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.

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.

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.

No abstract

Introduction: This study aimed to evaluate the potential apoptotic effects of Zingiber officinale Roscoe (ginger) and Rosmarinus Officinalis L. (rosemary) combination extracts on the mouse colorectal cancer cell line. Methods: After the preparation of the extracts, cytotoxicity and cell viability were measured by MTT assay, and the IC50 of each extract was calculated. Next, the combination index (CI) of the mixture of the extracts was evaluated by CompuSyn software. The apoptosis induction was evaluated by Annexin V/PI assay and caspase-3, Bcl-2, and Bax genes expression. Results: The viability of the CT-26 cells exposed to ginger and rosemary extracts was significantly reduced in a dose-dependent manner (P<0.05) with the confirmed synergistic effect of the mixture (CI=0.89). Moreover, treatment of the cells with IC50 concentration of the extracts induced apoptosis, especially in the mixture group (P<0.001). Additionally, expression levels of Bax and caspase-3 genes increased in the mixture group compared to the control (P<0.001). Expression levels of Bcl-2 were increased in the rosemary and mixture groups compared to the control group (P<0.05). Conclusion: The results of the present study revealed that the mixture of the extracts has synergistic cytotoxic and apoptotic effects on colorectal cancer cells. Therefore, the mixture of ginger and rosemary extracts can be used as a potential complementary therapy in the context of other therapeutic approaches for colorectal cancer.