bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a training program for the ultrasound screening of placenta accreta spectrum disorders
Authors: Dimitrova Ivelina , Jauniaux Eric , Zosmer Nurit , De Stefani Luciana Bocchi , Andrade Walkyria , Bourmpaki Elli , Bunce Catey , Nicholaides Kypros H. 
Published: July 2019

AbstractObjectiveTo evaluate the impact of a training program using a systematic protocol on ultrasound signs of placenta accreta spectrum (PAS).MethodsIntra‐ and inter‐observer variability rates and sensitivity were tested, before and after additional training, by two research fellows with a prior basic training in obstetric ultrasound using digitally recorded second‐trimester ultrasound images from cases of anterior placenta previa with and without PAS.ResultsFifty‐two cases of anterior placenta previa with PAS (n=26) and without PAS (n=26) were included in the study. The highest level of inter‐observer agreement for ultrasound signs was found for the absence of placental bulge and/or focal exophytic mass on gray‐scale imaging and the absence of subplacental hypervascularity, bridging vessels and lacunar feeder vessels on color Doppler imaging. The level of inter‐observer agreement increased from 39% before training to 40% after training; the numbers agreed as PAS by both trainees increased from four to 20. No cases were classified as inconclusive after training. There was a significant (P<0.001) change in sensitivity for both trainees after training.ConclusionAdditional training in detecting the ultrasound signs associated with PAS using a standardized protocol improves the diagnostic accuracy of operators with only a basic obstetric ultrasound training.
Overexpression of heme oxygenase‐1 in microenvironment mediates vincristine resistance of B‐cell acute lymphoblastic leukemia by promoting vascular endothelial growth factor secretion
Authors: Yu Kunlin , Wang Jishi , Lu Tingting , Ma Dan , Wei Danna , Guo Yongling , Cheng Bingqin , Wang Weili , Fang Qin 
Published: July 2019

AbstractChemoresistance often causes treatment failure of B‐cell acute lymphoblastic leukemia (B‐ALL). However, the mechanism remains unclear at present. Herein, overexpression of heme oxygenase‐1 (HO‐1) was found in the bone marrow stromal cells (BMSCs) from B‐ALL patients developing resistance to vincristine (VCR), a chemotherapeutic agent. Two B‐ALL cell lines Super B15 and CCRF‐SB were cocultured with BMSCs transfected with lentivirus to regulate the expression of HO‐1. Silencing HO‐1 expression in BMSCs increased the apoptotic rates of B‐ALL cell lines induced by VCR, whereas upregulating HO‐1 expression reduced the rate. Cell cycle can be arrested in the G2/M phase by VCR. In contrast, B‐ALL cells were arrested in the G0/G1 phase due to HO‐1 overexpression in BMSCs, which avoided damage from the G2/M phase. Vascular endothelial growth factor (VEGF) in BMSCs, as a key factor in the microenvironment‐associated chemoresistance, was also positively coexpressed with HO‐1. VEGF secretion was markedly increased in BMSCs with HO‐1 upregulation but decreased in BMSCs with HO‐1 silencing. B‐ALL cell lines became resistant to VCR when cultured with VEGF recombinant protein, so VEGF secretion induced by HO‐1 expression may promote the VCR resistance of B‐ALL cells. As to the molecular mechanism, the PI3K/AKT pathway mediated regulation of VEGF by HO‐1. In conclusion, this study clarifies a mechanism by which B‐ALL is induced to resist VCR through HO‐1 overexpression in BMSCs, and provides a novel strategy for overcoming VCR resistance in clinical practice.
Neuroprotective effect of ginkgetin in experimental cerebral ischemia/reperfusion via apoptosis inhibition and PI3K/Akt/mTOR signaling pathway activation
Authors: Tian Zhaohua , Tang Congyao , Wang Zhigang 
Published: July 2019

