Publication date: 30 September 2018
Source:Biosensors and Bioelectronics, Volume 116
Author(s): Huiyun Yang, Haijun Wang, Chengyi Xiong, Yaqin Chai, Ruo Yuan
In this work, poly[9,9-dioctylfluorenyl-2,7-diyl] (PFO) dots is discovered to display an appealing dual enhancement effect for the electrochemiluminescence (ECL) system of N-(aminobutyl)-N-(ethylisoluminol)/hydrogen peroxide (ABEI/H2O2), which not only enhances the ECL intensity of ABEI but also catalyzes decomposition of H2O2 to further amplify the ECL signal of ABEI. Owing to the electronegative property of PFO dots, electropositive ABEI-PEI as ECL reagent could be adsorbed on their surface and thus form a novel luminescence emitter (ABEI-PEI-PFO dots) with high ECL efficiency based on electrostatic attraction. Meanwhile, the water solubility and stability of this emitter are improved in virtue of the amine-rich property of ECL reagent (ABEI-PEI), which could increase the luminous efficiency of ECL reaction in aqueous solution. To increase the electron transfer efficiency, Pt nanoparticles (PtNPs) supported on reduced graphene oxide nanosheets (RGOs) via a onepot synthetic strategy are chosen as immobilizing platform for the ECL emitter (ABEI-PEI-PFO dots). Herein, the obtained dual-amplifed ABEI-PEI-PFO dots-RGOs/PtNPs complex is served as an ideal nanocarrier to capture detection antibody (Ab2). According to sandwiched immunoreaction, a highly sensitive ECL immunosensor is constructed for the detection of kidney injury molecule-1 (KIM-1) with a linearity from 50 fg mL−1 to 1 ng mL−1 and a detection limit of 16.7 fg mL−1. The developed ECL emitter combining dual amplified property for signal enhancement purpose would provide new thought and potential for sensitive bioanalysis and clinical application.
https://ift.tt/2sitXk1
Τρίτη 29 Μαΐου 2018
Highly sensitive electrochemiluminescence immunosensor based on ABEI/H2O2 system with PFO dots as enhancer for detection of kidney injury molecule-1
Technological advancement in electrochemical biosensor based detection of Organophosphate pesticide chlorpyrifos in the environment: A review of status and prospects
Source:Biosensors and Bioelectronics, Volume 116
Author(s): Shivani Uniyal, Rajesh Kumar Sharma
Chlorpyrifos (CP), an organophosphate insecticide is broadly used in the agricultural and industrial sectors to control a broad-spectrum of insects of economically important crops. CP detection has been gaining prominence due to its widespread contamination in different environmental matrices, high acute toxicity, and potential to cause long-term environmental and ecological damage even at trace levels. Traditional chromatographic methods for CP detection are complex and require sample preparation and highly skilled personnel for their operation. Over the past decades, electrochemical biosensors have emerged as a promising technology for CP detection as these circumvent deficiencies associated with classical chromatographic techniques. The advantageous features such as appreciable detection limit, miniaturization, sensitivity, low-cost and onsite detection potential are the propulsive force towards sustainable growth of electrochemical biosensing platforms. Recent development in enzyme immobilization methods, novel surface modifications, nanotechnology and fabrication techniques signify a foremost possibility for the design of electrochemical biosensing platforms with improved sensitivity and selectivity. The prime objective of this review is to accentuate the recent advances in the design of biosensing platforms based on diverse biomolecules and biomimetic molecules with unique properties, which would potentially fascinate their applicability for detection of CP residues in real samples. The review also covers the sensing principle of the prime biomolecule and biomimetic molecule based electrochemical biosensors along with their analytical performance, advantages and shortcomings. Present challenges and future outlooks in the field of electrochemical biosensors based CP detection are also discussed. This deep analysis of electrochemical biosensors will provide research directions for further approaching towards commercial development of the broad range of organophosphorus compounds.
https://ift.tt/2IXgS5J
Enhanced photoelectrochemical DNA sensor based on TiO2/Au hybrid structure
Publication date: 30 September 2018
Source:Biosensors and Bioelectronics, Volume 116
Author(s): Xing-Pei Liu, Jing-Shuai Chen, Chang-jie Mao, He-Lin Niu, Ji-Ming Song, Bao-Kang Jin
A novel enhanced photoelectrochemical DNA sensor, based on a TiO2/Au hybrid electrode structure, was developed to detect target DNA. The sensor was developed by successively modifying fluorine-tin oxide (FTO) electrodes with TiO2 nanoparticles, gold (Au) nanoparticles, hairpin DNA (DNA1), and CdSe-COOH quantum dots (QDs), which acted as signal amplification factors. In the absence of target DNA, the incubated DNA1 hairpin and the CdSe-COOH QDs were in close contact with the TiO2/Au electrode surface, leading to an enhanced photocurrent intensity due to the sensitization effect. After incubation of the modified electrode with the target DNA, the hairpin DNA changed into a double helix structure, and the CdSe QDs moved away from the TiO2/Au electrode surface, leading to a decreased sensitization effect and photoelectrochemical signal intensity. This novel DNA sensor exhibited stable, sensitive and reproducible detection of DNA from 0.1 μM to 10 fM, with a lower detection limit of 3 fM. It provided good specificity, reproducibility, stability and is a promising strategy for the detection of a variety of other DNA targets, for early clinical diagnosis of various diseases.
https://ift.tt/2skIdIT
Nanotechnology-based electrochemical detection strategies for hypertension markers
Publication date: 30 September 2018
Source:Biosensors and Bioelectronics, Volume 116
Author(s): Sasya Madhurantakam, K. Jayanth Babu, John Bosco Balaguru Rayappan, Uma Maheswari Krishnan
Hypertension results due to dysfunction of different metabolic pathways leading to the increased risk of cerebral ischemia, atherosclerosis, cardiovascular and inflammatory disorders. Hypertension has been considered a one of the major contributors to metabolic syndrome and is often referred to as a 'silent killer'. Its incidence is on the rise across the globe owing to the drastic life style changes. The diagnosis of hypertension had been traditionally carried out through measurement of systolic and diastolic blood pressure but in most cases, this form of diagnosis is too late and the disease has already caused organ damage. Therefore, early detection of hypertension by monitoring subtle changes in specific biochemical markers from body fluids can minimize the risk of organ damage. However, a single marker may be insufficient for accurate diagnosis of hypertension thereby necessitating quantification of multiple markers. Concerted efforts to identify key markers for hypertension and their quantification, especially using chemical and biosensors, are underway in different parts of the world. Constant evolution of the sensing elements and transduction strategies have contributed to significant improvements in the diagnosis field, especially in the context of sensitivity, response time and selectivity and this when applied to the detection of hypertension markers may prove beneficial. This review summarizes advances in the field of sensor technology towards the detection of biologically relevant entities, arrays and the next generation 'lab-on-a-chip' systems for hypertension.
https://ift.tt/2xwm8wa
Electrochemical immunoassay for the detection of IgM antibodies using polydopamine particles loaded with PbS quantum dots as labels
Publication date: 30 September 2018
Source:Biosensors and Bioelectronics, Volume 116
Author(s): Greter A. Ortega, Julio C. Zuaznabar-Gardona, Edilso Reguera
Here, we report for the first time, an electrochemical immunoassay to detect IgM antibodies using lead sulfide quantum dots (PbS QDs) as electrochemical labels. In this sense, dendritic-like polydopamine particles loaded with PbS QDs were synthesized by the self-polymerization of dopamine in basic media in the presence of QDs (PbS@PDA) and further tagged with anti-IgM antibodies, dengue specific antigens, and streptavidin moieties. The analytical features of the sandwich immunoassay on ELISA microplate were carried out with the PbS@PDA-labeled anti-IgM as secondary antibody. The system was interrogated by acid dissolution of PbS@PDA, followed by differential pulse anodic stripping voltammetry in the presence of Bi(III) ions using carbon screen-printed electrodes. The results indicate that the voltammetric current increased with the increasing of the concentration of target IgM within a range of 0–0.5 mg mL−1. The limit of detection of this electrochemical immunoassay was evaluated to 130 ng. The measures of satisfactory recoveries from 88.5% to 114% of spiked samples indicate that such a method has good specificity and is applicable to the quantification of IgM antibodies in complex biological samples. No significant differences at the 0.05 significance level were encountered in the analysis of IgM samples between the electrochemical immunoassay and a Bradford assay.
Graphical abstract
https://ift.tt/2sgGVym
Real-time circulating tumor cells detection via highly sensitive needle-like cytosensor-demonstrated by a blood flow simulation
Publication date: 30 September 2018
Source:Biosensors and Bioelectronics, Volume 116
Author(s): Wen-Hui Weng, I-Lin Ho, Chi-Chia Pang, Sow-Neng Pang, Tung-Ming Pan, Wai-Hung Leung
The concept of rapid detection of circulating tumor cells (CTCs) has always been the focal point of modern and future medicine. However, the dispersity and rarity of CTCs in the bloodstream makes it hard to detect metastasis. Herein, our newly designed needle-like cytosensor demonstrates that the capture and analysis of CTCs are a much less laborious process and have more potential than ever. Our aim is to detect and capture CTCs directly in the bloodstream without altering the genetic information; further benefit of current cytosensor is allows for the whole circulation of blood to run through the cytosensor, giving a much better sensitivity and chance of detecting CTCs. Our functionalized needle-like cytosensor has been modified with 3-aminopropyltriethoxysilane, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, N-hydroxysuccinimide and conjugated streptavidin to allow the binding of the biotinylated-antibody of epithelial cell adhesion molecules, which captures targeted colon cancer CTC. The capability of our needle-like cytosensor to detect CTCs spanned from 102 to 106 cells/mL. Beyond this, the needle-like cytosensor avoids the distortion of the cell information. In addition, we constructed a blood flow simulation that mimics human circulating system about 10 mL/min speed; by using cyclic voltammetry we could detect significant signals from captured cancer CTCs more than 21 cells/mL without delay; the fluorescence dye detection was further performed for data confirmation. The future of biosensors begins with this, by providing early monitoring quality care in cancer therapy.
