bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary excess selenium regulates the transcription of pancreatic selenoproteome in chicken
Authors: Li Jin‐Long , Li Wei , Xiang Li‐Run , Cao Chang‐Yu , Jiang Xiu‐Qing , Zhu Shi‐Yong 
Published: November 2023

BackgroundRecently, numerous studies have found high Selenium (Se) influences the pancreas in mammals. However, little is known about the influence of high Se in the pancreatic tissue in avian.ObjectiveWe attempted to characterize the relationship between dietary Se, the selenoprotein, and the pancreas in chicken. This project will provide certain help for poultry farming and provide a reference for medicine.Methods1‐day‐old chickens received different quantities of dietary Se (0.15 mg, 3.0 mg, or 5.0 mg Se/kg of diet) for 8 weeks. Blood samples were analyzed immediately for glucose content at 2nd, 4th, 6th, and 8th week. The pancreas tissue was collected and examined for the activity of selenoenzymes (GPX, TrxR), and antioxidant related factors (T‐AOC, MDA, GSH) and mRNA expression of the transcriptome of selenoproteins at 4th and 8th week.ResultsIn the 5.0 mg Se/kg group, a significant increase (P<0.05) in blood glucose was observed. Dietary excess Se influenced on four antioxidant factors, such as T‐AOC, H2O2, MDA, and CAT. From these data, we observed that excess Se induces decreased antioxidant capacity of pancreatic tissue. At super‐nutritional Se (3.0 mg/kg), most selenoproteins were up‐regulated in chicken pancreatic, but Gpx3, Sepp2, and Selu was only down‐regulated.ConclusionDietary Se level can inluence the pancreatic antioxidant capacity by regulating the activity and transcription of selenoenzymes. These results indicate that excess Se induces pancreatic dysfunction through selenoproteins. Dietary Se status stabilizes pancreatic normal physiology function via regulation of the selenoprotemic transcriptions. We hypothesize that hierarchy of regulated the transcriptions of selenoproteome makes an important roles of renal Se metabolism and transport in avian.Support or Funding InformationChina New Century Excellent Talents in University (No. NECT‐1207‐02), National Natural Science Foundation of China (No. 31572586) and Academic Backbone Project of Northeast Agricultural University (No. 15XG16).
Choline and betaine alter fetal brain expression of genes related to docosahexaenoic acid availability in a mouse model of gestational diabetes
Authors: Joselit Yaelle , Jack‐Roberts Chauntelle , Axen Kathleen , Jiang Xinyin 
Published: November 2023

Gestational diabetes mellitus (GDM) is associated with lower cord blood docosahexaenoic acid (DHA) concentrations, which can potentially delay brain development of affected infants. Phosphatidylcholine synthesized via the de novo pathway is enriched with DHA, thereby providing an available source of DHA. Using a mouse model of GDM, we assessed whether supplementation of dams with choline or its oxidative derivative, betaine, modified the expression of genes related to DHA availability in fetal brains. C57BL/6J female mice were fed a high‐fat diet (60% kcal from fat) six weeks before and throughout gestation to induce GDM‐like symptoms. The animals received 25 mM choline chloride, 1% betaine, or control drinking water until embryonic day 17.5. Fetal brain samples were collected for gene expression analysis. Betaine supplementation in the high‐fat fed dams increased the expression of fatty acid binding protein 7 (Fabp7), which transports DHA, and Fabp5, which transports saturated fatty acids in fetal brains. Choline supplementation did not alter the expression of Fabp genes. However, choline upregulated expression of phospholipase A2 (Pla2g6), which releases DHA from the middle position of the glycerol backbone of phospholipids such as phosphatidylcholine, enhancing availability of free DHA in the brain. Expression of arachidonate 15‐lipoxygenase, cyclooxygenase‐2, and brain‐derived neurotrophic factor were not altered by choline or betaine supplementation. Our results support a role for maternal choline or betaine supplementation in modifying DHA availability in fetal brain by altering gene expression in the offspring of GDM dams.Support or Funding InformationNIH, New York Academy of Sciences, PSC‐CUNY
Effects of Zinc Supplementation on Carnitine and Lactate Concentrations in Cultured Liver Cells
Authors: Barton‐Wechsler Silena , Stachura David L , Ho Emily , Housley Lauren 
Published: November 2023

