Scarring, tightly associated with fibrosis, is a significant symptomatic clinical problem. Interleukin 10 (IL-10) has been identified as a candidate scar-improving therapy based on preclinical studies. However, the molecular mechanism of IL-10 in scar improvement is still uncertain. In this study, human dermal fibroblasts stimulated with TGF-β1 were treated with IL-10 to analyze the mRNA and some of proteins' expression levels of type I collagen (Col1), type III collagen (Col3), alpha-smooth muscle actin (α-SMA), matrix metalloproteinase-1 (MMP1), MMP2, MMP8 and tissue inhibitor of metalloproteinase 1 (TIMP1), TIMP2 by real-time PCR and Western blot, to observe α-SMA-positive fibroblasts by immunocytochemistry. The contracture and improvement of fibroblast-populated collagen lattice (FPCL) and a murine model of wound healing were used to evaluate the scar-improving effects by histological staining. The results showed that IL-10 can significantly down-regulate the mRNA and protein expression levels of Col1, Col3, α-SMA, and up-regulate the mRNA expression levels of MMP1 and MMP8, and decrease α-SMA-positive fibroblasts. FPCL analysis showed that the IL-10 (20 ng/ml) can significantly inhibit the contracture, improve the architecture of FPCL. Wounds injected with IL-10 demonstrated that the appearance of scar was improved, the wound margin of scarring was narrow, and the deposition of collagens (Col1 and Col3) in regenerated tissue was relieved. These results provide direct evidences that IL-10 has the inhibitory effects on the excessive deposition of extracellular matrix components and fibroblast-to-myofibroblast transition, and show that IL-10 has the potential therapy in prevention and reduction of skin scarring.

Particle Swarm Optimization (PSO) is a popular and bionic algorithm based on the social behavior associated with bird flocking for optimization problems. To maintain the diversity of swarms, a few studies of multi-swarm strategy have been reported. However, the competition among swarms, reservation or destruction of a swarm, has not been considered further. In this paper, we formulate four rules by introducing the mechanism for survival of the fittest, which simulates the competition among the swarms. Based on the mechanism, we design a modified Multi-Swarm PSO (MSPSO) to solve discrete problems, which consists of a number of sub-swarms and a multi-swarm scheduler that can monitor and control each sub-swarm using the rules. To further settle the feature selection problems, we propose an Improved Feature Selection (IFS) method by integrating MSPSO, Support Vector Machines (SVM) with F-score method. The IFS method aims to achieve higher generalization capability through performing kernel parameter optimization and feature selection simultaneously. The performance of the proposed method is compared with that of the standard PSO based, Genetic Algorithm (GA) based and the grid search based methods on 10 benchmark datasets, taken from UCI machine learning and StatLog databases. The numerical results and statistical analysis show that the proposed IFS method performs significantly better than the other three methods in terms of prediction accuracy with smaller subset of features.

Collagen alteration is critical for epithelial tumor initiation and progression. Quantitatively linking collagen alteration and epithelial tumor progression is essential for developing an optical endoscopy to evaluate epithelial tumor progression. In this work, we established a quantitative link between collagen alteration and epithelial tumor progression using second harmonic generation (SHG) microscopy. It was found that SHG microscopy can provide quantitative features to effectively evaluate epithelial tumor progression, and to locate tumor and determine the margin of tumor regions. These results suggest that SHG microscopy has the potential in offering a noninvasive in vivo imaging tool to quantify epithelial tumor progression.

BackgroundThe hypertrophic scar (HS) is a serious fibrotic skin condition and a major clinical problem. Interleukin-10 (IL-10) has been identified as a prospective scar-improving compound based on preclinical trials. Our previous work showed that IL-10 has anti-fibrotic effects in transforming growth factor (TGF)-β1-stimulated fibroblasts, as well as potential therapeutic benefits for the prevention and reduction of scar formation. However, relatively little is known about the mechanisms underlying IL-10-mediated anti-fibrotic and scar-improvement actions.ObjectiveTo explore the expression of the IL-10 receptor in human HS tissue and primary HS fibroblasts (HSFs), and the molecular mechanisms contributing to the anti-fibrotic and scar-improvement capabilities of IL-10.MethodsExpression of the IL-10 receptor was assessed in HS tissue and HSFs by immunohistochemistry, immunofluorescence microscopy, and polymerase chain reaction analysis. Primary HSFs were treated with IL-10, a specific phosphatidylinositol 3 kinase (PI3K) inhibitor (LY294002) or a function-blocking antibody against the IL-10 receptor (IL-10RB). Next, Western blot analysis was used to evaluate changes in the phosphorylation status of AKT and signal transducers and activators of transcription (STAT) 3, as well as the expression levels of fibrosis-related proteins.ResultsHS tissue and primary HSFs were characterized by expression of the IL-10 receptor and by high expression of fibrotic markers relative to normal controls. Primary HSFs expressed the IL-10 receptor, while IL-10 induced AKT and STAT3 phosphorylation in these cells. In addition, LY294002 blocked AKT and STAT phosphorylation, and also up-regulated expression levels of type I and type III collagen (Col 1 and Col 3) and alpha-smooth muscle actin (α-SMA) in IL-10-treated cells. Similarly, IL-10RB reduced STAT3/AKT phosphorylation and blocked the IL-10-mediated mitigation of fibrosis in HSFs.ConclusionIL-10 apparently inhibits fibrosis by activating AKT and STAT3 phosphorylation downstream of the IL-10 receptor, and by facilitating crosstalk between the PI3K/AKT and STAT3 signal transduction pathways.

