bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenolic and anthocyanin fractions from wild blueberries (V. angustifolium) differentially modulate endothelial cell migration partially through RHOA and RAC1
Authors: Tsakiroglou Panagiotis , Weber James , Ashworth Sharon , Del Bo Cristian , Klimis‐Zacas Dorothy 
Published: January 2019

AbstractThe present study investigates the effect of anthocyanin (ACN), phenolic acid (PA) fractions, and their combination (ACNs:PAs) from wild blueberry powder (Vaccinum angustifolium) on the speed of endothelial cell migration, gene expression, and protein levels of RAC1 and RHOA associated with acute exposure to different concentrations of ACNs and PAs. Time‐lapse videos were analyzed and endothelial cell speed was calculated. Treatment with ACNs at 60 μg/mL inhibited endothelial cell migration rate (
P ≤ 0.05) while treatment with PAs at 0.002 μg/mL (
P ≤ 0.0001), 60 μg/mL (
P ≤ 0.0001), and 120 μg/mL (
P ≤ 0.01) significantly increased endothelial cell migration rate compared with control. Moreover, exposure of HUVECs to ACNs:PAs at 8:8 μg/mL (
P ≤ 0.05) and 60:60 μg/mL increased (
P ≤ 0.001) endothelial cell migration. Gene expression of RAC1 and RHOA significantly increased 2 hours after exposure with all treatments. No effect of the above fractions was observed on the protein levels of RAC1 and RHOA. Findings suggest that endothelial cell migration is differentially modulated based on the type of blueberry extract (ACN or PA fraction) and is concentration‐dependent. Future studies should determine the mechanism of the differential action of the above fractions on endothelial cell migration.
Retracted: Emodin protects H9c2 cells against hypoxia‐induced injury via regulation of miR‐26a/survivin and the JAK1/STAT3 pathway
Authors: Huang Jiancheng , Li Xiaobing , Liu Pujuan , Wang Jun , Li Hongying 
Published: January 2019

AbstractBackground/aimCongenital heart disease (CHD) is a catastrophic disease. Emodin possesses biological properties in protecting against some diseases. Our study investigated to explore the effects of emodin on hypoxia‐stimulated cardiomyocytes, which mimicked CHD in vitro.MethodsH9c2 cells were stimulated with hypoxia and then the cells were treated with or without emodin, and/or transfected with miR‐26a mimic, pcDNA‐survivin and their corresponding negative control (NC). Cell viability and cell apoptosis were detected by Cell Counting kit‐8 assay and flow cytometry, respectively. In addition, the expression of apoptotic proteins, Janus kinase 1 (JNK)/signal transducer and activator of transcription 3 (STAT3) pathway factors, and survivin were evaluated by using Western blot analysis. The expression of miR‐26a was analyzed by quantitative real time polymerase chain reaction (qRT‐PCR). Moreover, the target of miR‐26a was verified by using a luciferase report assay.ResultsHypoxia significantly decreased cell viability and increased cell apoptosis, and the accumulated levels of cleaved caspase‐3 and cleaved‐caspase‐9 were upregulated by hypoxia compared with the control. However, emodin administration led to the opposite result. A further result showed that emodin increased the phosphorylation of JNK/STAT3 pathway–related proteins and the pathway inhibitor AG490 impaired the protective effects of emodin on hypoxia‐induced injury. In addition, emodin negatively regulated the miR‐26a expression, and overexpression of miR‐26a enhanced cell apoptosis and upregulated the expression of cleaved‐caspase‐3 and cleaved‐caspase‐9 compared with the NC. Moreover, emodin statistically upregulated the expression of survivin, and overexpression of miR‐26a decreased the expression of survivin. The luciferase of miR‐26a overexpression was decreased in the wild type of the survivin group.ConclusionEmodin protects hypoxia‐induced cell injury as evidenced by increasing cell viability and decreasing apoptosis through downregulation of miR‐26a as well as activation of the JNK/STAT3 pathway.
Mechanistic elucidation of amphetamine metabolism by tyramine oxidase from human gut microbiota using molecular dynamics simulations
Authors: Kumar Kundan , Dhoke Gaurao V. , Sharma Ashok K. , Jaiswal Shubham K. , Sharma Vineet K. 
Published: January 2019

