bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibacterial 3D bone scaffolds for tissue engineering application
Authors: Pant Jitendra , Sundaram Jaya , Goudie Marcus J. , Nguyen Dieu Thao , Handa Hitesh 
Published: September 2018

AbstractOpen bone fractures are not only difficult to heal but also are at a high risk of infections. Annual cases of fractures which result from osteoporosis amount to approximately 9 million. Endogenously released nitric oxide (NO) has been shown to play a role in osteogenic differentiation in addition to eradicating infection against a wide variety of pathogens. In the current work, antimicrobial NO releasing 3D bone scaffolds were fabricated using S‐nitroso‐N‐acetyl‐penicillamine (SNAP) as the NO donor. During fabrication, nano‐hydroxyapatite (nHA) was added to each of the scaffolds in the concentration range of 10–50 wt % in nHA‐starch‐alginate and nHA‐starch‐chitosan scaffolds. The mechanical strength of the scaffolds increased proportionally to the concentration of nHA and 50 wt % nHA‐starch‐alginate possessed the highest load bearing capacity of 203.95 ± 0.3 N. The NO flux of the 50 wt % nHA‐starch‐alginate scaffolds was found to be 0.50 ± 0.06 × 10−10 mol/min/mg initially which reduced to 0.23 ± 0.02 × 10−10 over a 24 h period under physiological conditions. As a result, a 99.76% ± 0.33% reduction in a gram‐positive bacterium, Staphylococcus aureus and a 99.80% ± 0.62% reduction in the adhered viable colonies of gram‐negative bacterium, Pseudomonas aeruginosa were observed, which is a significant stride in the field of antibacterial natural polymers. The surface morphology and pore size were observed to be appropriate for the potential bone cell growth. The material showed no toxic response toward mouse fibroblast cells. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1068–1078, 2019.
A fibrin‐coated pericardial extracellular matrix prevented heart adhesion in a rat model
Authors: Funamoto Seiichi , Hashimoto Yoshihide , Kishida Akio , Negishi Jun 
Published: September 2018

AbstractAs most surgical treatments pose a risk of tissue adhesion, methods to prevent adhesion are needed across various surgical fields. In this study, we investigated the use of a decellularized pericardium with fibrin glue to prevent rat heart adhesion. Porcine pericardia were decellularized by a high‐hydrostatic pressure method. Cells adhered to the resulting pericardial extracellular matrix (ECM) during an in vitro cell‐seeding test, but fibrin‐coated pericardial ECM showed reduced cell adhesion. In a rat surgical model of heart adhesion, the fibrin‐coated pericardial ECM did not adhere to the heart and mesothelial cell adhesion was observed on the ECM surface. Notably, the anti‐adhesion effect of fibrin‐coated pericardial ECM was observed 4 weeks after surgery. These results support the utility of fibrin‐coated pericardial ECM as an adhesion prevention material for cardiovascular surgery. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1088–1094, 2019.
Identification and validation of l‐asparaginase as a potential metabolic target against Mycobacterium tuberculosis
Authors: Kataria Arti , Singh Jasdeep , Kundu Bishwajit 
Published: September 2018

AbstractMultidrug‐resistant Mycobacterium tuberculosis (Mtb) has emerged as a major health challenge, necessitating the search for new molecular targets. A secretory amidohydrolase,
l‐asparaginase of Mtb (MtA), originally implicated in nitrogen assimilation and neutralization of acidic microenvironment inside human alveolar macrophages, has been proposed as a crucial metabolic enzyme. To investigate whether this enzyme could serve as a potential drug target, it was studied for structural details and active site–specific inhibitors were tested on cultured
Mycobacterial strain. The structural details of MtA obtained through comparative modeling and molecular dynamics simulations provided insights about the orchestration of an alternate reaction mechanism at the active site. This was contrary to the critical Tyr flipping mechanism reported in other asparaginases. We report the novel finding of Tyr to Val replacement in catalytic triad I along with the structural reorganization of a β‐hairpin loop upon substrate binding in MtA active site. Further, 5 MtA‐specific, active‐site–based inhibitors were obtained by following a rigorous differential screening protocol. When tested on
Mycobacterium culture, 3 of these, M3 (ZINC 4740895), M26 (ZINC 33535), and doxorubicin showed promising results with inhibitory concentrations (IC
50) of 431, 100, and 56 µM, respectively. Based on our findings and considering stark differences with human asparaginase, we project MtA as a promising molecular target against which the selected inhibitors may be used to counteract Mtb infection effectively.
DNA methylation in breast cancers: Differences based on estrogen receptor status and recurrence
Authors: Williams Kristin E. , Jawale Rahul M. , Schneider Sallie S. , Otis Christopher N. , Pentecost Brian T. , Arcaro Kathleen F. 
Published: September 2018

