bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transmission of Rat Hepatitis E Virus Infection to Humans in Hong Kong: A Clinical and Epidemiological Analysis
Authors: Sridhar Siddharth , Yip Cyril Chik‐Yan , Wu Shusheng , Chew Nicholas Foo‐Siong , Leung Kit‐Hang , Chan Jasper Fuk‐Woo , Zhao Pyrear Suhui , Chan Wan‐Mui , Poon Rosana Wing‐Shan , Tsoi Hoi‐Wah , Cai Jian‐Piao , Chan Helen Shuk‐Ying , Leung Anthony Wai‐Shing , Tse Cindy Wing‐Sze , Zee Jonpaul Sze‐Tsing , Tsang Owen Tak‐Yin , Cheng Vincent Chi‐Chung , Lau Susanna Kar‐Pui , Woo Patrick Chiu‐Yat , Tsang Dominic Ngai‐Chong , Yuen Kwok‐Yung 
Published: January 2020

Background and Aims
Hepatitis E virus (HEV) variants causing human infection predominantly belong to HEV species A (HEV‐A). HEV species C genotype 1 (HEV‐C1) circulates in rats and is highly divergent from HEV‐A. It was previously considered unable to infect humans, but the first case of human HEV‐C1 infection was recently discovered in Hong Kong. The aim of this study is to further describe the features of this zoonosis in Hong Kong.

Approach and Results
We conducted a territory‐wide prospective screening study for HEV‐C1 infection over a 31‐month period. Blood samples from 2,860 patients with abnormal liver function (n = 2,201) or immunosuppressive conditions (n = 659) were screened for HEV‐C1 RNA. In addition, 186 captured commensal rats were screened for HEV‐C1 RNA. Sequences of human‐derived and rat‐derived HEV‐C1 isolates were compared. Epidemiological and clinical features of HEV‐C1 infection were analyzed. HEV‐C1 RNA was detected in 6/2,201 (0.27%) patients with hepatitis and 1/659 (0.15%) immunocompromised persons. Including the previously reported case, eight HEV‐C1 infections were identified, including five in patients who were immunosuppressed. Three patients had acute hepatitis, four had persistent hepatitis, and one had subclinical infection without hepatitis. One patient died of meningoencephalitis, and HEV‐C1 was detected in cerebrospinal fluid. HEV‐C1 hepatitis was generally milder than HEV‐A hepatitis. HEV‐C1 RNA was detected in 7/186 (3.76%) rats. One HEV‐C1 isolate obtained from a rat captured near the residences of patients was closely related to the major outbreak strain.

Conclusions
HEV‐C1 is a cause of hepatitis E in humans in Hong Kong. Immunosuppressed individuals are susceptible to persistent HEV‐C1 infection and extrahepatic manifestations. Subclinical HEV‐C1 infection threatens blood safety. Tests for HEV‐C1 are required in clinical laboratories.
Bespoken Nanoceria: An Effective Treatment in Experimental Hepatocellular Carcinoma
Authors: Fernández‐Varo Guillermo , Perramón Meritxell , Carvajal Silvia , Oró Denise , Casals Eudald , Boix Loreto , Oller Laura , Macías‐Muñoz Laura , Marfà Santi , Casals Gregori , Morales‐Ruiz Manuel , Casado Pedro , Cutillas Pedro R. , Bruix Jordi , Navasa Miquel , Fuster Josep , Garcia‐Valdecasas Juan Carlos , Pavel Mihai C. , Puntes Víctor , Jiménez Wladimiro 
Published: January 2020

Background and Aims
Despite the availability of new‐generation drugs, hepatocellular carcinoma (HCC) is still the third most frequent cause of cancer‐related deaths worldwide. Cerium oxide nanoparticles (CeO2NPs) have emerged as an antioxidant agent in experimental liver disease because of their antioxidant, anti‐inflammatory, and antisteatotic properties. In the present study, we aimed to elucidate the potential of CeO2NPs as therapeutic agents in HCC.

