bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug‐induced liver injury: Oltipraz and C2‐ceramide intervene HNF‐1α/GSTA1 expression via JNK signaling pathway
Authors: Zhang Yuanyuan , Ma Bingke , Hao Shuangshuang , Wang Jiaqi , Zhang Ruichen , Ishfaq Muhammad , Shi Chenxi , Yuan Liang , Li Rui , Li Changwen , Liu Fangping 
Published: May 2021

AbstractDrug‐induced liver injury (DILI) is a serious and frequently occurring issue in drug development. The c‐Jun N‐terminal kinase (JNK) signaling pathway plays an important role in many diseases; hepatocyte nuclear factor‐1α (HNF‐1α) and glutathione S‐transferase A1 (GSTA1) are important in regulating liver‐specific genes expressions and affecting drug metabolism. Oltipraz is used to treat liver cirrhosis by improving liver function, and C2‐ceramide is a pro‐apoptotic lipid that regulates multiple signaling pathways. In this study, we investigated the function of the JNK signaling pathway with HNF‐1α and GSTA1 in a cellular model of DILI and whether oltipraz and C2‐ceramide exert effects via the JNK pathway. The results showed that inhibiting JNK could ameliorate APAP‐induced hepatocyte injury, reduced oxidative stress, suppressed JNK and c‐Jun activation, and hepatocyte apoptosis. Meanwhile, the mRNA and protein expressions of HNF‐1α and GSTA1 were increased significantly compared to control conditions. The effect of oltipraz (8 μmol/L) was similar to a JNK inhibitor and significantly increased HNF‐1α/GSTA1 expression, but oltipraz combined with JNK inhibitor did not show a synergistic effect. Although C2‐ceramide (8 μmol/L) aggravated hepatocyte injury and apoptosis, exacerbated oxidative stress, increased phosphorylation of JNK and c‐Jun, and markedly decreased HNF‐1α/GSTA1 expression, C2‐ceramide combined with JNK inhibitor could partially alleviate these alterations. These results demonstrated that the JNK signaling pathway with HNF‐1α/GSTA1 are involved in the process of DILI. Inhibiting JNK up‐regulated HNF‐1α and GSTA1 expressions which could attenuate hepatocyte injury. Oltipraz and C2‐ceramide might affect the expression of HNF‐1α/GSTA1 though JNK signaling.
Type 2 Diabetes Is Causally Associated With Reduced Serum Osteocalcin: A Genomewide Association and Mendelian Randomization Study
Authors: Zeng Hailuan , Ge Jieyu , Xu Wenjie , Ma Hui , Chen Lingyan , Xia Mingfeng , Pan Baishen , Lin Huandong , Wang Sijia , Gao Xin 
Published: May 2021

ABSTRACT
Recent advances indicate that bone and energy metabolism are closely related. However, little direct evidence on causality has been provided in humans. We aimed to assess the association of three bone-related biomarkers—25 hydroxyvitamin D (25OHD), parathyroid hormone (PTH), and osteocalcin (OCN)—with several metabolic phenotypes and investigate any causal relevance to the associations using a Mendelian randomization (MR) study. Serum 25OHD, PTH, and total OCN were measured at baseline in 5169 eligible Chinese participants in Changfeng study. Partial correlation and bivariate GREML analysis were used to estimate phenotypic and genetic correlations, respectively. Multiple linear regression and logistic regression were used to assess linear associations. Genomewide association analysis (GWAS) was performed. Bidirectional two-sample MR analyses were conducted to examine causal relationships between OCN and body mass index (BMI), diastolic blood pressure (DBP), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), glycated hemoglobin A1c (HbA1c), and type 2 diabetes (T2DM), using our GWAS result of OCN and GWAS statistics from Biobank Japan project (BBJ) and the largest meta-analysis of T2DM GWAS in East Asian population. Circulating OCN was significantly associated with higher DBP and HDL-C and decreased TG, blood glucose level, insulin resistance, liver fat content, bone mineral density, BMI, and a favorable body fat distribution pattern. GWAS identified one novel serum PTH locus and two novel serum OCN loci, explaining 0.81% and 1.98% of variances of PTH and OCN levels, respectively. MR analysis suggested a causal effect of T2DM on lower circulating OCN concentration (causal effect: −0.03; −0.05 to −0.01; p = 0.006 for T2DM_BBJ and −0.03; −0.05 to −0.01; p = 0.001 for T2DM_EAS). These findings indicate that T2DM might impact bone remodeling and provide a resource for understanding complex relationships between osteocalcin and metabolic (and related) traits in humans. © 2021 American Society for Bone and Mineral Research (ASBMR).
Faster lipid β‐oxidation rate by acetyl‐CoA carboxylase 2 inhibition alleviates high‐glucose‐induced insulin resistance via SIRT1/PGC‐1α in human podocytes
Authors: Wang Qinglian , Zhao Bing , Zhang Jie , Sun Jingshu , Wang Simeng , Zhang Xinyu , Xu Ying , Wang Rong 
Published: May 2021

