bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of Novel Non‐Coding Products of the Pax‐5 Gene and Their Clinical Significance in Lymphoid Cancers
Authors: Hannay Brandon , Dumas Pascal , Veilleux Vanessa , LeBlanc Nicolas , Robichaud Gilles A. 
Published: June 2021

Circular RNAs (circRNAs) are a newly identified class of RNA which are highly expressed and conserved in mammalian cells. With the intrinsic property of being resistant to exonucleolytic activity due to their circular configuration, circRNAs are remarkably stable compared to their linear RNA species counterpart. CircRNAs regulate many biological processes and their aberrant expression is often associated with disease progression. Recently, we have characterized the expression of circRNAs of the potent Pax‐5 oncogene in B cell cancers. In this present study, we set out to identify and establish the expression profiles of Pax‐5 circRNAs in B cell cancers and also, to evaluate the potential of these non‐coding products to act as disease biomarkers. Using RT‐PCR in B cell lines, Pax‐5 circRNAs were amplified with divergent primers. PCR products were then sequenced and aligned for identification and validation. Pax‐5 circRNAs were also evaluated by qPCR from peripheral blood mononuclear cells (PBMCs) from healthy donors and clinical samples. Four circRNA isoforms of the Pax‐5 gene were isolated, sequenced and identified from various B cell models. These latter Pax‐5 circRNA variants consisted of a circular single RNA strand characterized with either exons 2, 3, 4; exons 2, 3, 4, 5; exons 2, 3, 4, 5, 6; or exons 2, 3, 4, 5, 6, 7, 8 of the human Pax‐5 gene. Profiling of Pax‐5 circRNA expression levels in clinical samples reveal an overexpression in chronic lymphocytic leukemia in comparison to other B cell cancer lesions and healthy donors. Altogether, we describe 4 novel gene products (i.e. circRNAs) of the Pax‐5 oncogene in B cell cancers. Preliminary results also support a potential role for Pax‐5 circRNAs as prognostic or diagnostic biomarkers for specific B cell cancers. Further studies are ongoing to validate the correlation between Pax‐5 circRNA levels and disease progression. In addition, the mechanistic elucidation of Pax‐5 circRNAs in cancer processes will also potentially identify new avenues for B cell cancer therapeutic interventions.Support or Funding InformationThis work was supported by grants from the New Brunswick (NB) Innovation Foundation, the Canadian Breast Cancer Foundation, the Canadian Breast Cancer Society/QEII Foundation, the NB Health Research Foundation and by the Beatrice Hunter Cancer Research Institute.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Differential response to apigenin in African American triple‐negative breast cancer in reducing TNF‐α mediated rise in CXCL1
Authors: Soliman Karam F. , Bauer David F. , Mazzio Elizabeth A. 
Published: June 2021

Triple‐negative breast cancer (TNBC) is characterized by the absence of estrogen, progesterone and HER2 receptors. African Americans have higher death rates from TNBC attributable to inadequate preventative health care, late‐stage detection worsened by this being an inherent aggressive malignancy with limited treatment options with the exclusion of hormone receptor‐based chemotherapies. This health disparity may equally be a function of phenotype, where breast cancer can evade the immune system by sequestering tumor‐associated neutrophils and macrophages, in an environment rich in TNF‐α. In this study, we investigated the effects of apigenin, a natural compound from parsley to reduce TNF‐α mediated rise in chemokine (C‐X‐C motif) ligand 1 (CXCL1) in TNBC cell lines of ethnic origin: Caucasian (MDA‐MB‐231) and African American (MDA‐MB‐468). CXCL1 is a known key mediator in neutrophil recruitment and degranulation. The data obtained show that TNF‐α induced greater CXCL1 transcript and protein levels, which were attenuated by apigenin only in the MDA‐MB‐468 cell line. The implications of this warrant further investigation as to the capacity of natural or anti‐cancer agents to act differentially based on the ethnic phenotype of TNBC.Support or Funding InformationSupported by the National Institutes of Health, National Institute on Minority Health and Health Disparities, RCMI grant (8G12MD007582‐28.) and COE grant (P20 MD006738).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Relation of Lsd, Ecstasy and Alcohol Used by Undergraduate Students
Authors: Mendes Maria Clara Chaves , Lauar Gabriela Caetano Vilela , Miranda Renato Pricoli , Taricano Ingrid Dragan 
Published: June 2021

