Diseases Commons^™

Targeting The Glutamine-Arginine-Proline Metabolism Axis In Cancer, Di Wang, Jiang-Jie Duan, Yu-Feng Guo, Jun-Jie Chen, Tian-Qing Chen, Jun Wang, Shi-Cang Yu

Student and Faculty Publications

Metabolic abnormalities are an important feature of tumours. The glutamine-arginine-proline axis is an important node of cancer metabolism and plays a major role in amino acid metabolism. This axis also acts as a scaffold for the synthesis of other nonessential amino acids and essential metabolites. In this paper, we briefly review (1) the glutamine addiction exhibited by tumour cells with accelerated glutamine transport and metabolism; (2) the methods regulating extracellular glutamine entry, intracellular glutamine synthesis and the fate of intracellular glutamine; (3) the glutamine, proline and arginine metabolic pathways and their interaction; and (4) the research progress in tumour therapy …

Fluvoxamine Inhibits Th1 And Th17 Polarization And Function By Repressing Glycolysis To Attenuate Autoimmune Progression In Type 1 Diabetes, Yuan Zou, Jing Zhang, Fei Sun, Qianqian Xu, Longmin Chen, Xi Luo, Ting Wang, Qing Zhou, Shu Zhang, Fei Xiong, Wen Kong, Ping Yang, Qilin Yu, Shiwei Liu, Cong-Yi Wang

Student and Faculty Publications

BACKGROUND: Fluvoxamine is one of the selective serotonin reuptake inhibitors (SSRIs) that are regarded as the first-line drugs to manage mental disorders. It has been also recognized with the potential to treat inflammatory diseases and viral infection. However, the effect of fluvoxamine on autoimmune diseases, particularly type 1 diabetes (T1D) and the related cellular and molecular mechanisms, are yet to be addressed.

METHOD: Herein in this report, we treated NOD mice with fluvoxamine for 2 weeks starting from 10-week of age to dissect the impact of fluvoxamine on the prevention of type 1 diabetes. We compared the differences of immune …

Gestational Diabetes Augments Group B Streptococcus Infection By Disrupting Maternal Immunity And The Vaginal Microbiota, Vicki Mercado-Evans, Marlyd E Mejia, Jacob J Zulk, Samantha Ottinger, Zainab A Hameed, Camille Serchejian, Madelynn G Marunde, Clare M Robertson, Mallory B Ballard, Simone H Ruano, Natalia Korotkova, Anthony R Flores, Kathleen A Pennington, Kathryn A Patras

Student and Faculty Publications

Group B Streptococcus (GBS) is a pervasive perinatal pathogen, yet factors driving GBS dissemination in utero are poorly defined. Gestational diabetes mellitus (GDM), a complication marked by dysregulated immunity and maternal microbial dysbiosis, increases risk for GBS perinatal disease. Using a murine GDM model of GBS colonization and perinatal transmission, we find that GDM mice display greater GBS in utero dissemination and subsequently worse neonatal outcomes. Dual-RNA sequencing reveals differential GBS adaptation to the GDM reproductive tract, including a putative glycosyltransferase (yfhO), and altered host responses. GDM immune disruptions include reduced uterine natural killer cell activation, impaired recruitment to placentae, …

Transmembrane Stem Factor Nanodiscs Enhanced Revascularization In A Hind Limb Ischemia Model In Diabetic, Hyperlipidemic Rabbits, Eri Takematsu, Miles Massidda, Gretchen Howe, Julia Goldman, Patricia Felli, Lei Mei, Gregory Callahan, Andrew D Sligar, Richard Smalling, Aaron B Baker

Faculty and Staff Publications

Therapies to revascularize ischemic tissue have long been a goal for the treatment of vascular disease and other disorders. Therapies using stem cell factor (SCF), also known as a c-Kit ligand, had great promise for treating ischemia for myocardial infarct and stroke, however clinical development for SCF was stopped due to toxic side effects including mast cell activation in patients. We recently developed a novel therapy using a transmembrane form of SCF (tmSCF) delivered in lipid nanodiscs. In previous studies, we demonstrated tmSCF nanodiscs were able to induce revascularization of ischemia limbs in mice and did not activate mast cells. …

Sex Hormone-Binding Globulin (Shbg) Mitigates Er Stress And Improves Viability And Insulin Sensitivity In Adipose-Derived Mesenchymal Stem Cells (Asc) Of Equine Metabolic Syndrome (Ems)-Affected Horses, Nabila Bourebaba, Mateusz Sikora, Badr Qasem, Lynda Bourebaba, Krzysztof Marycz

Student and Faculty Publications

BACKGROUND: Equine metabolic syndrome (EMS), which encompasses insulin resistance, low-grade inflammation and predisposition to laminitis is a critical endocrine disorder among the most prevalent conditions affecting horses from different breeds. According to the most recent research, low human sex hormone-binding globulin (SHBG) serum levels correlate with an increased risk of obesity, insulin resistance and diabetes, and may contribute to overall metabolic dysregulations. This study aimed to test whether exogenous SHBG could protect EMS affected adipose-derived stromal stem cells (EqASC

METHODS: EqASC

RESULTS: Obtained data demonstrated that exogenous SHBG treatment significantly promoted ASCs cells proliferation, cell cycle and survival with reduced …

