bluuebunny/crossref_metadata_2025_split huggingface dataset:
(–)-Epigallocatechin-3-gallate induces apoptosis and differentiation in leukaemia by targeting reactive oxygen species and PIN1
Authors: Della Via Fernanda Isabel , Shiraishi Rodrigo Naoto , Santos Irene , Ferro Karla Priscila , Salazar-Terreros Myriam Janeth , Franchi Junior Gilberto Carlos , Rego Eduardo Magalhães , Saad Sara Teresinha Olalla , Torello Cristiane Okuda 
Published: April 2021

Abstract(–)-Epigallocatechin-3-gallate (EGCG), the major active polyphenol extracted from green tea, has been shown to induce apoptosis and inhibit cell proliferation, cell invasion, angiogenesis and metastasis. Herein, we evaluated the in vivo effects of EGCG in acute myeloid leukaemia (AML) using an acute promyelocytic leukaemia (APL) experimental model (PML/RARα). Haematological analysis revealed that EGCG treatment reversed leucocytosis, anaemia and thrombocytopenia, and prolonged survival of PML/RARα mice. Notably, EGCG reduced leukaemia immature cells and promyelocytes in the bone marrow while increasing mature myeloid cells, possibly due to apoptosis increase and cell differentiation. The reduction of promyelocytes and neutrophils/monocytes increase detected in the peripheral blood, in addition to the increased percentage of bone marrow cells with aggregated promyelocytic leukaemia (PML) bodies staining and decreased expression of PML-RAR oncoprotein corroborates our results. In addition, EGCG increased expression of neutrophil differentiation markers such as CD11b, CD14, CD15 and CD66 in NB4 cells; and the combination of all-trans retinoic acid (ATRA) plus EGCG yield higher increase the expression of CD15 marker. These findings could be explained by a decrease of peptidyl-prolyl isomerase NIMA-interacting 1 (PIN1) expression and reactive oxygen species (ROS) increase. EGCG also decreased expression of substrate oncoproteins for PIN1 (including cyclin D1, NF-κB p65, c-MYC, and AKT) and 67 kDa laminin receptor (67LR) in the bone marrow cells. Moreover, EGCG showed inhibition of ROS production in NB4 cells in the presence of N-acetyl-L-cysteine (NAC), as well as a partial blockage of neutrophil differentiation and apoptosis, indicating that EGCG-activities involve/or are in response of oxidative stress. Furthermore, apoptosis of spleen cells was supported by increasing expression of BAD and BAX, parallel to BCL-2 and c-MYC decrease. The reduction of spleen weights of PML/RARα mice, as well as apoptosis induced by EGCG in NB4 cells in a dose-dependent manner confirms this assumption. Our results support further evaluation of EGCG in clinical trials for AML, since EGCG could represent a promising option for AML patient ineligible for current mainstay treatments.
Protein-olive oil-in-water nanoemulsions as encapsulation materials for curcumin acting as anticancer agent towards MDA-MB-231 cells
Authors: Bharmoria Pankaj , Bisht Meena , Gomes Maria C. , Martins Margarida , Neves Márcia C. , Mano João F. , Bdikin Igor , Coutinho João A. P. , Ventura Sónia P. M. 
Published: April 2021

AbstractThe sustainable cellular delivery of the pleiotropic drug curcumin encounters drawbacks related to its fast autoxidation at the physiological pH, cytotoxicity of delivery vehicles and poor cellular uptake. A biomaterial compatible with curcumin and with the appropriate structure to allow the correct curcumin encapsulation considering its poor solubility in water, while maintaining its stability for a safe release was developed. In this work, the biomaterial developed started by the preparation of an oil-in-water nanoemulsion using with a cytocompatible copolymer (Pluronic F 127) coated with a positively charged protein (gelatin), designed as G-Cur-NE, to mitigate the cytotoxicity issue of curcumin. These G-Cur-NE showed excellent capacity to stabilize curcumin, to increase its bio-accessibility, while allowing to arrest its autoxidation during its successful application as an anticancer agent proved by the disintegration of MDA-MB-231 breast cancer cells as a proof of concept.
Uniaxially fixed mechanical boundary condition elicits cellular alignment in collagen matrix with induction of osteogenesis
Authors: Kim Jeonghyun , Ishikawa Keiichi , Sunaga Junko , Adachi Taiji 
Published: April 2021

