Background: MicroRNAs (miRNAs) are small noncoding RNAs whose function as modulators of gene expression is crucial for the proper control of cell growth. Although many microRNAs were found to express in central nervous system (CNS), the role of the regulatory networks in which they are involved and their function in the pathological process of nerve cells are only just emerging. In the present study, the possible mechanisms by which one neuronal miRNAs, miR-125b, affected the growth of nervous cells were investigated using in vitro cell line model. Methods: The expression pattern of miR-125b in ATRA-treated human glioma cell lines was detected by Northern blotting and in situ localization. The effect of miR-125b on the proliferation and apoptosis of human glioma cells was analyzed by MTS assay, TUNEL and Flow cytometry analysis. In addition, the identification of target gene of miR-125b was studied by dual-luciferase activity assay and Immunoblot Analysis. Results: We found differential expression of miR-125b in 1.0 μM all-trans-retinoic acid (ATRA)-treated human glioma cell lines. Up-regulation of miR-125b partially restored cell viability and inhibited cell apoptosis in U343 cells treated by ATRA. Down-regulation of miR-125b decreased human glioma cells proliferation and enhanced the sensitivity of human glioma cells to ATRA-induced apoptosis. In addition, we found an inverse relationship between the expression of miR-125b and the cell apoptosis-related protein Bcl-2 modifying factor (Bmf), and miR-125b can interact with 3′-untranslated region (UTR) of Bmf. Conclusion: These findings indicate that overexpression of miR-125b promotes human glioma cell proliferation and inhibits ATRA-induced cell apoptosis and low expression of miR-125b sensitizes cells to ATRA-induced apoptosis. BMF may play an important role in the process of miR-125b influencing cell apoptosis.

BackgroundKey innovations have facilitated novel niche utilization, such as the movement of the algal predecessors of land plants into terrestrial habitats where drastic fluctuations in light intensity, ultraviolet radiation and water limitation required a number of adaptations. The NDH (NADH dehydrogenase-like) complex of Viridiplantae plastids participates in adapting the photosynthetic response to environmental stress, suggesting its involvement in the transition to terrestrial habitats. Although relatively rare, the loss or pseudogenization of plastid NDH genes is widely distributed across diverse lineages of photoautotrophic seed plants and mutants/transgenics lacking NDH function demonstrate little difference from wild type under non-stressed conditions. This study analyzes large transcriptomic and genomic datasets to evaluate the persistence and loss of NDH expression across plants.ResultsNuclear expression profiles showed accretion of the NDH gene complement at key transitions in land plant evolution, such as the transition to land and at the base of the angiosperm lineage. While detection of transcripts for a selection of non-NDH, photosynthesis related proteins was independent of the state of NDH, coordinate, lineage-specific loss of plastid NDH genes and expression of nuclear-encoded NDH subunits was documented in Pinaceae, gnetophytes, Orchidaceae and Geraniales confirming the independent and complete loss of NDH in these diverse seed plant taxa.ConclusionThe broad phylogenetic distribution of NDH loss and the subtle phenotypes of mutants suggest that the NDH complex is of limited biological significance in contemporary plants. While NDH activity appears dispensable under favorable conditions, there were likely sufficiently frequent episodes of abiotic stress affecting terrestrial habitats to allow the retention of NDH activity. These findings reveal genetic factors influencing plant/environment interactions in a changing climate through 450 million years of land plant evolution.Electronic supplementary materialThe online version of this article (doi:10.1186/s12870-015-0484-7) contains supplementary material, which is available to authorized users.

Abstract. Glioblastoma multiforme (GBM) demonstrates an unsatisfactory clinical prognosis due to the intrinsic or acquired resistance to temozolomide (TMZ) exhibited by the tumors. One possible cause of TMZ resistance in GBM is the overexpression of O 6 -methylguanine-DNA methyltransferase (MGMT), which can repair the TMZ-induced guanine damage in DNA. Additionally, excessive activated NF-κB is reported to be a component of the major inflammatory transcription pathway that is associated with TMZ resistance in GBM. However, the association between the NF-κB pathway and MGMT expression in GBM cells is unknown. Therefore, in the present study, the TMZ resistant (TR) U251 cell line (TR/U251) was successfully constructed to detect how the TR/U251 cell line and the parental U251 cell line each interact with TMZ in vitro. The TR/U251 cells were approximately five times more resistant to TMZ compared with the parental cells. Furthermore, it was found that the NF-κB inhibitor BAY 11-7082 suppressed the expression of MGMT in TR/U251 cells and enhanced TMZ-induced cytotoxicity and apoptosis, thereby indicating that the NF-κB pathway and MGMT interact to promote TMZ resistance. The inhibition of NF-κB may be a promising strategy to reverse drug resistance in TR glioma cells. The present results propose a potential mechanism for using the NF-κB inhibitor BAY 11-7082 as a potential therapy for the treatment of TR glioma. Although BAY 11-7082 is a well-known NF-κB inhibitor, the present study further investigated its underlying mechanisms through a series of new experiments.

The implantation process is complex, requiring reciprocal interactions between implantation-competent blastocysts and the receptive uterus. There were reports to show that some microRNAs (miRNAs) may play a key role during embryo implantation in mouse. However, the miR-320 expression profiles in the rat uterus during peri-implantation are unknown. In the present study, we found that the expression level of miR-320 was lower on day 5 of gestation (g.d. 5) in rats than g.d.3 and g.d.4 and restored gradually from g.d.6. MiR-320 was specifically localized in glandular and luminal epithelia and decidua. The expression of miR-320 was not significantly different in the pseudopregnant uterus and decreased in the uteri of rats subjected to activation of delayed implantation. Artificial decidualization and treatment with progesterone increased the miR-320 expression. Thus, miR-320 was differentially expressed in the rat uterus during implantation. The expression level was affected by active blastocysts and decidualization during the window of implantation. Steroid hormones, progesterone stimulated miR-320 expression.

Embryo implantation is a complex initial step in establishment of a successful pregnancy. Many mRNAs have been shown to be differentially expressed in the rat uterus during embryo implantation. However, the expression profiles of microRNAs (miRNAs), a key post-transcriptional regulator of gene expression, in the rat uterus between the pre-receptive and receptive phases are still unknown. Here, an miRNA microarray was used to examine differential expression of miRNAs in the rat uterus between the pre-receptive and receptive phases. Twenty-eight miRNAs were up-regulated and 29 miRNAs were down-regulated at least twofold during the receptive phase in rat uterus; these results were confirmed by Northern blotting. miR-29a was only highly expressed in rat uterus during the implantation period, and activation of delayed implantation and artificial decidualization enhanced the miR-29a level. Further investigation revealed that both the pro-apoptotic factor genes Bak1 and Bmf and the anti-apoptotic factor gene Bcl-w are targets of miR-29a. There was weak binding between miR-29a and the 3 0 UTR of the anti-apoptotic factor gene Mcl1. Over-expression of miR-29a inhibited the late apoptosis of endometrial stromal cells, which may be due to the stronger binding capacity between miR-29a and the 3 0 UTR of pro-apoptotic factors than that between miR-29a and the 3 0 UTR of anti-apoptotic factors. Collectively, miR-29a plays an important role during embryo implantation by regulating both pro-apoptotic and anti-apoptotic factors. miR-29a may predominantly bind pro-apoptotic factors, leading to inhibition of cell apoptosis.