https://ift.tt/2skAgTW
Label-free photoelectrochemical immunosensing platform for detection of carcinoembryonic antigen through photoactive conducting poly(5-formylindole) nanocomposite
Publication date: 30 September 2018
Source:Biosensors and Bioelectronics, Volume 116
Author(s): Guangming Nie, Yun Tang, Bin Zhang, Yang Wang, Qingfu Guo
Poly(5-formylindole)/electrochemically reduced graphene oxide (P5FIn/erGO) nanocomposite is firstly used to construct a label-free photoelectrochemical (PEC) immunosensor to detect carcinoembryonic antigen (CEA). As photoactive material and electroactive mediator, the prepared P5FIn/erGO nanocomposite exhibits high photocurrent intensity under visible-light irradiation due to the synergistic effect of P5FIn and erGO. The anti-CEA is connected to the P5FIn/erGO modified electrode surface, and gold nanoparticles (AuNP) is used as cross-linking in the process. The linear decrease of photocurrent is caused by the specific recognition of anti-CEA and CEA. This PEC immunosensor shows a wide linear response to CEA ranging from 0.0005 to 50 ng mL−1 with a low detection limit of 0.14 pg mL−1. The proposed immunosensor has good stability, reproducibility and high specificity. The satisfied results are also obtained when this immunosensor is used to detect CEA in actual human serum samples analysis, thus opening up a new promising PEC analysis platform based on conducting polymers.
Graphical abstract
https://ift.tt/2J0Z4qC
An ultrasensitive and selective electrochemical aptasensor based on rGO-MWCNTs/Chitosan/carbon quantum dot for the detection of lysozyme
Publication date: 15 September 2018
Source:Biosensors and Bioelectronics, Volume 115
Author(s): Behzad Rezaei, Hamid Reza Jamei, Ali Asghar Ensafi
An aptamer-based method is described for the electrochemical determination of lysozyme. A glassy carbon electrode was modified with a nanocomposite composed of reduced graphene oxide (rGO), multi-walled carbon nanotubes (MWCNTs), chitosan (CS), and a synthesized carbon quantum dot (CQD) from CS. The composition of the nanocomposite (rGO-MWCNT/CS/CQD) warrants a high surface-to-volume ratio, high conductivity, high stability, and great electrocatalytic activity. This nanocomposite provides a suitable site for better immobilization of aptamers due to the existence of many amino and carboxyl functional groups, and remaining oxygen-related defects properties in rGO. In addition, this nanocomposite allows considerable enhancement of the electrochemical signal and contributes to improving sensitivity. The amino-linked lysozyme aptamers were immobilized on the nanocomposite through covalent coupling between the amino groups of the aptamer and the amino groups of the nanocomposite using glutaraldehyde (GLA) linker. The modified electrode was characterized by electrochemical methods including differential pulse voltammetry (DPV), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). In the presence of lysozyme, the immobilized aptamer selectively caught the target lysozyme on the electrode interface that leads to a decrease in the DPV peak current and an increase in Charge Transfer Resistance (Rct) in EIS as an analytical signal. Using the obtained data from DPV and EIS techniques, two calibration curves were drawn. The anti-lysozyme aptasensor proposed has two very low LODs. These measures are 3.7 and 1.9 fmol L−1 within the wide detection ranges of 20 fmol L−1 to 10 nmol L−1, and 10 fmol L−1 to 100 nmol L−1 for DPV and EIS calibration curves, respectively. The GCE/rGO-MWCNT/CS/CQD showed sensitivity, high reproducibility, specificity and rapid response for lysozyme which can be used in biomedical fields.
https://ift.tt/2shgA3q
Probing the specific binding of folic acid to folate receptor using amino-functionalized mesoporous silica nanoparticles for differentiation of MCF 7 tumoral cells from MCF 10A
Publication date: 15 September 2018
Source:Biosensors and Bioelectronics, Volume 115
Author(s): Jafar Soleymani, Mohammad Hasanzadeh, Mohammad Hossein Somi, Nasrin Shadjou, Abolghasem Jouyban
Folate receptor (FR) is overexpressed in various cancer cells while its expression in normal cells is restricted. The present study provides a new folic acid/folate (FA) functionalized nanomaterials to sense and the differentiation of the cancer cells from normal ones. The reported nanoprobe is based on the mesoporous materials that are functionalized with FA to specify the FR overexpressed cancerous cells. MCF 7 cell lines were used as a model to show the ability of the developed probe for cancer cell detection. The selective binding of FA to FR-positive cells causes the endocytosis of the mesoporous materials into the cells where it can be observed by fluorescence microscopy images. The specific nature of the binding of the FA functionalized mesoporous silica prevents the false detection of normal cells from cancerous cells even in the presence of each other. The cytotoxicity of the n-Pr-NH2-MCM 41-FA on the MCF 7 cells was investigated using MTT assay. The reported method can detect the MCF 7 cells from 100 to 1000 cells/mL. This method provides a selective and nontoxic approach towards detection of breast cancer cell lines while it can be developed as a point of care (POC) device for early detection of cancer. Finally, the MCF 7 cancer cells were treated with doxorubicin anti-cancer drug and our device detect the trace amount of MCF 7 based on their electrochemical activity.
https://ift.tt/2J2TweX
A direct isothermal amplification system adapted for rapid SNP genotyping of multifarious sample types
Publication date: 15 September 2018
Source:Biosensors and Bioelectronics, Volume 115
Author(s): Xiaonan Liu, Chao Zhang, Mengye Zhao, Kewu Liu, Hang Li, Ningning Li, Linlin Gao, Xuemin Yang, Ting Ma, Juanli Zhu, Wenli Hui, Kai Hua, Yali Cui
Genotyping of single nucleotide polymorphisms (SNPs) in point-of-care (POC) settings could be further improved through simplifying the treatment of samples. In this study, we devised an accurate, rapid and easy-to-use SNP detection system based on direct loop-mediated isothermal amplification (LAMP) without DNA extraction, known as Direct-LAMP. Samples from various sources (including whole blood, dried blood spot, buccal swab and saliva), treated with NaOH, can be used directly in amplification. The turnaround time was about 30 min from sample collection to provision of results. The accuracy was evaluated by assessing the polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and aldehyde dehydrogenase-2 (ALDH2) Glu504Lys, which are better known for their critical role in folate and ethanol metabolism, respectively. Completely consistent genotyping results reveal that Direct-LAMP is generally concordant with sequencing. This system can serve as a very promising platform in the fields of disease predisposition, drug metabolism and personalized medicine.
Graphical abstract
https://ift.tt/2sh7Ji8
Dual-wavebands-resolved electrochemiluminescence multiplexing immunoassay with dichroic mirror assistant photomultiplier-tubes as detectors
Publication date: 15 September 2018
Source:Biosensors and Bioelectronics, Volume 115
Author(s): Fang Zhang, Yupeng He, Kena Fu, Li Fu, Bin Zhang, Huaisheng Wang, Guizheng Zou
A dual-wavebands-resolved electrochemiluminescence (ECL) multiplexing immunoassay (MIA) was developed for simultaneously detecting alpha fetoprotein antigen (AFP) in greenish waveband with CdSe550 (λmax = 550 nm) nanocrystals (NCs) and carbohydrate antigen 125 (CA125) in near-infrared waveband with CdTe790 (λmax = 790 nm) NCs via one-pot ECL reaction, in which dichroic mirror works as a key part to reflect ECL from CdSe550 to one photomultiplier-tube (PMT) and transmit ECL from CdTe790 to the other PMT for dual-wavebands-resolved assay. The proposed ECL-MIA strategy was capable of simultaneously determining AFP with linearly response from 5 pg/mL to 5 ng/mL and limit of detection at 1 pg/mL, and CA125 with linearly response from 5 mU/mL to 1 U/mL and limit of detection at 1 mU/mL, with desired specificity and without obvious energy-transfer between ECL tags. The dichroic mirror assistant ECL setup is easy-to-assemble and convenient for the popularization of color-resolved multiplexing ECL assay.
https://ift.tt/2xwlTRM
Sample-to-answer palm-sized nucleic acid testing device towards low-cost malaria mass screening
Publication date: 15 September 2018
Source:Biosensors and Bioelectronics, Volume 115
Author(s): Gihoon Choi, Theodore Prince, Jun Miao, Liwang Cui, Weihua Guan
The effectiveness of malaria screening and treatment highly depends on the low-cost access to the highly sensitive and specific malaria test. We report a real-time fluorescence nucleic acid testing device for malaria field detection with automated and scalable sample preparation capability. The device consists a compact analyzer and a disposable microfluidic reagent compact disc. The parasite DNA sample preparation and subsequent real-time LAMP detection were seamlessly integrated on a single microfluidic compact disc, driven by energy efficient non-centrifuge based magnetic field interactions. Each disc contains four parallel testing units which could be configured either as four identical tests or as four species-specific tests. When configured as species-specific tests, it could identify two of the most life-threatening malaria species (P. falciparum and P. vivax). The NAT device is capable of processing four samples simultaneously within 50 min turnaround time. It achieves a detection limit of ~0.5 parasites/µl for whole blood, sufficient for detecting asymptomatic parasite carriers. The combination of the sensitivity, specificity, cost, and scalable sample preparation suggests the real-time fluorescence LAMP device could be particularly useful for malaria screening in the field settings.
