bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRIM21–SERPINB5 aids GMPS repression to protect nasopharyngeal carcinoma cells from radiation-induced apoptosis
Authors: Zhang Panpan , Li Xiaomin , He Qiuping , Zhang Lulu , Song Keqing , Yang Xiaojing , He Qingmei , Wang Yaqin , Hong Xiaohong , Ma Jun , Liu Na 
Published: January 2020

Abstract
Background
The main strategy against nasopharyngeal carcinoma (NPC) is radiotherapy. However, radioresistance mediated recurrence is a leading clinical bottleneck in NPC. Revealing the mechanism of NPC radioresistance will help improve the therapeutic effect.

Methods
In this study, the role of TRIM21 (tripartite motif–containing 21) in NPC receiving ionizing radiation was firstly examined both in vivo and in vitro. Mass spectrometry analysis was performed to identify the downstream targets of TRIM21. NPC cells with TRIM21 or SERPINB5 (serpin family B member 5) overexpression or knockout were used to determine the epistatic relationship among SERPINB5, GMPS (guanine monophosphate synthase) and TRIM21. Flow cytometry, co-immunoprecipitation, western blot and immunofluorescence were employed to strengthen the results. Finally, immunohistochemistry using 4 radiosensitive and 8 radioresistent NPC patient samples was perform to examine the association between SERPINB5 or GMPS expression and patient radio-sensitivity.

Results
As an E3 ligase, TRIM21 was highly expressed in NPC. After ionizing radiation, TRIM21 repressed TP53 expression by mediating GMPS ubiquitination and degradation. Overexpression of TRIM21 protected NPC cells from radiation mediated cell apoptosis in vitro and in vivo. Further analysis revealed that TRIM21 mediated GMPS repression was dependent on SERPINB5, and SERPINB5 served as an adaptor which prevented GMPS from entering into the nucleus and introduced TRIM21 for GMPS ubiquitination. Moreover, the in vitro and in vivo results validated the finding that SERPINB5 promoted NPC cell radioresistance, and the radioresistant patients had higher SERPINB5 expression.

Conclusions
Overall, our data showed that TRIM21–SERPINB5-mediated GMPS degradation facilitated TP53 repression, which promoted the radioresistance of NPC cells. This novel working model related to TP53 suppression provided new insight into NPC radioresistence clinically.
The extended recovery ring-stage survival assay provides a superior association with patient clearance half-life and increases throughput
Authors: Davis Sage Z. , Singh Puspendra P. , Vendrely Katelyn M. , Shoue Douglas A. , Checkley Lisa A. , McDew-White Marina , Button-Simons Katrina A. , Cassady Zione , Sievert Mackenzie A. C. , Foster Gabriel J. , Nosten François H. , Anderson Timothy J. C. , Ferdig Michael T. 
Published: January 2020

Abstract
Background
Tracking and understanding artemisinin resistance is key for preventing global setbacks in malaria eradication efforts. The ring-stage survival assay (RSA) is the current gold standard for in vitro artemisinin resistance phenotyping. However, the RSA has several drawbacks: it is relatively low throughput, has high variance due to microscopy readout, and correlates poorly with the current benchmark for in vivo resistance, patient clearance half-life post-artemisinin treatment. Here a modified RSA is presented, the extended Recovery Ring-stage Survival Assay (eRRSA), using 15 cloned patient isolates from Southeast Asia with a range of patient clearance half-lives, including parasite isolates with and without kelch13 mutations.

Methods
Plasmodium falciparum cultures were synchronized with single layer Percoll during the schizont stage of the intraerythrocytic development cycle. Cultures were left to reinvade to early ring-stage and parasitaemia was quantified using flow cytometry. Cultures were diluted to 2% haematocrit and 0.5% parasitaemia in a 96-well plate to start the assay, allowing for increased throughput and decreased variability between biological replicates. Parasites were treated with 700 nM of dihydroartemisinin or 0.02% dimethyl sulfoxide (DMSO) for 6 h, washed three times in drug-free media, and incubated for 66 or 114 h, when samples were collected and frozen for PCR amplification. A SYBR Green-based quantitative PCR method was used to quantify the fold-change between treated and untreated samples.