AbstractOsteocytes differentiated from osteoblasts play significant roles as mechanosensors in modulating the bone remodeling process. While the well-aligned osteocyte network along the trabeculae with slender cell processes perpendicular to the trabeculae surface is known to facilitate the sensing of mechanical stimuli by cells and the intracellular communication in the bone matrix, the mechanisms underlying osteocyte network formation remains unclear. Here, we developed a novel in vitro collagen matrix system exerting a uniaxially-fixed mechanical boundary condition on which mouse osteoblast-like MC3T3-E1 cells were subcultured, evoking cellular alignment along the uniaxial boundary condition. Using a myosin II inhibitor, blebbistatin, we showed that the intracellular tension via contraction of actin fibers contributed to the cellular alignment under the influence of isometric matrix condition along the uniaxially-fixed mechanical boundary condition. Furthermore, the cells actively migrated inside the collagen matrix and promoted the expression of osteoblast and osteocyte genes with their orientations aligned along the uniaxially-fixed boundary condition. Collectively, our results suggest that the intracellular tension of osteoblasts under a uniaxially-fixed mechanical boundary condition is one of the factors that determines the osteocyte alignment inside the bone matrix.
The Nek2 centrosome-mitotic kinase contributes to the mesenchymal state, cell invasion, and migration of triple-negative breast cancer cells
Authors: Rivera-Rivera Yainyrette , Marina Mihaela , Jusino Shirley , Lee Miyoung , Velázquez Jaleisha Vélez , Chardón-Colón Camille , Vargas Geraldine , Padmanabhan Jaya , Chellappan Srikumar P. , Saavedra Harold I. 
Published: April 2021

AbstractNek2 (NIMA‐related kinase 2) is a serine/threonine-protein kinase that localizes to centrosomes and kinetochores, controlling centrosome separation, chromosome attachments to kinetochores, and the spindle assembly checkpoint. These processes prevent centrosome amplification (CA), mitotic dysfunction, and chromosome instability (CIN). Our group and others have suggested that Nek2 maintains high levels of CA/CIN, tumor growth, and drug resistance. We identified that Nek2 overexpression correlates with poor survival of breast cancer. However, the mechanisms driving these phenotypes are unknown. We now report that overexpression of Nek2 in MCF10A cells drives CA/CIN and aneuploidy. Besides, enhanced levels of Nek2 results in larger 3D acinar structures, but could not initiate tumors in a p53+/+ or a p53−/− xenograft model. Nek2 overexpression induced the epithelial-to-mesenchymal transition (EMT) while its downregulation reduced the expression of the mesenchymal marker vimentin. Furthermore, either siRNA-mediated downregulation or INH6’s chemical inhibition of Nek2 in MDA-MB-231 and Hs578t cells showed important EMT changes and decreased invasion and migration. We also showed that Slug and Zeb1 are involved in Nek2 mediated EMT, invasion, and migration. Besides its role in CA/CIN, Nek2 contributes to breast cancer progression through a novel EMT mediated mechanism.
Complex wavefront sensing based on coherent diffraction imaging using vortex modulation
Authors: Li Rujia , Cao Liangcai 
Published: April 2021

AbstractPhase retrieval seeks to reconstruct the phase from the measured intensity, which is an ill-posed problem. A phase retrieval problem can be solved with physical constraints by modulating the investigated complex wavefront. Orbital angular momentum has been recently employed as a type of reliable modulation. The topological charge l is robust during propagation when there is atmospheric turbulence. In this work, topological modulation is used to solve the phase retrieval problem. Topological modulation offers an effective dynamic range of intensity constraints for reconstruction. The maximum intensity value of the spectrum is reduced by a factor of 173 under topological modulation when l is 50. The phase is iteratively reconstructed without a priori knowledge. The stagnation problem during the iteration can be avoided using multiple topological modulations.
Inference of molecular orientation/ordering change nearby topological defects by the neural network function from the microscopic color information
Authors: Sakanoue Haruka , Hayashi Yuki , Katayama Kenji 
Published: April 2021

