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Σάββατο 10 Μαρτίου 2018
Scholar : These new articles for Journal of Architectural Conservation are available online
MiR-145 improves macrophage-mediated inflammation through targeting Arf6
Abstract
Purpose
To explore the relationship between miR-145 and ADP ribosylation factor 6 (Arf6) in regulating macrophage-mediated inflammation.
Methods
THP-1 cells were induced by 160 nM of phorbol 12−myristate 13-acetate (PMA) for 48 h to differentiate to macrophages and then were treated with LPS (100 ng/ml) for 8 h to simulate chronic metabolic inflammation in vitro. Dual-luciferase reporter assay was performed. MiR-145 siRNA and LV-ARF6-RNAi were used to up or down regulate miR-145 and Arf6 expression in THP-1 cells, respectively. Omental adipose tissue from patients in surgical ward were collected to detect the expression of miR-145, Arf6 and production of proinflammatory cytokines. Patients were divided into three groups according to their body mass index and history of diabetes.
Results
Dual-luciferase reporter assays showed the direct down-regulation of Arf6 by miR-145. Forty-eight-hour-transfection of miR-145 inhibitor resulted in significant increase of Arf6, IL-1beta, TNF-alpha and IL-6 as well as phosphorylation of p65 in NF-kappaB pathway in THP-1 cells, which, inversely, were reversed by overexpressing miR-145. In addition, down-regulation of Arf6 in macrophages reduced expression and secretion of cytokines. Expression of miR-145 was found to be attenuated in the omental adipose tissue of obese patients and diabetics with greater Arf6 expression, confirming the role of miR-145 in regulating macrophage-mediated inflammation targeting Arf6.
Conclusions
By means of reducing the expression of Arf6 and subsequent signal transduction via NF-kappaB, miR-145 plays a role in inhibiting the secretion of inflammatory factors and then improving the inflammatory status. MiR-145 might be one of the candidates for anti-inflammatory treatment for metabolic diseases.
http://ift.tt/2p4iHVV
G3 GEP NENs category: are basic and clinical investigations well integrated?
Abstract
Gastroenteropancreatic neuroendocrine neoplasms grade 3, all of them with >20% Ki-67, can be heterogeneous on the basis of their morphological features, comprising well and poorly differentiated neoplasms; the former are named tumors and the latter carcinomas. Several papers about gastroenteropancreatic neuroendocrine neoplasms grade 3 heterogeneity have been reporting over the last years by clinicians and pathologists, indicating that the differential diagnosis between named tumors grade 3 and named carcinomas grade 3 may be relevant in defining a different approach in terms of characterization of disease, staging, and treatment. To well define the sub-type of gastroenteropancreatic neuroendocrine neoplasms grade 3 pathologist's expertise in recognizing tumor morphology, immunohistochemical, and molecular techniques were reported remarkable. Although current evidence about grade 3 gastroenteropancreatic neuroendocrine neoplasms heterogeneity is still far from producing validated specific therapies for specific subcategories, the hypotheses generated from the several retrospective analyses published so far on this topic represent solid bases for designing prospective therapeutic clinical trials in homogenous clinical settings.
