Mini Reviews in Medicinal Chemistry - Volume 15, Issue 6, 2015

It is estimated that a typical myocardial infarction results in the loss of approximately one billion functional cardiomyocytes, which are replaced by a non-contractile fibrous scar, eventually leading to heart failure. The currently available surgical, drug, and device-based therapies cannot reverse the loss of functional myocardium, which is the fundamental cause of the problem. As a result of this lack of an available medical solution, heart failure has evolved into a global epidemic. Therefore, the development of regenerative therapeutic strategies to halt the progression of ischemic heart disease to advanced heart failure has become one of the most urgent medical needs of this century. This review first addresses the extremely limited endogenous regenerative capacity of the mammalian heart, and the benefits and limitations of stem cell-based therapies for cardiac repair. Then it discusses the known roles of microRNAs after cardiac injury and the possibility of employing microRNAs to enhance cardiac regeneration.

MicroRNAs are a class of non-coding RNA molecules that have been reported to play a crucial role in cell signaling via post-transcriptional regulation of gene expression. There is increasing evidence showing that this class of RNA is involved in the pathogenesis of cardiovascuular diseases, including atherosclerosis. More recently, it has been demonstrated that microRNAs can function to protect against the development of atherosclerosis. The primary goal of this review is to discuss the discovery, mechanism, and therapeutic use of microRNA molecules as atheroprotective agents.

Hepatocellular carcinoma is a leading unnatural death worldwide, and it causes second most common cancer related death. Hepatocellular carcinoma development is distinct from other types of cancer, which is usually based on hepatic cirrhosis resulted from various etiologies including viral hepatitis, non-alcoholic liver diseases and alcohol abuse. MicroRNAs (miRNAs) are a group of small, non-coding sequences with approximate 20∼ bp in length, which post-transcriptionally regulates target genes to control multiple biological activities. Recent studies have indicated that miRNAs contribute to hepatocellular carcinoma, indicating that targeting miRNAs might be a novel therapeutic strategy for the management of hepatocellular carcinoma. In this review, we summarized recent advances in the role of miRNAs in hepatocellular carcinoma, and also discussed the potential therapeutic and prognostic values of miRNAs in hepatocellular carcinoma.

MicroRNAs are short noncoding 18-25 nucleotide long RNA which bind and inhibit mRNA. Currently, there are over 1000 known human microRNAs, and microRNAs control over 50% of mammalian protein coding genes. MicroRNAs can be overexpressed or repressed in different diseases and inhibition or replacement of microRNAs is a promising area of study for therapeutics. Here we review the current knowledge of microRNA therapy, and discuss ways in which they can be utilized. We also discuss different methods of delivery of miRNA, and current clinical trials of microRNA-based therapies for disease. Finally we discuss the current limitations in the field, and how these limitations are being overcome.

MicroRNAs (miRNAs) are a novel class of endogenous, short, non-coding, posttranscriptional RNAs, which play important roles in regulating lots of important biological functions. Evidences show that altered expression of miRNAs are involved in pathological hypertrophy and cardiac failure, making it possible to target miRNAs as a novel therapy. In this review, we focus on very recent progresses in the regulation of miRNAs in pathological hypertrophy and cardiac failure. In addition, we also discuss the potential of using miRNAs as a new therapy for pathological hypertrophy and cardiac failure.

Discovery of novel drugs that are able to prevent angiogenesis is a fast growing branch of cancer research. Current approaches to cancer chemotherapy include the use of alkylating agents, antimetabolites, antitumor antibiotics, platinum analogs and drugs derived from natural compounds. However, most of the currently used chemotherapeutic drugs have adverse side effects on normal healthy cells. In addition to the classical targets of cancer chemotherapy, prevention of angiogenesis through the regulation of indigenous angiogenic factors is a leading approach of developing selective novel anticancer drugs. Because of their low toxicity, there is increasing interest in exploring specific dietary phytochemicals as possible antiangiogenic agents. In this mini-review, selected flavonoids (e.g., apigenin, luteolin, quercetin and epigallocatechin-3- gallate, which are a group of plant polyphenols) that are able to regulate angiogenesis in in vitro and in vivo systems are discussed in the light of their potential to be exploited as novel anticancer drugs.

Telomeric diseases are a group of rare progeroid genetic syndromes, presenting premature aging phenotypes, characterized for defects on telomere maintenance. In humans, telomeres are heterochromatic structures consisting of long TTAGGG repeats located at the chromosomal ends, which shorten progressively after each DNA replication because of the ‘end replication problem’. Critically short telomeres activate a DNA damage response that leads to the arrest of the cell cycle and resulting in cellular senescence or apoptosis. Furthermore, excessively short telomeres are prone to create telomeric fusions, causing genomic instability and malignant transformation. In order to counteract this process, there are two enzymatic complexes, the telomerase complex, with the capacity to elongate telomeres; and the shelterin complex, which protects them from being recognized as DNA breaks. Over the last few decades, several studies have confirmed that critically short telomeres and defects in telomere-associated enzymatic complexes are involved in the development of a group of rare human genetic diseases, with the accumulation of excessive telomere attrition as the underlying cause of these pathologies. Despite the severity of these disorders, there is no curative treatment for any of them. In light of this, this review summarizes the most important defective telomere diseases, their current management, and it presents possible therapeutic strategies based on nanotechnology which may open up new possibilities for their treatment.

Viruses cause many diseases in humans from the rather innocent common cold to more serious or chronic, life-threatening infections. The long-term sideeffects, sometimes low effectiveness of standard pharmacotherapy and the emergence of drug resistance require a search for new alternative or complementary antiviral therapeutic approaches. One new approach to inactivate microorganisms is photodynamic antimicrobial chemotherapy (PACT). PACT has evolved as a potential method to inactivate viruses. The great challenge for PACT is to develop a methodology enabling the effective inactivation of viruses while leaving the host cells as untouched as possible. This review aims to provide some main directions of antiviral PACT, taking into account different photosensitizers, which have been widely investigated as potential antiviral agents. In addition, several aspects concerning PACT as a tool to assure viral inactivation in human blood products will be addressed.