Approach and Results
HCC was induced in 110 Wistar rats by intraperitoneal administration of diethylnitrosamine for 16 weeks. Animals were treated with vehicle or CeO2NPs at weeks 16 and 17. At the eighteenth week, nanoceria biodistribution was assessed by mass spectrometry (MS). The effect of CeO2NPs on tumor progression and animal survival was investigated. Hepatic tissue MS‐based phosphoproteomics as well as analysis of principal lipid components were performed. The intracellular uptake of CeO2NPs by human ex vivo perfused livers and human hepatocytes was analyzed. Nanoceria was mainly accumulated in the liver, where it reduced macrophage infiltration and inflammatory gene expression. Nanoceria treatment increased liver apoptotic activity, while proliferation was attenuated. Phosphoproteomic analysis revealed that CeO2NPs affected the phosphorylation of proteins mainly related to cell adhesion and RNA splicing. CeO2NPs decreased phosphatidylcholine‐derived arachidonic acid and reverted the HCC‐induced increase of linoleic acid in several lipid components. Furthermore, CeO2NPs reduced serum alpha‐protein levels and improved the survival of HCC rats. Nanoceria uptake by ex vivo perfused human livers and in vitro human hepatocytes was also demonstrated.

Conclusions
These data indicate that CeO2NPs partially revert the cellular mechanisms involved in tumor progression and significantly increase survival in HCC rats, suggesting that they could be effective in patients with HCC.
Synthesis and characterization of thiol‐acrylate hydrogels using a base‐catalyzed Michael addition for 3D cell culture applications
Authors: Khan Anowar H. , Cook Jeffery K. , Wortmann Wayne J. , Kersker Nathan D. , Rao Asha , Pojman John A. , Melvin Adam T. 
Published: January 2020

AbstractThere is significant interest in developing new approaches for culturing mammalian cells in a three‐dimensional (3D) environment due to the fact that it better recapitulates the in vivo environment. The goal of this work was to develop thiol‐acrylate, biodegradable hydrogels that possess highly tunable properties to support in vitro 3D culture. Six different hydrogel formulations were synthesized using two readily available monomers, a trithiol (ETTMP 1300 [ethoxylated trimethylolpropane tri(3‐mercaptopropionate) 1300]) and a diacrylate (PEGDA 700 [polyethylene glycol diacrylate 700]), polymerized by a base‐catalyzed Michael addition reaction. The resultant hydrogels were homogeneous, hydrophilic, and biodegradable. Different mechanical properties such as gelation time, storage modulus (or the elasticity G'), swelling ratio, and rate of degradation were tuned by varying the weight percentage of polymer, the molar ratio of thiol‐to‐acrylate groups, and the pH of the solution. Cytocompatibility was assessed using two model breast cancer cell lines by both 2D and 3D cell culturing approaches. The hydrogel formulations with a thiol‐to‐acrylate molar ratio of 1.05 were found to be optimal for both 2D and 3D cultures with MDA‐MB‐231 cellular aggregates found to be viable after 17 days of 3D continuous culture. Finally, MCF7 cells were observed to form 3D spheroids up to 600 μm in diameter as proof of principle for the thiol‐acrylate hydrogel to function as a scaffold for in vitro 3D cell culture. A comparison of the different mechanical properties of the six hydrogel formulations coupled with in vitro cell culture results and findings from previously published hydrogels conclude that the thiol‐acrylate hydrogels have significant potential as a scaffold for 3D cell culture.
Exosomes from CD133+ cells carrying circ‐ABCC1 mediate cell stemness and metastasis in colorectal cancer
Authors: Zhao Hong , Chen Shixia , Fu Qiang 
Published: January 2020