AbstractDNA methylation plays a role in the etiology of primary breast cancers. We analyzed paired primary and second breast tumors to elucidate the role of methylation in recurrence. Methylation profiles from paired primary and second breast tumors of 23 women were assessed using the HumanMethylation450 BeadChip. Twelve women had estrogen receptor positive (ERpos) primary and second tumors, five had estrogen receptor negative (ERneg) primary and second tumors, and six had an ERpos primary tumor but an ERneg second tumor. Stratifying tumors by occurrence revealed that the greater methylation previously associated with ERpos tumors, is more pronounced in primary tumors than in second tumors. Further, ERneg second tumors are more methylated than ERpos second tumors among women who had ERpos primary tumors. Pathway analyses using gene lists generated from comparisons of methylation in ERpos primary tumors from the paired sets with ERpos tumors from six women without recurrences, identified differences between groups based on the ER status of the second tumor. Hypermethylated genes of significantly enriched pathways were differentially associated with survival. DNA methylation profiles of ERpos primary breast tumors support the development and use of tumor methylation profiles for stratifying women with breast cancer both for prognosis and therapy.
CCL17‐CCR4 axis promotes metastasis via ERK/MMP13 pathway in bladder cancer
Authors: Zhao Hongda , Bo Qiyu , Wang Weifen , Wang Rui , Li Yan , Chen Shouzhen , Xia Yangyang , Wang Wenfu , Wang Yong , Zhu Kejia , Liu Lei , Cui Jianfeng , Wang Shuai , Liu Qinggang , Wu Zonglong , Guo Hu , Shi Benkang 
Published: September 2018

AbstractAs an important chemokine receptor, the role of CCR4 in the progression of bladder cancer (BC) remains unknown. In this study, we have shown that CCR4 expression was upregulated in bladder carcinoma tissues compared with adjacent nontumor tissues. Kaplan‐Meier survival analysis revealed that CCR4 expression was an independent prognostic risk factor in BC patients, and the addition of CCL17 induced CCR4 production and promoted migration and invasion of BC cells. In addition, CCR4 knockdown significantly attenuated the migratory and invasive capabilities of BC cells. Mechanistically, CCL17‐CCR4 axis is involved in ERK1/2 signaling and could mediate the migration and invasion of BC cells by regulating MMP13 activation. This study suggests that CCR4 might represent a promising prognostic biomarker and a potential therapeutic option for BC.
The regulatory roles of VEGF‐Notch signaling pathway on aplastic anemia with kidney deficiency and blood stasis
Authors: Deng Shu , Zeng Yuqing , Wu Liqiang , Hu Zhiping , Shen Jianping , Shen Yiping , Shen Yingying , Zhou Yuhong , Chen Jian , Lin Shengyun 
Published: September 2018

