bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS-B06-6: LOSS OF SKELETAL MUSCLE MASS INFLUENCES IMMUNE HOMEOSTASIS AND ACCELERATES THE RENAL-RELATED RISK OF HYPERTENSION
Authors: Mogi Masaki , Liu Shuang , Kiyoi Takeshi 
Published: January 2023

Objective:
Patients with systemic lupus erythematosus (SLE) are predisposed to developing sarcopenia associated with their underlying proinflammatory condition and a decrease in motility. Also, SLE related autoimmune renal diseases are in part imputed to classical vascular risk factors such as hypertension. The relationship between circulating autoantibodies and hypertension has been recognized. How sarcopenia hastens immune dysfunction in SLE and autoimmunity per se is an underlying cause of hypertension remains uncertain. The present study elucidated the relationship between skeletal muscle loss and systemic immune status with regards to how sarcopenia-mediated immune dysfunction contributes as a critical risk factor in hypertension.

Design and Methods:
A denervation-induced skeletal muscle loss model was established, and the function of the immune system was evaluated. Systemic immune cell proportions and serum cytokine levels were profiled. Calcium influx and mitochondrial function were also assessed in the T cells. Finally, MRL/lpr mice were used to assess the influence of denervation-induced sarcopenia on SLE-related lupus nephritis progression and circulating autoantibodies, along with the cytokines that contributes to the development of hypertension, such as TNF-α and MCP-1, were evaluated.

Results:
The results of immune status profiling and functional assessment demonstrated that the loss of skeletal muscle shifts the immune balance in favor of the Th1/Th17 axis. Along with the peak Ca2+ influx, denervation-induced amyotrophy also impaired the spare respiratory capacity in mitochondrial of T cells, as well as the basal respiration and adenosine triphosphate production. The results of proteinuria tracing, serum blood urea nitrogen level, and C3 and IgE deposition in mesangium and capsular adhesion suggests that the sarcopenia promoted nephritis progression. A significant increase of the level in TNF-α, which promotes renal vasoconstriction, a pro-hypertensive effect, was also observed in sarcopenic mice.

Conclusion:
Consequently, sarcopenia might promote the progression of lupus nephritis because of the enhancement of systemic Th1/Th17 functions and accelerate the deposition of the vascular damage factors. The data herein suggested that the protection from developing hypertension in SLE patient may afforded by preventing skeletal muscle losing. A multidisciplinary approach is required to minimize the overall adverse impact of sarcopenia in the management of SLE-related hypertension.
PS-B06-7: ENDOTHELIAL DYSFUNCTION EXACERBATES KIDNEY DYSFUNCTION IN AGEING KIDNEY VIA ACTIVATION OF INFLAMMASOME
Authors: Wada Yoshihisa , Nagasu Hajime , Kadoya Hiroyuki , Kashihara Naoki 
Published: January 2023

Background:
Ageing affects the function of the immune system and leads to immunosenescence, which is characterized by defective immune responses and increased systemic inflammation (also termed inflammageing). Inflammageing is maladaptive and results from multiple mechanisms, including aberrant inflammasome activation. The ASC is an essential component of inflammasomes that activates caspase 1. Endothelial dysfunction is also a common pathophysiologic mechanism of age-related organ damage. Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) is an important mediator in the maintenance of vascular homeostasis. We have reported that the eNOS-NO pathway attenuates the progression of kidney injury via suppression of inflammasomes. However, the relationship between the eNOS-NO pathway and inflammageing in the kidney remains unclear. To determine if the eNOS-NO pathway attenuates kidney damage via the regulation of inflammasome activation in ageing kidneys, we used eNOS-deficient mice (eNOSKO) and eNOS-ASC double-knockout mice (eNOS-ASC-DKO).

