bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential regulation of genes for intestinal cholesterol flux by epigallocatechin gallate (EGCG) and resveratrol (RES) in Caco‐2 cells: Potential role of histone deacetylases and sirtuins in intestinal cholesterol metabolism
Authors: Wegner Casey , Park Youngki , Koo Sung I , Lee Jiyoung 
Published: June 2021

Despite well‐established cardio‐protective properties of phenolic compounds, their role in intestinal cholesterol metabolism is unclear. We investigated the effect of EGCG and RES on the transcriptional regulation of genes encoding intestinal cholesterol transporters and lipoprotein receptors in Caco‐2 cells. Cells treated with EGCG for 12 hr markedly increased ATP‐binding cassette transporter G5 (ABCG5) mRNA but decreased the expression of ABCA1, scavenger receptor class B type 1, Niemann‐Pick C1‐like 1 (NPC1L1), microsomal triglyceride transport protein and LDL receptor related protein 2 in a dose‐dependent manner (0–100 μM). In contrast, RES at 100 μM increased ABCA1 and NPClL1 mRNA. Of interest, EGCG significantly decreased the expression of all major histone deacetylase (HDAC), i.e., 1, 2, 3, 6, 7, 10, whereas RES had a minimal effect. Sirtuin (Sirt) 2–7 expression was also markedly repressed by EGCG but RES increased Sirt3, 4 and 5. The results indicate differential regulation of key transporters involved in intestinal cholesterol efflux by EGCG and RES. The over‐arching objective of this research will be to relate changes in the gene expression profile to the promotion of cholesterol flux from the basolateral to apical side of enterocytes. Importantly, this study suggests that expression of the aforementioned intestinal transporters may be linked the regulation of HDAC and Sirt in the intestine.Grant Funding Source: Supported by USDA Hatch fund
Inhibitory Effects of Metabolites of Nobiletin and 5‐hydroxy Nobiletin on Human Lung Cancer Cells
Authors: Charoensinphon Noppawat , Zheng Jinkai , Dong Ping , Qiu Peiju , Tran Thony , Xiao Hang 
Published: June 2021

Nobiletin (NBT) and 5‐hydroxy nobiletin (5HN) are unique polymethoxyflavones found in citrus fruits. We investigated the effects of NBT, 5HN, and their major metabolites, namely 4′‐hydroxy nobiletin (M1), 3′,4′‐dihydroxy nobiletin (M2), 3′,5‐dihydroxy nobiletin (M3), 4′,5‐dihydroxy nobiletin (M4), and 3′,4′,5‐trihydroxy nobiletin (M5) on human lung cancer cells. All metabolites showed much stronger inhibitory effects on lung cancer cells than NBT and 5HN. M3 produced the strongest inhibition among all metabolites. Cell cycle analyses revealed that M1 and M4 induced G0/G1 cell cycle arrest, while M3 and M5 caused G2/M cell cycle arrest after 24h treatments. Moreover, annexin V‐FITC/PI co‐staining assay showed that M2, M3 and M5 induced extensive apoptosis after 48h treatments. Consistent with these results, immunoblotting showed that M3 and M5 decreased expression levels of cyclinB1 and cdc‐2 (cdk‐1), while increased expression levels of p21(Cip1/Waf1). M1 and M4 decreased expression levels of cdk‐4. Furthermore, M2, M3, and M5 caused significant Increases in the expression levels of Bax, cleaved PARP, and cleaved caspase‐3. In contrast, NBT and 5HN did not cause any changes in these proteins at the same concentrations as the metabolites. In conclusion, our results demonstrated strong inhibitory effects of metabolites of NBT and 5HN on human lung cancer cells.Grant Funding Source : NIH: CA139174, AICR: 10A044
Investigation of Hypersensitivity to PEGylated Particles For Use in Drug Delivery
Authors: Simmons Ken , Nejati Elham , Johnson Rebecca , Pearce Robert , Albrecht Ralph , Mecozzi Sandro 
Published: June 2021

