Σάββατο 8 Απριλίου 2017
Hematopoietic stem cell transplantation in advanced cutaneous T-cell lymphoma
Abstract
We retrospectively reviewed data pertaining to five patients with cutaneous T-cell lymphoma (CTCL) who had received hematopoietic stem cell transplantation (HSCT) between 2004 and 2015 at Kurume University Hospital, along with their clinical data until March 2016. For patients with advanced CTCL eligible for HSCT, autologous HSCT was performed when they responded well to chemotherapy, and allogeneic HSCT was selected for patients with advanced mycosis fungoides (MF)/Sézary syndrome (SS) and CTCL other than MF/SS with poor chemosensitivity. Two patients (primary cutaneous anaplastic large cell lymphoma and primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma) who responded well to chemotherapy received autologous HSCT: one patient was alive in partial remission and the other died due to therapy-related acute myeloid leukemia without disease relapse. In the remaining three patients with MF or SS, allogeneic HSCT was performed. Although one patient with MF died due to disease progression, the remaining two patients were alive in complete remission. Although there were two deaths in this study, the outcomes were considered satisfactory.
http://ift.tt/2nQ5xt5
Identification of a heterozygous p.Gly568Val missense mutation in the TRPV3 gene in a Japanese patient with Olmsted syndrome: In silico analysis of TRPV3
Abstract
Olmsted syndrome is a very rare congenital disorder, characterized by palmoplantar keratoderma and periorificial keratotic lesions. Recently, TRPV3 was reported to be a causative gene of Olmsted syndrome. We identified a heterozygous missense mutation of TRPV3, c.1703G>T, p.Gly568Val, in a Japanese patient with Olmsted syndrome. To the best of our knowledge, this is the first report of a Japanese patient with Olmsted syndrome harboring a missense mutation in TRPV3. We conducted in silico analysis of TRPV3 to evaluate whether the p.Gly568Val leads to structural changes in the TRPV3 selectivity filter. The selectivity filter was shown to become dilated and hyperpermeable as a result of genetic mutation (p.Gly573Ser, p.Tr692Gly or p.Gly568Val) as well as after a change in temperature (300 K to 310 K). In silico analysis of TRPV3 could be a useful approach in predicting mutation-induced activated states of ion channels, and thus enrich our understanding of the pathogenesis of Olmsted syndrome.
http://ift.tt/2odWgOG
Apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of Japanese patients with moderate to severe plaque psoriasis: Efficacy, safety and tolerability results from a phase 2b randomized controlled trial
Abstract
Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, works intracellularly within immune cells to regulate inflammatory mediators. This phase 2b randomized, placebo-controlled study evaluated efficacy and safety of apremilast among Japanese patients with moderate to severe plaque psoriasis. In total, 254 patients were randomized to placebo, apremilast 20 mg b.i.d. (apremilast 20) or apremilast 30 mg b.i.d. (apremilast 30) through week 16; thereafter, all placebo patients were re-randomized to apremilast 20 or 30 through week 68. Efficacy assessments included achievement of 75% or more reduction from baseline in Psoriasis Area and Severity Index score (PASI-75; primary) and achievement of static Physician Global Assessment (sPGA; secondary) score of 0 (clear) or 1 (minimal) at week 16. Safety was assessed through week 68. At week 16, PASI-75 response rates were 7.1% (placebo), 23.5% (apremilast 20; P = 0.0032 vs placebo) and 28.2% (apremilast 30; P = 0.0003 vs placebo); sPGA response rates (score of 0 or 1) were 8.8% (placebo), 23.9% (apremilast 20; P = 0.0165 vs placebo) and 29.6% (apremilast 30; P = 0.0020 vs placebo). Responses were maintained with apremilast through week 68. Most common adverse events (AEs) with placebo, apremilast 20 and apremilast 30 (0–16 weeks) were nasopharyngitis (8.3%, 11.8%, 11.8%), diarrhea (1.2%, 8.2%, 9.4%), and abdominal discomfort (1.2%, 1.2%, 7.1%), respectively. Exposure-adjusted incidence of these AEs did not increase with continued apremilast treatment (up to 68 weeks). Apremilast demonstrated efficacy and safety in Japanese patients with moderate to severe plaque psoriasis through 68 weeks that was generally consistent with prior studies.
http://ift.tt/2nPN3ZK
The Demographic Study of Otorhinolaryngological Trauma Among Patients with Head and Neck Trauma and Their Management in a Tertiary Care Centre
Abstract
The trauma has been increasing in frequency, especially in recent decades because of the higher number of automobile accidents and violence. The ear, nose and face region is the area in the body that is commonly involved in head and neck injury. Trauma to this region is often associated with mortality and varying degree of physical, functional and psychological damage. To study the demography, aetiology, clinical presentation, outcome of ENT trauma in our tertiary care centre and to compare our study with previous studies to see the changing trends with passage of time. A prospective study was conducted on 200 head and neck patients with ENT injuries during a period of 1 year from July 2014 to July 2015, who were admitted in ENT Department and Trauma Centre of Gajra Raja Medical College and J.A. Group of Hospital, Gwalior. Most of the patients were young adult males of age group 18–40 years (45, 22.5%) with a male:female ratio 1.78:1. Among them 53% patients were from rural area while 47% were from urban area. RTA is the most prevalent cause of ENT trauma (37%), followed by interpersonal violence (25%). 27% of the patients had facial injury and multiple region injury each. Among 200 patients 33% were managed conservatively on the other hand 66% patients required surgical interventions. Mortality rate was 8%. Among all 184 survivors 25.5% suffered from hearing loss, 14.5% had tympanic membrane perforation with hearing loss, 12% had pinna disfigurement, 10% had change in voice, 6.5% had permanent nasal deformity, 2% had facial nerve palsy. Young male adults were the most prevalent victims of ENT trauma, and Road traffic accidents were responsible for majority of the ENT injuries. Screening of all the patients with head and neck injuries for the presence of trauma in the ENT region should be introduced to enable early detection and therefore prevention of complications.
http://ift.tt/2oOwSRf
The Demographic Study of Otorhinolaryngological Trauma Among Patients with Head and Neck Trauma and Their Management in a Tertiary Care Centre
Abstract
The trauma has been increasing in frequency, especially in recent decades because of the higher number of automobile accidents and violence. The ear, nose and face region is the area in the body that is commonly involved in head and neck injury. Trauma to this region is often associated with mortality and varying degree of physical, functional and psychological damage. To study the demography, aetiology, clinical presentation, outcome of ENT trauma in our tertiary care centre and to compare our study with previous studies to see the changing trends with passage of time. A prospective study was conducted on 200 head and neck patients with ENT injuries during a period of 1 year from July 2014 to July 2015, who were admitted in ENT Department and Trauma Centre of Gajra Raja Medical College and J.A. Group of Hospital, Gwalior. Most of the patients were young adult males of age group 18–40 years (45, 22.5%) with a male:female ratio 1.78:1. Among them 53% patients were from rural area while 47% were from urban area. RTA is the most prevalent cause of ENT trauma (37%), followed by interpersonal violence (25%). 27% of the patients had facial injury and multiple region injury each. Among 200 patients 33% were managed conservatively on the other hand 66% patients required surgical interventions. Mortality rate was 8%. Among all 184 survivors 25.5% suffered from hearing loss, 14.5% had tympanic membrane perforation with hearing loss, 12% had pinna disfigurement, 10% had change in voice, 6.5% had permanent nasal deformity, 2% had facial nerve palsy. Young male adults were the most prevalent victims of ENT trauma, and Road traffic accidents were responsible for majority of the ENT injuries. Screening of all the patients with head and neck injuries for the presence of trauma in the ENT region should be introduced to enable early detection and therefore prevention of complications.
http://ift.tt/2oOwSRf
Thymus Transplantation for Complete Digeorge Syndrome: European Experience
Source:Journal of Allergy and Clinical Immunology
Author(s): E Graham Davies, Melissa Cheung, Kimberly Gilmour, Jesmeen Maimaris, Joe Curry, Anna Furmanski, Neil Sebire, Neil Halliday, Konstantinos Mengrelis, Stuart Adams, Jolanta Bernatoniene, Ronald Bremner, Michael Browning, Blythe Devlin, Hans Christian Erichsen, H Bobby Gaspar, Lizzie Hutchison, Winnie Ip, Marianne Ifversen, T Ronan Leahy, Elizabeth McCarthy, Despina Moshous, Kim Neuling, Malgorzata Pac, Alina Papadopol, Kathryn L. Parsley, Luigi Poliani, Ida Ricciardelli, David M. Sansom, Tiia Voor, Austen Worth, Tessa Crompton, M Louise Markert, Adrian J. Thrasher
BackgroundThymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS).MethodsTwelve patients with cDGS were transplanted with allogeneic cultured thymus.ObjectiveTo confirm and extend the results previously obtained in a single centre.ResultsTwo patients died of pre-existing viral infections without developing thymopoeisis and one late death occurred from autoimmune thrombocytopaenia. One infant suffered septic shock shortly after transplant resulting in graft loss and the need for a second transplant. Evidence of thymopoeisis developed from 5-6 months after transplantation in ten patients. The median (range) of circulating naïve CD4 counts (x106/L) were 44(11-440) and 200(5-310) at twelve and twenty-four months post-transplant and T-cell receptor excision circles were 2238 (320-8807) and 4184 (1582 -24596) per106 T-cells. Counts did not usually reach normal levels for age but patients were able to clear pre-existing and later-acquired infections. At a median of 49 months (22-80), eight have ceased prophylactic antimicrobials and five immunoglobulin replacement. Histological confirmation of thymopoeisis was seen in seven of eleven patients undergoing biopsy of transplanted tissue including five showing full maturation through to the terminal stage of Hassall body formation. Autoimmune regulator (AIRE) expression was also demonstrated. Autoimmune complications were seen in 7/12 patients. In two, early transient autoimmune haemolysis settled after treatment and did not recur. The other five suffered ongoing autoimmune problems including: thyroiditis (3); haemolysis (1), thrombocytopaenia (4) and neutropenia (1).ConclusionsThis study confirms the previous reports that thymus transplantation can reconstitute T cells in cDGS but with frequent autoimmune complications in survivors.
Teaser
In twelve patients with complete DiGeorge syndrome treated with thymus transplantation, there was a 75% survival with T-cell reconstitution. Autoimmunity, mostly manageable, was a frequent occurrence in survivors.http://ift.tt/2ocCamm
Autophagy – Nobel Prize 2016 and Allergy and Asthma Research
Source:Journal of Allergy and Clinical Immunology
Author(s): Harald Renz
http://ift.tt/2oRRJCS
Exercise on balance and function for knee osteoarthritis: A randomized controlled trial
Publication date: Available online 7 April 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Roberta de Matos Brunelli Braghin, Elisa Cavalheiro Libardi, Carina Junqueira, Marcello Henrique Nogueira – Barbosa, Daniela Cristina Carvalho de Abreu
ObjectivesTo assess balance and function of symptomatic and asymptomatic subjects with knee osteoarthritis (OA) and investigate the influence of physical exercise.DesignSubjects were divided into three groups: Group 1 (n = 15), symptomatic knee OA; Group 2 (n = 11), asymptomatic knee OA; and Group 3 (n = 16), knee OA and no intervention. History of falls, the WOMAC questionnaire, balance and functionality were assessed.ResultsAfter intervention, there was a significant difference in the total WOMAC score and in the pain and function domains only in Group 1. After intervention, Group 2 showed significant differences in decreased time on the Step Up/Over test and postural sway increased.ConclusionAfter the intervention, the symptomatic group reported improvement in pain and function on the WOMAC, while the asymptomatic group showed improvement in performance in the Step Up/Over test. There were no new episodes of falls in groups 1 and 2.
