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https://www.readbyqxmd.com/read/28107588/mitochondrial-uncoupler-exerts-a-synthetic-lethal-effect-against-%C3%AE-catenin-mutant-tumor-cells
#1
Yuki Shikata, Masaki Kiga, Yushi Futamura, Harumi Aono, Hiroyuki Inoue, Manabu Kawada, Hiroyuki Osada, Masaya Imoto
The wingless/int-1 (Wnt) signal transduction pathway plays a central role in cell proliferation, survival, differentiation and apoptosis. When β-catenin: a component of the Wnt pathway, is mutated into an active form, cell growth signaling is hyperactive and drives oncogenesis. As β-catenin is mutated in a wide variety of tumors, including up to 10% of all sporadic colon carcinomas and 20% of hepatocellular carcinomas, it has been considered a promising target for therapeutic interventions. Therefore, we screened an in-house natural product library for compounds that exhibited synthetic lethality towards β-catenin mutations and isolated nonactin, an antibiotic mitochondrial uncoupler, as a hit compound...
January 20, 2017: Cancer Science
https://www.readbyqxmd.com/read/28107387/neuronal-cell-death-and-degeneration-through-increased-nitroxidative-stress-and-tau-phosphorylation-in-hiv-1-transgenic-rats
#2
Young-Eun Cho, Myoung-Hwa Lee, Byoung-Joon Song
The underlying mechanisms for increased neurodegeneration and neurocognitive deficits in HIV-infected people are unclear. Therefore, this study was aimed to investigate the mechanisms of increased neurodegeneration in 5-month old male HIV-1 Transgenic (Tg) rats compared to the age- and gender-matched wild-type (WT) by evaluating histological changes and biochemical parameters of the key proteins involved in the cell death signaling and apoptosis. Histological and immunohistochemical analyses revealed decreased neuronal cells with elevated astrogliosis in HIV-1 Tg rats compared to WT...
2017: PloS One
https://www.readbyqxmd.com/read/28107044/quercetin-attenuates-cell-survival-inflammation-and-angiogenesis-via-modulation-of-akt-signaling-in-murine-t-cell-lymphoma
#3
Akhilendra Kumar Maurya, Manjula Vinayak
AKT signaling is important to maintaining normal physiology. Hyperactivation of AKT signaling is frequent in cancer, which maintains a high oxidative state in a tumor microenvironment that is needed for tumor adaptation. Therefore, antioxidants are proposed to exhibit anticancer properties by interfering with the tumor microenvironment. Quercetin is an ubiquitous bioactive antioxidant rich in vegetables and beverages. The present study aimed to analyze cancer preventive property of quercetin in ascite cells of Dalton's lymphoma-bearing mice...
January 20, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28106828/bajijiasu-abrogates-osteoclast-differentiation-via-the-suppression-of-rankl-signaling-pathways-through-nf-%C3%AE%C2%BAb-and-nfat
#4
Guoju Hong, Lin Zhou, Xuguang Shi, Wei He, Haibin Wang, Qiushi Wei, Peng Chen, Longkai Qi, Jennifer Tickner, Li Lin, Jiake Xu
Pathological osteolysis is commonly associated with osteoporosis, bone tumors, osteonecrosis, and chronic inflammation. It involves excessive resorption of bone matrix by activated osteoclasts. Suppressing receptor activator of NF-κB ligand (RANKL) signaling pathways has been proposed to be a good target for inhibiting osteoclast differentiation and bone resorption. Bajijiasu-a natural compound derived from Morinda officinalis F. C. How-has previously been shown to have anti-oxidative stress property; however, its effect and molecular mechanism of action on osteoclastogenesis and bone resorption remains unclear...
January 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28105938/the-influence-of-pro-longevity-gene-gclc-overexpression-on-the-age-dependent-changes-in-drosophila-transcriptome-and-biological-functions
#5
Alexey Moskalev, Mikhail Shaposhnikov, Ekaterina Proshkina, Alexey Belyi, Alexander Fedintsev, Svetlana Zhikrivetskaya, Zulfiya Guvatova, Asiya Sadritdinova, Anastasia Snezhkina, George Krasnov, Anna Kudryavtseva
BACKGROUND: Transcriptional changes that contribute to the organism's longevity and prevent the age-dependent decline of biological functions are not well understood. Here, we overexpressed pro-longevity gene encoding glutamate-cysteine ligase catalytic subunit (Gclc) and analyzed age-dependent changes in transcriptome that associated with the longevity, stress resistance, locomotor activity, circadian rhythmicity, and fertility. RESULTS: Here we reproduced the life extension effect of neuronal overexpression of the Gclc gene and investigated its influence on the age-depended dynamics of transcriptome and biological functions such as fecundity, spontaneous locomotor activity and circadian rhythmicity, as well as on the resistance to oxidative, proteotoxic and osmotic stresses...
