The restoration of dentine lost in deep caries lesions in teeth is a routine and common treatment that involves the use of inorganic cements based on calcium or silicon-based mineral aggregates. Such cements remain in the tooth and fail to degrade and thus normal mineral volume is never completely restored. Here we describe a novel, biological approach to dentine restoration that stimulates the natural formation of reparative dentine via the mobilisation of resident stem cells in the tooth pulp. Biodegradable, clinically-approved collagen sponges are used to deliver low doses of small molecule glycogen synthase kinase (GSK-3) antagonists that promote the natural processes of reparative dentine formation to completely restore dentine. Since the carrier sponge is degraded over time, dentine replaces the degraded sponge leading to a complete, effective natural repair. This simple, rapid natural tooth repair process could thus potentially provide a new approach to clinical tooth restoration.

Estimating the semantic similarity between text data is one of the challenging and open research problems in the field of Natural Language Processing (NLP). The versatility of natural language makes it difficult to define rule-based methods for determining semantic similarity measures. To address this issue, various semantic similarity methods have been proposed over the years. This survey article traces the evolution of such methods beginning from traditional NLP techniques such as kernel-based methods to the most recent research work on transformer-based models, categorizing them based on their underlying principles as knowledge-based, corpus-based, deep neural network–based methods, and hybrid methods. Discussing the strengths and weaknesses of each method, this survey provides a comprehensive view of existing systems in place for new researchers to experiment and develop innovative ideas to address the issue of semantic similarity.

Immunosuppression withdrawal from calcineurin inhibitors is only possible in ~20% of liver transplant recipients. However, mTOR inhibitors (sirolimus) appear to be more immunoregulatory and might promote a tolerant state for withdrawal. Our purpose was to determine if systemic (blood, marrow, allograft) signatures of immunoregulation are promoted by conversion from tacrolimus to sirolimus. We therefore performed the following serial assays before and after sirolimus conversion in liver transplant recipients to test for enhanced markers of immunoregulation: 1) Flow cytometry immunophenotyping of PBMC and bone marrow aspirates for regulatory T cells (Tregs: CD4+CD25+++FOXP3+) and regulatory dendritic cells (DCregs: ILT3+/4+); 2) liver biopsy immunohistochemical staining (FOXP3:CD3, CD4:CD8 ratios) and immunophenotyping of biopsy-derived Tregs after growth in culture; 3) effects of pre-vs. post-conversion sera on Treg generation in mixed lymphocyte reactions; 4) peripheral blood non-specific CD4 responses (Cylex® ImmuKnow); 5) peripheral blood gene transcripts and proteomic profiles. We successfully converted 20 non-immune, non-viremic recipients (age 57.2±8; 3.5±2.1 years post-LT) from tacrolimus to sirolimus for renal dysfunction. Our results demonstrated significant increases in Tregs in PBMC and marrow and DCregs in PBMC (p<0.01) following conversion. In biopsy immunohistochemistry, FOXP3:CD3 and CD4:CD8 ratios were significantly higher after conversion and a number of biopsy cultures developed new or higher FOXP3+ cell growth. Non-specific CD4 responses (Cylex® ImmuKnow) did not change. Both pre- and post-conversion sera inhibited mixed lymphocyte reactions, although only tacrolimus sera suppressed Treg generation. Finally, 289 novel genes and 22 proteins, several important in immunoregulatory pathways, were expressed after conversion. Conclusions Tacrolimus to sirolimus conversion increases systemic Tregs, DCregs and immunoregulatory proteogenomic signatures in liver transplant recipients and may therefore facilitate immunosuppression minimization or withdrawal.

In non-growing teeth, such as mouse and human molars, primary odontoblasts are long-lived post-mitotic cells that secrete dentine throughout the life of the tooth. New odontoblast-like cells are only produced in response to a damage or trauma. Little is known about the molecular events that initiate mesenchymal stem cells to proliferate and differentiate into odontoblast-like cells in response to dentine damage. The reparative and regenerative capacity of multiple mammalian tissues depends on the activation of Wnt/β-catenin signaling pathway. In this study, we investigated the molecular role of Wnt/β-catenin signaling pathway in reparative dentinogenesis using an in vivo mouse tooth damage model. We found that Axin2 is rapidly upregulated in response to tooth damage and that these Axin2-expressing cells differentiate into new odontoblast-like cells that secrete reparative dentine. In addition, the Axin2-expressing cells produce a source of Wnt that acts in an autocrine manner to modulate reparative dentinogenesis.

Background Human papillomaviruses (HPVs) are sexually transmitted human carcinogens that may play a role in the oncogenesis of penile cancer. Objectives To investigate the role of HPV infection and expression of the tumour suppressor protein p16 INK4A in the pathogenesis of penile cancer. Methods By means of polymerase chain reaction amplification and reverse hybridization line probe assay to detect HPV infection, and immunohistochemical staining for p16 INK4A and Ki67, we analysed 26 penile squamous cell carcinomas (SCCs) and 20 independent penile lichen sclerosus (LS) lesions from 46 patients. Results HPV DNA was found in 54% of penile SCCs and 33% of penile LS cases in single and multiple infections. High-risk HPV 16 was the predominant HPV type detected. No relationship between Ki67 expression and HPV infection was observed. Strong immunostaining for p16 INK4A correlated with HPV 16/18 infection in both penile LS and penile SCC. In our penile SCC series the cancer margins were also associated with penile LS in 13 of 26 lesions, and HPV was detected in seven of the 13 SCC cases associated with LS and in six of the 11 SCC lesions not involving LS. Conclusions Our study shows a high prevalence of HPV 16 and p16 INK4A expression in penile lesions, consistent with an active role for HPV in interfering with the retinoblastoma pathway. High-risk HPV infection could be involved in the tumorigenic process in 50% of penile cancers, and the use of prophylactic HPV vaccines has the potential to prevent these cancers.