Methods:
Wild-type mice (WT) and eNOSKO were used to determine the role of the eNOS-NO pathway in ageing kidneys. WT and eNOSKO were sacrificed at 18 months of age to harvest kidney tissue. The localization of inflammasome activation in the kidney was evaluated with immunohistochemical analyses. To determine the role of inflammasomes in ageing kidneys, we generated eNOS-ASC-DKO. The mRNA expression of inflammasome components were determined in isolated glomeruli.

Results:
The glomerular injury was more exacerbated in eNOSKO-18 M than in WT-18 M. In the immunohistochemical analyses, the expression of ASC coexisted with the macrophages detected by F4/80 staining in eNOSKO-18 M. These data suggested that the inflammasome activation was located in the macrophages. In the isolated glomeruli, the mRNA of the inflammasome components was higher in eNOSKO-18 M than in WT-18 M. The glomerular damage and tubulointerstitial damage were ameliorated in eNOS-ASC-DKO-18 M compared to eNOSKO-18 M. In summary, in eNOS-deficient mice, inflammasomes were activated in macrophages, and interstitial fibrosis was exacerbated. However, in eNOS-ASC-DKO-18 M mice, the tubulointerstitial damage was attenuated.

Conclusion:
Endothelial NOS/NO signaling ameliorates kidney damage in the aging process via the modulation of inflammageing associated with inflammasome-activation.
PS-B07-8: LEAFY VEGETABLE CONSUMPTION AND RISK OF METABOLIC SYNDROME AND ITS SYMPTOMS: A SYSTEMATIC REVIEW OF COHORT AND RANDOMISED CONTROL TRIALS
Authors: Muriuki Esther Njeri , Celik Begum , Kuhnle Gunter G C , Mills Charlotte E 
Published: January 2023

Objective:
Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, including dyslipidemia, hypertension, hyperglycemia, and obesity. It increases the risk of type 2 diabetes, cardiovascular disease, and all cause mortality and exerts an enormous global burden on health systems. A better understanding of dietary approaches that can reduce the risk of MetS or its symptoms is crucial. Leafy vegetables contain bioactive compounds such as nitrates, dietary fibre and flavonoids that are protective against illnesses. However, investigations of whether leafy vegetable consumption can reduce MetS and its symptoms are unclear. This systematic review investigates the effect of leafy vegetable consumption on the risk of MetS and its symptoms.

Design and method:
Randomised control trials (RCT), and observational studies were searched in the Web of Science, Scopus, and MEDLINE databases until October 2020. Inclusion criteria were: studies in adults aged ≧ 18 years without MetS symptoms, the intervention of leafy vegetables, the outcome of a change in or incidence of MetS or any of its symptoms. The Cochrane tool and Newcastle Ottawa Scale were used to assess the risk of bias in RCTs and cohort studies, respectively.

Results:
A total of eight studies (six RCTs and two cohort studies) were included in the qualitative analysis. There were no trials assessing obesity or MetS. The results are shown in Table 1.

Conclusion:
Few studies evaluated the impact of leafy vegetable consumption on MetS and its symptoms. Beneficial effects of leafy vegetables are reported for blood glucose and blood pressure regulation, but the evidence is limited. More studies are needed to build a robust body of evidence.
PS-B07-11: EFFECT OF TRF INTERVENTION ON DIET INDUCED OBESITY: A NON-PHARMACOLOGICAL THERAPEUTIC STRATEGY
Authors: Fatima Nazmin , Sonkar Gyanendra Kumar , Mahdi Abbas Ali 
Published: January 2023

Objectives:
Time-restricted feeding (TRF) regulates the circadian rhythm of food intake that protects against metabolic disorders. The aim of our study are 12 hours time restricted feeding effects on diet induces obesity in rats model.

Material & Method:
Total 21 Wistar rats were included i.e. control, TRF and High Fat diet (HFD) group. HFD group was fed with fatty diet at ad lib for two months and shifted to TRF (12 hours feeding i.e 8:00pm - 8:00am) for three months, after which they were again put back on ad lib. TRF group fed chow diet during 8:00pm to 8:00am for three months and then these rats shifted to ad lib for three months. Control group fed chow diet at ad lib. Body weight was calculated and blood samples were collected to measure blood glucose, insulin, lipid profile and gene expression.

