bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐oxidative activity of db mice treated with glycosaminoglycan of cricket, Gryllus bimaculatus
Authors: Ahn Mi Young , Hwang Jae Sam 
Published: June 2021

Gryllus bimaculatus (Gb, cricket) is newly emerged as an edible insect in several countries. Edible or medicinal insects have been employed by purification and identification of potent active substances as food or drugs. Anti‐diabetic activities of G. bimaculatus glycosaminoglycan (GbG) or dung beetle (Catharsius molossus) glycosaminoglycan (CaG) were evaluated in diabetic mice based on their abilities to reduce glucose, ALT, AST, LDL‐cholesterol, and BUN levels. Db mice were assigned into the following groups: 1) Db heterozygous (PBS, normal control), 2) Db homozygous (PBS, diabetes control), 3) CaG (5 mg/kg), 4) GbG (5 mg/kg), and 5) metformin (10 mg/kg). They were orally administered with PBS or CaG or GbG or metformin for one month. Sero‐biochemical levels were evaluated to determine their anti‐diabetic, and anti‐oxidative activities after one month of CaG or GbG treatment in Db mice. Blood glucose level was decreased after treatment with CaG or GbG. GbG produced meaningful anti‐diabetic effect. It inhibited LDL‐cholesterol and alkaline phosphatase levels. Regarding oxidative damage, levels of hepatocellular biomarkers levels and protein carbonyl content were reduced in db mice treated with CaG or GbG. Anti‐oxidative activities of catalase, superoxide dismutase, and glutathione peroxidase were significantly increased in GbG treated group compared to those in the control. Therefore, G. bimaculatus glycosaminoglycan could be used as a therapeutic agent with anti‐diabetic effect and anti‐oxidative activity for diabetic mice.Support or Funding InformationThis work was supported by Rural Development Administration basic Research project, PJ011853.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Evaluation of Plasma Cell‐Free Circulating DNA Integrity in Patients with Prostate Cancer in Jamaica
Authors: Condappa Andrew , Aiken William , McLaughlin Wayne , McGrowder Donovan , Gossell‐Williams Maxine 
Published: June 2021

Cell free circulating DNA (cfcDNA) is a promising diagnostic tool for prostate cancer (PCa). The study aimed to measure the cfcDNA concentration and cfcDNA integrity in prostate cancer patients using quantitative polymerase chain reaction (qPCR) analysis on plasma samples. The study also assessed correlation between cfcDNA concentration and integrity with baseline PSA, Gleason score, total prostate volume, age and the number of presenting comorbidities. Eleven patients with PCa and 9 patients with Benign Prostatic Hyperplasia (BPH) were enrolled. Plasma samples were collected before prostate biopsy and quantified by qPCR amplification of ALU115 DNA sequence, and the quantitative ratio of ALU 247 to ALU 115 reflected the integrity of cfcDNA. There were no significant differences in median (IQR) plasma cfcDNA concentration or its integrity between the patients with PCa [47.9 (214.93) ng/mL, 0.61 (0.49)] and patients with BPH [41.5 (55.13) ng/mL, 0.67 (0.45); p = 0.382, p = 0.342]. There was no correlation between cfcDNA and cfcDNA integrity with baseline PSA, Gleason score, total prostate volume, age and the number of presenting comorbidities.ConclusionThe small sample size of the current study did not allow for the differentiation of PCa from BPH using cfcDNA concentration and integrity. There was also no correlation with cfcDNA concentration and integrity with the selected clinical and pathological variables.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Acetylcholine signaling pathway: A novel target for lung cancer in smokers
Authors: Dasgupta Piyali , Lau Jamie K. , Brown Kathleen C. , Bow Eric , Robateau Zachary R. , Rollyson William D. , Stover Cody A. , Rimoldi John M. , Cutler Stephen , Hardman W. Elaine , Carpenter A. Betts , Chen Yi C. 
Published: June 2021