https://ift.tt/2sgGMei
Sensitive and label-free electrochemical lead ion biosensor based on a DNAzyme triggered G-quadruplex/hemin conformation
Publication date: 15 September 2018
Source:Biosensors and Bioelectronics, Volume 115
Author(s): LeLe Wang, Yanli Wen, Lanying Li, Xue Yang, Nengqin Jia, Wen Li, Jiaoran Meng, Manlei Duan, Xiaoguang Sun, Gang Liu
Lead ion (Pb2+) is a common environmental contaminant, which causes serious bioaccumulation and toxicity in human body. In this work, we developed a novel Pb2+ electrochemical biosensor using the specific DNAzyme on a DNA tetrahedron probe, in the presence of Pb2+, the substrate strand was cleaved into two parts and released a "G-rich" oligo which subsequently formed a G-quadruplex/hemin complex, generating a detectable catalysis current signal with the assistant of H2O2. The 3-D DNA tetrahedron regulated the density and orientation of the probe and thus improved the DNAzyme reaction, and facilitated the complex DNA conformational change in the confined space of the interface on the electrode surface, Finally, the LOD of our biosensor was proved to be 0.008 nM (3σ), which is 9000 times lower than the safety limit of EPA (15 μg/L or 72 nM), and 6000 times lower than IARC (10 μg/L or 48.26 nM), and more importantly, the specificity and reproducibility of the proposed biosensor was well demonstrated.
https://ift.tt/2J1AF3Y
Multiplexed antibody detection from blood sera by immobilization of in vitro expressed antigens and label-free readout via imaging reflectometric interferometry (iRIf)
Publication date: 15 September 2018
Source:Biosensors and Bioelectronics, Volume 115
Author(s): Julian Bender, Sabine Bognar, Maurizio Camagna, Julia A.M. Donauer, Julian W. Eble, Ramona Emig, Sabrina Fischer, Rabea Jesser, Luisa Keilholz, Daniel M.U. Kokotek, Julika Neumann, Simon Nicklaus, Ricardo R.Q.P.T. Oude Weernink, Lara G. Stühn, Nathalie Wössner, Stefan D. Krämer, Philipp Schwenk, Nicole Gensch, Günter Roth, Maximilian H. Ulbrich
The detection of antibodies from blood sera is crucial for diagnostic purposes. Miniaturized protein assays in combination with microfluidic setups hold great potential by enabling automated handling and multiplexed analyses. Yet, the separate expression, purification, and storage of many individual proteins are time consuming and limit applicability. In vitro cell-free expression has been proposed as an alternative procedure for the generation of protein assays. We report the successful in vitro expression of different model proteins from DNA templates with an optimized expression mix. His10-tagged proteins were specifically captured and immobilized on a Ni-NTA coated sensor surface directly from the in vitro expression mix. Finally, the specific binding of antibodies from rabbit-derived blood sera to the immobilized proteins was monitored by imaging reflectometric interferometry (iRIf). Antibodies in the blood sera could be identified by binding to the respective epitopes with minimal cross reactivity. The results show the potential of in vitro expression and label-free detection for binding assays in general and diagnostic purposes in specific.
https://ift.tt/2sgGHY2
Cascading reaction of arginase and urease on a graphene-based FET for ultrasensitive, real-time detection of arginine
Publication date: 15 September 2018
Source:Biosensors and Bioelectronics, Volume 115
Author(s): Teresa Berninger, Christina Bliem, Esteban Piccinini, Omar Azzaroni, Wolfgang Knoll
Herein, a biosensor based on a reduced graphene oxide field effect transistor (rGO-FET) functionalized with the cascading enzymes arginase and urease was developed for the detection of L-arginine. Arginase and urease were immobilized on the rGO-FET sensing surface via electrostatic layer-by-layer assembly using polyethylenimine (PEI) as cationic building block. The signal transduction mechanism is based on the ability of the cascading enzymes to selectively perform chemical transformations and prompt local pH changes, that are sensitively detected by the rGO-FET. In the presence of L-arginine, the transistors modified with (PEI/urease(arginase)) multilayers showed a shift in the Dirac point due to the change in the local pH close to the graphene surface, produced by the catalyzed urea hydrolysis. The transistors were able to monitor L-arginine in the 10–1000 μM linear range with a LOD of 10 μM, displaying a fast response and a good long-term stability. The sensor showed stereospecificity and high selectivity in the presence of non-target amino acids. Taking into account the label-free, real-time measurement capabilities and the easily quantifiable, electronic output signal, this biosensor offers advantages over state-of-the-art L-arginine detection methods.
Graphical abstract
https://ift.tt/2IZ7miz
Protective role of β-carotene against oxidative stress and neuroinflammation in a rat model of spinal cord injury
Publication date: August 2018
Source:International Immunopharmacology, Volume 61
Author(s): Lihui Zhou, Lian Ouyang, Shuangzhi Lin, Song Chen, YingJie Liu, Wei Zhou, Xucan Wang
Acute spinal cord injury (SCI) results in long-lasting functional impairments through both mechanical damage as well as secondary mechanisms, with limited available therapeutic options. β-Carotene has been demonstrated to exert biological and pharmacological activities. We aimed to examine the protective effects of β-carotene in a SCI rat model. We tested the hind-limb locomotor function, neuro-inflammation, oxidative stress, astrocyte activation and nuclear factor–κB (NF-κB) pathway activation of SCI rats, with or without β-carotene treatment. β-Carotene substantially improved locomotion that was reduced by SCI. β-Carotene also relieved SCI-induced oxidative stress via regulation of reactive oxygen species, malondialdehyde, nitric oxide, and superoxide dismutase, as well as restored SCI-suppressed protein expressions of Nrf2 and HO-1. Additionally, β-carotene decreased the generation of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-18 and cyclooxygenase-2, and inhibited the activation of astrocyte in the spinal cord. Furthermore, β-carotene treatment markedly inhibited the NF-κB pathway activation. Our findings demonstrated that β-carotene effectively reduced the progression of secondary injury events following SCI through preventing NF-κB pathway activation. Therefore, β-carotene may be an effective candidate for treating SCI.
https://ift.tt/2IVAwTN
Prophylactic herpes simplex virus type 2 vaccine adjuvanted with a universal CD4 T cell helper peptide induces long-term protective immunity against lethal challenge in mice
Publication date: August 2018
Source:International Immunopharmacology, Volume 61
Author(s): Xiaoquan Li, Shouhua Zhang, Jun Lei, Ying Zhu, Xin Zhou, Juhua Xiao, Tianxin Xiang
Induction of robust and long-term immune responses at the portal of entry remains a big challenge for HSV-2 vaccine development. The adoption of a CD4 T cell helper peptide in the vaccine is thought to be beneficial for the enhancement of immune responses, however, its effect on HSV-2 vaccines has not yet been studied. In this study, we designed a DNA vaccine (gD-TpD) simultaneously expressing HSV-2 gD ectodomain and a universal CD4 T cell helper peptide (TpD), and tested its efficacy on a murine model. Mice were immunized 3 times with gD-TpD or control DNA formulations, and then were rested until Day 150 when they were vaginally challenged with lethal doses of HSV-2. Our data showed that gD-TpD significantly increased gD-specific IgG and IgA in both sera and vaginal washes. Furthermore, the increased antibody responses showed enhanced neutralization activity in vitro. In addition, gD-TpD induced balanced Th1/2 cellular responses and CD8+ T cell-dependent CTL activity. Although immune responses dropped over time after the final immunization, robust and rapid antibody and T cell responses were induced upon virus challenge in gD-TpD group. Moreover, gD-TpD provided full protection against lethal viral challenge in immunized mice. Together, our findings indicate that the inclusion of the CD4 T cell helper peptide TpD in HSV-2 gD subunit vaccine could induce long-term protective immunity, providing information for a rational design of vaccines against HSV-2 or even other viruses.
https://ift.tt/2H1f7m8
MSCs protect endothelial cells from inflammatory injury partially by secreting STC1
Publication date: August 2018
Source:International Immunopharmacology, Volume 61
Author(s): Meimei Shi, Yujia Yuan, Jingping Liu, Younan Chen, Lan Li, Shuyun Liu, Xingxing An, Ruixi Luo, Dan Long, Bo Chen, Xiaojiong Du, Jingqiu Cheng, Yanrong Lu
Inflammatory factors play an important role in the pathogenesis of diabetic vascular complications. Considerable interest in the therapeutic potential of mesenchymal stem cells (MSCs) has recently arisen. The purposes of this study were to investigate the effects of MSCs on endothelial cells under inflammatory conditions and to determine the relevant mechanism underlying these effects. In vitro, after TNF-α stimulation, MSCs-CM treatment significantly restored cell viability, reduced THP-1 cell adhesion and enhanced tube formation capacity via inhibiting ROS overproduction and NF-κB activation, subsequently down-regulating adhesion molecules and chemokines. These effects may be partially due to the up-regulation of uncoupling protein 2 (UCP2) in HUVECs that was induced by the secretion of stanniocalcin 1 (STC1) from MSCs. In vivo, MSCs transplantation ameliorated the progression of diabetes-associated vascular dysfunction by reducing ROS production and down-regulating the expression of adhesion molecules. These results suggest that MSCs protect HUVECs from inflammatory injury partially by secreting STC1. MSCs may be a potential therapeutic approach for the treatment of diabetic vascular complications.
https://ift.tt/2IZIsUg
IL-34 regulates IL-6 and IL-8 production in human lung fibroblasts via MAPK, PI3K-Akt, JAK and NF-κB signaling pathways
Publication date: August 2018
Source:International Immunopharmacology, Volume 61
Author(s): Jie Zhou, Xiaoyu Sun, Juan Zhang, Yang Yang, Dapeng Chen, Ju Cao
IL-34 plays diverse roles in disease due to its inflammatory and immunosuppressive properties. Elevated IL-34 expression has been observed in lung cancers and pulmonary infections although its role is unclear. We found that IL-34 addition to primary lung fibroblasts significantly promoted IL-6 and IL-8 expression in a dose and time dependent manner. These effects were reversed when JAK, NF-κB, Akt and p38 inhibitors were included before IL-34 addition. Protein phosphorylation in these pathways was also observed through western-blotting. Stimulation of human lung fibroblasts with IL-34 in combination with TNF-α, IL-17A and IL-4 enhanced inflammatory cytokine production. Our data confirmed the inflammatory effect of IL-34 on human lung fibroblasts and suggested that the IL-34/CSF-1R axis may be a novel therapeutic target in pulmonary disease.