AbstractDiabetic nephropathy (DN) is becoming a research hotspot in recent years because the prevalence is high and the prognosis is poor. Lipid accumulation in podocytes induced by hyperglycemia has been shown to be a driving mechanism underlying the development of DN. However, the mechanism of lipotoxicity remains unclear. Increasing evidence shows that acetyl‐CoA carboxylase 2 (ACC2) plays a crucial role in the metabolism of fatty acid, but its effect in podocyte injury of DN is still unclear. In this study, we investigated whether ACC2 could be a therapeutic target of lipid deposition induced by hyperglycemia in the human podocytes. Our results showed that high glucose (HG) triggered significant lipid deposition with a reduced β‐oxidation rate. It also contributed to the downregulation of phosphorylated ACC2 (p‐ACC2), which is an inactive form of ACC2. Knockdown of ACC2 by sh‐RNA reduced lipid deposition induced by HG. Additionally, ACC2‐shRNA restored the expression of glucose transporter 4 (GLUT4) on the cell surface, which was downregulated in HG and normalized in the insulin signaling pathway. We verified that ACC2‐shRNA alleviated cell injury, apoptosis, and restored the cytoskeleton disturbed by HG. Mechanistically, SIRT1/PGC‐1α is close related to the insulin metabolism pathway. ACC2‐shRNA could restore the expression of SIRT1/PGC‐1α, which was downregulated in HG. Rescue experiment revealed that inhibition of SIRT1 by EX‐527 counteracted the effect of ACC2‐shRNA. Taken together, our data suggest that podocyte injury mediated by HG‐induced insulin resistance and lipotoxicity could be alleviated by ACC2 inhibition via SIRT1/PGC‐1α.
Examining rumination, devaluation of positivity, and depressive symptoms via community‐based network analysis
Authors: Collins Amanda C. , Lass Alisson N. S. , Jordan D. Gage , Winer E. Samuel 
Published: May 2021

AbstractObjectiveComponents of rumination, including brooding and reflection, as well as devaluating prospective positivity, may help maintain depressive symptoms. We examined these components together for the first time using network analysis.MethodsWe examined the robustness of rumination communities of closely related items in one network and then examined the interrelationships between rumination communities, devaluation of positivity, and depression, in a second network.ResultsThree rumination communities emerged, replicating findings of Bernstein et al. (2019). Within a dense network, nodes representing brooding, reflective pondering, and difficulty trusting positive feelings were most influential. In addition, the node representing the depressive symptom negative self‐views shared strong edges with nodes representing devaluation of positivity and brooding.ConclusionBrooding, reflective pondering, and elements of devaluing positivity are influential to depressive symptoms and may be important future experimental and therapeutic targets. Depressed individuals with negative self‐views may engage in brooding and devalue their experience of positivity.
Intentions to see a psychologist for weight management: A cross‐sectional study investigating beliefs about psychologists, psychological services and obesity
Authors: Murray Kristen , Brichacek Emily , Rieger Elizabeth 
Published: May 2021

AbstractObjectivesThe current study investigated beliefs about psychologists, psychological services and obesity, and their association with intentions to see a psychologist for weight management.MethodsA cross‐sectional online survey design was employed in a sample of 136 adults with overweight or obesity (n = 121 females, M
age = 37.58, SD = 9.85).ResultsPsychologists and psychological services were viewed favourably by participants, with little evidence of role knowledge deficits or significant treatment barriers. Behavioural and social causal beliefs about obesity were indirectly associated with intentions to see a psychologist for weight management through positive associations with psychologists' perceived helpfulness in lifestyle intervention. Indirect effects were not observed for psychological and medical causal beliefs.ConclusionPromotion of psychological services in obesity could highlight their utility in addressing behavioural and social factors. However, there is a need for more research into avoidance of all sources of professional support in this context.
The potential role of nucleophosmin (NPM1) in the development of cancer
Authors: Karimi Dermani Fateme , Gholamzadeh Khoei Saeideh , Afshar Saeid , Amini Razieh 
Published: May 2021