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Acute effects of self-myofascial release and stretching in overhead athletes with GIRD
Publication date: Available online 7 April 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Ryan R. Fairall, Lee Cabell, Richard J. Boergers, Fortunato Battaglia
Summary ObjectiveTo examine the acute effects of self-myofascial release (SMR), static stretching (SS), and the combination of self-myofascial release and static stretching (SMR+SS) on glenohumeral internal rotation range of motion (GH IR ROM) in overhead athletes with glenohumeral internal rotation deficit (GIRD).ParticipantsTwelve asymptomatic adult male amateur softball position players exhibiting GIRD.ResultsAll three methods significantly improved GH IR ROM. Post hoc testing revealed that SS alone and SMR+SS improved GH IR ROM significantly more than SMR alone. However, there were no significant differences in GH IR ROM between SS alone and SMR+SS.ConclusionsIf an athlete has a limited time to perform a warm-up (e.g., 3-4 minutes), SS alone is recommended to improve GH IR ROM. However, if the athlete has more time available to warm up (e.g., 7-8 minutes), combining SMR+SS may result in a greater increase in GH IR ROM.
http://ift.tt/2odL8l9
Surgical site infections following oral cavity cancer resection and reconstruction is a risk factor for plate exposure
Plate-related complications following head and neck cancer ablation and reconstruction remains a challenging problem often requiring further management and reconstructive surgeries. We aim to identify an assoc...
http://ift.tt/2oRDpdA
Inter-individual variability in discourse informativeness in elderly populations.
| Related Articles |
Inter-individual variability in discourse informativeness in elderly populations.
Clin Linguist Phon. 2017;31(5):391-408
Authors: Pistono A, Pariente J, Bézy C, Pastor J, Tran TM, Renard A, Fossard M, Nespoulous JL, Jucla M
Abstract
An increasing number of studies focus on discourse production in patients with neurodegenerative diseases and underline its clinical usefulness. However, if this is to be used as a clinical tool, one needs to consider how normal discourse varies within cognitively unimpaired elderly populations. In the current study, the aim has been to investigate discourse macrolinguistic variability. For this, 123 participants aged between 55 and 84 were recruited. A cluster analysis of their discourse macrolinguistic features was conducted. Then, cluster characterisation based on socio-demographic and linguistic performance was tested (fluency, naming, syntax and spelling). This method aims to identify various profiles of speaker and informativeness and then see if inter-individual variability may be related to socio-demographic and/or linguistic aspects. Four clusters of informativeness were found but no socio-demographic features appeared significant. The fourth cluster, defined as 'off topic', had lower performance during linguistic tasks than others and thus the boundary between normality and pathology should be questioned.
PMID: 28388219 [PubMed - in process]
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Intentional cannabis use to reduce crack cocaine use in a Canadian setting: A longitudinal analysis
Source:Addictive Behaviors, Volume 72
Author(s): M. Eugenia Socías, Thomas Kerr, Evan Wood, Huiru Dong, Stephanie Lake, Kanna Hayashi, Kora DeBeck, Didier Jutras-Aswad, Julio Montaner, M.-J. Milloy
BackgroundNo effective pharmacotherapies exist for the treatment of crack cocaine use disorders. Emerging data suggests that cannabinoids may play a role in reducing cocaine-related craving symptoms. This study investigated the intentional use of cannabis to reduce crack use among people who use illicit drugs (PWUD).MethodsData were drawn from three prospective cohorts of PWUD in Vancouver, Canada. Using data from participants reporting intentional cannabis use to control crack use, we used generalized linear mixed-effects modeling to estimate the independent effect of three pre-defined intentional cannabis use periods (i.e., before, during and after first reported intentional use to reduce crack use) on frequency of crack use.ResultsBetween 2012 and 2015, 122 participants reported using cannabis to reduce crack use, contributing a total of 620 observations. In adjusted analyses, compared to before periods, after periods were associated with reduced frequency of crack use (Adjusted Odds Ratio [AOR]=1.89, 95% Confidence Interval [CI]: 1.02–3.45), but not the intentional use periods (AOR=0.85, 95% CI: 0.51–1.41). Frequency of cannabis use in after periods was higher than in before periods (AOR=4.72, 95% CI: 2.47–8.99), and showed a tendency to lower frequency than in intentional cannabis use periods (AOR=0.56, 95% CI: 0.32–1.01).ConclusionsA period of intentional cannabis use to reduce crack use was associated with decreased frequency of crack use in subsequent periods among PWUD. Further clinical research to assess the potential of cannabinoids for the treatment of crack use disorders is warranted.
http://ift.tt/2oRvm0p
Surgical site infections following oral cavity cancer resection and reconstruction is a risk factor for plate exposure
Plate-related complications following head and neck cancer ablation and reconstruction remains a challenging problem often requiring further management and reconstructive surgeries. We aim to identify an assoc...
http://ift.tt/2oRDpdA
Randomized, Controlled Trial of Fractional Carbon Dioxide Laser Resurfacing Followed by Ultrashort Incubation Aminolevulinic Acid Blue Light Photodynamic Therapy for Actinic Keratosis.
BACKGROUND: Aminolevulinic acid (ALA) photodynamic therapy (PDT) is an established treatment option for actinic keratosis (AK), and recently fractional carbon dioxide (CO2) laser was shown to improve outcomes; but studies of short incubation photosensitizer are lacking. OBJECTIVE: Assess the efficacy of short incubation ALA followed by blue light PDT with and without previous fractional CO2 treatment for the treatment of AK. METHODS: Randomized, paired split-design, controlled trial of fractional CO2 followed by ultrashort 15-minute versus 30-minute incubation ALA and blue light PDT for the treatment of AK on the face. RESULTS: The complete clearance rates (CRs) at 8 weeks after ALA PDT with and without FxCO2 at 30- and 15-minute ALA incubation times were 89.78% (+FxCO2) versus 71.20% CR (-FxCO2) at 30', and 86.38% (+FxCO2) versus 69.23% (-FxCO2) at 15' ALA incubation. All lesion improvements were statistically significant. CONCLUSION: This randomized, comparative paired group controlled clinical study demonstrates that ultrashort 15- and 30-minute incubation ALA PDTs are of limited efficacy for the treatment of AK. Pretreatment with fractional ablative resurfacing yields statistically significant greater AK clearance with ALA-PDT at ultrashort ALA incubations followed by blue light. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2oR5wcT
http://ift.tt/2oR5wcT
The Facial Platysma and Its Underappreciated Role in Lower Face Dynamics and Contour.
BACKGROUND: The platysma is a superficial muscle involved in important features of the aging neck. Vertical bands, horizontal lines, and loss of lower face contour are effectively treated with botulinum toxin A (BoNT-A). However, its pars facialis, mandibularis, and modiolaris have been underappreciated. OBJECTIVE: To demonstrate the role of BoNT-A treatment of the upper platysma and its impact on lower face dynamics and contour. MATERIAL AND METHODS: Retrospective analysis of cases treated by an injection pattern encompassing the facial platysma components, aiming to block the lower face as a whole complex. It consisted of 2 intramuscular injections into the mentalis muscle and 2 horizontal lines of BoNT-A injections superficially performed above and below the mandible (total dose, 16 onabotulinumtoxinA U/side). Photographs were taken at rest and during motion (frontal and oblique views), before and after treatment. RESULTS: A total of 161 patients have been treated in the last 2 years with the following results: frontal and lateral enhancement of lower facial contour, relaxation of high horizontal lines located just below the lateral mandibular border, and lower deep vertical smile lines present lateral to the oral commissures and melomental folds. CONCLUSION: The upper platysma muscle plays a relevant role in the functional anatomy of the lower face that can be modulated safely with neuromodulators. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2oQYxjU
http://ift.tt/2oQYxjU
Safety of Cochlear Implants in Electrosurgery: A Systematic Review of the Literature.
BACKGROUND: The implications of electrosurgical instrument use in patients with cochlear implants (CIs) are becoming increasingly relevant for dermatologic surgeons as the number of implanted CI devices continues to grow. The literature, however, fails to provide clear recommendations for appropriate treatment of these patients. OBJECTIVE: To systematically consolidate and critique the current literature regarding electrosurgical instrument use in patients with CI, to determine implications of various electrosurgical devices and settings on CI function and health of cochlear tissues, and to devise recommendations for appropriate use. MATERIALS AND METHODS: The manuscript was created based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. A broad search of PubMed, Access Medicine, Clinical Key, Ovid, Scopus, the Cochrane Library, and Web of Science was performed using key words such as CI, electrosurgery, and/or electrosurgical device. Criteria for inclusion included being written in English language and institutional access to manuscript. All years were included. Additional references were obtained from personal communication with CI manufacturers. Study biases were assessed through evaluation of funding and/or sponsoring agencies for included studies. RESULTS: The authors' search yielded a total of 8 studies, 5 of which were a level of evidence 5, 2 of which were level of evidence 4, and 1 of which was a level of evidence 3. The remaining study was relegated only to device testing. These studies were complicated by inaccurate terminology and inconsistent recommendations. CONCLUSION: The body of evidence evaluating electrosurgical instrument use in patients with CI is severely limited in number and quality. Thus, vague and inconsistent recommendations have emerged that place patients at risk of serious and costly adverse effects. In light of this, the authors suggest use of the most conservative recommendations available for electrosurgical instrument use in patients with CI. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2oR6bLv
http://ift.tt/2oR6bLv
Masthead
Publication date: February 2017
Source:Seminars in Oncology, Volume 44, Issue 1
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Editorial Board
Publication date: February 2017
Source:Seminars in Oncology, Volume 44, Issue 1
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Table of Contents
Publication date: February 2017
Source:Seminars in Oncology, Volume 44, Issue 1
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outside front cover
Publication date: February 2017
Source:Seminars in Oncology, Volume 44, Issue 1
http://ift.tt/2ochvPr
Estimation of heavy metal-contaminated soils’ mechanical characteristics using electrical resistivity
Abstract
Under the process of urbanization in China, more and more attention has been paid to the reuse of heavy metal-contaminated sites. The shear characteristics of heavy metal-contaminated soils are investigated by electrical detection in this paper. Three metal ions (Zn2+, Cd2+, and Pb2+) were used, the metal concentrations of which are 50, 166.67, 500, 1666.67, and 5000 mg/kg, respectively. Direct shear tests were used to investigate the influence of heavy metal ions on the shear characters of soil samples. It is found that with the addition of heavy metal ions, the shear strength, cohesion, and friction angle of contaminated soils are higher than the control samples. The higher concentration of heavy metal ions penetrated in soils, the higher these engineering characteristics of contaminated soils observed. In addition, an electrical resistivity detection machine is used to evaluate the shear characteristics of contaminated soils. The electrical resistivity test results show that there is a decreasing tendency of resistivity with the increase of heavy metal ion concentrations in soils. Compared with the electrical resistivity and the shear characteristics of metal-contaminated soils, it is found that, under fixed compactness and saturation, shear strength of metal-contaminated soils decreased with the increase of resistivity. A basic linear relationship between C/log(N + 10) and resistivity can be observed, and there is a basic linear relationship between φ/log(N + 10) and resistivity. Besides, a comparison of the measured and predicted shear characteristics shows a high accuracy, indicating that the resistivity can be used to evaluate the shear characteristics of heavy metal contaminated soils.