AbstractThe human gut harbors diverse bacterial species in the gut, which play an important role in the metabolism of food and host health. Recent studies have also revealed their role in altering the pharmacological properties and efficacy of oral drugs through promiscuous metabolism. However, the atomistic details of the enzyme‐drug interactions of gut bacterial enzymes which can potentially carry out the metabolism of drug molecules are still scarce. A well‐known example is the FDA drug amphetamine (a central nervous system stimulant), which has been predicted to undergo promiscuous metabolism by gut bacteria. Therefore, to understand the atomistic details and energy landscape of the gut microbial enzyme‐mediated metabolism of this drug, molecular dynamics studies were performed. It was observed that amphetamine binds to tyramine oxidase from the Escherichia coli strain present in the human gut microbiota at the binding site harboring polar and nonpolar amino acids. The stability analysis of amphetamine at the binding site showed that the binding is stable and the free energy for the binding of amphetamine was found to be ~ −51.71 kJ/mol. The insights provided by this study on promiscuous metabolism of amphetamine by a gut enzyme will be very useful to improve the efficacy of the drug.
Distinct partial sums in cyclic groups: polynomial method and constructive approaches
Authors: Hicks Jacob , Ollis M. A. , Schmitt John R. 
Published: January 2019

AbstractLet be an abelian group and consider a subset with . Given an ordering of the elements of , define its
partial sums by and for . We consider the following conjecture of Alspach: for any cyclic group and any subset with , it is possible to find an ordering of the elements of such that no two of its partial sums and are equal for . We show that Alspach’s Conjecture holds for prime when and when . The former result is by direct construction, the latter is nonconstructive and uses the polynomial method. We also use the polynomial method to show that for prime a sequence of length having distinct partial sums exists in any subset of of size at least in all but at most a bounded number of cases.
Tanshinone IIA protects lens epithelial cells from H2O2‐induced injury by upregulation of lncRNA ANRIL
Authors: Qi Defeng , Wang Mingming , Zhang Duzhen , Li Haihui 
Published: January 2019

AbstractTanshinone IIA is a lipophilic diterpene extracted from the Salvia miltiorrhiza bunge, possessing antiapoptotic and antioxidant activities. The purpose of this study was to explore the effects of Tanshinone IIA on age‐related nuclear cataract. Human lens epithelial cell line SRA01/04 was subjected to H
2O
2 to mimic a cell model of cataract. Cell Counting Kit‐8 assay, flow cytometer, and reactive oxygen species (ROS) detection were performed to evaluate the effect of Tanshinone IIA pretreatment on SRA01/04 cells injured by H
2O
2. Besides, the real‐time quantitative polymerase chain reaction was used to assess the expression of long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL). Western blot analysis was performed to detect the expression of core proteins involved in cell survival and nuclear factor‐κB (NF‐κB) pathway. H
2O
2 significantly decreased SRA01/04 cells viability, whereas increased apoptosis and ROS generation. This phenomenon was coupled with the upregulated p53, p21, Bax, cleaved caspase‐3, and the downregulated cyclinD1, CDK4, and Bcl‐2. Tanshinone IIA pretreatment protected SRA01/04 cells against H
2O
2‐induced injury. In the meantime, the expression of lncRNA ANRIL was upregulated by Tanshinone IIA. And, the protective effects of Tanshinone IIA on H
2O
2‐stimulated SRA01/04 cells were abolished when lncRNA ANRIL was silenced. Moreover, the elevated expression of lncRNA ANRIL induced by Tanshinone IIA was abolished by BAY 11‐7082 (an inhibitor of NF‐κB). To conclude, Tanshinone IIA protects SRA01/04 cells from apoptosis triggered by H
2O
2. Tanshinone IIA confers its protective effects possibly via modulation of NF‐κB signaling and thereby elevating the expression of lncRNA ANRIL.
Alpha7 nicotinic acetylcholine receptors in lung inflammation and carcinogenesis: Friends or foes?
Authors: Hajiasgharzadeh Khalil , Sadigh‐Eteghad Saeed , Mansoori Behzad , Mokhtarzadeh Ahad , Shanehbandi Dariush , Doustvandi Mohammad Amin , Asadzadeh Zahra , Baradaran Behzad 
Published: January 2019