http://ift.tt/2Idpohb
In Vivo Short-Term Topical Application of BAY 11-7082 Prevents the Acidic Bile–Induced mRNA and miRNA Oncogenic Phenotypes in Exposed Murine Hypopharyngeal Mucosa
Publication date: April 2018
Source:Neoplasia, Volume 20, Issue 4
Author(s): Clarence T. Sasaki, Sotirios G. Doukas, Dimitra P. Vageli
PURPOSE: Bile-containing gastroesophageal reflux may promote cancer at extraesophageal sites. Acidic bile can accelerate NF-κB activation and molecular events, linked to premalignant changes in murine hypopharyngeal mucosa (HM). We hypothesize that short-term in vivo topical application of NF-κB inhibitor BAY 11-7082 can prevent acidic bile–induced early preneoplastic molecular events, suggesting its potential role in disease prevention. EXPERIMENTAL DESIGN: We topically exposed HM (C57Bl/6j wild-type) to a mixture of bile acids at pH 3.0 with and without BAY 11-7082 3 times/day for 7 days. We used immunofluorescence, Western blotting, immunohistochemistry, quantitative polymerase chain reaction, and polymerase chain reaction microarrays to identify NF-κB activation and its associated oncogenic mRNA and miRNA phenotypes, in murine hypopharyngeal cells in vitro and in murine HM in vivo. RESULTS: Short-term exposure of HM to acidic bile is a potent stimulus accelerating the expression of NF-κB signaling (70 out of 84 genes) and oncogenic molecules. Topical application of BAY 11-7082 sufficiently blocks the effect of acidic bile. BAY 11-7082 eliminates NF-κB activation in regenerating basal cells of acidic bile–treated HM and prevents overexpression of molecules central to head and neck cancer, including bcl-2, STAT3, EGFR, TNF-α, and WNT5A. NF-κB inhibitor reverses the upregulated "oncomirs" miR-155 and miR-192 and the downregulated "tumor suppressors" miR-451a and miR-375 phenotypes in HM affected by acidic bile. CONCLUSION: There is novel evidence that acidic bile–induced NF-κB–related oncogenic mRNA and miRNA phenotypes are generated after short-term 7-day mucosal exposure and that topical mucosal application of BAY 11-7082 can prevent the acidic bile–induced molecular alterations associated with unregulated cell growth and proliferation of hypopharyngeal cells.
http://ift.tt/2FIloXo
Scholar : Comedy Studies, Volume 9, Issue 1, April 2018 is now available online on Taylor & Francis Online
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Improved performance of Pseudomonas aeruginosa catalyzed MFCs with graphite/polyester composite electrodes doped with metal ions for azo dye degradation
Publication date: 1 July 2018
Source:Chemical Engineering Journal, Volume 343
Author(s): Saranya Narayanasamy, Jayapriya Jayaprakash
High internal resistance that reduces the power produced in the microbial fuel cells (MFCs) is mainly due to the low electron transfer between the bacterial catalysts and the anode/cathode. In this study, a bulk modified Graphite Polyester composite electrodes (GPECE) doped with metal salts (MS-GPECE) were prepared by casting. Crystallinity, surface morphology, chemical composition and electrochemical properties of all modified electrodes were investigated. Influence of redox behavior of electrodes suited to bacterial metabolism and enhanced biofilm formation have been examined. A laboratory-scale H-shaped Pseudomonas catalyzed microbial fuel cell (MFC) was investigated with different metal doped Graphite Polyester composite electrodes, for its performance in decolorizing synthetic wastewater containing azo dye methyl orange. Among the different combinations of electrodes were tested in MFC, the best performing MFC with the highest power density (1575 ± 223.26 µW/m2) was seen with Ni-GPECE as the cathode and graphite block as an anode and simultaneous increase in decolorization (89 ± 1.41%) was also observed. These studies have suggested that the MFC technology can discharge the dual duty of degrading the azo dyes and simultaneous power production.
Graphical abstract
http://ift.tt/2Fn3QRg
Scholar : Sociological Spectrum, Volume 38, Issue 1, January 2, 2018 is now available online on Taylor & Francis Online
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Scholar : AJOB Neuroscience, Volume 9, Issue 1, January-March 2018 is now available online on Taylor & Francis Online
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Type 1 IGF Receptor Localization in Paediatric Gliomas: Significant Association with WHO Grading and Clinical Outcome
Abstract
Nuclear localization of insulin-like growth factor receptor type 1 (IGF-1R) has been described as adverse prognostic factor in some cancers. We studied the expression and localization of IGF-1R in paediatric patients with gliomas, as well as its association with World Health Organization (WHO) grading and survival. We conducted a single cohort, prospective study of paediatric patients with gliomas. Samples were taken at the time of the initial surgery; IGF-1R expression and localization were characterized by immunohistochemistry (IHC), subcellular fractionation and western blotting. Tumours (47/53) showed positive staining for IGF-1R by IHC. IGF-1R nuclear labelling was observed in 10/47 cases. IGF-1R staining was mostly non-nuclear in low-grade tumours, while IGF-1R nuclear labelling was predominant in high-grade gliomas (p = 0.0001). Survival was significantly longer in patients with gliomas having non-nuclear IGF-1R localization than in patients with nuclear IGF-1R tumours (p = 0.016). In gliomas, IGF-1R nuclear localization was significantly associated with both high-grade tumours and increased risk of death. Based on a prospective design, we provide evidence of a potential usefulness of intracellular localization of IGF-1R as prognostic factor in paediatric patients with gliomas.