AbstractTopological defects in liquid crystals (LCs) dominate molecular alignment/motion in many cases. Here, the neural network (NN) function has been introduced to predict the LC orientation condition (orientation angle and order parameter) at local positions around topological defects from the phase/polarization microscopic color images. The NN function was trained in advance by using the color information of an LC in a planar alignment cell for different orientation angles and temperatures. The photo-induced changes of LC molecules around topological defects observed by the time-resolved measurement was converted into the image sequences of the orientation angle and the order parameter change. We found that each pair of brushes with different colors around topological defects showed different orientation angle and ordering changes. The photo-induced change was triggered by the photoisomerization reaction of molecules, and one pair of brushes increased in its order parameter just after light irradiation, causing gradual rotation in the brush. The molecules in the other pair of brushes were disordered and rotated by the effect of the initially affected region. This combination approach of the time-resolved phase/polarization microscopy and the NN function can provide detailed information on the molecular alignment dynamics around the topological defects.
CircPVT1 attenuates negative regulation of NRAS by let-7 and drives cancer cells towards oncogenicity
Authors: Danac Joshua Miguel C. , Garcia Reynaldo L. 
Published: April 2021

AbstractCircular RNAs have emerged as functional regulatory molecules whose aberrant expression has been linked to diverse pathophysiological processes. Here, we report that circPVT1 interferes with let-7 binding to NRAS, confirming this axis as one route by which circPVT1 can instigate an oncogenic program in A549 lung cancer cells and HCT116 colorectal cancer cells. CircPVT1 knockdown significantly reduced NRAS levels and attenuated cancer hallmark phenotypes such as proliferation, migration, resistance to apoptosis, cytoskeletal disorganization, and epithelial-mesenchymal transition. The effects of circPVT1 knockdown were at least partially rescued by blocking binding of let-7 to NRAS 3′UTR with a target protector, suggesting that a circPVT1/let-7/NRAS axis exists and acts in cells to reverse NRAS downregulation and favor oncogenicity. While the phenotypic effects of circPVT1 knockdown may be attributable to the global action of circPVT1, the target protection assays resolved the relative contribution of the circPVT1/let-7/NRAS axis specifically.
Estimated visceral adiposity is associated with risk of cardiometabolic conditions in a population based study
Authors: Ruiz-Castell Maria , Samouda Hanen , Bocquet Valery , Fagherazzi Guy , Stranges Saverio , Huiart Laetitia 
Published: April 2021

AbstractVisceral adiposity is a major risk factor of cardiometabolic diseases. Visceral adipose tissue (VAT) is usually measured with expensive imaging techniques which present financial and practical challenges to population-based studies. We assessed whether cardiometabolic conditions were associated with VAT by using a new and easily measurable anthropometric index previously published and validated. Data (1529 participants) came from the European Health Examination Survey in Luxembourg (2013–2015). Logistic regressions were used to study associations between VAT and cardiometabolic conditions. We observed an increased risk of all conditions associated with VAT. The total adjusted odds ratio (AOR, [95% CI]) for hypertension, prediabetes/diabetes, hypercholesterolemia, and hypertriglyceridemia for the fourth quartile of VAT compared to the lowest were 10.22 [6.75, 15.47]), (5.90 [4.02, 8.67]), (3.60 [2.47, 5.25]) and (7.67 [5.04, 11.67]. We observed higher odds in women than in men for all outcomes with the exception of hypertension. Future studies should investigate the impact of VAT changes on cardiometabolic health and the use of anthropometrically predicted VAT as an accurate outcome when no biomedical imaging is available.
Evidence for magnesium–phosphorus synergism and co-limitation of grain yield in wheat agriculture
Authors: Weih Martin , Liu Hui , Colombi Tino , Keller Thomas , Jäck Ortrud , Vallenback Pernilla , Westerbergh Anna 
Published: April 2021

AbstractModern crop production is characterized by high nitrogen (N) application rates, which can influence the co-limitation of harvested yield by other nutrients. Using a multidimensional niche volume concept and scaling exponents frequently applied in plant ecological research, we report that increased N and phosphorus (P) uptake in a growing wheat crop along with enhanced grain biomass is associated with more than proportional increase of other nutrients. Furthermore, N conversion efficiency and grain yield are strongly affected by the magnesium (Mg) to P ratio in the growing crop. We analyzed a field trial in Central Sweden including nine wheat varieties grown during two years with contrasting weather, and found evidence for Mg co-limitation at lower grain yields and P co-limitation at higher yields. We argue that critical concentrations of single nutrients, which are often applied in agronomy, should be replaced by nutrient ratios. In addition, links between plant P and Mg contents and root traits were found; high root number enhanced the P:N ratio, whilst steep root angle, indicating deep roots, increased the Mg:N ratio. The results have significant implications on the management and breeding targets of agriculturally grown wheat, which is one of the most important food crops worldwide.
A randomised, prospective study of the effects of 3% diquafosol on ocular surface following cataract surgery
Authors: Kim Sangyoon , Shin Jonghoon , Lee Ji Eun 
Published: April 2021

