The Ca2+-activated potassium (KCa) channels are involved in many cellular functions, but their roles in trophoblasts are unclear. This study aimed to clarify the effects of KCa channels on the biological behavior of trophoblasts. The localization and expression of the three types of KCa channels, including large-conductance KCa channels (BKCa), intermediate-conductance KCa channels (IKCa), and small-conductance KCa channels (SKCa), were detected in human chorionic villi taken from pregnant women between 5 and 8 weeks of gestation (n = 15) and HTR-8/SVneo cells. The effects of KCa channels on proliferation, apoptosis, and migration of HTR-8/SVneo cells were examined by using the activators or inhibitors of KCa channels. Results showed that KCa channels were mainly localized on the membrane and in the cytoplasm of trophoblasts in human chorionic villi and HTR-8/SVneo cells. The proliferation and migration of HTR-8/SVneo cells were inhibited by activating KCa channels. Apoptosis of trophoblasts was promoted through activating BKCa channels but was not affected by neither activating nor inhibiting IKCa and SKCa channels. This study substantiated the abovementioned biological roles of KCa channels in trophoblast cells, which is fundamental to further research on whether dysfunction of KCa channels is involved in the pathogenesis of pregnancy-related complications.

Introduction: Excessive activation of maternal systemic inflammation is one of the underlying causes of pathology during the disease course of preeclampsia (PE). The triggering receptor expressed on myeloid cells-1 (TREM-1) participates in the development and persistence of inflammation. We hypothesized that dysregulated TREM-1 may be involved in the pathogenesis of PE by promoting the secretion of trophoblastic pro-inflammatory cytokines that augment inflammation. Methods: The localization of TREM-1 in placenta and the extravillous trophoblast cell line (TEV-1) was determined by immunohistochemical staining. The expression level of TREM-1 and pro-inflammatory cytokines in placentas were compared between normal pregnancies and PE. We used lipopolysaccharide (LPS) to simulate trophoblastic inflammation. TEV-1 cells were transfected with TREM-1 plasmid and si-TREM-1 respectively, and then were incubated with LPS. The expression levels of pro-inflammatory cytokines and key molecules featured in nuclear transcription factor-kappaB (NF-xB) pathway were detected. Transwell assays were used to detect the effects of TREM-1 on cell migration and invasion. Results: TREM-1 was localized on both villous trophoblasts (VTs) and extravillous trophoblasts (EVTs). TREM-1 and pro-inflammatory cytokines were up-regulated in preeclamptic placenta. Overexpression of TREM-1 promoted the activation of NF-xB pathway and the release of pro-inflammatory factors induced by LPS, and enhanced migration and invasion of TEV-1 cells. Inhibition of TREM-1 significantly attenuated LPS-induced effects and suppressed migration and invasion. Discussion: This study suggested that TREM-1 was up-regulated in PE, and may promote the production of downstream inflammatory factors by activating NF-xB pathway in trophoblastic cells, thus exerting pro inflammatory effects in the pathogenesis of PE.

Patients with colorectal cancer usually have a poor prognosis because of the absence of suitable biomarkers for diagnosing asymptomatic patients. Here we determined the ability of MIC-1 to detect precancerous lesions and CRC in an asymptomatic cohort from CRC Screening Program.We screened 2759 subjects with risk factors. Endoscopic and histopathological analyses revealed that 19 and 47 subjects had CRC or precancerous lesions. We randomly selected 24 subjects with normal colonoscopies as healthy controls. We used receiver operating characteristic curve analysis to evaluate the diagnostic efficacy of MIC-1 for CRC and precancerous lesions.The optimal thresholds of MIC-1 levels with precancerous lesions or CRC were 314.12 pg/mL (sensitivity, 91.50%; specificity, 54.20%) and 357.64 pg/mL (sensitivity, 82.40%; specificity, 70.80%). Moreover, MIC-1 levels distinguished precancerous lesions better than CEA, CA19-9, or CA24-2 (AUC: 0.760 vs. 0.529, 0.624, and 0.585) or CRC (AUCs: 0.821 vs. 0.743, 0.657, and 0.688) from the healthy controls. The combination of MIC-1, CEA, CA19-9, and CA24-2 showed the highest in sensitivity and specificity for CRC diagnosis (sensitivity, 94.10%; specificity, 87.50%).Serum MIC-1 levels increased the sensitivity of detection of precancerous colorectal lesions and CRC and can be used to improve screening.

Bleomycin is a clinically used anticancer drug, but it induces lung fibrosis in certain cancer patients with unknown mechanism. Glycosaminoglycans (GAGs) are required for lung morphogenesis during animal development. In current study, GAG disaccharides including heparan sulfate (HS) and chondroitin sulfate (CS) from bleomycin-induced and control lung tissues in lung fibrosis mouse model were tagged with 1-phenyl-3-methyl-5-pyrazolone (PMP) and deuterated PMP, respectively. The differentially isotope-tagged disaccharides were quantitatively compared by LC-MS. At day 10, the amount of CS disaccharides (U0a0, U0a6, and U0a4) and non-sulfated HS disaccharide (U0A0) were increased by 1.3-, 1.6-, 11.7-, and 2.2-fold, respectively, whereas the amount of CS disaccharide (U0a2), hyaluranan disaccharide (UβA0), and six HS disaccharides (U0A6, U2A0, U0H6, U0S0, U2S0, and U2S6) were decreased from1.1- to 14.3-fold compared to that of the controls. At day 15, under-sulfation of both HS and CS disaccharides was persisted. At day 30, the CS disaccharide compositions were recovered to that of the control levels whereas the HS were still remarkably under-sulfated. In conclusion, GAGs, especially HS, from fibrotic lungs induced by a single injection of bleomycin were significantly under-sulfated up to 30 days, suggesting GAGs might be another class of defective signaling molecules involved in bleomycin-induced lung fibrosis.

