bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protecting youth from gang membership: Individual and school‐level emotional competence
Authors: Lenzi Michela , Sharkey Jill D. , Wroblewski Allie , Furlong Michael J. , Santinello Massimo 
Published: October 2018

AbstractThe current study examined the association between adolescent emotional competence, operationalized and measured at both the individual and the school levels, and gang membership. The study involved a sample of 12,040 students (51.4% females; mean = 16.9 years) participating in the biennial state department of education coordinated California Healthy Kids Survey, which assesses a range of adolescent health‐related behaviors. Hierarchical linear modeling indicated that higher levels of individual emotional competence were associated with a lower likelihood of identifying as a gang member. Moreover, a stronger negative association between emotional competence and identifying as a gang member was found when emotional competence was operationalized at the school level. Implications include the role of schools in promoting emotional regulation, empathy, and behavioral regulation of their entire student body as part of an overall strategy to reduce individual student's attraction to gangs.
ceRNA network construction and comparison of gastric cancer with or without Helicobacter pylori infection
Authors: Liu Yanyan , Zhu Jingyu , Ma Xiaoli , Han Shuyi , Xiao Dongjie , Jia Yanfei , Wang Yunshan 
Published: October 2018

AbstractGastric cancer (GC) is a lethal disease, and among its variety of etiological factors, Helicobacter pylori (H. pylori) infection is the strongest risk factor. However, the genetic and molecular mechanisms underlying H. pylori‐related GC need further elucidation. We investigated the competing endogenous RNA (ceRNA) network differences between H. pylori (+) and H. pylori (−) GC. The long noncoding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) expression data from 32 adjacent noncancerous samples and 18 H. pylori (+) and 141 H. pylori (−) stomach adenocarcinoma samples were downloaded from the TCGA database. After construction of lncRNA–miRNA–mRNA ceRNA networks of H. pylori (+) and H. pylori (−) GC, Panther and Kobas databases were used to analyze the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Finally, survival analysis was used to discover the key genes. In H. pylori (+) GC, we identified a total of 1,419 lncRNAs, 82 miRNAs, and 2,501 mRNAs with differentially expressed profiles. In H. pylori (−) GC, 2,225 lncRNAs, 130 miRNAs, and 3,146 mRNAs were differentially expressed. Furthermore, three unique pathways (cytokine–cytokine receptor interaction, HIF‐1 signaling pathway, and Wnt signaling pathway) were enriched in H. pylori (+) GC. According to the overall survival analysis, three lncRNAs (AP002478.1, LINC00111, and LINC00313) and two mRNAs (MYB and COL1A1) functioned as prognostic biomarkers for patients with H. pylori (+) GC. In conclusion, our study has identified the differences in ceRNA regulatory networks between H. pylori (+) and H. pylori (−) GC and provides a rich candidate reservoir for future studies.
Fibroblast growth factor‐2 inhibits CD40‐mediated periodontal inflammation
Authors: Fujihara Chiharu , Kanai Yu , Masumoto Risa , Kitagaki Jirouta , Matsumoto Masahiro , Yamada Satoru , Kajikawa Tetsuhiro , Murakami Shinya 
Published: October 2018

AbstractFibroblast growth factor‐2 (FGF‐2) stimulates periodontal regeneration by a broad spectrum of effects on periodontal ligament (PDL) cells, such as proliferation, migration, and production of extracellular matrix. A critical factor in the success of periodontal regeneration is the rapid resolution of inflammatory responses in the tissue. We explored an anti‐inflammatory effect of FGF‐2 during periodontal regeneration and healing. We found that FGF‐2 on mouse periodontal ligament cells (MPDL22) markedly downregulated CD40 expression, a key player of inflammation. In addition, FGF‐2 inhibited CD40 signaling by the non‐canonical nuclear factor‐kappa B2 (NFκB2) pathway, resulting in decreased production of interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α), which have the potential to recruit immune cells to inflamed sites. Furthermore, in vivo treatment of FGF‐2 enhanced healing of skin wounds by counteracting the CD40‐mediated inflammation. These results reveal that FGF‐2 has an important function as a negative regulator of inflammation during periodontal regeneration and healing.
Exogenous nanoparticles and endogenous crystalline molecules as danger signals for the NLRP3 inflammasomes
Authors: Shirasuna Koumei , Karasawa Tadayoshi , Takahashi Masafumi 
Published: October 2018