https://ift.tt/2H28jF9
Editorial Board
Publication date: July 2018
Source:International Immunopharmacology, Volume 60
https://ift.tt/2kB6C8Q
Corrigendum to “Oleamide suppresses inflammatory responses in LPS-induced RAW264.7 murine macrophages and alleviates paw edema in a carrageenan-induced inflammatory rat model” [Int. Immunopharmacol. 56 (2018) 179–185]
Publication date: July 2018
Source:International Immunopharmacology, Volume 60
Author(s): Sung-Min Moon, Seul Ah. Lee, Joon Ho Hong, Jae-Sung Kim, Do Kyung Kim, Chun Sung Kim
https://ift.tt/2H4yHhs
Editorial Board
Source:NeuroImage, Volume 177
https://ift.tt/2L47DBo
Metacognitive beliefs in addictive behaviours: A systematic review
Source:Addictive Behaviors, Volume 85
Author(s): Tristan Hamonniere, Isabelle Varescon
A wide research base has shown the link between metacognitive beliefs and psychopathology and there is currently evidence that elevated levels of maladaptive metacognitive beliefs are present in the majority of psychological disorders. An increasing body of evidence also suggests that metacognitive beliefs may play a role in alcohol use, nicotine use, gambling, online gaming and problematic internet use. This article provides a systematic review of empirical studies that have examined metacognitive beliefs and addictive behaviours. Thirty-eight studies were included, with results showing a significant positive association between metacognitive beliefs and addictive behaviours. These results are consistent with the metacognitive model of addictive behaviour that supports the central role of metacognitive beliefs in the development and maintenance of addictive behaviours. However, our review highlights the paucity of longitudinal and experimental studies, preventing the determination of the causal status of metacognitive beliefs in addictive behaviours. Despite this limitation, the current evidence has important treatment implications because it suggests that interventions that target metacognitive beliefs could be beneficial for people presenting with addictive behaviours.
https://ift.tt/2xmH1tv
Disability status and prescription drug misuse among U.S. adults
Source:Addictive Behaviors, Volume 85
Author(s): Jason A. Ford, Melanie Sberna Hinojosa, Harvey L. Nicholson
BackgroundThe U.S. is in the midst of a public health crisis related to drug overdose deaths. Largely responsible for the dramatic increase in overdose deaths is the misuse of prescription drugs such as opioids and benzodiazepines. While much research attention has focused on correlates of prescription drug misuse in recent years, notable gaps in the literature remain. The current research addresses one of these gaps by examining the relationship between disability status and prescription drug misuse.MethodWe examine data from the 2015 National Survey on Drug use and Health, a leading source of epidemiological data on drug use in the United States that added questions related to disability status to the 2015 survey. The current research assessed the relationship between disability status (i.e. activities of daily living and instrumental activities of daily living) and prescription drug misuse (i.e. opioids and benzodiazepines) among adults.ResultsFindings from multinomial logistic regression analysis showed that a disability related to activities of daily living was correlated with opioid misuse, while a disability associated with instrumental activities of daily living was associated with benzodiazepine misuse and misuse of both. In addition, health related measures had a greater impact on the relationship between disability status and prescription drug misuse than did the social engagement/isolation measures.ConclusionFindings indicated that disability status is a significant correlate of prescription drug misuse. However, this relationship was largely mediated by measures associated with poor health and social engagement/isolation.
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Biased G Protein-Coupled Receptor Signaling: Changing the Paradigm of Drug Discovery.
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Public Reporting III: Improving the Value of Public Physician Quality Information.
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Long-Term Risk of Cardiovascular Disease in Women Who Have Had Infants With Heart Defects.
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Hospital Readmission After Perioperative Acute Myocardial Infarction Associated With Noncardiac Surgery.
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Suboptimal Outcome of Myocardial Infarction After Noncardiac Surgery: Physicians Can and Should Do More.
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Status of Hypertension in China: Results From the China Hypertension Survey, 2012-2015.
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Hypertension in China: Time to Transition From Knowing the Problem to Implementing the Solution.
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Right Ventricular Myofilament Functional Differences in Humans With Systemic Sclerosis-Associated Versus Idiopathic Pulmonary Arterial Hypertension.
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NMDA-Type Glutamate Receptor Activation Promotes Vascular Remodeling and Pulmonary Arterial Hypertension.
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New Therapeutic Approaches in Pulmonary Arterial Hypertension: The Pantheon Is Getting Crowded.
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Energetics of Blood Flow in Cardiovascular Disease: Concept and Clinical Implications of Adverse Energetics in Patients With a Fontan Circulation.
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Battery Malfunction of a Leadless Cardiac Pacemaker: Worrisome Single-Center Experience.
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Letter by Hernandez-Gonzalez et al Regarding Article, "Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension".
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Response by Hadinnapola et al to Letter Regarding Article, "Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension".
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Letter by Lowe et al Regarding Article, "Low-Density Lipoprotein Cholesterol Lowering for the Primary Prevention of Cardiovascular Disease Among Men With Primary Elevations of Low-Density Lipoprotein Cholesterol Levels of 190 mg/dL or Above: Analyses From the WOSCOPS (West of Scotland Coronary Prevention Study) 5-Year Randomized Trial and 20-Year Observational Follow-Up".
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Letter by Koh Regarding Article, "Low-Density Lipoprotein Cholesterol Lowering for the Primary Prevention of Cardiovascular Disease Among Men With Primary Elevations of Low-Density Lipoprotein Cholesterol Levels of 190 mg/dL or Above: Analyses From the WOSCOPS (West of Scotland Coronary Prevention Study) 5-Year Randomized Trial and 20-Year Observational Follow-Up".
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Response by Vallejo-Vaz et al to Letters Regarding Article, "Low-Density Lipoprotein Cholesterol Lowering for the Primary Prevention of Cardiovascular Disease Among Men With Primary Elevations of Low-Density Lipoprotein Cholesterol Levels of 190 mg/dL or Above: Analyses From the WOSCOPS (West of Scotland Coronary Prevention Study) 5-Year Randomized Trial and 20-Year Observational Follow-Up".
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Letter by Campochiaro et al Regarding Article, "Clinical Features, Management, and Outcomes of Immune Checkpoint Inhibitor-Related Cardiotoxicity".
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Response by Thuny et al to Letter Regarding Article, "Clinical Features, Management, and Outcomes of Immune Checkpoint Inhibitor-Related Cardiotoxicity".
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Letter by Lema Regarding Article, "The Value of Preoperative Assessment Before Noncardiac Surgery in the Era of Value-Based Care".
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From Improved Diagnostics to Presurgical Planning: High-Resolution Functionally Graded Multimaterial 3D Printing of Biomedical Tomographic Data Sets
3D Printing and Additive Manufacturing, Ahead of Print.
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Transcription Factor IRF8 Orchestrates the Adaptive Natural Killer Cell Response
Publication date: Available online 29 May 2018
Source:Immunity
Author(s): Nicholas M. Adams, Colleen M. Lau, Xiying Fan, Moritz Rapp, Clair D. Geary, Orr-El Weizman, Carlos Diaz-Salazar, Joseph C. Sun
Natural killer (NK) cells are innate lymphocytes that display features of adaptive immunity during viral infection. Biallelic mutations in IRF8 have been reported to cause familial NK cell deficiency and susceptibility to severe viral infection in humans; however, the precise role of this transcription factor in regulating NK cell function remains unknown. Here, we show that cell-intrinsic IRF8 was required for NK-cell-mediated protection against mouse cytomegalovirus infection. During viral exposure, NK cells upregulated IRF8 through interleukin-12 (IL-12) signaling and the transcription factor STAT4, which promoted epigenetic remodeling of the Irf8 locus. Moreover, IRF8 facilitated the proliferative burst of virus-specific NK cells by promoting expression of cell-cycle genes and directly controlling Zbtb32, a master regulator of virus-driven NK cell proliferation. These findings identify the function and cell-type-specific regulation of IRF8 in NK-cell-mediated antiviral immunity and provide a mechanistic understanding of viral susceptibility in patients with IRF8 mutations.
Graphical abstract
Teaser
The link between human IRF8 mutations and immunodeficiency is poorly understood. Adams et al. demonstrate that IRF8 is required for NK-cell-mediated antiviral immunity by promoting proliferation of virus-specific NK cells.https://ift.tt/2L6nAXS
Human Enteric α-Defensin 5 Promotes Shigella Infection by Enhancing Bacterial Adhesion and Invasion
Publication date: Available online 29 May 2018
Source:Immunity
Author(s): Dan Xu, Chongbing Liao, Bing Zhang, W. David Tolbert, Wangxiao He, Zhijun Dai, Wei Zhang, Weirong Yuan, Marzena Pazgier, Jiankang Liu, Jun Yu, Philippe J. Sansonetti, Charles L. Bevins, Yongping Shao, Wuyuan Lu
Shigella is a Gram-negative bacterium that causes bacillary dysentery worldwide. It invades the intestinal epithelium to elicit intense inflammation and tissue damage, yet the underlying mechanisms of its host selectivity and low infectious inoculum remain perplexing. Here, we report that Shigella co-opts human α-defensin 5 (HD5), a host defense peptide important for intestinal homeostasis and innate immunity, to enhance its adhesion to and invasion of mucosal tissues. HD5 promoted Shigella infection in vitro in a structure-dependent manner. Shigella, commonly devoid of an effective host-adhesion apparatus, preferentially targeted HD5 to augment its ability to colonize the intestinal epithelium through interactions with multiple bacterial membrane proteins. HD5 exacerbated infectivity and Shigella-induced pathology in a culture of human colorectal tissues and three animal models. Our findings illuminate how Shigella exploits innate immunity by turning HD5 into a virulence factor for infection, unveiling a mechanism of action for this highly proficient human pathogen.
