bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS-B06-2: IN VIVO MYOCARDIAL EFFECTS OF INTRAPERITONEAL ARGLABIN VIA NLPR3 INFLAMMASOME AND MAPK/IKKB;/NFKB PATHWAYS
Authors: Bisht Khushboo , Arya Dharam Vir Singh , Verma Vipin Kumar , Abdullah Zia , Ray Ruma , Narang Rajiv , Nag Tapas Chandra , Bhatia Jagriti 
Published: January 2023

Introduction:
Myocardial injury is a consequence of multiple underlying events that lead immune response by activated immune cells. Oxidative stress triggers an inflammatory cascade and apoptosis, this exacerbates cardiac injuries and dysfunction. Arglabin is a sesquiterpene lactone, an anticancer compound shown to have potential anti-diabetic effects in in vivo model.

Methods:
Male Wistar Rats in the 6 out of 9 groups were pre-treated with different doses (2.5 μg/kg, 5 μg/kg and 10 μg/kg of Arglabin) for 21 days. other 3 groups were normal control, vehicle and isoproterenol control. On 22nd day, isoproterenol was injected to induced myocardial injury (85 mg/kg/day). Normal control and isoproterenol control groups. Histopathological examination, electron microscopy, biomarkers (cTnI and LDH), cardiac parameters, oxidative stress (MDA, GSH, SOD, and CAT), inflammatory mediators (IL-6, IL-1β;, and TNF α), and apoptotic markers (BAX, Bcl2, and caspase-3) were evaluated.

Results:
Histopathological examination revealed increased neutrophilic infiltration in arglabin pretreated groups that correlated with electron microscopic findings. increased activity of IL-6, IL-1β;, TNFα, Caspase-1, caspase-3 and BAX was found in different pre-treated group. increased JNK expression was observed in arglabin pre-treated groups (2.5,5,10). altered expression of NFκB, P38, pP38 and IKKβ; were observed.

Conclusion:
Arglabin administration altered myocardial structure and modulated myocardial function via NLRP3 and MAPK pathway. Consideration regarding cardiovascular adverse effects must be undertaken when exploring other potential role of arglabin. Also, continuous cardiovascular monitoring is suggested for those on anti-cancer treatment with arglabin.
PS-B07-1: BRAIN-TARGETED MECHANICAL INTERVENTION USING PASSIVE HEAD MOTION CAN BE ANTIHYPERTENSIVE
Authors: Sakitani Naoyoshi , Maekawa Takahiro , Yoshino Daisuke , Takano Kouji , Shinohara Keisuke , Kishi Takuya , Tomiyasu Koji , Ogata Toru , Tsuchimochi Hirotsugu , Saito Shigeyoshi , Yoshino Kohzoh , Funamoto Kenichi , Shinohara Masahiro , Nagao Motoshi , Sawada Yasuhiro 
Published: January 2023

Objective:
Reproduce the antihypertensive effect of physical exercise by applying mechanical intervention.

Design and method:
We conducted animal experiments in which we reproduced mechanical accelerations generated in the head during treadmill running at a moderate velocity. We performed in vitro experiments using cultured cells to determine what type of mechanical force was responsible for the antihypertensive effect of mechanical intervention. We carried out clinical studies to validate the clinical relevance of our findings.

Results:
Passive head motion in hypertensive rats, which reproduced the mechanical accelerations generated in their heads during treadmill running at a moderate velocity, decreased the expression of angiotensin II type 1 receptor (AT1R) in astrocytes in the rostral ventrolateral medulla (RVLM). This decrease resulted in lowering their blood pressure. Passive head motion generated interstitial fluid movement, which was estimated to exert shearing forces with an average magnitude of < 1 Pa on the cells in the rat medulla. Application of fluid shear stress of relevant magnitudes decreased the AT1R expression in cultured astrocytes, but not in neuronal cells. Furthermore, interference with interstitial fluid movement by hydrogel introduction in the RVLM of hypertensive rats eliminated the ability of passive head motion and treadmill running to decrease their blood pressure and AT1R expression in the RVLM astrocytes. Consistent with these results from animal experiments, vertically oscillating chair riding by hypertensive adult humans, which reproduced the mechanical accelerations generated in their heads during light jogging, lowered their blood pressure.

