scholarly journals Current Status and Potential Therapeutic Strategies for Using Non-coding RNA to Treat Diabetic Cardiomyopathy

2021 ◽  
Vol 11 ◽  
Author(s):  
Amit K. Rai ◽  
Brooke Lee ◽  
Ramesh Gomez ◽  
Deepu Rajendran ◽  
Mahmood Khan ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Systolic Dysfunction ◽  
Therapeutic Strategies ◽  
Current Status ◽  
Circular Rnas ◽  
Diabetic Patients ◽  
Mortality And Morbidity ◽  
Micro Rnas ◽  
Non Coding Rnas

Diabetic cardiomyopathy (DMCM) is the leading cause of mortality and morbidity among diabetic patients. DMCM is characterized by an increase in oxidative stress with systemic inflammation that leads to cardiac fibrosis, ultimately causing diastolic and systolic dysfunction. Even though DMCM pathophysiology is well studied, the approach to limit this condition is not met with success. This highlights the need for more knowledge of underlying mechanisms and innovative therapies. In this regard, emerging evidence suggests a potential role of non-coding RNAs (ncRNAs), including micro-RNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) as novel diagnostics, mechanisms, and therapeutics in the context of DMCM. However, our understanding of ncRNAs’ role in diabetic heart disease is still in its infancy. This review provides a comprehensive update on pre-clinical and clinical studies that might develop therapeutic strategies to limit/prevent DMCM.

scholarly journals The Role of Non-Coding RNAs in Breast Cancer Drug Resistance

2021 ◽  
Vol 11 ◽  
Author(s):  
Jin-hai Tian ◽  
Shi-hai Liu ◽  
Chuan-yang Yu ◽  
Li-gang Wu ◽  
Li-bin Wang
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Tumor Development ◽  
Therapy Resistance ◽  
Resistance Mechanisms ◽  
Cancer Drug ◽  
Circular Rnas ◽  
Mortality And Morbidity ◽  
Micro Rnas ◽  
Non Coding Rnas

Breast cancer (BC) is one of the commonly occurring malignancies in females worldwide. Despite significant advances in therapeutics, the mortality and morbidity of BC still lead to low survival and poor prognosis due to the drug resistance. There are certain chemotherapeutic, endocrine, and target medicines often used for BC patients, including anthracyclines, taxanes, docetaxel, cisplatin, and fluorouracil. The drug resistance mechanisms of these medicines are complicated and have not been fully elucidated. It was reported that non-coding RNAs (ncRNAs), such as micro RNAs (miRNA), long-chain non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) performed key roles in regulating tumor development and mediating therapy resistance. However, the mechanism of these ncRNAs in BC chemotherapeutic, endocrine, and targeted drug resistance was different. This review aims to reveal the mechanism and potential functions of ncRNAs in BC drug resistance and to highlight the ncRNAs as a novel target for achieving improved treatment outcomes for BC patients.

Diabetic Cardiomyopathy: From Mechanism to Management in a Nutshell

2020 ◽  
Vol 20 ◽  
Author(s):  
Shahzad Khan ◽  
Syed S. Ahmad ◽  
Mohammad A. Kamal
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Immune Modulation ◽  
Cell Injury ◽  
Interstitial Fibrosis ◽  
Systolic Dysfunction ◽  
Therapeutic Strategies ◽  
Cardiac Cell ◽  
Clinical Heart Failure ◽  
Artery Disease ◽  
Apoptosis And Necrosis

: Diabetic cardiomyopathy (DCM) is a significant complication of diabetes mellitus characterized by gradual failing heart with detrimental cardiac remodellings such as fibrosis and diastolic and systolic dysfunction, which is not directly attributable to coronary artery disease. Insulin resistance and resulting hyperglycemia is the main trigger involved in the initiation of diabetic cardiomyopathy. There is a constellation of many pathophysiological events such as lipotoxicity, oxidative stress, inflammation, inappropriate activation of the renin-angiotensin-aldosterone system, dysfunctional immune modulation promoting increased rate of cardiac cell injury, apoptosis, and necrosis which ultimately culminates into interstitial fibrosis, cardiac stiffness, diastolic dysfunction initially and later systolic dysfunction too. These events finally lead to clinical heart failure of DCM. Herein, we have briefly discussed the pathophysiology of DCM. We have also briefly mentioned potential therapeutic strategies currently used for DCM.

scholarly journals The Impact of Mutant p53 in the Non-Coding RNA World

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 472
Author(s):  
Silvia Di Agostino
Keyword(s):  
Tumor Suppressor ◽  
Human Cancer ◽  
Rna World ◽  
Circular Rnas ◽  
Mutant P53 ◽  
Suppressor Activity ◽  
Protein Coding ◽  
Micro Rnas ◽  
Non Coding Rnas ◽  
The Impact

