bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrophoretic deposition of lawsone loaded bioactive glass (BG)/chitosan composite on polyetheretherketone (PEEK)/BG layers as antibacterial and bioactive coating
Authors: Ur Rehman Muhammad Atiq , Bastan Fatih Erdem , Nawaz Qaisar , Goldmann Wolfgang H. , Maqbool Muhammad , Virtanen Sannakaisa , Boccaccini Aldo R. 
Published: September 2018

AbstractIn this study, chitosan/bioactive glass (BG)/lawsone coatings were deposited by electrophoretic deposition (EPD) on polyetheretherketone (PEEK)/BG layers (previously deposited by EPD on 316‐L stainless steel) to produce bioactive and antibacterial coatings. First, the EPD of chitosan/BG/lawsone was optimized on stainless steel in terms of suspension stability, homogeneity and thickness of coatings. Subsequently, the optimized EPD parameters were used to produce bioresorbable chitosan/bioactive glass (BG)/lawsone coatings on PEEK/BG layers. The produced layered coatings were characterized in terms of composition, microstructure, corrosion resistance, in vitro bioactivity, drug release kinetics and antibacterial activity. Ultraviolet/Visible (UV/VIS) spectroscopic analyses confirmed the release of lawsone from the coatings. Moreover, the deposition of chitosan/BG coatings was confirmed by Scanning Electron Microscopy (SEM) and Fourier Transform Infrared spectroscopy (FTIR). The coated specimens presented higher corrosion resistance (10 times) in comparison to that of bare 316‐L stainless steel and showed convenient wettability for initial protein attachment. The presence of lawsone in the top layer provided antibacterial effects againstStaphylococcus carnosus.Moreover, the developed coatings formed apatite‐like crystals upon immersion in simulated body fluid, indicating the possibility of achieving close interaction between the coating surface and bone. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3111–3122, 2018.
Acute Tissue Mineral Deposition in Response to a Phosphate Pulse in Experimental CKD
Authors: Zelt Jason GE , Svajger Bruno A , Quinn Kieran , Turner Mandy E , Laverty Kimberly J , Shum Bonnie , Holden Rachel M , Adams Michael A 
Published: September 2018

ABSTRACT

Pathogenic accumulation of calcium (Ca) and phosphate (PO4) in vasculature is a sentinel of advancing cardiovascular disease in chronic kidney disease (CKD). This study sought to characterize acute distribution patterns of radiolabeled 33PO4 and 45Ca in cardiovascular tissues of rats with CKD (0.25% dietary adenine). The disposition of 33PO4 and 45Ca was assessed in blood and 36 tissues after a 10-minute intravenous infusion of one of the following: (i) PO4 pulse + tracer 33PO4; (ii) PO4 pulse + tracer 45Ca; or (iii) saline + tracer 45Ca in CKD and non-CKD animals. After the infusion, 33PO4 in blood was elevated (2.3× at 10 minutes, 3.5× at 30 minutes, p &lt; 0.05) in CKD compared with non-CKD. In contrast, there was no difference in clearance of 45Ca from the blood. Compared with controls, CKD rats had a markedly increased 33PO4 incorporation in several tissues (skeletal muscle, 7.8×; heart, 5.5×), but accrual was most pronounced in the vasculature (24.8×). There was a significant, but smaller, increase in 45Ca accrual in the vasculature of CKD rats (1.25×), particularly in the calcified rat, in response to the acute phosphate load. Based on the pattern of tissue uptake of 33PO4 and 45Ca, this study revealed that an increase in circulating PO4 is an important stimulus for the accumulation of these minerals in vascular tissue in CKD. This response is further enhanced when vascular calcification is also present. The finding of enhanced vascular mineral deposition in response to an acute PO4 pulse provides evidence of significant tissue-specific susceptibility to calcification. © 2018 American Society for Bone and Mineral Research.
TIMP Loss Activates Metalloproteinase-TNFα-DKK1 Axis To Compromise Wnt Signaling and Bone Mass
Authors: Chen Yan , Aiken Alison , Saw Sanjay , Weiss Ashley , Fang Hui , Khokha Rama 
Published: September 2018