Teaser
How Shigella can be infectious in humans despite lacking clear mechanisms for mucosal adhesion remains a long-standing enigma concerning its pathogenesis. Xu et al. demonstrate that Shigella exploits the host defense peptide HD5 in the gut to attain its ability to colonize and destroy the intestinal epithelium.https://ift.tt/2JbZYE1
The Tumor Necrosis Factor Superfamily Member RANKL Suppresses Effector Cytokine Production in Group 3 Innate Lymphoid Cells
Publication date: Available online 29 May 2018
Source:Immunity
Author(s): Jennifer K. Bando, Susan Gilfillan, Christina Song, Keely G. McDonald, Stanley C.-C. Huang, Rodney D. Newberry, Yasuhiro Kobayashi, David S.J. Allan, James R. Carlyle, Marina Cella, Marco Colonna
While signals that activate group 3 innate lymphoid cells (ILC3s) have been described, the factors that negatively regulate these cells are less well understood. Here we found that the tumor necrosis factor (TNF) superfamily member receptor activator of nuclear factor κB ligand (RANKL) suppressed ILC3 activity in the intestine. Deletion of RANKL in ILC3s and T cells increased C-C motif chemokine receptor 6 (CCR6)+ ILC3 abundance and enhanced production of interleukin-17A (IL-17A) and IL-22 in response to IL-23 and during infection with the enteric murine pathogen Citrobacter rodentium. Additionally, CCR6+ ILC3s produced higher amounts of the master transcriptional regulator RORγt at steady state in the absence of RANKL. RANKL-mediated suppression was independent of T cells, and instead occurred via interactions between CCR6+ ILC3s that expressed both RANKL and its receptor, RANK. Thus, RANK-RANKL interactions between ILC3s regulate ILC3 abundance and activation, suggesting that cell clustering may control ILC3 activity.
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Teaser
Although signals that activate group 3 ILCs (ILC3s) have been described, the factors that negatively regulate these cells are less well understood. Bando et al. demonstrate that the TNF superfamily member RANKL suppresses the abundance and effector functions of intestinal CCR6+ ILC3s and that RANKL-mediated suppression occurs through ILC3-ILC3 interactions.https://ift.tt/2L7obs6
Extrathymically Generated Regulatory T Cells Establish a Niche for Intestinal Border-Dwelling Bacteria and Affect Physiologic Metabolite Balance
Publication date: Available online 29 May 2018
Source:Immunity
Author(s): Clarissa Campbell, Stanislav Dikiy, Shakti K. Bhattarai, Takatoshi Chinen, Fanny Matheis, Marco Calafiore, Beatrice Hoyos, Alan Hanash, Daniel Mucida, Vanni Bucci, Alexander Y. Rudensky
The mammalian gut microbiota provides essential metabolites to the host and promotes the differentiation and accumulation of extrathymically generated regulatory T (pTreg) cells. To explore the impact of these cells on intestinal microbial communities, we assessed the composition of the microbiota in pTreg cell-deficient and -sufficient mice. pTreg cell deficiency led to heightened type 2 immune responses triggered by microbial exposure, which disrupted the niche of border-dwelling bacteria early during colonization. Moreover, impaired pTreg cell generation led to pervasive changes in metabolite profiles, altered features of the intestinal epithelium, and reduced body weight in the presence of commensal microbes. Absence of a single species of bacteria depleted in pTreg cell-deficient animals, Mucispirillum schaedleri, partially accounted for the sequelae of pTreg cell deficiency. These observations suggest that pTreg cells modulate the metabolic function of the intestinal microbiota by restraining immune defense mechanisms that may disrupt a particular bacterial niche.
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Teaser
Extrathymically generated regulatory (pTreg) cells are induced by bacterial products at mucosal sites. In this issue, Campbell et al. show that pTreg cell deficiency impedes the establishment of a subset of intestinal bacteria due to heightened immune responses, with significant effects on host metabolites and fitness.https://ift.tt/2JfIVAU
Hemogenic Endothelial Fate Mapping Reveals Dual Developmental Origin of Mast Cells
Publication date: Available online 29 May 2018
Source:Immunity
Author(s): Rebecca Gentek, Clément Ghigo, Guillaume Hoeffel, Maxime Jacques Bulle, Rasha Msallam, Gregory Gautier, Pierre Launay, Jinmiao Chen, Florent Ginhoux, Marc Bajénoff
Hematopoiesis occurs in distinct waves. "Definitive" hematopoietic stem cells (HSCs) with the potential for all blood lineages emerge in the aorta-gonado-mesonephros, while "primitive" progenitors, whose potential is thought to be limited to erythrocytes, megakaryocytes, and macrophages, arise earlier in the yolk sac (YS). Here, we questioned whether other YS lineages exist that have not been identified, partially owing to limitations of current lineage tracing models. We established the use of Cdh5-CreERT2 for hematopoietic fate mapping, which revealed the YS origin of mast cells (MCs). YS-derived MCs were replaced by definitive MCs, which maintained themselves independently from the bone marrow in the adult. Replacement occurred with tissue-specific kinetics. MCs in the embryonic skin, but not other organs, remained largely YS derived prenatally and were phenotypically and transcriptomically distinct from definite adult MCs. We conclude that within myeloid lineages, dual hematopoietic origin is shared between macrophages and MCs.
Graphical abstract
Teaser
Gentek et al. demonstrate that Cdh5-CreERT2 can be used to selectively fate map yolk sac and definitive hematopoiesis. Temporally defined Cdh5-CreERT2 lineage tracing reveals that mast cells are yolk sac derived in the embryo but replaced by definitive hematopoiesis in the adult, a feature they share with macrophages.https://ift.tt/2L5PYcw
Biochemical analysis and identification of linear B-cell epitopes from recombinant Sm21.7 antigen from Schistosoma mansoni
Source:Molecular Immunology, Volume 101
Author(s): Cíntia M.F. Rezende, Juliana B. Coitinho, Mariana Costa, Marina Rodrigues Silva, Mário Giusta, Roberta Oliveira-Prado, Rodrigo Corrêa-Oliveira, Ronaldo Nagem, Alfredo M. Goes
Schistosoma mansoni tegument is a dynamic host-interactive layer that is an essential source of parasite antigens and a relevant field for schistosome vaccine research. Sm21.7 is a cytoskeleton antigen found in S. mansoni tegument that engenders protection in experimental challenge infection. Because of its crucial role in the parasite tegument and its promising protective capability, Sm21.7 is an exciting target for the development of therapeutic strategies. The present study describes Sm21.7 structural and biophysical features using circular dichroism spectroscopy and identifies linear B-cell epitopes of Sm21.7 using in-silico methods and immunoassay. The Sm21.7 gene was cloned into the pETDEST42 vector, and the recombinant protein was overexpressed in Escherichia coli DE3. The soluble protein was purified by affinity chromatography followed by ion-exchange chromatography. Purified recombinant Sm21.7 was analyzed by circular dichroism spectroscopy which demonstrated that the rSm21.7 structure was comprised of approximately 38% α-helices and its conformation remains stable at temperatures of up to 60 °C. Prediction of rSm21.7 B-cell epitopes was based on amino acid physicochemical properties. Sixteen peptides corresponding to predicted epitopes were synthesized and immunoreactivity assessed by spot peptide array using pooled rSm21.7-immunized mice sera or patients' sera with different clinical forms of S. mansoni infection. Immunoassays revealed that sera from rSm21.7-immunized mice reacted predominantly with peptides located in the dynein-light chain domain (DLC) at the C-terminal region of rSm21.7. Comparative analysis of the antibody response of acute, intestinal and hepatosplenic patients' sera to the Sm21.7 peptides showed that a differential recognition pattern of Sm21.7-derived peptides by intestinal patients' sera might contribute to down-regulate the immune response in chronic intestinal patients. Together, the results may help the development of S. mansoni vaccine strategies based on the rSm21.7 antigen.
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Occurrence and distribution of antibiotics in surface water impacted by crab culturing: a case study of Lake Guchenghu, China
Abstract
The objective of this study was to evaluate the occurrence, distribution, potential sources, and ecological risk of antibiotics in aqueous phase of Lake Guchenghu, China. Target antibiotics in surface water of Lake Guchenghu, adjacent streams, and crab ponds were detected seasonally. The results showed that erythromycin-H2O (1.60–2450 ng/L), sulfadiazine (ND–654 ng/L), and florfenicol (ND–919 ng/L) were the predominant antibiotics in Lake Guchenghu. The concentrations of antibiotics in Lake Guchenghu Basin showed obvious seasonal variation, with the highest concentration in summer. In general, the concentrations of antibiotics in crab ponds and streams were higher than those in the lake and spatial distributions of antibiotics were affected by pollution sources. The types and origins of antibiotics indicated that wastewater from ponds was the main source of antibiotics in the lake. Risk assessment suggested that as individual compound, erythromycin-H2O and clarithromycin posed a high risk to algae while other compounds might pose low or no risk. The mixture of antibiotics may pose a high risk to aquatic organisms in Lake Guchenghu. Overall, our study revealed the occurrence and spatiotemporal variation of antibiotics in Lake Guchenghu, which was related with crab culturing.
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Editorial Board
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50
https://ift.tt/2xn9Wh9
Editorial overview: Neurotechnologies
Source:Current Opinion in Neurobiology, Volume 50
Author(s): Polina Anikeeva, Liqun Luo
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Contents page
Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50
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A bi-directional model of exercise and episodic memory function
Source:Medical Hypotheses, Volume 117
Author(s): Pamela Ponce, Paul D. Loprinzi
Recent empirical work suggests that acute exercise engagement may help to subserve episodic memory function. In this paper, we discuss these effects as well as introduce a hypothesized model suggesting a potential bi-directional relationship between exercise and memory. We provide empirical support for each of the pathways delineated within this model. Future research is needed to empirically evaluate the totality of this model. If such work demonstrates utility and predictive validity, then this model will have important implications not only for clinicians, but for the exercise neurobiology field as well.
https://ift.tt/2ISI49H
Autologous white blood cell infusion for trauma, brain trauma, stroke and select immune dysfunction co-morbidities: A promising and timely proposal?