Results
15 cloned patient isolates from Southeast Asia with a range of patient clearance half-lives were assayed using the eRRSA. Due to the large number of pyknotic and dying parasites at 66 h post-exposure (72 h sample), parasites were grown for an additional cell cycle (114 h post-exposure, 120 h sample), which drastically improved correlation with patient clearance half-life compared to the 66 h post-exposure sample. A Spearman correlation of − 0.8393 between fold change and patient clearance half-life was identified in these 15 isolates from Southeast Asia, which is the strongest correlation reported to date.

Conclusions
eRRSA drastically increases the efficiency and accuracy of in vitro artemisinin resistance phenotyping compared to the traditional RSA, which paves the way for extensive in vitro phenotyping of hundreds of artemisinin resistant parasites.
Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340
Authors: Jian Xiangyu , He Han , Zhu Jiehong , Zhang Qi , Zheng Zhongxin , Liang Xiangjing , Chen Liuyan , Yang Meiling , Peng Kaiyue , Zhang Zhaowen , Liu Tengfei , Ye Yaping , Jiao Hongli , Wang Shuyang , Zhou Weijie , Ding Yanqing , Li Tingting 
Published: January 2020

Abstract
Background
Accumulating evidence indicates that circular RNAs (circRNAs) act as microRNA (miRNA) sponges to directly inhibit specific miRNAs and alter their ability to regulate gene expression at the post-transcriptional level; this mechanism is believed to occur in various cancers. However, the expression level, precise function and mechanism of circ_001680 in colorectal carcinoma (CRC) are largely unknown.

Methods
qRT-PCR was used to detect the expression of circ_001680 and miR-340 in human CRC tissues and their matched normal tissues. Bioinformatics analyses and dual-fluorescence reporter assays were used to evaluate whether circ_001680 could bind to miR-340. Circ_001680 overexpression and knockdown cell lines were constructed to investigate the proliferation and migration abilities in vivo and in vitro through function-based experiments, including CCK8, plate clone formation, transwell, and wounding healing assays. The relationships among circ_001680, miR-340 and BMI1 were investigated by bioinformatics analyses, dual-fluorescence reporter system, FISH, RIP and RNA pull down assays. Sphere forming assays and flow cytometry analyses were used to assess the effect of circ_001680 on the stemness characteristics of CRC cells.

Results
Circ_001680 was more highly expressed in of CRC tissue than in matched adjacent normal tissues from the same patients. Circ_001680 was observed to enhance the proliferation and migration capacity of CRC cells. Furthermore, dual-fluorescence reporter assays confirmed that circ_001680 affects the expression of BMI1 by targeting miR-340. More importantly, we also found that circ_001680 could promote the cancer stem cell (CSC) population in CRC and induce irinotecan therapeutic resistance by regulating the miR-340 target gene BMI1.

Conclusions
Our results demonstrated that circ_001680 is a part of a novel strategy to induce chemotherapy resistance in CRC through BMI1 upregulation. Moreover, circ_001680 may be a promising diagnostic and prognostic marker to determine the success of irinotecan-based chemotherapy.
Contribution of Pyk2 pathway and reactive oxygen species (ROS) to the anti-cancer effects of eicosapentaenoic acid (EPA) in PC3 prostate cancer cells
Authors: Oono Keiichi , Ohtake Kazuo , Watanabe Chie , Shiba Sachiko , Sekiya Takashi , Kasono Keizo 
Published: January 2020

Abstract
Background
n-3 polyunsaturated fatty acids (n-3 PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are thought to exert protective effects in cardiovascular diseases. In addition, n-3 PUFAs have demonstrated anti-cancer effects in vitro and in vivo.

Objective
We investigated the anti-cancer effects and mechanism of action of EPA on PC3 prostate cancer cells in vitro.

Methods
PC3 cells were treated with various concentrations of EPA, and cell survival and the abilities of migration and invasion were evaluated. The time course of the growth inhibitory effect of EPA on PC3 cells was also assessed. The mechanism underlying the anti-cancer effects of EPA was investigated by human phosphokinase and human apoptosis antibody arrays, and confirmed by western blot analysis. We also examined the contribution of reactive oxygen species (ROS) to the effects of EPA using the ROS inhibitor N-acetyl cysteine.

