Lactoferrin ameliorates pathological cardiac hypertrophy related to mitochondrial quality control in aged mice

2021 ◽  
Author(s):  
Lishan Huang ◽  
Ruiyu Chen ◽  
Libin Liu ◽  
Yu Zhou ◽  
Zhou Chen
Keyword(s):  
Quality Control ◽  
Cardiovascular Diseases ◽  
Cardiac Hypertrophy ◽  
Myocardial Hypertrophy ◽  
Treatment Strategies ◽  
The Elderly ◽  
Mitochondrial Quality Control ◽  
Effective Prevention ◽  
Pathological Cardiac Hypertrophy ◽  
Prevention And Treatment

Pathological myocardial hypertrophy, which lacks effective prevention and treatment strategies, makes the elderly susceptible to various cardiovascular diseases. Based on the beneficial attributes of lactoferrin in aging-related diseases, we aimed...

A gene therapeutic approach to inhibit calcium and integrin binding protein 1 ameliorates maladaptive remodelling in pressure overload

2018 ◽  
Vol 115 (1) ◽  
pp. 71-82 ◽  
Author(s):  
Andrea Grund ◽  
Malgorzata Szaroszyk ◽  
Janina K Döppner ◽  
Mona Malek Mohammadi ◽  
Badder Kattih ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Binding Protein ◽  
Treatment Strategies ◽  
Pressure Overload ◽  
Cellular Growth ◽  
Neonatal Rat ◽  
Rat Cardiomyocytes ◽  
Pathological Cardiac Hypertrophy

Abstract Aims Chronic heart failure is becoming increasingly prevalent and is still associated with a high mortality rate. Myocardial hypertrophy and fibrosis drive cardiac remodelling and heart failure, but they are not sufficiently inhibited by current treatment strategies. Furthermore, despite increasing knowledge on cardiomyocyte intracellular signalling proteins inducing pathological hypertrophy, therapeutic approaches to target these molecules are currently unavailable. In this study, we aimed to establish and test a therapeutic tool to counteract the 22 kDa calcium and integrin binding protein (CIB) 1, which we have previously identified as nodal regulator of pathological cardiac hypertrophy and as activator of the maladaptive calcineurin/NFAT axis. Methods and results Among three different sequences, we selected a shRNA construct (shCIB1) to specifically down-regulate CIB1 by 50% upon adenoviral overexpression in neonatal rat cardiomyocytes (NRCM), and upon overexpression by an adeno-associated-virus (AAV) 9 vector in mouse hearts. Overexpression of shCIB1 in NRCM markedly reduced cellular growth, improved contractility of bioartificial cardiac tissue and reduced calcineurin/NFAT activation in response to hypertrophic stimulation. In mice, administration of AAV-shCIB1 strongly ameliorated eccentric cardiac hypertrophy and cardiac dysfunction during 2 weeks of pressure overload by transverse aortic constriction (TAC). Ultrastructural and molecular analyses revealed markedly reduced myocardial fibrosis, inhibition of hypertrophy associated gene expression and calcineurin/NFAT as well as ERK MAP kinase activation after TAC in AAV-shCIB1 vs. AAV-shControl treated mice. During long-term exposure to pressure overload for 10 weeks, AAV-shCIB1 treatment maintained its anti-hypertrophic and anti-fibrotic effects, but cardiac function was no longer improved vs. AAV-shControl treatment, most likely resulting from a reduction in myocardial angiogenesis upon downregulation of CIB1. Conclusions Inhibition of CIB1 by a shRNA-mediated gene therapy potently inhibits pathological cardiac hypertrophy and fibrosis during pressure overload. While cardiac function is initially improved by shCIB1, this cannot be kept up during persisting overload.

scholarly journals Clinical characteristic and management of elderly patients with myocardial infarction

2019 ◽  
Vol 147 (3-4) ◽  
pp. 167-172
Author(s):  
Jadranka Dejanovic ◽  
Igor Ivanov ◽  
Tanja Popov ◽  
Milenko Cankovic ◽  
Aleksandra Vulin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Cardiovascular Diseases ◽  
Ejection Fraction ◽  
Hospital Mortality ◽  
Cardiogenic Shock ◽  
Treatment Strategies ◽  
The Elderly ◽  
Left Ventricular ◽  
Clinical Characteristic

