The aging of organisms leads to a decreased ability of tissue to regenerate after injury. The regeneration of the bladder urothelium after induced desquamation with biopolymer chitosan has been studied in young mice but not in old mice. Chitosan is a suitable inducer of urothelial desquamation because it is known to be non-toxic. We used chitosan for desquamation of urothelial cells in order to compare the dynamics of urothelial regeneration after injury between young and old mice. Our aim was to determine whether the urothelial function and structure of old mice is restored as fast as in young mice, and to evaluate the inflammatory response due to chitosan treatment. We discovered that the urothelial function restored comparably fast in both age groups and that the urothelium of young and old mice recovered within 5 days after injury, although the onset of proliferation and differentiation appeared later in old mice. Acute inflammation markers showed some differences in the inflammatory response in young versus old mice, but in both age groups, chitosan caused short-term acute inflammation. In conclusion, the restoration of urothelial function is not impaired in old mice, but the regeneration of the urothelial structure in old mice slightly lags behind the regeneration in young mice.

Background/Objectives: The tumour microenvironment (TME) plays an important role in the development and progression of cancer and it differs among lymphomas, both with respect to the composition and quantity of specific tumour-infiltrating immune cells (TICs), such as FoxP3⁺ regulatory T cells (Tregs). The role of FoxP3⁺ Tregs in the TME of peripheral T-cell lymphomas (PTCLs) is complex, and their impact on overall survival (OS) remains unclear. Consequently, we aim to evaluate and compare the FoxP3⁺ cell quantity in nodal PTCLs and reactive lymph nodes (LNs), with a focus on investigating their impact on OS. Methods: excisional lymph node (LN) biopsies from 105 nodal PTCLs and 17 reactive LNs are immunohistochemically stained for FoxP3. Visual scoring of FoxP3⁺ cells is performed, and different cut-off values are used to evaluate the impact of FoxP3⁺ cell quantity on OS. Results: FoxP3⁺ cells are present in the TME of all cases, except for four cases where FoxP3⁺ is expressed in lymphoma cells. Lower FoxP3⁺ cell quantities are observed in certain nodal PTCL subtypes compared to reactive LNs. Patients with high FoxP3⁺ cell quantities show improved OS. However, the FoxP3⁺ cell quantity is not confirmed as an independent prognostic biomarker. Conclusions: these findings underscore the promise of FoxP3⁺ cell quantities as added value in prognosis and highlight the potential benefits of Treg-stimulating therapies in PTCLs.

Nodal T-follicular helper (TFH) cell lymphomas (nTFHLs) are the most common mature nodal T-cell lymphomas (nTCL) in Europe, characterized by an aggressive course, poor prognosis, and recurrent expression of TFH markers. Their mutational landscape and the impact of these mutations on survival outcomes remain underexplored. In this study, we characterized nTCL features in a Slovenian cohort, comprising 91 nTFHL, 9 peripheral TCL, not otherwise specified (PTCL-NOS), and 8 composite lymphomas [co-occurrence of nTFHL, angioimmunoblastic type (nTFHL-AI) with monoclonal B-cell proliferation], with a median follow up of 23 months. Using immunohistochemistry, clonality testing, and high-throughput sequencing with a lymphoma panel targeting 172 genes, we analyzed their mutational landscape and examined the mutational impact on survival outcomes. The mutational analysis uncovered TET2 (43%), RHOA (26%), IDH2 (9%), PLCG1 (8%), and DNMT3A (6%) as the most commonly mutated genes. RHOA mutations correlated with TET2 , IDH2 , and DNMT3A mutations, and CD10 expression was linked to TET2 mutations. Multiple mutations, high International Prognostic Index, progressive disease after first-line treatment, and the absence of autologous stem cell transplantation (ASCT) were independent predictors for shorter survival. To date, this study is one of the largest nTCL series, confirming that nTFHLs outnumber PTCL-NOS (92% vs. 8%). Our findings underscore the complex role of genetic factors in nTCL’s clinical behaviour and emphasize the importance of ASCT. We also highlight the need for prospective clinical trials, which explore tailored therapeutic interventions, such as hypomethylating agents or IDH inhibitors, for improving survival in specific genetic contexts.