bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promising immunotherapy: Highlighting cytokine‐induced killer cells
Authors: Shirjang Solmaz , Alizadeh Nazila , Mansoori Behzad , Mahmoodpoor Ata , Kafil Hossein Samadi , Hojjat‐Farsangi Mohammad , Yousefi Mehdi 
Published: December 2018

AbstractFor many years, cancer therapy has appeared to be a challenging issue for researchers and physicians. By the introduction of novel methods in immunotherapy, the prospect of cancer therapy even more explained than before. Cytokine‐induced killer (CIK) cell‐based immunotherapy demonstrated to have potentiality in improving clinical outcomes and relieving major side effects of standard treatment options. In addition, given the distinctive features such as high safety, low toxicity effects on healthy cells, numerous clinical trials conducted on CIK cells. Due to the shortcomings that observed in CIK cell immunotherapy alone, arising a tendency to make modifications (combined modality therapy or combination therapy) including the addition of various types of cytokines, genetic engineering, combination with immune checkpoints, and so on. In this review, we have tried to bring forth the latest immunotherapy methods and their overview. We have discussed the combination therapies with CIK cells and the conducted clinical trials. This helps the future studies to use integrated therapies with CIK cells as a promising treatment of many types of cancers.
Prognostic factors of budesonide therapy for the management of Crohn’s disease: A meta‐analysis
Authors: Li Yajun , Meng Xiangwei , Duan Xiumei , Tang Tongyu , He Chuan , Li Yuqin 
Published: December 2018

AbstractBackgroundThis study aimed to identify factors that affect the prognosis of budesonide therapy for Crohn’s disease patients.MethodChange in Crohn’s disease activity index (CDAI) scores at latest follow‐up after budesonide therapy reported by individual studies were pooled to gain overall effect size under random effects model and then metaregression analyses were performed to identify factors affecting the change in CDAI scores after budesonide treatment.ResultsFifteen studies (1875 patients; age, 35.6 years [95% confidence interval (CI): 34.1, 37.0]; 41.66% [95% CI: 37.44, 45.88] males; 33.3% [95% CI: 24.3, 42.3] smokers; weight, 64.7 kg [95% CI: 62.71 66.6] and height, 168 cm [95% CI: 165, 171]) were included. Disease duration was 7.0 years [95% CI: 5.7, 8.2] and duration of the current episode was 3.1 months [95% CI: 1.7, 4.4]. Proportion of patients with prior resection was 42% [95% CI: 34%, 50%]. The disease was 21% in the ileum, 61% in ileocecum, and 18% in the colon. Budesonide dose was 8.83 mg/d [95% CI: 7.52, 10.14]. In a follow‐up duration of 21.0 weeks [95% CI: 15.2, 26.8], budesonide treatment was associated with improvement in CDAI score of −117.8 [95% CI: −134.0, −102.0]. The magnitude of the change in CDAI score at the latest follow‐up was significantly inversely associated with the percentage of smokers, but positively associated with the baseline CDAI score and duration of the current episode.ConclusionBudesonide therapy to Crohn’s disease patients appears to be more effective in patients with the more serious condition. Smoking may also affect the prognosis.
Molecular mechanisms, prevalence, and molecular methods for familial combined hyperlipidemia disease: A review
Authors: Taghizadeh Eskandar , Mardani Rajab , Rostami Daryoush , Taghizadeh Hassan , Bazireh Homa , Hayat Seyed Mohammad Gheibi 
Published: December 2018

AbstractFamilial combined hyperlipidemia (FCHL) is the most common genetic dyslipidemia disorder which is accompanied by increasing of triglyceride and cholesterol. This disorder is a complex genetic disease although it also has monogenic forms. The familial form has several criteria for diagnosis that can be distinguished of nonfamilial position. It has been shown that a variety of internal and external risk factors are involved in the pathogenesis of FCHL. Environmental factors and the genetic background also play an important role in the FCHL pathogenesis. Many mechanisms and pathways are involved in lipid metabolism (ie, dysfunctional adipose tissue, hepatic fat and very low‐density lipoprotein overproduction, triglyceride‐rich lipoproteins, and clearance of low‐density lipoprotein particles) that could lead to FCHL. Individuals with a positive family history like those who have a positive family history of cardiovascular diseases are more predispositions for this disorder. To date several methods have been used to identify the genetic background of the FCHL. In the current review, we summarized the prevalence and the molecular mechanisms involved in the FCHL disease. Moreover, we highlighted the used molecular methods for determining the genes involved in the FCHL.
lncRNA A1BG‐AS1 suppresses proliferation and invasion of hepatocellular carcinoma cells by targeting miR‐216a‐5p
Authors: Bai Jigang , Yao Bowen , Wang Liang , Sun Liankang , Chen Tianxiang , Liu Runkun , Yin Guozhi , Xu Qiuran , Yang Wei 
Published: December 2018

