bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of miR‐181a targeting XIAP gene on apoptosis of cardiomyocytes induced by hypoxia/reoxygenation and its mechanism
Authors: Hao Peiyuan , Cao Xueming , Zhu Zhongyu , Gao Chuanyu , Chen Yan , Qi Datun 
Published: November 2018

AbstractTo investigate the effect of miR‐181a targeting XIAP gene on the apoptosis of cardiomyocytes induced by hypoxia/reoxygenation (H/R) and its mechanism. The primary cultured cardiomyocytes were treated with hypoxia for 3 hours and reoxygenation for 4 hours to construct H/R cell model. The expression of miR‐181a and XIAP messenger RNA in cardiomyocytes was detected by reverse‐transcription polymerase chain reaction, and the expression of XIAP protein in cardiomyocytes was detected by Western blot analysis. H/R cardiomyocytes with low expression of miR‐181a and overexpression of XIAP were constructed, and the effects of low expression of miR‐181a and upregulation of XIAP on cardiomyocyte apoptosis were detected by flow cytometry. A dual luciferase reporter assay was used to detect the target relationship between miR‐181a and XIAP. Further, H/R myocardial cells with low XIAP expression were constructed to observe the effect of downregulation of XIAP expression on apoptosis of myocardial cells with low expression of microarray‐181a. The expression of apoptosis‐related proteins Bax and Bcl‐2 in myocardial cells was detected by Western blot analysis. After H/R treatment, the expression of microRNAs‐181a was high but that of XIAP was low. The apoptosis of cardiomyocytes could be inhibited by both the low expression of miR‐181a and the upregulation of XIAP. The results of dual luciferase reporter gene showed that XIAP was a potential target gene for miR‐181a. The inhibitory effect of low expression of miR‐181a on myocardial apoptosis could be reversed and the inhibitory effect of low expression of miR‐181a on Bax protein expression and the promotion of Bcl‐2 protein expression could be reversed by the downregulation of XIAP. MiR‐181a can inhibit the apoptosis of hypoxic‐reoxygenated cardiomyocytes by targeting XIAP to downregulate Bax and upregulate Bcl expression.
Mechanism of miR‐137 regulating migration and invasion of melanoma cells by targeting PIK3R3 gene
Authors: Qi Jia , Wang Wei‐wei , Chen Wei , Lu Wen‐ying , Shang An‐quan 
Published: November 2018

AbstractObjectiveTo investigate the effect of microRNA‐137 (miR‐137) on the migration and invasion of melanoma cells and its mechanism.MethodsQuantitative real‐time polymerase chain reaction (qRT‐PCR) was used to detect the expression of miR‐137 in melanoma tissues and cells. miR‐137 mimics, phosphoinositide‐3‐kinase regulatory subunit 3 (PIK3R3) small interfering RNA and corresponding controls were transfected into A375 and WM451 cells by lipofection. The expression of PIK3R3 was examined by qRT‐PCR and Western blot analysis. The Trans‐well assay was conducted to measure cell migration and invasion. Dual luciferase reporter assay was used to detect the interaction between miR‐137 and PIK3R3.ResultsCompared with normal pigmented nevus tissue, miR‐137 expression was significantly reduced in melanoma tissues. Compared with keratinous HaCaT cells, the level of miR‐137 was significantly decreased in melanoma SK‐MEL‐1, A375, and WM451 cells. Knockdown of miR‐137 significantly reduced the migrated and invasive abilities of melanoma A375 and WM451 cells. Moreover, inhibition of PIK3R3 obviously suppressed the migration and invasion abilities of melanoma A375 and WM451 cells. Luciferase activity assay showed that PIK3R3 was a direct target of miR‐137. In addition, overexpression of miR‐137‐inhibited PIK3R3 expression, while knockdown of miR‐137‐enhanced PIK3R3 abundance. Restoration of PIK3R3 reversed the regulatory effect of miR‐137 on cell migration and invasive in melanoma A375 and WM451 cells.ConclusionmiR‐137 inhibited melanoma cell migration and invasion by targeting PIK3R3 gene.
Expression of DEC2 enhances chemosensitivity by inhibiting STAT5A in gastric cancer
Authors: Li Hongyu , Ma Xiaoli , Xiao Dongjie , Jia Yanfei , Wang Yunshan 
Published: November 2018

