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Isabelle R Miousse, Charles M Skinner, Haixia Lin, Laura E Ewing, Stanley D Kosanke, D Keith Williams, Bharathi Avula, Ikhlas A Khan, Mahmoud A ElSohly, Bill J Gurley, Igor Koturbash
Herbal dietary supplements have gained wide acceptance as alternatives to conventional therapeutic agents despite concerns regarding their efficacy and safety. In 2013, a spate of severe liver injuries across the United States was linked to the dietary supplement OxyELITE Pro-New Formula (OEP-NF), a multi-ingredient product marketed for weight loss and exercise performance enhancement. The principal goal of this study was to assess the hepatotoxic potential of OEP-NF in outbred and inbred mouse models. In an acute toxicity study, significant mortality was observed after administering 10X and 3X mouse-equivalent doses (MED) of OEP-NF, respectively...
August 24, 2017: Food and Chemical Toxicology
Eun Jeong Cho, Ashwini K Devkota, Gabriel Stancu, Ramakrishna Edupunganti, Garth Powis, Kevin N Dalby
A high rate of glycolysis, which supplies energy and materials for anabolism, is observed in a wide range of tumor cells, making it a potential pathway to control cancer growth. ALDOA is a multifunctional enzyme in the glycolytic pathway and also promotes HIF-1α, which is of importance in hypoxic solid tumors. The current method for assaying ALDOA activity involves monitoring the consumption of NADH in vitro using absorbance or intrinsic fluorescence via a coupled enzymatic reaction. Here, we report the development of a homogeneous biochemical assay that can overcome limitations of current methods, in particular for the application of high-throughput drug screening...
August 1, 2017: SLAS Discovery
Yu-Chan Chang, Yung-Chieh Chan, Wei-Ming Chang, Yuan-Feng Lin, Chih-Jen Yang, Chia-Yi Su, Ming-Shyan Huang, Alexander T H Wu, Michael Hsiao
Distant metastasis and recurrence are the greatest challenges in the clinical management of lung cancer. Despite advances in targeted therapies, high mortality rates persist. Therefore, alternative therapeutic interventions are urgently required. Accumulating evidence indicates that normalizing tumor metabolism may be a way to increase therapeutic efficacy and to reduce tumor malignancy. Here, we analyzed integrated transcriptomics data and an shRNA library against glycolytic enzymes and found that elevated Aldolase A expression is highly correlated with metastatic potential and a poor prognosis in patients with non-small cell lung cancer (NSCLC)...
June 10, 2017: Cancer Letters
Ezarul Faradianna Lokman, Hussin Muhammad, Norizah Awang, Maizatul Hasyima Omar, Fazliana Mansor, Fatin Saparuddin
Dioscorea hispida (D.hispida) is the most well-known starchy tuber in Malaysia and called 'ubi gadong'. Despite concerns over toxicity effects, the tuber is known to possess therapeutic values due to the presence of bioactive compounds such as saponins. This study was performed to identify the changes in gene expression profiles associated with hepatoxicity in pregnant rat treated with D.hispida using RT² Profiler PCR Array. The identification of steroidal saponins from D.hispida was carried out by UHPLC/MS method...
March 2017: International Journal of Biomedical Science: IJBS
Xiaolei Yao, Hua Yang, Yanli Zhang, Caifang Ren, Haitao Nie, Yixuan Fan, Wenjun Zhou, Shuting Wang, Xu Feng, Feng Wang
The polypeptide N-acetylgalactosaminyltransferase-like protein 5 (GALNTL5), which belongs to the polypeptide N-acetylgalactosaminyltransferase (pp-GalNAc-T) gene family, is a newly identified gene that is specifically expressed in testis and involved in spermatogenesis. However, there is no data showing the existence of GALNTL5 in ram testis at various developmental stages and its influence on sperm motility. Therefore, the objectives of the present study were to evaluate the presence of GALNTL5 in the testis of 3-24 months (M) ram and to investigate the expression of GALNTL5 in spermatozoa with different motilities...
