bluuebunny/crossref_metadata_2025_split huggingface dataset:
The novel non‐depolarizing, normokalemic cardioplegia formulation based on the combination of adenosine‐lidocaine (Adenocaine™) exerts superior anti‐neutrophil effects by synergistic actions of its components
Authors: SHI WEIWEI , JIANG RONG , Dobson Geoffrey P , Vinten‐Johansen Jakob 
Published: June 2021

ObjectivesWe tested the hypothesis that the combination of adenosine and lidocaine (AL) synergistically attenuates neutrophil (PMN) functions.Methods1. Superoxide anion (O2‐) generation, 2. PMN adherence, 3. Transmigration. Group differences (one‐way ANOVA) were accepted at P value<0.05.ResultsThe isolated porcine PMNs released superoxide dismutase (0.1mg/ml)‐sensitive O2‐ in a burst pattern upon activation. Both adenosine and lidocaine alone inhibited O2‐ production in a dose‐dependent pattern. AL further inhibited O2‐ generation in a synergistic manner. In addition, adenosine (0.1–10 μM) inhibited O2‐ generation by cytochalasin B (priming), whereas lidocaine (1–100 μM) inhibited O2‐ release stimulated by both cytochalasin B and fMLP (activation). Both adenosine and lidocaine alone inhibited PAF‐induced PMN adherence to endothelial cells. Adenosine (50μM) and lidocaine (100 μM) decreased adherence to 71.6±5.4% (n=8, P<0.05) and 73.2±8.1% (n=7, P<0.05) of stimulated control, respectively. AL further suppressed adherence to 47.2±4.3% (n=7, P<0.05). Adenosine (100μM) reduced PMN transendothelial migration to 80.1±6.7% of control (n=6, P<0.05), whereas lidocaine (100μM) showed no significant inhibition. AL did not further decrease transmigration.ConclusionsAL suppresses PMN O2‐ generation and adherence in a synergistic manner relative to adenosine or lidocaine alone.
In vitro and in vivo analysis of macelignan induced toxicity on heart
Authors: Javaregowda Palaksha Kanive , Hong Yunkyung , Kim Sunmi , Hong Yonggeun 
Published: June 2021

Macelignan which isolated from Myristica fragrans Houtt has been suggested that it acts as PPAR α/γ dual agonist for diabetic patients. However, macelignan contains a small amount of safrole considering as carcinogen. Here we investigated that its toxic effect on heart in vitro and in vivo. The systolic blood pressure, pulse and the component of blood serum in spontaneously hypertensive rats (SHR) and control rats were measured. The expression of cell death markers were analyzed by RT‐PCR and immunoblot. We confirmed that PPAR α/γ was expressed on H9c2 cells, neonatal cardiomyocytes and heart. Compared to control, macelignan significantly reduced the beating number and frequency as a concentration dependent manner (p<.05). Cell viability was strikingly decreased at 16 h after treatment. And the expression of autophagic markers as well as apoptotic molecules was maximized at 16 h (p<.05). A significant reduction of the systolic blood pressure was shown in both strains, and pulse was also strikingly decreased after its injection (p<.05). However, the component of serum was not changed by macelignan. Here, we found a cytotoxicity induced by macelignan in vitro and in vivo. Therefore, the use of macelignan as an anti‐cancer or anti‐inflammatory agent should be carefully considered.Funding: BioGreen21 Program (Code No. 20070401‐034‐006‐009‐02‐00), Rural Development Administration, Korea
IRF2BP2 is a new NFAT1 partner acting as a repressor protein
Authors: Carneiro Flavia Raquel Gonçalves , Ramalho‐Oliveira Renata , Mognol Giuliana P. , de Araujo‐Souza Patrícia S. , Viola João P.B. 
Published: June 2021