Results
EPA decreased the survival of PC3 cells in a dose-dependent manner within 3 h of application, with an effective concentration of 500 μmol/L. EPA inhibited proline-rich tyrosine kinase (Pyk)2 and extracellular signal-regulated kinase 1/2 phosphorylation as determined by western blotting and the antibody arrays. The growth of PC3 cells was inhibited by EPA, which was dependent on ROS induction, while EPA inhibited Pyk2 phosphorylation independent of ROS production.

Conclusions
Inhibition of Pyk2 phosphorylation and ROS production contribute to the anticancer effects of EPA on PC3 cells.
Reference values for lipid profile in Iranian children and adolescents: the CASPIAN-V study
Authors: Azizi-Soleiman Fatemeh , Khoramdad Maliheh , Heshmat Ramin , Ejtahed Hanieh-Sadat , Motlagh Mohammad Esmaeil , Daniali Seyede Shahrbanoo , Qorbani Mostafa , Kelishadi Roya 
Published: January 2020

Abstract
Background
We aimed to develop the age- and sex-specific reference values for lipid profile of Iranian pediatric population.

Methods
Fasting lipid profiles of 3843 participants, aged 7 to 18 years, were extracted from a surveillance survey on Iranian children and adolescents living in 30 provinces across the country.

Results
The mean (SD) age of participants was 12.3(3.1) years, and 52.3% of them were boys. Significant differences were observed between genders comparing the levels of triglyceride (TG) (P = 0.04), total cholesterol (TC) (P = 0.02), low-density lipoprotein- cholesterol (LDL-C) (P = 0.01), and non-high-density lipoprotein cholesterol (non-HDL-C) (P = 0.03). In both genders, TG levels increased with age in the 75th and higher percentiles. Among boys, TC showed a decreasing trend at all percentiles and all age groups. In girls, TC levels increased with age at all percentiles except for the 75th and 90th percentiles. Among boys, the levels of LDL-C and HDL-C decreased with age in all percentiles. However, LDL-C and HDL-C concentrations increased up to the 50th percentile in girls and then decreased with age. The non-HDL-C level decreased in the 50th and higher percentiles among boys and in the 90th and 95th percentiles among girls. The TG/HDL-C ratio increased with age at all percentiles in boys. In girls, TG/HDL-C ratio increased with age in the 50th and higher percentiles.

Conclusions
Based on the observed differences, it seems necessary to determine age- and sex-specific cut-off values for lipid parameters of children and adolescents in different populations.
Dendritic cells transduced with glioma-expressed antigen 2 recombinant adenovirus induces specific cytotoxic lymphocyte response and anti-tumor effect in mice
Authors: Shao Gaohai , Zhou Changlong , Ma Kunlong , Zhao Wang , Feng Guibo , Xiong Qijiang , Yang Ling , Yang Zhao 
Published: January 2020

AbstractIntroductionGlioma is an aggressive common cancer with high mortality worldwide. Up to date, the effective medical therapeutical strategy is limited. Numerous previous studies have indicated that glioma-expressed antigen 2 (GLEA2) might be an attractive prognostic glioma biomarker.MethodsIn this experiment, dendritic cells (DCs) transduced with GLEA2 recombinant adenovirus were utilized to generate cytotoxic lymphocytes (CTLs) in vitro. Additionally, trimera mice were immunized with the transduced DCs to generate CTLs in vivo.ResultsThe data demonstrated that GLEA2 transduced DCs could effectively generate specific CTL response against glioma without lysing autologous lymphocytes. Moreover, GLEA2 transduced DCs significantly attenuated the tumor growth and prolonged the life span of tumor bearing mice.ConclusionsThese findings suggested that DCs transduced with GLEA2 recombinant adenovirus could generate effective CTL mediated anti-tumor response, and might represent insight in glioma therapy.
Enhance transgene responses through improving cellular uptake and intracellular trafficking by bio-inspired non-viral vectors
Authors: Ma Xi-Xi , Xu Jing-Liang , Jia Yi-Yang , Zhang Ya-Xuan , Wang Wei , Li Chen , He Wei , Zhou Si-Yuan , Zhang Bang-Le 
Published: January 2020

Abstract
Background
Gene therapy remains a significant challenge due to lots of barriers limiting the genetic manipulation technologies. As for non-viral delivery vectors, they often suffer insufficient performance due to inadequate cellular uptake and gene degradation in endosome or lysosome. The importance of overcoming these conserved intracellular barriers is increasing as the delivery of genetic cargo.