http://ift.tt/2Fvm7YE
Modified Lung-RADS Improves Performance of Screening LDCT in a Population with High Prevalence of Non–smoking-related Lung Cancer
Source:Academic Radiology
Author(s): Hui-Ting Hsu, En-Kuei Tang, Ming-Ting Wu, Carol C. Wu, Chia-Hao Liang, Chi-Shen Chen, Guang-Yuan Mar, Ruay-Sheng Lai, Jo-Ching Wang, Chuan-Ling Wu, Yi-Luan Huang, Fu-Zong Wu
ObjectivesWe proposed a modification of the ACR Lung Imaging Reporting and Data System (Lung-RADS) to clarify the characteristics of subsolid nodules with categories 1–11, and to compare the diagnostic accuracy with Lung-RADS and National Lung Screening Trial criteria in an Asian population with high prevalence of adenocarcinoma.MethodsWe analyzed a retrospective cohort of 1978 consecutive healthy subjects (72.8% nonsmoker) who underwent low-dose computed tomography from August 2013 to October 2014 (1084 men, 894 women). Lung-RADS categories 2 and 3 were modified to include subcategories of 2A/2B/2C and 3A/3B/3C, respectively. Clinical information and nodule characteristics were recorded. Receiver operating characteristic curves were used to compare diagnostic accuracy at different cutoffs.ResultsThirty-two subjects (30 nonsmokers) had pathology-proven adenocarcinoma spectrum lesions in the follow-up period (1.6 ± 0.5 years). Modified Lung-RADS, using modified Lung-RADS category 2C as cutoff, had an area under the curve (AUC) of 0.973 in predicting adenocarcinoma spectrum lesions (sensitivity of 100%, specificity of 89.3%), which was significantly higher than that of Lung-RADS (AUC = 0.815, P < .001) and National Lung Screening Trial (AUC = 0.906, P < .001). Furthermore, modified Lung-RADS showed an AUC of 0.992 in predicting invasive adenocarcinoma (sensitivity of 95%, specificity of 97.8%) when category 3B was used as cutoff.ConclusionsModified Lung-RADS may substantially improve sensitivity while maintaining specificity for detection of adenocarcinoma spectrum lesions in an Asian population. Compared to Lung-RADS, it has enhanced ability to differentiate invasive from indolent adenocarcinoma by more refined subclassification of subsolid nodules using two cutoff values of category 2C and 3B. The effect of using modified Lung-RADS in clinical practice must be carefully studied in prospective large cohort studies.
http://ift.tt/2FvUPl7
Attitudes of Radiology Program Directors Toward MD-PhD Trainees, Resident Research Productivity, and Dedicated Research Time
Source:Academic Radiology
Author(s): Petrice M. Cogswell, Lori A. Deitte, Edwin F. Donnelly, Victoria L. Morgan, Reed A. Omary
Rationale and ObjectivesThe percentage of clinical scientists in radiology has historically been low. Increasing the pipeline of trainees interested in research could occur by recruiting MD-PhD trainees and providing protected research time during residency. The purpose of this work is to assess the attitudes of radiology program directors toward MD-PhD trainees, resident research productivity, and dedicated research time.MethodsAn online survey was sent to residency program directors of all diagnostic radiology departments that received National Institutes of Health (NIH) awards in 2014 (n = 63). Survey questions included program size; perception of overall performance, clinical performance, and research productivity of MD-PhD residents compared to non-PhD residents; and presence of dedicated research time. Responses comparing MD-PhD residents to non-PhD residents were reported as a five-point Likert scale. Student t test was used to assess for significance (alpha = 0.05).ResultsResponse rate was 37%. Clinical performance of MD-PhD residents was judged inferior (P < .05) to non-PhD residents, although that of all residents engaged in research trended toward superiority compared to those not involved in research. Dedicated research time is offered by 61% of programs in years R1–R3 and all programs in year R4. Research productivity during residency was judged to be similar (P = .5) between MD-PhD and non-PhD residents.ConclusionsSurvey results suggest that clinical performance during residency and research involvement is often individually based and difficult to generalize based on prior PhD training. All programs offered dedicated research time, and the vast majority of residents were reported to engage in research during residency, which may increase the pipeline of trainees interested in an academic career.
