bluuebunny/crossref_metadata_2025 huggingface dataset:
Directional coupling of oligodendrocyte connexin‐47 and astrocyte connexin‐43 gap junctions
Authors: Fasciani Ilaria , Pluta Paula , González‐Nieto Daniel , Martínez‐Montero Paloma , Molano Jesús , Paíno Carlos L. , Millet Oscar , Barrio Luis C.
Published: August 2018

Intercellular communication via gap junction channels between oligodendrocytes and between astrocytes as well as between these cell types is essential to maintain the integrity of myelin in the central nervous system. Oligodendrocyte gap junction connexin‐47 (Cx47) is a key element in this crosstalk and indeed, mutations in human Cx47 cause severe myelin disorders. However, the permeation properties of channels of Cx47 alone and in heterotypic combination with astrocyte Cx43 remain unclear. We show here that Cx47 contains three extra residues at 5′ amino‐terminus that play a critical role in the channel pore structure and account for relative low ionic conductivity, cationic permselectivity and voltage‐gating properties of oligodendrocyte‐oligodendrocyte Cx47 channels. Regarding oligodendrocyte‐astrocyte coupling, heterotypic channels formed by Cx47 with Cx43 exhibit ionic and chemical rectification, which creates a directional diffusion barrier for the movement of ions and larger negatively charged molecules from cells expressing Cx47 to those with Cx43. The restrictive permeability of Cx47 channels and the diffusion barrier of Cx47‐Cx43 channels was abolished by a mutation associated with leukodystrophy, the Cx47P90S, suggesting a novel pathogenic mechanism underlying myelin disorders that involves alterations in the panglial permeation.
SOX17 transcription factor negatively regulates oligodendrocyte precursor cell differentiation
Authors: Fauveau Melissa , Wilmet Baptiste , Deboux Cyrille , Benardais Karelle , Bachelin Corinne , Temporão Ana C. , Kerninon Christophe , Nait Oumesmar Brahim
Published: August 2018

Oligodendrocyte development is a critical process timely and spatially regulated to ensure proper myelination of the central nervous system. HMG‐box transcription factors are key regulators of oligodendrocyte lineage progression. Among these factors, Sox17 was previously identified as a positive regulator of oligodendrocyte development. However, the role of Sox17 in oligodendroglial cell lineage progression and differentiation is still poorly understood. To define the functional role of Sox17, we generated new transgenic mouse models with inducible overexpression of Sox17, specifically in oligodendroglial cells. Here, we report that gain of Sox17 function has no effect on oligodendrocyte progenitor cells (OPCs) specification. During early postnatal development, Sox17 overexpression increases the pool of OPCs at the expense of differentiated oligodendrocytes. However, the oligodendroglial cell population, OPC proliferation and apoptosis remained unchanged in Sox17 transgenic mice. RNA sequencing, quantitative RT‐PCR and immunohistochemical analysis showed that Sox17 represses the expression of the major myelin genes, resulting in a severe CNS hypomyelination. Overall, our data highlight an unexpected role for Sox17 as a negative regulator of OPC differentiation and myelination, suggesting stage specific functions for this factor during oligodendroglial cell lineage progression.
Renewed interest for low‐dose radiation therapy in follicular lymphomas: From biology to clinical applications
Authors: Ciammella Patrizia , Luminari Stefano , Arcaini Luca , Filippi Andrea Riccardo
Published: August 2018

Follicular lymphoma (FL) is the most common subtype of indolent non‐Hodgkin lymphoproliferative disorders. Treatment strategies for FL may include several therapeutic choices, ranging from a “watchful waiting” approach to stem cell transplantation, mostly depending on staging, age, risk factors, and disease burden at diagnosis. The high radiosensitivity of FL compared with other solid tumors has been known since the beginning of radiotherapy treatment in lymphoma patients. Doses of 24 to 40 Gy were considered appropriate in first line curative treatment for localized disease (stages I‐II), but several publications investigating low‐dose radiotherapy (LDRT) of 4Gy (2 × 2Gy) reported an overall response rate surprisingly high. Due to its high local efficacy and negligible toxicity, LDRT might be offered to both early and advanced stage FL patients in combination with new agents, at diagnosis or after several lines of systemic therapy. The aim of this review is to summarize and discuss the current knowledge on LDRT for FL and its potential application in a curative setting in combination with new drugs for both early and advanced disease.
HIV/AIDS and economic growth: Evidence from West Africa
Authors: Dauda Rasaki Stephen
Published: August 2018

Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is one of the leading causes of morbidity and mortality in West Africa. Prevalence among the most productive age group in West and Central Africa stood at 1.5%, 3.4.0%, 2.5%, and 2.1% in 1990, 2000, 2010, and 2015 respectively. This study examined the effect of HIV/AIDS on economic growth in West Africa with focus on 11 countries. The augmented Solow model, rooted in the neoclassical growth theory, was used, which was operationalized using dynamic panel data modeling approach. Incidence, prevalence, number of people living with HIV/AIDS (PLWHA), and AIDS‐related deaths were used to measure HIV/AIDS. Estimations using system GMM returned statistically significant results while those of first difference and difference GMM were not. From the outcome of system GMM analysis, a percentage increase in incidence, prevalence, PLWHA, and AIDS deaths correspondingly reduced growth significantly through their effects on life expectancy by 0.15%, 0.02%, 0.004%, and 0.03%. Acquired immune deficiency syndrome deaths and PLWHA lowered economic growth through enrolment but not significantly. The import of the findings is that HIV/AIDS threatens growth through life expectancy in West Africa. Therefore, its spread in the subregion should be effectively contained while proper treatment should be provided for all infected persons.
A totally recombinant fibrin matrix for mesenchymal stem cell culture and delivery
Authors: Wang Ou , Ismail Ayman , Fabian Frank Marco , Lin Haishuang , Li Qiang , Elowsky Christian , Carlson Mark A. , Burgess Wilson , Velander William H. , Kidambi Srivatsan , Lei Yuguo
Published: August 2018