Zinc is an essential cofactor involved in hundreds of biochemical reactions in the human body and serves many critical roles in human health, including the support of energy metabolism. Zinc deficiency is a major public health concern, leading to over 450,000 deaths annually in children under the age of five. Even marginal deficiencies may result in negative health effects if left untreated. Currently, it is challenging to reliably detect and study the health impact of marginal zinc deficiency, because a sensitive, reliable biomarker of zinc status has not yet been characterized. Metabolomics is an emerging tool that has shown promise in biomarker discovery. Analysis from a randomized, placebo‐controlled clinical trial, employing metabolomics analysis, revealed changes in plasma metabolite profiles that identified prospective biomarkers of zinc status. Specifically, our analysis revealed that carnitine (p = 0.04) and lactate (p = 0.02) concentrations were increased in human plasma following zinc supplementation. To further establish if the change in zinc nutriture led to the observed changes in the levels of these energy metabolism‐associated metabolites, we grew human liver cells (HepG2) in media with different levels of zinc to mimic states of zinc deficiency (0.7μM ZnSO4), zinc adequacy (2.9 μM ZnSO4), and zinc supplementation (10.0 μM ZnSO4). One group of cells cultured in zinc‐deficient media was transferred to zinc‐supplemented media to mimic conditions in the previous clinical trial. Following growth in these differential media, carnitine and lactate levels were quantified by colorimetric assays and revealed differential effects of zinc status. This study provides information on the effects of zinc on energy metabolism in humans and informs research aimed at characterizing a sensitive, reliable biomarker for assessing zinc status in humans.Support or Funding InformationCalifornia State University:Office of Graduate Studies, Research and Conferences AwardDepartment of Nutrition and Food Science
YAP/TAZ Regulate Hepatic Stellate Cell and Portal Fibroblast Proliferation After Hepatic Ischemia/Reperfusion Injury
Authors: Konishi Takanori 
Published: November 2023

IntroductionHepatic ischemia/reperfusion (I/R) injury is a major complication after liver resection, liver transplantation, and trauma, however, the precise mechanisms of liver recovery after I/R have not been elucidated. The Hippo signaling pathway and their downstream effectors, Yes‐associated protein (YAP) and transcriptional co‐activator with PDZ‐binding motif (TAZ), have been identified as key regulators of regulating cell proliferation and organ size. In the current study, we sought to determine the expression of YAP and TAZ and their contribution to liver recovery after I/R.MethodsA murine model of partial hepatic ischemia/reperfusion (I/R) was used to study liver recovery after injury. Hepatic stellate cell and portal fibroblast in liver tissue were assessed by immunonhistochemical staining for desmin. Tissue levels of PDGF‐BB and TGF‐b1 were measured by enzyme‐linked immunosorbent assay (ELISA). The expression of YAP/TAZ and their related protein were measured by immunohistochemical staining and Western blot. Proliferation of desmin positive cell was assessed by dual immunofluorescence staining for desmin and proliferationg cell nuclear antigen (PCNA).ResultsStellate cells and portal fibroblasts, which stained positive for desmin, proliferated around portal veins during early recovery periods. Proliferation of these cells correlated with increased liver expression of PGDF‐BB and TGF‐b1. The expression of phosphorylated LATS1 and phosphorylated MOB1 which sequester YAP/TAZ in the cytoplasm were decreased in liver tissue and nuclear staining of both YAP and TAZ was evident in desmin‐positive cells during liver recovery after I/R. Pharmacological inhibition of YAP and TAZ using verteporfin attenuated desmin positive cell proliferation after I/R.ConclusionThe data suggest that hepatic stellate cell and/or portal fibroblasts expand during liver recovery after I/R and YAP/TAZ regulate their proliferation.
Substituted Chalcones and Flavones as Human Monoamine Oxidase A (hMAO‐A) Inhibitors with Prostate Cancer Antiproliferative Effects
Authors: Zarmouh Najla O , Gangapuram Madhavi , Eyunni Suresh , Elshami Faisel , Redda Kinfe K , Messeha Samia S , Soliman Karam F 
Published: November 2023