http://ift.tt/2od05nz
Fishing for contaminants: identification of three mechanism specific transcriptome signatures using Danio rerio embryos
Abstract
In ecotoxicology, transcriptomics is an effective way to detect gene expression changes in response to environmental pollutants. Such changes can be used to identify contaminants or contaminant classes and can be applied as early warning signals for pollution. To do so, it is important to distinguish contaminant-specific transcriptomic changes from genetic alterations due to general stress. Here we present a first step in the identification of contaminant class-specific transcriptome signatures. Embryos of zebrafish (Danio rerio) were exposed to three substances (methylmercury, chlorpyrifos and Aroclor 1254, each from 24 to 48 hpf exposed) representing sediment typical contaminant classes. We analyzed the altered transcriptome to detect discriminative genes significantly regulated in reaction to the three applied contaminants. By comparison of the results of the three contaminants, we identified transcriptome signatures and biologically important pathways (using Cytoscape/ClueGO software) that react significantly to the contaminant classes. This approach increases the chance of finding genes that play an important role in contaminant class-specific pathways rather than more general processes.
http://ift.tt/2oc0YuT
Preparation, characterization, and dye removal study of activated carbon prepared from palm kernel shell
Abstract
Palm oil mill wastes (palm kernel shell (PKS)) were used to prepare activated carbons, which were tested in the removal of colorants from water. The adsorbents were prepared by 1-h impregnation of PKS with ZnCl2 as the activating agent (PKS:ZnCl2 mass ratios of 1:1 and 2:1), followed by carbonization in autogenous atmosphere at 500 and 550 °C during 1 h. The characterization of the activated carbons included textural properties (porosity), surface chemistry (functional groups), and surface morphology. The dye removal performance of the different activated carbons was investigated by means of the uptake of methylene blue (MB) in solutions with various initial concentrations (25–400 mg/L of MB) at 30 °C, using a 0.05-g carbon/50-mL solution relationship. The sample prepared with 1:1 PKS:ZnCl2 and carbonized at 550 °C showed the highest MB adsorption capacity (maximum uptake at the equilibrium, q max = 225.3 mg MB / g adsorbent), resulting from its elevated specific surface area (BET, 1058 m2/g) and microporosity (micropore surface area, 721 m2/g). The kinetic experiments showed that removals over 90% of the equilibrium adsorptions were achieved after 4-h contact time in all the cases. The study showed that palm oil mill waste biomass could be used in the preparation of adsorbents efficient in the removal of colorants in wastewaters.
http://ift.tt/2ojSLqk
The significance of renewable energy use for economic output and environmental protection: evidence from the Next 11 developing economies
Abstract
Increasing economic activities in developing economies raise demand for energy mainly sourced from conventional sources. The consumption of more conventional energy will have a significant negative impact on the environment. Therefore, attention of policy makers has recently shifted towards the promotion of renewable energy generation and uses across economic activities to ensure low carbon economy. Given the recent scenario, in this paper, we aim to examine the role of renewable energy consumption on the economic output and CO2 emissions of the next fastest developing economies of the world. The study employs several robust panel econometric models by using annual data from 1990 to 2012. Empirical findings confirm the significant long-run association among the variables. Similarly, results show that renewable energy consumption positively contributes to economic output and has an adverse effect on CO2 emissions. Given our findings, we suggest policy makers of those economies to initiate further effective policies to promote more renewable energy generation and uses across economic activities to ensure sustainable economic development.
http://ift.tt/2oRmMP2
The genus Achyranthes: A review on traditional uses, phytochemistry, and pharmacological activities
Publication date: 5 May 2017
Source:Journal of Ethnopharmacology, Volume 203
Author(s): Xirui He, Xiaoxiao Wang, Jiacheng Fang, Yu Chang, Ning Ning, Hao Guo, Linhong Huang, Xiaoqiang Huang
Ethnopharmacological relevanceAchyranthes L. (Amaranthaceae), also known as Chaff Flower and Niuxi/牛膝, mainly includes two famous medicinal species namely A. bidentata and A. aspera. A. bidentata has been widely used as blood-activating and stasis-resolving medicine for the treatment of various diseases including amenorrhea, dysmenorrhea, lumbago, gonalgia, paraplegia, edema, stranguria, headache, dizziness, odontalgia, oral ulcer, hematemesis, and epistaxis. A. aspera has been widely used to treat various diseases, including gynecological disorder, asthma, ophthalmia, odontalgia, haemorrhoids, and abdominal tumor, and has been applied to difficult labour, wound healing, insect and snake bites.Aim of this reviewThis review aims to provide systematically reorganized information on distributions, botanical characteristics, ethnopharmacology, chemical constituents, qualitative and quantitative analysis, pharmacological activities, and toxicity of Achyranthes species to support their therapeutic potential.Materials and methodsThe relevant information on Achyranthes species was gathered from worldwide accepted scientific databases via electronic search (Google Scholar, Web of Science, ScienceDirect, ACS Publications, PubMed, Wiley Online Library, SciFinder, CNKI). Information was also obtained from International Plant Names Index, Chinese Pharmacopoeia, Chinese herbal classic books, PhD and MSc dissertations, etc.ResultsA comprehensive analysis of literatures obtained through the above- mentioned sources confirms that the ethnomedicinal uses of Achyranthes species are mainly recorded in China, India, Korea, Pakistan, Ethiopia, Kenya, Sri Lanka, Bangladesh, Philippines, etc. Phytochemical investigations revealed that the major bioactive substances of Achyranthes plants are polysaccharides, polypeptides, triterpenoid saponins, and ketosteroids. Achyranthes plants have been shown to not only act on immune system, nervous system, bone metabolism, and reproduction, but also possess a wide range of biological activities, including blood-activating, anti-tumor, anti-inflammation, anti-arthritis, anti-oxidation, anti-aging, wound healing, etc. Toxicity studies indicated that A. bidentata and A. aspera seem non-toxic at the common therapeutic doses.ConclusionsA. bidentata and A. aspera are very promising to be fully utilized in the development of nutraceutical and pharmaceutical products. There are, however, needs for further in-depth studies to confirm some ethnomedicinal uses of Achyranthes plants and to elucidate the scientific connotation of the widely documented property of conducting drug downward of A. bidentata. In addition, other widespread Achyranthes species like A. japonica and A. rubrofusca ought to be studied. Likewise, systematic comparative studies of the chemical constituents of medicinal Achyranthes plants resources with the same local name are also needed. Furthermore, not only should the investigations on the structure-activity relationship of the main bioactive compounds triterpenoid saponins and ketosteroids be carried out, but the pathways of absorption, distribution, metabolism, and excretion ought to be clarified. Last but not least, there is also a need to evaluate the long-term chronic toxicity and acute toxicity in vivo of the main bioactive compounds.
Graphical abstract
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Abietic acid isolated from pine resin (Resina Pini) enhances angiogenesis in HUVECs and accelerates cutaneous wound healing in mice
Publication date: 5 May 2017
Source:Journal of Ethnopharmacology, Volume 203
Author(s): Jun Yeon Park, Yun Kyung Lee, Dong-Soo Lee, Jeong-Eun Yoo, Myoung-Sook Shin, Noriko Yamabe, Su-Nam Kim, Seulah Lee, Ki Hyun Kim, Hae-Jeung Lee, Seok Sun Roh, Ki Sung Kang
Ethnopharmacological relevanceResin known as Resina Pini is listed in the Korean and Japanese pharmacopoeias and has been used for treating skin wounds and inflammation. Resin is composed of more than 50% abietic acid and 10% neutral substances.ObjectiveIn the present study, the wound-healing effects of abietic acid and the possible underlying mechanism of action were investigated in various in vitro and in vivo models.Materials and methodsThe effects of abietic acid on tube formation and migration were measured in human umbilical vein vascular endothelial cells (HUVECs). Protein expression of mitogen-activated protein kinase (MAPK) activation was evaluated via Western blotting analysis. The wound-healing effects of abietic acid were assessed using a mouse model of cutaneous wounds.ResultsThe results showed that abietic acid enhanced cell migration and tube formation in HUVECs. Abietic acid induced significant angiogenic potential, which is associated with upregulation of extracellular signal-regulated kinase (ERK) and p38 expression. Additionally, 0.8μM abietic acid-treated groups showed accelerated wound closure compared to the controls in a mouse model of cutaneous wounds.ConclusionThe current data indicate that abietic acid treatment elevated cell migration and tube formation in HUVECs by the activation of ERK and p38 MAPKs. We suggest that abietic acid can be developed as a wound-healing agent.
Graphical abstract
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Protective effect of a phenolic extract containing indoline amides from Portulaca oleracea against cognitive impairment in senescent mice induced by large dose of D-galactose /NaNO2
Publication date: 5 May 2017
Source:Journal of Ethnopharmacology, Volume 203
Author(s): Peipei Wang, Hongxiang Sun, Dianyu Liu, Zezhao Jiao, Su Yue, Xiuquan He, Wen Xia, Jianbo Ji, Lan Xiang
Ethnopharmacological relevance:Portulaca oleracea L. is a potherb and also a widely used traditional Chinese medicine. In accordance with its nickname "longevity vegetable", pharmacological study demonstrated that this plant possessed antioxidant, anti-aging, and cognition-improvement function. Active principles pertaining to these functions of P. oleracea need to be elucidated.Aim of the study:The present study evaluated the effect of a phenolic extract (PAAs) from P. oleracea which contained specific antioxidant indoline amides on cognitive impairment in senescent mice.Materials and methods:PAAs was prepared through AB-8 macroporous resin column chromatography. Total phenol content was determined using colorimetric method, and contents of indoline amides were determined using HPLC-UV method. Senescent Kunming mice with cognitive dysfunction were established by intraperitoneal injection of D-galactose (D-gal, 1250mg/kg/day) and NaNO2 (90mg/kg/day) for 8 weeks, L-PAAs (360mg/kg/day), H-PAAs (720mg/kg/day), and nootropic drug piracetam (PA, 400mg/kg/day) as the positive control were orally administered. Spatial learning and memory abilities were evaluated by Morris water maze experiment. Activities of AChE, SOD, CAT, and levels of GSH and MDA in the brain or plasma were measured. Hippocampal morphology was observed by HE staining.Results:Chronic treatment of large dose of D-gal/NaNO2 significantly reduced lifespan, elevated AChE activity, decreased CAT activity, compensatorily up-regulated SOD activity and GSH level, increased MDA level, induced neuronal damage in hippocampal CA1, CA3 and CA4 regions, and impaired cognitive function. Similar to PA, PAAs prolonged the lifespan and improved spatial memory ability. Moreover, PAAs improved learning ability. H-PAAs significantly reversed compensatory increase in SOD activity to the normal level, elevated serum CAT activity, and reduced MDA levels in brain and plasma, more potent than L-PAAs. Besides these, PAAs evidently inhibited hippocampal neuronal damage. However, it had no effect on brain AChE activity.Conclusion:PAAs as the bioactive principles of P. oleracea attenuated oxidative stress, improved survival rate, and enhanced cognitive function in D-gal/NaNO2-induced senile mice, similar to piracetam. This phenolic extract provides a promising candidate for prevention of aging and aging-related cognitive dysfunction in clinic.
