Propofol Suppresses Proinflammatory Cytokine Production by Increasing ABCA1 Expression via Mediation by the Long Noncoding RNA LOC286367

We previously reported that propofol upregulated the expression of ATP-binding cassette transporter subfamily A member 1 (ABCA1) via peroxisome proliferator-activated receptor gamma/liver X receptor in macrophage-derived foam cells. Here, we provide evidence that in addition to inducing ABCA1 expression, propofol represses proinflammatory cytokine production by increasing ABCA1 expression in a LOC286367-dependent manner. Western blot analysis showed that ABCA1 expression was elevated in macrophages by propofol treatment and this effect was markedly reduced by LOC286367 overexpression. Moreover, propofol treatment downregulated the production of the proinflammatory cytokines interleukin-6, tumor necrosis factor, and interferon gamma in lipopolysaccharide-stimulated macrophages by enhancing ABCA1 expression. Notably, propofol achieved this effect in a LOC286367-dependent manner. To the best of our knowledge, this is the first report of the mechanism in which propofol represses proinflammatory cytokine production mediated by ABCA1.

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Clinical and histopathologic prognostic implications of the expression of cytokeratins 8, 10, 13, 14, 16, 18 and 19 in oral and oropharyngeal squamous cell carcinoma

Publication date: Available online 16 December 2018

Source: Archives of Oral Biology

Author(s): Rima-A. Safadi, Niveen-I. Abdullah, Rolla-F. Alaaraj, Dima H. Bader, Darshan D. Divakar, Abed H. Hamasha, Maher A. Sughayer

ABSTRACT

Objectives

To identify cytokeratins (CK) of significant correlations with clinical and histopathologic prognostic parameters in oral and oropharyngeal squamous cell carcinoma (SCC).

Design

The sample consisted of 100 cases retrieved from the archives of the Pathology Department/ King Hussein Cancer Center/Amman/ Jordan. Recorded data included: age, gender, location, grade, depth of invasion, the presence of epithelial dysplasia, tumor size, lymph node metastasis, number of positive lymph nodes, distant metastases, clinical stage, local recurrence, treatment modalities and 5-year survival rate. Immunohistochemical staining of 6 cytokeratins: 8, 10, 13, 14, 16, 18, and 19 was performed using standard protocols. Stained sections were digitized and analyzed using ImageJ-color deconvolution to identify the percentage of cytokeratin-positive area (score). Statistical tests used were: student t-test, analysis of variance, bivariate analysis and logistic regression.

Results

Lower CK8,18, 19 scores correlated with lower 5-year survival rate. Higher CK19 and lower CK 10, 14, 16 scores were associated with distant metastasis. Increased CK8, 18, 19 scores correlated with higher stage and with higher depth of invasion. The higher CK18 score was associated with local recurrence. Higher CK10, 13, 16 scores correlated with well-differentiated grade. Higher CK19 and lower CK16 scores were associated with adjacent epithelial dysplasia. Regression analysis showed that better 5-year survival rate was significantly correlated with increased CK16, decreased CK18 and 19 scores.

Conclusion

Expression scores of a panel of cytokeratin are potential prognostic indicators for 5-year survival and correlates with other prognostic parameters.

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Salivary opiorphin in dental pain: a potential biomarker for dental disease

Publication date: Available online 15 December 2018

Source: Archives of Oral Biology

Author(s): Mahmut Sertac Ozdogan, Mustafa Gungormus, Selen Ince Yusufoglu, Sinan Yasin Ertem, Cigdem Sonmez, Metin Orhan

Abstract

Objectives

Opiorphin is a recently discovered peptide shown to inhibit the enkephalin-degrading enzymes and prolong the effects of enkephalins. Although opiorphin is found in high concentrations in saliva, the relationship between salivary opiorphin and orofacial pains is not yet fully understood. We aimed to determine salivary opiorphin concentrations in dental pain related to symptomatic irreversible pulpitis (SIP), and symptomatic periapical periodontitis (SAP).

Design

39 patients participated in this study. The participants were categorized into SIP and SAP based on their diagnosis. All the patients were treated with root canal treatment. Saliva specimens were collected, and pain levels were recorded at pre-treatment, 7 days post-treatment and 30 days post-treatment. Saliva opiorphin levels were measured using a commercially available ELISA kit. Pre-treatment and post-treatment opiorphin levels were evaluated using repeated measures ANOVA. Correlations between VAS scores, opiorphin levels and age were evaluated using Spearman's Rank Correlation.