Interfering With Lipid Metabolism Through Targeting Ces1 Sensitizes Hepatocellular Carcinoma For Chemotherapy, Gang Li, Xin Li, Iqbal Mahmud, Jazmin Ysaguirre, Baharan Fekry, Shuyue Wang, Bo Wei, Kristin L Eckel-Mahan, Philip L Lorenzi, Richard Lehner, Kai Sun

Student and Faculty Publications

Hepatocellular carcinoma (HCC) is the most common lethal form of liver cancer. Apart from surgical removal and transplantation, other treatments have not yet been well established for patients with HCC. In this study, we found that carboxylesterase 1 (CES1) is expressed at various levels in HCC. We further revealed that blockage of CES1 by pharmacological and genetical approaches leads to altered lipid profiles that are directly linked to impaired mitochondrial function. Mechanistically, lipidomic analyses indicated that lipid signaling molecules, including polyunsaturated fatty acids (PUFAs), which activate PPARα/γ, were dramatically reduced upon CES1 inhibition. As a result, the expression of SCD, …

Adar1 Deletion Causes Degeneration Of The Exocrine Pancreas Via Mavs-Dependent Interferon Signaling, Dhwani N Rupani, Fredrik I Thege, Vidhi Chandra, Hajar Rajaei, Robert W Cowan, Sonja M Wörmann, Olivereen Le Roux, Prerna Malaney, Sara L Manning, Jack Hashem, Jennifer Bailey-Lundberg, Andrew D Rhim, Florencia Mcallister

Student and Faculty Publications

Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA-binding protein that deaminates adenosine (A) to inosine (I). A-to-I editing alters post-transcriptional RNA processing, making ADAR1 a crucial regulator of gene expression. Consequently, Adar1 has been implicated in organogenesis. To determine the role of Adar1 in pancreatic development and homeostasis, we conditionally deleted Adar1 from the murine pancreas (Ptf1aCre/+; Adar1Fl/Fl). The resulting mice had stunted growth, likely due to malabsorption associated with exocrine pancreatic insufficiency. Analyses of pancreata revealed ductal cell expansion, heightened interferon-stimulated gene expression and an increased influx of immune cells. Concurrent deletion of Adar1 and Mavs, a …

Anti-Diabetic Effects Of Glp1 Analogs Are Mediated By Thermogenic Interleukin-6 Signaling In Adipocytes, Absalon D Gutierrez, Zhanguo Gao, Vala Hamidi, Liang Zhu, Karla Bermudez Saint Andre, Kayla Riggs, Monika Ruscheinsky, Hongyu Wang, Yongmei Yu, Charles Miller, Hernan Vasquez, Heinrich Taegtmeyer, Mikhail G Kolonin

Student and Faculty Publications

Mechanisms underlying anti-diabetic effects of GLP1 analogs remain incompletely understood. We observed that in prediabetic humans exenatide treatment acutely induces interleukin-6 (IL-6) secretion by monocytes and IL-6 in systemic circulation. We hypothesized that GLP1 analogs signal through IL-6 in adipose tissue (AT) and used the mouse model to test if IL-6 receptor (IL-6R) signaling underlies the effects of the GLP1-IL-6 axis. We show that liraglutide transiently increases IL-6 in mouse circulation and IL-6R signaling in AT. Metronomic liraglutide treatment resulted in AT browning and thermogenesis linked with STAT3 activation. IL-6-blocking antibody treatment inhibited STAT3 activation in AT and suppressed liraglutide-induced …

Immunotherapy For Type 1 Diabetes Mellitus By Adjuvant-Free Schistosoma Japonicum-Egg Tip-Loaded Asymmetric Microneedle Patch (Stamp), Haoming Huang, Dian Hu, Zhuo Chen, Jiarong Xu, Rengui Xu, Yusheng Gong, Zhengming Fang, Ting Wang, Wei Chen

Student and Faculty Publications

BACKGROUND: Type 1 diabetes mellitus (T1DM) is an autoimmune disease mediated by autoreactive T cells and dominated by Th1 response polarization. Insulin replacement therapy faces great challenges to this autoimmune disease, requiring highly frequent daily administration. Intriguingly, the progression of T1DM has proven to be prevented or attenuated by helminth infection or worm antigens for a relatively long term. However, the inevitable problems of low safety and poor compliance arise from infection with live worms or direct injection of antigens. Microneedles would be a promising candidate for local delivery of intact antigens, thus providing an opportunity for the clinical immunotherapy …

Effect Of A Glp-1 Mimetic On The Insulin Response To Oral Sugar Testing In Horses, Darko Stefanovski, Mary A Robinson, Andrew Van Eps

Student and Faculty Publications

BACKGROUND: Insulin dysregulation (ID) is the most important risk factor for the development of laminitis in horses and therapies to control it are needed.

HYPOTHESIS/OBJECTIVES: To assess the effects of a single dose of the synthetic GLP-1 analog exenatide on postprandial insulin dynamics. We hypothesized that exenatide would improve insulin sensitivity and lower postprandial blood insulin concentrations.

STUDY DESIGN: Randomized, crossover, experimental study.

ANIMALS: Six horses (3 mares, 3 geldings; 2 with normal insulin regulation [NIR] and 4 with mild ID).

METHODS: Horses completed both study arms: subcutaneous administration of exenatide (or no treatment) 30 min before an oral sugar …