BACKGROUND:Early diagnosis is very important to improve the survival rate of patients with gastric cancer (GC), especially in asymptomatic participants. However, low sensitivity of common biomarkers has caused difficulties in early screening of GC. In this study, we explored whether MIC-1 can improve the detection rate of early GC. METHODS:We screened 8257 participants based on risk factors such as age, gender, and family history for physical examination including gastroscopy. Participant blood samples were taken for measure MIC-1, CA-199, CA72-4, and PG1/PG2 levels. The diagnostic performance of MIC-1 was assessed and compared with CA-199, CA72-4, and PG1/PG2, and its role in early GC diagnosis and the assessment of the risk of precancerous lesions have also been studied. RESULTS:Based on endoscopic and histopathological findings, 55 participants had GC, 566 participants had low-grade neoplasia, and 2605 participants had chronic gastritis. MIC-1 levels were significantly elevated in GC serum samples as compared to controls (P < .001). The sensitivity of serum MIC-1 for GC diagnosis was much higher than that of CA-199 (49.1% vs 20.0%) with similar specificities. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MIC-1 had a better performance compared with CA-199, CA72-4, and PG1/PG2 in distinguishing early-stage GC (AUC: 72.9% vs 69.5%, 67.5%, 44.0%, respectively). CONCLUSIONS:Serum MIC-1 is significantly elevated in most patients with early GC. MIC-1 can serve as a novel diagnostic marker of early GC and value the risk of GC.

Background Small cell lung cancer (SCLC) is an aggressive and recalcitrant cancer. In recent years, studies focused on the abnormal expression of microRNA which has proven valuable in terms of prognosis, diagnosis and treatment in SCLC. To address the limitations of independent studies data, a meta-analysis seems necessary for further exploration of microRNA as biological target and regulatory factor in SCLC. Methods We performed comprehensive literature retrieval in GEO database and EBI ArrayExpress database. The microRNA expression data was extracted from 4 related researches (GSE15008, GSE74190, GSE19945, GSE77380), which was obtained from GEO database. In each included study, the R. Affymetrix Expression Console’s Limma package and RMA algorithms were used to screen for raw data for gene chip quality control, standardization, log2 conversion and differential expression of the gene chip, respectively. Significant microRNA meta-signatures were identified by Robust Rank Aggregation method. Subsequently, gene ontology (GO) enrichment analysis and pathway analysis were performed using bioinformatics tools. Results We found a significant microRNA meta-signature of six up-regulated (hsa-miR-182-5p, hsa-miR-96-5p, hsa-miR-7-5p, hsa-miR-301b-3p, hsa-miR-130b-3p, hsa-miR-210-3p) and four down-regulated (hsa-miR-126-3p, hsa-miR-451a, hsa-miR-145-5p, hsa-miR-486-5p) microRNA s in meta-analysis approaches. GO analysis showed that target gene of meta-signatures microRNA was mainly enriched in endosome, chordate embryonic development and transforming growth factor beta receptor. The related functional gene of microRNA meta signature synergistically targeting SCLC signaling pathway was confirmed by enrichment analysis. In particular, neurotrophin and TGF-beta signaling pathway play the most important roles in the pathway network. Conclusions Our study identified 10 highly significant and consistently dysregulated microRNA s from 4 datasets, which offering convincing molecular targets and regulatory factors in future research of SCLC.

Leather's handle and character has been evaluated and classified using an artificial neural network (ANN). Experimental mechanical parameters correlated to elasticity, softness, fullness and extensibility were obtained. The feed-forward neural network used provided accurate modelling between the input parameters, bend constant (K b ); compression index (K c ); lastometer coefficient (K l ); attenuation constant (α b ); attenuation speed constant (K') and the output parameter (leather's handle and graded character). Although only a small number of experimental data were used in training the neural network, the results obtained are comparable to the results of evaluations done by the traditional method.

Leather softness is always evaluated fuzzily. In this paper the fuzzy comprehensive method is given which is based on the leather's lastometer property under different loads. Fuzzy analysis theory is used to evaluate the softness quantitatively, scientifically and objectively.

Our work is aimed at evaluating the character of leather in a quantitative manner. We have studied the principle and method of testing leather fullness and softness by compression and Lastometer type experiments. A variety of Lastometer apparatus for testing softness had been designed and manufactured. Some parameters, such as compression/decompression and fullness work. have been calculated using the experimental data. The results are coincident with those of HEM (hand evaluation method). This testing procedure appears to be reliable for measuring leather fullness and softness.