KRAS-mediated pancreatic cancer, with the goal of impeding early cell proliferation by identifying the optimal metabolic enzymes to target...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28446877/exploring-the-role-of-cyp3a4-mediated-drug-metabolism-in-the-pharmacological-modulation-of-nitric-oxide-production
#11
José Pérez-Del Palacio, Caridad Díaz, Noemí Vergara, Francesca Algieri, Alba Rodríguez-Nogales, Nuria de Pedro, M Elena Rodríguez-Cabezas, Olga Genilloud, Julio Gálvez, Francisca Vicente
Nitric-oxide synthase, the enzyme responsible for mammalian nitric oxide generation, and cytochrome P450, the major enzymes involved in drug metabolism, share striking similarities. Therefore, it makes sense that cytochrome P450 drug mediated biotransformations might play an important role in the pharmacological modulation of nitric oxide synthase. In this work, we have undertaken an integrated in vitro assessment of the hepatic metabolism and nitric oxide modulation of previously described dual inhibitors (imidazoles and macrolides) of these enzymes in order assess the implication of CYP450 activities over production of nitric oxide...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28446774/liver-er%C3%AE-regulates-agrp-neuronal-activity-in-the-arcuate-nucleus-of-female-mice
#12
Valeria Benedusi, Sara Della Torre, Nico Mitro, Donatella Caruso, Alessandra Oberto, Claire Tronel, Clara Meda, Adriana Maggi
Recent work revealed the major role played by liver Estrogen Receptor α (ERα) in the regulation of metabolic and reproductive functions. By using mutant mice with liver-specific ablation of Erα, we here demonstrate that the hepatic ERα is essential for the modulation of the activity of Agouti Related Protein (AgRP) neurons in relation to the reproductive cycle and diet. Our results suggest that the alterations of hepatic lipid metabolism due to the lack of liver ERα activity are responsible for a neuroinflammatory status that induces refractoriness of AgRP neurons to reproductive and dietary stimuli...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28446761/metabolic-syndrome-modulates-association-between-endothelial-lipase-and-lipid-lipoprotein-plasma-levels-in-acute-heart-failure-patients
#13
Ines Potočnjak, Matias Trbušić, Sanda Dokoza Terešak, Bojana Radulović, Gudrun Pregartner, Andrea Berghold, Beate Tiran, Gunther Marsche, Vesna Degoricija, Saša Frank
We hypothesised that the established association of endothelial lipase (EL) plasma levels with atherogenic lipid profile is altered in acute heart failure (AHF) and additionally affected by overlapping metabolic syndrome (MetS). We examined the association of EL plasma levels and lipid/lipoprotein plasma levels in AHF patients without and with overlapping MetS. The study was performed as a single-centre, observational study on 152 AHF patients, out of which 85 had overlapping MetS. In the no-MetS group, EL plasma levels were significantly positively correlated with plasma levels of atherogenic lipids/lipoproteins, including total cholesterol, low-density lipoprotein (LDL)-cholesterol, total LDL particles and triglycerides, but also with plasma levels of antiatherogenic high-density lipoprotein (HDL)-cholesterol, total HDL particles and small HDL particles...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28446382/compensatory-mechanisms-activated-with-intermittent-energy-restriction-a-randomized-control-trial
#14
Sílvia Ribeiro Coutinho, Eline Holli Halset, Sigrid Gåsbakk, Jens F Rehfeld, Bård Kulseng, Helen Truby, Cátia Martins
BACKGROUND & AIMS: Strong compensatory responses, with reduced resting metabolic rate (RMR), increased exercise efficiency (ExEff) and appetite, are activated when weight loss (WL) is achieved with continuous energy restriction (CER), which try to restore energy balance. Intermittent energy restriction (IER), where short spells of energy restriction are interspaced by periods of habitual energy intake, may offer some protection in minimizing those responses. We aimed to compare the effect of IER versus CER on body composition and the compensatory responses induced by WL...
April 7, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28446202/analyzing-the-genes-related-to-alzheimer-s-disease-via-a-network-and-pathway-based-approach
#15
Yan-Shi Hu, Juncai Xin, Ying Hu, Lei Zhang, Ju Wang
BACKGROUND: Our understanding of the molecular mechanisms underlying Alzheimer's disease (AD) remains incomplete. Previous studies have revealed that genetic factors provide a significant contribution to the pathogenesis and development of AD. In the past years, numerous genes implicated in this disease have been identified via genetic association studies on candidate genes or at the genome-wide level. However, in many cases, the roles of these genes and their interactions in AD are still unclear...
