bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparation and characterization of folic acid functionalized bioactive glass for targeted delivery and sustained release of methotrexate
Authors: Chen Jianhui , Chen Xiaofeng , Yang Zhengyu , Tan Xiaojun , Wang Jiachen , Chen Yao 
Published: November 2018

AbstractWe have successfully prepared a novel targeted drug delivery system, composed of folic acid (FA) as targeting molecule, methotrexate (MTX) as anticancer drug, and bioactive glass (BG) as carrier. The BG nanoparticles were synthesized by sol‐gel method with the dodecylamine as template. The surface of BG nanoparticles was grafted with amino groups by (3‐aminopropyl) triethoxysilane, then, FA and MTX were covalently conjugated to the surface of modified BG through amidation reaction, so FA functionalized BG (BG‐FA) and targeted drug delivery system (MTX‐BG‐FA) were prepared. The physicochemical properties of BG, BG‐NH2, and BG‐FA were characterized by various methods, such as X‐ray diffraction, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, ultraviolet–visible, and so on. Moreover, the drug release results showed that the MTX‐BG‐FA had sustained release property because of the peptide bond between MTX and BG‐FA. And the cytocompatibility evaluation demonstrated that the BG and BG‐FA were biocompatible and BG‐FA even could promote cell proliferation, while the MTX‐BG‐FA had high cytotoxicity owning to the sustained release of anticancer drug. From the above, it could be concluded that MTX‐BG‐FA could kill tumor cells targetedly and sustainedly, which made it a good cancer targeted therapy material. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 319–329, 2019.
ACT001 can prevent and reverse tamoxifen resistance in human breast cancer cell lines by inhibiting NF‐κB activation
Authors: Jin Xiao‐Han , Jia Yong‐Sheng , Shi Ye‐Hui , Li Qiu‐Ying , Bao Shi‐Qi , Lu Wen‐Ping , Tong Zhong‐Sheng 
Published: November 2018

AbstractEndocrine therapy is one of the main treatments for estrogen receptor–positive breast cancers. Tamoxifen is the most commonly used drug for endocrine therapy. However, primary or acquired tamoxifen resistance occurs in a large proportion of breast cancer patients, leading to therapeutic failure. We found that the combination of tamoxifen and ACT001, a nuclear factor‐κB (NF‐κB) signaling pathway inhibitor, effectively inhibited the proliferation of both tamoxifen‐sensitive and tamoxifen‐resistant cells. The tamoxifen‐resistant cell line MCF7R/LCC9 showed active NF‐κB signaling and high apoptosis‐related gene transcription, especially for antiapoptotic genes, which could be diminished by treatment with ACT001. These results demonstrate that ACT001 can prevent and reverse tamoxifen resistance by inhibiting NF‐κB activation.
Retracted: Knockdown of long noncoding RNA GAS5 attenuates H2O2‐induced damage in retinal ganglion cells through upregulating miR‐124: Potential role in traumatic brain injury
Authors: Miao Xinglu , Liang Anran 
Published: November 2018

AbstractBackgroundOptic nerve injury is one of the most common and serious complications in traumatic brain injury (TBI). Alleviating degree of optic nerve injury is important to cure of TBI. This study explored the role of long noncoding RNA (lncRNA) GAS5 in mice retinal ganglion cells (RGCs) suffered to H2O
2 injury.MethodsPrimary RGC (PRGCs) were treated with H2O
2 to simulate an in vitro oxidation stress model. LncRNA GAS5 and miR‐124 expressions were knocked down by cell transfection with short‐hairpin RNA against GAS5 and miR‐124 inhibitor, and the transfection efficiency was determined by qRT‐PCR. Cell viability, apoptotic cell rate, and production of reactive oxygen species (ROS) was analyzed by CCK‐8 assay, PI/FITC‐Annexin V method, and DCFH‐DA fluorometric assay. Cell apoptosis‐associated proteins as well as activations of JAK/STAT3 signaling and JNK signaling were analyzed by Western blot.ResultsH2O
2 treatment‐induced cell injury was inhibited by lncRNA GAS5 silence. Specifically, knockdown of GAS5 improved viability of primary PRGCs, inhibited apoptosis, decreased ROS expression, increased antiapoptosis proteins’ expressions, and decreased proapoptosis proteins’ expressions. It was also found that miR‐124 inhibitor treatment impaired the cell protective effect of GAS5 silence, indicating low level of GAS5 protected PRGCs via upregulating miR‐124. GAS5 silence might exert cytoprotection effect via activating JAK/STAT3 signaling pathway and inhibiting activation of JNK signaling pathway.ConclusionKnocking down lncRNA GAS5 alleviated H2O
2‐induced injury in PRGCs via upregulation of miR‐124, which might dependent on activation of JAK/STAT3 signaling pathway and inhibition of JNK signaling pathway.
Activation of the mammalian target of rapamycin signaling pathway underlies a novel inhibitory role of ring finger protein 182 in ventricular remodeling after myocardial ischemia‐reperfusion injury
Authors: Wang Jing‐Hua , Wei Zhi‐Feng , Gao Yan‐Li , Liu Cong‐Cong , Sun Jing‐Hui 
Published: November 2018