http://ift.tt/2GatHZP
Qualitative CT Criterion for Subsolid Nodule Subclassification
Source:Academic Radiology
Author(s): Po An Chen, Eric P. Huang, Lu Yang Shih, En Kuei Tang, Chu Chun Chien, Ming Ting Wu, Fu Zong Wu
Rationale and ObjectivesThe main aim of this study was to evaluate the clinical validity and correlation with pathologic invasiveness in the pulmonary adenocarcinoma spectrum based on the novel qualitative computed tomography criterion for subsolid nodule (SSN) classification, which classified SSN into pure ground-glass nodule, heterogeneous ground-glass nodule, and part-solid nodule. In addition, we compared the performance of the conventional and novel classifications.Materials and MethodsThe computed tomography images of 41 SSN nodules were interpreted by six observers independently, and the SSN characteristics were classified according to both the conventional and the novel classification systems. Each observer assessed 41 nodules in two different classifications separated by a minimum of 8 weeks. The kappa (κ) coefficient test was used to determine the reliability. The correlation between pulmonary adenocarcinoma spectrum and the SSN classification was analyzed with Spearman correlation coefficients.ResultsInterobserver agreement (κ) was 0.702 (range 0.42–0.89) and 0.707 (range 0.58–0.88) for the conventional and the novel classifications for SSN, respectively, and intraobserver agreement (κ) was 0.92 and 0.88 for the conventional and the novel classifications for SSN, respectively. The novel SSN classification (correlation coefficient range 0.622–0.732) is more strongly correlated with the pathologic invasiveness degree of lesions in adenocarcinoma spectrum than the conventional SSN classification (correlation coefficient range 0.458–0.644).ConclusionsThe agreement between observers on the novel SSN classification system was good and had better correlation with pathologic invasiveness than the conventional SSN classification. Further studies are needed to confirm these results on interobserver agreement.
http://ift.tt/2Fwh9uO
Serum proteome profiling in canine idiopathic dilated cardiomyopathy using TMT-based quantitative proteomics approach
Publication date: Available online 9 March 2018
Source:Journal of Proteomics
Author(s): Petra Bilić, Nicolas Guillemin, Alan Kovačević, Blanka Beer Ljubić, Ines Jović, Asier Galan, Peter David Eckersall, Richard Burchmore, Vladimir Mrljak
Idiopathic dilated cardiomyopathy (iDCM) is a primary myocardial disorder with an unknown aetiology, characterized by reduced contractility and ventricular dilation of the left or both ventricles. Naturally occurring canine iDCM was used herein to identify serum proteomic signature of the disease compared to the healthy state, providing an insight into underlying mechanisms and revealing proteins with biomarker potential. To achieve this, we used high-throughput label-based quantitative LC-MS/MS proteomics approach and bioinformatics analysis of the in silico inferred interactome protein network created from the initial list of differential proteins. To complement the proteomic analysis, serum biochemical parameters and levels of know biomarkers of cardiac function were measured. Several proteins with biomarker potential were identified, such as inter-alpha-trypsin inhibitor heavy chain H4, microfibril-associated glycoprotein 4 and apolipoprotein A-IV, which were validated using an independent method (Western blotting) and showed high specificity and sensitivity according to the receiver operating characteristic curve analysis. Bioinformatics analysis revealed involvement of different pathways in iDCM, such as complement cascade activation, lipoprotein particles dynamics, elastic fibre formation, GPCR signalling and respiratory electron transport chain.SignificanceIdiopathic dilated cardiomyopathy is a severe primary myocardial disease of unknown cause, affecting both humans and dogs. This study is a contribution to the canine heart disease research by means of proteomic and bioinformatic state of the art analyses, following similar approach in human iDCM research. Importantly, we used serum as non-invasive and easily accessible biological source of information and contributed to the scarce data on biofluid proteome research on this topic. Bioinformatics analysis revealed biological pathways modulated in canine iDCM with potential of further targeted research. Also, several proteins with biomarker potential have been identified and successfully validated.