Long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), micro RNAs (miRNAs), and extracellular RNAs (exRNAs) are new groups of RNAs with regulation activities that have low or no protein-coding ability. Emerging evidence suggests that deregulated expression of these non-coding RNAs is associated with the induction and progression of diverse tumors throughout epigenetic, transcriptional, and post-transcriptional modifications. A consistent number of non-coding RNAs (ncRNAs) has been shown to be regulated by p53, the most important tumor suppressor of the cells frequently mutated in human cancer. It has been shown that some mutant p53 proteins are associated with the loss of tumor suppressor activity and the acquisition of new oncogenic functions named gain-of-function activities. In this review, we highlight recent lines of evidence suggesting that mutant p53 is involved in the expression of specific ncRNAs to gain oncogenic functions through the creation of a complex network of pathways that influence each other.

scholarly journals Histone Deacetylases in the Pathogenesis of Diabetic Cardiomyopathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiangyu Ke ◽  
Zhirui Lin ◽  
Zebing Ye ◽  
Meifang Leng ◽  
Bo Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Diabetic Cardiomyopathy ◽  
Histone Deacetylases ◽  
Cardiac Fibrosis ◽  
Metabolic Diseases ◽  
Therapeutic Strategies ◽  
Global Burden ◽  
Comprehensive Understanding ◽  
Cellular Processes

The global burden of diabetes mellitus and its complications are currently increasing. Diabetic cardiomyopathy (DCM) is the main cause of diabetes mellitus associated morbidity and mortality; therefore, a comprehensive understanding of DCM development is required for more effective treatment. A disorder of epigenetic posttranscriptional modification of histones in chromatin has been reported to be associated with the pathology of DCM. Recent studies have implicated that histone deacetylases could regulate cardiovascular and metabolic diseases in cellular processes including cardiac fibrosis, hypertrophy, oxidative stress and inflammation. Therefore in this review, we summarized the roles of histone deacetylases in the pathogenesis of DCM, aiming to provide insights into exploring potential preventative and therapeutic strategies of DCM.

Metformin impairs homing ability and efficacy of mesenchymal stem cells for cardiac repair in streptozotocin-induced diabetic cardiomyopathy in rats

2021 ◽  
Author(s):  
Hania Ibrahim Ammar ◽  
Asmaa Mohammed Shamseldeen ◽  
Heba Samy Shoukry ◽  
Hend Ashour ◽  
Samaa Samir Kamar ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Diabetic Patients ◽  
World Population ◽  
Metformin Treatment ◽  
Poor Survival ◽  
Male Wistar Rats ◽  
Multiple Drugs

Bone marrow derived mesenchymal stem cells (BM-MSCs) have demonstrated potential in treating diabetic cardiomyopathy. However, diabetic patients are on multiple drugs and there is lack of understanding on how transplanted stem cells would respond in presence of such drugs. Metformin is an AMP Kinase (AMPK) activator, the widest used anti-diabetic drug. In this study, we investigated the effect of metformin on the efficacy of stem cell therapy in a diabetic cardiomyopathy animal model using streptozotocin (STZ) in male Wistar rats. To comprehend the effect of metformin on the efficacy of BM-MSCs, we transplanted BM-MSCs (1 million cells/rat) with or without metformin. Our data demonstrate that transplantation of BM-MSCs prevented cardiac fibrosis and promoted angiogenesis in diabetic hearts. However, metformin supplementation downregulated BM-MSCs mediated cardioprotection. Interestingly, both BM-MSCs and metformin treatment individually, improved cardiac function with no synergistic effect of metformin supplementation along with BM-MSCs. Investigating the mechanisms of loss of efficacy of BM-MSCs in the presence of metformin, we found that metformin treatment impairs homing of implanted BM-MSCs in the heart and leads to poor survival of transplanted cells. Furthermore, our data demonstrate that metformin mediated activation of AMPK is responsible for poor homing and survival of BM-MSCs in the diabetic heart. Hence, current study confirms that a conflict arises between metformin and BM-MSCs for treating diabetic cardiomyopathy. Approximately 10% of the world population is diabetic to which metformin is prescribed very commonly. Hence, future cell replacement therapies in combination with AMPK inhibitors may be more effective for diabetic patients.

scholarly journals Evidence for a Specific Diabetic Cardiomyopathy: An Observational Retrospective Echocardiographic Study in 656 Asymptomatic Type 2 Diabetic Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Isabelle Pham ◽  
Emmanuel Cosson ◽  
Minh Tuan Nguyen ◽  
Isabela Banu ◽  
Isabelle Genevois ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Silent Myocardial Ischemia ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Asymptomatic Patients ◽  
Artery Disease ◽  
Type 2 Diabetic

