Publication date: Available online 10 June 2017
Source:Trends in Immunology
Author(s): Abhishek D. Garg, Pierre G. Coulie, Benoit J. Van den Eynde, Patrizia Agostinis
Cancer immunotherapy is experiencing a renaissance spearheaded by immune checkpoint inhibitors (ICIs). This has spurred interest in 'upgrading' existing immunotherapies that previously experienced only sporadic success, such as dendritic cells (DCs) vaccines. In this review, we discuss the major molecular, immunological, and clinical determinants of existing first- and second-generation DC vaccines. We also outline the future trends for next-generation DC vaccines and describe their major hallmarks and prerequisites necessary for high anticancer efficacy. In addition, using existing data we compare DC vaccines with ICIs targeting CTLA4, PD1, and PD-L1, and argue that in various contexts next-generation DC vaccines are ready to meet some challenges currently confronting ICIs, thereby raising the need to integrate DC vaccines in future combinatorial immunotherapy regimens.
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Σάββατο 10 Ιουνίου 2017
Integrating Next-Generation Dendritic Cell Vaccines into the Current Cancer Immunotherapy Landscape
Scholar : Journal of Oral Science Research, Year 2017, Issue 04 -New Issue Alert.
Scholar : Journal of Modern Stomatology, Year 2017, Issue 01 -New Issue Alert.
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RP5063, an atypical antipsychotic drug with a unique pharmacologic profile, improves declarative memory and psychosis in mouse models of schizophrenia
Source:Behavioural Brain Research, Volume 332
Author(s): Lakshmi Rajagopal, Sunoh Kwon, Mei Huang, Eric Michael, Laxminarayan Bhat, Marc Cantillon, Herbert Y. Meltzer
Various types of atypical antipsychotic drugs (AAPDs) modestly improve the cognitive impairment associated with schizophrenia (CIAS). RP5063 is an AAPD with a diverse and unique pharmacology, including partial agonism at dopamine (DA) D2, D3, D4, serotonin (5-HT)1A, and 5-HT2A receptors (Rs), full agonism at α4β2 nicotinic acetylcholine (ACh)R (nAChR), and antagonism at 5-HT2B, 5-HT6, and 5-HT7Rs. Most atypical APDs are 5-HT2A inverse agonists. The efficacy of RP5063 in mouse models of psychosis and episodic memory were studied. RP5063 blocked acute phencyclidine (PCP)-as well as amphetamine-induced hyperactivity, indicating antipsychotic activity. Acute administration of RP5063 significantly reversed subchronic (sc)PCP-induced impairment in novel object recognition (NOR), a measure of episodic memory, but not reversal learning, a measure of executive function. Co-administration of a sub-effective dose (SED) of RP5063 with SEDs of a 5-HT7R antagonist, a 5-HT1BR antagonist, a 5-HT2AR inverse agonist, or an α4β2 nAChR agonist, restored the ability of RP5063 to ameliorate the NOR deficit in scPCP mice. Pre-treatment with a 5-HT1AR, a D4R, antagonist, but not an α4β2 nAChR antagonist, blocked the ameliorating effect of RP5063. Further, co-administration of scRP5063 prior to each dose of PCP prevented the effect of PCP to produce a deficit in NOR for one week. RP5063, given to scPCP-treated mice for one week restored NOR for one week only. Acute administration of RP5063 significantly increased cortical DA efflux, which may be critical to some of its cognitive enhancing properties. These results indicate that RP5063, by itself, or as an adjunctive treatment has a multifaceted basis for improving some cognitive deficits associated with schizophrenia.
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Full title with Editorial board members
Source:Behavioural Brain Research, Volume 331
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Chondrogenesis of Human Bone Marrow Mesenchymal Stem Cells in 3-Dimensional, Photocrosslinked Hydrogel Constructs: Effect of Cell Seeding Density and Material Stiffness
Publication date: Available online 10 June 2017
Source:Acta Biomaterialia
Author(s): Aaron X. Sun, Hang Lin, Madalyn R. Fritch, He Shen, Pete G. Alexander, Michael DeHart, Rocky S. Tuan
Three-dimensional hydrogel constructs incorporated with live stem cells that support chondrogenic differentiation and maintenance offer a promising regenerative route towards addressing the limited self-repair capabilities of articular cartilage. In particular, hydrogel scaffolds that augment chondrogenesis and recapitulate the native physical properties of cartilage, such as compressive strength, can potentially be applied in point-of-care procedures. We report here the synthesis of two new materials, [poly-L-lactic acid/polyethylene glycol/poly-L-lactic acid] (PLLA-PEG 1000) and [poly-D,L-lactic acid/polyethylene glycol/poly-D,L-lactic acid] (PDLLA-PEG 1000), that are biodegradable, biocompatible (>80% viability post fabrication), and possess high, physiologically relevant mechanical strength (∼1,500 to 1,800 kPa). This study examined the effects of physiologically relevant cell densities (4, 8, 20, and 50 x 106/mL) and hydrogel stiffnesses (∼150kPa to ∼1,500 kPa Young's moduli) on chondrogenesis of human bone marrow stem cells incorporated in hydrogel constructs fabricated with these materials and a previously characterized PDLLA-PEG 4000. Results showed that 20 x 106 cells/mL, under a static culture condition, was the most efficient cell seeding density for extracellular matrix (ECM) production on the basis of hydroxyproline and glycosaminoglycan content. Interestingly, material stiffness did not significantly affect chondrogenesis, but rather material concentration was correlated to chondrogenesis with increasing levels at lower concentrations based on ECM production, chondrogenic gene expression, and histological analysis. These findings establish optimal cell densities for chondrogenesis within three-dimensional cell-incorporated hydrogels, inform hydrogel material development for cartilage tissue engineering, and demonstrate the efficacy and potential utility of PDLLA-PEG 1000 for point-of-care treatment of cartilage defects.Statement of SignificanceEngineering cartilage with physiologically relevant mechanical properties for point-of-care applications represents a major challenge in orthopedics, given the generally low mechanical strengths of traditional hydrogels used in cartilage tissue engineering. In this study, we characterized a new material that possesses high mechanical strength similar to native cartilage, and determined the optimal cell density and scaffold stiffness to achieve the most efficient chondrogenic response from seeded human bone marrow stem cells. Results show robust chondrogenesis and strongly suggest the potential of this material to be applied clinically for point-of-care repair of cartilage defects.
