Programmed death ligand 1 (PD‐L1) plays a significant role in colorectal tumorigenesis through induction of regulatory T cells (Tregs) and suppression of antitumor immunity. Furthermore, microRNAs (miRNAs) as the posttranscriptional regulators of gene expression show considerable promise as a therapeutic target for colorectal cancer (CRC) treatment. Considering this, in vitro effects of miRNA‐124 (miR‐124‐3p) on CRC cell tumorigenesis and Tregs differentiation via targeting PD‐L1 were investigated in the current study. Functional analysis showed that miR‐124 is significantly downregulated in CRC tissues as compared with marginal normal samples (p < .0001), and its downregulation was negatively correlated with PD‐L1 expression. Moreover, a specific region in PD‐L1 3′‐untranslated region was predicted as the miR‐124 target and validated using the luciferase assay. Further investigation showed that transfection of HT29 and SW480 cells with miR‐124 mimics significantly reduced PD‐L1 mRNA, protein, and cell surface expression, and inhibited Tregs in coculture models via modulating interleukin [IL]‐10, IL‐2, tumor necrosis factor α, transforming growth factor beta, and interferon gamma expression levels. Besides, miR‐124 overexpression decreased CRC cell proliferation and arrested cell cycle at the G1 phase through downregulation of c‐Myc and induced apoptosis in CRC cells via upregulation of both intrinsic and extrinsic pathways. Also, miR‐124 exogenous overexpression could reduce colony and spheroid formation ability of CRC cells via downregulating CD44 mRNA expression. miR‐124 also diminished MMP‐9 expression and subsequently suppressed cell migration and invasion. We also illustrated that STAT3 signaling was repressed by miR‐124 in CRC cells. Taken together, our findings imply that considering the involvement of miR‐124 in the regulation of PD‐L1 through colorectal tumorigenesis and its remarkable antitumor effects, this miRNA could be regarded as the promising target for the development of therapeutic approaches for colorectal cancer.
It seems that defects on micro-minerals levels have an etiologic role involved in type 1 diabetes mellitus pathogenicity. The aim of our study were to evaluate the serum levels of zinc and iron and investigate their possible relationship between these biochemical parameters with demographic conditions and glycemic control in patients with type 1 diabetes mellitus disorder. In this case-control based study , 68 female with type 1 diabetes mellitus with a mean age of 52.2 ± 2 as case group and 122 healthy women as a control group with a mean age of 49/4 ± 3/2 were investigated .for biochemical analysis ,10 mL fasting venous blood sample were obtained from each subjects. FBS (fasting blood glucose), fructosamine (glycemic control parameter) were determined (spectrophotometry method, (pars azmoon, Iran), nitroblue tetrazoline method respectively).serum zinc level with colorimetric method (Biorex-UK) and serum iron with photometric method (pars azmoon, Iran) were determined. Statistical analysis using SPSS software performed. Significant levels considered as P < 0.05. According to this study there is statistically significant difference between serum levels of iron and zinc in patients with type 1 diabetes compared to controls .indeed serum level of iron and zinc had lower level in patient group toward controls. In patients group, there are a positive correlation between age and decreased level of serum zinc (P < 0.05). Also there was a significant negative correlation between the glycemic control status and serum zinc. Other studied parameters concluded BMI (body mass index), Weight and height have not significant difference between groups. The decrease in serum iron and zinc level in women with type 1 diabetes may be related to low dietary intake or increased excretion of micro minerals or the presence of confounding factors that require more extensive intervention studies to confirm it.
On 31st December 2019, 27 cases of pneumonia with unknown etiology were recognized in Wuhan City, Hubei province in China. These patients had clinical symptoms including dyspnea, dry cough, fever, and bilateral lung infiltrates on imaging 1 . However, some patients had different fatal complications such as septic shock, organ failure, severe pneumonia, pulmonary edema, and Acute Respiratory Distress Syndrome (ARDS) 2 . The ARDS is an immunopathologic event. The major mechanism of ARDS is an uncontrolled systemic inflammatory response subsequently releasing pro-inflammatory cytokines such as interleukins (IL), interferons (IFN), chemokines, and tumor necrosis factor (TNF)-α followed by a cytokine storm 3,4 . The agent that causes this status was identified from throat swab samples by the Chinese Centre for Disease Control and Prevention (CCDC) on 7 th January 2020 5 . It named, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses 6 , and coronavirus disease of 2019 (COVID-19) by the World Health Organization (WHO) 5 . On 30 th January 2020, the WHO reported the Chinese prevalence of COVID-19 to be a Public Health Emergency of International Concern 7 .
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