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Full-Text Articles in Medicine and Health Sciences

Highly Efficient 5' Capping Of Mitochondrial Rna With Nad+ And Nadh By Yeast And Human Mitochondrial Rna Polymerase, Jeremy G Bird, Urmimala Basu, David Kuster, Aparna Ramachandran, Ewa Grudzien-Nogalska, Atif Towheed, Douglas C. Wallace, Megerditch Kiledjian, Dmitry Temiakov, Smita S. Patel, Richard H. Ebright, Bryce E. Nickels Dec 2018

Highly Efficient 5' Capping Of Mitochondrial Rna With Nad+ And Nadh By Yeast And Human Mitochondrial Rna Polymerase, Jeremy G Bird, Urmimala Basu, David Kuster, Aparna Ramachandran, Ewa Grudzien-Nogalska, Atif Towheed, Douglas C. Wallace, Megerditch Kiledjian, Dmitry Temiakov, Smita S. Patel, Richard H. Ebright, Bryce E. Nickels

Department of Biochemistry and Molecular Biology Faculty Papers

Bacterial and eukaryotic nuclear RNA polymerases (RNAPs) cap RNA with the oxidized and reduced forms of the metabolic effector nicotinamide adenine dinucleotide, NAD+ and NADH, using NAD+ and NADH as non-canonical initiating nucleotides for transcription initiation. Here, we show that mitochondrial RNAPs (mtRNAPs) cap RNA with NAD+ and NADH, and do so more efficiently than nuclear RNAPs. Direct quantitation of NAD+- and NADH-capped RNA demonstrates remarkably high levels of capping in vivo: up to ~60% NAD+ and NADH capping of yeast mitochondrial transcripts, and up to ~15% NAD+ capping of human mitochondrial transcripts. The capping efficiency is determined by promoter …


Metabolic Dependencies In Pancreatic Cancer., Ali Vaziri-Gohar, Mahsa Zarei, Jonathan R. Brody, Jordan M. Winter Dec 2018

Metabolic Dependencies In Pancreatic Cancer., Ali Vaziri-Gohar, Mahsa Zarei, Jonathan R. Brody, Jordan M. Winter

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer with a long-term survival rate under 10%. Available cytotoxic chemotherapies have significant side effects, and only marginal therapeutic efficacy. FDA approved drugs currently used against PDA target DNA metabolism and DNA integrity. However, alternative metabolic targets beyond DNA may prove to be much more effective. PDA cells are forced to live within a particularly severe microenvironment characterized by relative hypovascularity, hypoxia, and nutrient deprivation. Thus, PDA cells must possess biochemical flexibility in order to adapt to austere conditions. A better understanding of the metabolic dependencies required by PDA to survive and …


Hypoglycemic, Hypolipidemic And Antioxidant Effects Of Iridoid Glycosides Extracted From: Corni Fructus: Possible Involvement Of The Pi3k-Akt/Pkb Signaling Pathway, Jiefang Kang, Chen Guo, Rodolfo Thome, Ning Yang, Yuan Zhang, Xing Li, Xiaoyan Cao Aug 2018

Hypoglycemic, Hypolipidemic And Antioxidant Effects Of Iridoid Glycosides Extracted From: Corni Fructus: Possible Involvement Of The Pi3k-Akt/Pkb Signaling Pathway, Jiefang Kang, Chen Guo, Rodolfo Thome, Ning Yang, Yuan Zhang, Xing Li, Xiaoyan Cao

Department of Neurology Faculty Papers

Iridoid glycosides (CIG) are the major component of Corni fructus. In this work, we researched the antioxidative, hypoglycemic and lowering blood lipids effects of CIG on diabetic mice induced by a high-fat diet (HFD) and streptozotocin (STZ). Furthermore, to investigate the molecular mechanism of action, the phosphorylation and protein expression of phosphoinositide 3-kinase (PI3K) and its downstream proteins, such as insulin receptor (INSR), protein kinase B (Akt/PKB) and glucose transporter 4 (GLUT4) have been detected. The results showed that CIG significantly improved oral glucose tolerance in diabetic mice. Biochemical indices also revealed that CIG had a positive effect on lipid …


Metformin As A Therapeutic Target In Endometrial Cancers., Teresa Lee, Ubaldo E. Martinez-Outshoorn, Russell J. Schilder, Christine H. Kim, Scott D. Richard, Norman G. Rosenblum, Jennifer Johnson Aug 2018

Metformin As A Therapeutic Target In Endometrial Cancers., Teresa Lee, Ubaldo E. Martinez-Outshoorn, Russell J. Schilder, Christine H. Kim, Scott D. Richard, Norman G. Rosenblum, Jennifer Johnson

Department of Medical Oncology Faculty Papers

Endometrial cancer is the most common gynecologic malignancy in developed countries. Its increasing incidence is thought to be related in part to the rise of metabolic syndrome, which has been shown to be a risk factor for the development of hyperestrogenic and hyperinsulinemic states. This has consequently lead to an increase in other hormone-responsive cancers as well e.g., breast and ovarian cancer. The correlation between obesity, hyperglycemia, and endometrial cancer has highlighted the important role of metabolism in cancer establishment and persistence. Tumor-mediated reprogramming of the microenvironment and macroenvironment can range from induction of cytokines and growth factors to stimulation …


Monocarboxylate Transporter 4 (Mct4) Knockout Mice Have Attenuated 4nqo Induced Carcinogenesis; A Role For Mct4 In Driving Oral Squamous Cell Cancer., Sara Bisetto, Diana Whitaker Menezes, Nicole A. Wilski, Madalina Tuluc, Joseph Curry, Tingting Zhan, Christopher M. Snyder, Ubaldo E. Martinez-Outshoorn, Nancy J. Philp Aug 2018

Monocarboxylate Transporter 4 (Mct4) Knockout Mice Have Attenuated 4nqo Induced Carcinogenesis; A Role For Mct4 In Driving Oral Squamous Cell Cancer., Sara Bisetto, Diana Whitaker Menezes, Nicole A. Wilski, Madalina Tuluc, Joseph Curry, Tingting Zhan, Christopher M. Snyder, Ubaldo E. Martinez-Outshoorn, Nancy J. Philp

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common human cancer and affects approximately 50,000 new patients every year in the US. The major risk factors for HNSCC are tobacco and alcohol consumption as well as oncogenic HPV infections. Despite advances in therapy, the overall survival rate for all-comers is only 50%. Understanding the biology of HNSCC is crucial to identifying new biomarkers, implementing early diagnostic approaches and developing novel therapies. As in several other cancers, HNSCC expresses elevated levels of MCT4, a member of the SLC16 family of monocarboxylate transporters. MCT4 is a H+-linked …