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metabolic models

Claudio Luparello, Dalia Maria Lucia Asaro, Ilenia Cruciata, Storm Hassell-Hart, Supojjanee Sansook, John Spencer, Fabio Caradonna
We examined the effects of the ferrocene-based histone deacetylase-3 inhibitor Pojamide ( N ¹-(2-aminophenyl)- N ⁸-ferrocenyloctanediamide) and its two derivatives N ¹-(2-aminophenyl)- N ⁶-ferrocenyladipamide and N ¹-(2-aminophenyl)- N ⁸-ferroceniumoctanediamide tetrafluoroborate on triple-negative MDA-MB-231 breast cancer cells. Viability/growth assays indicated that only the first two compounds at 70 μM concentration caused an approximate halving of cell number after 24 h of exposure, whereas the tetrafluoroborate derivative exerted no effect on cell survival nor proliferation...
February 13, 2019: International Journal of Molecular Sciences
Anuri Shah, Pei Han, Mung-Yee Wong, Raymond Chuen-Chung Chang, Cristina Legido-Quigley
INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disorder, without any widely available curative therapy. Metabolomics is a powerful tool which can be used to identify unexpected pathway-related disease progression and pathophysiological mechanisms. In this study, metabolomics in brain, plasma and liver was investigated in an experimental PD model, to discover small molecules that are associated with dopaminergic cell loss. METHODS: Sprague Dawley (SD) rats were injected unilaterally with 6-hydroxydopamine (6-OHDA) or saline for the vehicle control group into the medial forebrain bundle (MFB) to induce loss of dopaminergic neurons in the substantia nigra pars compacta...
February 13, 2019: Metabolites
Janina Rynarzewski, Lisa Dicks, Benno F Zimmermann, Birgit Stoffel-Wagner, Norbert Ludwig, Hans-Peter Helfrich, Sabine Ellinger
Randomized controlled trials indicate that flavanol-rich cocoa intake may improve postprandial glucose and lipid metabolism in patients with type 2 diabetes (T2D), based on studies with meals that impose a strong metabolic load. Hence, the aim of the present study was to investigate whether flavanol-rich cocoa powder ingested as part of a diabetic-suitable meal may beneficially affect glucose, lipid metabolism, and blood pressure (BP) in patients with T2D. Twelve adults with T2D, overweight/obesity, and hypertension ingested capsules with 2...
February 16, 2019: Nutrients
Francesca Chiarini, Camilla Evangelisti, Vittoria Cenni, Antonietta Fazio, Francesca Paganelli, Alberto M Martelli, Giovanna Lattanzi
The mechanistic target of rapamycin (mTOR) is a ubiquitous serine/threonine kinase that regulates anabolic and catabolic processes, in response to environmental inputs. The existence of mTOR in numerous cell compartments explains its specific ability to sense stress, execute growth signals, and regulate autophagy. mTOR signaling deregulation is closely related to aging and age-related disorders, among which progeroid laminopathies represent genetically characterized clinical entities with well-defined phenotypes...
February 15, 2019: International Journal of Molecular Sciences
Catarina Roma-Rodrigues, Rita Mendes, Pedro V Baptista, Alexandra R Fernandes
Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect). These events create hypoxia, oxidative stress and acidosis within the TME triggering an adjustment of the extracellular matrix (ECM), a response from neighbor stromal cells (e...
February 15, 2019: International Journal of Molecular Sciences
Ogunleye Adewale Joseph, Kikiowo Babatomiwa, Adelakun Niyi, Omotuyi Olaposi, Inyang Olumide
BACKGROUND: BACE-1 is an aspartate protease that is responsible for the proteolysis of amyloid precursor proteins (APP) into beta-amyloid (Aβ), a neurotoxic peptide in patients with Alzheimer's disease (AD). As such, BACE-1 is a prime pharmacological target in the control of Aβ in the brain and its inhibition will be a sound approach in AD therapy. METHODS: The computational pipeline which comprised molecular docking (MD), Quantitative Structure Activity Relationship (QSAR) modelling and Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) studies enabled the prediction of molecular interaction and relative inhibitory potentials of the hit compound...
February 19, 2019: Drug Research
Liwen Zhang, Shulan Su, Yue Zhu, Jianming Guo, Sheng Guo, Dawei Qian, Zhen Ouyang, Jin-Ao Duan
Mulberry leaf is one of the commonly used traditional Chinese medicines, has been shown to exert hypoglycemic effects against diabetes. The aim of this study is to investigate the effects and mechanism of mulberry leaf flavonoids (MF), polysaccharides (MP) and alkaloids (MA) on diabetic and its liver and kidney injury. The db/db mice was adopted and the results showed that the FBG (fasting blood glucose) of model group continued to increase and associated liver and kidney injury. After the intervention of MP and MA, the value of FBG exhibited the most obvious hypoglycemic effect...
