bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pre‐meal glucose drink, but not video game playing, suppresses food intake in overweight and obese boys (1040.8)
Authors: Gheller Brandon , Akhavan Tina , Pollard Damion , Gladanac Branka , Constantino Monika , Luhovyy Bohdan , Bellissimo Nick 
Published: June 2021

We previously reported decreased food intake (FI) after a glucose drink and 30 min of video game playing (VGP) in normal weight boys, but the effect on FI in boys with increased adiposity is unknown. Therefore, we examined the effect of 30 min of pre‐meal VGP on subjective appetite, emotions and FI in overweight/obese (>85th BMI percentile) boys after a glucose drink. On four mornings, in random order and one‐week apart, boys (n = 22; age = 11.9 ± 0.3 y) consumed equally sweetened drinks (250 mL) of sucralose (0 kcal) or 50 g (200 kcal) glucose, with or without 30 min of subsequent VGP, 2 h after a standardized breakfast. Immediately after all test conditions FI (mean ± SEM kcal) from an ad libitum pizza meal was measured. Subjective appetite was measured at baseline (0 min), 20, 35, and 65 min (post‐meal). While glucose (p < 0.01) decreased FI (∆ = ‐103 ± 48 kcal) compared with the sucralose control, cumulative FI (drink kcal + meal kcal) was higher (p < 0.01). Fullness (p < 0.05) was lower, and subjective aggressiveness (p < 0.01), excitement (p < 0.01), upset (p = 0.05), and frustration (p < 0.05) higher after VGP; however, subjective emotions did not correlate with FI. In conclusion, the stronger effect of glucose compared with VGP on FI is indicative of the primary role of physiologic factors in the short‐term regulation of FI in overweight/obese boys.Grant Funding Source: Supported by The Danone Institute of Canada, Grant‐in‐aid program
d‐δ‐Tocotrienol promotes the differentiation of murine MC3T3‐E1 preosteoblasts (1045.37)
Authors: Shah Anureet , Yeganehjoo Hoda , Juma Shanil , DiMarco Nancy , Mo Huanbiao 
Published: June 2021

Osteoblasts and osteoclasts play essential and opposite roles in maintaining bone homeostasis. Osteoblasts fill cavities excavated by osteoclasts. The mevalonate pathway provides essential prenyl pyrophosphates for the activities of GTPases that promote differentiation of osteoclasts but suppress that of osteoblasts. Preclinical and clinical studies suggest that mevalonate suppressors such as statins increase bone mineral density and reduce risk for bone fracture. Tocotrienols down‐regulate 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG CoA) reductase, the rate‐limiting enzyme in the mevalonate pathway. In vivo studies have shown the bone‐protective activity of tocotrienols. We hypothesize that d‐δ‐tocotrienol, a mevalonate suppressor, induces differentiation of murine MC3T3‐E1 pre‐osteoblasts. Alizarin staining showed that d‐δ‐tocotrienol (0‐15 μmol/L) induced mineralized nodule formation in a concentration‐dependent manner in MC3T3‐E1 preosteoblasts. d‐δ‐Tocotrienol (0‐25 μmol/L), but not d‐α‐tocopherol (25 μmol/L), significantly induced alkaline phosphatase activity, an indicator of preosteoblast differentiation. Concomitantly, western‐blot analysis showed that d‐δ‐tocotrienol down‐regulated HMG CoA reductase. d‐δ‐Tocotrienol (0‐25 μmol/L) had no impact on the viability of MC3T3‐E1 preosteoblasts following 48‐h incubations, suggesting lack of cytotoxicity at these doses. Tocotrienols and other mevalonate suppressors have potential in maintaining bone health.Grant Funding Source: Supported by USDA NIFA Agriculture and Food Research Initiative Grant 2009‐02941, TDA & TWU REP.
Expressional profiling of carcinoembryonic antigen‐related microRNAs in human gastric cancer (1047.14)
Authors: Zhang Guo , Ye Hui‐Lan , Yao Ping , Nong Bing , Li Jing 
Published: June 2021