Conclusion:
Brain-targeted mechanical intervention can be antihypertensive by modulating the function of RVLM astrocytes through interstitial fluid shear stress.
PS-B07-2: EXERCISE TRAINING PREVENTS HIGH FRUCTOSE-INDUCED HYPERTENSION AND RENAL DAMAGES IN DAHL SALT-SENSITIVE RATS
Authors: Xu Lusi , Hu Gaizun , Kohzuki Masahiro , Ito Osamu 
Published: January 2023

Background:
High fructose diet (HFr) causes metabolic syndrome, and HFr-induced hypertension and renal damage are exaggerated in Dahl salt-sensitive (DS) rats. Exercise training (Ex) have antihypertensive and renal protective effects in rats fed HFr, but these effects of Ex are weak in DS rats fed a high-salt diet. This study thus examined the effects of Ex on DS rats fed HFr.

Methods:
Male DS rats were divided into three groups. The control group was fed a control diet, both the HFr group and the HFr-Ex group were fed a HFr (60% fructose). The HFr-Ex group also underwent treadmill running (20 m/min, 60 min/day, 5 day/ week). After 12 weeks, renal function, histology, and renin-angiotensin system (RAS) were examined.

Results:
HFr increased blood pressure, urinary albumin, and creatinine clearance, and Ex inhibited these increases. HFr induced glomerular sclerosis, podocyte injury, afferent arteriole thickening, and renal interstitial fibrosis, and Ex ameliorated them. HFr reduced plasma renin activity, and Ex further reduced the activity. HFr also increased the expression of angiotensinogen, renin, angiotensin converting enzyme (ACE), and angiotensin II type1 receptor (AT1R), and Ex restored the ACE expression to the control levels. HFr decreased the expression of ACE2, angiotensin II type2 receptor (AT2R), and Mas receptor (MasR), and Ex restored the ACE2 and MasR expressions to the control levels and further decreased the AT2R expression. HFr increased the ACE activity and decreased the ACE2 activity, and Ex restored these activities to the control levels.

Conclusion:
Ex prevents HFr-induced hypertension and renal damages in DS rats. The changes in renal RAS may be involved in the mechanism of the antihypertensive and renal protective effects of Ex.
PS-B07-3: ANGIOTENSIN I CONVERTING ENZYME INHIBITORY PEPTIDES DERIVED FROM KATSUOBUSHI
Authors: Seki Eiji 
Published: January 2023

Purpose:
Antihypertensive components are typically assessed by screening based on in vitro results; however, since intestinal absorption is closely involved in the antihypertensive mechanism of action, we attempted to analyze the absorption of bonito derived peptides, which have been found to have antihypertensive effects in animal experiments.

Methods:
The intestinal tracts of rats, 7 week old male SDrats, were excised after performing cervical dislocation. Incisions 5.5 cm were quickly made into the jejunum, one side was ligated and inverted, and after injecting 1 mL reaction solution, the other side was ligated to create an inverted sack. The sack was then quickly placed in 30 mL of the reaction solution, antihypertensive amount: KBP 0.3 mg/per animal and synthetic peptides: each 0.25 mM, and left to react for 30 min at 37°C after which the inverted sack was removed and washed gently with physiological saline before recovering all the internal fluid. Liquid chromatography tandem mass spectrometry LC/MS/MS was used for analysis and the intestinal fluid samples were measured after examining pretreatment and measurement conditions.