AbstractMyocardial ischemia‐reperfusion injury (MIRI) is a major cause of cardiovascular disease, leading to mortality and disability associated with coronary occlusion worldwide. A correlation of mammalian target of rapamycin (mTOR)/nuclear factor‐kappa B (NF‐κB) signaling pathway has been observed with brain damage resulting from myocardial ischemia. Therefore, by establishing MIRI rat model, this study aimed to explore whether ring finger protein 182 (RNF182) regulates the mTOR signaling pathway affecting MIRI. Initially, MIRI rat model was successfully established, followed by either treatment of shRNF182 or phosphoesterase (PITE) (inhibitor of the mTOR signaling pathway). Then, the serum levels of superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px) and malondialdehyde (MDA), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular systolic pressure (LVSP), and left ventricular end‐diastolic pressure (LVEDP) were determined, followed by detection of myocardial infarct sizes and myocardial cell apoptosis. Moreover, the levels of related genes/proteins were determined to further determine the mechanisms of RNF182 in MIRI. First, RNF182 was upregulated in MIRI. Another key observation of this study was that rats with shRNF182 presented with downregulated SOD, GSH‐Px, and MDA in serum, accompanied by decreased levels of LVEF, LVFS, LVSP, and LVEDP. In addition, both reduced myocardial infarct sizes and apoptosis of myocardial cells were observed after silencing RNF182. Furthermore, silencing of the RNF182 was observed to downregulate Bcl 2–associated X and cysteine proteinase 3 but upregulate mTOR, ribosome protein subunit 6 kinase 1, eukaryotic elongation factor 2, and B‐cell lymphoma‐2. Importantly, the effects of RNF182 silencing were reversed after PITE treatment. In conclusion, our study demonstrates that RNF182 silencing can prevent ventricular remodeling in rats after MIRI by activating the mTOR signaling pathway.
Effect of autophagy on the resveratrol‐induced apoptosis of ovarian cancer SKOV3 cells
Authors: Wang HongYan , Peng Yan , Wang Jing , Gu AnXin , Li Qi , Mao DongWei , Guo LiYuan 
Published: November 2018

AbstractObjectiveThis study aims to evaluate the relationship between apoptosis and autophagy induced by resveratrol (Res) in SKOV3 human ovarian cancer cell lines.MethodsThe experiment was divided into four groups: normal control group, Res group, Res combined with autophagy inhibitor 3‐methyladenine (Res+3‐MA) group, and Z‐VAD‐FMK group. SKOV3 cells were cultured and treated with Res and 3‐MA for 24 hours. The processing concentration of Res was screened out by the Cell Counting Kit‐8 (CCK8) assay. The cell survival rate was measured by the CCK8 assay. The expression of bule‐associated protein light chain 3 beta 2 (LC3‐II) and Beclin‐1 was detected using Western blot analysis. The percentages of apoptotic and autophagic cells were analyzed using flow cytometry.ResultsThe cell survival rate significantly decreased as Res concentration increased, and the differences were statistically significant (P < 0.05). The processing concentration of Res was 25 μmol/L. After treatment with Res for 24 hours, the expression levels of autophagy‐related protein LC3 and Beclin‐l were significantly higher than in the other groups. Furthermore, the expression of LC3 and Beclin‐l significantly declined in the Res+3‐MA group compared with the Res group. However, the percentage of autophagic cells significantly decreased from 37.0% ± 4.24% to 6.1% ± 0.28%, and the percentage of apoptotic cells significantly increased from 24% ± 4.55% to 67.0% ± 4.3%; and the differences were statistically significant (
P < 0.05).ConclusionRes can induce autophagy to inhibit apoptosis in tumor SKOV3 cells, and inhibition of Res+3‐MA could not only enhance the effects of chemotherapy but also prevent normal cells from tumorigenesis.
Moderate Renal Impairment Does Not Impact the Ability of CSL112 (Apolipoprotein A‐I [Human]) to Enhance Cholesterol Efflux Capacity
Authors: Gille Andreas , Duffy Danielle , Tortorici Michael A. , Wright Samuel D. , Deckelbaum Lawrence I. , D'Andrea Denise M. 
Published: November 2018