AbstractObjectiveVascular endothelial growth factor (VEGF)‐Notch signaling pathway plays an important role in aplastic anemia (AA). This study aimed to evaluate the regulatory roles of VEGF‐Notch signaling pathway on mesenchymal stem cells (MSCs) isolated from AA patients with kidney deficiency and blood stasis (KB) (AA MSCs).MethodsExpression of VEGF‐Notch signaling related factors, including VEGF, VEGFR, Notch‐1, Jagged1, Delta‐like1, and hes1 was detected in bone marrow (BM) tissues and AA MSCs by Western blot analysis. VEGF (100 ng/mL) and γ‐secretase inhibitor (DAPT) (10 μM) was used to active and inhibit VEGF‐Notch signaling in AA MSCs, respectively. After treatment, the proliferation, apoptosis, and adipogenic differentiation of AA MSCs was detected by Cell Counting Kit‐8, flow cytometry, and Oil red O staining, respectively. Lentivirus short hairpin RNA (shRNA) were constructed to downregulate Notch‐1 and VEGF in normal bone marrow mesenchymal stem cells (BMSCs), and the effects of VEGF/Notch‐1 shRNA transfected BMSCs on the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated.ResultsSignificantly lower expression of VEGF, VEGFR, Notch‐1, Jagged1, Delta‐like1, and hes1 was revealed in AA BM tissues and AA MSCs when compared with the normal control (P < 0.05). The intervention of DAPT significantly inhibited the proliferation, and promoted the apoptosis and adipogenic differentiation of AA MSCs, while VEGF intervention exhibited opposite results (P < 0.05). Meanwhile, the proliferation, migration, and angiogenesis of HUVECs were significantly promoted by normal BMSCs, while inhibited by VEGF/Notch‐1 shRNA transfected BMSCs (P < 0.05).ConclusionThe activation of VEGF‐Notch signaling pathway may be a potential therapeutic target for AA with KB.
Long‐term insulin treatment leads to a change in myosin heavy chain fiber distribution in OLETF rat skeletal muscle
Authors: Hong Oak‐Kee , Choi Yoon‐Hee , Kwon Hyuk‐Sang , Jeong Hee‐Kyoung , Son Jang‐Won , Lee Seong‐Su , Kim Sung‐Rae , Yoon Kun‐Ho , Yoo Soon Jib 
Published: September 2018

AbstractThe objective of this study was to investigate molecular and physiological changes in response to long‐term insulin glargine treatment in the skeletal muscle of OLETF rats. Male Otsuka Long‐Evans Tokushima Fatty (OLETF) and Long‐Evans Tokushima Otsuka (LETO) rats aged 24 weeks were randomly allocated to either treatment with insulin for 24 weeks or no treatment, resulting in three groups. Insulin glargine treatment in OLETF rats (OLETF‐G) for 24 weeks resulted in changes in blood glucose levels in intraperitoneal glucose tolerance tests compared with age‐matched, untreated OLETF rats (OLETF‐C), and the area under the curve was significantly decreased for OLETF‐G rats compared with OLETF‐C rats (P < 0.05). The protein levels of MHC isoforms were altered in gastrocnemius muscle of OLETF rats, and the proportions of myosin heavy chain type I and II fibers were lower and higher, respectively, in OLETF‐G compared with OLETF‐C rats. Activation of myokines (IL‐6, IL‐15, FNDC5, and myostatin) in gastrocnemius muscle was significantly inhibited in OLETF‐G compared with OLETF‐C rats (
P < 0.05). MyoD and myogenin levels were decreased, while IGF‐I and GLUT4 levels were increased, in the skeletal muscle of OLETF‐G rats (
P < 0.05). Insulin glargine treatment significantly increased the phosphorylation levels of AMPK, SIRT1, and PGC‐1α. Together, our results suggested that changes in the distribution of fiber types by insulin glargine could result in downregulation of myokines and muscle regulatory proteins. The effects were likely associated with activation of the AMPK/SIRT1/PGC‐1α signaling pathway. Changes in these proteins may at least partly explain the effect of insulin in skeletal muscle of diabetes mellitus.
Interaction of long noncoding RNA MEG3 with miRNAs: A reciprocal regulation
Authors: Moradi Mohammad‐Taher , Fallahi Hossein , Rahimi Zohreh 
Published: September 2018