Results:
Pretreatment conditions involved adding 5 μL water, 5 μL IS L-Leu-D-Leu, and 5 μL of 20% sulfosalicylic acid to a 50 μL intestinal fluid sample, stirring the sample, transferring 0.22 μm to a centrifugal filter, performing centrifugation for 3 min at 20000 g and 4°C and then injecting the filtrate into the LC/MS/MS system. LC conditions included a 1.7 μL ACQUITY UPLC BEH C18 column; 2.1, 50 mM, 0%-100% acetonitrile/0.1% TFA linear gradient elution in the mobile phase. Based on the above analysis conditions, the GW, AW, VW, MW, IW, LW, and WL values ng/mL of KBP in the reaction solution were 34.0, 4.64, 7.11, 1.28, 12.7, 4.57, and 0.923, respectively, and 53.2, 3.92, 6.02, 1.10, 8.76, 5.76, and 0.785, respectively. Values for the reaction solution of additive-free peptides serving as a base were estimated at 13.5, 1.09, 2.06,0.350, 5.54, 1.72, and 0.189, respectively. The calibration curve range was set at 0.200–1000ng/ mL.

Conclusion:
The intestinal membrane permeability of dried bonito-derived dipeptides, which have an antihypertensive effect in vivo, suggests that dipeptides absorbed from the intestinal membrane may have an antihypertensive effect.
PS-B07-7: MACHINE LEARNING CLASSIFICATION OF CORONARY HEART SYNDROME BASED ON ELECTROCARDIOGRAM IMAGE USING CONVOLUTIONAL NEURAL NETWORK ALGORITHM
Authors: Fajar Rifaldy , Selena Maria , Alorra Zoya 
Published: January 2023

Background and Aim:
Electrocardiogram (ECG) is one of the most important examination models used to diagnose various abnormal heart rhythms. An EKG records the electrical activity of the heart through wires and electrodes that are attached to the skin of the arms, legs, and chest wall. Early examination of heart defects can improve quality of life through appropriate treatment. One of the abnormalities in the heart is coronary heart disease. CHD is a heart disease that is mainly caused by the narrowing of the coronary arteries due to atherosclerosis or spasm or a combination of both. In this study, a system was designed to classify coronary heart disease from the results of ECG images.

Methods:
The study consisted of several stages, starting with the collection of ECG image data for cardiac abnormalities which were used for training images and testing images. The next step is pre-processing using a grayscale process to show the intensity value. Furthermore, at the segmentation stage, a thresholding process is used which aims to divide the image into two parts, namely between the object and the background by forming a binary image. The next stage is the process of taking feature values from the segmentation results using Invariant Moment. The final stage is classification using the Convolutional Neural Network. The data used in this study are images obtained from Beecardia physiobank. There are four classifications of images processed in this system, namely Normal, Asymptomatic, Angina Pectoris, and Acute Myocardial Infarction. The amount of data used is 126 where the image is divided into two, namely, 101 training data and 25 testing data.

Results:
The Convolutional Neural Network method is able to classify coronary heart disease from the results of ECG images very well. The results of the classification process for coronary heart disease from the results of ECG images are able to achieve an accuracy of 92%.

Conclusion:
The classification system can perform its performance well, as evidenced by the percentage obtained, including a height exceeding 90%. Suggestions for the future, more training data can be used so that at the time of testing, the test data can get higher accuracy.
PS-B07-9: THE EFFECT OF ROUTINE PHYSICAL ACTIVITY TOWARD THE AORTIC WALL AREA IN RAT MODEL OF TYPE 2 DIABETES MELLITUS
Authors: Alfaruqy Maulida Abdillah , Pramaningtyas Miranti Dewi 
Published: January 2023

Background:
The damages in pancreatic b-cell as one of the main pathophysiologies of type 2 diabetes mellitus (T2DM) may result in hypoinsulinemia and hyperglycemia. Physical activity plays an important role in the comprehensive management of diabetes mellitus. This study aimed to understand the effect of routine physical activity on the aortic wall area of T2DM rat model.