Source:Medical Hypotheses, Volume 117
Author(s): Gerald Dieter Griffin, Dominique Charron, Reem Al-Daccak
All traumas suppress the immune system, resulting in higher morbidity and mortality. Infections, poor nutritional status, chronic illness, fatigue, therapies or procedures performed during and after transport also negatively affect the immune system. Large populations are impacted by trauma worldwide and suffer enormous costs in both direct and indirect expenditures from physical, psychological and functional losses. Most therapies and studies of trauma, brain trauma, stroke, immune suppression and their co-morbidities do not address nor discuss methods that promote immune system resuscitation or efficacy to support its role in post-trauma healing and rehabilitation. These omissions present an opportunity for using autologous stored naïve (unexposed to the current trauma and co-morbidities) white blood cell infusions (autologous white blood cell infusion) (AWBCI) to supplement treatment of most traumas, trauma-associated infections, other co-morbidities and immune suppression derived problems in order to improve the global standard of trauma care. We hypothesize to give the traumatized patients back their own immune system that has been 'stored' in some fashion, either cryogenically or just after or during the trauma event [surgery, etc for example]. We emphasize that other treatments should not be replaced – rather we suggest AWBCI as concurrent therapy. We present focused select animal and human studies as proofs of concept to arrive at and support our therapeutic suggestion and hypotheses, flowing historically from donor white blood cell therapy [DLI] to close cohort white blood cell therapy to autologous white blood cell infusion [AWBCI]. We integrate the concept of personalized medicine from an evidence-based framework while maintaining scientific rigor and statistical proof as a basis of our hypotheses.
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Editorial Board
Source:Medical Hypotheses, Volume 116
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Characterization of twelve autophagy-related genes from yellow catfish Pelteobagrus fulvidraco and their transcriptional responses to waterborne zinc exposure
Publication date: October 2018
Source:Ecological Indicators, Volume 93
Author(s): Chuan-Chuan Wei, Zhi Luo, Yu-Feng Song, Ya-Xiong Pan, Mei-Qing Zhuo
Autophagy acts as important cytoprotective mechanism in response to adverse environment conditions. The hypothesis of the present study is that autophagy acts as protective responses to waterborne Zn exposure. To this end, the full-length cDNA sequences of 12 key genes related to autophagy in yellow catfish Pelteobagrus fulvidraco were cloned, and their mRNA expression profiles and transcriptional responses to waterborne Zn exposure were explored. The 12 genes (SQSTM1, Beclin1, ULK1A, ULK1B, ATG13-1, ATG13-2, ATG101, ATG9A, ATG9B, ATG3, ATG5 and ATG7) mediated the core autophagy machinery, including autophagosome membrane initiation, nucleation, expansion, closure and maturation. All of these members shared similar domain structure to their orthologous genes of other vertebrates. Their mRNAs were widely expressed in various tissues, but at different levels. Zn exposure increased the amount of hepatic autophagic vacuoles, and elevated the mRNA levels of SQSTM1, ULK1A, ULK1B, ATG13, ATG101, ATG9A, ATG9B, ATG3 and ATG7 in a dose- and time-dependent manner, indicating autophagy activation. These results indicated that autophagy acted as an adaptive response to protect from Zn toxicity and confirmed our hypothesis. Moreover, those up-regulated genes may play crucial roles in autophagy response to Zn exposure. For the first time, we characterized the full-length cDNA sequences of twelve autophagy related genes from fish, and determined their transcriptional responses to waterborne Zn exposure, which would contribute to our understanding of the molecular basis of autophagy and Zn toxicity, and also shed new insights on the potential role of autophagy as an adaptive response against metal toxicity in vertebrates.
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Analysis of aluminum, minerals and trace elements in the milk samples from lactating mothers in Hamadan, Iran
Publication date: December 2018
Source:Journal of Trace Elements in Medicine and Biology, Volume 50
Author(s): Masoumeh Taravati Javad, Aliasghar Vahidinia, Fateme Samiee, Jomana Elaridi, Mostafa Leili, Javad Faradmal, Alireza Rahmani
The present cross-sectional study is aimed at analyzing the breast milk of lactating mothers in Hamadan, Iran for aluminum and several minerals and trace elements. Ten governmental health care centers were utilized to facilitate collection of breast milk samples. The breast milk samples were collected at 1, 2, 6, 7, and 12 months postpartum from one hundred healthy lactating women, who delivered full-term newborns. Detection of sodium (Na), zinc (Zn), calcium (Ca), iron (Fe), copper (Cu), magnesium (Mg) and aluminum (Al) levels was conducted with the use of Inductively Coupled Plasma Mass Spectrometry (ICP-MS). This method has shown high accuracy, precision, sensitivity, and linearity for the wide range of concentrations. The accumulated data were not normally distributed; thus, the non-parametric Mann-Whitney U test was used in the statistical analysis of the results. Mean concentrations of Fe, Zn, Cu, Ca, Mg, and Na were 0.75, 1.38, 0.35, 255, 34.58, and 155.72 μg/mL, respectively. The mean level of Al, a well-known neurotoxic metal, was determined to be an alarming 0.191 μg/mL. Moreover, 95% of participants contained very harmful concentrations of Al in their milk. This study also revealed Zn deficiency in about 50% of milk samples. Further investigation is needed to elucidate sources of exposure and factors that may influence maternal and fetal exposure to aluminum.
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Improved Brain Penetration and Antitumor Efficacy of Temozolomide by Inhibition of ABCB1 and ABCG2
Publication date: July 2018
Source:Neoplasia, Volume 20, Issue 7
Author(s): Mark C. de Gooijer, Nienke A. de Vries, Tessa Buckle, Levi C.M. Buil, Jos H. Beijnen, Willem Boogerd, Olaf van Tellingen
The anticancer drug temozolomide is the only drug with proven activity against high-grade gliomas and has therefore become a part of the standard treatment of these tumors. P-glycoprotein (P-gp; ABCB1) and breast cancer resistance protein (BCRP; ABCG2) are transport proteins, which are present at the blood-brain barrier and limit the brain uptake of substrate drugs. We have studied the effect of P-gp and BCRP on the pharmacokinetics and pharmacodynamics of temozolomide, making use of a comprehensive set of in vitro transport experiments and in vivo pharmacokinetic and antitumor efficacy experiments using wild-type, Abcg2−/−, Abcb1a/b−/−, and Abcb1a/b;Abcg2−/− mice. We here show that the combined deletion of Abcb1a/b and Abcg2 increases the brain penetration of temozolomide by 1.5-fold compared to wild-type controls (P < .001) without changing the systemic drug exposure. Moreover, the same increase was achieved when temozolomide was given to wild-type mice in combination with the dual P-gp/BCRP inhibitor elacridar (GF120918). The antitumor efficacy of temozolomide against three different intracranial tumor models was significantly enhanced when Abcb1a/b and Abcg2 were genetically deficient or pharmacologically inhibited in recipient mice. These findings call for further clinical testing of temozolomide in combination with elacridar for the treatment of gliomas, as this offers the perspective of further improving the antitumor efficacy of this already active agent.
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Effects of Dance Exergaming on Depressive Symptoms, Fear of Falling, and Musculoskeletal Function in Fallers and Nonfallers Community-Dwelling Older Women
Rejuvenation Research, Ahead of Print.
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Scholar : These new articles for Alcheringa: An Australasian Journal of Palaeontology are available online
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Anti-allergy and anti-tussive activity of Clitoria ternatea L. in experimental animals
Publication date: 5 October 2018
Source:Journal of Ethnopharmacology, Volume 224
Author(s): Niraj Kumar Singh, Debapriya Garabadu, Priyanka Sharma, Sushant Kumar Shrivastava, Pradeep Mishra
Ethnopharmacological relevanceClitoria ternatea flower is traditionally used in the treatment of respiratory disorders including bronchitis and is one of the ingredients in different Ayurvedic preparations that are used in respiratory disorders. However, till date there is no scientific report on the anti-asthmatic activity of this flower.Aim of the studyEthanolic extract of Clitoria ternatea flowers (ECT) was evaluated for its anti-allergy and anti-tussive potential in experimental animals. Additionally, the anti-inflammatory potential of ECT was carried out to draw a plausible mechanism of action of the drug.Materials and MethodsIn-vitro anti-asthmatic activity of ECT was evaluated in goat tracheal chain and isolated guinea pig ileum preparations. Acute and chronic anti-asthmatic activity of ECT (100, 200 and 400 mg/kg; p.o.) was estimated in histamine aerosol exposed guinea pigs and in OVA sensitized and challenged mice respectively. Anti-tussive activity of ECT (100, 200 and 400 mg/kg; p.o.) was evaluated against sulfur dioxide- and citric acid-induced cough in experimental animals. Moreover, the anti-inflammatory activity of ECT (100, 200 and 400 mg/kg; p.o.) was evaluated against carrageenan- and acetic acid-induced inflammation in rats.ResultsECT attenuated histamine-induced contraction in both goat tracheal chain and isolated guinea pig ileum preparations. ECT (400 mg/kg) attenuated histamine-induced dyspnoea and OVA-induced changes in differential cell count in broncheoalveolar fluid, levels of interleukins (IL-1beta and IL-6) and immunoglobulin (OVA-sensitive IgG1) in animals. ECT (400 mg/kg) further ameliorated sulfur dioxide- and citric acid-induced cough in experimental animals. Additionally, ECT (400 mg/kg) attenuated inflammation in carrageenan and acetic acid challenged rodents.ConclusionsStandardized ECT could be considered as a potential therapeutic alternative in the management of allergy-induced asthma.