Mesenchymal stem cells (MSCs) have been widely studied for tissue engineering and treating diseases in laboratories, clinical trials, and clinics. Fibrin matrices are often used to culture MSCs or increase the retention of MSCs at the injection site. However, fibrins made with the human plasma derived fibrinogen have high cost and risk of human pathogen transmission. In this article, we studied if fibrin matrices made with recombinant human fibrinogen, recombinant human thrombin, and recombinant human factor XIII could be used to culture and deliver MSCs. We systematically investigated the relationships between the fibrin matrix formulation, its nanostructure, and the behaviors of the cells in the matrix including the cell morphology, viability, and growth. We found that the fibrinogen concentration significantly affected the matrix structure and cell behaviors. We then used an optimized fibrin matrix to deliver human MSCs into mice subcutaneously. We found that the matrix could significantly enhance the retention of MSCs at the injection site. To our best knowledge, this is the first study on using fibrin matrices made with entirely recombinant proteins for culturing and delivering MSCs. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3135–3142, 2018.
Retracted: Upregulated microRNA‐485 suppresses apoptosis of renal tubular epithelial cells in mice with lupus nephritis via regulating the TGF‐β‐MAPK signaling pathway by inhibiting RhoA expression
Authors: Tian Yu , Han Yu‐Xiang , Guo Hui‐Fang , Jin Hong‐Tao , Sun Chao , Qi Xuan , Ma Li‐Yan , Bo Shi‐Wei
Published: August 2018

Lupus nephritis (LN) is a common and severe complication of systemic lupus erythematosus. Without intervention, LN may cause acute kidney injury and end‐stage renal disease. This study aims to determine whether microRNA‐485 (miR‐485) affects renal tubular epithelial cells (RTECs) in LN mice via the TGF‐β‐MAPK signaling pathway by targeting RhoA. Renal tissue samples were initially extracted from 15 LN and 15 normal mice. RTECs were cultivated in vitro and grouped after transfection of different mimics, inhibitors, or siRNA‐
RhoA. The target gene of miR‐485 was confirmed by dual‐luciferase reporter assay. Flow cytometry and MTT assay were applied to detect cell viability and apoptosis. It was determined that RhoA was a target gene of miR‐485. We found that urine protein, creatinine, RhoA, interleukin 6 (IL‐6), transforming growth factor‐β1 (TGF‐β1), and p38 mitogen‐activated protein kinases (p38MAPK) were highly expressed in renal tissues of LN mice, while poor levels of miR‐485 were recorded. The overexpression of miR‐485 or siRNA‐
RhoA or the combination of miR‐485 and siRNA‐
RhoA was demonstrated to lead to a reduction of levels of RhoA, IL‐6, TGF‐β, and p38MAPK, as well as a promotion of RTECs proliferation and inhibition of RTECs apoptosis. Taken together, these findings indicated that overexpressed miR‐485 downregulates RhoA which could promote cell viability and inhibit apoptosis of RTECs by regulating the RhoA‐mediated TGF‐β‐MAPK signaling pathway in LN mice.
Retracted: Downregulation of long noncoding RNA Sox2ot protects PC‐12 cells from hydrogen peroxide–induced injury in spinal cord injury via regulating the miR‐211‐myeloid cell leukemia‐1 isoform2 axis
Authors: Yin Dong , Zheng Xiaoqing , Zhuang Jianxiong , Wang Liangze , Liu Bin , Chang Yunbing
Published: August 2018

This study aimed to investigate the effects and possible mechanisms of long noncoding RNA (lncRNA) Sox2 overlapping transcript (Sox2ot) on hydrogen peroxide (H2O2)‐induced injury in pheochromocytoma (PC‐12) cells. PC‐12 cells were treated with H2O2 to cell injury. The cells were transfected with short‐hairpin RNA directed against Sox2ot (sh‐Sox2ot), small interfering RNA directed against myeloid cell leukemia‐1 (MCL‐1) isoform2 (si‐MCL‐1), a miR‐211 mimic, a miR‐211 inhibitor, and their negative controls. Under different transfected treatments, cell viability, migration, invasion, and apoptosis as well as the expressions of apoptosis‐ and autophagy‐related proteins were investigated. Besides, the regulatory relationships between Sox2ot and miR‐211, miR‐211 and MCL‐1, as well as between MCL‐1 and the protein kinase B (Akt)/mammalian target of the rapamycin (mTOR)/p70 ribosomal S6 protein kinase (p70S6K) signaling pathway were explored. Suppression of Sox2ot inhibited H2O2‐induced PC‐12 cell injury by increasing cell viability, migration, invasion, and decreasing apoptosis and autophagy. Moreover, suppression of Sox2ot increased miR‐211 expression and alleviated H2O2‐induced injury in PC‐12 cells possibly via upregulation of miR‐211. Furthermore, MCL‐1 isoform2 was identified as a direct target of miR‐211 and could be negatively regulated by miR‐211. Suppression of miR‐211 aggravated H2O2‐induced cell injury by regulation of MCL‐1 isoform2. Besides, inhibition of miR‐211 suppressed the activation of the Akt/mTOR/p70S6K signaling pathway in H2O2‐treated PC‐12 cells, which was reversed after knockdown of MCL‐1 isoform2 at the same time. Our findings indicate that downregulation of Sox2ot may protect PC‐12 cells from H2O2‐induced injury in SCI via targeting the miR‐211/MCL‐1 isoform2 axis. MCL‐1 isoform2 may further regulate the activation of the Akt/mTOR/p70S6K pathway to mediate H2O2‐induced injury. The Sox2ot‐miR‐211‐MCL‐1 isoform2 axis may be a promising therapeutic strategy for SCI.
Inhibition of cyclin‐dependent kinase 7 suppresses human hepatocellular carcinoma by inducing apoptosis
Authors: Zhong Liqiang , Yang Sihao , Jia Yuming , Lei Kaijian
Published: August 2018