Results:
The body weight of HFD group were significantly increased and TRF with chow diet were significantly decreased as compared to control rats (p = 0.0263) and (p = 0.0054) respectively. The level of HDL was reduced in rats fed with HFD whereas total cholesterol, TG and LDL were increased. TRF intervention with HFD diet reduced body weight, blood glucose level, TG and LDL and elevated the level of insulin, total cholesterol and HDL. Per1 and Bmal1 gene were up regulated in HFD group and after TRF intervention had reduced mRNA expression. TRF intervention with HFD and chow diet showed its legacy effect when put on ad lib.

Conclusion:
TRF intervention is easily adaptable lifestyle modification and non-pharmacological strategy can reduces the risk factor of obesity and its associated metabolic disorders.
PS-B08-5: EFFECT OF HIGH SALT INTAKE ON THE SODIUM CONTENT OF EACH BONE IN RATS
Authors: Munesada Mahiro , Kitada Kento , Kidoguchi Satoshi , Nakano Daisuke , Nishiyama Akira 
Published: January 2023

Objective:
It has been reported that salt intake affects sodium content at the tissue level. Salt intake alters bone sodium content, which shifts the balance of osteoblasts and osteoclasts population and thereby affects bone density. However, it remains to be clarified whether there are site-specific changes in bone sodium content. In the present study, we examined the effect of high salt intake on the sodium content of each bone in normal rats.

Design and method:
Male Sprague Dawley rats (9 weeks old) were fed with a 0.2% normal salt diet with tap water to drink or a 4% high salt diet with 0.9% NaCl water to drink for 3 weeks. Each bone sodium content was measured by the ashing-flame photometer method.

Results:
High salt intake significantly increased total bone sodium content. Compared with normal salt group, high salt group exhibited a significant increase in the bone sodium content of skulls, ribs, or tailbones. On the other hand, high salt intake did not alter bone sodium content in the scapula, pelvis, vertebrae, and limb bones.

Conclusions:
There is a site-specificity of bone sodium accumulation with high salt intake. These findings suggest that each bone has local sodium regulation independently of whole bones and that bones could be separated into whether or not to store sodium. It may be necessary to evaluate the sodium content of each bone in various pathological models, rather than a simple measurement of the total bone sodium content.
PS-B09-8: N-METHYL-D-ASPARTATE (NMDA) RECEPTORS INDUCE RENAL VASODILATION AND REGULATES BLOOD PRESSURE.
Authors: Romero Cesar A , Wang Hong , Ren Yilin , Wall Susan M 
Published: January 2023

Introduction:
N-methyl-D-aspartate receptors (NMDAr) are glutamate/glycine receptors expressed in the kidney. NMDAr induce renal vasodilation through an unknown mechanism. Connecting tubule-glomerular feedback (CNTGF) is a vasodilator feedback mechanism, initiated by ENaC in the connecting tubule producing afferent arteriole (AffA) vasodilatation and promoting sodium excretion. We hypothesized that NMDAr activation stimulate CNTGF and that the inhibition of NMDAr decrease CNTGF vasodilation inducing hypertension.

Methods:
We explore the presence of NMDAr receptors in mouse by transcriptome analysis of microdisseted tubules segments, total kidney western blot and immunofluorescence. We used mpkCCD cells (mouse principal cells) to explore the interaction between NMDAr and ENaC in PC using trasnwell current analysis and split-open tubule using patch clamp method. To determine the effect of NMDAr on CNTGF, we measured CNTGF-mediated AffA dilation in the presence or absence of NMDAr agonists glutamate and glycine with and without NMDAr antagonist (MK801), using a double-microperfusion method in rabbits, and in-vivo by micropunture technique in rats. To evaluate the effect of NMDAr on blood pressure (BP), we measure BP in NMDA 2C global knock out mice. BP was measure using tail cuff methods. To confirm the effect of NMDAr on BP we infused subcutaneously NMDAr inhibitor MK801 for 7 days in a gain of function β ENaC mutated allele mice on129/Sv background on normal salt diet.

