The aim of this study was to identify miRNAs that could potentially influence the activity of SMAD proteins involved in TGFβ signal transduction in five types of breast cancer in Polish women. Patients with five breast cancer subtypes were included in the study: luminal A (n = 130), luminal B HER2− (n = 100), luminal B HER2+ (n = 96), non-luminal HER2+ (n = 36), and TNBC (n = 43). During surgery, tumor tissue was removed along with a margin of healthy tissue (control). Molecular analysis included determination of the expression of genes related to SMAD protein signal transduction using mRNA microarrays and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Protein expression was determined using an enzyme-linked immunosorbent assay (ELISA). The miRNA profiling was performed using miRNA microarrays and the miRDB database. SMAD3 and SMAD5 were overexpressed in all types of breast cancer, which could be related to the reduced expression of miR-145, and the findings for SMAD4 and miR-155 were similar. Additionally, the level of SMAD7 was reduced, which may be due to the low activity of miR-15b and miR21b. This study determined the gene expression profiles involved in SMAD protein signal transduction across five different types of breast cancer and identified the miRNAs potentially regulating their activity. Overexpression of SMAD3, SMAD4, and SMAD5 suggests excessive activation of the TGFβ pathway, potentially promoting tumor growth and development. Concurrently, a significant reduction in SMAD7 expression removes inhibitory control in the TGFβ pathway, a phenomenon that is particularly evident in more aggressive breast cancer types.

The study investigates molecular changes in the lumbosacral (L/S) spine's yellow ligamentum flavum during degenerative stenosis, focusing on the role of transforming growth factor beta 1-3 (TGF-β-1-3). Sixty patients with degenerative stenosis and sixty control participants underwent molecular analysis using real-time quantitative reverse transcription reaction technique (RTqPCR), enzyme-linked immunosorbent assay (ELISA), Western blot, and immunohistochemical analysis (IHC). At the mRNA level, study samples showed reduced expression of TGF-β-1 and TGF-β-3, while TGF-β-2 increased by only 4%. Conversely, at the protein level, the study group exhibited significantly higher concentrations of TGF-β-1, TGF-β-2, and TGF-β-3 compared to controls. On the other hand, at the protein level, a statistically significant higher concentration of TGF-β-1 was observed (2139.33 pg/mL ± 2593.72 pg/mL vs. 252.45 pg/mL ± 83.89 pg/mL; p < 0.0001), TGF-β-2 (3104.34 pg/mL ± 1192.74 pg/mL vs. 258.86 pg/mL ± 82.98 pg/mL; p < 0.0001), TGF-β-3 (512.75 pg/mL ± 107.36 pg/mL vs. 55.06 pg/mL ± 9.83 pg/mL, p < 0.0001) in yellow ligaments obtained from patients of the study group compared to control samples. The study did not establish a significant correlation between TGF-β-1-3 concentrations and pain severity. The findings suggest that molecular therapy aimed at restoring the normal expression pattern of TGF-β-1-3 could be a promising strategy for treating degenerative stenosis of the L/S spine. The study underscores the potential therapeutic significance of addressing molecular changes at the TGF-β isoforms level for better understanding and managing degenerative spinal conditions.

This study investigated the role of brain-derived neurotrophic factor (BDNF) in patients with degenerative lumbar stenosis, focusing on its expression and correlation with pain intensity. The study examined 96 patients with lumbar stenosis and 85 control participants. BDNF levels in the yellow ligamentum flavum were measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and western blot analysis. The results showed significantly higher BDNF expression at both messenger ribonucleic acid (mRNA; fold change = +1.35 ± 0.23; p < 0.05) and protein levels in patients (28.98 ± 6.40 pg/mg) compared to controls (4.56 ± 1.98 pg/mg; p < 0.05). Furthermore, BDNF levels correlated positively with pain intensity reported by patients, with higher expression observed in those experiencing more severe pain. The study also explored the influence of lifestyle factors, such as smoking and alcohol consumption, and related diseases, such as diabetes, on BDNF expression. Smoking, alcohol use, and diabetes were associated with significantly elevated BDNF levels ( p < 0.05). These findings suggest that BDNF could serve as a biomarker for pain severity in degenerative lumbar stenosis at the protein level, although this was not consistently observed at the mRNA level; this highlights the potential for BDNF-targeted therapies in managing pain. Future research should involve larger longitudinal studies to validate these findings and explore therapeutic interventions. This study underscores the importance of considering molecular and lifestyle factors in the treatment of degenerative lumbar stenosis, aiming to improve patient outcomes through comprehensive, targeted approaches.