AbstractInflammasome mechanisms are involved as some of the pathways of sterile inflammation. Inflammasomes are large multiprotein complexes in the cytosol and are a key system for the production of the pivotal inflammatory cytokines, interleukin (IL)‐1β and IL‐18, and inflammatory cell death called pyroptosis. Although a number of inflammasomes have been described, the nucleotide‐binding oligomerization domain‐, leucine‐rich repeat‐, and pyrin domain‐containing 3 (NLRP3) is the most extensively investigated inflammasome. Exogenous pathogen‐associated molecular patterns released during infection and endogenous crystalline danger/damage‐associated molecular patterns (DAMPs) are well‐known activators of NLRP3 inflammasomes. In addition, nanoparticle‐associated molecular patterns (NAMPs), which are mediated by synthetic materials, including nanomaterials and nanoparticles, are proposed to be new danger signals of NLRP3 inflammasomes. Importantly, NAMP‐ and DAMP‐triggered inflammation, a defining characteristic in inflammatory diseases, is termed as sterile inflammation because it occurs in the absence of foreign pathogens. This review focuses on the role of inflammasomes in exogenous NAMP‐ and endogenous crystalline DAMP‐mediated sterile inflammation. Moreover, many regulatory mechanisms have been identified to attenuate NLRP3 inflammasomes. Therefore, we also summarize endogenous negative regulators of NLRP3 inflammasome activation, particularly induced by NAMPs or crystalline DAMPs.
Hsa_circ_0136666 promotes the proliferation and invasion of colorectal cancer through miR‐136/SH2B1 axis
Authors: Jin Canhui , Wang Aihong , Liu Linbo , Wang Gongping , Li Guangshuai 
Published: October 2018

AbstractColorectal cancer (CRC) is one of the leading causes of cancer‐related death worldwide. Currently, an increasing evidence showed that circular RNAs (circRNAs) play important roles in tumor progression. However, the effects and underlying mechanisms of circRNAs in CRC progression remain unclear. In the present study, through circRNA high‐throughput sequencing and quantitative real‐time polymerase chain reaction, we identified that hsa_circ_0136666 was significantly overexpressed in CRC tissues and cell lines. High hsa_circ_0136666 expression was associated with poor overall survival of patients with CRC. In vitro function assays showed that hsa_circ_0136666 inhibition suppressed CRC cell proliferation, migration, invasion, and arrested CRC cells in the G0/G1 phase. Furthermore, we showed that hsa_circ_0136666 inhibition reduced CRC cell growth in vivo. Mechanistically, we revealed that hsa_circ_0136666 could increase SH2B1 expression via competitively binding miR‐136 in CRC cells. In addition, SH2B1 overexpression could reverse the effects of hsa_circ_0136666 inhibition on CRC cell progression. In conclusion, our data suggested that hsa_circ_0136666 could promote CRC cell progression via the miR‐136/SH2B1 axis, elucidating a novel approach to improve the effectiveness of CRC treatment.
Characterizing the multiple roles of FGF‐2 in SOD1G93A ALS mice in vivo and in vitro
Authors: Kefalakes Ekaterini , Böselt Sebastian , Sarikidi Anastasia , Ettcheto Miren , Bursch Franziska , Naujock Maximilian , Stanslowsky Nancy , Schmuck Martin , Barenys Marta , Wegner Florian , Grothe Claudia , Petri Susanne 
Published: October 2018