AbstractGastric cancer (GC) is one of the most common cancers. Resistance to 5‐fluorouracil (5‐Fu)‐based chemotherapy is a major cause of treatment failure followed by the poor prognosis of patients. In GC, it was reported that human differentiated embryonic chondrocyte‐expressed gene 2 (DEC2), suppressed tumor proliferation and metastasis, but the effect of DEC2 on chemosensitivity of GC cells was unknown. In our study, we found that DEC2 can obviously increase the sensibility of GC cells to 5‐Fu by promoting 5‐Fu‐induced apoptosis. DEC2 overexpression is significantly associated with decreased phosphorylation of STAT5A (P‐STAT5A). More importantly, negative correlations between DEC2 with P‐STAT5A expression were observed in tissue sections from GC patients. GC patients with low expression levels of DEC2 and high expression levels of P‐STAT5A showed a poor prognosis. Furthermore, enhanced chemosensitivity mediated by DEC2 can be reversed by STAT5A which confer GC cells resistance to apoptosis induced by 5‐Fu. Together, our results suggest that through inhibiting activation of STAT5A, DEC2 enhances 5‐Fu‐induced apoptosis and suppression of proliferation in GC cells. These findings will provide new insight for identifying potential targets that can be used to sensitize GC cells to chemotherapy.
Transcellular traversal of the blood‐brain barrier by the pathogenic Propionibacterium acnes
Authors: Lu Xuetao , Qi Xianlong , Yi Xiuli , Jian Zhe , Gao Tianwen 
Published: November 2018

AbstractBackgroundPropionibacterium acnes (P. acnes) is an anaerobe commonly stay in the body as part of the commensal microbiota, and a dominant bacterium of the human skin and hair follicles. It has been found that this bacterium could participate in brain inflammation that causes Alzheimer's disease (AD) and Parkinson's disease (PD). But how P. acnes invade the brain remains elusive.MethodsWe established the in vitro blood‐brain barrier (BBB) model by culturing the HBMEC/D3 cell line on collagen‐coated PFTE membrane. The BBB model was verified by the transepithelial electrical resistance (TEER) and horseradish peroxidase (HRP) permeability rate, and observed by the scanning electron microscope (SEM), transmission electron microscope (TEM), as well as confocal microscope. The P. acnes was then cocultured with the in vitro BBB model and the permeability of P. acnes was measured by counting the bacteria clones collected from the lower chamber of the model.ResultsHigh local concentration of P. acnes invaded the in vitro BBB model through the transcellular traversal pathway. The permeability for P. acnes was increased by the treatment of lipopolysaccharide (LPS), but not mannitol. P. acnes invasion elevated the expression of cell adhesion molecules E‐selectin, ICAM‐1, and VCAM‐1 in HBMEC cells.ConclusionP. acnes has the ability to penetrate the brain though transcellular invasion of the blood‐brain barrier.
Study of p16 promoter methylation in Egyptian colorectal cancer patients
Authors: Karam Rehab A. , Zidan Haidy E. , Abd Elrahman Tamer M. , Badr Samir A. , Amer Samar A. 
Published: November 2018