Methods:
This study is an animal model experimental research with a post-test only control group to measure the wall area of the abdominal aorta in diabetic rats after routine physical activity. Induction of T2DM in male Sprague Dawley rat was done by injecting streptozotocin 35 mg/kg intraperitoneally. The diabetic rats were divided into two groups: the first group get physical activity and the second group was not. The control was represented by a group that receive citrate buffer injection. A routine physical activity in low to moderate intensity is given using a special rat treadmill five times a week for nine weeks with a gradual rising of speed at 5–20m/minute for a maximum of 60 minutes. The rat abdominal aorta was stained by hematoxylin-eosin and the wall area was measured by ImageJ.

Results:
The mean of the wall area in diabetic rats with exercise is 452436.60(+42375.92) um2, in diabetic rats without exercise is 35998.81(+34724.68) um2, and in the control group is 434595.83(+34724.68) um2. The statistical analysis using the Kruskal-Wallis test shows no significant difference between the three groups (p = 0.052).

Conclusion:
In conclusion, diabetic rats with routine physical activity have a wider abdominal aorta wall area, but it is not statistically significant.
PS-B08-2: EXOSOME-MEDIATED INTERCELLULAR CROSSTALK BETWEEN MESANGIAL CELLS AND MACROPHAGES PARTICIPATES IN THE PROGRESSION OF DIABETIC KIDNEY DISEASE.
Authors: Fujimoto Daisuke , Umemoto Shuro , Kuwabara Takashige , Date Ryosuke , Hata Yusuke , Mizumoto Teruhiko , Kakizoe Yutaka , Izumi Yuichiro , Mukoyama Masashi 
Published: January 2023

Background:
Extracellular vesicles (EVs) are important mediators of intercellular communication and can play a key role in the regulation of pathophysiological processes. Particularly, exosome-mediated intercellular crosstalk has been addressed in several disorders such as cancer and lifestyle-related diseases including hypertensive and diabetic vascular diseases. In diabetic kidney disease (DKD), it has been reported that macrophages infiltrate the mesangial region and may play an important role through local inflammation in glomeruli.

Design and method:
In this study, we focused on exosome as a factor that acts in a paracrine manner in glomeruli and examined the effects of mesangial cell-derived exosomes cultured under high-glucose conditions on macrophages. In order to identify new therapeutic agents, we screened a validated compound library that can efficiently inhibit this mechanism and also studied their effects on DKD.

Results:
Exosomes released from mesangial cells induced inflammation in macrophages, as indicated by the NFκB transcriptional activity and TNFα and IL-1β mRNA expression. In addition, the effect was significantly enhanced in exosomes from mesangial cells cultured under high-glucose conditions compared to low-glucose conditions. We also observed that fluorescent-labeled (DiO) exosomes were endocytosed by macrophages in vitro and in vivo. Next, we conducted drug screening using a validated compound library to find compounds that could specifically and effectively inhibit the inflammation in macrophages induced by exosomes. The screening was divided into four steps, and we succeeded in narrowing down the list to 30 candidate compounds from a total of 1,364 compounds. Finally, an HSP90 inhibitor, alvespimycin, was identified as a compound with a strong inhibitory effect on both exosome uptake and the NFκB transcriptional activity. Treatment of a diabetic rat model with alvespimycin significantly reduced proteinuria, and showed a trend toward suppression of mesangial expansion.

Conclusions:
We found that mesangial cell-derived exosomes are important for inducing the local inflammation by intercellular crosstalk between mesangial cells and macrophages in DKD. Furthermore, alvespimycin, one of the HSP90 inhibitors obtained by drug screening, can effectively ameliorate the disease progression, suggesting that this mechanism could become a novel therapeutic target for DKD.
PS-B08-11: SALT DIRECTLY REGULATES UMOD TRAFFICKING IN A NORMOTENSIVE BACKGROUND
Authors: Boder Philipp , Mary Sheon , Mark Patrick B , Leiper James , Delles Christian 
Published: January 2023

Objective:
Uromodulin (UMOD) is the most abundant protein secreted into urine of healthy individuals and is primarily produced by the renal thick ascending limb cells (TAL) of the loop of Henle. Genetic studies have demonstrated an association between UMOD risk variants, kidney diseases, and hypertension. We have previously demonstrated that salt induces a reduction in urinary UMOD excretion in normotensive rats after three weeks, which was exacerbated in a chronic hypertensive rat model. Our next objective was to determine the influence of salt on UMOD secretion independent of blood pressure effects. Here we investigate the underlying molecular differences in the effects of intermittent and chronic salt-loading on UMOD trafficking dynamics in the TAL.