Results:
NMDAr was found to be expressed in connecting tubule and co-localized with AQP2 and ENaC. In mpkCCD cells and open split tubules, NMDAr activation increase ENaC activity, while NMDAr inhibition decrease ENaC activity (p < 00.1). In-vitro, tubular microperfusion of NMDAr agonist increased AffA dilation (p < 0.001). NMDAr agonist-induced dilation was blunted with MK-801 (NMDAr blocker) and totally blocked with benzamil (CNTGF inhibitor). In vivo, NMDAr agonist increase CNTGF mediated vasodilation (P < 0.01). NMDAr 2C knock out mice showed high BP in comparison with wildtype (SBP 114.6 ± 7.3 vs 100.4 ± 2.2 mmHg, respectively, p = 0.01). In β ENaC mutated mice, the infusion of NMDAr inhibitor (Mk-801) induces hypertension (SBP 146 ± 8 mmHg) while the vehicle infused mice remained normotensives (110.7 ± 7.7 mmHg; p < 0.01).

Conclusions:
NMDAr in the connecting tubule increase renal vasodilation by activating CNTGF. The genetic ablation of NMDAr 2C or the pharmacological inhibition of NMDAr increase blood pressure. Future studies need to confirm the role of NMDAr in the pathogenesis of hypertension.
PS-B09-9: ENOS-NO PATHWAY REGULATES INFLAMMASOME ACTIVATION IN DIABETIC MICE VIA MODULATION OF CEBP TRANSLOCATION
Authors: Nagasu Hajime , Umeno Reiko , Kadoya Hiroyuki , Kashihara Naoki 
Published: January 2023

Background:
Diabetic kidney disease (DKD) is one of the most common vascular complications of diabetes mellitus (DM). Endothelial dysfunction is also a common pathophysiologic mechanism of diabetic vascular complications. Nitric oxide (NO) produced in the endothelial cells by endothelial nitric oxide synthase (eNOS) is an important mediator for the maintenance of vascular homeostasis. In persons with diabetes, eNOS produces superoxide anion rather than nitric oxide, referred to as eNOS uncoupling which may contribute to endothelial dysfunction, albuminuria, and diabetic nephropathy. eNOS uncoupling can then lead to dysfunction of the eNOS-NO-pathway in diabetic glomeruli. To determine the mechanism of regulation of inflammasome activation by eNOS-NO pathway in DKD, we used eNOS deficient mice and eNOS-ASC double knockout mice.

Methods:
We used wild-type (WT) and eNOS-deficient mice (eNOSKO) to determine the role of the eNOS-NO pathway. Diabetes was induced by a single intraperitoneal injection of streptozocin. We then divided the mice into four groups: WT, WT/STZ, eNOSKO, and eNOS/STZ. Four weeks after the induction of DM, the mice were sacrificed, and their kidney tissues were harvested. Urinary albumin excretion was checked before the sacrifice, and glomerular damage was assessed by periodic acid-Schiff (PAS) staining. To determine the role of inflammasome on the development of glomerulopathy, we generated eNOS-ASC double knockout mice (eNOS-ASC-DKO). Also, to investigate inflammasome activation in glomeruli, the glomeruli were isolated from the kidney tissue by using Dynabeads.