Increasing evidence has shown that THZ1, a covalent cyclin‐dependent kinase 7 (CDK7) inhibitor, exhibits therapeutic effects in various tumors. However, the possible effect of THZ1 on hepatocellular carcinoma (HCC) remains unknown. Our study was to investigate the roles of THZ1 in HCC cells and in subcutaneous HCC model and illustrate the molecular mechanisms. The phosphorylation levels of Ser2, Ser5, and Ser7 within RNA polymerase II (RNAPII) C‐terminal domain (CTD) and the expression levels of Ki67, Mcl‐1, survivin, XIAP, and p53 in HCC cells under different conditions were examined by Western blot analysis. Cell growth and apoptosis were assessed via 3‐(4,5‐dimethylthiazolyl‐2)‐2, 5‐diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis, respectively. Tumor volume was assessed in HCC mice with THZ1 or vehicle treatment and immunohistochemical (IHC) analysis was conducted on excised tumors. THZ1 significantly inhibited the phosphorylation of Ser2, Ser5, and Ser7 within RNAPII‐CTD in the dose‐dependent and irreversible manner. MTT assay and flow cytometry analysis showed that THZ1 inhibited HCC cell proliferation and induced apoptosis, respectively. Western blot analysis indicated THZ1 significantly upregulated p53 expression and downregulated the expressions of Mcl‐1, survivin, XIAP, and Ki67. THZ1 suppressed tumor growth in Hep3B xenografted mice in a time‐dependent manner. IHC analysis indicated that tumors in THZ1 group had less Ki67+ cells and more cleaved caspase‐3+ cells than those in vehicle group. THZ1 exhibited anti‐HCC effects through irreversibly inhibiting CDK7 activity, decreasing RNAPII‐CTD phosphorylation, inducing p53 expression and inhibiting antiapoptotic gene expressions, which subsequently induced apoptosis and inhibited proliferation of HCC cells.
Effects of telomerase inhibitor on epigenetic chromatin modification enzymes in malignancies
Authors: Biray Avci Cigir , Dogan Fatma , Ozates Ay Neslihan Pinar , Goker Bagca Bakiye , Abbaszadeh Zeka , Gunduz Cumhur
Published: August 2018

Telomerase has a critical role in cell proliferation, tumor maintaining, and therapy resistance, which act by modifying many signaling pathways. 2‐[(E)‐3‐Naphtalen‐2‐yl‐but‐2‐enoylamino]‐benzoic acid (BIBR1532) is one of the most studied telomerase inhibitors, and it targets telomerase components TERC and TERT. In this novel study, we aimed to investigate the epigenetic effects of BIBR1532 on both hematologic malignancies and solid tumors. K‐562 human chronic myeloid leukemia cell line and U87MG glioblastoma cell line were compared with control groups without BIBR1532 treatment. Cytotoxic effects of BIBR1532 were determined by using WST‐1 assay. Apoptotic effects of BIBR1532 were detected by using annexin V method. To assess expression changes in the human epigenetic chromatin modification enzyme genes, total RNA was isolated from K‐562 and U87MG cells treated with BIBR1532 and untreated control cells. BIBR1532 induced 2.41‐fold apoptotic cell death in U87MG cell lines compared with control groups. Apoptosis was slightly induced in K‐562 cells with BIBR1532 treatment compared with control cells. We observed that BIBR1532 also regulates similar genes in both cell lines, and it is useful on epigenetic mechanisms. As a result, telomerase inhibitor BIBR1532 has a significant effect on both hematological malignancies and solid tumors.
RNA sequencing and bioinformatics analysis of the long noncoding RNA–mRNA network in colorectal cancer
Authors: Zhang Zheying , Jia Huijie , Gu Tengteng , Hu Qing , Yu Jian , Zang Dan , Song Na , Wang Haijun
Published: August 2018

Long noncoding RNA (lncRNA) plays an important regulatory role in tumorigenesis. This study aims to analyze the lncRNA–messenger RNA (mRNA) expression network and potential roles in colorectal cancer (CRC). The LncRNA expression profile was analyzed in CRC tissue by RNA sequencing and the functions of differentially expressed genes were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The lncRNA‐mRNA network was predicted with bioinformatics. From the result, we identified 485 differential expression lncRNAs and 2383 mRNAs in CRC, GO, and KEGG analyses showed that the changes in lncRNAs were mainly associated with metabolism and transcription regulation that were different from mRNA function. Additionally, based on the predicted coexpression network, we identified that NONHSAT074176.2, downregulated in CRC tissue and cell lines, was a hub lncRNA in the development of CRC. Our results describe the lncRNA‐mRNA network in detail and indicate that lncRNA NONHSAT074176.2 may be useful as a candidate diagnostic biomarker and may be a promising therapeutic target for CRC.
LPS promotes the expression of PD‐L1 in gastric cancer cells through NF‐κB activation
Authors: Li Hui , Xia Jun‐Quan , Zhu Fang‐Shi , Xi Zhao‐Hong , Pan Cheng‐Yu , Gu Li‐Mei , Tian Yao‐Zhou
Published: August 2018

Gastric cancers are a group of highly aggressive malignancies with a huge disease burden worldwide. Gastric infections, such as helicobacter pylori, can induce the occurrence of gastric cancers. However, the role of gastric infection in gastric cancer development is unclear. Programmed death‐ligand 1 (PD‐L1, B7‐H1) is a member of the B7 family of cell surface ligands, which binds the PD‐1 transmembrane receptor and inhibits T‐cell activation within cancer tissues. It has been reported that the expression of PD‐L1 is inversely related to the prognosis of patients with gastric cancers. Therefore, the regulation of PD‐L1 expression in gastric cancers needs to be studied. In the current study, we explored the possible effects of lipopolysaccharide (LPS) on PD‐L1 expression in gastric cancer cells. We observed that LPS stimulation could markedly increase PD‐L1 expression in gastric cancer cells. Furthermore, we found that nuclear factor‐κB (NF‐κB) activation was involved in PD‐L1 expression in gastric cancer cells exposed to LPS stimulation through p65‐binding to the PD‐L1 promoter. Taken together, these data indicate that gastric infection might promote the development of gastric cancers thought the LPS‐NF‐κB‐PD‐L1 axis.
Imaging the interaction of αv integrin‐GFP in osteosarcoma cells with RFP‐expressing host stromal cells and tumor‐scaffold collagen in the primary and metastatic tumor microenvironment
Authors: Tome Yasunori , Kiyuna Tasuku , Uehara Fuminari , Bouvet Michael , Tsuchiya Hiroyuki , Kanaya Fuminori , Hoffman Robert M.
Published: August 2018

