bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exercise effectiveness for atrophic muscle in estrogen (E2) replete and ovariectomized (OVX) female rats
Authors: Ferreira J Andries , Hemmann Kaitlyn M , Brown Marybeth 
Published: June 2021

Studies suggest that women who are E2 deficient do not respond to exercise as well as women who are E2 replete.PURPOSEdetermine if differential recovery occurs in atrophic skeletal muscle in OVX rats, with and without E2 and with and without exercise.METHODS78 female rats age 5 mos were randomly placed into 6 groups: 1) control, 2) Hindlimb unweighted 4 weeks (HLU), 3) recovery no E2, 4) recovery + E2, 5) exercise no E2, 6) exercise + E2. Recovery groups cage recovered or were exercised daily for 14 days after HLU.RESULTSHLU resulted in significant atrophy and loss of muscle force (p<0.05) in soleus, plantaris, gastrocnemius, tibialis anterior. Return of muscle mass toward control levels occurred in both cage ambulation but not both exercise groups. Exercise + E2 was more effective than exercise without E2. Representative muscle mass/body mass ratio data and Po are given for gastrocnemius (mean ± sem).Exercise was effective for E2 supplemented rats but not for rats that were E2 deficient. Exercise without E2 rats had histological evidence of damage (central nuclei).CONCLUSIONSExercise + E2 appears to be the most effective stimulus for the recovery of atrophic muscle, whereas exercise without E2 may be detrimental.Support: NIH HD058834, Spinal Injuries Research Board, Research Council at Univ. of Missouri
Insulin‐like growth factor I downregulates proatherogenic 12/15‐lipoxygenase in vivo and in vitro
Authors: Vaughn Charlotte , Sukhanov Sergiy , Higashi Yusuke , Shai Shaw‐Yung , Delafontaine Patrick 
Published: June 2021

We have shown that 12/15‐lipoxygenase (LOX) mediates important proatherogenic oxidized low density lipoprotein (OxLDL)‐induced effects in smooth muscle cells (SMC), namely, apoptosis and downregulation of the insulin‐like growth factor (IGF‐1) receptor, and that infusion of IGF‐1 into Apolipoprotein E‐null (ApoE‐/‐) mice suppresses macrophage (MF) plaque infiltration and atherosclerosis. To determine molecular mechanisms mediating IGF‐1's anti‐atherogenic effects ApoE‐\‐ mice were injected with IGF‐1 (0.7 mg/kg/day, 7d). IGF‐1 decreased LOX aortic gene expression by 64±6% (RT‐PCR). IGF‐1 dose‐dependently decreased LOX gene expression in THP‐1 derived MF, while no significant effect was seen in SMC. To examine IGF‐1's effects on LOX activity, SMC or MF were pre‐treated with IGF‐1 (10 or 50 ng/ml, 24h), and then exposed to OxLDL or control. 14,15‐leukotriene (a product of LOX‐specific enzymatic reaction) levels were measured in conditioned media by ELISA. OxLDL induced a five‐fold increase in LOX activity levels in MF, and a smaller increase in LOX activity in SMC. IGF‐1 partially blocked OxLDL‐induced LOX upregulation by 27±4%. In summary, IGF‐1 suppresses vascular LOX expression in ApoE‐\‐ mice and induces LOX downregulation in MΦ and SMC. Our data suggests that the ability of IGF‐1 to downregulate LOX plays an important role in its anti‐atherogenic effect.Study supported by NIH HL 70241
Resuscitation strategy alters response to hemorrhage
Authors: Makley Amy Teres , Friend Lou Ann , Goodman Michael , Blanchard John , Lentsch Alex , Pritts Timothy 
Published: June 2021