The purpose of this investigation was to compare the individual and combined consumption of LSD – lysergic acid diethylamide, the psychedelic drug that causes visual hallucinations, a distorted sense of time and a feeling of euphoria, ecstasy and alcohol by undergraduation people in São Paulo, Brazil. Young people can mix hallucinogens with other drugs like ecstasy or alcohol to increase the effects. In fact, the average age which many people start using LSD is around 20, but the number of people who abuse LSD today is far less than in the 1960s and 1970s and one factor limiting higher LSD use is a lack of availability.METHODOLOGYThe instrument used for data collection was Google FormsTM. The instant addition of responses to the data set makes this tool appealing for research purposes. Additionally, the respondents involved in the study has been regularly using Google FormsTM, and it was therefore considered the most appropriate method for data collection. The results of the survey was statistically analyzed. Within the various areas the group of students from medical, biology, nursing, engineering, architecture, psychology, and other undergraduate areas, were chosen because their experience using these tools.RESULTSData obtained showed that in a sample of 907 students, 71 (7.82%) students have used LSD, and 42 (59.15%) of these also used ecstasy, but 40 (56.33%) in this group used alcohol with LSD or ecstasy in their experiences. The undergraduate areas that consumed the most, is health (medical students), 29 (40.84%) for LSD and 46 (64.78%) for ecstasy. The undergraduate areas that consumed less than others is biology, 4 (5,6%) for LSD and only one (1,4%) for ecstasy.CONCLUSIONSIn fact, medical students have a high incidence of LSD and ecstasy use with or without alcohol. It's surprising because they supposedly know the damages of this practice, more than the students of other areas. This work was conducted in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration. CAAE(Br)67881517.1.0000.5511. All participants had full understanding and signed informed consent document.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effects of Daily Docosahexaenoic Acid Administration on High Fat Chow‐Induced Enhanced Sensitivity to Dopaminergic Drugs
Authors: Hernandez‐Casner Caroline , Beltran Nina , Ramos Jeremiah , Serafine Katherine 
Published: June 2021

Eating a diet high in fat can lead to several negative health consequences, including obesity, type 2 diabetes and dopamine system dysfunction. For example, rats eating high fat laboratory chow are more sensitive to the behavioral effects of drugs acting on dopamine systems, including direct‐(e.g., quinpirole) and indirect‐acting (e.g., cocaine) dopamine receptor agonists. Dietary supplementation with omega‐3 fatty acids, such as fish oil, can successfully prevent and treat this high fat chow‐induced enhanced sensitivity to dopaminergic drugs. Fish oil contains two omega‐3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), therefore the relative contribution of each fatty acid to the beneficial effects of fish oil are not known. To test the hypothesis that daily injections of DHA will prevent high fat diet‐induced enhanced sensitivity to the behavioral effects of cocaine (1.0–17.8 mg/kg), adolescent female rats ate standard laboratory chow (17% kcal from fat), or high fat chow (60% kcal from fat) in combination with daily injections of DHA or vehicle. Eating high fat chow enhanced sensitivity of female rats to cocaine‐induced locomotion as compared to rats eating standard chow alone. That is, the cocaine‐induced locomotion dose‐response curve was shifted upward in rats eating high fat chow, as compared to rats eating standard chow. Daily injections of DHA did not prevent this effect. Rats receiving daily injections of DHA (regardless of type of chow) gained significantly more weight than rats eating standard chow alone or high fat chow alone. While these results might suggest that EPA, rather than DHA, is the likely omega‐3 fatty acid driving the aforementioned effects of fish oil, only one dose of DHA has been examined thus far. Future experiments will focus on examining different doses of DHA alone and in combination with various doses of EPA to determine the relative contribution of each omega‐3 fatty acid in mediating the beneficial effects of fish oil. These data add to a growing literature regarding the health benefits of fish oil and omega‐3 fatty acids.Support or Funding InformationResearch reported in this abstract was supported by the National Institute of General Medical Sciences of the National Institute of Health under linked Award Numbers RL5GM118969, Tl4GM118971, and UL1GM118970.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Pharmacokinetics and Pharmacodynamics of Morphine and its Major Metabolites Following Intravenous Administration of Four Doses to Horses
Authors: Hamamoto Briana D. , Steffey Eugene P. , Knych Heather K. 
Published: June 2021