Graphical abstract
http://ift.tt/2tvWANv
Human follicular fluid proteomic and peptidomic composition quantitative studies by SWATH-MS methodology. Applicability of high pH RP-HPLC fractionation
Publication date: Available online 10 March 2018
Source:Journal of Proteomics
Author(s): Aleksandra E. Lewandowska, Katarzyna Macur, Paulina Czaplewska, Joanna Liss, Krzysztof Łukaszuk, Stanisław Ołdziej
Analysis of proteomic composition of human follicular fluid (hFF) has been previously proposed as a potential tool of oocyte quality evaluation. In order to develop an efficient method to investigate the hFF proteome and peptidome components, we applied and tested a few prefractionation schemes of hFF material consisting of ultrafiltration, optional immunodepletion, and high pH RP-HPLC separation by building spectral libraries and comparing their quantification capabilities of unfractionated samples. Low Molecular-Weight Fraction peptides (LMWF, <10 kDa) and High Molecular-Weight Fraction proteins (HMWF, >10 kDa) resulting from ultrafiltration were analyzed separately. We identified 302 proteins in HMWF and 161 proteins in LMWF in all qualitative experiments. All LMWF peptidomic libraries turned out to be of poor quantification quality, however they enabled measurement of higher numbers of peptides with increasing input of experiment data, in contrast to HMWF proteomic libraries. We were able to quantify a total of 108 HMWF proteins and 250 LMWF peptides (from 84 proteins) in all experiments. Employment of high RP-HPLC fractionation allowed for identification of a much broader set of proteins, however did not significantly improve the quantification capabilities of the applied method. Data are available via ProteomeXchange with identifier PXD008073.SignificanceIn the search of biomarkers for assessment of oocyte quality in assisted reproductive technology, many studies are devoted to analysis of follicular fluid composition. Candidates for such biomarkers can be located in both the proteome and the recently investigated peptidome of hFF. Reliable qualitative and especially quantitative analysis of complex mixtures such as hFF, requires development of a fast and preferably inexpensive analytical procedure. The powerful SWATH-MS technique is well suited for quantitative label-free analysis of complex protein and peptide mixtures. However, for efficient usage it needs well designed and constructed MS-spectral libraries as well as a proper protocol for sample preparation. We investigated the influence of the size and quality of MS-spectral libraries (different spectral libraries are constructed using various sample prefractionation protocols) on SWATH experiments on hFF proteome and peptidome. In the case of peptidome investigation, increasing the size of spectral libraries led to quantification of more peptides in a single experiment. For the proteome, increasing the size of spectral libraries improved quantification only to a limited extend, and further extension of spectral libraries even worsened results. Nevertheless, using the best selected prefractionation schemes and spectral libraries we were able to quantify as many as 79 proteins of hFF proteome and 106 peptides (from 53 proteins) of hFF peptidome in single experiments. The spectral libraries and prefractionation protocols we developed allow for a large scale fast scan of hundreds of clinical hFF samples in the search for biomarkers for evaluation of oocyte quality.
