bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNA-HGBC stabilized by HuR promotes gallbladder cancer progression by regulating miR-502-3p/SET/AKT axis
Authors: Hu Yun-ping , Jin Yun-peng , Wu Xiang-song , Yang Yang , Li Yong-sheng , Li Huai-feng , Xiang Shan-shan , Song Xiao-ling , Jiang Lin , Zhang Yi-jian , Huang Wen , Chen Shi-li , Liu Fa-tao , Chen Chen , Zhu Qin , Chen Hong-zhuan , Shao Rong , Liu Ying-bin 
Published: November 2019

Abstract
Backgrounds
Long non-coding RNAs (lncRNAs) are essential factors that regulate tumor development and metastasis via diverse molecular mechanisms in a broad type of cancers. However, the pathological roles of lncRNAs in gallbladder carcinoma (GBC) remain largely unknown. Here we discovered a novel lncRNA termed lncRNA Highly expressed in GBC (lncRNA-HGBC) which was upregulated in GBC tissue and aimed to investigate its role and regulatory mechanism in the development and progression of GBC.

Methods
The expression level of lncRNA-HGBC in GBC tissue and different cell lines was determined by quantitative real-time PCR. The full length of lncRNA-HGBC was obtained by 5′ and 3′ rapid amplification of the cDNA ends (RACE). Cellular localization of lncRNA-HGBC was detected by fluorescence in situ hybridization (FISH) assays and subcellular fractionation assay. In vitro and in vivo assays were preformed to explore the biological effects of lncRNA-HGBC in GBC cells. RNA pull-down assay, mass spectrometry, and RNA immunoprecipitation (RIP) assay were used to identify lncRNA-HGBC-interacting proteins. Dual luciferase reporter assays, AGO2-RIP, and MS2-RIP assays were performed to verify the interaction between lncRNA-HGBC and miR-502-3p.

Results
We found that lncRNA-HGBC was upregulated in GBC and its upregulation could predict poor survival. Overexpression or knockdown of lncRNA-HGBC in GBC cell lines resulted in increased or decreased, respectively, cell proliferation and invasion in vitro and in xenografted tumors. LncRNA-HGBC specifically bound to RNA binding protein Hu Antigen R (HuR) that in turn stabilized lncRNA-HGBC. LncRNA-HGBC functioned as a competitive endogenous RNA to bind to miR-502-3p that inhibits target gene SET. Overexpression, knockdown or mutation of lncRNA-HGBC altered the inhibitory effects of miR-502-3p on SET expression and downstream activation of AKT. Clinically, lncRNA-HGBC expression was negatively correlated with miR-502-3p, but positively correlated with SET and HuR in GBC tissue.

Conclusions
Our study demonstrates that lncRNA-HGBC promotes GBC metastasis via activation of the miR-502-3p-SET-AKT cascade, pointing to lncRNA-HGBC as a new prognostic predictor and a therapeutic target.
Distinct functions of AKT isoforms in breast cancer: a comprehensive review
Authors: Hinz Nico , Jücker Manfred 
Published: November 2019

AbstractBackgroundAKT, also known as protein kinase B, is a key element of the PI3K/AKT signaling pathway. Moreover, AKT regulates the hallmarks of cancer, e.g. tumor growth, survival and invasiveness of tumor cells. After AKT was discovered in the early 1990s, further studies revealed that there are three different AKT isoforms, namely AKT1, AKT2 and AKT3. Despite their high similarity of 80%, the distinct AKT isoforms exert non-redundant, partly even opposing effects under physiological and pathological conditions. Breast cancer as the most common cancer entity in women, frequently shows alterations of the PI3K/AKT signaling.Main contentA plethora of studies addressed the impact of AKT isoforms on tumor growth, metastasis and angiogenesis of breast cancer as well as on therapy response and overall survival in patients. Therefore, this review aimed to give a comprehensive overview about the isoform-specific effects of AKT in breast cancer and to summarize known downstream and upstream mechanisms. Taking account of conflicting findings among the studies, the majority of the studies reported a tumor initiating role of AKT1, whereas AKT2 is mainly responsible for tumor progression and metastasis. In detail, AKT1 increases cell proliferation through cell cycle proteins like p21, p27 and cyclin D1 and impairs apoptosis e.g. via p53. On the downside AKT1 decreases migration of breast cancer cells, for instance by regulating TSC2, palladin and EMT-proteins. However, AKT2 promotes migration and invasion most notably through regulation of β-integrins, EMT-proteins and F-actin. Whilst AKT3 is associated with a negative ER-status, findings about the role of AKT3 in regulation of the key properties of breast cancer are sparse. Accordingly, AKT1 is mutated and AKT2 is amplified in some cases of breast cancer and AKT isoforms are associated with overall survival and therapy response in an isoform-specific manner.ConclusionsAlthough there are several discussed hypotheses how isoform specificity is achieved, the mechanisms behind the isoform-specific effects remain mostly unrevealed. As a consequence, further effort is necessary to achieve deeper insights into an isoform-specific AKT signaling in breast cancer and the mechanism behind it.
Systematic review: a systems innovation perspective on barriers and facilitators for the implementation of healthy food-store interventions
Authors: Middel Cédric N. H. , Schuitmaker-Warnaar Tjerk Jan , Mackenbach Joreintje D. , Broerse Jacqueline E. W. 
Published: November 2019