AbstractWe have previously shown that knockout of fibroblast growth factor‐2 (FGF‐2) and potential compensatory effects of other growth factors result in amelioration of disease symptoms in a transgenic mouse model of amyotrophic lateral sclerosis (ALS). ALS is a rapidly progressive neurological disorder leading to degeneration of cortical, brain stem, and spinal motor neurons followed by subsequent denervation and muscle wasting. Mutations in the superoxide dismutase 1 (SOD1) gene are responsible for approximately 20% of familial ALS cases and SOD1 mutant mice still are among the models best mimicking clinical and neuropathological characteristics of ALS. The aim of the present study was a thorough characterization of FGF‐2 and other growth factors and signaling effectors in vivo in the SOD1G93A mouse model. We observed tissue‐specific opposing gene regulation of FGF‐2 and overall dysregulation of other growth factors, which in the gastrocnemius muscle was associated with reduced downstream extracellular‐signal‐regulated kinases (ERK) and protein kinase B (AKT) activation. To further investigate whether the effects of FGF‐2 on motor neuron death are mediated by glial cells, astrocytes lacking FGF‐2 were cocultured together with mutant SOD1
G93A motor neurons. FGF‐2 had an impact on motor neuron maturation indicating that astrocytic FGF‐2 affects motor neurons at a developmental stage. Moreover, neuronal gene expression patterns showed FGF‐2‐ and SOD1
G93A‐dependent changes in ciliary neurotrophic factor, glial‐cell‐line‐derived neurotrophic factor, and ERK2, implying a potential involvement in ALS pathogenesis before the onset of clinical symptoms.
Hepcidin and iron regulatory proteins coordinately regulate ferroportin 1 expression in the brain of mice
Authors: Wang Lan , Liu Xiaopeng , You Lin‐Hao , Ci Yun‐Zhe , Chang Shiyang , Yu Peng , Gao Guofen , Chang Yan‐Zhong 
Published: October 2018

AbstractIron plays an essential role in various cellular metabolic processes of the body. Maintenance of cellular iron homeostasis is particularly important for keeping the normal functions of the cells. Ferroportin 1 (FPN1) is the currently only known iron exporter on the cell membrane. It has been indicated that the regulation of FPN1 in response to the alteration of iron level mainly involves two processes, posttranscriptional repression by iron regulatory proteins (IRPs) and posttranslational degradation by hepcidin, the major iron‐sensing hormone. However, whether there is any communication between the two types of regulations or which one plays dominant role has not been reported. In our study with IRP2−/− mice, we found that knockout of IRP2 increased FPN1 expression in the cerebral cortex of IRP2−/− mice, whereas the upregulation of FPN1 was more significant in IRP1/IRP2 dual knockdown fibroblasts. Interestingly, we found that the knockout of IRP2 severely affected the regulation effect of hepcidin on FPN1 in mouse brain. FPN1 level decreased dramatically in the brain of wild‐type mice injected with hepcidin, but it did not decrease much in IRP2 knockout mice. Further investigation disclosed that the compromised hepcidin–FPN1 regulation in IRP2−/− cells was directly dependent on the existence of iron‐responsive element (IRE) in FPN1 messenger RNA. These results indicate that IRPs and hepcidin coordinately regulate the FPN1 level in mice. This study will provide a more comprehensive understanding of the regulatory mechanisms of FPN1 expression.
Matrine is a novel inhibitor of the TMEM16A chloride channel with antilung adenocarcinoma effects
Authors: Guo Shuai , Chen Yafei , Pang Chunli , Wang Xuzhao , Shi Sai , Zhang Hailin , An Hailong , Zhan Yong 
Published: October 2018

