bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNA MEG3 contributes to adenosine‐induced cytotoxicity in hepatoma HepG2 cells by downregulated ILF3 and autophagy inhibition via regulation PI3K‐AKT‐mTOR and beclin‐1 signaling pathway
Authors: Pu Zejin , Wu Lingfei , Guo Yitian , Li Guoping , Xiang Mengqi , Liu Lixuan , Zhan Haolian , Zhou Xiaotao , Tan Hui 
Published: May 2019

AbstractAdenosine is a promising cytotoxic reagent for tumors, long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been indicated to play critical roles in tumorigenesis, ILF3 has been recognized as a MEG3‐binding protein, however, the roles of adenosine and MEG3 on hepatoma are still ambiguous. To clarify the effects of MEG3 on the adenosine‐induced cytotoxicity in hepatoma, MEG3 and ILF3 lentivirus were transduced into human hepatoma HepG2 cells to stimulate overexpression of MEG3 (OE MEG3) and overexpression of ILF3 (OE ILF3), furthermore, ILF3 small interfering RNA (siRNA) was also applied to downregulate the expression of ILF3. In this study, autophagy was markedly inhibited by low concentration of adenosine, which present by not only inhibited transformation from LC3‐I to LC3‐II and autophagosomes formation, but also the elevation of mTOR and reduction of beclin‐1 proteins. Furthermore, low concentration of adenosine also exerted marked cytotoxicity representing induced cell apoptosis together with reductions of cell viability and migration, which were also markedly enhanced by OE MEG3. Novelly and excitingly, adenosine markedly stimulated MEG3 expression, OE MEG3 markedly decreased the ILF3 expression in HepG2 cells, and the adenosine‐induced autophagy inhibition, together with the ratio of p‐PI3K/PI3K, p‐AKT/AKT, and p‐mTOR/mTOR were also boosted by OE MEG3. More interestingly, OE ILF3 increased autophagy, whereas downregulated ILF3, especially in the case of adenosine, led to marked autophagy inhibition by decreasing beclin‐1. The present study demonstrates autophagy inhibition is involved in the adenosine‐induced cytotoxicity in HepG2 cells, the cytotoxicity can be synergized by OE MEG3 via downregulated ILF3 to activate PI3K/Akt/mTOR and inactivate the beclin‐1 signaling pathway. In conclusion, MEG3 and inhibition of autophagy might be potential targets for augmenting adenosine‐induced cytotoxicity in hepatoma.
TGF‐β1 downregulation in the hypothalamus of obese mice through acute exercise
Authors: Silva Vagner R. R. , Lenhare Luciene , Katashima Carlos K. , Morari Joseane , M‐Assis Alexandre , Gaspar Rodrigo S. , da Silva Adelino S. R. , Moura Leandro P. , Pauli José R. , Cintra Dennys E. , Velloso Licio A. , Ropelle Eduardo R. 
Published: May 2019

AbstractObesity and aging lead to abnormal transforming growth factor‐β1 (TGF‐β1) signaling in the hypothalamus, triggering the imbalance on glucose metabolism and energy homeostasis. Here, we determine the effect of acute exercise on TGF‐β1 expression in the hypothalamus of two models of obesity in mice. The bioinformatics analysis was performed to evaluate the correlation between hypothalamic Tgf‐β1 messenger RNA (mRNA) and genes related to thermogenesis in the brown adipose tissue (BAT) by using a large panel of isogenic BXD mice. Thereafter, leptin‐deficient (ob/ob) mice and obese C57BL/6 mice fed on a high‐fat diet (HFD) were submitted to the acute exercise protocol. Transcriptomic analysis by using BXD mouse reference population database revealed that hypothalamic Tgf‐β1 mRNA is negatively correlated with genes related to thermogenesis in brown adipose tissue of BXD mice, such as peroxisome proliferator‐activated receptor gamma coactivator and is positively correlated with respiratory exchange ratio. In agreement with these results, leptin‐deficient (ob/ob) and HFD‐fed mice displayed high levels of Tgf‐β1 mRNA in the hypothalamus and reduction of Pgc1α mRNA in BAT. Interestingly, an acute exercise session reduced TGF‐β1 expression in the hypothalamus, increased Pgc1α mRNA in the BAT and reduced food consumption in obese mice. Our results demonstrated that acute physical exercise suppressed hypothalamic TGF‐β1 expression, increasing Pgc1α mRNA in BAT in obese mice.
Carboxymethyl dextran‐trimethyl chitosan coated superparamagnetic iron oxide nanoparticles: An effective siRNA delivery system for HIV‐1 Nef
Authors: Kamalzare Sara , Noormohammadi Zahra , Rahimi Pooneh , Atyabi Fatemeh , Irani Shiva , Tekie Farnaz Sadat Mirzazadeh , Mottaghitalab Fatemeh 
Published: May 2019

