Streptococcus pneumoniae is a Gram-positive, extracellular bacterium that is responsible for significant mortality and morbidity worldwide. Pneumolysin (PLY), a cytolysin produced by all clinical isolates of the pneumococcus, is one of the most important virulence factors of this pathogen. We have previously reported that PLY is an essential factor for activation of caspase-1 and consequent secretion of IL-1β and IL-18 in macrophages infected with S. pneumoniae. However, the host molecular factors involved in caspase-1 activation are still unclear. To further elucidate the mechanism of caspase-1 activation in macrophages infected with S. pneumoniae, we examined the involvement of inflammasomes in inducing this cellular response. Our study revealed that apoptosis-associated speck like protein containing a caspase recruitment domain (ASC), an adaptor protein for inflammasome receptors such as NLR family, pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2), is essentially required for the induction of caspase-1 activation by S. pneumoniae. Caspase-1 activation was partially impaired in NLRP3−/− macrophages, while knockdown and knockout of AIM2 resulted in a clear decrease in caspase-1 activation in response to S. pneumoniae. These results suggest that ASC inflammasomes, including AIM2 and NLRP3, are critical for caspase-1 activation induced by S. pneumoniae. Furthermore, ASC−/− mice were more susceptible than wild-type mice to S. pneumoniae, with impaired secretion of IL-1β and IL-18 into the bronchoalveolar lavage after intranasal infection, suggesting that ASC inflammasomes contribute to the protection of host from infection with PLY-producing S. pneumoniae.

Maternal embryo leucine zipper kinase (MELK) is highly expressed in a variety of malignant tumors and involved in cell cycle regulation, cell proliferation, apoptosis, tumor formation etc However, the biological effects of MELK in cervical cancer are still uninvestigated. This study aimed to explore the expression of MELK in cervical cancer, as well as its effects on the proliferation, apoptosis, DNA damage repair on cervical cancer cell line in vitro and to provide novel ideas for further improving the clinical efficacy of cervical cancer. Immunohistochemistry, Western blot, RT‐qPCR, CCK8, and immunofluorescence techniques were used to detect the expression of MELK in cervical cancer tissues, paracancerous tissues, and cervical cancer cell lines. Several cervical cancer cell lines were treated with MELK knockdown by siRNA and MELK selective inhibitor OTSSP167. The effects on proliferation, apoptosis, and colony formation capacity, and tumor cell DNA damage repair‐related factor were detected in cell lines. Our data showed that the high expression rate of MELK in cervical cancer patients was 56.92%. MELK expression in cervical cancer samples was significantly higher than that in paraneoplastic tissues. Highly expressed MELK correlated with the cervical histopathological grading and greatly increased with the cervical histopathological grading, from normal cervix and cervical intraepithelial neoplasia to cervical cancer. Moreover, the abnormal expression of MELK was related to cervical cancer metastasis at early stage. The knockdown of MELK with siRNA and OTSSP167 had strong inhibition effects on the proliferation, apoptosis, and colony formation of cervical cancer cells. MELK knockdown could also aggravate the DNA damage of cervical cancer cells possibly by homologous recombination repair pathway. Therefore, MELK may be a predicting marker of poor prognosis of cervical cancer and may also be a new therapeutic target for cervical cancer, providing ideas for improving the therapeutic effect of cervical cancer.

a b s t r a c tMicroRNAs have been reported to play critical roles in various cancers, but there has been no study on the role of miR-889 in cancers. Here, we report that over-expression of miR-889 leads to rapid proliferation of EC109 and EC9706 cells in vitro and in vivo by inducing cells into S-phase. Using bioinformatics methods, DAB2IP was further confirmed to be a direct target of miR-889. In addition, the expression of DAB2IP, which was negatively correlated with that of miR-889, was significantly associated with clinicopathological features of ESCC patients. In conclusion, miR-889 is an important regulator in ESCC and both miR-889 and DAB2IP may serve as promising biomarkers and therapeutic targets in patients with ESCC.

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Differentiation from preadipocytes into mature adipocytes is a complex biological process in which miRNAs play an important role. Previous studies showed that miR-214-3p facilitates adipocyte differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. The detailed function and molecular mechanism of miR-214-3p in adipocyte development is unclear. In this study, the 3T3-L1 cell line was used to analyze the function of miR-214-3p in vitro. Using 5-Ethynyl-2′-deoxyuridine (EdU) staining and the CCK-8 assay, we observed that transfection with the miR-214-3p agomir visibly promoted proliferation of 3T3-L1 preadipocytes by up-regulating the expression of cell cycle-related genes. Interestingly, overexpression of miR-214-3p promoted 3T3-L1 preadipocyte differentiation and up-regulated the expression of key genes for lipogenesis: PPARγ, FABP4, and Adiponectin. Conversely, inhibition of miR-214-3p repressed 3T3-L1 preadipocyte proliferation and differentiation, and down-regulated the expression of cell cycle-related genes and adipogenic markers. Furthermore, we proved that miR-214-3p regulates 3T3-L1 preadipocyte differentiation by directly targeting the 3′-untranslated regions (3′UTR) of Ctnnb1, which is an important transcriptional regulatory factor of the Wnt/β-Catenin pathway. Taken together, the data indicate that miR-214-3p may positively regulate preadipocyte proliferation and enhance differentiation through the Wnt/β-Catenin signaling pathway.

Brain functional network has been widely applied to investigate brain function changes among different conditions and proved to be a small-world-like network. But seldom researches explore the effects of mental fatigue on the small-world brain functional network organization. In the present study, 20 healthy individuals were included to do a consecutive mental arithmetic task to induce mental fatigue, and scalp electroencephalogram (EEG) signals were recorded before and after the task. Correlations between all pairs of EEG channels were determined by mutual information (MI). The resulting adjacency matrices were converted into brain functional networks by applying a threshold, and then, the clustering coefficient (C), characteristic path length (L), and corresponding small-world feature were calculated. Through performing analysis of variance (ANOVA) on the mean MI for every EEG rhythm, only the data of α1 rhythm during the task state were emerged for the further explorations of mental fatigue. For a wide range of thresholds, C increased and L and small-world feature decreased with the deepening mental fatigue. The pattern of the small-world characteristic still existed when computed with a constant degree. Our present findings indicated that more functional connectivities were activated at the mental fatigue stage for efficient information transmission and processing, and mental fatigue can be characterized by a reduced small-world network characteristic. Our results provide a new perspective to understand the neural mechanisms of mental fatigue based on complex network theories.

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