The clinicopathological features of lung cancer in smokers is completely different from never‐smokers. Whereas lung cancer patients (who are never smokers) respond well to targeted therapies involving EGFR inhibitors and ALK kinase inhibitors, the response of these drugs in lung cancer patients who are smokers is poor. Nicotine is the addictive component of cigarette smoke. Nicotine (at concentrations present in the plasma of moderate smokers) accelerates the growth, angiogenesis and metastasis of lung cancers. The biological activity of nicotine is mediated by nicotinic acetylcholine receptors (nAChRs). The endogenous ligand for nAChRs in the lung is the neurotransmitter acetylcholine (ACh). ACh is known to be an autocrine growth factor for both SCLC and NSCLC. One of the ways that nicotine and cigarette smoke promote the growth of lung cancers is by promoting the production of ACh, which binds to its cognate receptor (on lung cancer cells) in an autocrine manner and induces the proliferation of lung cancer cells. The objective of the present study is to investigate the whether the ACh‐mitogenic signaling pathway are altered in human lung cancer. We show that levels three acetylcholine‐signaling proteins namely ChAT, VAChT and AChE are significantly altered in lung cancer occurring in active smokers. Small‐molecule regulators of these proteins suppress the growth of human lung cancer cells. Our studies will facilitate the identification of targeted therapies for the majority of lung cancer patients who are exposed to tobacco smoke.Support or Funding InformationFunding for our study was supported by an NIH R15‐AREA Grant (2R15CA161491‐02) and the West Virginia IDeA Network of Biomedical Research Excellence (WV‐INBRE) grant GM103434 (PI: Dr. G. Rankin). Furthermore, this study was supported in part by an Institutional Development grant (IDeA) Grant number P20GM104932 from the National Institute of General Medical Sciences (NIGMS) and the Research Core B of COBRE, a component of the National Institutes of Health (NIH)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Regulation of Trophoblast Invasion by Pyruvate Kinase Isozyme M2 (PKM2)
Authors: Mejia Juan F. , Hall Parker , Hirschi Kelsey M. , Reynolds Paul R. , Arroyo Juan A. 
Published: June 2021

The Pyruvate kinase isozymes M2 (PKM2) protein is a metabolic enzyme that regulates the final step of glycolysis. This enzyme is present in highly proliferating cells such as those present in embryonic tissues, cancer and in the placental trophoblast. We recently studied PKM2 protein in the human placenta at term. Our results demonstrated upregulated placental PKM2 during preeclampsia (PE) where trophoblast invasion is decreased and hypoxia is present. Our objective was to determine the cytosolic and nuclear PKM2 expression pattern and determine PKM2 regulation of trophoblast cell invasion. Trophoblast cells were cultured in normoxic and hypoxic conditions and real time cell invasion was determined during activation (Fructose‐6‐bisphosphate) or inhibition (Shikonin) of PKM2. Treated cells were lysed for western blot analysis of PKM2. During normoxia, we observed: 1) 2‐fold increase (p<0.002) in trophoblast invasion when PKM2 was activated; 2) a 68‐fold reduction (p<0.002) in trophoblast invasion when PKM2 activation was inhibited; 3) a 1.4‐fold induction (p<0.03) of nuclear PKM2 in the trophoblast when PKM2 was activated; 4) a 1.6‐fold induction (p<0.04) of nuclear PKM2 after PKM2 inactivation; and 5) a 1.4‐fold decrease (p<0.03) in cytosolic PKM2 after PKM2 inactivation. During hypoxia we observed: 1) decreased cell invasion (~3.0‐fold; p<0.005) in treated cells; 2) decreased cytosolic PKM2 expression (~1.6‐fold; p<0.03) in treated cells; and 3) no significant differences in the expression of cytosolic PKM2. We conclude that PKM2 regulates trophoblast cell invasion depending of its cellular localization. Furthermore, our results suggest that PKM2 regulation is affected by hypoxia. These results suggest that PKM2 could be a mediator of trophoblast cell invasion and its abundance influences the development of complicated pregnancies like PE.Support or Funding InformationThis work was supported by a grant from the Flight Attendant's Medical Research Institute (FAMRI, PRR and JAA) and a BYU Mentoring Environment Grant (JAA and PRR).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Identification of AQP5‐regulating miRNAs and their role in breast cancer cell migration
Authors: PARK EUI‐JUNG , Jung Hyun Jun , Choi Hyo‐Jung , Kwon Tae‐Hwan 
Published: June 2021

BackgroundWe previously reported that AQP5 expression is critical for proliferation and migration of human breast cancer cells. However, the regulatory machinery for AQP5 expression in human breast cancer cells is unclear. The present study aimed to identify the AQP5‐regulating miRNAs, as one of regulatory mechanisms for AQP5 expression, and to examine roles of these miRNAs in human breast cancer cell migration.Methods1) To predict putative miRNAs interacting with AQP5 3′‐UTR of mRNA, TargetScan, Diana‐tools, miRDB and miRanda programs were exploited; 2) to identify AQP5‐regulating miRNAs, miRNA mimic was transfected in MCF‐7 and MDA‐MB‐231 cells and immunoblotting and luciferase reporter assay was performed; 3) to verify the effect of selected miRNAs in cell migration, migration assay and live cell imaging were performed; and 4) to identify putative target genes of the selected miRNAs, DIANA‐mirPath program was used.ResultsIn silico analysis revealed that 19 miRNAs were identified as a putative regulator of AQP5 and 6 of 19 miRNAs were commonly identified from more than 3 different programs. Among them, selected miRNAs (miR‐185‐3p, miR‐1226‐3p, miR‐19a‐3p and miR‐19b‐3p mimic) were transfected in MCF‐7 and MDA‐MB‐231 cell. Immunoblotting demonstrated that miR‐1226‐3p, miR‐19a and miR‐19b significantly reduced AQP5 protein expression in MDA‐MB‐231 cells. In MDA‐MB‐231 cells, cell migration assay showed a significant decrease when cells were transfected with miR‐1226‐3p mimic (75 ± 6% of control), miR‐19a‐3p mimic (59 ± 6%) or miR‐19b‐3p mimic (39 ± 5%). The miRNA‐induced decreased cell migration was also observed by live cell imaging when cell migration was stimulated by LDL treatment. DIANA‐mirPath program showed that three miRNAs (miR‐1226‐3p, miR‐19a‐3p and miR‐19b‐3p) could be involved in 54 different signaling pathways including MAPK and PI3K/Akt signaling pathways.ConclusionmiR‐1226‐3p, miR‐19a‐3p and miR‐19b‐3p regulate AQP5 protein expression and decrease cell migration of MDA‐MB‐231 cells. Further studies will be needed to examine their involvement in AQP5 regulation and cell migration in an animal model of breast cancer for demonstrating the miRNA‐mediated AQP5 regulation as a potential therapeutic target for breast cancer.Support or Funding InformationThis study was supported by the National Research Foundation of Korea Grants 2014R1A5A2009242 and 2016R1A2B4009365 funded by the Ministry of Science, ICT and Future Planning, KoreaThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Influence of Cigarette Smoking on Myocardial Infarction Induced Renal Damage
Authors: Habeichi Nada , Abidi Emna , Alawasi Hiam , El‐Yazbi Ahmed , Zouein Fouad 
Published: June 2021

Both, cigarette smoking (CS) and myocardial infarction (MI) remain a major public health concern and a leading cause of cardio‐renal morbidity in both males and females. In addition to nicotine, cigarette smoke contains thousands of carcinogenic and non‐carcinogenic chemicals that play a key role in reducing cell viability in renal proximal tubular epithelial cells through acute or chronic pathological mechanisms. In this study, the impact of CS on renal remodeling in both genders was investigated in a mouse model of MI using 2 groups: MI as a control, and MI + CS. Histological analysis of MI group showed alterations in the kidney structure including patchy glomerular retraction which was heightened by two‐fold post‐CS in both genders. As well, molecular analysis revealed that reactive oxygen species production was significantly accentuated in MI+CS compared to MI group similarly in both genders. These findings indicate that CS aggravates MI‐induced renal damage without an exhibition of gender based differences. In order to get more conclusive results, further molecular analysis is under way to study the role of inflammation, and fibrosis on the observed renal changesSupport or Funding InformationSupported by AUB Seed fund #10041This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
GNAS‐PKA Oncosignaling Network in Colorectal Cancer
Authors: Steffen Dana J. , Amornphimoltham Panomwat , Valera Juan Luis Callejas , Taylor Susan , Hunter Tony , Tamayo Pablo , Gutkind J. Silvio 
Published: June 2021