Results
A surface-functionalized non-viral vector involving the biomimetic mannitol moiety is initiated, which can control the cellular uptake and promote the caveolae-mediated pathway and intracellular trafficking, thus avoiding acidic and enzymatic lysosomal degradation of loaded gene internalized by clathrin-mediated pathway. Different degrees of mannitol moiety are anchored onto the surface of the nanoparticles to form bio-inspired non-viral vectors and CaP-MA-40 exhibits remarkably high stability, negligible toxicity, and significantly enhanced transgene expression both in vitro and in vivo.

Conclusions
This strategy highlights a paradigmatic approach to construct vectors that need precise intracellular delivery for innovative applications.
Oleic acid-based nanosystems for mitigating acute respiratory distress syndrome in mice through neutrophil suppression: how the particulate size affects therapeutic efficiency
Authors: Yu Huang-Ping , Liu Fu-Chao , Umoro Ani , Lin Zih-Chan , Elzoghby Ahmed O. , Hwang Tsong-Long , Fang Jia-You 
Published: January 2020

Abstract
Background
Oleic acid (OA) is reported to show anti-inflammatory activity toward activated neutrophils. It is also an important material in nanoparticles for increased stability and cellular internalization. We aimed to evaluate the anti-inflammatory activity of injectable OA-based nanoparticles for treating lung injury. Different sizes of nanocarriers were prepared to explore the effect of nanoparticulate size on inflammation inhibition.

Results
The nanoparticles were fabricated with the mean diameters of 105, 153, and 225 nm. The nanocarriers were ingested by isolated human neutrophils during a 5-min period, with the smaller sizes exhibiting greater uptake. The size reduction led to the decrease of cell viability and the intracellular calcium level. The OA-loaded nanosystems dose-dependently suppressed the superoxide anion and elastase produced by the stimulated neutrophils. The inhibition level was comparable for the nanoparticles of different sizes. In the ex vivo biodistribution study, the pulmonary accumulation of nanoparticles increased following the increase of particle size. The nanocarriers were mainly excreted by the liver and bile clearance. Mice were exposed to intratracheal lipopolysaccharide (LPS) to induce acute respiratory distress syndrome (ARDS), like lung damage. The lipid-based nanocarriers mitigated myeloperoxidase (MPO) and cytokines more effectively as compared to OA solution. The larger nanoparticles displayed greater reduction on MPO, TNF-α, and IL-6 than the smaller ones. The histology confirmed the decreased pulmonary neutrophil recruitment and lung-architecture damage after intravenous administration of larger nanoparticles.

Conclusions
Nanoparticulate size, an essential property governing the anti-inflammatory effect and lung-injury therapy, had different effects on activated neutrophil inhibition and in vivo therapeutic efficacy.
What constitutes effective problematic substance use treatment from the perspective of people who are homeless? A systematic review and meta-ethnography
Authors: Carver Hannah , Ring Nicola , Miler Joanna , Parkes Tessa 
Published: January 2020

Abstract
Background
People experiencing homelessness have higher rates of problematic substance use but difficulty engaging with treatment services. There is limited evidence regarding how problematic substance use treatment should be delivered for these individuals. Previous qualitative research has explored perceptions of effective treatment by people who are homeless, but these individual studies need to be synthesised to generate further practice-relevant insights from the perspective of this group.

Methods
Meta-ethnography was conducted to synthesise research reporting views on substance use treatment by people experiencing homelessness. Studies were identified through systematic searching of electronic databases (CINAHL; Criminal Justice Abstracts; Health Source; MEDLINE; PsycINFO; SocINDEX; Scopus; and Web of Science) and websites and were quality appraised. Original participant quotes and author interpretations were extracted and coded thematically. Concepts identified were compared to determine similarities and differences between studies. Findings were translated (reciprocally and refutationally) across studies, enabling development of an original over-arching line-of-argument and conceptual model.

Results
Twenty-three papers published since 2002 in three countries, involving 462 participants, were synthesised. Findings broadly related, through personal descriptions of, and views on, the particular intervention components considered effective to people experiencing homelessness. Participants of all types of interventions had a preference for harm reduction-oriented services. Participants considered treatment effective when it provided a facilitative service environment; compassionate and non-judgemental support; time; choices; and opportunities to (re)learn how to live. Interventions that were of longer duration and offered stability to service users were valued, especially by women. From the line-of-argument synthesis, a new model was developed highlighting critical components of effective substance use treatment from the service user’s perspective, including a service context of good relationships, with person-centred care and an understanding of the complexity of people’s lives.