Aggressive prostate cancer (PCa) tumors exhibit an increased expression of monoamine oxidase A (MAOA). The use of MAO‐A inhibition as a strategy to treat PCa have not been adequately investigated. In the current investigation, we tested 22 of synthesized chalcone and flavone derivatives for their inhibition of recombinant human (h) MAO‐A activity and their anticancer effect in the PCa LNCaP. Our results showed that five of these derivatives inhibited hMAO‐A with an IC90 < 100 μM, 2‐(3,4,5‐trimethoxystyryl)‐3‐hydroxy‐5,7‐dimethoxy‐4H‐chromen‐4‐one (2a, 6%), 6,8‐dichloro‐3‐hydroxy‐2‐phenyl‐4H‐chromen‐4‐one (2b, 8%), (E)‐3‐(3,4‐dichlorophenyl)‐1‐(2‐hydroxy‐4,6‐dimethoxyphenyl)prop‐2‐en‐1‐one (2c, 9%), (E)‐1‐(3,5‐dichloro‐2‐hydroxyphenyl)‐3‐phenylprop‐2‐en‐1‐one (2d, 3%) and 6,7‐dichloro‐2‐phenyl‐4H‐chromen‐4‐one (2e, 3%), to be comparable to standard MAO‐AIs of pirlindole (4%) and clorgyline (2%). Furthermore, the IC50 of the top compounds was 2e (IC50= 0.03 μM) to be the most potent among all the screened compounds on hMAO‐A. This compound was followed by 2a (IC50= 0.7 μM), 2d (IC50= 1.2 μM), 2c (IC50= 4.9 μM), 2d (IC50= 15.5 μM), respectively. In silico, docking scores were generated for the compounds under study using Open Eye's OEDocking Hybrid method. The highly active compound 2e scored high −7.21 (Chemgauss4 Score) compared to all other compounds under study at the active site of human MAO‐A crystal structure (PDB; 2Z5X). The effects of these five compounds on PCa cells were investigated using the resazurin fluorometric assay. At 20 μM Incubation for 72 h, 2a, 2b, 2c and 2d showed a significant LNCaP cells viability inhibition (P > 0.0001), while 2e was not effective. Compound 2d (IG50= 5.5 μM), 2b (IG50= 8.8 μM), and 2c (IG50= 9.5 μM) were the most potent antiproliferative compounds which were more effective than the standard MAO‐AIs pirlindole and clorgyline (IG50 > 10 μM). The obtained data using 2b, 2c, 2d, and 2e chalcone and flavone derivatives suggest that MAOA has a potential as a therapeutic target in PCa.Support or Funding InformationSupported by NIH Grants G12 MD007582 and P20 MD 006738
Using Peer‐assisted Learning in a Pharmacology Undergraduate Research Program to Enhance Student Engagement and Performance
Authors: Kemp‐Harper Barbara Kathryn , Drummond Grant Raymond , Davis Elizabeth Anne 
Published: November 2023

IntroductionThe coursework component of the Pharmacology undergraduate research program at Monash University comprises the critical analysis of a scientific paper under exam conditions. Traditionally, teacher‐led tutorials were utilised to highlight pharmacological techniques, experimental design and data analysis. However, although students were given opportunities to undertake practice exams, overall performance in the assessment task has been relatively poor.AimsThe current study aimed to revise the learning activities associated with the literature critique exam to encourage student engagement and improve performance.MethodsIn 2013, a tutorial program was implemented which involved peer learning groups such that groups of 4–5 students critiqued components of a scientific paper, presented their findings to the class and lead class discussion. In 2014, to further align the learning activity (group work) with the assessment task (individual work), the exam format was changed to incorporate a peer‐assisted learning component. Students were given the opportunity to discuss the scientific paper with their peers for 30 minutes before being given the exam questions which were then completed under usual exam conditions. The 2014 exam paper was identical to the 2013 paper. In 2015, a new exam paper was used yet the format remained unchanged, with the inclusion of a peer‐assisted learning component. Evaluation of the effectiveness of this change in tutorial and exam format, was via comparison of the exam results and a student feedback survey at the end of the unit.ResultsStudents entering the Honours program in 2012–2015 had a similar background knowledge in pharmacology with the average mark in the foundation 3rd year pharmacology unit ranging from 73.2 ± 10% (n=14, 2015) to 78.0 ± 8.1% (n=19, 2012). Following the 2013 revision of the tutorial format from ‘teacher‐led’ to ‘peer‐assisted’, there was no change in the exam marks (2013: 65.7 ± 9.9%; 2012: 63.4 ± 10.2%). However, the majority of students strongly agreed that the peer‐group format of the tutorials enhanced their learning. The introduction of the peer group discussion at the start of the 2014 exam appeared to increase exam performance (74.0 ± 7.3%, n=14), an effect which was sustained in 2015 (72.9 ± 5.3%, n=14).ConclusionOur results suggest that the inclusion of peer‐assisted learning in both the learning activities and assessment task may increase the level of engagement of students and improve their critical analysis skills.Support or Funding InformationDepartment of Pharmacology, Monash University
Rescue from Synthetic Cannabinoid Intoxication
Authors: Ginsburg Brett C 
Published: November 2023

