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Pubblicazioni recenti - cardiovascular
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[Inhibitors of RAS Might Be a Good Choice for the Therapy of COVID-19 Pneumonia].
Zhonghua Jie He He Hu Xi Za Zhi2020 Feb;43(0):E014. doi: 10.3760/cma.j.issn.1001-0939.2020.0014.
Sun M L, Yang J M, Sun Y P, Su G H,
Abstract
The novel coronavirus 2019 (COVID-19) infected patients by binding human ACE2, leading to severe pneumonia and highly mortality rate in patients. At present, there is no definite and effective treatment for COVID-19. ACE2 plays an important role in the RAS, and the imbalance between ACE/Ang II/AT1R pathway and ACE2/Ang (1-7)/Mas receptor pathway in the RAS system will lead to multi-system inflammation. Increased ACE and Ang II are poor prognostic factors for severe pneumonia. Animal studies have shown that RAS inhibitors could effectively relieve symptoms of acute severe pneumonia and respiratory failure. The binding of COVID-19 and ACE2 resulted in the exhaustion of ACE2, and then ACE2/Ang (1-7)/Mas receptor pathway was inhibited. The balance of the RAS system was broken, and this would lead to the exacerbation of acute severe pneumonia. Therefore, we speculate that ACEI and AT1R inhibitors could be used in patients with COVID-19 pneumonia under the condition of controlling blood pressure, and might reduce the pulmonary inflammatory response and mortality.
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Intermittent dosing of the transforming growth factor beta receptor 1 inhibitor, BMS-986260, mitigates class-based cardiovascular toxicity in dogs but not rats.
J Appl Toxicol2020 Feb;():. doi: 10.1002/jat.3954.
Rak Gregory D, White Melvin R, Augustine-Rauch Karen, Newsome Courtni, Graziano Michael J, Schulze Gene E,
Abstract
Small-molecule inhibitors of transforming growth factor beta receptor 1 (TGF?RI) have a history of significant class-based toxicities (eg, cardiac valvulopathy) in preclinical species that have limited their development as new medicines. Nevertheless, some TGF?RI inhibitors have entered into clinical trials using intermittent-dosing schedules and exposure limits in an attempt to avoid these toxicities. This report describes the toxicity profile of the small-molecule TGF?RI inhibitor, BMS-986260, in rats and dogs. Daily oral dosing for 10 days resulted in valvulopathy and/or aortic pathology at systemic exposures that would have been targeted clinically, preventing further development with this dosing schedule. These toxicities were not observed in either species in 1-month studies using the same doses on an intermittent-dosing schedule of 3 days on and 4 days off (QDx3 once weekly). Subsequently, 3-month studies were conducted (QDx3 once weekly), and while there were no cardiovascular findings in dogs, valvulopathy and mortality occurred early in rats. The only difference compared to the 1-month study was that the rats in the 3-month study were 2 weeks younger at the start of dosing. Therefore, a follow-up 1-month study was conducted to evaluate whether the age of rats influences sensitivity to target-mediated toxicity. Using the same dosing schedule and similar doses as in the 3-month study, there was no difference in the toxicity of BMS-986260 in young (8 weeks) or adult (8 months) rats. In summary, an intermittent-dosing schedule mitigated target-based cardiovascular toxicity in dogs but did not prevent valvulopathy in rats, and thus the development of BMS-986260 was terminated.
© 2020 John Wiley & Sons, Ltd.
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Association between alcohol consumption and subclinical femoral atherosclerosis in smoking and non-smoking men: the AWHS Study.
Addiction2020 Feb;():. doi: 10.1111/add.15012.
Moreno-Franco B, Perez-Esteban A, Civeira F, Guallar-Castillón P, Casasnovas J A, Mateo-Gállego R, Jarauta E, Malo S, Laclaustra M,
Abstract
BACKGROUND AND AIMS:
Many addictive substances, such as tobacco and alcohol, influence atherosclerosis development. Whether tobacco's pro-atherosclerotic effect is influenced by alcohol consumption is unknown. We aimed to estimate the impact of alcohol intake on the presence of subclinical atherosclerosis in femoral arteries in smoking and non-smoking middle-aged men.
DESIGN, SETTING, PARTICIPANTS:
Cross-sectional analysis of a subset of the Aragon Workers Health Study (AWHS), comprising 2099 men with mean age 50.9 years without previous cardiovascular disease.
