scholarly journals MicroRNAs in Valvular Heart Diseases: Biological Regulators, Prognostic Markers and Therapeutical Targets

2021 ◽  
Author(s):  
Francesco Nappi ◽  
Adelaide Iervolino ◽  
Sanjeet Singh Avtaar Singh ◽  
Massimo Chello
Keyword(s):  
Mitral Valve ◽  
Mitral Valve Prolapse ◽  
Heart Diseases ◽  
Osteoblastic Differentiation ◽  
New Drugs ◽  
Expression Vectors ◽  
Chordae Tendineae ◽  
Valvular Heart Diseases

miRNAs have recently attracted investigators' interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors comprise of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions.

scholarly journals MicroRNAs in Valvular Heart Diseases: Biological Regulators, Prognostic Markers and Therapeutical Targets

2021 ◽  
Vol 22 (22) ◽  
pp. 12132
Author(s):  
Francesco Nappi ◽  
Adelaide Iervolino ◽  
Sanjeet Singh Avtaar Singh ◽  
Massimo Chello
Keyword(s):  
Mitral Valve ◽  
Mitral Valve Prolapse ◽  
Heart Diseases ◽  
Osteoblastic Differentiation ◽  
New Drugs ◽  
Expression Vectors ◽  
Chordae Tendineae ◽  
Valvular Heart Diseases

miRNAs have recently attracted investigators’ interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors are comprised of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions.

scholarly journals Effects of MicroRNAs in Valvular Heart Diseases: From Molecular Pathways to Clinical Effects and Therapeutical Strategies

2021 ◽  
Author(s):  
Francesco Nappi ◽  
Adelaide Iervolino ◽  
Sanjeet Singh Avtaar Singh ◽  
Massimo Chello
Keyword(s):  
Mitral Valve ◽  
Mitral Valve Prolapse ◽  
Heart Diseases ◽  
Expression Vectors ◽  
Clinical Effects ◽  
Chordae Tendineae ◽  
Valvular Heart Diseases ◽  
Micro Rnas

Micro-RNAs have been recently investigated in preclinical and clinical research as regulators of valvulopathies pathogenesis, diagnostic biomarkers and therapeutical targets. Evidences from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse, aortic leaflet fusion and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes or different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address mi-RNAs over or under-representation. In this review we discuss the fundamental intracellular homeostatic and cardiogenetic pathways regulated by mi-RNAs leading to defects in mitral and aortic valves, congenital heart diseases and the possible therapeutical strategies targeting them. Mi-RNAs inhibitors comprise antisense oligonucleotides and sponge vectors while mi-RNA mimics, mi-RNA expression vectors and small molecules are possible practical strategies to increase their activity. Advantages and technical limitations, including instability and complex pharmacokinetics are also presented. Novel strategies, such as nanoparticles and liposomes, are conclusively described to improve knowledge on these molecules delivery and establish future personalized treatment directions.

scholarly journals Straight back syndrome as a clue to diagnosing asymptomatic congenital valvular heart disease and limiting the risk of weightlifting

2021 ◽  
Vol 121 (2) ◽  
pp. 135-140
Author(s):  
William A. Schiavone
Keyword(s):  
Mitral Valve ◽  
Heart Diseases ◽  
Severe Aortic Stenosis ◽  
Aortic Disease ◽  
Chordae Tendineae ◽  
Blood Pressure Elevation ◽  
The Public ◽  
Valvular Heart Diseases ◽  
Patients At Risk ◽  
The Common

Abstract Although both are initially asymptomatic, mitral valve prolapse/myxomatous mitral valve disease (MVP/MMVD) and bicuspid aortic valve (BAV), with its associated aortic disease, are currently the two most common congenital valvular heart diseases. Severe mitral regurgitation due to rupture of chordae tendineae (CTR) prompts surgery for MVP/MMVD. Surgery for BAV is performed for severe aortic stenosis and/or regurgitation, often with management of root and/or ascending aortic enlargement. There may be an association between straight back syndrome (SBS) and MVP/MMVD, which may be a key to earlier diagnosis. Other associations link weightlifting with ascending aortic enlargement and with CTR, where the common theme is blood pressure elevation. As the number of people with fitness center memberships continues to increase, this potentially exposes more undiagnosed individuals with MVP/MMVD or BAV to risk from weightlifting. Challenges include making the public aware of this risk and preparing the osteopathic physician to recognize patients at risk through a structured history-taking and targeted cardiovascular examination.