Nanoparticles have shown promise in the field of drug delivery. Many have the potential to improve the solubility and safety‐profile of our current drugs. Polyethylene glycol is commonly used as the hydrophilic segment in many polymer‐based nanoparticle systems. There have been reports of hypersensitivities to PEGylated particles. In order for these novel drug delivery systems to reach clinical use, it is essential to investigate the mechanism behind their allergic‐like responses. This study examines hypersensitivities to PEGylated particles in a canine model. Dogs are a very sensitive model for this type of allergy, which is thought to be caused through either direct complement activation or an antibody‐based mechanism. We have tested a number of PEG‐fluorocarbon polymers using this model and have performed blood analysis pre and post injection. Current results indicate an antibody‐mediated pathway is likely responsible for this type of hypersensitivity.This project was supported by the UW Institute for Clinical and Translational Research funded through a National Institutes of Health Clinical and Translational Science Award, 1UL1 RR025011, and the STEP program administered by the Wisconsin Alumni Research Foundation.
Biodistribution of mesenchymal stem cells in the treatment of experimental caustic esophageal injury
Authors: Caliskan Bahadir , Kantarcioglu Murat , Guven Ahmet , Karacali Ozgur , Ural Ali Ugur , Surer Ilhami 
Published: June 2021

AimIn our study, we investigate experimentally biodistribution of mesenchymally stem cells (MSCs) after injection in early period of caustic esophageal injury especially due to alkaline agents or toher various chemical substances ingestions for accidentally drink.Method and MaterialIn the study, 23 Spraque Dawley rats in total of 3 groups were used. Our study groups designed as Positron Emission Tomograhy (PET) group (n=12), control group (n=7) and MSCs/bone marrow production group (n=4). Caustic esophageal injury created by injection of %20 NaOH solution. This method is described by Gehanno and Guedon. After 24 hours caustic esophageal injury, Fluorodeoxyglucose (FDG) marked MSCs dose at 1 million cells/rat injected into rats tail vein. One hour and 4 hours after injection PET imaging was performed.ResultsAt first hour after FDG injection, FDG uptake was observed in our rats brain, muscle and bladder tissue and FDG marked MSCs settled in the lung. On the other hand at 4 hours after injection FDG marked MSCs settled at lung and also migrated to injured esophageal tissue. When screening with barium esophageal gavage, damaged esophageal tissue in the migration of MSCs marked with FDG was confirmed.ConclusionWe demonstrated that after 4 hours MSCs injection via peripheral vein for treatment of esophageal injury due to caustic chemical substances, MSCs settled at lung and small amount of MSCs migrated to injured area (homing). Our findings seems to support of homing feature of MSCs in acute injured tissue when infused via peripheral vein.
CaMKII regulates intracellular calcium stores of native endothelial cells from mesenteric arteries
Authors: Toussaint Fanny , Charbel Chimène , Blanchette Alexandre , Villeneuve Louis R. , Ledoux Jonathan 
Published: June 2021

Ca2+ homeostasis is crucial for endothelial function and the regulation of vascular tone. The Ca2+‐dependent kinase CaMKII is activated by Ca2+ pulsars and might play an important role in endothelial Ca2+ homeostasis. Thus, the involvement of endothelial CaMKII in the regulation of intracellular Ca2+ dynamics has been investigated in native endothelial cells of mesenteric arteries. Acute exposure to KN‐93 (10 μM), a CaMKII inhibitor, has little if any effect on Ca2+ pulsars frequency or amplitude. However, CaMKII inhibition induces pulsar sites recruitment as more pulsars sites are active in the presence of KN‐93 compared to control (25%). Interestingly, in absence of extracellular Ca2+, KN‐93 appears to empty intracellular Ca2+ stores. Indeed, exposure to ionomycin, to empty endoplasmic reticulum in absence of extrallular Ca2+, provoked a large and transient intracellular Ca2+ increase. However, preincubation with KN‐93 abolished the ionomycin‐induced Ca2+ transient. These results suggest that CaMKII might inhibit IP3R receptors and/or phosphorylates phospholamban to regulate ER Ca2+ content. Confocal microscopy revealed that CaMKIIα & β are colocalized with IP3R1 in native endothelium. Our data suggest that CaMKII is an important regulator of endothelial Ca2+ homeostasis and may represent a novel target for the treatment of pathologies like hypertension.Supported by FRSQ, CFI, CIHR and HSFC.
HYDROGEN SULFIDE (H2S) IMPROVES THE RENAL FUNCTION IN A COMBINED STATE OF HYPERTENSION AND DIABETES
Authors: Rathore Hassaan Anwer , Din Fiaz ud , Abdullah Mohammed H , Zubaid Munavvar , Abdullah Nor Azizan , Johns Edward J 
Published: June 2021