MEASUREMENTS:
The presence of plaques in femoral arteries was assessed by high-resolution sonography. Self-reported alcohol consumption over the previous year was measured with a food frequency questionnaire. The sample was divided into four groups according to their daily grams of alcohol consumption ?1 (abstainers), ?2 to <30, ?30 to <60, and ?60 g/day. Participants were divided on ever-smoking (current and former), versus never-smoking strata in the main analysis.
FINDINGS:
We did not find a significant association between the different levels of alcohol intake and the likelihood of developing femoral artery atherosclerosis in never-smokers. Ever-smoking was positively associated with femoral atherosclerosis overall (OR=3.00; 95%CI:2.40,3.74; p<0.001) and within each level of alcohol consumption. Atherosclerosis was lower in ever-smokers who consumed 2g/day or more but less than 30g/day with respect to those ever-smokers who were abstainers (OR=0.70; 95%CI:0.49,0.99; p<0.05). However, among them, atherosclerosis prevalence was still higher than among never-smokers who consumed alcohol in the same amount (2g/day or more but less than 30g/day) (OR=2.73; 95%CI:2.07,3.61; p<0.001).
CONCLUSIONS:
Among middle-aged men, moderate alcohol consumption appears to be associated with lower prevalence of femoral artery subclinical atherosclerosis compared with alcohol abstinence only in ever-smokers.
This article is protected by copyright. All rights reserved.
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Proteostasis in thermogenesis and obesity.
Biol Chem2019 Dec;():. doi: 10.1515/hsz-2019-0427.
Bartelt Alexander, Widenmaier Scott B,
Abstract
The proper production, degradation, folding and activity of proteins, proteostasis, is essential for any cellular function. From single cell organisms to humans, selective pressures have led to the evolution of adaptive programs that ensure proteins are properly produced and disposed of when necessary. Environmental factors such as temperature, nutrient availability, pathogens as well as predators have greatly influenced the development of mechanisms such the unfolded protein response, endoplasmic reticulum-associated protein degradation and autophagy, working together in concert to secure cellular proteostasis. In our modern society, the metabolic systems of the human body face the distinct challenge of changed diets, chronic overnutrition and sedentary lifestyles. Obesity and excess white adipose tissue accumulation are linked to a cluster of metabolic diseases and disturbed proteostasis is a common feature. Conversely, processes that promote energy expenditure such as exercise, shivering as well as non-shivering thermogenesis by brown adipose tissue (BAT) and beige adipocytes counteract metabolic dysfunction. Here we review basic concepts of proteostasis in obesity-linked metabolic diseases and focus on adipocytes, which are critical regulators of mammalian energy metabolism.
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Cardiac protection of Bauhinia championii against reperfusion injury.
Environ Toxicol2020 Feb;():. doi: 10.1002/tox.22912.
Chen Yun-Fang, Chen Wei-Yu, Chung Ching-Hu, Kuo Chao-Lin, Lee An-Sheng,
Abstract
This study aims to investigate the protective effects of the Bauhinia championii (BC) against ischemia/reperfusion (I/R)-induced injury in an isolated heart model. Langendorff-perfused C57BL/6JNarl mice hearts were performed with 30?minutes ischemia and 60?minutes reperfusion by left anterior descending artery ligation. Before reperfusion, boiling water extracts of BC (10?mg/L) was pretreated for 15?minutes. During reperfusion, BC significantly decreased the occurrence of ventricular arrhythmias by lead II electrocardiogram (ECG). Electrophysiological effect of BC was further determined in isolated ventricular myocytes by whole-cell patch clamp technique. The underlying mechanism may result from its Na channel blocking activity characterized with reduced rise slope of action potential and Na current density. Moreover, BC dramatically reduced I/R-caused infarct size, which was accessed by 2,3,5-triphenyltetrazolium chloride (TTC) assay. Since BC decreased I/R-induced myoglobin release and oxidation of Ca -calmodulin-dependent protein kinase, inhibition of myocardial necroptosis may account for the protective effects of BC on myocytes lose. This study indicated that BC may prevent I/R induced ventricular arrhythmias and myocyte death by blocking Na channels and decreasing necroptosis, respectively. Since most of the available antiarrhythmic remedies have unwanted adverse actions, BC could be a novel candidate for the treatment of myocardial infarction and ventricular arrhythmia.
© 2020 Wiley Periodicals, Inc.
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NOS1AP polymorphisms reduce NOS1 activity and interact with prolonged repolarization in arrhythmogenesis.
Cardiovasc Res2020 Feb;():. doi: cvaa036.