MicroRNAs (miRNAs) are a group of non‐coding small RNAs (ncRNAs) that negatively regulate gene expression at the post‐transcriptional level in cellular differentiation and carcinogenesis. Given that carcinoembryonic antigen (CEA) is commonly used for diagnosis of GI cancer for decades, the present study aimed to screen and identify the CEA related miRNAs in gastric cancer tissue and determine their potential pathophysiologic relevance as well. In this study, a total of fivety gastric tissue samples inculing 17 pairs of cancer and adjacent tissure and 16 healthy volunteers control were collected and confirmed by endoscopic biopsy. The microRNA expression was then deteted and profiled in these samples by using QuantoBio three steps based q‐PCR. QuantoIC‐1 and QuantoIC‐2 were simultaneously conducted as the internal controls. As results, miR‐10a,miR‐18a* as well as miR‐27a* are significantly up‐regulated and miR‐148a* down‐regulated in the carcinoma tissue and additionally, miR‐10a, miR‐122*, miR‐129‐5p and miR‐378 are dramatically up‐regulated in pericarcinous tissue versus healthy control. Compared with pericarcinous control, miR‐10a, miR‐148a*, miR‐193b and miR‐378 are apparently down‐regulated in cancer. Interestingly, further bioinformatics analysis has shown that CEA‐mRNA molecule was found to be a common target for all these miRNAs. Altogether, our date indicated that multiple miRNAs were substantially involved in the gastric cancer development. Such miRNAs as miR‐18a* and miR‐10a with increase expressional pattern in stomach carcinoma may potentially servers as novel oncogenes during the process of this malignant desease.Grant Funding Source: Supported by 2010GXNSFC013020 to G.Z.
Antiangiogenic therapies and aged‐associated changes in the prostate: a comparison between the prostate of aging mice (FVB) and TRAMP mice (1048.7)
Authors: Cagnon Valeria , Montico Fabio , Kido Larissa , Hetzl Amanda 
Published: June 2021

Senescence and angiogenesis are related to prostate alterations. The aim was to characterize TGF‐β, FGF‐2, IGFR‐1, MMP‐9, VEGF and endostatin responses in the prostate of the elderly mice submitted to antiangiogenic and finasteride therapies in relation to the prostate of TRAMP mice. Experimental groups: Young group; Prostatic Intraepithelial Neoplasia and Prostate Cancer groups; Senile group; SU5416 group; TNP‐470 group; SU5416+TNP‐470 group; Finasteride group; SU5416+TNP‐470 and Finasteride group. After 21 days, prostates were collected for light microscopy, immunohistochemistry and western blotting. Senescence led to inflammation and proliferative processes. Increased MMP‐9, IGFR‐I, VEGF, FGF‐2 and TGF‐β levels were verified in senile mice. TRAMP mice presented MMP‐9, IGFR‐1, VEGF, FGF‐2 increase. TGF‐β level did not increase in the cancer group. Antiangiogenic therapies showed VEGF, TGF‐β, MMP‐9 and IGFR‐1decrease. The indirect angiogenesis inhibitor acted mainly on MMP‐9 and the direct inhibitor in IGFR‐1 levels. Senescence predisposes prostatic malignant changes. The balance between anti and pro‐angiogenic factors was evident in the combination of the three drugs. The activation of distinct pathways by each drug differentially influenced factors involved in tumor‐promoting processes. TGF‐β could be involved in the preneoplastic lesions.Grant Funding Source: Supported by Research Foundation of the State of Sao Paulo (Fapesp 2012/03010‐4 / 2011/01968‐30
Goniothalamin and Celocoxib therapies on the preneoplastic and neoplastic prostatic lesions in the transgenic adenocarcinoma of the mouse prostate model (TRAMP) (1048.8)
Authors: Cagnon Valeria , Kido Larissa , Montico Fabio , Dall Pozzo Caroline , Carvalho João , Costa Debora , Pilli Ronaldo 
Published: June 2021