NFAT family of transcription factors encodes 5 members and is present in a wide range of cell types, regulating genes involved in cell proliferation, angiogenesis, cell cycle progression and apoptosis. NFAT family has two well conserved regions: the regulatory domain and DNA binding domain. N and C‐terminal ends are transactivation sites and show less sequence similarity. To understand the molecular mechanisms related to NFAT functions we performed a yeast two hybrid screening using the less conserved NFAT1 C‐terminal end as bait. We identified that NFAT1 interacts with IRF2BP2 transcriptional repressor by its RING domain. This interaction seems to be NFAT1 specific, since the other conserved regions of NFAT1 do not interact with IRF2BP2. Furthermore, NFAT1 and IRF2BP2 co‐localize in the nucleus in activated cells and luciferase report assays demonstrate that IRF2BP2 represses the NFAT1‐dependent activation of IL‐2 and IL‐4 promoters and TNF‐alfa k3 element. We also identified a nuclear localization signal in IRF2BP2 and mutation of this signal abolishes the repression function of IRF2BP2. Our data demonstrated that IRF2BP2 interacts with NFAT1 and repress its transcriptional activity, suggesting that IRF2BP2 can be a new regulator of NFAT1 transcriptional activity.Financial support: CNPq, FAPERJ, ICGEB
Circulating hepcidin at term pregnancy and in cord blood independently reflects maternal and fetal iron status
Authors: Westerman Mark , Ervasti Mari , Punnonen Kari , Olbina Gordana , Ostland Vaughn , Luukkonen Susanna , Heinonen Seppo , Pulkki Kari , Sankilampi Ulla 
Published: June 2021

BackgroundThe aim of this study was to determine serum hepcidin concentrations and its associations with iron status in pregnant women and cord blood. 191 full‐term pregnant women and newborns were studied. Blood from pregnant women was obtained within 24h of delivery, and venous cord blood shortly after birth. Serum hepcidin was measured by C‐ELISA and compared to hematological and iron indices, including ferritin, TfR, %TSat, hsCRP, and EPO.ResultsHepcidin in pregnant women was significantly lower than in the cord blood [GMC; 13.5 vs. 72.9 ng/mL, respectively]. Serum hepcidin was <5 ng/ml in 12% of pregnant women and in 2% of newborns. Hepcidin was significantly higher in vaginal and emergency section deliveries, compared to elective Cesarean. In pregnant women at term, 7–8% were iron deficient (Hb<110 g/L or %HYPOm >3.4%). Hepcidin was correlated with hsCRP and gestational weeks. 20% of newborns had Hb <145 g/L and 5% had TSat <30%, and were classified as iron deficient. Reference ranges for serum hepcidin at term pregnancy was 1.4 – 70.6 ng/mL (n=126; median 11.9 ng/mL) and for cord blood, 20.1 – 231.2 ng/mL (n=142; median 77.45 ng/mL).ConclusionsMaternal hepcidin levels are suppressed at term facilitating iron transfer to the fetus, while newborn hepcidin levels are normal for the existing iron stores. Research funded by a grant to Kupio University Hospital and by Intrinsic LifeSciences.
Neuroprotective effects of treadmill exercise on brain damage in spontaneously hypertensive rats with focal cerebral ischemia
Authors: Shin Jinhee , Lee Seunghoon , Park Sookyoung , Chang Kyu‐tae , Hong Yonggeun 
Published: June 2021

To determine the neuroprotective effects of treadmill exercise, normotensive Wistar Kyoto (WKY) rats and SHR were subjected to middle cerebral artery occlusion‐reperfusion (MCAo), and then subjected to treadmill exercise for 4‐weeks. In gait analysis, the stride length of the hindlimb increased continuously up to 72 h due to motor dysfunction. Brain tissues from the rats were stained with TTC to estimate the infarct volume. The infarct volume of the SHR was increased significantly following MCAo, as compared to that for the WKY rats (p<.05), which suggests that hypertension is a risk factor for cerebral vascular disorders caused by FCI. Moreover, the gene expression of BDNF, Trk, and nNOS were decreased, whereas iNOS gene expression was increased in MCAo‐brain tissue (p<.05). Also, the expression of BDNF, Trk, and nNOS was increased, whereas the iNOS level was decreased in the MCAo+exercise group (p<.05). These results suggest that MCAo is a strong causative factor for impairment of the brain, and that physical therapeutic intervention is beneficial for the functional rescue of neuromuscular communication in cases of brain damage, including those caused by FCI.Funding: BioGreen21 Program (Code No. 20070401‐034‐006‐009‐02‐00), Rural Development Administration, Korea
Effect of Treatment with Peptidase Inhibitors on Vasoactive Peptide Response in Renal Arteries from Diabetic Rats
Authors: Oltman Christine L. , Kleinschmidt Travis L. , Coppey Lawrence J. , Davidson Eric P. , Yorek Mark A. 
Published: June 2021