AbstractMany tumor‐suppressor genes contain CpG islands in their promoter regions which raised the necessity of investigating the role of methylation in silencing these genes. We examined p16 methylation as a potential biomarker in the peripheral blood of colorectal cancer (CRC) patients. Using methylation‐specific polymerase chain reaction method, the methylation status of p16 was investigated in the tumor tissue and blood of 65 CRC patients and blood samples from 70 healthy control individuals. Also, the relationship between p16 methylation level and the clinical‐pathological findings in CRC was evaluated. The frequency of blood p16 methylation in CRC cases was significantly higher than in control (P = 0.0001). The sensitivity and specificity of p16 methylation in diagnosing CRC was 55.38% and 98.5%, respectively, with 77.7% diagnostic accuracy. There was significant association between p16 methylation and age, sex, Dukes staging, lymph node involvement, and carcinoembryonic antigen levels. Our study revealed that p16 promoter methylation could be considered as both potential diagnostic and prognostic biomarker of CRC.
Fractionated radiotherapy might induce epithelial‐mesenchymal transition and radioresistance in a cellular context manner
Authors: Tahmasebi‐Birgani Mohammad‐Javad , Teimoori Ali , Ghadiri Ata , Mansoury‐Asl Halime , Danyaei Amir , Khanbabaei Hashem 
Published: November 2018

AbstractDespite the fact that radiotherapy is a main therapeutic modality in cancer treatment, recent evidence suggests that fractionated radiotherapy (FR) might confer radioresistance through epithelial‐mesenchymal transition (EMT). Nevertheless, the effects of FR on EMT phenotype and the potential link between EMT induction and radioresistance development yet to be clarified. The aim of this study was to assess whether FR could promote EMT, and to elucidate if induction of EMT contributes to the acquisition of radioresistance. To this end, two human cancer cell lines (A549 and HT‐29) were irradiated (2 Gy/day) and analyzed using wound healing, transwell migration and invasion assays, real‐time polymerase chain reaction (for E‐cadherin, N‐cadherin, Vimentin, CD44, CD133, Snail, and Twist), clonogenic assay, Annexin V/PI, and 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide (MTT) assay. Irradiation of A549 (for 5 or 10 consecutive days) resulted in morphological changes including elongation of cytoplasm and nuclei and pleomorphic nuclei. Also, irradiation‐enhanced migratory and invasive potential of A549. These phenotypic changes were in agreement with decreased expression of the epithelial marker (E‐cadherin), enhanced expression of mesenchymal markers (N‐cadherin, Vimentin, Snail, and Twist) and increased stemness factors (CD44 and CD133). Moreover, induction of EMT phenotype was accompanied with enhanced radioresistance and proliferation of irradiated A549. However, FR (for 5 consecutive days) did not increase HT‐29 motility. Furthermore, molecular alterations did not resemble EMT phenotype (downregulation of E‐cadherin, Vimentin, ALDH, CD44, CD133, and Snail). Eventually, FR led to enhanced radiosensitivity and decreased proliferation of HT‐29. Altogether, our findings suggest that FR might induce EMT and confer radioresistance in a cell context‐dependent manner.
Predictors of change in cognitive processing therapy for veterans in a residential PTSD treatment program
Authors: Hale Andrew C. , Rodriguez Jessica L. , Wright Theodore P. , Driesenga Scott A. , Spates C. Richard 
Published: November 2018

AbstractObjectiveCognitive processing therapy is an evidence‐based treatment for posttraumatic stress disorder (PTSD); however, questions remain regarding variability in treatment response.MethodA total of 123 veterans participated in group‐based cognitive processing therapy (CPT) in residential PTSD treatment. Change over time in PTSD symptoms was modeled as a function of selected demographic and clinical variables.ResultsPTSD checklist (PCL) scores decreased by an average of 1 point per session (standard deviation [SD] = 0.1). Initial PCL scores were predicted by the Beck Depression Inventory‐II (γ01 = 0.25; standard error [SE] = 0.08), Insomnia Severity Index (γ02 = 0.53; SE = 0.15), and Infrequency (F) scale of the Minnesota Multiphasic Personality Inventory‐2 (γ03 = 0.09; SE = 0.04). Rate of change was predicted by the Somatic Complaints (RC1) scale (γ11 = −0.03; SE = 0.01) and the Antisocial Behavior (RC4) scale (γ12 = 0.02; SE = 0.01).ConclusionsThese results provide insight into characteristics that may influence degree of benefit received from group‐based CPT.
Partitioning a graph into monochromatic connected subgraphs
Authors: Girão António , Letzter Shoham , Sahasrabudhe Julian 
Published: November 2018

