Screening potential lncRNA biomarkers for breast cancer and colorectal cancer combining random walk and logistic matrix factorization

Breast cancer and colorectal cancer are two of the most common malignant tumors worldwide. They cause the leading causes of cancer mortality. Many researches have demonstrated that long noncoding RNAs (lncRNAs) have close linkages with the occurrence and development of the two cancers. Therefore, it is essential to design an effective way to identify potential lncRNA biomarkers for them. In this study, we developed a computational method (LDA-RWLMF) by integrating random walk with restart and Logistic Matrix Factorization to investigate the roles of lncRNA biomarkers in the prognosis and diagnosis of the two cancers. We first fuse disease semantic and Gaussian association profile similarities and lncRNA functional and Gaussian association profile similarities. Second, we design a negative selection algorithm to extract negative LncRNA-Disease Associations (LDA) based on random walk. Third, we develop a logistic matrix factorization model to predict possible LDAs. We compare our proposed LDA-RWLMF method with four classical LDA prediction methods, that is, LNCSIM1, LNCSIM2, ILNCSIM, and IDSSIM. The results from 5-fold cross validation on the MNDR dataset show that LDA-RWLMF computes the best AUC value of 0.9312, outperforming the above four LDA prediction methods. Finally, we rank all lncRNA biomarkers for the two cancers after determining the performance of LDA-RWLMF, respectively. We find that 48 and 50 lncRNAs have the highest association scores with breast cancer and colorectal cancer among all lncRNAs known to associate with them on the MNDR dataset, respectively. We predict that lncRNAs HULC and HAR1A could be separately potential biomarkers for breast cancer and colorectal cancer and need to biomedical experimental validation

HSPA12B Promotes Functional Recovery After Ischaemic Stroke Through an eNOS-Dependent Mechanism

Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. Stroke is the leading cause of disability worldwide. HSPA12B, a heat-shock protein recently identified expression specifically in endothelial cells, is able to promote angiogenesis. Here, we have investigated its effects on functional recovery at chronic phase of ischaemic stroke. Ischaemic stroke was induced by 60 min. of middle cerebral artery occlusion in transgenic mice with overexpression of HSPA12B (HSPA12B Tg) and wild-type littermates (WT). HSPA12B Tg mice demonstrated a significant higher survival rate than WT mice within 28 days post-stroke. Significant improved neurological functions, increased spontaneous locomotor activity and decreased anxiety were detected inHSPA12B Tg mice compared with WT controls within 21 days post-stroke. Stroke-induced hippocampal degeneration was attenuated in HSPA12B Tg mice examined at day 28 post-stroke. Interestingly, HSPA12B Tg mice showed enhanced peri-infarct angiogenesis (examined 28 days post-stroke) and hippocampal neurogenesis (examined 7 days post-stroke), respectively, compared to WT mice. The stroke-induced eNOS phosphorylation and TGF-β1 expression were augmented in HSPA12B Tg mice. However, administration with eNOS inhibitor L-NAME diminished the HSPA12B-induced protection in neurological functional recovery and mice survival post-stroke. The data suggest that HSPA12B promoted functional recovery and survival after stroke in an eNOS-dependent mechanism. Targeting HSPA12B expression may have a therapeutic potential for the stroke-evoked functional disability and mortality

Low-Complexity Detection Algorithms for Spatial Modulation MIMO Systems

In this paper, the authors propose three low-complexity detection schemes for spatial modulation (SM) systems based on the modified beam search (MBS) detection. The MBS detector, which splits the search tree into some subtrees, can reduce the computational complexity by decreasing the nodes retained in each layer. However, the MBS detector does not take into account the effect of subtree search order on computational complexity, and it does not consider the effect of layers search order on the bit-error-rate (BER) performance. The ost-MBS detector starts the search from the subtree where the optimal solution is most likely to be located, which can reduce total searches of nodes in the subsequent subtrees. Thus, it can decrease the computational complexity. When the number of the retained nodes is fixed, which nodes are retained is very important. That is, the different search orders of layers have a direct influence on BER. Based on this, we propose the oy-MBS detector. The ost-oy-MBS detector combines the detection order of ost-MBS and oy-MBS together. The algorithm analysis and experimental results show that the proposed detectors outstrip MBS with respect to the BER performance and the computational complexity

