scholarly journals Harnessing the Therapeutic Potential of Decoys in Non-Atherosclerotic Cardiovascular Diseases: State of the Art

2021 ◽  
Vol 8 (9) ◽  
pp. 103
Author(s):  
Maryam Mahjoubin-Tehran ◽  
Stephen L. Atkin ◽  
Evgeny E. Bezsonov ◽  
Tannaz Jamialahmadi ◽  
Amirhossein Sahebkar

Cardiovascular disease (CVD) is the main cause of global death, highlighting the fact that conventional therapeutic approaches for the treatment of CVD patients are insufficient, and there is a need to develop new therapeutic approaches. In recent years, decoy technology, decoy oligodeoxynucleotides (ODN), and decoy peptides show promising results for the future treatment of CVDs. Decoy ODN inhibits transcription by binding to the transcriptional factor, while decoy peptide neutralizes receptors by binding to the ligands. This review focused on studies that have investigated the effects of decoy ODN and decoy peptides on non-atherosclerotic CVD.

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Qingming Ma ◽  
Haixia Ma ◽  
Fenglan Xu ◽  
Xinyu Wang ◽  
Wentao Sun

AbstractDue to extremely severe morbidity and mortality worldwide, it is worth achieving a more in-depth and comprehensive understanding of cardiovascular diseases. Tremendous effort has been made to replicate the cardiovascular system and investigate the pathogenesis, diagnosis and treatment of cardiovascular diseases. Microfluidics can be used as a versatile primary strategy to achieve a holistic picture of cardiovascular disease. Here, a brief review of the application of microfluidics in comprehensive cardiovascular disease research is presented, with specific discussions of the characteristics of microfluidics for investigating cardiovascular diseases integrally, including the study of pathogenetic mechanisms, the development of accurate diagnostic methods and the establishment of therapeutic treatments. Investigations of critical pathogenetic mechanisms for typical cardiovascular diseases by microfluidic-based organ-on-a-chip are categorized and reviewed, followed by a detailed summary of microfluidic-based accurate diagnostic methods. Microfluidic-assisted cardiovascular drug evaluation and screening as well as the fabrication of novel delivery vehicles are also reviewed. Finally, the challenges with and outlook on further advancing the use of microfluidics technology in cardiovascular disease research are highlighted and discussed.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1802
Author(s):  
Elena Munoz-Perez ◽  
Ainhoa Gonzalez-Pujana ◽  
Manoli Igartua ◽  
Edorta Santos-Vizcaino ◽  
Rosa Maria Hernandez

Considering the high prevalence and the complex pharmacological management of immune-mediated inflammatory diseases (IMIDs), the search for new therapeutic approaches for their treatment is vital. Although the immunomodulatory and anti-inflammatory effects of mesenchymal stromal cells (MSCs) have been extensively studied as a potential therapy in this field, direct MSC implantation presents some limitations that could slow down the clinical translation. Since the beneficial effects of MSCs have been mainly attributed to their ability to secrete a plethora of bioactive factors, their secretome has been proposed as a new and promising pathway for the treatment of IMIDs. Formed from soluble factors and extracellular vesicles (EVs), the MSC-derived secretome has been proven to elicit immunomodulatory effects that control the inflammatory processes that occur in IMIDs. This article aims to review the available knowledge on the MSC secretome, evaluating the advances in this field in terms of its composition, production and application, as well as analyzing the pending challenges in the field. Moreover, the latest research involving secretome administration in IMIDs is discussed to provide an updated state-of-the-art for this field. Finally, novel secretome delivery alternatives are reviewed, paying special attention to hydrogel encapsulation as one of the most convenient and promising strategies.


ESC CardioMed ◽  
2018 ◽  
pp. 1090-1093
Author(s):  
Giuseppe Rosano

The physiological functioning of the gut is central for the pharmacokinetics of orally administered cardiovascular drugs and alteration of the gut homeostasis may have relevant repercussions on the effect of these drugs. The gut microbiome may affect the absorption and metabolism of nutrients favouring the development of obesity and diabetes. Furthermore, alterations in intestinal barrier permeability lead to the penetration of bacteria and bacterial wall products into the circulation and may contribute to the progression of atherosclerosis and worsening of heart failure. Despite the suggestions of the possible interaction between the gut and the cardiovascular system and of stimulating novel mechanisms for disease progression that may open to new therapeutic approaches, the available evidence must be considered preliminary.