ABSTRACT

Deregulated proteolysis invariably underlies most human diseases including bone pathologies. Metalloproteinases constitute the largest of the five protease families, and the metzincin metalloproteinases are inhibited by the four tissue inhibitors of metalloproteinase called TIMPs. We hypothesized that Timp genes are essential for skeletal homeostasis. We bred individual Timp knockout mice to generate unique mouse models, the quadruple Timp null strain (QT) as well as mice harboring only a single Timp3 allele (QT3+/–). QT mice are grossly smaller and exhibit a dramatic reduction of trabeculae in long bones by μCT imaging with a corresponding increase in metalloproteinase activity. At the cellular level, Timp deficiency compromised differentiation markers, matrix deposition and mineralization in neonatal osteoblasts from calvariae, as well as the fibroblastic colony-forming unit (CFU-F) capacity of bone marrow–derived stromal cells. In contrast, we observed that osteoclasts were overactive in the Timp null state, consistent with the noted excessive bone resorption of QT bones. Immunohistochemistry (IHC) and immunofluorescence (IF) analyses of bone sections revealed higher Cathepsin K and RANKL signals upon Timp loss. Seeking the molecular mechanism, we identified abnormal TNFα bioactivity to be a central event in Timp-deficient mice. Specifically, TNFα triggered induction of the Wnt signaling inhibitor Dkk1 in the osteoblasts at the mRNA and protein levels, with a simultaneous increase in RANKL. Neutralizing TNFα antibody was capable of rescuing the induction of Dkk1 as well as RANKL. Therefore, the generation of novel Timp-deficient systems allowed us to uncover the essential and collective function of TIMP proteins in mammalian long-bone homeostasis. Moreover, our study discovers a functional TIMP/metalloproteinase-TNFα-Dkk1/RANKL nexus for optimal control of the bone microenvironment, which dictates coexistence of the osteoblast and osteoclast lineages. © 2018 American Society for Bone and Mineral Research.
Effect of sitagliptin, a DPP‐4 inhibitor, against DENA‐induced liver cancer in rats mediated via NF‐κB activation and inflammatory cytokines
Authors: Jiang Weidong , Wen Dacheng , Cheng Zhaohua , Yang Yongsheng , Zheng Ge , Yin Fangying 
Published: September 2018

AbstractThe target of the current research was to investigate the anticancer activity of sitagliptin on diethylnitrosamine (DENA)‐induced cancer in the liver. Wistar rats were treated with or without sitagliptin before DENA treatment. We detected liver weight, blood glucose, and histopathology of the liver. Serum biochemical markers like serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), serum alkaline phosphatase (SALP), gamma‐glutamyl transpeptidase (GGTP), total bilirubin (TBR), total protein (TPR), and albumin (ALB) were also evaluated. In addition, lipid profile parameters comprising total cholesterol (TC), triglycerides, and high‐density lipoprotein were also measured. Inflammatory mediators like interleukin‐6 (IL‐6), interleukin‐1beta (IL‐1β), and tumor necrosis factor‐alpha (TNF‐α) were determined in liver homogenate. Furthermore, the activity of nuclear factor (NF‐κB) was also measured. Our results showed that sitagliptin (10 and 20 mg/kg) in a dose‐dependent manner expressively decreased the DENA‐induced elevation of SGPT, SGOT, SALP, and GGTP. Whereas sitagliptin (10 and 20 mg/kg) in a dose‐dependent mode reduced the level of TBR and increased the TPR and ALB as well as improved the liver histopathology alterations in DENA‐exposed rats. Lipid profile was also restored by the sitagliptin (10 and 20 mg/kg) in a DENA‐treated rats. The level of IL‐1β, IL‐6, and TNF‐α were suggestively suppressed. Moreover, pretreatment with sitagliptin (10 and 20 mg/kg) prevented the activation of NF‐κB. In conclusion, sitagliptin (10 and 20 mg/kg) has a potential protective effect against DENA‐induced liver cancer by inhibition of inflammation and NF‐κB activation.
Retracted: microRNA‐542‐5p protects against acute lung injury in mice with severe acute pancreatitis by suppressing the mitogen‐activated protein kinase signaling pathway through the negative regulation of P21‐activated kinase 1
Authors: Wu Xing‐Mao , Ji Kai‐Qiang , Wang Hai‐Yuan , Zhao Yang , Jia Jia , Gao Xiao‐Peng , Zang Bin 
Published: September 2018