AbstractCSL112 (apolipoprotein A‐I [human]) is a novel intravenous formulation of plasma‐derived apolipoprotein A‐I (apoA‐I) that enhances cholesterol efflux capacity. Renal impairment is a common comorbidity in acute myocardial infarction patients and is associated with impaired lipid metabolism. The aim of this phase 1 study was to assess the impact of moderate renal impairment on the pharmacokinetic and pharmacodynamic profile of CSL112. Sixteen subjects with moderate renal impairment and 16 age‐, sex‐, and weight‐matched subjects with normal renal function participated in the study. Within each renal function cohort, subjects were randomized 3:1 to receive a single intravenous infusion of CSL112 2 g (n = 6) or placebo (n = 2) or CSL112 6 g (n = 6) or placebo (n = 2). At baseline, subjects with moderate renal impairment versus normal renal function had higher total cholesterol efflux, ABCA1‐dependent cholesterol efflux capacity, and pre‐β1‐high‐density lipoprotein (HDL) levels. Infusing CSL112 resulted in similar, immediate, robust, dose‐dependent elevations in apoA‐I and cholesterol efflux capacity in both renal function cohorts and significantly greater elevations in pre‐β1‐HDL (P < .05) in moderate renal impairment. Lecithin‐cholesterol acyltransferase activity, demonstrated by a time‐dependent change in the ratio of unesterified to esterified cholesterol, did not differ by renal function. No meaningful changes in proatherogenic lipid levels were observed. Moderate renal impairment did not impact the ability of CSL112 to enhance cholesterol efflux capacity. CSL112 may represent a novel therapy to reduce the risk of early recurrent cardiovascular events following acute myocardial infarction in patients with or without moderate renal impairment.
Macrophage immunomodulation in chronic osteolytic diseases—the case of periodontitis
Authors: Sima Corneliu , Viniegra Ana , Glogauer Michael 
Published: November 2018

Abstract
Periodontitis (PD) is a chronic osteolytic disease that shares pathogenic inflammatory features with other conditions associated with nonresolving inflammation. A hallmark of PD is inflammation-mediated alveolar bone loss. Myeloid cells, in particular polymorphonuclear neutrophils (PMN) and macrophages (Mac), are essential players in PD by control of gingival biofilm pathogenicity, activation of adaptive immunity, as well as nonresolving inflammation and collateral tissue damage. Despite mounting evidence of significant innate immune implications to PD progression and healing after therapy, myeloid cell markers and targets for immune modulation have not been validated for clinical use. The remarkable plasticity of monocytes/Mac in response to local activation factors enables these cells to play central roles in inflammation and restoration of tissue homeostasis and provides opportunities for biomarker and therapeutic target discovery for management of chronic inflammatory conditions, including osteolytic diseases such as PD and arthritis. Along a wide spectrum of activation states ranging from proinflammatory to pro-resolving, Macs respond to environmental changes in a site-specific manner in virtually all tissues. This review summarizes the existing evidence on Mac immunomodulation therapies for osteolytic diseases in the broader context of conditions associated with nonresolving inflammation, and discusses osteoimmune implications of Macs in PD.
Stratigraphic pollen analysis performed on a late Pleistocene cypress forest preserved on the northern Gulf of Mexico continental shelf
Authors: Reese Carl A. , Harley Grant L. , DeLong Kristine L. , Bentley SR. Samuel J. , Xu Kehui , Gonzalez Suyapa , Truong Jonathan T. , Obelcz Jeffrey , Caporaso Alicia 
Published: November 2018