CORONARY ARTERY LESIONS IN PATIENTS OVER 50 YEAR OLD WITH VALVULAR HEART DISEASES INDICATED FOR VALVE SURGERY

2016 ◽  
pp. 20-24
Author(s):  
Bang Giap Vo ◽  
Anh Binh Ho ◽  
Van Minh Huynh
Keyword(s):  
Coronary Artery ◽  
Mitral Valve ◽  
Heart Valve ◽  
Right Coronary Artery ◽  
Heart Diseases ◽  
Heart Valve Diseases ◽  
Coronary Artery Lesions ◽  
Circumflex Coronary Artery ◽  
Valvular Heart Diseases ◽  
Valve Diseases

Objectives: To investigate the features of coronary artery lesions in patients over 50 with heart valve diseases and to find out the relationship between the levels of coronary artery lesions and heart valve diseases. Results: In patients over 50 year old with heart valve diseases, the rate of significant coronary artery lesions is 55.5%. In which, significant lesions in the group of both mitral and aorta valve diseases is 44.19%, only mitral valve diseases is of 70%, only aortic valve diseases is of 51.85%. There is a relationship between the severity of mitral valve diseases and right coronary artery lesions (OR 3.74: 1.64 to 8.5, p = 0.0017) and circumflex coronary artery lesions (OR 2.59: 1.16 to 5.75, p = 0.0192). The severity of heart valve lesions in significant coronary artery lesions group is higher than insignificant coronary artery lesions group or normal group. Conclusion: Coronary artery lesions is common in patients > 50 years old with heart valve diseases, there is a relationship between the severity of mitral valve diseases and and right coronary artery lesions and circumflex coronary artery lesions. Key words: coronary artery lesions, mitral valvediseases

Natural Anti-inflammatory compounds as Drug candidates in Alzheimer’s disease

2020 ◽  
Vol 27 ◽  
Author(s):  
Reyaz Hassan Mir ◽  
Abdul Jalil Shah ◽  
Roohi Mohi-ud-din ◽  
Faheem Hyder Potoo ◽  
Mohd. Akbar Dar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Protective Action ◽  
New Drugs ◽  
Huperzine A ◽  
Brain Disorder ◽  
Anti Inflammatory

: Alzheimer's disease (AD) is a chronic neurodegenerative brain disorder characterized by memory impairment, dementia, oxidative stress in elderly people. Currently, only a few drugs are available in the market with various adverse effects. So to develop new drugs with protective action against the disease, research is turning to the identification of plant products as a remedy. Natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Phytochemicals including Curcumin, Resveratrol, Quercetin, Huperzine-A, Rosmarinic acid, genistein, obovatol, and Oxyresvertarol were reported molecules for the treatment of AD. Several alkaloids such as galantamine, oridonin, glaucocalyxin B, tetrandrine, berberine, anatabine have been shown anti-inflammatory effects in AD models in vitro as well as in-vivo. In conclusion, natural products from plants represent interesting candidates for the treatment of AD. This review highlights the potential of specific compounds from natural products along with their synthetic derivatives to counteract AD in the CNS.

Antimicrobial peptides for the treatment of pulmonary tuberculosis, allies or foes?

2018 ◽  
Vol 24 (10) ◽  
pp. 1138-1147
Author(s):  
Bruno Rivas-Santiago ◽  
Flor Torres-Juarez
Keyword(s):  
Pulmonary Tuberculosis ◽  
Antimicrobial Peptides ◽  
Experimental Models ◽  
New Drugs ◽  
World Health ◽  
Public Health Issue ◽  
Health Organization ◽  
Drug Resistant Strains

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of World Health Organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the Antimicrobial Peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects.

The Role of nitro (NO2-), chloro (Cl), and fluoro (F) Substitution in the Design of Antileishmanial and Antichagasic Compounds

2020 ◽  
Vol 21 ◽  
Author(s):  
Boniface Pone ◽  
Ferreira Igne Elizabeth
Keyword(s):  
Chagas Disease ◽  
Mammalian Cells ◽  
Neglected Tropical Diseases ◽  
New Drugs ◽  
Pharmacokinetic Studies ◽  
Scientific Publications ◽  
Antitrypanosomal Activity ◽  
Chemical Groups

: Neglected tropical diseases (NTDs) are responsible for over 500,000 deaths annually and are characterized by multiple disabilities. Leishmaniasis and Chagas disease are among the most severe NTDs, and are caused by the Leishmania sp, and Trypanosoma cruzi, respectively. Glucantime, pentamidine and miltefosine are commonly used to treat leishmaniasis, whereas nifurtimox, benznidazole are current treatments for Chagas disease. However, these treatments are associated with drug resistance, and severe side effects. Hence, the development of synthetic products, especially those containing N02, F, or Cl, which chemical groups are known to improve the biological activity. The present work summarizes the information on the antileishmanial and antitrypanosomal activity of nitro-, chloro-, and fluoro-synthetic derivatives. Scientific publications referring to halogenated derivatives in relation to antileishmanial and antitrypanosomal activities were hand searched in databases such as SciFinder, Wiley, Science Direct, PubMed, ACS, Springer, Scielo, and so on. According to the literature information, more than 90 compounds were predicted as lead molecules with reference to their IC50/EC50 values in in vitro studies. It is worth to mention that only active compounds with known cytotoxic effects against mammalian cells were considered in the present study. The observed activity was attributed to the presence of nitro-, fluoro- and chloro-groups in the compound backbone. All in all, nitro and h0alogenated derivatives are active antileishmanial and antitrypanosomal compounds and can serve as baseline for the development of new drugs against leishmaniasis and Chagas disease. However, efforts on in vitro and in vivo toxicity studies of the active synthetic compounds is still needed. Pharmacokinetic studies, and the mechanism of action of the promising compounds need to be explored. The use of new catalysts and chemical transformation can afford unexplored halogenated compounds with improved antileishmanial and antitrypanosomal activity.