Results

The average saliva opiorphin level pre-treatment, 7 days post-treatment and 30 days post-treatment were 31.28 ± 7.10 ng/ml, 20.41 ± 2.67 ng/ml and 18.61 ± 2.05 ng/ml respectively. Significantly higher pre-treatment opiorphin levels were observed in the SIP group compared to the SAP group. A strong correlation was observed between the pre-treatment pain levels and the saliva opiorphin concentrations.

Conclusions

Our findings indicate that saliva opiorphin levels increase in inflammation related dental pain. The level of salivary opiorphin is strongly correlated with the reported level of pain. The extent of the inflammation (pulpal vs. periodontal) also affects the opiorphin level.

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Pathogenic Role of Reinke's Edema in Snoring and Obstructive Sleep Apnea

Publication date: Available online 15 December 2018

Source: Journal of Voice

Author(s): Abdul-Latif Hamdan, Elie Khalifee, Pierre R. Abi Akl, Anthony Ghanem, Aya El Hage

Abstract

Objective

To investigate the association between vocal fold Reinke's edema, snoring, and obstructive sleep apnea.

Design/Methods

Twenty-five patients diagnosed with Reinke's edema and 25 patients with normal laryngeal examination, matched according to age, gender, and body mass index were recruited for this prospective study. Demographic data included age, gender, and body mass index. All patients filled the Berlin Questionnaire, STOP-BANG Sleep Apnea Questionnaire, and the Epworth Sleepiness Questionnaire.

Results

Out of 25 patients with Reinke's edema, 36% had Obstructive Sleep Apnea (OSA) as evidenced by having two or more positive categories in the Berlin Questionnaire. In the control group, only 4% had OSA.The difference between the two groups was statistically significant (P value = 0.005). With respect to Epworth Sleepiness Scale and the STOP-BANG Sleep Apnea Questionnaire (P value > 0.05), there was no statistically significant difference between the two groups.

Conclusions

This investigation revealed higher prevalence of snoring and obstructive sleep apnea in patients with Reinke's edema as evidenced by the Berlin Questionnaire. The caring physician should be alert to symptoms of airway obstruction for possible early intervention.

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Vocal Tract Discomfort and Dysphonia in Patients Undergoing Empiric Therapeutic Trial with Proton Pump Inhibitor for Suspected Laryngopharyngeal Reflux

Publication date: Available online 15 December 2018

Source: Journal of Voice

Author(s): F Mozzanica, C Robotti, JR Lechien, N Pizzorni, F Pirola, A Mengucci, A Dell'Era, F Ottaviani, A Schindler

Abstract

Introduction

the aim of this study was to evaluate the correlation among dysphonic and vocal tract discomfort symptoms in patients who underwent empiric therapeutic trial with proton pump inhibitor (PPI) for a suspected laryngopharyngeal reflux (LPR).

Materials and methods

A total of 34 patients with suspected LPR were enrolled in this study. All of them were evaluated using the reflux finding score, the reflux symptom Index (RSI), the vocal tract discomfort scale (VTDS), and the voice symptom scale (VoiSS) before and after the PPI treatment.

Results

A significant difference was found between pretreatment and posttreatment reflux finding score, RSI, VTDS, and VoiSS scores. Significant correlations among RSI, VTDS, and VoiSS before the PPI treatment were found.

Conclusion

PPI treatment determined a significant improvement of symptoms related to dysphonia and vocal tract discomfort in patients with suspected LPR, in addition, significant correlations among the RSI, VTDS, and VoiSS scores were demonstrated thus suggesting that LPR might influence the response of questionnaires not specifically developed in order to assess the complains in LPR patient.

