bluuebunny/crossref_metadata_2025_split huggingface dataset:
KIF18B promotes hepatocellular carcinoma progression through activating Wnt/β‐catenin‐signaling pathway
Authors: Yang Bin , Wang Shengzhi , Xie Hui , Wang Chunping , Gao Xudong , Rong Yihui , Liu Zhenwen , Lu Yinying 
Published: February 2020

AbstractThis study aimed to investigate the functional roles of kinesin family member 18B (KIF18B) in hepatocellular carcinoma (HCC) development, as well as the related molecular mechanisms. Tissue specimens were collected from 105 patients with HCC, and the messenger RNA (mRNA) and protein levels of KIF18B were detected using quantitative real‐time polymerase chain reaction and immunohistochemistry assays, respectively. The χ2 test was performed to estimate the association of KIF18B with clinical characteristics of patients with HCC. Effects of KIF18B expression on biological behaviors of HCC cells were detected by clone formation, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, and transwell assays. The expression patterns of proteins were investigated using Western blot analysis. HCC tissues and cell lines showed significant upregulation of KIF18B at both mRNA and protein levels (p > .05, for all). Furthermore, the elevated KIF18B expression was positively correlated with the tumor‐node‐metastasis stage (p = .015) and lymph node metastasis (p = .007). Knockdown of KIF18B might suppress HCC cell clone formation, proliferation, migration, and invasion in vitro. Besides, the activity of Wnt/β‐catenin pathway was also significantly inhibited after the KIF18B knockdown. However, the antitumor actions caused by KIF18B knockdown might be reversed by lithium chloride treatment, which was the inducer of Wnt/β‐catenin‐signaling pathway. KIF18B may serve as an oncogene in HCC through enhancing the activity of Wnt/β‐catenin pathway.
miR‐129‐5p inhibits proliferation, migration, and invasion in rectal adenocarcinoma cells through targeting E2F7
Authors: Wan Ping , Bai Xuan , Yang Chao , He Tian , Luo Lilin , Wang Yun , Fan Minmin , Wang Zhilin , Lu Liming , Yin Yajing , Li Sisi , Guo Qiang , Song Zhengyi 
Published: February 2020

AbstractmicroRNAs (miRNAs), a kind of small noncoding RNAs, are considered able to regulate expression of genes and mediate RNA silencing. miR‐129‐5p was shown to be a cancer‐related miRNA. However, the influence of miR‐129‐5p in rectal adenocarcinoma (READ) development remains to be determined. Based on the TCGA data, downregulation of miR‐129‐5p in READ samples was observed. Manual restoration of the miR‐129‐5p in SW1463 and SW480 cell lines significantly inhibited invasion, migration, and proliferation of READ cell lines, while the apoptosis ability was enhanced. Meanwhile, we found E2F7 acted as a potential target of miR‐129‐5p and was upregulated in READ samples. E2F7 upregulation reversed the repression of miR‐129‐5p on READ development. Finally, in vivo experiments showed that inhibition of tumor growth in nude mice was achieved through upregulating miR‐129‐5p. Overall, our findings suggest increasing of miR‐129‐5p leads to the suppression of READ progression through regulating the expression of E2F7, which may provide novel insights into the treatment of READ.
Contributions and prognostic values of m6A RNA methylation regulators in non‐small‐cell lung cancer
Authors: Liu Yang , Guo Xiuchen , Zhao Meng , Ao Haijiao , Leng Xue , Liu Mingdong , Wu Caixia , Ma Jianqun , Zhu Jinhong 
Published: February 2020

AbstractN6‐methyladenosine (m6A) RNA modification can alter gene expression and function by regulating RNA splicing, stability, translocation, and translation. Deregulation of m6A has been involved in various types of cancer. However, its implications in non‐small‐cell lung cancer (NSCLC) are mostly unknown. This posttranscriptional modification is dynamically and reversibly mediated by different regulators, including methyltransferase, demethylases, and m6A binding proteins. In this study, we comprehensively investigated the contributions and prognostic values of 13 common m6A RNA modification regulators using The Cancer Genome Atlas database. We found that the expression levels of most of the studied genes were significantly altered in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Using consensus clustering, the gene‐expression profiles of 13 m6A regulators could classify patients with LUAD into two subgroups with significantly distinct clinical outcomes, but not the LUSC cohort or the combination of the two cohorts. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis were applied to explore differential signaling pathways and cellular processes between the two LUAD subgroups. Moreover, we found that this gene‐expression signature could better predict prognosis in the late‐stage (III + IV) than in the early‐stage (I + II) LUAD. Finally, we developed an optimal prognostic gene signature by using the least absolute shrinkage and selection operator Cox regression algorithm and compute risk score. In conclusion, our study unveiled the implication of m6A RNA modification regulators in NSCLC and identified the m6A gene expression classifiers for predicting the prognosis of NSCLC.
miR‐125b lowers sensitivity to apoptosis following mitotic arrest: Implications for breast cancer therapy
Authors: Matuszyk Janusz , Klopotowska Dagmara 
Published: February 2020