Ethanol extract of propolis and its constituent caffeic acid phenethyl ester inhibit breast cancer cells proliferation in inflammatory microenvironment by inhibiting TLR4 signal pathway and inducing apoptosis and autophagy

Abstract Background Propolis and its major constituent – caffeic acid phenethyl ester (CAPE) have good abilities on antitumor and anti-inflammation. However, little is known about the actions of propolis and CAPE on tumor in inflammatory microenvironment, and inflammatory responses play decisive roles at different stages of tumor development. To understand the effects and mechanisms of ethanol-extracted Chinese propolis (EECP) and its major constituent - CAPE in inflammation-stimulated tumor, we investigated their effects on Toll-like receptor 4 (TLR4) signaling pathway which plays a crucial role in breast cancer MDA-MB-231 cell line. Methods 80% confluent breast cancer MDA-MB-231 cells were stimulated with 1 μg/mL lipopolysaccaride (LPS). Then the cells were divided for treatment by CAPE (25 μg/mL) and EECP (25, 50 and 100 μg/mL), respectively. Cell viability, nitric oxide (NO) production and cell migration were measured by sulforhodamine B assay, chemical method and scratch assay. The levels of TLR4, MyD88, IRAK4, TRIF, caspase 3, PARP, LC3B and p62 were investigated through western blotting. The expression of TLR4, LC3B and nuclear factor-κB p65 (NF-κB p65) were tested by immunofluorescence microscopy assay. Results Treatment of different concentrations of EECP (25, 50 and 100 μg/mL) and CAPE (25 μg/mL) significantly inhibited LPS-stimulated MDA-MB-231 cell line proliferation, migration and NO production. Furthermore, EECP and CAPE activated caspase3 and PARP to induce cell apoptosis, and also upregulated LC3-II and decreased p62 level to induce autophagy during the process. TLR4 signaling pathway molecules such as TLR4, MyD88, IRAK4, TRIF and NF-κB p65 were all down-regulated after EECP and CAPE treatment in LPS-stimulated MDA-MB-231 cells. Conclusions These findings indicated that EECP and its major constituent - CAPE inhibited breast cancer MDA-MB-231 cells proliferation in inflammatory microenvironment through activating apoptosis, autophagy and inhibiting TLR4 signaling pathway. EECP and CAPE may hold promising prospects in treating inflammation-induced tumor

Efficacy of vigabatrin in the treatment of infantile epileptic spasms syndrome: A systematic review and meta‐analysis

Abstract This systematic review and meta‐analysis aimed to evaluate the efficacy of vigabatrin (VGB) in treating infantile epileptic spasms syndrome (IESS). Databases of PubMed, Embase, Web of Science, MEDLINE, and Cochrane Library were systematically searched. All the relevant randomized controlled trials (RCTs) and observational studies (OSs) of VGB for IESS were included and analyzed separately. The primary outcome was the cessation of epileptic spasms (ES). Five RCTs and nine OSs compared the efficacy of VGB vs hormonal monotherapy for IESS. Meta‐analysis of the five RCTs showed that hormonal monotherapy was significantly better than VGB monotherapy (OR = 0.37, 95% CI = 0.20‐0.67) for patients with new‐onset IESS. Meta‐analysis of the nine OSs agrees with the result from RCTs (OR = 0.61, 95% CI = 0.43‐0.85). VGB was more effective in patients with TSC than in those with other etiologies (five OSs, OR = 5.59, 95% CI = 2.17‐14.41). There was no significant difference in the efficiency of VGB combined with hormonal therapy vs hormonal monotherapy for IESS (two RCTs, OR = 0.75, 95% CI = 0.09‐6.45). Hormonal monotherapy is better than VGB monotherapy for non‐TSC‐associated IESS. But for patients with IESS due to TSC, VGB is the first choice. VGB combined with hormone therapy does not definitely increase ES control rates compared with that of hormonal monotherapy

Type 2 diabetes with hypertensive patients results in changes to features of adipocytokines: Leptin, Irisin, LGR4, and Sfrp5