Introduction/Objective. Population of elderly people is increasing and modern medicine is faced with the problem of large morbidity and mortality from cardiovascular diseases in this age group. Modern treatment strategies have not been sufficiently investigated in the elderly, therefore these people often receive suboptimal treatment. The aim of the study was to evaluate clinical characteristic, cardiac risk factors, management strategies and early outcome in the elderly patient with ST elevated myocardial infarction (STEMI). Methods. This retrospective study included 217 consecutive patients, aged ? 70 years (mean age 77.6 ? 4.9 years, 103 men, 114 women) with STEMI admitted to the Institute of Cardiovascular Diseases of Vojvodina. We have analyzed patients? clinical characteristics, risk factors, left ventricular function and treatment strategies in relation to in-hospital outcome. Results. First clinical symptom was chest pain in 209 (96.3%) of patients. On admission, 35 (16.1%) patients were with severe signs of heart failure (Killip class III?IV). Duration of symptom onset to hospital admission was 14.7 ? 28.6 hours. Out of 217 patients, 168 (77.4%) patients received reperfusion treatment, including primary percutaneous coronary ntervention (PPCI) in 164 (75.6%) patients, and fibrinolytic therapy in 4 (1.8%) patients. Hospital mortality was 26.3% (57 patients). PPCI was univariate predictor of lower in-hospital mortality, whereas multivariate predictors of in-hospital mortality were cardiogenic shock (OR 67.095; 95% CI (6.845?657.646); p < 0.001) and low ejection fraction (OR 0.901; 95% CI (0.853?0.963); p = 0.001). Conclusion. In elederly patients presenting with STEMI, PPCI was asscoiated with lower mortality, whereas cardiogenic shock and lower ejection fraction were independent predictors of worse prognosis after STEMI.

scholarly journals Integrated Medicine for Chemotherapy-Induced Peripheral Neuropathy

2021 ◽  
Vol 22 (17) ◽  
pp. 9257
Author(s):  
Chih-Hung Tsai ◽  
Yuan-Ho Lin ◽  
Yung-Sheng Li ◽  
Trung-Loc Ho ◽  
Le Huynh Hoai Thuong ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Peripheral Neuropathy ◽  
Recent Progress ◽  
Therapeutic Strategy ◽  
Treatment Strategies ◽  
Common Side Effect ◽  
Integrated Medicine ◽  
Effective Prevention ◽  
Effective Strategies ◽  
Prevention And Treatment

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of typical chemotherapeutics among cancer survivors. Despite the recent progress, the effective prevention and treatment strategies for CIPN remain limited. Better understanding of the pathogenesis of CIPN may provide new niches for developing a new ideal therapeutic strategy. This review summarizes the current understanding of CIPN and current recommendations along with completed/active clinical trials and aims to foster translational research to improve the development of effective strategies for managing CIPN.

scholarly journals Effects of Sodium Ferulate on Cardiac Hypertrophy Are via the CaSR-Mediated Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Panpan Chen ◽  
Zhaoqin Wen ◽  
Wanlan Shi ◽  
Zhongli Li ◽  
Xiaoyan Chen ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Cardiovascular Diseases ◽  
Protein Kinase ◽  
Cardiac Hypertrophy ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Myocardial Hypertrophy ◽  
Mitogen Activated Protein Kinase ◽  
Kinase C ◽  
Mitogen Activated Protein

