Search

Objective(s): IL-12 as an anti-tumor cytokine and IL-33 a novel identified cytokine with both pro- or anti-tumor activities, play important roles in response against tumor cells. Our aim was to evaluate the IL-12 and IL-33 levels and single nucleotide polymorphisms (SNP) in their genes in patients with breast cancer. Materials and Methods: Blood samples were collected from 100 patients with breast cancer, and 100 healthy women were controls. The serum IL-12 and IL-33 levels were measured by ELISA. The SNP rs3212227 (in IL-12 gene) and rs 1929992 (in IL-33 gene) were determined using PCR-RFLP. Results: The IL-12 levels similarly expressed in patients and controls. IL-12 levels in patients at stage1 were significantly lower than in the healthy group (P<0.05). IL-33 levels and the IL-33/IL-33/IL-12 ratio in stage IV patients were significantly higher than other stages and controls (P<0.0001 and P<0.001, respectively). There were no significant differences in the frequencies of genotypes in rs3212227 and res1929992 between patients and the control group. No sigficant differences were observed between subjects with various genotypes at rs3212227 and res1929992 with respect to related cytokine levels. Conclusion: These results indicate that the diminished IL-12 production may contribute to the tumor establishment. The higher IL-33 levels and IL-33/IL-12 ratio in patients also indicate an imbalance in Th1/Th2 responses that may contribute to tumor development. Thus, correcting the imbalance of Th1/Th2 could be an important strategy for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Pre-eclampsia, a hypertensive disorder of pregnancy is the main cause of fetal and maternal morbidity and mortality. Growing evidences suggest that placental oxidative stress involves in the pathogenesis of pre-eclampsia. The HSP70 is a novel marker of oxidative stress which binds with high avidity to LOX-1. The aim of this study was to evaluate the co-expression of HSP70 and LOX-1 in the placental tissues of normotensive and pre-eclamptic pregnancies. Materials and methods: The placental tissues were collected from 35 healthy women with normal pregnancies and 33 women with pre-eclampsia disorder. Expression of HSP70 and LOX-1 on the placental tissues was examined by using immunohistochemistry technique. The intensity of the molecules' expression was determined by semi-quantitative scoring. Results: The 34.3% and 37.1% of the healthy women did not express the HSP70 and LOX-1 on their placenta, respectively. All pre-eclamptic patients expressed HSP70 and LOX-1 with various scores. Indeed, the majority of the pre-eclamptic subjects had ≥3+ scores of the expression of HSP70 and LOX-1 on their placenta (60.6% and 66.7%, respectively). The percentage of the ≥3+ scores of the expression of HSP70 and LOX-1 was significantly higher in patients than those in healthy women ( p < 0.0001 for both). Similarly, the majority of the pre-eclamptic subjects had ≥3+ scores of the co-expression of HSP70 and LOX-1 molecules (57.6%) which was significantly higher in patients than those in control group ( p = 0.0001). Conclusions: These results showed higher expression of HSP70 and LOX-1 in the placental tissues of pre-eclampsia patients which represent the possible contribution of these molecules in the disease pathogenesis. Further studies need to clarify their role in the pathogenesis of preeclampsia disorder. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the effects of natural adjuvants ( G2  and  PC ) to activate natural killer cells in colorectal cancer., Background: Natural killer (NK) cells are an element of the innate immune system that can recognize and kill cancer cells and provide hope for cancer therapy. One of the current methods in cancer immunotherapy is NK cell therapy. Immunotherapy with NK cells has been limited because of the low number and cytotoxicity level of NK cells. Natural adjuvants such as PC and G2 may stimulate the immune system. It seems that these adjuvants could increase cytotoxic NK cells., Methods: Twelve patients with colorectal cancer and six healthy individuals qualified for inclusion in this study. Peripheral blood mononuclear cells (PBMCs) from each patient with two distinctive concentrations (10 5 and 5×10 4 cells/well) were treated with Interleukin2 (IL2), PC , and G2 adjuvant separately. The NK cell's surface markers, including CD16, CD56, and NKG2D, were evaluated by flow cytometry. The cytotoxicity effect of treated PBMCs as effector cells against NK sensitive cell line (K562) was assessed using the LDH assay method., Results: The results revealed a significant increase in the level of CD16+NKG2D+ NK cells in PBMCs treated with the G2 group compared with the control group in CRC PBMC ( p <0.001) as well as the normal PBMC group ( p < 0.01). In addition, the results indicated a significant increase in the level of CD56+NKG2D+ cells in the PBMC treated with PC ( p < 0.05) and G2 ( p < 0.001) groups compared with the PBMC group. The cytotoxicity result of PBMC from CRC patients in 10:1 ratio of the effector: target showed that the cells ' cytotoxicity in the PBMCs treated with PC ( p <0.01) and G2 ( p <0.05) was significantly higher than the untreated PBMC., Conclusion: According to the result of this study, it can be stated that the PC and G2 adjuvants could be candidates for inducing cytotoxic natural killer cells., Competing Interests: The authors declare that they have no conflict of interest., (©2022 RIGLD, Research Institute for Gastroenterology and Liver Diseases.)