Ronchi Carlotta, Bernardi Joyce, Mura Manuela, Stefanello Manuela, Badone Beatrice, Rocchetti Marcella, Crotti Lia, Brink Paul, Schwartz Peter J, Gnecchi Massimiliano, Zaza Antonio,
Abstract
NOS1AP SNPs correlate with QT prolongation and cardiac sudden death in patients affected by long QT syndrome type 1 (LQT1). NOS1AP targets NOS1 to intracellular effectors. We hypothesize that NOS1AP SNPs cause NOS1 dysfunction and this may converge with prolonged action potential duration (APD) to facilitate arrhythmias.
AIMS:
To test 1) the effects of NOS1 inhibition and their interaction with prolonged APD in a guinea pig cardiomyocyte (GP-CMs) LQT1 model; 2) whether pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from LQT1 patients differing for NOS1AP variants and mutation penetrance display a phenotype compatible with NOS1 deficiency.
METHODS AND RESULTS:
In GP-CMs NOS1 was inhibited by SMTC (or L-VNIO); LQT1 was mimicked by IKs blockade (JNJ203) and ?-adrenergic stimulation (isoproterenol). hiPSC-CMs were obtained from symptomatic (S) and asymptomatic (AS) KCNQ1-A341V carriers, harboring the minor and major alleles of NOS1AP SNPs (rs16847548 and rs4657139) respectively. In GP-CMs: NOS1 inhibition prolonged APD, enhanced ICaL and INaL, slowed Ca2+ decay and induced delayed afterdepolarizations. Under action-potential clamp, switching to shorter APD suppressed "transient inward current" events induced by NOS1 inhibition and reduced cytosolic Ca2+. In S (vs AS) hiPSC-CMs: APD was longer and ICaL larger; NOS1AP and NOS1 expression and colocalization were decreased.
CONCLUSIONS:
the minor NOS1AP alleles are associated with NOS1 loss of function. The latter likely contributes to APD prolongation in LQT1 and converges with it to perturb Ca2+ handling. This establishes a mechanistic link between NOS1AP SNPs and aggravation of the arrhythmia phenotype in prolonged repolarization syndromes.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email: journals.permissions@oup.com.
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High miR-133a levels in the circulation anticipates presentation of clinical events in familial hypercholesterolemia patients.
Cardiovasc Res2020 Feb;():. doi: cvaa039.
Escate Rafael, Padró Teresa, Suades Rosa, Camino Sandra, Muñiz Ovidio, Diaz-Diaz Jose Luis, Sionis Alessandro, Mata Pedro, Badimon Lina,
Abstract
AIMS:
Presentation of acute events in patients with atherosclerosis remains unpredictable even after controlling for classical risk factors. MicroRNAs (miRNAs) measured in liquid biopsies could be good candidate biomarkers to improve risk prediction. Here, we hypothesized that miRNAs could predict atherosclerotic plaque progression and clinical event presentation in familial hypercholesterolemia (FH) patients.
METHODS AND RESULTS:
Circulating miRNAs (plasma, exosomes, microvesicles) were investigated by TaqMan Array and RT-qPCR assays. Patients with genetic diagnosis of FH and healthy relatives from the SAFEHEART cohort were included. A differential signature of 10 miRNA was obtained by comparing two extreme phenotypes consisting of FH-patients suffering a cardiovascular event (CVE) within a 8-year follow-up period (FH-CVE, N=42) and non-FH hypercholesterolemic relatives from the same cohort, matched for age and treatment, without CVE during the same period (nFH-nCVE, N=30). The validation studies included two independent groups of patients with FH-background (Discovery-Group, N=89, Validation-Group N=196), developing a future CVE (FH-CVE) or not (FH-nCVE) within the same time period of follow-up. Of the 10 miRNAs initially selected, miR-133a was significantly higher in FH-CVE than in FH-nCVE patients. ROC-analysis confirmed miR-133a as the best microRNA for predicting CVE in FH-patients (0.76±0.054; P<0.001). Furthermore, Kaplan-Meier and COX-analysis showed that high plasma miR-133a levels associated to the higher risk of presenting a CVE within the next 8 years (HR: 3.89 [95%CI: 1.88-8.07], P<0.001). In silico analysis of curate biological interactions related miR-133a with target genes involved in regulation of the cell-membrane lipid-receptor LRP6 and inflammatory cytokines (CXCL8, IL6, TNF). These predictions were experimentally proven in human macrophages and endothelial cells transfected with agomiR-133a.
CONCLUSION:
Elevated levels of miR-133a in the circulation anticipate those FH-patients that are going to present a clinical CVE within the next 2 years (average). Mechanistically, miR-133a is directly related with lipid- and inflammatory-signalling in key cells for atherosclerosis progression.