AbstractSevere acute pancreatitis (SAP) is a condition associated with high rates of mortality and lengthy hospital stays. In the current study, SAP mouse models were established in BALB/c wild‐type and P21‐activated kinase 1 (PAK1) knockdown mice with the objective of determining the expression of microRNA‐542‐5p (miR‐542‐5p) and the subsequent elucidation of the mechanism by which it influences acute lung injury (ALI) by mediating mitogen‐activated protein kinase (MAPK) signaling and binding to PAK1.The targeting relationship between miR‐542‐5p and PAK1 was verified using the bioinformatics prediction website and by the means of a dual‐luciferase reporter assay. Following the SAP model establishment, the mice were assigned into various groups with the introduction of different mimic and inhibitors in an attempt to investigate the effects involved with miR‐542‐5p on inflammatory reactions among mice with SAP‐associated ALI. Our results indicated that PAK1 was targeted and negatively mediated by miR‐542‐5p. Mice with SAP‐associated ALI exhibited an increased wet‐to‐dry weight ratio, myeloperoxidase activity, serum amylase activity, TNF‐α, interleukin‐1 beta (IL‐1β), and intercellular adhesion molecule‐1 (ICAM‐1) contents, p‐p38MAPK, p‐ERK1/2, and p‐JNK protein levels as well as PAK1 positive expression, while decreased miR‐542‐5p levels were observed. Functionally, overexpression of miR‐542‐5p improves ALI in mice with SAP via inhibition of the MAPK signaling pathway by binding to PAK1.Based on the evidence from experimental models, miR‐542‐5p was shown to improve ALI among mice with SAP, while suggesting that the effect may be related to the inactivation of the MAPK signaling pathway and downregulation of PAK1 gene. Thus, miR‐542‐5p could serve as a promising target for ALI treatment.
Nitric oxide inhibits hypoxia‐induced impairment of human RBC deformability through reducing the cross‐linking of membrane protein band 3
Authors: Zhao Yajin , Wang Xiang , Wang Ruofeng , Chen Dong , Noviana Milody , Zhu Hongliang 
Published: September 2018

AbstractAimNitric oxide (NO) prevents the decline of RBC deformability under high altitude and other ischemic and hypoxic conditions, but the clear mechanisms remain unknown. Here, we have carried out a systematic study to find the mechanisms of NO‐induced regulation of RBC deformability under hypoxia.MethodsNO levels, RBCs membrane elongation index (EI), membrane protein band 3 methemoglobin (MetHb) were determined during hypoxia (0 to 120 minutes). To validate the role of NO in regulating RBC deformability, tests were also performed with a NO donor (sodium nitroprusside) or a NO synthase inhibitor (l‐nitro‐arginine methylester) under 60 minutes hypoxia.ResultsHypoxia for 45 minutes increased NO levels from 25.65 ± 1.95 to 35.26 ± 2.01 μmol/L, and there was a plateau after 60 minutes hypoxia. The EI did not change before 45 minutes hypoxia, but decreased from 0.567 ± 0.019 to 0.409 ± 0.042 (30 Pa) after 60 minutes hypoxia. The cross‐linking of band 3 and phosphotyrosine increased after 45 minutes hypoxia. All can be alleviated by supplement NO and aggregated by inhibiting NOS. However, the MetHb was not present this trend.ConclusionNO may prevent decreased of RBCs deformability through reducing the cross‐linking of membrane band 3 under hypoxia; this helps microvascular perfusion of RBCs during ischemic and hypoxic disease states.
Retracted: Suppression of BMX‐ARHGAP fusion gene inhibits epithelial‐mesenchymal transition in gastric cancer cells via RhoA‐mediated blockade of JAK/STAT axis
Authors: Xu Xiao‐Feng , Wang Jian‐Jiang , Ding Li , Ye Jin‐Song , Huang Li‐Juan , Tao Lan , Gao Feng , Ji Yong 
Published: September 2018

AbstractGastric cancer (GC) is one of the main causes of cancer‐related mortality worldwide. Epithelial‐mesenchymal transition (EMT) is an important biological process involving the process by which malignant tumor cells obtain the ability of migration, invasion, resistance of apoptosis, and degradation in the extracellular matrix. The current study aimed at investigating whether bone marrow X kinase Rho GTPase activating protein 12 (BMX‐ARHGAP) fusion gene affects GC. First, short hairpin RNA (shRNA) against BMX‐ARHGAP or BMX‐ARHGAP were introduced to treat SGC‐7901 cells with the highest BMX‐ARHGAP among the five GC cell lines (SGC‐7901, MKN‐45, NCI‐N87, SNU‐5, and AGS). Next, cell vitality, drug resistance, migration, and invasion of SGC‐7901 cells, activities of Rho and JAK/STAT axis, as well as EMT and lymph node metastasis (LNM) were evaluated. The survival rate of the mice was then determined through the transfection of the specific pathogen‐free NOD‐SCID mice with treated SGC‐7901 cells. The results showed that BMX‐ARHGAP expression was associated with the infiltration degree of GC tumor and poor prognosis for patients with GC. BMX‐ARHGAP silencing was found to play an inhibitory role in the Rho and JAK/STAT axis to reduce cell vitality, drug resistance, migration and invasion, reverse EMT process, as well as inhibit LNM. BMX‐ARHGAP overexpression was observed to have induced effects on GC cells as opposed to those inhibited by BMX‐ARHGAP silencing. The survival rate of mice was increased after transfection with silenced BMX‐ARHGAP. These findings provided evidence that the suppression of BMX‐ARHGAP resulted in the inhibition of RhoA to restraint the development of GC cells by blocking the JAK/STAT axis.
Peroxisome proliferator‐activated receptor gamma coactivator‐1α/HSF1 axis effectively alleviates lipopolysaccharide‐induced acute lung injury via suppressing oxidative stress and inflammatory response
Authors: Dang Xingbo , Du Gongliang , Hu Wei , Ma Longyang , Wang Pei , Li Yi 
Published: September 2018