AbstractThe competitive endogenous RNA (ceRNA) hypothesis suggests that a long noncoding RNA (lncRNA) can function as sinks for pools of microRNAs (miRNAs); thereby, in the presence of ceRNA, messenger RNAs (mRNAs) targeted by specific miRNAs can liberate and translate to protein. Maternally expressed gene 3 (MEG3) is a lncRNA, which its expression has been detected in various normal tissues, while it is lost or downregulated in human tumors. The
MEG3 is an imprinted gene which, is methylated and suppressed by DNA methyltransferases (DNMTs) family. Also, miRNAs are involved in the regulation of
MEG3 gene expression. Interestingly, the lncRNA MEG3 (lnc‐MEG3), as a ceRNA affects various cell processes such as proliferation, apoptosis, and angiogenesis by sponging miRNAs. These miRNAs, in turn, regulate different mRNAs in different pathways. This review focuses on the interaction between lnc‐MEG3 and experimentally validated miRNAs. In addition, the discussion supplemented by some data obtained from mirPath (v.3) and TarBase (v.8) databanks to provide more details about the pathways affected by this ceRNA.
Long noncoding RNAs antisense noncoding RNA in the INK4 locus (ANRIL) correlates with lower acute exacerbation risk, decreased inflammatory cytokines, and mild GOLD stage in patients with chronic obstructive pulmonary disease
Authors: Ge Jianli , Geng Shasha , Jiang Hua 
Published: September 2018

BackgroundWe aimed to assess the predictive value of long noncoding RNAs antisense noncoding RNA in the INK4 locus (lncRNAs ANRIL) for acute exacerbation of chronic obstructive pulmonary disease (COPD) and evaluate its correlation with inflammatory cytokines as well as the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage in COPD patients.MethodsA total of 136 acute exacerbations of COPD (AECOPD) patients, 138 stable COPD patients, and 140 healthy controls (HCs) were consecutively recruited, and plasma samples were collected. Real‐time polymerase chain reaction was used to detect lncRNA ANRIL expression. Enzyme‐linked immunosorbent assay was performed to detect inflammatory cytokines expressions.ResultsLncRNA ANRIL expression was lower in AECOPD patients compared with stable COPD patients and HCs (Both P < 0.001). Receiver operating characteristic curves revealed lncRNA ANRIL could distinguish AECOPD patients from HCs (area under curve (AUC):0.700, 95% CI: 0.638‐0.762) and stable COPD patients (AUC: 0.659, 95% CI: 0.594‐0.724). For inflammatory cytokines, lncRNA ANRIL expression was negatively correlated with TNF‐α (P < 0.001), IL‐1β (P = 0.015), IL‐8 (P = 0.008), IL‐17A (P = 0.002), and LTB‐4 (P = 0.004) in AECOPD patients, while it was negatively correlated with TNF‐α (P = 0.049), IL‐1β (P = 0.005), IL‐17A (P = 0.030), and LTB‐4 (P = 0.011) in stable COPD patients. Furthermore, lncRNA ANRIL expression negatively correlated with GOLD stage in AECOPD patients (P = 0.001), but not in stable COPD patients (P = 0.131).ConclusionLncRNA ANRIL associates with lower acute exacerbation risk, decreased inflammatory cytokines, and mild GOLD stage in COPD patients.
MiR‐499 regulates myoblast proliferation and differentiation by targeting transforming growth factor β receptor 1
Authors: Wu Jiyao , Yue Binglin , Lan Xianyong , Wang Yanhuan , Fang Xingtang , Ma Yun , Bai Yueyu , Qi Xingshan , Zhang Chunlei , Chen Hong 
Published: September 2018