AbstractCalcium‐activated chloride channels (CaCCs) are ion channels with key roles in physiological processes. They are abnormally expressed in various cancers, including esophageal squamous cell cancer, head and neck squamous cell carcinoma, colorectal cancer, and gastrointestinal stromal tumors. The CaCC component TMEM16A/ANO1 was recently shown to be overexpressed in lung adenocarcinoma cells and may serve as a tumorigenic protein. In this study, we determined that matrine is a potent TMEM16A inhibitor that exerts anti‐lung adenocarcinoma effects. Patch clamp experiments showed that matrine inhibited TMEM16A current in a concentration‐dependent manner with an IC
50 of 27.94 ± 4.78 μM. Molecular simulation and site‐directed mutation experiments demonstrated that the matrine‐sensitive sites of the TMEM16A channel involve the amino acids Y355, F411, and F415. Results of cell viability and wound healing assays showed that matrine significantly inhibited the proliferation and migration of LA795 cells, which exhibit high TMEM16A expression. In contrast, matrine has only weak inhibitory effect on CCD‐19Lu and HeLa cells lacking TMEM16A expression. Matrine‐induced effects on the proliferation and migration of LA795 cells were abrogated upon shRNA‐mediated TMEM16A knockdown in LA795 cells. Finally, in vivo experiments demonstrated that matrine dramatically inhibited the growth of lung adenocarcinoma xenograft tumors in mice but did not affect mouse body weight. Collectively, these data indicate that matrine is an effective and safe TMEM16A inhibitor and that TMEM16A is the target of matrine anti‐lung adenocarcinoma activity. These findings provide new insight for the development of novel treatments for lung adenocarcinoma.
Combinatorial screening algorithm to engineer multiepitope subunit vaccine targeting human T‐lymphotropic virus‐1 infection
Authors: Pandey Rajan K. , Ojha Rupal , Chatterjee Nina , Upadhyay Nitesh , Mishra Amit , Prajapati Vijay K. 
Published: October 2018

AbstractHuman T‐lymphotropic virus (HTLV), the first human retrovirus has been discovered which is known to cause the age‐old assassinating disease HTLV‐1 associated myelopathy. Cancer caused by this virus is adult T cell leukemia/lymphoma which targets 10–20 million throughout the world. The effect of this virus extends to the fact that it causes chronic disease to the spinal cord resulting in loss of sensation and further causes blood cancer. So, to overcome the complications, we designed a subunit vaccine by the assimilation of B‐cell, cytotoxic T‐lymphocyte , and helper T‐lymphocyte epitopes. The epitopes were joined together along with adjuvant and linkers and a vaccine was fabricated which was further subjected to 3D modeling. The physiochemical properties, allergenicity, and antigenicity were evaluated. Molecular docking and dynamics were performed with the obtained 3D model against toll like receptor (TLR‐3) immune receptor. Lastly, in silico cloning was performed to ensure the expression of the designed vaccine in pET28a(+) expression vector. The future prospects of the study entailed the in vitro and in vivo experimental analysis for evaluating the immune response of the designed vaccine construct.
Emerging roles of noncoding RNAs in multiple myeloma: A review
Authors: Yang Qian , Shen Xianjuan , Su Zhangyao , Ju Shaoqing 
Published: October 2018

AbstractMultiple myeloma (MM) is a hematologic malignancy characterized by unrestricted secretion of monoclonal immunoglobulin and uncontrolled plasma cell proliferation. Extra‐medullary infiltration and drug resistance are two major obstacles in the treatment of MM. To solve these problems, it is necessary to elucidate the underlying pathological mechanisms and find new therapeutic targets. Noncoding RNAs (ncRNAs), which were once considered “transcriptional noise,” have been recognized as crucial regulators in the process of tumorigenesis including MM. Increasing evidence has shown that ncRNAs participate in MM pathogenesis via a series of complex cellular or extracellular processes. This review article summarizes examples of ncRNAs involved in myelosis and discusses their potential as biomarkers and therapeutic targets in the diagnosis and treatment of myelosis.
Downregulation of HMGB1 is required for the protective role of Nrf2 in EMT‐mediated PF
Authors: Qu Jiao , Zhang Zhihui , Zhang Panpan , Zheng Cheng , Zhou Wencheng , Cui Wenhui , Xu Liang , Gao Jian 
Published: October 2018

