bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Buyang Huanwu Decoction on Renal Injury in Spontaneously Hypertensive Rats
Authors: Wang Youping , Xu Hui , Wang Xiaoxiao , Cui Lin , Liu Suxiao , Zhang Songjiang 
Published: June 2021

Hypertension is an independent risk factor contributing to chronic kidney disease. Buyang Huanwu Decoction (BHD) is a popular traditional Chinese medicine prescription for the treatment of stroke for centuries. Recent studies reported that the use of BHD had been extended to treat various kinds of disorders following traditional Chinese medicine syndrome theory of Treating Different Diseases with the Same Method. Therefore, this study aimed to determine the effects of BHD on renal injury in spontaneously hypertensive rats (SHR). Treatment with BHD at the dose of 12.6 g/kg/day by gavage for 5 weeks had no effect on the increased systolic blood pressure and renal hypertrophy in 17‐week‐old SHR. However, BHD treatment obviously reduced urinary albumin excretion compared with the control SHR (P<0.05). Periodic acid‐Schiff and Masson's trichrome staining showed that obvious glomerulosclerosis and tubulointerstitial injury were found in the kidney in SHR and reduced by BHD treatment (P<0.05). Consistent with the results, renal collagen level determined using hydroxyproline assay was higher in SHR and attenuated by BHD treatment (P<0.05). In addition, the renal monocyte/macrophage infiltration was seen in SHR and inhibited by BHD treatment (P<0.05). Our data showed that treatment with BHD attenuated renal damage in SHR independently of their effects on blood pressure. The results indicate that BHD exhibits a protective effect on renal damage in SHR. This work was supported in part by the National Natural Science Foundation of China (No. 81673734).Support or Funding InformationThis work was supported in part by the National Natural Science Foundation of China (No. 81673734).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Gomisin M2 ameliorates imiquimod‐induced psoriasis‐like skin inflammation via the inhibition of mitogen‐activated protein kinase
Authors: Kim Namkyung , Kang Jinjoo , Kim Hyemi , Kim Sang‐Hyun 
Published: June 2021

Psoriasis (PS) is a chronic inflammatory skin disease with complex pathogenesis. Gomisin M2 (GM2) is a natural product extracted from Schisandra chinensis (Turcz.) Baill. In this study, we aimed to investigate the pharmacological effects of GM2 on PS‐like skin inflammation. For induction of PS‐like skin inflammation, imiquimod (IMQ) cream topically applied to the back skin of female C57BL/6J mice for 7 consecutive days. Oral administration of GM2 (0.1, 1 or 10 mg/kg) reduced the symptoms of PS‐like skin inflammation based on Psoriasis Area and Severity Index and histological observation. GM2 reduced serum levels of tumor necrosis factor (TNF)‐α, IgG2a, and myeloperoxidase. It also decreased MPO‐associated cell infiltration in skin tissue in a dose‐dependent manner. Furthermore, GM2 decreased production of Th1 and Th17‐related cytokines such as TNF‐α, interferon (IFN)‐γ, interleukin (IL)‐8, IL‐1β and IL‐17A in the back skin. For in vitro, we investigated the pharmacological effects of GM2 on TNF‐α and IFN‐γ stimulated keratinocytes (HaCaT). Pre‐treatment of GM2 (0.1, 1, or 10 μM) alleviated PS‐associated cytokines such as TNF‐α, IL‐1β, IL‐6, IL‐8, and Chemokine (C‐C motif) ligand 17. GM2 inhibited phosphorylation to mitogen‐activated protein kinase in the activated HaCaT. Our study reveals that GM2 possesses anti‐inflammatory effect on PS. Based on our results, we propose that GM2 could be a potential therapeutic candidate on PS.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Omega‐3 Polyunsaturated Fatty‐Acid Supplementation on Neuropathic Pain Symptoms and Sphingosine Levels in Mexican‐Americans with Type 2 Diabetes
Authors: Duran Alfonso , Salto Lorena , Camara Justin , Basu Anamika , Paquien Yvette , Beeson Lawrence , Firek Anthony , Cordero‐MacIntyre Zaida , De Leon Marino 
Published: June 2021