Graphical abstract
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Improvement of endothelial progenitor outgrowth cell (EPOC)-mediated vascularization in gelatin-based hydrogels through pore size manipulation
Publication date: Available online 10 June 2017
Source:Acta Biomaterialia
Author(s): Jiayin Fu, Christian Wiraja, Hamizan B. Muhammad, Chenjie Xu, Dong-An Wang
In addition to chemical compositions, physical properties of scaffolds, such as pore size, can also influence vascularization within the scaffolds. A larger pore has been shown to improve host vascular tissue invasion into scaffolds. However, the influence of pore sizes on vascularization by endothelial cells directly encapsulated in hydrogels remains unknown. In this study, micro-cavitary hydrogels with different pore sizes were created in gelatin-methacrylate hydrogels with dissolvable gelatin microspheres (MS) varying in sizes. The effect of pore sizes on vascular network formation by endothelial progenitor outgrowth cells (EPOCs) encapsulated in hydrogels was then investigated both in vitro and in vivo. When cultured in vitro, vascular networks were formed around pore structures in micro-cavitary hydrogels. The middle pore size supported best differentiation of EPOCs and thus best hydrogel vascularization in vitro. When implantation in vivo, functional connections between encapsulated EPOCs and host vasculature micro-cavitary hydrogels were established. Vascularization in vivo was promoted best in hydrogels with the large pore size due to the increased vascular tissue invasion. These results highlight the difference between in vitro and in vivo culture conditions and indicate that pore sizes shall be designed for in vitro and in vivo hydrogel vascularization respectively. Pore sizes for hydrogel vascularization in vitro shall be middle ones and pore sizes for hydrogel vascularization in vivo shall be large ones.Statement of SignificanceThis study reveals that the optimal pore size for hydrogel vascularization in vitro and in vivo is different. The middle pore size supported best differentiation of EPOCs and thus best hydrogel vascularization in vitro, while vascularization in vivo was promoted best in hydrogels with the large pore size due to the increased vascular tissue invasion. These results highlight the difference between in vitro and in vivo culture conditions and indicate that pore sizes shall be designed for in vitro and in vivo hydrogel vascularization respectively. Pore sizes for hydrogel vascularization in vitro shall be middle ones and pore sizes for hydrogel vascularization in vivo shall be large ones.
Graphical abstract
http://ift.tt/2sPCgCx
Atomic Layer Deposited ZrO2 Nanofilm onMg-Sr Alloy for Enhanced Corrosion Resistance and Biocompatibility
Publication date: Available online 10 June 2017
Source:Acta Biomaterialia
Author(s): Qiuyue Yang, Wei Yuan, Xiangmei Liu, Yufeng Zheng, Zhenduo Cui, Xianjin Yang, Haobo Pan, Shuilin Wu
The biodegradability and good mechanical property of magnesium alloys make them potential biomedical materials. However, their rapid corrosion rate in the human body's environment impairs these advantages and limits their clinical use. In this work, a compact zirconia (ZrO2) nanofilm was fabricated on the surface of a magnesium-strontium (Mg-Sr) alloy by the atomic layer deposition (ALD) method, which can regulate the thickness of the film precisely and thus also control the corrosion rate. Corrosion tests reveal that the ZrO2 film can effectively reduce the corrosion rate of Mg-Sr alloys that is closely related to the thickness of the film. The cell culture test shows that this kind of ZrO2 film can also enhance the activity and adhesion of osteoblasts on the surfaces of Mg-Sr alloys.Statement of SignificanceThe significance of the current work is to develop a zirconia nanofilm on biomedical MgSr alloy with controllable thickness precisely through atomic layer deposition technique. By adjusting the thickness of nanofilm, the corrosion rate of MgSr alloy can be modulated, thereafter, the degradation rate of Mg-based alloys can be controlled precisely according to actual clinical requirement. In addition, this zirconia nanofilm modified MgSr alloy showed excellent biocompatibility than the bare samples. Hence, this work provides a new surface strategy to control the degradation rate while improving the biocompatibility of substrates.
Graphical abstract
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An in situ-forming phospholipid-based phase transition gel prolongs the duration of local anesthesia for ropivacaine with minimal toxicity
Publication date: Available online 10 June 2017
Source:Acta Biomaterialia
Author(s): Hanmei Li, Tao Liu, Yuxuan Zhu, Qiang Fu, Wanxia Wu, Jie Deng, Li Lan, Sanjun Shi
An injectable, phospholipid-based phase transition gel (PPTG) has been developed for prolonging the release of ropivacaine (RO) for local anesthesia. PPTG was prepared by mixing phospholipids, medium-chain triglyceride and ethanol. Prior to injection, the PPTG is in a sol state with low viscosity. After subcutaneous injection, the PPTG rapidly forms a gel in situ, which acts as a drug release depot as verified by in vitro release profiles and in vivo pharmacokinetics. Administering RO-PPTG to rats led to a significantly smaller initial burst release than administering RO solution or RO base suspension. Nerve blockade in guinea pigs lasted 3-fold longer after injection of RO-PPTG than after injection of RO solution. RO-PPTG showed good biocompatibility and excellent degradability in vivo. These results suggest that this PPTG-based depot system may be useful for sustained release of local anesthetics to prolong analgesia without causing systemic toxicity.Statement of SignificanceThe sustained release of local anesthetics at the surgical site after a single injection is the optimal method to control post-surgical pain. In situ forming implant is an attractive alternative for the sustained release of local anesthetics. However, its practical use is highly limited by certain drawbacks including high viscosity, involved toxic organic solvents and fast drug release. To date, phospholipids-based phase transition gel (PPTG) is emerging for clinical development because of the non-toxicity, biocompatibility and ready availability of phospholipids in body. Thus, we present a novel strategy for sustained release of local anesthetics to control post-surgical pain based on PPTG, which showed a prolonged duration of nerve blockade and excellent biocompatibility.
Graphical abstract
http://ift.tt/2sPChq5
Bottom-up synthesis of WS2 nanosheets with synchronous surface modification for imaging guided tumor regression
Publication date: Available online 10 June 2017
Source:Acta Biomaterialia
Author(s): Shige Wang, Jiulong Zhao, Hailun Yang, Chenyao Wu, Fei Hu, Haizhou Chang, Guixiang Li, Dan Ma, Duowu Zou, Mingxian Huang
Two-dimensional transition metal dichalcogenides (TMDs) have been receiving great attention as NIR photothermal transducing agent in tumor photothermal therapy. Keeping in mind the low efficiency of the conventional top-down exfoliation method to produce 2D TMDs and the complexity of their surface modifications, we herein proposed a bottom-up strategy for the one-pot and controlled synthesis of surface polyvinyl pyrrolidone (PVP) modified WS2 nanosheets, by hydrothermally treating the mixture solution of tetrathiotungstate and PVP. The material design was based on the chelating-coordinating effect between the lone pair electrons of oxygen belonging to the carbonyl group of PVP and the unoccupied orbital (5d orbitals) of tungsten. The WS2 nanosheets with synchronous surface PVP grafting showed an excellent photothermal conversion performance, while the surface anchored PVP guaranteed its colloidal stability. Moreover, the strong X-ray attenuation ability and near-infrared (NIR) absorbance of WS2-PVP360kDa enable the sensitive in vitro and in vivo computed tomography and photoacoustic imaging. The WS2-PVP360kDa nanosheets were biocompatible and exhibited promising in vitro and in vivo anti-cancer efficacy. Findings in this report may greatly promote the design of colloidal stable and biocompatible 2D TMDs and their future clinical translations.Statement of SignificanceA bottom-up strategy for the one-pot and controlled synthesis of surface polyvinyl pyrrolidone (PVP) modified WS2 nanosheets was proposed for the first time by hydrothermally treating the mixture solution of tetrathiotungstate and PVP. PVP was synchronously graphed on WS2 nanosheets surface owing to the chelating-coordinating effect between the lone pair electrons of oxygen belonging to the carbonyl group of PVP and the unoccupied orbital (5d orbitals) of tungsten. WS2-PVP nanosheets were biocompatible and showed excellent photothermal conversion performance and colloidal stability. WS2-PVP nanosheets exhibited promising computed tomography, photoacoustic imaging and anti-cancer efficacy both in vitro and in vivo.