ABSTRACTStratigraphic pollen analysis of terrestrial peat–mud layers from a buried bald cypress (Taxodium distichum) forest allows study of autochthonous fossil pollen profiles from a glacial refugium along the northern Gulf of Mexico coast in the context of fluctuating sea levels. The site is in 18 m of water, offshore from Orange Beach, Alabama, USA. Exposed cypress stumps are in growth position, still rooted in sediment. Radiocarbon dating of peat and optically stimulated luminescence dating of subjacent sediments yielded an age range of 72–45 ka. We hypothesize the site was rapidly buried by floodplain aggradation from pulsed sea‐level rise during the glacial interval. Pollen results from the lowermost peat layer are consistent with a bald cypress − tupelo gum (Nyssa aquatica) backwater forest. This was followed by a brief transitional period where the pollen assemblage is similar to Atlantic Coastal Plain Blackwater Levee/Bar Forests, but may be evidence of a no‐modern analog community. Final Pleistocene pollen spectra indicate a more open environment, dominated by grasses (Poaceae) and sedges (Cyperaceae).
Advances in research and development of bioplastic for food packaging
Authors: Jariyasakoolroj Piyawanee , Leelaphiwat Pattarin , Harnkarnsujarit Nathdanai 
Published: November 2018

AbstractBACKGROUNDThe article reviews the recent developments in bioplastic food packaging. Several bioplastic materials (polylactide, polyhydroxyalkanoates, and starch) have been successfully converted into food packaging using conventional plastic conversion technologies including extrusion, injection molding, and compression molding. Recently, bioplastic packaging has been developed into active packaging which can either control the release of active ingredients or scavenge undesirable substances. This review emphasizes the advances in bioplastic packaging with regard to active packaging applications and applications requiring gas and water barrier.RESULTSThe review shows that antioxidant and antimicrobial functions are major developments for the control‐release application in bioplastic packaging. Factors affecting the release of active ingredients have been reviewed. The sorption of low molecular weight substances such as humidity, aromas, and gases, also affects the properties of packaging materials. Some patents are available for oxygen‐scavenging bioplastic packaging. Moreover, improved high‐barrier packaging technologies (modified polymer, coating, and lamination) have been developed to increase the shelf‐life of food products.CONCLUSIONThe finding shows that the development of bioplastic into food packaging included control‐release (desorption), scavenging (absorption) and permeation technologies. © 2018 Society of Chemical Industry
Pediatricians’ proficiency in the care of the dysphonic child
Authors: Schiff Carly S. , Zur Karen B. , Biggs Lisa M. , Guo Jia , Pitman Michael J. 
Published: November 2018

Objectives/HypothesisPediatricians are the first physicians to see a dysphonic child (DC), yet there are limited data on their proficiency in caring for them. The objective of this study was to understand how pediatricians’ experience and their comfort in recognizing/diagnosing voice disorders affects their referral patterns and use of basic treatment options.Study DesignSurvey study.MethodsA 13‐question survey was sent to pediatricians in the Children's Hospital of Philadelphia's primary care network; 45/216 were returned. Statistical analyses were performed using the Student t test, linear/logistic regression model, Fisher exact test, Kruskal‐Wallis test, and Spearman's correlation test.ResultsPediatricians practicing longer are more comfortable recognizing dysphonia (P = .0022). They are significantly more likely to refer a DC, even without subjective complaints of hoarseness by the family/patient or compounding medical issues. For each year in practice, the probability of referring increases by 1.55% (P = .0017). Pediatricians with a higher percentage of dysphonic children in their practice are more likely to trust their own perceptual recognition when deciding to refer (P = .0496). Nearly all pediatricians (40/45) would refer to a pediatric otolaryngologist. None would refer to a laryngologist or a voice therapist. No factors significantly affected treatment options.ConclusionsVeteran pediatricians feel more comfortable diagnosing a voice disorder and are more likely to refer a DC, regardless of patient/parent complaints or compounding factors. Pediatricians are most likely to refer to a pediatric otolaryngologist versus a voice specialist. These findings suggest that education of younger, less‐experienced pediatricians about recognizing voice disorders and options for referral is needed. This may improve the overall care of the DC.Level of Evidence4Laryngoscope, 129:1756–1762, 2019
Modeling the biogeochemical functioning of the Seine estuary and its coastal zone: Export, retention, and transformations
Authors: Romero Estela , Garnier Josette , Billen Gilles , Ramarson Antsiva , Riou Philippe , Le Gendre Romain 
Published: November 2018

