Simultaneous silencing of the A2aR and PD-1 immune checkpoints by siRNA-loaded nanoparticles enhances the immunotherapeutic potential of dendritic cell vaccine in tumor experimental models.

Following various immunotherapies, lack of proper anti-tumor immune responses is considered a significant problem in novel cancer therapeutic approaches. The expression of inhibitory checkpoint molecules on tumor-infiltrating T cells is one of the main reasons for the ineffectiveness of various immunotherapies. Therefore, we decided to inhibit two of the most important immune checkpoints expressed on tumor-associated T cells, PD-1 and A2aR.

Epigenetic mechanisms shape the underlining expression regulatory mechanisms of the STAT3 in multiple sclerosis disease.

Objectives: Immunological tolerance is mediated by CD4CD25 regulatory T (Treg) cells. Studies have shown that thymic and peripheral generations of Treg cells depend on the CD28 signaling pathway. T helper 17 (Th17) cells are involved in the pathophysiology of various inflammatory diseases.

Tumor-associated neutrophils as new players in immunosuppressive process of the tumor microenvironment in breast cancer.

Despite the conventional reputation of neutrophils to have antibacterial properties, recent studies have put emphasis and are interested in the role of neutrophils in the spread and treatment of cancer. It has been shown that the infiltration of neutrophils, either by exerting pro- or anti-tumoral effects, probably affects tumor prognosis. Tumor-associated neutrophils (TANs) probably participate in tumor promotion and development in different ways, such as increasing genomic instability, induction of immunosuppression, and increasing angiogenesis.

Innate and adaptive immune responses against coronavirus.

Coronaviruses (CoVs) are a member of the Coronaviridae family with positive-sense single- stranded RNA. In recent years, the CoVs have become a global problem to public health. The immune responses (innate and adaptive immunity) are essential for elimination and clearance of CoVs infections, however, uncontrolled immune responses can result in aggravating acute lung injury and significant immunopathology.

Angiotensin-converting enzyme as a new immunologic target for the new SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic has affected the daily lives of millions of people worldwide and had caused significant mortality; hence, the assessment of therapeutic options is of great interest. The leading cause of death among COVID-19 patients is acute respiratory distress syndrome caused by hyperinflammation secondary to cytokine release syndrome (CRS). Cytokines, such as tumor necrosis factor-α, interleukin-6, interferon-γ and interleukin-10, are the main mediators of CRS.

Targeting STAT3 in cancer and autoimmune diseases.

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated downstream of a broad range of receptors particularly interleukin-6 (IL-6) family. STAT3 is the key regulator of cell proliferation, survival and apoptosis and is constitutively activated in most human cancers, indicating that it can be an important potential therapeutic target for cancer treatment. STAT3 also has important roles in lymphocyte biology, regulation of immune responses and autoimmunity.

Nanomedicine for improvement of dendritic cell-based cancer immunotherapy.

Dendritic cell (DC)-based cancer immunotherapy has shown impressive outcomes, including the development of the first FDA-approved anti-cancer vaccine. However, the clinical application of DC-based cancer immunotherapy is associated with various challenges. Promising novel tools for the administration of cancer vaccines has emerged from recent developments in nanoscale biomaterials.

Silencing of p68 and STAT3 synergistically diminishes cancer progression.

Aims: Since several factors are involved in the tumorigenesis process, targeting only one factor most probably cannot overwhelm cancer progression. Therefore, it seems that combination therapy through targeting more than one cancer-related factor may lead to cancer control. The expression and function of p68 (DDX5; DEAD-Box Helicase 5) are dysregulated in various cancers.

Regulatory T cells in breast cancer as a potent anti-cancer therapeutic target.

Despite marked advances in treatment approaches, breast cancer is still going to be more prevalent, worldwide. High levels of regulatory T (Treg) cells have repeatedly been demonstrated in circulation, lymph nodes, and tumor samples from patients with various cancer types. The transcription factor Forkhead box protein 3 (Foxp3)-expressing Treg cells have the high suppressive potential of the immune system and are fundamental in preserving immune homeostasis and self-tolerance.

IL-21 and IL-21-producing T cells are involved in multiple sclerosis severity and progression.

Multiple sclerosis is a common neuroinflammatory disease of the central nervous system causing nervous system defects and severe physical disability. IL-21 is a proinflammatory cytokine produced mainly by Th-17 and Tfh cells which its exact role in MS was not yet clearly understood. In the present study we aimed to investigate the possible correlation of IL-21 gene expression, methylation, and its serum levels with MS severity and progression.

The role of DEAD-box RNA helicase p68 (DDX5) in the development and treatment of breast cancer.

RNA helicase p68 or DEAD (Asp-Glu-Ala-Asp) box polypeptide 5 (DDX5) is a unique member of the highly conserved protein family, which is involved in a broad spectrum of biological processes, including transcription, translation, precursor messenger RNA processing or alternative splicing, and microRNA (miRNA) processing. It has been shown that p68 is necessary for cell growth and participates in the early development and maturation of some organs. Interestingly, p68 is a transcriptional coactivator of numerous oncogenic transcription factors, including nuclear factor-κβ (NF-κβ), estrogen receptor α (ERα), β-catenin, androgen receptor, Notch transcriptional activation complex, p53 and signal transducer, and activator of transcription 3 (STAT3).

The significant role of interleukin-6 and its signaling pathway in the immunopathogenesis and treatment of breast cancer.

Despite remarkable improvements in cancer treatment approaches, breast cancer is still the main cause of cancer-related death in women. Its principal cause is the resistance of the cancer cells against conventional anticancer therapeutics, mainly in advanced disease stages. It has been shown that chronic inflammation in the tumor microenvironment facilitates tumor growth and induces resistance toward chemo- and radiotherapy.

Polymorphism of Foxp3 gene affects the frequency of regulatory T cells and disease activity in patients with rheumatoid arthritis in Iranian population.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that mainly affects joints and characterized by chronic joint inflammation and infiltration of various immune cells in the synovium. Forkhead box P3 (Foxp3)-expressing regulatory T cells (Tregs) play a crucial role in preventing autoimmunity and undesirable T cell responses. However, there are controversial reports regarding the defective function or frequency of these cells in various studies, which may be in part related to different polymorphisms of FoxP3 and influence of ethnicity on these differences.

Regulatory T and T helper 17 cells: Their roles in preeclampsia.

Regulatory T (Treg) cells have been identified as key immune regulators and are important to fetal survival within the maternal uterus. T helper 17 (Th17) cells have also emerged as a new subset of effector helper T cells and play significant roles in host defense against extracellular pathogens, autoimmune conditions, and inflammatory chronic diseases. Recent findings have provided strong support for the contribution of Th17 and Treg cells to successful pregnancy.

Natural killer T cells in Preeclampsia: An updated review.

Preeclampsia (PE), as a pregnancy-specific syndrome, has become one of the main causes of maternal and fetal mortality worldwide and is known as a major risk factor for preterm birth. PE is typically characterized by hypertension, significant proteinuria, and an excessive maternal systemic inflammatory response. Recent evidences provide support for the notion that Natural killer T (NKT) cells (a small, but significant immunoregulatory T cell subset of human peripheral blood lymphocytes) play pivotal roles in pregnancy.