June 2017: Theriogenology
Hedi Hegyi
Combining genome-wide mapping of SNP-rich regions in schizophrenics and gene expression data in all brain compartments across the human life span revealed that genes with promoters most frequently mutated in schizophrenia are expression hubs interacting with far more genes than the rest of the genome. We summed up the differentially methylated "expression neighbors" of genes that fall into one of 108 distinct schizophrenia-associated loci with high number of SNPs. Surprisingly, the number of expression neighbors of the genes in these loci were 35 times higher for the positively correlating genes (32 times higher for the negatively correlating ones) than for the rest of the ~16000 genes...
April 6, 2017: Scientific Reports
Ning Na, Heng Li, Chengfang Xu, Bin Miao, Liangqing Hong, Zhengyu Huang, Qiu Jiang
BACKGROUND: Aldolase A (ALDOA) is a glycolytic enzyme that drives the glycolytic metabolic pathway in mammalian cells. The overexpression of ALDOA was observed in a variety of cancers including clear-cell renal cell carcinoma (ccRCC). However, little was known about the clinicopathological significance and prognostic value of ALDOA in ccRCC patients. METHODS: The expression of ALDOA was detected using immunohistochemical staining in 162 formalin-fixed, paraffin-embedded ccRCC sections...
2017: Therapeutics and Clinical Risk Management
Lei Chang, Jie Ni, Julia Beretov, Valerie C Wasinger, Jingli Hao, Joseph Bucci, David Malouf, David Gillatt, Peter H Graham, Yong Li
Identifying biomarkers and signaling pathways are important for the management of prostate cancer (CaP) radioresistance. In this study, we identified differential proteins and signaling pathways from parental CaP cell lines and CaP radioresistant (RR) sublines using a label-free LC-MS/MS proteomics approach. A total of 309 signaling pathway proteins were identified to be significantly altered between CaP and CaP-RR cells (p ≤ 0.05, fold differences >1.5, ≥80% power). Among these proteins, nineteen are common among three paired CaP cell lines and associated with metastasis, progression and radioresistance...
February 22, 2017: Scientific Reports
Kehua Jin, Li Li, Xihuan Sun, Qingyan Xu, Siyang Song, Yuemao Shen, Xianming Deng
Upregulation of glycolysis and the pentose phosphate pathway (PPP) is a major characteristic of the metabolic reprogramming of cancer and provides cancer cells with energy and vital metabolites to support their rapid proliferation. Targeting glycolysis and the PPP has emerged as a promising antitumor therapeutic strategy. Marine natural products are attractive sources for anticancer therapeutics, as evidenced by the antitumor drug Yondelis. Mycoepoxydiene (MED) is a natural product isolated from a marine fungus that has shown promising inhibitory efficacy against HeLa cells in vitro...
February 21, 2017: Applied Microbiology and Biotechnology
Fan Zhang, Jie-Diao Lin, Xiao-Yu Zuo, Yi-Xuan Zhuang, Chao-Qun Hong, Guo-Jun Zhang, Xiao-Jiang Cui, Yu-Kun Cui
BACKGROUND: Aldolase A (ALDOA) is one of the glycolytic enzymes primarily found in the developing embryo and adult muscle. Recently, a new role of ALDOA in several cancers has been proposed. However, the underlying mechanism remains obscure and inconsistent. In this study, we tried to investigate ALDOA-associated (AA) genes using available microarray datasets to help elucidating the role of ALDOA in cancer. RESULTS: In the dataset of patients with non-small-cell lung cancer (NSCLC, E-GEOD-19188), 3448 differentially expressed genes (DEGs) including ALDOA were identified, in which 710 AA genes were found to be positively associated with ALDOA...
2017: BioData Mining
Wei Cao, Tuanjie Chang, Xiao-Qiang Li, Rui Wang, Lingyun Wu
Increased production of methylglyoxal (MG) in vascular tissues is one of the causative factors for vascular remodelling in different subtypes of metabolic syndrome, including hypertension and insulin resistance. Fructose-induced up-regulation of aldolase B (AldoB) contributes to increased vascular MG production but the underlying mechanisms are unclear. Serum levels of MG and fructose were determined in diabetic patients with hypertension. MG level had significant positive correlations with blood pressure and fructose level respectively...