AbstractBackgroundGinkgetin, extracted from Ginkgo biloba L leaves, has been demonstrated to have potential anti‐inflammatory and immune‐suppressive properties. But the neuroprotective effect and potential mechanisms of ginkgetin on cerebral ischemia/reperfusion (IR) injury remain unclear.MethodsIn this research, we studied the neuroprotective effect of ginkgetin in the middle part of the middle cerebral artery occlusion/reperfusion rat model, by analyzing the apoptosis of brain tissues harvested from treatment groups and control groups using the terminal deoxynucleotidyl transferase dUTP nick‐end labeling and apoptosis assays. In addition, we detected the association of the neuroprotective effect of ginkgetin with apoptosis inhibition via the activation of the phosphatidylinositol‐3‐kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway using Western blot analysis.ResultsOur results showed that administration of ginkgetin remarkably reduced brain infarction volumes and neurologic deficits; in addition, reducing apoptotic cell numbers, downregulating the levels of cleaved caspase‐3 and Bax, and upregulating the level of Bcl‐2 in rats subjected to IR injury in a dose‐dependent manner. Moreover, high‐dose ginkgetin treatment (100 mg/kg) significantly increased the phosphorylations of Akt and mTOR. Blocking of PI3K by LY294002 clearly decreased its antiapoptotic effect and reduced both Akt and mTOR phosphorylation levels.ConclusionsTaken together, these results for the first time suggest that ginkgetin antagonizes cerebral IR‐induced injury by inhibiting apoptosis in rats, and this effect was attenuated by the activation of PI3K/Akt/mTOR signaling pathway.
Overexpression of human MX2 gene suppresses cell proliferation, migration, and invasion via ERK/P38/NF‐κB pathway in glioblastoma cells
Authors: Wang Huanyu , Guan Qiang , Nan Yang , Ma Quanfeng , Zhong Yue 
Published: July 2019

AbstractIn human, there are two myxovirus resistance genes—MX1 and MX2, which respectively encode MXA and MXB protein. For MXB, it was traditionally deemed to work in the progression of cell cycle and adjustment of nuclear import. Thus, we speculated that it might play important roles in tumor progression. The purpose of this study was to preliminarily explore the underlying functions and mechanism of the MX2 gene on glioblastoma multiforme. Quantitative reverse transcription polymerase chain reaction, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazoliumbromide (MTT), and transwell experiments were to detect the relative MX2 mRNA level and its biological functions on glioma cells, respectively. The data displayed that MX2 was obviously downregulated both in glioblastoma (GBM) and GBM cell lines, meanwhile, its overexpression could markedly reduce cell proliferation, migration, and invasion of glioma cells, implying that it was related with glioblastoma progression. In addition, the overall survival of patient with glioblastoma had a negative correlation with the MX2 expression. Then, Western blot indicated the potential mechanism of MX2 in glioblastoma. We found that MX2 overexpression could decrease the relative levels of phosphorylated‐ERK1/2 (p‐ERK1/2), p‐p38, and nuclear factor‐κB (NF‐κB), while have no effects on extracellular signal‐regulated kinase (ERK), p38, and lamin B1. Moreover, the influences of MX2 overexpression on cell proliferation, migration, and invasion could be weakened by the three inhibitors (PD98059, SB203580, and (pyridin‐2‐ylmethyl) dithiocarbamate [PDTC]). These results implied that MX2 might suppress the proliferation and metastasis of glioma cells by manipulating the ERK/P38/NF‐κB signaling pathway. In conclusion, MX2 is potential to be a new marker used for glioblastoma prognosis or a new target for glioblastoma treatments.
Inhibition of miR‐337‐3p involved in the protection of CoCl2‐induced injury in PC12 cells via activating JAK2/STAT3 signaling pathway
Authors: Li Juan , Wang Ting , Jiang Xiu‐Fang 
Published: July 2019