December 28, 2016: BMC Genomics
https://www.readbyqxmd.com/read/28105937/effect-of-lentivirus-mediated-shrna-inactivation-of-hk1-hk2-and-hk3-genes-in-colorectal-cancer-and-melanoma-cells
#6
Anna V Kudryavtseva, Maria S Fedorova, Alex Zhavoronkov, Alexey A Moskalev, Alexander S Zasedatelev, Alexey A Dmitriev, Asiya F Sadritdinova, Irina Y Karpova, Kirill M Nyushko, Dmitry V Kalinin, Nadezhda N Volchenko, Nataliya V Melnikova, Kseniya M Klimina, Dmitry V Sidorov, Anatoly Y Popov, Tatiana V Nasedkina, Andrey D Kaprin, Boris Y Alekseev, George S Krasnov, Anastasiya V Snezhkina
BACKGROUND: The switch from oxidative phosphorylation to glycolysis in proliferating cancer cells, even under aerobic conditions, has been shown first in 1926 by Otto Warburg. Today this phenomenon is known as the "Warburg effect" and recognized as a hallmark of cancer. The metabolic shift to glycolysis is associated with the alterations in signaling pathways involved in energy metabolism, including glucose uptake and fermentation, and regulation of mitochondrial functions. Hexokinases (HKs), which catalyze the first step of glycolysis, have been identified to play a role in tumorigenesis of human colorectal cancer (CRC) and melanoma...
December 22, 2016: BMC Genetics
https://www.readbyqxmd.com/read/28105812/copper-catalyzed-cascade-phosphorylation-initiated-radical-cyclization-access-to-2-phosphorylated-pyrrolo-1-2-a-indole
#7
Honglin Zhang, Weipeng Li, Chengjian Zhu
A copper-catalyzed tandem radical cyclization of 1-(3-phenylprop-2-yn-1-yl)-1H-indole with diphenylphosphine oxides was developed. C-P bond formation was achieved coupled with C(sp2)-H functionalization. It provided an access to construct the pyrrolo[1,2-a]indole motif and a series of 2-phosphinoyl-9H-pyrrolo[1,2-a]indoles.
January 20, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28105746/mitochondrial-energetics-and-calcium-coupling-in-the-heart
#8
Michael Kohlhaas, Alexander G Nickel, Christoph Maack
Contraction and relaxation of the heart consume large amounts of energy that need to be replenished by oxidative phosphorylation in mitochondria, and matching energy supply to demand involves the complimentary control of respiration through ADP and Ca(2+) . In heart failure, an imbalance between ADP and Ca(2+) oxidizes mitochondrial pyridine nucleotides, where NADH oxidation may limit ATP production and contractile function, while NADPH oxidation can induce oxidative stress with consecutive maladaptive remodeling...
January 19, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28105734/calcium-calmodulin-dependent-protein-kinase-mediates-the-intracellular-signaling-pathways-of-cardiac-apoptosis-in-mice-with-impaired-glucose-tolerance
#9
Marilen Federico, Enrique L Portiansky, Leandro Sommese, Francisco J Alvarado, Paula G Blanco, Carolina N Zanuzzi, John Dedman, Marcia Kaetzel, Xander H T Wehrens, Alicia Mattiazzi, Julieta Palomeque
Background The impact of cardiac apoptosis in pre-diabetic stages of diabetic cardiomyopathy is unknown. We described that myocytes from fructose-rich diet (FRD) animals exhibit arrhythmias produced by exacerbated Ca(2+) /calmodulin-protein kinase (CaMKII) activity, ryanodine receptors (RyR2) phosphorylation and sarcoplasmic reticulum (SR) Ca(2+) leak. We tested the hypothesis that this mechanism also underlies cardiac apoptosis in pre-diabetes. Methods and Results We generated a pre-diabetic model in mice fed with FRD...