AbstractThere is still no established therapeutic solution for postoperative Dry Eye Syndrome (DES) after cataract surgery, in spite of progress in surgical techniques. Diquafosol tetrasodium (DQS), a recently developed ophthalmic solution, has been reported to be effective in DES, but no study evaluated post-cataract surgery lipid layer thickness (LLT) changes in healthy patients who used DQS postoperatively. We randomly divided participants into two groups; the DQS group was treated six times daily with DQS after cataract surgery, and the sodium hyaluronate (HA) group was treated with HA in the same way. Throughout study period, the DQS group showed significantly higher tear break up time (TBUT) and LLT than HA group. In multivariate analysis, better preoperative TBUT, Schirmer’s I test score, ocular surface disease index (OSDI) score, and LLT were significantly associated with improved postoperative outcomes in each parameter. Also, the postoperative use of DQS served as an independent parameter of better TBUT, OSDI score, and LLT in postoperative 15 weeks. Treatment with 3% DQS following cataract surgery showed more improvement in TBUT and LLT, compared with 0.1% HA. Improving TBUT and LLT preoperatively and using 3% DQS postoperatively, could be a reliable choice for managing DES after cataract surgery.Trial Registration: ISRCTN registry with ISRCTN 18755487.
Inhibition of Wnt signalling by Notch via two distinct mechanisms
Authors: Acar Ahmet , Hidalgo-Sastre Ana , Leverentz Michael K. , Mills Christopher G. , Woodcock Simon , Baron Martin , Collu Giovanna M. , Brennan Keith 
Published: April 2021

AbstractNotch and Wnt are two essential signalling pathways that help to shape animals during development and to sustain adult tissue homeostasis. Although they are often active at the same time within a tissue, they typically have opposing effects on cell fate decisions. In fact, crosstalk between the two pathways is important in generating the great diversity of cell types that we find in metazoans. Several different mechanisms have been proposed that allow Notch to limit Wnt signalling, driving a Notch-ON/Wnt-OFF state. Here we explore these different mechanisms in human cells and demonstrate two distinct mechanisms by which Notch itself, can limit the transcriptional activity of β-catenin. At the membrane, independently of DSL ligands, Notch1 can antagonise β-catenin activity through an endocytic mechanism that requires its interaction with Deltex and sequesters β-catenin into the membrane fraction. Within the nucleus, the intracellular domain of Notch1 can also limit β-catenin induced transcription through the formation of a complex that requires its interaction with RBPjκ. We believe these mechanisms contribute to the robustness of cell-fate decisions by sharpening the distinction between opposing Notch/Wnt responses.
Chemotherapy agents stimulate dendritic cells against human colon cancer cells through upregulation of the transporter associated with antigen processing
Authors: Liang Yi-Hsin , Tsai Jia-Huei , Cheng Yung-Ming , Chan Kuang-Yu , Hsu Wen-Ling , Lee Chang-Cheng , Chen Kuo-Hsing , Yeh Kun-Huei 
Published: April 2021

AbstractSingle immunotherapy fails to demonstrate efficacy in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Research on immune reactions before and after systemic agents for mCRC is warranted. Our study examined cell line models to compare the expression of immune surface markers on colon cancer cells before and after chemotherapy agents. We also elucidated mechanisms underlying the effects of chemotherapy agents on immune surface markers. We used real-world clinical samples with NanoString analysis and the Perkin-Elmer Opal multiplex system. We established that chemotherapy agents, particularly 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan, stimulated the expression of stimulatory MHC class I alleles through stimulation the pathway of transporters associated with antigen processing 1 and 2 (TAP1 and TAP2) in cell line models. Application of infected cell protein 47 (ICP-47), a specific inhibitor of the TAP1/TAP2, significantly inhibited expression of TAP1/TAP2 and also inhibited the expression of the downstream MHC class I. In the functional assay, SN-38 significantly promoted the phagocytosis of colon cancer cells by monocyte-derived dendritic cells (MoDCs). We confirmed that the expression of major histocompatibility complex (MHC) class I, significantly increased after first-line chemotherapy and targeted therapy in the samples of real-world patients with de novo mCRC. Our study provides new insights for novel immunotherapy combinations.
Impact of air injection on subretinal fluid following successful scleral buckling surgery for macular-involving retinal detachment
Authors: Tang Fen , Xu Fan , Su Ning , Liu Lingjuan , Jiang Li , Tang Ningning , Zhao Xin , Cui Ling , Zeng Siming , Lai Zhaoguang , Li Min , Zhong Haibin 
Published: April 2021