This study investigated the action of H2S on mean arterial pressure (MAP) and renal function in a combined state of hypertension and diabetes.Groups (n=6) of spontaneously hypertensive rats (SHR) or Wistar Kyoto (WKY) rats received vehicle, streptozotocin (STZ)(40mg/kg) or STZ plus Sodium Hydrogen Sulphide (NaHS), at 56μmol/Kg i.p daily for 35 days; therafter, MAP and cortical blood perfusion (CBP) were measured in ketamine + xylazine anaesthetized rats. Data, mean±SEM, were subjected to ANOVA and significance set at p<0.05.MAP was similar in the WKY (104±1 mmHg), WKY‐STZ and WKY‐STZ‐NaHS groups as was CBP (163±2 BPU). MAP of SHR‐STZ was higher than SHR (145±2 vs 142±2 mmHg) but was lower in SHR‐STZ‐NaHS at 132±3mmHg (P<0.05). CBP in the SHR‐STZ was lower than the SHR (138±3 vs 150±3BPU) but was 12% higher than SHR‐STZ (P<0.05) in SHR‐STZ‐NaHS. GFR in the WKY‐STZ‐NaHS was higher (P<0.05) than the WKY‐STZ (1.8±0.07 vs 0.7±0.02 ml/min/100g). In the SHR‐STZ‐NaHS GFR was higher (P<0.05) than in SHR‐STZ, 2±0.1 vs 1.2±0.1 ml/min/100g.The improved renal function with NaHS was likely due to the vasodilator effect of H2S reducing renovascular resistance and improving the renal blood flow in hypertension concomitant with diabetes in rats.
Hydrogen Sulphide Influences the Excitability of Neurons in the Paraventricular Nucleus of the Hypothalamus
Authors: Khademullah Charline Sahara , Ferguson Alastair 
Published: June 2021

Hydrogen sulphide (H2S) has been observed as having a protective role against gastro‐intestinal inflammation. H2S‐catalyzing enzymes are expressed in the paraventricular nucleus of the hypothalamus (PVN). Previous findings suggest that, if stimulated, the PVN can produce inflammatory responses in the GI tract. To understand the effects of H2S in the PVN, we examined the effects of the H2S donor, sodium hydrogen sulphide (NaHS) on the excitability of PVN neurons. Whole‐cell current clamp recordings from rat PVN neurons in slice preparations were performed. Bath application of 50 μM NaHS influenced 90% (9/10) of cells tested within approximately 45s. of administration. 100% of the responsive cells exhibited a hyperpolarizing response (n=9, −15.42 ± 2.55mV). Of these cells, 89% returned to baseline after approximately 15 mins. Four these neurons were identified as parvocellular neurons and 5 were identified as magnocellular neurons, both displayed similar responses to NaHS. These findings shed light on the role that NaHS plays in the PVN to modify the membrane potential of neurons and in turn, may affect the possible pathways associated with the PVN that are involved in inflammatory effects.Support CIHR
The role of Green Tea in experimental myocardial infarction
Authors: Lustosa Beatriz , Batista Diego , Polegato Bertha , Minicucci Marcos , Pereira Elenize , Okoshi Katashi , Matsubara Luiz , Zornoff Leonardo , Paiva Sergio , Gonçalves andrea , azevedo Paula 
Published: June 2021