ObjectiveTo understand the pharmacokinetics of morphine and correlate the serum values of morphine and its metabolites to pharmacodynamic data.Materials and MethodsUsing a balanced randomized 5‐way crossover design; ten horses received an intravenous injection of saline and morphine at doses of 0.05 mg/kg, 0.1 mg/kg, 0.2 mg/kg, and 0.5 mg/kg. This was repeated until all horses received all treatments. A minimum washout period of 2 weeks was observed between treatments. Blood samples were collected at various time post drug administration, concentrations of morphine, M3G and M6G determined using liquid chromatography‐mass spectrometry and pharmacokinetic analysis performed. Horses were outfitted with step counters and Holter monitors. Gastrointestinal borborygmi, respiration, defecation, and overall demeanor were assessed. Concentrations of parent compound, M3G and M6G were correlated to pharmacodynamic data to better understand the effects of the active metabolites.ResultsMorphine is metabolized into two metabolites in the horse: morphine‐ 6 glucuronide (M6G) and morphine‐3 glucuronide (M3G). Both metabolites and parent compound were detected in the serum as soon as 5 minutes after administration. M3G was found in much higher concentrations than both M6G and parent compound. Concentrations of metabolites and parent compound were dose dependent with the highest concentrations seen in the 0.5 g/kg dose group. Plasma concentrations of morphine fit best in a three‐compartment model and were characterized by rapid distribution and slower elimination phases. Individual pharmacokinetic parameters for metabolites were obtained by noncompartmental analysis. Higher concentrations of M3G correlated with an increase in step count, increase in heart rate, and decrease in gastrointestinal borborygmi seen in the high dose group.Conclusions and Potential ImpactThis project delivers basic pharmacokinetic and pharmacodynamic knowledge of morphine administration to horses and provides valuable information regarding morphine metabolism in horses and the characteristics of these metabolites. The large amount of M3G may be contributing to the neuroexcitatory effects seen in horses after high doses of morphine. Further exploration of the individual effects of the metabolites would be helpful in potentially identifying a novel analgesic. This would be a large advance in veterinary medicine as the number of analgesics available to equine patients currently is limited an often come with severe side effects such as renal failure, gastrointestinal slowing, and increased CNS activity.Support or Funding InformationCalifornia Horse Racing Board Pharmacology Research FundsThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Expression Analysis of Prostaglandin E and F Receptors in Rat Uterus, Mesenteric Artery and Uterine Artery for Development of a Surrogate Assay of Uterine Contractility
Authors: Roberts Melissa , Ferguson Greg , Karras James , van Duin Marcel , Lindstrom Beatriz 
Published: June 2021