The purpose of this study was to examine the effect of peptidase inhibitors on peptide induced relaxation of renal arteries from diabetic rats. Rats were injected with 60 mg/kg streptozotocin (IP), and treated with α‐lipoic acid (2.5g/kg), Enalapril (500mg/kg), Candoxatril (300mg/kg), AVE7688 (500mg/kg), or Alogliptin (200mg/kg) in the diet for 12 weeks. Tension studies were performed on tertiary branches of renal arteries Acetylcholine and sodium nitroprusside responses were not altered in phenylephrine constricted arteries. Atrial natruretic peptide (ANP) and calcitonin gene related peptide (CGRP) responses were attenuated in arteries from diabetic rats. Responses were improved when rats received the peptidase inhibitors, but not when rats were treated with α‐lipoic acid. Thus, responses to vasoactive peptides are reduced in diabetic rats, and treatment with peptidase inhibitors, improves dilation to these peptides. Supported by VA merits to Drs. Oltman and Yorek.
Blood glucose and response to ANP and CGRP (% Relaxation)

Group
n
Glucose (mg/dl)
ANP(10nM)
CGRP(10nM)

Control
11
110 ± 5
97.7 ± 1.8
79.4 ± 5.5

Diabetic
12
578±13*
77.1 ± 4.9*
47.1 ± 5.9*

α‐lipoic acid
8
501 ± 33
79. 6 ± 4.9
54.1 ± 6.9

Enalapril
6
570 ± 22
94.8 ± 3.7#
87.5 ± 4.6#

Candoxatril
8
546 ± 14
96.7 ± 1.7#
80.4 ± 4.1#

Alogliptin
7
536 ± 22
96.2 ± 2.1#
72.3 ± 8.8#

AVE7688
7
575 ± 22
94.8 ± 3.3#
77.1 ± 5.9#

Control vs Diabetic P ≤ 0.05
Diabetic vs treatment, p ≤ 0.05.
Gene networking and canonical pathway analysis in a JMJD3 knockdown human monocytic cell line
Authors: Das Nando Dulal , Jung Kyoung Hwa , Choi Mi Ran , Chai Young Gyu 
Published: June 2021

JMJD3, a JmjC family histone demethylase, can be induced by the transcription factor NF‐kB in response to various stimuli. JMJD3 is crucial for erasing H3K27me3, a histone modification associated with transcriptional repression, and is responsible for the activation of a diverse set of genes. The objectives of this study were to identify the genes in THP‐1 human monocytic cells that are significantly affected by the knockdown of JMJD3, particularly in expression levels and in downstream effects on signaling pathways. THP‐1 cells were subjected to lentiviral JMJD3 shRNA transduction followed by analysis of gene expression by qRT‐PCR. Global gene expression levels were detected in JMJD3 knockdown (kd) THP‐1 human monocytic cells and in TNF‐stimulated JMJD3‐kd THP‐1 cells using a 44‐k human whole genome array. Finally, datasets were analyzed using Ingenuity pathway analysis (IPA) software. IPA analysis reveals that JMJD3 attenuation down‐regulates various key genes in NF‐kB, chemokine and CD40 signaling and mostly affects inflammatory disease response molecules. Moreover, this study significantly highlights the connection of NF‐kB with JMJD3, which suggests an epigenetic regulation of the inflammatory genes.Funded by NRF‐2009‐0077023; Korea.
Attenuated increases in sweat rate but not skin blood flow to increasing doses of methacholine in aged skin
Authors: Shibasaki Manabu , Inoue Yoshimitsu , Crandall Craig G 
Published: June 2021