AbstractWe show that every ‐edge‐colored graph on vertices with minimum degree at least can be partitioned into two monochromatic connected subgraphs, provided is sufficiently large. This minimum degree condition is tight and the result proves a conjecture of Bal and DeBiasio. We also make progress on another conjecture of Bal and DeBiasio on covering graphs with large minimum degree with monochromatic components of distinct colors.
Functionalization of Quinazolin‐4‐ones Part 3: Synthesis, Structures Elucidation, DNA‐PK, PI3K, and Cytotoxicity of Novel 8‐Aryl‐2‐morpholino‐quinazolin‐4‐ones
Authors: Heppell Jacob T. , Islam Md. Amirul , McAlpine Shelli R. , Al‐Rawi Jasim M. A. 
Published: November 2018

A series of novel 8‐aryl‐2‐morpholino quinazolines (11a–n, 12a–d, 14a–f, and 15) were synthesized from the precursor 2‐thioxo quinazolin‐4‐ones 8. The 8‐aryl‐2‐morpholino quinazolines compounds were assayed for DNA‐PK and PI3K. All compounds showed low DNA‐PK % inhibition activity at 10 μM compound concertation, and the most active was 8‐(dibenzo[b,d]thiophen‐4‐yl) 12d with 38% inhibition. Similar pattern of PI3K α, β, γ, and δ isoforms inhibition activity at 10 μM were observed. The most active isoform was PI3K δ of 41% inhibition for 8‐(dibenzo[b,d]furan‐4‐yl) compound 11. Most compounds were less active than expected in spite of the strong structural resemblance to known inhibitors (NU7441, 3, 4, and 6). Loss of activity could be attributed to the tautomerization to the aromatic enol (4‐OH), which could specify that the important functional group for the activity is the 4‐carbonyl (C=O) group. Alternatively, the aromatization of the pyrimidine heterocyclic ring could alter the conformation, and thus binding site, of the 2‐morpholine ring, which could reduce the compound‐receptor hydrogen bonding to the morpholine 4‐oxygen. Selected compounds displayed appreciable cytotoxicity with 6‐chloro‐8‐(dibenzo[b,d]thiophen‐4‐yl)‐2‐morpholinoquinazolin‐4(1H)‐one 11j exhibiting the greatest activity with an IC50 of 9.95 μM. Therefore, the mechanism of the cytotoxicity of compound 11j were not through DNA‐PK or PI3K inhibition activity.
The importance of local epidemic conditions in monitoring progress towards HIV epidemic control in Kenya: a modelling study
Authors: Anderson Sarah‐Jane , Garnett Geoffrey P , Enstone Joanne , Hallett Timothy B 
Published: November 2018