Preterm labor occurs in nearly 10% of U.S. pregnancies and is the leading cause of neonatal morbidity and mortality worldwide. Prostaglandins, specifically of the E and F series, play a key role in myometrial contractility and have been recognized as activators of parturition. As such, modulation of select prostaglandin signaling pathways provides a potential approach to pharmaceutical intervention of preterm labor. Prostaglandin E2 is the most abundantly produced prostanoid and functions through four subtypes of G protein coupled receptors (EP1, EP2, EP3, and EP4). It is generally accepted that EP1 and EP3 serve as pro‐contractility receptors while EP2 and EP4 are relaxatory receptors that promote myometrial quiescence. Prostaglandin F2α (PGF2α) functions through the FP receptor and plays an essential role in uterine contractility during preterm or term labor and delivery. The dynamicity and complexity of prostaglandin pharmacology is an important factor to consider during assay development for the testing of molecules which may not be selective to one receptor subtype.Translational ex vivo assays that enhance throughput of drug candidate screening and decrease the use of experimental animals are increasingly desirable. The objective of this research was to determine the relevance of employing either mesenteric resistance artery or uterine artery segments as surrogate tissues to the uterus in the evaluation of prostaglandin‐induced smooth muscle contraction. The relative expression of EP1, EP2, EP3, EP4, and FP receptor mRNA was determined by RT‐qPCR and compared between the uterine body, uterine artery, and mesenteric artery in the rat. Additionally, the efficacy of PGF2α in eliciting contraction was measured by isometric wire myography and compared between the uterine and mesenteric artery.The results of this study demonstrate that rat mesenteric artery may have utility as a model in the screening of prostaglandin receptor‐targeting molecules. Together, these findings will contribute to the identification of suitable and efficient ex vivo assays by which new pharmacological approaches for the treatment of preterm labor can be evaluated.Support or Funding InformationFerring Research Institute, San Diego, CAThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Comparative proteomics of Zebrafish liver in 5 POPs mixture exposure
Authors: Gao Yan , Kwon Oh Kwang , Na An Yae , Kim Ki‐Tae , Lee Sangkyu 
Published: June 2021

Type 2 diabetes mellitus (T2DM) is a major public medical problem with ill‐defined pathophysiological mechanisms and multifactorial etiology. Increasing epidemiological studies have consistently suggested an association between persistent organic pollutant (POPs) and risk of developing T2DM. The POPs have also been reported to negatively affect reproductive, central nervous, or the immune system. In this study, the potential mechanism of POPs induced T2DM was investigated by quantitative proteomics. Five general POPs mixtures, p,p’‐DDT, heptachlor, β‐HCH, hexachlorobenzene and chlorodane were administered to zebrafish for 3 months. Proteomic analysis revealed upregulation of protein Pentaxin in zebrafish. Pentaxin is homologous to C‐reactive protein (CRP) in human, which is widely recognized as an independent risk factor for type 2 diabetes. This finding showed that POPs might be a diabetes inducer. Thus, this study increased the understanding of the relationship between POPs and T2DM in biological and proteomics aspects.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 THE POTENCY AND SELECTIVITY OF THE NOVEL FAAH INHIBITOR BIA 10‐2474 IN COMPARISON WITH PF‐04457845 AND JNJ‐42165279
Authors: Bonifacio Maria Joao , Sousa Filipa , Aires Catia , Loureiro Ana I. , Fernandes‐Lopes Carlos , Palma Nuno , Moser Paul , Soares‐da‐Silva Patricio 
Published: June 2021