AbstractThe process of apoptosis begins when the balance between proapoptotic and antiapoptotic stimuli is disturbed, leading to oligomerization of apoptosis effectors and disruption of the outer mitochondrial membrane. BCL‐2 family proteins are the major regulators of mitochondrial pathway of apoptosis. In turn, microRNA‐125b (miR‐125b) is a member of microRNAs, which are short single‐stranded noncoding RNAs that negatively regulate gene expression at the posttranscriptional level. miR‐125b targets messenger RNAs encoding proapoptotic (BAK1, PUMA, BMF) and antiapoptotic (MCL1) BCL‐2 family proteins. This mini‐review briefly describes the involvement of BCL‐2 family proteins in triggering apoptosis. Then, attention is paid to the differences in the activation of apoptosis with doxorubicin and paclitaxel, and finally the effect of miR‐125b on paclitaxel‐ and doxorubicin‐induced apoptosis in breast cancer cells is considered. It appears that miR‐125b downregulates proteins that are significantly involved in the activation of apoptosis after paclitaxel‐induced prolonged mitotic arrest or subsequent DNA damage if mitotic slippage occurs. It seems that high levels of miR‐125b may not favor paclitaxel therapy, but reduction of miR‐125b levels may increase paclitaxel‐induced apoptosis, possibly also genotoxic‐induced apoptosis, although adverse effects may also occur including decrease in doxorubicin‐induced apoptosis.
M2 differentiation of MonoMac‐1 cell line induced by M‐CSF and glucocorticoid pathways
Authors: Vakili Sarah , Fischer Tracy , Rappaport Jay 
Published: February 2020

AbstractModels of macrophage subtypes require molecular characterization to reliably facilitate their differentiation. Although CD16+ (Fc‐gamma III receptor) monocytes that express CD163 (a hemoglobin/haptoglobin receptor) have been implicated in a variety of disease states, the conditions necessary to establish lineages of these cell subtypes remains unknown. The current investigations utilize a cell line derived from acute myelogenous leukemia lineage, MonoMac‐1, to interrogate the factors that promote the development of CD16+ macrophages that express CD163. Results implicate the glucocorticoid pathway as well as c‐fms signaling based on the action of dexamethasone and macrophage colony‐stimulating factor‐1 in promoting CD16+ expression, in addition to phorbol myristate acetate and lipopolysaccharides treatment. The ability of glucocorticoid and c‐fms receptor antagonists to inhibit CD16+ cell formation further establishes the role of these pathways in CD16 expression in this cell line. In view of the inherent difficulty in working with primary cells as well as donor variation, cell lines may be preferable to primary cells for their consistency. We envision that the process we use to induce CD16 expression in this cell type will be useful for screening and identification of drug candidates potentially useful for the treatment of diseases where the etiology involves the expansion of the CD16+ monocytes subset or the accumulation of CD163+ tissue macrophages.
KIAA1429 regulates cell proliferation by targeting c‐Jun messenger RNA directly in gastric cancer
Authors: Miao Ran , Dai Cong‐Cong , Mei Lin , Xu Jun , Sun Shan‐Wen , Xing Yun‐Long , Wu Li‐Sheng , Wang Ming‐Hai , Wei Ji‐Fu 
Published: February 2020

