Background The aim of this study was to evaluate the expression of four up/down-regulated inflammatory miRNAs and their mRNA targets in the serum samples of COVID-19 patients with different grades. Also, we investigated the relative expression of these miRNAs and mRNAs during hospitalization. Methods In this cross-sectional study, 5 mL of blood sample were taken from COVID-19 patients with different grades and during hospitalization from several health centers of Yazd, Tehran, and Zahedan province of Iran from December 20, 2020 to March 2, 2021. The relative expression of miRNAs and mRNAs was evaluated by q-PCR. Results We found that the relative expression of hsa-miR-31-3p, hsa-miR-29a-3p, and hsa-miR-126-3p was significantly decreased and the relative expression of their mRNA targets (ZMYM5, COL5A3, and CAMSAP1) was significantly increased with the increase of disease grade. Conversely, the relative expression of hsa-miR-17-3p was significantly increased and its mRNA target (DICER1) was significantly decreased with the increase of disease grade. This pattern was exactly seen during hospitalization of COVID-19 patients who did not respond to treatment. In COVID-19 patients who responded to treatment, the expression of selected miRNAs and their mRNA targets returned to the normal level. A negative significant correlation was seen between (1) the expression of hsa-miR-31-3p and ZMYM5, (2) hsa-miR-29a-3p and COL5A3, (3) hsa-miR-126-3p and CAMSAP1, and (4) hsa-miR-17-3p and DICER1 in COVID-19 patients with any grade (P  <  0.05) and during hospitalization. Conclusions In this study, we gained a more accurate understanding of the expression of up/down-regulated inflammatory miRNAs in the blood of COVID-19 patients. The obtained data may help us in the diagnosis and prognosis of COVID-19. Trial registration: The ethics committee of Zahedan University of Medical Sciences, Zahedan, Iran. (Ethical Code: IR.ZAUMS.REC.1399.316) was registered for this project.

Introducción: La expresión de miARN específicos y sus dianas de ARNm se modifican en las enfermedades infecciosas. El objetivo de este estudio fue analizar la expresión de miARN pro-neuroinflamatorios, miARN anti-neuroinflamatorios y sus ARNm dianas en el suero de pacientes con COVID-19 de diferentes grados. Métodos: Se incluyeron en este estudio pacientes con COVID-19 de diferentes grados y se analizó la expresión de miARN pro-neuroinflamatorios, miARN anti-neuroinflamatorios y sus ARNm diana mediante q-PCR. Resultados: La expresión relativa de miARN anti-neuroinflamatorios (mir-21, mir-124 y mir-146a) disminuyó y la expresión relativa de sus ARNm diana (IL-12p53, Stat3 y TRAF6) aumentó. Además, la expresión relativa de miARN pro-neuroinflamatorios (mir-326, mir-155 y mir-27b) aumentó y la expresión relativa de su ARNm diana (PPARS, SOCS1 y CEBPA) disminuyó en pacientes con COVID-19 con aumento del grado de enfermedad. Se observó una correlación negativa significativa entre ARNm de mir-21 e IL-12p53, ARNm de mir-124 y Stat3, ARNm de mir-146a y TRAF6, ARNm de mir-27b y PPARS, ARNm de mir-155 y SOCS1, y entre mir-326 y ARNm de CEBPA en pacientes con COVID-19 (P <0,05). Conclusiones: Este estudio mostró que la expresión relativa de miARN anti-neuroinflamatorios disminuyó y la expresión relativa de sus ARNm diana se incrementó en pacientes con COVID-19 de enfermedad asintomática a crítica. Además, este estudio mostró que la expresión relativa de miARN pro-neuroinflamatorios aumentó y la expresión relativa de su ARNm diana disminuyó en pacientes con COVID-19 de enfermedad asintomática a crítica.

