bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling pharmaceutical emissions and their toxicity-related effects in life cycle assessment (LCA): A review
Authors: Emara Yasmine , Lehmann Annekatrin , Siegert Marc-William , Finkbeiner Matthias 
Published: September 2018

Abstract

Over the last few decades, worldwide detection of active pharmaceutical ingredients (APIs) in aquatic environments and the associated toxicological effects on wildlife and human health have become a matter of public and scientific debate. While life cycle assessment (LCA) and life cycle impact assessment (LCIA) models are increasingly used to assess the potential eco- and human-toxicological effects of chemical emissions, few studies have looked into the issue of modeling pharmaceutical emissions specifically and their toxicity-related effects in an LCA context. This paper reviews the state of the art to inventory and characterize API emissions in LCA with the goal to identify relevant gaps and challenges. A search for 208 environmentally relevant APIs in 2 life cycle inventory (LCI) databases revealed a meager representation of this group of chemicals. Similarly, the LCIA model USEtox was found to include characterization factors (CFs) for less than 60 APIs. First approaches to model API emissions in LCA were identified on the basis of an examination of 40 LCA case studies in the pharmaceutical sector and in the field of wastewater treatment. Moreover, CFs for 79 additional APIs, expressing their ecotoxicity and/or human toxicity potential, were gathered from literature. An analysis of the variability of API-CFs in different LCIA models showed a variation of about 2–3 orders of magnitude. Based on the review results, 3 main gaps in the modeling and characterization of API emissions in an LCA context were identified: (1) incomplete modeling of API flows and API emissions along the life cycle of human pharmaceuticals, especially during their use and end-of-life phase, (2) limited API coverage in existing LCIA toxicity models, and (3) missing pharma-specific impact pathways (e.g., endocrine disruption and antibiotic resistance) in existing LCIA models. Recommendations to tackle these gaps are provided, and priority action steps are discussed. Integr Environ Assess Manag 2019;15:6–18. © 2018 SETAC
A degradable triple temperature‐, pH‐, and redox‐responsive drug system for cancer chemotherapy
Authors: Yu Bing , Song Na , Hu Hao , Chen Guihuan , Shen Youqing , Cong Hailin 
Published: September 2018

AbstractIn order to achieve a precise therapeutic effect of cancer treatment and improve the utilization of drugs, a temperature‐, pH‐, and redox‐responsive drug delivery system were synthesized. Methacrylic acid (MAA), poly(N‐isopropylacrylamide) (PNIPAM), 2‐hydroxyethylmethacrylate (HEMA), and N,N′‐bis(acryloyl)cystamine (BACy), a disulfide bond contained cross‐linker, were polymerized by a distillation‐precipitation polymerization. Doxorubicin (DOX), an anti‐cancer drug, can be loaded into the loose nanoparticle (NP) effectively. The prepared drug delivery remains stable during blood circulation and, when the vectors accumulated at tumor tissues, the pH‐response of MMA and temperature‐response of PNIPAM makes volume shrinkage of vectors which benefit the diffusion of vectors into tumor tissues. After being endocytosed into tumor cell, the disulfide bond that contained in the drug delivery can be cleaved by glutathione (GSH), causing the decomposition of NPs, and then release all of the drug. Under the influence of three trigger factors, the triple stimuli‐responsive drug delivery vectors can realize tumor accumulation, tumor penetration and controlled drug release. Thus, the prepared multi‐responsive NP is ideal drug carriers for developing novel drug delivery systems. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3203–3210, 2018.
Optimization of spider silk sphere formation processing conditions to obtain carriers with controlled characteristics
Authors: Florczak Anna , Jastrzebska Katarzyna , Bialas Wojciech , Mackiewicz Andrzej , Dams‐Kozlowska Hanna 
Published: September 2018