Sweating and skin blood flow responses to whole‐body heat stress are decreased in aged skin. This study tested the hypothesis that these responses are attenuated to exogenous methacholine (MCh) in aged skin. Two microdialysis membranes were placed in dorsal forearm and lower leg skin in 7 healthy young (22±1) and elderly (63±2) subjects. Local sweat rate (SR) and skin blood flow were simultaneously measured over each microdialysis membrane. After insertion trauma subsided, and while skin temperature was clamped at 34°C, progressively increasing doses of MCh were administered (5 min/dose). Cutaneous vascular conductance (CVC) was not different between groups prior to and across all doses of MCh regardless of site, although forearm CVC was greater relative to lower leg CVC in both groups (both P<0.001). On the other hand, SR in aged skin was lower relative to young skin (significant dose × age interaction), while there was no regional difference between leg and arm responses in either group. These results confirm prior findings that sweat gland function is reduced in aged skin. Conversely, there is no effect of aging on cutaneous vasodilator responsiveness to exogenous methacholine.Supported by JSPS 21790225 and HL84072
Exercise‐induced fatigue and hyperthermia limit muscle force production capacity through peripheral and spinal alterations respectively
Authors: Racinais Sebastien , Matic Ivana , Girard Olivier 
Published: June 2021

ObjectiveTo discriminate the mechanisms by which exercise‐induced fatigue and hot environments impair muscle force production alone or in conjunction.Methods7 participants (preliminary data at the date of abstract submission) were tested at rest, following 20 min of moderate cycling (100 W) and after incremental cycling to exhaustion in two environmental conditions (CON: 24°C, 24% rH; HOT: 40°C, 40% rH). Electrically evoked potentials (M‐wave and H‐reflex) were obtained at rest and during maximal voluntary contractions (MVC) of the plantar flexors.ResultsExercise‐induced fatigue significantly altered the indexes of peripheral fatigue (e.g., electrically evoked peak twitch, and quantity of neural drive needed to produce an absolute level of force). Heat exposure significantly decreased the different indexes of spinal modulation (e.g., H‐reflex, V‐wave).ConclusionMaximal voluntary force is decreased by both exercise‐induced fatigue (−9%) and heat exposure (−7%). These decrements originate respectively from muscle contractility and spinal modulation, and are cumulative when exercising in hot environment (−15%).
Sodium metaarsenite (KML001) induces a G1 phase arrest in HCT116 colorectal cancer cells
Authors: Hong Yunkyung , Kim Sunmi , Rho Gyu‐jin , Hong Yonggeun 
Published: June 2021

Arsenic‐based reagents have been used as medicines, but they can cause chromosomal abnormalities in vitro and in vivo. Recent studies have reported alterations in telomere kinetics caused by the arsenic compound sodium metaarsenite (KML001), suggesting that it may be useful as an anti‐cancer reagent. Here, we investigated the anti‐cancer effects of KML001 on HCT116 cells. The expression of autophagic and apoptotic molecules were measured by RT‐PCR and immunoblotting in HCT116 cells and SW480 treated with KML001. KML001 reduced colorectal cancer cell proliferation in a concentration‐dependent manner, with a significant reduction at 1 μM (p<.05). p53 expression and conversion of LC3I to LC3II were dramatically increased, whereas no significant changes in caspase 3 and Bcl‐1 were observed (p<.05). Compared to the controls, the number of cells in G1 phase decreased 48 h after KML001 treatment, and the expression of several cyclin‐dependent kinase inhibitors was significantly increased (p<.05). In neonatal cardiomyocytes, morphologic signs of atrophy and a reduction in the number of differentiated cells were observed. Finally, a dramatic decrease in beating frequency and the number of embryoid bodies was noted after 18 h of treatment. KML001, which targets telomere kinetics, suppresses the proliferation of HCT116 cells, which might induced by a G1 phase arrest.Funding: BioGreen21 Program (Code No. 20070401‐034‐006‐009‐02‐00), Rural Development Administration, Korea
Exogenous melatonin leads to the activation of autophagy and cellular senescence in colorectal cancer cells
Authors: Hong Yunkyung , Kim Sunmi , Park Sookyoung , Hong Yonggeun 
Published: June 2021