Graphical abstract
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Automatic Detection of Surgical Haemorrhage using Computer Vision
Source:Artificial Intelligence in Medicine
Author(s): Alvaro Garcia-Martinez, José María Vicente Samper, José María Sabater-Navarro
Background and objectivesOn occasions, a surgical intervention can be associated with serious, potentially life-threatening complications. One of these complications is a haemorrhage during the operation, an unsolved issue that could delay the intervention or even cause the patient's death. On laparoscopic surgery this complication is even more dangerous, due to the limited vision and mobility imposed by the minimally invasive techniques.MethodsIn this paper it is described a computer vision algorithm designed to analyse the images captured by a laparoscopic camera, classifying the pixels of each frame in blood pixels and background pixels and finally detecting a massive haemorrhage. The pixel classification is carried out by comparing the parameter B/R and G/R of the RGB space colour of each pixel with a threshold obtained using the global average of the whole frame of these parameters. The detection of and starting haemorrhage is achieved by analysing the variation of the previous parameters and the amount of pixel blood classified.ResultsWhen classifying in vitro images, the proposed algorithm obtains accuracy over 96%, but during the analysis of an in vivo images obtained from real operations, the results worsen slightly due to poor illumination, visual interferences or sudden moves of the camera, obtaining accuracy over 88%. The detection of haemorrhages directly depends of the correct classification of blood pixels, so the analysis achieves an accuracy of 78%.ConclusionsThe proposed algorithm turns out to be a good starting point for an automatic detection of blood and bleeding in the surgical environment which can be applied to enhance the surgeon vision, for example showing the last frame previous to a massive haemorrhage where the incision could be seen using augmented reality capabilities.
http://ift.tt/2sq4dmM
Integration of data mining classification techniques and ensemble learning to identify risk factors and diagnose ovarian cancer recurrence
Source:Artificial Intelligence in Medicine
Author(s): Chih-Jen Tseng, Chi-Jie Lu, Chi-Chang Chang, Gin-Den Chen, Chalong Cheewakriangkrai
Ovarian cancer is the second leading cause of deaths among gynecologic cancers in the world. Approximately 90% of women with ovarian cancer reported having symptoms long before a diagnosis was made. Literature shows that recurrence should be predicted with regard to their personal risk factors and the clinical symptoms of this devastating cancer. In this study, ensemble learning and five data mining approaches, including support vector machine (SVM), C5.0, extreme learning machine (ELM), multivariate adaptive regression splines (MARS), and random forest (RF), were integrated to rank the importance of risk factors and diagnose the recurrence of ovarian cancer. The medical records and pathologic status were extracted from the Chung Shan Medical University Hospital Tumor Registry. Experimental results illustrated that the integrated C5.0 model is a superior approach in predicting the recurrence of ovarian cancer. Moreover, the classification accuracies of C5.0, ELM, MARS, RF, and SVM indeed increased after using the selected important risk factors as predictors. Our findings suggest that The International Federation of Gynecology and Obstetrics (FIGO), Pathologic M, Age, and Pathologic T were the four most critical risk factors for ovarian cancer recurrence. In summary, the above information can support the important influence of personality and clinical symptom representations on all phases of guide interventions, with the complexities of multiple symptoms associated with ovarian cancer in all phases of the recurrent trajectory.
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Health-related quality of life and associated factors among patients with diabetes mellitus in Botswana
Publication date: Available online 9 June 2017
Source:Alexandria Journal of Medicine
Author(s): Godfrey Mutashambara Rwegerera, Thato Moshomo, Marea Gaenamong, Taibat Aderonke Oyewo, Sivasomnath Gollakota, Yordanka Piña Rivera, Anthony Masaka, Brian Godman, Meshack Shimwela, Dereje Habte
Background: Health-related quality of life (HRQOL) is an important aspect of diabetes mellitus care. The objective of the study was to determine theHRQOL of diabetes mellitus (DM) patients in Botswana as little known in Africa. Materials and methods: A cross-sectional study of 380 randomly selected DM patients in a tertiary clinic in Gaborone, Botswana was conducted to obtain Data on HRQOL and structured questionnaire was used to collect information on sociodemographic and clinical characteristics. Multivariate logistic regression to determine sociodemographic and clinical characteristics associated. Results: Majority of patients were female with no formal education or primary level of education. Mean HbA1c was 7.97% (SD: 2.02) and most patients had poor glycemic control. The majority had both worse physical composite score (PCS-12) and mental composite score (MCS-12), with worse proportions of the two. Female gender, older age ≥65years, and the presence of three or more documented diabetic complications were associated with significant worse PCS-12. Presence of two diabetic complications, three or more diabetic complications, and musculoskeletal disease were associated with significant MCS-12. Conclusions: Diabetic patients in Botswana have relatively poor HRQOL. The fact that most patients present late with complications calls for policy attention to diagnose diabetes mellitus early and prevent associated complications, ultimately improving health-related quality of life among diabetes mellitus patients.
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Title page / Editorial Board
Source:Cancer Epidemiology, Volume 48
http://ift.tt/2sPEpxV
Table of contents
Source:Cancer Epidemiology, Volume 48
http://ift.tt/2sg9I7R
Zeaxanthin improves diabetes-induced cognitive deficit in rats through activiting PI3K/AKT signaling pathway
Source:Brain Research Bulletin, Volume 132
Author(s): Xiaoyan Zhou, Shanshan Wang, Xin Ding, Li Qin, Yizhen Mao, Lei Chen, Wei Li, Changjiang Ying
Published studies have shown that cognitive deficit is a characteristic manifestation of neurodegenerative disease in diabetes. However, there is no effective prevention and treatment for this diabetes-associated behavior disorder. In the present study, we attempted to elucidate the effect of zeaxanthin on cognitive deficit and the change in the hippocampus correlated with cognitive decline in diabetic rats. Diabetic rats in this study were induced by high-fat diet and low-dose streptozocin (STZ), cognitive ability of rats were evaluated use morris water maze (MWM) and morphology change in hippocampus was assessed by cresyl violet stain. Moreover, we detected the expression of phosphorylated serine/threonine kinase (p-AKT) and Cleaved caspase-3, and the activity of nuclear factor-κB (NF-κB) use western-blot (WB).Results displayed that supplementation with zeaxanthin reduce blood glucose, improve cognitive deficit, survive neural cell, increase p-AKT level, inhibit Cleaved caspase-3 level and NF-κB nuclear transcription in hippocampus. This study demonstrated that zeaxanthin ameliorate diabetes-related cognitive deficit may by means of protecting neural cell from hyperglycemia involved in AKT/NF-κB signaling pathway. This study may provide a potential therapeutic approach for the prevention of diabetes- associated cognitive deficit.
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The contribution of component variation and phytoplankton growth to the distribution variation of chromophoric dissolved organic matter content in a mid-latitude subtropical drinking water source reservoir for two different seasons
Abstract
The distribution variation in chromophoric dissolved organic matter (CDOM) content in mid-latitude subtropical drinking water source reservoirs (MDWSRs) has great significance in the security of aquatic environments and human health. CDOM distribution is heavily influenced by biogeochemical processes and anthropogenic activity. However, little is known regarding the impact of component variation and phytoplankton growth on CDOM distribution variation in MDWSR. Therefore, samples were collected from a representative MDWSR (the Shanzai Reservoir) for analysis. CDOM absorption and fluorescence coupling with parallel factor analysis were measured and calculated. The results indicated that only two CDOM components were found in the surface water of Shanzai Reservoir, fulvic acid, and high-excitation tryptophan, originating from terrestrial and autochthonous sources, respectively. The types of components did not change with the season. The average molecular weight of CDOM increased in proportion to its fulvic acid content. The distribution variation in CDOM content mainly resulted from the variation in two CDOM components in summer and from high-excitation tryptophan in winter. Phytoplankton growth strongly influenced the distribution variation of CDOM content in summer; the metabolic processes of Cyanobacteria and Bacillariophyta consumed fulvic acid, while that of Cryptophyta produced high-excitation tryptophan.
http://ift.tt/2ri92du
An EMG-assisted modeling approach to assess passive lumbar tissue loading in-vivo during trunk bending
Publication date: Available online 10 June 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Xiaopeng Ning
Lower back pain (LBP) is a condition with high prevalence and high cost both in the United States and around the world. The magnitude of mechanical loading on spine is strongly associated with the occurrence of LBP. Previously, to assess spinal loading, biologically assisted biomechanical models were developed to estimate trunk muscle contraction forces. Loadings on lumbar passive tissues are estimated using anatomical models. However, despite the substantial individual variability in lumbar ligament geometry and viscoelastic properties, the existing anatomical models do not account for these differences. As such, the accuracy of model prediction is compromised especially when mid to full range of trunk motions are involved. This paper describes a new modeling approach to assess lumbar passive tissue loading with the consideration of individual differences in lumbar passive tissue properties. A data set that has trunk bending data from 13 human participants was analyzed; on average, lumbar passive tissue contributes to ∼89% of the total spinal compression force at fully flexed trunk postures; the estimated spinal tissue loadings were in feasible ranges as reported from previous cadaver studies; the estimated spinal loadings were also mostly in agreement with results from previous in-vivo studies.
http://ift.tt/2sPgZJ6
Electromyographic analysis of rotator cuff muscles in patients with rotator cuff tendinopathy: a systematic review
Publication date: Available online 10 June 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Fábio Carlos Lucas de Oliveira, Laurent Julien Bouyer, Amanda Ager, Jean-Sébastien Roy
The shoulder is inherently an unstable joint which heavily relies on the neuromuscular activation of the rotator cuff (RC) complex for stability during movement. Currently, there is no consensus regarding how the activity of RC muscles is affected among individuals with a RC tendinopathy (RCTe). This study reviewed the evidence of studies comparing the electromyographic (EMG) activity of any RC muscle of shoulders with a symptomatic RCTe to asymptomatic shoulders. Eight databases were searched. Data from 343 participants (201 symptomatic and 209 asymptomatic shoulders) were analyzed from 10 out of 402 included studies. Strong evidence for the supraspinatus during isometric contractions and limited evidence for the supraspinatus and infraspinatus during isokinetic contractions suggest that the muscular activity is not altered among individuals with a RCTe during these types of contraction. Very limited evidence indicates reduced muscle activity for the infraspinatus and subscapularis in the presence of a RCTe during isotonic contractions, and no alterations for the supraspinatus or teres minor were identified. Lastly, conflicting to moderate evidence suggests alterations in RC muscle activity during unrestrained movements and swimming. These findings indicate that EMG deficits associated with a RCTe can best be appreciated during unrestrained movements.
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Maximum Voluntary Isometric Torque Production for Task specific and Single-joint Muscle groups and their Relation to Peak Power Output in Sprint Cycling
Publication date: Available online 10 June 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Mehdi Kordi, Stuart Goodall, Paul Barratt, Jonathan Leeder, Nicola Rowley, Glyn Howatson
From a cycling paradigm, little has been done to understand the relationships between maximal isometric strength of different single joint lower body muscle groups and their relation with, and ability to predict PPO and how they compare to an isometric cycling specific task. The aim of this study was to establish relationships between maximal voluntary torque production from isometric single-joint and cycling specific tasks and assess their ability to predict PPO. Twenty male trained cyclists participated in this study. Peak torque was measured by performing maximum voluntary contractions (MVC) of knee extensors, knee flexors, dorsi flexors and hip extensors whilst instrumented cranks measured isometric peak torque from MVC when participants were in their cycling specific position (ISOCYC). A stepwise regression showed that peak torque of the knee extensors was the only significant predictor of PPO when using SJD and accounted for 47% of the variance. However, when compared to ISOCYC, the only significant predictor of PPO was ISOCYC, which accounted for 77% of the variance. This suggests that peak torque of the knee extensors was the best single-joint predictor of PPO in sprint cycling. Furthermore, a stronger prediction can be made from a task specific isometric task.
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Effect of phosphate additive on the nitrogen transformation during pig manure composting
Abstract
Previous studies revealed that phosphate, as an additive to composting, could significantly reduce NH3 emission and nitrogen loss through change of pH and nitrogen fixation to form ammonium phosphate. However, few studies have explored the influence of pH change and phosphate additive on NOx−–N, NH4+–N, NH3, and N2O, which are dominate forms of nitrogen in composting. In this study, the equimolar H3PO4, H2SO4, and K2HPO4 were added into pig manure composting to evaluate the effect of H+ and PO43− on nitrogen transformation. As a result, we reached the conclusion that pH displays significant influence on adsorption from PO43− to NH4+. The NH4+–N concentration in H3PO4 treatment kept over 3 g kg−1DM (dry matter) which is obviously higher than that in H2SO4 treatment, and NH4+–N concentration in K2HPO4 treatment (pH>8.5) is lower than 0.5 g kg−1DM because adsorption capacity of PO43− is greatly weakened and NH4+–N rapidly transformed to NH3–N influenced by high pH value. The N2O emission of composting is significantly correlated with incomplete denitrification of NOx−–N, and PO43− addition could raise NOx−–N contents to restrict denitrification and further to promote N2O emission. The study reveals the influence mechanism of phosphate additive to nitrogen transformation during composting, presents theoretical basis for additive selection in nitrogen fixation, and lays foundation for study about nitrogen circulation mechanism during composting.
http://ift.tt/2rY4nze
Enhanced removal of ethanolamine from secondary system of nuclear power plant wastewater by novel hybrid nano zero-valent iron and pressurized ozone initiated oxidation process
Abstract
Monoethanolamine (shortly ethanolamine (ETA)), usually used as a corrosion inhibitor, is a contaminant of wastewater from the secondary cooling system of nuclear power plants (NPPs) and is not readily biodegradable. We conducted various experiments, including treatments with nano zero-valent iron (nZVI), nano-iron/calcium, and calcium oxide (nFe/Ca/CaO) with ozone (O3) or hydrogen peroxide (H2O2) to reduce the concentration of ETA and to decrease the chemical demand of oxygen (COD) of these wastewaters. During this study, wastewater with ETA concentration of 7465 mg L−1 and COD of 6920 mg L−1 was used. As a result, the ETA concentration was reduced to 5 mg L−1 (a decrease of almost 100%) and COD was reduced to 2260 mg L−1, a reduction of 67%, using doses of 26.8 mM of nZVI and 1.5 mM of H2O2 at pH 3 for 3 h. Further treatment for 48 h allowed a decrease of COD by almost 97%. Some mechanistic considerations are proposed in order to explain the degradation pathway. The developed hybrid nano zero-valent iron-initiated oxidation process with H2O2 is promising in the treatment of ETA-contaminated wastewaters.
http://ift.tt/2rdHbzY
Removal of cationic pollutants from water by xanthated corn cob: optimization, kinetics, thermodynamics, and prediction of purification process
Abstract
The removal of Cr(III) ions and methylene blue (MB) from aqueous solutions by xanthated corn cob (xCC) in batch conditions was investigated. The sorption capacity of xCC strongly depended of the pH, and increase when the pH rises. The kinetics was well fitted by pseudo-second-order and Chrastil's model. Sorption of Cr(III) ions and MB on xCC was rapid during the first 20 min of contact time and, thereafter, the biosorption rate decrease gradually until reaching equilibrium. The maximum sorption capacity of 17.13 and 83.89 mg g−1 for Cr(III) ions and MB, respectively, was obtained at 40 °C, pH 5, and sorbent dose 4 g dm−3 for removal of Cr(III) ions and 1 g dm−3 for removal of MB. The prediction of purification process was successfully carried out, and the verification of theoretically calculated amounts of sorbent was confirmed by using packed-bed column laboratory system with recirculation of the aqueous phase. The wastewater from chrome plating industry was successfully purified, i.e., after 40 min concentration of Cr(III) ions was decreased lower than 0.1 mg dm−3. Also, removal of MB from the river water was successfully carried out and after 40 min, removal efficiency was about 94%.
http://ift.tt/2rYdGiN
Evaluation of ethyl lactate as solvent in Fenton oxidation for the remediation of total petroleum hydrocarbon (TPH)-contaminated soil
Abstract
Due to the health and environmental risks posed by the presence of petroleum-contaminated areas around the world, remediation of petroleum-contaminated soil has drawn much attention from researchers. Combining Fenton reaction with a solvent has been proposed as a novel way to remediate contaminated soils. In this study, a green solvent, ethyl lactate (EL), has been used in conjunction with Fenton's reagents for the remediation of diesel-contaminated soil. The main aim of this research is to determine how the addition of EL affects Fenton reaction for the destruction of total petroleum hydrocarbons (TPHs) within the diesel range. Specifically, the effects of different parameters, including liquid phase volume-to-soil weight (L/S) ratio, hydrogen peroxide (H2O2) concentration and EL% on the removal efficiency, have been studied in batch experiments. The results showed that an increase in H2O2 resulted in an increase in removal efficiency of TPH from 68.41% at H2O2 = 0.1 M to 90.21% at H2O2 = 2 M. The lowest L/S, i.e. L/S = 1, had the highest TPH removal efficiency of 85.77%. An increase in EL% up to 10% increased the removal efficiency to 96.74% for TPH, and with further increase in EL%, the removal efficiency of TPH decreased to 89.6%. EL with an optimum value of 10% was found to be best for TPH removal in EL-based Fenton reaction. The power law and pseudo-first order equations fitted well to the experimental kinetic data of Fenton reactions.
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Analytical methodology for the electro-catalytic determination of estradiol and progesterone based on graphene quantum dots and poly(sulfosalicylic acid) co-modified electrode
Publication date: 1 November 2017
Source:Talanta, Volume 174
Author(s): Majid Arvand, Shiva Hemmati
The goal of this study was to develop an electroanalytical method for the simultaneous determination of steroid hormones for the first time. The key factor in the electrochemical methods is the choice of suitable electrode materials. For this purpose, graphene quantum dots (GQDs) doped poly(sulfosalicylic acid) (PSSA) was immobilized on a glassy carbon electrode (GCE). Apart from exhibition strong and stable electrocatalytic response towards estradiol (E2) and progesterone (P4), the proposed sensor was able to distinguish two hormone's oxidation peaks clearly. Under the optimal conditions, for selective determination of E2, good linear relationships were obtained in the range of 0.001–6.0μmolL–1, with detection limit of 0.23nmolL–1, and for P4 in the range of 0.001–6.0μmolL–1, with the detection limit of 0.31nmolL–1. The prepared sensor possessed accurate and rapid response toward E2 and P4 with an improved stability, selectivity and repeatability. More importantly, the facile and environment-friendly electrochemical construction strategy provided here, may be open a cost-effective way for setting up nanocomposites or nanohybrid-based sensing platform, which extend the application of electrochemical sensor for the green, facile and sensitive analysis of electroactive compounds in biological systems and pharmaceutical formulations.
Graphical abstract
http://ift.tt/2rd4CJA
Compositional engineering of VOPcPhO-TiO2 nano-composite to reduce the absolute threshold value of humidity sensors
Publication date: 1 November 2017
Source:Talanta, Volume 174
Author(s): Mohamad Izzat Azmer, Fakhra Aziz, Zubair Ahmad, Ehsan Raza, Mansoor Ani Najeeb, Noshin Fatima, Tahani M. Bawazeer, Mohammad S. Alsoufi, R.A. Shakoor, Khaulah Sulaiman
This research work demonstrates compositional engineering of an organic-inorganic hybrid nano-composites for modifying absolute threshold of humidity sensors. Vanadyl-2,9,16,23-tetraphenoxy-29H,31H-phthalocyanine (VOPcPhO), an organic semiconductor, doped with Titanium-dioxide nanoparticles (TiO2 NPs) has been employed to fabricate humidity sensors. The morphology of the VOPcPhO:TiO2 nano-composite films has been analyzed by atomic force microscopy (AFM) and field emission scanning electron microscopy (FESEM). The sensors have been examined over a wide range of relative humidity i.e. 20–99% RH. The sensor with TiO2 (90nm) shows reduced sensitivity-threshold and improved linearity. The VOPcPhO:TiO2 (90nm) nano-composite film is comprised of uniformly distributed voids which makes the surface more favorable for adsorption of moisture content from environment. The VOPcPhO:TiO2 nano-composite based sensor demonstrates remarkable improvement in the sensing parameter when equated with VOPcPhO sensors.
Graphical abstract
http://ift.tt/2rcSBUJ
Stable isotope ratio analysis for authentication of red yeast rice
Publication date: 1 November 2017
Source:Talanta, Volume 174
Author(s): Matteo Perini, Gianfranco Carbone, Federica Camin
Red yeast rice (RYR) is a dietary supplement obtained from rice fermented with the mould Monascus purpureus. It contains Monacolin K which is a hypocholesterolemic statin used to prevent cardiovascular diseases. The homologous prescription biosynthetic statin, lovastatin, is not chemically distinguishable from monacolin K.In this work we investigated whether δ13C and δ2H can distinguish monacolin K from lovastatin and can detect the presence of lovastatin in RYR.18 samples of red yeast rice powder and 18 samples of lovastatin were collected. Monacolin K was isolated from RYR using preparative HPLC and together with lovastatin, was subjected to analysis of δ13C and δ2H using Isotope Ratio Mass Spectrometry.Thanks to the different photosynthetic cycles of the matrices used for their synthesis, monacolin K and lovastatin have different δ13C values (−29.6‰ ± 0.6 and −16.7‰ ± 2.6 respectively). δ2H is significantly (p < 0.001) lower in monacolin K but the ranges of values partially overlap with those of lovastatin. By defining a δ13C threshold value of −28.3‰ for monacolin K, addition of lovastatin from a minimum of 10% can be identified.δ13C analysis can be therefore proposed as a suitable tool for detecting the authenticity of RYR on the market.
Graphical abstract
http://ift.tt/2rdabYl
High-bright fluorescent carbon dot as versatile sensing platform
Publication date: 1 November 2017
Source:Talanta, Volume 174
Author(s): Mumei Han, Liping Wang, Siheng Li, Liang Bai, Yunjie Zhou, Yue Sun, Hui Huang, Hao Li, Yang Liu, Zhenhui Kang
The surface functionalization will introduce additional functional groups on carbon dots (CDs) surface and then enrich the properties of CDs. Here, we show the various surface functionalized CDs (-COOH, -OH, -SH, -NH2, etc, named as NS-CDs) were synthesized with fascinating features, including high quantum efficiency (38.9%), long-term stability and good biocompatibility. Notably, it can serve as multifunction fluorescent probe in sensing system, including label-free detections in hydrogen peroxide (H2O2) with a wide linear range (1.20 × 10−3 – 8.80 × 10–12M) and a low limit of detection (LOD, 1.00 × 10–12M); and glutathione, covering a concentration range of 2.00 × 10−3 – 1.00 × 10−7M and LOD of 1.00 × 10−7M. In addition, the NS-CDs as fluorescent probe could selectively detect metal ions (such as, Hg2+, 1.00 × 10−8 − 1.50 × 10−3M, 1.00 × 10−7M), antibiotics (tetracycline, 1.00 ×10−10 − 2.50 × 10−5M, 1.00 ×10−10M) and toxic pollutant (nitrobenzene, 5.00 × 10−7 to 1.00 × 10−3gL−1, 5.00 × 10−7gL−1) with wide linear range and satisfactory detection limits.
Graphical abstract
http://ift.tt/2rcSB7b
A highly selective and sensitive fluorescent probe for hypochlorous acid and its lysosome-targetable biological applications
Publication date: 1 November 2017
Source:Talanta, Volume 174
Author(s): Chang Liu, Xiaojie Jiao, Song He, Liancheng Zhao, Xianshun Zeng
A novel lysosome-targetable fluorescence probe PT-1 based on a photoinduced electron transfer (PET) mechanism has been designed and synthesized. For comparison, the probe PT-2 without morpholine moiety as a lysosome-directing group was also synthesized and investigated. Probes PT-1 and PT-2 exhibited high selectivity, high sensitivity (with the detection limits down to the 10−10M range) and response in real time (within 10s) toward HOCl over other reactive oxygen species (ROS). Both PT-1 and PT-2 were cell permeable and enabled them to be used for monitoring of HOCl in living cells. Meanwhile, the probe PT-1 demonstrated an accurately lysosome-targeting ability, and was successfully applied to image of exogenous, endogenous produced HOCl in living cells. The success of subcellular imaging suggested that the probe PT-1 could be used in further applications for the investigation of biological functions and pathological roles of HOCl at organelle levels.
Graphical abstract
http://ift.tt/2rdfEi5
Development of pH-responsive polymer and citrate aqueous two-phase system for extractive bioconversion of cefprozil
Publication date: 1 November 2017
Source:Talanta, Volume 174
Author(s): Jialing Chen, Zhaoyang Ding, Hongxia Pan, Xuejun Cao
A pH-responsive aqueous two-phase system (pH-ATPS) has been developed by sodium citrate and a recyclable pH-responsive polymer PADB6.8 that can response to the change of pH values. Phase separation mechanism is studied through Low field-NMR. All variables affecting the phase separation are evaluated. Phase characteristics (viscosity, density, interfacial tension) and phase separation kinetic are studied for understanding of separation process and operational parameters in applications. This pH-ATPS has the characters of low interfacial tension, high recovery leading efficient mass transfer and low cost. The proposed system can be used as a mild medium for extractive bioconversion with low cost. We applied this pH-ATPS in extractive bioconversion of cefprozil. Cefprozil is partitioned towards the polymer-rich phase while the substrates tended to be partitioned in the salt-rich phase. Extractive bioconversion of cefprozil in this pH-ATPS can improve yield of the enzymatic process and reduce the product hydrolysis in optimal conditions. The maximal conversion yield of cefprozil in the studied system is 91.0%.
Graphical abstract
http://ift.tt/2rdtnFm
A simple method for the multi-elemental analysis of beer using total reflection X-ray fluorescence
Publication date: 1 November 2017
Source:Talanta, Volume 174
Author(s): Ednilton M. Gama, Clésia C. Nascentes, Roberta P. Matos, Gabrielle de C. Rodrigues, Guilherme D. Rodrigues
A method of direct analysis for quantification of 15 inorganic elements (P, S, Cl, K, Ca, Mn, Fe, Ni, Cu, Zn, Br, As, Rb, Sr and Pb) in beers by Total Reflection X-Ray Fluorescence (TXRF) was developed. The experimental conditions were optimized. Direct analysis was compared with the acid digestion procedure to evaluate the effect matrix and the results were satisfactory. The evaluation of the accuracy and precision was realized by analysis of two certified reference materials of natural and waste water. For the majority of the elements, good agreement was achieved between the certified value and the value measured in the CRM´s. Low detection limits were obtained and it was adequate to determine trace elements in beers and to quality control Pb and As, whose maximum limits are 200 and 100µgL-1, respectively. The relative standard deviation (RSD%) ranged from 2.4% to 10%. The method was applied to 30 beer samples collected in several regions of Brazil. The concentration ranges (mgL-1) for the studied analytes were: P: (37.40–140.85); S (10.32–50.73); Cl (82.74–281.7); K (183.8–418.5); Ca (9.82–96.0); Mn (0.06–1.42); Fe (0.07–1.57); Ni (< LLD-1.13); Cu (< LLD-0.32); Zn (0.02–1.98); As (< LLD-0.10); Br (0.01–2.04); Rb (< LLD-0.52); Sr (< LLD-0.41) and Pb (< LLD-0.18). Some beer samples showed As and Pb concentrations above the levels established by Brazilian legislation. The developed method is simple, fast, consumes low amounts of reagents and allows the determination of a large number of analytes simultaneously. TXRF proved to be attractive and useful for routine analysis.
Graphical abstract
http://ift.tt/2rdogoR
The role of SMARCAL1 in replication fork stability and telomere maintenance
Source:DNA Repair
Author(s): Natalia Lugli, Sotirios K. Sotiriou, Thanos D. Halazonetis
SMARCAL1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A-Like 1), also known as HARP, is an ATP-dependent annealing helicase that stabilizes replication forks during DNA damage. Mutations in this gene are the cause of Schimke immune-osseous dysplasia (SIOD), an autosomal recessive disorder characterized by T-cell immunodeficiency and growth dysfunctions. In this review, we summarize the main roles of SMARCAL1 in DNA repair, telomere maintenance and replication fork stability in response to DNA replication stress.
http://ift.tt/2rNaKXu
Resident Involvement in Microsurgery: An American College of Surgeons National Surgical Quality Improvement Program Analysis
Publication date: Available online 9 June 2017
Source:Journal of Surgical Education
Author(s): Kevin T. Jubbal, Daniel Chang, Shayan A. Izaddoost, William Pederson, Dmitry Zavlin, Anthony Echo
ObjectiveIn the current healthcare climate, there is increased focus on medical errors, patient outcomes, and the influence of resident participation on these metrics. Other studies have examined the influence of resident involvement on surgical outcomes, but the arena of microsurgery, with added complexity and learning curve, has yet to be investigated.DesignA retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program database was performed to find patients undergoing procedures with free tissue transfer by screening for Current Procedural Terminology codes. Primary outcomes measured include flap failure, wound, infectious, and major and minor complications.SettingThis study was conducted at the Methodist Hospital, an academic hospital located in Houston, Texas.ParticipantsPatients in the National Surgical Quality Improvement Program database between the years 2005 and 2012 undergoing microsurgical procedures were included in this analysis.ResultsA total of 1466 patients met inclusion criteria. There was a statistically significant association of major complications with age, peripheral vascular disease, American Society of Anesthesiologists (ASA) classification of 3 or greater, total operative time, and year of operation. Multivariate analysis on minor complications demonstrated significant association with ASA class of 3 or 4. Resident involvement was not a significant factor among any outcome measures including major complications, minor complications, flap failure, wound complications, infectious complications, bleeding requiring transfusion, and unexpected reoperation rates within 30 days.ConclusionsThis study provides further evidence in support of the claim that resident involvement in microsurgery is safe and effective, with similar rates of major complications, minor complications, flap failure, and unexpected reoperation. High ASA classification and history of peripheral vascular disease were strong predictors of major complications and should be optimized preoperatively before free tissue transfer. Later years were associated with decreased major complication rates, which may be reflective of enhanced supervision standards.
http://ift.tt/2r6txdE
Resident Operative Experience at Independent Academic Medical Centers—A Comparison to the National Cohort
Publication date: Available online 9 June 2017
Source:Journal of Surgical Education
Author(s): Amit R.T. Joshi, Amber W. Trickey, Benjamin T. Jarman, Kara J. Kallies, Robert Josloff, Jonathan M. Dort, Ravi Kothuru
PurposeIndependent Academic Medical Centers (IAMCs) comprise one-third of U.S. general surgery training programs. It is unclear whether IAMCs offer qualitatively or quantitatively different operative experiences than the national cohort. We analyzed a large representative sample of IAMCs to compare operative volume and variety, with a focus on low-volume procedures.MethodsAccreditation Council for Graduate Medical Education Program Case Reports from 27 IAMCs were collected and analyzed for 3 academic years (2012-2015). IAMCs were compared to the national cohort for specific defined category volumes and selected low-volume cases. One-sample two-way t-tests were calculated comparing IAMC totals to national program averages.ResultsIAMCs had a median of 3 chief residents per year (range: 1-6). IAMCs reported significantly more "total major" procedures in 2013-2014 (p = 0.046). Other case totals were statistically similar between IAMCs and the national cohort for "total major", "surgeon chief", "surgeon junior", and "teaching assistant" cases. In 2013-2014, IAMCs reported more laparoscopic complex (138.3 vs. 110.6, p = 0.010) and alimentary tract cases (276.5 vs. 253.5, p = 0.019). IAMC esophagogastroduodenoscopy case totals were higher in 2013-2014 (55.9 vs. 41, p = 0.038) and 2014-2015 (47.8 vs. 41, p = 0.047). IAMCs had fewer pancreas cases than the national cohort in all three years by about three cases per resident (p ≤ 0.026). In 2012-2013 IAMCs reported fewer (by about one) esophagectomy, gastrectomy, and abdominal perineal resections. No differences were observed in the following selected procedures: open common bile duct exploration, inguinal hernia, laparoscopic appendectomy, laparoscopic cholecystectomy, and colonoscopy.ConclusionsThe IAMCs studied appear to provide equivalent exposure to specific subcategories mandated by the Accreditation Council for Graduate Medical Education and American Board of Surgery. Graduates of IAMCs gain similar operative experience in low-volume, defined categories when compared to the national cohort. Certain specific cases subject to regionalization pressure are less well represented among IAMCs. This has important implications for medical students applying to surgery residency.
http://ift.tt/2spqlhf
Structural diversity of marine cyclic peptides and their molecular mechanisms for anticancer, antibacterial, antifungal, and other clinical applications
Source:Peptides
Author(s): Yeji Lee, Chanvorleak Phat, Soon-Cheol Hong
Many cyclic peptides and analogues derived from marine sources are known to possess biological properties, including anticancer, antitumor, antibacterial, antifungal, antiparasitic, anti-inflammation, anti-proliferative, anti-hypertensive, cytotoxic, and antibiotic properties. These compounds demonstrate different activities and modes of action according to their structure such as cyclic oligopeptide, cyclic lipopeptide, cyclic glycopeptide and cyclic depsipeptide. The recent advances in application of the above-mentioned cyclic peptides were reported in dolastatins, soblidotin, didemnin B, aplidine, salinosporamide A, kahalalide F and bryostatin 1 and they are currently in clinical trials. These cyclic peptides are possible novel drugs discovered and developed from marine origin. Literature data concerning the potential properties of marine cyclic peptides were reviewed here, and the structural diversity and biological activities of marine cyclic peptides are discussed in relation to the molecular mechanisms of these marine cyclic peptides.
http://ift.tt/2rMZpXL
High-grade glioma mimicking limbic encephalitis on 18F-FDG PET/CT scan
Publication date: Available online 10 June 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): J.P. Suárez, M. Coronado, M.L. Domínguez, L. Domínguez
http://ift.tt/2s92a6d
Primary myoepithelial carcinoma of the lung and 18F-FDG PET/CT
Publication date: Available online 10 June 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): Y. Zhang, B. Li, J. Hou, H. Shi
http://ift.tt/2s938zv
Embryonic expression patterns of Eukaryotic EndoU ribonuclease family gene endouC in zebrafish
Source:Gene Expression Patterns
Author(s): Hung-Chieh Lee, Chuan-Yang Fu, Chih-Wei Zeng, Huai-Jen Tsai
Endou proteins belong to the Eukaryotic EndoU ribonuclease family of enzymes that present high sequence homology with the founding member XendoU domain. The enzymatic activity and three-dimensional structure of some Endou proteins have been previously reported. However, their molecular structure and gene expression patterns during embryogenesis remain to be elucidated. Therefore, we took zebrafish (Danio rerio) endouC as the model to study molecular structure and gene expression dynamics at different developmental stages. Zebrafish endouC cDNA contains 930 base pairs encoding 309 amino acid residues, sharing 27%, 27%, 27%, and 25% identity with that of human, mouse, chicken and frog, respectively. A phylogenetic tree showed that zebrafish EndouA was clustered with vertebrate Endou groups, while zebrafish EndouB and EndouC were found to belong to a unique monophyletic group. Furthermore, the endouC transcript was detected in one-cell embryos, suggesting that it is a maternal gene. While the endouC transcript was only weakly present at early developmental stages, its expression was greatly increased in embryos from 18 to 48 h post-fertilization (hpf) and then decreased after 72 hpf. Finally, endouC was ubiquitously expressed throughout the whole embryo during early embryogenesis, but its expression was enriched in brain, eyes and fin buds from 24 to 96 hpf.
http://ift.tt/2sfnCHC
Nicorandil modulated macrophages activation and polarization via NF-κb signaling pathway
Source:Molecular Immunology, Volume 88
Author(s): Fengyun Zhang, Yongli Xuan, Jinjin Cui, Xinxin Liu, Zhiying Shao, Bo Yu
Nicorandil, a drug with both nitrate-like and ATP-sensitive potassium (KATP) channel-activating properties, has been well demonstrated in various aspects of myocardial infarction (MI), especially in inhibiting cell apoptosis and increasing coronary flow. However, the role of nicorandil in regulating inflammation and angiogenesis following myocardial infarction is still unrevealed. In the present study, we explored the effect of nicorandil on macrophage phenotype transition and inflammation regulation and the potential underlying mechanisms. For the phenotype transition and phagocytosis ability of macrophages detection, flow cytometry analysis was used. The inflammation factors were measured with ELISA and qRT-PCR. Western blot was used to assess the levels of NF-κb and its target genes and VEGF expression. The tube formation ability of endothelial cells was examined on matrigel. We discovered that nicorandil can obviously inhibit the differentiation of monocytes into mature macrophages and decrease M1 phenotype transition both in peritoneal macrophages and cultured macrophage cell line in normal or hypoxia and serum deprivation (H/SD) conditions. Meanwhile, nicorandil can induce an anti-inflammatory M2 phenotype. Thereby, nicorandil regulated macrophages switching to M1/M2 status. Our data further showed that NF-κb and the expression of its target genes were pivotal players in the regulation of macrophages phenotype. Besides, we also showed that nicorandil can promote the tube formation and VEGF expression in endothelial cells. We concluded that nicorandil may serve as an effective modulator of NF-κb signaling pathway during the pathogenesis of MI via regulating M1/M2 status and promoting angiogenesis.
http://ift.tt/2rMHS1T
Eculizumab-C5 complexes express a C5a neoepitope in vivo: Consequences for interpretation of patient complement analyses
Source:Molecular Immunology
Author(s): Per H. Nilsson, Anub Mathew Thomas, Grethe Bergseth, Alice Gustavsen, Elena B. Volokhina, Lambertus P. van den Heuvel, Andreas Barratt-Due, Tom E. Mollnes
The complement system has obtained renewed clinical focus due to increasing number of patients treated with eculizumab, a monoclonal antibody inhibiting cleavage of C5 into C5a and C5b. The FDA approved indications are paroxysmal nocturnal haemoglobinuria and atypical haemolytic uremic syndrome, but many other diseases are candidates for complement inhibition. It has been postulated that eculizumab does not inhibit C5a formation in vivo, in contrast to what would be expected since it blocks C5 cleavage. We recently revealed that this finding was due to a false positive reaction in a C5a assay. In the present study, we identified expression of a neoepitope which was exposed on C5 after binding to eculizumab in vivo. By size exclusion chromatography of patient serum obtained before and after infusion of eculizumab, we document that the neoepitope was exposed in the fractions containing the eculizumab-C5 complexes, being positive in this actual C5a assay and negative in others. Furthermore, we confirmed that it was the eculizumab-C5 complexes that were detected in the C5a assay by adding an anti-IgG4 antibody as detection antibody. Competitive inhibition by anti-C5 antibodies localized the epitope to the C5a moiety of C5. Finally, acidification of C5, known to alter C5 conformation, induced a neoepitope reacting identical to the one we explored, in the C5a assays. These data are important for interpretation of complement analyses in patients treated with eculizumab.
http://ift.tt/2rMOOMd
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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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