AbstractThe lung tissue expresses the cholinergic system including nicotinic acetylcholine receptors (nAChRs) which included in many physiologic and pathologic processes. Mounting evidence revealed that these receptors have important roles in lung carcinogenesis via modulating either stimulatory or inhibitory signaling pathways. Among different members of nicotinic receptors family, alpha7‐subtype of nAChR (α7nAChR) is a critical mediator involved in both inflammatory responses and cancers. Several studies have shown that this receptor is the most powerful regulator of responses that stimulate lung cancer processes such as proliferation, angiogenesis, metastasis, and inhibition of apoptosis. Moreover, aside from its roles in the regulation of cancer pathways, there is growing evidence indicating that α7nAChR has profound impacts on lung inflammation through the cholinergic anti‐inflammatory pathway. Regarding such diverse effects as well as the critical roles of nicotine as an activator of α7nAChR on lung cancer pathogenesis, its modulation has emerged as a promising target for drug developments. In this review, we aim to highlight the detrimental as well as the possible beneficial influences of α7nAChR downstream signaling cascades in the control of lung inflammation and cancer‐associated properties. Consequently, by considering the significant global burden of lung cancer, delineating the complex influences of α7 receptors would be of great interest in designing novel anticancer and anti‐inflammatory strategies for the patients suffering from lung cancer.
Noncoding RNAs in alcoholic liver disease
Authors: Li Hai‐Di , Du Xiao‐Sa , Huang Hui‐Min , Chen Xin , Yang Yang , Huang Cheng , Meng Xiao‐Ming , Li Jun 
Published: January 2019

AbstractAlcoholic liver disease (ALD) is a complex process with high morbitity and can cause liver dysfunction, which contains a wide spectrum of hepatic lesions, including steatohepatitis, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. To date, the molecular mechanisms for ALD have not been fully explored and an effective therapy is still missing. Overwhelming evidence shows dysregulation of noncoding RNAs (ncRNAs), particularly microRNAs (miRNAs), is correlated with etiopathogenesis and progress of ALD including hepatocyte damage, disrupted lipid metabolism, aggressive inflammatory responses, oxidative stress, programmed cell death, fibrosis, and epigenetic changes induced by alcohol. For example, circulating miRNA‐122 is a marker of hepatocyte damage, and miRNA‐155 is a potential marker of inflammation, indicating their diagnosis therapeutic potential in ALD. In addition, roles for long noncoding RNAs (lncRNAs) and circular RNAs in ALD are being uncovered. Further, circulating ncRNAs and exosome‐derived ncRNAs have attracted more attention lately, suggesting a role in the prevention and treatment of ALD. This review covers the roles of ncRNAs in ALD, and the potential uses as markers for diagnosis and therapeutic options.
LncIRS1 controls muscle atrophy via sponging miR‐15 family to activate IGF1‐PI3K/AKT pathway
Authors: Li Zhenhui , Cai Bolin , Abdalla Bahareldin Ali , Zhu Xuenong , Zheng Ming , Han Peigong , Nie Qinghua , Zhang Xiquan 
Published: January 2019

AbstractBackgroundRecent studies indicate important roles for long noncoding RNAs (lncRNAs) in the regulation of gene expression by acting as competing endogenous RNAs (ceRNAs). However, the specific role of lncRNAs in skeletal muscle atrophy is still unclear. Our study aimed to identify the function of lncRNAs that control skeletal muscle myogenesis and atrophy.MethodsRNA sequencing was performed to identify the skeletal muscle transcriptome (lncRNA and messenger RNA) between hypertrophic broilers and leaner broilers. To study the ‘sponge’ function of lncRNA, we constructed a lncRNA‐microRNA (miRNA)‐gene interaction network by integrated our previous submitted skeletal muscle miRNA sequencing data. The primary myoblast cells and animal model were used to assess the biological function of the lncIRS1 in vitro or in vivo.ResultsWe constructed a myogenesis‐associated lncRNA‐miRNA‐gene network and identified a novel ceRNA lncRNA named lncIRS1 that is specifically enriched in skeletal muscle. LncIRS1 could regulate myoblast proliferation and differentiation in vitro, and muscle mass and mean muscle fibre in vivo. LncIRS1 increases gradually during myogenic differentiation. Mechanistically, lncIRS1 acts as a ceRNA for miR‐15a, miR‐15b‐5p, and miR‐15c‐5p to regulate IRS1 expression, which is the downstream of the IGF1 receptor. Overexpression of lncIRS1 not only increased the protein abundance of IRS1 but also promoted phosphorylation level of AKT (p‐AKT) a central component of insulin‐like growth factor‐1 pathway. Furthermore, lncIRS1 regulates the expression of atrophy‐related genes and can rescue muscle atrophy.ConclusionsThe newly identified lncIRS1 acts as a sponge for miR‐15 family to regulate IRS1 expression, resulting in promoting skeletal muscle myogenesis and controlling atrophy.
Leukemia-derived exosomes and cytokines pave the way for entry into the brain
Authors: Kinjyo Ichiko , Bragin Denis , Grattan Rachel , Winter Stuart S , Wilson Bridget S 
Published: January 2019