Aim. Our aim was to assess the prevalence of subclinical diabetic cardiomyopathy, occurring among diabetic patients without hypertension or coronary artery disease (CAD).Methods. 656 asymptomatic patients with type 2 diabetes for 14 ± 8 years (359 men, 59.7 ± 8.7 years old, HbA1c 8.7 ± 2.1%) and at least one cardiovascular risk factor had a cardiac echography at rest, a stress cardiac scintigraphy to screen for silent myocardial ischemia (SMI), and, in case of SMI, a coronary angiography to screen for silent CAD.Results. SMI was diagnosed in 206 patients, and 71 of them had CAD. In the 157 patients without hypertension or CAD, left ventricular hypertrophy (LVH: 24.1%) was the most frequent abnormality, followed by left ventricular dilation (8.6%), hypokinesia (5.3%), and systolic dysfunction (3.8%). SMI was independently associated with hypokinesia (odds ratio 14.7 [2.7–81.7],p<0.01) and systolic dysfunction (OR 114.6 [1.7–7907],p<0.01), while HbA1c (OR 1.9 [1.1–3.2],p<0.05) and body mass index (OR 1.6 [1.1–2.4],p<0.05) were associated with systolic dysfunction. LVH was more prevalent among hypertensive patients and hypokinesia in the patients with CAD.Conclusion. In asymptomatic type 2 diabetic patients, diabetic cardiomyopathy is highly prevalent and is predominantly characterized by LVH. SMI, obesity, and poor glycemic control contribute to structural and functional LV abnormalities.

scholarly journals Evidence for human diabetic cardiomyopathy

2021 ◽  
Author(s):  
Raffaele Marfella ◽  
Celestino Sardu ◽  
Gelsomina Mansueto ◽  
Claudio Napoli ◽  
Giuseppe Paolisso
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Epidemiological Data ◽  
Diabetic Patients ◽  
Preclinical Models ◽  
Unique Data ◽  
High Incidence ◽  
Definition Of ◽  
End Stage ◽  
Heart Specimen

AbstractGrowing interest has been accumulated in the definition of worsening effects of diabetes in the cardiovascular system. This is associated with epidemiological data regarding the high incidence of heart failure (HF) in diabetic patients. To investigate the detrimental effects both of hyperglycemia and insulin resistance, a lot of preclinical models were developed. However, the evidence of pathogenic and histological alterations of the so-called diabetic cardiomyopathy (DCM) is still poorly understood in humans. Here, we provide a stringent literature analysis to investigate unique data regarding human DCM. This approach established that lipotoxic-related events might play a central role in the initiation and progression of human DCM. The major limitation in the acquisition of human data is due to the fact of heart specimen availability. Postmortem analysis revealed the end stage of the disease; thus, we need to gain knowledge on the pathogenic events from the early stages until cardiac fibrosis underlying the end-stage HF.

scholarly journals Circular RNAs: Their Role in the Pathogenesis and Orchestration of Breast Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiao He ◽  
Tao Xu ◽  
Weijie Hu ◽  
Yufang Tan ◽  
Dawei Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Target Gene ◽  
Evolutionary Conservation ◽  
Therapeutic Strategies ◽  
Circular Rnas ◽  
Therapeutic Resistance ◽  
Transcriptional Level ◽  
Metastatic Progression ◽  
Single Chain ◽  
Non Coding Rnas

As one of the most frequently occurring malignancies in women, breast cancer (BC) is still an enormous threat to women all over the world. The high mortality rates in BC patients are associated with BC recurrence, metastatic progression to distant organs, and therapeutic resistance. Circular RNAs (circRNAs), belonging to the non-coding RNAs (ncRNAs), are connected end to end to form covalently closed single-chain circular molecules. CircRNAs are widely found in different species and a variety of human cells, with the features of diversity, evolutionary conservation, stability, and specificity. CircRNAs are emerging important participators in multiple diseases, including cardiovascular disease, inflammation, and cancer. Recent studies have shown that circRNAs are involved in BC progress by regulating gene expression at the transcriptional or post-transcriptional level via binding to miRNAs then inhibiting their function, suggesting that circRNAs may be potential targets for early diagnosis, treatment, and prognosis of BC. Herein, in this article, we have reviewed and summarized the current studies about the biogenesis, features, and functions of circRNAs. More importantly, we emphatically elucidate the pivotal functions and mechanisms of circRNAs in BC growth, metastasis, diagnosis, and drug resistance. Deciphering the complex networks, especially the circRNA-miRNA target gene axis, will endow huge potentials in developing therapeutic strategies for combating BC.

scholarly journals Research Progress on Epigenetics of Diabetic Cardiomyopathy in Type 2 Diabetes

2021 ◽  
Vol 9 ◽  
Author(s):  
Jianxin Deng ◽  
Yunxiu Liao ◽  
Jianpin Liu ◽  
Wenjuan Liu ◽  
Dewen Yan
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Research Progress ◽  
Prevention Strategies ◽  
Mortality And Morbidity ◽  
Key Players ◽  
Diastolic Relaxation ◽  
Non Coding Rnas ◽  
Clinical Heart Failure ◽  
Artery Disease

Diabetic cardiomyopathy (DCM) is characterized by diastolic relaxation abnormalities in its initial stages and by clinical heart failure (HF) without dyslipidemia, hypertension, and coronary artery disease in its last stages. DCM contributes to the high mortality and morbidity rates observed in diabetic populations. Diabetes is a polygenic, heritable, and complex condition that is exacerbated by environmental factors. Recent studies have demonstrated that epigenetics directly or indirectly contribute to pathogenesis. While epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs, have been recognized as key players in the pathogenesis of DCM, some of their impacts remain not well understood. Furthering our understanding of the roles played by epigenetics in DCM will provide novel avenues for DCM therapeutics and prevention strategies.

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