Results:
Urinary albumin excretion was increased in WT/STZ compared with WT. These urinary albumin excretions were increased much more in eNOS/STZ than in WT/STZ, while the glomeruli were more damaged in eNOSKO/STZ than in WT/STZ. Urinary albumin excretion was lower in eNOS-ASC-DKO/STZ compared with eNOSKO/STZ, and the glomerular damage also was ameliorated in eNOS-ASC-DKO after treatment with STZ. S-Nitroso glutathione (GSNO) attenuated NLRP3 inflammasome activation after treatment with LPS-ATP. These results indicate that NO directly inhibits NLRP3-inflammasome activation. In addition, GSNO decreased the expression of inflammasome-related genes. To investigate the detailed the mechanism (epigenetic regulation), we performed Assay for Transposase-Accessible Chromatin-Sequencing (ATAC-seq) analysis. The binding region of the transcription factor CCAAT/ enhancer binding protein (C/EBP) β; was closed in the LPS+GSNO group significantly, compared with the LPS group.

Conclusion:
In eNOS-deficient mice, inflammasomes were activated, and glomerular injuries were exacerbated. However in eNOS-ASC-STZ mice, the glomerular damage were attenuated. Our data suggested that eNOS/NO signaling attenuates inflammasome activation via regulation of CEBP β;, leading to the suppressed development of DKD.
PS-C17-8: PREVALENCE OF PREDIABETES IN PATIENTS WITH ACUTE CORONARY SYNDROME
Authors: Pandey Naveen Kumar , Karki Biplave , Karki Prahlad 
Published: January 2023

Objective:
Prediabetes is defined as an intermediate metabolic state between normoglycaemia and diabetes and includes those with impaired glucose tolerance and impaired fasting glucose. Diabetes mellitus is a well recognised risk factor for cardiovascular disease and acute coronary syndrome. However, evidence is limited regarding the prognostic value of ‘prediabetes’ on the clinical outcome of ACS. The objective of this study was to know the prevalence of prediabetes in ACS.

Design and methods:
This was a single center descriptive cross-sectional study to know the prevalence of prediabetes in 115 patients consisting of 71 males and 44 females, admitted with ACS in the Department of Cardiology between August 2020 to July 2021

Results:
Based on the definition of the American Diabetes Association, 35 (30.4%) patients were newly diagnosed diabetic, 46 (40%) patients were prediabetic and 34(29.6%) were non-diabetic. Based on HbA1c alone, 26.1% patients were classified as newly diagnosed diabetic patients, 38.3% patients were classified as prediabetic and 35.7% as non-diabetic. Compared with patients without diabetes, patients with prediabetes tended to have a longer hospital stay (p = 0.04), higher creatinine level (p = 0.01) and higher incidence of heart failure (p = 0.046).

Conclusion:
Prediabetes is common in patients presenting with ACS who are not previously known to have diabetes. Further multi-center studies with long term clinical follow-up are needed to draw a firm conclusion regarding the impact of prediabetes on clinical outcome.
PS-C18-1: SLEEP SCORE AMONG HEALTH-RELATED QUALITY OF LIFE SUBSCALES PREDICTS TECHNIQUE SURVIVAL IN PATIENTS WITH PERITONEAL DIALYSIS
Authors: Nagasaka Tomoki , Uchiyama Kiyotaka , Hama Eriko Yoshida , Kusahana Ei , Nakayama Takashin , Yasuda Itaru , Morimoto Kohkichi , Washida Naoki , Itoh Hiroshi 
Published: January 2023

Purpose:
There is sufficient evidence that peritoneal dialysis (PD) is superior to hemodialysis in terms of health-related quality of life (HRQOL), and higher HRQOL scores are associated with better clinical outcomes in patients with PD, however, the specific HRQOL subscales that predict prognosis remain uncertain.

Design and method:
In addition to various PD-related parameters and exercise capacity, HRQOL of outpatients with PD were assessed using Kidney Disease Quality of Life-Short Form Japanese version 1.3 from March 2017 to March 2018, and the association of HRQOL items with technique survival was prospectively analyzed until June 2021.