AbstractMicroRNAs (miRNAs or miRs) are small noncoding RNAs that play critical roles in muscle cell proliferation and differentiation via post‐transcriptional regulation of gene expression. Here, based on our previous high‐throughput sequencing results, we evaluated miRNA‐499 (miR‐499) functions during myoblast proliferation and differentiation. In addition, we analyzed miR‐499 expression profiles and characterized the associated functional roles. MiR‐499 is known to be a skeletal muscle fiber‐type‐associated miRNA. However, its roles in skeletal myoblast proliferation and differentiation are poorly understood. MiR‐499 overexpression promoted C2C12 cell proliferation and significantly attenuated C2C12 cell myogenic differentiation. Furthermore, miR‐499 inhibition enhanced C2C12 cell proliferation and suppressed C2C12 cell differentiation. Using dual‐luciferase reporter assays and western blot analysis, we confirmed that miR‐499 targeted transforming growth factor β receptor 1 (TGFβR1), a known regulator of skeletal myoblast development. Additionally, our RNA interference analysis, in which TGFβR1 was downregulated, showed that TGFβR1 significantly promoted the differentiation of C2C12 cells and inhibited their proliferation.
Retracted: MicroRNA‐363 inhibits angiogenesis, proliferation, invasion, and migration of renal cell carcinoma via inactivation of the Janus tyrosine kinases 2–signal transducers and activators of transcription 3 axis by suppressing growth hormone receptor gene
Authors: Zhu Jie , Zhu Da‐Qing , Zhang Yu , Liu Qi‐Ming , Wang Peng‐Chao , Li Hong‐Zhao , Ma Xin , Zhang Xu 
Published: September 2018

AbstractRenal cell carcinoma (RCC) is the most common malignancy involving the kidneys and a major cause of cancer mortality. The involvement of microRNA (miRNA) expression in the tumorigenesis and progression of RCC has been previously highlighted. Therefore, we conducted this study to investigate whether microRNA‐363 (miR‐363) affects the development of RCC via the Janus tyrosine kinases (JAK2)–signal transducers and activators of transcription (STAT) axis by targeting the growth hormone receptor (GHR), by observing the changes that occurred in the RCC and the normal adjacent tissues of patients with RCC. RCC cells were transfected with a series of miR‐363 mimic, miR‐363 inhibitor, or small interfering RNA against GHR to determine the influence of miR‐363 on the expression of GHR and JAK2–STAT3 axis‐related genes with the use of reverse transcription quantitative polymerase chain reaction and Western blot analysis. The angiogenesis, viability, invasion, and migration of cells were evaluated by means of in vitro angiogenesis, 3‐(4,5)‐dimethylthiahiazo (‐z‐y1)‐3,5‐di‐phenytetrazoliumromide (MTT), wound‐healing, and Transwell assays. The results revealed reduced miR‐363 expression and elevated GHR expression in RCC. It was also found that miR‐363 altered the activation of the JAK2–STAT3 axis through the inhibition of GHR. Cells treated with the miR‐363 inhibitor presented with increased capillary vessels, cell viability, invasion, and migration, whereas it was on the contrary in the RCC cells with overexpressed miR‐363. These results implicated that the overexpression of miR‐363 could specifically bind to GHR to downregulate the expression of GHR, which, in turn, inactivates the JAK2–STAT3 axis, thereby influencing the angiogenesis, cell invasion, and migration abilities in RCC.
New advances of lncRNAs in liver fibrosis, with specific focus on lncRNA–miRNA interactions
Authors: Bian Er‐Bao , Xiong Zhi‐Gang , Li Jun 
Published: September 2018

AbstractNoncoding RNAs (ncRNAs) were initially thought to be transcriptional byproducts. However, recent advances of ncRNAs research have increased our understanding of the importance of ncRNA in gene regulation and disease pathogenesis. Consistent with these developments, liver fibrosis research is also experiencing rapid growth in the investigation of links between ncRNAs and the pathology of this disease. The initial focus was on studying the function and regulation mechanisms of microRNAs (miRNAs). However, recently, elucidation of the mechanisms of long noncoding RNAs (lncRNAs) and lncRNA‐mediated liver fibrosis has just commenced. In this review, we emphasize on abnormal expression of lncRNAs in liver fibrosis. Furthermore, we also discuss that the interaction of lncRNAs with miRNAs is involved in the regulation of the expression of protein‐coding genes in liver fibrosis. Recent advances in understanding dysregulated lncRNAs expression and the lncRNAs–miRNAs interaction in liver fibrosis will help for developing new therapeutic targets and biomarkers of liver fibrosis.
The predictive value of intra‐left atrial mechanical delay for 1‐year recurrence of atrial fibrillation after catheter ablation: A clinical follow‐up study using dual Doppler echocardiography
Authors: Zhou Yanxiang , Chen Jinling , Hu Bo , Cao Sheng , Zhou Qing , Guo Ruiqiang 
Published: September 2018