Design and Methods:
Wistar-Kyoto (WKY) normotensive rats were maintained on 1% NaCl for three weeks in an intermittent pattern (one week on, one week off, one week on) or continuously (chronic) over three months. Urine was collected over a 24-hour period every experimental week. Total kidneys were harvested for lysate extraction, subcellular fractionation, and immunofluorescence analyses. UMOD levels were measured using ELISAs, qPCR, and Western blotting.

Results:
No abnormal changes in blood pressure, body weight, or renal parameters including albumin-creatinine-ratio and injury markers KIM-1 and NGAL were observed in either animal study group. During intermittent salt-loading, there was no significant difference in UMOD mRNA expression or total kidney UMOD protein levels. However, UMOD excretion significantly decreased after one week and remained lower than control levels even after salt removal. Similarly, chronic salt-loading did not alter UMOD mRNA levels, however total kidney UMOD protein levels were increased after three months. More specifically, analysis of subcellular fractions of the medulla from these salt-loaded animals showed higher levels of cytosolic UMOD compared to membrane-bound UMOD. Immunofluorescence analyses revealed a trend towards increased localisation of UMOD with endoplasmic reticulum (ER) marker calnexin.

Conclusions:
Our findings underline the effect of salt in molecular trafficking of UMOD in the kidney independent of blood pressure effects. Long-term salt exposure of TAL cells leads to intracellular accumulation of this abundant renal protein. The relationship between salt, UMOD accumulation, and renal end-organ damage in hypertension requires further research.
PS-B09-2: ENOS-NO PATHWAY MODULATES AKI TO CKD TRANSITION IN IRI MODEL MICE VIA REGULATION OF B;CATENIN TRANSLOCATION
Authors: Takasu Masanobu , Kondo Megumi , Nagasu Hajime , Kadoya Hiroyuki , Kishi Seiji , Kidokoro Kengo , Kashihara Naoki 
Published: January 2023

Background:
The incidence of acute kidney injury (AKI) has increased over the past few decades. AKI is also currently recognized as an inducer of chronic kidney disease (CKD) through a process known as the AKI to CKD transition. It has been shown that aging and hypertension are risk factor for the AKI to CKD transition. Because these conditions are related to endothelial dysfunction, we hypothesized that the AKI to CKD transition is promoted by deficiency in the eNOS Nitric Oxide (NO) pathway as an endothelial dysfunction, and we used eNOS deficient mice (eNOSKO) and wild-type (WT) mice (C57B6/J: WT) to determine the mechanism of the AKI to CKD transition.

Methods:
WT and eNOSKO mice were used to determine the role of the eNOS NO pathway. Ischemic reperfusion was performed two weeks after uni-nephrectomization. The ischemic time was 20 min. The WT and eNOSKO mice were divided into four groups: WT sham, WT ischemic reperfusion injury (IRI), eNOSKO-sham and eNOSKO IRI. The first theses mice were sacrificed on Day 28 (D28) after the IRI (WT IRI D28 and eNOS IRI D28). Pathological analysis was conducted using Masson staining and KIM1 staining. Inflammation was assessed using quantitative PCR (qPCR) (IL1β;, IL6, and F4/80) and flow cytometry (FACS) analysis.