Graphical abstract
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Development of medial pterygoid muscle fibers in rabbits fed with a liquid diet
Source:Archives of Oral Biology, Volume 80
Author(s): Kozue Kuroki, Takumi Morita, Hiroki Takasu, Keisuke Saito, Takuya Fujiwara, Katsunari Hiraba, Shigemi Goto
ObjectiveThis study aimed to investigate the influence of decreased functional load on the medial pterygoid muscle during mastication in rabbits fed with a liquid-diet.Materials and MethodsMedial pterygoid muscles from 54 rabbits (solid- and liquid-diet groups, n=48; unweaned group, n=6) were histochemically examined at 4, 9, 12, 18, and 33 weeks after birth. Six fiber types (I, IC, IIC, IIA, IIAB, and IIB) were distinguished via mATPase staining.ResultsSignificant increases in the diameters of all fiber types were seen up to 33 weeks of age in the solid-diet group; however, no significant increase was noted in fiber types I and IC, from 4 to 33 weeks of age, in the liquid-diet group. The proportion of slow fibers increased up to 12 weeks followed by an increase in the number of fast fibers in the solid-diet group, whereas in the liquid-diet group, the number of slow fiber declined after weaning.ConclusionsLiquid-diet consumption caused muscle fiber atrophy and an increase in the number of fast fibers during early developmental stages after weaning. Furthermore, the growth pattern of the medial pterygoid muscle in the liquid-diet group was different from that in the solid-diet group.
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Evaluation of the effect of tacrolimus on periodontitis induced in rats
Source:Archives of Oral Biology, Volume 80
Author(s): Luiz Alexandre Moura Penteado, Gilmara Medeiros Lucena, Marcílio Otávio Brandão Peixoto, Thiago Correia Barbosa, Ana Carolina de Souza Leitão Arruda, Renata Cimões
ObjectiveThis study was to investigate the effect of tacrolimus (FK506) on periodontitis induced in rats.DesignPeriodontal disease was induced in 30 Wistar rats which were then randomly divided into two groups: treatment with a daily injection of 0.9% saline (1mL/day) and treatment with a daily injection of FK506. After periods of 10, 15 and 30days the animals were killed and separate radiographs of the right and left hemimandibles were obtained. One calibrated examiner measured the periodontal bone support (PBS) in the images, after the following treatments: S, saline without ligature; SL, saline with ligature; T, FK506 without ligature; TL, FK506 with ligature. The data were subjected to analysis of variance (ANOVA) and the Tukey test (p<0.01).ResultsThe radiographic results were similar at all evaluation time points. The S treatment had a higher PBS averaging at 10, 15 and 30days, which was statistically significant different compared with the SL treatment and TL treatment, but not significantly different from the T treatment. The SL and TL treatments showed no statistically significant differences between them.ConclusionsTacrolimus used for up to 30days showed no protective or aggravating effects on alveolar bone loss.
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Cigarette smoke extract (CSE) induces RAGE-mediated inflammation in the Ca9-22 gingival carcinoma epithelial cell line
Source:Archives of Oral Biology, Volume 80
Author(s): Nolan T. Sanders, Derek J. Dutson, Justin W. Durrant, Joshua B. Lewis, Shalene H. Wilcox, Duane R. Winden, Juan A. Arroyo, Benjamin T. Bikman, Paul R. Reynolds
ObjectiveThe oral environment is anatomically positioned as a significant gateway for exposure to environmental toxicants. Cigarette smoke exposure compromises oral health by orchestrating inflammation. The receptor for advanced glycation end-products (RAGE) has been implicated in smoke-induced inflammatory effects; however, its role in the oral cavity is unknown. The purpose of this study was to determine RAGE expression by immortalized gingival carcinoma cells and the degree to which RAGE-mediated signaling influences inflammation.DesignGingival epithelia cells (Ca9-22) were exposed to 10% cigarette smoke extract (CSE) for six hours and screened for RAGE expression and inflammatory mediators.ResultsQuantitative PCR and immunoblotting revealed increased RAGE expression following exposure. Furthermore, exposure activated RAGE signaling intermediates including Ras and NF-κB. IL-6 and IL-1β were also elevated in cell culture medium from CSE-exposed cells when compared to controls. A family of anionic, partially lipophilic sulfated polysaccharide derivatives known as semi-synthetic glycosaminoglycan ethers (SAGEs) were used in an effort to block RAGE signaling. Co-treatment of CSE and SAGEs ameliorated inflammatory responses.ConclusionsThese results provide a new perspective on a mechanism of cigarette smoke induced oral inflammation. Further work may show RAGE signaling as a potential target in the treatment of diseases of the oral cavity exacerbated by tobacco smoke exposure.
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Improved Outcomes with Pedicled Nipple-sparing Mastectomies Using a New Surgical Delay: Mastectomy through Wise Incisions
http://ift.tt/2o2FErm
Psychoactive Drugs in Plastic Surgery
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The Aesthetic Items Scale: A Tool for the Evaluation of Aesthetic Outcome after Breast Reconstruction
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Inhibition of Voltage-Gated Na+ Channels by Bupivacaine Is Enhanced by the Adjuvants Buprenorphine, Ketamine, and Clonidine.
Background and Objectives: Regional anesthesia includes application of local anesthetics (LAs) into the vicinity of peripheral nerves. Prolongation or improvement of nerve blocks with LAs can be accomplished by coapplication with adjuvants, including buprenorphine, ketamine, and clonidine. While the mechanisms mediating prolonged or improved LA-induced effects by adjuvants are poorly understood, we hypothesized that they are likely to increase LA-induced block of voltage-gated Na+ channels. In this study, we investigated the inhibitory effects of the LA bupivacaine alone and in combination with the adjuvants on neuronal Na+ channels. Methods: Effects of bupivacaine, buprenorphine, ketamine, and clonidine on endogenous Na+ channels in ND7/23 neuroblastoma cells were investigated with whole-cell patch clamp. Results: Bupivacaine, buprenorphine, ketamine, and clonidine are concentration- and state-dependent inhibitors of Na+ currents in ND7/23 cells. Tonic block of resting channels revealed an order of potency of bupivacaine (half-maximal inhibitory concentration [IC50] 178 +/- 8 [mu]M) > buprenorphine (IC50 172 +/- 25) > clonidine (IC50 824 +/- 55 [mu]M) > ketamine (IC50 1377 +/- 92 [mu]M). Bupivacaine and buprenorphine, but not clonidine and ketamine, induced a strong use-dependent block at 10 Hz. Except for clonidine, all substances enhanced fast and slow inactivation. The combination of bupivacaine with one of the adjuvants resulted in a concentration-dependent potentiation bupivacaine-induced block. Conclusions: We demonstrate that buprenorphine, ketamine, and clonidine directly inhibit Na+ channels and that they potentiate the blocking efficacy of bupivacaine on Na+ channels. These data indicate that block of Na+ channels may account for the additive effects of adjuvants used for regional anesthesia. Copyright (C) 2017 by American Society of Regional Anesthesia and Pain Medicine.
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A New Step Toward Evidence of In Vivo Perineural Dexamethasone Safety: An Animal Study.
Background and Objectives: The aim of this study was to analyze histological nerve toxicity of perineural dexamethasone administration in combination with ropivacaine on mice. Efficacy of perineural dexamethasone in combination with regional anesthesia is clearly demonstrated. However, the safety of this procedure is still a matter of debate. Methods: A sciatic nerve block was performed on 90 mice. Five groups, each containing 18 mice assigned randomly, were used in these experiments: the sham group (isotonic saline solution), R group (perineural ropivacaine), D group (perineural dexamethasone), RDPN group (perineural ropivacaine and perineural dexamethasone), and the RDS group (perineural ropivacaine and systemic dexamethasone). Sensory and motor blocks were evaluated every 30 minutes for 14 hours. Fourteen and 28 days after this procedure, 9 mice in each group were killed for sciatic nerve histological assessment. Results: No statistical difference was observed between different groups for Wallerian degeneration (P = 0.28 at day 14 and P = 0.22 at day 28) and perineural inflammation (P = 0.9 at day 14). Motor and sensory block durations were tested for each group. A statistical difference was observed for motor block duration between the RDPN group (150 minutes [127-172 minutes]), the RDS group (120 minutes [90-120 minutes]), and the R group (60 minutes [60-90 minutes]). Sensory block duration was also statistically different: 660 minutes (660-720 minutes) in the RDPN group, 480 minutes (427-660 minutes) in RDS group, 330 minutes (240-410) in the R group. Conclusions: A combination of ropivacaine and perineural dexamethasone allows longer sensory block duration compared with ropivacaine alone or ropivacaine and systemic dexamethasone, without increased neural toxicity. Copyright (C) 2017 by American Society of Regional Anesthesia and Pain Medicine.