TRANSLATIONAL PERSPECTIVE:
The present study in patients with familial hypercholesterolemia shows that epigenetic markers can allow the identification of those patients that are going to present an acute clinical event within the next two years (average). There are currently few prognostic biomarkers able to identify subjects at risk of developing major acute cardiovascular events. Here, by using a non-targeted approach of miRNA-discovery, we show for first time that plasma levels of miR-133a have prognostic value to predict incident cardiovascular events in patients with familial hypercholesterolemia treated as per guidelines. Future studies with larger independent cohorts are needed to validate the prognostic value of miR-133a in the general population.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email: journals.permissions@oup.com.
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A telephone reminder to enhance adherence to interventions in cardiovascular randomized trials: A protocol for a study within a trial (SWAT).
J Evid Based Med2020 Feb;():. doi: 10.1111/jebm.12375.
Bensaaud Abdelsalam, Gibson Irene, Jones Jennifer, Flaherty Gerard, Sultan Sherif, Tawfick Wael, Jordan Fionnuala,
Abstract
The impact of reduced adherence in randomized clinical trials is well documented in the literature. Nonadherence can negatively affect the trial sample size and estimation of the treatment effect. This protocol aims to evaluate the effects of a telephone call reminder on the adherence rates of participants to interventions in a cardiovascular randomized trial. This is a study within a trial (SWAT). The host trial is evaluating the effectiveness of a multidisciplinary 16-wk cardiovascular disease prevention program on risk factor profile among patients with carotid artery stenosis. Simultaneously, this SWAT will evaluate the effectiveness of telephone call reminders on the participants' adherence to the host trial intervention. The primary outcome is adherence to the protocol of the host trial. Secondary outcomes are level of adherence, number of dropouts, and time to drop out from the host trial.
© 2020 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.
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Estimation of increased pulmonary wedge pressure by an algorithm based on noninvasively measured pulmonary diastolic pressure in cardiac patients independent of left ventricular ejection fraction.
Echocardiography2020 Feb;():. doi: 10.1111/echo.14581.
Barbier Paolo, Cucco Cuono, Guglielmo Marco, Simioniuc Anca, Fabiani Iacopo, Pugliese Nicola Riccardo, Savioli Gabriele, Dini Frank Lloyd,
Abstract
AIM:
Pulmonary artery diastolic pressure (PADP) correlates closely with pulmonary wedge pressure (PAWP); therefore, we sought to evaluate whether an algorithm based on PADP assessment by the Doppler pulmonary regurgitation (PR) end-diastolic gradient (PRG) may aid in estimating increased PAWP in cardiac patients with reduced or preserved left ventricular (LV) ejection fraction (EF).
METHODS AND RESULTS:
Right heart catheterization, with estimation of PAWP, right atrial pressure (RAP), PADP, and Doppler echocardiography, was carried out in 183 patients with coronary artery disease (n = 63), dilated cardiomyopathy (n = 52), or aortic stenosis (n = 68). One-hundred and seventeen patients had LV EF <50%. We measured the pressure gradients across the tricuspid and pulmonary valves from tricuspid regurgitation (TRV) and PR velocities. Doppler-estimated PADP (e-PADP) was obtained by adding the estimated RAP to PRG. An algorithm based on e-PADP to predict PAWP, that included TRV, left atrial volume index, and mitral E/A, was developed and validated in derivation (n = 90) and validation (n = 93) subgroups. Both invasive PADP (r = .92, P < .001) and e-PADP (r = .72, P < .001) correlated closely with PAWP, and e-PADP predicted PAWP (AUC: 0.85, CI: 0.79-0.91) with a 94% positive predictive value (PPV) and a 55% negative predictive value (NPV), after exclusion of five patients with precapillary pulmonary hypertension. The e-PADP-based algorithm predicted PAWP with higher accuracy (PPV = 94%; NPV = 67%; accuracy = 85%; kappa: 0.65, P < .001) than the ASE-EACVI 2016 recommendations (PPV = 97%; NPV = 47%; accuracy = 68% undetermined = 18.9%; kappa: 0.15, P < .001).
CONCLUSIONS:
An algorithm based on noninvasively e-PADP can accurately predict increased PAWP in patients with cardiac disease and reduced or preserved LV EF.
© 2020 Wiley Periodicals, Inc.
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Histone Hyperacetylation Mediates Enhanced IL-1? Production in LPS/IFN-? stimulated Macrophages.