AbstractGene therapy, including small interfering RNA (siRNA) technology, is one of the leading strategies that help to improve the outcomes of the current therapeutic systems against HIV‐1 infection. The successful therapeutic application of siRNAs requires their safe and efficient delivery to specific cells. Here, we introduce a superparamagnetic iron oxide nanoparticle (SPION) for delivering siRNA against HIV‐1 nef (anti‐nef siRNA) into two cell lines, HEK293 and macrophage RAW 264.7. SPIONs were coated with trimethyl chitosan (TMC), and thereafter, different concentrations of SPION–TMC were coated with different ratios of a carboxymethyl dextran (CMD) to modify the physicochemical properties and improve the biological properties of the nanocarriers. The nanoparticles exhibited a spherical shape with an average size of 112 nm. The obtained results showed that the designed delivery route enhanced the uptake of siRNA into both HEK293 and RAW 264.7 cells compared with control groups. Moreover, CMD–TMC–SPIONs containing anti‐nef siRNA significantly reduced the expression of HIV‐1 nef in HEK293 stable cells. The modified siRNA‐loaded SPIONs also displayed no toxicity or apoptosis‐inducing effects on the cells. The CMD–TMC–SPIONs are suggested as potential nanocarriers for siRNA delivery in gene therapy of HIV‐1 infection.
miR‐382‐3p suppressed IL‐1β induced inflammatory response of chondrocytes via the TLR4/MyD88/NF‐κB signaling pathway by directly targeting CX43
Authors: Lei Jinlai , Fu Yahui , Zhuang Yan , Zhang Kun , Lu Daigang 
Published: May 2019

AbstractmiR‐382‐3p has been reported to be upregulated in synovial membrane in knee osteoarthritis (OA). Nevertheless, its role in OA remains largely unknown. The aim of this study was to investigate the specific function and mechanisms of miR‐382‐3p in the course of OA. In this study, human OA chondrocytes were pretreated with interleukin‐1β (IL‐1β) at 5 ng/ml for 12 hr to stimulate inflammatory response and matrix metalloproteinases (MMPs) expression in chondrocytes. Meanwhile, miR‐382‐3p was downregulated in IL‐1β‐stimulated chondrocytes. In addition, we found that miR‐382‐3p directly interacts with connexin 43 (CX43) and attenuates the increase of cytochrome c oxidase polypeptide II, inducible nitric oxide synthase, and MMP‐1/13 that is induced by IL‐1β. Furthermore, our observations indicated that miR‐382‐3p inhibited the expression of Toll‐like receptor 4 (TLR4), Myeloid differentiation primary response 88 (MyD88) and nuclear factor κB (NF‐κB) in IL‐1β‐stimulated chondrocytes, while CX43 overexpression could partly reverse these decreases. In conclusion, miR‐382‐3p participated in OA may through the TLR4/MyD88/NF‐κB signaling pathway by directly targeting CX43.
The potential role of exosomes derived from ovarian cancer cells for diagnostic and therapeutic approaches
Authors: Yang Changwon , Kim Hee Seung , Song Gwonhwa , Lim Whasun 
Published: May 2019