http://ift.tt/2ocbJNw
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CD26/DPPIV-mediated regulation of pruritus in psoriasis
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
Author(s): Eriko Komiya, Ryo Hatano, Haruna Otsuka, Takumi Itoh, Taketo Yamada, Mitsutoshi Tominaga, Kenji Takamori, Kei Ohnuma, Chikao Morimoto
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The ex vivo-induced regulatory B cells ameliorate tissue fibrosis and autoimmunity via an anti-oxidative effect in systemic sclerosis
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
Author(s): Ayumi Yoshizaki, Takemichi Fukasawa, Satoshi Ebata, Shinichi Sato
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Decreased IL-10-producing B cell level in patients with pemphigus but not with pemphigoid
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
Author(s): Miho Kabuto, Noriki Fujimoto, Toshifumi Takahashi, Takeshi Nakanishi, Toshihiro Tanaka
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Editors Choice
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
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Combinational effects of maxacalcitol and betamethasone butyrate propionate on imiquimod-induced psoriasis-like dermatitis in mice
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
Author(s): Kei Hashimoto, Hideya Uratsuji, Yoshihito Yamada, Takamichi Kitano, Yusuke Kumagai, Tatsumi Matsumoto
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Intravenous immunoglobulin suppresses disease activity in mouse models of bullous pemphigoid
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
Author(s): Hideyuki Ujiie, Tetsumasa Sasaoka, Wataru Nishie, Ken Natsuga, Satoru Shinkuma, Hiroshi Shimizu
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Binding affinity and interaction of LL-37 with HLA-C*06:02 in psoriasis
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
Author(s): Tomotaka Mabuchi, Noriaki Hirayama
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FcgRIIb is critical to establish clonal ignorance and suppress pemphigus phenotype in pathogenic anti-desmoglein 3 antibody knock-in mice
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
Author(s): Hisashi Nomura, Yuko Kase, Jun Yamagami, Naoko Wada, Shigeo Koyasu, Hayato Takahashi, Masayuki Amagai
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Self-genomic double-stranded DNA is a potential trigger of keratinocyte hyperproliferation in psoriasis
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
Author(s): Yuqian Luo, Takeshi Hara, Yuko Ishido, Norihisa Ishii, Takeshi Kambara, Koichi Suzuki
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Involvement of opioid systems in itch-related behavior of imiquimod-induced psoriasis-like dermatitis model
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
Author(s): Nobuaki Takahashi, Mitsutoshi Tominaga, Yayoi Kamata, Yoshie Umehara, Hironori Matsuda, Yasushi Suga, Hideoki Ogawa, Kenji Takamori
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Editorial board
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
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High fat diet exacerbates psoriasis-like skin lesion induced by imiquimod through inducing IL-17A and inflammasomes in mice
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
Author(s): Yuko Higashi, Munekazu Yamakuchi, Tomoko Fukushige, Teruto Hashiguchi, Takuro Kanekura
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Single B cell analysis can reveal distinct cytokine profile of autoreactive B cells in systemic sclerosis
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
Author(s): Takemichi Fukasawa, Ayumi Yoshizaki, Satoshi Toyama, Satoshi Ebata, Kouki Nakamura, Ryosuke Saigusa, Takashi Yamashita, Yohei Ichimura, Takehiro Takahashi, Takashi Taniguchi, Yoshihide Asano, Yutaka Kazoe, Kazuma Mawatari, Takehiko Kitamori, Shinichi Sato
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Role of sulfated cholecystokinin 8 in spinal itch transmission
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
Author(s): Fumiya Kusube, Mitsutoshi Tominaga, Hiroaki Kawasaki, Fumiyuki Yamakura, Hisashi Naito, Hideki Ogawa, Yasuhiro Tomooka, Kenji Takamori
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α2AP regulates vascular alteration by inhibiting VEGF signaling in systemic sclerosis
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
Author(s): Yosuke Kanno, En Shu, Hiroyuki Kanoh, Ayaka Matsuda, Mariko Seishima
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Comparative study of cutaneous adverse reactions induced by a proteasome inhibitor with skin eruptions in Nakajo-Nishimura syndrome
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
Author(s): Kayo Kunimoto, Nobuo Kanazawa, Fukumi Furukawa, Keiko Manabe, Kenji Asagoe, Osamu Yamasaki, Takeshi Kabahara, Miwa Kanaoka, Michiko Aihara, Yuichi Teraki, Seiichi Izaki, Ryuhei Okuyama, Toshiyuki Yamamoto, John Hanna
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Genetic prediction of the effectiveness of anti-TNF-α therapy for psoriasis patients
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
Author(s): Rika Nishikawa, Hiroshi Nagai, Toshinori Bito, Tetsuya Ikeda, Tatsuya Horikawa, Atsuko Adachi, Tsukasa Matsubara
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The pathogenic ceramide metabolizing enzyme sphingomyelin deacylase in atopic dermatitis is identical to the beta-subunit of acid ceramidase
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
Author(s): Yasuhiro Teranishi, Hiroshi Kuwahara, Makoto Kawashima, Genji Imokawa, Mari Nogami-Itoh
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Inhibitory regulation of MFG-E8 on fibrosis in systemic sclerosis
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
Author(s): Chisako Fujiwara, Akihito Uehara, Yoko Yokoyama, Akihiko Uchiyama, Akiko Sekiguchi, Sachiko Ogino, Osamu Ishikawa, Sei-ichiro Motegi
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Langerhans cells regulate autoimmune CD8 T cell-mediated interface dermatitis
Publication date: May 2017
Source:Journal of Dermatological Science, Volume 86, Issue 2
Author(s): Noriko Kubota, Naoko Okiyama, Akimasa Saito, Yosuke Ishitsuka, Rei Watanabe, Björn E. Clausen, Manabu Fujimoto
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Non-coding RNAs: new biomarkers and therapeutic targets for esophageal cancer.
| Related Articles |
Non-coding RNAs: new biomarkers and therapeutic targets for esophageal cancer.
Oncotarget. 2017 Mar 30;:
Authors: Hou X, Wen J, Ren Z, Zhang G
Abstract
Esophageal cancer is one of the most common gastrointestinal malignant diseases and there is still no effective treatment. The incidence of esophageal cancer in the world is relatively high and on the increase year by year. Thus, the elaboration on the carcinogenesis of esophageal cancer and the identification of new biomarkers and therapeutic targets is quite beneficial to optimizing the current therapeutic regimen for treating such deadly disease. More and more evidence has shown that non-coding RNAs play an important role in the development and progression of multiple human cancers, including esophageal cancer. microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two functional kinds of non-coding RNAs that have been well investigated. They exert tumor suppressive or promoting effect by specifically regulating the expression of certain downstream target genes, which is tumor specific. It is also proved that miRNAs and lncRNAs level in tissue and plasma from esophageal cancer patients are closely correlated with the survival and disease progression, which could be used as a prognostic factor and therapeutic target for esophageal cancer.
PMID: 28388588 [PubMed - as supplied by publisher]
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Integrated expression profiles analysis reveals novel predictive biomarker in pancreatic ductal adenocarcinoma.
| Related Articles |
Integrated expression profiles analysis reveals novel predictive biomarker in pancreatic ductal adenocarcinoma.
Oncotarget. 2017 Mar 31;:
Authors: Li H, Wang X, Fang Y, Huo Z, Lu X, Zhan X, Deng X, Peng C, Shen B
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal human malignant tumor, with a dismal 5-year survival rate of less than 5%. The lack of specific symptoms at early tumor stages and the paucity of biomarkers contribute to the poor diagnosis of pancreatic ductal adenocarcinoma. To improve prognosis, a screening biomarker for early diagnosis of pancreatic cancer is in urgent need. We searched the databases of expression profiling by array on GEO, aiming at comparing gene expression profile of matched pairs of pancreatic tumor and adjacent non-tumor tissues, and we screen out 4 suitable series of gene expression microarray data ("GSE15471", "GSE18670", "GSE28735" and "GSE58561"). After carefully analyzing, 13 DEGs (MYOF, SLC6A6, S100P, HK2, IFI44L, OSBPL3, IGF2BP3, PDK4, IL1R2, ERO1A, EGLN3, PLAC8 and ACSL5) are significantly differentially expressed in four microarray databases in common. After analyzing mRNA expression data and clinical follow-up survey provided in the TCGA database and clinicopathological data of 137 pancreatic ductal adenocarcinoma patients, we carefully demonstrated that three of these differentially expressed genes (ERO1A, OSBPL3 and IFI44L) are correlated with poor prognosis of pancreatic ductal adenocarcinoma patients. In addition, we revealed that cell-matrix adhesion and extracellular matrix were top significantly regulated pathways in pancreatic ductal adenocarcinoma and depicted two protein-protein interactions networks of extracellular matrix related Genes which are dysregulated according to 4 gene expression microarray data mentioned above ("GSE15471", "GSE18670", "GSE28735" and "GSE58561"), hoping to shed light on the etiology of PDAC and mechanisms of drug resistance in PDAC in this study.
PMID: 28388590 [PubMed - as supplied by publisher]
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Genetic landscape of extreme responders with anaplastic oligodendroglioma.
| Related Articles |
Genetic landscape of extreme responders with anaplastic oligodendroglioma.
Oncotarget. 2017 Mar 31;:
Authors: Holdhoff M, Cairncross GJ, Kollmeyer TM, Zhang M, Zhang P, Mehta MP, Werner-Wasik M, Souhami L, Bahary JP, Kwok Y, Hartford AC, Chakravarti A, Yegnasubramanian S, Vogelstein B, Papadopoulos N, Kinzler K, Jenkins RB, Bettegowda C
Abstract
BACKGROUND: The NRG Oncology RTOG 9402 trial showed significant survival benefit in patients with 1p/19q co-deleted anaplastic oligodendrogliomas (AO) who received both radiation (RT) and chemotherapy (PCV regimen) versus RT alone. Substantial separation of the survival curves was only seen after 7.3 years. We aimed to determine whether there are specific genetic alterations that distinguish co-deleted AO patients who benefit from the addition of PCV from those who do not.
METHODS: We performed whole exome sequencing on matched tumor and normal DNA from all available short-term (STS) and long-term survivors (LTS) who received RT+PCV. hTERT status and rs55705857 genotypes (G-allele) were analyzed in both cohorts.
RESULTS: Six STS (survival of <7.3y) and 7 LTS (survival of ≥7.3y and no progression) had sufficient material for analysis. There was no significant difference between the groups regarding age, performance status and extent of resection. On average, STS had 7 and LTS 4 mutations. Most common mutations in STS vs. LTS were: IDH1 (67 vs. 86%), CIC (50 vs. 71%) and FUBP1 (17 vs. 71%). The hTERT promoter was mutated in 83% STS and 86% LTS. Genotyping of rs55705857 showed a higher prevalence of G allele carriers in LTS than STS (43 vs. 17%).
CONCLUSIONS: These findings confirm that IDH, CIC, FUBP1 mutations and rs55705857 genotype are common in AO. No distinct genetic signature was identified to differentiate STS and LTS.
PMID: 28388591 [PubMed - as supplied by publisher]
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EGFR-induced phosphorylation of type Iγ phosphatidylinositol phosphate kinase promotes pancreatic cancer progression.
| Related Articles |
EGFR-induced phosphorylation of type Iγ phosphatidylinositol phosphate kinase promotes pancreatic cancer progression.
Oncotarget. 2017 Mar 31;:
Authors: Chen C, Wang X, Fang J, Xue J, Xiong X, Huang Y, Hu J, Ling K
Abstract
Pancreatic cancer is one of the deadliest malignancies and effective treatment has always been lacking. In current study, we investigated how the type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) participates in the progression of pancreatic ductal adenocarcinoma (PDAC) for novel therapeutic potentials against this lethal disease. We found that PIPKIγ is up-regulated in all tested PDAC cell lines. The growth factor (including EGFR)-induced tyrosine phosphorylation of PIPKIγ is significantly elevated in in situ and metastatic PDAC tissues. Loss of PIPKIγ inhibits the aggressiveness of PDAC cells by restraining the activities of AKT and STAT3, as well as MT1-MMP expression. Therefore when planted into the pancreas of nude mice, PIPKIγ-depleted PDAC cells exhibits substantially repressed tumor growth and metastasis comparing to control PDAC cells. Results from further studies showed that the phosphorylation-deficient PIPKIγ mutant, unlike its wild-type counterpart, cannot rescue PDAC progression inhibited by PIPKIγ depletion. These findings indicate that PIPKIγ, functioning downstream of EGFR signaling, is critical to the progression of PDAC, and suggest that PIPKIγ is potentially a valuable therapeutic target for PDAC treatment.
PMID: 28388589 [PubMed - as supplied by publisher]
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Micro RNA-19a interferes with IL-10 expression in peripheral dendritic cells of patients with nasal polyposis.
| Related Articles |
Micro RNA-19a interferes with IL-10 expression in peripheral dendritic cells of patients with nasal polyposis.
Oncotarget. 2017 Mar 24;:
Authors: Luo XQ, Shao JB, Xie RD, Zeng L, Li XX, Qiu SQ, Geng XR, Yang LT, Li LJ, Liu DB, Liu ZG, Yang PC
Abstract
The pathogenesis of nasal polyp is to be further investigated. Micro RNA (miR) plays a role in the development of allergic inflammation. Interleukin (IL)-10-producing dendritic cells (DC) have immune tolerogenic properties. This study test a hypothesis that miR-17-92 cluster is associated with suppressing IL-10 in peripheral DC. In this study, peripheral blood samples were obtained from 26 patients with nasal polyp. The CD11c DCs were isolated from the blood samples and analyzed for the expression of IL-10. We observed that, as compared with healthy subjects, the IL-10 expression in peripheral DC was significantly lower in polyp patients. The levels of miR-19a, but not the rest 5 members of the miR-17-92 cluster, were markedly higher in DCs in polyp group. Exposure to recombinant IL-4 suppressed the IL-10 expression in DCs, which was abolished by blocking histone deacetylase-11 or knocking down the miR-19a gene in DCs. We conclude that miR-19a plays a critical role in the suppression of IL-10 in peripheral DCs, which may be a target in the immune therapy for nasal polyp.