AbstractN6‐methyladenosine (m6A) modification regulatory proteins are involved in the development of many types of cancer. KIAA1429 serves as a scaffold in bridging the catalytic core components of the m6A methyltransferase complex. The role of KIAA1429 in gastric cancer and its related mechanism has not been reported upon. The expression of KIAA1429 was detected in human gastric cancer tissues and cell lines by quantitative real‐time polymerase chain reaction and western blot. The effects of KIAA1429 on gastric cancer proliferation were evaluated by cell counting kit assays, colony formation assays, flow cytometry assay, and in vivo experiments with nude mice. And messenger RNA (mRNA) high‐throughput sequencing, RNA immunoprecipitation assay (RIP), luciferase assay, and a rescue experiment were used to identify the relationship between KIAA1429 and its specific targeted gene, c‐Jun. We found that KIAA1429 was upregulated in gastric cancer tissues, and expressed lower in adjacent tissues. The upregulated KIAA1429 promoted proliferation and downregulated KIAA1429 was proved to inhibit proliferation of gastric cancer in vitro and in vivo. Then, we identified the potential KIAA1429 regulating gene as c‐Jun by mRNAs high‐throughput sequencing and RIP assay. By luciferase assay, we verified that KIAA1429 regulated the expression of c‐Jun in an m6A‐independent manner. Finally, the overexpression of c‐Jun rescued the inhibition of proliferation caused by KIAA1429 knockdown in gastric cancer cells. KIAA1429 could act as an oncogene in gastric cancer by stabilizing c‐Jun mRNA in an m6A‐independent manner. This highlights the functional role for KIAA1429 as a potential prognostic biomarker and therapeutic target in gastric cancer.
Pharmacokinetics, Safety, and Tolerability of Orally Administered Ursodeoxycholic Acid in Patients With Parkinson's Disease—A Pilot Study
Authors: Sathe Abhishek G. , Tuite Paul , Chen Chi , Ma Yiwei , Chen Wei , Cloyd James , Low Walter C. , Steer Clifford J. , Lee Byeong‐Yeul , Zhu Xiao‐Hong , Coles Lisa D. 
Published: February 2020

AbstractMitochondrial dysfunction is implicated in the pathogenesis of Parkinson's disease. Preliminary data have shown lower brain adenosine triphosphate (ATP) levels in Parkinson's disease versus age‐matched healthy controls. Ursodeoxycholic acid (UDCA) may improve impaired mitochondrial function. Our objective was to evaluate UDCA tolerability, pharmacokinetics, and its effect on brain bioenergetics in individuals with Parkinson's disease. An open‐label, prospective, multiple‐ascending‐dose study of oral UDCA in 5 individuals with Parkinson's disease was completed. A blood safety panel, plasma concentrations of UDCA and UDCA conjugates, and brain ATP levels were measured before and after therapy (week 1: 15 mg/kg/day; week 2: 30 mg/kg/day; and weeks 3‐6: 50 mg/kg/day). UDCA and conjugates were measured using liquid chromatography–mass spectrometry. ATP levels and ATPase activity were measured using 7‐Tesla 31P magnetic resonance spectroscopy. Secondary measures included the Unified Parkinson's Disease Rating Scale and Montreal Cognitive Assessment. UDCA was generally well tolerated. The most frequent adverse event was gastrointestinal discomfort, rated by subjects as mild to moderate. Noncompartmental pharmacokinetic analysis resulted in (mean ± standard deviation) a maximum concentration of 8749 ± 2840 ng/mL and half‐life of 2.1 ± 0.71 hr. Magnetic resonance spectroscopy data were obtained in 3 individuals with Parkinson's disease and showed modest increases in ATP and decreases in ATPase activity. Changes in Unified Parkinson's Disease Rating Scale (parts I‐IV) and Montreal Cognitive Assessment scores (mean ± standard deviation) were –4.6 ± 6.4 and 2 ± 1.7, respectively. This is the first report of UDCA use in individuals with Parkinson's disease. Its pharmacokinetics are variable, and at high doses it appears reasonably well tolerated. Our findings warrant additional studies of its effect on brain bioenergetics.
Temperature and freezing effects on phosphorus release from soils to overlying floodwater under flooded‐anaerobic conditions
Authors: Kumaragamage Darshani , Concepcion Angela , Gregory Carolyn , Goltz Doug , Indraratne Srimathie , Amarawansha Geethani 
Published: February 2020