AbstractColorectal cancer (CRC), a fatal tumor, has been diagnosed as one of the most prevalent types of cancers globally, inducing multiple cancer‐linked deaths. Mounting evidence has revealed that circular RNA (circRNA) elicits a regulatory impact on the initiation and development of cancers. Emerged as a new circRNA, hsa_circ_0000677 (circ‐ABCC1) has not been studied in cancer progression. This study is the first attempt to explore the regulatory role of circ‐ABCC1 in CRC. In this study, data from sphere‐forming, transwell, and Western blot analyses revealed that cell stemness, sphere formation, and metastasis were notably enhanced in CD133+ cells isolated from CRC cells. In addition, exosomes from CD133+ cells could promote cell stemness, sphere formation, and metastasis. Moreover, circ‐ABCC1 was verified to be characterized with a loop structure through quantitative reverse‐transcription polymerase chain reaction analysis. Functional assays testified that the upregulation of circ‐ABCC1 contributed to cell stemness, sphere formation, and metastasis in CD133−/Caco2 or CD133−/HCT15 cells. Furthermore, the interaction between circ‐ABCC1 and β‐catenin was analyzed via RNA immunoprecipitation and RNA pull‐down and finally, circ‐ABCC1 was confirmed to facilitate CRC progression by activating the Wnt/β‐catenin pathway. To sum up, exosomes from CD133+ cells carrying circ‐ABCC1 can mediate cell stemness and metastasis in CRC, unveiling that circ‐ABCC1 serves as a novel candidate target for CRC treatment.
Crizotinib sensitizes the erlotinib resistant HCC827GR5 cell line by influencing lysosomal function
Authors: Van Der Steen Nele , Keller Kaylee , Dekker Henk , Porcelli Letizia , Honeywell Richard J. , Van Meerloo Johan , Musters René J. P. , Kathmann Ietje , Frampton Adam E. , Liu Daniel S. K. , Ruijtenbeek Rob , Rolfo Christian , Pauwels Patrick , Giovannetti Elisa , Peters Godefridus J. 
Published: January 2020

AbstractIn non‐small cell lung cancer, sensitizing mutations in epidermal growth factor receptor (EGFR) or cMET amplification serve as good biomarkers for targeted therapies against EGFR or cMET, respectively. Here we aimed to determine how this different genetic background would affect the interaction between the EGFR‐inhibitor erlotinib and the cMET‐inhibitor crizotinib. To unravel the mechanism of synergy we investigated the effect of the drugs on various parameters, including cell cycle arrest, migration, protein phosphorylation, kinase activity, the expression of drug efflux pumps, intracellular drug concentrations, and live‐cell microscopy. We observed additive effects in EBC‐1, H1975, and HCC827, and a strong synergism in the HCC827GR5 cell line. This cell line is a clone of the HCC827 cells that harbor an EGFR exon 19 deletion and has been made resistant to the EGFR‐inhibitor gefitinib, resulting in cMET amplification. Remarkably, the intracellular concentration of crizotinib was significantly higher in HCC827GR5 compared to the parental HCC827 cell line. Furthermore, live‐cell microscopy with a pH‐sensitive probe showed a differential reaction of the pH in the cytoplasm and the lysosomes after drug treatment in the HCC827GR5 in comparison with the HCC827 cells. This change in pH could influence the process of lysosomal sequestration of drugs. These results led us to the conclusion that lysosomal sequestration is involved in the strong synergistic reaction of the HCC827GR5 cell line to crizotinib–erlotinib combination. This finding warrants future clinical studies to evaluate whether genetic background and lysosomal sequestration could guide tailored therapeutic interventions.
circRNA‐14723 promotes hepatocytes proliferation in rat liver regeneration by sponging rno‐miR‐16‐5p
Authors: Guo Xueqiang , Xi Lingling , Li Lifei , Guo Jianlin , Jin Wei , Chang Cuifang , Zhang Jingbo , Xu Cunshuan , Chen Guangwen 
Published: January 2020