Graphical abstract
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Contamination levels and health risk assessments of heavy metals in an oasis-desert zone: a case study in northwest China
Abstract
Rapid and extensive social and economic development has caused severe soil contamination by heavy metals in China. The spatial distribution, pollution levels, and health risks of metals were identified in an oasis-desert zone of northwest China. The mean concentrations of six heavy metals exceeded their corresponding background contents, and each metal concentration in farmland samples was higher than that in Gobi samples. Moreover, these heavy metals followed a similar spatial pattern and showed significant positive correlations with each other, indicating that they have the same sources. The contamination features of heavy metals and ecological risks were calculated using several quality indicators, and their health risks for population groups were quantified. The results showed that the Gobi and farmland soils were uncontaminated to moderately contaminated by heavy metals, and that farmland pollution was more serious than that of Gobi. The Gobi and farmland soils posed low ecological risks. As a whole, the non-carcinogenic risk which was caused by heavy metals was low for local residents, and the carcinogenic risk was within an acceptable level. Comparatively speaking, children were the more vulnerable population to health risks. The Zn and Cu pollution was relatively serious, and Cr and V were major contributors to health risks.
Graphical abstract
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Combined toxicity of chlorantraniliprole, lambda-cyhalothrin, and imidacloprid to the silkworm Bombyx mori (Lepidoptera: Bombycidae)
Abstract
Insecticides with different modes of action may act in combination, in ways such as drifting, spray equipment residual, or utilizing concurrently in mulberry orchards or nearby agricultural fields. Silkworms may suffer from a diverse impact on the survival. In this study, the toxicity of chlorantraniliprole, lambda-cyhalothrin, and imidacloprid and their combinations to the second instar of silkworms (Bombyx mori (L.)(Lepidoptera: Bombycidae)) were evaluated after 48 and 72 h treatment by the leaf-dipping method and the combination index (CI)-isobologram equation. After 48 h treatment, results indicated that (1) the increasing order of toxicity was imidacloprid < chlorantraniliprole < lambda-cyhalothrin, and that (2) synergism was predominated in most combinations excepted for the lambda-cyhalothrin + imidacloprid combination which displayed an additive effect at fa value 0.5. Then, after 72 h treatment, results exhibited that (1) the increasing order of toxicity was imidacloprid < lambda-cyhalothrin < chlorantraniliprole, and that (2) only the chlorantraniliprole + imidacloprid mixture yielded antagonism at fa value 0.5; the other combinations performed an additive effect at least. Consequently, combined toxicity of mixtures may pose a worse effect on silkworm than single toxicity of insecticides. Therefore, we suggest that insecticide mixtures should be added into ecotoxicological risk assessment.
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Scholar : These new articles for Aphasiology are available online
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Editorial Board
Source:Artificial Intelligence in Medicine, Volume 87
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Monitoring and spatiotemporal variations of pyrethroid insecticides in surface water, sediment, and fish of the river Chenab Pakistan
Abstract
There is a serious concern regarding freshwater resources of Pakistan which have been mismanaged and now are depleting extensively due to other reasons like intensive application of agricultural pesticides and insecticides. The present study was conducted to determine the concentrations of cypermethrin, deltamethrin, permethrin, and bifenthrin in the samples of water, sediments, and fish collected from various locations of River Chenab, Pakistan, during summer and winter seasons. These locations include namely Marala, Khanki, Qadirabad, and Trimu Headworks. High-performance liquid chromatography (HPLC) was deployed for analysis and determination of pyrethroid concentrations in these samples. The analytics show the order of pyrethroid concentrations in river as fish> sediment>water. Whereas maximum concentrations of 0.472 μg g−1 found in fish and minimum concentrations were determined in water, i.e., 0.087 μg L−1 at the sampling locations of Trimu and Marala headworks, respectively. Moreover, highest mean concentrations of pyrethroid, i.e., 1.248 μg g−1 in fish were detected in winter season as compared to summers, i.e., 0.087 μg L−1. However, all the values of pyrethroid were found to be lower than the maximum permissible levels specified by EU and WHO-FAO. Whereas the levels of deltamethrin and permethrin in water were found much higher than the specific limits set by EU.
https://ift.tt/2kznvR2
Study of Proton SBRT and Immunotherapy for Recurrent/Progressive Locoregional or Metastatic Head and Neck Cancer
Interventions: Radiation: Proton Stereotactic Body Radiation Therapy (SBRT) (5 fractions; 3500-4500 cGy); Radiation: Proton Stereotactic Body Radiation Therapy (SBRT) (3-5 fractions; various dose and fractionation regimens depending on treatment site).; Drug: Nivolumab 3 mg/kg IV q2 weeks; Radiation: Proton or Photon SBRT (3-5 fractions; various dose and fractionation regimens depending on treatment site).
Sponsor: Mayo Clinic
Not yet recruiting
https://ift.tt/2L6ZKeK
A Phase Ib Trial of Cabozantinib in Combination With Durvalumab (MEDI4736) in Previously Treated Patients With Advanced Gastroesophageal Cancer and Other Gastrointestinal (GI) Malignancies (CAMILLA)
Interventions: Drug: Cabozantinib; Drug: Durvalumab
Sponsors: Anwaar Saeed; AstraZeneca; Exelixis
Not yet recruiting
https://ift.tt/2Je5tSn
Radiotherapy Concurrent With Apatinib in Advanced Soft Tissue and Bone Sarcomas of Head and Neck--RASS Study
Intervention: Drug: Apatinib Mesylate
Sponsor: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Not yet recruiting
https://ift.tt/2L5l1W4
Dose Constraints for the Temporal Lobes of Intensity-modulated Radiotherapy Treatment Plans for Nasopharyngeal Carcinoma
Intervention: Radiation: IMRT
Sponsors: Jiangxi Provincial Cancer Hospital; Sixth Affiliated Hospital, Sun Yat-sen University
Not yet recruiting
https://ift.tt/2ISMBcy
A new suppressor design for low noise performance with carbonate eluents for Ion Chromatography
Publication date: 1 October 2018
Source:Talanta, Volume 188
Author(s): Kannan Srinivasan, Brittany K. Omphroy, Rong Lin, Christopher A. Pohl
Carbonate and bicarbonate based eluents have been applied for ion analysis from the inception of ion chromatography. The product of suppression with carbonate and/or bicarbonate eluent is carbonic acid which is weakly dissociated and tends to outgas. While the act of suppression enhanced the signal for fully dissociated ions and lowered the background to a weakly dissociated level, the overall noise performance, however, varied depending on the suppression mechanism. Chemical suppression with a membrane suppressor yielded low noise performance with carbonate and/or bicarbonate eluents. Electrolytic suppression, on the other hand, resulted in a relatively higher noise with carbonate based eluents when compared to chemical suppression. In this work, we investigated the root cause of noise with electrolytic suppressors and carbonate based eluents. Further, a new electrolytic suppressor design based on a three-electrode design is discussed in this paper and provided low noise performance with carbonate and/or bicarbonate eluents.
https://ift.tt/2kyVGZ6
β-Cyclodextrin functionalization of metal-organic framework MOF-235 with excellent chemiluminescence activity for sensitive glucose biosensing
Publication date: 1 October 2018
Source:Talanta, Volume 188
Author(s): Xuanxiang Mao, Yuwan Lu, Xiaodan Zhang, Yuming Huang
Herein, we developed a new CL method for the detection of glucose, exhibiting high sensitivity, low limit of detection, good stability and reliability for analysis of real biological samples. The MOF-235/β-cyclodextrin (β-CD) hybrids were facilely prepared by a simple method, and characterized by XRD, TGA, FT-IR and SEM. The as-prepared hybrids exhibited highly catalytic activity for the hydrogen peroxide-luminol system, and gave more than 30-fold enhancement in CL response as compared with that of hydrogen peroxide-luminol system, thus could be used for sensitive detection of H2O2 and glucose. The excellent catalytic performance of the MOF-235/β-CD hybrids is ascribed to the large surface area of MOF-235 as well as the synergistic effect between β-CD and MOF-235. The proposed sensing strategy coupled with CL detection method showed low detection limits of 5 nM and 10 nM for H2O2 and glucose, respectively. Successful application of the MOF-235/β-CD hybrid in CL assay of glucose in real human serum samples is demonstrated as an efficient catalyst for sensitive chemiluminescence-based analyses. The success of this work favors to facilitate the future development in CL catalysts via MOF functionalization.
Graphical abstract
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Temporal decomposition sampling and chemical characterization of eucalyptus harvest residues using NIR spectroscopy and chemometric methods
Publication date: 1 October 2018
Source:Talanta, Volume 188
Author(s): Gabriel W.D. Ferreira, Jussara V. Roque, Emanuelle M.B. Soares, Ivo R. Silva, Eulene F. Silva, Aline A. Vasconcelos, Reinaldo F. Teófilo
Near-infrared (NIR) spectroscopy and chemometric methods were used to predict the chemical properties of decomposing eucalyptus harvest residues to better understand the decomposition process of these materials. Leaves, twigs, branches, and bark from a decomposition experimental set up in commercial plantations were sampled for one year. The contents of carbon (C), nitrogen (N), extractives (EX), acid-soluble lignin (SL), Klason insoluble lignin (KL) and holocellulose (HC) were determined by the reference method in the collected samples. Principal component analysis (PCA) was employed to distinguish the types of harvest residues throughout the decomposition period. Multi-residue regression models were built from the NIR spectra using partial least squares regression (PLS). Two feature selection methods, i.e., ordered predictors selection (OPS) and genetic algorithm (GA), were applied and compared. The OPS and GA did not differ statistically; however, compared with the GA, OPS was more computationally efficient and selected fewer variables. Using the PLS-OPS models, the root mean square errors of prediction (RMSEP) for C, N, EX, SL, KL and HC were 19.70, 0.08, 0.74, 0.39, 28.13 and 33.99, respectively, and the prediction correlations (Rp) for these properties were 0.94, 0.99, 0.99, 0.99, 0.96 and 0.98, respectively. PLS-discriminant analysis (PLS-DA) was used to classify the samples over the decomposition time and provided a good separation. Some mismatches obtained in the modeled classes were explained by the differences in the decomposition rate and changes in the chemical composition of the different harvest residue components that were evaluated. The results showed the feasibility of NIR spectroscopy and chemometric methods to evaluate the chemistry of decomposing eucalyptus harvest residues, indicating that these methods can be used as rapid and inexpensive alternatives to conventional methods to help understand the decomposition process.