AbstractBioengineered spider silk is a focus of research due to its biocompatibility, biodegradability, and excellent mechanical properties. Functionalized silk can be processed into spheres and employed as selective drug delivery vehicles in targeted cancer treatment. Efficient, repeatable and controllable processing conditions are essential to drug carrier development. This study aimed to optimize the processing conditions of silk spheres formation, scale‐up, and automation of the silk spheres production process. The automated micromixing system provided substantial amounts of silk spheres under repetitive production conditions. Micromixing resulted in smaller sphere sizes and narrower sphere size distributions than mixing with a pipette. Furthermore, the particle size and size distribution of silk spheres could be tailored by varying mixing process parameters, such as protein concentration, silk and salting out buffer ratio, mixing speed, and the size of the tubes and mixing zone. In addition, the implementation of ultrafiltration techniques provided a fast and efficient concentration of spheres in water. Furthermore, the shear forces introduced by micromixing did not impede the properties of the Her2 binding peptide (H2.1) since the functionalized H2.1MS1:H2.1MS2 silk spheres selectively were internalized by Her2‐positive cancer cells. This study indicated that micromixing in combination with ultrafiltration enabled scale‐up of the sphere production process under controllable and repeatable conditions. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3211–3221, 2018.
Fabrication of polydopamine nanoparticles knotted alginate scaffolds and their properties
Authors: Shen Jiali , Shi Dongjian , Dong Liangliang , Zhang Zhuying , Li Xiaojie , Chen Mingqing 
Published: September 2018

AbstractPolydopamine (PDA) can greatly affect polymer's properties, due to the chemical and physical interactions between the polymers and PDA. In this study, PDA was demonstrated to adjust the pore structures and increase the mechanical properties of alginate hydrogel‐based cartilage tissue scaffolds. Dopamine modified alginate (Alg‐DA) was firstly synthesized by modification of Alg with DA. Alg‐DA interacted with preprepared PDA nanoparticles and further crosslinked with calcium ions (Ca2+) to form the hydrogel scaffold (Alg‐DA/PDA). The Alg‐DA/PDA scaffold combined multiple advantageous features, including continuous pore structure, high level of porosity, well mechanical properties, good biocompatibility and appropriate cycle life of degradation. Moreover, it could provide an optimized forming environment for hydroxyapatite (HAp) by mineralization process, thus accelerating cartilage repair. The improved performances were mainly ascribed to physical enhancement of the PDA nanoparticles and crosslinking points among the polymers and catechol groups in DA. These findings might offer a guideline for fabricating robust biocompatible cartilage tissue scaffold. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3255–3266, 2018.
Cytoskeletal remodeling induced by substrate rigidity regulates rheological behaviors in endothelial cells
Authors: Jannatbabaei Atefeh , Tafazzoli‐Shadpour Mohammad , Seyedjafari Ehsan , Fatouraee Nasser 
Published: September 2018

AbstractAltered microenvrionmental mechanical cues induce cytoskeletal remodeling in cells and have a profound impact on their functions as well as rheological properties. This article is aimed to characterize the viscoelastic behavior of endothelial cells, cultivated on variably compliant substrates. Synthetic tunable poly(dimethylsyloxane) substrates, with elastic moduli ranging from 1.5 MPa to 3 kPa, were used to trigger cytoskeletal remodeling of endothelial cells, verified by morphological analysis and actin fluorescent labeling. Elasticity and stress relaxation tests were conducted using an AFM, resulting in a wide range of data. To account for this heterogeneity, fuzzy c‐means clustering algorithm was applied to partition elastic data into biologically meaningful groups, representative of different regions in cells. Nanocharacterization of biomechanical properties, along with cytoskeletal studies, proved a significant correlation between substrate flexibility and viscoelasticity of the cells. Regardless of the viscoelastic model applied, increasing substrate rigidity was related to an overall increase in cell stiffness and apparent viscosity (2.95 ± 1.56 kPa and 921.45 ± 102.46 Pa.s for the stiff substrate; 2.17 ± 1.30 kPa and 557.37 ± 494.11 Pa.s for the intermediate substrate), associated with an organized actin cytoskeleton. Conversely, cells on soft substrate were more deformable (1.84 ± 1.3 kPa) and less viscous (327.13 ± 124.25 Pa.s), exhibiting an increased actin disorganization. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 71–80, 2019.
Esophageal cancer lymph node metastasis–associated gene signature optimizes overall survival prediction of esophageal cancer
Authors: Cai Weiyang , Li Yanyan , Huang Bo , Hu Changyuan 
Published: September 2018