AbstractMost patients with ovarian cancer (OC) are diagnosed at the advanced stages due to the absence of appropriate early diagnostic markers. Thus, OC is a gynecological disease with a low‐survival rate. Exosomes are extracellular vesicles that are widely being considered as mediators for the noninvasive diagnosis of OC. Exosomes are expected to aid in the effective diagnosis of OC because they carry components, such as RNAs, proteins, and lipids, the compositions of which vary depending on the pathological characteristics of the patient. In this review, we document the methods that have been developed to detect exosomes and their components in OC. We also assess the potential biomarkers contained in exosomes that could be clinically useful, such as proteins, microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and phospholipids. Moreover, we described the role played by exosomes in the tumor microenvironment and in OC angiogenesis, migration, and tumor growth. Various types of cells in the tumor microenvironment, including macrophages, fibroblasts, and mesenchymal stem cells (MSCs), interact directly with exosomes and promote or inhibit the progression of OC. Therefore, we summarize the studies that have suggested a therapeutic approach to OC using exosomes. Collectively, understanding the mechanism of exosome‐based OC progression would broaden our knowledge regarding the diagnosis and therapy of OC.
Association of lifestyle factors and inflammation with sarcopenic obesity: data from the PREDIMED‐Plus trial
Authors: Abete Itziar , Konieczna Jadwiga , Zulet M. Angeles , Galmés‐Panades Aina M. , Ibero‐Baraibar Idoia , Babio Nancy , Estruch Ramón , Vidal Josep , Toledo Estefanía , Razquin Cristina , Bartolomé Rafael , Díaz‐Lopez Andrés , Fiol Miquel , Casas Rosa , Vera Josep , Buil‐Cosiales Pilar , Pintó Xavier , Corbella Emili , Portillo Maria Puy , de Paz Jose Antonio , Martín Vicente , Daimiel Lidia , Goday Albert , Rosique‐Esteban Nuria , Salas‐Salvadó Jordi , Romaguera Dora , Martínez J. Alfredo ,   on behalf of PREDIMED‐PLUS Investigators
Published: May 2019

AbstractBackgroundSarcopenia is a progressive age‐related skeletal muscle disorder associated with increased likelihood of adverse outcomes. Muscle wasting is often accompanied by an increase in body fat, leading to ‘sarcopenic obesity’. The aim of the present study was to analyse the association of lifestyle variables such as diet, dietary components, physical activity (PA), body composition, and inflammatory markers, with the risk of sarcopenic obesity.MethodsA cross‐sectional analysis based on baseline data from the PREDIMED‐Plus study was performed. A total of 1535 participants (48% women) with overweight/obesity (body mass index: 32.5 ± 3.3 kg/m2; age: 65.2 ± 4.9 years old) and metabolic syndrome were categorized according to sex‐specific tertiles (T) of the sarcopenic index (SI) as assessed by dual‐energy X‐ray absorptiometry scanning. Anthropometrical measurements, biochemical markers, dietary intake, and PA information were collected. Linear regression analyses were carried out to evaluate the association between variables.ResultsSubjects in the first SI tertile were older, less physically active, showed higher frequency of abdominal obesity and diabetes, and consumed higher saturated fat and less vitamin C than subjects from the other two tertiles (all P < 0.05). Multiple adjusted linear regression models evidenced significant positive associations across tertiles of SI with adherence to the Mediterranean dietary score (P‐trend < 0.05), PA (P‐trend < 0.0001), and the 30 s chair stand test (P‐trend < 0.0001), whereas significant negative associations were found with an inadequate vitamin C consumption (P‐trend < 0.05), visceral fat and leucocyte count (all P‐trend < 0.0001), and some white cell subtypes (neutrophils and monocytes), neutrophil‐to‐lymphocyte ratio, and platelet count (all P‐trend < 0.05). When models were additionally adjusted by potential mediators (inflammatory markers, diabetes, and waist circumference), no relevant changes were observed, only dietary variables lost significance.ConclusionsDiet and PA are important regulatory mediators of systemic inflammation, which is directly involved in the sarcopenic process. A healthy dietary pattern combined with exercise is a promising strategy to limit age‐related sarcopenia.
Performance of Surveillance MR Enterography (MRE) in Asymptomatic Children and Adolescents With Crohn's Disease
Authors: Chu Katrina F. , Moran Christopher J. , Wu Kaiming , Kaplan Jess L. , Savarino Jeffrey R. , Board Tamsin , Israel Esther J. , Winter Harland S. , Gee Michael S. 
Published: May 2019