AbstractEpithelial–mesenchymal transition (EMT) is considered to be the key event in the formation of pulmonary fibrosis (PF). High‐mobility group box 1 (HMGB1) is a novel mediator of EMT. Nuclear factor erythroid 2‐related factor 2 (Nrf2) is a critical transcription factor for protecting against PF. However, it is unknown the relationship between Nrf2 and HMGB1 in EMT‐mediated PF. Bleomycin (BLM)‐induced PF in Nrf2‐knockout (Nrf2−/−) and wild‐type (WT) mice and transforming growth factor β1 (TGF‐β1)‐induced EMT in rat type II alveolar epithelial cell line (RLE‐6TN) and human alveolar epithelial cell line (A549) were established to observe the relationship among Nrf2, HMGB1, and EMT by western blot and immunohistochemistry. BLM‐induced EMT was more severe and the expression of HMGB1 was more increased in Nrf2
−/− mice compared with WT mice. In vitro, Nrf2 activation attenuated TGF‐β1‐induced EMT and ROS production accompanied by the downregulation of HMGB1. In contrast, silencing Nrf2 enhanced TGF‐β1‐induced EMT and ROS production along with increased the protein expression and the release of HMGB1. Moreover, HMGB1 activation aggravated TGF‐β1‐induced EMT and HMGB1 deficiency alleviated TGF‐β1‐induced EMT. Furthermore, HMGB1 silence attenuated the protective effect of Nrf2 on EMT. These findings suggest downregulation of HMGB1, which is required for the protective role of Nrf2 in EMT‐mediated PF and provide an important therapeutic target for PF.
Potential biomarkers for heart failure
Authors: Wang Che , Yang Honghui , Gao Chuanyu 
Published: October 2018

AbstractIn this study, we identified candidate biomarkers for heart failure (HF). The gene expression profile GSE57338, containing 117 ischemic cardiomyopathic HF and 136 control samples, was downloaded and analyzed using various bioinformatics approaches. In total, 376 differentially expressed genes (DEGs) were identified, and four modules were explored in protein–protein interaction networks. DEGs (including ankyrin repeat and SOCS box‐containing 14 [ASB14]) in the modules were mainly categorized by the function. Several relationships including interferon regulatory factor 1 (IRF1)‐C‐C motif chemokine ligand 5 (CCL5) were revealed in the transcription factor microRNA target gene regulatory network. Gene–drug analysis revealed 11 DEGs (such as the cluster of differentiation 163 [CD163]) for the target drugs. Data verification analysis identified 118 overlapping DEGs including ASB14, CD163, and CCL5. ASB14 may be involved in HF progression via protein ubiquitination and CCL5 may be involved in HF via the IRF1‐CCL5 interaction. Genes including CD163 are potential biomarkers for HF.
Synergistically regulated spontaneous calcium signaling is attributed to cartilaginous extracellular matrix metabolism
Authors: Gong Xiaoyuan , Li Gaoming , Huang Yang , Fu Zhenlan , Song Xiongbo , Chen Cheng , Yang Liu 
Published: October 2018

AbstractCa2+ has been recognized as a key molecule for chondrocytes, however, the role and mechanism of spontaneous [Ca
2+]
i signaling in cartilaginous extracellular matrix (ECM) metabolism regulation are unclear. Here we found that spontaneous Ca
2+ signal of in‐situ porcine chondrocytes was [Ca
2+]
o dependent, and mediated by [Ca
2+]
i store release. T‐type voltage‐dependent calcium channel (T‐VDCC) mediated [Ca
2+]
o influx was associated with decreased cell viability and expression levels of ECM deposition genes. Further analysis revealed that chondrocytes expressed both inositol 1,4,5‐trisphosphate receptor (InsP3R) and Orai isoforms. Inhibition of endoplasmic reticulum (ER) Ca
2+ release and store‐operated calcium entry significantly abolished spontaneous [Ca
2+]
i signaling of in‐situ chondrocytes. Moreover, blocking ER Ca
2+ release with InsP3R inhibitors significantly upregulated ECM degradation enzymes production, and was accompanied by decreased proteoglycan and collagen type II intensity. Taken together, our data provided evidence that spontaneous [Ca
2+]
i signaling of in‐situ porcine chondrocytes was tightly regulated by [Ca
2+]
o influx, InsP3Rs mediated [Ca
2+]
i store release, and Orais mediated calcium release‐activated calcium channels activation. Both T‐VDCC mediated [Ca
2+]
o influx and InsP3Rs mediated ER Ca
2+ release were found crucial to cartilaginous ECM metabolism through distinct regulatory mechanisms.
Amelioration of regulatory T cells by Lactobacillus delbrueckii and Lactobacillus rhamnosus in pristane‐induced lupus mice model
Authors: Khorasani Sahar , Mahmoudi Mahmoud , Kalantari Mahmoud Reza , Lavi Arab Fahimeh , Esmaeili Seyed‐Alireza , Mardani Fatemeh , Tabasi Nafiseh , Rastin Maryam 
Published: October 2018