Nanotechnology uses the unique properties of nanostructures with a size of 1 to 200 nanometers. Different nanoparticles have shown great promise for the production of new vaccines and drugs. Nanostructures can be used to deliver immunological compounds more effectively than microstructures to target sites. Different nanostructures can be applied to form a new generation of vaccines, adjuvants, and immune system drugs. The goal of nanotechnology is to better respond to a wide range of infectious and non-infectious diseases.

The aim of this study was to present and evaluate novel oral vaccines, based on self-amplifying RNA lipid nanparticles (saRNA LNPs), saRNA transfected Lactobacillus plantarum LNPs, and saRNA transfected Lactobacillus plantarum, to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) variants alpha and delta. After invitro evaluation of the oral vaccines on HEK293T/17 cells, we found that saRNA LNPs, saRNA transfected Lactobacillus plantarum LNPs, and saRNA transfected Lactobacillus plantarum could express S-protein at both mRNA and protein levels. In the next step, BALB/c mice were orally vaccinated with saRNA LNPs, saRNA transfected Lactobacillus plantarum LNPs, and saRNA transfected Lactobacillus plantarum at weeks 1 and 3. Importantly, a high titer of IgG and IgA was observed by all of them, sharply in week 6 (P < 0.05). In all study groups, their ratio of IgG2a/IgG1 was upper 1, indicating Th1-biased responses. Wild-type viral neutralization assay showed that the secreted antibodies in vaccinated mice and recovered COVID-19 patients could neutralize SARS-COV-2 variants alpha and delta. After oral administration of oral vaccines, biodistribution assay was done. It was found that all of them had the same biodistribution pattern. The highest concentration of S-protein was seen in the small intestine, followed by the large intestine and liver.

Objectives. The B-cell-specific moloney leukemia virus insertion site 1 (the Bmi-1) gene is an important member in the family of polycomb group (PcG) genes that plays an oncogenic role in several types of cancer, but it's expression as a prognostic marker in pediatric brain tumors has not been indicated. Materials and Methods. The Bmi-1 gene expression, clinic pathological and prognostic significance in a series of pediatric brain tumors were examined by real-time PCR method in 56 pediatric brain tumors. Results. The Bmi-1 gene expression in various types of pediatric brain tumors compared to that in normal brain tissue was 4.85-fold. The relative expression varied from 8.64-fold in ependymomas to 2.89-fold in other types. Expression level in high-grade tumors compared to that in low-grade tumors was 2.5 times. In univariate survival analysis of the pediatric brain tumors, a significant association of high expression of the Bmi-1 with patient survival was demonstrated. In multivariate analysis, the Bmi-1 high expression provided significant independent prognostic factors. Conclusion. Increased expression of the Bmi-1 in pediatric brain tumors may be important in the acquisition of an aggressive phenotype. In addition, it can be used as a strong and independent molecular marker of prognosis in pediatric brain tumors.

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Background: Our aim was to investigate the expression of miRNAs, C-reactive protein as a blood inflammation marker, and alanine aminotransferase as a tissue inflammation marker in recovered and not-recovered COVID-19 patients. Methods: This cross-sectional project was done in three medical center of Iran from December to March, 2021. Generally, a total of 20 confirmed cases of COVID-19 with grade III and 20 healthy subjects were enrolled in the study. Then, the neuroinflammatory expression of miRNAs (miR-199, miR-203, and miR-181), C-reactive protein, and alanine aminotransferase were investigated during hospitalization from week 0 to week 2. Results: In not-recovered COVID-19 subjects, the expression of miR-199, miR-203, and miR-181 were decreased and the levels of C-reactive protein and alanine aminotransferase were increased during hospitalization. Conversely, in recovered COVID-19 subjects, the relative expression of miR-199, miR-203, and miR-181 were increased and the levels of C-reactive protein and alanine aminotransferase were decreased during hospitalization. Conclusions: The expression pattern of neuroinflammatory miRNAs is depends on whether the COVID-19 patient is recovering or deteriorating. Their expression is down-regulated in not-recovered COVID-19 patients and up-regulated in recovered COVID-19 patients.