ObjectiveHemorrhagic shock is associated with a systemic inflammatory response. Two common resuscitation strategies are crystalloid and blood component therapy. The effect of these strategies on inflammation is not fully understood. We hypothesized that crystalloid would exacerbate inflammation after hemorrhagic shock.MethodsMice underwent pressure controlled hemorrhage via femoral artery cannulation and resuscitation with whole blood (WB) or Ringers lactate (LR). Survival and fluid requirements were determined. Tissue myeloperoxidase (MPO) levels were analyzed.ResultsResuscitation with LR resulted in less survival at 7 days vs WB or sham (Fig A). LR mice required more fluid (Fig B) and exhibited higher MPO activity in jejunum, but not liver or kidney (Fig C).ConclusionsLR resuscitation led to increased fluid requirements, jejunal MPO and mortality compared to WB. These results are critical to understanding potential benefits of blood resuscitation following trauma.Supported by a grant from the Henry Jackson Foundation
The anabolic effect of insulin is dependent on its ability to increase blood flow and muscle perfusion in human subjects
Authors: Timmerman Kyle L , Lee Jessica L , Dhanani Shaheen , Dreyer Hans C , Glynn Erin L , Fry Chris S , Drummond Micah J , Rasmussen Blake B , Volpi Elena 
Published: June 2021

Insulin‐induced blood flow has been shown to correlate positively with insulin's ability to enhance muscle protein synthesis. Thus, we hypothesized that pharmacological inhibition of insulin‐induced vasodilation would reduce the anabolic response of muscle proteins to insulin.Skeletal muscle fractional synthetic rate (FSR), net balance, blood flow (indocyanine green), and muscle perfusion (contrast enhanced ultrasound) were measured in 10 healthy, glucose tolerant subjects (31±2 yrs) in the basal state and during administration of insulin alone (N= 5) or insulin plus the NO synthase inhibitor NG‐monomethyl‐L‐arginine (L‐NMMA) (N= 5).There were no differences in the basal period. FSR increased significantly (P<0.05) in subjects receiving insulin alone (basal: 0.059%/h vs. insulin: 0.079%/h) compared to subjects receiving insulin plus L‐NMMA (basal: 0.056%/h vs. insulin+ L‐NMMA: 0.045%/h). Those receiving insulin alone experienced a significantly (P<0.05) greater percent change from baseline (54.90%) in muscle perfusion than subjects receiving insulin + L‐NMMA (3.14%). There was also a trend (P=0.09) for increased blood flow in subjects receiving insulin alone.These preliminary data suggest that the ability of insulin to stimulate blood flow and muscle perfusion is necessary for insulin to stimulate muscle protein synthesis in healthy, young adults.Funded by NIH R01 AG018311 and UTMB Claude D. Pepper Older Americans Independence Center Grant #P30 AG024832.
Hyperoxia attenuates the elevation in muscle sympathetic nerve activity following exposure to hypoxia
Authors: Querido Jordan Scott , Kennedy Paul M , Sheel A William 
Published: June 2021

Hypoxia may sensitize the carotid chemoreceptors resulting in a sustained elevation of muscle sympathetic nerve activity (MSNA) which outlasts the hypoxic stimulus. To test this hypothesis we determined (n=4) the effect of carotid body deactivation on the sustained elevation in MSNA (common peroneal nerve) following isocapnic hypoxia (arterial O2 saturation 80% for 20 mins) in humans. Ventilation, heart rate and MSNA were elevated in hypoxia; however, only the elevation in MSNA outlasted the hypoxic stimulus, and remained elevated for 20 mins following the hypoxic stimulus. In contrast, carotid body deactivation with hyperoxia (100% O2 for 1 min) transiently reduced MSNA in eight of nine trials (mean decrease 12.6 ± 9.5%, p = 0.005). Our results suggest that input from the carotid chemoreceptors is obligatory for the sustained elevation in MSNA initiated by chemoreflex stimulation. We attribute the decrease in MSNA to a transient hyperoxia‐induced attenuation in carotid chemoreceptor sensitivity.Research support: NSERC, MSFHR
Rosiglitazone Induces Cardiac Protein Kinase C beta2 Over‐expression And Increases Ventricular Mass in Type 2 Diabetic db/db Mice
Authors: Xia Zhengyuan , Carroll Rogayah , Wang Fang , Severson David L 
Published: June 2021

