Leucine zipper transcription factor-like 1 expression in gastric cancer and its relationship to relative adhesion molecule

Purpose: To evaluate the expression of leucine zipper transcription factor-like1 (LZTFL1) molecule in the gastric cancer tissues, and its relationship to cellular adhesion protein.Methods: Expressions of LZTFLl, E-cadherin, β-catenin, intercellular cell adhesion molecule-1(ICAM-1) as well as vascular cell adhesion molecule-1 (VCAM-1) in the 133 gastric cancer samples and 40 gastritis samples were evaluated by immunohistochemistry. Levels of mRNA in gastric cancer and latero-cancer tissue were determined by real-time polymerase chain reaction (RT-PCR).Results: Protein levels in gastric tissue decreased. The expression of LZTFL1in gastric cancer tissue correlated with tumor stage (tumor node metastasis staging), degree of tumor differentiation and invasion depth (p < 0.05). Protein expression correlated with E-cadherin positively, and correlated with β-catenin and ICAM-1 negatively, but had no correlation with VCAM-1. Compared with tissues remote to the cancer, mRNA level of LZTFL1 in gastric cancer decreased significantly. There was no significant difference in LZTFL1 mRNA levels in the various clinical pathological tissues. LZTFL1 mRNA expression did not correlation with various adhesion factors.Conclusion: LZTFL1 is expressed at a low level in gastric cancer tissue. Its protein expression is related to cellular adhesion protein, but not to mRNA level. As a suppressor of invasion of cancer cells, LZTFL1 may be a potential target for targeted therapy of gastric cancer.Keywords: Leucine zipper transcription factor-like1 expression, Gastric cancer, Relative adhesion molecule, Protein expressio

ADSC Exosomes Mediate lncRNA-MIAT Alleviation of Endometrial Fibrosis by Regulating miR-150-5p

BackgroundSecondary infertility remains a major complication of endometrial fibrosis in women. The use of exosomes from adipose-derived mesenchymal stem cells (ADSCs) has shown promising results for the treatment of endometrial fibrosis. However, the mechanisms of action of ADSC-exosome (ADSC-Exo) therapy remain unclear.Materials and MethodsAn endometrial fibrosis model was established in mice treated with alcohol and endometrial epithelial cells (ESCs) treated with TGF-β1. ADSCs were isolated from Sprague Dawley (SD) rats, and exosomes were isolated from ADSCs using ExoQuick reagent. Exosomes were identified by transmission electron microscopy (TEM), NanoSight, and Western blot analysis. The expression level of lncRNA-MIAT was detected by qPCR analysis. Western blot analysis was carried out to determine the protein levels of fibrosis markers (TGFβR1, α-SMA, and CK19). A dual-luciferase reporter gene assay was used to verify the relationship between target genes. The endometrial tissues of the endometrial fibrosis model were stained with HE and Masson’s trichrome.ResultsADSCs and ADSC-Exos were successfully isolated, and the expression level of lncRNA-MIAT was significantly down-regulated in endometrial tissue and the TGF-β1-induced ESC injury model, whereas ADSC-Exos increased the expression of lncRNA-MIAT in the TGF-β1-induced ESC model. Functionally, ADSC-Exo treatment repressed endometrial fibrosis in vivo and in vitro by decreasing the expression of hepatic fibrosis markers (α-SMA and TGFβR1) and increasing the expression of CK19. Moreover, miR-150-5p expression was repressed by lncRNA-MIAT in the TGF-β1-induced ESC injury model. The miR-150-5p mimic promoted TGF-β1-induced ESC fibrosis.ConclusionADSC-Exos mediate lncRNA-MIAT alleviation of endometrial fibrosis by regulating miR-150-5p, which suggests that lncRNA-MIAT from ADSC-Exos may be a viable treatment for endometrial fibrosis

Predicting human microRNA precursors based on an optimized feature subset generated by GA–SVM