Inflammation plays an important role on prostate diseases. The aim of this study was to evaluate and compare the structural and molecular features of the ventral lobe from TRAMP mice undergoing Celecoxib treatment, a nonsteroidal anti‐inflammatory, and Goniothalamin, a synthetic substance, exhibiting anti‐inflammatory and antiproliferative properties. The mice were divided into: Control groups; Tramp: 8 week‐old mice; Tramp:12‐week‐old mice. Treated groups: Celecoxib‐10mg/kg; Goniothalamin‐150mg/kg. The ventral lobe was collected after 4 weeks for light microscopy, immunohistochemistry and western blotting. Structural analysis showed that TRAMP mice developed progressive forms of preneoplastic and neoplastic lesions during their lifetime. Both treatments led to a decrease for cell proliferation and also inflammatory cells. The Celocoxib treatment showed decreased COX‐2, IGFR‐1, STAT‐3 and IL‐17 immunoreactivities. Goniothalamin treatment displayed a stronger IGFR‐1, STAT‐3 and IL‐17 reduction, in contrast to COX‐2 with no change. Thus, both treatments were effective in reducing the progression of prostatic lesions and inflammation. However, the Goniothalamin treatment suggested the most significant effect on the pro‐inflammatory cytokine and on a transcription factor signal transducer, acting in many pro‐oncogenic signals, thus delaying prostate cancer progression.Grant Funding Source: Research Foundation of the State of Sao Paulo (2012/03010‐4/ 2013/01294‐8)
Hyperhomocysteinemia aggravates endothelial dysfunction via EDHF impairment in resistant arteries of db/db mice (1051.13)
Authors: Cheng Zhongjian , Jiang Xiaohua , Fang Pu , Yang Xiaofeng , Wang Hong 
Published: June 2021

Aims: The objective of this study was to examine the effect of hyperhomocysteinemia (HHcy)─elevated plasma Hcy level on endothelial function in resistant arteries of type 2 diabetic db/db mice.Methods and Results: Moderate HHcy (plasma tHcy=54.31±5.4 µmol/L) was developed in diabetic db/db mice fed with a high methionine diet (HM, 2% methionine) for 8 weeks starting from age of 8 weeks, whereas non‐diabetic db/+ mice developed mild HHcy (plasma tHcy=34.21±4.15 µmol/L). HHcy increased blood glucose levels from 474±29 mg/dl to 630±83 mg/dl in diabetic mice (p<0.05), whereas HHcy did not affect blood glucose levels in non‐diabetic mice. Endothelium‐dependent vascular relaxation to acetylcholine (Ach) was significantly impaired in the small mesenteric artery (SMA) of diabetic mice. Mild HHcy did not impair endothelium‐dependent vascular relaxation response to Ach in non‐diabetic mice. Moderate HHcy aggravated the impairment of vascular relaxation response to Ach in diabetic mice both in the presence or absence of eNOS inhibitor L‐NG‐nitroarginine methyl ester (L‐NAME). HHcy‐induced impairment of relaxation response to Ach in diabetic mice was diminished in the presence of L‐NAME plus intermediate‐conductance calcium‐activated potassium channel (IKCa) inhibitor tram‐34 and small conductance KCa (SKCa) blocker apamin. Our results suggest that impairment of endothelium‐derived hyperpolarizing factor (EDHF) via inactivation of IKCa and SKCa plays a critical role in HHcy‐aggravated endothelial dysfunction in the resistant artery of diabetic mice. Moreover, 40Gap27 and 43Gap26 significantly improved vascular relaxation response to Ach in mice with moderate HHcy and diabetes. Finally, HHcy significantly impaired endothelium‐independent vascular relaxation to sodium nitroprusside in diabetic mice.Conclusions: These findings demonstrate that HHcy‐induced impairment of EDHF may be resulted from inactivation of IKCa/SKCa and suppression of connexin 40 and connexin 43.Grant Funding Source: NIH
Reversal of diabetic stem‐cell mobilopathy by angiotensin‐(1‐7) via rho‐kinase downregulation (1051.5)
Authors: Vasam Goutham , Raizada Mohan , Jarajapu Yagna 
Published: June 2021