MicroRNAs (miRNAs) involved in regulation of the genes. The CCAAT/enhancer-binding protein-α ( CEBPα ) is a crucial transcription factor for normal hematopoiesis and cell cycle that frequently disrupted in human acute myeloid leukemia (AML). The miR-182 up-regulation in several malignant diseases such as AML was reported, in the other hand bioinformatics analysis revealed CEBPα targeted by miR-182.miR-182-5p inhibition in human acute promyelocytic leukemia (APL) cell line was performed by using locked nucleic acid (LNA) and subsequently miR-182-5p and CEBPα expression, apoptosis, necrosis and cell proliferation were measured. After LNA-anti-miR-182-5p transfection to cells at different time points, miR-182-5p down regulation and CEBPα overexpression was revealed in the LNA-anti-miR group compared to the control groups. The cell viability was meaningfully varied between LNA-anti-miR and control groups. Increasing of the apoptotic ratio was linked to miR-182-5p inhibition in the LNA-anti-miR group rather than other groups. Similarly, the necrotic ratio in the LNA-anti-miR group was higher.Our results supported the hypothesis that miR-182-5p inhibition can reduce the cell viability predominantly due to induces apoptosis and necrosis. The present results can apply in translational medicine for investigation of antisense therapy and drug development in leukemia., Competing Interests: The authors declare that they have no conflict of interest.

Background: Interleukin (IL)-17/IL-23 axis performs a prominent role in the pathogenesis of several autoimmune disorders. This study aimed to investigate the concentrations of IL-17 in patients with multiple sclerosis (MS) and its relationship with gender, medication, disease forms and single nucleotide polymorphisms (SNP) in IL-23R gene, including rs11209026 and rs1004819. Methods: The blood specimens were obtained from 135 healthy individuals and 135 MS patients. The patients exhibited relapsing-remitting (RRMS; n = 65), primary progressive (PPMS; n = 19), secondary progressive (SPMS; n = 35) or progressive relapsing (PRMS; n = 14) MS. The DNA was analyzed for SNPs using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and IL-17 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Results: We have observed elevated serum IL-17 concentrations in MS patients compared with healthy individuals (P < 0.001). The men with MS had higher IL-17 concentrations than women patients (P < 0.050). Untreated patients had significantly higher IL-17 concentrations than healthy individuals and treated patients (P < 0.001 and P < 0.010, respectively). The IL-17 concentrations were significantly decreased in patients treated with interferon-β (IFN-β), methylprednisolone or both drugs as compared with untreated MS patients (P < 0.050, P < 0.020 and P < 0.050, respectively). The IL-17 concentrations were also significantly higher in patients with RRMS and PRMS compared with healthy individuals (P < 0.005 and P < 0.010, respectively). The genetic variations at SNPs rs11209026 and rs1004819 were not significantly different between healthy individuals and patients. The IL-17 concentrations were not influenced by genetic variations at investigated SNPs. Conclusion: These results indicated higher levels of IL-17 in MS patients that may be influenced by disease patterns, medication and gender. No association was observed between investigated SNPs and MS.

Objectives: IL-12 as an anti-tumor cytokine and IL-33 a novel identified cytokine with both pro- or anti-tumor activities, play important roles in response against tumor cells. Our aim was to evaluate the IL-12 and IL-33 levels and single nucleotide polymorphisms (SNP) in their genes in patients with breast cancer., Materials and Methods: Blood samples were collected from 100 patients with breast cancer, and 100 healthy women were controls. The serum IL-12 and IL-33 levels were measured by ELISA. The SNP rs3212227 (in IL-12 gene) and rs1929992 (in IL-33 gene) were determined using PCR-RFLP., Results: The IL-12 levels similarly expressed in patients and controls. IL-12 levels in patients at stage I were significantly lower than in the healthy group (P<0.05). IL-33 levels and the IL-33/IL-12 ratio were significantly higher in patients than the control group (P<0.001). The IL-33 levels and IL-33/IL-12 ratio in stage IV patients were significantly higher than other stages and controls (P<0.0001 and P<0.001, respectively). There were no significant differences in the frequencies of genotypes in rs3212227 and rs1929992 between patients and the control group. No significant differences were observed between subjects with various genotypes at rs3212227 and rs1929992 with respect to related cytokine levels., Conclusion: These results indicate that the diminished IL-12 production may contribute to the tumor establishment. The higher IL-33 levels and IL-33/IL-12 ratio in patients also indicate an imbalance in Th1/Th2 responses that may contribute to tumor development. Thus, correcting the imbalance of Th1/Th2 could be an important strategy for cancer immunotherapy.

Background: Uterine natural killer (uNK) cells are the most abundant leukocytes in pre-implantation endometrium and early pregnancy deciduas in humans and rodents. They are associated with structural changes in maternal spiral arteries but regulation of their recruitment and activation is incompletely understood. The major subpopulation of uNK cells in humans expresses CD56, the neural cell adhesion molecule (NCAM)-1 while their counterpart in mouse expresses asialoGM1, a brain ganglioside. Sympathetic nerves express NCAM-1 which mediates homotypic binding. Sympathetic fibers innervate the mesometrial vasculature but their relationship to the myometrial and decidual uNK cell recruitment is unknown., Objective: The present study aims to explore positional relationship between natural killer cells and distribution of nerves in decidualized mouse uterus., Methods: Immunohistochemistry and mRNA expression for the enzyme tyrosine hydroxylase were used to map sympathetic nerve fibre distribution within C57BL/6 implantation sites and to address a relationship with uNK cells., Results: Tyrosine hydroxylase positive neurons were identified in the mesometrium closely associated with uterine arteries. Staining became gradually vanished as the nerves crossed the myometrium and entered the decidualized uterus. No neuronal stain was associated with the spiral arteries. Periodic Acid Schiff's reactive uNK cells were absent from the mesentery, but abundant in decidua basalis where they are associated with non-innervated vessels., Conclusion: Data suggest that the recruitment of uNK progenitor cells to the uterus is unlikely to be dependent on signaling by the sympathetic nervous system.