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A New Model Based on 25-Hydroxyvitamin D3 for Predicting Active Crohn’s Disease in Chinese Patients

Background. The association between vitamin D3 and activity of Crohn's disease (CD) is unclear in Chinese patients. In this study, we aimed to evaluate the correlations between serum levels of 25-hydroxyvitamin D3 (25(OH)D3) and disease activity and predict active disease based on vitamin D status. Methods. Between January 2014 and December 2017, 346 CD patients from the First Affiliated Hospital of Sun Yat-sen University were recruited and categorized into a group with 25(OH)D3 ≤ 20 ng/ml and a group with 25(OH)D3 > 20 ng/ml. The clinical characteristics, medication, and health-care needs were compared between the groups. The correlations among 25(OH)D3 and routine serum biomarkers and disease activity were examined. The predictive efficiency of 25(OH)D3 and other biomarkers for active diseases was also explored using receiver-operating characteristic (ROC) curve analysis. A new predictive model, , and a nomogram were established using Logistic Regression. Results. Patients with 25(OH)D3 ≤ 20 ng/ml had higher serum levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and platelets (PLT) and lower levels of hemoglobin (Hb) and albumin (ALB). Serum levels of 25(OH)D3 were inversely correlated with the score of Crohn's Disease Activity Index (CDAI) (). ROC analysis showed a better predictive value of −25(OH)D3 and the new model with areas under curve (AUC) of 0.804 and 0.879, respectively, than those of CRP (0.693) and ESR (0.713) in disease activity. A nomogram for prediction was established with a c-index of 0.882. Conclusions. Serum levels of 25(OH)D3 negatively correlated with CD activity in Chinese patients. The new model and a nomogram based on 25(OH)D3 showed a better efficiency in predicting disease activity in CD patients but warrants further study.

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CXCR4 enhances cisplatin resistance of human tongue squamous cell carcinoma

Abstract

Background

The chemokine receptor 4 (CXCR4) plays an important role in tumor progression. Overexpressed CXCR4 is associated with a poor prognosis of patient with head and neck squamous cell carcinomas. However, the correlation between CXCR4 and chemotherapy resistance in tongue squamous cell carcinoma (TSCC) remains obscure.

Methods

Stable cisplatin‐resistant CAL27 CDDP and SCC25 CDDP cells were established and identified by CCK8 assay, and the CXCR4 expression was detected using qRT‐PCR and western blot. CXCR4‐siRNA was transfected into TSCC CDDP cells, whose transfect efficiency was examined. Cisplatin sensitivity was further detected, as well as several proliferation and apoptosis related proteins.

Results

CAL27 CDDP and SCC25 CDDP cells were successfully established, which exhibited significantly higher cell viability and less apoptosis under cisplatin stimulation than that of parental cells. CXCR4 expression was increased in TSCC CDDP cells. After transfection of CXCR4‐siRNA, the expression of CXCR4 was reduced by 73% and 78% in CAL27 CDDP and SCC25 CDDP cells, respectively. CCK8 assay and flow cytometry assay revealed that the proliferative capacity under cisplatin stimulation significantly decreased after CXCR4 silencing. Moreover, increased TSCC CDDP cells were arrested in the G0/G1 phase after knockdown of CXCR4. Compared with negative control group, the expression of cyclin D1 and p‐AKT decreased, while that of p‐caspase‐3 and Bax significantly increased.

Conclusions

Silencing CXCR4 may evidently inhibit proliferation, induce apoptosis and enhance cisplatin sensitivity of TSCC CDDP cells by reduced cyclin D1 and p‐AKT, and increased p‐caspase‐3 and Bax.

This article is protected by copyright. All rights reserved.

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A device to improve fabrication of a conversion prosthesis for immediate loading of dental implants

Publication date: Available online 15 December 2018

Source: The Journal of Prosthetic Dentistry

Author(s): Avinash S. Bidra

Abstract

A common challenge of fabricating a conversion prosthesis for immediate loading of dental implants is preventing the acrylic resin from flowing over the polished metal cuff of the titanium cylinders. Excess acrylic resin that accidentally flows over the polished metal cuff and adheres to it can impede insertion and the proper fit of the conversion prosthesis after surgery. Subsequent removal of the excess acrylic resin using rotary or hand instruments can scratch and damage the polished metal cuff, resulting in increased plaque accumulation and subsequent inflammation and the potential for hard and soft tissue loss during the early stages of healing. This article describes a novel device, a conversion cap, that can be screwed into the titanium cylinders to prevent any acrylic resin from flowing over the polished metal cuff. In addition, it can be attached during finishing and polishing the conversion prosthesis or definitive prosthesis to eliminate any risk of scratches over the metal cuff and allow dental laboratory technicians and clinicians to improve the quality of the prostheses.