The objective of this study is to evaluate whether green tea attenuates cardiac remodeling after acute myocardial infarction.MethodsWistar rats were allocated in 4 groups: C (control); GT (diet with green tea 0,25%); MI (infarcted group) IGT (infarcted group with green tea 0,25%). After 3 months, animals were submitted to echocardiography and isolated heart study. Two way anova and Holm Sidak tests were performed.ResultsBoth infarcted groups showed the same infarction size(p=0,7). Echocardiographic data without interaction:Left atrium/weight (with MI 14,4±0,5; without MI 10,7±0,6)(p<0,001)(with GT 13,0±0,5; without GT 12,1±0,6)(p=0,2); end diastolic ventricle diameter/weight (with MI 21,2±0,6; without MI 17,4±0,7)(p<0,001)(with GT 19,1±0,6; without GT 19,7±0,7)(p=0,5). Systolic function: Fractional area change (with MI 41,2±1,8; without MI 70,8±2) (p<0,001)(with GT 56,1±1,8; without GT 55,8±2)(p=0,9). Data with interaction (p=0,04) E wave deceleration time (EDT)(C 48,5±2,9; GT 45±2,6; MI 35,3±2,5; MIGT 43±2,4). Isolated heart study: Maximum systolic pressure (with MI 143±12; without MI 104±24)(p<0,001)(with GT 133±28; without GT 114±24)(p=0,03).Conclusiongreen tea improved systolic and diastolic function in isolated heart study, increasing EDT. Supported by FAPESP.
RENAL ISCHEMIA/REPERFUSION INDUCED CARDIAC HYPERTROPHY IN MICE: CONTRIBUTION OF APOPTOTIC PROCESS
Authors: Trentin-Sonoda Mayra , Cirino-Silva Rogério , Carneiro-Ramos Marcela Sorelli 
Published: June 2021

ObjectivesNowadays, some studies has emphasize the apoptosis plays a decisive role in cardiac hypertrophy. The aim of this study was to investigate if apoptotic factors were altered in heart after renal ischemia/reperfusion.MethodsC57bl/6J mice were subjected to unilateral 60 min kidney ischemia, followed by reperfusion of 5, 8, 12, 15 and 20 days. Levels of urea were measured to confirm renal failure and gene expression were analyzed by real time PCR.ResultsUrea levels were increased in groups 5, 15 and 20 days (P<0.05). The group 15 days showed a significant increase in heart weight/body weight ratio when compared to sham group. The AIF was increased at 8 and 12 days groups (P<0.05), whereas the anti‐apoptotic Bcl‐2 mRNA levels were increased after 8 days (P<0.05). The Caspase 3 and 9 mRNA levels were increased only after 15 days of reperfusion (p<0.05).ConclusionFirst, the results indicate that renal ischemia/reperfusion model is able to induce a transient cardiac hypertrophy in mice. Levels of mRNA analysis suggests that pro‐apoptotic AIF, Bid, Caspase 3 and 9 might be involved to modulation of cardiac hypertrophy, since we observed an increase in major pro‐apoptotic factors at the same time we observed an increase in cardiac mass.
Intracoronary vs Intravenous Delivery of Adeno‐associated Virus for Cardiac Gene Transfer in Mice
Authors: Fang Hongfei , Lai Ngai Chin , Tang Eric , Roth David M. , Gao Mei Hua , Hammond H. Kirk 
Published: June 2021

Adeno‐associated virus (AAV) is a useful vector for cardiac gene transfer, but the optimal delivery route has not been established. We examined the relative efficacy of three AAV serotypes (AAV5, AAV6, AAV9) and two delivery methods: indirect intracoronary (IC) vs intravenous (IV) in mice. AAV5.EGFP, AAV6.EGFP, and AAV9.EGFP (5 × 1011 genome copies) were delivered by IV and IC injection. Three weeks later left ventricular samples were assessed for EGFP expression using fluorescent microscopy. IC delivery was superior to IV delivery for all serotypes in EGFP fluorescence analysis (Figure), findings that were confirmed by similiar increases in immunoblotting and qPCR (data not shown).ConclusionIC was superior to IV delivery for all three AAV serotypes tested, and AAV9 was superior to AAV6 and AAV5. In settings where maximum cardiac gene transfer is desired, IC delivery should be used.
Abnormal heart rate control in SCN5A‐[Delta]KPQ Mice
Authors: Wu Maddalena Alessandra , Bari Vlasta , Calvillo Laura , Crotti Lia , Schwartz Peter J , Porta Alberto , Montano Nicola 
Published: June 2021