Human osteosarcoma 143B cells were previously stably transfected with an αv integrin green flourescent protein (GFP) vector. 143B cells expressing αv integrin‐GFP were transplanted orthotopically in the tibia of transgenic nude mice ubiquitously expressing red fluorescent protein (RFP). The primary tumors acquired RFP‐expressing stroma and were passaged orthotopically in the tibia in noncolored nude mice, which maintained the RFP stroma. The interaction of αv integrin‐GFP expression in 143B cells with RFP‐expressing host stromal cells was observed by confocal microscopy using the Olympus FV1000. Collagen fibers were imaged simultaneously in reflectance mode. The RFP‐expressing stroma included cancer‐associated fibroblasts (CAFs) and tumor‐associated macrophages (TAMs) which persisted even 3 weeks after passage to nontransgenic nude mice. CAFs expressing RFP were aligned between collagen fibers and cancer cells expressing αv integrin‐GFP. Six weeks after transplantation, pulmonary metastases expressing αv integrin‐GFP could be identified. TAMs expressing RFP accompanied metastasized osteosarcoma cells expressing αv integrin‐GFP in the lung. The current study demonstrates the importance of αv integrin interaction with stromal elements in osteosarcoma.
Long noncoding RNA MALAT1 downregulates cardiac transient outward potassium current by regulating miR‐200c/HMGB1 pathway
Authors: Zhu Peng , Yang Manli , Ren Hui , Shen Guidong , Chen Jinye , Zhang Junkang , Liu Jun , Sun Chaofeng
Published: August 2018

The dysregulation of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) participates in the remodeling of electrophysiological/ion channel in cardiomyocytes during arrhythmia. The lncRNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) is reported to be highly expressed in myocardial ischemia‐reperfusion injury and offsets cardioprotective effects of fentanyl. However, the roles of MALAT1 and its related miRNAs during arrhythmia are poorly understood. In this study, the overexpression of MALAT1 was firstly indicated in cardiomyocytes from arrhythmic model rats. After downregulation of MALAT1 by RNA interference, transient outward potassium current (Ito), peak current density, and the levels of Kv4.2 and Kv4.3 channel proteins were increased in rat cardiomyocytes. Then, miR‐200c was predicted and convinced to be a direct target of MALAT1, and high‐mobility group box 1 (HMGB1) was verified to be a target of miR‐200c during arrhythmia. HMGB1 expression reduced by the knockdown of MALAT1 was further decreased by miR‐200c overexpression. In addition, cardiac Ito, peak current density, and the levels of Kv4.2 and Kv4.3 in arrhythmic model rats were detected to be negatively correlated with the expression of HMGB1, and to be positively with miR‐200c expression. Taken together, these results suggested that MALAT1 may act as a competing endogenous RNA for miR‐200c to upregulate the expression of HMGB1 and downregulate cardiac Ito.
Preconditioned neurons with NaB and nicorandil, a favorable source for stroke cell therapy
Authors: Hosseini Seyed Mojtaba , Ziaee Seyyed Mohyeddin , Haider Khawaja Husnanin , Karimi Aliashghar , Tabeshmehr Parisa , Abbasi Zahra
Published: August 2018

Poor survival of stem cells in the harsh microenvironment at the site of stroke, especially during acute phase of injury, remains a serious obstacle to achieve the desired prognosis. We hypothesized that combined treatment of neural stem cells (NSCs) with small molecules would precondition them to become robust and survive better as compared with the native nonpreconditioned cells. Mouse ganglionic NSCs were isolated, cultured, and characterized. The cells were preconditioned by treatment with sodium butyrate (NaB) and nicorandil (Nico) and transplanted in an experimentally induced stroke model. Sham‐operated animals without treatment or animals with experimental stroke treated with basal medium, native NSCs, NSCs preconditioned with NaB or Nico alone were used as controls. The tissue samples and cells with different treatments were used to measure brain‐tissue–derived neurotrophic factor (BDNF) level and the activity of phosphatidylinositol‐3 kinase (PI3K), apurinic/apyrimidinic endonuclease 1 (APE1), and nuclear factor‐κB (NF‐κB) p50 both in vitro and in vivo, respectively. Additionally, survival of the cells and recovery indices for stroke were studied. The combined treatment with NaB + Nico resulted in increased BDNF level and higher PI3K, APE1, and the downstream NF‐κB activation, which were blocked by pretreatment with their respective inhibitors. Donor cell survival increased postengraftment as assessed by 5‐bromo‐2′‐deoxyuridine immunostaining and reduced Terminal deoxynucleotide transferase dUTP Nick End Labeling positivity at the site of engraftment. There was reduction in proinflammatory cytokines and infiltration of both GFAP
+ and CD68
+ at the injury site. There was reduction in the infarct size and neurological function was preserved in the preconditioned cell treatment group. Our preconditioning approach with small molecules effectively improved the survival as well as functionality of NSCs.
Comparative mechanism based study on disinfectants against multidrug‐resistant Acinetobacter baumannii
Authors: Biswas Deepika , Tiwari Monalisa , Tiwari Vishvanath
Published: August 2018