February 1, 2017: Clinical Science (1979-)
Kenji Kawai, Mamoru Uemura, Koji Munakata, Hidekazu Takahashi, Naotsugu Haraguchi, Junichi Nishimura, Taishi Hata, Chu Matsuda, Masakazu Ikenaga, Kohei Murata, Tsunekazu Mizushima, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori
Hypoxia is an essential feature of cancer malignancy, but there are no methods for the routine detection of hypoxia-inducible prognostic factors and potential therapeutic targets. We reported previously that the hypoxic tumor cells of metastatic liver tissue from patients with colorectal cancer (CRC) could be used as an 'in vivo' hypoxia culture model. Several potential hypoxia-inducible genes were identified using this model. Among them, one glycolytic enzyme was of special interest. There is currently increasing attention on glycolytic enzymes as potential therapeutic targets due to their association with cancer-specific metabolism...
February 2017: International Journal of Oncology
W Zhu, H Shen, J-G Zhang, L Zhang, Y Zeng, H-L Huang, Y-C Zhao, H He, Y Zhou, K-H Wu, Q Tian, L-J Zhao, F-Y Deng, H-W Deng
In male Caucasians with discordant hip bone mineral density (BMD), we applied the subcellular separation and proteome profiling to investigate the monocytic cytosol. Three BMD-associated proteins (ALDOA, MYH14, and Rap1B) were identified based on multiple omics evidence, and they may influence the pathogenic mechanisms of osteoporosis by regulating the activities of monocytes. INTRODUCTION: Osteoporosis is a serious public health problem, leading to significant mortality not only in aging females but also in males...
March 2017: Osteoporosis International
Yan Zeng, Yehui Lv, Li Tao, Jianlong Ma, Heng Zhang, Hongmei Xu, Bi Xiao, Qun Shi, Kaijun Ma, Long Chen
Hypoxia influences different cellular biological processes. To reveal the dynamics of hypoxia's effects on miRNA regulation in vivo, we examined the expression levels of all miRNAs in human brain and heart specimens from cases of mechanical asphyxia compared with those from cases of craniocerebral injury and hemorrhagic shock. We further validated differently expressed miRNAs in another 84 human specimens and rat models. We found that mir-122 was significantly down-regulated and that its putative targets G6PC3, ALDOA and CS were increased in the brain and cardiac tissues in cases of mechanical asphyxia compared with craniocerebral injury and hemorrhagic shock...
October 26, 2016: Oncotarget
Nguyen Phuoc Long, Wun Jun Lee, Nguyen Truong Huy, Seul Ji Lee, Jeong Hill Park, Sung Won Kwon
Colorectal cancer (CRC) is one of the most common and lethal cancers. Although numerous studies have evaluated potential biomarkers for early diagnosis, current biomarkers have failed to reach an acceptable level of accuracy for distant metastasis. In this paper, we performed a gene set meta-analysis of in vitro microarray studies and combined the results from this study with previously published proteomic data to validate and suggest prognostic candidates for CRC metastasis. Two microarray data sets included found 21 significant genes...
2016: Cancer Informatics
Bing Sun, Yuxin Bai, Liyuan Zhang, Linlin Gong, Xiaoyu Qi, Huizhen Li, Faming Wang, Xinming Chi, Yulin Jiang, Shujuan Shao
Lung cancer remains the leading cancer killer around the world. It's crucial to identify newer mechanism-based targets to effectively manage lung cancer. Annexin A5 (ANXA5) is a protein kinase C inhibitory protein and calcium dependent phospholipid-binding protein, which may act as an endogenous regulator of various pathophysiological processes. However, its molecular mechanism in lung cancer remains poorly understood. This study was designed to determine the mechanism of ANXA5 in lung cancer with a hope to obtain useful information to provide a new therapeutic target...