April 27, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28445900/central-and-peripheral-glucagon-reduces-hyperlipidemia-in-rats-and-hamsters
#16
Vishal Patel, Amit Joharapurkar, Samadhan Kshirsagar, Hiren M Patel, Dheerendra Pandey, Dipam Patel, Kiran Shah, Rajesh Bahekar, Gaurang B Shah, Mukul R Jain
Increased lipid levels in blood contribute to increasing the risk of diabetic complications. Glucagon exerts lipid lowering effects in diabetic state. However, the mechanism behind the lipid reduction by glucagon independent of glucose homeostasis is not well understood. We assessed the actions of glucagon on lipid modulation in blood and markers in liver in hyperlipidemic hamsters and rats. Male Sprague Dawley rats and Golden Syrian hamsters on a hyperlipidemic diet for 2 weeks were administered a single dose of glucagon by subcutaneous (SC, 150 and 300 µg/kg) or intracerebroventricular (ICV, 15 and 30 µg/animal) route...
April 26, 2017: Drug Research
https://www.readbyqxmd.com/read/28445853/cannabidiol-%C3%AE-9-tetrahydrocannabinol-interactions-on-acute-pain-and-locomotor-activity
#17
Stevie C Britch, Jenny L Wiley, Zhihao Yu, Brian H Clowers, Rebecca M Craft
BACKGROUND: Previous studies suggest that cannabidiol (CBD) may potentiate or antagonize Δ(9)-tetrahydrocannabinol's (THC) effects. The current study examined sex differences in CBD modulation of THC-induced antinociception, hypolocomotion, and metabolism. METHODS: In Experiment 1, CBD (0, 10 or 30mg/kg) was administered 15min before THC (0, 1.8, 3.2, 5.6 or 10mg/kg), and rats were tested for antinociception and locomotion 15-360min post-THC injection. In Experiments 2 and 3, CBD (30mg/kg) was administered 13h or 15min before THC (1...
April 15, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28445510/whole-genome-re-sequencing-to-identify-suppressor-mutations-of-mutant-and-foreign-escherichia-coli-ftsz
#18
Kiani A J Arkus Gardner, Masaki Osawa, Harold P Erickson
FtsZ is an essential protein for bacterial cell division, where it forms the cytoskeletal scaffold and may generate the constriction force. We have found previously that some mutant and foreign FtsZ that do not complement an ftsZ null can function for cell division in E. coli upon acquisition of a suppressor mutation somewhere in the genome. We have now identified, via whole genome re-sequencing, single nucleotide polymorphisms in 11 different suppressor strains. Most of the mutations are in genes of various metabolic pathways, which may modulate cell division indirectly...
2017: PloS One
https://www.readbyqxmd.com/read/28445429/exploring-the-behavioral-and-metabolic-phenotype-generated-by-re-introduction-of-the-ghrelin-receptor-in-the-ventral-tegmental-area
#19
Louise J Skov, Morten Jensen, Søren H Christiansen, Cecilia Ratner, David P D Woldbye, Birgitte Holst
Ghrelin receptor (Ghr-R) signaling in neurons of the ventral tegmental area (VTA) can modulate dopaminergic function and the reward-related effects of both palatable foods and drugs of abuse. In this study, we re-introduced the Ghr-R in VTA neurons in Ghr-R knockout mice (Ghr-R(VTA) mice) to specifically study the importance of the constitutively active Ghr-R for VTA neuronal signaling. Our results showed that re-introduction of the Ghr-R in the VTA had no impact on body weight or food intake under basal conditions...
April 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28445176/novel-lipid-modifying-drugs-to-lower-ldl-cholesterol
#20
Arjen J Cupido, Laurens F Reeskamp, John J P Kastelein
PURPOSE OF REVIEW: Statins have long been the cornerstone for the prevention of cardiovascular disease (CVD). However, because of perceived adverse effects and insufficient efficacy in certain groups of patients, considerable interest exists in the search for alternatives to lower LDL-cholesterol (LDL-C), and the recent approvals of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors underlines the success of this quest. Here, we give an updated overview on the most recent developments in the area of LDL-C lowering agents...
April 25, 2017: Current Opinion in Lipidology
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