AbstractAir injection is an accessory technique during scleral buckling (SB). Subclinical subretinal fluid (SRF) may presence and persistent after SB. The impact of air injection on SRF is unclear. In the study, we retrospectively enrolled 51 patients with macular-involving RD who had undergone successful SB. They were categorized into Group A (SB without air injection) and Group B (SB with air injection). First, we found that although group B seem to be severer than group A before surgery, Kaplan–Meier graph showed that SRF absorbed more rapidly in group B after surgery, and the incidence of SRF in group B was much lower during the whole follow-up period. Moreover, the cases with superior breaks had the lowest incidence. Second, during the follow-up period, there was no significant difference about postoperative complication between two groups. Lastly, risk factors for persistent SRF were investigated with binary logistic regression, and no risk factor was found. In conclusion, air injection during the SB might accelerate SRF absorption and reduce the incidence of persistent SRF, especially for the longstanding macular-off RD with superior breaks.
Chronic mild and acute severe glaucomatous neurodegeneration derived from silicone oil-induced ocular hypertension
Authors: Fang Fang , Zhang Jie , Zhuang Pei , Liu Pingting , Li Liang , Huang Haoliang , Webber Hannah C. , Xu Yangfan , Liu Liang , Dalal Roopa , Sun Yang , Hu Yang 
Published: April 2021

AbstractRecently, we established silicone oil-induced ocular hypertension (SOHU) mouse model with significant glaucomatous neurodegeneration. Here we characterize two additional variations of this model that simulate two distinct glaucoma types. The first is a chronic model produced by high frequency (HF) pupillary dilation after SO-induced pupillary block, which shows sustained moderate IOP elevation and corresponding slow, mild glaucomatous neurodegeneration. We also demonstrate that although SO removal quickly returns IOP to normal, the glaucomatous neurodegeneration continues to advance to a similar degree as in the HF group without SO removal. The second, an acute model created by no pupillary dilation (ND), shows a greatly elevated IOP and severe inner retina degeneration at an early time point. Therefore, by a straightforward dilation scheme, we extend our original SOHU model to recapitulate phenotypes of two major glaucoma forms, which will be invaluable for selecting neuroprotectants and elucidating their molecular mechanisms.
The Tri-ponderal Mass Index is associated with adiposity in adolescent type 2 diabetes mellitus: a cross-sectional analysis
Authors: Alfaraidi Haifa , Wicklow Brandy , Dart Allison B. , Sellers Elizabeth , McGavock Jonathan , Thabane Lehana , Samaan M. Constantine 
Published: April 2021

AbstractPediatric type 2 diabetes mellitus (T2DM) patients are often overweight or obese, yet there are no validated clinical measures of adiposity to stratify cardiometabolic risk in this population. The tri-ponderal mass index (TMI, kg/m3) has recently been reported as a measure of adiposity in children, but there has been no validation of the association of TMI with adiposity in pediatric T2DM. We hypothesized that in children with T2DM, the TMI can serve as a more accurate measure of adiposity when compared to BMI z-score, and that it is associated with components of the metabolic syndrome. This is a cross-sectional secondary data analysis from the Improving Renal Complications in Adolescents with Type 2 Diabetes Through REsearch (iCARE) study (n = 116, age 10.20–17.90 years). Spearman’s correlations and multivariable regression were used in the analyses. When compared to DXA, TMI demonstrated significant correlation with total adiposity versus BMI z-score (TMI r = 0.74, p-value < 0.0001; BMI z-score r = − 0.08, p-value 0.403). In regression analyses, TMI was associated with WHtR (B = 35.54, 95% CI 28.81, 42.27, p-value < 0.0001), MAP dipping (B = 1.73, 95% CI 0.12, 3.33, p-value = 0.035), and HDL (B = − 5.83, 95% CI − 10.13, − 1.54, p-value = 0.008). In conclusion, TMI is associated with adiposity and components of the metabolic syndrome in pediatric T2DM patients.