AbstractEsophageal cancer (EC) is characteristic of early regional lymph node metastasis (LNM) and most patients with metastasis have a poor prognosis. However, the current diagnostic techniques do not enable precise differentiation of EC LNM, prognostic stratification, and individual survival estimation. To identify potential molecular biomarkers for EC patients with LNM, we explored differently expressed genes in The Cancer Genome Atlas database between 77 non‐LNM cases and 88 LNM cases by limma package R. Then, according to univariate and multivariate Cox regression analyses, we constructed an 8‐messenger RNA (mRNA) prognostic signature model, which could predict the outcome in a more exact way. The area under the curve of the risk score is significantly higher than other clinical information, indicating that the 8‐mRNA–based risk score is a good indicator for prognosis. Then, combined with other individual risk factors, such as age, sex, T stage, M stage, etc, we could precisely calculate the individual 1‐, 3‐, and 5‐year survival rates. The Gene Set Enrichment Analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analysis indicate that the risk model is mainly associated with cancer‐related pathways, such as cell division, cellular meiosis, and cell cycle regulation. In summary, the 8‐mRNA–based risk score model that we developed successfully predicts the survival of EC. It is independent of clinical information and performing better than other clinical information for prognosis.
Association of single nucleotide autophagy‐related protein 5 gene polymorphism rs2245214 with susceptibility to non–small cell lung cancer
Authors: Nikseresht Mohsen , Shahverdi Maryam , Dehghani Mehdi , Abidi Hassan , Mahmoudi Reza , Ghalamfarsa Ghasem , Manzouri Leila , Ghavami Saeid 
Published: September 2018

AbstractIntroduction: Autophagy is a mechanism that is involved in the regulation of cellular life, apoptosis, and stemness while its intervening genes play important functions in various cancers including lung cancer.
ATG5 is one of the key genes for the regulation of the autophagy pathway. In this study, our team has investigated the potential relationship between
ATG5 gene polymorphism rs2245214 with non–small cell lung cancer (NSCLC) in a subpopulation of patients from southern Iran. In this study, 34 patients with NSCLC (20 males and 14 females [mean age: 12.86 ± 60.47 years]) and 50 healthy subjects (30 males and 20 females [mean age: 13.09 ± 56.62 years]) were studied in terms of the genotype of the
ATG5 gene. We used restriction fragment length polymorphism and analyzed the results using SPSS software (v.23). The results revealed that subjects harboring the guanine/cytosine (GC) genotype of the rs2245214
ATG5 gene polymorphism had suffered less from NSCLC, whereas the prevalence of the C‐allele of this polymorphism was significantly higher in patients with NSCLC (
P < 0.05). On the basis of the results of logistic regression, the presence of this C‐allele may predict the risk of lung cancer (
P value = 0.011; OR, 3.52; 95% CI, 1.33‐9.26). This study concludes that the C‐allele of the rs2245214
ATG5 gene polymorphism is associated with increased susceptibility to NSCLC, whereas the GC genotype of this polymorphism is associated with decreased risk and might therefore have a protective role in the development of NSCLC.
Curcumin‐induced autophagy and nucleophagy in Spodoptera frugiperda Sf9 insect cells occur via PI3K/AKT/TOR pathways
Authors: Veeran Sethuraman , Cui Gaofeng , Shu Benshui , Yi Xin , Zhong Guohua 
Published: September 2018

AbstractCompounds from plants or microbes are important resources for new natural pesticides against a wide variety of pests. The growing attention on the role of autophagy (type II cell death) in regulation of insect toxicology has propelled researchers to investigate autophagic cell death pathways. Our previous study proved that the cytotoxic effect of curcumin in Spodoptera frugiperda cells is regulated by autophagy. However, the signaling pathways and molecular mechanisms had not been determined. The current study elucidates curcumin inhibition of survival signaling by blocking the activation of PI3K/AKT/TOR pathways to induce autophagy in S. frugiperda cells. The result demonstrates that nucleophagy associated with cell death following the curcumin treatment. Following the curcumin treatment, Atg8/LC3 immunostaining in both nucleus and cytoplasm was markedly increased. Further, messenger RNA expression level of Atg8 and Atg1 genes regulation by curcumin was examined using quantitative reverse transcription polymerase chain reaction, and the result exhibited increased level of expression after curcumin treatment in a time‐dependent manner. Our current study provides new insights to the autophagy occurring via PI3K/AKT/TOR pathways in S. frugiperda Sf9 insect cells induced by curcumin. Taken together, our results show for the first time that curcumin induced nucleophagy in lepidopteron insect cell line.
Multiple upstream start codons (AUG) in 5′ untranslated region enhance translation efficiency of cry2Ac11 without helper protein
Authors: Adalat Rooma , Saleem Faiza , Bashir Aftab , Ahmad Munir , Zulfiqar Soumble , Shakoori Abdul Rauf 
Published: September 2018