Graphical abstract
http://ift.tt/2FI8Uiz
Patterns of pathologically confirmed metastasis to bone in Near East population
Source:Cancer Epidemiology, Volume 54
Author(s): Abdallah Flaifel, Farah Tabaja, Sami Bannoura, Asif Loya, Sajid Mushtaq, Ibrahim Khalifeh
BackgroundMetastatic tumors to bone constitute the majority of bone malignancies. The site of metastasis to bone and the prognosis depend chiefly on the primary tumor. Despite all the advances in diagnostic techniques, identifying the primary tumor has not improved significantly.MethodsA total of 576 cases (Lebanon; n = 306, Pakistan; n = 270) presenting with microscopic evidence of metastasis to bone were reviewed between 1996 and 2016. Clinical and radiologic data were recorded.ResultsOut of 20 types of primary tumors, unknown primary (38.2%), followed by breast (23.8%), lung (10.4%) and thyroid (4.9%) tumors were the most commonly presenting with bone metastasis. The primary source of the tumor showed significant correlation with the site of metastasis, time lag to metastasis and radiologic presentation (p < 0.001). Interestingly, a significant variation was noted between the 2 observed populations.ConclusionThe patterns of pathologically confirmed metastasis to skeletal sites in Near East population showed a special distribution, and variation was even observed between the 2 studied centers. Understanding the biologic variations of the primary tumors in our population may further explain the variation in patterns of metastasis.
http://ift.tt/2Gcht2W
Frequency and distribution of primary site among gender minority cancer patients: An analysis of U.S. national surveillance data
Source:Cancer Epidemiology, Volume 54
Author(s): Rebecca Nash, Kevin C. Ward, Ahmedin Jemal, David E. Sandberg, Vin Tangpricha, Michael Goodman
BackgroundTransgender people and persons with disorders of sex development (DSD) are two separate categories of gender minorities, each characterized by unique cancer risk factors. Although cancer registry data typically include only two categories of sex, registrars have the option of indicating that a patient is transgender or has a DSD.MethodsData for primary cancer cases in 46 states and the District of Columbia were obtained from the North American Association of Central Cancer Registries (NAACCR) database for the period 1995–2013. The distributions of primary sites and categories of cancers with shared risk factors were examined separately for transgender and DSD patients and compared to the corresponding distributions in male and female cancer patients. Proportional incidence ratios were calculated by dividing the number of observed cases by the number of expected cases. Expected cases were calculated based on the age- and year of diagnosis-specific proportions of cases in each cancer category observed among male and female patients.ResultsTransgender patients have significantly elevated proportional incidence ratios (95% confidence intervals) for viral infection induced cancers compared to either males (2.3; 2.0–2.7) or females (3.3; 2.8–3.7). Adult DSD cancer patients have a similar distribution of primary sites compared to male or female patients but DSD children with cancer have ten times more cases of testicular malignancies than expected (95% confidence interval: 4.7–20).ConclusionThe proportions of certain primary sites and categories of malignancies among transgender and DSD cancer patients are different from the proportions observed for male or female patients.
http://ift.tt/2p4k7PZ
Substrate fiber alignment mediates tendon cell response to inflammatory signaling
Publication date: Available online 10 March 2018
Source:Acta Biomaterialia
Author(s): Angelina D. Schoenenberger, Jasper Foolen, Pascal Moor, Unai Silvan, Jess G. Snedeker
Healthy tendon tissue features a highly aligned extracellular matrix that becomes disorganized with disease. Recent evidence suggests that inflammation coexists with early degenerative changes in tendon, and that crosstalk between immune-cells and tendon fibroblasts (TFs) can contribute to poor tissue healing. We hypothesized that a disorganized tissue architecture may predispose tendon cells to degenerative extracellular matrix remodeling pathways, particularly within a pro-inflammatory niche. This hypothesis was tested by analyzing human TFs cultured on electrospun polycaprolactone (PCL) mats with either highly aligned or randomly oriented fiber structures. We confirmed that fibroblast morphology, phenotype, and markers of matrix turnover could be significantly affected by matrix topography. More strikingly, the TF response to paracrine signals from polarized macrophages or by stimulation with pro-inflammatory cytokines featured significant downregulation of signaling related to extracellular synthesis, with significant concomitant upregulation of gene and protein expression of matrix degrading enzymes. Critically, this tendency towards degenerative re-regulation was exacerbated on randomly oriented PCL substrates. These novel findings indicate that highly aligned tendon cell scaffolds not only promote tendon matrix synthesis, but also play a previously unappreciated role in mitigating adverse resident fibroblast response within an inflammatory milieu.Statement of SignificanceUse of biomaterial scaffolds for tendon repair often results in tissue formation characteristic of scar tissue, rather than the highly aligned type-1 collagen matrix of healthy tendons.We hypothesized that non-optimal biomaterial surfaces may play a role in these outcomes, specifically randomly oriented biomaterial surfaces that unintentionally mimic structure of pathological tendon. We observed that disorganized scaffold surfaces do adversely affect early cell attachment and gene expression. We further identified that disorganized fiber surfaces can prime tendon cells to pro-inflammatory signaling. These findings represent provocative evidence unstructured fiber surfaces may underlie inflammatory responses that drive aberrant collagen matrix turnover. This work could be highly relevant for the design of cell instructive biomaterial therapies that yield positive clinical outcomes.