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CAD-CAM acrylic resin prosthesis superstructure: A technique for fabricating an implant-supported fixed complete denture

Publication date: Available online 15 December 2018

Source: The Journal of Prosthetic Dentistry

Author(s): Kazunari Takanashi, Hamoud Alfarsi, Winston W.L. Chee, Alireza Moshaverinia

Abstract

The implant-supported fixed complete denture is a common treatment option in implant prosthodontics but has shortcomings that include the high wear rate of the acrylic resin denture material and the displacement of denture teeth from the denture base. This report describes a method for fabricating implant-supported fixed dental prostheses using computer-aided design and computer-aided manufacturing technology.

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A digital implant custom tray fabrication method using the design process for simulating the position of the impression copings and 3D printing technology

Publication date: Available online 15 December 2018

Source: The Journal of Prosthetic Dentistry

Author(s): Jong-Eun Kim, Dong-Ho Kwon, Jee-Hwan Kim, June-Sung Shim

Abstract

The technique described allowed an implant custom tray to be fabricated referencing the location of connected impression copings. The technique uses dental computer-aided design (CAD) software and 3D printing technology. The method controls the thickness of the impression material around the impression copings, improving the impression-making process.

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Micro-Net: A unified model for segmentation of various objects in microscopy images

Publication date: Available online 15 December 2018

Source: Medical Image Analysis

Author(s): Shan E Ahmed Raza, Linda Cheung, Muhammad Shaban, Simon Graham, David Epstein, Stella Pelengaris, Michael Khan, Nasir M. Rajpoot

Abstract

Object segmentation and structure localization are important steps in automated image analysis pipelines for microscopy images. We present a convolution neural network (CNN) based deep learning architecture for segmentation of objects in microscopy images. The proposed network can be used to segment cells, nuclei and glands in fluorescence microscopy and histology images after slight tuning of input parameters. The network trains at multiple resolutions of the input image, connects the intermediate layers for better localization and context and generates the output using multi-resolution deconvolution filters. The extra convolutional layers which bypass the max-pooling operation allow the network to train for variable input intensities and object size and make it robust to noisy data. We compare our results on publicly available data sets and show that the proposed network outperforms recent deep learning algorithms.

Graphical abstract

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House dust mite drives pro‐inflammatory eicosanoid reprogramming and macrophage effector functions

Abstract

Background

Eicosanoid lipid mediators play key roles in type 2 immune responses, e.g. in allergy and asthma. Macrophages represent major producers of eicosanoids and they are key effector cells of type 2 immunity. We aimed to comprehensively track eicosanoid profiles during type 2 immune responses to house dust mite (HDM) or helminth infection and to identify mechanisms and functions of eicosanoid reprogramming in human macrophages.

Methods

We established an LC‐MS/MS workflow for the quantification of 52 oxylipins to analyze mediator profiles in human monocyte derived macrophages (MDM) stimulated with HDM and during allergic airway inflammation (AAI) or nematode infection in mice. Expression of eicosanoid enzymes was studied by qPCR and western blot and cytokine production was assessed by multiplex assays.

Results

Short (24h) exposure of alveolar‐like MDM (aMDM) to HDM suppressed 5‐LOX expression and product formation, while triggering prostanoid (thromboxane and prostaglandin D₂ and E₂) production. This eicosanoid reprogramming was p38‐dependent, but Dectin‐2‐independent. HDM also induced pro‐inflammatory cytokine production, but reduced granulocyte recruitment by aMDM. In contrast, high levels of cysteinyl leukotrienes (cysLTs) and 12‐/15‐LOX metabolites were produced in the airways during AAI or nematode infection in mice.

Conclusion

Our findings show that a short exposure to allergens as well as ongoing type 2 immune responses are characterized by a fundamental reprogramming of the lipid mediator metabolism with macrophages representing particularly plastic responder cells. Targeting mediator reprogramming in airway macrophages may represent a viable approach to prevent pathogenic lipid mediator profiles in allergy or asthma.

This article is protected by copyright. All rights reserved.