AbstractIncreased phosphorus (P) availability under flooded, anaerobic conditions may accelerate P loss from soils to water bodies. Existing knowledge on P release to floodwater from flooded soils is limited to summer conditions and/or room temperatures. Spring snowmelt runoff, which occurs under cold temperatures with frequent freeze–thaw events, is the dominant mode of P loss from agricultural lands to water bodies in the Canadian Prairies. This research examined the effects of temperature on P dynamics under flooded conditions in a laboratory study using five agricultural soils from Manitoba, Canada. The treatments were (a) freezing for 1 wk at −20 °C, thawing and flooding at 4 ± 1 °C (frozen, cold); (b) flooding unfrozen soil at 4 ± 1 °C (unfrozen, cold); and (c) flooding unfrozen soil at 20 ± 2 °C (warm). Pore water and surface water were collected weekly over 8 wk and analyzed for dissolved reactive phosphorus (DRP), pH, calcium, magnesium, iron (Fe), and manganese (Mn). Soils under warm flooding showed enhanced P release with significantly higher DRP concentrations in pore and surface floodwater compared with cold flooding of frozen and unfrozen soils. The development of anaerobic conditions was slow under cold flooding with only a slight decrease in Eh, whereas under warm flooding Eh declined sharply, favoring reductive dissolution reactions releasing P, Fe, and Mn. Pore water and floodwater DRP concentrations were similar between frozen and unfrozen soil under cold flooding, suggesting that one freeze–thaw event prior to flooding had minimal effect on P release under simulated snowmelt conditions.
Remote sensing estimation of the soil erosion cover‐management factor for China's Loess Plateau
Authors: Yang Xihua , Zhang Xiaoping , Lv Du , Yin Shuiqing , Zhang Mingxi , Zhu Qinggaozi , Yu Qiang , Liu Baoyuan 
Published: February 2020

AbstractThe cover‐management factor (C‐factor) is used in the revised universal soil loss equation to represent the effect of vegetation cover and its management practices on hillslope erosion. Remote sensing has been widely used to estimate vegetation cover and the C‐factor, but most previous studies only used the photosynthetic vegetation (PV) or green vegetation indices (VI, e.g., normalized difference VI) for estimating the C‐factor and the important non‐PV (NPV) component was often ignored. In this study, we developed a new technique to estimate monthly time‐series C‐factor using the fractional vegetation cover (FVC) including both PV and NPV, and weighted by monthly rainfall erosivity ratio. The monthly FVC was derived from the moderate resolution imaging spectroradiometer and LANDSAT data with field validation. We conducted the case‐study over China's Loess Plateau and analysed the spatiotemporal variations of FVC and the C‐factor and their impacts on erosion over the Plateau. Our study reveals a significant increase in total vegetation cover (TC) from 56 to 76.8%, with a mean of 71.2%, resulting in about 20% decrease in the C‐factor and erosion risk during the 17‐year period. Our method has an advantage in estimating the C‐factor from TC at a monthly scale providing a basis for continuously and consistently monitoring of vegetation cover, erosion risk and climate impacts.
Activated Platelet‐Derived Vesicles for Efficient Hemostatic Activity
Authors: Lee Joo Hang , Jung Heesun , Song Jihyeon , Choi Eun Seo , You Gayeon , Mok Hyejung 
Published: February 2020

AbstractIn this study, activated platelet‐derived vesicles (Act‐VEs) are developed as a novel hemostatic biomaterial. Spherical Act‐VEs (114.40 ± 11.69 nm in size) with surface charges of −24.73 ± 1.32 mV are successfully prepared from thrombin‐activated murine platelets with high surface expression of active glycoprotein IIb/IIIa (GP IIb/IIIa, also known as αIIbβ3) and P‐selectin. Although nanosized vesicles from resting platelets (VEs) and Act‐VEs showed similar sizes and surface charges, Act‐VEs formed much larger aggregates in the presence of thrombin and CaCl2, compared to VEs. After incubation with fibrinogen, Act‐VEs formed much denser fibrin networks compared to platelets or VEs, probably due to active αIIbβ3 on the surfaces of the Act‐VEs. After intravenous injection of the Act‐VEs, tail bleeding time and the blood loss are greatly reduced by Act‐VEs in vivo. In addition, Act‐VEs showed approximately sevenfold lower release of pro‐inflammatory interleukin‐1β (IL‐1β) during incubation for 4 days, compared to platelets. Taken together, the formulated Act‐VEs can serve as a promising hemostatic biomaterial for the efficient formation of fibrin clots without releasing pro‐inflammatory cytokine.
Supersoft, Stretchable, Tough, and Adhesive Elastomers with Dual Metal‐Ionic Crosslinked Double‐Network Structure
Authors: Jiang Chuanxia , Mai Yuliang , Li Weihao , Liao Bing 
Published: February 2020

