Royal jelly induces ROS-mediated apoptosis in acute lymphoblastic leukemia (ALL)-derived Nalm-6 cells: Shedding light on novel therapeutic approaches for ALL.

Objectives: Until recently, a conventional chemotherapy regimen for Acute lymphoblastic leukemia (ALL) is considered an efficient therapeutic method in children. However, suboptimal long-term survival rates in adults, disease relapse, and drug-induced toxicities require novel therapeutic agents for ALL treatments. Today, natural products with pharmacological benefits play a significant role in treating different cancers. Among the most valued natural products, honey bees' royal jelly (RJ) is one of the most appreciated which has revealed anti-tumor activity against different human cancers. This study aimed to evaluate anti-leukemic properties and the molecular mechanisms of RJ cytotoxicity on ALL-derived Nalm-6 cells. Materials and Methods: The metabolic activity was measured by MTT assay. Apoptosis, cell distribution in the cell cycle, and intracellular reactive oxygen species (ROS) level were investigated using flow cytometry analysis. Moreover, quantitative real-time PCR (qRT-PCR) was performed to scrutinize the expression of various regulatory genes. Results: RJ significantly decreased the viability of Nalm-6 cells but had no cytotoxic effect on normal cells. In addition, RJ induced ROS-mediated apoptosis by up-regulating pro-apoptotic genes while decreasing anti-apoptotic gene expression. The results outlined that ROS-dependent up-regulation of FOXO4 and Sirt1 inhibits the cells' transition to the S phase of the cell cycle through p21 up-regulation. The qRT-PCR analysis of autophagy-related gene expression also demonstrated that RJ induced BECN1 mediated autophagy in Naml-6 cells. Conclusion: Taken together, this study showed that RJ can be utilized as a potent natural substance to induce ALL cells' programmed cell death. However, further studies are required to examine this compound's pharmaceutical application.

Cytokine-Induced Memory-Like NK Cells: Emerging strategy for AML immunotherapy.

Acute myeloid leukemia (AML) is a heterogeneous disease developed from the malignant expansion of myeloid precursor cells in the bone marrow and peripheral blood. The implementation of intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) has improved outcomes associated with AML, but relapse, along with suboptimal outcomes, is still a common scenario. In the past few years, exploring new therapeutic strategies to optimize treatment outcomes has occurred rapidly. In this regard, natural killer (NK) cell-based immunotherapy has attracted clinical interest due to its critical role in immunosurveillance and their capabilities to target AML blasts. NK cells are cytotoxic innate lymphoid cells that mediate anti-viral and anti-tumor responses by producing pro-inflammatory cytokines and directly inducing cytotoxicity. Although NK cells are well known as short-lived innate immune cells with non-specific responses that have limited their clinical applications, the discovery of cytokine-induced memory-like (CIML) NK cells could overcome these challenges. NK cells pre-activated with the cytokine combination IL-12/15/18 achieved a long-term life span with adaptive immunity characteristics, termed CIML-NK cells. Previous studies documented that using CIML-NK cells in cancer treatment is safe and results in promising outcomes. This review highlights the current application, challenges, and opportunities of CIML-NK cell-based therapy in AML.

Spotlight on contributory role of host immunogenetic profiling in SARS-CoV-2 infection: Susceptibility, severity, mortality, and vaccine effectiveness.

BACKGROUND: The SARS-CoV-2 virus has spread continuously worldwide, characterized by various clinical symptoms. The immune system responds to SARS-CoV-2 infection by producing Abs and secreting cytokines. Recently, numerous studies have highlighted that immunogenetic factors perform a putative role in COVID-19 pathogenesis and implicate vaccination effectiveness. AIM: This review summarizes the relevant articles and evaluates the significance of mutation and polymorphism in immune-related genes regarding susceptibility, severity, mortality, and vaccination effectiveness of COVID-19. Furthermore, the correlation between host immunogenetic and SARS-CoV-2 reinfection is discussed. METHOD: A comprehensive search was conducted to identify relevant articles using five databases until January 2023, which resulted in 105 total articles. KEY FINDINGS: Taken to gather this review summarized that: (a) there is a plausible correlation between immune-related genes and COVID-19 outcomes, (b) the HLAs, cytokines, chemokines, and other immune-related genes expression profiles can be a prognostic factor in COVID-19-infected patients, and (c) polymorphisms in immune-related genes have been associated with the effectiveness of vaccination. SIGNIFICANCE: Regarding the importance of mutation and polymorphisms in immune-related genes in COVID-19 outcomes, modulating candidate genes is expected to help clinical decisions, patient outcomes management, and innovative therapeutic approach development. In addition, the manipulation of host immunogenetics is hypothesized to induce more robust cellular and humoral immune responses, effectively increase the efficacy of vaccines, and subsequently reduce the incidence rates of reinfection-associated COVID-19.