AbstractExtensive evidence indicate that long noncoding RNAs (lncRNAs) regulates the tumorigenesis and progression of hepatocellular carcinoma (HCC). However, the expression and biological function of lncRNA A1BG antisense RNA 1 (A1BG‐AS1) were poorly known in HCC. Here, we found the underexpression of A1BG‐AS1 in HCC via analysis of The Cancer Genome Atlas database. Further analyses confirmed that A1BG‐AS1 expression in HCC was markedly lower than that in noncancerous tissues based on our HCC cohort. Clinical association analysis revealed that low A1BG‐AS1 expression correlated with poor prognostic features, such as microvascular invasion, high tumor grade, and advanced tumor stage. Follow‐up data indicated that low A1BG‐AS1 level evidently correlated with poor clinical outcomes of HCC patients. Moreover, forced expression of A1BG‐AS1 repressed proliferation, migration, and invasion of HCC cells in vitro. Conversely, A1BG‐AS1 knockdown promoted these malignant behaviors in HepG2 cells. Mechanistically, A1BG‐AS1 functioned as a competing endogenous RNA by directly sponging miR‐216a‐5p in HCC cells. Notably, miR‐216a‐5p restoration rescued A1BG‐AS1 attenuated proliferation, migration and invasion of HCCLM3 cells. A1BG‐AS1 positively regulated the levels of phosphatase and tensin homolog and SMAD family member 7, which were reduced by miR‐216a‐5p in HCC cells. Altogether, we conclude that A1BG‐AS1 exerts a tumor suppressive role in HCC progression.
WISP1 silencing confers protection against epithelial–mesenchymal transition of renal tubular epithelial cells in rats via inactivation of the wnt/β‐catenin signaling pathway in uremia
Authors: Chen Yuan‐Zhen , Sun Dan‐Qin , Zheng Yi , Zheng Guang‐Kuai , Chen Rong‐Quan , Lin Mei , Huang Lian‐Fang , Huang Cong , Song Dan , Wu Ben‐Qing 
Published: December 2018

AbstractUremia can affect hepatic metabolism of drugs by regulating the clearance of drugs, but it has not been clarified whether gene silencing could modulate the epithelial–mesenchymal transition (EMT) process in uremia. Hence, we investigated the effect of WISP1 gene silencing on the renal tubular EMT in uremia through the wnt/β‐catenin signaling pathway. Initially, microarray‐based gene expression profiling of uremia was used to identify differentially expressed genes. Following the establishment of uremia rat model, serum creatinine, and urea nitrogen of rats were detected. Renal tubular epithelial cells (TECs) were transfected with shRNA‐WISP1 lentivirus interference vectors and LiCI (the wnt/β‐catenin signaling pathway activator) to explore the regulatory mechanism of WISP1 in uremia in relation to the wnt/β‐catenin signaling pathway. Then, expression of WISP1, wnt2b, E‐cadherin, α‐SMA, c‐myc, Cyclin D1, MMP‐2, and MMP‐9 was determined. Furthermore, TEC migration and invasion were evaluated. Results suggested that WISP1 and the wnt/β‐catenin signaling pathway were associated with uremia. Uremic rats exhibited increased serum creatinine and urea nitrogen levels, upregulated WISPl, and activated wnt/β‐catenin signaling pathway. Subsequently, WISP1 silencing decreased wnt2b, c‐myc, Cyclin D1, α‐SMA, MMP‐2, and MMP‐9 expression but increased E‐cadherin expression, whereas LiCI treatment exhibited the opposite trends. In addition, WISP1 silencing suppressed TEC migration and invasion, whereas LiCI treatment promoted TEC migration and invasion. The findings indicate that
WISP1 gene silencing suppresses the activation of the wnt/β‐catenin signaling pathway, thus reducing EMT of renal TECs in uremic rats.
microRNA‐338‐3p promotes ox‐LDL‐induced endothelial cell injury through targeting BAMBI and activating TGF‐β/Smad pathway
Authors: Yin Jian , Hou Xuhui , Yang Songbai 
Published: December 2018