PMID: 28388587 [PubMed - as supplied by publisher]
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HER2 and EGFR amplification and expression in urothelial carcinoma occurs in distinct biological and molecular contexts.
| Related Articles |
HER2 and EGFR amplification and expression in urothelial carcinoma occurs in distinct biological and molecular contexts.
Oncotarget. 2017 Mar 24;:
Authors: Eriksson P, Sjödahl G, Chebil G, Liedberg F, Höglund M
Abstract
We analyzed a cohort of 599 cases of urothelial carcinoma for EGFR, ERBB2, and ERBB3 gene expression and genomic alterations. The cohort consisted of a reference set (n = 292) comprising all stages and grades and one set (n = 307) of advanced tumors. All cases were previously classified into urothelial carcinoma molecular subtypes. Genomic amplifications were established by array-CGH or in-situ hybridization, and gene expression both at mRNA and protein levels. Clinical HER2 status was independently evaluated using standard clinical procedures. EGFR amplifications were observed in 14% and ERBB2 amplifications in 23% of the reference cohort. EGFR gains were enriched in the Basal/SCC-like and ERBB2 gains in the Genomically Unstable subtypes. The expression data suggests that the Genomically Unstable show high ERBB2/ERBB3 but low EGFR expression and that Basal/SCC-like tumors show high EGFR but low ERBB2/ERBB3 expression. Whereas the frequency of ERBB2 genomic amplification were similar for cases of the Genomically Unstable subtype in the two cohorts, the Urothelial-like subtype acquires ERBB2 amplifications and expression during progression. Even though a good correlation between gene amplification and ERBB2 gene expression was observed in the Urothelial-like and Genomically Unstable subtypes less than half of the Basal/SCC-like cases with ERBB2 amplification showed concomitant ERBB2 mRNA and protein expression. We conclude that clinical trials using ERBB2 (HER2) or EGFR as targets have not fully appreciated the molecular heterogeneity in which activated ERBB2 and EGFR systems operate. Proper tumor classification is likely to be critical for arriving at thorough conclusions regarding new HER2 and EGFR based treatment regimes.
PMID: 28388586 [PubMed - as supplied by publisher]
http://ift.tt/2oRiJCB
A comparison of pectoralis versus lumbar skeletal muscle indices for defining sarcopenia in diffuse large B-cell lymphoma - two are better than one.
| Related Articles |
A comparison of pectoralis versus lumbar skeletal muscle indices for defining sarcopenia in diffuse large B-cell lymphoma - two are better than one.
Oncotarget. 2017 Mar 24;:
Authors: Go SI, Park MJ, Song HN, Kim HG, Kang MH, Kang JH, Kim HR, Lee GW
Abstract
BACKGROUNDS: Sarcopenia is known to be associated with poor clinical outcome in patients with diffuse large B-cell lymphoma (DLBCL). There is no consensus concerning the optimal method to define sarcopenia in DLBCL.
METHODS: We retrospectively reviewed 193 DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Sarcopenia was classified by the region where the pretreatment skeletal muscle index (SMI) was measured.
RESULTS: Both the sarcopenia-L3 and sarcopenia-pectoralis muscle (PM) groups had increased incidences of severe treatment-related toxicities and treatment discontinuation compared with the non-sarcopenia-L3 and non-sarcopenia-PM groups, respectively. The sarcopenia-L3 and non-sarcopenia-L3 groups had 5-year overall survival (OS) rates of 40.5% and 67.8% (p < 0.001), respectively. The sarcopenia-PM and non-sarcopenia-PM groups had 5-year OS rates of 35.9% and 69.0% (p < 0.001), respectively. When the sarcopenia-L3 alone and sarcopenia-PM alone groups were compared, there were no differences in baseline characteristics, treatment toxicity, or survival. In multivariate analysis, when compared with the non-sarcopenia-both group, OS was significantly worse in the sarcopenia-both group (HR, 2.480; 95% CI, 1.284 - 4.792; p = 0.007), but not in patients with either sarcopenia-L3 alone or sarcopenia-PM alone (p = 0.151).
CONCLUSIONS: L3- and PM-SMIs are equally useful to define sarcopenia, which is related to intolerance to R-CHOP therapy and to worse survival in patients with DLBCL. More prognostic information can be obtained when these two SMIs are combined to define sarcopenia.
PMID: 28388585 [PubMed - as supplied by publisher]
http://ift.tt/2oj3DVv
MALAT1 predicts poor survival in osteosarcoma patients and promotes cell metastasis through associating with EZH2.
| Related Articles |
MALAT1 predicts poor survival in osteosarcoma patients and promotes cell metastasis through associating with EZH2.
Oncotarget. 2017 Mar 24;:
Authors: Huo Y, Li Q, Wang X, Jiao X, Zheng J, Li Z, Pan X
Abstract
Osteosarcoma is the most common type of bone cancer, especially in children and young adults. Recently, long noncoding RNAs (lncRNAs) have emerged as new prognostic markers and gene regulators in several cancers, including osteosarcoma. In this study, we investigated the contributions of the lncRNA MALAT1 in osteosarcoma with a specific focus on its transcriptional regulation and its interaction with EZH2. Our results showed that MALAT1 was significantly increased in osteosarcoma specimens and cell lines. ROC curve analysis showed that MALAT1 had a higher area under the curve than alkaline phosphatase, and Kaplan-Meier survival analysis indicated that patients with high serum levels of MALAT1 showed reduced survival rate. Knockdown of MALAT1 decreased osteosarcoma cell invasion and promoted E-cadherin expression. Mechanistic investigations showed that MALAT1 was transcriptionally activated by TGF-β. Additionally, EZH2 is highly expressed and associated with the 3' end region of lncRNA MALAT1 in osteosarcoma, and this association finally suppressed the expression of E-cadherin. Subsequently, our gain and loss function assay showed that MALAT1 overexpression promoted cell metastasis and decreased E-cadherin level, however, this effect was partially reversed by EZH2 knockdown. In conclusion, our work illuminates that lncRNA MALAT1 is a potential diagnostic and prognostic factor in osteosarcoma and further demonstrates how MALAT1 confers an oncogenic function. Thus, lncRNA MALAT1 may serve as a promising prognostic and therapeutic target for osteosarcoma patients.
PMID: 28388584 [PubMed - as supplied by publisher]
http://ift.tt/2oc79Po
Oral cancer cells sustainedly infected with Porphyromonas gingivalis exhibit resistance to Taxol and have higher metastatic potential.
| Related Articles |
Oral cancer cells sustainedly infected with Porphyromonas gingivalis exhibit resistance to Taxol and have higher metastatic potential.
Oncotarget. 2017 Mar 24;:
Authors: Woo BH, Kim DJ, Choi JI, Kim SJ, Park BS, Song JM, Lee JH, Park HR
Abstract
Major obstacles to improving the prognosis of patients with oral squamous cell carcinoma (OSCC) are the acquisition of resistance to chemotherapeutic agents and development of metastases. Recently, inflammatory signals are suggested to be one of the most important factors in modulating chemoresistance and establishing metastatic lesions. In addition, epidemiological studies have demonstrated that periodontitis, the most common chronic inflammatory condition of the oral cavity, is closely associated with oral cancer. However, a correlation between chronic periodontitis and chemoresistance/metastasis has not been well established. Herein, we will present our study on whether sustained infection with Porphyromonas gingivalis, a major pathogen of chronic periodontitis, could modify the response of OSCC cells to chemotherapeutic agents and their metastatic capability in vivo. Tumor xenografts composed of P. gingivalis-infected OSCC cells demonstrated a higher resistance to Taxol through Notch1 activation, as compared with uninfected cells. Furthermore, P. gingivalis-infected OSCC cells formed more metastatic foci in the lung than uninfected cells.
PMID: 28388583 [PubMed - as supplied by publisher]
http://ift.tt/2okO9AD
Peptide-based PET imaging of the tumor restricted IL13RA2 biomarker.
| Related Articles |
Peptide-based PET imaging of the tumor restricted IL13RA2 biomarker.
Oncotarget. 2017 Mar 24;:
Authors: Sai KK, Sattiraju A, Almaguel FG, Xuan A, Rideout S, Krishnaswamy RS, Zhang J, Herpai DM, Debinski W, Mintz A
Abstract
Peptides that target cancer cell surface receptors are promising platforms to deliver diagnostic and therapeutic payloads specifically to cancer but not normal tissue. IL13RA2 is a tumor-restricted receptor found to be present in several aggressive malignancies, including in the vast majority of high-grade gliomas and malignant melanoma. This receptor has been successfully targeted for diagnostic and therapeutic purposes using modified IL-13 ligand and more recently using a specific peptide, Pep-1L. In the current work, we establish the in vitro and in vivo tumor binding properties of radiolabeled Pep-1L, designed for tumor imaging. We radiolabeled Pep-1L with Copper-64 and demonstrated specific cell uptake in the IL13RA2-over expressing G48 glioblastoma cell line having abundant IL13RA2 expression. [64Cu]Pep-1L binding was blocked by unlabeled ligand, demonstrating specificity. To demonstrate in vivo tumor uptake, we intravenously injected into tumor-bearing mice and demonstrated that [64Cu]Pep-1L specifically bound tumors at 24 hours, which was significantly blocked (3-fold) by pre-injecting unlabeled peptide. To further demonstrate specificity of Pep-1L towards IL13RA2 in vivo, we exploited an IL13RA2-inducible melanoma tumor model that does not express receptor at baseline but expresses abundant receptor after treatment with doxycycline. We injected [64Cu]Pep-1L into mice bearing IL13RA2-inducible melanoma tumors and performed in vivo PET/CT and post-necropsy biodistribution studies and found that tumors that were induced to express IL13RA2 receptor by doxycycline pretreatment bound radiolabeled Pep-1L 3-4 fold greater than uninduced tumors, demonstrating receptor specificity. This work demonstrates that [64Cu]Pep-1L selectively binds hIL13RA2-expressing tumors and validates Pep-1L as an effective platform to deliver diagnostics and therapeutics to IL13RA2-expressing cancers.
PMID: 28388582 [PubMed - as supplied by publisher]
http://ift.tt/2npRyyD
Temozolomide combined with irinotecan caused regression in an adult pleomorphic rhabdomyosarcoma patient-derived orthotopic xenograft (PDOX) nude-mouse model.
| Related Articles |
Temozolomide combined with irinotecan caused regression in an adult pleomorphic rhabdomyosarcoma patient-derived orthotopic xenograft (PDOX) nude-mouse model.