January 20, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28104913/exosome-derived-micrornas-in-cancer-metabolism-possible-implications-in-cancer-diagnostics-and-therapy
#10
REVIEW
Marco Tomasetti, Wan Lee, Lory Santarelli, Jiri Neuzil
Malignant progression is greatly affected by dynamic cross-talk between stromal and cancer cells. Exosomes are secreted nanovesicles that have key roles in cell-cell communication by transferring nucleic acids and proteins to target cells and tissues. Recently, MicroRNAs (miRs) and their delivery in exosomes have been implicated in physiological and pathological processes. Tumor-delivered miRs, interacting with stromal cells in the tumor microenvironment, modulate tumor progression, angiogenesis, metastasis and immune escape...
January 20, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28104670/mutants-for-drosophila-isocitrate-dehydrogenase-3b-are-defective-in-mitochondrial-function-and-larval-cell-death
#11
Dianne M Duncan, Paula Kiefel, Ian Duncan
The death of larval salivary gland cells during metamorphosis in Drosophila melanogaster has been a key system for studying steroid controlled programmed cell death. This death is induced by a pulse of the steroid hormone ecdysone that takes place at the end of the prepupal period. For many years, it has been thought that the ecdysone direct response gene Eip93F (E93) plays a critical role in initiating salivary gland cell death. This conclusion was based largely on the finding that the three "type" alleles of E93 cause a near-complete block in salivary gland cell death...
January 18, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28102119/glutathione-and-glutathione-transferase-omega-1-as-key-posttranslational-regulators-in-macrophages
#12
Mark M Hughes, Anne F McGettrick, Luke A J O'Neill
Macrophage activation during phagocytosis or by pattern recognition receptors, such as Toll-like receptor 4, leads to the accumulation of reactive oxygen species (ROS). ROS act as a microbicidal defense mechanism, promoting clearance of infection, allowing for resolution of inflammation. Overproduction of ROS, however, overwhelms our cellular antioxidant defense system, promoting oxidation of protein machinery, leading to macrophage dysregulation and pathophysiology of chronic inflammatory conditions, such as atherosclerosis...
January 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28101183/protective-effect-of-berberine-against-oxidative-stress-induced-apoptosis-in-rat-bone-marrow-derived-mesenchymal-stem-cells
#13
Wangyang Li, Yamei Liu, Bin Wang, Yiwen Luo, Nianhong Hu, Dongfeng Chen, Xunchao Zhang, Yunpu Xiong
Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential to be used for the treatment of delayed union, nonunion or persistent bone defects in MSC-based cell therapy. However, implantation of BMSCs into the fracture site is confronted with apoptosis on account of harsh conditions and oxidative stress. In the present study, the anti-apoptotic effects of berberine (BBR) on BMSCs subjected to hydrogen peroxide (H2O2) are investigated, and the potential underlying mechanisms are explored. Oxidative injury was induced by exposure to H2O2, and cell viability was assessed using a cell counting kit-8 assay...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28100784/mitochondrial-o-glcnac-transferase-mogt-regulates-mitochondrial-structure-function-and-survival-in-hela-cells
#14
Juliana L Sacoman, Raul Y Dagda, Amanda R Burnham-Marusich, Ruben K Dagda, Patricia M Berninsone
O-linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAcylation of target proteins and regulates numerous biological processes. OGT is encoded by a single gene that yields nucleocytosolic and mitochondrial isoforms. To date, the role of the mitochondrial isoform of OGT (mOGT) remains largely unknown. Using high-throughput proteomics, we identified 84 candidate mitochondrial glycoproteins, of which 44 are novel. Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH: ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100284/role-of-flavonoids-and-nitrates-in-cardiovascular-health
#15
Julie A Lovegrove, Alex Stainer, Ditte A Hobbs
CVD remain the leading cause of death globally. Effective dietary strategies for their reduction are of high priority. Increasing evidence suggests that phytochemicals, particularly dietary flavonoids and nitrates, are key modulators of CVD risk reduction through impact on multiple risk factors. The aim of this review is to explore the evidence for the impact of flavonoid- and nitrate-rich foods and supplements on CVD risk, with specific reference to their importance as mediators of vascular health and platelet function...