AbstractCircular RNA (circRNA) is a subclass of noncoding RNA (ncRNA) detected within mammalian tissues and cells. However, its regulatory role during the proliferation phase of rat liver regeneration (LR) remains unreported. This study was designed to explore their regulatory mechanisms in cell proliferation of LR. The circRNA expression profile was detected by high‐throughput sequencing. It was indicated that 260 circRNAs were differentially expressed during the proliferation phase of rat LR. Among them, circ‐14723 displayed a significantly differential expression. We further explored its regulatory mechanism in rat hepatocytes (BRL‐3A cells). First, EdU, flow cytometry and western blot (WB) indicated that knocking down circ‐14723 inhibited BRL‐3A cells proliferation. Second, RNA‐Pulldown and dual‐luciferase report assay showed that circ‐14723 could sponge rno‐miR‐16‐5p. At last, WB showed that the reported target genes of rno‐miR‐16‐5p, CCND1, and CCNE1 were downregulated after knocking down circ‐14723. In conclusion, we found that circ‐14723 exerted a critical role in G1/S arrest to promote cell proliferation via rno‐miR‐16‐5p/CCND1 and CCNE1 axis in rat LR. This finding further revealed the regulatory mechanisms of circRNA on cell proliferation of LR, and might provide a potential target for clinical problems.
Retracted: LINC00449 regulates the proliferation and invasion of acute monocytic leukemia and predicts favorable prognosis
Authors: Shi Yuan , Zhu Yuandong , Zheng Xiao , Zheng Zhuojun 
Published: January 2020

AbstractAcute myeloid leukemia (AML) is a highly aggressive disease that causes high mortality. Long noncoding RNA (lncRNA) have studied in recent years that could be a potential biomarker and therapeutic target. Therefore, it is urgently necessary to explore the novel lncRNAs in AML. Microarray analysis was performed to determine the differentially expressed lncRNAs between mononuclear cells of AML and normal samples. The biological function of lncRNA on cell proliferation and migration was measured in vitro. The predicted downstream target of lncRNA was validated by dual‐luciferase reporter assay, RNA immunoprecipitation, RNA pull‐down, and rescue experiments. The tumor formation and metastasis study were conducted in vivo. The expression of lncRNA in clinical samples was determined by a quantitative reverse transcription‐polymerase chain reaction. LINC00449 was one of the most differentially expressed lncRNA which is mainly located in the cytoplasm. We found that overexpression of LINC00449 could inhibit the cell proliferation and invasion of AML cells in vitro and in vivo. Besides, miR‐150 was identified as the downstream target gene that was negatively regulated by LINC00449 and FOXD3 was targeted by miR‐150. The results were confirmed by dual‐luciferase reporter assay, RNA immunoprecipitation, RNA pull‐down, rescue experiments, and in vivo assays. Patients with AML with high expression of LINC0049 may characterize a favorable survival. All the above‐mentioned findings indicated that the LINC00449/miR‐150/FOXD3 signaling pathway might represent a novel prognostic biomarker or therapeutic target for the treatment of AML.
PD‐1/PD‐L1‐dependent immune response in colorectal cancer
Authors: Payandeh Zahra , Khalili Saeed , Somi Mohammad Hossein , Mard‐Soltani Maysam , Baghbanzadeh Amir , Hajiasgharzadeh Khalil , Samadi Nasser , Baradaran Behzad 
Published: January 2020

AbstractColorectal cancer (CRC) is still considered as the third most frequent cancer in the world. Microsatellite instability (MSI), inflammation, and microRNAs have been demonstrated as the main contributing factors in CRC. Subtype 1 CRC is defined by NK cells infiltration, induction of Th1 lymphocyte and cytotoxic T cell responses as well as upregulation of immune checkpoint proteins including programmed cell death‐1 (PD‐1). Based on the diverse features of CRC, such as the stage and localization of the tumor, several treatment approaches are available. However, the efficiency of these treatments may be decreased due to the development of diverse resistance mechanisms. It has been proven that monoclonal antibodies (mAbs) can increase the effectiveness of CRC treatments. Nowadays, several mAbs including nivolumab and pembrolizumab have been approved for the treatment of CRC. Immune checkpoint receptors including PD‐1 can be inhibited by these antibodies. Combination therapy gives an opportunity for advanced treatment for CRC patients. In this review, an update has been provided on the molecular mechanisms involved in MSI colorectal cancer immune microenvironment by focusing on PD‐ligand 1 (PD‐L1) and treatment of patients with advanced immunotherapy, which were examined in the different clinical trial phases. Considering induced expression of PD‐L1 by conventional chemotherapeutics, we have summarized the role of PD‐L1 in CRC, the chemotherapy effects on the PD‐1/PD‐L1 axis and novel combined approaches to enhance immunotherapy of CRC by focusing on PD‐L1.
Endoplasmic reticulum distribution during bovine oocyte activation is regulated by protein kinase C via actin filaments
Authors: Feitosa Weber Beringui , Lopes Everton , Visintin Jose Antonio , Assumpção Mayra Elena Ortiz D'Avila 
Published: January 2020

