Long non-coding RNAs (lncRNA) play critical roles in pathogenesis of neurodegenerative diseases. Human plasma carries lncRNAs that are stable in the blood, and their disease-specific profile have made them valuable biomarkers for some diseases. This study reports screening of the plasma levels of 90 lncRNAs in patients with Alzheimer disease (AD) to find out plasma-based AD biomarkers. Total RNA was isolated from plasma samples of 50 AD and 50 matched healthy controls. The plasma samples of 10 advanced AD patients and 10 matched healthy controls were screened for expression levels of 90 lncRNAs using Human LncRNA Profiler qPCR Array Kit (SBI). Based on the profiling results, lncRNAs BC200, NDM29, NEAT1, FAS-AS1 and GAS5-AS1 were selected for further analysis in all samples and their biomarker potency was evaluated by ROC curve analysis. We further surveyed RNAseq data by in silico analysis. We found that the NEAT1 and BC200 levels in the plasma of the AD patients were significantly higher compared with the control group (P=0.0021, p= 0.02, respectively). ROC curve analysis showed that the plasma level of NEAT1 and BC200 discriminated AD patients from healthy controls with sensitivity of 72 % and 60 %, and specificity of 84 % and 91 % respectively. Moreover, NEAT1 discriminated MCI (60 % sensitivity and 91 % specificity) and advanced-AD patients from healthy controls (73 % sensitivity and 71 % specificity). Besides, plasma level of BC200 discriminated the pre-clinical subjects from healthy controls with 83 % sensitivity and 66 % specificity. A positive correlation was also observed between plasma levels of BC200 with the age patients (r = 0.34, p=0.02). In silico RNAseq data analysis showed that a total of 33 lncRNAs were up-regulated but 13 lncRNAs were down-regulated significantly in AD patients compared with the healthy controls. In conclusion, this study elucidated that the plasma levels of lncRNAs NEAT1 and BC200 might be considered as potential blood-based biomarkers for AD development and progression.
Introduction. Previous studies have shown that stromal-derived factor-1 (CXCL12) and its receptor, CXCR4, play a crucial role in metastasis of various tumors. Similarly, it has been cleared that CXCR4 is expressed on the cell surface of gastric cancers. However, nuclear expression of CXCR4 and its clinical importance have not been yet studied. Materials and Methods. Herein, we studied the expression of CXCR4 in gastric samples from patients with gastric adenocarcinoma as well as human gastric carcinoma cell line, AGS, by employing RT-PCR, immunohistochemistry, and flow cytometry techniques. Results. RT-PCR data showed that CXCR4 is highly expressed on AGS cells. This was confirmed by IHC and FACS as CXCR4 was detected on cell membrane, in cytoplasm, and in nucleus of AGS cells. Moreover, we found that both cytoplasmic and nuclear CXCR4 are strongly expressed in primary gastric cancer and the cytoplasmic pattern of CXCR4 tends to be associated with a shorter overall survival than nuclear staining. In conclusion, we present evidence for the first time that both cytoplasmic and nuclear expression of CXCR4 are detectable in gastric cancer tissues. However, the role of both cytoplasmic and nuclear CXCR4 needs to be further elucidated.
Background: Dendrosomal nano-curcumin (DNC) represents an enormous potential to serve as a therapeutic anticancer agent. Here, we investigated the effect of DNC on wild type- and p53-mutant breast cancer cells. Methods: MCF-7 and T47D cells were treated with DNC and investigated for cell viability through MTT assay. The mode of death was analyzed using Annexin V/FITC staining and PARP cleavage assays. Flow cytometric efflux and cell swelling tests were employed to assess the p-glycoprotein (P-gp) transporter activity. Moreover, real-time PCR was employed to study the expression of Bax, Bcl-2 as well as survivin and its ΔEx3 splicing variant. Results: Our findings confirmed that DNC repressed cancer cell proliferation by induction of apoptosis. Additionally, DNC significantly modulated P-gp function that might lead to improved cellular permanence of curcumin. Malfunction of P-gp activity by DNC demonstrates its capability in reducing the drug resistance of p53-mutant cancer cells. Conclusions: In conclusion, our findings demonstrated that dendrosomal nano-curcumin could be considered an anti-tumor therapeutic for p53-mutant tumor malignancies.
Background: Colon cancer has been a rising health concern in the modern world for quite some time. Considering the harmful side effects of chemotherapy, the most common treatment for this cancer, new treatment methods are required to lessen the side effects of treatment on patients. Traditional and herbal medicine can help in this effort. Objectives: Our study investigated the antiproliferative and pro-apoptotic effects of Linum usitatissimum seed aqueous extract on colon cancer and the expression of apoptotic genes compared to normal cell lines to reduce chemotherapy's harmful and irreversible side effects on colon cancer patients. Methods: MTT assay was used to determine the cytotoxicity of our extract on LS174T and COLO205 cells. Cancer and normal cell lines were treated with 2, 4, 6, and 8 mg/mL of LU extract for 24 and 48 hours. RNA extraction was performed, and mRNAs were reverse transcribed to cDNAs using RT-PCR. qPCR was then performed to assess the expression of BAX and BAD genes. Results: MTT assay concluded that this extract has a good cytotoxic effect on LS174t and COLO205 cell lines and can decrease cell viability, while no significant decrease in cell viability was observed in normal cells. For qPCR assay, the cells were treated with 0.5, 1, and 2 mg/mL of LU extract for two days. The qPCR analysis revealed that the expression of pro-apoptotic BAX and BAD was significantly decreased following treatment with our extract, while the expression of these genes showed no significant changes in normal cell lines after the same treatment. Conclusions: These results show that the components within L. usitatissimum seed aqueous extract have antiproliferative and pro-apoptotic properties. This extract can successfully decrease the population of LS174t and COLO205 cells while increasing the expression of pro-apoptotic BAX and BAD in these cell lines. The results also demonstrate that normal non-cancerous cells are unharmed by this extract. These results hint at some potential anti-cancer properties of L. usitatissimum seed aqueous extract.
Background and Aim: Recurrent spontaneous abortion (RSA) is the most common complication of pregnancy that refers to two or more miscarriages before the 20 th week of pregnancy. HLA-G immunoglobulin molecule plays an important role in protecting the fetus against mother's immune system. The aim of this study was to investigate the association between rs1632943 and rs1736932 polymorphisms with recurrent spontaneous abortion in Northwest of Iran. Materials and Methods: This case-control study included 100 women with history of RSA as our case group and 80 healthy women with one or more than one children as the control group. Genomic DNA was purified from their peripheral blood samples and their genotypes were determined by PCR-sequencing method. Using SPSS 16, statistical analysis was performed by chi-square test. Results: In rs1632943 polymorphism the frequency of CC, CA and AA genotypes were 8%, 33% and 59% in the patient group and 16.25%, 43.75% and % 40 in the control group, respectively. Statistical analysis showed that AA genotype was associated with the recurrent spontaneous abortion (P = 0.005). In the rs1736932 polymorphism, the frequency of CC, CG and GG genotypes were 8%, 32% and 60% in the patient group and 17.5%, 41.25% and 41.25% in the control group, respectively. Statistical analysis showed that GG genotype was associated with the recurrent miscarriage (P = 0.005). Also, haplotype analysis showed that H1 haplotype (GA) is associated with the disorder. Conclusion:Results of the study showed that rs1632943 and ra1736932 polymorphisms might be considered as risk factors for RSA in the women in Northwest of Iran.
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