Inhibitory immune checkpoint (ICP) molecules are important immunosuppressive factors in a tumor microenvironment (TME). They can robustly suppress T‐cell‐mediated antitumor immune responses leading to cancer progression. Among the checkpoint molecules, cytotoxic T‐lymphocyte‐associated protein‐4 (CTLA‐4) is one of the critical inhibitors of anticancer T‐cell responses. Besides, the expression of adenosine receptor (A2AR) on tumor‐infiltrating T cells potently reduces their function. We hypothesized that concomitant silencing of these molecules in T cells might lead to enhanced antitumor responses. To examine this assumption, we purified T cells from the tumor, spleen, and local lymph nodes of CT26 colon cancer‐bearing mice and suppressed the expression of A2AR and CTLA‐4 using the small interfering RNA (siRNA)‐loaded polyethylene glycol‐chitosan‐alginate (PCA) nanoparticles. The appropriate physicochemical properties of the produced nanoparticles (NPs; size of 72 nm, polydispersive index [PDI] < 0.2, and zeta potential of 11 mV) resulted in their high efficiency in transfection and suppression of target gene expression. Following the silencing of checkpoint molecules, various T‐cell functions, including proliferation, apoptosis, cytokine secretion, differentiation, and cytotoxicity were analyzed, ex vivo. The results showed that the generated nanoparticles had optimal physicochemical characteristics and significantly suppressed the expression of target molecules in T cells. Moreover, a concomitant blockade of A2AR and CTLA‐4 in T cells could synergistically enhance antitumor responses through the downregulation of PKA, SHP2, and PP2Aα signaling pathways. Therefore, this combination therapy can be considered as a novel promising anticancer therapeutic strategy, which should be further investigated in subsequent studies.
The concern of today's communities is to find a way to prevent or treat COVID-19 and reduce its symptoms in the patients. However, the genetic mutations and more resistant strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerge; the designed vaccines and adjuvant therapies would potentially control the symptoms and severity of COVID-19. The most important complication of this viral infection is acute respiratory distress syndrome, which occurs due to the infiltration of leukocytes into the alveoli and the raised cytokine storm. Interferons, as a cytokine family in the host, play an important role in the immune-related antiviral defense and have been considered in the treatment protocols of COVID-19. In addition, it has been indicated that some nutrients, including vitamin D, magnesium and zinc are essential in the modulation of the immune system and interferon (IFN) signaling pathway. Several recent studies have investigated the treatment effect of vitamin D on COVID-19 and reported the association between optimal levels of this vitamin and reduced disease risk. In the present study, the synergistic action of vitamin D, magnesium and zinc in IFN signaling is discussed as a treatment option for COVID-19 involvement.
Coronavirus 2019 (COVID-19), an epidemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), has spread worldwide since it was first identified in Wuhan, China, in December 2019, leading to outbreaks of epidemics. Due to the increasing spread of this disease, definitive treatment and approved vaccines have not been found for it. In this study, we reviewed recent articles on the effect of vitamins (including vitamins A, B, and E) for treating coronavirus. This result suggests that some dietary supplements such as vitamins (A, B, C, D, E, etc.) have antiviral, antioxidant, and anti-inflammatory effects. Dietary supplements consisting of vitamins and individual dietary habits can therefore be used as adjunctive therapy along with antiviral drugs in the treatment of COVID-19 disease.
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