AbstractmicroRNAs (miRNAs) have been revealed to participate in the pathological process of atherosclerosis (AS). However, the exact role of miR‐338‐3p, a target miRNA of BMP and activin membrane‐bound inhibitor (BAMBI), and its possible molecular mechanism in AS remain unidentified. In this study, we found that BAMBI was significantly decreased, whereas miR‐338‐3p increased in patients with AS and oxidized low‐density lipoprotein (ox‐LDL)‐induced HUVEC cells. Furthermore, overexpression of miR‐338‐3p significantly decreased cell viability and elevated cell apoptosis, whereas its inhibition significantly promoted cell viability and inhibited cell apoptosis in ox‐LDL‐induced HUVEC cells. Moreover, miR‐338‐3p overexpression increased TGF‐β/Smad pathway activation in ox‐LDL‐induced HUVEC cells. A dual‐luciferase reporter assay confirmed the direct interaction between miR‐338‐3p and the 3′‐untranslated region of BAMBI messenger RNA. Furthermore, the suppression of BAMBI ameliorated the effect of miR‐338‐3p inhibition against ox‐LDL‐induced HUVEC cell injury. In conclusion, our study thus suggests that miR‐338‐3p promoted ox‐LDL‐induced HUVEC cell injury by targeting BAMBI and activating the TGF‐β/Smad pathway, which may provide a novel and promising therapeutic target for AS.
Identification of LINC01615 as potential metastasis‐related long noncoding RNA in hepatocellular carcinoma
Authors: Ji Dong , Chen Guo‐Feng , Liu Xiaoliu , Zhu Jing , Sun Jin‐Yu , Zhang Xiao‐Yu , Lu Xiao‐Jie 
Published: December 2018

AbstractHepatocellular carcinoma is one of the most prevalent and fatal cancers. Studying the long noncoding RNA (lncRNA) alterations in hepatocellular carcinoma may lead to new therapeutic strategies. We checked whether there were correlations between The Cancer Genome Atlas expression profiles of the differentially expressed lncRNAs and their DNA methylation status or the copy number variations for hepatocellular carcinoma. We obtained 41 lncRNAs that were differentially expressed between tumor and normal samples, and their DNA methylation status was negatively correlated with the expression levels. We identified five lncRNAs that were recurrently amplified or deleted in tumor samples, but none of them were associated with the messenger RNA (mRNA) expression levels. To obtain the biological function of these lncRNAs, the coexpressed mRNAs in the hepatocellular carcinoma were figured out. A total of 10 lncRNAs were highly correlated with at least one gene. Six out of the ten lncRNAs were already known to be related with cancer previously. LINC01615 had 72 coexpressed genes, and we carried out the gene ontology (GO) term enrichment for these protein‐coding genes. The results suggested that these lncRNAs were associated with extracellular matrix organization. To summarize, we identified 41 potentially cancer‐related lncRNAs. In particular, we proposed that LINC01615 potentially affected the extracellular matrix and had further impacts on the metastasis of hepatocellular carcinoma.
Integration of metabolomic and transcriptomic data reveals metabolic pathway alteration in breast cancer and impact of related signature on survival
Authors: Luo Xiao , Yu Hong , Song Yan , Sun Tong 
Published: December 2018

AbstractObjectiveBreast cancer (BC) is a malignant tumor which threat to women's physical and mental health. However, the mechanism of metabolism alteration in BC remains unclear. This study is intended to figure out the relationship between the alternation of metabolism and the progression of BC.MethodsIn this study, metabolites of plasma in 60 BC patients and 40 healthy volunteers were detected using liquid chromatography mass spectrometer (LC‐MS). Transcriptomic data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Kyoto Encyclopedia of Genes and Genomes (KEGG) database was performed to enrich the pathways.ResultsA total of 97 metabolites have been identified and measured, of which 17 compounds exhibited the differential expression between tumor group and control group (p < 0.05; FDR < 0.05). Metabolites set enrichment analysis (MSEA) displayed that there were 12 significantly enriched pathways in all. Through the KEGG database, 382 genes were found closely correlated with the altered metabolic pathways. TCGA and GEO transcriptomic profiling revealed that 5,018 genes significantly changed between tumor group and control group. Integrating these genes with the transcriptomic data from the corresponding KEGG data set, we identified most of the differential expressed genes were related to purine metabolism. A total of 28 different expression genes were hub genes, wherein AMPD1 and RRM2 were significantly effective in the prediction of survival of BC patients, with 0.04 and 0.02, respectively.ConclusionsCombining with the transcriptomic and metabolomics data, we found that the dysregulation of purine metabolism pathway might affect the progression of BC.
Fabrication of plumbagin on silver nanoframework for tunable redox modulation: Implications for therapeutic angiogenesis
Authors: Duraipandy Natarajan , Dharunya Govindarajan , Lakra Rachita , Korapatti Purna Sai , Syamala Kiran Manikantan 
Published: December 2018

