Noncoding RNAs in diagnosis and prognosis of graft-versus-host disease (GVHD).

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a functional therapy for a plethora of hematologic malignancies and immune disorders. Graft-versus-host disease (GVHD), on the other hand, is one of the major complications ahead of a successful HSCT, contributing to transplant-associated morbidity and mortality. Notably, little is known about the underlying mechanism of this event; therefore, exploring precise biomarkers and uncovering the molecular pathogenesis of GVHD is valuable for early diagnosis and treatment optimization. Thanks to the advances in sequencing techniques, the noncoding sequences of the human genome-formerly considered "junk"-are now identified as functional molecules. Noncoding RNAs (ncRNA) control cellular responses by regulating gene expression, and previous studies have shown that these tiny molecules, especially microRNAs (miRNAs), can affect allogeneic T cell responses in both animal models and clinical experiments. The present study gives an overview of the functions of various miRNAs in regulating T cell responses in GVHD. We also provide an outlook on miRNAs and long noncoding RNAs (lncRNAs) potential role in GVHD with the hope of providing a future research direction for expanding their application as the sensitive and noninvasive diagnostic or prognostic biomarkers and also the promising therapeutic targets for improving outcomes after allogeneic HSCT.

Targeting macrophage-mediated tumor cell phagocytosis: An overview of phagocytosis checkpoints blockade, nanomedicine intervention, and engineered CAR-macrophage therapy.

Immunotherapy has been developing at an unprecedented speed with promising therapeutic outcomes in the wide spectrum of cancers. Up until now, most immunotherapies have focused on adaptive immunity; however, investigating the potential of macrophage phagocytosis and consequent adaptive immune cross-priming has led to a growing interest in exploiting macrophages in cancer therapy. In light of the positive evidence from preclinical studies and early clinical data, targeting macrophage phagocytosis has become a promising therapeutic strategy. Here, we review therapies based on harnessing and amplifying macrophage phagocytosis, such as blocking phagocytosis checkpoints and exploiting nanoparticles as efficient approaches in elevating macrophages-mediated phagocytosis. The present study introduces CAR-macrophage as the state-of-the-art modality serving as the bridge between the innate and adaptive immune system to mount a superior anti-tumor response in the treatment of cancer. We also take a look at the recent reports of therapies based on CAR-engineered macrophages with the hope of providing a future research direction for expanding the application of CAR-macrophage therapy.

Mesenchymal stromal/stem cells (MSCs) and MSC-derived extracellular vesicles in COVID-19-induced ARDS: Mechanisms of action, research progress, challenges, and opportunities.

In late 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan city, Hubei province, China. Rapidly escalated into a worldwide pandemic, it has caused an unprecedented and devastating situation on the global public health and society economy. The severity of recent coronavirus disease, abbreviated to COVID-19, seems to be mostly associated with the patients' immune response. In this vein, mesenchymal stromal/stem cells (MSCs) have been suggested as a worth-considering option against COVID-19 as their therapeutic properties are mainly displayed in immunomodulation and anti-inflammatory effects. Indeed, administration of MSCs can attenuate cytokine storm and enhance alveolar fluid clearance, endothelial recovery, and anti-fibrotic regeneration. Despite advantages attributed to MSCs application in lung injuries, there are still several issues __foremost probability of malignant transformation and incidence of MSCs-related coagulopathy__ which should be resolved for the successful application of MSC therapy in COVID-19. In the present study, we review the historical evidence of successful use of MSCs and MSC-derived extracellular vesicles (EVs) in the treatment of acute respiratory distress syndrome (ARDS). We also take a look at MSCs mechanisms of action in the treatment of viral infections, and then through studying both the dark and bright sides of this approach, we provide a thorough discussion if MSC therapy might be a promising therapeutic approach in COVID-19 patients.