Abstract
Background
Due to their central position in the modern food system, food stores present a unique opportunity to promote healthy dietary behaviour. However, there is a lack of insight into the factors that impede or enhance the implementation of nutritional interventions in food stores. We applied a systems innovation and implementation science framework to the identification of such barriers and facilitators.

Methods
We conducted a systematic literature review. A search string was developed to identify qualitative and quantitative articles on environmental nutritional interventions in the food store. Four databases were systematically searched for studies published between 2000 and 2018. Eligible publications described study designs or original studies, focused on stimulating healthier dietary behaviour through environmental changes in retail settings and contained information on the perceptions or experiences of retailers or interventionists regarding the implementation process of the intervention. Context-descriptive data was extracted and a quality assessment was performed.

Results
We included 41 articles, of which the majority was conducted in the USA and involved single stores or a mix of single and multi-store organisations. We categorized barriers and facilitators into 18 themes, under five domains. In the ‘outer setting’ domain, most factors related to consumers’ preferences and demands, and the challenge of establishing a supply of healthy products. In the ‘inner setting’ domain, these related to conflicting values regarding health promotion and commercial viability, store lay-out, (insufficient) knowledge and work capacity, and routines regarding waste avoidance and product stocking. In the ‘actors’ domain, no major themes were found. For the ‘intervention ‘domain’, most related to intervention-context fit, money and resource provision, material quality, and the trade-offs between commercial costs and risks versus commercial and health benefits. For the ‘process’ domain, most factors related to continuous engagement and strong relationships.

Conclusions
This review provides a comprehensive overview of barriers and facilitators to be taken into account when implementing nutritional interventions in food stores. Furthermore, we propose a novel perspective on implementation as the alignment of intervention and retail interests, and a corresponding approach to intervention design which may help avoid barriers, and leverage facilitators.

Trial registration
PROSPERO; CRD42018095317.
Distinct migratory pattern of naive and effector T cells through the blood–CSF barrier following Echovirus 30 infection
Authors: Wiatr Marie , Stump-Guthier Carolin , Latorre Daniela , Uhlig Stefanie , Weiss Christel , Ilonen Jorma , Engelhardt Britta , Ishikawa Hiroshi , Schwerk Christian , Schroten Horst , Tenenbaum Tobias , Rudolph Henriette 
Published: November 2019

AbstractBackgroundEchovirus 30 (E-30) is one of the most frequently isolated pathogens in aseptic meningitis worldwide. To gain access to the central nervous system (CNS), E-30 and immune cells have to cross one of the two main barriers of the CNS, the epithelial blood–cerebrospinal fluid barrier (BCSFB) or the endothelial blood–brain barrier (BBB). In an in vitro model of the BCSFB, it has been shown that E-30 can infect human immortalized brain choroid plexus papilloma (HIBCPP) cells.MethodsIn this study we investigated the migration of different T cell subpopulations, naive and effector T cells, through HIBCPP cells during E-30 infection. Effects of E-30 infection and the migration process were evaluated via immunofluorescence and flow cytometry analysis, as well as transepithelial resistance and dextran flux measurement.ResultsTh1 effector cells and enterovirus-specific effector T cells migrated through HIBCPP cells more efficiently than naive CD4+T cells following E-30 infection of HIBCPP cells. Among the different naive T cell populations, CD8+T cells crossed the E-30-infected HIBCPP cell layer in a significantly higher number than CD4+T cells. A large amount of effector T cells also remained attached to the basolateral side of the HIBCPP cells compared with naive T cells. Analysis of HIBCPP barrier function showed significant alteration after E-30 infection and trans- as well as paracellular migration of T cells independent of the respective subpopulation. Morphologic analysis of migrating T cells revealed that a polarized phenotype was induced by the chemokine CXCL12, but reversed to a round phenotype after E-30 infection. Further characterization of migrating Th1 effector cells revealed a downregulation of surface adhesion proteins such as LFA-1 PSGL-1, CD44, and CD49d.ConclusionTaken together these results suggest that naive CD8+and Th1 effector cells are highly efficient to migrate through the BCSFB in an inflammatory environment. The T cell phenotype is modified during the migration process through HIBCPP cells.
Commentary: the chronic inhalation study in rats for assessing lung cancer risk may be better than its reputation
Authors: Saber Anne T. , Poulsen Sarah S. , Hadrup Niels , Jacobsen Nicklas R. , Vogel Ulla 
Published: November 2019