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons with limited treatment options. Emerging evidence shows that FTY720 protects against neural injury via modulation of the sphingosine-1-phosphate 1 receptor (S1PR1). However, it remains unclear whether FTY720 could influence neurodegeneration in PD. Therefore, the present study was designed to determine the impact of fingolimod (FTY720), a sphingosine-1-phosphate receptor (S1PR) agonist, on 2 mouse models of PD. We found that FTY720 significantly reduced the deficit of motor function, diminished the loss of tyrosine hydroxylase-positive neurons in the substantia nigra, and attenuated the decrease of striatal dopamine and metabolite levels in mice receiving 6-hydroxydopamine (6-OHDA) or rotenone to simulate PD. An S1PR1-selective antagonist, W146, blocked the neuroprotective effects of FTY720. Of note, FTY720 retained the phosphorylation of ERK, together with a decreased expression of cleaved caspase-3 in mice treated with 6-OHDA or rotenone. In vitro studies revealed that FTY720 also attenuated 6-OHDA- or rotenone-induced toxicity in SH-SY5Y cells. These findings suggest the potential of S1PR modulation as a treatment for PD.-Zhao, P., Yang, X., Yang, L., Li, M., Wood, K., Liu, Q., Zhu, X. Neuroprotective effects of fingolimod in mouse models of Parkinson's disease.

OBJECTIVES: Application of artificial intelligence in gastrointestinal endoscopy is increasing. The aim of the study was to examine the accuracy of convolutional neural network (CNN) using endoscopic images for evaluating Helicobacter pylori (H. pylori) infection. METHODS: Patients who received upper endoscopy and gastric biopsies at Sir Run Run Shaw Hospital (January 2015–June 2015) were retrospectively searched. A novel Computer-Aided Decision Support System that incorporates CNN model (ResNet-50) based on endoscopic gastric images was developed to evaluate for H. pylori infection. Diagnostic accuracy was evaluated in an independent validation cohort. H. pylori infection was defined by the presence of H. pylori on immunohistochemistry testing on gastric biopsies and/or a positive 13C-urea breath test. RESULTS: Of 1,959 patients, 1,507 (77%) including 847 (56%) with H. pylori infection (11,729 gastric images) were assigned to the derivation cohort, and 452 (23%) including 310 (69%) with H. pylori infection (3,755 images) were assigned to the validation cohort. The area under the curve for a single gastric image was 0.93 (95% confidence interval [CI] 0.92–0.94) with sensitivity, specificity, and accuracy of 81.4% (95% CI 79.8%–82.9%), 90.1% (95% CI 88.4%–91.7%), and 84.5% (95% CI 83.3%–85.7%), respectively, using an optimal cutoff value of 0.3. Area under the curve for multiple gastric images (8.3 ± 3.3) per patient was 0.97 (95% CI 0.96–0.99) with sensitivity, specificity, and accuracy of 91.6% (95% CI 88.0%–94.4%), 98.6% (95% CI 95.0%–99.8%), and 93.8% (95% CI 91.2%–95.8%), respectively, using an optimal cutoff value of 0.4. DISCUSSION: In this pilot study, CNN using multiple archived gastric images achieved high diagnostic accuracy for the evaluation of H. pylori infection.

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Seizures are common in humans with various etiologies ranging from congenital aberrations to acute injuries that alter the normal balance of brain excitation and inhibition. A notable consequence of seizures is the induction of aberrant neurogenesis and increased immature neuronal projections. However, regulatory mechanisms governing these features during epilepsy development are not fully understood. Recent studies show that microglia, the brain's resident immune cell, contribute to normal neurogenesis and regulate seizure phenotypes. However, the role of microglia in aberrant neurogenic seizure contexts has not been adequately investigated. To address this question, we coupled the intracerebroventricular kainic acid model with current pharmacogenetic approaches to eliminate microglia in male mice. We show that microglia promote seizure-induced neurogenesis and subsequent seizure-induced immature neuronal projections above and below the pyramidal neurons between the DG and the CA3 regions. Furthermore, we identify microglial P2Y12 receptors (P2Y12R) as a participant in this neurogenic process. Together, our results implicate microglial P2Y12R signaling in epileptogenesis and provide further evidence for targeting microglia in general and microglial P2Y12R in specific to ameliorate proepileptogenic processes.