As a common complication of many cardiovascular diseases, cardiac hypertrophy is characterized by increased cardiac cell volume, reorganization of the cytoskeleton, and the reactivation of fetal genes such as cardiac natriuretic peptide and β-myosin heavy chain. Cardiac hypertrophy is a distinguishing feature of some cardiovascular diseases. Our previous study showed that sodium ferulate (SF) alleviates myocardial hypertrophy induced by coarctation of the abdominal aorta, and these protective effects may be related to the inhibition of protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) signaling pathways. This study investigated the inhibitory effect and mechanism of SF on myocardial hypertrophy in spontaneously hypertensive rats (SHRs). The effects of SF on cardiac hypertrophy were evaluated using echocardiographic measurement, pathological analysis, and detection of atrial natriuretic peptide (ANP) and β-myosin heavy chain (β-MHC) expression. To investigate the mechanisms underlying the anti-hypertrophic effects of SF, the calcium-sensing receptor (CaSR), calcineurin (CaN), nuclear factor of activated T cells 3 (NFAT3), zinc finger transcription factor 4 (GATA4), protein kinase C beta (PKC-β), Raf-1, extracellular signal-regulated kinase 1/2 (ERK 1/2), and mitogen-activated protein kinase phosphatase-1 (MKP-1) were detected by molecular biology techniques. Treatment with SF ameliorated myocardial hypertrophy in 26-week-old SHRs. In addition, it downregulated the levels of ANP, β-MHC, CaSR, CaN, NFAT3, phosphorylated GATA4 (p-GATA4), PKC-β, Raf-1, and p-ERK 1/2; and upregulated the levels of p-NFAT3 and MKP-1. These results suggest that the effects of SF on cardiac hypertrophy are related to regulation of the CaSR-mediated signaling pathway.

scholarly journals Analysis SARS-CoV-2 Genomes of G20 Areas on Phylogeny Tree, t-SNE based on Machine Learning

2020 ◽  
Author(s):  
Renyang Liu ◽  
Mu Qiao ◽  
Alima ◽  
Jeffrey Zheng ◽  
Wei Zhou
Keyword(s):  
Public Health ◽  
Machine Learning ◽  
Phylogenetic Tree ◽  
Treatment Strategies ◽  
Gene Sequences ◽  
Effective Prevention ◽  
Multiple Resources ◽  
The World ◽  
Prevention And Treatment ◽  
Epidemiological Characteristics

Abstract The new coronavirus disease (COVID-19) broke out earlier in Wuhan, and the plague spread rapidly from multiple resources of different countries. COVID-19 has caused millions of diagnosed people worldwide, causing many deaths and posing a severe threat to public health in countries around the world. Facing this urgent situation, in-depth research on the emerging SARS-CoV-2 to understand the related pathogenic mechanism and epidemiological characteristics is urgent. This type of activity would be useful to determine its origin to formulate effective prevention and treatment strategies for affected patients.This paper adopts t-SNE based on machine learning to draw a phylogenetic tree from collected genomic sequences to analyze G20 countries’ samples. The phylogenetic tree of the generating mechanism was described, and intermediate results were illustrated. The results of this research showed that viruses in many countries have similar or similar relationships among the gene sequences.

scholarly journals Delirium – a common condition associated with negative outcome in the elderly

2012 ◽  
Vol 22 (2) ◽  
Author(s):  
Vibeke Juliebø ◽  
Maria Krogseth ◽  
Bjørn Erik Neerland ◽  
Leiv Otto Watne ◽  
Torgeir Bruun Wyller
Keyword(s):  
Treatment Strategies ◽  
The Elderly ◽  
Clinical Syndrome ◽  
Predisposing Factors ◽  
Cochrane Library ◽  
Targeted Prevention ◽  
Acute Confusional State ◽  
Prevention And Treatment ◽  
Significant Efficacy ◽  
The Cochrane Library

<p>Delirium (“acute confusional state”), characterized by an acute decline in attention and cognition, is a common clinical syndrome in elderly patients. The prevalence of delirium increases with age, and is highest among hospitalized older patients. A systematic literature search of MEDLINE, EMBASE, and the Cochrane Library limited to the period 2000-2012 was conducted.</p><p>The antecedent of delirium is often multifactorial, the development involving a complex interrelationship between a vulnerable patient with predisposing factors and exposure to precipitating events. Important predisposing factors include high age, cognitive impairment, comorbidity, sensory impairment, and low Body Mass Index (BMI). Infections, cardiovascular events, trauma/fracture, surgery, stroke, metabolic abnormalities, and dehydration, are all recognized as precipitating factors.</p><p>Delirium is associated with negative outcomes like cognitive decline, increased morbidity and mortality, and should be prevented. Prevention and treatment of delirium is multifactorial and multidisiplinary, focusing on the treatment of factors precipitating and maintaining the delirium. No pharmacological treatment has so far demonstrated significant efficacy. The knowledge of risk factors and the underlying pathophysiological mechanisms involved remains scarce, and further research is warranted to explore the mechanisms and thereby develop targeted prevention and treatment strategies.</p>