The number of patients seeking emergency treatment for acute synthetic cannabinoid intoxication have increased over the past decade, despite laws prohibiting their legal sale and use. Reported clinical signs of acute synthetic cannabinoid intoxication include tachycardia and hypertension, lethargy, confusion, agitation, hallucinations, and seizures. Clinicians have little guidance on the best course of treatment for such patients. The current standard of care involves administering benzodiazepines to sedate agitated patients and reverse seizures, antidepressants to treat anxiety reported by patients, and antipsychotics to reverse apparent psychotomimetic effects. However, the effectiveness of these treatments remains unclear. Here, in adult male C57 mice, the ability of several clinically available medications to reverse effects including hypothermia, antinociception, and ataxia of the synthetic cannabinoid JWH‐018 are examined. Additionally, effects of JWH‐018 on blood pressure and heart rate are determined, to evaluate potential cardiac effects. JWH‐018 (0.3, 1.0, or 3.0 mg/kg) or vehicle was administered 10‐min prior to test agents which included diazepam (1 & 10 mg/kg), imipramine (10 & 30 mg/kg), fluvoxamine (10 & 30 mg/kg), and haloperidol (0.3 & 3 mg/kg). Effects of these agents are compared to those of rimonabant (1 & 3 mg/kg), the CB1 antagonist. Behavioral effects were assessed immediately before, then 10, 20, 30, 40, and 50‐min after JWH‐018 administration. In other mice, cardiac effects were assessed 25–35 min after JWH‐018 administration. The potential reversal agents are administered after JWH‐018 administration because the clinical situation necessitates administration of reversal agents after cannabinoid exposure. JWH‐018 had no effect on blood pressure and only modestly decreased heart rate. As expected, JWH‐018 had dose‐dependent effects on rectal temperature, antinociception, and ataxia that persisted for at least 50‐min. Within 10–20 min of administration, rimonabant reversed hypothermic and antinociceptive effects and partially reversed ataxic effects of JWH‐018. No other agent tested affected any of the JWH‐018 effects. These results suggest that clinical reports of hypertension and tachycardia are unlikely to be due to direct effects of synthetic cannabinoids, but rather are likely due to the situation arising from intoxication requiring emergency medical care. Further, while treatment with a sedative might help calm an agitated patient, these medications are unlikely to alter the course of synthetic cannabinoid intoxication. Finally, although rimonabant was withdrawn from human use, this decision was based on adverse events during chronic rimonabant treatment for obesity. These results indicate that rimonabant or a similar drug could be useful for acute reversal of synthetic cannabinoid intoxication.Support or Funding InformationSupported by The Department of Defense (JPC‐5) project FA8650‐15‐C‐6589
Methamphetamine Self‐Administration History May Increase the Reinforcing Effects of Cannabinoid Receptor Agonists in Rhesus Monkeys
Authors: Minkiewicz Molly , John William S , Nader Michael 
Published: November 2023