Immunology2020 Feb;():. doi: 10.1111/imm.13183.
Dong Zhen, Li Ruoshui, Xu Lei, Xin Kaiyue, Shi Haiming, Sun Aijun, Ge Junbo,
Abstract
Under the condition of LPS/IFN-? activation, macrophage metabolism is conversed from oxidative phosphorylation to glycolysis. In the present work, we analyzed whether glycolysis could affect IL-1? expression through altering histone acetylation level in mouse bone marrow-derived macrophages. Immunocytochemistry and Western blot analysis are used to characterize histone acetylation in macrophages stimulated by LPS/IFN-?. RT-PCR and ELISA were used to determine IL-1? production. Macrophages' metabolism was monitored in real time by Seahorse test. Our results showed that glycolytic metabolism could enhance the histone acetylation and promote the IL-1? production in LPS/IFN-? activated macrophage. Moreover, increased production of IL-1? by glycolysis was mediated through enhanced H3K9 acetylation. Importantly, it is found that high-dose of HDAC inhibitor could also significantly increase the expression of IL-1? in the absence of glycolytic metabolism. In conclusion, this study demonstrates that glycolytic metabolism could regulate IL-1? expression by increasing histone acetylation levels in LPS/IFN-? stimulated macrophages.
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Subxiphoid approach for robotic single-site-assisted thymectomy.
Eur J Cardiothorac Surg2020 Feb;():. doi: ezaa036.
Park Seong Yong, Han Kook Nam, Hong Jeong In, Kim Hyun Koo, Kim Dae Joon, Choi Young Ho,
Abstract
OBJECTIVES:
We previously reported a transthoracic approach using the da Vinci Single-Site? platform. This study describes the outcomes of robotic single-site thymectomy via a subxiphoid approach based on our previous experiences.
METHODS:
This study included patients, who underwent single-site robotic thymectomy via the subxiphoid approach between September 2018 and October 2019. A 3- to 4-cm vertical incision was made over the subxiphoid area, and the Lapsingle port with CO2 gas was introduced. After docking at the single site, a 5-mm curved cannula, 5-mm cardiere grasper and Maryland bipolar forceps or permanent cautery hook was inserted. The single-site robotic platform was used to conduct all surgical procedures except the dissection around the inferior portion of the thymic tissue performed via a thoracoscopic approach through the same incision.
RESULTS:
Overall, 13 patients, including 2 with myasthenia gravis, were enrolled. The mean duration of the surgery and chest drainage were 167.3?±?52.8 (range 73-253) min and 2.2?±?0.9 (range 1-5) days, respectively. All surgeries were successfully completed without conversion to an open surgery, and there were no major post-surgical complications. The diagnoses based on histopathology included thymoma in 10 patients, thymolipoma in 2 patients and atypical carcinoid tumour in 1 patient with free resection margin.
CONCLUSIONS:
This study demonstrated that robotic single-site-assisted thymectomy via the subxiphoid approach is a safe and technically feasible procedure. Although this initial series comprised relatively simple cases, more advanced and complex procedures can soon be performed with the advent of single-port robotic platform.
© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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The robotic thymectomy via the subxiphoid approach: technique and early outcomes.
Eur J Cardiothorac Surg2020 Feb;():. doi: ezaa006.
Kang Chang Hyun, Na Kwon Joong, Song Jae Won, Bae So Young, Park Samina, Park In Kyu, Kim Young Tae,
Abstract
OBJECTIVES:
Robotic thymectomy via the subxiphoid approach (RTX) is a recently introduced surgical approach. This study aimed to report on the surgical technique and early outcomes of RTX in our institute.
METHODS:
RTX was performed using the 3-arm technique in the da Vinci robotic surgical system. The camera was inserted into a subxiphoid port, and 2 robotic arms were inserted in bilateral intercostal ports. A complete dissection of both cervical poles up to the thyroid gland was conducted, and bilateral phrenic nerves were identified in all cases. Radical combined resection of adjacent organs, including the lung, pericardium, phrenic nerve and the innominate vein, was performed if necessary. The resected specimen could be retrieved through the subxiphoid port site.
RESULTS:
A total of 110 patients underwent RTX in our institute from October 2016 to August 2019. Thymoma was the most common diagnosis (60.9%), and the mean size of the tumours was 4.9?±?2.4?cm. Combined resection was performed in the lung (n?=?9, 8.1%), pericardium (n?=?6, 5.5%) and innominate vein (n?=?5, 4.5%). There were 2 minor postoperative complications (1.8%), and the mean length of hospital stay was 2.2?±?1.4?days. For the cumulative sum curve analysis of the learning curve using operative time, 50 cases were necessary to gain proficiency.