The Hippo Pathway Orchestrates Mitochondrial Quality Control: A Novel Focus on Cardiovascular Diseases

2020 ◽  
Vol 39 (9) ◽  
pp. 1494-1505
Author(s):  
Ying Tan ◽  
Cai Lei ◽  
Huifang Tang ◽  
Xiao Zhu ◽  
Guanghui Yi
Keyword(s):  
Quality Control ◽  
Cardiovascular Diseases ◽  
Hippo Pathway ◽  
Mitochondrial Quality Control ◽  
The Hippo Pathway

scholarly journals Amlexanox and Forskolin Prevents Isoproterenol-Induced Cardiomyopathy by Subduing Cardiomyocyte Hypertrophy and Maladaptive Inflammatory Responses

2021 ◽  
Vol 9 ◽  
Author(s):  
Gabriel Komla Adzika ◽  
Hongjian Hou ◽  
Adebayo Oluwafemi Adekunle ◽  
Ruqayya Rizvi ◽  
Seyram Yao Adzraku ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Troponin I ◽  
Inflammatory Responses ◽  
Myocardial Hypertrophy ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Myocardial Inflammation ◽  
Treatment Interventions ◽  
Pathological Cardiac Hypertrophy

Chronic catecholamine stress (CCS) induces the occurrence of cardiomyopathy—pathological cardiac hypertrophy (PCH), which is characterized by left ventricular systolic dysfunction (LVSD). Recently, mounting evidence has implicated myocardial inflammation in the exacerbation of pathological cardiac remodeling. However, there are currently no well-defined treatment interventions or regimes targeted at both the attenuation of maladaptive myocardial hypertrophy and inflammation during CCS to prevent PCH. G protein-coupled receptor kinase 5 (GRK5) and adenylyl cyclases (ACs)-cAMP mediates both cardiac and inflammatory responses. Also, GRK5 and ACs are implicated in stress-induced LVSD. Herein, we aimed at preventing PCH during CCS via modulating adaptive cardiac and inflammatory responses by inhibiting GRK5 and/or stimulating ACs. Isoproterenol-induced cardiomyopathy (ICM) was modeled using 0.5 mg/100 g/day isoproterenol injections for 40 days. Alterations in cardiac and inflammatory responses were assessed from the myocardia. Similarities in the immunogenicity of cardiac troponin I (cTnI) and lipopolysaccharide under CCS were assessed, and Amlexanox (35 μM/ml) and/or Forskolin (10 μM/ml) were then employed in vitro to modulate adaptive inflammatory responses by inhibiting GRK5 or activating ACs-cAMP, respectively. Subsequently, Amlexanox (2.5 mg/100 g/day) and/or Forskolin (0.5 mg/100 g/day) were then translated into in vivo during CCS to modulate adaptive cardiac and inflammatory responses. The effects of Amlexanox and Forskolin on regulating myocardial systolic functions and inflammatory responses during CCS were ascertained afterward. PCH mice had excessive myocardial hypertrophy, fibrosis, and aggravated LVSD, which were accompanied by massive CD68+ inflammatory cell infiltrations. In vitro, Forskolin-AC/cAMP was effective than Amlexanox-GRK5 at downregulating proinflammatory responses during stress; nonetheless, Amlexanox and Forskolin combination demonstrated the most efficacy in modulating adaptive inflammatory responses. Individually, the translated Amlexanox and Forskolin treatment interventions were ineffective at subduing the pathological remodeling and sustaining cardiac function during CCS. However, their combination was potent at preventing LVSD during CCS by attenuating maladaptive myocardial hypertrophy, fibrosis, and inflammatory responses. The treatment intervention attained its potency mainly via Forskolin-ACs/cAMP-mediated modulation of cardiac and inflammatory responses, coupled with Amlexanox inhibition of GRK5 mediated maladaptive cascades. Taken together, our findings highlight the Amlexanox and Forskolin combination as a potential therapeutic intervention for preventing the occurrence of pathological cardiac hypertrophy during chronic stress.

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