BackgroundMR enterography (MRE) is the primary modality for evaluating small bowel disease in pediatric Crohn's patients. Standard clinical practice includes imaging patients at diagnosis and during symptomatic recurrence. The role for MRE in surveillance of asymptomatic Crohn's patients has not yet been established.PurposeTo determine whether MRE imaging features are associated with clinical recurrence.Study TypeRetrospective.PopulationsPediatric Crohn's patients who underwent MRE while asymptomatic, defined by pediatric gastroenterologists using a physician global assessment; 35 MREs were identified.Field Strength/Sequence1.5T including T2‐weighted single‐shot fast spin echo, balanced steady‐state free precession, diffusion‐weighted, and contrast‐enhanced multiphase T1‐weighted gradient recalled echo sequences.AssessmentMREs were reviewed by three radiologists independently for mural thickening, T2‐weighted hyperintensity, diffusion restriction, hyperenhancement, vasa recta engorgement, and overall assessment of disease activity. Two pediatric gastroenterologists reviewed patient medical records for 6 months following MRE to evaluate for recurrence, defined as Crohn's‐related treatment escalation, surgery, or hospitalization.Statistical TestsFisher's exact test, Wald chi‐square test, and model selection by Akaike information criterion minimization were used to assess statistical significance of MRE imaging features.ResultsOf 35 MREs identified, seven cases demonstrated clinical recurrence at 6 months (20%); 28 cases remained in remission (80%). Imaging features of active disease were present in 86% of patients with recurrence compared to 29% of patients in remission (P = 0.01). Wall thickening, T2‐weighted hyperintensity, hyperenhancement, and diffusion restriction were significantly associated with recurrence. Multivariate regression analysis determined diffusion restriction to be the best predictor of recurrence within 6 months (P = 0.001, area under the curve 0.786).Data ConclusionMRE performed on young asymptomatic Crohn's patients can identify patients who have a high probability of developing clinical recurrence in a 6‐month period, indicating a potential role for surveillance imaging to assess for subclinical active disease.Level of Evidence: 3Technical Efficacy Stage 5J. Magn. Reson. Imaging 2019;50:1955–1963.
Axillary reverse mapping and lymphaticovenous bypass: Lymphedema prevention through enhanced lymphatic visualization and restoration of flow
Authors: Schwarz Graham S. , Grobmyer Stephen R. , Djohan Risal S. , Cakmakoglu Cagri , Bernard Steven L. , Radford Diane , Al‐Hilli Zahraa , Knackstedt Rebecca , Djohan Michelle , Valente Stephanie A. 
Published: May 2019

AbstractBackgroundA lymphedema (LE) prevention surgery (LPS) paradigm for patients undergoing axillary lymphadenectomy (ALND) was developed to protect against LE through enhanced lymphatic visualization during axillary reverse mapping (ARM) and refinement in decision making during lymphaticovenous bypass (LVB).MethodsA retrospective analysis of a prospective database was performed evaluating patients with breast cancer who underwent ALND, ARM, and LVB from September 2016 to December 2018. Patient and tumor characteristics, oncologic and reconstructive operative details, complications and LE development were analyzed.ResultsLPS was completed in 58 patients with a mean age of 51.7 years. An average of 14 lymph nodes (LN) were removed during ALND. An average of 2.1 blue lymphatic channels were visualized with an average of 1.4 LVBs performed per patient. End to end anastomosis was performed in 37 patients and a multiple lymphatic intussusception technique in 21. Patency was confirmed 96.5% of patients. Adjuvant radiation was administered to 89% of patients. Two patients developed LE with a median follow‐up of 11.8 months.ConclusionWe report on our experience using a unique LPS technique. Refinements in ARM and a systematic approach to LVB allows for maximal preservation of lymphatic continuity, identification of transected lymphatics, and reestablishment of upper extremity lymphatic drainage pathways.
Ultrasound Biomicroscopy and High‐Frequency Ultrasound for Evaluating Extramammary Paget Disease With Pathologic Correlation
Authors: Chen Si‐Tong , Guo Le‐Hang , Yan Jian‐Na , Wang Qiao , Li Xiao‐Long , Li Ming‐Xu , Zhu Rui‐Zheng , Yang Wei‐Ping , Xu Hui‐Xiong 
Published: May 2019