Mobilization of bone marrow stem/progenitor cells (BMSPCs) that maintain cardiovascular health is impaired in diabetes. We have previously shown that Angiotensin (Ang)‐(1‐7) increases the vasoreparative potential of dysfunctional BMSPCs from individuals with diabetes. In this study we tested the effect of Ang‐(1‐7) on the impaired mobilization of BMSPCs in diabetes. Furthermore, the role of Rho‐kinase in the beneficial effects of Ang‐(1‐7) was evaluated. Lean control or obese db/db (type 2 diabetic) (DB) mice were treated with continuous infusion of saline or Ang‐(1‐7) (1 µg/Kg/min) for four weeks by using subcutaneous osmotic pumps. Subsets of peripheral blood lineage‐negative cells, Lin‐Sca‐1+, Lin‐cKit+ and Lin‐Sca‐1+cKit+ cells, were enumerated after four weeks of treatment. All subsets of BMSPCs were lower in DB (compared to control, P<0.05), and were increased by Ang‐(1‐7) treatment to control levels. The number and proliferation of BM‐resident SPCs, and the migration to stromal‐derived factor‐1α (SDF, 100 nM) ex vivo were reduced in DB compared to control group (P<0.01) and this dysfunction was reversed to normal by Ang‐(1‐7) treatment. Expression of Rho‐kinase isoforms, ROCK‐1 and ROCK‐2, were higher in DB‐BMSPCs (compared to control, P<0.01) that was down‐regulated by Ang‐(1‐7) to normal levels. Furthermore, ex vivo treatment of BMSPCs from DB with a non‐specific ROCK inhibitor, Y27632 (10 μM), restored their migration to SDF. These results suggest that Ang‐(1‐7) increases BMSPC‐mobilization in diabetes, in part, via down‐regulation of ROCK. Together with our previous observations, Ang‐(1‐7) appears to be a promising target for the treatment of diabetic stem‐cell mobilopathy and for enhancing the outcomes of cell‐based therapies in individuals with diabetes.Grant Funding Source: Supported by American Heart Association‐13SDG16960025
TPA‐induced invasion of HT29 cells are mediated through ROS production and AMPK deactivation (1055.5)
Authors: Banskota Suhrid , Kim Jung‐Ae 
Published: June 2021

AMP‐activated protein kinase (AMPK) is a member of serine/threonine protein kinase which serves as an energy sensor in all eukaryotic cells. In the present study, the role of AMPK in cancer cell metastasis was investigated. We found that 12‐O‐tetradecanoyl phorbol‐13‐acetate (TPA), a tumor promoter, induced invasive behavior of HT‐29 colorectal cancer cells, which corresponded to increased ROS production and MMP‐7 expression, whereas TPA suppressed phosphorylation of AMPK in the cells. The TPA‐induced reactive oxygen species (ROS) production and invasion of HT29 cells were inhibited by NADPH oxidase inhibitors (apocynin and diphenyleneiodinium), ROS scavengers (Vitamin C and Vitamin E), and AMPK activator (AICAR). Taken together, TPA induces transition of epithelial HT29 colon carcinoma cells to invasive mesenchymal phenotype through NADPH oxidase activation and AMPK inactivation.Grant Funding Source: This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea
Symmetry considerations provide a new novel open channel blocker of GABA‐A receptors (1059.2)
Authors: Sigel Erwin , Pangerl Michael , Carta Valentina , Baur Roland , Trauner Dirk 
Published: June 2021

The major GABA‐A receptor isoform in the mature central nervous system is α1β2γ2. Upon activation, the GABA‐A receptor conducts Cl‐ through its pore, causing an inhibitory effect on neurotransmission by diminishing the chance of action potential firing. The GABA‐A receptor is inhibited by epileptogenic agents such as picrotoxin, which act as a noncompetitive inhibitor of GABA‐induced currents. We screened molecules with near five‐fold symmetry for inhibition of GABA‐A receptors. α1β2γ2, receptors were expressed in Xenopus oocytes. One of the molecules, MP7, inhibited currents elicited by GABA with comparable potency as picrotoxin. This inhibition showed all characteristics of an open channel block. At lower concentration of GABA an additional potentiation was evident. MP7 also inhibited α1β1γ2 and α1β2δ GABA‐A receptors, homomeric and heterogenic glycine receptors and Drosophila insecticide resistant GABA‐A receptors. At higher concentrations (> 10 μM) MP7 by itself induced small permanent and huge transient currents upon voltage jumps, indicating that MP7 can dissolve in the membrane and permeate to some extent. To identify important residues of the pore‐lining segment M2 involved in the interaction with the blocking molecule MP7, point mutations to cysteine were introduced. The reactivity with water‐soluble cysteine‐reactive reagents and the reduction of this reactivity by MP7 showed that the blocker acts in the transmembrane segment M2 at the level of α1V257 / α1T261. MP7 could potentially have use as insecticide.Grant Funding Source: Supported by the Swiss National Science Foundation grant 31003A‐132806/1 to E.S.
In vivo inhibition of hepatitis C virus infection by anti‐Claudin‐1 monoclonal antibodies (1062.9)
Authors: Iida Manami , Nagase Shotaro , Yamashita Mayo , Shirasago Yoshitaka , Fukasawa Masayoshi , Tada Minoru , Ishii Akiko , Watari Akihiro , Yagi Kiyohito , Kondoh Masuo 
Published: June 2021