Oncotarget. 2017 Mar 24;:
Authors: Igarashi K, Kawaguchi K, Kiyuna T, Murakami T, Miwa S, Nelson SD, Dry SM, Li Y, Singh AS, Kimura H, Hayashi K, Yamamoto N, Tsuchiya H, Eilber FC, Hoffman RM
Abstract
Adult pleomorphic rhabdomyosarcoma (RMS) is a rare and recalcitrant, highly-malignant mesenchymal tumor in need of improved therapeutic strategies. Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). We previously described the development of a PDOX model of adult pleomorphic RMS where the tumor behaved similar to the patient donor. A high-grade pleomorphic rhabdomyosarcoma from a striated muscle was previously grown orthotopically in the right biceps-femoris muscle of nude mice to establish the PDOX model. In the present study, the PDOX models were randomized into the following treatment groups when tumor volume reached 100 mm3: G1, control without treatment; G2, cyclophosphamide (CPA) 140 mg/kg, intraperitoneal (i.p.) injection, weekly, for 3 weeks; G3, temozolomide (TEM), 25 mg/kg, per oral (p.o.), daily, for 21 days; G4, temozolomide (TEM) 25 mg/kg, p.o., daily, for 21 days combined with irinotecan (IRN), 4 mg/kg, i.p., daily for 21 days. After 3 weeks, treatment of PDOX with TEM combined with IRN was so powerful that it resulted in tumor regression and the smallest tumor volume compared to other groups. The RMS PDOX model should be of use to design the treatment program for the patient and for drug discovery and evaluation for this recalcitrant tumor type.
PMID: 28388581 [PubMed - as supplied by publisher]
http://ift.tt/2oc3Vvd
TIPE3 protein promotes breast cancer metastasis through activating AKT and NF-κB signaling pathways.
| Related Articles |
TIPE3 protein promotes breast cancer metastasis through activating AKT and NF-κB signaling pathways.
Oncotarget. 2017 Mar 23;:
Authors: Lian K, Ma C, Hao C, Li Y, Zhang N, Chen YH, Liu S
Abstract
TIPE3 (TNFAIP8L3) is the transfer protein of phosphoinositide second messengers that promote cancer. Its role in breast cancer has not been evaluated. We report here that TIPE3 protein was significantly upregulated in human breast cancer tissues as compared with adjacent non-tumor tissues from the same patients. The level of TIPE3 protein in invasive ductal carcinoma was significant higher than that in ductal carcinoma in situ (DCIS), and the level of TIPE3 in lymphatic metastasized carcinoma was higher than that in invasive ductal carcinoma from the same patients. Additionally, the level of TIPE3 protein was positively correlated with the level of human epidermal growth factor receptor 2 (HER-2), and TIPE3 expression was significantly higher in high-invasive breast cancer cell lines than that in low-invasive cell lines. Importantly, TIPE3 knockdown in breast cancer cells inhibited cell proliferation, migration, and invasion in vitro, whereas TIPE3 overexpression had the opposite effect. In mice, TIPE3 expression significantly promoted the metastasis of breast cancer cells. TIPE3 expression also increased the level of MMP2 and uPA, and the activation of the AKT and NF-κB signaling pathways. These results demonstrate that TIPE3 may promote breast cancer growth and metastasis through AKT and NF-κB, and may serve as a potential biomarker for breast cancer metastasis.
PMID: 28388580 [PubMed - as supplied by publisher]
http://ift.tt/2oc8Lsw
Rabies viruses leader RNA interacts with host Hsc70 and inhibits virus replication.
| Related Articles |
Rabies viruses leader RNA interacts with host Hsc70 and inhibits virus replication.
Oncotarget. 2017 Mar 23;:
Authors: Zhang R, Liu C, Cao Y, Jamal M, Chen X, Zheng J, Li L, You J, Zhu Q, Liu S, Dai J, Cui M, Fu ZF, Cao G
Abstract
Viruses have been shown to be equipped with regulatory RNAs to evade host defense system. It has long been known that rabies virus (RABV) transcribes a small regulatory RNA, leader RNA (leRNA), which mediates the transition from viral RNA transcription to replication. However, the detailed molecular mechanism remains enigmatic. In the present study, we determined the genetic architecture of RABV leRNA and demonstrated its inhibitory effect on replication of wild-type rabies, DRV-AH08. The RNA immunoprecipitation results suggest that leRNA inhibits RABV replication via interfering the binding of RABV nucleoprotein with genomic RNA. Furthermore, we identified heat shock cognate 70 kDa protein (Hsc70) as a leRNA host cellular interacting protein, of which the expression level was dynamically regulated by RABV infection. Notably, our data suggest that Hsc70 was involved in suppressing RABV replication by leader RNA. Finally, our experiments imply that leRNA might be potentially useful as a novel drug in rabies post-exposure prophylaxis. Together, this study suggested leRNA in concert with its host interacting protein Hsc70, dynamically down-regulate RABV replication.
PMID: 28388579 [PubMed - as supplied by publisher]
http://ift.tt/2oc1Yiz
The tumor suppressor interferon regulatory factor 8 inhibits β-catenin signaling in breast cancers, but is frequently silenced by promoter methylation.
| Related Articles |
The tumor suppressor interferon regulatory factor 8 inhibits β-catenin signaling in breast cancers, but is frequently silenced by promoter methylation.
Oncotarget. 2017 Mar 23;:
Authors: Luo X, Xiong X, Shao Q, Xiang T, Li L, Yin X, Li X, Tao Q, Ren G
Abstract
Interferon (IFN) regulatory factor 8 is encoded by a novel candidate tumor suppressor gene (IRF8), its promotor is frequently methylated in multiple cancers. However, the promoter methylation status, functions and underlying mechanisms of IRF8 in breast cancer remain unclear. We found that IRF8 was downregulated in breast cancer cell lines and primary tumors, compared with normal breast tissues, mainly because of aberrant promoter methylation. However, its expression was not associated with pathological characteristics. Restoration of IRF8 expression suppressed cell proliferation, colony formation, 5-ethynyl-2'-deoxyuridine incorporation, cell migration and invasion, and induced apoptosis and cell cycle arrest in vitro. IRF8 also inhibited xenograft growth in nude mice in vivo. Competition with IRF8 function by IRF8 mutant (K79E) enhanced cell migration and invasion in 4T1 murine cells in vitro. Importantly, IRF8, as both downstream target gene and regulator of IFN-γ/STAT1 signaling, inhibited canonical β-catenin signaling. These findings identify IRF8 as a novel tumor suppressor regulating IFN-γ/STAT1 signaling and β-catenin signaling in breast cancer.
PMID: 28388578 [PubMed - as supplied by publisher]
http://ift.tt/2oc0yo5
IL-6R/STAT3/miR-204 feedback loop contributes to cisplatin resistance of epithelial ovarian cancer cells.
| Related Articles |
IL-6R/STAT3/miR-204 feedback loop contributes to cisplatin resistance of epithelial ovarian cancer cells.
Oncotarget. 2017 Mar 27;:
Authors: Zhu X, Shen H, Yin X, Long L, Chen X, Feng F, Liu Y, Zhao P, Xu Y, Li M, Xu W, Li Y
Abstract
Enhanced chemoresistance is, among other factors, believed to be responsible for treatment failure and tumor relapse in patients with epithelial ovarian cancer (EOC). Here, we exposed EOC cells to interleukin-6 (IL-6) to activate oncogenic STAT3, which directly repressed miR-204 via a conserved STAT3-binding site near the TRPM3 promoter region upstream of miR-204. Repression of miR-204 was required for IL-6-induced cisplatin (cDDP) resistance. Furthermore, we identified the IL-6 receptor (IL-6R), which mediates IL-6-dependent STAT3 activation, as a direct miR-204 target. Importantly, the resulting IL-6R/STAT3/miR-204 feedback loop was identified in patients with EOC, and its activity correlated with chemosensitivity. Moreover, exogenous miR-204 blocked this circuit and enhanced cDDP sensitivity both in vitro and in vivo by inactivating IL-6R/STAT3 signaling and subsequently decreasing the expression of anti-apoptotic proteins. Our findings illustrate the function of this feedback loop in cDDP-based therapy and may offer a broadly useful approach to improve EOC therapy.
PMID: 28388577 [PubMed - as supplied by publisher]
http://ift.tt/2oceTkx
Proton pump inhibitor ilaprazole suppresses cancer growth by targeting T-cell-originated protein kinase.
| Related Articles |
Proton pump inhibitor ilaprazole suppresses cancer growth by targeting T-cell-originated protein kinase.
Oncotarget. 2017 Mar 27;:
Authors: Zheng M, Luan S, Gao S, Cheng L, Hao B, Li J, Chen Y, Hou X, Chen L, Li H
Abstract
T-cell-originated protein kinase (TOPK) is highly and frequently expressed in various cancer tissues and plays an indispensable role in the mitosis of cancer cells, and therefore, it is an important target for drug treatment of tumor. Ilaprazole was identified to be a potent TOPK inhibitor. The data indicated that ilaprazole inhibited TOPK activities with high affinity and selectivity. In vitro studies showed that ilaprazole inhibited TOPK activities in HCT116, ES-2, A549, SW1990 cancer cells. Moreover, knockdown of TOPK in these cells decreased their sensitivities to ilaprazole. Results of an in vivo study demonstrated that gavage of ilaprazole in HCT116 colon tumor-bearing mice effectively suppressed cancer growth. The TOPK downstream signaling molecule phospho-histone H3 in tumor tissues was also decreased after ilaprazole treatment. Our results suggested that ilaprazole inhibited the cancer growth by targeting TOPK both in vitro and in vivo.
PMID: 28388576 [PubMed - as supplied by publisher]
http://ift.tt/2occYwt
Cofilin 1 induces the epithelial-mesenchymal transition of gastric cancer cells by promoting cytoskeletal rearrangement.
| Related Articles |
Cofilin 1 induces the epithelial-mesenchymal transition of gastric cancer cells by promoting cytoskeletal rearrangement.
Oncotarget. 2017 Mar 27;:
Authors: Haibo W, Lide T, Feng J, Hao G, Xiaojun D, Tengyang N, Jun F, Yanbing D, Weiming X, Yayun Q, Yanqing L
Abstract
Epithelial-mesenchymal transition (EMT) is an important biological process whereby malignant tumor cells obtain the ability to migrate, invade, resist apoptosis and degrade the extracellular matrix. We found that Cofilin1 (CFL1) expression was elevated in clinical gastric cancer specimens and correlated with biomarkers of EMT in BGC-823 gastric cancer cells. BGC-823 cells exhibited EMT phenotypes and increased metastatic ability when induced by TGF-β1. By contrast, BGC-823 cells transfected with Lv-siRNA-CFL1 did not exhibit EMT phenotypes under the same inducing conditions. As CFL1 expression increased, EMT cell filopodia stretched out. In addition, the ultrastructures observed using transmission electron microscopy indicated that silencing of CFL1 markedly inhibited depolymerization of fibrous actin and cytoskeletal reorganization during EMT. Similar results were obtained in vivo. These findings demonstrate that CFL1 induces EMT by promoting cytoskeletal rearrangement. Our results may provide the basis for developing new anticancer drugs to inhibit CFL1.
PMID: 28388575 [PubMed - as supplied by publisher]
http://ift.tt/2oc1ZmD
Over-expression of growth differentiation factor 15 (GDF15) preventing cold ischemia reperfusion (I/R) injury in heart Transplantation through Foxo3a signaling.
| Related Articles |
Over-expression of growth differentiation factor 15 (GDF15) preventing cold ischemia reperfusion (I/R) injury in heart Transplantation through Foxo3a signaling.