The purpose of the present study was to determine the anti‐cancer effect of melatonin on HCT116 colorectal cancer cells. At 10 μM, melatonin induced a significant reduction in MT‐R1A expression and an increase in RORα expression over time (p<.01). Proliferation was strikingly reduced by 10 μM melatonin in a time‐dependent manner. Bcl‐2 mRNA expression was decreased at 48 h after treatment (p<.01). Furthermore, the induction of cleaved caspase 3, a significant increase in converted LC3II, and a decrease in Bcl‐1 expression were observed in response to melatonin treatment (p<.01). A time‐dependent increase in the number of cells in G1 phase was also caused by melatonin at 10 μM. Cyclin D expression was unchanged, whereas cyclin E expression was significantly reduced by melatonin at 10 μM (p<.01). The level of cyclin‐dependent kinase inhibitors, p16 was also altered in melatonin‐treated HCT116 cells. Treatment with melatonin at a pharmacologic concentration significantly inhibited the overgrowth of HCT116 cells, but activated by stress‐induced senescence as well as autophagy indicating it could be useful chemotherapeutic drug with minimal cytotoxicity.Funding: BioGreen21 Program (Code No. 20070401‐034‐006‐009‐02‐00), Rural Development Administration, Korea
Pyruvate pretreatment protects glial cells from ischemia‐reperfusion injury by stabilizing HIF‐1
Authors: Ryou Myoung‐Gwi , Mallet Robert T , Yang Shaohua 
Published: June 2021

BackgroundDuring brain ischemia and reperfusion (I/R), substantial amounts of reactive oxygen species (ROS) are produced, damaging brain cells. Pyruvate, an energy substrate and potent antioxidant, inhibits HIF‐1α degradation under normoxic conditions. Recently we reported that pyruvate increased neuroprotective erythropoietin via HIF‐1 pathway. Hypothesis: Pyruvate pretreatment protects glial cells from I/R injury.MethodsC6 cells maintained in glucose and pyruvate free DMEM were randomly assigned to control or pyruvate groups. 30 min prior to hypoxic stress (0.5% O2), cells were pretreated with 10mM pyruvate followed by 1h hypoxia and 24 h reoxygenation. Cell viability was assessed from LDH release and Calcein AM. ROS generation was evaluated with DCF stain. Glucose oxidase (GOx) (1mU) +/− pyruvate was applied to test the role of pyruvate's antioxidant effect in stabilizing HIF‐1α. Immunoblot was used to determine protein content of HIF‐1α, erythropoietin, and β‐site of APP cleaving enzyme (BACE).ResultsCell viability was greater in pyruvate than control group. Pyruvate dampened ROS generation and BACE content vs. control. Pyruvate stabilized HIF‐1α in the face of GOx challenge. Similarly, HIF‐1α was increased after I/R in pyruvate vs. control. Erythropoietin content paralleled HIF‐1α in each group.ConclusionPyruvate dampens ROS generation, and augments HIF‐1α, and increased cell viability during I/R. Pyruvate enhancement of HIF‐1 increased erythropoietin and decreased BACE protein content. Therefore, pyruvate pretreatment can protect C6 cells by stabilizing HIF‐1.
Melatonin prevents muscle atrophy and the alteration of myosin heavy chain in spinal cord injured rats
Authors: Seo Hyeongsun , Park Kanghui , Park Sookyoung , Javaregowda Palaksha Kanive , Hong Yonggeun 
Published: June 2021