Patients with mutations on the sodium channel gene SCN5A (LQT3) are at highest risk for cardiac arrest/sudden death during sleep or rest. The availability of knock‐in mice, heterozygous for the highly malignant SCN5A‐[Delta]KPQ mutation, is a precious translational tool. We assessed the cardiac phenotypic characterization of the [Delta]KPQ mice in the attempt of identifying predictors of risk.Heart rate (HR), body temperature and the locomotor activity signals were continuously recorded by a telemetric system for 3 consecutive days, in 6 wild type (WT) and 6 transgenic LQT3 mice (LQT). Animals were kept in a temperature‐controlled room at 20–24°C, with constant light/dark cycle. Circadian rhythm variation analysis was performed through the averaging of each 5 min for the whole 24 hours. The 24‐hours were divided in two 12‐hours periods, LIGHT (the quiet/sleep cycle) and DARK (the activity/wake cycle).In the LQT group HR was lower during LIGHT than during DARK (497±70 vs 535±51 bpm; p<0.05). WT group behaved similarly (545±23 vs 571±40 bpm; p<0.05). The HR variability was larger in the LQT group than in the WT one both during DARK (5453±781 vs 4185±1427 bpm2; p<0.05) and LIGHT (5266±388 vs 4189±966 bpm2; p<0.05).LQT and WT mice showed a preserved HR circadian behavior. In addition, in the LQT mice HR variations were unusually large, thus suggesting an abnormal cardiac regulation. Telethon Grant
Protective Mechanism of PPAR‐delta‐HIF1 signaling in the Ischemic Diabetic Heart
Authors: Nanayakkara Gayani K. , Wyble Johnathon , Quindry John , Amin Rajesh H. 
Published: June 2021

Diabetes associated heart disease is at epidemic proportions often manifesting as ischemic heart disease. Therapies which improve myocardial energy availability mitigate the development of myocardial infarction. We observed that Peroxisomal Proliferator Activated Receptor‐delta (PPARδ) activation induces Hypoxia Inducible Factor‐1 (HIF1) expression and nuclear localization in diabetic (db/db) mouse hearts. HIF1 regulates genes associated with protection against ischemic stress and increase energy availability. Adiponectin is among HIF1 inducible genes and increases fatty acid oxidation. We hypothesize
that PPARδ mediated increase in HIF‐1 protects cardiomyocytes against ischemic injury by stimulating heart specific adiponectin production.Results(1) Db/db hearts expresses attenuated levels of HIF1 and adiponectin. (2) PPARδ activation (GW0742, 10 mg/kg, 7 days) in db/db mice increases HIF1 expression and nuclear localization. Promoter activity assays (luciferase) in HEK293 cells reveal that PPARδ transcriptionally regulates HIF‐1. (3) PPARδ activation increases heart specific expression of adiponectin. (4) PPARδ activation significantly protects the diabetic heart from Ischemia Reperfusion injury compared to control db/db hearts.ConclusionPPAR‐δ mediated protection against IR injury in the diabetic heart involves HIF1. Funding: Auburn University Internal Grant Program
Metabolic Profiles of the second and third windows of ischemic preconditioning
Authors: Bravo Claudio Andres , Kudej Raymond K , Vatner Stephen F , Vatner Dorothy E , Yan Lin 
Published: June 2021