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Sequential conflict resolution under multiple concurrent conflicts: An ERP study

Publication date: Available online 15 December 2018

Source: NeuroImage

Author(s): Alodie Rey-Mermet, Miriam Gade, Marco Steinhauser

Abstract

The purpose of the present study was to determine whether responding to multiple concurrent conflicts results in a simultaneous or sequential conflict resolution. To this end, we measured event-related potentials (ERPs) in a paradigm combining a Stroop and a flanker task. In this paradigm, participants were asked to respond to the color of the central letter while ignoring the meaning of the word (Stroop task) and the color of the flanking letters (flanker task). Trials were either incongruent (i.e., inducing a conflict between two response alternatives) or congruent (i.e., inducing no response conflict) in both tasks, or incongruent in one task and congruent in the other task. The behavioral results showed a smaller Stroop congruency effect (i.e., a smaller difference between Stroop incongruent and congruent trials) for flanker incongruent than for flanker congruent trials, replicating previous findings. The ERP results showed that an early ERP component (i.e., P2) was associated with the resolution of the flanker conflict, whereas a later component (i.e., N450) was associated with the resolution of the Stroop conflict. Together, these findings emphasize a sequential organization of conflict resolution processes in the brain which is adaptive when facing multiple concurrent conflicts.

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Involvement of M1 Macrophage Polarization in Endosomal Toll-Like Receptors Activated Psoriatic Inflammation

Psoriasis is a chronic inflammatory skin disorder that affects ~2%–3% of the worldwide population. Inappropriate and excessive activation of endosomal Toll-like receptors 7, 8, and 9 (TLRs 7–9) at the psoriatic site has been shown to play a pathogenic role in the onset of psoriasis. Macrophage is a major inflammatory cell type that can be differentiated into phenotypes M1 and M2. M1 macrophages produce proinflammatory cytokines, and M2 macrophages produce anti-inflammatory cytokines. The balance between these two types of macrophages determines the progression of various inflammatory diseases; however, whether macrophage polarization plays a role in psoriatic inflammation activated by endosomal TLRs has not been investigated. In this study, we investigated the function and mechanism of macrophages related to the pathogenic role of TLRs 7–9 in the progression of psoriasis. Analysis of clinical data in database revealed significantly increased expression of macrophage markers and inflammatory cytokines in psoriatic tissues over those in normal tissues. In animal studies, depletion of macrophages in mice ameliorated imiquimod, a TLR 7 agonist-induced psoriatic response. Imiquimod induced expression of genes and cytokines that are signature of M1 macrophage in the psoriatic lesions. In addition, treatment with this TLR 7 agonist shifted macrophages in the psoriatic lesions to a higher M1/M2 ratio. Both of the exogenous and endogenous TLR 7–9 ligands activated M1 macrophage polarization. M1 macrophages expressed higher levels of proinflammatory cytokines and TLRs 7–9 than M2 macrophages. These results suggest that by rendering macrophages into a more inflammatory status and capable of response to their ligands in the psoriatic sites, TLR 7–9 activation drives them to participate in endosomal TLR-activated psoriatic inflammation, resulting in an amplified inflammatory response. Our results also suggest that blocking M1 macrophage polarization could be a strategy which enables inhibition of psoriatic inflammation activated by these TLRs.

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Lepidium meyenii Walp Exhibits Anti-Inflammatory Activity against ConA-Induced Acute Hepatitis

Strong inflammation is a prominent pathogenesis of acute hepatitis, which can induce hepatocyte death and lead to liver failure. Lepidium meyenii Walp (Maca) is a traditional herbal medicine mostly used in improving sperm motility and serum hormone levels, etc. However, there are no reports that showed Maca was designed for treating hepatitis so far. Therefore, the protective effects and pharmacological mechanisms of Maca are unknown in hepatitis. In this study, we found that the protective effects of Maca extract ameliorate ConA-induced acute hepatitis (CIH) and underlying mechanisms. We determined that pretreatment with Maca extract significantly suppressed the production of aminotransferases and inflammatory cytokines, including IFN-γ, TNF-α, IL-1β, IL-2, IL-6, IL-12, and IL-17a, and moderated acute liver injury in CIH. Maca recruited more myeloid-derived suppressor cells (MDSCs) to the liver and suppressed infiltration of natural killer T cells (NKT cells) and macrophages in the liver. Furthermore, our data indicated the molecular mechanism of the inhibitory inflammatory effects of Maca, which should suppress the activation of NF-κB, IFN-γ/STAT1, and IL-6/STAT3 signalings. Collectively, this present research explores Maca as an effective hepatoprotective medicine to inhibit inflammation and liver injury caused by acute hepatitis.

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