Excessive consumption of fructose (FR) leads to obesity, metabolic syndrome (MS) and insulin resistance, which are known risk factors for kidney stones. The epidemiological study has suggested the association between fructose consumption and urolithiasis, but the precise mechanism is still not well understood. Male Wistar rats were assigned for 8 weeks to three groups with different FR content in diet: RD (n = 5)—regular diet with a FR < 3%; F10 (n = 6)—regular diet with an addition of 10% Fr in drinking water; F60 (n = 5)—60% FR as a solid food. Serum concentration of FR, creatinine (Cr), insulin (Ins), triglycerides (Tg), homocysteine (HCS), uric acid (UA), calcium (Ca), phosphate (Pi), magnesium (Mg) and sodium (Na) were measured. Based on 24 h urine collection the following tests were performed: urine pH, proteinuria (PCR), excretion of N-Acetyl-(D)-Glucosaminidase (NAG), monocyte chemoattractant protein (MCP-1), uric acid (uUAEx), phosphate (uPiEx), calcium (uCaEx), magnesium (uMgEx) and sodium (uNaEx). The creatinine clearance (CrCl) was calculated. Calcium deposits in kidney sections were examined using hematoxylin and eosin (HE) and von Kossa stains. The rats on F10 and F60, as compared to the RD diet, showed a tendency for lower CrCl, higher HCS level and some features of MS as higher Ins and TG levels. Interestingly, F10 (fluid) versus F60 (solid) diet led to higher serum Ins levels. F10 and F60 versus RD demonstrated higher urinary excretion of MCP-1 and NAG which were suggestive for inflammatory injury of the proximal tubule. F10 and F60 as compared to RD showed significantly lower uUAEx, although there were no differences in clearance and fractional excretion of UA. F60 versus RD induced severe phosphaturia (>30×) and natriuria (4×) and mild calciuria. F10 versus RD induced calciuria (3×), phosphaturia (2×) and mild natriuria. Calcium phosphate stones within the tubules and interstitium were found only in rats on FR diet, respectively, in two rats from the F10 group and another two in the F60 group. The rats which developed stones were characterized by significantly higher serum insulin concentration and urinary excretion of calcium and magnesium. A fructose-rich diet may promote development of calcium stones due to proximal tubule injury and metabolic syndrome.

Endometrial carcinoma (EC) is the most common malignancy of the female genital tract, yet reliable prognostic biomarkers remain limited. Matrin-3 (MATR3), a nuclear matrix protein involved in genome stability and RNA processing, has been implicated in various cancers, but its role in EC has not been described. Here, we performed an integrated analysis combining immunohistochemical evaluation of MATR3 protein expression in a retrospective institutional cohort of 112 patients with EC and in silico analysis of MATR3 mRNA expression in 172 TCGA cases. Immunohistochemical analysis revealed nuclear MATR3 expression in both EC and normal endometrial tissues, with significantly lower protein levels in EC compared to control tissues (p < 0.0001). MATR3 mRNA was significantly reduced in EC tumour tissues compared to adjacent normal tissues (p < 0.0001). Low MATR3 protein expression was associated with shorter OS after adjustment for age, histological grade, pT, pN and pM in an LVSI-stratified Cox model (HR = 2.296; 95% CI: 1.284–4.104; p = 0.0050). Low MATR3 mRNA expression was associated with improved overall survival in TCGA (median OS = 110.1 months; HR = 2.174; 95% CI: 1.066–4.43; p = 0.0303). Co-expression analysis identified BCLAF1 and TOP2B as key positive correlates, while TRAPPC5 and FASTK showed the strongest negative correlations. Genes positively correlated with MATR3 mRNA expression were enriched for nuclear transcription and RNA-processing annotations, whereas negatively correlated genes were enriched for mitochondrial processes. These associations do not establish a mechanistic link between MATR3 and pathway activity. Our findings support further investigation of MATR3 as a candidate prognostic marker in EC, with independent validation and functional studies required.

The present study aimed to explore the role of SATB1, SMAD3, Ezrin and β-catenin as individual and combined biomarkers for the survival prediction in pancreatic adenocarcinoma (PAC). Notably, this study distinguished for the first time a potential prognostic value of SATB1 corresponding to its subcellular localization in PAC. Immunohistochemical staining on tissue macroarrays, as well as RNA-seq data from public sources, were investigated, and the results correlated with overall survival (OS) and clinicopathological features. The connectivity between the examined factors, as well as their common signaling pathways, were demonstrated by the functional enrichment analysis. Herein, the prognostic ability of cytoplasmic SATB1 in OS analysis was even superior to nuclear SATB1. Both staining patterns tended to have opposite roles in the prognosis of PAC: SATB1^c was an independent prognostic factor for poor OS, whereas SATB1ⁿ expression reached no statistical significance, but Kaplan–Meier curves separated patients with low expression and adverse prognosis from patients with high expression and favorable prognosis. High levels of SATB1 mRNA appeared as an independent prognostic indicator for better OS. Furthermore, individual expression of SMAD3 or Ezrin, as well as combined expression of SATB1/SMAD3/Ezrin/β-catenin, were associated with OS independently of conventional risk factors, both in our cohort and TCGA dataset. In our series, patients with tumors harboring combined expression of SATB1^n-high/SMAD3^low/Ezrin^low/β-catenin^low experienced the highest survival rates, while those with SATB1^c-present/SMAD3^high/Ezrin^high/β-catenin^high had the worst survival. In conclusion, protein and/or mRNA expression levels of SATB1, SMAD3, Ezrin and β-catenin may serve as potential prognostic biomarkers for PAC, both as single predictors and even better when combined.