Results:
There was no evidence of kidney damage in the WT IRI D28 group. However, KIM1 staining detected tubular cell damage in the eNOSKO IRI D28 group. Fibrosis, which was assessed using the Masson staining, was also exacerbated in the eNOSKO IRI D28 group compared with the WT IRI D28 group. These results suggested that deficient eNOS NO signaling promoted the AKI to CKD transition. Next, the WT-IRI and eNOS IRI mice were sacrificed on Day 1 (D1) after the IRI (WT IRI D1 and eNOSKO IRI D1) to evaluate inflammation and kidney damage in the acute phase after IRI. There were no differences in kidney damage and inflammation between the WT-IRI-D1 and eNOSKO-IRI-D1 groups. In addition, at each time point (D7, Day 14 (D14), and D28) after IRI, qPCR was used to detect Wnt β;catenin related gene expression in the entire kidney. Expression of these genes was increased in the eNOSKO IRI D7 group compared with the WT IRI D7 group.

Conclusions:
Our results showed that after ischemic reperfusion, deficiency in the eNOS NO pathway promotes the AKI to CKD transition via acceleration of Wnt β;catenin. Therefore, activation of the eNOS NO pathway could be a potential therapeutic target in AKI.
PS-B09-5: THE LANDSCAPE OF HIGH-CONFIDENCE MICRORNA - GENE INTERACTIONS OPERATING IN THE HUMAN KIDNEY AND THEIR ROLE IN HYPERTENSION
Authors: Drzal Maciej Szymon , Xu Xiaoguang , Eales James M , Scannali David , Rainey Timothy , Bogdanski Pawel , Wystrychowski Wojciech , Szczechowska Ewa Zukowska , Zywiec Joanna , Guzik Tomasz J , Morris Andrew P , Charchar Fadi J , Tomaszewski Maciej 
Published: January 2023

Objectives:
MicroRNAs (miRNAs) are short non-coding RNAs acting as post-transcriptional regulators of mRNAs. It is becoming increasingly clear that they play an important role as molecular drivers/mediators of complex human diseases including hypertension. Given the key role of the kidney in the pathogenesis and treatment of hypertension we sought (i) to comprehensively characterise the network of renal miRNA-mRNA interactions and (ii) evaluate their relevance to human hypertension.

Design and method:
Using poly-A RNA-sequencing and small RNA-sequencing we have identified 22,558 genes and 1,604 miRNAs in the discovery analysis of 328 human kidney samples (Human Kidney Tissue Resource). The outputs from these experiments have been normalised and adjusted by linear regression. We conducted a replication analysis of the identified miRNA-gene pairs in normal control kidney samples from two National Institutes of Health cohorts - CPTAC (n = 66) and TCGA (n = 83). We then examined the extent to which the expression of kidney genes known as targets of blood pressure lowering medications can be modulated by microRNAs. Finally, we investigated whether the effects of these interactions are observed at the protein level (CPTAC dataset).

Results:
We identified 186,192 unique statistically significant inverse miRNA-gene correlations in our discovery resource. Of these, 4,319 were replicated in both NIH kidney resources. 32.5% of kidney protein-coding genes and 12.2% of kidney long non-coding RNAs had at least one such high-confidence miRNA associated with their expression. SLC12A3 (Solute Carrier Family 12 Member 3) - kidney gene target for thiazides, SLC12A1 (Solute Carrier Family 12 Member 1) - gene target for loop diuretics and SLC5A2 (Solute Carrier Family 12 Member 2) - gene target for SGLT2 inhibitors showed consistent, negative correlations with four, five and five kidney miRNAs in each of three independent datasets, respectively. Some of the identified miRNAs showed negative correlations with more than one gene-drug targets. For example, miR-31-5p showed a strong, significant inverse association with SLC5A2 (R = -0.67, P = 9.41E-10) and SLC12A3 (R = -0.70, P = 5.80E-11) in the CPTAC resource. We confirmed that miRNA-31-5p also negatively correlates with the renal expressions of SLC12A3 and SLC5A2 at the protein level (R = -0.58, P = 3.5E-7 and R = -0.45, P = 1.51E-4, respectively).

Conclusion:
We characterised highly credible miRNA-gene interactions in the human kidney and mapped them onto genes and proteins of established relevance to blood pressure lowering treatment. These kidney miRNAs represent exciting targets for the development of novel antihypertensives.