Rosiglitazone (RSG) treatment in type 2 diabetes has been associated with increased incidence and worsening of heart failure, but the mechanism is unknown. It has been shown that protein kinase C (PKC) β2 is over‐expressed in failing human hearts (Circulation 1999;99:384‐91) and that RSG‐induced weight gain is attributable to increased activation of PKCβ in adipose tissue (FASEB J 2006;20:1203‐5). Further, left ventricular mass is reported to be a predictor of heart failure (Eur Heart J 2008;29:741‐747). We, therefore, hypothesized that RSG may induce PKCβ2 over‐expression and increase ventricular mass of the hearts from db/db (D) mice, a mongenic model of obesity and features of type 2 diabetes. Diabetic mice were either untreated (D), treated with RSG (D+RSG) at 26 mg/kg/day or with RSG plus N‐acetylcysteine (NAC, 1.4 g/kg/day) (D+RN), for 3 weeks; NAC can inhibit PKCβ via mechanisms independent of its antioxidant property. Both RSG or RSG+NAC reduced body weight (BW) relative to D group. However, RSG increased ventricular mass and heart weight/BW ratio, accompanied by 1.5‐fold increase of myocardial PKCβ2 protein expression and activation as well as increased protein kinase B/AKT phosphorylation at serine‐473 relative to D (all P<0.05). NAC prevented all these changes. RGS may have increased ventricular mass by inducing PKCβ2 over‐expression.Supported by a CIHR grant (DLS) and an AHFMR postdoctoral fellowship (ZX)
Identification of two naturally occurring AMPKα2 variants exclusively expressed in the brain of amyotrophic lateral sclerosis
Authors: Wang Tingting , Cheng Huaiyan , Qiu Rongde , Wang Liqin , Feng Yinghong 
Published: June 2021

5′‐AMP‐activated protein kinase (AMPK), a heterotrimeric complex consisting of catalyticα, scaffolding ?, and AMP‐binding ? subunits, is a highly conserved master fuel gauge that meets cell demands by monitoring and regulating cellular energy status. The objective of this study is to identify novel AMPKα2 variants and establish links to diseases. Methods of gene cloning, protein‐protein interaction assay, cell proliferation assay, gene expression, Western blot, and RT‐PCR detection of gene transcripts in human brain total RNA were employed. The result reveals two naturally occurring splicing variants of AMPKα2 that are exclusively expressed in the brains of all 5 cases of amyotrophic lateral sclerosis (ALS), but not in the brains and other tissues of 30 normal or non‐ALS human subjects. Gene analysis suggests that the variants result from differential skipping of two constitutive exons. Overexpression of the variants in COS‐1 cells and SH‐SY5Y neuronal cells induced cell death. Moreover, AICAR, an AMPK activator, and the full‐length AMPKα2 inhibited the variant‐ and glutamate‐induced neuro‐excitotoxicity, respectively. Mechanistic studies showed that the AMPKα2b variant binds AMPKβ subunits in a dominant negative fashion. The conclusion is that two ALS‐specific novel AMPKα2 variants have been uncovered.Supported by NIH grant (HL065492) to YHF.
Effect of controlling for background diet in the interpretation of dietary fiber and plasma lipids relationship
Authors: Yu Winifred Wingyun , Lau Joseph , Trikalinos Thomas , Schmid Christopher H , Lichtenstein Alice H 
Published: June 2021

BackgroundParticipants in nutrition studies often consume background diets that include nutrients under investigation. Valid estimates of nutritional interventions therefore require proper control for backgrounds diet in study design.MethodWe assessed the effect of background diet in a systematic review of 34 trials studying the association of fiber and plasma lipids (total cholesterol [TC], high density lipoprotein cholesterol [HDL], low density lipoprotein cholesterol, and triglycerides [TG]). Background diet was defined to be adequately controlled when there were no reported statistically significant differences in energy and macronutrient intakes between experimental and control groups, or when results were adjusted for these variables. For each lipid outcome, the proportion of studies with significant findings was compared between studies with and without adequate diet control.ResultBackground diet control was adequate in 12 studies. The proportion of studies with significant findings appeared to be higher among studies with, than without, adequate diet control for TC (4/9 vs. 2/17), HDL (2/7 vs. 1/14) and TG (1/8 vs. 1/17) concentrations. These differences were not significant. More studies are needed to confirm these findings.Source of research support: NHLBI T32 HL69772
Subclassification of Leukotriene‐Based Asthmatics
Authors: Broughton Kenneth Shane , Ross Erica , Johnson Kurt 
Published: June 2021