AbstractAcute lung injury (ALI) interferes with lung function by causing pulmonary inflammation and oxidative stress. Suppressing intracellular reactive oxygen species (ROS) may block intracellular inflammation. Thus, the purpose of the current study was to investigate the roles of peroxisome proliferator‐activated receptor gamma coactivator‐1α (PGC1α)/HSF1 axis in an lipopolysaccharide (LPS)‐induced ALI murine model and in RAW264.7 macrophages. In the LPS‐administrated mouse model, the addition of PGC1α obviously ameliorated secretion of pro‐inflammatory mediators tumor necrosis factor‐α and Interleukin 6 as well as MCP‐1 expression triggered by LPS stimulation, accompanied with reduced infiltration of inflammatory cells. Meanwhile, introduction of PGC1α strongly diminished the expression of cyclooxygenase‐2 and inducible nitric oxide synthase as well as their products PGE2 and NO. In addition, administering PGC1α also dramatically alleviated LPS‐triggered oxidative stress, as reflected by a reduction of ROS production, and also reduced malondialdehyde and O
2 content, concomitant with enhancement of superoxide dismutase, catalase, and glutathione peroxidase. Similarly, PGC1α effectively ameliorated LPS‐induced inflammation response and oxidative stress, as exemplified by reduced pro‐inflammatory cytokines and ROS production in LPS‐induced RAW264.7 macrophages. Interestingly, PGC1α modulated the expression of HSF1 and the transcriptional activity of X‐linked inhibitor of apoptosis (XIAP)‐associated factor 1, whereas silencing of HSF1 abolished these effects. More importantly, deletion of HSF1 impeded the anti‐inflammatory and anti‐oxidant effects of PGC1α in LPS‐induced macrophages. Taken together, PGC1α/HSF1 axis have an anti‐oxidant and anti‐inflammatory effects, indicating that PGC1α/HSF1 may protect against LPS‐induced ALI, and thus may be a promising therapy to treat ALI.
FOXO1 associated with sensitivity to chemotherapy drugs and glial‐mesenchymal transition in glioma
Authors: Chen Chao , Han Guosheng , Li Yanan , Yue Zhijian , Wang Laixing , Liu Jianmin 
Published: September 2018

AbstractMesenchymal subtype of glioblastoma (GBM), identified as one of four clinically relevant molecular subtypes, has worst prognosis because of its close relation with the malignant biological properties induced by glial‐mesenchymal transition (GMT). However, the molecular mechanism of GMT and its characterized molecule of GBM have not been studied. Forkhead box protein O1 (FOXO1) is at a convergence point of receptor tyrosine kinase signaling as one of the three core pathways implicated in GBM. Our previous study indicated that the inactivation of FOXO1 involved in the inhibition of GMT is an independent prognosis factor of GBM. In this study, we will further confirm the role of FOXO1 in GMT through cytological experiments to clarify how FOXO1 regulates GMT and its clinical significance. We established virus‐infected FOXO1 overexpression and FOXO1 knockdown cells of U373 MG and U251 mediated by lentivirus, based on the effect of which FOXO1‐correlated‐GMT experiments were performed in vitro and in vivo. Our data suggested that FOXO1 played a crucial role in resistance to TMZ, BCNU, and CDDP; migration and invasion; and stem cell properties of glioma cells. FOXO1 may serve as a targeted biomarker for prediction of sensitivity to chemotherapy drugs, metastasis, and prognosis, which provides a new idea for mesenchymal GBM treatment.
Interleukin‐1β/nuclear factor‐κB signaling promotes osteosarcoma cell growth through the microRNA‐181b/phosphatase and tensin homolog axis
Authors: Wang Weiguo , Wang Zhengguang , Chen Shijie , Zang Xiaofang , Miao Jinglei 
Published: September 2018