AbstractObjectiveTo investigate the possibility of microRNA (miR)‐337‐3p in the protection of hypoxia‐induced injury in PC12 cells via modulating the JAK2/STAT3 signaling pathway.MethodsDual‐luciferase reporter assay analyzed the relationship between the miR‐337‐3p and JAK2. PC12 cells were divided into normal, CoCl2, CoCl2 + NC, CoCl2 + inhibitors, CoCl2 + JAK2, and CoCl2 + mimics + JAK2 groups. Then, PC12 cell viability and apoptosis were measured by the 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) and Annexin‐V‐fluorescein isothiocyanate/propidium iodide methods. Quantitative real‐time polymerase chain reaction and Western blot analysis were used to determine expressions. Besides, the intracellular reactive oxygen species (ROS) was examined by dichloro‐dihydro‐fluorescein diacetate (DCFH‐DA) while the mitochondrial membrane potential (MMP) by using JC‐1.ResultsThe negative targeting relationship between miR‐337‐3p and JAK2 was confirmed. When compared with the normal group, miR‐337‐3p was increased while JAK2 and STAT3 were decreased in CoCl2‐induced PC12 cells, with decreased cell viability. Moreover, either miR‐337‐3p inhibitor or JAK2 overexpression could partially reverse CoCl2‐induced decrease in PC12 cell viability. Besides, CoCl2 could also trigger PC12 cell apoptosis by increasing cleaved caspase 3 and Bax but decreasing Bcl‐2 and Bcl‐XL, which, however, were abolished with the transfection of miR‐337‐3p inhibitors or lentivirus transfection to activate JAK2. Compared with the CoCl2 group, the average of fluorescent signals of ROS in the CoCl2 + inhibitors group and the CoCl2 + JAK2 group was lower, while the activities of superoxide dismutase, catalase, glutathione peroxidase, and total anti‐oxidative capacity were higher, together with an increase in MMP.ConclusionInhibiting miR‐337‐3p could activate the JAK2/STAT3 signaling pathway to suppress CoCl
2‐induced cytotoxicity and apoptosis and ameliorate oxidative stress and MMP in PC12 cells.
LncRNA TUG1 regulates FGF1 to enhance endothelial differentiation of adipose‐derived stem cells by sponging miR‐143
Authors: Xue Ya‐Nan , Yan Yu , Chen Zi‐Zi , Chen Jia , Tang Feng‐Jie , Xie Hui‐Qing , Tang Shi‐Jie , Cao Ke , Zhou Xiao , Wang Ai‐Jun , Zhou Jian‐Da 
Published: July 2019

AbstractAdipose‐derived stem cells (ADSCs) have emerged as a cell source for regeneration medicine. ADSCs possess the capacity to differentiate into endothelial cells and serve an essential role in vascular development and function. LncRNA taurine upregulated gene 1 (TUG1) has recently been linked with angiogenesis in hepatoblastoma. However, the roles of TUG1 in endothelial differentiation of ADSCs remain unidentified. Human adipose‐derived stem cells (hADSCs) were obtained and characterized by flow cytometry, Oil red O and Alizarin Red staining. HADSCs were maintained in the endothelial differentiation medium and the expressions of TUG1, miR‐143, and FGF1 were examined by qRT‐PCR. To assess endothelial differentiation, the expressions of CD31, von Willebrand factor (vWF), VE‐cadherin were examined by Western blot analysis, qRT‐PCR, and immunofluorescence. Tube formation in Matrigel was examined. The interactions between TUG1 and miR‐143, miR‐143 and FGF1 were validated by luciferase assays. During the endothelial differentiation process, TUG1 and FGF1 were upregulated, whereas miR‐143 was downregulated. TUG1 overexpression downregulated miR‐143, upregulated FGF1, CD31, vWF, and VE‐cadherin, and enhanced capillary tube formation. Luciferase assays showed that TUG1 interacted with miR‐143, and FGF1 was a direct target of miR‐143. Furthermore, the enhancement of endothelial differentiation induced by TUG1 overexpression was abolished by miR‐143 overexpression. Our findings implicated that lncRNA TUG1 promoted endothelial differentiation of ADSCs by regulating the miR‐143/FGF1 axis.
miR‐200a mediates protection of thymosin β‐4 in cardiac microvascular endothelial cells as a novel mechanism under hypoxia‐reoxygenation injury
Authors: Li Yang , Zhu Xiaolong , Liu Xiping , Du Aolin , Yu Bo 
Published: July 2019

