Oleuropein induces apoptosis in gastric cancer cell lines by regulating mir-34a, mir-21, and related genes: An experimental and bioinformatic study.

Gastric Cancer (GC) is one of the most prevalent malignancies worldwide. Oleuropein, as a natural phenolic compound with anti-cancer characteristics, is a good option with low side effects to overcome the adverse impact of conventional treatments in cancer. This research evaluated Oleuropein's anti-cancer and apoptotic activities and the anti-migratory effects by modulating potential target genes in epithelial-mesenchymal transition (EMT). Bioinformatic analysis was performed to predict possible Oleuropein's target genes. Then the importance of these genes was shown by UALCAN, Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) datasets in gastric cancer. Finally, the association between the selected genes was shown by Cytoscape network analysis. The MTT assay, DAPI staining, flow cytometry, and real-time PCR were applied in the current study. The results showed that the viability of cells was decreased, and the apoptosis rate increased in the Oleuropein-treated group. These findings revealed that Oleuropein regulated the expression of the apoptotic and metastatic genes and microRNAs in GC cells.

DNA methylation changes and inflammaging in aging-associated diseases.

Aging as an inevitable phenomenon is associated with pervasive changes in physiological functions. There is a relationship between aging and the increase of several chronic diseases. Most age-related disorders are accompanied by an underlying chronic inflammatory state, as demonstrated by local infiltration of inflammatory cells and greater levels of proinflammatory cytokines in the bloodstream. Within inflammaging, many epigenetic events, especially DNA methylation, change. During the aging process, due to aberrations of DNA methylation, biological processes are disrupted, leading to the emergence or progression of a variety of human diseases, including cancer, neurodegenerative disorders, cardiovascular disease and diabetes. The focus of this review is on DNA methylation, which is involved in inflammaging-related activities, and how its dysregulation leads to human disorders.

Aging as a natural process is associated with variation in physiological functions. One of the hallmarks of aging is epigenetic changes, which are directly involved in the aging process and aging-related diseases. DNA methylation is one of the epigenetic changes during aging. Consequently, changes in DNA methylation affect various cellular processes and cause age-related diseases. This review discusses the role of DNA methylation in aging processes and age-related diseases.

The role of IL-1 family of cytokines and receptors in pathogenesis of COVID-19.

A global pandemic has erupted as a result of the new brand coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic has been consociated with widespread mortality worldwide. The antiviral immune response is an imperative factor in confronting the recent coronavirus disease 2019 (COVID-19) infections. Meantime, cytokines recognize as crucial components in guiding the appropriate immune pathways in the restraining and eradication of the virus. Moreover, SARS-CoV-2 can induce uncontrolled inflammatory responses characterized by hyper-inflammatory cytokine production, which causes cytokine storm and acute respiratory distress syndrome (ARDS). As excessive inflammatory responses are contributed to the severe stage of the COVID-19 disease, therefore, the pro-inflammatory cytokines are regarded as the Achilles heel during COVID-19 infection. Among these cytokines, interleukin (IL-) 1 family cytokines (IL-1, IL-18, IL-33, IL-36, IL-37, and IL-38) appear to have a strong inflammatory role in severe COVID-19. Hence, understanding the underlying inflammatory mechanism of these cytokines during infection is critical for reducing the symptoms and severity of the disease. Here, the possible mechanisms and pathways involved in inflammatory immune responses are discussed.

Immune Checkpoint Inhibitors in Colorectal Cancer: Challenges and Future Prospects.

Immunotherapy is a new pillar of cancer therapy that provides novel opportunities to treat solid tumors. In this context, the development of new drugs targeting immune checkpoints is considered a promising approach in colorectal cancer (CRC) treatment because it can be induce specific and durable anti-cancer effects. Despite many advances in the immunotherapy of CRC, there are still limitations and obstacles to successful treatment. The immunosuppressive function of the tumor microenvironment (TME) is one of the causes of poor response to treatment in CRC patients. For this reason, checkpoint-blocking antibodies have shown promising outcomes in CRC patients by blocking inhibitory immune checkpoints and enhancing immune responses against tumors. This review summarizes recent advances in immune checkpoint inhibitors (ICIs), such as CTLA-4, PD-1, PD-L1, LAG-3, and TIM-3 in CRC, and it discusses various therapeutic strategies with ICIs, including the double blockade of ICIs, combination therapy of ICIs with other immunotherapies, and conventional treatments. This review also delineates a new hopeful path in the combination of anti-PD-1/anti-PD-L1 with other ICIs such as anti-CTLA-4, anti-LAG-3, and anti-TIM-3 for CRC treatment.