Graphical abstract
http://ift.tt/2HmeNz8
In vitro and in vivo studies on zinc-hydroxyapatite composites as novel biodegradable metal matrix composite for orthopedic applications
Publication date: Available online 9 March 2018
Source:Acta Biomaterialia
Author(s): Hongtao Yang, Xinhua Qu, Wenjiao Lin, Cong Wang, Donghui Zhu, Kerong Dai, Yufeng Zheng
Recent studies indicate that there is a great demand to optimize pure Zn with tunable degradation rates and more desirable biocompatibility as orthopedic implants. Metal matrix composite (MMC) can be a promising approach for this purpose. In this study, MMC with pure Zn as a matrix and hydroxyapatite (HA) as reinforcements were prepared by spark plasma sintering (SPS). Feasibility of novel Zn-HA composites to be used as orthopedic implant applications was systematically evaluated. After sintering, HA distributed in the Zn particle boundaries uniformly. Corrosion tests indicated that the degradation rates of Zn-HA composites were adjustable due to the biphasic effects of HA. Zn-HA composites showed significantly improved cell viability of osteoblastic MC3T3-E1 cells compared with pure Zn. Both pure Zn and composites exhibited a low thrombosis risk and hemolysis rates while a Zn ion concentration-dependent effect was found on coagulation time. An effective antibacterial property was observed as well. The volume loss of pure Zn and Zn-5HA composite was 1.7% and 3.2% after 8 weeks' implantation. Histological analysis found newly formed bone surrounding pure Zn and Zn-5HA composite at week 4 and increased bone mass over time. With prolonged implantation time, Zn-5HA composite was more effective on stimulating new bone formation than pure Zn. In summary, MMC is a feasible way to design Zn based materials with adjustable degradation rates and improved biocompatibility.Statement of SignificanceBiodegradable zinc materials are promising candidates for the new generation of orthopedic implants. However, the slow degradation rates and unsatisfactory cytocompatibility of pure Zn in bone environments limit its future clinical applications. Generally, alloying is a common way to improve the performance of pure Zn. In this study, metal matrix composite was chosen as a novel strategy to solve the problems. Hydroxyapatite, as a bioactive component, was added into Zn matrix via spark plasma sintering. We find that Zn-HA composites exhibited adjustable degradation rates and improved biocompatibility both in vitro and in vivo. This study provides exhaustive and significant information including microstructure, mechanical performance, degradation behavior, biocompatibility, hemocompatibility and antibacterial property for the future Zn based implants design.