The purpose of this study was to confirm the behavioral features of spinal cord injury (SCI) and to investigate the effects of melatonin on muscle atrophy and shifts in myosin heavy chain (MHC) in an SCI model. SCIs were surgically induced in eight‐week‐old male Sprague‐Dawley (SD) rats that had been randomly divided into three groups: Control, SCI (n=13), and melatonin‐treated after SCI (SCI+MT, n=13). Melatonin (10 mg/kg body weight) was injected subcutaneously twice a day (07:00 and 19:00) for four weeks, after which the body weight and motor function of the rats were evaluated. The expression of muscle atrophy‐related genes in hindlimb muscles, including MAFbx and MuRF1, and MHC, were also analyzed. The body weight and motor functions of the rats were decreased at the acute phase after SCI. The gene expression of MAFbx and MuRF1 were increased in the hindlimb muscles (p<.05), indicating SCI‐induced muscle atrophy. Melatonin contributed to motor recovery, decreased MAFbx and MuRF1 gene expression, and altered MHC expression in the hindlimb muscles (p<.05). Thus, melatonin may promote functional recovery, prevent muscle atrophy, and alter MHC expression after SCI.Funding: BioGreen21 Program (Code No. 20070401‐034‐006‐009‐02‐00), Rural Development Administration, Korea
GENETIC VARIANTS OF MICRO‐RNA 196a2 SEQUENCES CAN PREDICT SURVIVAL OF CHOLANGIOCARCINOMA
Authors: Ko Kwang Hyun , Kim Nam Keun 
Published: June 2021

BackgroundMicroRNAs (mir) are a new class of non‐protein‐coding, small RNAs that has function of tumor suppressors or oncogenes. They participate in diverse biological pathways and function as gene regulators. Only a few studies have been published about the association between microRNA polymorphism and malignant tumor.AimWe evaluated that the association between genetic variants of MicroRNA and survival of patients with cholangiocarcinoma. Patients andMethodWe enrolled 94 patients, who were diagnosed with cholangiocarcinoma between Jan.1999 to Nov. 2006 in Bundang CHA hospital, CHA University and obtained blood sample. Using DNA extract from white blood cell, we analyzed mir‐196a2, mir‐149, mir‐499 and mir‐146a expressions by PCR‐RFLP and patients’ survival.ResultsMean age of patients was 66.9 ± 10.7 yrs old and fifty five was male and thirty nine was female. Median survival was 210 days (18 – 1290 days) after diagnosis of chlangiocarcinoma. According to genetic variant of mir‐196a2, wild type (TT) showed significantly longer survival than in variant type (CT, CC) (P = 0.018), especially in male patients (p=0.011). There was no association between mir‐149mir‐499 and mir‐146a polymorphism and survival of cholangiocarcinoma patients.ConclusionThese findings suggest that genetic variants of microRNA 196a2 sequence could be important to predict survival of cholangiocarcinoma patients, but these findings need to be validated in larger prospective study.
Effects of Typha latifolia aqueous extracts on livers and kidneys of mice
Authors: Habacha Souhaila , Khmiss Fathia , Maaroufi Khira 
Published: June 2021

The aim of this study was to investigate the in vivo effects of roots and flowers extracts of Typha latifolia with an emphasis on liver and kidney of mice and to determine the LD50 of extracts. Animals were divided into three groups. They were respectively orally administrated by roots aqueous extract (ARE), flowers (AFE) and water. On day 14, liver and kidney were removed and weighted for histological study. The results showed that the liver and kidney weights remained uniform during treatments. The results showed that weights were not significantly different from those of control group. LD50 for the ARE was >600mg/Kg body wt and was equal to 200 mg/Kg for AFE. Histological study showed that livers conserve structural features with ARE. However, they undergo structural alteration with AFE: a centrolobular sinusoidal congestion and disruption of the central vein and hepatocellualr necrosis. ARE had no pernicious effect on kidneys. However, AFE caused alteration consisting of inflammatory infiltration and necrosis.Our results may be in relation with a toxic effect of AFE on liver and kidney while the ARE seems to be a safe extract.