AbstractNucleophosmin (NPM1) is a well‐known nucleocytoplasmic shuttling protein that performs several cellular functions such as ribosome biogenesis, chromatin remodeling, genomic stability, cell cycle progression, and apoptosis. NPM1 has been identified to be necessary for normal cellular functions, and its altered regulation by overexpression, mutation, translocation, loss of function, or sporadic deletion can lead to cancer and tumorigenesis. In this review, we focus on the gene and protein structure of NPM1 and its physiological roles. Finally, we discuss the association of NPM1 with various types of cancer including solid tumors and leukemia.
From neural stem cells to glioblastoma: A natural history of GBM recapitulated in vitro
Authors: Almengló Cristina , Caamaño Pilar , Fraga Máximo , Devesa Jesús , Costoya José A. , Arce Víctor M. 
Published: May 2021

AbstractDue to its aggressive and invasive nature glioblastoma (GBM), the most common and aggressive primary brain tumour in adults, remains almost invariably lethal. Significant advances in the last several years have elucidated much of the molecular and genetic complexities of GBM. However, GBM exhibits a vast genetic variation and a wide diversity of phenotypes that have complicated the development of effective therapeutic strategies. This complex pathogenesis makes necessary the development of experimental models that could be used to further understand the disease, and also to provide a more realistic testing ground for potential therapies. In this report, we describe the process of transformation of primary mouse embryo astrocytes into immortalized cultures with neural stem cell characteristics, that are able to generate GBM when injected into the brain of C57BL/6 mice, or heterotopic tumours when injected IV. Overall, our results show that oncogenic transformation is the fate of NSC if cultured for long periods in vitro. In addition, as no additional hit is necessary to induce the oncogenic transformation, our model may be used to investigate the pathogenesis of gliomagenesis and to test the effectiveness of different drugs throughout the natural history of GBM.
Concentration‐dependent duality of bFGF in regulation of barrier properties of human brain endothelial cells
Authors: Kriaučiūnaitė Karolina , Pociūtė Agnė , Kaušylė Aida , Pajarskienė Justina , Verkhratsky Alexei , Pivoriūnas Augustas 
Published: May 2021

AbstractMultiple paracrine factors regulate the barrier properties of human brain capillary endothelial cells (BCECs). Understanding the precise mode of action of these factors remains a challenging task, because of the limited availability of functionally competent BCECs and the use of serum‐containing medium. In the present study, we employed a defined protocol for producing BCECs from human inducible pluripotent stem cells. We found that autocrine secretion of basic fibroblast growth factor (bFGF) is necessary for the establishment a tight BCECs barrier, as revealed by measurements of transendothelial electric resistance (TEER). In contrast, addition of exogenous bFGF in concentrations higher than 4 ng/ml inhibited TEER in a concentration‐dependent manner. Exogenous bFGF did not significantly affect expression and distribution of tight junction proteins claudin‐5, occludin and zonula occludens (ZO)‐1. Treatment with FGF receptor blocker PD173074 (15 µM) suppressed inhibitory effects of bFGF and induced nuclear translocation of protein ZO‐1. Inhibition of phosphoinositide 3‐Kinase (PI‐3K) with LY294002 (25 µM) significantly potentiated an inhibitory effect of bFGF on TEER indicating that PI‐3K signalling pathway counteracts bFGF modulation of TEER. In conclusion, we show that autocrine bFGF secretion is necessary for the proper barrier function of BCECs, whereas exogenous bFGF in higher doses suppresses barrier resistance. Our findings demonstrate a dual role for bFGF in the regulation of BCEC barrier function.
Mycobacterium tuberculosis effector PPE36 attenuates host cytokine storm damage via inhibiting macrophage M1 polarization
Authors: Gong Zhen , Han Shuang , Liang Tian , Zhang Hongyang , Sun Qingyu , Pan Huimin , Wang Haolin , Yang Jiao , Cheng Liting , Lv Xi , Yue Qijia , Fan Lin , Xie Jianping 
Published: May 2021

