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Acute myeloid leukemia (AML) is an aggressive hematological malignancy and affected patients have poor overall survival (OS) rates. Circular RNAs (circRNAs) are a novel class of non-coding RNAs (ncRNAs) with a unique loop structure. In recent years, with the development of high-throughput RNA sequencing, many circRNAs have been identified exhibiting either up-regulation or down-regulation in AML patients compared with healthy controls. Recent studies have reported that circRNAs regulate leukemia cell proliferation, stemness, and apoptosis, both positively and negatively. Additionally, circRNAs could be promising biomarkers and therapeutic targets in AML. In this study, we present a comprehensive review of the regulatory roles and potentials of a number of dysregulated circRNAs in AML.

Although cellular and molecular mediators of the immune system have the potential to be prognostic indicators of disease outcomes, temporal interference between diseases might affect the immune mediators, and make them difficult to predict disease complications. Today one of the most important challenges is predicting the prognosis of COVID-19 in the context of other inflammatory diseases such as traumatic injuries. Many diseases with inflammatory properties are usually polyphasic and the kinetics of inflammatory mediators in various inflammatory diseases might be different. To find the most appropriate evaluation time of immune mediators to accurately predict COVID-19 prognosis in the trauma environment, researchers must investigate and compare cellular and molecular alterations based on their kinetics after the start of COVID-19 symptoms and traumatic injuries. The current review aimed to investigate the similarities and differences of common inflammatory mediators (C-reactive protein, procalcitonin, ferritin, and serum amyloid A), cytokine/chemokine levels (IFNs, IL-1, IL-6, TNF-α, IL-10, and IL-4), and immune cell subtypes (neutrophil, monocyte, Th1, Th2, Th17, Treg and CTL) based on the kinetics between patients with COVID-19 and trauma. The mediators may help us to accurately predict the severity of COVID-19 complications and follow up subsequent clinical interventions. These findings could potentially help in a better understanding of COVID-19 and trauma pathogenesis.

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Background Leukemic cell metabolism plays significant roles in their proliferation and survival. These metabolic adaptations are under regulation by different factors. Programmed Death Ligand -1 (CD-274) is one of the immune checkpoint ligands that do not only cause the immune escape of cancer cells, but also have some intracellular effects in these cells. PD-L1 is overexpressed on leukemic stem cells and relates with poor prognosis of AML. In this study, we investigated effects of PD-L1 stimulation on critical metabolic pathways of glucose and fatty acid metabolisms that have important roles in proliferation and survival of leukemic cells. Methods After confirmation of PD-L1 expression by flow cytometry assay, we used recombinant protein PD-1 for stimulation of the PD-L1 on two AML cell lines, HL-60 and THP-1. Then we examined the effect of PD-L1 stimulation on glucose and fatty acid metabolism in cells at the genomic and metabolomic levels in a time dependent manner. We investigated expression changes of rate limiting enzymes of theses metabolic pathways (G6PD, HK-2, CPT1A, ATGL1 and ACC1) by qRT-PCR and also the relative abundance changes of free fatty acids of medium by GC. Results We identified a correlation between PD-L1 stimulation and both fatty acid and glucose metabolism. The PD-L1 stimulated cells showed an influence in the pentose phosphate pathway and glycolysis by increasing expression of G6PD and HK-2 (P value = 0.0001). Furthermore, PD-L1 promoted fatty acid β-oxidation by increasing expression of CPT1A (P value = 0.0001), however, their fatty acid synthesis was decreased by reduction of ACC1 expression (P value = 0.0001). Conclusion We found that PD-L1 can promote proliferation and survival of AML stem cells probably through some metabolic changes in leukemic cells. Pentose phosphate pathway that has a critical role in cell proliferation and fatty acids β-oxidation that promote cell survival, both are increased by PD-L1 stimulation on AML cells.

Some risk causes may be associated with the severity of COVID-19. The central host-pathogen factors might affect infection are human receptor angiotensin-converting enzyme 2 (ACE2), trans-membrane protease serine 2 (TMPRSS2), and SARS-CoV-2 surface spike (S)-protein. The main purpose of this study was to determine the differences in the expression the metalloproteinases-2  (MMP-2), MMP-9, ACE2, and TMPRSS2 genes and their correlation with lymphopenia in the mild and severe types of the COVID-19 patients. Eighty-eight patients, aged 36 to 60 years old with the mild (n=44) and severe (n=44) types of COVID-19 were enrolled. Total RNA was isolated from the peripheral blood mononuclear cells (PBMCs). The changes of MMP-2, MMP-9, ACE2 and TMPRSS2 gene expression in PBMCs from mild and severe COVID-19 patients were examined by the real time-quantitative polymerase chain reaction (RT-qPCR) assay and, compared between the groups. Data were collected from May 2021 to March 2022. The mean age of the patients in both groups was 48 (interquartile range, 36–60), and there were no appreciable differences in age or gender distribution between the two groups. The present study showed that a significant increase in the expression of ACE2, TMPRSS2, MMP-2, and MMP-9 genes in the severe type of the COVID-19 patients compared, to the mild type of the COVID-19 patients. Overall, it suggests the expression levels of these genes on the PBMC surface in the immune system are susceptible to infection by SARS-COV-2 and therefore could potentially predict the patients’ outcome.

Background: Inflammatory cell death, PANoptosis, has been suggested to orchestrate the lymphocyte decrement among coronavirus disease-2019 (COVID-19) patients. The main aim of this study was to examine the differences in the expression of key genes related to inflammatory cell death and their correlation with lymphopenia in the mild and severe types of COVID-19 patients. Materials and Methods: Eighty-eight patients (36 to 60 years old) with mild ( n = 44) and severe ( n = 44) types of COVID-19 were enrolled. The expression of key genes related to apoptosis (FAS-associated death domain protein, FADD), pyroptosis (ASC (apoptosis-associated speck-like protein containing caspase activation and recruitment domains (CARD)), the adapter protein ASC binds directly to caspase-1 and is critical for caspase-1 activation in response to a broad range of stimuli), and necroptosis (mixed lineage kinase domain-like, MLKL) genes were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay, and compared between the groups. The serum levels of interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay (ELISA) assay. Results: A major increase in the expression of FADD, ASC, and MLKL-related genes in the severe type of patients was compared to the mild type of patients. The serum levels of IL-6 similarly indicated a significant increase in the severe type of the patients. A significant negative correlation was detected between the three genes’ expression and the levels of IL-6 with the lymphocyte counts in both types of COVID-19 patients. Conclusion: Overall, the main regulated cell-death pathways are likely to be involved in lymphopenia in COVID-19 patients, and the expression levels of these genes could potentially predict the patients’ outcome.