CONCLUSIONS:
RTX was a safe and feasible surgical approach, even in advanced thymic epithelial tumours. It should be considered one of the valuable surgical options in minimally invasive thymectomy.
© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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Intravenous administration of iPS-MSC mobilized into CKD parenchyma and effectively preserved residual renal function in CKD rat.
J Cell Mol Med2020 Feb;():. doi: 10.1111/jcmm.15050.
Sheu Jiunn-Jye, Sung Pei-Hsun, Wallace Christopher Glenn, Yang Chih-Chao, Chen Kuan-Hung, Shao Pei-Lin, Chu Yi-Ching, Huang Chi-Ruei, Chen Yi-Ling, Ko Sheung-Fat, Lee Mel S, Yip Hon-Kan,
Abstract
This study traced intravenously administered induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (MSC) and assessed the impact of iPSC-MSC on preserving renal function in SD rat after 5/6 nephrectomy. The results of in vitro study showed that FeraTrack?Direct contrast particles (ie intracellular magnetic labelling) in the iPSC-MSC (ie iPS-MSC ) were clearly identified by Prussian blue stain. Adult-male SD rats (n = 40) were categorized into group 1 (SC), group 2 [SC + iPS-MSC (1.0 × 10 cells)/intravenous administration post-day-14 CKD procedure], group 3 (CKD), group 4 [CKD + iPS-MSC (0.5 × 10 cells)] and group 5 [CKD + iPS-MSC (1.0 × 10 cells)]. By day-15 after CKD induction, abdominal MRI demonstrated that iPS-MSC were only in the CKD parenchyma of groups 4 and 5. By day 60, the creatinine level/ratio of urine protein to urine creatinine/kidney injury score (by haematoxylin and eosin stain)/fibrotic area (Masson's trichrome stain)/IF microscopic finding of kidney injury molecule-1 expression was lowest in groups 1 and 2, highest in group 3, and significantly higher in group 4 than in group 5, whereas IF microscopic findings of podocyte components (ZO-1/synaptopodin) and protein levels of anti-apoptosis ((Bad/Bcl-xL/Bcl-2) exhibited an opposite pattern to creatinine level among the five groups (all P < .0001). The protein expressions of cell-proliferation signals (PI3K/p-Akt/m-TOR, p-ERK1/2, FOXO1/GSK3?/p90RSK), apoptotic/DNA-damage (Bax/caspases8-10/cytosolic-mitochondria) and inflammatory (TNF-?/TNFR1/TRAF2/NF-?B) biomarkers displayed an identical pattern to creatinine level among the five groups (all P < .0001). The iPS-MSC that were identified only in CKD parenchyma effectively protected the kidney against CKD injury.
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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Evaluating Biventricular Myocardial Velocity and Interventricular Dyssynchrony in Adult Patients During the First Year After Heart Transplantation.
J Magn Reson Imaging2020 Feb;():. doi: 10.1002/jmri.27091.
Sarnari Roberto, Blake Allison M, Ruh Alexander, Abbasi Muhannad A, Pathrose Ashitha, Blaisdell Julie, Dolan Ryan S, Ghafourian Kambiz, Wilcox Jane E, Khan Sadiya S, Vorovich Esther E, Rich Jonathan D, Anderson Allen S, Yancy Clyde W, Carr James C, Markl Michael,
Abstract
BACKGROUND:
Magnetic resonance tissue phase mapping (TPM) measures three-directional myocardial velocities of the left and right ventricle (LV, RV). This noninvasive technique may supplement endomyocardial biopsy (EMB) in monitoring grafts post-heart transplantation (HTx).
PURPOSE:
To assess biventricular myocardial velocity alterations in grafts and investigate the relationship between velocities and acute cellular rejection (ACR) episodes.
STUDY TYPE:
Prospective.
SUBJECTS:
Twenty-seven patients within 1?year post-HTx (49?±?13?years, 19?M) and 18 age-matched controls (49?±?15?years, 12?M).
FIELD STRENGTH/SEQUENCE:
1.5T, 2D balanced steady-state free precession, and TPM.
ASSESSMENT:
Ventricular function: end-diastolic and end-systolic volumes, stroke volumes, ejection fraction (EF), and myocardial mass. TPM velocities: peak-systolic and peak-diastolic velocities, cardiac twist, and interventricular dyssynchrony. ACR rejection episodes: International Society for Heart and Lung Transplantation grading of EMB specimens.