Previously we identified the idea of four subtypes of asthmatics, three of which were cytokine‐based asthmatics and another larger leukotriene‐based family. Previous studies identified that the leukotriene specific subtype is n‐3 PUFA responsive. It was our intent to determine if a leukotriene‐specific family of asthmatics could be further subclassified into families of asthmatics or not.Twenty‐two asthmatics went through a methacholine bronchoprovocation challenge on two occasions separated by one month. Saliva for one half hour, a blood sample four hours post‐bronchoprovocation, and 24 urine samples were collected. Saliva and urine were analyzed by reverse‐phase high‐pressure liquid chromatography (RP‐HPLC) coupled with a diode array‐UV detector at 280 nm and a flow rate of 1.0 mL/min for analysis of cysteinyl leukotrienes on a Schimadzu HPLC.Ten individuals were identified as being non‐LT based asthmatics while twelve were identified as being LT‐based asthmatics. Based on saliva LT production, three individuals were identified as being overlapping LT asthmatics: a C4/D4, a B4/C4/D4, and a B4/C4 based asthmatic. However, the remaining asthmatics separated almost evenly into each subfamily of LTB4, LTC4, LTD4 and LTE4 based asthmatics. While this is a small study, these data indicate differing types of LT based asthmatics at the mechanistic level.
The Effect of dietary fatty acids on the recruitment of brown‐like adipocytes in inguinal white adipose tissue
Authors: Zhao Ming , Guo Hong , Chen Xiaoli 
Published: June 2021

The physiological significance of brown adipose tissue (BAT) in energy metabolism in adult humans has been recently re‐evaluated. The evidence from recent studies indicates a potential of converting white to brown adipocytes in white adipose tissue (WAT). Herein, we explored the regulatory effect of dietary fatty acids on this conversion in WAT. We found that BAT‐specific UCP1 was expressed at a significantly higher level in inguinal adipose tissue (ING) compared to epididymal adipose tissue in mice. High fat diet (HFD) modulated UCP1 expression in BAT and ING in a different manner. After one week of HFD, UCP1 was increased in BAT, but not in ING of mice. However, UCP1 was dramatically decreased after chronic HFD feeding in both tissues. Additionally, we examined the effects of saturated and polyunsaturated fatty acids on the differentiation of brown‐like adipocytes in primary culture of stromal‐vascular (SV) cells from ING of normal mice. Fatty acids were added to SV cell culture either during 8 days of differentiation or after differentiation for 24 hours. In differentiated adipocytes, 24h treatment with palmitate significantly reduced UCP1, while n‐3 fatty acid (EPA) treatment did not change UCP1 expression. However, UCP1 and PGC1α expression was significantly increased in SV cell cultures after 8‐ day EPA treatment. Our data suggests that EPA is capable of inducing the differentiation of inguinal SV cells into brown‐like adipocytes, but failed to induce UCP1 expression in mature white adipocytes. We conclude that HFD or saturated FA reduces UCP1, while EPA has a potential to increase the recruitment of brown‐like adipocytes in inguinal WAT.Grant Funding Source : General Mills Foundation, MN Obesity Consortium
S‐allylcysteine inhibits tumor growth and progression of oral cancer in both in vitro and in vivo models
Authors: Chang Chiao-Ying , Huang Wei-Yao , Chen Shih-Yan , Pai Man-Hui , Tang Feng-Yao 
Published: June 2021

