MTOR inhibitors (mTOR-Is) may induce proteinuria in kidney transplant recipients through podocyte damage. However, the mechanism has only been partially defined. Total cell lysates and supernatants of immortalized human podocytes treated with different doses of everolimus (EVE) (10, 100, 200, and 500 nM) for 24 h were subjected to mass spectrometry-based proteomics. Support vector machine and partial least squares discriminant analysis were used for data analysis. The results were validated in urine samples from 28 kidney transplant recipients receiving EVE as part of their immunosuppressive therapy. We identified more than 7000 differentially expressed proteins involved in several pathways, including kinases, cell cycle regulation, epithelial–mesenchymal transition, and protein synthesis, according to gene ontology. Among these, after statistical analysis, 65 showed an expression level significantly and directly correlated with EVE dosage. Polo-Like Kinase 1 (PLK1) content was increased, whereas osteopontin (SPP1) content was reduced in podocytes and supernatants in a dose-dependent manner and significantly correlated with EVE dose (p < 0.0001, FDR < 5%). Similar results were obtained in the urine of kidney transplant patients. This study analyzed the impact of different doses of mTOR-Is on podocytes, helping to understand not only the biological basis of their therapeutic effects but also the possible mechanisms underlying proteinuria.

Background: The orthodontist can play an important role in the early detection of sleep-disordered breathing (SDB), aiding in the prevention of dentoskeletal complications and systemic issues. Early intervention supports proper pediatric development, emphasizing the need for SDB screening in orthodontics. SDB involves abnormal breathing during sleep, with obstructive sleep apnea (OSA) in children presenting unique diagnostic challenges compared to adults. Aim: This study aimed to identify children at risk for SDB through a validated screening questionnaire during orthodontic evaluations. Methods: This prospective study recruited children under 12 years of age between July 2023 and July 2024. The Sleep Clinical Record was used to screen for SDB indicators. Results: Among the 48 participants (31 females, 17 males) aged 5–12 years, 69% were identified as being at risk for SDB. Risk factors included oral breathing, nasal obstruction, tonsillar hypertrophy, malocclusion, high Friedman scores, narrow palates, and positive Brouillette phenotypes, all showing significant correlations (p < 0.05). Conclusion: The findings underline the critical importance of early SDB screening in orthodontic settings. These preliminary results encourage further research on larger cohorts to refine diagnostic tools and interventions. Early recognition and management of SDB can significantly enhance systemic health and craniofacial outcomes in pediatric patients.

Background and Aims: Peritoneal metastases (PMs) represent the most frequent, clinically challenging dissemination pattern in advanced gastric cancer, especially poorly cohesive (PCGC) subtype, and are associated with poor prognosis. We aimed to characterize the transcriptomic landscape of primary gastric tumors (PGTs) and matched PMs to identify differential molecular programs, tumor-microenvironment (TME) features, and potential biomarkers. Methods: We analyzed 55 FFPE samples from 23 treatment-naïve patients with synchronous peritoneal-only stage IV PCGC and 10 non-neoplastic gastric controls (NNC). RNA sequencing was analyzed using DESeq2 and GSEA, with cell proportions estimated through immune deconvolution (TIMER/xCell). Results: A total of 4279 differentially expressed genes were identified across all groups. CLDN18 expression progressively decreased from NNCs to PGTs and PMs. Direct PGT-PM comparison revealed that PGTs were characterized by cytoskeletal and extracellular-matrix remodeling genes upregulation, mitotic/cell-cycle, NOTCH and apical-junction pathways enrichment, and memory T-cell predominance. Compared with PGTs, PMs showed increased IGF1, IGFN1, NTRK2 and adipogenesis-related transcripts, adipogenesis and MAPK7/11–NTRK2 signaling enrichment, and macrophage-dominant and dendritic-cell-dominant microenvironments. epithelial-mesenchymal transition (EMT), inflammatory pathways, and cancer-associated fibroblasts were shared by both tumor lesions. PMs did not match established TCGA or PCGC subtypes, suggesting a distinct molecular identity. Conclusions: PMs are characterized by TME remodeling and transcriptional reprogramming. Shared EMT and inflammatory pathways act as bridge linking PGT to PM, consistent with adaptive exploitation of physiological peritoneal programs. Collectively, our findings suggest a transcriptomic framework in which PM can be characterized as a distinct niche-conditioned biological entity and support microenvironment-informed diagnostic and therapeutic strategies.