AbstractSo far, microRNA has attracted plenty of interest due to its role in tumorigenesis. Reportedly, miR‐181b may be involved in the tumorigenesis of osteosarcoma (OS). In the current study, we attempted to investigate the detailed function and mechanism of miR‐181b in OS carcinogenesis. Herein, miR‐181a, miR‐181b, miR‐181c, and miR‐181d expressions in OS tissues were higher than that in nontumor tissue samples as examined real‐time polymerase chain reaction. Via direct targeting, miR‐181b negatively regulated the expression of phosphatase and tensin homolog (PTEN), a well‐known tumor suppressor. Furthermore, a small interfering RNA strategy was used to find that interleukin (IL)‐1B and nuclear factor‐κB (NF‐κB) regulate miR‐181b and PTEN expression. Consequently, the repression of PTEN by miR‐181b promotes OS cell proliferation. In summary, our data support a critical role for NF‐κB‐dependent upregulation of miR‐181b, which further inhibited PTEN expression and promoted the cell proliferation of OS cell lines. The above findings represent a new pathway for the repression of PTEN and the promotion of cell proliferation upon IL‐1β induction.
Let‐7g inhibits synthesis of estradiol by downregulating activity of aromatase in JEG3 cells
Authors: Guan Yong‐Hong , Lu Ying‐Li , Wang Yi‐Nan , Xue Kai 
Published: September 2018

AbstractBackgroundIncreased production of estrogen in human placenta during pregnancy closely associates with parturition. Aromatase, encoded by CYP19A1 gene, is an enzyme critical for biosynthesis of estrogen. Despite numerous efforts in the past few decades ascribed to characterizing the mechanisms of transcriptional control of aromatase, the posttranscriptional control of CYP19A1 remains poorly understood.ObjectiveIn this study, we sought to investigate the role of microRNA, let‐7g, in posttranscriptional regulation of aromatase in human trophoblast choriocarcinoma cell line, JEG3.Methods and resultsWe show that the expression of let‐7g was downregulated in JEG3 cell line, but upregulated in primary term trophoblast; conversely, aromatase was upregulated in JEG3 but downregulated in primary trophoblast. We further show that let‐7g antagomirs and mimics increased and decreased aromatase expression, respectively; and let‐7g directly targeted 3′‐untranslated region of CYP19A1 mRNA by using dual luciferase assay. Using ELISA, we also demonstrate that let‐7g antagomirs and mimics robustly increased and decreased production of estradiol, respectively.DiscussionOur results suggest that aromatase expression is regulated at multiple molecular layers in the placenta. These results further suggest that JEG3 cell line is a valuable tool to study additional mechanisms associated with human birth.
ROS‐challenged keratinocytes as a new model for oxidative stress‐mediated skin diseases
Authors: Barygina Victoria , Becatti Matteo , Lotti Torello , Moretti Silvia , Taddei Niccolò , Fiorillo Claudia 
Published: September 2018

AbstractIn the current study, the effects of the reactive oxygen species (ROS) generator 2,2′‐azobis(2‐amidinopropane) dihydrochloride (AAPH) on extracellular and intracellular ROS production in human keratinocytes (HACAT) were studied. AAPH is a water‐soluble compound able to generate ROS at known and constant rates at 37°C. The short treatment (2 h) with AAPH brought a significant dose‐dependent increase in NADPH oxidase activity in intact keratinocytes. The long‐term treatment (24 h) with AAPH led to a persistent increase in NADPH oxidase activity for up to 48 hour following the AAPH removal from cell incubation medium. ROS and nitric oxide levels, lipoperoxidation, intracellular calcium, mitochondrial superoxide production, and membrane potential were significantly modified in AAPH‐treated HACAT. Superoxide dismutase (SOD) and/or catalase addition to HACAT revealed that untreated keratinocytes produce mostly superoxide anion (O
2
−), while AAPH‐treated keratinocytes overproduce hydrogen peroxide (H
2O
2) in extracellular medium. H
2O
2 is particularly stable and plays important roles in several cell signaling pathways. Taken together, our findings suggest a cost‐effective and easily reproducible in vitro model of stressed human keratinocytes releasing significantly elevated ROS amounts in extracellular medium with respect to control keratinocytes. The possible application of the proposed model for keratinocytes‐melanocytes cross‐talk studies is also suggested. The model of AAPH‐stressed human keratinocytes described here can represent a useful tool for redox cross‐talk studies between keratinocytes and other skin cell types, and applied for researches regarding skin pathologies associated with oxidative stress.