Abstract
Infiltration of acute lymphoblastic leukemia (ALL) blasts into the CNS remains as a major clinical problem, with high risk for chemotherapy-resistant relapse and treatment-related morbidity. Despite the common inclusion of CNS prophylaxis treatments in therapy regimens, there are significant gaps in understanding the mechanisms that mediate leukemia cell entry into the CNS as well as roles for resident cells in the brain. In this study, we employ a xenograft model of human B cell precursor (BCP)-ALL in immunocompromised mice. This model system recapitulates key pathological characteristics of leptomeningeal involvement seen in patients and provides insights into rare cases that involve parenchymal invasion. We examine the infiltration of engrafted leukemia blasts into brains of recipient mice and provide evidence that the interaction between blasts and brain resident cells causes aberrant activation of host cells in the brain microenvironment. BCP-ALL blasts also release multiple cytokines and exosomes containing IL-15 that bind and are internalized by astrocytes and brain vessel endothelial cells. Leukemic invasion is linked to production of VEGF-AA by astrocytes and disruption of the blood-brain-barrier (BBB) integrity. Knockdown of either IL-15 or IL-15Rα in the NALM6 cell line decreases CNS infiltration in engrafted mice. These results provide important insights into the multiple mechanisms by which lymphoblasts modulate the brain microenvironment to breach the BBB for metastatic invasion.
Multispectroscopic exploration and molecular docking analysis on interaction of eriocitrin with bovine serum albumin
Authors: Cao Xiangyu , Yang Zhijun , He Yonglin , Xia Ying , He Yin , Liu Jianli 
Published: January 2019

AbstractEriocitrin is a flavanone glycoside, which exists in lemon or lime citrus fruits. It possesses antioxidant, anticancer, and anti‐allergy activities. In order to investigate the pharmacokinetics and pharmacological mechanisms of eriocitrin in vivo, the interaction between eriocitrin and bovine serum albumin (BSA) was studied under the simulated physiological conditions by multispectroscopic and molecular docking methods. The results well indicated that eriocitrin and BSA formed a new eriocitrin‐BSA complex because of intermolecular interactions, which was demonstrated by the results of ultraviolet‐visible (UV‐vis) absorption spectra. The intrinsic fluorescence of BSA was quenched by eriocitrin, and static quenching was the quenching mechanism. The number of binding sites (n) and binding constant (Kb) at 310 K were 1.22 and 2.84 × 106 L mol−1, respectively. The values of thermodynamic parameters revealed that the binding process was spontaneous, and the main forces were the hydrophobic interaction. The binding distance between eriocitrin and BSA was 3.43 nm. In addition, eriocitrin changed the conformation of BSA, which was proved by synchronous fluorescence and circular dichroism (CD) spectra. The results of site marker competitive experiments suggested that eriocitrin was more likely to be inserted into the subdomain IIA (site I), which was further certified by molecular docking studies.
Associations between vertebral body fat fraction and intervertebral disc biochemical composition as assessed by quantitative MRI
Authors: Krug Roland , Joseph Gabrielle B. , Han Misung , Fields Aaron , Cheung Justin , Mundada Maya , Bailey Jeannie , Rochette Alice , Ballatori Alexander , McCulloch Charles E. , McCormick Zachary , O'Neill Conor , Link Thomas M. , Lotz Jeffrey 
Published: January 2019

