Downregulation of circ-Foxo3 in breast cancer stem-like cells.

OBJECTIVE: Cancer cells having stem cell characteristics are linked to metastasis and relapse in breast cancer. Circ-Foxo3, as a circular RNA, has been linked to the breast cancer lethal traits. This study's objective was to assess circ-Foxo3 expression in breast cancer stem-like cells. After isolation from tumor mass, breast cancer cells were subjected to the reliable in vitro assay of spheroid formation to determine the presence cancer stem cells (CSCs). We used a quantitative real-time polymerase chain reaction to examine circ-Foxo3 expression in spheroids. RESULTS: Circ-Foxo3 expression was significantly downregulated in spheroid-forming tumor cells, according to our data. This study demonstrated that breast CSCs have downregulated circ-Foxo3 expression, which may allow these cells to evade apoptosis. A precise analysis of this circRNA's role could be exploited to develop focused therapeutic approaches to fight breast CSCs.

Vitamin D Receptor gene polymorphisms and susceptibility to type 2 diabetes: evidence from a meta-regression and meta-analysis based on 47 studies.

BACKGROUND: Evidence from various studies suggest that vitamin D receptor (VDR) gene polymorphisms are associated with type 2 diabetes (T2D); However, these results have been disputable. Here we conducted a meta-analysis to comprehensively evaluate the effect of VDR gene polymorphisms and susceptibility to T2D. METHODS: All relevant studies reporting the association between VDR gene polymorphisms and susceptibility to T2D published up to August 2020 were identified by comprehensive systematic database search in web of science, Scopus, and Medline. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure strength of association. The methodological quality of each study was assessed according to the Newcastle-Ottawa Scale. Subgroup and meta-regression analysis were also performed. RESULTS: A total of 47 case-control studies were included in this meta-analysis. The overall population results revealed a significant association between FokI, and BsmI (heterozygote model) polymorphisms and T2D in the overall analysis. However, no association was found with the TaqI and ApaI polymorphisms. Moreover, the pooled results of subgroup analysis by ethnicity suggested significant association between FokI, TaqI, and BsmI polymorphisms and T2D in some subgroups. Meta-regression analyses indicated that none of the publication year, ethnicity, and genotyping method were the source of heterogenicity in all four polymorphisms. CONCLUSIONS: This meta-analysis suggested a significant association between VDR gene FokI, and BsmI (heterozygote model) polymorphisms and T2D susceptibility in overall population and ethnic-specific analysis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-020-00704-z.

FAS-670A＞G gene polymorphism and the risk of allograft rejection after organ transplantation: a systematic review and meta-analysis.

The association between the risk of allograft rejection after organ transplantation and FAS gene polymorphism has been evaluated previously. However, inconsistent results have been reported. Hence, we conducted the most up-to-date meta-analysis to evaluate this association. All eligible studies reporting the association between FAS-670A＞G polymorphism and the risk of allograft rejection published up to December 2019 were extracted using a comprehensive systematic database search in the Web of Science, Scopus, and PubMed. The pooled odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated to determine the association strength. This meta-analysis included six case-control studies with 277 patients who experienced allograft rejection and 1,001 patients who did not experience allograft rejection (controls) after organ transplantation. The overall results showed no significant association between FAS-670A＞G polymorphism and the risk of allograft rejection in five genetic models (dominant model: OR=0.81, 95% CI=0.58‒1.12; recessive model: OR=0.10, 95% CI=0.80‒1.53; allelic model: OR=0.96, 95% CI=0.79‒1.18; GG vs. AA: OR=0.92, 95% CI=0.62‒1.36; and AG vs. AA: OR=0.75, 95% CI=0.52‒1.08). Moreover, subgroup analysis according to ethnicity and age did not reveal statistically significant results. Our findings suggest that FAS-670A＞G polymorphism is not associated with the risk of allograft rejection after organ transplantation.

Interleukin-4 gene polymorphism (C33T) and the risk of the asthma: a meta-analysis based on 24 publications.

BACKGROUND: Previous studies evaluated the association of IL-4 C33T polymorphism and risk of bronchial asthma but failed to establish a consistent conclusive association. In the present meta-analysis, we intend to define a more reliable estimate of the association in the presence of filling published literature. METHODS: An exhaustive search in Web of Science, Scopus, and PubMed databases was performed to identify all relevant publications before September 2020, and 24 publications (28 studies) with 6587 cases and 8408 controls were included in final analysis. The association between polymorphism and risk of asthma were measured by Odd ratios (ORs) and 95% confidence intervals (CIs). Moreover, Cochran's Q and the I2 statistics were used to evaluate the degree of heterogeneity between studies. RESULTS: In the overall study populations, a significant positive association was detected under all genotype models and announced the IL-4 C33T polymorphism as a potential risk factor in the pathogenesis of asthma. In the subgroup analysis by age, a significant association between IL-4 C33T polymorphism and risk of asthma in different age groups was identified in allelic model, which highlighted the predisposing role of the T allele for the asthma risk in all three age groups. Furthermore, the results of subgroup analysis by continent were heterogenous. Accordingly, IL-4 C33T polymorphism was a risk factor in Europeans (all models except heterozygote comparison), Americans (all models except recessive and homozygote comparison) and Asians (just recessive and allelic model). Finally, the ethnicity-specific analysis disclosed a significant association between IL-4 C33T polymorphism and asthma risk in Caucasians (all genotype models except heterozygote comparison), while this association was not significant in African-Americans. CONCLUSIONS: This study suggests that IL-4 C33T polymorphism potentially acts as a risk factor for asthma in different ethnicities and age groups.

Factor V Leiden 1691G > A mutation and the risk of recurrent pregnancy loss (RPL): systematic review and meta-analysis.

BACKGROUND: Although numerous replication case-control studies have attempted to determine the association between Factor V Leiden (FVL) 1691G > A mutation and susceptibility to Recurrent pregnancy loss (RPL), there have been confliction among the results of various ethnic groups. To address this limitation, here we implemented first meta-analysis to provide with consistent conclusion of the association between FVL 1691G > A mutation and RPL risk. METHODS: After a systematic literature search, pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were used to evaluate the strength of the association. Additionally, meta-regression analyses were performed to find potential source of heterogeneity. RESULTS: In this meta-analysis, 62 studies, containing 10,410 cases and 9406 controls, were included in quantitative analysis. Overall population analysis revealed a significant positive association in the dominant (OR = 2.15, 95% CI = 1.84-2.50, P < 0.001), over-dominant (OR = 1.88, 95% CI = 1.61-2.19, P < 0.001), allelic (OR = 2.05, 95% CI = 1.79-2.35, P < 0.001), and heterozygote (OR = 1.97, 95% CI = 1.68-2.30, P < 0.001) models. Moreover, a significant association of dominant (OR = 3.04, 95% CI = 2.04-4.54, P < 0.001), over-dominant (OR = 2.65, 95% CI = 1.74-4.05, P < 0.001), and heterozygote (OR = 2.67, 95% CI = 1.81-4.22, P < 0.001) models was found in the Iranian population. The subgroup analysis indicated strong significant association in Asian, European, Africa population, and case-control studies but not in South Americans and cohort studies. CONCLUSION: The FVL 1691G > A mutation and the risk of RPL confers a genetic contributing factor in increasing the risk of RPL, particularly in Iranians, except for South Americans.