AbstractIntroductionSetting and monitoring progress towards targets for HIV control is critical in ensuring responsive programmes. Here, we explore how to apply targets for reduction in HIV incidence to local settings and which indicators give the strongest signal of a change in incidence in the population and are therefore most important to monitor.MethodsWe use location‐specific HIV transmission models, tailored to the epidemics in the counties and major cities in Kenya, to project a wide range of plausible future epidemic trajectories through varying behaviours, treatment coverage and prevention interventions. We look at the change in incidence across modelled scenarios in each location between 2015 and 2030 to inform local target setting. We also simulate the measurement of a library of potential indicators and assess which are most strongly associated with a change in incidence.ResultsConsiderable variation was observed in the trajectory of the local epidemics under the plausible scenarios defined (only 10 of 48 locations saw a median reduction in incidence of greater than or equal to an 80% target by 2030). Indicators that provide strong signals in certain epidemic types may not perform consistently well in settings with different epidemiological features. Predicting changes in incidence is more challenging in advanced generalized epidemics compared to concentrated epidemics where changes in high‐risk sub‐populations track more closely to the population as a whole. Many indicators demonstrate only limited association with incidence (such as “condom use” or “pre‐exposure prophylaxis coverage”). This is because many other factors (low effectiveness, impact of other interventions, countervailing changes in risk behaviours, etc.) can confound the relationship between interventions and their ultimate long‐term impact, especially for an intervention with low expected coverage. The population prevalence of viral suppression shows the most consistent associations with long‐term changes in incidence even in the largest generalized epidemics.ConclusionsTarget setting should be appropriate for the local epidemic and what can feasibly be achieved. There is no one universally reliable indicator to predict future HIV incidence across settings. Thus, the signature of epidemic control must contain indications of success across a wide range of interventions and outcomes.
Terahertz ultrasensitive biosensing metamaterial and metasurface based on spoof surface plasmon polaritons
Authors: Cheng Dong , Zhang Bao , Liu Guo , Wang Jianxun , Luo Yong 
Published: November 2018

AbstractAs a promising candidate for rapid and ultrasensitive sensing of biomolecules, terahertz time‐domain spectroscopy (THz‐TDS) can be considered with superior performance in label‐free, noncontact, noninvasive, and nondestructive detection. In particular, almost significant conformational information can be captured with THz‐TDS. Meanwhile, terahertz (THz) metamaterial or metasurface biosensing chips based on THz‐TDS were proposed to promote the detection sensitivity within strong local field‐matter enhancement. In this paper, the ultrasensitive THz biosensing metamaterial and metasurface for DNA/RNA detecting based on spoof surface plasmon polaritons (SSPPs) is probed. The simulated results show that the maximum frequency sensitivity of the proposed metamaterial and metasurface for DNA/RNA biosensing can respectively approach to 2.52 THz/refractive index unit (RIU) and 2.23 THz/RIU. In addition, the film thickness sensitivities of metamaterial and metasurface biosensors are respectively higher than 71.1 GHz/μm and 79.2 GHz/μm when the thickness of biomaterial is thinner than 4 μm. All these ascendant performances achieved in the proposed metamaterial and metasurface biosensors can be realized and exploited for ultrasensitive biomolecules detection, health monitoring, medical film sensing, and safety inspection in THz regime.
SDHx gene detection and clinical Phenotypic analysis of multiple paraganglioma in the head and neck
Authors: Ding Yiming , Feng Yaru , Wells Michael , Huang Zhigang , Chen Xiaohong 
Published: November 2018

ObjectivesThe goal of this study was to detect and explore the mechanisms of the succinate dehydrogenase (SDH) complex subunit‐related gene mutations in cases of multiple paraganglioma (PGL) in the head and neck.MethodsIn Beijing Tongren Hospital (Capital Medical University, Beijing, People's Republic of China) between January 2013 and February 2017, 23 cases of head and neck multiple PGL were evaluated by genetic sequencing. From these cases, four hereditary families and 10 cases with sporadic occurrences were found. Gene mutations, including SDHD, SDHB, SDHC, SDHAF2, VHL and RET in germ cells and somatic cells, were detected by gene capture and high throughput sequencing.ResultsIn family 1, 12 instances of SDHD gene mutation were detected, eight of which manifested as bilateral carotid body tumor (CBT) with one bilateral malignant CBT. In family 2, three cases of SDHD mutation were found with one case of bilateral CBT and two cases of unilateral CBT. In family 3, two cases of SDHD gene mutation were found, both characterized by vagus PGL and pheochromocytoma. Of the 10 patients with sporadic manifestations, five cases of SDHD gene mutation and one case of RET gene mutation were detected. Two novel gene mutations, c.387_393del7 mutation of SDHD gene and c.3247A>G mutation of RET gene, were also detected.ConclusionIn patients with multiple PGL in the head and neck, these are accompanied by a genetic mutation of the germ cell. In this case study, this mutation was most commonly a mutation of the SDHD gene.Level of Evidence4 Laryngoscope, 129:E67–E71, 2019
Impact of coblation versus electrocautery on acute post‐operative outcomes in pediatric tonsillectomy
Authors: Lin Chen , Thung Arlyne K. , Jatana Kris R. , Cooper Jennifer N. , Barron L. Christine , Elmaraghy Charles A. 
Published: November 2018