BackgroundThere is an interplay between the intervertebral disc (IVD) and the adjacent bone marrow that may play a role in the development of IVD degeneration and might influence chronic lower back pain (CLBP).PurposeTo apply novel quantitative MRI techniques to assess the relationship between vertebral bone marrow fat (BMF) and biochemical changes in the adjacent IVD.Study TypeProspective.SubjectsForty‐six subjects (26 female and 20 male) with a mean age of 47.3 ± 12.0 years.Field Strength/Sequence3 T MRI; a combined T1ρ and T2 mapping pulse sequence and a 3D spoiled gradient recalled sequence with six echoes and iterative decomposition of water and fat with echo asymmetry and least‐squares estimation (IDEAL) reconstruction algorithm.AssessmentUsing quantitative MRI, the vertebral BMF fraction was measured as well as the biochemical composition (proteoglycan and collagen content) of the IVD. Furthermore, clinical Pfirrmann grading, Oswestry disability index (ODI), and visual analog scale (VAS) was assessed.Statistical TestsMixed random effects models accounting for multiple measurements per subject were used to assess the relationships between disc measurements and BMF.ResultsThe relationships between BMF (mean) and T1ρ/T2 (mean and SD) were significant, with P < 0.05. Significant associations (P < 0.001) were found between clinical scores (Pfirrmann, ODI, and VAS) with T1ρ/T2 (mean and SD). BMF mean was significantly related to ODI (P = 0.037) and VAS (P = 0.043), but not with Pfirrmann (P = 0.451). In contrast, BMF SD was significantly related to Pfirrmann (P = 0.000) but not to ODI (P = 0.064) and VAS (P = 0.13).Data ConclusionOur study demonstrates significant associations between BMF and biochemical changes in the adjacent IVD, both assessed by quantitative MRI; this may suggest that the conversion of hematopoietic bone marrow to fatty bone marrow impairs the supply of available nutrients to cells in the IVD and may thereby accelerate disc degeneration.Level of Evidence: 2Technical Efficacy Stage: 3J. Magn. Reson. Imaging 2019;50:1219–1226.
Transgenic increase in the β‐endorphin concentration in cerebrospinal fluid alleviates morphine‐primed relapse behavior through the μ opioid receptor in rats
Authors: He Yan , Lu Yugang , Shen Yang , Wu Feixiang , Xu Xuewu , Kong Erliang , Huang Zhangxiang , Sun Yuming , Yu Weifeng 
Published: January 2019

AbstractBackgroundOpioid‐primed relapse is a global burden. Although current strategies have improved, optimal therapy is urgently needed.MethodsA recombinant adenovirus (Ad‐NEP) expressing β‐endorphin (β‐EP) was designed and injected intracerebroventricularly (icv) into the right lateral ventricle in rats. Spatial and temporal β‐EP expression in the lateral ventricle wall, subventricular zone and adjacent choroid plexus and the β‐EP concentration in the cerebrospinal fluid (CSF) were observed during a 21‐day period. A morphine priming‐induced conditioned place preference (CPP) rat model was established. The β‐EP‐ir neuron counts, CSF β‐EP concentration, and CPP score, which were used to evaluate morphine‐primed reinstatement following extinction, were recorded 7 days after the icv injection. Additionally, the rats were pretreated with the irreversible μ opioid receptor antagonist β‐funaltrexamine (β‐FNA) and the selective κ opioid receptor antagonist nor‐binaltorphimine (nor‐BNI) to identify the receptor‐dependent mechanism.ResultsBoth peak β‐EP expression in target neurons and the peak CSF β‐EP concentration occurred 7 to 8 days after Ad‐NEP icv injection. The sustainable increase in the CSF β‐EP concentration was correlated with a decrease in the CPP score 7 days after the Ad‐NEP icv injection. Furthermore, reinstatement was almost reversed by β‐FNA pretreatment 24 hours before the behavioral test, but nor‐BNI had little effect.ConclusionThe increasing cerebrospinal fluid β‐endorphin concentrations showed that the therapeutic effect on opioid relapse occurred predominantly through a μ opioid receptor‐dependent mechanism. The Ad‐NEP adenovirus can be considered an alternative therapy for opioid relapse.
Hollow mesoporous silica nanoparticles as delivery vehicle of foot‐and‐mouth disease virus‐like particles induce persistent immune responses in guinea pigs
Authors: Bai Manyuan , Dong Hu , Su Xin , Jin Ye , Sun Shiqi , Zhang Yingpeng , Yang Yunshang , Guo Huichen 
Published: January 2019

AbstractFoot‐and‐mouth disease (FMD) is an acute and febrile infectious disease, which can cause great economic losses. Virus‐like particles (VLPs) as an advantageous antigen can induce significant specific immune response. To improve immunity of VLPs, especially, make it induce persistent immune response, the hollow mesoporous silica nanoparticles (HMSNs) as a potential nano‐adjuvant were synthesized and loaded the FMD virus (FMDV) VLPs. They were injected into guinea pigs and the specific immune response was detected. The results confirmed that HMSNs/VLPs can induce persistent humoral immunity with high‐level antibody titer for more than three months. HMSNs also improve the T‐lymphocyte proliferation and IFN‐γ induced by FMDV VLPs, and provides the ideal protection against FMDV challenge. These consequences indicated that HMSNs were good protein delivery vehicle and potential nano‐adjuvant of vaccines.