This study explores the role of circadian clock genes in the progression of astrocytic tumors, a prevalent type of brain tumor. The aim was to assess the expression patterns of these genes in relation to the tumor grade. Using microarray analysis, qRT-PCR, and methylation-specific PCR, we examined gene expression, DNA methylation patterns, and microRNA interactions in tumor samples from 60 patients. Our results indicate that the expression of key circadian clock genes, such as clock circadian regulator (CLOCK), protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2), protein kinase AMP-activated non-catalytic subunit beta 1 (PRKAB1), protein kinase AMP-activated non-catalytic subunit beta 2 (PRKAB2), period circadian regulator 1 (PER1), period circadian regulator 2 (PER2) and period circadian regulator 3 (PER3), varies significantly with the tumor grade. Notably, increased CLOCK gene expression and protein levels were observed in higher-grade tumors. DNA methylation analysis revealed that the promoter regions of PER1-3 genes were consistently methylated, suggesting a mechanism for their reduced expression. Our findings also underscore the complex regulatory mechanisms involving miRNAs, such as hsa-miR-106-5p, hsa-miR-20b-5p, and hsa-miR-30d-3p, which impact the expression of circadian clock-related genes. This underscores the importance of circadian clock genes in astrocytic tumor progression and highlights their potential as biomarkers and therapeutic targets. Further research is needed to validate these results and explore their clinical implications.

Background/Objectives: In this study, serum selenium levels in patients with Crohn’s disease (CD) and ulcerative colitis (UC) were evaluated to identify potential predictive markers of disease activity. Conducted in 100 inflammatory bowel disease (IBD) patients (54 CD, 46 UC) and 100 healthy controls, this research provides novel insights through focusing on the regional selenium status of people with IBD in the Polish population, a demographic with limited existing data. Methods: Selenium concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). Results: Significantly lower levels of selenium were observed in CD (64.79 µg/L ± 12.15 µg/L) and UC (68.61 µg/L ± 11.43 µg/L) patients when compared with the controls (90.52 ± 12.00 µg/L, p < 0.0001). Regression analysis identified leukocyte and erythrocyte counts and bilirubin as significant predictors of selenium levels in UC patients, while no significant predictors were found for CD. Conclusions: The findings suggest that selenium deficiency is linked to IBD and may serve as a non-invasive biomarker for disease severity, particularly in UC. This practical approach offers a potential alternative to invasive procedures such as endoscopy for monitoring disease progression. However, further research is needed to confirm these findings in larger populations and explore the therapeutic role of selenium supplementation in IBD management.

Introduction: The pathogenesis of intervertebral disc degeneration (IVDD) involves multifactorial biochemical and metabolic disturbances; however, the contribution of trace elements and oxidative stress to this process remains insufficiently characterized. Understanding alterations in elemental composition and redox homeostasis within degenerated discs may reveal novel aspects of IVDD biology and potential therapeutic targets. Methods: This study analyzed lumbar intervertebral disc (IVD) tissue obtained from 200 patients undergoing microdiscectomy for lumbosacral IVDD and 100 postmortem controls without disc degeneration. The concentrations of zinc (Zn), magnesium (Mg), calcium (Ca), phosphorus (P), iron (Fe), manganese (Mn), copper (Cu), lead (Pb), sodium (Na), and potassium (K) were quantified using inductively coupled plasma optical emission spectrometry (ICP-OES). Oxidative stress status was assessed by measuring thiobarbituric acid reactive substances (TBARs; nmol MDA/mg protein), reduced glutathione (GSH; μmol/g tissue), and glutathione peroxidase (GPx; U/mg protein). Elemental concentrations were analyzed in relation to Pfirrmann degeneration grade, body mass index (BMI), and pain severity. Results: Degenerated discs exhibited significantly higher concentrations of Zn (35.10 ± 22.00 vs. 22.30 ± 14.00 mg/kg, p = 0.027), Mg (62,000 ± 80,000 vs. 130 ± 90 mg/kg, p < 0.0001), Ca (6,100 ± 13,900 vs. 1,500 ± 730 mg/kg, p < 0.0001), and P (5,000 ± 5,500 vs. 1,600 ± 1,340 mg/kg, p < 0.0001) compared with controls. Zn concentrations peaked in Pfirrmann grade 4 discs, while Mg was highest in grades 2 and 5 ( p < 0.001). Ca and P levels were independent of degeneration grade but significantly elevated in obese patients ( p < 0.001). In contrast, Mg concentrations were greatest in patients with normal BMI and declined with increasing BMI ( p < 0.001). No significant correlations were observed between element concentrations and pain intensity ( p > 0.05). Oxidative stress parameters indicated elevated TBARs (5.52 ± 2.52 vs. 2.63 ± 0.97, p < 0.0001), increased GPx activity (69.45 ± 3.92 vs. 60.25 ± 3.52, p = 0.027), and a non-significant reduction in GSH ( p = 0.054). Strong positive correlations were found between P and Ca ( r = 0.93, p < 0.001) and between K and Mn ( r = 0.80, p < 0.001). Discussion: These findings reveal substantial alterations in the micro- and macronutrient composition of degenerated IVDs, particularly for Zn, Mg, Ca, and P, suggesting that metabolic dysregulation and mineral imbalance contribute to disc pathology. The observed oxidative stress profile, characterized by lipid peroxidation and compensatory GPx activation, supports the involvement of redox imbalance in IVDD progression. Together, these results underscore the interplay between mineral homeostasis, oxidative stress, and disc degeneration, providing potential avenues for biomarker development and metabolic intervention in IVDD management.