January 19, 2017: Proceedings of the Nutrition Society
https://www.readbyqxmd.com/read/28099881/mesencephalic-astrocyte-derived-neurotrophic-factor-alleviated-6-ohda-induced-cell-damage-via-ros-ampk-mtor-mediated-autophagic-inhibition
#16
Jingxing Zhang, Qiong Cai, Ming Jiang, Yigang Liu, Hua Gu, Jia Guo, Hui Sun, Jianmin Fang, Lingjing Jin
Autophagy and apoptosis are commonly involved in the dopaminergic neuron damage in the pathogenesis of Parkinson's disease. Recently, the autophagy pathway is thought to be critical to the process of PD. Therefore, the regulation of autophagy may be a potential strategy for PD treatment. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been reported to have neuroprotective effects through anti-apoptosis, anti-oxidative, and anti-inflammatory mechanisms in PD. In this study, we investigated the role of autophagy system in MANF-mediated neuroprotection against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity...
January 15, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28099512/age-dependent-oxidative-dna-damage-does-not-correlate-with-reduced-proliferation-of-cardiomyocytes-in-humans
#17
Yanhui Huang, Haifa Hong, Minghui Li, Jinfen Liu, Chuan Jiang, Haibo Zhang, Lincai Ye, Jinghao Zheng
BACKGROUND: Postnatal human cardiomyocyte proliferation declines rapidly with age, which has been suggested to be correlated with increases in oxidative DNA damage in mice and plays an important role in regulating cardiomyocyte proliferation. However, the relationship between oxidative DNA damage and age in humans is unclear. METHODS: Sixty right ventricular outflow myocardial tissue specimens were obtained from ventricular septal defect infant patients during routine congenital cardiac surgery...
2017: PloS One
https://www.readbyqxmd.com/read/28099346/liuwei-dihuang-pill-treats-diabetic-nephropathy-in-rats-by-inhibiting-of-tgf-%C3%AE-smads-mapk-and-nf-kb-and-upregulating-expression-of-cytoglobin-in-renal-tissues
#18
Zhong Ju Xu, Shi Shu, Zhi Jie Li, Yu Min Liu, Rui Yi Zhang, Yue Zhang
Liuwei Dihuang pill (LDP) was assessed for its effects on renal deficiency.90 STZ induced DN rats were divided into groups (n = 22) without treatment (STZ) and LDP treated (STZ-L) (n = 23), Zhenwu decoction treated (STZ-Z) (n = 22), and valsartan treated (STZ-V) (n = 23) groups, with 16 normal control rats. Total urine protein (TP), blood urea nitrogen (BUN), and serum creatinine (Cr) were measured. Superoxide dismutase (SOD), nitric oxide synthase (NOS), and malondialdehyde (MDA) concentrations as well as expression/phosphorylation of SMAD3, SMAD2, and α-SMA, TGF-β, RI /II, P38, ERK, and NF-kB in renal tissues were determined...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28099079/lymphangioleiomyomatosis-a-monogenic-model-of-malignancy
#19
Vera P Krymskaya, Francis X McCormack
Lymphangioleiomyomatosis (LAM) is a rare, low-grade, metastasizing neoplasm that arises from an unknown source, spreads via the lymphatics, and targets the lungs. All pulmonary structures become infiltrated with benign-appearing spindle and epithelioid cells (LAM cells) that express smooth-muscle and melanocyte-lineage markers, harbor mTOR-activating mutations in tuberous sclerosis complex (TSC) genes, and recruit abundant stromal cells. Elaboration of lymphangiogenic growth factors and matrix remodeling enzymes by LAM cells enables their access to lymphatic channels and likely drives the cystic lung remodeling that often culminates in respiratory failure...
January 14, 2017: Annual Review of Medicine
https://www.readbyqxmd.com/read/28098893/systematic-analysis-of-microarray-datasets-to-identify-parkinson-s-disease%C3%A2-associated-pathways-and-genes
#20
Yinling Feng, Xuefeng Wang
In order to investigate commonly disturbed genes and pathways in various brain regions of patients with Parkinson's disease (PD), microarray datasets from previous studies were collected and systematically analyzed. Different normalization methods were applied to microarray datasets from different platforms. A strategy combining gene co‑expression networks and clinical information was adopted, using weighted gene co‑expression network analysis (WGCNA) to screen for commonly disturbed genes in different brain regions of patients with PD...
January 16, 2017: Molecular Medicine Reports
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