STATISTICAL TESTS:
The Lilliefors test for normality, unpaired t-tests, and Wilcoxon rank-sum tests for normally and nonnormally distributed data, respectively, were used, as well as multivariate regression for confounding variables and Pearson's correlation for associations between TPM velocities and global function.
RESULTS:
Compared to controls, HTx patients demonstrated reduced biventricular systolic longitudinal velocities (LV: 5.2?±?2.1 vs. 4.0?±?1.5?cm/s, P?4 preceding ACR episodes showed globally reduced RV and LV systolic radial velocity, and segmentally reduced radial and longitudinal systolic velocities.
DATA CONCLUSION:
Biventricular global and segmental velocities were reduced in HTx patients. Patients with >4 rejection episodes showed reduced myocardial velocities. The TPM sequence may add functional information for monitoring graft dysfunction.
LEVEL OF EVIDENCE:
2 TECHNICAL EFFICACY STAGE: 2.
© 2020 International Society for Magnetic Resonance in Medicine.
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SCAI publications committee manual of standard operating procedures.
Catheter Cardiovasc Interv2020 Feb;():. doi: 10.1002/ccd.28754.
Szerlip Molly, Feldman Dmitriy N, Aronow Herbert D, Blankenship James C, Choi James W, Elgendy Islam Y, Elmariah Sammy, Garcia Santiago, Goldstein Bryan H, Herrmann Howard, Hira Ravi S, Jaff Michael R, Kalra Ankur, Kaluski Edo, Kavinsky Clifford J, Kolansky Daniel M, Kong David F, Messenger John C, Mukherjee Debabrata, Patel Rajan A G, Piana Robert, Senerth Emily, Shishehbor Mehdi, Singh Gagan, Singh Vikas, Yadav Pradeep K, Cox David,
Abstract
Evidence-based recommendations for clinical practice are intended to help health care providers and patients make decisions, minimize inappropriate practice variation, promote effective resource use, improve clinical outcomes, and direct future research. The Society for Cardiovascular Angiography and Interventions (SCAI) has been engaged in the creation and dissemination of clinical guidance documents since the 1990s. These documents are a cornerstone of the society's education, advocacy, and quality improvement initiatives. The publications committee is charged with oversight of SCAI's clinical documents program and has created this manual of standard operating procedures to ensure consistency, methodological rigor, and transparency in the development and endorsement of the society's documents. The manual is intended for use by the publications committee, document writing groups, external collaborators, SCAI representatives, peer reviewers, and anyone seeking information about the SCAI documents program.
© 2020 Wiley Periodicals, Inc.
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Extending the Role of Cardiac Magnetic Resonance in Sarcoidosis Risk Stratification: Editorial for "Regional Myocardial Remodeling Characteristics Correlates With Cardiac Events in Sarcoidosis".
J Magn Reson Imaging -
USA joins Canada, UK, Ireland and Austria in allowing people with insulin-treated diabetes to fly commercial aircraft.
Diabet Med2020 Feb;():. doi: 10.1111/dme.14273.
Russell-Jones D L, Frier B M, Shaw K M,
Abstract
Several occupational activities demand a stringent approach to safety to ensure protection of the public and the employee. Transport by whatever means is one such area, and air travel in particular requires strict measures to ensure a very high standard of safety because of the potentially devastating consequences of an accident involving a commercial aircraft. Pilots of aeroplanes conveying passengers are therefore subjected to rigorous medical screening and review, and are debarred from flying by the presence of some medical disorders.
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Hydroxysafflor Yellow A Confers Neuroprotection from Focal Cerebral Ischemia by Modulating the Crosstalk Between JAK2/STAT3 and SOCS3 Signaling Pathways.
Cell Mol Neurobiol2020 Feb;():. doi: 10.1007/s10571-020-00812-7.