AbstractCry2Ac11, a 65 kDa insecticidal protein produced by Bacillus thuringiensis, shows toxicity against dipteran and lepidopteran larvae. It is encoded by
cry2Ac11 gene (
orf3), which is part of an operon comprising
orf1,
orf2, and
orf3. Orf2, a helper protein, helps in proper folding and prevents aberrant aggregation of newly produced molecules. In this study, we have elucidated the effect of different mutations in translation initiation region (TIR), particularly the ribosomal binding site and the start codon (RBS‐ATG) on
cry2Ac11 gene expression without helper protein. All recombinant constructs were expressed in acrystalliferous
B. thuringiensis subsp
israelensis 4Q7 under the control of strong chimeric promoter
cyt1AP/STAB. Of all the mutants,
mut/RBS2, with two consecutive AUGs after the spacer region in TIR, exhibited 89‐ and 2246‐fold higher transcript levels compared with 4Q7‐operSalI/RBS (
cry2Ac11 operon) and 4Q7‐w‐RBS (
cry2Ac11 gene), respectively. The analysis of
mut/RBS2 messenger RNA (mRNA) structure in the RBS‐AUG region showed the presence of RBS in the single‐stranded part of the moderately stable hairpin loop. The high expression efficiency of Cry2Ac11 mutant without helper protein is a cumulative and cooperative result of chimeric promoter
cyt1AP/STAB‐SD with the optimal context of RBS‐AUG region provided by multiple AUGs and stabilizer sequence at 3′ ends.
Baicalin attenuates myocardial ischemia‐reperfusion injury through Akt/NF‐κB pathway
Authors: Luan Yun , Sun Chao , Wang Jue , Jiang Wen , Xin Qian , Zhang Zhaohua , Wang Yibiao 
Published: September 2018

AbstractBackgroundBaicalin can attenuate myocardial ischemia‐reperfusion (I/R) on damage. However, the mechanisms are still not fully understood. The study aimed to investigate the antiapoptosis and anti‐inflammatory effects of baicalin on myocardial I/R‐induced injury.MethodsWe established male rats I/R model, and baicalin was intragastric administration after ischemia onset. All experimental animals were randomly divided into five groups: group I, sham; group II, I/R; group III, 50 mg/kg; group IV, 100 mg/kg; and group V, 200 mg/kg baicalin. Postoperation, left ventricular (LV) function was recorded by transthoracic echocardiography. Myocardial infarct size, number of vessels and apoptosis were detected by histology and immunohistochemistry. Furthermore, the messenger RNA (mRNA) and protein levels of tumor necrosis factor α (TNF‐α), interleukin 1β (IL‐1β), IL‐6, IL‐8, IL‐10, Bcl2, Bax, caspase‐3, phosphatidylinositol 3‐kinase (PI3K), Akt, p‐Akt, and nuclear factor‐κB (NF‐κB) p65 in myocardial tissues were measured by quantitative real‐time polymerase chain reaction and Western blot analysis assays.ResultWhen compared with I/R groups, baicalin could significantly improve LV hemodynamic parameters. Myocardial infarct size and apoptosis were significantly decreased, but the vessel density was increased. The mRNA levels of TNF‐α, IL‐1β, IL‐6, and IL‐8 were downregulated, but the levels of IL‐10, proapoptotic genes caspase‐3, and the ratio of Bax/Bcl2 were upregulated. Moreover, the protein expression of PI3K, p‐Akt, and Akt were upregulated but NF‐κB p65 was downregulated in the groups III, IV, and V than in group II.ConclusionOur current study suggested that baicalin attenuated myocardial I/R‐induced damage, inhibited myocardial apoptosis, and inflammation by activating PI3K/Akt but suppressing NF‐κB signaling.
Decreased expression of LIF mRNA in patients withmyoma uteri
Authors: Kara Mustafa , Sabah Ozcan Seda , Aran Turhan , Kara Ozlem , Yilmaz Neziha 
Published: September 2018