AbstractSoft, stretchable, tough, and adhesive elastomers are developed based on the metal‐ionic crosslinked double network structure, where the metal ion coordination of sulfonated poly(phenylene oxide) (SPPO) is used for the first network and the soft chemical crosslinked poly(ethyl acrylate) (PEA) is used for the second network. The influence of SPPO content on the tensile, cyclic tensile, adhesive, and rheological behavior of the elastomers is systematically investigated. It is observed that the elastomers are immensely soft and stretchable with tunable modulus from 0.038 to 0.086 MPa, fracture strain of ≈1400%, fracture stress in the range 0.20–1.2 MPa, work of extension of 0.72–5.6 MJ m−3, fast self‐recovery of 5 s after experiencing 200% strain, and robust adhesive behavior on glass substrates with interface debonding energy ≈35.2 J m−2. The mechanical behavior of the double‐network elastomers at the macroscopic scale is related to the dynamic breaking and reforming of the metal‐ion coordination at the molecular scale in the first network. This study provides a facile approach for the synthesis of elastomers with multidimensional mechanical behavior and broadens the applications of the elastomers in the field of flexible electronic devices, soft robotics, among others.
Conjugated Polymer Nanoparticles as Unique Coinitiator‐Free, Water‐Soluble, Visible‐Light Photoinitiators of Vinyl Polymerization
Authors: Gallastegui Antonela , Spada Ramiro M. , Cagnetta Gonzalo , Ponzio Rodrigo A. , Martínez Sol R. , Previtali Carlos M. , Gómez María Lorena , Palacios Rodrigo E. , Chesta Carlos A. 
Published: February 2020

AbstractThe use of conjugated polymer nanoparticles (CP NPs) of poly(9,9‐dioctylfluorene‐alt‐benzothiadiazole) and poly(9,9‐di‐n‐octylfluorenyl‐2,7‐diyl) as efficient photoinitiator systems (PIS) of vinyl polymerization in water is reported herein. CP NPs are biocompatible, excitable with blue commercial LEDs and, unlike visible light Type II PIS, do not need co‐initiators to trigger a monomer chain reaction. CP NPs photoinitiate polymerization of a variety of acrylic monomers with initiation rates comparable to those observed for well‐known Type II PIS. Given the extraordinarily large molar absorption coefficients of CP NPs (≈108 m‐1 cm‐1) very low particle concentration is required for effective polymerization. Additionally, CP NPs behave as conventional macrophotoinitiators significantly reducing contamination risks due to leaching of low molecular weight byproducts. These combined features make CP NPs PIS suitable to synthesize polymeric materials for many healthcare and biomedical applications including drug delivery, tissue engineering, prosthetic implants, and food/medicine packaging. These CP NPs PIS are also used to synthesize nano‐hydrogels with a relatively narrow and controlled size distribution in the absence of surfactants. It is proposed that polymerization is initiated at the CP NPs surface by photogenerated free polarons, in close analogy to the mechanism previously described for PIS based on inorganic semiconductor NPs.
Impact of Residual Drug in the Pharynx on the Delayed‐On Phenomenon in Parkinson's Disease Patients
Authors: Fukae Jiro , Fujioka Shinsuke , Umemoto George , Arahata Hajime , Yanamoto Shosaburo , Mishima Takayasu , Tsuboi Yoshio 
Published: February 2020

ABSTRACTBackground and ObjectiveThe delayed‐on phenomenon (DOP) related to levodopa treatment frequently disturbs quality of life in advanced‐stage Parkinson's disease (PD) patients. The objective of this study was to explore the impact of swallowing dysfunction on the development of DOP.MethodsSwallowing function was investigated by endoscopic evaluation in 11 PD patients with the DOP and 9 PD patients without the DOP during the on phase. Residual drug in the pharynx after taking the drug in tablet, capsule, and powder forms was also observed.ResultsResidual drug was seen in the pharynx in six cases (30.0%). Pooling of saliva, delayed swallowing reflex, and residual drug were more frequent in the DOP group than in the group without the DOP (P < 0.05). The odds ratios for residual drug in the pharynx, pooling of saliva, and delayed swallowing reflex for the DOP were 42.7 (95% confidence interval, 1.89–962.9), 14.0 (95% confidence interval, 1.25–156.6), and 15.8 (95% confidence interval, 1.75–141.4), respectively.ConclusionsThese results suggest that swallowing dysfunction leading to residual antiparkinsonian drug in the pharynx has substantial impacts on the DOP in PD patients.