Graphical abstract
http://ift.tt/2p0T5da
Protein Machineries defining Pathways of Nanocarrier Exocytosis and Transcytosis
Publication date: Available online 10 March 2018
Source:Acta Biomaterialia
Author(s): Jonas Reinholz, Christopher Diesler, Susanne Schöttler, Maria Kokkinopoulou, Sandra Ritz, Katharina Landfester, Volker Mailänder
The transport of nanocarriers through barriers like the gut in a living organism involves the transcytosis of these nanocarriers through the cell layer dividing two compartments. Understanding how this process works is not only essential to further developing strategies for a more effective nanocarrier transport system but also for providing fundamental insights into the barrier function as a means of protection against micro- and nanoplastics in the food chain. We therefore set out to investigate the different uptake mechanisms, intracellular trafficking and the routes for exocytosis for small polystyrene nanoparticles (PS-NPs ca. 100 nm) as mimicking nanocarriers in a Caco-2 cell model for gut-blood transition. We used label-free, quantitative mass spectrometry (MS) for determining the proteome that adhered to transversed nanoparticles. From this rich proteomics dataset, as well as previous studies, we generated stable-transfected Caco-2 cell lines carrying the green fluorescent protein (GFP) coupled to proteins of interest for uptake, early, late and exocytotic endosomes. We detected the spatial and temporal overlap of such marked endosomes with the nanocarrier signal in confocal laser scanning and super-resolution microscopy. There was a clear distinction in the time course of nanoparticle trafficking between groups of proteins for endocytosis, intracellular storage and putatively transcytosis and we identified several key transcytotic markers like Rab3 and Copine1. Moreover, we postulate the necessity of a certain protein composition on endosomes for successful transcytosis of nanocarriers. Finally, we define the two-sided impasse of the lysosome as a dead end for nano-plastic and the limit of nanocarriers in the 100 nm range.Significance TranscytosisHere we focus on mechanisms of transcytosis and how we can follow these with methods not used before. First, we use mass spectrometry of transcytosed nanoparticles to pick proteins of the transcytosis machinery describing key proteins involved. We can detect the complex mixtures of proteins. As this is a dynamic process involving whole families of proteins interacting with each other and as this is an orchestrated process we coined the term protein machineries for this active interplay.By genetically modifying the proteins attaching GFP we are able to follow the transcytosis pathway We evaluate the process in a quantitative manner over time. This reveals that the most obvious obstacle to transcytosis is a routing of the nanocarriers to the lysosomes.
Graphical abstract
http://ift.tt/2HmeLY2
Zinc-based alloys for degradable vascular stent applications
Publication date: Available online 10 March 2018
Source:Acta Biomaterialia
Author(s): Ehsan Mostaed, Malgorzata Sikora-Jasinska, Jaroslaw W. Drelich, Maurizio Vedani
The search for biodegradable metals with mechanical properties equal or higher to those of currently used permanent biomaterials, such as stainless steels, cobalt chromium and titanium alloys, desirable in vivo degradation rate and uniform corrosion is still an open challenge. Magnesium (Mg), iron (Fe) and zinc (Zn)-based alloys have been proposed as biodegradable metals for medical applications. Over the last two decades, extensive research has been done on Mg and Fe. Fe-based alloys show appropriate mechanical properties, but their degradation rate is an order of magnitude below the benchmark value. In comparison, alongside the insufficient mechanical performance of most of its alloys, Mg degradation rate has proven to be too high in a physiological environment and corrosion is rarely uniform. During the last few years, Zn alloys have been explored by the biomedical community as potential materials for bioabsorbable vascular stents due to their tolerable corrosion rates and tunable mechanical properties. This review summarizes recent progress made in developing Zn alloys for vascular stenting application. Novel Zn alloys are discussed regarding their microstructural characteristics, mechanical properties, corrosion behavior and in vivo performance.Statement of SignificanceNumerous studies on magnesium and iron materials have been reported to date, in an effort to formulate bioabsorbable stents with tailorable mechanical characteristics and corrosion behavior. Crucial concerns regarding poor ductility and remarkably rapid corrosion of magnesium, and very slow degradation of iron, seem to be still not desirably fulfilled. Zinc was introduced as a potential implant material in 2013 due to its promising biodegradability and biocompatibility. Since then, extensive investigations have been made toward development of zinc alloys that meet clinical benchmarks for vascular scaffolding. This review critically surveys the zinc alloys developed since 2013 from metallurgical and biodegradation points of view. Microstructural features, mechanical, corrosion and in vivo performances of these new alloys are thoroughly reviewed and evaluated.
Graphical abstract
http://ift.tt/2Gf1gdy
Scholar : Applied Developmental Science, Volume 22, Issue 2, April-June 2018 is now available online on Taylor & Francis Online
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Scholar : Archives of Agronomy and Soil Science, Volume 64, Issue 4, April 2018 is now available online on Taylor & Francis Online
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Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
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Abstract Noise pollution is a major factor of environmental complaints in many cities, which has significant impacts on human health. As a...