AbstractThe redox state of the endothelial cells plays a key role in the regulation of the angiogenic process. The modulation of the redox state of endothelial cells (ECs) could be a viable target to alter angiogenic response. In the present work, we synthesized a redox modulator by caging 5‐hydroxy 2‐methyl 1, 4‐napthoquinone (Plumbagin) on silver nano framework (PCSN) for tunable reactive oxygen species (ROS) inductive property and tested its role in ECs during angiogenic response in physiological and stimulated conditions. In physiological conditions, the redox modulators induced the angiogenic response by establishing ECs cell–cell contact in tube formation model, chorio allontoic membrane, and aortic ring model. The molecular mechanism of angiogenic response was induced by vascular endothelial growth factor receptor 2 (VEGFR2)/p42‐mitogen‐activated protein kinase signaling pathway. Under stimulation, by mimicking tumor angiogenic conditions it induced cytotoxicity by generation of excessive ROS and inhibited the angiogenic response by the loss of spatiotemporal regulation of matrix metalloproteases, which prevents the tubular network formation in ECs and poly‐ADP ribose modification of VEGF. The mechanism of opposing effects of PCSN was due to modulation of PKM2 enzyme activity, which increased the EC sensitivity to ROS and inhibited EC survival in stimulated condition. In normal conditions, the endogenous reactive states of NOX4 enzyme helped the EC survival. The results indicated that a threshold ROS level exists in ECs that promote angiogenesis and any significant enhancement in its level by redox modulator inhibits angiogenesis. The study provides the cues for the development of redox‐based therapeutic molecules to cure the disease‐associated aberrant angiogenesis.
Chrysanthemulide A induces apoptosis through DR5 upregulation via JNK‐mediated autophagosome accumulation in human osteosarcoma cells
Authors: Zhuo Fang‐Fang , Zhang Chao , Zhang Hao , Xia Yuanzheng , Xue Gui‐Min , Yang Lei , Kong Ling‐Yi 
Published: December 2018

AbstractOsteosarcoma is the most frequent malignant primary bone tumor, and it generally develops a multidrug resistance. Chrysanthemulide A (CA) is a sesquiterpenoid from the herb Chrysanthemum indicum that has demonstrated a great anti‐osteosarcoma potential. In this study, CA‐induced apoptotic cell death resulted in the activation of the caspase‐8‐mediated caspase cascade, as evidenced by the cleavage of the substrate protein Bid and the caspase‐8 inhibitor Z‐VAD‐FMK. The CA treatment upregulated the expression of death receptor 5 (DR5) in both whole cells and the cell membrane. Blocking DR5 expression by the small interfering RNA (siRNA) treatment decreased the caspase‐8‐mediated caspase cascade and efficiently attenuated CA‐induced apoptosis, suggesting the critical role of DR5 in CA‐induced apoptotic cell death. CA‐induced upregulation of the DR5 protein was accompanied by the accumulation of LC3B‐II, indicating the formation of autophagosomes. Importantly, DR5 upregulation was mediated by transcriptionally controlled autophagosome accumulation, as blockade of autophagosomes by LC3B or ATG‐5 siRNA substantially decreased DR5 upregulation. Furthermore, CA activated the c‐Jun N‐terminal kinase (JNK) signaling pathway, and treatment with JNK siRNAs or inhibitor SP600125 significantly attenuated CA‐mediated autophagosome accumulation and DR5‐mediated cell apoptosis. Finally, CA sensitized the osteosarcoma cells to the DR5 ligand tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐induced apoptotic cell death. Above all, these results suggest that CA induces apoptosis through upregulating DR5 via JNK‐mediated autophagosome accumulation and that combined treatment with CA and TRAIL might be a promising therapy for osteosarcoma.
Extending partial representations of circle graphs
Authors: Chaplick Steven , Fulek Radoslav , Klavík Pavel 
Published: December 2018