More than 170 million people worldwide are infected with hepatitis C virus (HCV). Despite concerted research efforts, anti‐HCV agents resistant to the high mutability of the HCV RNA genome have not yet been produced. Claudin 1 (CLDN1) is a co‐receptor for HCV entry into hepatocytes and is an attractive potential target for HCV therapy, because such host factors are genetically stable. Here, we investigated the effects of 4 previously generated mouse anti‐CLDN1 antibodies on HCV infection. All 4 clones attenuated the infection of Huh7 cells by HCV (genotype 2a) and HCV pseudoviral particles (HCVpp, genotypes 1b and 2a). Two of 4 clones also prevented HCV (genotype 1b) infection of human‐liver‐chimeric mice. Injection of mouse anti‐CLDN1 antibodies did not adversely affect serum human albumin levels, apparent character, and motility. For future clinical application, we prepared human‐mouse chimeric anti‐CLDN1 antibodies. The chimeric antibodies prevented HCV and HCVpp infection of Huh7 cells as effectively as did the mouse antibodies. Our findings suggest that mouse and mouse‐human chimeric anti‐CLDN1 antibodies prevent HCV infection and may therefore be promising candidate anti‐HCV agents.Grant Funding Source: supported by the Ministry of Health, Labor, and Welfare of Japan
Contribution of guanine nucleotide exchange factor Vav2 to homocysteine‐induced NLRP3 inflammasome activation in mouse podocytes (1063.6)
Authors: Abais Justine , Xia Min , Boini Krishna , Li Pin‐Lan 
Published: June 2021

NADPH oxidase‐derived reactive oxygen species (ROS) have been demonstrated to mediate the activation of podocyte NLRP3 inflammasomes in response to elevated levels of homocysteine (Hcys). We have also previously provided evidence that the guanine nucleotide exchange factor Vav2 exhibits high specificity to Rac1‐mediated NADPH oxidase activation by elevated Hcys. The precise role of Vav2 in NLRP3 inflammasome activation remains unknown. The present study was designed to test whether Vav2 contributes to Hcys‐induced NLRP3 inflammasome activation through activation of NADPH oxidase. In our experiments, podocytes were transfected with either a scramble, constitutively active form of Vav2 (oncoVav2) or Vav2 shRNA plasmid directly to the nucleus via nucleofection. Confocal microscopic analysis showed Hcys treatment as well as oncoVav2 transfection alone increased colocalization between inflammasome proteins NLRP3 with ASC and NLRP3 with caspase‐1, suggesting NLRP3 inflammasome formation. Additionally, both Hcys treatment as well as oncoVav2 transfection alone resulted in increased caspase‐1 activation and IL‐1β production, signifying NLRP3 inflammasome activation. These Hcys‐induced measures of inflammasome formation and activation were all inhibited by Vav2 shRNA transfection, observed in decreased colocalization of inflammasome components, caspase‐1 activity, and IL‐1β production in podocytes. Furthermore, Vav2 shRNA transfection also prevented podocyte damage by restoring impaired VEGF secretion as well as decreased podocyte marker podocin expression seen in Hcys injured podocytes. Together, these findings suggest that NADPH oxidase activation by Vav2 overexpression by oncoVav2 was sufficient to activate NLRP3 inflammasomes, independent of Hcys treatment. However, Vav2 inhibition was able to inhibit Hcys‐induced NLRP3 inflammasome activation and podocyte injury, further substantiating the role of Vav2 in this mechanism.Grant Funding Source: Supported by NIH grants DK54927 and 1F31AG043289
Early life stress induces bladder dysmotility in adult rats (1065.17)
Authors: Kennedy Dawn , Mohammadi Ehsan , Hurst Robert , Greenwood‐Van Meerveld Beverley 
Published: June 2021