AbstractFertilization‐induced [Ca2+]i oscillations generally depend on the release of calcium ions from the endoplasmic reticulum (ER). Since ER is the main store of calcium ions, it plays an important role in oocyte fertilization. However, the mechanism of ER organization at oocyte activation is unknown. Here, we show that protein kinase C (PKC) is involved in ER distribution during bovine oocyte activation, but not involved in cell cycle resumption and spindle organization. Actin filaments were affected by PKC pharmacological inhibition. In addition, similar to PKC results, the actin‐depolymerizing drug cytochalasin B affected the ER distribution during oocyte activation. Specifically, we have demonstrated that ER organization during bovine oocyte activation is regulated by PKC possibly through its action on actin filaments regulation. Taken together, the results presented here provide further information on the pathway involved in the regulation of ER organization during oocyte activation and new insight into the functional role of PKC and actin filaments during this process.
Anatomy, micromorphology, and histochemistry of leaves and stems of Cantinoa althaeifolia (Lamiaceae)
Authors: de Almeida Valter Paes , Raman Vijayasankar , Raeski Paola Aparecida , Urban Amanda Migliorini , Swiech Juliane Nadal , Miguel Marilis Dallarmi , Farago Paulo Vitor , Khan Ikhlas Ahmed , Budel Jane Manfron 
Published: January 2020

AbstractThis article enumerates the detailed anatomy of Cantinoa althaeifolia (Lamiaceae) illustrated with light and scanning electron microscopy images. The anatomical markers include the presence of branched nonglandular trichomes and capitate, peltate, and clavate types of glandular trichomes; prismatic crystals on the leaf and stem surfaces; and oil droplets in the leaf mesophyll. Histochemical tests and EDS analyses were performed in order to detect the composition of certain cells and their contents. The key findings of the present study can contribute to the taxonomy, species identification, and quality control of Cantinoa althaeifolia.
Linkages to HIV confirmatory testing and antiretroviral therapy after online, supervised, HIV self‐testing among Thai men who have sex with men and transgender women
Authors: Phanuphak Nittaya , Jantarapakde Jureeporn , Himmad Linrada , Sungsing Thanthip , Meksena Ratchadaporn , Phomthong Sangusa , Phoseeta Petchfa , Tongmuang Sumitr , Mingkwanrungruang Pravit , Meekrua Dusita , Sukthongsa Supachai , Hongwiangchan Somporn , Upanun Nutchanin , Jirajariyavej Supunnee , Jadwattanakul Tanate , Barisri Supphadith , Pankam Tippawan , Phanuphak Praphan 
Published: January 2020