Oral cancer is a prevalent type of cancer in many countries. Although studies indicated that garlic extracts such as diallyl disulfide and diallyl trisulfide have anti‐cancer effects, the chemopreventive effects of aqueous garlic extracts, S‐allylcysteine (SAC), on oral cancer have not been studied yet. To this specific aim, we investigated the inhibitory effects of SAC on the proliferation and progression of oral cancer cells in both in vitro and in vivo models. In the present study, our results demonstrated that SAC dose‐dependently inhibited the proliferation of human oral squamous cancer CAL‐27 cells in vitro. The results indicated that SAC stabilized the adherent junction complex of E‐cadherin/β‐catenin and suppressed epithelial‐mesenchymal transition (EMT) in oral cancer cells through suppression of MAPK/ERK signaling pathways. By study end (4th week), consumption of SAC (at doses of 5 and 40 mg/kg of body weight per day) significantly prevented tumor growth of oral cancer in a mouse xenograft model. Histopathological and immunohistochemical (IHC) staining results indicated that SAC could effectively suppress tumor progression including EMT of oral cancer in vivo. The chemopreventive effects of SAC were associated with decreases in cyclin D1 expression and suppression of Akt, mTOR, IκBα, and ERK 1/2 signaling cascades in tumor tissues. SAC consumption could inhibit the expression of cyclooxygenase‐2 (COX‐2), Vimentin, and nuclear NF‐κB p65 (RelA) proteins. These results suggested that SAC could act as an effective agent to prevent tumor growth, progression, and EMT of oral cancer.Grant Funding Source : NSC
Insufficient HO1 Response to Ischemic Stress Correlates with Increased Inflammation and Reduced Survival of EPCs in Diabetic Patients
Authors: Issan Yossi , Hochhauser Edith , Kornowski Ran , Leshem-Lev Dorit , Lev Eli , Sharoni Ram , Vanella Luca , Puri Nitin , Laniado-Schwartzman Michal , Abraham Nader G , Porat Eyal 
Published: June 2021

BackgroundDiabetes is characterized by oxidative stress and systemic inflammation. Nuclear ‐E2‐related factor‐2 (Nrf2) is a transcription factor that activate of various antioxidant genes, including heme oxygenase‐1 (HO‐1). HO‐1 and adiponectin are cardioprotective ensuing ischemia reperfusionMethodsadipose tissue from diabetic (n=15) and non‐diabetic (n=15) patients undergoing CABG was analyzed using RT‐PCR and immunoblotting for Nrf2 genes. Oxidative stress was evaluated by thiobarbituric acid‐reactive substance (TBARS). Peripheral blood, was evaluated for inflammatory cytokines and EPC markers.ResultsCompared to controls, TBARS were higher in diabetic patients. Although Nrf2‐dependent antioxidant proteins (TxR1, NQO1, GST) were upregulated, HO‐1 and adiponectin protein expression and serum levels of bilirubin were lower in diabetic patients. Inflammatory cytokines serum levels were higher in diabetic patients. EPC levels and function were significantly reduced with diminished viability in diabetic group.ConclusionThese results demonstrate for the first time that there is an inadequate HO‐1‐adiponectin axis response in humans with chronic conditions of oxidative stress such as diabetic patients with severe coronary artery disease, leading to insufficient antioxidant and anti‐inflammatory outcome.
The role of colour in knowledge retention: a body‐painting study
Authors: Finn Gabrielle Maria , White Pamela M 
Published: June 2021

