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Jasmine Lee-Barber, Taylor E English, Jacquelyn F Britton, Nara Sobreira, Jason Goldstein, David Valle, Hans Tomas Bjornsson
Transaldolase deficiency (MIM#: 606003) is a rare autosomal recessive defect in the pentose phosphate pathway. Affected individuals are at risk for progressive liver failure and hepatocarcinoma. In the transaldolase-deficient mouse model (Taldo1 -/- ), these hepatic complications are accentuated by oxidative stress related to acetaminophen administration. We report a 13-month-old transaldolase-deficient male who developed mild liver failure after receiving standard doses of acetaminophen during a febrile respiratory syncytial virus infection...
June 20, 2018: JIMD Reports
Abdolreza Hassanzade, Ali Mandegary, Elham Sharif, Rokhsana Rasooli, Reza Mohammadnejad, Yaser Masoumi-Ardekani
Objectives: Combination chemotherapy is a rational strategy to increase patient response and tolerability and to decrease adverse effects and drug resistance. Recently, the use of non-steroidal anti-inflammatory drugs (NSAIDs) has been reported to be associated with reduction in occurrence of a variety of cancers including lung cancer. On the other hand, growing evidences suggest that deuterium-enriched water (DEW, D2O) and deuterium-depleted water (DDW) play a role both in treatment and prevention of cancers...
May 2018: Iranian Journal of Basic Medical Sciences
Yunxia Qi, Xiaowei Zhao, Dongwei Huang, Xiaocheng Pan, Huiling Zhao, Han Hu, Guanglong Cheng, Yongxin Yang
In contrast to colostral immunoglobulins, changes in metabolite composition of ingested colostrum in the gut have received little attention. Here, we characterized the metabolite profiles of colostrum and milk, ingested colostrum and milk, and serum of neonatal calves by LC-MS and GC-MS metabolomics approaches. Colostrum and milk underwent similar changes in metabolite profiles in the gut after being ingested. These changes were characterized by increase in methionine, glutamate, thymine and phosphorylcholine...
June 19, 2018: Journal of Agricultural and Food Chemistry
Y-C Jiang, J-X Ma
OBJECTIVE: To investigate the expression of microRNA-324-3p (miR-324-3p) in polycystic ovary syndrome (PCOS) and its effects on the proliferation and apoptosis of ovarian granulosa cells. MATERIALS AND METHODS: A total of 60 Sprague-Dawley (SD) rats were randomly divided into normal group (n=30) and experimental group (n=30). Rats in the experimental group were intramuscularly injected with dehydroepiandrosterone (DHEA) (6 mg/100 g of body weight) and 0.2 mL oil for injection, while those in normal group were intramuscularly injected with 0...
June 2018: European Review for Medical and Pharmacological Sciences
Min Shen, Xin Ju, Xinqi Xu, Xuemei Yao, Liangzhi Li, Jiajia Chen, Cuiying Hu, Jiaolong Fu, Lishi Yan
In this study, we attempted to find new and efficient microbial enzymes for producing rare sugars. A ribose-5-phosphate isomerase B (OsRpiB) was cloned, overexpressed, and preliminarily purified successfully from a newly screened Ochrobactrum sp. CSL1, which could catalyze the isomerization reaction of rare sugars. A study of its substrate specificity showed that the cloned isomerase (OsRpiB) could effectively catalyze the conversion of L-rhamnose to L-rhamnulose, which was unconventional for RpiB. The optimal reaction conditions (50°C, pH 8...
May 8, 2018: Journal of Microbiology and Biotechnology
Souhaila Choul-Li, Arnaud J Legrand, Dorothée Vicogne, Vincent Villeret, Marc Aumercier
The Ets-1 transcription factor plays an important role in various physiological and pathological processes. These diverse roles of Ets-1 are likely to depend on its interaction proteins. We have previously showed that Ets-1 interacted with DNA-dependent protein kinase (DNA-PK) complex including its regulatory subunits, Ku70 and Ku86 and with poly (ADP-ribose) polymerase-1 (PARP-1). In this study, the binding domains for the interaction between Ets-1 and these proteins were reported. We demonstrated that the interaction of Ets-1 with DNA-PK was mediated through the Ku70 subunit and was mapped to the C-terminal region of Ets-1 and the C-terminal part of Ku70 including SAP domain...
June 18, 2018: Bioscience, Biotechnology, and Biochemistry
Ghulam Mohammad, Saleh Hamed Alrashed, Abdullah Ibrahim Almater, Mohammad Mairaj Siddiquei, Ahmed M Abu El-Asrar
PURPOSE: To examine the effects of poly(ADP-ribose)polymerase-1 (PARP-1) inhibitor 1,5-isoquinolinediol (IQ) on nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived oxidative stress in diabetic retina. METHODS: Streptozotocin-induced diabetic rats were treated with IQ. The NADPH oxidase enzyme activity was determined by luminometer. Expression of gp91phox , P47phox and nitrated proteins was examined by western blot. Interaction between gp91phox and P47phox was determined by coimmunoprecipitation...