February 16, 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ying Lian, Qun Yuan, Gangpu Wang, Fang Tang
Sleep quality has been suggested to play an important role in development of metabolic syndrome (MetS). However, the results have been inconsistent. A systematic review of observational studies aimed to evaluate the association between sleep quality and MetS. A comprehensive search was conducted in PubMed and EMBASE. The pooled odd ratios (ORs) were calculated using random effects models. The construction of funnel plot was used to explore publication bias, with further application of Egger's test. 22 studies were included...
February 1, 2019: Psychiatry Research
Liuying Song, Dunjie Li, Xiangyunong Cao, Yu Tang, Rutao Liu, Qigui Niu, Yu-You Li
Optimization of mesophilic methane production from Chicken manure (CM) and Sheep manure (SM) at total solid (TS) of 8% and 1.6% were obtained by sequence tests in mono-digestion. However, the positive synergy of co-digestion with an optimum CM/SM of 2.5 (310 mLCH4 /gVSadded ) resulted in a high hydrolytic capacity and methane production. The modified Gompertz model (R2  > 0.98) and modified Aiba model (R2  > 0.88) illustrated co-digestion significantly improved the methane generation rate with strong ammonia tolerance...
February 16, 2019: Journal of Environmental Management
Yeongkag Kwon, Ok-Jin Park, Jiseon Kim, Jae Ho Cho, Cheol-Heui Yun, Seung Hyun Han
Cyclic dinucleotides (CDNs) such as cyclic diadenylate monophosphate and cyclic diguanylate monophosphate are commensal bacteria-derived second messengers in the gut that modulate bacterial survival, colonization, and biofilm formation. Recently, CDNs have been discovered to have an immunomodulatory activity by inducing the expression of type I interferon (IFN) through STING signaling pathway in macrophages. Since CDNs are possibly absorbed and delivered into the bone marrow, where bone-resorbing osteoclasts are derived from monocyte/macrophage lineages, CDNs could affect bone metabolism by regulating osteoclast differentiation...
February 19, 2019: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Meng Wu, Lingwei Ma, Liru Xue, Wenlei Ye, Zhiyong Lu, Xiang Li, Yan Jin, Xian Qin, Dan Chen, Weicheng Tang, Yingying Chen, Zixin Hong, Jinjin Zhang, Aiyue Luo, Shixuan Wang
Chemotherapy-induced ovarian aging not only increases the risk for early menopause-related complications but also results in infertility in young female cancer survivors. Oogonial stem cells have the ability to generate new oocytes and thus provide new opportunities for treating ovarian aging and female infertility. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural phenol derived from plants, that has been shown to have positive effects on longevity and redox flow in lipid metabolism and a preventive function against certain tumors...
February 14, 2019: Aging
Xu Wang, Yuna Zeng, Li Sheng, Peter Larson, Xue Liu, Xiaowen Zou, Shufang Wang, Kaijing Guo, Chen Ma, Gang Zhang, Huaqing Cui, David M Ferguson, Yan Li, Jing-Ren Zhang, Courtney C Aldrich
Optochin, a cinchona alkaloid derivative discovered over 100 years ago, possesses highly selective antibacterial activity towards Streptococcus pneumoniae. Pneumococcal disease remains the leading source of bacterial pneumonia and meningitis worldwide. The structure activity relationships of optochin were examined through modification to both the quinoline and quinuclidine subunits, which led to the identification of analogue 48 with substantially improved activity. Resistance and molecular modeling studies indicate 48 likely binds to the c-ring of ATP synthase near the conserved glutamate 52 ion binding site while mechanistic studies demonstrated 48 causes cytoplasmic acidification...
February 19, 2019: Journal of Medicinal Chemistry
Hui Li, Zhengyu Zhang, Xiaojing Yang, Xu Mao, Ying Wang, Jian Wang, Ying Peng, Jiang Zheng
Nitrofurantoin (NFT) is a widely used antimicrobial agent in the treatment of specific urinary tract infections (UTIs). Many adverse effects associated with NFT use have been reported, including hepatotoxicity. A structure-toxicity relationship study was performed to gain the insight into the mechanisms of toxic action of NFT. The toxic effects of NFT and its nine analogues or constituent moieties (1-9) designed and synthesized by structural manipulation of NFT were evaluated in rat liver microsomes and primary rat hepatocytes...