AbstractThe model ECO‐MARS3D, successfully applied thus far to coastal ecosystems, has been extended to encompass the Seine estuary up to Poses, at the limit between the river and the estuary. We used updated bathymetric data and thoroughly calibrated the hydrodynamics and the sedimentary dynamics in the turbidity maximum zone (TMZ). Biogeochemical processes related to oxygen were newly implemented, and freshwater phytoplankton and zooplankton groups were added to the existing marine groups. The simulations allowed us to evaluate the filter effect of the estuary with regard to the main nutrients (N, P, and Si). Today, this filter role appears quite limited and variable depending on the hydrology. On average, considering three different hydrological years, the estuary was able to retain (at least temporarily) 19 kt N yr−1, 10 kt Si yr−1, and 0.7 kt P yr−1, amounting to −13%, −11%, and −27% of the total N, Si, and P inputs, respectively. Seasonal differences in the filtering capacity (lower in winter than in summer) were similar between wet and dry years. Nutrient retention was higher in the upstream fluvial estuary than in the TMZ, the former being mostly characterized by uptake, the latter by remineralization. At the coastal zone, the dry year showed greater risk of eutrophication. Despite lower discharge and lower nutrient fluxes, inputs were confined into a shallower layer, close to the coastline, where nutrients were concentrated and allowed phytoplankton to thrive. Differences in the N : P : Si ratios (lower P‐deficit during dry years) could also underpin the larger proliferations, and notably the larger dinoflagellate blooms during dry years.
India and the United Kingdom—What big data health research can do for a country
Authors: Bandopadhyay Souvik , Murthy Gudlavalleti Venkata Satyanarayana , Prabhakaran Dorairaj , Taylor Paul , Banerjee Amitava 
Published: November 2018

AbstractIntroductionBig data and growth in telecommunications have increased the enormous promise of an informatics approach to health care. India and the United Kingdom are two countries facing these challenges of implementing learning health systems and big data health research.AnalysisAt present, these opportunities are more likely to be exploited in the private sector or in public‐private partnerships (eg, Public Health Foundation of India [PHFI]) than public sector ventures alone. In both India and the United Kingdom, the importance of health informatics (HIs), a relatively new discipline, is being recognised and there are national initiatives in academic and health sectors to fill gaps in big data health research. The challenges are in many ways greater in India but outweighed by three potential benefits in health‐related scientific research: (a) increased productivity; (b) a learning health system with better use of data and better health outcomes; and (c) to fill workforce gaps in both research and practice.ConclusionsDespite several system‐level obstacles, in India, big data research in health care can improve the status quo, whether in terms of patient outcomes or scientific discovery. Collaboration between India and the United Kingdom in HI can result in mutual benefits to academic and health care delivery organisations in both countries and can serve as examples to other countries embracing the promises and the pitfalls of health care research in the digital era.
Dysfunctional DNA repair pathway via defective FANCD2 gene engenders multifarious exomic and transcriptomic effects in Fanconi anemia
Authors: Velmurugan Karthik Raja , Michalak Pawel , Kang Lin , Fonville Natalie C. , Garner Harold R. 
Published: November 2018

AbstractBackgroundFanconi anemia (FA) affects only one in 130,000 births, but has severe and diverse clinical consequences. It has been theorized that defects in the FA DNA cross‐link repair complex lead to a spectrum of variants that are responsible for those diverse clinical phenotypes.MethodsUsing NextGen sequencing, we show that a clinically derived FA cell line had accumulated numerous genetic variants, including high‐impact mutations, such as deletion of start codons, introduction of premature stop codons, missense mutations, and INDELs.ResultsAbout 65% of SNPs and 55% of INDELs were found to be commonly present in both the FA dysfunctional and retrovirally corrected cell lines, showing their common origin. The number of INDELs, but not SNPs, is decreased in FANCD2‐corrected samples, suggesting that FANCD2 deficiency preferentially promotes the origin of INDELs. These genetic modifications had a considerable effect on the transcriptome, with statistically significant changes in the expression of 270 genes. These genetic and transcriptomic variants significantly impacted pathways and molecular functions, spanning a diverse spectrum of disease phenotypes/symptoms, consistent with the disease diversity seen in FA patients.ConclusionThese results underscore the consequences of defects in the DNA cross‐link repair mechanism and indicate that accumulating diverse mutations from individual parent cells may make it difficult to anticipate the longitudinal clinical behavior of emerging disease states in an individual with FA.