2015 ◽  
Vol 4 ◽  
pp. 6-21 ◽  
Author(s):  
Ana Sastre ◽  
Nuria E Campillo ◽  
Carmen Gil ◽  
Ana Martinez

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 236-236
Author(s):  
Anja Naumann ◽  
Yongchan Kim ◽  
Christoph Königs ◽  
David W Scott

Abstract The development of inhibitory antibodies (inhibitors) against FVIII is the most critical complication in the treatment of hemophilia A patients as hemostasis can no longer be reestablished by FVIII replacement therapy. Immune tolerance induction by frequent FVIII infusions is demanding, costly and not successful in all treated patients leading to an urgent need for the development of new therapeutic approaches for the prevention or treatment of FVIII inhibitors. Regulatory T cells (Tregs) are important for the maintenance of tolerance and have a high therapeutic potential in the context of autoimmune or inflammatory immune disorders. As Tregs are polyclonal, treatment with Treg pools comprises the risk of a general immunosuppression. Thus, the establishment of antigen-specific Tregs could be of great benefit for a broad range of patients, including inhibitor positive hemophilia A patients. To create such specific Tregs, a FVIII-specific scFv isolated out of a synthetic phage display library was used to generate a second generation chimeric antigen receptor (CAR). To verify the specificity of the CAR for FVIII and the functionality of the recombined cytoplasmic domain (CD28 and CD3zeta), naïve CD4 T cells were retrovirally transduced with the generated CAR construct and a proliferation assay was conducted in the presence of plate-bound or soluble FVIII, as well as soluble FVIII presented by autologous irradiated PBMCs. Proliferation of transduced cells was more effective when FVIII was presented plate-bound or by PBMCs. In a therapeutically-relevant setting, this would be very promising, as transduced T cells should not be activated by soluble FVIII in the bloodstream but rather by FVIII presented on antigen-presenting cells in lymphatic organs. Next, functionality of the CAR construct in Tregs was addressed. Transduced Tregs showed extracellular expression of the scFv and could be stimulated MHC-independently with FVIII. Such stimulated cells showed increased expression of Treg activation markers LAP and GARP. Thus, by using the generated CAR for transduction of Tregs, it was possible to create FVIII-specific Tregs that can be stimulated MHC-independently, opening new possibilities for therapeutic approaches in hemophilia A patients with FVIII inhibitors. Disclosures No relevant conflicts of interest to declare.


2017 ◽  
Vol 24 (1) ◽  
pp. R1-R12 ◽  
Author(s):  
Giovanni Vitale ◽  
Germano Gaudenzi ◽  
Luisa Circelli ◽  
Marco F Manzoni ◽  
Andrea Bassi ◽  
...  

Medullary thyroid carcinoma is a neuroendocrine tumour originating from parafollicular C cells accounting for 5–10% of thyroid cancers. Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid carcinoma. These drugs increase progression-free survival; however, they are often poorly tolerated and most treatment responses are transient. Animal models are indispensable tools for investigating the pathogenesis, mechanisms for tumour invasion and metastasis and new therapeutic approaches for cancer. Unfortunately, only few models are available for medullary thyroid carcinoma. This review provides an overview of the state of the art of animal models in medullary thyroid carcinoma and highlights future developments in this field, with the aim of addressing salient features and clinical relevance.


