parisa lotfinejad
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Programmed Cell Death Ligand 1-Inhibiting MicroRNAs in Hepatocellular Carcinoma: A Systematic Review
The Programmed cell death ligand-1 (PD-L1), an immune checkpoint molecule, is the ligand of Programmed cell death protein 1 (PD-1). They are crucial molecules in maintaining immune homeostasis. PD-L1/PD-1 axis regulates the initiation and maintenance of tolerance and protects tissues from autoimmune responses; however, cancer cells can use the PD-1/PD-1 axis to evade the anti-tumor response of immune cells. Increased PD-L1 expression is directly associated with poor prognosis in hepatocellular carcinoma (HCC). Although immunotherapy with immune checkpoint inhibitors (ICIs) are leading therapy in cancer treatment, using biomarkers to regulate immune checkpoints at the RNA level is considered a promising tool in novel therapeutic approaches. Increasing evidence has reported that miRNAs are critical regulators of tumor development. Hence, we performed a current systematic review to explore PD-L1 inhibiting miRNAs involved in hepatocellular carcinoma. Five databases were systemically searched to obtain the relevant original articles. Consequently, seventeen studies were included in the current systematic review. According to obtained literatures, some microRNAs, namely miR-194-5p, -675-5p, 194-5p, -1, -455-5p, -223-3p, -513, -195, -506, -329-3p, -424, -411-5p, -182-5p, -200, -378a-3p, -570, -200c, and -513a-5p can inhibit PD-L1 expression in HCC cells. These can ultimately reduce tumor proliferation, inhibit tumor migration, stimulate the chemosensitivity of cancer cells, and induce apoptosis in tumor cells. Moreover, the investigated miRNAs were further analyzed using miRNA target prediction online tools to highlight the future direction of their functions in HCC.
Keywords: Hepatocellular carcinoma (HCC), In silico study, MicroRNA, Programmed death-ligand 1 (PD-L1) -
The new coronavirus was first reported in China and caused a widespread global outbreak of pneumonia that spread rapidly across this country and many other countries. Acute kidney injury is one of the important complications of COVID-19, which has been shown in some cases. Exploring the diagnostic features of biomarkers of kidney function in COVID-19 patients may lead to better patient management. We collected laboratory data from 206 people with confirmed COVID-19 disease and evaluated their renal biomarkers, Blood Urea Nitrogen (BUN), and creatinine. The age range of the patients was almost 62 years old. The mean age in the dead patients and recovered patients was 71 and 54 years old, respectively. The average LDH value was 755 U/L, and creatine phosphokinase (CPK) was 267 U/L in the patients. The average BUN was 59.1 U/L, and creatinine was 1.5 U/L in COVID-2019 patients. Among all 193 patients, laboratory results revealed that 163 (85.4 %) patients had an elevated BUN level. Based on creatinine levels for total patients, laboratory results revealed that 49 (25.4 %) patients had an elevated value. The average BUN value in dead patients was 85 mg/dL, while in recovered patients was 40.5 mg/dL (P<0.0001). Also, the average creatinine level in dead patients was 1.86 mg/dL, while in recovered patients was 1.24 mg/dL (P=0.0004). Inflammation following COVID-19 disease causes kidney damage and elevated urea and creatinine levels, which may increase the risk of death in these patients.
Keywords: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Coronavirus disease 2019 (COVID-19), Kidney injury, Renal biomarkers, Blood urea nitrogen, Creatinine -
Many studies have been performed about regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs) and their application in different treatment approaches. The present study aimed to investigate the immunomodulatory effect of umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) on the gene expression profile of cytokines in stimulated T-lymphocytes. For this purpose, MSCs were isolated from umbilical cord blood samplesand cultured in Dulbecco's Modified Eagle Medium supplemented with 10% fetal bovine serum. The nature of MSCs was identified by flow cytometry analysis and differentiation to the adipocyte and osteocyte lineage. Moreover, to investigate the immunomodulatory effects of MSCs on T cells, a co-culture system was designed and expression levels of interleukin (IL)2, IL4, IL-6, IL-10, IL13, interferongamma (IFNγ), tumor necrosis factoralpha (TNFα), and transforming growth factorbeta (TGFβ) genes were measured; using the real-time polymerase chain reaction (RT-PCR) technique. Our results demonstrated the ability of MSCs to differentiate into adipocyte and osteocyte lineages. Further investigation also displayed that although UCB-MSCs could significantly reduce the expression of pro-inflammatory cytokines like IL2, IL6, IFNγ, and TNFα in activated T-lymphocytes, they noticeably potentiated the expression levels of IL4, IL10, IL13, and TGFβ in the co-culture setting. In conclusion, UCB-MSCs have immunomodulatory effects on activated T-lymphocytes in favor of anti-inflammatory responses.
Keywords: Cytokines, Immunomodulation, Mesenchymal stem cells, T-lymphocytes -
Objectives
Electromagnetic fields (EMFs) are developing in scientific areas while biologic and immunologic effects have been proven in many studies. The purpose of the present study was to determine the effect of 50 Hz EMFs in the manner of the whole body exposure on the T-helper balance (Th1/Th2) in rats.
Materials and MethodsThis experimental research evaluated the impact of the EMF on T-helper balance, including 30 rats that were randomly divided into 3 groups. The control group and experimental groups were exposed to 50 Hz EMF with the intensity of 0.5 mT for one and two month(s), respectively. At the end of the exposure period, blood samples were collected from the left ventricle of the hearts of the rats and the serum levels of interleukin 4 (IL-4) and interferon gamma (INF-γ) were measured by the enzyme-linked immunosorbent assay and compared in all three groups.
ResultsThe level of IL-4 and INF-γ showed a notable change (P=0.032) during one month of EMF exposure, indicating a shift of T-helper balance toward the Th2 arm, meaning more strong allergic reactions and weaker immune responses against tumors and many other diseases. After 2 months, the levels of cytokines and the balance of the T-helper came close to the baseline (the control group samples), representing the adaptive trends of T-helper balance in longer exposures.
ConclusionsThe results of the present research revealed that EMFs produced important changes in IL-4 and INF-γ levels and affected the T-helper balance shift toward the Th2 arm, implying stronger allergic reactions and weaker defense against tumor and various other diseases. However, understanding the true nature of these changes and their actual health effects requires further studies.
Keywords: Electromagnetic radiation, Immunity, IL-4, INF-γ
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