PurposeTo determine whether dietary supplementation with omega‐3 polyunsaturated fatty acids (PUFAs) reduces neuropathic pain symptoms in Mexican‐Americans with type 2 diabetes.MethodsForty volunteers with type 2 diabetes enrolled in the “En Balance‐PLUS” program, which provided weekly nutrition–diabetes education and daily supplementation with 1,000 mg docosahexaenoic acid (DHA)–200 mg eicosapentaenoic acid over 3 months. The study assessed self‐reported neuropathic pain symptoms pre/postintervention using the short‐form McGill Pain Questionnaire (SF‐MPQ), monitored clinical laboratory values at baseline and 3 months, and performed baseline and 3‐month metabolomic analysis of plasma samples.ResultsA total of 26 participants self‐reported neuropathic pain symptoms at baseline. After 3 months of omega‐3 PUFA supplementation, participants reported significant improvement in SF‐MPQ scores (sensory, affective, and visual analogue scale; P<0.001, P=0.012, and P<0.001, respectively). Untargeted metabolomic analysis revealed that participants in the moderate–high SF‐MPQ group had the highest relative plasma sphingosine levels at baseline compared to the low SF‐MPQ group (P=0.0127) and the nonpain group (P=0.0444). Omega‐3 PUFA supplementation increased plasma DHA and reduced plasma sphingosine levels in participants reporting neuropathic pain symptoms (P<0.001 and P<0.001, respectively). Increased plasma DHA levels significantly correlated with improved SF‐MPQ sensory scores (r=0.425, P=0.030). Improved SF‐MPQ scores, however, did not correlate with clinical/laboratory parameters.ConclusionThe data suggest that omega‐3 PUFAs dietary supplementation may reduce neuropathic pain symptoms in individuals with type 2 diabetes and correlates with sphingosine levels in the plasma.Support or Funding InformationThis study was funded by NIH grants 5P20MD006988 and 5R25GM060507. The content of this article is solely the responsibility of the authors, and does not necessarily represent the official views of the National Institutes of Health.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of Isometric Handgrip Exercise on Diastolic Function in Pediatric Heart Transplant Recipients
Authors: Tomczak Corey R , Blushke Corey R , Lahti Dana S , Kosokowsky Kylee , Iqbal Ramlah M , Singh Shreya , Boyes Natasha G , Erlandson Marta C , Wright Kristi , Pharis Scott , Pockett Charissa 
Published: June 2021

Pediatric heart transplant recipients (HTR) have reduced exercise tolerance and diastolic dysfunction at rest despite normal ejection fraction. In adult HTR the impaired diastolic function is related to peak exercise tolerance, but this relationship is poorly understood in pediatric HTR. To determine the effects of low‐grade exercise stress on diastolic function in pediatric HTR, we tested the hypothesis that diastolic function would be augmented during isometric handgrip exercise.MethodsSeven pediatric HTRs were studied (mean±SD age: 10±3 yrs; sex: 3F, 4M; time since transplant: 5.4±2.1 yrs; left ventricular mass: 68±19 g/m2; end‐diastolic volume: 42±6 mL; end‐systolic volume: 12±2 mL; ejection fraction: 71±9 %). Pulsed Doppler was used to quantify early (E) and late (A) diastolic inflow velocities, deceleration time and slope. Tissue Doppler imaging of the lateral mitral annulus was used to assess velocity during early diastole (e′) and late diastole (a′). Left ventricular filling pressure responses were estimated using the early diastolic mitral valve inflow velocity/early diastolic lateral wall tissue velocity ratio (E/e′). Resting diastolic assessment was performed followed by 2 min of isometric handgrip exercise at 30% maximal voluntary contraction with diastolic function re‐assessed during the last 30 s of exercise.ResultsHeart rate (92±10 to 105±13 bpm; P=0.01) and mean arterial pressure (73±7 to 90±21 mmHg; P=0.035) increased from rest to exercise. There was no significant change in E/A (2.2±0.8 to 2.2±1.1; P=0.831), deceleration time (0.183±0.031 to 0.173±0.035 s; P=0.529), deceleration slope (613±152 to 619±169 cm/s2; P=0.926), e′/a′ (2.8±0.7 to 2.5±1.2 cm/s2; P=0.433), or E/e′ (7.02±1.37 to 7.13±1.71; P=0.709) from rest to exercise.ConclusionPediatric HTR have diastolic dysfunction at rest that is not augmented during low‐grade handgrip exercise stress.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Estradiol Decreases MAPKs phosphorylation in Response to Angiotensin II by Increasing MKP‐1 in the Hypothalamus, but not in the Lamina Terminalis
Authors: Almeida‐Pereira Gislaine , Vilhena‐Franco Tatiane , Coletti Ricardo , Cognuck Susana , Silva Hellen , Elias Lucila , Antunes‐Rodrigues Jose 
Published: June 2021