Symptoms of painful bladder syndrome (PBS) including urgency and pain are common in female patients who report early life stress (ELS) such as neglect or abuse during childhood. We hypothesized that ELS contributes to PBS by inducing abnormal bladder detrusor muscle contractility in adulthood. This study used an odor‐attachment model in which female rats were conditioned on postnatal days (PND) 8‐12 using predictable or unpredictable odor‐shock conditioning, or an odor only control. In adulthood, bladder muscle strips were harvested and mounted in a muscle bath to measure contractile responses to neurally mediated signalling (electrical field stimulation‐EFS), muscarinic receptor‐dependant signalling with carbachol, and membrane depolarization with KCl. Detruser muscle responses to EFS were significantly decreased (P<0.001) in the unpredictable (12.6±2g/cm2) compared to the predictable (24.9±2g/cm2) or odor only (24.0±1.3g/cm2) groups. Detrusor muscle responses to CCh or KCl were not significantly different between groups. Our data indicate that ELS alters neurally mediated detrusor muscle contractility in the absence of abnormalities in smooth muscle myogenic responses. These findings suggest that therapeutics targeting neural innervation of the bladder musculature could effectively reduce PBS symptoms by normalizing bladder contractility in adulthood.Grant Funding Source: This work was supported by a department of Veterans Affairs Merit Grant to Dr. Beverley Greenwood‐Va
Inhibition of soluble epoxide hydrolase by t‐AUCB modulates coronary reactive hyperemia in isolated mouse hearts (1071.3)
Authors: Hanif Ahmad , Morisseau Christophe , Nayeem Mohammed 
Published: June 2021

Coronary reactive hyperemia (RH) is impaired in hypertrophic hearts and in hearts with metabolic syndrome. Epoxyeicosatrienoic acids (EETs) exert cardioprotective effects against ischemia / reperfusion injury. Soluble epoxide hydrolase (sEH) is the main enzyme responsible for EETs breakdown. We hypothesized that the inhibition of sEH results in increased RH in C57BL/6J isolated mouse hearts through increased generation of EETs compared to non‐treated mouse hearts in response to no‐flow ischemia. Coronary flow (CF) in isolated C57BL/6J wild type mouse hearts was measured before and after sEH‐inhibition using a well characterized and selective sEH inhibitor, trans‐4‐[4‐(3‐adamantan‐1‐yl‐ureido)‐cyclohexyloxy]‐benzoic acid (t‐AUCB) in Langendorff system. In each experiment we used the same isolated heart as its own control. Perfused isolated hearts were exposed to 15‐second ischemia and RH parameters were assessed before and after 15‐minute infusion of t‐AUCB (10‐5 M). Following ischemia, flow repayment (calculated as the area under the curve and normalized to heart weight (ml/g)) was significantly increased in response to t‐AUCB (5.84 ± 0.80 in vehicle vs. 9.52 ± 1.68 in t‐AUCB, p<0.05). Moreover, t‐AUCB significantly increased baseline coronary flow (16.62 ± 0.85 in vehicle vs. 14.59 ± 0.63 in t‐AUCB, p<0.05). Also, we observed that t‐AUCB tends to increase repayment to debt ratio (1.53 ± 0.22 in vehicle vs. 2.32 ± 0.43 in t‐AUCB). No significant differences were observed in debt area, peak hyperemic flow and repayment duration between the two groups. Our results demonstrate that sEH inhibition by t‐AUCB significantly increases RH. These data suggest that sEH inhibition by t‐AUCB could have a beneficial effect on myocardial recovery from ischemic insult. Supported by HL‐114559 to MANGrant Funding Source: Supported by HL‐114559 to MAN