AbstractTuberculosis caused by Mycobacterium tuberculosis remains a serious global public health threat. Macrophage polarization is crucial for the innate immunity against M. tuberculosis. However, how M. tuberculosis interferes with macrophage polarization is elusive. We demonstrated here that M. tuberculosis PPE36 (Rv2108) blocked macrophage M1 polarization, preventing the cytokine storm, and alleviating inflammatory damage to mouse immune organs. PPE36 inhibited the polarization of THP‐1 cell differentiation to M1 macrophages, reduced mitochondrial dehydrogenase activity, inhibited the expression of CD16, and repressed the expression of pro‐inflammatory cytokines IL‐6 and TNF‐α, as well as chemokines CXCL9, CXCL10, CCL3, and CCL5. Intriguingly, in the mouse infection model, PPE36 significantly alleviated the inflammatory damage of immune organs caused by a cytokine storm. Furthermore, we found that PPE36 inhibited the polarization of macrophages into mature M1 macrophages by suppressing the ERK signaling. The study provided novel insights into the function and mechanism of action of M. tuberculosis effector PPE36 both at the cellular and animal level.
Enhancement of nitrate removal under limited organic carbon with hydrogen‐driven autotrophic denitrification in low‐cost electrode bio‐electrochemical reactors
Authors: Peungtim Prarunchaya , Meesungnoen Orapan , Mahachai Palisa , Subsoontorn Pakpoom , Do Thu Nga , Nakaruk Auppatham , Khanitchaidecha Wilawan 
Published: May 2021

AbstractBACKGROUNDNitrate‐contaminated water is a concerning environmental and health problem in agricultural areas. Due to its low organic carbon content, such water cannot be purified using a conventional bioreactor with heterotrophic denitrification. Low‐cost bio‐electrochemical reactors were established with the aim of enhancing denitrification performance by cooperation of heterotrophic and hydrogenotrophic denitrification.RESULTSAt the lowest C/N ratio of 1.0, the bioreactor reached only 67.4% for NO3‐N removal and 47.5% for total N removal (total N removal rate of ca 1.2 mg L−1 h−1), whereas the Cu reactor (bio‐electrochemical reactor using copper wire as cathode) achieved the best efficiencies of 73.7% and 53.8% for NO3‐N and total N removal (total N removal rate of ca 1.3 mg L−1 h−1), and followed by the SS reactor (bio‐electrochemical reactor using stainless steel wire as cathode). On the other hand, the greatest total organic carbon (TOC) removal efficiency was observed for the bioreactor and followed by the SS reactor and the Cu reactor. The low TOC consumption of 1.2–1.4 mg‐TOC (mg‐N)−1 in the Cu reactor and the SS reactor indicated the enhanced denitrification from coexisting hydrogenotrophic denitrification. In addition, the performance of hydrogenotrophic denitrification was improved by increasing the applied current from 10 to 30 mA.CONCLUSIONSThe abundance of autotrophic denitrifying bacteria (identified as hydrogenotrophs) was higher than that of heterotrophic denitrifying bacteria in both the Cu reactor and the SS reactor. Archromobacter and Flavobacterium were the most dominant genera in the biofilm of the Cu reactor cathode and in the suspended sludge, respectively. Hydrogenophaga were detected in both biomass samples, but were absent from the biomass samples of the conventional bioreactor. © 2021 Society of Chemical Industry (SCI).
Topographic characterization of (Zr, Mn) co‐doped bismuth ferrite thin film surfaces
Authors: Ţălu Ştefan , Priya Arumugasamy Sathiya , Geetha Deivasigamani 
Published: May 2021

AbstractThe present work focuses on the investigations on the optical and morphological characteristics of (Zr, Mn) co‐doped Bismuth ferrite thin films. Undoped Bismuth ferrite (BiFeO3) and (Zr, Mn) co‐doped Bismuth ferrite (ZMBFO) thin films were spin‐coated on Pt/TiO2/Ti/SiO2/Si substrate. X‐ray diffraction (XRD) was utilized to confirm the rhombohedral structure and the Scherrer formula was used to calculate the crystallite size of the films. The optical properties were explored using UV–visible spectroscopy and the bandgap energies were calculated using a Tauc plot. The surface morphology of the films was explored with the help of atomic force microscopy (AFM) and the three‐dimensional (3‐D) surface features were determined using stereometric analyses. The variation of 3‐D surface parameters was identified to be the consequence of doping.
Temporary cement residues affect the bond strength and dentin penetration of self‐adhesive resin cement in fiberglass post cementation
Authors: Zaniboni Joissi Ferrari , Silva Aryvelto Miranda , Fernández Eduardo , de Melo Alencar Cristiane , Morais Jéssika Mayhara Pereira , de Campos Edson Alves , Kuga Milton Carlos 
Published: May 2021