ObjectiveBased on previous studies in the pediatric population, it remains unclear whether there is a difference in postoperative pain between two widely used tonsillectomy techniques: coblation and bovie electrocautery. This large prospective study investigates whether postoperative pain scores differ between these two surgical techniques for tonsillectomy.MethodsProspective, non‐randomized study of children aged 2–8 enrolled in a randomized controlled trial of single‐dose intravenous acetaminophen for pain associated with adenotonsillectomy. Included procedures occurred between October 2012 and June 2015 at a tertiary referral center. Only patients whose operations exclusively used coblation or electrocautery and who required postoperative admission for extended observation were included. Follow‐up period was the length of inpatient stay. Patients and nurses who recorded the pain scores were blinded to the tonsillectomy technique.ResultsA total of 183 patients were included: 117 coblation cases and 66 electrocautery cases. Pain scores in the surgical recovery unit and pain scores after admission to the floor unit were not significantly different between coblation and electrocautery, either before or after adjustment for patient age, body mass index, intravenous acetaminophen use, and surgeon. There was also no difference in length of stay, readmission rate, or post‐tonsillectomy hemorrhage.ConclusionsCoblation and electrocautery tonsillectomy are associated with similar post‐operative pain scores in the recovery and inpatient units in the pediatric population. As coblation is costlier, the results of this study may affect which tool is used by otolaryngologists from a cost–benefit perspective.Level of evidenceIII
Distribution of label‐retaining cells and their properties in the vocal fold mucosa
Authors: Sato Kiminobu , Kurita Takashi , Chitose Shun‐ichi , Sato Kiminori , Umeno Hirohito , Yano Hirohisa 
Published: November 2018

ObjectiveThe latest research suggests cells in the maculae flavae (MFe) are putative stem cells of the vocal fold mucosa and the MFe are a candidate for a stem cell niche. Distribution and properties of label‐retaining cells (LRCs) in the vocal fold mucosa were investigated.Study DesignHistologic analysis of the rat vocal folds.MethodsOral administration of bromodeoxyuridine (BrdU) was given to rats and the LRCs in the vocal fold mucosa were observed by immunohistochemistry. Immunoreactivity to antibodies directed to BrdU, Ki67, cytokeratin, vimentin, glial fibrillary acidic protein, desmin, Sox17, CD34, CD45, Type I collagen, and CD44 was studied. Extracellular matrices around LRCs were observed by Alcian blue staining and hyaluronidase digestion study.ResultsLRCs were present in the MFe and were resting cells (G0‐phase). They expressed epithelium, muscle, neural, and mesenchymal cell–associated intermediate filament proteins, and an endodermal marker, indicating cells in the MFe are undifferentiated and express proteins of all three germ layers. They expressed hematopoietic markers (CD34, CD45) and Type I collagen, which are the major markers of bone marrow derived circulating fibrocytes. The hyaluronan concentration in the MFe was high and the cells in the MFe expressed the surface hyaluronan receptor CD44, indicating that the MFe were a hyaluronan‐rich matrix.ConclusionLRCs reside in the MFe and MFe had a hyaluronan‐rich matrix. The results of this study are consistent with the hypothesis that the cells in the MFe are putative stem cells and the MFe are a candidate for a stem cell niche.Level of EvidenceN/A