PurposeThe availability of dual Doppler echocardiography (DDE), which facilitates the simultaneous recording of Doppler waveforms at two different sites, has enhanced ability to assess single‐beat atrial mechanical delay. We sought to investigate the predictive value of intra‐left atrial mechanical delay for atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) with DDE.MethodsEighty‐six patients with paroxysmal AF scheduled to undergo RFCA were prospectively enrolled. Intra‐atrial and interatrial mechanical delays were evaluated by DDE and traditional tissue Doppler imaging (tTDI), respectively. The time of whole analysis process with each method was recorded. After RFCA, patients were followed for 1 year.ResultsThirty (34.88%) patients had AF recurrence, and 56 (65.12%) patients maintained sinus rhythm. Cut‐off values of 39.38 ms for intra‐left atrial mechanical delay obtained by DDE and 32.70 ms by tTDI predicted AF recurrence. Areas under curves were comparable in receiver operator characteristic analysis (P > .05). The whole analysis time of DDE was less than tTDI. Parameters obtained by DDE had better reproducibility.ConclusionIntra‐left atrial mechanical delay best predicted 1‐year AF recurrence after RFCA. Compared with tTDI, DDE can noninvasively assess single‐beat atrial mechanical delay with high predictive power, less analysis time, and better reproducibility.
Radiomics Analysis of Multiparametric MRI Evaluates the Pathological Features of Cervical Squamous Cell Carcinoma
Authors: Wu Qingxia , Shi Dapeng , Dou Shewei , Shi Ligang , Liu Mingbo , Dong Li , Chang Xiaowan , Wang Meiyun 
Published: September 2018

BackgroundRobust parameters to evaluate pathological aggressiveness are needed to provide individualized therapy for cervical cancer patients.PurposeTo investigate the radiomics analysis of multiparametric MRI to evaluate tumor grade, lymphovascular space invasion (LVSI), and lymph node (LN) metastasis of cervical squamous cell carcinoma (CSCC).Study TypeRetrospective.SubjectsFifty‐six patients with histopathologically confirmed CSCC.Field Strength/Sequence3T, axial T2 and T2 with fat suppression (FS), diffusion‐weighted imaging (DWI) (multi‐b values), axial dynamic contrast enhanced (DCE) MRI (8 sec temporal resolution).AssessmentRegions of interest were drawn around the tumor on each axial slice and fused to generate the whole tumor volume. Sixty‐six radiomics features were derived from each image sequence, including axial T2 and T2 FS, ADC maps, and Ktrans, Ve, and Vp maps from DCE MRI.Statistical TestsA univariate analysis was performed to assess each parameter's association with tumor grade and the presence of lymphovascular space invasion (LVSI) and lymph node (LN) metastasis. A principal component analysis was employed for dimension reduction and to generate new discriminative valuables. Using logistic regression, a discriminative model of each parameter was built and a receiver operating characteristic curve (ROC) was generated.ResultsThe area under the ROC curve (AUC) of anatomical, diffusion, and permeability parameters in discriminating the presence of LVSI ranged from 0.659 to 0.814, with Ve showing the best discriminative value. The AUC in discriminating the presence of LN metastasis and distinguishing tumor grade ranged from 0.747 to 0.850, 0.668 to 0.757, with ADC and Ve showing the best discriminative value, respectively.Data ConclusionFunctional maps exhibit better discriminative values than anatomical images for discriminating the pathological features of CSCC, with ADC maps showing the best discrimination performance for LN metastasis and Ve maps showing the best discriminative value for LVSI and tumor grade.Level of Evidence: 3Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2019;49:1141–1148.