Conclusion
This is the first meta-ethnography to examine the components of effective problematic substance use treatment from the perspective of those experiencing homelessness. Critical components of effective problematic substance use treatment are highlighted. The way in which services and treatment are delivered is more important than the type of treatment provided. Substance use interventions should address these components, including prioritising good relationships between staff and those using services, person-centred approaches, and a genuine understanding of individuals’ complex lives.
Influence of peritoneal carcinomatosis on perioperative outcome in palliative gastric bypass for malignant gastric outlet obstruction - a retrospective cohort study
Authors: Bednarsch Jan , Czigany Zoltan , Heise Daniel , Zimmermann Henning , Boecker Joerg , Ulmer Tom Florian , Neumann Ulf Peter , Klink Christian 
Published: January 2020

AbstractBackgroundMalignant gastric outlet obstruction (GOO) is commonly associated with the presence of peritoneal carcinomatosis (PC) and preferably treated by surgical gastrojejunostomy (GJJ) in patients with good performance. Here, we aim to investigate the role of PC as a risk factor for perioperative morbidity and mortality in patients with GOO undergoing GJJ.MethodsPerioperative data of 72 patients with malignant GOO who underwent palliative GJJ at our institution between 2010 and 2019 were collected within an institutional database.To compare perioperative outcomes of patients with and without PC, extensive group analyses were carried out.ResultsA set of 39 (54.2%) patients was histologically diagnosed with concomitant PC while the remaining 33 (45.8%) patients showed no clinical signs of PC. In-house mortality due to surgical complications was significantly higher in patients with PC (9/39, 23.1%) than in patients without PC (2/33, 6.1%,p= .046). Considerable differences were observed in terms of surgical complications such as anastomotic leakage rates (2.8% vs. 0%,p= .187), delayed gastric emptying (33.3% vs. 15.2%,p= .076), paralytic ileus (23.1% vs. 9.1%,p= .113), and pneumonia (17.9% vs. 12.1%,p= .493) without reaching the level of statistical significance.ConclusionsPC is an important predictor of perioperative morbidity and mortality patients undergoing GJJ for malignant GOO.
Socioeconomic position and the impact of increasing availability of lower energy meals vs. menu energy labelling on food choice: two randomized controlled trials in a virtual fast-food restaurant
Authors: Marty Lucile , Jones Andrew , Robinson Eric 
Published: January 2020

AbstractBackgroundFood consumed outside of the home is often high in energy and population level interventions that reduce energy intake of people from both lower and higher socioeconomic position (SEP) are needed. There is a lack of evidence on the effectiveness and SEP equity of structural-based (e.g. increasing availability of lower energy options) and information provision (e.g. menu energy labelling) interventions on food choice.MethodsAcross two online experiments, participants of lower and higher SEP made meal choices in a novel virtual fast-food restaurant. To be eligible to take part, participants were required to be UK residents, aged 18 or above, fluent in English, have access to a computer with an internet connection and have no dietary restrictions. Participants were randomized to one of four conditions in a 2 × 2 between-subjects design: menu energy labelling present vs. absent and increased availability of lower energy options (75% of menu options lower energy) vs. baseline availability (25% of menu options lower energy). Participants also completed measures of executive function and food choice motives.ResultsThe analysis of pooled data from both studies (n = 1743) showed that increasing the availability of lower energy options resulted in participants ordering meals with significantly less energy on average (− 71 kcal,p <  0.001, partial η2 = 0.024) and this effect was observed irrespective of participant SEP. Menu labelling had no significant effect on energy ordered (− 18 kcal,p = 0.116, partial η2 = 0.001) in participants from both higher and lower SEP. Furthermore, we found no evidence that executive function or food choice motives moderated the effect of increasing lower energy menu options or energy labelling on total energy ordered.ConclusionsIn a virtual fast-food environment, energy labelling was ineffective in reducing total energy ordered for both higher and lower SEP participants. Increasing the availability of lower energy options had an equitable effect, reducing total energy ordered in participants from higher and lower SEP.Trial registrationStudy protocols and analysis plans were pre-registered on the Open Science Framework (https://osf.io/ajcr6/).