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Objective(s): Autophagy is an intracellular degradation system of damaged proteins and organelles; however, the role of autophagy in the progression of cancer remains unclear. In recent years, mesenchymal stem cell (MSC)-based approaches have attracted considerable attention for anti-cancer therapy. The present study aimed to examine the interaction of MSCs with the breast cancer cells under autophagy-induced conditions. Materials and Methods: In this study, MSCs isolated from human adipose tissue were co-cultured with MDA-MB 231, a breast cancer cell line, and the autophagy process was induced by tunicamycin treatment. The cell viability was monitored by the MTT assay, and the cells were recovered at different time intervals (24 or 48 hours) to determine autophagy markers such as Beclin, mTOR and the ratio of LC3II/I expression. Additionally, the animal study was conducted using a mouse model of breast cancer treated with isogenic adipose-derived MSCs, and the expression of Beclin and Ki67 was determined using immunohistochemistry in breast tumor tissue. Results: In cancer cells co-cultured with MSCs, the cell proliferation was increased, the Beclin expression and the LC3II/I protein ratio were decreased, and the mTOR expression was increased in MDA-MB 231 upon co-cultured with MSCs. Direct injection of MSCs to a mouse model of breast cancer showed an increase in tumor volume, an increase in the accumulation of Ki67 and a decrease in the Beclin expression in tumor tissues. Conclusion: The data may suggest that suppressed autophagy in breast cancer cells is probably a mechanism by which MSCs can induce cancer cell proliferation. [ABSTRACT FROM AUTHOR]

Background and purpose: Breast cancer (BC) is one of the major causes of female cancer-related death. It has recently been demonstrated that metabolic reprogramming including alteration in lipid metabolism is indicated in various types of cancer. The enzymes of the acyl-coenzyme A synthetase long-chain family (ACSLs) are responsible for converting fatty acids to their corresponding fatty acyl-coenzyme A esters which are essential for some lipid metabolism pathways. ACSL4 is one of the isoforms of ACSLs and has a marked preference for arachidonic and eicosapentaenoic acids. The objective of this study was to evaluate ACSL4 expression, its prognostic significance, and its correlation with p53 tumor suppressor in BC patients. Experimental approach: In this study 55 pairs of fresh samples of BC and adjacent non-cancerous tissue were used to analyze ACSL4 expression, using real-time polymerase chain reaction and immunohistochemistry (IHC) staining. The expression of other studied variables was also examined using the IHC technique. Findings / Results: ACSL4 expression was significantly higher in BC tissues compared to the adjacent normal tissue. This upregulation was negatively correlated with Ki-67 and age, and positively correlated with p53 status. The correlation between ACSL4 and p53 may indicate the role of p53 in the regulation of lipid metabolism in cancer cells, in addition to its role in the regulation of ferroptosis cell death. Conclusion and implications: Our results indicated that the expression of ACSL4 may be considered as a prognostic indicator and potential therapeutic target in BC. However, further studies are needed to confirm the significance of these findings. [ABSTRACT FROM AUTHOR]

Statement of the Problem: Periodontal diseases are complex oral diseases characterized by bacterial-induced inflammatory destruction of tooth-supporting tissues. Porphyromonas gingivalis (P. gingivalis) is a common gram-negative anaerobic oral bacteria strongly associated with periodontal disease. Purpose: The present study was conducted to estimate prevalence of P. gingivalis in patients with periodontal diseases by using meta-analysis method. Martials and Method: Different databases including PubMed, EmBase, Scopus, the Institute for Scientific Information (ISI) Web of Science, and the Cochrane Library were searched to identify original English-language studies addressing prevalence of P. gingivalis in periodontal diseases up to December 2014. The random effects model was applied in the meta-analysis and the heterogeneity between studies was assessed using a Cochran test and the I2 index. Funnel plots and Egger test were used to examine publication bias. Statistical analyses were performed using STATA version 12. Results: Forty-two eligible studies published during 1993- 2016 were selected for meta-analysis. Considering all the included studies, the total sample size was 5,884 individuals containing 2,576 healthy people with a mean age of 37.21±7.45 years and 3,308 periodontal patients with a mean age of 44.16±8.35 years. Overall, the prevalence of P. gingivalis was 78% [95% CI: 74-81] in periodontal diseases group and 34% [95% CI: 26-41] in healthy individuals. There was a significantly higher prevalence of P.gingivalis in individuals with periodontal diseases compared to healthy subjects [78% versus 34%, respectively]. Conclusion: This study indicates that P. gingivalis is highly present in subjects with periodontal diseases and it also appears in periodontally healthy people, although to a lesser extent. Thus, the presence of P. gingivalis increases the chance of periodontal disease and it can be considered as a main potential risk factor. [ABSTRACT FROM AUTHOR]

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]

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.