Acinetobacter baumannii has emerged as a hospital‐acquired pathogen and has spread in the hospital settings, leading to enhanced nosocomial outbreaks associated with high death rates. Therefore, the aim of the current study is to determine the effective concentration of disinfectants like sodium hypochlorite, hydrogen peroxide, and chlorine dioxide, against multidrug‐resistant (MDR) strains of A. baumannii. In this study, we have investigated the effect of disinfectants on different MDR strains i.e. RS307, RS6694, RS7434, RS10953, RS122, and sensitive strain ATCC‐19606 of A. baumannii, via differential growth curves analysis, disc diffusion assay, estimation of reactive oxygen species (ROS), lipid peroxidation, and protein carbonylation. All the results collectively showed that 1% sodium hypochlorite (P value < 0.0027), 2.5% hydrogen peroxide (P value = 0.0032), and 10 mM (P value = 0.017) chlorine dioxide significantly inhibit the growth of MDR strains of A. baumannii. A significant increase in the ROS generations, altered lipid peroxidation, and a decrease in protein carbonylation was also observed after treatment with disinfectants, which confirmed its ROS‐dependent damage mechanism. These disinfectants also enhance the membrane leakage of reducing sugar, protein, and DNA. The current study highlights and recommends the use of 2.5% hydrogen peroxide to control the MDR strains of A. baumannii in the hospital setup. Therefore, the present results will help in selecting concentrations of different disinfectants for regular use in hospital setups to eradicate the multidrug‐resistant A. baumannii from the hospital setup.
Upregulation of LINC00319 indicates a poor prognosis and promotes cell proliferation and invasion in cutaneous squamous cell carcinoma
Authors: Li Fumin , Liao Jinfeng , Duan Xiling , He Yuanmin , Liao Yongmei
Published: August 2018

Cutaneous squamous cell carcinoma (CSCC), an epidermal keratinocyte‐derived skin tumor, is one of the most leading causes of cancer‐associated morbidity and mortality worldwide. Long noncoding RNAs have emerged as key regulators of tumor development and progression. Recent studies have identified LINC00319, a long intergenic noncoding RNA, as an oncogene in lung cancer. However, the biological role of LINC00319 in CSCC remains largely unknown. The current study aimed to explore the role of LINC00319 in CSCC and uncover the molecular mechanisms. In current study, we found that LINC00319 was significantly upregulated in both CSCC tissues and cell lines. Besides, the χ2 test showed that increased expression of LINC00319 was associated with larger tumor size, advanced TNM stage, and lymphovascular invasion. Gain‐of‐function and loss‐of‐function approaches were applied to investigate the effects of LINC00319 on CSCC cells. Functional studies demonstrated that LINC00319 promoted CSCC cell proliferation, accelerated cell cycle progression, facilitated cell migration and invasion, and inhibited cell apoptosis. Mechanistic studies revealed that LINC00319 exerts its oncogenic functions in CSCC via miR‐1207‐5p‐mediated regulation of cyclin‐dependent kinase 3. Taken together, upregulation of LINC00319 implies a potential link with poor prognosis and reflects CSCC progression. Collectively, this study may provide some evidence for LINC00319 as a candidate target in CSCC treatment.
Eu3+/Sm3+ dual‐label time‐resolved fluoroimmunoassay for measurement of hepatitis C virus antibodies
Authors: Yang Xue , Ye Yan , Wang Tingting , Li Mei , Yu Lei , Xia Min , Qian Jun , Hu Zhigang
Published: August 2018

Aim

To develop a new immunoassay based on the time‐resolved fluorescence immunoassay (TRFIA) system for the simultaneous measurement of IgM and IgG antibodies to HCV.

Methods

Coated recombinant HCV antigens and Eu3+‐labeled IgM and Sm3+‐labeled IgG antibodies were prepared. HCV‐IgM/IgG TRFIA was established and optimized, followed by a methodological assessment. Data were expressed as +SD and analyzed using the SPSS 13.0 software. The percentile method was used to calculate cutoff values.

Results

The detection sensitivities of HCV‐IgM and HCV‐IgG were 0.06 S/CO and 0.15 S/CO, respectively. There was a good linear response from 1:40 to 1:40 960 for HCV‐IgM and 1:20 to 1:40 960 for HCV‐IgG, when samples strongly positive for HCV‐IgM and HCV‐IgG were serially diluted from 1:10 to 1:81 920. The average intra‐assay coefficients of variation (CV) for HCV‐IgM and ‐IgG were 3.45% and 3.71% and the inter‐assay coefficients of variation (CV) were 6.49% and 6.79%, respectively. When HCV‐negative/positive sera were tested by ELISA and using established kits, the negative, positive, and total conformity rates for HCV‐IgM were 93.3% (28/30), 100% (25/25), and 96.4% (53/55), and those for HCV‐IgG were 93.3% (28/30), 100% (35/35), and 96.9% (63/65), respectively. Additionally, the established kit exhibited good stability, with declines in fluorescence values to 11.1% and 9.5%, respectively, after storage at 37°C for 7 days.

Conclusion

We established a dual‐label HCV‐IgM/IgG TRFIA assay with a wide detection range, high specificity, high sensitivity, good stability, and good clinical value for the simultaneous measurement of HCV‐IgM and HCV‐IgG titers in a single test.
Differences in erythrocyte sedimentation rates using a modified Westergren method and an alternate method
Authors: Schapkaitz Elise , RabuRabu Shilla , Engelbrecht Marcel
Published: August 2018

Introduction

Worldwide laboratories have adopted the use of modified or alternate methods for measurement of the erythrocyte sedimentation rate (ESR). The iSED from Alcor Scientific is a novel, alternate ESR method based on photometric aggregometry which offers improved operator safety and reduced analysis time. This study evaluated the diagnostic utility of the iSED in a South African patient population with a range of inflammatory disorders.

Methods

We compared the iSED with the predicate modified Westergren method (StaRRsed, Mechatronics, Zwaag, the Netherlands) measured at 60 minutes. Analysis was performed on K2EDTA samples at three ESR measurement ranges (<20, 20‐80 and >80 mm/h) in 120 pediatric and adult inpatients and outpatients over a 2‐week period. Precision, stability, and carryover were performed in accordance with the revised International Council for Standardisation in Haematology guidelines.