June 18, 2018: Journal of Ocular Pharmacology and Therapeutics
Kathleen G Essel, Kathleen N Moore
Niraparib, an orally available selective inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP) is the first PARP inhibitor approved for use in patients with ovarian cancer who do not harbor a germline or somatic mutation in the breast cancer gene (BRCA). Overall niraparib is well tolerated and its toxicities, primarily hematologic, are manageable especially with recently released initial dose modification guidelines based on weight and baseline platelet count. The role of niraparib as maintenance following front-line platinum-based chemotherapy as well as in the treatment of recurrent high grade serous ovarian cancer (HGSOC) is an active area of investigation...
June 17, 2018: Expert Review of Anticancer Therapy
J M Lebert, R Lester, E Powell, M Seal, J McCarthy
Triple-negative breast cancer constitutes a heterogeneous group of malignancies that are often aggressive and associated with a poor prognosis. Molecular characterization, while not a standard of care, can further subtype triple-negative breast cancer and provide insight into prognostication and behaviour. Optimal chemotherapy regimens have yet to be established; however, there have been advances in the systemic treatment of triple-negative breast cancer in the neoadjuvant, adjuvant, and metastatic settings...
June 2018: Current Oncology
Paul DiSilvestro, Angeles Alvarez Secord
Approximately 1% of women in the United States will be diagnosed with epithelial ovarian cancer (EOC) during their lifetime. It is most likely to present at a more advanced stage, requiring aggressive therapeutic measures, and most women will succumb to this illness. Due to advancements in therapy, the oncology community has begun to shift its focus to molecular targeted agents, alternative dosing schedules, and maintenance therapy. Women who achieve a response to initial adjuvant chemotherapy may be candidates for maintenance therapy, with the goal of inducing a lasting remission or prolonging the disease-free interval before recurrence...
June 5, 2018: Cancer Treatment Reviews
Yasin Pourfarjam, Jessica Ventura, Igor Kurinov, Ahra Cho, Joel Moss, In-Kwon Kim
ADP-ribosyl-acceptor hydrolase 3 (ARH3) plays important roles in regulation of poly(ADP-ribosy)lation, a reversible post-translational modification, and in maintenance of genomic integrity. ARH3 degrades poly(ADP-ribose) to protect cells from poly(ADP-ribose)-dependent cell death, reverses serine-mono(ADP-ribosy)lation, and hydrolyzes O -acetyl-ADP-ribose, a product of Sirtuin-catalyzed histone deacetylation. ARH3 preferentially hydrolyzes O-linkages attached to the anomeric C1″ of ADP-ribose; however, how ARH3 specifically recognizes and cleaves structurally diverse substrates remains unknown...
June 15, 2018: Journal of Biological Chemistry
M Catherine Pietanza, Saiama N Waqar, Lee M Krug, Afshin Dowlati, Christine L Hann, Alberto Chiappori, Taofeek K Owonikoko, Kaitlin M Woo, Robert J Cardnell, Junya Fujimoto, Lihong Long, Lixia Diao, Jing Wang, Yevgeniva Bensman, Brenda Hurtado, Patricia de Groot, Erik P Sulman, Ignacio I Wistuba, Alice Chen, Martin Fleisher, John V Heymach, Mark G Kris, Charles M Rudin, Lauren Averett Byers
Purpose Both temozolomide (TMZ) and poly (ADP-ribose) polymerase (PARP) inhibitors are active in small-cell lung cancer (SCLC). This phase II, randomized, double-blind study evaluated whether addition of the PARP inhibitor veliparib to TMZ improves 4-month progression-free survival (PFS). Patients and Methods A total of 104 patients with recurrent SCLC were randomly assigned 1:1 to oral veliparib or placebo 40 mg twice daily, days 1 to 7, and oral TMZ 150 to 200 mg/m2 /day, days 1 to 5, of a 28-day cycle until disease progression, unacceptable toxicity, or withdrawal of consent...
June 15, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Malatee Tayeh, Sirinun Nilwarangkoon, Chantra Tanunyutthawongse, Wilawan Mahabusarakum, Ramida Watanapokasin
Rhodomyrtone is a bioactive compound extracted from Rhodomyrtus tomentosa leaves. It has been used as a traditional herb medicine for many years. Rhodomyrtone exhibits antibacterial activity, anti-inflammatory and antioxidant activities. However, the anticancer activity of rhodomyrtone has not been previously reported. The present study investigated the anticancer effect of rhomyrtone on human epidermoid carcinoma A431 cells. The cytotoxic and antiproliferative effects of rhodomyrtone on A431 cells were investigated by an MTT assay...