ObjectivesThe purpose of this study was to investigate the performance of ultrasound biomicroscopy (UBM) and high‐frequency ultrasound (HFUS) in the assessment of extramammary Paget disease (EMPD) and to correlate the imaging features with pathologic findings.MethodsIn this retrospective study, we described the imaging features from UBM and HFUS based on 17 pathologically proven EMPD cases. The performance for visualizing layer involvement by UBM and HFUS was compared. Additionally, we checked the consistency between layer involvement of the lesions on UBM images and the pathologic results. Additionally, blood flow and the status of lymph nodes were investigated with HFUS.ResultsUltrasound biomicroscopy revealed that all 17 lesions (100%) were hypoechoic and grew in a creeping form. The feature of layer involvement was shown in 10 lesions (58.8%) limited to the epidermis and 6 lesions (35.3%) involving the dermis, and the remaining lesion (5.9%) involved the full skin layers. Layer involvement was clearly displayed by UBM for all lesions (100%) but for only 5 lesions (29.4%) by HFUS (P < .001). Additionally, the layer involvement of 15 lesions (88.2%) on UBM was consistent with the pathologic results (κ = 0.746). High‐frequency ultrasound revealed profuse blood flow in most lesions (64.7% [11 of 17]), and 1 case showed inguinal lymph node metastasis.ConclusionsCombined use of UBM and HFUS can provide key information on EMPD based on ultrasound features. Comparatively, UBM provides clearer morphologic information, whereas HFUS provides information on lymph node metastasis and blood flow.
Impact of erosion‐induced land degradation on rainfall infiltration in different types of soils under field simulation
Authors: Wei Yujie , Wu Xinliang , Cai Chongfa , Wang Jie , Xia Jinwen , Wang Junguang , Guo Zhonglu , Yuan Zaijian 
Published: May 2019

AbstractLand degradation induced by water erosion is a worldwide problem for sustainable agriculture. Erosion results in the alteration of soil properties to a varying extent that depends on soil type. However, limited attempts have been made to assess the impact of erosion‐induced land degradation on soil infiltration on a wide range of soil types. Herein, field rainfall simulation experiments were performed on prewetted bare heavy‐textured soils at three erosion degrees (no, moderate, and very severe) for five types of soils (Calcic Luvisol, Ferric Luvisol, Plinthic Alisol, Plinthic Acrisol, and Acric Ferralsol). Soil infiltration rate was determined at two rainfall intensities (45 and 90 mm hr−1) and 3‐min intervals for 60‐min runoff duration on microplots (3 m long × 0.8 m wide, 10° slope). At the low rainfall intensity, the impact of erosion‐induced land degradation on rainfall infiltration increased from Calcic Luvisol to Plinthic Acrisol, and the steady state infiltration rate (fc) was well characterized by bulk density and 1.4‐nm intergrade minerals (Adj‐R2 = 0.79, p < 0.001). At the high rainfall intensity, fc was negatively related with illite solely (Adj‐R2 = 0.25, p < .05) and generally increased with an increase of erosion severity; the impact of erosion‐induced land degradation on fc was magnified for Calcic Luvisol and Acric Ferralsol but lessened for other soil types. Collectively, the impact of erosion‐induced land degradation generally increased with increased soil structural stability at the low rainfall intensity and was determined by the interaction between soil structure and rainfall at the high rainfall intensity.
Trial of magnetic resonance–guided putaminal gene therapy for advanced Parkinson's disease
Authors: Heiss John D. , Lungu Codrin , Hammoud Dima A. , Herscovitch Peter , Ehrlich Debra J. , Argersinger Davis P. , Sinharay Sanhita , Scott Gretchen , Wu Tianxia , Federoff Howard J. , Zaghloul Kareem A. , Hallett Mark , Lonser Russell R. , Bankiewicz Krystof S. 
Published: May 2019