Results

The iSED demonstrated acceptable imprecision with minimal carryover (2.86%). The correlation coefficients at the 3 ESR measurement ranges were r = 0.58, r = 0.71, and r = 0.56, respectively. The y‐intercepts were −10.74 (CI −29.17 to 7.69), −5.95 (CI −18.60 to 6.69) and 246.05 (CI 591.42‐99.31). This indicated a difference of a constant nature with an overall mean difference of 7.99 mm/h (CI 5.87‐10.13) (P < 0.001). iSED ESR measurements were stable up to 24 hours when stored at room temperature or at 4‐8°C.

Conclusion

This study demonstrated differences in ESR results, predominantly at extremes of the analytical range, using an alternate method. Careful consideration and performance monitoring of these novel methods are advised.
Preparation of superparamagnetic iron oxide/doxorubicin loaded chitosan nanoparticles as a promising glioblastoma theranostic tool
Authors: Gholami Leila , Tafaghodi Mohsen , Abbasi Bita , Daroudi Majid , Kazemi Oskuee Reza
Published: August 2018

Theranostic nanoparticles (NPs) are promising for opening new windows toward personalized disease management. Using a single particle capable of both diagnosis and drug delivery, is the major benefit of such particles. In the present study, chitosan NPs were used as a dual action carrier for doxorubicin (DOX; chemotherapeutic agent) and superparamagnetic iron oxide nanoparticles (SPIONs; imaging agent). SPIONs and DOX were loaded at different concentrations within poly‐l‐arginine‐chitosan‐triphosphate matrix (ACSD) using the ionic gelation method. NPs’ size were in the range of 184.33 ± 4.4 nm. Drug release analysis of DOX loaded NPs (NP‐DOX) showed burst release at pH 5.5 (as in tumor environment) and slow release at pH 7.4 (physiological condition), demonstrating pH‐sensitive drug release profile. NP‐DOX internalization was confirmed by flowcytometry and fluorescent microscopy. Uptake process results were corroborated by accumulation of drug in the intracellular space. Iron content was evaluated by inductively coupled plasma and prussian blue staining. In vitro magnetic resonance imaging (MRI) showed a decline in T
2 relaxation times by increasing iron concentration. MRI analysis also confirmed uptake of NPs at the optimum concentration in C6 glioma cells. In conclusion, ACSD NPs could be utilized as a promising theranostic formulation for both diagnosis and treatment of glioblastoma.
Regulation effects of melatonin on bone marrow mesenchymal stem cell differentiation
Authors: Wang Biao , Wen Hao , Smith Wanli , Hao Dingjun , He Baorong , Kong Lingbo
Published: August 2018

Melatonin’s therapeutic potential has been highly underestimated because its biological functional roles are diverse and relevant mechanisms are complicated. Among the numerous biological activities of melatonin, its regulatory effects on pluripotent mesenchymal stem cells (MSCs), which are found in bone marrow stem cells (BMSCs) and adipose tissue (AD‐MSC), have been recently proposed, which has received increasingly more attention in recent studies. Moreover, receptor‐dependent and receptor‐independent responses to melatonin are identified to occur in these cells by regulating signaling pathways, which drive the commitment and differentiation of MSCs into osteogenic, chondrogenic, or adipogenic lineages. Therefore, the aim of our current review is to summarize the evidence related to the utility of melatonin as a regulatory agent by focusing on its relationship with the differentiation of MSCs. In particular, we aimed to review its roles in promoting osteogenic and chondrogenic differentiation and the relevant signaling cascades involved. Also, the roles that melatonin and, particularly, its receptors play in these processes are highlighted.
Ketamine induces reactive oxygen species and enhances autophagy in SV‐HUC‐1 human uroepithelial cells
Authors: Shan Zhengfei , Wei Liqin , Yu Shengqiang , Jiang Shanling , Ma Yue , Zhang Chengjun , Wang Jiantao , Gao Zhenli , Wan Fengchun , Zhuang Guimin , Wu Jitao , Liu Dongfu
Published: August 2018

This study was aimed at exploring the underlying mechanisms of ketamine in the SV‐40 immortalized human ureteral epithelial (SV‐HUC‐1) cells. The viability and apoptosis of SV‐HUC‐1 cells treated with 0.01, 0.1, and 1 mM ketamine were respectively detected via cell counting kit‐8 (CCK‐8) assay and terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining. Reactive oxygen species (ROS) level was measured through ROS probe staining. Apoptosis‐related proteins (B‐cell lymphoma 2 [Bcl‐2] and Bax) and autophagy‐associated proteins (light chain 3‐I [LC3‐I] and LC3‐II) were determined by western blot or immunofluorescent assay. Additionally, transmission electron microscopy (TEM) was used to evaluate the formation of autophagosomes. After cotreatment of 3‐methyladenine (3‐MA) or N‐acetyl‐l‐cysteine (NAC), the biological functions of SV‐HUC‐1 cells were analyzed to determine the association of ROS with cell viability and autophagy. CCK‐8 assay and TUNEL staining indicated that ketamine effectively decreased the viability of SV‐HUC‐1 cells and accelerated apoptosis of SV‐HUC‐1 cells through regulating the expression level of IKBα (phospho), nuclear factor кB (P65), Bcl‐2, and Bax proteins. Enhanced ROS production was also confirmed in ketamine‐treated SV‐HUC‐1 cells treated with ketamine. Ketamine‐induced autophagosomes in SV‐HUC‐1 cells were observed by means of TEM, and increased levels of LC3 II/I ratio and Beclin 1 were examined through western blot and immunofluorescent assay. Furthermore, ketamine exerted effects on SV‐HUC‐1 cells in a dose‐dependent and time‐dependent manner. Additionally, cotreatment of NAC with 3‐MA significantly attenuated the ROS level and suppressed the cell autophagy. Ketamine promoted SV‐HUC‐1 cell autophagy and impaired the cell viability of SV‐HUC‐1 cells by inducing ROS.
Inactivated Sendai virus strain Tianjin induces apoptosis and autophagy through reactive oxygen species production in osteosarcoma MG‐63 cells
Authors: Han Zhe , Li Qing , Sun Shuya , Zhao Wei , Shi Liying
Published: August 2018

