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A major characteristic of cancer is dysregulated cell division, which results in aberrant growth of cells. Consequently, medicinal targets that prevent cell division would be useful in the fight against cancer. The primary regulator of proliferation is a complex consisting of cyclin and cyclin-dependent kinases (CDKs). The FDA has granted approval for CDK inhibitors (CDKIs) to treat metastatic hormone receptor-positive breast cancer. Specifically, CDK4/6 CDKIs block the enzyme activity of CDK4 and CDK6. Unfortunately, the majority of first-generation CDK inhibitors, also known as pan-CDK inhibitors because they target multiple CDKs, have not been authorized for clinical use owing to their serious side effects and lack of selection. In contrast to this, significant advancements have been created to permit the use of pan-CDK inhibitors in therapeutic settings. Notably, the toxicity and negative consequences of pan-CDK inhibitors have been lessened in recent years thanks to the emergence of combination therapy tactics. Therefore, pan-CDK inhibitors have renewed promise for clinical use when used in a combination regimen. The members of the CDK family have been reviewed and their primary roles in cell cycle regulation were covered in this review. Next, we provided an overview of the state of studies on CDK inhibitors. [ABSTRACT FROM AUTHOR]

Coronary heart disease (CHD) continues to be the leading cause of morbidity and mortality. There are numerous therapeutic reperfusion methods, including thrombolytic therapy, primary percutaneous coronary intervention, and anti-remodeling drugs like angiotensin-converting enzyme inhibitors and beta-blockers. Despite this, there is no pharmacological treatment that can effectively stop cardiomyocyte death brought on by myocardial ischemia/reperfusion (I/R) injury. For the purpose of regenerating cardiac tissue, mesenchymal stem cell (MSC) therapy has recently gained more attention. The pleiotropic effects of MSCs are instead arbitrated by the secretion of soluble paracrine factors and are unrelated to their capacity for differentiation. One of these paracrine mediators is the extracellular vesicle known as an exosome. Exosomes deliver useful cargo to recipient cells from MSCs, including peptides, proteins, cytokines, lipids, miRNA, and mRNA molecules. Exosomes take part in intercellular communication processes and help tissues and organs that have been injured or are ill heal. Exosomes alone were found to be the cause of MSCs' therapeutic effects in a variety of animal models, according to studies. Here, we have focused on the recent development in the therapeutic capabilities of exosomal MSCs in cardiac diseases. [ABSTRACT FROM AUTHOR]

Genetically modified immune cells, especially CAR‐T cells, have captured the attention of scientists over the past 10 years. In the fight against cancer, these cells have a special place. Treatment for hematological cancers, autoimmune disorders, and cancers must include CAR‐T cell therapy. Determining the therapeutic targets, side effects, and use of CAR‐T cells in neurological disorders, including cancer and neurodegenerative diseases, is the goal of this study. Due to advancements in genetic engineering, CAR‐T cells have become crucial in treating some neurological disorders. CAR‐T cells have demonstrated a positive role in treating neurological cancers like Glioblastoma and Neuroblastoma due to their ability to cross the blood–brain barrier and use diverse targets. However, CAR‐T cell therapy for MS diseases is being researched and could be a potential treatment option. This study aimed to access the most recent studies and scientific articles in the field of CAR‐T cells in neurological diseases and/or disorders. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells play a role in the pathogenesis of rheumatoid arthritis (RA). Upregulated levels of programmed cell death protein 1 (PD-1) is a sign of exhausted NK cells that could be regulated by microRNAs (miRNAs). In this investigation, we determined PD-1 expression on NK cells (as a representation of NK cell exhaustion) in RA patients and evaluated if miRNAs are involved in the modulation of PD-1 expression in NK cells. Peripheral blood specimens were obtained from 40 RA patients and 20 healthy subjects. NK cells were isolated by negative selection from a pool of peripheral blood mononuclear cells. The frequency of PD-1-expressing NK cells and the expression of PD-1 on NK cells were analyzed by flow cytometry. Real-time PCR was used to measure the expression levels of PD-1 mRNA and miRNAs in the NK cells. The percentage of the PD-1-expressing NK cells and Mean fluorescence intensity (MFI) of PD-1 expression on the NK cells were significantly higher in the RA cases compared to the controls. The mRNA expression of PD-1 was significantly upregulated in NK cells from RA patients compared to healthy subjects. The expression levels of miR-28, miR-138, and miR-4717 were significantly downregulated in the NK cells from RA patients compared to the healthy group. In RA, miRNAs probably regulate the NK cell exhaustion process through driving PD-1 expression. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is considered an autoimmune chronic disorder and the most common inflammatory arthropathy. Disease progression in RA begins with asymptomatic autoimmune responses in cases with a genetic or environmental predisposition, that alters to arthralgia phase as autoantibodies reach the joints and subjects begin demonstrating nonspecific musculoskeletal presentations lacking any clinical symptoms of synovial inflammation. After that, patients' symptoms develop to undifferentiated arthritis (UA)/idiopathic arthritis (IA) whenever the subjects progress to clinical synovitis systemic comorbidities affecting the vasculature, metabolism, and bone, and eventually with augmented immune cell infiltration, IA/UA patients progress to clinically classifiable RA. RA is mainly correlated with different immune cells and each of them contributes variously to the pathogenesis of the disease. The pathogenesis of RA is altered by the contribution of both T and B cells in an autoimmune irregularity. Modulation of the immune responses occurs through regulatory and inhibitory molecules that control activation of the adaptive system as well as immune hemostasis. To confine the exorbitant T cell‐associated inflammatory reactions, the immune system provides a system of inhibitory feedbacks, collectively named immune checkpoints. In this review, we aimed to discuss about inhibitory members of immune checkpoint molecules, including programmed cell death 1 (PD‐1)/PD‐L1, cytotoxic‐T‐lymphocyte‐antigen‐4, lymphocyte activation gene‐3, T cell immunoglobulin‐3, V‐domain Ig suppressor of T cell activation, B‐ and T‐lymphocyte attenuator, and T cell immunoglobulin and ITIM domain and their role in RA. [ABSTRACT FROM AUTHOR]

