Genomic Instability in Cancer: Molecular Mechanisms and Therapeutic Potentials.

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.

The Role of Non-coding Genome in Cancer-associated Fibroblasts; Stateof- the-Art and Perspectives in Cancer Targeted Therapy.

Cancer-associated fibroblasts (CAFs) are senescent fibroblasts in tumor nest, which trigger a signaling center to remodel a desmoplastic tumor niche. CAF's functions in cancer are closely similar to myofibroblasts during the wound healing process. They can produce cytokines, enzymes, and protein- or RNA-containing exosomes to alter the function of surrounding cells. Non-- coding RNAs, including microRNAs and long non-coding RNAs, modulate pathologic mechanisms in cancer. Dysregulation of these RNAs influences the formation and function of CAFs. Furthermore, it has been demonstrated that CAFs, by releasing non-coding RNAs-containing exosomes, affect the tumor cells' behavior. CAFs also secrete mediators such as chemokines to alter the expression of non-coding RNAs in the tumor microenvironment. This study aimed to discuss the role of non-coding RNAs in CAF development in cancer. Additionally, we have shed light on the therapeutic approaches to develop the strategies based on the alteration of non-coding RNAs in cancer.

Immunomodulatory effects of nanocurcumin on Th17 cell responses in mild and severe COVID-19 patients.

In novel coronavirus disease 2019 (COVID-19), the increased frequency and overactivation of T helper (Th) 17 cells and subsequent production of large amounts of proinflammatory cytokines result in hyperinflammation and disease progression. The current study aimed to investigate the therapeutic effects of nanocurcumin on the frequency and responses of Th17 cells in mild and severe COVID-19 patients. In this study, 40 severe COVID-19 intensive care unit-admitted patients and 40 patients in mild condition were included. The frequency of Th17 cells, the messenger RNA expression of Th17 cell-related factors (RAR-related orphan receptor γt, interleukin [IL]-17, IL-21, IL-23, and granulocyte-macrophage colony-stimulating factor), and the serum levels of cytokines were measured in both nanocurcumin and placebo-treated groups before and after treatment. A significant decrease in the number of Th17 cells, downregulation of Th17 cell-related factors, and decreased levels of Th17 cell-related cytokines were found in mild and severe COVID-19 patients treated by nanocurcumin compared to the placebo group. Moreover, the abovementioned parameters were significantly decreased in the nanocurcumin-treated group after treatment versus before treatment. Curcumin could reduce the frequency of Th17 cells and their related inflammatory factors in both mild and severe COVID-19 patients. Hence, it could be considered as a potential modulatory compound in improving the patient's inflammatory condition.

A systematic review of preclinical studies on the efficacy of propolis for the treatment of inflammatory bowel disease.

Propolis is a resinous substance produced by bees from plants. There has been some evidence indicating that propolis may be a candidate for the treatment of inflammatory bowel disease (IBD) because of its potent antioxidant properties and ability to modulate immune response and gut microbiome. The objective of this systematic review was to investigate the role of propolis in the treatment of IBD, emphasizing possible mechanisms underlying the anti-inflammatory properties of it. Searches were performed in ISI, PubMed/Medline, Scopus, EMBASE, and Cochrane Library databases up to March 2020. According to the studies examined in this review, the administration of propolis can be useful in attenuating many aspects of clinical, macroscopic, and histological features of colitis in animal models. The efficacy of propolis in the treatment of IBD might be attributed to its potent antioxidants and anti-inflammatory activities. Propolis may also be involved in the modulation of the gut microbiota and in the improvement of the intestinal mucosal barrier function. The major mechanism of action is most likely to be mediated via the prevention of some transcriptional factors and associated proteins. However, future studies are warranted to investigate the clinical utility of propolis as a candidate in the treatment of IBD.

Macrophage: A Key Therapeutic Target in Atherosclerosis?

BACKGROUND: Atherosclerosis is a chronic inflammatory disease and a leading cause of coronary artery disease, peripheral vascular disease and stroke. Lipid-laden macrophages are derived from circulating monocytes and form fatty streaks as the first step of atherogenesis. METHODS: An electronic search in major databases was performed to review new therapeutic opportunities for influencing the inflammatory component of atherosclerosis based on monocytes/macrophages targeting. RESULTS: In the past two decades, macrophages have been recognized as the main players in atherogenesis but also in its thrombotic complications. There is a growing interest in immunometabolism and recent studies on metabolism of macrophages have created new therapeutic options to treat atherosclerosis. Targeting recruitment, polarization, cytokine profile extracellular matrix remodeling, cholesterol metabolism, oxidative stress, inflammatory activity and non-coding RNAs of monocyte/macrophage have been proposed as potential therapeutic approaches against atherosclerosis. CONCLUSION: Monocytes/macrophages have a crucial role in progression and pathogenesis of atherosclerosis. Therefore, targeting monocyte/macrophage therapy in order to achieve anti-inflammatory effects might be a good option for prevention of atherosclerosis.