Sendai virus strain Tianjin, a novel genotype of Sendai virus, has been proven to possess potent antitumor effect on certain cancer cell types although inactivated by ultraviolet (UV). This study was carried out to investigate the in vitro anticancer properties of UV‐inactivated Sendai virus strain Tianjin (UV‐Tianjin) on human osteosarcoma cells and the underlying molecular mechanism. Our studies demonstrated UV‐Tianjin significantly inhibited the viability of human osteosarcoma cell lines and triggered apoptosis through activation of both extrinsic and intrinsic pathways in MG‐63 cells. Meanwhile, autophagy occurred in UV‐Tianjin‐treated cells. Blockade of autophagy with 3‐methyladenine remarkably attenuated the inhibition of cell proliferation by UV‐Tianjin, suggesting that UV‐Tianjin‐induced autophagy may be contributing to cell death. Furthermore, UV‐Tianjin induced reactive oxygen species (ROS) production, which was involved in the execution of MG‐63 cell apoptosis and autophagy, as evidenced by the result that treatment of N‐acetyl‐L‐cysteine, a ROS scavenger, attenuated both apoptosis and autophagy. In addition, inhibition of apoptosis promoted autophagy, whereas suppression of autophagy attenuated apoptosis. Our results suggest that UV‐Tianjin triggers apoptosis and autophagic cell death via generation of the ROS in MG‐63 cells, which might provide important insights into the effectiveness of novel strategies for osteosarcoma therapy.
Astragaloside IV enhances taxol chemosensitivity of breast cancer via caveolin‐1‐targeting oxidant damage
Authors: Zheng Yifeng , Dai Yan , Liu Weiping , Wang Neng , Cai Youli , Wang Shengqi , Zhang Fengxue , Liu Pengxi , Chen Qianjun , Wang Zhiyu
Published: August 2018

Accumulating evidence suggests that caveolin‐1 (CAV‐1) is a stress‐related oncotarget and closely correlated to chemoresistance. Targeting CAV‐1 might be a promising strategy to improve chemosensitivity for breast cancer treatment. Astragaloside IV (AS‐IV), a bioactive compound purified from Astragalus membranaceus, has been shown to exhibit multiple bioactivities, including anticancer. However, the involved molecular targets are still ambiguous. In this study, we investigated the critical role of CAV‐1 in mediating the chemosensitizing effects of AS‐IV to Taxol on breast cancer. We found that AS‐IV could enhance the chemosensitivity of Taxol with minimal direct cytotoxicity on breast cancer cell lines MCF‐7 and MDA‐MB‐231, as well as the nontumor mammary epithelial cell line MCF‐10A. AS‐IV was further demonstrated to aggravate Taxol‐induced apoptosis and G2/M checkpoint arrest. The phosphorylation of mitogen‐activated protein kinase (MAPK) signaling extracellular signal‐regulated kinase (ERK) and c‐Jun N‐terminal Kinase (JNK), except p38, was also abrogated by a synergistic interaction between AS‐IV and Taxol. Moreover, AS‐IV inhibited CAV‐1 expression in a dose‐dependent manner and reversed CAV‐1 upregulation induced by Taxol administration. Mechanism study further demonstrated that AS‐IV treatment triggered the eNOS/NO/ONOO− pathway via inhibiting CAV‐1, which led to intense oxidant damage. CAV‐1 overexpression abolished the chemosensitizing effects of AS‐IV to Taxol by inhibiting oxidative stress. In vivo experiments further validated that AS‐IV increased Taxol chemosensitivity on breast cancer via inhibiting CAV‐1 expression, followed by activation of the eNOS/NO/ONOO− pathway. Taken together, our findings not only suggested the potential of AS‐IV as a promising candidate to enhance chemosensitivity, but also highlighted the significance of CAV‐1 as the target to reverse cancer drug resistance.
MicroRNA‐133a alleviates airway remodeling in asthtama through PI3K/AKT/mTOR signaling pathway by targeting IGF1R
Authors: Shao Youyou , Chong Lei , Lin Peng , Li Haiyan , Zhu Lili , Wu Qiuping , Li Changchong
Published: August 2018

Asthma is characterized by chronic inflammation, and long‐term chronic inflammation leads to airway remodeling. But the potential regulatory mechanism of airway remodeling is not clearly understood, and there is still no effective way to prevent airway remodeling. Present studies have confirmed the role of microRNAs (miRNAs) in the development of disease, which is known as suppressing translation or degradation of messenger RNA (mRNA) at the posttranscriptional stage. In this study, we described the role of miRNA‐133a in asthma and demonstrated it in regulating airway remodeling of asthma through the phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway by targeting IGF‐1 receptor (IGF1R). IGF1R helps in mediating the intracellular signaling cascades. Asthmatic mice models were established by sensitization and Ovalbumin challenge. Adenovirus transfer vector carrying miR‐133a or miR‐133a sponge sequence was used to build the overexpression or downexpression of miR‐133a modeling. Real‐time polymerase chain reaction and Western blot were used to determine the alterations in the expression of miR‐133a and mRNAs and their corresponding proteins. Results showed that miR‐133a was downregulated in asthma. Upregulation of miR‐133a expression in airway smooth muscle cells in vivo and in vitro could inhibit the activation of PI3K/AKT/mTOR pathway, and reduce the expression of α‐smooth muscle actin (α‐SMA), indicating that airway remodeling was inhibited. Functional studies based on luciferase reporter revealed miR‐133a as a direct target of IGF1R mRNA. In conclusion, these data suggested that miR‐133a regulated the expression of α‐SMA through PI3K/AKT/mTOR signaling by targeting IGF1R. miR‐133a plays a key role in airway remodeling of asthma and may serve as a potential therapeutic target for managing asthmatic airway remodeling.
Successful isolation and ex vivo expansion of human mesenchymal stem/stromal cells obtained from different synovial tissue‐derived (biopsy) samples
Authors: Ferro Tiago , Santhagunam Aruna , Madeira Catarina , Salgueiro João B. , da Silva Cláudia L. , Cabral Joaquim M. S.
Published: August 2018