AbstractObjectiveTo investigate the safety and tolerability of convection‐enhanced delivery of an adeno‐associated virus, serotype‐2 vector carrying glial cell line‐derived neurotrophic factor into the bilateral putamina of PD patients.MethodsThirteen adult patients with advanced PD underwent adeno‐associated virus, serotype‐2 vector carrying glial cell line‐derived neurotrophic factor and gadoteridol (surrogate MRI tracer) coinfusion (450 μL/hemisphere) at escalating doses: 9 × 1010 vg (n = 6); 3 × 1011 vg (n = 6); and 9 × 1011 vg (n = 1). Intraoperative MRI monitored infusion distribution. Patients underwent UPDRS assessment and [18F]FDOPA‐PET scanning preoperatively and 6 and 18 months postoperatively.ResultsAdeno‐associated virus, serotype‐2 vector carrying glial cell line‐derived neurotrophic factor was tolerated without clinical or radiographic toxicity. Average putaminal coverage was 26%. UPDRS scores remained stable. Ten of thirteen and 12 of 13 patients had increased [18F]FDOPA Kis at 6 and 18 months postinfusion (increase range: 5–274% and 8–130%; median, 36% and 54%), respectively. Ki differences between baseline and 6‐ and 18‐month follow‐up were statistically significant (P < 0.0002).ConclusionAdeno‐associated virus, serotype‐2 vector carrying glial cell line‐derived neurotrophic factor infusion was safe and well tolerated. Increased [18F]FDOPA uptake suggests a neurotrophic effect on dopaminergic neurons. © 2019 International Parkinson and Movement Disorder Society
Hair, Nails, and Skin: Differentiating Cutaneous Manifestations of Micronutrient Deficiency
Authors: DiBaise Michelle , Tarleton Sherry M. 
Published: May 2019

AbstractMicronutrient deficiencies (MNDs) commonly lead to cutaneous abnormalities involving the skin, hair, and nails, and these cutaneous manifestations often provide clues to the existence of the underlying deficiency. MNDs may be present in at‐risk individuals who have impaired absorption or poor dietary intake. The micronutrients that most commonly present with cutaneous findings include the B vitamins riboflavin, niacin, pyridoxine, biotin, and vitamin B12; vitamin C; the fat‐soluble vitamins A, E, and K; the minerals zinc, iron, copper, and selenium; and essential fatty acids. This review will highlight the most common clinical hair, skin, and nail presentations associated with MNDs and an approach to their treatment.
Effect of alkali treatment on composites made from recycled polyethylene and chestnut cupula
Authors: Boran Torun Sevda , Pesman Emrah , Donmez Cavdar Ayfer 
Published: May 2019

AbstractThe objective of this study is to investigate the effects of alkali treatment on the mechanical, physical properties of cupula fibers reinforced recycled high density polyethylene (r‐HDPE) composites. The composites were produced with different chestnut (Castanea sativa Mill.) cupula fiber contents, up to 50%, and polyethylene‐grafted maleic anhydride. The mechanical, physical, thermal, and morphological properties of the treated and untreated samples were investigated. In addition, the Fourier transform infrared spectroscopy (FTIR) was used to observe the interactions and functional groups between cupula fiber and r‐HDPE in the composite samples. The alkali treatment with 5 wt% NaOH solution had an affirmative effect on the tensile and flexural properties. It was found that an increase of 20% in flexural strength values with up to 40 wt% alkali treated cupula fiber loading in polymer matrix compared to that of untreated samples. After 5 wt% NaOH treatment, the crystallinity decreased with the increase of the chestnut cupula fiber ratio. As excepted, the FTIR analysis showed that the alkali treatment resulted in removal of hemicellulose, and lignin from cupula fiber. The results revealed that the alkali treated chestnut cupula fiber can be used successfully in polymer composites as a natural fiber filler.