Oncotarget. 2017 Mar 27;:
Authors: Zhang Y, Moszczynski LA, Liu Q, Jiang J, Zhao D, Quan D, Mele T, McAlister V, Jevnikar A, Baek SJ, Liu K, Zheng X
Abstract
Ischemia reperfusion (I/R) injury which inevitably occurs during heart transplantation is the major factor leading to organ failure and graft rejection. In order to develop new therapies to prevent I/R injury, we used both a murine heart transplantation model with 24 hour cold I/R and an in vitro cell culture system to determine whether growth differentiation factor 15 (GDF15) is a protective factor in preventing I/R injury in heart transplantation and to further investigate underlying mechanisms of I/R injury. We found that cold I/R caused severe damage to the endocardium, epicardium and myocardium of heart grafts from wild type C57BL/6 mice, whereas grafts from GDF15 transgenic (TG) mice showed less damage as demonstrated by decreased cell apoptosis/death, decreased neutrophils infiltration and the preservation of the normal structure of the heart. Over-expression of GDF15 reduced expression of phosphorylated RelA p65, pre-inflammatory and pro-apoptotic genes while it enhanced Foxo3a phosphorylation in vitro and in vivo. Over-expression of GDF15 inhibited cell apoptosis/death and reduced neutrophil infiltration. In conclusion, this study, for the first time, demonstrates that GDF15 is a promising target for preventing cold I/R injury in heart transplantation. This study also shows that the resultant protective effects are mediated by the Foxo3 and NFκB signaling pathways.
PMID: 28388574 [PubMed - as supplied by publisher]
http://ift.tt/2oT6XEN
aMSH prevents ROS-induced apoptosis by inhibiting Foxo1/ mTORC2 in mice adipose tissue.
| Related Articles |
aMSH prevents ROS-induced apoptosis by inhibiting Foxo1/ mTORC2 in mice adipose tissue.
Oncotarget. 2017 Mar 27;:
Authors: Cao W, Li M, Wu T, Feng F, Feng T, Xu Y, Sun C
Abstract
Alpha-melanocyte stimulating hormone (αMSH) is an important adenohypophysis polypeptide hormone that regulates body metabolic status. To date, it is well known that the disorder of hypothalamic αMSH secretion is related to many metabolic diseases, such as obesity and type II diabetes. However, the underlying mechanisms are poorly understood. In our study, we focused on the reactive oxygen species (ROS)-induced adipocyte apoptosis and tried to unveil the role of αMSH in this process and the signal pathway which αMSH acts through. Kunming white mice were used and induced to oxidative stress status by hydrogen peroxide (H2O2) injection and a significant reduction of αMSH were found in mice serum, while elevated ROS level and mRNA level of pro-apoptotic genes were observed in mice adipose tissue. What is more, when detect the function of αMSH in ROS-induced apoptosis, similar inhibitory trend was found with the oxidative stress inhibitor N-acetyl-L-cysteine (NAC) in ROS-induced adipocyte apoptosis and this trend is αMSH receptor melanocortin 5 receptor (MC5R) depended, while an opposite trend was found between αMSH and Foxo1, which is a known positive regulator of adipocyte apoptosis. Further, we found that the repress effect of αMSH in adipocytes apoptosis is acting through Foxo1/mTORC2 pathway. These findings indicate that, αMSH has a strong inhibitory effect on ROS-induced adipocyte apoptosis and underlying mechanism is interacting with key factors in mTOR signal pathway. Our study demonstrated a great role of αMSH in adipocyte apoptosis and brings a new therapeutic mean to the treatment of obesity and diabetes.
PMID: 28388573 [PubMed - as supplied by publisher]
http://ift.tt/2oR9FNK
Combination GITR targeting/PD-1 blockade with vaccination drives robust antigen-specific antitumor immunity.
| Related Articles |
Combination GITR targeting/PD-1 blockade with vaccination drives robust antigen-specific antitumor immunity.
Oncotarget. 2017 Mar 27;:
Authors: Villarreal DO, Chin D, Smith MA, Luistro LL, Snyder LA
Abstract
Tumor progression is facilitated immunologically by mechanisms that include low antigen expression, an absence of coimmunostimulatory signals, and the presence of regulatory T cells (Tregs), all of which act to suppress and restrict effector T cells in the tumor. It may be possible to overcome these conditions by a combination of modulatory immunotherapy agents and tumor-antigen targeting to activate and drive effective antitumor T cell responses. Here, we demonstrated that co-administration of aGITR and aPD-1 monoclonal antibodies (mAb) in combination with a peptide vaccine (Vax) in mice bearing established tumors significantly delayed tumor growth and induced complete regression in 50% of the mice. This response was associated with increased expansion and functionality of potent Ag-specific polyfunctional CD8+ T cells, reduced Tregs, and the generation of memory T cells. Tumor regression correlated with the expansion of tumor-infiltrating antigen-specific CD8+ effector memory T cells, as depletion of this cell population significantly reduced the effectiveness of the triple combination Vax/aGITR/aPD-1 therapy. These findings support the concept that dual aGITR/aPD-1 combination with cancer vaccines may be a novel strategy against poorly immunogenic tumors.
PMID: 28388572 [PubMed - as supplied by publisher]
http://ift.tt/2oR9DW8
The role of interleukin-1β and extracellular signal-regulated kinase 1/2 in glucose-stimulated insulin secretion
Publication date: Available online 7 April 2017
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Ben Niu, Heng Su, Xue-Shan Xia, Qiu He, Yuan-Ming Xue, Xin-Ming Yan
Glucose-stimulated insulin secretion (GSIS) is one of the important physiological characteristics of islet β cells, and extracellular-regulated protein kinase 1/2 (ERK1/2) is an important member of the mitogen-activated protein kinase family that regulates this process. The inflammatory cytokine interleukin (IL)-1β can inhibit the insulin secretion of pancreatic β cells, but the exact mechanism is unclear. This study was designed to investigate the inhibitory effect of IL-1β on GSIS in βTC-6 cells and its relation with the ERK1/2 signal transduction pathway. β-TC6 cells were cultured and stimulated with 0mM, 1.38mM, or 5.5mM glucose. In addition, GSIS in β-TC6 cells was blocked by IL-1β at concentrations of 0.15 ng/mL, 1.5 ng/mL, and 15 ng/mL. After glucose stimulation and IL-1β intervention, the insulin level in the cell supernatant was detected by radioimmunoassay, and the phosphorylation level of ERK1/2 was detected by western blotting assay. The insulin level in the 1.38mM glucose group was 108.52 ± 5.94 uIU/mL, which was significantly higher than the 0mM and 5.5mM glucose groups (p < 0.05). Compared with the 0mM glucose group, the level of ERK1/2 phosphorylation was increased in the 1.38mM and 5.5mM glucose groups. After intervention by 0.15 ng/mL, 1.5 ng/mL, and 15 ng/mL IL-1β, the level of ERK1/2 phosphorylation induced by 1.38mM glucose stimulation decreased in a dose-dependent manner, and the insulin level correspondingly decreased. IL-1β can inhibit GSIS in βTC-6 cells, which is related to its inhibition of the phosphorylation of ERK1/2.
http://ift.tt/2oRhjYN
Enhancement and Suppression of Tactile Signals During Reaching.
Author: Voudouris, Dimitris; Fiehler, Katja
DOI: 10.1037/xhp0000373
Publication Date: POST AUTHOR CORRECTIONS, 6 April 2017
http://ift.tt/2pfGbFQ
Digit-Color Synaesthesia Only Enhances Memory for Colors in a Specific Context: A New Method of Duration Thresholds to Measure Serial Recall.
Author: Teichmann, A. Lina; Nieuwenstein, Mark R.; Rich, Anina N.
DOI: 10.1037/xhp0000402
Publication Date: POST AUTHOR CORRECTIONS, 6 April 2017
http://ift.tt/2oc3Esk
Words We Do Not Say-Context Effects on the Phonological Activation of Lexical Alternatives in Speech Production.
Author: Jescheniak, Jorg D.; Kurtz, Franziska; Schriefers, Herbert; Gunther, Josefine; Klaus, Jana; Madebach, Andreas
DOI: 10.1037/xhp0000352
Publication Date: POST AUTHOR CORRECTIONS, 6 April 2017
http://ift.tt/2nsMklO
On the Origin of Body-Related Influences on Visual Perception.
Author: Kirsch, Wladimir; Herbort, Oliver; Ullrich, Benjamin; Kunde, Wilfried
DOI: 10.1037/xhp0000358
Publication Date: POST AUTHOR CORRECTIONS, 6 April 2017
http://ift.tt/2odxjTO
Adding Depth to Overlapping Displays Can Improve Visual Search Performance.
Author: Godwin, Hayward J.; Menneer, Tamaryn; Liversedge, Simon P.; Cave, Kyle R.; Holliman, Nick S.; Donnelly, Nick
DOI: 10.1037/xhp0000353
Publication Date: POST AUTHOR CORRECTIONS, 6 April 2017
http://ift.tt/2odvq9r
The Impact of Evidence Reliability on Sensitivity and Bias in Decision Confidence.
Author: Boldt, Annika; de Gardelle, Vincent; Yeung, Nick
DOI: 10.1037/xhp0000404
Publication Date: POST AUTHOR CORRECTIONS, 6 April 2017
http://ift.tt/2pfJr4e
Is Orthographic Information From Multiple Parafoveal Words Processed in Parallel: An Eye-Tracking Study.
Author: Cutter, Michael G.; Drieghe, Denis; Liversedge, Simon P.
DOI: 10.1037/xhp0000408
Publication Date: POST AUTHOR CORRECTIONS, 6 April 2017
http://ift.tt/2odxiPK
The Effect of Episodic Retrieval on Inhibition in Task Switching.
Author: Grange, James A.; Kowalczyk, Agnieszka W.; O'Loughlin, Rory
DOI: 10.1037/xhp0000411
Publication Date: POST AUTHOR CORRECTIONS, 6 April 2017
http://ift.tt/2pfMCsN
Simulum fly bites
Publication date: Available online 8 April 2017
Source:Medical Journal Armed Forces India
Author(s): Rupesh Prasad, A.S. Kushwaha
http://ift.tt/2nsP9n0
Myxoid Spitz Nevi: Report of 6 Cases.
Mucin deposition in Spitz nevus seems to be a very rare phenomenon, as there have only been 3 cases previously published. We report 6 additional cases, half of them in women, and half in men. The ages of the patients varied from 5 to 47 years (mean = 30.17). Sizes of the nevi varied from 3 to 6 mm. Four lesions were located on the extremities, whereas one was located on the trunk (there was no clinical information about the other). A vascular lesion was suspected in 2 cases. Excision with clear margins was achieved in all cases but one. So far, there have been no recurrences after follow-ups varying from 1 to 5 years. The biopsy showed a symmetrical melanocytic Spitz nevus in all cases. Three cases were compound, and 3 cases were junctional nevi. The epidermis was either acanthotic or hyperplastic in all cases, with no epidermal consumption. Kamino bodies were found in 4 cases. The deposit of mucin was moderate in 5 cases and mild in one case. Mucin was found in the stroma between the dermal melanocytes in cases of compound nevi and in the melanocytic nests of the junctional component. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2obNZcH
http://ift.tt/2obNZcH
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