Despite substantial developments in conventional treatments such as surgery, chemotherapy, radiotherapy, endocrine therapy, and molecular‐targeted therapy, breast cancer remains the leading cause of cancer mortality in women. Currently, chimeric antigen receptor (CAR)–redirected immune cell therapy has emerged as an innovative immunotherapeutic approach to ameliorate survival rates of breast cancer patients by eliciting cytotoxic activity against cognate tumour‐associated antigens expressing tumour cells. As a crucial component of adaptive immunity, T cells and NK cells, as the central innate immune cells, are two types of pivotal candidates for CAR engineering in treating solid malignancies. However, the biological distinctions between NK cells‐ and T cells lead to differences in cancer immunotherapy outcomes. Likewise, optimal breast cancer removal via CAR‐redirected immune cells requires detecting safe target antigens, improving CAR structure for ideal immune cell functions, promoting CAR‐redirected immune cells filtration to the tumour microenvironment (TME), and increasing the ability of these engineered cells to persist and retain within the immunosuppressive TME. This review provides a concise overview of breast cancer pathogenesis and its hostile TME. We focus on the CAR‐T and CAR‐NK cells and discuss their significant differences. Finally, we deliver a summary based on recent advancements in the therapeutic capability of CAR‐T and CAR‐NK cells in treating breast cancer. [ABSTRACT FROM AUTHOR]

For many years, the question of how the maternal immune system tolerates the foreign fetus has remained unanswered, and numerous studies have considerably attempted to elucidate underlying mechanisms for fetomaternal tolerance. This review aimed at discussing various significant mechanisms in fetomaternal compatibility. At the fetomaternal interface, in addition to having efficient control against infections, innate and adaptive maternal immune systems selectively prevent fetal rejection. In general, understanding the complex mechanisms of fetomaternal tolerance is critical for immunologic tolerance induction and spontaneous abortion prevention in high-risk populations. Different cells and molecules, such as regulatory T-cells, dendritic cells, decidua cells, IDO, Class I HLA molecules, TGF-β, and IL-10, induce maternal immune tolerance in the fetus in numerous ways. The findings on fetomaternal immune tolerance have remained controversial and require further research. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are one of the most prominent cells in the bone marrow. MSCs can affect acute lymphocytic leukemia (ALL) cells under hypoxic conditions. With this aim, we used MOLT‐4 cells as simulators of ALL cells cocultured with bone marrow mesenchymal stem cells (BMMSCs) under hypoxic conditions in vitro. Then, mRNA and protein expression of the MAT2A, PDK1, and HK2 genes were evaluated by real‐time PCR and Western blot which was also followed by apoptosis measurement by a flow‐cytometric method. Next, the methylation status of the target genes was investigated by MS‐qPCR. Additionally, candidate gene expressions were examined after treatment with rapamycin using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. We found that the mRNA expression of the candidate genes was augmented under the hypoxic condition in which MAT2A was upregulated in cocultured cells compared to MOLT‐4, while HK2 and PDK1 were downregulated. Moreover, we found an association between gene expression and promoter methylation levels of target genes. Besides, expressions of the candidate genes were decreased, while their methylation levels were promoted following treatment with rapamycin. Our results suggest an important role for the BMMSC in regulating the methylation of genes involved in cell survival in hypoxia conditions; however, we found no evidence to prove the MSCs' effect on directing malignant lymphoblastic cells to apoptosis. [ABSTRACT FROM AUTHOR]

It has been well established that the etiopathogenesis of diverse autoimmune diseases is rooted in the autoreactive immune cells' excessively proliferative state and impaired apoptotic machinery. Survivin is an anti-apoptotic and mitotic factor that has sparked a considerable research interest in this field. Survivin overexpression has been shown to contribute significantly to the development of autoimmune diseases via autoreactive immune cell overproliferation and apoptotic dysregulation. Several microRNAs (miRNAs/miRs) have been discovered to be involved in survivin regulation, rendering the survivin-miRNA axis a perspective target for autoimmune disease therapy. In this review, we discuss the role of survivin as an immune regulator and a highly implicated protein in the pathogenesis of autoimmune diseases, the significance of survivin-targeting miRNAs in autoimmunity, and the feasibility of targeting the survivin-miRNA axis as a promising therapeutic option for autoimmune diseases. [ABSTRACT FROM AUTHOR]