Author(s):  
Prem S. Singh ◽  
K. S. Zafar ◽  
Manoj Kumar ◽  
Sudhir K. Yadav

Background: Incidence and prevalence of diabetes is on surge day by day and increased longevity of diabetic patients put them at higher risk of chronic complications of hyperglycemia. Of these complications, atherosclerotic cardiovascular diseases (CVD) are of utmost importance and atherosclerotic cardiovascular diseases are the major cause of premature mortality in patients with type 2 diabetes as well. Regional variation of risk factors and sociocultural diversity of Indian population create a significant difference in atherosclerotic risk among the diabetic population across the country. There is a significant gap in the knowledge of CVD epidemiology and associated risk factors among the Indian population especially among the rural population. The objective of this study was to assess cardiovascular risk among diabetic patients of rural central India.Methods: The present cross-sectional study included 160 diabetic patients (78 males and 82 females) aged 35–75 years from the villages of district Etawah of UP, Central India. Sex-specific Framingham general cardiovascular risk prediction equations were used to calculate the 10years risk for cardiovascular disease. The probable risk factors were determined by cross-tabulation of cardiometabolic parameters with the 10-year cardiovascular risk level.Results: Males were found to be at higher risk of developing CVD in the future as compared to females with a discernible accumulation of adverse cardiovascular risk factors among them. 38.75% patients were at high risk, 37.50% at moderate risk and 23.75% at low risk for developing CVD in the next 10 years. Systolic blood pressure, total cholesterol, triglyceride and smoking contributed significantly to high degree of cardiovascular risk. Presence of cardiovascular risk factors among diabetic patients at diagnosis accentuates the need of intensive management of cardiovascular complications taking into consideration the traditional dietary pattern of the rural population.Conclusions: Both diabetes and CVD have common genetic and environmental antecedents. Furthermore, insulin resistance preceding long before the diagnosis of diabetes enhances atherogenic risk profile and has been delineated as a potential cause for subsequent increased risk of CVD among diabetic patients. There is need of intensive management of cardiovascular risk factors among diabetic individuals. Therefore, there is a need of a comprehensive study design which includes various factors (biological, sociodemographic and genetic) which directly or indirectly influence the disease incidence especially in a country (India) with diverse ethnic population.


2021 ◽  
Vol 14 ◽  
Author(s):  
Shengyu Zhang ◽  
Lingli Li ◽  
Mingying Deng ◽  
Yanan Wang ◽  
AiZong Shen ◽  
...  

Background: Cardiovascular disease is the leading cause of death in both developed and developing countries. Di'ao Xinxuekang (DAXXK) is a pure Chinese medicine herbal preparation refined from dioscin extracted from the roots of Dioscorea panthaica Prain et Burk and Diosorea nipponica Makino. Objective: To evaluate the application of DAXXK in Cardiovascular disease. Methods: : We searched and summarized all the studies on DAXXK and Cardiovascular disease in pumend, Google, and CNKI. Results: Modern pharmacological studies have shown that DAXXK has pharmacological effects such as dilating blood vessels, lowering blood pressure and cardiac load, improving hemodynamics, lowering blood lipids and anti-platelet aggregation, and is widely used for the therapy of various kinds of cardiovascular diseases, including hypertension, atherosclerosis, coronary heart disease (CHD), angina pectoris (AP) and myocardial infarction. We provide an overview of the clinical efficacy, molecular mechanisms, safety and therapeutic potential of DAXXK in the treatment of cardiovascular disease, aiming to provide clues and evidence for clinical decision-making. Conclusion: DAXXK exerts cardiovascular protection by regulating a variety of cardiovascular disease-related signaling pathways.


2010 ◽  
Vol 2010 ◽  
pp. 1-4 ◽  
Author(s):  
Rosalinda Sorrentino ◽  
Silvana Morello ◽  
Aldo Pinto

Cardiovascular diseases, formerly only attributed to the alterations of the stromal component, are now recognized as immune-based pathologies. Plasmacytoid Dendritic Cells (pDCs) are important immune orchestrators in heart and vessels. They highly produce IFN type I that promote the polarization of T cells towards a Th1 phenotype; however, pDCs can also participate to suppressive networks via the recruitment of T regulatory cells that downmodulate proinflammatory responses. pDCs populate the vessel wall layers during pathological conditions, such as atherosclerosis. It is thus clear that a better identification of pDCs activity in cardiovascular diseases can not only elucidate pathological mechanisms but also lead to new therapeutic approaches.


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