TSNAdb v2.0:The Updated Version of Tumor-specific Neoantigen Database

In recent years,neoantigens have been recognized as ideal targets for tumor immunotherapy.With the development of neoantigen-based tumor immunotherapy,comprehensive neoantigen databases are urgently needed to meet the growing demand for clinical studies.We have built the tumor-specific neoantigen database(TSNAdb)previously,which has attracted much attention.In this study,we provide TSNAdb v2.0,an updated version of the TSNAdb.TSNAdb v2.0 offers several new features,including(1)adopting more stringent criteria for neoantigen identification,(2)providing predicted neoantigens derived from three types of somatic mutations,and(3)collecting experimentally validated neoantigens and dividing them according to the experimental level.

P2Y1R is involved in visceral hypersensitivity in rats with experimental irritable bowel syndrome

AIM To evaluate the role of P2Y1 R in visceral hypersensitivity in rats with experimental irritable bowel syndrome.METHODS A rat model of irritable bowel syndrome was generated by intra-colonic administration of acetic acid(AA) and assessed by histology and myeloperoxidase(m PO) activity assay. Then P2Y1 R expression in the colonic tissue was detected by Western blot. In order to explore the regulatory role of P2Y1 R in visceral hypersensitivity, an agonist(m RS2365) and an antagonist(m RS2179) of P2Y1 R were intra-colonically administered and effects were tested through a colorectal distension test. The abdominal withdrawal reflex and abdominal electromyography were tested during the course. RESULTS model assessment tests showed an obvious inflammatoryreaction that appeared on the 2^(nd) d after the AA injection, and the inflammatory reaction gradually recovered and almost disappeared on the 7^(th) d. The model finished on day 8 and showed a clear feature of IBS that had no organic lesion. The average expression of P2Y1 R was significantly higher in the AA group than in the na?ve group(0.319 ± 0.02 vs 0.094 ± 0.016, P < 0.001). m RS2365 could effectively raise the colonic hypersensitivity status at intervention doses of 10(AUC value from 0.30 ± 0.089 to 1.973 ± 0.127 mv?s, P < 0.01) and 100 μmol/L(AUC value from 0.290 ± 0.079 to 1.983 ± 0.195 mv?s, P < 0.01); m RS2179 could effectively reduce the hypersensitivity status at intervention dose of 100 μmol/L(from a mean baseline AUC value of 1.587 ± 0.099 mv?s to 0.140 ± 0.089 mv?s, P < 0.0001). Differences between the m RS2179 group(1.88 ± 1.45) and either the m RS2365 group(3.96 ± 0.19) or the combined treatment(m RS2179 and m RS2365) group(3.28 ± 0.11) were significant(P < 0.01).CONCLUSION P2Y1 R plays a regulatory role in visceral hypersensitivity in rats with experimental IBS. Specific antagonists of P2Y1 R may have potential therapeutic value in treating abdominal pain in IBS.

Effect of 15-Deoxy-A^12,14-prostaglandin J2 Nanocapsules on Inflammation and Bone Regeneration in a Rat Bone Defect Model

Background： 15-Deoxy-^△^12、14-prostaglandin J2 （15d-PGJ2）, one of the major metabolites from prostaglandin D2 in arachidonic acid metabolic pathway, has potential anti-inflammatory properties. The objective of this study was to explore the effects of 15d-PGJ2-1oaded poly（D,L-lactide-co-glycolide） nanocapsules （15d-PGJ2-NC） on inflammatory responses and bone regeneration in local bone defect. Methods： The study was conducted on 96 Wistar rats from June 2014 to March 2016. Saline, unloaded nanoparticles, free 15d-PGJ2 or 15d-PGJ2-NC, were delivered through a collagen vehicle inside surgically created transcortical defects in rat femurs, lnterleukin-6 （IL-6）, interleukin-1 beta （IL-I~）, and tumor necrosis factor-alpha （TNF-o0 levels in the surrounding soft tissue were analyzed by Western blot and in the defect by quantitative real-time polymerase chain reaction over 14 days. Simultaneously, bone morphogenetic protein-6 （BMP-6） and platelet-derived growth factor-B （PDGF-B） messenger RNA （mRNA） in the defect were examined. New bone formation and EphrinB2 and osteoprotegerin （OPG） protein expression in the cortical defect were observed by Masson＇s Trichrome staining and immunohistochemistry over 28 days. Data were analyzed by one-way analysis of variance. Least-significant difference and Dunnett＇s T3 methods were used with a bilateral P 〈 0.05. Results： Application of 15d-PGJfNC （100μg/ml） in the local bone defect significantly decreased 1L-6, IL-Iβ, and TNF-α mRNA and protein, compared with saline-treated controls （P 〈 0.05）. 15d-PGJfNC upregulated BMP-6 and PDGF-B mRNA （P 〈 0.05）. New bone formation was observed in the cortical defect in 15d-PGJ2-NC-treated animals from 7th day onward （P 〈 0.001）. Expression of EphrinB2 and OPG presented early on day 3 and persisted through day 28 in 15d-PGJfNC group （P 〈 0.05）. Conclusion： Stable 15d-PGJz-NC complexes were prepared that could attenuate IL-6, IL-1 β, and TNF-α expression, while increasing new bone formation and growth factors related to bone regeneration.