Abstract. Mammalian embryonic implantation requires reciprocal interactions between implantation-competent blastocysts and a receptive uterus. Some microRNAs might play a key role during embryo implantation in the mouse, but the let-7a expression profiles in the rat uterus during peri-implantation are unknown. In the study, the expression of let-7a in the uterus during early pregnancy, pseudopregnancy, artificial decidualization and activation of delayed implantation was detected by Northern blotting and in situ hybridization. The effect of steroid hormones on let-7a expression was also detected by Northern blotting and in situ hybridization. Here, we found that the expression level of let-7a was higher on gestation day 6-7 (g.d. 6-7) in rats than on g.d. 4-5 and g.d.8-9. Let-7a was specifically localized in glandular and luminal epithelia and decidua. The expression of let-7a was not significantly different in the pseudopregnant uterus and increased significantly in the uteri of rats subjected to artificial decidualization and activation of delayed implantation. Treatment with estradiol-17β or progesterone significantly increased let-7a expression. Thus, let-7a expression was significantly induced by the process of embryo invasion, and this increased expression level was mainly induced by active blastocysts and decidualization during the window of implantation, implying that let-7a may participate in endometrial decidualization. Steroid hormones, estradiol-17β or progesterone stimulated let-7a expression. Key words: Embryo implantation, Hormone, Let-7a, Rat, Uterus (J. Reprod. Dev. 56: [73][74][75][76][77][78] 2010) ammalian implantation is a highly coordinated sequence of events that begins with the attachment of an embryo to the uterine luminal epithelium and ultimately results in formation of the placenta. The fertilized ova arrive in the rat uterus as blastocysts about 4.5 days after mating and uterine closure, embryo implantation can be initiated on day 5.5 and completed on day 7.75 [1,2]. Implantation of the embryo into the uterine wall is regulated by various factors including matrix metalloproteinases [3], hormones [4], cytokines [5] and integrins [6]. Although many molecules are now known to be involved in the process, the specific mechanisms associated with the onset of uterine receptivity remain to be determined.MicroRNAs (miRNAs) are small noncoding RNAs whose function as modulators of gene expression is crucial for proper control of cell growth and are known to participate in mouse embryo implantation [7,8]. The let-7 family is expressed differentially in the mouse uterus during the peri-implantation period [7,8]. Let-7a was initially found to regulate developmental timing in Caenorhabditis elegans [9]. Our previous study showed that let-7a is expressed differentially during follicular development in the mouse [10]. In humans, it plays an important role in the onset and development of forms of cancer [11,12]. Embryo implantation shares similar phenomena and mechanisms with tumor invasion [13].Th...

Interleukin-10 (IL-10) is a multifunctional cytokine which participates in the development and progression of various malignant tumors. To date, a number of case–control studies were conducted to detect the association between IL-10-592C>A polymorphism and cancer risk in humans. However, the results of these studies on the association remain conflicting. In an effort to solve this controversy, we performed a meta-analysis based on 70 case–control studies from 65 articles, including 16 785 cancer cases and 19 713 controls. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. The overall results suggested that the variant homozygote genotype AA of the IL-10-592C>A polymorphism was associated with a moderately decreased risk of all cancer types (OR = 0.90, 95% CI = 0.83–0.98 for homozygote comparison, OR = 0.92, 95% CI = 0.86–0.98 for recessive model). In the stratified analyses, the risk remained for studies of smoking-related cancer, Asian populations and hospital-based studies. These results suggested that the IL-10-592C>A polymorphism might contribute to the cancer susceptibility, especially in smoking-related cancer, Asians and hospital-based studies. Further studies are needed to confirm the relationship.

<b><i>Purpose:</i></b> To evaluate the association between dyslipidemia and nephrolithiasis risk in a Chinese population. <b><i>Materials and Methods:</i></b> Fasting plasma lipid profiles were measured in a case-control study of 540 nephrolithiasis cases and 656 kidney stone-free controls. <b><i>Results:</i></b> Triglycerides (TG) levels were significantly higher, but total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were significantly lower in nephrolithiasis patients than those in the control group (each <i>p</i> &#x3c; 0.05). Similar associations were found in both primary and recurrent nephrolithiasis patients except for TC levels. Significantly lower TC and LDL-C levels were found in all patients except those with uric acid stones. Patients with calcium oxalate (CaOx) and uric acid stones had significantly higher TG levels. Individuals with hypertriglyceridemia and low HDL-cholesterolemia were associated with increased risk of nephrolithiasis (OR 1.31, 95% CI 1.01–1.71 and OR 7.57, 95% CI 5.64–10.17, respectively). Conversely, those with hypercholesterolemia and high LDL-cholesterolemia were associated with decreased nephrolithiasis risk (OR 0.60, 95% CI 0.46–0.79 and OR 0.61, 95% CI 0.42–0.90, respectively). The risk remained in patients with CaOx stones. <b><i>Conclusions:</i></b> Our results suggest that dyslipidemia was associated with nephrolithiasis risk in a Chinese population, especially in patients with CaOx stones.