AbstractMicroRNAs (miRNAs) are non-coding RNAs that play important roles in post-transcriptional regulation. Identification of miRNAs is crucial to understanding their biological mechanism. Recently, machine-learning approaches have been employed to predict miRNA precursors (pre-miRNAs). However, features used are divergent and consequently induce different performance. Thus, feature selection is critical for pre-miRNA prediction. We generated an optimized feature subset including 13 features using a hybrid of genetic algorithm and support vector machine (GA–SVM). Based on SVM, the classification performance of the optimized feature subset is much higher than that of the two feature sets used in microPred and miPred by five-fold cross-validation. Finally, we constructed the classifier miR-SF to predict the most recently identified human pre-miRNAs in miRBase (version 16). Compared with microPred and miPred, miR-SF achieved much higher classification performance. Accuracies were 93.97%, 86.21% and 64.66% for miR-SF, microPred and miPred, respectively. Thus, miR-SF is effective for identifying pre-miRNAs

The impact of the Wenchuan earthquake on early puberty: a natural experiment

Background The factors influencing pubertal timing have gained much attention due to a secular trend toward earlier pubertal onset in many countries. However, no studies have investigated the association between the Great earthquake and early puberty. We aimed to assess whether the Wenchuan earthquake is associated with early puberty, in both boys and girls. Methods We used data from two circles of a survey on reproductive health in China to explore the impact of the Wenchuan earthquake on early puberty , and a total of 9,785 adolescents (4,830 boys, 49.36%) aged 12–20 years from 29 schools in eight provinces were recruited. Wenchuan earthquake exposure was defined as those Sichuan students who had not experienced oigarche/menarche before May 12, 2008. Early puberty was identified as a reported onset of oigarche/menarche at 11 years or earlier. We tested the association between the Wenchuan earthquake and early puberty in boys and girls. Then, subgroup analysis stratified by the age at earthquake exposure also was performed. Results In total, 8,883 adolescents (4,543 boys, 51.14%) with a mean (SD) age of 15.13 (1.81) were included in the final sample. In general, children exposed to the earthquake had three times greater risk of early puberty (boys, RR [95% CI] = 3.18 [2.21–4.57]; girls: RR [95%CI] =3.16 [2.65–3.78]). Subgroup analysis showed that the adjusted RR was 1.90 [1.19–3.03] for boys and 2.22 [1.75–2.80] for girls. Earthquake exposure predicted almost a fourfold (RR [95%CI] = 3.91 [1.31–11.72]) increased risk of early puberty in preschool girls, whereas the increase was about twofold (RR [95%CI] = 2.09 [1.65–2.64]) in schoolgirls. Among boys, only older age at earthquake exposure was linked to early puberty (RR [95%CI] = 1.93 [1.18–3.16]). Conclusions Wenchuan earthquake exposure increased the risk of early puberty in boys and girls, and preschoolers were more at risk than schoolchildren. The implications are relevant to support policies for those survivors, especially children, to better rebuild after disasters

Inside-out Ca2+ signalling prompted by STIM1 conformational switch

Store-operated Ca(2+) entry mediated by STIM1 and ORAI1 constitutes one of the major Ca(2+) entry routes in mammalian cells. The molecular choreography of STIM1–ORAI1 coupling is initiated by endoplasmic reticulum (ER) Ca(2+) store depletion with subsequent oligomerization of the STIM1 ER-luminal domain, followed by its redistribution towards the plasma membrane to gate ORAI1 channels. The mechanistic underpinnings of this inside-out Ca(2+) signalling were largely undefined. By taking advantage of a unique gain-of-function mutation within the STIM1 transmembrane domain (STIM1-TM), here we show that local rearrangement, rather than alteration in the oligomeric state of STIM1-TM, prompts conformational changes in the cytosolic juxtamembrane coiled-coil region. Importantly, we further identify critical residues within the cytoplasmic domain of STIM1 (STIM1-CT) that entail autoinhibition. On the basis of these findings, we propose a model in which STIM1-TM reorganization switches STIM1-CT into an extended conformation, thereby projecting the ORAI-activating domain to gate ORAI1 channels

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements