Does dynamic information about the speaker’s face contribute to semantic speech processing? ERP evidence

Publication date: Available online 9 April 2018
Source:Cortex
Author(s): David Hernández-Gutiérrez, Rasha Abdel Rahman, Manuel Martín-Loeches, Francisco Muñoz, Annekathrin Schacht, Werner Sommer
Face-to-face interactions characterize communication in social contexts. These situations are typically multimodal, requiring the integration of linguistic auditory input with facial information from the speaker. In particular, eye gaze and visual speech provide the listener with social and linguistic information, respectively. Despite the importance of this context for an ecological study of language, research on audiovisual integration has mainly focused on the phonological level, leaving aside effects on semantic comprehension. Here we used event-related potentials (ERPs) to investigate the influence of facial dynamic information on semantic processing of connected speech. Participants were presented with either a video or a still picture of the speaker, concomitant to auditory sentences. Along three experiments, we manipulated the presence or absence of the speaker's dynamic facial features (mouth and eyes) and compared the amplitudes of the semantic N400 elicited by unexpected words. Contrary to our predictions, the N400 was not modulated by dynamic facial information; therefore, semantic processing seems to be unaffected by the speaker's gaze and visual speech. Even though, during the processing of expected words, dynamic faces elicited a long-lasting late posterior positivity compared to the static condition. This effect was significantly reduced when the mouth of the speaker was covered. Our findings may indicate an increase of attentional processing to richer communicative contexts. The present findings also demonstrate that in natural communicative face-to-face encounters, perceiving the face of a speaker in motion provides supplementary information that is taken into account by the listener, especially when auditory comprehension is non-demanding.



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Codoping effects of the Zn acceptor on the structural characteristics and electrical properties of the Ge donor-doped GaN thin films and its hetero-junction diodes all made by reactive sputtering

Publication date: 1 August 2018
Source:Materials Science in Semiconductor Processing, Volume 82
Author(s): Cao Phuong Thao, Dong-Hau Kuo, Der-Jun Jan
Zn acceptor/Ge donor (Zn/Ge)-codoped GaN films with different Zn contents have been deposited on Si substrates at 300 °C and at 90–150 W by RF reactive sputtering technique with cermet targets at the composition atomic ratios of Zn:Ge:(Ga+GaN) at x:0.03:(0.97-x) with x = 0, 0.03, 0.06, and 0.09 and Ga:GaN = 3:7. The films made with such targets were presented in an abbreviated symbol of Zn-x-GeGaN at x = 0, 0.03, 0.06, and 0.09. The morphology, structure, electrical properties, optical property, and hetero-junction diode devices involved in the Zn-x-GeGaN films were thoroughly investigated. The systematic Zn increment into the n-type Zn-0-GeGaN through property evaluation provides the supporting information in studying solid solutioning. Zn-x-GeGaN films converted into p-type semiconductor at x = 0.06 and 0.09. The values of bandgap were in the range of 2.87–3.17 eV with the lower value for the higher Zn content in Zn-x-GeGaN films. The higher RF power led to the faster growth, highly deficient in nitrogen, and a higher Zn atom ratio in the deposited film. The 120W-deposited Zn-0.06-GeGaN film had hole concentration of 7.21 × 10¹⁶ cm⁻³, hole mobility of 39.1 cm² V⁻¹ s⁻¹, and the electrical conductivity of 0.45 S/cm.



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Metals in geopropolis from beehive of Melipona scutellaris in urban environments

Publication date: 1 September 2018
Source:Science of The Total Environment, Volume 634
Author(s): Josemário S. Bonsucesso, Thomas V. Gloaguen, Andreia S. do Nascimento, Carlos Alfredo L. de Carvalho, Fabio de S. Dias
Geopropolis, a different type of propolis, presents a mixture of resin and exudates, containing wax, silt, and sand particles. This product has been the subject of research interest for its physicochemical properties, economic importance, and likely for environmental monitoring. The determination of toxic metals in hive products has been reported as an efficient tool for environmental monitoring. As the honey production is now common in urban environments, this study aimed to determine the concentration of toxic metals in the Melipona scutellaris geopropolis of the Metropolitan Region of Salvador, Bahia. Geopropolis and soil samples were collected from seven important beehives between June 2015 and July 2016. After EPA 3050B acid digestion procedure, metals were determined by ICP OES. As the geopropolis is partially made from soil, the values of Cr and Fe were extremely more important than the values reported in propolis, wax, and honey found in other worldwide studies. It gives different characteristics to this product depending on the location of the hive and characterizes it as an efficient integrating indicator of soil pollution. Using the enrichment factor, we determined that the soils around the meliponary are not or only slightly polluted by Cu, Cr, Ni, Pb and Zn. However, there was a shift in the particle size of geopropolis, being loamier and less sandy than the surrounding soil. In such case, a higher metal content could be expected, though no metal enrichment in the geopropolis was found, even a decrease in zinc, possibly due to the exclusion of metals by bees, was noted. Nevertheless, the results on the proportions of lithogenic metal and anthropogenic metal indicate that some metals have an external origin (about 20% for Ni and Cu). Geopropolis can be considered as a good environmental indicator even in low contaminated areas.

Graphical abstract

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Virtual Touch Tissue Quantification for Assessing Renal Pathology in Idiopathic Nephrotic Syndrome

Publication date: Available online 9 April 2018
Source:Ultrasound in Medicine & Biology
Author(s): Xue Yang, Ning Yu, Jing Yu, Hongqiao Wang, Xiumei Li
The aim of this study was to evaluate Virtual Touch tissue quantification in assessing renal interstitial fibrosis in patients with idiopathic nephrotic syndrome. Ninety patients with idiopathic nephrotic syndrome were assigned to mild, moderate and severe groups depending on the degree of renal interstitial fibrosis on histopathologic examination of renal biopsy specimens. Thirty healthy patients were also selected as the control group. Virtual Touch tissue quantification was performed to measure the shear wave velocity of the renal parenchyma. There was no statistically significant difference in shear wave velocity between the mild and control groups (p > 0.05); however, the moderate and severe groups did significantly differ compared with the control (p < 0.001). The area under the receiver operating characteristic curve value for the shear wave velocity of renal interstitial fibrosis in the moderate group versus the control and mild groups together was 0.869 (95% confidence interval: 0.791–0.947) and that in the severe group versus the control, mild and moderate groups together was 0.954 (95% confidence interval: 0.917–0.998). The corresponding best cutoff points were 2.41 and 2.77 m/s, with sensitivities of 91.7% and 86.8%, specificities of 78.0% and 92.0%, negative predictive values 0.907 and 0.907, positive predictive values 0.800 and 0.971 and Youden index values of 0.697 and 0.788, respectively. Virtual Touch tissue quantification may non-invasively and quantitatively estimate the degree of renal interstitial fibrosis in patients with idiopathic nephrotic syndrome as a baseline for monitoring progression and treatment response.



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The Real World Dilemma

Publication date: Available online 9 April 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Melina Vega de Ceniga




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Development and Validation of a Predictive Model to Aid in the Management of Intact Abdominal Aortic Aneurysms

Publication date: Available online 9 April 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Manar Khashram, Giorgi Kvizhinadze, Ziad Khashram, Jonathan A. Williman, Gregory T. Jones, Justin A. Roake
Objective/BackgroundPredicting outcomes prior to elective abdominal aortic aneurysm repair (AAA) requires critical decision making, as the treatment offered is a prophylactic procedure to prevent death from a ruptured AAA. The aim of this work was to develop and validate a model that may predict outcomes for patients with an AAA and hence aid in clinical decision making.MethodsA discrete event simulation model was built to simulate the natural history of a patient with an AAA and to predict the 30 day and 2–5 year survival of patients undergoing treatment and surveillance. The input parameters of AAA behavior and impact of comorbidities on survival were derived from the published literature and the New Zealand national life tables. The model was externally validated using a cohort of patients that underwent AAA repair (n = 320) and a cohort of patients undergoing small AAA surveillance (n = 376). All patients had completed at least 5 years of follow up.ResultsThe model was run three times for each data set to test. This produced a SD < 1%, indicating excellent reproducibility. The observed 30 day mortality for the patients undergoing AAA repair was 9/320 (2.8%) and the expected (model predicted) mortality was 3.8% (c-statistic 0.87 [95 confidence interval 0.75–1.0]). The c-statistic for the predicted 2–5 year survival ranged from 0.68 to 0.71 for the repaired AAA cohort and 0.69 to 0.73 for patients with a small AAA on surveillance.ConclusionThe AAA clinical decision tool has the ability to accurately predict the 5 year survival of patients with an AAA. This tool can be used during clinical decision making to better inform clinicians and patients of long-term outcomes. Further validation studies in a wider AAA population are required to test the broader clinical utility of this AAA clinical decision tool.



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About Image Manipulation of the CTA on Software to Simulate the Appropriate Intra-operative C-arm Position

Publication date: Available online 9 April 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Giovani P. Molinari




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Ongoing environmental monitoring and assessment of the long-term impacts of the February 2014 radiological release from the waste isolation pilot plant

Abstract

Three years ago, the Waste Isolation Pilot Plant (WIPP) experienced its first minor accident involving a radiological release. Late in the evening on February 14, 2014, a waste container in the repository underwent a chemical reaction that caused the container to overheat and breach, releasing its contents into the underground. Following a lengthy recovery process, the facility recently resumed waste disposal operations. The accident released significant levels of radioactivity into the disposal room and adjacent exhaust drifts, and although no one was present in the underground at the time of the release, a total of 22 workers tested positive for very low level of radiation, presumably from some of the radioactive material that was released above ground through a small leak in the HEPA filtration system. The dominant radionuclides released were ²⁴¹Am and ^{239 + 240}Pu in a ratio that matched the content of the drum from Los Alamos National Laboratory (LANL) that was eventually identified as the breached container. From the air particulate monitoring and plume modeling, it was concluded that the dose, at the nearest location accessible to the general public, from this radiation release event would have been less than 0.01 mSv (< 1 mrem/year). This level is well below the 0.1 mSv/year (10 mrem/year) regulatory limit for DOE facilities established by the US Environmental Protection Agency (EPA).

While no long-term impacts to public health or the environment are expected as a result of the WIPP radiation release, the limited ventilation and residual contamination levels in the underground are still a concern and pose a major challenge for the full recovery of WIPP. This article provides an up-to-date overview of environmental monitoring results through the WIPP recovery and an estimate of the long-term impacts of the accident on the natural and human environment.

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Cocaine- and amphetamine-regulated transcript peptide (CART) induced reward behavior is mediated via Gi/o dependent phosphorylation of PKA/ERK/CREB pathway

Publication date: 1 August 2018
Source:Behavioural Brain Research, Volume 348
Author(s): Amita R. Somalwar, Amit G. Choudhary, Pravesh R. Sharma, Nagalakshmi B., Sneha Sagarkar, Amul J. Sakharkar, Nishikant K. Subhedar, Dadasaheb M. Kokare
Although the role of cocaine- and amphetamine-regulated transcript peptide (CART) in modulating the mesolimbic reward pathway has been suggested, underlying cellular mechanisms have not been elucidated. Herein, we investigate the involvement of Gi/o dependent protein kinase A (PKA)/extracellular signal-regulated kinase (ERK)/cAMP response element binding protein (CREB) signaling in CART induced reward behavior. The rat was implanted with a stimulating electrode targeted at the lateral hypothalamus (LH)-medial forebrain bundle (MFB) and conditioned to intracranial self-stimulation (ICSS) in an operant chamber. Intracerebroventricular (icv) administration of CART (55-102) dose-dependently lowered ICSS threshold suggesting reward promoting action, however, pretreatment with subeffective doses of Gi/o inhibitor (pertussis toxin, PTX) or PKA inhibitor (Rp-cAMPS) or ERK inhibitor (U0126) via icv route, attenuated CART mediated reward experience. Operant conditioned rats showed increased pCREB levels in the nucleus accumbens shell (AcbSh), ventral tegmental area (VTA) and hypothalamic paraventricular nucleus (PVN). Infusion of CART (icv) in the conditioned rats augmented the population of pCREB positive cells in the AcbSh, VTA and PVN areas, but not in the arcuate nucleus (ARC). Pretreatment with U0126 significantly decreased CART induced pCREB activation in the AcbSh and VTA, but not in PVN and ARC. ICSS or CART induced CREB mRNA expression in Acb and VTA was attenuated by U0126. We suggest that recruitment of Gi/o dependent PKA/ERK/CREB phosphorylation signaling in Acb and VTA might play an important role in CART induced reward behavior.



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Stereotactic ablative radiotherapy after concomitant chemoradiotherapy in non-small cell lung cancer: A TITE-CRM phase 1 trial

Publication date: Available online 9 April 2018
Source:Radiotherapy and Oncology
Author(s): Jérôme Doyen, Michel Poudenx, Jocelyn Gal, Josiane Otto, Caroline Guerder, Arash O. Naghavi, Anais Gérard, Axel Leysalle, Charlotte Cohen, Bernard Padovani, Antoine Ianessi, Renaud Schiappa, Emmanuel Chamorey, Pierre-Yves Bondiau
Background and purposePlatinum based chemoradiotherapy is the standard of care for inoperable non-small cell lung cancer (NSCLC). With evidence that NSCLC can have a dose dependent response with stereotactic ablative radiotherapy (SABR), we hypothesize that a SABR boost on residual tumor treated with chemoradiotherapy could increase treatment efficacy. The purpose of this study was to determine feasibility of such an approach.Material and methodsA prospective phase I trial was performed including 26 patients. Time-to-event continual reassessment method (TITE-CRM) was used for dose escalation which ranged from 3 × 7 to 3 × 12 Gy for the stereotactic boost, after 46 Gy (2 Gy per day) of chemoradiotherapy.ResultsMedian follow-up was of 37.1 months (1.7–60.7), and 3, 4, 3, 3, 9 and 4 patients were included at the dose levels 1, 2, 3, 4, 5 and 6, respectively. During chemoradiotherapy, 9 patients experienced grade 3 toxicity. After stereotactic radiotherapy, 1 patient experienced an esophageal fistula (with local relapse) at the 3 × 11 Gy level, and 1 patient died from hemoptysis at the 3 × 12 Gy level. The 2-year rate of local control, locoregional free survival, metastasis-free survival, and overall survival was 70.3%, 55.5%, 44.5% and 50.8%, respectively.ConclusionIn the treatment of NSCLC with chemoradiotherapy followed by a stereotactic boost, the safe recommended dose in our protocol was a boost dose of 3 × 11 Gy.



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A score derived from routine biochemical parameters increases the diagnostic accuracy of chromogranin A in detecting patients with neuroendocrine neoplasms

Abstract

Background

Chromogranin A (CgA) is a valuable biomarker for detection and follow-up of patients with neuroendocrine neoplasms (NENs). However, various comorbidities may influence serum CgA, which decreases its diagnostic accuracy. We aimed to investigate which laboratory parameters are independently associated with increased CgA in real-life setting and to develop a scoring system, which could improve the diagnostic accuracy of CgA in detecting patients with NENs.

Methods

This retrospective study included 55 treatment naïve patients with NENs and160 patients with various comorbidities but without NEN (nonNENs). Scoring system (CgA-score) was developed based on z-scores obtained from receiver operating curve analysis for each parameter that was associated with elevated serum CgA in nonNENs.

Results

CgA correlated positively with serum BUN, creatinine, α2-globulin, red-cell distribution width, erythrocyte sedimentation rate, plasma glucose and correlated inversely with hemoglobin, thrombocytes and serum albumin. Serum CgA was also associated with the presence of chronic renal failure, arterial hypertension and diabetes and the use of PPI. In the entire study population, CgA showed an area under the curve of 0.656. Aforementioned parameters were used to develop a CgA-score. In a cohort of patients with CgA-score <12.0 (N = 87), serum CgA >156.5 ng/ml had 77.8% sensitivity and 91.5% specificity for detecting NENs (AUC 0.841, 95% CI 0.713–0.969, P < 0.001). Serum CgA had no diagnostic value in detecting NENs in patients with CgA-score >12.0 (AUC 0.554, 95% CI 0.405–0.702, P = 0.430).

Conclusions

CgA-score encompasses a wide range of comorbidities and represents a promising tool that could improve diagnostic performance of CgA in everyday clinical practice.

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Magnetic Resonance (MR) Imaging & Blood Biomarkers for Head and Neck Cancer

Condition:   Head and Neck Cancer
Interventions:   Procedure: MRI;   Procedure: Blood Draw;   Behavioral: Questionnaires
Sponsors:   M.D. Anderson Cancer Center;   Radiological Society of North America;   The Royal Australian and New Zealand College of Radiologists
Recruiting

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Feasibility of PET/CT to Detect the Oral/Pulmonary Distribution of Nicotine Following E-cigarette Use

Condition:   E-cigarette Use
Interventions:   Drug: C-11 labeled nicotine;   Radiation: PET/CT imaging
Sponsor:   Ohio State University
Recruiting

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Co-delivery of docetaxel and gemcitabine by anacardic acid modified self-assembled albumin nanoparticles for effective breast cancer management

Publication date: Available online 9 April 2018
Source:Acta Biomaterialia
Author(s): Varun Kushwah, Sameer S. Katiyar, Chander Parkash Dora, Ashish Kumar Agrawal, Dimitrios A. Lamprou, Ramesh C. Gupta, Sanyog Jain
In the present study, we have modified bovine serum albumin (BSA) by covalently conjugating with anacardic acid (AA) and gemcitabine (GEM) and further used for development of docetaxel (DTX) loaded nanoparticles (AA-GEM-BSA NPs). AA is supposed to provide tumor targeting through VEGF receptors overexpressed in tumors, while the combination of GEM and DTX is supposed to provide synergistic activity by targeting multiple pathways. The conjugate was synthesized via carbodiimide chemistry and characterized by ¹H NMR, FTIR, MALDI-TOF and elemental analysis. Conformational changes owing to conjugation of AA and GEM were estimated via fluorescence, Raman and CD spectroscopy, while changes in physiochemical properties were studied by differential scanning calorimetry (DSC), thermogravimetry (TGA) and contact angle goniometry (CAG). Synthesized conjugate was further transformed into DTX loaded NPs and freeze dried. Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) demonstrated formation of spherical NPs having particle size, 163±8 nm, PDI, 0.13±0.09 and ZP, -27±1 mV. Cellular uptake in MCF-7 and MDA-MB-231 revealed hNTs, OATP1B3 independent, clathrin mediated internalization followed via nuclear co-localization of C-6 loaded AA-GEM-BSA NPs, responsible for significantly higher apoptosis index. Pharmacokinetic profile of DTX loaded AA-GEM-BSA NPs revealed 6.12 and 3.27-fold and 6.28 and 8.9-fold higher AUC and T1/2 values of DTX and GEM as compared to Taxotere^® and Gemzar^®, respectively. Interestingly, the developed NPs were found safe with no marked effect on RBCs, lower hepato and nephro toxicity. Data in hand suggest promising potential of developed NPs in ameliorating the pharmacokinetic and therapeutic profile of combinatorial regimen of DTX and GEM.Statement of SignificanceThe present report is the original state of art technology to selectively target dual drug (DTX and GEM) loaded BSA NPs via exploring tumor targeting potential of AA, having high affinity towards VEGF receptors (angiogenesis marker) overexpressed in tumor. The AA and GEM bio-conjugated BSA was synthesized and further used to develop DTX loaded nanoparticles (AA-GEM-BSA NPs). The optimized NPs were further evaluated via extensive in-vitro and in-vivo studies, demonstrating ameliorated cellular uptake, pharmacokinetic and toxicity profile of drugs. Conclusively, DTX loaded AA-GEM-BSA NPs, holds promising potential in increasing the therapeutic efficiency of drugs and overcoming solvent and drug mediated side effects and can be explored further as a scalable platform technology for difficult to deliver drugs.

Graphical abstract

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Cobalt (II) ions and nanoparticles induce macrophage retention by ROS-mediated down-regulation of RhoA expression

Publication date: Available online 9 April 2018
Source:Acta Biomaterialia
Author(s): Jing Xu, Junyao Yang, Agata Nyga, Mazdak Ehteramyan, Ana Moraga, Yuanhao Wu, Lingfang Zeng, Martin M Knight, Julia C Shelton
Histological assessments of synovial tissues from patients with failed CoCr alloy hip prostheses demonstrate extensive infiltration and accumulation of macrophages, often loaded with large quantities of particulate debris. The resulting adverse reaction to metal debris (ARMD) frequently leads to early joint revision. Inflammatory response starts with the recruitment of immune cells and requires the egress of macrophages from the inflamed site for resolution of the reaction. Metal ions (Co²⁺ and Cr³⁺) have been shown to stimulate the migration of T lymphocytes but their effects on macrophages motility are still poorly understood. To elucidate this, we studied in vitro and in vivo macrophage migration during exposure to cobalt and chromium ions and nanoparticles. We found that cobalt but not chromium significantly reduces macrophage motility. This involves increase in cell spreading, formation of intracellular podosome-type adhesion structures and enhanced cell adhesion to the extracellular matrix (ECM). The formation of podosomes was also associated with the production and activation of matrix metalloproteinase-9 (MMP9) and enhanced ECM degradation. We showed that these were driven by the down-regulation of RhoA signalling through the generation of reactive oxygen species (ROS). These novel findings reveal the key mechanisms driving the wear/corrosion metallic byproducts-induced inflammatory response at non-toxic concentrations.Statement of significanceAdverse tissue responses to metal wear and corrosion products from CoCr alloy implants remain a great challenge to surgeons and patients. Macrophages are the key regulators of these adverse responses to the ions and debris generated. We demonstrated that cobalt, rather than chromium, causes macrophage retention by restructuring the cytoskeleton and inhibiting cell migration via ROS production that affects Rho Family GTPase. This distinctive effect of cobalt on macrophage behaviour can help us understand the pathogenesis of ARMD and the cellular response to cobalt based alloys, which provide useful information for future implant design and biocompatibility testing.

Graphical abstract

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Hydrogel derived from porcine decellularized nerve tissue as a promising biomaterial for repairing peripheral nerve defects

Publication date: Available online 9 April 2018
Source:Acta Biomaterialia
Author(s): Tao Lin, Sheng Liu, Shihao Chen, Shuai Qiu, Zilong Rao, Jianghui Liu, Shuang Zhu, Liwei Yan, Haiquan Mao, Qingtang Zhu, Daping Quan, Xiaolin Liu
Decellularized matrix hydrogels derived from tissues or organs have been used for tissue repair due to their biocompatibility, tunability, and tissue-specific extracellular matrix (ECM) components. However, the preparation of decellularized peripheral nerve matrix hydrogels and their use to repair nerve defects have not been reported. Here, we developed a hydrogel from porcine decellularized nerve matrix (pDNM-G), which was confirmed to have minimal DNA content and retain collagen and glycosaminoglycans content, thereby allowing gelatinization. The pDNM-G exhibited a nanofibrous structure similar to that of natural ECM, and a ∼280-Pa storage modulus at 10 mg/mL similar to that of native neural tissues. Western blot and liquid chromatography tandem mass spectrometry analysis revealed that the pDNM-G consisted mostly of ECM proteins and contained primary ECM-related proteins, including fibronectin and collagen I and IV). In vitro experiments showed that pDNM-G supported Schwann cell proliferation and preserved cell morphology. Additionally, in a 15-mm rat sciatic nerve defect model, pDNM-G was combined with electrospun poly(lactic-acid)–co–poly(trimethylene-carbonate)conduits to bridge the defect, which did not elicit an adverse immune response and promoted the activation of M2 macrophages associated with a constructive remodeling response. Morphological analyses and electrophysiological and functional examinations revealed that the regenerative outcomes achieved by pDNM-G were superior to those by empty conduits and closed to those using rat decellularized nerve matrix allograft scaffolds. These findings indicated that pDNM-G, with its preserved ECM composition and nanofibrous structure, represents a promising biomaterial for peripheral nerve regeneration.

Graphical abstract

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Angiogenesis impairment by the NADPH oxidase-triggered oxidative stress at the bone-implant interface: critical mechanisms and therapeutic targets for implant failure under hyperglycemic conditions in diabetes

Publication date: Available online 9 April 2018
Source:Acta Biomaterialia
Author(s): Xiao-Fan Hu, Lin Wang, Geng Xiang, Wei Lei, Ya-Fei Feng
Mechanism underlying the diabetes-induced poor osteointegration of implants remains elusive, making it a challenge to develop corresponding solutions. Here, we studied the role of angiogenesis in the diabetes-induced poor bone repair at the bone-implant interface (BII) and the related mechanisms. In vivo, titanium screws were implanted in the femurs of mice, and, in vitro, vascular endothelial cell (VEC) was cultured on titanium surface. Results showed that, compared with normal milieu (NM), diabetic milieu (DM) led to angiogenesis inhibition around implants which resulted in reduced osteoprogenitors and poor bone formation on BII in vivo. In vitro, DM caused significant increase of NADPH oxidases (NOX), dysfunction of mitochondria and overproduction of reactive oxygen species (ROS) in VEC on titanium surface, inducing obvious cell dysfunction. Both Mito-TEMPO (Mito, a mitochondria-targeted ROS antagonist) and apocynin (APO, a NOX inhibitor) effectively attenuated the oxidative stress and dysfunction of VEC, with the beneficial effects of APO significantly better than those of Mito. Further study showed that the diabetes-induced metabolic disturbance of VEC was significantly related to the increase of advanced glycation end products (AGEs) at the BII. Our results suggested that the AGEs-related and NOX-triggered cellular oxidative stress leads to VEC dysfunction and angiogenesis impairment at the BII, which plays a critical role in the compromised implant osteointegration under diabetic conditions. These demonstrated new insights into the BII in pathological states and also provided NOX and AGEs as promising therapeutic targets for developing novel implant materials to accelerate the angiogenesis and osteointegration of implants in diabetic patients with hyperglycemia.Statement of significanceThe high failure rate of bone implants in diabetic patients causes patients terrible pain and limits the clinical application of implant materials. The mechanism underlying this phenomenon needs elucidation so that it would be possible to develop corresponding solutions. Our study demonstrated that the AGEs-related and NOX-triggered oxidative stress of VEC leads to angiogenesis impairment at the bone-implant interface (BII) in diabetes. These are critical mechanisms underlying the compromised implant osteointegration in diabetic hyperglycemia. These provide new insights into the BII in diseased states and also suggest NOX and AGEs as crucial therapeutic targets for developing novel implant materials which could modulate the oxidative stress on BII to get improved osteointegration and reduced implant failure, especially in diabetic patients.

Graphical abstract

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Ultrafine heat-induced structural perturbations of bone mineral at the individual nanocrystal level

Publication date: Available online 9 April 2018
Source:Acta Biomaterialia
Author(s): M. Verezhak, E.F. Rauch, M. Véron, C. Lancelon-Pin, J.-L. Putaux, M. Plazanet, A. Gourrier
The nanoscale characteristics of the mineral phase in bone tissue such as nanocrystal size, organization, structure and composition have been identified as potential markers of bone quality. However, such characterization remains challenging since it requires combining structural analysis and imaging modalities with nanoscale precision. In this paper, we report the first application of automated crystal orientation mapping using transmission electron microscopy (ACOM-TEM) to the structural analysis of bone mineral at the individual nanocrystal level. By controlling the nanocrystal growth of a cortical bovine bone model artificially heated up to 1000 °C, we highlight the potential of this technique. We thus show that the combination of sample mapping by scanning and the crystallographic information derived from the collected electron diffraction patterns provides a more rigorous analysis of the mineral nanostructure than standard TEM. In particular, we demonstrate that nanocrystal orientation maps provide valuable information for dimensional analysis. Furthermore, we show that ACOM-TEM has sufficient sensitivity to distinguish between phases with close crystal structures and we address unresolved questions regarding the existence of a hexagonal to monoclinic phase transition induced by heating. This first study therefore opens new perspectives in bone characterization at the nanoscale, a daunting challenge in the biomedical and archaeological fields, which could also prove particularly useful to study the mineral characteristics of tissue grown at the interface with biomaterials implants.Statement of SignificanceIn this paper, we propose a new approach to assess the mineral properties of bone at the individual nanocrystal level, a daunting challenge for decades. We use a modified Transmission Electron Microscopy acquisition mode to perform an Automated Crystal Orientation Mapping (ACOM-TEM) by analyzing electron diffraction patterns. We tune the mineral nanocrystal size by heating a model bovine bone system and show that this method allows precisely assessing the mineral nanocrystals size, orientation and crystallographic phase. ACOM-TEM therefore has sufficient sensitivity to solve problems that couldn't be answered using X-ray diffraction. We thus revisit the fine mechanisms of bone nanocrystal growth upon heating, a process currently used for bone graft manufacturing, also of practical interest for forensic science and archaeology.

Graphical abstract

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Micro-imaging of brain cancer radiotherapy using phase-contrast computed tomography

Publication date: Available online 7 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): G.E. Barbone, A. Bravin, P. Romanelli, A. Mittone, D. Bucci, T. Gaaβ, G. Le Duc, S. Auweter, M. Reiser, M.J. Kraiger, M. Hrabě de Angelis, G. Battaglia, P. Coan
PurposeExperimental neuroimaging provides a wide range of methods for the visualization of brain anatomical morphology down to sub-cellular detail. Still, each technique-specific detection mechanism presents compromises between achievable field-of-view size, spatial resolution or nervous-tissue sensitivity, leading e.g. to partial sample coverage, unresolved morphological structure or sparse labeling of neuronal populations, and often also to obligatory sample dissections or other sample-invasive manipulations. X-ray Phase Contrast CT (PCI-CT) is an experimental imaging methodology, which simultaneously provides micrometric spatial resolution, high soft-tissue sensitivity and ex-vivo full-organ rodent brain coverage without any need for sample dissection, staining/labeling or contrast agent injection. In this work, we explore the benefits and limitations of PCI-CT use for the in-vitro imaging of normal and cancerous brain neuro-morphology after in-vivo treatment with synchrotron-generated X-ray Microbeam Radiation Therapy (MRT), a spatially fractionated experimental high-dose radiosurgery. The goals are the visualization of MRT treatment effects on nervous tissue, and qualitative comparison of results to histology and high-field MRI.MethodsMRT was administered in-vivo to the brain of both healthy and cancer-bearing rats. Forty-five days post-treatment, brain organs were dissected out and imaged ex-vivo via propagation-based PCI-CT.ResultsPCI-CT visualizes brain anatomy and micro-vasculature in 3D, and distinguishes cancerous tissue morphology, necrosis, and intra-tumor accumulation of iron and calcium deposits. Moreover, PCI-CT detects the effects of MRT throughout treatment target areas, e.g. the formation of micrometer-thick radiation-induced tissue ablations. Observed neuro-structures were confirmed by histology and immunohistochemistry, and related to micro-MRI data.ConclusionsPCI-CT enables a unique 3D neuroimaging approach for ex-vivo studies on small animal models, in that it concurrently delivers high-resolution insight on local brain tissue morphology in both normal and cancerous micro-milieu, localizes radiosurgical damage, and highlights deep micro-vasculature. This method could assist experimental small-animal neurology studies in the post-mortem evaluation of neuropathology or treatment effects.

Teaser

Experimental X-ray Phase Contrast micro-CT provides ex-vivo 3D representations of post-mortem brain tissue and glioblastoma tumor anatomy of high sensitivity and resolution without the need for extensive sample preparation. This imaging technique proved suitable for a follow-up study of a spatially fractionated radiotherapy technique, X-ray Microbeam Radiation Therapy. We detect 50μm-thick ablations on healthy and tumor tissue, arising from locally-delivered ultra-high-dose X-ray microbeams, as well as calcium and iron accumulation within necrotic tumor tissue.


https://ift.tt/2GJRfbB

pH-sensitive release of insulin-loaded mesoporous silica particles and its coordination mechanism

Publication date: 1 July 2018
Source:European Journal of Pharmaceutical Sciences, Volume 119
Author(s): Fen Jiang, Yu Liu, Xiahui Wang, Zongning Yin
In this work, we investigated the feasibility of employing metal ion that coordinated with amino group grafted mesoporous silica as a pH-sensitive release carrier of insulin. Mesoporous silica particles were firstly grafted with amino groups. After coordination of metal ions onto the surface of mesoporous pore, insulin was loaded onto mesoporous silica particles through coordination bonds with metal ions. Insulin-loaded mesoporous silica particle with an acid sensitivity between the pH range of physiological environment (pH 7.4) and diabetic acidosis (pH 7.0) and with an insulin encapsulation rate of 74.50% was identified by investigating the influence factors of pH response value. The morphology of particles was confirmed by different analytical methods, indicating that insulin-loaded mesoporous silica particles maintained the rod-like and orderly hexagonal phase mesoporous structure. The coordination mechanism results showed that half of the amino groups on the carrier were coordinated with Cu²⁺, and insulin was successfully coordinated with Cu²⁺ without any damage on the secondary structure. The amount of insulin coordination with Cu²⁺ was positively correlated with the pH of the reaction solution. The cytotoxicity result shows that SBA15-NH2-Cu²⁺-Ins was biocompatible with cells in the concentration ranging from 25 to 100 μg·mL⁻¹. In vivo study preformed on rats showed that the insulin-loaded particles elicited a period hypoglycemic response. Furthermore, fluorescence and UV methods revealed that insulin-loaded mesoporous silica particles had no significant effect on the secondary structure of serum albumin.

Graphical abstract

https://ift.tt/2GN8BQQ

Scholar : African Journal of Aquatic Science, Volume 43, Issue 1, March 2018 is now available online on Taylor & Francis Online

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The online platform for Taylor & Francis Online content African Journal of Aquatic Science, Volume 43, Issue 1, March 2018 is now available online on Taylor & Francis Online. This new issue contains the following articles: Guest Editorial SASAqS and water: Law, management, crisis, and scientists as water activists Prof Carolyn (Tally) Palmer Pages: v-vi | DOI: 10.2989/16085914.2018.1446392 Obituary Nancy Alison Rayner (1927–2017) Rob Hart Pages: vii-x | DOI: 10.2989/16085914.2018.1440918 Research Papers Metal accumulation in two contiguous eutrophic peri-urban lakes, Chivero and Manyame, Zimbabwe B Utete, C Phiri, SS Mlambo, N Maringapasi, N Muboko, TB Fregene & B Kavhu Pages: 1-15 | DOI: 10.2989/16085914.2018.1429249 Occurrence of oestrogenic pollutants and widespread feminisation of male tilapia in peri-urban dams in Bulawayo, Zimbabwe C Teta, BF Holbech, L Norrgren & YS Naik Pages: 17-26 | DOI: 10.2989/16085914.2017.1423269 Biometric variations and oxidative stress responses in juvenile Clarias gariepinus exposed to Termex® JU Nnadi, IN Dimelu, SI Nwani, JC Madu, CI Atama, GN Attamah, JI Okwor & CD Nwani Pages: 27-34 | DOI: 10.2989/16085914.2018.1445615 PAHs, OCPs and PCBs in sediments from three catchments in Durban, South Africa T Vogt, R Pieters & BK Newman Pages: 35-49 | DOI: 10.2989/16085914.2018.1445616 Derivation of scenario-specific water quality guidelines for acid mine drainage in South Africa, using a risk-based approach EC Vellemu, PK Mensah, N Griffin & ON Odume Pages: 51-58 | DOI: 10.2989/16085914.2018.1446126 Use of diatom indices to categorise impacts on and recovery of a floodplain system in South Africa R Musa & R Greenfield Pages: 59-69 | DOI: 10.2989/16085914.2018.1443907 Mesozooplankton of the Kosi Bay lakes, South Africa HL Jerling & SP Weerts Pages: 71-77 | DOI: 10.2989/16085914.2018.1437386 Effect of temperature on seed production in the invasive grass Glyceria maxima (Hartm.) Holmb. (Poaceae) in South Africa LF Mugwedi, JM Goodall, ETF Witkowski & MJ Byrne Pages: 79-84 | DOI: 10.2989/16085914.2018.1438246 Short Note Diet of bluegill Lepomis macrochirus in a South African reservoir during winter and summer PM Ndaleni, RJ Wasserman, BR Ellender & OLF Weyl Pages: 85-88 | DOI: 10.2989/16085914.2018.1436514 Browse papers on image & data fusion, GIS, LiDAR & more in the International Journal of Image and Data Fusion's exclusive Editor's Choice collection. To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Critical Discourse Studies are available online

The online platform for Taylor & Francis Online content New for Critical Discourse Studies and online now on Taylor & Francis Online: Original Articles Marx, discourse theory and political analysis: negotiating an ambiguous legacy David Howarth Pages: 1-13 | DOI: 10.1080/17405904.2018.1457550 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Lipid nanocarriers loaded with natural compounds: Potential new therapies for age related neurodegenerative diseases?

Publication date: Available online 8 April 2018
Source:Progress in Neurobiology
Author(s): Telma Bezerra Soares, Luís Loureiro, Ana Carvalho, Maria Elisabete C.D. Real Oliveira, Alberto Dias, Bruno Sarmento, Marlene Lúcio
Age related neurodegenerative disorders (ARND) are presented as the most debilitating and challenging diseases associated with the central nervous system. Despite the advent of active molecules with a positive role on neurodegenerative mechanisms, many of the current therapeutic strategies remain ineffective in treating or preventing ARND. Lipid nanocarriers have emerged as efficient delivery systems with the capability to cross biological barriers, especially the blood brain barrier (BBB). Also, when associated to natural compounds, lipid nanocarriers have demonstrated to be an interesting alternative to ARND therapies with multiple beneficial effects. This comprehensive review focus on state-of-the-art lipid based nanocarriers for the delivery of natural compounds targeting neurodegeneration. A critical analysis of published reports will be also provided giving indications to researchers about the most promising ARND nanotherapy strategies.



https://ift.tt/2qgnyop

Fractionation and leachability of Fe, Zn, Cu and Ni in the sludge from a sulphate-reducing bioreactor treating metal-bearing wastewater

Abstract

This work presents and discusses experimental results on the characterisation and metal leaching potential of a biogenic, metal-rich sulphidic sludge, generated in a sulphate-reducing bioreactor, operated to treat acidic synthetic solutions bearing Fe, Zn, Ni and Cu. The sustainability of the metal removal bioprocess strongly depends on the fate of the sludge. To propose appropriate management practices, a detailed characterisation of the sludge is necessary. The granulometry, chemical composition and mineralogy of the sludge were initially determined. The mobility of the metals was assessed via a modified Tessier experimental procedure. The leachability of the sludge metal content was determined via a standard compliance method (EN 12457-2) and experiments designed to evaluate the effect of pH and time on metal leaching from the sludge. The sludge metal content sums up to 69.5% dw, namely iron (14.8%), zinc (18.7%), nickel (17.7%) and copper (18.2%) and, based on the criteria set by European Union, the sludge is characterised as hazardous and inappropriate for landfilling without any pretreatment. The sludge consists mainly of very fine poorly crystalline aggregates of Fe, Zn, Cu and Ni sulphides. The fine grain size, the poorly crystalline structure and the oxidation of sulphide upon exposure to water/air render the high metal content of the sludge recoverable.

https://ift.tt/2GIIv5v

Effects of selected synthetic insecticides on the total and differential populations of circulating haemocytes in adults of the red cotton stainer bug Dysdercus koenigii (Fabricius) (Hemiptera: Pyrrhocoridae)

Abstract

Red cotton bug, Dysdercus koenigii (Hemiptera: Pyrrhocoridae), has become the major insect pest of various crops, including cotton, and thereby reducing the yield qualitatively and quantitatively and synthetic insecticides belonging to different groups are the major control agents for such insect pests. A laboratory experiment was carried out to evaluate the effect of different conventional insecticides, i.e., imidacloprid, deltamethrin, lambda cyhalothrin, gamma cyhalothrin and cyfluthirn on haemocytes of D. koenigii. The individuals were exposed to insecticides separately and data was recorded after 30 and 60 min of the exposure. The findings of current study depicted chlorpyrifos to be more effective and significant alterations in total haemocyte counts and differential haemocyte counts were observed in the cyfluthirn treated D. koenigii. In addition to this, cell structure was also disrupted as an immune response. Similar studies would also be helpful to understand the defence mechanisms of insects against the xenobiotics which will help to device efficient management tools for D. koenigii.

https://ift.tt/2qilFGJ

A systematic review of the risk of postoperative bleeding with perioperative non-steroidal anti-inflammatory drugs (NSAIDs) in plastic surgery

Abstract

Background

NSAIDs are used extensively in the perioperative period, for analgesia, or for preexisting conditions. However, potential risks of NSAID-induced haemorrhage have raised concerns regarding their use. NSAIDs inhibit platelet aggregation and have been shown to significantly increase bleeding time. In the available literature, there is an apparent lack of consensus regarding the use of NSAIDs and their clinical effects. A systematic review was undertaken to collate all relevant published data to provide a combined measure of the overall risk of serious complications when using NSAIDs in the perioperative period.

Methods

The search for potentially relevant studies was undertaken in PubMed for all publications up to August 2016, using appropriate medical subject (MeSH) headings. There were no restrictions on publication date or status. This was conducted in concordance with and adherence to the 2009 PRISMA guidance. Data harvested relevant papers was tabulated and analysed utilising Review Manager software to calculate a risk ratio (Mantel-Haenszel method, random effects).

Results

Twelve articles were included in the analysis, comprising 6581 patients, of which 1785 received an NSAID and 4796 were controls. Within the 1785 patients receiving NSAIDs, a total of 102 (5.7%) experienced moderate to severe complications, compared with 108 (2.2%) in the control groups.

Conclusions

Based on the assembled data, the authors conclude that the use of perioperative NSAIDs in plastic surgical procedures increases the risk of postoperative bleeding complications. Despite this, the rate of bleeding complications remains low.

Level of Evidence: Not ratable.

https://ift.tt/2GISGai

Late hand replantation with restoration of intrinsic muscle function: a case and review of the literature

Abstract

Limb amputation injuries and their subsequent replantation is a time-critical exercise if function is to be restored. The exact time limit to functional replantation is still poorly defined in the literature owing to the multitude of factors that influence functional recovery. The relative metabolic activity of a tissue is lower under hypothermic conditions, and subsequently, moderate delays in restoring circulation can still achieve good functional outcomes if the amputated part is transported appropriately. Some surgeons have adopted the practice of, in cases where the delay to replantation is beyond 8–10 h, resecting skeletal muscle from the amputated part to avoid the sequelae of its ischaemic period. We report the case of a traumatic trans-carpal hand amputation in a 40-year-old male, with a second-level injury more distally at the metacarpal heads, who was replanted with a total ischaemic time of 19 h and 25 min. The decision was made to retain his intrinsic hand muscles in contradiction to common practice. At 2.5 years follow-up, he has regained a remarkable level of function of his hand including activation of his intrinsic hand muscles. His Semmes Weinstein testing has also shown good sensory recovery of his repaired nerves and he enjoys little, if any, disability as a result of his injury (despite a double-level injury on the dorsal ulna aspect of his forearm). This suggests, in cases of hand amputation with appropriate hypothermic transportation of the amputated part, ischaemia times up to 20 h may be compatible with restoration of intrinsic hand function.

Level of Evidence: Level V, risk / prognostic study.

https://ift.tt/2qhzbdM

Towards standardization of training and practice of reconstructive microsurgery: an evidence-based recommendation for anastomosis thrombosis prophylaxis

Abstract

Background

Despite significant improvements in survival rates, free flap failures still occur even in experienced hands and are most commonly due to arterial or venous thrombosis. In the absence of an evidence-based guideline on the prevention of thrombosis, we reviewed the literature to assess the evidence base for commonly used interventions aimed at its prevention.

Methods

A comprehensive literature search was performed using the following keywords "free flap" and microsurgery with "pre-operative screening," "prevention of thrombosis," "ketorolac," "heparin," "low molecular weight heparin," "aspirin," "dextran," and "statins."

Results

Thirteen clinical studies were included in this review. No high-level evidence is available to support any perioperative or postoperative interventions aimed at reducing the risk of flap thrombosis.

Conclusions

Higher level studies are needed to investigate the clinical use of antithrombotic medications in microsurgery; however, given the small failure rates in modern practice, these will need to be large multicenter trials in order to reach sufficient power.

Level of Evidence: Level III, risk/prognostic study.

https://ift.tt/2GISg3I

Adenovirus and rotavirus recovery from a treated effluent through an optimized skimmed-milk flocculation method

Abstract

Sewage treatment may be insufficient for the complete removal of enteric viruses, such as human adenoviruses (HAdV) and group A rotavirus (RVA). The differences in the efficiency of the treatment methodologies used may interfere with the detection of these viruses. The objective of this study was to optimize a skimmed-milk flocculation technique for the recovery of HAdV and RVA in the samples of treated effluent. The treated effluent collected at the wastewater treatment plant (WWTP) was processed via four protocols including modifications in the initial centrifugation step and the final concentration of skimmed-milk. The viral load and recovery rate were determined by quantitative PCR TaqMan® System. The highest recovery rates of HAdV, RVA, and bacteriophage PP7 (internal control process) were obtained when the concentration of skimmed-milk was doubled and no centrifugation step was used for the sample clarification. The optimized protocol was assessed in a field study conducted with 24 treated effluent samples collected bi-monthly during 2015. HAdV and RVA were detected in 50.0% (12/24) and 33.3% (08/24) of the samples tested, respectively, throughout the year, without seasonal variation (p > 0.05). This study corroborates the use of the organic flocculation method for virus recovery in environmental samples with the adaptation of the protocols to different aquatic matrices.

https://ift.tt/2IDwivp

Pyroprotein-based electronic textiles with high thermal durability

Publication date: Available online 7 April 2018
Source:Materials Today
Author(s): Jun Woo Jeon, Joo Young Oh, Se Youn Cho, Sungho Lee, Hyun-Seok Jang, Won Taek Jung, Jeong-Gyun Kim, Hyeonbeom Kim, Hyuk Jin Kim, SeongYeon Kim, Songlee Han, JunHo Kim, Young Jun Chang, Dongseok Suh, Hyoung-Joon Jin, Byung Hoon Kim
Electronic textiles (e-textiles) need to have high heat durability for various applications. However, current e-textiles are usually damaged by high-temperature processes. We report silk-based e-textiles fabricated by simple pyrolysis with axial stretching that demonstrate high electrical conductivity and thermal durability. The electrical conductivity of the proposed e-textiles was on the order of 10³S/cm and the electrical characteristics were maintained even after heating and bending. Furthermore, we prepared e-textiles with various electronic properties, such as semiconducting, superconducting, and light-emitting properties, by depositing ZnO, MoSe2, and NbN onto the commercial silk-based e-textiles using sputtering and evaporation. We introduced a simple method for fabricating silk-based e-textiles with various electronic properties, which are compatible with the current textile industry.

Graphical abstract

https://ift.tt/2JxflUH

Routes for high-performance thermoelectric materials

Publication date: Available online 7 April 2018
Source:Materials Today
Author(s): Xiaoyuan Zhou, Yanci Yan, Xu Lu, Hangtian Zhu, Xiaodong Han, Gang Chen, Zhifeng Ren
Thermoelectric materials can be used in direct conversion of heat to electricity and vice versa. The past decade has witnessed the rapid growth of thermoelectric research, targeting high thermoelectric performance either via reduction in the lattice thermal conductivity or via enhancement of the power factor. In this review, we firstly summarize the recent advances in bulk thermoelectric materials with reduced lattice thermal conductivity by nano-microstructure control and also newly discovered materials with intrinsically low lattice thermal conductivity. We then discuss ways to enhance the electron transport abilities for achieving higher power factor by both novel and traditional methods. Finally, we highlight the recent development in single-crystal thermoelectric materials. These strategies are successful in synergistically manipulating the thermal conductivity and electron transport properties, which have significantly advanced thermoelectric performance on materials. For device applications on these high-performance materials, new opportunities may arise though stability, electrode contacts, mechanical properties, and other problems need to be solved in the near future.

Graphical abstract

https://ift.tt/2EvDEPg

In situ formation of interpenetrating polymer network using sequential thermal and click crosslinking for enhanced retention of transplanted cells

Publication date: July 2018
Source:Biomaterials, Volume 170
Author(s): Hamid Sadeghi Abandansari, Mohammad Hossein Ghanian, Fahimeh Varzideh, Elena Mahmoudi, Sarah Rajabi, Payam Taheri, Mohammad Reza Nabid, Hossein Baharvand
Injectable hydrogels, which are used as scaffolds in cell therapy, provide a minimally invasive strategy to enhance cell retention and survival at injection site. However, till now, slow in situ gelation, undesired mechanical properties, and weak cell adhesion characteristics of reported hydrogels, have led to improper results. Here, we developed an injectable fully-interpenetrated polymer network (f-IPN) by integration of Diels-Alder (DA) crosslinked network and thermosensitive injectable hydrogel. The proposed DA hydrogels were formed in a slow manner showing robust mechanical properties. Interpenetration of thermosensitive network into DA hydrogel accelerated in situ gel-formation and masked the slow reaction rate of DA crosslinking while keeping its unique features. Two networks were formed by simple syringe injection without the need of any initiator, catalyst, or double barrel syringe. The DA and f-IPN hydrogels showed comparable viscoelastic properties along with outstanding load-bearing and shape-recovery even under high levels of compression. The subcutaneous administration of cardiomyocytes-laden f-IPN hydrogel into nude mice revealed high cell retention and survival after two weeks. Additionally, the cardiomyocyte's identity of retained cells was confirmed by detection of human and cardiac-related markers. Our results indicate that the thermosensitive-covalent networks can open a new horizon within the injection-based cell therapy applications.

Graphical abstract

https://ift.tt/2GJNEq2

Programmed ‘triple-mode’ anti-tumor therapy: Improving peritoneal retention, tumor penetration and activatable drug release properties for effective inhibition of peritoneal carcinomatosis

Publication date: July 2018
Source:Biomaterials, Volume 169
Author(s): Kondareddy Cherukula, Woo Kyun Bae, Jae Hyuk Lee, In-Kyu Park
Peritoneal carcinomatosis (PC) is a fatal condition arising in the gastrointestinal tract. PC patients administered drugs locally in the tumor region, such as in intraperitoneal chemotherapy (IPCh), suffer from low drug retention time and tumor penetration. Herein, we synthesized a lithocholic acid (LCA)-conjugated disulfide-linked polyethyleneimine (ssPEI) micelle (LAPMi) nanoconstruct by covalently conjugating ssPEI and LCA, thereby forming positive charged nanomicellar structures loaded with paclitaxel (PTX) (LAPMi-PTX) for IPCh. The incorporation of a positive surface charge aided in prolonging the peritoneal retention time, presumably via ascites-induced protein corona formation, and the subsequent size expansion caused resistance against undesired clearance through lymphatic openings. Furthermore, preferential tumor penetration by LAPMi-PTX is attributable to the permeation-enhancing properties of LCA, and the subsequent tumor activatable drug release was induced by the presence of disulfide linkages. By integrating these properties, LAPMi exhibited prolonged peritoneal residence time, enhanced tumor permeation and chemotherapeutic effect evidenced by in vitro, tumor spheroid and in vivo studies. Importantly, our strategy enabled significant PC inhibition and increased the overall survival rate of tumor-bearing mice. In conclusion, we provided a new paradigm of intractable PC treatment by enabling the prolonged residence time of the nanoconstruct, thereby enhancing tumor penetration and anti-tumor therapy.



https://ift.tt/2HgoJv8

Cytokine induced killer cells-assisted delivery of chlorin e6 mediated self-assembled gold nanoclusters to tumors for imaging and immuno-photodynamic therapy

Publication date: July 2018
Source:Biomaterials, Volume 170
Author(s): Fangfang Xia, Wenxiu Hou, Yanlei Liu, Wentao Wang, Yu Han, Meng Yang, Xiao Zhi, Chenlu Li, Daizong Qi, Tianliang Li, Jesus Martinez de la Fuente, Chunlei Zhang, Jie Song, Daxiang Cui
The cytotoxicity and unique tumor-tropic properties of cytokine-induced killer (CIK) cells render them promising in the field of cancer immunotherapy and delivery systems. Here, we report a novel and facile approach to assemble gold nanoclusters (GNCs) into stable and monodispersed nanoparticles (NPs) using Chlorin e6 (Ce6) molecules. Notably, the fluorescence intensity of the GNCs-Ce6 NPs was about 4.5 folds stronger than the GNCs counterparts. The as-prepared GNCs-Ce6 NPs were conjugated with CD3 antibody (Ab) and further employed to label CIK cells to create a CIK cell-based drug delivery system (Ce6-GNCs-Ab-CIK). The Ce6-GNCs-Ab-CIK exhibited high tumor-targeting efficiency and excellent therapeutic efficacy toward MGC-803 tumor-bearing mice. Benefiting from the synergistic therapeutic effect between GNCs-Ce6-Ab NPs and CIK cells, the GNCs-Ce6-Ab-CIK strategy may present an ideal cancer theranostic platform for tumor targeted imaging and combination therapy.



https://ift.tt/2EtKAMx

Decellularized materials derived from TSP2-KO mice promote enhanced neovascularization and integration in diabetic wounds

Publication date: July 2018
Source:Biomaterials, Volume 169
Author(s): Aaron H. Morris, Danielle K. Stamer, Britta Kunkemoeller, Julie Chang, Hao Xing, Themis R. Kyriakides
Decellularized biologic scaffolds are gaining popularity over synthetic biomaterials as naturally derived materials capable of promoting improved healing. Nevertheless, the most widely used biologic material – acellular dermal matrix (ADM) – exhibits slow repopulation and remodeling, which prevents integration. Additionally, engineering control of these materials is limited because they require a natural source for their production. In the current report, we demonstrate the feasibility of using genetically engineered animals to create decellularized biologic scaffolds with favorable extracellular matrix (ECM) properties. Specifically, we utilized skin from thrombospondin (TSP)-2 KO mice to derive various decellularized products. Scanning electron microscopy and mechanical testing showed that TSP-2 KO ADM exhibited an altered structure and a reduction in elastic modulus and ultimate tensile strength, respectively. When a powdered form of KO ADM was implanted subcutaneously, it was able to promote enhanced vascularization over WT. Additionally, when implanted subcutaneously, intact slabs of KO ADM were populated by higher number of host cells when compared to WT. In vitro studies confirmed the promigratory properties of KO ADM. Specifically, degradation products released by pepsin digestion of KO ADM induced greater cell migration than WT. Moreover, cell-derived ECM from TSP-2 null fibroblasts was more permissive to fibroblast migration. Finally, ADMs were implanted in a diabetic wound model to examine their ability to accelerate wound healing. KO ADM exhibited enhanced remodeling and vascular maturation, indicative of efficient integration. Overall, we demonstrate that genetic manipulation enables engineered ECM-based materials with increased regenerative potential.



https://ift.tt/2Hj6PIq

Second near-infrared emissive lanthanide complex for fast renal-clearable in vivo optical bioimaging and tiny tumor detection

Publication date: July 2018
Source:Biomaterials, Volume 169
Author(s): Youbin Li, Xiaolong Li, Zhenluan Xue, Mingyang Jiang, Songjun Zeng, Jianhua Hao
In vivo optical imaging by using a new imaging window located at short-wavelength infrared region (1000–1700 nm, named as NIR II) presents an unprecedented improvement in imaging sensitivity and spatial resolution over the traditional visible and near-infrared light. However, the most developed NIR II-emitters are hardly excreted from live animals, leading to unknown long-term toxicity concerns, which hinder the widespread applications of this advanced imaging technology. Here, we developed a new generation molecular NIR II-emitting probe based on Nd-diethylene triamine pentacetate acid (DTPA) complex. The designed molecular Nd-DTPA probe with bright narrow band emission at 1330 nm is successfully used for highly sensitive in vivo NIR II bioimaging with rapid renal excretion, high biocompatibility and optical-guided tiny tumor (down to ∼3 mm) detection for the first time. Moreover, the Nd-DPTA complex also holds great promise as an X-ray contrast agent. These findings open up the possibility for designing a new generation of multi-modal small molecular probe for early tumor diagnosis and favor the clinic translation of the advanced NIR II imaging method.



https://ift.tt/2GE1LRH

In-vitro and in-vivo design and validation of an injectable polysaccharide-hydroxyapatite composite material for sinus floor augmentation

Publication date: Available online 7 April 2018
Source:Dental Materials
Author(s): J.C. Fricain, R. Aid, S. Lanouar, D.B. Maurel, D. Le Nihouannen, S. Delmond, D. Letourneur, J. Amedee Vilamitjana, S. Catros
ObjectivePolysaccharide-based composite matrices consisting of natural polysaccharides, pullulan and dextran supplemented with hydroxyapatite (Matrix-HA) have recently been developed. The principal objective of this study was to evaluate the capacities of this composite material to promote new bone formation in a sinus lift model in the sheep. Secondary objectives were to evaluate in vitro properties of the material regarding cell adhesion and proliferation.MethodsIn this report, once such composite matrix was prepared as injectable beads after dispersion in a physiological buffer, and evaluated using a large animal model (sheep) for a sinus lift procedure.ResultsIn vitro studies revealed that these microbeads (250–550μm in diameter) allow vascular cell adhesion and proliferation of Endothelial Cells (EC) after 1 and 7 days of culture. In vivo studies were performed in 12 adult sheep, and newly formed tissue was analyzed by Cone Beam Computed Tomography (CBCT scanning electron microscopy (SEM) and by histology 3 and 6 months post-implantation. CBCT analyses at the implantation time revealed the radiolucent properties of these matrices. Quantitative analysis showed an increase of a dense mineralized tissue in the Matrix-HA group up to 3 months of implantation. The mineralized volume over total volume after 6 months reached comparable values to those obtained for Bio-Oss^® used as positive control. Histological examination confirmed that the Matrix-HA did not induce any long term inflammatory events, and promoted direct contact between the osteoid tissue and lamellar bone structures and beads. After 6 months, we observed a dense network of osteocytes surrounding both biomaterials as well as a newly vascularized formed tissue in close contact to the biomaterials.SignificanceIn conclusion, the absence of animal components in Matrix-HA, the osteoconductive property of Matrix-HA in sheep, resulting in a dense bone and vascularized tissue, and the initial radiolucent property to follow graft integration offer great promises of this composite material for clinical use.



https://ift.tt/2GI2OjA

What is Health Services Research?

Publication date: Available online 7 April 2018
Source:Academic Radiology
Author(s): James V. Rawson, Paul Cronin




https://ift.tt/2JvKojQ

Long-term home non-invasive positive pressure ventilation in children: Results from a single center in Japan

Publication date: Available online 7 April 2018
Source:Brain and Development
Author(s): Azusa Ikeda, Megumi Tsuji, Tomohide Goto, Mizue Iai
BackgroundNon-invasive positive pressure ventilation (NPPV) in children has recently increased worldwide and is used not only for neuromuscular diseases but for various other diseases. However, there have been few observational studies on long-term NPPV in children in Japan.MethodsBased on medical records, we retrospectively evaluated patients aged ≤20 years who were initiated long-term NPPV at our hospital from January 2001 to December 2015.ResultsA total of 53 patients on long-term NPPV were identified; 38 (72%) had severe motor and intellectual disabilities (SMID). Compared to those with non-neuromuscular diseases, those with neuromuscular diseases had significantly more planned initiations and less frequent use of oxygen. Regarding patient outcome, 34 patients continued NPPV (64%), and there were three discontinues (6%), seven tracheostomies (13%), and nine deaths (17%). The continuation rate was high among those with neuromuscular disorders (15/19 cases, 79%) and that of tracheotomy was high in those with metabolic/degenerative diseases (3/9 cases, 33%). Ten patients transitioned to adult care, accounting for 29% of the 34 continuing patients.ConclusionThis is the first observational study on long-term NPPV use in children in Japan that examined outcomes in patients with a range of disorders. The initiation situation, management, and outcomes differed between patients with neuromuscular and non-neuronal muscular diseases. Long-term use of NPPV is possible in many cases, including children with SMID, but can be challenging to continue in patients with progressive diseases such as metabolic/degenerative diseases. Careful discussions regarding the management of each patient are necessary.



https://ift.tt/2IBvwz8

Genetic variation and systemic lupus erythematosus: A field synopsis and systematic meta-analysis

Publication date: Available online 7 April 2018
Source:Autoimmunity Reviews
Author(s): Dong Yeon Jeong, Sang Woo Lee, Young Ha Park, Ji Hoon Choi, Young Wook Kwon, Gabin Moon, Michael Eisenhut, Andreas Kronbichler, Jae Il Shin
Systemic lupus erythematosus (SLE) is a multi-systemic severe autoimmune disease which results from the irreversible loss of self-tolerance and impaired molecular responses, especially an altered interferon signature. We synthesized all meta-analyses reporting a genetic association of SLE, and further investigated their validity to discover false positive results under Bayesian methods. We executed a PubMed search to extract the respective results regarding gene polymorphisms of SLE, published until June 30th 2017 and selected a single result per genetic variant among duplicates. Among 133 significant genotype comparisons, 45 (34%) were found noteworthy under both false positive report probability (FPRP) and Bayesian false discovery probability (BFDP). From the meta-analysis of genome-wide association studies (GWAS), we could confirm that all significant comparisons were noteworthy under both Bayesian approaches. Both approaches may be advantageous for determining whether the reported associations is genuine, especially for interpreting results from observational studies instead of GWAS whose significance was determined in a more strict manner. When determining results from GWAS with a p-value ranging between 0.05 and 5 × 10⁻⁸, other statistical approaches, rather than single standard significance may be beneficial. Taking into account these considerations, a proportion of meta-analyses claimed statistical significance, but these results need to be interpreted with caution.



https://ift.tt/2JpSwlX

Should rheumatoid factor (RF) (and antinuclear antibodies (ANA)) become routinary screening test for morbidities in the general population?

Publication date: Available online 8 April 2018
Source:Autoimmunity Reviews
Author(s): Gianfranco Ferraccioli, Stefano Alivernini, Barbara Tolusso, Elisa Gremese




https://ift.tt/2EuNrVJ

MHC class I chain-related A: Polymorphism, regulation and therapeutic value in cancer

Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Xi Yang, Shuzhen Kuang, Liangjiang Wang, Yanzhang Wei
MICA and MICB are stress-induced molecules recognized by NKG2D, one of major activation receptors of natural killer (NK) cells. Upon binding to NKG2D, NKG2D-mediated cytolytic immune response of immune effector cells will be activated against virally infected and tumor cells expressing MICA. In the early oncogenic development, membrane-bound MICA serves as a key signal to recruit anti-tumor immune effectors. Nevertheless, both MICA polymorphic features and its dysregulated expression in evolving tumors have resulted in tumor evasion in various cancer types. Therefore, in order to reconstitute tumor immunosurveilance, it is of great significance that we understand MICA genetics, polymorphisms, mechanisms of MICA-associated tumor escape and molecular/cellular modulation of MICA. In this review, the MICA-associated co-expression networks involving microRNAs (miRNAs) and novel candidate long non-coding RNAs (lncRNAs) were also discussed. Given the current importance in the study of MICA gene, this review paper focuses on the role of MICA in different cancer types, and strategies that we manipulate MICA regulation against tumor proliferation.



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Naringin attenuates MLC phosphorylation and NF-κB activation to protect sepsis-induced intestinal injury via RhoA/ROCK pathway

Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Zhiling Li, Ming Gao, Bingchang Yang, Huali Zhang, Kangkai Wang, Zuoliang Liu, Xianzhong Xiao, Mingshi Yang
BackgroundSepsis is commonly associated with excessive stimulation of host immune system and result in multi-organ failure dysfunction. Naringin has been reported to exhibit a variety of biological effects. The present study aimed to investigate the protective effect of naringin on sepsis-induced injury of intestinal barrier function in vivo and in vitro.MethodsMice were randomly divided into 4 groups named sham (n = 20), CLP + vehicle (n = 20), CLP + NG (30 mg/kg) (n = 20) and CLP + NG (60 mg/kg) (n = 20) groups. Sepsis was induced by cecal ligation and puncture (CLP). H&E staining and transmission electron microscopy (TEM) were performed to observe intestinal mucosal morphology. ELISA was used to determine the intestinal permeability and inflammatory response in vivo and in vitro. Western blot and RhoA activity assay were performed to determine the levels of tight junction proteins and the activation of indicated signaling pathways. MTT assay was used to determine cell viability.ResultsNaringin improved survival rate of CLP mice and alleviated sepsis-induced intestinal mucosal injury. Furthermore, naringin improved impaired intestinal permeability and inhibited the release of TNF-α and IL-6, while increased IL-10 level in CLP mice and lipopolysaccharide (LPS)-stimulated MODE-K cells in a dose-dependent manner. Naringin increased the expression of tight junction proteins ZO-1 and claudin-1 via RhoA/ROCK/NF-κB/MLCK/MLC signaling pathway in vivo and in vitro.ConclusionNaringin improved sepsis-induced intestinal injury via RhoA/ROCK/NF-κB/MLCK/MLC signaling pathway in vivo and in vitro.



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Renal protective effect of SGLT2 inhibitor dapagliflozin alone and in combination with irbesartan in a rat model of diabetic nephropathy

Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Ali F. Abdel-Wahab, Ghazi A. Bamagous, Randa M. Al-Harizy, Naser A. ElSawy, Naiyer Shahzad, Ibrahim A. Ibrahim, Saeed S. Al Ghamdi
Considering the complementary mechanisms of SGLT2 inhibitors and angiotensin inhibitors on kidney, it is postulated that combination of both agents could afford greater protection against diabetic renal injury. So, we investigated renal protective effects of SGLT2 inhibitor, dapagliflozin, alone and in combination with irbesartan in a rat model of diabetic nephropathy. Diabetic rats, injected with nicotinamide-streptozotocin, were treated orally for 12 weeks with either vehicle, dapagliflozin 2 mg/kg/day, irbesartan 30 mg/kg/day, or combination of both drugs; respectively. Biochemical analysis included blood glucose, HbA1c, urinary albumin excretion, creatinine clearance, TGF-β1, sRAGE, oxidative markers, and histopathological examination of kidneys. Treatment with dapagliflozin, irbesartan, and especially their combination, produced significant reduction in albuminuria, improved renal function parameters, increased sRAGE level and improved inflammatory and oxidative markers, together with amelioration of renal histopathological changes. Beside glycemic control, dapagliflozin produced higher sRAGE levels than irbesartan, suggesting that inhibition of AGE-RAGE axis is important in its renoprotective action. Combination of dapagliflozin and irbesartan produced more remarkable protective effects on renal function and structure, than use of either agent alone. It is concluded that, combination of SGLT2 inhibitor, dapagliflozin and ARB, irbesartan could offer more effective renal protection and represent a promising therapeutic option for management of diabetic nephropathy.

Graphical abstract

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Avicularin reversed multidrug-resistance in human gastric cancer through enhancing Bax and BOK expressions

Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Xiang-Feng Guo, Ji-Peng Liu, Si-Quan Ma, Peng Zhang, Wen-De Sun
5-Fluorouracil (5-Fu) and cisplatin (DDP) as important therapies in treatment of human gastric cancer have been widely determined. However, the therapeutic effects are usually hampered due to drug resistance or toxicity at high concentrations for application. Avicularin (AL, quercetin-3-α-l-arabinofuranoside), a bio-active flavonol isolated from a number of plants, has been reported to display diverse pharmacological properties. In this study, we explored the hypothesis by which AL reversed 5-Fu or DDP resistance in gastric cancer and the underlying molecular mechanism. Here, in vitro, the drug-resistant cancer cells were incubated to AL or DDP alone or the combination of AL and DDP. Then, MTT, colony formation, Hoechst 33258, flow cytometry and western blot analysis were used to investigate the effects of AL in the regulation of drug-resistance gastric cancer cells. The results indicated that AL treatment markedly re-sensitizes the drug resistant cells (SGC-7901/5-Fu and SGC-7901/DDP) to cytotoxicity of 5-Fu or DDP. Molecular mechanism analysis indicated that AL and DDP combination treatment enhanced apoptosis in SGC-7901/DDP cells, accompanied with the up-regulation of cleaved Caspase-3 and PARP, as well as the activation of pro-apoptotic signals, including Bax and BOK. Significantly, down regulation of Bax or BOK expressions using Bax siRNA or BOK siRNA decreased the inhibitory role of DDP in apoptosis of SGC-7901/DDP cells pretreated with AL, demonstrating that AL-reversed DDP resistance was associated with Bax and BOK expression. In vivo, AL and DDP combination significantly reduced gastric tumor growth. Immunohistochemical analysis indicated that co-treatment of AL and DDP significantly induced apoptosis, and reduced tumor cell proliferation in tumor tissue samples. Furthermore, we also found that the Bax, BOK, cleaved Caspase-3 and PARP expression in tumor tissues were highly induced by AL and DDP co-treatment. Together, our findings may provide a novel combination therapeutic strategy in treatment of human gastric cancer.



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Betaine treatment protects liver through regulating mitochondrial function and counteracting oxidative stress in acute and chronic animal models of hepatic injury

Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Reza Heidari, Hossein Niknahad, Ala Sadeghi, Hamidreza Mohammadi, Vahid Ghanbarinejad, Mohammad Mehdi Ommati, Arghavan Hosseini, Negar Azarpira, Forouzan Khodaei, Omid Farshad, Elaheh Rashidi, Asma Siavashpour, Asma Najibi, Asrin Ahmadi, Akram Jamshidzadeh
Betaine is a derivative of the amino acid glycine widely investigated for its hepatoprotective properties against alcoholism. The protective properties of betaine in different other experimental models also have been documented. On the other hand, the exact cellular mechanism of cytoprotection provided by betaine is obscure. The current study was designed to evaluate the hepatoprotective effects of betaine and its potential mechanisms of hepatoprotection in two animal models of acute and chronic liver injury. Bile duct ligation (BDL) was used as a model of chronic liver injury and thioacetamide (TAA)-induced hepatotoxicity was applied as the acute liver injury model. Severe increase in serum markers of liver tissue damage along with significant liver tissue histopathological changes were evident in both acute and chronic models of hepatic injury. It was also found that tissue markers of oxidative stress were significantly increased in BDL and TAA-treated animals. Moreover, liver mitochondrial indices of functionality were deteriorated in both investigated models. Betaine supplementation (10 and 50 mg/kg, i.p) ameliorated hepatic injury as judged by decreased liver tissue histopathological alterations, a significant decrease in tissue markers of oxidative stress, and mitigation of serum biomarkers of hepatotoxicity. On the other hand, betaine (10 and 50 mg/kg, i.p) protected hepatocytes mitochondria in both chronic and acute models of hepatotoxicity. These data indicate that the antioxidative and mitochondria regulating properties of betaine could play a primary role in its mechanisms of hepatoprotection.

Graphical abstract

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Impact of stress on female reproductive health disorders: Possible beneficial effects of shatavari (Asparagus racemosus)

Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Ajai K Pandey, Anumegha Gupta, Meenakshi Tiwari, Shilpa Prasad, Ashutosh N. Pandey, Pramod K. Yadav, Alka Sharma, Kankshi Sahu, Syed Asrafuzzaman, Doyil T. Vengayil, Tulsidas G. Shrivastav, Shail K Chaube
Stress is deeply rooted in the society and women are frequently exposed to psychological, physical and physiological stressors. Psychological stress disturbs reproductive health by inducing generation of reactive oxygen species (ROS) and thereby oxidative stress (OS). The increased OS may affect physiology of ovary, oocyte quality and cause female reproductive health disorders. To overcome stress-mediated reproductive health disorders in women, shatavari (Asparagus racemosus) is frequently recommended in Ayurvedic system of medicine. Although shatavari is one of the major health tonics and most popular rasayana drugs to treat reproductive ailments of women, underlying mechanism of shatavari action at the level of ovary remains poorly understood. Based on the existing studies, we propose that shatavari may improve female reproductive health complications including hormonal imbalance, polycystic ovarian syndrome (PCOS), follicular growth and development, oocyte quality and infertility possibly by reducing OS level and increasing antioxidants level in the body. Further studies are required to elucidate the mechanism of shatavari actions at the level of ovary and oocyte that directly impacts the reproductive health of women.



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Bombesin attenuated ischemia-induced spatial cognitive and synaptic plasticity impairment associated with oxidative damage

Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Yang Yao, Faqi Wang, Xuening Yang, Dawei Zang, Jiajia Yang, Zhiyun Wang
The dysfunction of spatial cognition is a character to various neurological disorders and therapeutic strategy. However, it is limited to known risk factors clinically so far. Gastrin releasing peptide (GRP) signaling is a neuropeptide system mediating emotional memory events. However, the effects of GRP agonist on spatial cognition and hippocampal synaptic plasticity are rarely investigated, especially in pathologic condition. This study was designed to investigate the long-term effects of GRPR agonist, bombesin, against cognitive impairment induced by chronic cerebral ischemia in rats and its possible mechanisms. Our results revealed that bombesin administration (30 μg/kg/day, for 14 continuous days) significantly protected the cognitive and synaptic plasticity impairments as assessed by the Morris water maze and long-term potentiation tests. The mechanism studies demonstrated that bombesin significantly alleviated the decreased activity of total superoxide dismutase (T-SOD), catalase (CAT) and altered the increased the content of malondialdehyde (MDA). Besides, the decreased expression of synapse plasticity-related proteins, calcium- calmodulin- dependent protein kinase II (CaMKII) and synaptophysin (SYP) in the hippocampus were increased with drug treatment. In conclusion, bombesin could protect the oxidative stress and expression of proteins, which were important for synaptic plasticity and cognitive function impairment induced by chronic cerebral ischemia. Our study is presented to provide novel insights into the effects of bombesin on spatial learning and memory, which should be further explored as a potential drug in disorders involving deficits in cognitive function.

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The long non-coding RNA-DANCR exerts oncogenic functions in non-small cell lung cancer via miR-758-3p

Publication date: July 2018
Source:Biomedicine & Pharmacotherapy, Volume 103
Author(s): Sheng Wang, Ming Jiang
Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in the occurrence and progression of multiple cancers. In this study, we investigated the role of the lncRNA DANCR in the development of non-small cell lung cancer (NSCLC). First, we found that DANCR was markedly upregulated in NSCLC tumor tissues and cell lines compared with related normal controls. The ectopic expression of DANCR significantly increased the proliferation, migration and invasion of SPC-A1 and NCL-H1299 cells. Furthermore, we investigated whether DANCR regulates NSCLC tumor formation in vivo. Subsequently, we concluded that DANCR promotes NSCLC cell proliferation, migration and invasion by regulating the tumor suppressor miR-758-3p. These results indicated that the DANCR/miR-758-3p axis could be a potential target in the treatment of NSCLC.

Graphical abstract

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