This study tested student claims that bright color plays a significant role in retention of knowledge from body painting sessions. Medical students (n=117) were divided into two conditions: block color (CLR) and black outlines (BLK). Students completed a pre‐test before a body painting teaching session on abdominal referred pain. CLR students used bright block colors, and BLK students mapped outlines in black. Immediately afterward, students sat a mid‐test to compare the conditions. Students completeda post‐test to compare long‐term retention of knowledge four weeks later. There was no difference in knowledge between the two conditions immediately after the teaching(P =0.653). There was no significant difference in long‐term retention of knowledge between those using black outlines and those using color (P=0.278). The use of color had no impact on short‐term or long‐term retention of knowledge, despite previously collected qualitative data that color helped memorization. Despite there being no immediate difference in the amount of information retained, the students’ enthusiasm for body painting and the use of bold colors warrant body painting's inclusion within the anatomy curriculum. Acceptability plays a significant role in the success of any teaching modality.Grant Funding Source : Internal funding
No cardiac hypertrophy induced by T3 in a mouse model of the syndrome of resistance to thyroid hormones
Authors: Império Güínever Eustáquio , Pereira Guilherme Faria , de Góes Freitas Isalira Peroba Ramos , Santiago Letícia Aragão , dos Santos Almeida Norma Aparecida , Fuziwara Cesar Seigi , Kimura Edna Teruko , Olivares Emerson Lopes , Ortiga‐Carvalho Tania Maria 
Published: June 2021

Triiodotironine (T3) is critical for cardiac function. Heart expresses TRα1 e TRβ1, the two main thyroid hormone (TH) receptors (TR). We aimed to investigate the role of TRβ1 on T3‐induced cardiac hypertrophy.Adult male mice, wild‐type (WT) or homozygous (HO) for Δ337T mutation on TRβ (unable to bind T3), were used. Animals were studied at baseline, after hypo‐ (PTU) and hyperthyroidism (PTU+T3) induction. Echo‐ and electrocardiogram were performed. Hearts were collected, weighed and total RNA was extracted. Expression of mRNA and miRNAs were quantified by real time RT‐PCR.T3 caused cardiac hypertrophy in WT, but not in HO animals when evaluated by cardiac index (P<0.001) or by echocardiography (25%, P<0.05). Genes responsive to T3 as ARb1, SERCa2 and HCN2 were responsive to T3 in WT but not in HO. Absence of a functional TRβ1 altered several parameters in HO cardiac function. Stroke volume and ejection fraction dropped in HO‐PTU+T3 vs. HO‐PTU. P wave reduced (50%, P<0.001) and heart rate increased (P<0.05) on WT‐PTU+T3 vs. WT‐PTU; but not in HO. Analysis of MicroRNAs miR‐1 and miR‐208, involved in cardiac hypertrophy, showed that T3 treatment increased both (2 to 3 times) in a different fashion, being miR‐1 TRβ independent and miR‐208 TRβ dependent.TH‐induced cardiac hypertrophy is TRβ‐dependent and involves miR‐208, while the absence of T3 ligation on TRβ promotes a significant deterioration in cardiac function.
Amphetamine potentiates NMDA receptor currents in midbrain dopamine neurons
Authors: Ingram Susan L. , Li Minghua , Underhill Suzanne M. , Amara Susan G. 
Published: June 2021

Amphetamine (AMPH) is known to increase extracellular concentrations of dopamine and glutamate. AMPH enhances extracellular dopamine primarily by competing with dopamine for the dopamine transporter (DAT); however, it is not known how AMPH alters concentrations of glutamate. Recently, we determined that acute AMPH exposure leads to internalization of the glutamate transporter, EAAT3, in dopamine neurons in a DAT‐dependent manner. Electrophysiological studies determined that AMPA:NMDA ratios are decreased with AMPH superfusion primarily due to potentiation of NMDA responses. NR2B‐selective inhibitors, ifenprodil and Ro25–6981, abolish the AMPH‐induced increase in NMDA currents. Blockade of synaptic NMDA receptors with the use‐dependent NMDA antagonist, MK‐801, blocked basal evoked NMDA currents but did not inhibit AMPH‐and NR2B‐dependent evoked NMDA currents. These results indicate that that new NMDA receptors are activated by AMPH. Further, Group I metabotropic glutamate receptor (mGluR) antagonists also inhibit AMPH potentiation of NMDA currents. Additional studies are focused on determining if NR2B‐containing receptors are activated by synaptic glutamate spillover, recruited to the synapse, or modified by second messenger signaling in midbrain dopamine neurons.Supported by ARRA‐funded NIH grant DA07595 (SGA) and DA024041 (SLI).