The incidence of hypertension and diabetes is increasing, it is reported that adipocytokines might be involved in the pathogenesis of diabetes and hypertension. We aimed to investigate the features of adipocytokines, included of Leptin, Irisin, LGR4, and Sfrp5 in type 2 diabetes mellitus (T2DM) patients with hypertension, simultaneously analyzed the connection of the alteration of adipocytokines with blood pressure and glucose. 424 patients with T2DM and 90 healthy subjects were included in the study. The patients with T2DM were divided into 4 groups based on the blood pressure. The levels of adipocytokines (Leptin, Irisin, LGR4, and Sfrp5) were determined by enzyme-linked immunosorbent assay (ELISA). Significantly higher levels of Leptin and lower levels of Irisin, LGR4 and Sfrp5 were seen in patients with diabetes compared with non-diabetes (P < 0.05), the mean values of Leptin level was ascending and Irisin, LGR4, and Sfrp5 levels were declining with promoting of blood pressure in hypertension as compared to the non-hypertension with diabetic patients. Multiple stepwise linear regression analysis showed that the concentrations of Leptin, Irisin, Sfrp5, and LGR4 were found to be closely associated with the control of blood pressure and glucose. Conclusion: Four adipocytokines might play different roles and closely relate to the occurrence and development of diabetes and hypertension

Attenuation mechanism of Brucella melitensis M5-10, implications for vaccine development and differential diagnosis

Brucellosis is a worldwide zoonosis. Vaccination is the most efficient means to prevent and control brucellosis. The current licensed attenuated vaccines for animal use were developed by sequential passage in non-natural hosts that decreased virulence in its original hosts. The attenuation mechanism of these strains remains largely unknown. In the present study, we sequenced the genome of Brucella melitensis vaccine strain M5-10. Sequence analysis showed that a large number of genetic changes occurred in the vaccine strains. A total of 2854 genetic polymorphic sites, including 2548 SNP, 241 INDEL and 65 MNV were identified. Of the 2074 SNPs in coding regions, 1310 (63.2%) were non-synonymous SNPs. Gene number, percent and N/S ratios were disproportionally distributed among the cog categories. Genetic polymorphic sites were identified in genes of the virB operon, flagella synthesis, and virulence regulating systems. These data indicate that changes in some cog categories and virulence genes might result in the attenuation. These attenuation mechanisms also have implications for screening and development of new vaccine strains. The genetic changes in the genome represent candidate sites for differential diagnosis between these vaccine strains and other virulence ones. Transcription analysis of virulence genes showed that expression of dnaK, vjbR were reduced in M5-10 strain when compared with that in 16M. A duplex PCR targeting virB6 and dnaK was successfully used to differentiate between M5-10 and the virulent 16M strain. The genome re-sequencing technique represents a strong strategy not only for evaluation of vaccines, but also for development of new vaccines

Immunization with Individual Proteins of the Lrp/AsnC Family Induces Protection Against Brucella melitensis 16M Challenges in Mice

Brucellosis is one of the most common zoonoses worldwide. Subunit vaccines are promising for the prevention of human brucellosis. In our previous protective antigen screening studies, we identified a new protective antigen, BMEI0357, which belongs to the Lrp/asnC protein family, a conserved transcriptional regulator in bacteria that is absent in eukaryotes. In the present study, the Brucella genome annotation was screened and a total of 6 proteins were identified as members of the Lrp/AsnC family. Lrp/AsnC proteins have 2 domains that are conserved among the family members. However, sequence similarities between these proteins ranged from 9% to 50%, indicating high sequence heterogeneity. To test whether proteins of this family have similar characteristics, all 6 proteins were cloned and expressed in Escherichia coli. The recombinant proteins were purified and their protective efficacy was evaluated in BALB/c mice challenged with Brucella melitensis 16M. The results show that all 6 Lrp/AsnC proteins could induce a protective immune response against Brucella melitensis 16M. Antibodies against the Lrp/AsnC proteins were detected in the immunized mice. However, levels of antibodies against these proteins were relatively variable in human brucellosis sera. Taken together, our results show that these 6 proteins of the Lrp/AsnC family in Brucella could induce protective immune responses in mice