IntroductionThe angiotensin II (ANGII) plays an important role in the control of body fluids and estradiol (E2) modulates several actions of ANGII in the brain. Recently, our group showed that ERK1/2, JNK and p38MAPK are involved in sodium intake induced by ANGII in female rats. On the other hand, ANGII‐induced water intake requires JNK and p38MAPK, but not ERK1/2. In regarding to neurohypohysial hormone release, our group showed that ERK1/2 is involved in vasopressin (AVP) release but not in oxytocin (OT) release induced by ANGII. While ANGII‐induced OT release requires p38MAPK signaling. Therefore, herein the aim of study was evaluated whether E2 modulates MAPKs phosphorylation in response to ANGII as well MAPK phosphatase 1 (MKP‐1) which is responsible for inhibiting all the MAPKs (ERK1/2, JNK and p38MAPK) in the paraventricular (PVN) and supraoptic nuclei (SON) of hypothalamus, and in structures of lamina terminalis.Materials and MethodsWistar rats (~250g) were submitted to ovariectomy (OVX) and on the following day they were treated with estradiol cypionate (10μg/rat, sc, OVX+E2) or vehicle (corn oil, 0.1mL/rat, sc) for eight days. On the eighth day, the rats received an icv (lateral ventricle) injection of ANGII (25ng/2μL/rat) or vehicle (0.9% saline, 2μL/rat). After ten min of ANGII injection the animals were decapitated for brain collection for ERK1/2, JNK and p38MAPK total and phosphorylated, MKP‐1 and β‐Actin analyses by western blot. Data were analyzed using ANOVA two‐way, followed by Newman‐Keuls post‐test and the level of significance was set at 5%.ResultsThe treatment with E2 attenuated JNK and p38MAPK phosphorylation in response to ANGII in the lamina terminalis (E2 x ANGII interaction: F1,17=19.00, p<0.001; E2 x ANGII interaction: F1,29=6.1, p<0.05, respectively). In regarding to PVN and SON, it was observed that E2 attenuated ERK1/2 and p38MAPK phosphorylation in response to ANGII (E2 x ANGII interaction: F1,29=7.91, p<0.01; F1,26=4.1, p<0.05, respectively). E2, but not ANGII alone, was able to increase MKP‐1 expression in the PVN and SON (E2: F1,18=24.29, p<0.001), but not in the lamina terminalis.ConclusionThese results suggest that E2 dephosphorylates ERK1/2 and p38MAPK in response to ANGII by increasing MKP‐1 in the PVN and SON, but not in structures of lamina terminalis, such as subfornical organ, median preoptic nucleus and organum vasculosum of the lamina terminalis. E2 is able to dephosphorylate JNK and p38MAPK in the lamina terminalis in response to ANGII, however this effect does not involve MKP‐1.Support or Funding InformationFinancial support: FAPESP, CNPq and CAPES.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
CGRP stimulates profibrogenic growth factors in kidney proximal tubular cells
Authors: Kim Jinu 
Published: June 2021