AbstractIntroductionOnline, supervised, HIV self‐testing has potential to reach men who have sex with men (MSM) and transgender women (TGW) who never tested before and who had high HIV‐positive yield. We studied linkages to HIV confirmatory test and antiretroviral therapy (ART) initiation among Thai MSM and TGW who chose online and/or offline platforms for HIV testing and factors associated with unsuccessful linkages.MethodsMSM and TGW were enrolled from Bangkok Metropolitan Region and Pattaya during December 2015 to June 2017 and followed for 12 months. Participants could choose between: 1) offline HIV counselling and testing (Offline group), 2) online pre‐test counselling and offline HIV testing (Mixed group) and 3) online counselling and online, supervised, HIV self‐testing (Online group). Sociodemographic data, risk behaviour and social network use characteristics were collected by self‐administered questionnaires. Linkages to HIV confirmatory testing and/or ART initiation were collected from participants who tested reactive/positive at baseline and during study follow‐up. Modified Poisson regression models identified covariates for poor retention and unsuccessful ART initiation.ResultsOf 465 MSM and 99 TGW, 200 self‐selected the Offline group, 156 the Mixed group and 208 the Online group. The Online group demonstrated highest HIV prevalence (15.0% vs. 13.0% vs. 3.4%) and high HIV incidence (5.1 vs. 8.3 vs. 3.2 per 100 person‐years), compared to the Offline and Mixed groups. Among 60 baseline HIV positive and 18 seroconversion participants, successful ART initiation in the Online group (52.8%) was lower than the Offline (84.8%) and Mixed groups (77.8%). Factors associated with unsuccessful ART initiation included choosing to be in the Online group (aRR 3.94, 95% CI 1.07 to 14.52), <17 years old at first sex (aRR 3.02, 95% CI 1.15 to 7.92), amphetamine‐type stimulants use in the past six months (aRR 3.6, 95% CI 1.22 to 10.64) and no/single sex partner (aRR 3.84, 95%CI 1.36 to 10.83) in the past six months.ConclusionsOnline, supervised, HIV self‐testing allowed more MSM and TGW to know their HIV status. However, linkages to confirmatory test and ART initiation once tested HIV‐reactive are key challenges. Alternative options to bring HIV test confirmation, prevention and ART services to these individuals after HIV self‐testing are needed.
Influence of N‐acylhomoserine lactonase silver nanoparticles on the quorum sensing system of Helicobacter pylori: A potential strategy to combat biofilm formation
Authors: Gopalakrishnan Vinoj , Masanam Esakkirajan , Ramkumar Vijayan S. , Baskaraligam Vaseeharan , Selvaraj Gopinath 
Published: January 2020

AbstractThe treatment of Helicobacter pylori usually fails due to their ability to form biofilms and resistance to antibiotics. This might potentially lead to gastric carcinoma and mucosa‐associated lymphoid tissue lymphoma. In the present study, we elucidate the potential role of N‐acylhomoserine lactonase stabilized silver nanoparticles (AiiA‐AgNPs) in treating biofilms produced by H. pylori. AiiA‐AgNPs inhibited quorum sensing (QS) by degradation of QS molecules, thereby reducing biofilm formation, urease production, and altering cell surface hydrophobicity of H. pylori. AiiA‐AgNPs showed no cytotoxic effects on RAW 264.7 macrophages at the effective concentration (1–5 µM) of antibiofilm activity. In addition, AiiA‐AgNP in high concentration (80–100 µM) exhibited cytotoxicity against HCT‐15 carcinoma cells, depicting its therapeutic role in treating cancer.
In situ and ex situ surface‐enhanced Raman spectroscopy (SERS) analysis of cell mitochondria
Authors: Yue Jing , Shen Yanting , Liang Lijia , Cong Lili , Guan Xin , Li Zhiyuan , Xu Shuping , Liang Chongyang , Shi Wei , Xu Weiqing 
Published: January 2020

AbstractAs the "powerhouse" of cells, mitochondrion is the main site of cellular aerobic respiration and plays a vital role in performing many important cellular functions. The consequence of mitochondrial dysfunction could lead to a wide range of disorders and diseases. Traditional mitochondria‐related cytobiology methods always require the isolation of organelles for biological components, followed by structural analysis and quantitative analysis. In this study, we tried to assess the feasibility and reliability of the isolation‐based method and the in situ approach from the spectral fingerprint characters. Surface‐enhanced Raman scattering spectroscopy (SERS) was employed to investigate the molecular information of mitochondria from cancer cells (HepG2 and MCF‐7 cells) in situ with the assistant of mitochondrion‐targeting nanoprobes, which was compared with the isolation‐based ex situ method. The results display two methods, which show high consistency in the spectral profiles of mitochondrion, proving the feasibility of both in bioanalysis. Abundant molecular information such as protein and DNA is disclosed, and protein is one of the main components. From spectral comparison between two cancer cells, differences in protein content are observed. We believe that this comparative study will provide a valuable and recommended reference for the selection of analytical methods for different study purposes.