AbstractRecently, Borm and Driscoll published a commentary discussing grouping of Poorly Soluble particles of Low Toxicity (PSLTs) and the use of rats as an animal model for human hazard assessment of PSLTs (Particle and Fibre Toxicology (2019) 16(1):11). The commentary was based on the scientific opinion of several international experts on these topics. The general conclusion from the authors was a cautious approach towards using chronic inhalation studies in rats for human hazard assessment of PSLTs. This was based on evidence of inhibition of particle clearance leading to overload in the rats after high dose exposure, and a suggested over reactivity of rat lung cancer responses compared to human risk.As a response to the commentary, we here discuss evidence from the scientific literature showing that a) diesel exhaust particles, carbon black nanoparticles and TiO2 nanoparticles have similar carcinogenic potential in rats, and induce lung cancer at air concentrations below the air concentrations that inhibit particle clearance in rats, and b) chronic inhalation studies of diesel exhaust particles are less sensitive than epidemiological studies, leading to higher risk estimates for lung cancer. Thus, evidence suggests that the chronic inhalation study in rats can be used for assessing lung cancer risk insoluble nanomaterials.
EZH2 abnormalities in lymphoid malignancies: underlying mechanisms and therapeutic implications
Authors: Li Boheng , Chng Wee-Joo 
Published: November 2019

AbstractEZH2 is the catalytic subunit of the polycomb repressive complex 2 (PRC2), which along with other PRC2 components mediates gene expression suppression via the methylation of Histone H3 at lysine 27. Recent studies have revealed a dichotomous role of EZH2 in physiology and in the pathogenesis of cancer. While it plays an essential role in the development of the lymphoid system, its deregulation, whether due to genetic or non-genetic causes, promotes B cell- and T cell-related lymphoma or leukemia. These findings triggered a boom in the development of therapeutic EZH2 inhibitors in recent years. Here, we discuss physiologic and pathogenic function of EZH2 in lymphoid context, various internal causes of EZH2 aberrance and how EZH2 modulates lymphomagenesis through epigenetic silencing, post-translational modifications (PTMs), orchestrating with surrounding tumor micro-environment and associating with RNA or viral partners. We also summarize different strategies to directly inhibit PRC2-EZH2 or to intervene EZH2 upstream signaling.
Regional hypothermia attenuates secondary-injury caused by time-out application of tourniquets following limb fragments injury combined with hemorrhagic shock
Authors: Weng Changmei , Lan Kai , Li Tao , Zhang Liangchao , Wang Jianmin , Lai Xinan 
Published: November 2019