February 19, 2019: Chemical Research in Toxicology
Bethany R Mordhorst, Joshua A Benne, Raissa F Cecil, Kristin M Whitworth, Melissa S Samuel, Lee D Spate, Clifton N Murphy, Kevin D Wells, Jonathan A Green, Randall S Prather
Genetically engineered pigs serve as excellent biomedical and agricultural models. To date, the most reliable way to generate genetically engineered pigs is via somatic cell nuclear transfer (SCNT), however, the efficiency of cloning in pigs is low (1-3%). Somatic cells such as fibroblasts frequently used in nuclear transfer utilize the tricarboxylic acid cycle and mitochondrial oxidative phosphorylation for efficient energy production. The metabolism of somatic cells contrasts with cells within the early embryo, which predominately use glycolysis...
February 19, 2019: Molecular Reproduction and Development
Elias Björnson, Chris J Packard, Martin Adiels, Linda Andersson, Niina Matikainen, Sanni Söderlund, Juhani Kahri, Carina Sihlbom, Annika Thorsell, Haihong Zhou, Marja-Riitta Taskinen, Jan Borén
BACKGROUND: Triglyceride-rich lipoproteins and their remnants have emerged as major risk-factors for cardiovascular disease. New experimental approaches are required that permit simultaneous investigation of the dynamics of chylomicrons (CM) and apoB48 metabolism and of apoB100 in very low density lipoproteins (VLDL). METHODS: Mass spectrometric techniques were used to determine the masses and tracer enrichments of apoB48 in the CM, VLDL1 and VLDL2 density intervals...
February 18, 2019: Journal of Internal Medicine
Jiaqi Huang, Alison M Mondul, Stephanie J Weinstein, Andriy Derkach, Steven C Moore, Joshua N Sampson, Demetrius Albanes
Impaired metabolism may play an important role in the pathogenesis of lethal prostate cancer, yet there is a paucity of evidence regarding the association. We conducted a large prospective serum metabolomic analysis of lethal prostate cancer in 523 cases and 523 matched controls nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Median time from baseline fasting serum collection to prostate cancer death was 18 years (maximum 30 years). We identified 860 known biochemicals through an ultrahigh-performance LC-MS/MS platform...
February 18, 2019: International Journal of Cancer. Journal International du Cancer
Mai Kim, Tetsuya Higuchi, Takahito Nakajima, Putri Andriana, Hiromi Hirasawa, Azusa Tokue, Jun Kurihara, Satoshi Yokoo, Yoshito Tsushima
OBJECTIVES: L-3-[18 F]-Fluoro-α-methyl tyrosine (FAMT), an amino acid positron emission tomography (PET) tracer, complements [18 F]-fluorodeoxyglucose (FDG) in the diagnosis of malignancies. We compared the predictive ability of FAMT PET versus FDG PET regarding metastatic oral squamous cell carcinoma (OSCC) outcomes for distant metastasis, including lymph node metastasis, and identified the relevant metabolic parameters for each. METHODS: We enrolled 160 patients with OSCC who underwent PET/computed tomography using FDG and FAMT before treatment...
February 18, 2019: Oral Radiology
Sanhita Sinharay, Dima A Hammoud
PURPOSE OF REVIEW: The purpose of this review is to summarize recent developments in PET imaging of neuropathologies underlying HIV-associated neurocognitive dysfunction (HAND). We concentrate on the recent post antiretroviral era (ART), highlighting clinical and preclinical brain PET imaging studies. RECENT FINDINGS: In the post ART era, PET imaging has been used to better understand perturbations of glucose metabolism, neuroinflammation, the function of neurotransmitter systems, and amyloid/tau protein deposition in the brains of HIV-infected patients and HIV animal models...
February 18, 2019: Current HIV/AIDS Reports
J Wang, D Yan, A Zhao, X Hou, X Zheng, P Chen, Y Bao, W Jia, C Hu, Z-L Zhang, W Jia
Our study focused on the associations of metabolites with BMD and osteoporosis, finding that several metabolites are associated with BMD, and metabolites combined with bone turnover markers tend to be more sensitive in distinguishing osteoporosis in both males and postmenopausal females, which might be meaningful for the early diagnosis of osteoporosis. INTRODUCTION: Our study aimed to evaluate the association of metabolites with bone, trying to find new metabolic markers that are distinguishing for low bone mineral density (BMD)...
February 18, 2019: Osteoporosis International
Xiaomei Teng, Chen Ji, Huiting Zhong, Dong Zheng, Rui Ni, David J Hill, Sidong Xiong, Guo-Chang Fan, Peter A Greer, Zhenya Shen, Tianqing Peng
AIMS/HYPOTHESIS: The role of non-cardiomyocytes in diabetic cardiomyopathy has not been fully addressed. This study investigated whether endothelial cell calpain plays a role in myocardial endothelial injury and microvascular rarefaction in diabetes, thereby contributing to diabetic cardiomyopathy. METHODS: Endothelial cell-specific Capns1-knockout (KO) mice were generated. Conditions mimicking prediabetes and type 1 and type 2 diabetes were induced in these KO mice and their wild-type littermates...
February 18, 2019: Diabetologia
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