Mesenchymal stromal cells (MSC) isolated from synovial tissues constitute a novel source of stem‐like cells with promising applications in cartilage regeneration and potentially in other regenerative medicine and tissue‐engineering settings. Detailed characterization of these cells is lacking, thus compromising their full potential. Here we present the detailed characterization of the ex vivo expansion of synovium‐derived stromal cells collected by three different biopsy methods: synovium‐direct biopsy, arthroscopic trocar shaver blade filtrate, and cells isolated from synovial fluid (SF) samples. Isolation success rates were >75% for all sources. MSC obtained from the different samples displayed the characteristic immunophenotype of adult MSC, expressing CD73, CD90, and CD105. Arthroscopic shaver blade‐derived cells showed the higher proliferation capacity measured by the fold increase (FI) in total cell number over several passages and considering their cumulative population doublings (CPD; 15 ± 0.85 vs. 13 ± 0.73 for synovium vs. 11 ± 0.97 for SF). Also, these cells were able to sustain an increased proliferation under hypoxic (2% O2) conditions (FI 55 ± 4 vs. 37 ± 7) after 17 days in culture. Expanded cells were able to differentiate successfully along the osteogenic, adipogenic, and chondrogenic lineages in vitro. Overall, these results demonstrate that synovial tissues represent a promising source for the isolation of human MSC, while depicting the variability associated to the biopsy method used, which impact cell behavior in vitro.
miR‐200a‐5p augments cardiomyocyte hypertrophy induced by glucose metabolism disorder via the regulation of selenoproteins
Authors: Yang Tianshu , Liu Tianqi , Cao Changyu , Xu Shiwen
Published: August 2018

Selenium and selenoproteins are identified as potential determinants in pathological cellular hypertrophy. Cardiomyocytes hypertrophy is a compensatory form of heart disease characterized by increased size of cardiomyocytes. However, the link between cardiac hypertrophy and Se‐specific microRNA (miRNA) remains to be characterized. In the current study, we established a miR‐200a‐5p mimic and an inhibitor cardiomyocytes model. Cardiomyocytes hypertrophy was induced in the miR‐200a‐5p mimic group. Hence, we detected the glucose level of cardiomyocytes to estimate the cellular glucose uptake. The effect of miR‐200a‐5p overexpression and the low expression on 25 selenoproteins mRNA levels was further explored using reverse transcription polymerase chain reaction. Overexpression of miR‐200a‐5p elevated glucose uptake and Txnrd2, 3 expression and reduced Sepp1, Seln, Selt, and Sep15 expression in cardiomyocytes. Contrary results were observed in cardiomyocytes with the knockdown of miR‐200a‐5p. We next assessed glucose metabolism‐related genes in cardiomyocytes. The results showed that miR‐200a‐5p had a negative correlation with insulin‐like growth factor gene‐1, insulin‐like growth factor binding protein (IGFBP)1, IGFBP2, IGFBP3, IGFBP4, and IGFBP5 and had a positive correlation with Akt, glucose transporter family (GLUT)2, GLUT3, and GLUT4. These results support the involvement of selenoproteins and glucose metabolism in the control of cardiomyocytes hypertrophy by Se‐specific miRNA, suggesting that miR‐200a‐5p inhibited the expression of stress‐related selenoproteins to alter glucose transport leading to glucose metabolism disorder, eventually inducing cardiomyocytes hypertrophy. Our finding highlights a pivotal role of Se‐specific miRNA and selenoproteins in cardiac hypertrophy.
Assessment of therapeutic window for poly‐arginine‐18D (R18D) in a P7 rat model of perinatal hypoxic‐ischaemic encephalopathy
Authors: Edwards Adam B. , Anderton Ryan S. , Knuckey Neville W. , Meloni Bruno P.
Published: August 2018

Hypoxic‐ischaemic encephalopathy (HIE) remains the leading cause of mortality and morbidity in neonates, with no available neuroprotective therapeutic agent. In the development of a therapeutic for HIE, we examined the neuroprotective efficacy of the poly‐arginine peptide R18D (arginine 18 mer synthesised with D‐arginine) in a perinatal model of hypoxia‐ischaemia (HI; common carotid and external carotid occlusion + 8%O2/92%N2 for 2.5 hr) in the P7 Sprague‐Dawley rat. R18D was administered intraperitoneally 30 min (doses 10, 30, 100, 300 and 1,000 nmol/kg), 60 min (doses 30 and 300 nmol/kg) or 120 min (doses 30 and 300 nmol/kg) after HI. Infarct volumes and behavioural outcomes were measured 48 hr after HI. When administered 30 min after HI, R18D at varying doses reduced infarct volume by 23.7% to 35.6% (p = 0.009 to < 0.0001) and resulted in improvements in the negative geotactic response and wire‐hang times, at a dose of 30 nmol/kg. When administered 60 min after HI, R18D at the 30 nmol/kg dose reduced total infarct volume by 34.2% (p = 0.002), whilst the 300 nmol/kg dose improved wire‐hang time. When administered 120 min after HI, R18D at the 30 and 300 nmol/kg doses had no significant impact on infarct volume, but the 300 nmol/kg dose improved the negative geotactic response. This study further confirms the neuroprotective properties of poly‐arginine peptides, demonstrating that R18D can reduce infarct volume and improve behavioural outcomes after HI if administered up to 60 min after HI and improve behavioural outcomes up to 2 hr after HI.