G protein coupled receptors (GPCRs) represent the largest class of drug target among currently approved small molecules. However, there is a dearth of oncology drugs targeting GPCRs. Analysis of cancer genomes reveals that G proteins often harbor activating mutations, inherently making their cognate receptor resistant to modulation. In particular, activated GNAS mutants, encoding a constitutively active, GTPase defective Gαs, can be identified in approximately 5% of all sequenced tumors, including 4% of colorectal cancers (CRCs). By stimulating adenylyl cyclases, GNAS activation leads to the intracellular accumulation of cAMP, a central second messenger, which in turn, activates protein kinase A (PKA). Similarly, 10% of CRC patients harbor gene amplification of GNAS, and another 45% have genetic alterations in PKA subunits, adenylyl cyclases, or phosphodiesterases (which inhibit cAMP accumulation). These findings highlight the importance of understanding oncogenic signaling downstream of GPCRs and the potential role of GNAS‐PKA signaling in CRC. The aim of our study is to define the contribution of the GNAS‐PKA pathway in CRCs and explore the cancer‐associated GNAS‐PKA signaling network. We hypothesize that increased PKA activity downstream of GNAS mutations, or in response to persistent GPCR activation, plays a central role in the growth and progression of CRCs. Preliminary results demonstrate that PKA inhibition significantly reduces tumor burden in xenograft mouse models. Interestingly, activation of GNAS alone in both transgenic and chemical carcinogen mouse models is insufficient to induce tumorigenesis. However, upon the co‐activation of GNAS and RAS, mice show rapid development of squamous cell carcinoma. This finding is strongly supported by bioinformatic analysis revealing a co‐occurrence of GNAS and KRAS mutations clinically. We are currently profiling the GNAS‐PKA pathway by large scale transcriptomic and proteomic experiments to understand signaling circuitries and mechanisms of tumorigenesis. Emerging results from our studies will be presented.Support or Funding InformationDana Steffen was supported by the National Science Foundation Graduate Research Fellowship Program (NSF GRFP) and the UCSD Graduate Training Program in Cellular and Molecular Pharmacology through an institutional training grant from the National Institute of General Medical Sciences (T32 GM007752). This study is supported in part by the San Diego NCI Cancer Centers Council (C3) Collaborative Translational Cancer Research Pilot Grant.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Pharmacological inhibition of HuR improves survival and reduces adverse cardiac remodeling following left‐ventricular pressure overload
Authors: Anthony Sarah R. , Green Lisa C. , Lanzillotta Lindsey , Wu Xiaoqing , Nieman Michelle L. , Blaxall Burns C. , Lorenz John N. , Rubinstein Jack , Xu Liang , Tranter Michael 
Published: June 2021

Human antigen R (HuR) is a widely expressed RNA binding protein that has been implicated in numerous human diseases including cancer, neurological disorders, and cardiovascular disease. We have previously shown that HuR is both necessary and sufficient for induction of hypertrophic signaling pathways in isolated primary myocytes. In addition, data from our lab is the first to suggest that HuR expression and activation is increased in failing human hearts. To determine the role of HuR in hypertrophic signaling in vivo, we created an inducible cardiomyocyte‐specific HuR deletion mouse (iCM‐HuR−/−), and showed that genetic deletion of HuR reduces pathology using a transverse aortic constriction (TAC) model of pressure‐overload‐induced hypertrophy, adverse cardiac remodeling, and heart failure. In this work, we sought to recapitulate this reduction in pathology using KH‐3, a novel pharmacological inhibitor of HuR, to determine the translational potential of HuR inhibition as a viable therapeutic target.Twenty wild‐type mice were randomized to either vehicle or KH‐3 at 4‐weeks post‐TAC, a time‐point consistent with substantial development of cardiac hypertrophy, and monitored via serial echocardiography for a further 7 weeks. Our results show that treatment with KH‐3 increased survival relative to vehicle controls. In addition, as compared with vehicle, KH‐3 treatment significantly abated the continued progression of left ventricular (LV) hypertrophy. This was accompanied by a significant preservation of LV ejection fraction and reduction in LV chamber dilation in KH‐3 treated mice. Importantly, KH‐3 had no effects on systemic blood pressure and no adverse reactions were observed. In conclusion, these results suggest that inhibition of HuR is a promising therapeutic approach to treat pathological LV hypertrophy.Support or Funding InformationThis work was partially funded by an AHA Scientist Development Grant (MT) and NIH R01 HL132111 (MT).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
MiR‐486a‐5p Alters Cell Survival in Ischemia‐Reperfusion Induced Myocardial Injury
Authors: Phan Anh , Luther Kristin , Haar Lauren , McGuinness Michael , Jones Walter K. 
Published: June 2021