June 2018: Experimental and Therapeutic Medicine
Jian Ma, Shan-Shan Gao, Hai-Jie Yang, Mian Wang, Bin-Feng Cheng, Zhi-Wei Feng, Lei Wang
Proanthocyanidins (PA) are natural flavonoids widely present in many vegetables, fruits, nuts and seeds, and especially in grape seed. In the present study, we examined the neuroprotective effects of PA and the underlying molecular mechanism in rotenone model of Parkinson's disease (PD). We found that pretreatment with PA significantly reduced rotenone-induced oxidative stress in human neuroblastoma SH-SY5Y dopaminergic cells. In addition, PA markedly enhanced cell viability against rotenone neurotoxicity and considerably blocked rotenone-induced activation of caspase-9, caspase-3, and cleavage of poly (ADP-ribose) polymerase (PARP), biochemical features of apoptosis...
2018: Frontiers in Neuroscience
Luka Horvat, Mariastefania Antica, Maja Matulić
Differentiation of blood cells is one of the most complex processes in the body. It is regulated by the action of transcription factors in time and space which creates a specific signaling network. In the hematopoietic signaling system, Notch is one of the main regulators of lymphocyte development. The aim of this study was to get insight into the regulation of Notch signalization and the influence of poly(ADP-ribose)polymerase (PARP) activity on this process in three leukemia cell lines obtained from B and T cells...
June 14, 2018: Cells
Hélène Marijon, Dhong Hyun Lee, LingWen Ding, Haibo Sun, Sigal Gery, Aimery de Gramont, H Phillip Koeffler
PURPOSE: Despite similarities with BRCA-mutated breast cancers, triple-negative breast cancers (TNBC) remain resistant to poly(ADP-ribose) polymerase (PARP) inhibitors as single agents. Histone deacetylase inhibitors (HDACi) can decrease expression of proteins involved in DNA repair. We thus hypothesized that a HDACi (suberoylanilide hydroxamic acid (SAHA) or belinostat) could sensitize TNBC to the PARP inhibitor olaparib. METHODS: Human TNBC cells were co-treated with olaparib and either SAHA or belinostat, and their effects on survival, proliferation, cell cycle, apoptosis and DNA repair pathways were evaluated...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Sony Maharjan, Byoung Kwon Park, Su In Lee, Yoongho Lim, Keunwook Lee, Younghee Lee, Hyung-Joo Kwon
Colorectal cancer is one of the leading causes of cancer related death due to a poor prognosis. In this study, we investigated the effect of Gomisin G on colon cancer growth and examined the underlying mechanism of action. We found that Gomisin G significantly suppressed the viability and colony formation of LoVo cells. Gomisin G reduced the phosphorylation level of AKT implying that Gomisin G suppressed the PI3K-AKT signaling pathway. Gomisin G also induced apoptosis shown by Annexin V staining and an increased level of cleaved poly-ADP ribose polymerase (PARP) and Caspase-3 proteins...
June 14, 2018: Biomolecules & Therapeutics
Allison K Zarkin, Phyllis D Elkins, Amanda Gilbert, Teresa L Jester, Herbert H Seltzman
5-Aminoimidazole-4-carboxamide-1-β-D-[13 C5 ] ribofuranosyl 5'-monophosphate ([13 C5 ribose] AICAR-PO3 H2 ) (6) has been synthesized from [13 C5 ]adenosine. Incorporation of the mass-label into [13 C5 ribose] AICAR-PO3 H2 provides a useful standard to aid in metabolite identification and quantification in monitoring metabolic pathways. A synthetic route to the 13 C-labeled compound has not been previously reported. Our method employs a hybrid enzymatic and chemical synthesis approach that applies an enzymatic conversion from adenosine to inosine followed by a ring-cleavage of the protected inosine...
June 14, 2018: Journal of Labelled Compounds & Radiopharmaceuticals
Kunal Kumar, Akash Sabarwal, Rana P Singh
Mancozeb (Manganese ethylene bis-dithiocarbamate with zinc salt) is a dithiocarbamate fungicide used to control fungal disease in many fruit plants, flowers and the maintenance of field crops. The effect of mancozeb on cell viability of human gastric adenocarcinoma AGS, SNU-1 cells and human normal FHs 74 Int cells were investigated. This study demonstrated that mancozeb was able to inhibit cell proliferation by 56-82% at 5-10 μM concentrations after 48 h. Mancozeb treatment for 48 h resulted in 33% (P < 0...
June 11, 2018: Mitochondrion
Joseph H Lynch, Na Sa, Sompop Saeheng, Nadia Raffaelli, Sanja Roje
The flavin cofactors FMN and FAD are required for a wide variety of biological processes, however, little is known about their metabolism. Here, we report the cloning and biochemical characterization of the Saccharomyces cerevisiae pyrophosphatase Fpy1p. Genetic and functional studies suggest that Fpy1p may play a key role in flavin metabolism and is the first-reported non-Nudix superfamily enzyme to display FAD pyrophosphatase activity. Characterization of mutant yeast strains found that deletion of fpy1 counteracts the adverse effects that are caused by deletion of flx1, a known mitochondrial FAD transporter...
2018: PloS One
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