In January 2016 one person died and others suffered adverse neurological effects during a Phase I clinical trial of the fatty acid amide hydrolase (FAAH) inhibitor BIA 10‐2474. We have compared the potency and selectivity of BIA 10‐2474 with two other mechanism‐based FAAH inhibitors PF‐04457845 and JNJ‐42165279 which appeared safe in human testing.In whole cells, BIA 10‐2474 inhibited FAAH with an IC50 of 74.4 and 18 nM after 1h and 24h incubation respectively. This compares with 26.2 and 41.5 nM for JNJ‐42165279 at 1 and 24h and 4.3 nm for PF‐04457845 at 1h. All three compounds were characterised as irreversible FAAH inhibitors. Interestingly, BIA 10‐2474 and JNJ‐42165279 were more potent FAAH inhibitors in whole cells as compared to a membrane preparation (4–6 fold more active) when tested after 1h incubation whereas PF‐04457845 was equipotent in the two models (4.3 and 2.0 nM respectively). Neither BIA 10‐2474 nor JNJ‐42165279 accumulated inside the cells.Activity based protein profiling in vitro identified only ABHD6 as an off‐target for BIA 10‐2474 with no activity against other rat brain serine hydrolase enzymes up to 100 mM. In contrast PF‐04457845 and JNJ‐42165279 both interacted with ABHD11. BIA 10‐2474 had no significant activity against 220 other human off‐targets in binding and enzyme studies up to 50 μM. In contrast, PF‐04457845 showed significant activity (>50% inhibition) at 37 sites at 50 μM, including cannabinoid receptors, serotonin receptors, and several ion channels.In vivo, oral administration of BIA 10‐2474 inhibited rat brain and liver FAAH with ED50s of 13.5 and 6.2 mg/kg PO respectively and increased brain levels of fatty acid amides over the same dose range. This compares with 4.3 and 2.0 mg/kg PO for PF‐04457845 and 12.5 and 3.7 mg/kg PO for JNJ‐42165279. Exposure levels of BIA 10‐2474 in plasma and brain were consistent with the potency identified in whole cells and there was no evidence for accumulation in the brain of either BIA 10‐2474 nor its main metabolites following repeated administration.These data suggest that the in situ and in vivo potency and the selectivity of BIA 10‐2474 is comparable to other clinically tested FAAH inhibitors. These data also demonstrate that there is no unusual accumulation of BIA 10‐2474 or its metabolites in cells nor in the CNS. In conclusion, these results fail to identify an off‐target activity or a mechanism that could explain the clinical trial accident.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Altered dopamine transporter function and immunoregulation in PD macrophages
Authors: Mackie Phillip , Gopinath Adithya , Saadatpour Leila , Pino Jose , Khoshbouei Habibeh 
Published: June 2021

Parkinson's Disease (PD), the second‐most common neurodegenerative disorder, has three key hallmarks: dysregulated dopamine (DA) signaling in part due to degeneration of Substantia Nigra neurons, intracellular aggregates of a‐synulcein, and neuroinflammation. However, the origin and interplay of these features remains unclear. DA substitution therapy, the standard pharmacological treatment, only alleviates symptoms with limited efficacy. Interestingly, plasma DA levels are altered in PD, and DA can regulate immune cell function in the periphery. Additionally, the dopamine transporter (DAT), a potent regulator of DA tone in the CNS, also exists on leukocytes. However, although it is characterized in the CNS and is a therapeutic target for some neurological disorders, its function in the periphery is largely unknown. Our study asks how DAT regulation of plasma DA modulates the peripheral immune system. To begin to address this hypothesis, we first used biochemical and microscopy approaches to examine DAT distribution and function in the healthy monocyte‐derived human macrophages (MDM). We found DAT constitutively exists in human MDM and is localized to the plasma membrane and in the intracellular space (n=10 biological replicates). We demonstrated the DAT molecules on the human MDM are functional as measured by uptake of IDT307, a fluorescent DAT substrate, and of 3H‐DA (Km=3.178). In addition we found DAT is subjected to canonical trafficking such as PKC‐dependent endocytosis as measured by Total Internal Reflection Florescence Microscopy (TIRF‐M). These data are consistent with the overarching hypothesis that immuno‐activation of human MDM regulates DAT activity and thus dopamine transmission. We discovered lipopolysaccharide (LPS)‐immuno‐activation of human macrophages recruits DAT to the membrane leading to increased surface DAT localization (n= 4 biological replicates P < 0.05). Contrary to our prediction, our preliminary data suggests a decrease in nomifensine‐sensitive, DAT‐mediated substrate uptake. Furthermore, we have also found that basal DAT‐dependent uptake in PD macrophages is elevated (p<0.0001, n=5 biological replicates), and our preliminary data suggests reduced sensitivity to LPS‐induced trafficking. Using simultaneous whole cell patch clamp electrophysiology and amperometry, we are currently testing the hypothesis that LPS‐induced TLR4 activation of macrophages stimulates DAT trafficking to the membrane and stabilizes the transporter in an efflux promoting conformation. We then plan to test the hypothesis that PD macrophages are immunocompromised, exhibiting an altered DAT response to LPS‐stimulation.Support or Funding InformationR21NS103108 R21DA043895This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.