Yu Lu, Liu Zhili, He Wendi, Chen Huifen, Lai Zelin, Duan Yanhong, Cao Xiaohua, Tao Jie, Xu Chuan, Zhang Qiujuan, Zhao Zheng, Zhang Jun,
Abstract
Natural bioactive compounds have increasingly proved to be promising in evidence- or target-directed treatment or modification of a spectrum of diseases including cerebral ischemic stroke. Hydroxysafflor yellow A (HSYA), a major active component of the safflower plant, has drawn more interests in recent year for its multiple pharmacological actions in the treatment of cerebrovascular and cardiovascular diseases. Although the Janus kinase signaling, such as JAK2/STAT3 pathway, has been implicated in the modulation of the disease, the inhibition or activation of the pathway that contributed to the neuronal prevention from ischemic damages remains controversial. In this study, a series of experiments were performed to examine the dose- and therapeutic time window-related pharmacological efficacies of HSYA with emphasis on the HSYA-modulated interaction of JAK2/STAT3 and SOCS3 signaling in the MCAO rats. We found that HSYA treatment significantly rescued the neurological and functional deficits in a dose-dependent manner in the MCAO rats within 3 h after ischemia. HSYA treatment with a dosage of 8 mg/kg or higher markedly downregulated the expression of the JAK2-mediated signaling that was activated in response to ischemic insult, while it also promoted the expression of SOCS3 coordinately. In the subsequent experiments with the use of the JAK2 inhibitor WP1066, we found that the treatment of WP1066 alone or combination of WP1066/HSYA all exhibited inhibitory effects on JAK2-mediated signaling, while there was no influence on the SOCS3 activity of corresponding efficacious data in the MCAO rats, suggesting that excessive activation of JAK2/STAT3 might be necessary for HSYA to provoke SOCS3-negative feedback signaling. Taking together, our study demonstrates that HSYA might modulate the crosstalk between JAK2/STAT3 and SOCS3 signaling pathways that eventually contributed to its therapeutic roles against cerebral ischemic stroke.
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Diet and the Human Gut Microbiome: An International Review.
Dig Dis Sci2020 Feb;():. doi: 10.1007/s10620-020-06112-w.
Wilson Annette S, Koller Kathryn R, Ramaboli Matsepo C, Nesengani Lucky T, Ocvirk Soeren, Chen Caixia, Flanagan Christie A, Sapp Flora R, Merritt Zoe T, Bhatti Faheem, Thomas Timothy K, O'Keefe Stephen J D,
Abstract
This review summarizes the key results of recently published studies on the effects of dietary change and nutritional intervention on the human microbiome from around the world, focusing on the USA, Canada, Europe, Asia, and Africa. It first explores mechanisms that might explain the ability of fiber-rich foods to suppress the incidence and mortality from westernized diseases, notably cancers of the colon, breast, liver, cardiovascular, infectious, and respiratory diseases, diabetes, and obesity (O'Keefe in Lancet Gastroenterol Hepatol 4(12):984-996, 2019; Am J Clin Nutr 110:265-266, 2019). It summarizes studies from Africa which suggest that disturbance of the colonic microbiome may exacerbate chronic malnutrition and growth failure in impoverished communities and highlights the importance of breast feeding. The American section discusses the role of the microbiome in the swelling population of patients with obesity and type 2 diabetes and examines the effects of race, ethnicity, geography, and climate on microbial diversity and metabolism. The studies from Europe and Asia extoll the benefits of whole foods and plant-based diets. The Asian studies examine the worrying changes from low-fat, high-carbohydrate diets to high-fat, low-carbohydrate ones and the increasing appearance of westernized diseases as in Africa and documents the ability of high-fiber traditional Chinese diets to reverse type 2 diabetes and control weight loss. In conclusion, most of the studies reviewed demonstrate clear changes in microbe abundances and in the production of fermentation products, such as short-chain fatty acids and phytochemicals following dietary change, but the significance of the microbiota changes to human health, with the possible exception of the stimulation of butyrogenic taxa by fiber-rich foods, is generally implied and not measured. Further studies are needed to determine how these changes in microbiota composition and metabolism can improve our health and be used to prevent and treat disease.
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The relationship between global longitudinal strain and pulmonary function tests in patients with scleroderma and normal ejection fraction and pulmonary artery pressure: a case-control study.
Int J Cardiovasc Imaging2020 Feb;():. doi: 10.1007/s10554-020-01788-7.
Hajsadeghi Shokoufeh, Mirshafiee Shayan, Pazoki Mahboubeh, Moradians Vahan, Mansouri Pejman, Kianmehr Nahid, Iranpour Aida,
Abstract
This study examined the relationship between global longitudinal strain (GLS) and pulmonary function tests (PFT) in patients with systemic sclerosis (SS) and normal ejection fraction (EF) and pulmonary artery pressure (PAP) and healthy controls. Sixty patients in two groups underwent extensive screening, including echocardiography, physical examination, the modified Rodnan Skin Score, and pulmonary function tests. Pulmonary interstitial disease was diagnosed by the pulmonary function test and by CT scan in case of indication. GLS score was computed as the mean peak systolic strain for 17 segments. The mean GLS score was - 18.36?±?2.1 in the case group and - 20.66?±?1.6 in the control group (P value?
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