AbstractThe partial representation extension problem is a recently introduced generalization of the recognition problem. A circle graph is an intersection graph of chords of a circle. We study the partial representation extension problem for circle graphs, where the input consists of a graph and a partial representation giving some predrawn chords that represent an induced subgraph of . The question is whether one can extend to a representation of the entire graph , that is, whether one can draw the remaining chords into a partially predrawn representation to obtain a representation of . Our main result is an time algorithm for partial representation extension of circle graphs, where is the number of vertices. To show this, we describe the structure of all representations of a circle graph using split decomposition. This can be of independent interest.
Loss of NFAT2 expression results in the acceleration of clonal evolution in chronic lymphocytic leukemia
Authors: Müller David J , Wirths Stefan , Fuchs Alexander R , Märklin Melanie , Heitmann Jonas S , Sturm Marc , Haap Michael , Kirschniak Andreas , Sasaki Yoshiteru , Kanz Lothar , Kopp Hans-Georg , Müller Martin R 
Published: December 2018

Abstract
Chronic lymphocytic leukemia (CLL) can be defined as a clonal expansion of B cells with stereotypic BCRs. Somatic hypermutation of the BCR heavy chains (IGVH) defines a subgroup of patients with a better prognosis. In up to 10% of CLL cases, a transformation to an aggressive B cell lymphoma (Richter’s syndrome) with a dismal prognosis can be observed over time. NFAT proteins are transcription factors originally identified in T cells, which also play an important role in B cells. The TCL1 transgenic mouse is a well-accepted model of CLL. Upon B cell-specific deletion of NFAT2, TCL1 transgenic mice develop a disease resembling human Richter’s syndrome. Whereas TCL1 B cells exhibit tonic anergic BCR signaling characteristic of human CLL, loss of NFAT2 expression leads to readily activated BCRs indicating different BCR usage with altered downstream signaling. Here, we analyzed BCR usage in wild-type and TCL1 transgenic mice with and without NFAT2 deletion employing conventional molecular biology techniques and next-generation sequencing (NGS). We demonstrate that the loss of NFAT2 in CLL precipitates the selection of unmutated BCRs and the preferential usage of certain VDJ recombinations, which subsequently results in the accelerated development of oligoclonal disease.
Osteochondral regeneration using constructs of mesenchymal stem cells made by bio three‐dimensional printing in mini‐pigs
Authors: Yamasaki Atsushi , Kunitomi Yoshihiro , Murata Daiki , Sunaga Takafumi , Kuramoto Tomohide , Sogawa Takeshi , Misumi Kazuhiro 
Published: December 2018

ABSTRACTOsteoarthritis is a major joint disease that has been extensively investigated in humans and in model animals. In this study, we examined the regeneration of articular cartilage and subchondral bone using artificial scaffold‐free constructs composed of adipose tissue‐derived mesenchymal stem cells (AT‐MSCs) created using bio three‐dimensional (3D) printing with a needle‐array. Printed constructs were implanted into osteochondral defects created in the right femoral trochlear groove of six mini‐pigs, using femoral defects created in the left femurs as controls. Repair within the defects was evaluated at 3 and 6 months post‐implantation using computed tomography (CT) and magnetic resonance (MR) imaging. The radiolucent volume (RV, mm3) in the defects was calculated using multi‐planar reconstruction of CT images. MR images were evaluated based on a modified 2D‐ MOCART (magnetic resonance observation of cartilage repair tissue) grading system. Gross and microscopic pathology were scored according to the ICRS (International Cartilage Repair Society) scale at 6 months after implantation. The percentage RV at 3 months postoperation was significantly lower in the implanted defects than in the controls, whereas total scores based on the MOCART system were significantly higher in the implanted defects as compared with the controls. Although there were no statistical differences in the gross scores, the average histological scores were significantly higher in the implanted defects than in the controls. To our knowledge, this is the first report to suggest that artificial scaffold‐free 3D‐printed constructs of autologous AT‐MSCs can be aid in the osteochondral regeneration in pigs. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1398–1408, 2019.