Kidney denervation prevents the development of tubulointerstitial fibrosis, but local infusion of calcitonin gene‐related peptide (CGRP) into the denervated kidneys upregulates profibrogenic growth factors and restores the fibrotic feature. However, it is not clear how CGRP contributes to the upregulation of profibrogenic factors.Both human HK‐2 and pig LLC‐PK1 kidney proximal tubular cells undergoing a 6 hours exposure to CGRP were treated with CGRP receptor antagonist (CGRP8–37), a specific protein kinase C (PKC) inhibitor chelerythrine, or a potent JNK inhibitor SP600125. Levels of transforming growth factor‐β1 (TGF‐β1) production and PKC activity were measured by enzyme‐linked immunosorbent assay. Western blot analysis performed to determine the protein levels of connective tissue growth factor (CTGF) expression and c‐Jun N‐terminal protein kinase (JNK) phosphorylation.Administration of 1 nM CGRP significantly increased the levels of TGF‐β1 production and CTGF expression at 6 and 24 hours after the onset. The exogenous CGRP also increased their protein levels in the incubation media, indicating release of their proteins from the cells. Treatment with 100 nM CGRP8–37 immediately after the onset significantly inhibited the increase in intracellular and released protein levels of TGF‐β1 and CTGF during CGRP exposure. Furthermore, treatment with 1 thru 10 μM chelerythrine markedly reduced the upregulation and release of TGF‐β1 and CTGF after 6 hours exposure to CGRP. Finally, inhibition of JNK phosphorylation using 1 μM SP600125 prevented the increase in TGF‐β1 and CTGF upregulation and release after 6 hours exposure to CGRP.Exogenous CGRP induces the upregulation and secretion of profibrogenic TGF‐β1 and CTGF proteins through CGRP receptor/PKC/JNK signaling pathway in proximal tubular cells, and this pathway might be a cause of triggering inflammation cascade and tubulointerstitial fibrosis.Support or Funding InformationThis research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF‐2016R1C1B2012080).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Renal Microvascular Rarefaction Accompanies Interstitial Fibrosis and Tubular Damage in One Kidney‐Deoxycorticosterone Acetate‐Salt (1K/DOCA/salt)‐Dependent Hypertension
Authors: Saini Narbada , Thomas Jordyn , Huuskes Brooke , Sharma Prerna , Sobey Christopher , Vinh Antony , Drummond Grant 
Published: June 2021

High dietary salt intake is a risk factor for hypertension and chronic kidney disease. However, the mechanisms involved remain poorly understood. Microvascular rarefaction ‐ defined as the loss of arterioles and capillaries within a tissue ‐ has the potential to increase total peripheral vascular resistance and cause local hypoxia and tissue damage. Here we utilised one kidney‐deoxycorticosterone acetate‐salt (1K/DOCA/salt)‐treated mice to investigate whether the development of hypertension and renal damage are associated with microvascular rarefaction. C57BL6/J mice were uninephrectomised and treated for 21 d with DOCA (2.4 mg/day, s.c.) and 0.9% NaCl in the drinking water. Normotensive controls were uninephrectomized and received a placebo pellet and normal drinking water (1K/placebo). Blood pressure (BP) was measured via tail cuff; renal vascular density was assessed immunohistochemically as the percentage area of CD31‐positive staining; renal collagen was detected with picrosirius red; and hematoxylin and eosin were used to visualise renal inflammation and histopathology. 1K/DOCA/salt‐treated mice had higher BPs (160±4 vs. 126±4 mmHg; n≥7; P≤0.0001) and renal weights (321±16 vs. 251±13 mg; n≥7; P<0.05) than 1K/placebo mice. 1K/DOCA/salt‐treated mice also displayed marked renal fibrosis, inflammation and damage as evidenced by a 10‐fold increase in interstitial collagen (n≥7; P<0.05), the presence of inflammatory cells, tubular dilatation and atrophy, and a loss of epithelial brush borders. Importantly, 1K/DOCA/salt‐treatment was associated with a 50% reduction in microvascular density (n≥7; P<0.05), mainly due to a loss of peritubular capillaries. Correlation analyses revealed a trend for an inverse association of peritubular capillary density with collagen deposition (n≥7; r= −0.7058; P= 0.117), but not with BP or inflammatory cell infiltration. Low magnification analysis of kidney sections revealed that peritubular capillary loss occurred in bands emanating from the arcuate arteries. Moreover, collagen deposition, inflammatory cell infiltration and tubular atrophy displayed a similar banding pattern. In summary, these studies reveal a likely association between microvascular rarefaction and fibrosis during the development of 1K/DOCA/salt‐dependent hypertension and renal damage. Future studies will assess whether strategies aimed at maintaining renal microvascular density can minimise renal fibrosis and damage.Support or Funding InformationThe work was funded by the National Health and Medical Research Council of Australia (GNT1143674)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Renin Gene Editing in Zebrafish
Authors: Mullins Linda Jane , Hoffmann Scott , Rider Sebastien , Bradley Mark , Mullins John 
Published: June 2021