AbstractThis study evaluated the persistence of eugenol‐containing (PR, Provy) or eugenol‐free (RT, Relyx Temp, and TB, Temp Bond) temporary cement residues and its effects on push‐out bond strength and dentinal penetration of the self‐adhesive resin cement (Relyx U200). Eighty human roots were endodontically treated and post space prepared. Fourty specimens were distributed in four groups (n = 10): Control (CO), without any clinical procedure, PR, RT, and TB, where a metallic post was cemented with one of the temporary cements. After metallic post removal, hemi sections post space were submitted to SEM analysis. Another specimens were distributed in similar groups, but fiberglass post was cemented using Relyx U200 cement and submitted to push‐out bond strength and dentinal penetration cement analysis, in post space thirds. SEM analysis were evaluated by Kruskal–Wallis and Dunn tests, while bond strength and dentinal penetration were evaluated by ANOVA One‐Way and Tukey test (p < .05). Only in apical thirds, PR, RT, and TB showed higher persistence of residues than CO. In bond strength, PR, RT, and TB showed lower values than CO, in all post space thirds (p < .05). But to dentinal penetration, PR, RT, and TB presented lower values than CO only in apical thirds (p < .05). There is the greatest persistence of temporary cement residues only in apical post space third, providing less dentinal penetration of the self‐adhesive resinous cement. However, the previous use of temporary cements has negative effects on the bond strength cementation system, regardless of the third evaluated.
Allogenic hematopoietic stem cell transplantation in two siblings with adult metachromatic leukodystrophy and a systematic literature review
Authors: Videbæk Cecilie , Stokholm Jette , Sengeløv Henrik , Fjeldborg Lone U. , Larsen Vibeke Andrée , Krarup Christian , Nielsen Jørgen E. , Grønborg Sabine 
Published: May 2021

AbstractTwo siblings were diagnosed with adult metachromatic leukodystrophy (MLD) and treated with hematopoietic stem cell transplantation (HSCT). While the older sibling was symptomatic at the time of diagnosis, her younger brother was diagnosed and transplanted at the presymptomatic state. We describe patients' clinical, biochemical, and genetic features, as well as neuropsychological and neurophysiological test results, and brain magnetic resonance imaging from pretransplantation and posttransplantation assessments. Both patients converted to complete donor chimerism and arylsulfatase A levels normalized 3 months posttransplantation. Twelve months posttransplantation, neurological and neuropsychological assessment for both patients showed stabilization, and they remained stable for the 38 months long observation period. To assess the effect of HSCT used as treatment for the rare, adult MLD subtype on survival and stabilization, we performed a systematic literature review and included 7 studies with a total of 26 cases. Of these 26 cases, 6 patients died of HSCT‐related complications and 2 patients had graft rejection. Of the remaining 18 patients, 2 patients improved after HSCT, 13 patients stabilized, and 3 patients progressed, suggesting that HSCT potentially benefits adult MLD patients. Larger studies focusing on this subtype are needed and recommendations on criteria for HSCT in adult MLD need to be evolved.
Analytical modeling and optimization of new Ku‐band tunable square waveguide iris‐post polarizer
Authors: Piltyay Stepan , Bulashenko Andrew , Sushko Oleksandr , Bulashenko Oleksandr , Demchenko Ivan 
Published: May 2021

AbstractA novel design of the polarizer based on a square waveguide with four posts and four irises for Ku‐band 10.7–12.8 GHz is proposed. The main advantage of the developed polarizer design is the option to tune its polarization characteristics by variation of the posts height. The equivalent circuit of the polarizer has been obtained using scattering and transfer matrices technique. Using this model, the polarization and matching characteristics of the suggested polarizer were optimized simultaneously using the trust region method. This method is reliable and robust since it provides good convergence properties. The novelty of this study lies in the use of a new waveguide polarizer structure based on a combination of irises and posts. Posts enable fine‐tuning of the polarizer performance, while irises promote wide operating frequency band. The following simulated characteristics of the optimal polarizer design were obtained: VSWR for the main modes of horizontal and vertical polarization is less than 1.47, the differential phase shift is within 90° ± 2.6°, the axial is less than 0.46 dB, and the XPD is higher than 32 dB in the operating frequency range. A developed polarizer can be applied in antenna feeds for satellite communication and radar systems.