AbstractObjectiveThe aim of this study was to evaluate endometrial receptivity by measuring HOXA‐10, HOXA‐11, and LIF gene expressions in women with polycystic ovary syndrome.MethodsA total of 48 women were included in this clinical study. Thepatients were allocated to two groups: study group consisted of 28 patients with myoma uteri and control group consisted of 20 patients without myoma uteri. Endometrial sampling was performed during the proliferative phase. The biopsies obtained from the patients with myoma uteri were taken from the place where the fibroids were localized. HOXA‐10, HOXA‐11, and LIF expressions were measured in the endometrial sampling material. Demographic data of the patients such as age, obstetric and gynecologic history, medical conditions, medications, surgical history, last menstrual period were recorded. Also, the number, size, localization, and type of the myoma were registered.ResultsThe mean age of the patients was 42.07 and 38.17, respectively. HOXA‐11 levels in the study and control groups were 0.004 ± 0.001 and 0.010 ± 0.001, respectively (
P < 0.90). Paradoxically, HOXA‐10 levels were found to be higher in the study group than the control group, but the difference was not statistically significant (
P < 0.25). LIF levels were significantly lower in the study group (
P < 0.05).ConclusionOur results showed that myoma uteri might lead to a decrease in implantation rate by diminishing LIF gene expressions. However, there were no differences between the two groups in terms of HOXA‐10 and HOXA‐11 levels.
Association of serum adropin with the presence of atrial fibrillation and atrial remodeling
Authors: Wang Bin , Xue Yusheng , Shang Fujun , Ni Sifeng , Liu Xiongtao , Fan Boyuan , Wang Haichang 
Published: September 2018

ObjectiveAdropin, a newly identified regulatory protein encoded by Enho gene, suppressed tumor necrosis factor α‐induced THP1 monocyte adhesion to human umbilical vein endothelial cells. In addition, inflammation is demonstrated to be involved in the mechanism of atrial fibrillation (AF). Atrial remodeling is correlated with the persistence and progression of AF. Adropin is hypothesized to correlated with AF and atrial remodeling. This study aims to determine the correlation of serum adropin and the presence of AF and remodeling.MethodsThis study consisted of 344 AF patients and 210 healthy controls. AF patients were then divided into three subgroups of paroxysmal AF, persistent AF, and permanent AF. Serum adropin concentrations were examined using enzyme‐linked immunosorbent assay method. Left atrial diameter (LAD) was measured to evaluate atrial remodeling.ResultsDecreased serum adropin concentrations were found in AF patients compared with healthy controls. Logistic regression analysis confirmed that serum adropin was inversely associated with the presence of AF (OR 0.218, 95% CI 0.15‐0.316; P < 0.001). Permanent AF patients had significantly reduced serum adropin concentrations compared with persistent and paroxysmal AF patients. There were decreased serum adropin concentrations in persistent AF group than those in paroxysmal AF group. Simple linear regression analyses showed that serum adropin in AF patients were negatively correlated with BMI, SBP, and LAD. Multiple stepwise regression analysis showed that LAD remained to be inversely associated with serum adropin (β = 0.2, P = 0.010).ConclusionSerum adropin concentrations are inversely correlated with the presence of AF and atrial remodeling.
Interleukin‐7 gene polymorphism rs766736182 associates with the risk of asthma in children
Authors: Cao Junhua , Tian Lijun , Li Zhenguang , Zhang Chonglin , Ji Qiang , Zhang Chuanling , Qian Tong 
Published: September 2018

BackgroundRecently studies uncovered associations between polymorphisms of interleukin genes and the risk of asthma. However, the relationship between polymorphisms of interleukin‐7 gene and the risk of children asthma has not been discovered yet. This study aims to investigate the relationship between single nucleotide polymorphisms (SNPs) on interleukin‐7 gene and the risk of children asthma.MethodsWe genotyped eight SNPs of interleukin‐7 gene in blood samples from 437 asthma patients and 489 healthy controls to analyze potential associations of these SNPs with the risk of asthma in children.ResultsA missense SNP rs766736182 (odds ratio (OR) = 2.185, 95% confidence interval (CI) = 1.561‐2.252, P‐value = 8.69468E‐19) of the interleukin‐7 gene is associated with the risk of children asthma.ConclusionsThis study reveals that SNP rs766736182 of interleukin‐7 is the risk factor for children asthma and implies potential role of immune system in the pathogenesis of children asthma.