scholarly journals Osteoprotective Effects of Loganic Acid on Osteoblastic and Osteoclastic Cells and Osteoporosis-Induced Mice

2020 ◽  
Vol 22 (1) ◽  
pp. 233
Author(s):  
Eunkuk Park ◽  
Chang Gun Lee ◽  
Eunguk Lim ◽  
Seokjin Hwang ◽  
Seung Hee Yun ◽  
...  
Keyword(s):  
Osteoclast Differentiation ◽  
Osteoblastic Differentiation ◽  
Common Disease ◽  
Root Extract ◽  
Mouse Bone Marrow ◽  
Mineral Density ◽  
Bone Mineral Density Loss ◽  
In Vivo Experiments

Osteoporosis is a common disease caused by an imbalance of processes between bone resorption by osteoclasts and bone formation by osteoblasts in postmenopausal women. The roots of Gentiana lutea L. (GL) are reported to have beneficial effects on various human diseases related to liver functions and gastrointestinal motility, as well as on arthritis. Here, we fractionated and isolated bioactive constituent(s) responsible for anti-osteoporotic effects of GL root extract. A single phytochemical compound, loganic acid, was identified as a candidate osteoprotective agent. Its anti-osteoporotic effects were examined in vitro and in vivo. Treatment with loganic acid significantly increased osteoblastic differentiation in preosteoblast MC3T3-E1 cells by promoting alkaline phosphatase activity and increasing mRNA expression levels of bone metabolic markers such as Alpl, Bglap, and Sp7. However, loganic acid inhibited osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. For in vivo experiments, the effect of loganic acid on ovariectomized (OVX) mice was examined for 12 weeks. Loganic acid prevented OVX-induced bone mineral density loss and improved bone structural properties in osteoporotic model mice. These results suggest that loganic acid may be a potential therapeutic candidate for treatment of osteoporosis.

scholarly journals MBRS-48. IDENTIFICATION OF NOVEL THERAPEUTIC APPROACHES FOR MYC-DRIVEN MEDULLOBLASTOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii406-iii406
Author(s):  
Kübra Taban ◽  
David Pauck ◽  
Mara Maue ◽  
Viktoria Marquardt ◽  
Hua Yu ◽  
...  
Keyword(s):  
New Drugs ◽  
Current Therapy ◽  
Cancer Drug ◽  
Mrna Levels ◽  
Cell Models ◽  
Therapeutic Approaches ◽  
Group 3 ◽  
Novel Therapeutic

Abstract Medulloblastoma (MB) is the most common malignant brain tumor in children and is frequently metastatic at diagnosis. Treatment with surgery, radiation and multi-agent chemotherapy may leave survivors of these brain tumors with long-term deficits as a consequence. One of the four consensus molecular subgroups of MB is the MYC-driven group 3 MB, which is the most malignant type and has a poor prognosis under current therapy. Thus, it is important to discover more effective targeted therapeutic approaches. We conducted a high-throughput drug screening to identify novel compounds showing efficiency in group 3 MB using both clinically established inhibitors (n=196) and clinically-applicable compounds (n=464). More than 20 compounds demonstrated a significantly higher anti-tumoral effect in MYChigh (n=7) compared to MYClow (n=4) MB cell models. Among these compounds, Navitoclax and Clofarabine showed the strongest effect in inducing cell cycle arrest and apoptosis in MYChigh MB models. Furthermore, we show that Navitoclax, an orally bioavailable and blood-brain barrier passing anti-cancer drug, inhibits specifically Bcl-xL proteins. In line, we found a significant correlation between BCL-xL and MYC mRNA levels in 763 primary MB patient samples (Data source: “R2 https://hgserver1.amc.nl”). In addition, Navitoclax and Clofarabine have been tested in cells obtained from MB patient-derived-xenografts, which confirmed their specific efficacy in MYChigh versus MYClow MB. In summary, our approach has identified promising new drugs that significantly reduce cell viability in MYChigh compared to MYClow MB cell models. Our findings point to novel therapeutic vulnerabilities for MB that need to be further validated in vitro and in vivo.

Sign in / Sign up

Export Citation Format

Share Document