AbstractThymosin β‐4 (Tβ4) is a ubiquitous protein, which has been suggested to regulate multiple cell signal pathways and a variety of cellular functions. However, the role Tβ4 plays in the cardiac microvascular endothelial cells (CMECs) under myocardial ischemia/reperfusion injury is currently unknown. Here we investigated the effects of Tβ4 on hypoxia/reoxygenation (H/R) induced CMECs injury and its potential molecular mechanism. Cultured CMECs were positively identified by flow cytometry using antibody against CD31 and VWF/Factor VIII, which are constitutively expressed on the surface of CMECs. Then the reduced level of Tβ4 was detected in H/R‐CMECs by a real‐time quantitative polymerase chain reaction. To determine the effects of Tβ4 on H/R‐CMECs, we transfected the overexpression or silence vector of Tβ4 into CMECs under H/R condition. Our results indicated that H/R treatment could reduce proliferation, increased apoptosis, adhesion, and reactive oxygen species (ROS) production in CMECs, which were attenuated by Tβ4 overexpression or aggravated by Tβ4 silencing, implying Tβ4 is able to promote CMECs against H/R‐induced cell injury. Furthermore, the microRNA‐200a (miR‐200a) level was also increased by Tβ4 in H/R‐CMECs or reduced by Tβ4 small interfering RNA. To investigated the mechanism of protective effects of Tβ4 on CMECs injury, the miR‐200a inhibitor was transfected into H/R‐CMECs. The results indicated that inhibition of miR‐200a inversed the protection of Tβ4 on H/R‐CMECs, specifically including cell proliferation, cell adhesion, cell apoptosis, and ROS production, as well as nuclear factor erythroid 2‐related factor 2 (Nrf2) nuclear translocation. In conclusion, our results determined that Tβ4 attenuated H/R‐induced CMECs injury by miR‐200a‐Nrf2 signaling.
Palbociclib, a selective CDK4/6 inhibitor, restricts cell survival and epithelial‐mesenchymal transition in Panc‐1 and MiaPaCa‐2 pancreatic cancer cells
Authors: Rencuzogulları Ozge , Yerlikaya Pınar Obakan , Gürkan Ajda Çoker , Arısan Elif Damla , Telci Dilek 
Published: July 2019

AbstractThe mortality rate of pancreatic cancer has close parallels to its incidence rate because of limited therapeutics and lack of effective prognosis. Despite various novel chemotherapeutics combinations, the 5‐year survival rate is still under 5%. In the current study, we aimed to modulate the aberrantly activated PI3K/AKT pathway and epithelial‐mesenchymal transition (EMT) signaling with the treatment of CDK4/6 inhibitor PD‐0332991 (palbociclib) in Panc‐1 and MiaPaCa‐2 pancreatic cancer cells.It was found that PD‐0332991 effectively reduced cell viability and proliferation dose‐dependently within 24 hours. In addition, PD‐0332991 induced cell cycle arrest at the G1 phase by downregulation of aberrant expression of CDK4/6 through the dephosphorylation of Rb in each cell lines. Although PD‐0332991 treatment increased epithelial markers and decreased mesenchymal markers, the nuclear translocation of β‐catenin was not prevented by PD‐0332991 treatment, especially in MiaPaCa‐2 cells. Effects of PD‐0332991 on the regulation of PI3K/AKT signaling and its downstream targets such as GSK‐3 were cell type‐dependent. Although the activity of AKT was inhibited in both cell lines, the phosphorylation of GSK‐3β at Ser9 increased only in Panc‐1.In conclusion, PD‐0332991 induced cell cycle arrest and reduced the cell viability of Panc‐1 and MiaPaCa‐2 cells. However, PD‐0332991 differentially affects the regulation of the PI3K/AKT pathway and EMT process in cells due to its distinct influence on Rb and GSK‐3/β‐catenin signaling. Understanding the effect of PD‐0332991 on the aberrantly activated signaling axis may put forward a new therapeutic strategy to reduce the cell viability and metastatic process of pancreatic cancer.
ATP is stored in lysosomes of greater epithelial ridge supporting cells in newborn rat cochleae
Authors: Chen Jiarui , Hou Shule , Yang Jun 
Published: July 2019