AbstractBackgroundTourniquet is the most widely used and effective first-aid equipment for controlling hemorrhage of injured limb in battlefield. However, time-out application of tourniquets leads to ischemic-necrosis of skeletal muscles and ischemia-reperfusion injury. Regional hypothermia (RH) on wounded limb can relieve the injury on local tissue and distant organs. We aimed to investigate the protective effects of RH on rabbits’ limbs injured by a steel-ball combined with hemorrhagic-shock, and then employed tourniquet over-time, tried to identify the optimal treatment RH.MethodsThirty rabbits were randomly divided into 5 groups. All rabbits were anesthetized, intubated femoral artery and vein in right-hind limbs. Sham operation group (Sham): only femoral arteriovenous cannula in right-hind limb. None RH group (NRH): rabbits were intubated as Sham group, then the soft tissues of rabbits’ left-hinds were injured by a steel-ball shooting, and were exsanguinated until shock, then bundled with rubber tourniquets for 4 h.Three RH subgroups: rabbits were injured as mentioned above, the injured limbs were bundled with rubber tourniquets and treated with different temperature (5 ± 1 °C, 10 ± 1 °C, and 20 ± 1 °C, respectively) for 4 h. The injury severity of lung and regional muscle was assessed by histologic examination. Activity of adenosine triphosphatase (ATPase) and content of malondialdehyde (MDA) in muscle, inflammatory cytokines, myoglobin, creatine kinase-MM (CK-MM), Heme, Heme oxygenase 1 (HO-1), lactic acid (Lac), and lectrolyte ion in serum were detected.ResultsFollowing with RH treatment, the injury of lung and local muscle tissue was alleviated evidencing by mitigation of histopathological changes, significant decrease of water-content and MDA content, and increase of ATPase activity. Lower level of Lac, Potassium (K+), inflammatory cytokines, Heme, CK-MM, myoglobin content, and higher level of Calcium (Ca2+), HO-1 content were shown in RH treatment. 10 °C was the most effective RH to increase ATPase activity, and decrease MDA, myoglobin, CK-MM content.ConclusionTransient RH (4 h) had a “long-term mitigation effects” (continued for 6 h) on time-out application of tourniquet with the fluid resuscitation and core temperature maintenance, and the most effective temperature for reducing the side effects on tourniquet time-out application was 10 °C.
WDR5 inhibition halts metastasis dissemination by repressing the mesenchymal phenotype of breast cancer cells
Authors: Punzi Simona , Balestrieri Chiara , D’Alesio Carolina , Bossi Daniela , Dellino Gaetano Ivan , Gatti Elena , Pruneri Giancarlo , Criscitiello Carmen , Lovati Giulia , Meliksetyan Marine , Carugo Alessandro , Curigliano Giuseppe , Natoli Gioacchino , Pelicci Pier Giuseppe , Lanfrancone Luisa 
Published: November 2019

Abstract
Background
Development of metastases and drug resistance are still a challenge for a successful systemic treatment in breast cancer (BC) patients. One of the mechanisms that confer metastatic properties to the cell relies in the epithelial-to-mesenchymal transition (EMT). Moreover, both EMT and metastasis are partly modulated through epigenetic mechanisms, by repression or induction of specific related genes.

Methods
We applied shRNAs and drug targeting approaches in BC cell lines and metastatic patient-derived xenograft (PDX) models to inhibit WDR5, the core subunit of histone H3 K4 methyltransferase complexes, and evaluate its role in metastasis regulation.

Result
We report that WDR5 is crucial in regulating tumorigenesis and metastasis spreading during BC progression. In particular, WDR5 loss reduces the metastatic properties of the cells by reverting the mesenchymal phenotype of triple negative- and luminal B-derived cells, thus inducing an epithelial trait. We also suggest that this regulation is mediated by TGFβ1, implying a prominent role of WDR5 in driving EMT through TGFβ1 activation. Moreover, such EMT reversion can be induced by drug targeting of WDR5 as well, leading to BC cell sensitization to chemotherapy and enhancement of paclitaxel-dependent effects.

Conclusions
We suggest that WDR5 inhibition could be a promising pharmacologic approach to reduce cell migration, revert EMT, and block metastasis formation in BC, thus overcoming resistance to standard treatments.
Inhibition of Plasmodium sporogonic stages by ivermectin and other avermectins
Authors: Azevedo Raquel , Mendes António M. , Prudêncio Miguel 
Published: November 2019

Abstract
Background
The transmissible forms of Plasmodium parasites result from a process of sporogony that takes place inside their obligatory mosquito vector and culminates in the formation of mammalian-infective parasite forms. Ivermectin is a member of the avermectin family of endectocides, which has been proposed to inhibit malaria transmission due its insecticidal effect. However, it remains unclear whether ivermectin also exerts a direct action on the parasite’s blood and transmission stages.

Methods
We employed a rodent model of infection to assess the impact of ivermectin treatment on P. berghei asexual and sexual blood forms in vivo. We then made use of a newly established luminescence-based methodology to evaluate the activity of ivermectin and other avermectins against the sporogonic stages of P. berghei parasites in vitro independent of their role on mosquito physiology.

Results
Our results show that whereas ivermectin does not affect the parasite’s parasitemia, gametocytemia or exflagellation in the mammalian host, several members of the avermectin family of compounds exert a strong inhibitory effect on the generation and development of P. berghei oocysts.