Recent studies in zebrafish show that the renin‐angiotensin system (RAS) is highly conserved across vertebrates. In common with mammals, the zebrafish kidney contains specialised renin‐expressing mural cells throughout the kidney micro‐vasculature that contain acidic granules indicative of the processing and regulated secretion of active renin. Zebrafish are a unique model organism suitable for developmental studies and due to the translucent nature of zebrafish larvae, the functional embryonic pronephros is readily accessible for high‐resolution in vivo imaging and high‐throughput genetic and chemical screens. To investigate the role of renin and the RAS in zebrafish we designed guide RNAs to target CRISPR‐Cas9 to renin exon 2. We identified an 8bp deletion resulting in a frameshift mutation and early termination of renin transcription. Adult ren−/− knockouts, identified by sequencing, were phenotypically screened using the automated screening system (VAST), which permits the imaging of large numbers of live fish with reproducible precision. Knockout fish are viable but exhibit delayed growth during early stages of development. Imaging revealed a delayed appearance and enlargement of the swim bladder and reduced fish length was indicative of an overall developmental delay. The knockout fish were further crossed with already existing renal reporter lines to investigate further phenotypes at a cellular level. When ren−/− knockout fish were crossed with wt1b:GFP fish a delay in glomerular fusion of the pronephric kidney was observed, whilst a cross of ren−/− knockout with ren:RFP fish revealed a dramatic increase in renin cell number along the renal vasculature, suggesting a continued but non‐critical requirement for renin in the adult fish.Support or Funding InformationBHF Centre of Research Excellence Award EPSRC/MRC CDT (Optima) AwardThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Pre‐transcriptional fibrotic factor alterations do not contribute to high fat diet associated renal fibrosis in Dahl salt sensitive male rats
Authors: Fernandes Roxanne , Galligan James J , Fink Gregory D , Xu Hui 
Published: June 2021

We previously reported that high fat diet (HFD) feeding for 24 weeks promotes hypertension similarly in male and female Dahl salt‐sensitive rats. However, HFD fed males exhibited more severe renal inflammation, fibrosis and injury than females. The underlying mechanisms responsible for sex differences in HFD associated renal fibrosis/injury are not fully understood. It is well established that extracellular matrix (ECM) remodeling is the hallmark of hypertension associated renal fibrosis. Proteins involved in ECM remodeling are key mediators in the fibrogenic process. Therefore, we determined if HFD increases ECM remodeling resulting in renal fibrosis and if sex differences of ECM remodeling in response to HFD contribute to hypertension‐associated renal fibrosis/injury in males. Renal cortex was collected from male and female rats fed a control diet (CD, 10% kcal fat) or a high fat diet (60% kcal fat) for 24 weeks. mRNA expression of fibrosis markers in the renal cortex was assessed, which included transforming growth factor (TGF), smooth muscle actin (SMA), cysteine‐rich angiogenic inducer 61 (CYRG1), connective tissue growth factor (CTGF), collagen (COL1A1, COL3A1, COL1A2), and matrix metalloproteinases (MMP9, MMP14). We found that only MMP9 mRNA levels were significantly elevated in HFD fed females compared to CD fed females. However, MM9 mRNA expression was similar in HFD fed and CD fed males. HFD feeding did not change expression of the other fibrosis markers in males or females. We next determined if elevated MMP9 mRNA levels in HFD females were translated into increased total MMP9 protein and/or increased MMP9 activity. MMP9 activity was determined by zymograph assay. We found that the total MMP9 protein expression and the activity were similar in HFD fed males and females. Our studies suggest that it is unlikely that HFD causes pre‐transcriptional alterations in the fibrosis signaling pathway. HFD associated post‐transcriptional alterations may contribute to renal fibrosis in males, but the underlying mechanisms are still undetermined. In addition, the role of ECM remodeling in HFD associated renal fibrosis needs to be assessed prior to the onset of renal fibrosis.Support or Funding InformationSupported by NHLBI 2P01HL070687 for G.D.F, J.J.G. and H.XThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.