Result:
Among the 50 recruited PD outpatients, age and PD vintage were 63.8 ± 9.6 and 3.8 ± 2.8 years, respectively, and 21 patients discontinued PD and transferred to hemodialysis during the study period. In a univariate Cox proportional hazards model, higher scores (per 10) for symptoms, sleep, and vitality among HRQOL subscales were significantly associated with lower technique failure rate (Hazard Ratio(HR) 0.66, P = 0.002; HR 0.70, P = 0.006; and HR 0.80, P = 0.04, respectively). In multivariate analysis adjusted for Charlson comorbidity index, incremental shuttle walk test distance, and baseline PD vintage, only higher sleep score was significantly associated with lower technique failure rate (HR 0.68 per 10, P = 0.003). Among PD-related parameters, serum potassium level was significantly inversely correlated with sleep score (r = -0.34, P = 0.01).

Discussion and Conclusion:
Our results suggest that sleep score among HRQOL subscales is particularly useful as a predictor of technique survival in patients with PD. Improvement in sleep quality may improve technique survival in prevalent PD patients.
PS-C19-3: HYDROCHLOROTHIAZIDE WAS NOT ASSOCIATED WITH PHOTOSENSITIVE OR PHOTOTOXIC REACTIONS AND DNA-DAMAGE IN VIVO AND IN VITRO (THE HCTOX-STUDY)
Authors: Goetzinger Felix , Hohl Mathias , Millenaar Dominic Norman , Lauder Lucas Douglass , Reichrath Joerg , Meyer Markus Robert , Boehm Michael , Ukena Christian , Mahfoud Felix 
Published: January 2023

Objective:
Pharmacoepidemiologic studies associated the use of HCT with an increased risk of skin cancer, resulting in a decrease of HCT prescriptions, in turn leading to worsening of blood pressure therapy in a significant proportion of patients. However, whether HCT causes skin cancer remains elusive. Hence, we aimed to examine the photosensitive and phototoxic potential of HCT in vivo in a randomized, placebo-controlled trial. To further enlighten the pathophysiologic mechanisms of carcinogenesis and phototoxicity caused by HCT in vitro, we conducted a series of laboratory experiments.

Design and method:
A randomized, double-blind, placebo-controlled clinical trial to assess the phototoxic properties of HCT was conducted, assigning 30 healthy normotensive adult volunteers in a 2:1 ratio to either HCT 25 mg daily or placebo once daily for 15 days. The skin photosensitivity by phototesting, office blood pressure, serum 25-hydroxyvitamin D (25(OH)D) status and urinary excretion of thymidine-dimers, i.e. cyclobutan-dimers by ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) following whole-body irradiation were assessed.
To further assess the pathophysiologic mechanisms of possibly HCT induced photosensitivity, human keratinocytes (HaCaT) were incubated with HCT and then irradiated with UV-B radiation (311 nm one burst of 100 J/cm2). rt-PCR-testing and western blots were performed to analyze reactive oxygen species, inflammation, and carcinogenesis.

Results:
All 30 participants were adherent to the protocol, which was confirmed by UHPLC-HRMS analysis of serum and plasma. Skin photosensitivity to exposure of UV-A and UV-B radiation did not change in both groups (HCT vs. placebo: MED-UVB change 0.0 J/cm2 vs. 0.2 J/cm2; p = 0.06). No thymidine-dimers were detectable in either group. Systolic blood pressure decreased in both groups (-5.2 mmHg vs. 5.4 mmHg; p = 0.94), as did diastolic blood pressure (-4.3 mmHg vs. -1.9 mmHg; p = 0.34). Serum 25(OH)D increased in both groups (3.1 ng/ml vs. 1.2 ng/ml; p = 0.52).
HCT in combination with a single high-intensity bursts of UV-B radiation was not associated with increased expression of inflammatory proteins, chronic inflammation and reactive oxygen species.

Conclusions:
HCT was not associated with increased photosensitivity for UV-A or UV-B radiation in healthy volunteers. Moreover, no relevant DNA-damages as measured by UHPLC-HRMS were detectable in either group. The combination of HCT treatment and a single burst of UV-B did not increase inflammatory markers. HCT appeared to be safe in healthy volunteers and was not associated with photosensitivity or DNA-damages in vivo.