Conclusions
Our results shed light on the action of avermectins against Plasmodium transmission stages and highlight the potential of these compounds to help prevent the spread of malaria.
Correction to: First molecular description, phylogeny and genetic variation of Taenia hydatigena from Nigerian sheep and goats based on three mitochondrial genes
Authors: Ohiolei John A. , Luka Joshua , Zhu Guo-Qiang , Yan Hong-Bin , Li Li , Magaji Abdullahi A. , Alvi Mughees A. , Wu Yan-Tao , Li Jian-Qiu , Fu Bao-Quan , Jia Wan-Zhong 
Published: November 2019

Following publication of the original article [1], the have authors flagged that the information in the legend of Fig. 1 is detailed in the wrong order.
Molecular characterization and genetic diversity of Ornithonyssus sylviarum in chickens (Gallus gallus) from Hainan Island, China
Authors: Bhowmick Biswajit , Zhao Jianguo , Øines Øivind , Bi Tianlin , Liao Chenghong , Zhang Lei , Han Qian 
Published: November 2019

AbstractBackgroundThe northern fowl mite (NFM),Ornithonyssus sylviarum, is an obligatory hematophagous ectoparasite of birds and one of the most important pests in the poultry industry on several continents. Although NFM poses a serious problem, it remains a neglected pest of poultry in China and other Asian countries. Therefore, a molecular analysis was conducted to provide baseline information on the occurrence, genetic diversity and emergence of NFM in poultry farms from China.MethodsThis study focused on morphological description and identification of adults based on electron microscopy, molecular sequencing of the mitochondrialcox1 gene and phylogenetic analysis. We have also used the DNA sequences of thecox1 gene to study the genetic diversity, population structure and demographic history. The neutrality tests were used to analyze signatures of historical demographic events.ResultsThe mites collected were identified as the northern fowl miteOrnithonyssus sylviarumbased on external morphological characterization using electron microscopy. Molecular analysis using a 756-bp long partial fragment of thecox1 gene revealed 99–100% sequence identity with NFM and phylogenetic inferences showed a bootstrap value of 99% indicating a well-supported monophyletic relationship. Molecular diversity indices showed high levels of haplotype diversity dominated by private haplotypes, but low nucleotide divergence between haplotypes. The Tajima’sDtest and Fu’sFstest showed negative value, indicating deviations from neutrality and both suggested recent population expansion of mite populations supported by a star-like topology of the isolates in the network analysis. Our genetic data are consistent with a single introduction of NFM infestations and the spread of NFM infestation in Hainan poultry farms and a private haplotype dominance, which suggest that infestations are recycled within the farms and transmission routes are limited between farms.ConclusionsTo our knowledge, this is the first time a molecular report of NFM in chicken from China including other Asian countries using DNA barcoding. The findings have potential implications with respect to understanding the transmission patterns, emergence and populations trends of parasitic infestations of poultry farms that will help for setting the parameters for integrated pest management (IPM) tactics against mite infestations.
Nutrition knowledge and attitude in medical students of Tabriz University of Medical Sciences in 2017–2018
Authors: Dolatkhah Neda , Aghamohammadi Dawood , Farshbaf-Khalili Azizeh , Hajifaraji Majid , Hashemian Maryam , Esmaeili Sepideh 
Published: November 2019

Abstract
Objectives
In this cross-sectional study among 220 medical students we aimed to determine the nutritional knowledge and attitude of medical students through clinical training courses (externship and internship) of Tabriz University of Medical Sciences, Iran. A nutritional knowledge questionnaire included 51 questions was used to determine the correct, perceived and accuracy of knowledge of the participant in different aspects of nutrition sciences. The nutrition attitude questionnaire included 30 questions. Both questionnaires were confirmed in terms of the validity and reliability for assessing nutritional knowledge and attitude in this sample of Iranian medical students. Nutritional knowledge and attitude were calculated as percentage of correct or appropriate responses.

Results
The correct knowledge was not significantly different among externs and interns (68.20 ± 7.50% and 67.87 ± 6.04% respectively, p = 0.729). Results showed that most of the participants (49.61% of externs and 57.14% of inters) had a poor nutritional knowledge, significantly varied by age (p = 0.035). The attitude index of the subjects was not significantly different among externs and interns (73.36 ± 9.42% and 74.59 ± 9.20%, p = 0.335). Most students (92.7%) had a very appropriate attitude toward nutrition, significantly varied by sex (p = 0.010). These findings indicate that there are multiple deficiencies in nutrition knowledge of medical students.