Animal models of drug self‐administration (SA) are a predictive measure of abuse liability. While Δ9‐tetrahydrocannabinol (THC) remains one of the most commonly abused drugs among humans, it has been an on‐going challenge to establish animal models of intravenous SA of THC. In a recent study (John et al., 2017), we found that THC did not function as a reinforcer in rhesus monkeys responding under a fixed‐ratio (FR) 10 schedule of reinforcement, but the cannabinoid receptor (CBR) agonist CP 55,940 was reinforcing in 3 of 8 monkeys; these 3 monkeys all had a previous methamphetamine (MA) SA history. In an effort to increase THC SA in those 8 monkeys, we treated them chronically with THC and found that THC functioned as a reinforcer in 3 monkeys (only 1 of which CP 55,940 had reinforcing effects). The goals of the present study were to (1) evaluate how chronic THC treatment affected CP 55,940 in those 3 monkeys and (2) examine whether exposure to MA would enhance CP 55,940 SA. After a year of abstinence from chronic THC treatment, CP 55,940 (0.001–0.04 μg/kg/injection) no longer functioned as a reinforcer at doses previously identified as reinforcing in those 3 monkeys. To test the hypothesis that the MA history had influenced the reinforcing effects of CP 55,940, these three monkeys and a fourth animal with no previous MA history, were given access to 0.03 mg/kg/injection MA for 8 sessions and then CP 55,940 was re‐evaluated under an FR 10 reinforcement schedule. Following a brief re‐exposure to MA, resulting in intakes ranging from 2.90–6.3 mg/kg, CP 55,940 functioned as a reinforcer in 2 of the 3 monkeys relative to their previous baselines; in the previously MA‐naïve monkey, this history did not increase the reinforcing effects of CP 55,940. CP 55,940 did function as a reinforcer in the monkey with the highest MA intake (6.3 mg/kg), but the sample size is too small to know if there is a direct relation between MA intake and CBR agonist reinforcement. Additional studies are underway to determine if the chronic MA history affected dopamine D3 receptor availability and if this transient increase was necessary for the CBR agonist to have reinforcing effects. Ultimately, our goal is to identify conditions that will permit CBR agonists to function as reinforcers in Old World monkeys.Support or Funding InformationDA06634
Effects of Brevetoxin and NMDA on Dendritic Arborization in Murine Organotypic Hippocampal Slice Culture
Authors: Gomez Dina , Murray Thomas 
Published: November 2023

BackgroundDuring neuronal development dendritic arbors become complex as function of both intrinsic genetic factors and neuronal activity. The N‐methyl‐D‐aspartate receptor (NMDAR) is essential for activity‐dependent neurite outgrowth, dendritic arborization and spine formation. Dysfunction in NMDARs is associated with diverse neuropsychiatric disorders such as depression and autism spectrum disorder. High and low NMDAR activity, respectively, leads to excitotoxity and failure of neuronal development. Voltage‐gated sodium channel (VGNaC) activation using gating modifiers such as brevetoxin (PbTx‐2) is one pathway to influence NMDAR function. PbTx‐2 augments NMDAR function in dissociated cerebrocortical neurons. Here we assessed the effect of PbTx‐2 and NMDA on dendritic arbor complexity in organotypic hippocampal slice cultures (OHSC). The activity of the NMDAR is also linked to its phosphorylation status. Phosphorylation of tyrosine residues on the NMDAR increases the open probability and mean open time of the NMDAR leading to increased Ca2+ levels. Calcineurin (CaN) regulates NMDAR function by dephosphorylating the tyrosine residues. In cerebrocortical neurons, FK‐506, an inhibitor of calcineurin, eliminated the reduction in neurite outgrowth observed at high concentrations of PbTx‐2. Here, we determined the influence of FK‐506 alone on dendritic arborization in OHSC.Hypothesis1) VGNaC activation or direct activation of NMDARs will promote dendritic arborization in OHSC. 2) FK‐506 alone will not affect dendritic arbor complexity in OHSC.MethodsThe Thy‐1 YFP transgenic mice were used. Hippocampal slices were prepared from postnatal day 5 mouse pups. Slices were treated 18 hours after plating with control, (10–1000 nM) PbTx‐2, (0.01 – 100 μM) NMDA or (0.001–10 μM) FK‐506 for a period of 4 days. A Leica SP8 microscope was used to generate Z‐stack confocal images and Imaris‐XT software was used create 3D‐reconstructed images of the dendritic arbor to run a sholl analysis.ConclusionThe results demonstrated that both 100 nM PbTx‐2 and 1 μM NMDA treatment produced significant increases in dendritic arbor complexity. The OHSC appeared more sensitive to NMDA than dissociated cerebrocortical neurons inasmuch as 100 μM NMDA was extremely toxic to OHSC neurons. The use of the OHSC confirmed that VGNaC activation augments dendritic arbor complexity and this effect generalizes to hippocampal pyramidal neurons. Our results also indicate that (0.001–10 μM) FK‐506 alone had no effect on dendritic arborization in OHSC. Overall these studies suggest that VGNaC activators may represent a novel pharmacological strategy to regulate NMDAR function and promote neuronal structural plasticity.Support or Funding InformationNIH‐RO1NS053398