AbstractAdenosine triphosphate (ATP), which plays a crucial role in both developing and mature cochleae, is released from greater epithelial ridge (GER) supporting cells of the rat cochlea, but the organelles in which ATP is stored have not yet been identified. Thus, we studied the organelles involved in ATP storage and suggest that lysosomes provide this function. GER supporting cells of newborn rats were isolated, purified, and cultured, and labeled vesicles within the supporting cells were identified via confocal microscopy and transmission electron microscopy (TEM). ATP release from GER supporting cells after glycyl‐L‐phenylalanine‐β‐naphthylamide (GPN) treatment was measured. The specifically labeled organelles observed by confocal microscopy and TEM were lysosomes, and GPN treatment enhanced ATP luminescence in the extracellular fluid of the supporting cells. The release of ATP from supporting cells was affected by changes in intra‐ and extracellular Ca2+ concentrations. In addition, changes in the intracellular Ca2+ caused by inhibiting the phospholipase signaling pathway affected the release of ATP from supporting cells. We demonstrated that ATP is stored in the lysosomes of GER supporting cells within newborn rat cochleae and that ATP release from GER supporting cells may be Ca2+‐dependent.
Overexpression of lncRNA Gm15621 alleviates apoptosis and inflammation response resulting from sevoflurane treatment through inhibiting miR‐133a/Sox4
Authors: Zhao Yanling , Ai Yanqiu 
Published: July 2019

AbstractSevoflurane is the most widely used anesthetic administered by inhalation. Exposure to sevoflurane can elicit learning deficits and abnormal cognitive disorder. In this study, we investigated the function of long noncoding RNA (lncRNA) Gm15621. Primary hippocampal neuron cells were used to analyze the function of lncRNA Gm15621 in vitro. The tunel, inflammation markers, and cell survival rates were detected to evaluate the function of lncRNA Gm15621. Dual‐luciferase reporter assay was used to identify the interaction between microRNA 133a and Gm15621. We found that lncRNA Gm15621 located in the cytoplasm. The expression of lncRNA Gm15621 was decreased with the development of sevoflurane exposure. Overexpression of lncRNA Gm15621 significantly reduced the apoptosis and cell survival rates. The inflammation response was also attenuated in lncRNA Gm15621 overexpressed group. The dual‐luciferase assay revealed that miR‐133a was the direct target of lncRNA Gm15621. In addition, we also found that Sox4 was a downstream target of miR‐133a and lncRNA Gm15621 exerted its biological functions by regulating the expression of Sox4. In summary, our findings revealed that lncRNA Gm15621 ameliorated the sevoflurane‐induced neurotoxicity and the important role of Gm15621/miR‐133a/Sox4 axis in cognitive disorder.
Exploring the entrepreneurial ecosystem: Some local Canadian perspectives
Authors: Alam Jasmine , Ibn‐Boamah Mustapha , Johnson Kayla 
Published: July 2019