Graphical abstract
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Front Matter 1 - Full Title Page (regular issues)/Special Issue Title page (special issues)
Publication date: 1 September 2018
Source:Talanta, Volume 187
https://ift.tt/2skEASt
Editorial Board
Publication date: 1 September 2018
Source:Talanta, Volume 187
https://ift.tt/2kzFas5
Appraisal of comparative single-case experimental designs for instructional interventions with non-reversible target behaviors: Introducing the CSCEDARS (“Cedars”)
Publication date: Available online 28 May 2018
Source:Research in Developmental Disabilities
Author(s): Ralf W. Schlosser, Phillip J. Belfiore, Jeff Sigafoos, Amy M. Briesch, Oliver Wendt
Evidence-based practice as a process requires the appraisal of research as a critical step. In the field of developmental disabilities, single-case experimental designs (SCEDs) figure prominently as a means for evaluating the effectiveness of non-reversible instructional interventions. Comparative SCEDs contrast two or more instructional interventions to document their relative effectiveness and efficiency. As such, these designs have great potential to inform evidence-based decision-making. To harness this potential, however, interventionists and authors of systematic reviews need tools to appraise the evidence generated by these designs. Our literature review revealed that existing tools do not adequately address the specific methodological considerations of comparative SCEDs that aim to compare instructional interventions of non-reversible target behaviors. The purpose of this paper is to introduce the Comparative Single-Case Experimental Design Rating System (CSCEDARS, "cedars") as a tool for appraising the internal validity of comparative SCEDs of two or more non-reversible instructional interventions. Pertinent literature will be reviewed to establish the need for this tool and to underpin the rationales for individual rating items. Initial reliability information will be provided as well. Finally, directions for instrument validation will be proposed.
https://ift.tt/2L52CbQ
The ADHD rating scale-IV preschool version: Factor structure, reliability, validity, and standardisation in a Danish community sample
Publication date: Available online 28 May 2018
Source:Research in Developmental Disabilities
Author(s): Julie Lysdal Alexandre, Anne-Mette Lange, Niels Bilenberg, Anne Mette Gorrissen, Natasja Søbye, Rikke Lambek
BackgroundADHD is a debilitating disorder with symptoms often appearing in early childhood. To facilitate early identification, developmentally appropriate and validated assessment tools for the preschool-age are needed.AimsThe current study aims to examine the psychometric properties of the ADHD Rating Scale (RS)-IV Preschool Version (-P) in a Danish community sample and provide national standardisation data.Methods and proceduresParents (n = 916) and kindergarten teachers (n = 275) of preschool children, aged 3–5 years, completed the ADHD RS-IV-P.Outcomes and resultsConfirmatory factor analysis indicated that a three-factor model (inattention, hyperactivity, and impulsivity) best fit the data regardless of rater. Scales generally showed acceptable internal consistency, test-retest reliability, inter-rater reliability, and criterion validity. Boys received higher ratings on the ADHD RS-IV-P than girls and younger preschool children were rated as more inattentive than older preschool children.Conclusions and implicationsOur findings support the reliability and validity of the ADHD RS-IV-P and a three-factor model of ADHD. However, high factor correlations and similarity in model fit suggest that more research is needed to clarify the organisation of ADHD symptoms in preschool children. Furthermore, the external validity of separate ADHD dimensions at this age should be examined.
https://ift.tt/2Jb9JSH
Executive function in school-aged children with cerebral palsy: Relationship with speech and language
Publication date: Available online 28 May 2018
Source:Research in Developmental Disabilities
Author(s): Ashley Sakash, Aimee Teo Broman, Paul J. Rathouz, Katherine C. Hustad
Background and AimsAlthough children with cerebral palsy (CP) are at an increased risk for developing speech, language, and executive function (EF) impairments, little is known regarding the relationship among these risk factors. The current study examined how different profiles of speech and language impairment might be associated with impairments in EF skills in school-aged children with CP.Methods and ProceduresForty-seven school-aged children with CP were included. Each child contributed between one and four data points for a total of 87 data points. Children were classified into speech and language profile groups at each data point. EF skills were examined using the Behavior Rating Inventory of Executive Function questionnaire. Outcomes and Results. Compared to a mean of 50 from a normative population of children, mean scores on all measures of EF were significantly elevated for all groups (p<.05). The proportion of children with CP with elevated EF scores was significantly higher for all groups compared to the expected proportion in a normal population of children (p<.05).Conclusions and ImplicationsChildren with CP who do not have impairments in speech or language may be at risk for EF difficulties which may negatively affect social communication, academic performance, and functional independence.
https://ift.tt/2L3GHSf
Role of innate immune system in the pathogenesis of ankylosing spondylitis
Publication date: September 2018
Source:Biomedicine & Pharmacotherapy, Volume 105
Author(s): Negar Vanaki, Saeed Aslani, Ahmadreza Jamshidi, Mahdi Mahmoudi
Ankylosing Spondylitis (AS) is a debilitating rheumatic disease that gives young adults a severe form of arthritis with pain and stiffness in the axial skeleton. After the discovery of Human leukocyte antigen B27 (HLA-B27), several hypotheses have been suggested to uncover the exact etiology of AS. The tendency of HLA-B27 to form unusual structures results in recognition and activation of crucial components in innate immune system. Moreover, cellular and soluble arms of the innate response are frequently observed within the affected tissues. Genome-wide analysis has also shown the association of several innate immune-related pathways and cytokines, which act as the effective therapeutic targets in AS. Given the importance of innate immune system, we present a general overview of innate immune components and their involvement in the pathogenesis of AS. In our belief, this kind of explanation can hopefully provide new perspectives for diagnosis and treatment of these patients in the future.
https://ift.tt/2kyLksx
MicroRNA-497 promotes proliferation and inhibits apoptosis of cardiomyocytes through the downregulation of Mfn2 in a mouse model of myocardial ischemia-reperfusion injury
Publication date: September 2018
Source:Biomedicine & Pharmacotherapy, Volume 105
Author(s): Lei Qin, Wen Yang, Yao-Xin Wang, Zhen-Jun Wang, Chen-Chen Li, Man Li, Jie-Yun Liu
IntroductionMyocardial ischemia-reperfusion (I/R) injury affects millions of people worldwide and has a very high mortality rate. Since microRNA-497 (miR-497) has been found to be related with cardiomyocyte apoptosis, this study aimed to explore the effect of miR-497 by targeting Mfn2 in a mouse model of myocardial ischemia-reperfusion (I/R) injury.MaterialsBALB/c mice were modeled with I/R and some were injected with miR-497 agomir before I/R to observe whether miR-497 alleviates the injury that occurs as a result of I/R. Bioinformatics website and dual-luciferase reporter gene assay were employed in order to detect the relations between miR-497 and Mfn2 gene. Next, cells were extracted to be transfected with different mimic, inhibitor and siRNAs to further explore how miR-497 acts to I/R. Western blot analysis and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were conducted to measure expressions of miR-497, Mfn2, Fas, Bcl-2, Bax and Caspase-3 in myocardial tissues and cardiomyocytes after transfection. CCK-8 assay and flow cytometry were used to determine proliferation, cell cycle distribution and apoptosis of cardiomyocytes in each group after transfection.ResultsMice with I/R had myocardial dysfunction but before the injection with miR-497 agomir, the impairment was alleviated. Mfn2 was verified as the target gene of miR-497. The inhibition of miR-497 in turn inhibits Mfn2 expressione and cardiomyocyte apoptosis. The overexpression of miR-497 and Mfn2 gene silencing can lead to the promotion of proliferation capability of mice cardiomyocytes in vitro. Overexpressed miR-497 and Mfn2 gene silencing can also facilitate cell cycle entry and inhibit the apoptosis cardiomyocytes of mice in vitro.ConclusionThe present study provided strong evidence that miR-497 promotes proliferation and inhibits apoptosis of cardiomyocytes by downregulating the expression of Mfn2 in a mouse model of myocardial I/R injury.
https://ift.tt/2GZaOry
Glucose-regulated protein of 94 kDa contributes to the development of an aggressive phenotype in breast cancer cells
Publication date: September 2018
Source:Biomedicine & Pharmacotherapy, Volume 105
Author(s): Pedro Buc Calderon, Anne-Laure Sennesael, Christophe Glorieux
Grp94 plays an essential role in protein assembly. We previously suggested that Grp94 overexpression is involved in tumor aggressiveness. However, the underlying mechanisms remain unknown. Since many tumors display high Grp94 levels, we investigated the effects of tumor microenvironment on the regulation of this chaperone expression. First, we found out that hypoxia did not change Grp94 expression in the human tumor cell lines MCF-7 (breast cancer) and HepG2 (liver cancer). Second, glucose deprivation significantly increased Grp94 protein levels. Subsequently, we focused in the putative role of Grp94 in the acquisition of an aggressive phenotype by cancer cells. Using a more aggressive cancer cell model (MDA-MB-231 breast tumor cells), we found out that Grp94 knockdown using siRNA decreased the invasive capacity of cancer cells. Moreover, cells with decreased Grp94 levels displayed an enhanced sensitivity of tumor cells to doxorubicin, a standard drug in the treatment of breast cancer. Taken together, our results suggest that the expression of Grp94 is linked to tumor aggressiveness. Therefore, targeting Grp94 could be an effective way to inhibit tumor growth improving chemotherapy outcome.
Graphical abstract
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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