Previous work in our lab has shown that mesenchymal stem cells (MSC)‐derived exosomes protect cardiomyocytes from ischemia‐reperfusion (I/R) induced myocardial injury both in vitro and in vivo. We found that microRNA‐486a‐5p (miR‐486) was highly and selectively expressed in MSC‐derived exosomes (1686‐fold relative to MSC (p<0.001)). The role of miR‐486 in cell survival is still debated and miR‐486 has been reported to act as either a tumor suppressor or an oncogene. We hypothesized that miR‐486 upregulation will protect cardiomyocytes from I/R injury. We searched for miR‐486 gene targets using miRanda and Targetscan and found 1687 gene targets. We focused upon targets involving in the cell death and survival pathways, leaving 104 gene targets. Of these 104 targets, program cell death 4 (PDCD4), a tumor suppressor and PTEN, which negatively regulates the PI3K/Akt survival pathway, were chosen for further study based upon considerations of scores for mRNA‐miRNA interaction and the predicted targets. Luciferase reporter gene assays indicated that the 3′‐UTR of PDCD4 and PTEN are both targeted by miR‐486. A mimic and inhibitor (antagomir) of miR‐486 were used to assess its ability to modulate PDCD4, and PTEN expression and Akt activity. Although the mRNA levels of PDCD4 and PTEN were not altered by treatments, immunoblotting results showed a 0.5‐fold reduction in PDCD4 protein expression with miR‐486 mimic and no change in expression with antagomir (n=3). We did not observe a change in PTEN protein levels, and we also saw no change in pAkt/Akt ratio which is regulated downstream of PTEN. Simulated ischemia/reperfusion (sim I/R) was performed on H9c2 cells treated with miR‐486 mimic or scrambled control to measure the cytoprotective effect of miR‐486. H9c2 cells treated with the mimic of miR‐486 showed a significant increase in cell survival by 28–43% (p<0.001, n=4–6) and a reduction of 20% in LDH release compared to control cells (p<0.05, n=6). Western blot results with cell lysate after sim I/R showed a marked decrease in levels of PDCD4, cleaved‐caspase 3 and Bax in the group treated with miR‐486 mimic compared to control cells (p<0.05, n=3). These findings support that miR‐486 upregulation is anti‐apoptotic. Additional studies are needed to discern whether miR‐486 upregulation will reduce cell injury using rodent models, and how much exosomal miR‐486a‐5p contributes to the effects of exosomes and stem cells. Such efforts will lead to a new therapeutic approach for prevention damage of I/R injury.Support or Funding InformationNIH 5R01HL091478 (WKJ)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Down‐Regulation of Gamma‐Adducin Disrupts the Actin Cytoskeleton in FHH rats and May Contribute to the Development of Hypertension‐induced Renal Injury
Authors: Wang Shaoxun , Travis Olivia , He Xiaochen , Fan Fan , Roman Richard 
Published: June 2021

Fawn Hooded Hypertensive (FHH) rat develops chronic kidney disease after onset of hypertension. We previously reported that the expression of Add3 is decreased in various tissues, including kidney and renal vessels in FHH rats. More recently, we demonstrated that Add3 dysfunction contributes to renal vascular dysfunction in FHH rats, and they exhibit enhanced glomerular injury, interstitial fibrosis and proteinuria after the development of hypertension. Add3 is an actin‐binding protein that regulates actin capping and polymerization. The tail of the dimerized adducin protein interacts with actin and spectrin. However, it remains to be elucidated whether Add3 dysfunction alters actin cytoskeleton and contributes to renal microvascular dysfunction in FHH rats. The present study examined the role of Add3 on the regulation of the actin cytoskeleton in a vascular smooth muscle (VSMC) cell line treated with an Add3 DsiRNA, and in primary VSMCs isolated from FHH and FHH. Add3 transgenic rats. Downregulation of Add3 disrupted the actin cytoskeletal structural integrity in VSMC cells transfected with an Add3 DsiRNA (20 nM) in comparison to untreated or scramble siRNA treated cells. F‐actin distribution was significantly reduced in VSMCs isolated from the renal vasculature of FHH (2.4 ± 0.3%/cell, n = 6) vs. FHH. Add3 transgenic rats (11.4 ± 1.7%/cell, n = 6) consistent with disruption of the actin cytoskeleton. In addition, we observed the formation of an F‐actin net in primary renal VSMCs isolated from FHH rats, and reduced expression of the myosin regulatory light chains (MYL12A/B) that regulate actin polymerization and vascular contraction upon phosphorylation. These results suggest that down‐regulation of Add3 disrupts the actin cytoskeleton and the expression of MYL12A/B protein in renal VSMCs. These effects combine to impair the myogenic response of the Af‐art and autoregulation of renal blood flow. This increases transmission of pressure to the glomerulus, which contributes to the development of chronic kidney disease induced by hypertension in the FHH rat.Support or Funding InformationThis study was supported by grants HL36279 (RJR) and DK104184 (RJR), AG050049 (FF), P20GM104357 (RJR, FF ) from the National Institutes of Health; 16GRNT31200036 (FF) from the American Heart Association. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.