AbstractIdentifying each organization's connection and contribution to the entrepreneurial ecosystem helps to highlight the gaps and the support needed for a sustainable entrepreneurial ecosystem. New Brunswick has much work ahead to host a large striving entrepreneurial ecosystem: a place for innovation, entrepreneurship, and collaboration. The key players in the ecosystem could provide educational institutions with entrepreneurial support, such as resource opportunities that can support the growth of young entrepreneurs, generate networks, and ultimately provide mentorship opportunities. Sharing success stories of social enterprises with the community is important; social entrepreneurs hold the potential to solve complex social issues in the community and if they have the availability of a strong entrepreneurial ecosystem for support, the future for a stronger economy and society is distinctly possible.
Correlates of response and outcomes with talimogene laherperpvec
Authors: Zhou Alice Y. , Wang Daniel Y. , McKee Svetlana , Ye Fei , Wen Chun‐Che , Wallace Debbie E. , Ancell Kristin K. , Conry Robert M. , Johnson Douglas B. 
Published: July 2019

AbstractBackground and ObjectivesPatients with in‐transit or limited cutaneous metastatic melanoma may benefit from intralesional injections with talimogene laherparepvec (TVEC), a modified oncolytic herpesvirus. However, its use in patients with adverse prognostic scores in a real‐life clinical setting has not been studied.MethodsWe performed a two‐center retrospective analysis of 40 patients with metastatic melanoma treated with TVEC from 2015–2017. Demographics, overall response, and survival after therapy were noted.ResultsOverall, there was a durable response rate of 40%; median progression‐free survival (PFS) was 10.5 months and median overall survival (OS) was not reached. Bulky disease was associated with decreased OS (15.7 months vs not reached, P < .05) and mPFS (2.3 months vs not reached, P < .05), when compared with smaller tumors. Poor performance status (ECOG 2–3) was associated with worse OS (10.2 months vs not reached, P < .05) and PFS (2.1 months vs not reached, P < .05) compared to patients with ECOG 0–1. There was no difference in the outcomes with age greater than 75 or with prior therapies. Adverse events were relatively tolerable.ConclusionsThese findings demonstrate that TVEC is an effective and safe treatment for metastatic melanoma in a real‐life clinical setting, and suggest parameters to aid in appropriate therapy selection for optimal response.
Clinical Value of the Elastographic Q‐Analysis Score in Assisting Real‐Time Elastography‐Guided Prostate Biopsy: A Retrospective Study of 125 Patients
Authors: Ding Zhimin , Jiao Yang , Wu Huaiyu , Zhang Lei , Song Hong , Ni Zhipeng , Ye Xiuqin , Xu Jinfeng , Dong Fajin 
Published: July 2019

ObjectivesThis study aimed to evaluate the clinical value of the elastographic Q‐analysis score (EQS) in assisting real‐time elastography‐ and transrectal US‐guided prostate biopsy.MethodsA total of 125 patients with 301 lesions were enrolled in this study; all were confirmed by pathologic results. The patients underwent transrectal US and elastographic examinations before biopsy. Elastographic Q‐analysis score analysis software was used for measuring the mean EQS of the elastic images. First, the suspicious regions on elastography underwent biopsy. Then 12‐core systematic prostate biopsy was performed. An EQS curve was used to calculate the mean EQS, and a receiver operating characteristic curve was drawn to find the cutoff point for the EQS to predict prostate cancer.ResultsOf the 301 lesions in this study, 125 were malignant, and 176 were benign. The mean EQS values of benign and malignant lesions ± SD were 1.47 ± 0.75 and 2.98 ± 1.06, respectively. The difference was statistically significant (P < .05). The area under the receiver operating characteristic curve was 0.87. When the cutoff point was 1.95 for diagnosing malignant and benign lesions, the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were 83.5%, 84.4%, 76.8%, 89.2%, 5.35, and 0.20.ConclusionsThe EQS could be used as a way to predict benign and malignant lesions and thus could serve as guidance for adding targeted biopsy.