Seyed Hossein Aalaei-Andabili

Toll like receptor (TLR)-induced differential expression of microRNAs (MiRs) and immune response against infection: A systematic review

Toll like receptors (TLRs) are one of the major families of pattern recognition receptors (PRRs). MicroRNAs (MiRs) are small noncoding RNAs with regulatory effects on biological process, and it has been recently shown that they can control inflammatory process and the response to an infection by modulating the function of TLRs. In this study, we designed a systematic review to clarify the reciprocal interaction between TLRs and MiRs, in order to identify possible future therapeutic targets and strategies. On the one hand, TLRs stimulation can change expression level of miRs in various ways, which can lead to modulating their effects. On the other hand, MiRs also influence the expression of TLRs and the intensity of the inflammatory reaction. We therefore conclude that the interaction between MiRs and TLRs is a key regulator of innate immune system. Investigations discovering therapeutic approaches by manipulation of miRs expression level may open a new approach for the treatment of inflammatory diseases.

Reciprocal effects of Toll-like receptors and miRNAs on biological processes in human health and disease: a systematic review.

The roles of miRNAs in human diseases are emerging. Manipulation of miRNA expression seems to be an effective approach to control disease severity. It has recently been found that Toll-like receptors and miRNAs work by exerting reciprocal effects. Toll-like receptor stimulation can lead to up-/down-regulation of various miRNA expressions. Lipopolysaccharide induction may result in interactions between different miRNAs. Several miRNAs are involved in cancers, indicating the importance of identifying strategies to properly manipulate their expression level. The control of various miRNA expression levels, taking into consideration the plethora of their target genes and the possibility that this may lead to contracting function, which is an important issue in treatment of any miRNA-based (phenotype) disease.

MicroRNAs (MiRs) Precisely Regulate Immune System Development and Function in Immunosenescence Process

Human aging is a complex process with pivotal changes in gene expression of biological pathways. Immune system dysfunction has been recognized as one of the most important abnormalities induced by senescent names immunosenescence. Emerging evidences suggest miR role in immunosenescence. We aimed to systemically review all relevant reports to clearly state miR effects on immunosenescence process. Sensitive electronic searches carried out. Quality assessment has been performed. Since majority of the included studies were laboratory works, and therefore heterogen, we discussed miR effects on immunological aging process nonstatically. Forty-six articles were found in the initial search. After exclusion of 34 articles, 12 studies enrolled to the final stage. We found that miRs have crucial roles in exact function of immune system. MiRs are involved in the regulation of the aging process in the immune system components and target certain genes, promoting or inhibiting immune system reaction to invasion. Also, miRs control life span of the immune system members by regulation of the genes involved in the apoptosis. Interestingly, we found that immunosenescence is controllable by proper manipulation of the various miRs expression. DNA methylation and histone acetylation have been discovered as novel strategies, altering NF-κB binding ability to the miR promoter sites. Effect of miRs on impairment of immune system function due to the aging is emerging. Although it has been accepted that miRs have determinant roles in the regulation of the immunosenescence; however, most of the reports are concluded from animal/laboratory works, suggesting the necessity of more investigations in human.

Aneurysm-Specific miR-221 and miR-146a Participates in Human Thoracic and Abdominal Aortic Aneurysms

Altered microRNA expression is implicated in cardiovascular diseases. Our objective was to determine microRNA signatures in thoracic aortic aneurysms (TAAs) and abdominal aortic aneurysms (AAAs) compared with control non-aneurysmal aortic specimens. We evaluated the expression of fifteen selected microRNA in human TAA and AAA operative specimens compared to controls. We observed significant upregulation of miR-221 and downregulation of miR-1 and -133 in TAA specimens. In contrast, upregulation of miR-146a and downregulation of miR-145 and -331-3p were found only for AAA specimens. Upregulation of miR-126 and -486-5p and downregulation of miR-30c-2*, -155, and -204 were observed in specimens of TAAs and AAAs. The data reveal microRNA expression signatures unique to aneurysm location and common to both thoracic and abdominal pathologies. Thus, changes in miR-1, -29a, -133a, and -221 are involved in TAAs and miR-145, -146, and -331-3p impact AAAs. This work validates prior studies on microRNA expression in aneurysmal diseases.

Toll-Like Receptor Pathway and its Targeting in Treatment of Cancers

Pathogen recognition receptors (PRRs) including Toll-like receptors (TLRs) and NOD-like receptors (NLRs) play important roles in the regulation of immune responses. In particular, most of the studies have been centered on TLRs that play a pivotal role in tumor biology. TLR activation acts as a double-edged sword with both pro- and antitumor responses. Certain TLRs activate PI3K/Akt pathway, leading to tumor progression. In contrast, few TLRs are involved in targeting other pathways to inhibit tumor cell growth. Moreover, TLRs also regulate other pathways such as STATs, hypoxia-inducible factor 1 (HIF-1α/β), which are involved in human cancer progression. Drug- and immune system-induced apoptosis of cancer are dependent on TLR function. Since TLR function varies according to the cancer type and the TLRs expressed, their signaling pathway should either be triggered or targeted to control cancer progression. Hence, more investigations are required to discover proper therapeutic approaches for cancer.

Early and midterm outcomes of transcatheter aortic valve replacement in patients with bicuspid aortic valves

Bicuspid aortic valve (BAV) stenosis has been considered a relative contraindication to transcatheter aortic valve replacement (TAVR). We compared the outcomes of TAVR in patients with BAV stenosis versus patients with trileaflet aortic valve stenosis.

Management of Septic emboli in patients with infectious endocarditis

Septic emboli (SE) associated with infectious endocarditis (IE) can result in splenic abscesses and infectious intracranial aneurysms (IIA). We investigated the impact of SE on patient outcomes following surgery for IE.

Introduction on Cancer Immunology and Immunotherapy

Cancer, a major public health threat affecting people at all ages, is characterized by uncontrolled cell growth and genetic instability. The immune system can recognize tumor cells and mediate antigen-specific tumor rejection under certain condition. The molecular and cellular basis of immune recognition and antitumor immunity is now better understood. In addition, it is now evident that tumors may mediate immunosuppression through various soluble and cellular mechanisms which protect established tumors from immune system recognition or rejection. These advances in understanding the role of the immune system in cancer have led to a variety of specific and nonspecific approaches designed to initiate or enhance antitumor immunity, which in turn result in significant therapeutic effects in a variety of cancers. Moreover, immunotherapy is being established as a major class of drugs for cancer therapy. This chapter will review the scope of the cancer problem, describe the basis of antitumor immunity, and introduce the concept of tumor immunotherapy.

The Role of MicroRNAs in Immunosenescence Process

Genetic factors play important roles in ageing process. The aged cells accumulate in senescing tissues and organs and lead to age-associated disorders. It has recently been recognized that proteins and genes involving in ageing process are precisely regulated by various MicroRNAs. MicroRNAs have been understood as pathway regulators in biological processes such as immune system component development and activation. MicroRNAs have crucial regulatory roles in development of hematopoietic lineage, maturation and differentiation of B and T lymphocytes, proliferation of neutrophils and monocytes, secretion of type 1 interferon and proinflammatory cytokines/chemokine, and effectiveness of immune system response. These emerging evidences indicate importance of MicroRNAs in controlling functions of the immune system and immunosenescence regulation.