Sara Azhdari

Abstract Atherosclerosis is a complex and long‐lasting disorder characterized by chronic inflammation of arteries that leads to the initiation and progression of lipid‐rich plaques, in which monocytes/macrophages play the central role in endothelial inflammation and taking up these lipids. Circulating monocytes can adopt a long‐term proinflammatory phenotype leading to their atherogenic activities. During atherogenic condition, inflammatory monocytes adhere to the surface of the activated endothelial cells and then transmigrate across the endothelial monolayer into the intima, where they proliferate and differentiate into macrophages and take up the lipoproteins, forming foam cells that derive atherosclerosis progression. Therefore, modulating the atherogenic activities of inflammatory monocytes can provide a valuable therapeutic approach for atherosclerosis prevention and treatment. Curcumin is a naturally occurring polyphenolic compound with numerous pharmacological activities and shows protective effects against atherosclerosis; however, underlying mechanisms are not clearly known yet. In the present review, on the basis of a growing body of evidence, we show that curcumin can exert antiatherosclerotic effect through inhibiting the atherogenic properties of monocytes, including inflammatory cytokine production, adhesion, and transendothelial migration, as well as intracellular cholesterol accumulation.

Background and purpose: Duchenne muscular dystrophy (DMD), a lethal X-linked recessive muscle dystrophy, is resulted in by different mutations including mostly frame-shifting gross deletions and duplications and rarely point mutations in DMD gene. Increasing weakness, progressive loss of skeletal muscle mass, and later-onset cardiomyopathy are serious clinical symptoms which ultimately lead to cardiac and respiratory failure, and premature death in DMD patients by age of 30. DMD is a prevalent genetic disorder and considers as an interesting target for gene therapy approaches. Massive gene size and existence of enormous number of muscle tissues are terrific hindrance against DMD treatments, nevertheless enormous efforts have been executed in the fields of gene replacement therapy, gene editing strategies, cell-based treatments, and small drug medications. Hot spot exons skipping and suppression of premature stop codons are the most interesting treatments for restoring functional DMD product, dystrophin protein. Clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated protein (Cas) systems are the most interesting genome editing platforms that are able to restore open reading frame of DMD gene. CRISPR-Cas9 and CRISPR-Cpf1 are two main genome editing sub-types that successfully used in mdx mice.Conclusions: This review aims to present recent progresses and future prospects over three main DMD therapeutic subgroups including gene therapy, cell therapy, and pharmacological therapy.

DNA damage usually happens in all cell types, which may originate from endogenous sources (i.e., DNA replication errors) or be emanated from radiations or chemicals. These damages range from changes in few nucleotides to significant structural abnormalities on chromosomes and, if not repaired, could disturb the cellular homeostasis or cause cell death. As the most significant response to DNA damage, DNA repair provides biological pathways by which DNA damages are corrected and returned into their natural circumstance. However, an aberration in the DNA repair mechanisms may result in genomic and chromosomal instability and the accumulation of mutations. The activation of oncogenes and/or inactivation of tumor suppressor genes is a serious consequence of genomic and chromosomal instability and may bring the cells into a cancerous phenotype. Therefore, genomic and chromosomal instability is usually considered a crucial factor in carcinogenesis and an important hallmark of various human malignancies. In the present study, we review our current understanding of the most updated mechanisms underlying genomic instability in cancer and discuss the potential promises of these mechanisms in finding new targets for the treatment of cancer.