2016: PloS One
Geoffrey Grandjean, Petrus De Jong, Brian James, Mei Yee Koh, Robert Lemos, John Kingston, Alexander Aleshin, Laurie A Bankston, Claudia P Miller, Eun Jeong Cho, Ramakrishna Edupuganti, Ashwini Devkota, Gabriel Stancu, Robert C Liddington, Kevin Dalby, Garth Powis
The hypoxia-inducible transcription factor HIF1α drives expression of many glycolytic enzymes. Here, we show that hypoxic glycolysis, in turn, increases HIF1α transcriptional activity and stimulates tumor growth, revealing a novel feed-forward mechanism of glycolysis-HIF1α signaling. Negative regulation of HIF1α by AMPK1 is bypassed in hypoxic cells, due to ATP elevation by increased glycolysis, thereby preventing phosphorylation and inactivation of the HIF1α transcriptional coactivator p300. Notably, of the HIF1α-activated glycolytic enzymes we evaluated by gene silencing, aldolase A (ALDOA) blockade produced the most robust decrease in glycolysis, HIF-1 activity, and cancer cell proliferation...
July 15, 2016: Cancer Research
Ilinca Georgescu, Robert J Gooding, R Christopher Doiron, Andrew Day, Shamini Selvarajah, Chris Davidson, David M Berman, Paul C Park
BACKGROUND: Gleason scores (GS) 3+3 and 3+4 prostate cancers (PCa) differ greatly in their clinical courses, with Gleason pattern (GP) 4 representing a major independent risk factor for cancer progression. However, Gleason grade is not reliably ascertained by diagnostic biopsy, largely due to sampling inadequacies, subjectivity in the Gleason grading procedure, and a lack of more objective biomarker assays to stratify prostate cancer aggressiveness. In most aggressive cancer types, the tumor microenvironment exhibits a reciprocal pro-tumorigenic metabolic phenotype consistent with the reverse Warburg effect (RWE)...
2016: Cancer & Metabolism
Azhwar Raghunath, Dhivyalakshmi Jeyabaskar, Kiruthika Sundarraj, Lakshmikanthan Panneerselvam, Ekambaram Perumal
Fluorosis is an endemic global problem causing male reproductive impairment. F mediates male reproductive toxicity in mice down-regulating 63 genes involved in diverse biological processes - apoptosis, cell cycle, cell signaling, chemotaxis, electron transport, glycolysis, oxidative stress, sperm capacitation and spermatogenesis. We predicted the miRNAs down-regulating these 63 genes using TargetScan, DIANA and MicroCosm. The prediction tools identified 3059 miRNAs targeting 63 genes. Of the predicted interactions, 11 miRNAs (mmu-miR-103, -107, -122, -188a, -199a-5p, -205, -340-5p, -345-3p, -452-5p, -499, -878-3p) were commonly found in the three tools utilized and seven miRNAs (miR-9-5p, miR-511-3p, miR-7b-5p, miR-30e-5p, miR-17-5p, miR-122-5p and miR-541-5p) targeting six genes (Traf3, Rock2, Rgs8, Atp1b2, Cacna2d1 and Aldoa) were already validated experimentally in mice...
December 2016: Food and Chemical Toxicology
Shunrong Ji, Bo Zhang, Jiang Liu, Yi Qin, Chen Liang, Si Shi, Kaizhou Jin, Dingkong Liang, Wenyan Xu, Huaxiang Xu, Wenquan Wang, Chuntao Wu, Liang Liu, Chen Liu, Jin Xu, Quanxing Ni, Xianjun Yu
Pancreatic cancer is an aggressive and devastating disease that is characterized by uncontrolled progression, invasiveness and resistance to conventional treatment. In the past decades, much effort has been given to cancer genetics and pathological classification of this disease. Our previous study has uncovered a subgroup of patients with poor outcome, which is characterized by serum signature of CEA(+)/CA125(+)/CA19-9 ≥ 1000 U/mL; however, the underlying biology mechanism remains poorly understood...
April 28, 2016: Cancer Letters
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