AbstractRegulatory T cells (Tregs) play an indispensable role in the control of immune responses and induction of peripheral tolerance. Dysregulation of Tregs is involved in the pathogenesis of systemic lupus erythematosus (SLE). Tolerogenic probiotics have shown beneficial effects in the control of autoimmune diseases. We evaluated the prophylactic and therapeutic effects of Lactobacillus delbrueckii and Lactobacillus rhamnosus on Tregs and their related molecules in pristane‐induced lupus mice model. Fifty‐four female BALB/c mice (3–5 weeks) were randomly divided into nine groups. Lupus was induced in all groups using pristane. Prophylactic groups were treated from Day 0 (at the time of pristane injection) and treatment groups were treated 2 months later with L. rhamnosus, L. delbrueckii, mix of both probiotics, and prednisolone. One group was considered as SLE‐induced control group without any treatment. Presence of antinuclear antibodies (ANA), antidouble‐stranded DNA (anti‐dsDNA), antiribonucleoprotein (anti‐RNP), proteinuria, and serum level of creatinine, urea, the expression of forkhead box P3 (Foxp3), interleukin 6 (IL‐6), IL‐10, transforming growth factor β, and the number of Tregs were determined. SLE induction by pristane led to the formation of lipogranuloma, presence of ANA, anti‐dsDNA, and anti‐RNP. Probiotics consumption decreased the level of lipogranuloma, ANA, and anti‐dsDNA. In addition, in probiotics receiving groups, Tregs and the expression level of Foxp3 increased, while IL‐6 decreased. The effect of probiotics in the prophylactic group was more prominent. The results may indicate the effectiveness of L. delbrueckii and L. rhamnosus in the enhancement of Tregs and the decrease of inflammatory cytokines and disease severity in SLE‐induced mice.
Targeting phosphoinositide‐3‐kinase pathway in biliary tract cancers: A remedial route?
Authors: Kaavya Jayaramayya , Mahalaxmi Iyer , Devi Subramaniam Mohana , Santhy K. S. , Balachandar Vellingiri 
Published: October 2018

AbstractBiliary tract cancers (BTC) are aggressive tumours with a low survival rate. At the advent of the genomic era, various genetic mutations in cell signalling pathways have been incriminated in carcinogenesis. Genomic analysis studies have connected main components of the phosphoinositide‐3‐kinase (PI3K) signalling pathway to BTC. PI3K pathway playing a central role in cell signalling and being deregulated in various tumours has been studied as a target for chemotherapy. Novel compounds have also been identified in preclinical trials that specifically target the PI3K pathway in BTCs, but these studies have not accelerated to clinical use. These novel compounds can be examined in upcoming studies to validate them as potential therapeutic agents, as further research is required to combat the growing need for adjuvant chemotherapy to successfully battle this tumour type. Furthermore, these molecules could also be used along with gemcitabine, cisplatin and 5‐fluorouracil to improve sensitivity of the tumour tissue to chemotherapy. This review focuses on the basics of PI3K signalling, genetic alterations of this pathway in BTCs and current advancement in targeting this pathway in BTCs. It emphasizes the need for gene‐based drug screening in BTC. It may reveal various novel targets and drugs for amelioration of survival in patients with BTC and serve as a stepping stone for further research.