There have been numerous studies on the differences between the first window of ischemic preconditioning (IPC) and late IPC, i.e. the second window of IPC.Recently our group has shown the presence of a third window of IPC, which is induced by 6 episodes of non lethal ischemia over 3 days. This model differs from classical second window IPC, induced by 1 or 2 episodes of non lethal ischemia, followed 24 hr. later by a longer period of ischemia. The underlying molecular mechanisms mediating the second and third windows of IPC are very different, but both paradigms of IPC appear to affect myocardial metabolism. The goal of this study was to provide a global analysis of the metabolic profile of these two late IPC models, using a metabolomic approach based on liquid chromatography‐mass spectrometry (LC‐MS) and gas chromatography‐mass spectrometry (GC‐MS) techniques. Myocardial samples from the ischemic section of porcine hearts subjected to second and third window IPC were compared against sham controls. Out of 287 assessed metabolites, there were more changes in metabolic pathways noted in third window (119 metabolites) than second (24 metabolites), but surprisingly only 7 metabolites were common to both models. The results of this study confirm the importance of metabolic pathways mediating late IPC, and again illustrate major differences between the third and second windows of IPC.
Effects of Coffee Consumption on NASH‐Induced Oxidative Stress in Rat Heart
Authors: Cheng Hsin-Yao , Tsai Shiow-Chwen , Huang Wei-Chih , Yang Ai-Lun , Chan Che-Chang 
Published: June 2021

OBJECTIVETo investigate whether coffee consumption improved NASH induced oxidative stress in heart.METHODS8‐week‐old male rats were randomly divided into 3 groups: control, methionine‐choline‐deficient (MCD) and MCD combined with coffee (MCD+Co); feeding with coffee (1.5 ml/day) for 4 weeks until sacrifice. The production of lipid peroxidation and the activities of antioxidant enzymes in left ventricular (LV) tissues were measured by commercial kits. All of the data were presented at Mean ± S.E.M., p <0.05 regard as significantly difference.RESULTSRat fed with the MCD diet showed a rapid loss of body weight and heart weight, but not altered the ratio of LV and body weight. The production of lipid peroxidation was increased in MCD, but not in MCD+Co compared with MCD0. The activity of SOD were significantly increased 3 fold in MCD+Co (p<0.0001) and increased 1.5 fold in MCD (p=0.004) compared with control group. Compared with MCD0, the activity of catalase were enhanced by MCD+Co significantly (p=0.018). Coffee consumption improved the maintenance of glutathione peroxidase (GPx) during the feeding of MCD diet.CONCLUSIONCoffee inhibit the production of lipid peroxidation through enhancing the activity of catalase and GPx in LV.
Effects of acute exercise on circulating endothelial progenitor cells and endothelial function in patients with increased cardiometabolic risk
Authors: Rocha Natalia G , Sales Allan R K , Silva Mayra S , Miranda Renan L , Carvalho Sara B , Silva Jemima R F , Silva Bruno M , Santos Aline A , Nóbrega Antonio C L 
Published: June 2021

Endothelial progenitor cells (EPC) play a critical role in vascular repair and its depletion is usually associated with endothelial dysfunction. In addition, regular moderate‐intensity aerobic exercise increases EPC mobilization from bone marrow to peripheral blood and, consequently, improves endothelial function. Therefore, this is a potential mechanism by which exercise reduces the risk of atherosclerosis in patients with cardiometabolic risk (CMR). However, it is unclear whether exercise‐induced EPC mobilization is preserved in patients with CMR and whether EPC mobilization is associated with endothelial function in this population. Accordingly, healthy subjects (CT group; n=3) and patients with CMR (CMR group; n=7) were studied. Circulating EPC were evaluated quantitatively (flow cytometry) and qualitatively (immunofluorescence) before and 20 min after a 40‐ min bout of cycling exercise. Endothelial function was evaluated by flow‐mediated dilation (FMD, Doppler). The CMR group had a significant reduction in CD34 cells (P=0.02) and a trend of reduction in CD34/VEGFR2 cells (P=0.09) after exercise. Moreover, there was a marginal correlation between mobilization of CD34/VEGFR2 cells and FMD (r=0.55; P=0.10). These preliminary results suggest that a bout of aerobic exercise reduced circulating EPC in patients with CMR and EPC mobilization tended to be associated with endothelial function.Supported by CNPq, FAPERJ, FINEP and CAPES.