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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Disparities in estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2 (HER2), and Ki67 proliferation indices facilitate the categorization of breast cancer into four principal subtypes: luminal A, luminal B, HER2-positive, and triple-negative breast cancer (TNBC). Preclinical studies investigating the therapeutic potential of histaminergic system targeting in breast cancer have shown promising results. This study aimed to assess the expression profiles of messenger ribonucleic acid (mRNA) and micro RNA (miRNA) related to the histaminergic system in five subtypes of breast cancer among Polish women. Patients with five breast cancer subtypes were included in the study: luminal A (n = 130), luminal B (n = 196, including HER2-, n =100; HER2+, n= 96), HER2+ (n = 36), and TNBC (n = 43). They underwent surgery during which the tumor tissue was removed along with a margin of healthy tissue (control material). Molecular analysis included the determination of a microarray profile of mRNAs and miRNAs associated with the histaminergic system, real-time polymerase chain reaction preceded by reverse transcription of selected genes, and determination of histamine receptors (human histamine H1 receptor [HRH1], human histamine H2 receptor [HRH2], and human histamine H4 receptor [HRH4]) using an enzyme-linked immunosorbent assay. Statistical analysis was performed with statistical significance at p < 0.05. Nine mRNAs were significantly differentiated in breast cancer sections, regardless of subtype, compared to control samples: HRH1, HRH2, HRH4, histamine N-methyltransferase (HNMT), 5-hydroxytryptamine receptor 6 (HTR6), endothelin 1 (EDN1), endothelin receptor type A (EDNRA), adenosine deaminase (ADA), solute carrier family 22 member 3 (SLC3A2). Predictive analysis showed that hsa-miR-34a potentially regulates HRH1 expression, whereas hsa-miR-3140-5p and hsa-miR-4251 potentially affect HRH2 expression. In contrast, HRH4 and EDN1 expression were regulated by hsa-miR-1-3p. The expression of HNMT is potentially regulated by one miRNA, hsa-miR-382, whereas EDNRA expression is regulated by two miRNA molecules: hsa-miR-34a and hsa-miR-16. In contrast, hsa-miR-650 is involved in the regulation of HTR6 expression, whereas hsa-miR-1275 potentially interacts with three mRNAs: ADA, SLC23A2, and HRH1. Molecular analysis confirmed that the selected mRNA and miRNA transcripts could be promising molecular markers and therapeutic targets. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the role of circadian clock genes in the progression of astrocytic tumors, a common type of brain tumor. We aimed to understand how these genes, which control the body's daily rhythms, behave differently in low-grade versus high-grade tumors. Our findings reveal that certain circadian clock genes are more active in advanced tumor stages, potentially driving tumor growth. Additionally, we discovered that changes in DNA methylation and microRNAs might regulate these genes. Understanding these molecular changes could help identify new biomarkers for tumor diagnosis and progression, offering new avenues for targeted treatments. This research provides valuable insights into the complex biology of brain tumors and highlights the importance of circadian genes in the development of cancer. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: It effectively communicates the importance of evaluating changes in the concentration profiles of micronutrients and macronutrients in the intervertebral disc (IVD) in the context of osteoarthritis for identifying enzymes and metabolites involved in the degenerative process of the IVD. Aim: This study aimed to evaluate changes in the concentrations of copper (Cu), iron (Fe), manganese (Mn), lead (Pb), zinc (Zn), sodium (na), potassium (K), phosphorus (P), calcium (Ca), and magnesium (Mg) in the degenerative process of the lumbar/sacral (L/S) IVD segment. Material and methods: The study group comprised 180 patients scheduled for microdiscectomy due to degenerative L/S IVD segments. Additionally, 90 individuals from the Caucasian Council were included in the control group, with post-mortem card collection from the L/S section of the circle. Results: Chemical analysis revealed significantly higher zinc (Zn) concentrations in study group samples compared to control samples (32.95 mg/kg DM ±21.55 mg/kg DM vs. 21.26 mg/kg DM ±13.86 mg/kg DM). Phosphorus (P) levels were also significantly higher in study group samples (4968.45 mg/kg DM ±5469.92 mg/kg DM vs. 1543.80 mg/kg DM ±1332.49 mg/kg DM), as well as calcium (Ca) (6012.25 mg/kg DM ±13884.34 mg/kg DM vs. 1451.45 mg/kg DM ±722.63 mg/kg DM). One-way AnOVA analysis indicated that the changes in iron (Fe), manganese (Mn), sodium (na), and magnesium (Mg) significantly correlated with the degree of IVD degeneration. Conclusions: The altered profiles of zinc (Zn), magnesium (Mg), calcium (Ca), and phosphorus (P) concentrations characterize the degenerative process of the L/S IVD segment. Assessing changes in iron (Fe), manganese (Mn), sodium (na), and magnesium (Mg) levels may aid in evaluating the progression of degenerative changes in the L/S IVD segment. However, micro- and macronutrient variations did not significantly correlate with the severity of pain in the L/S segment of the spine. [ABSTRACT FROM AUTHOR]

Introduction: Unhealthy habits such as overeating processed and high-calorie foods, alcohol abuse, and smoking negatively impact human health. It has been suggested that the inflammatory process and the resulting growth of nerve fibers within the intervertebral disc (IVD) fissures is the main reason for the pain accompanying IVD degeneration (IVDD). Aim: The aim of this study was to determine whether smoking, alcohol consumption, overweight/obesity, or diabetes comorbidity contribute to the development of IVDD and how the aforementioned factors affect the levels of brain-derived neurotrophic factor (BDnF), glial cell-derived neurotrophic factor (GDnF), and growth associated protein 43 (GAP-43) in the study and control groups. Material and methods: The study group comprised 113 patients diagnosed with IVDD who qualified for microdiscectomy. Control group included 81 IVDs obtained from Caucasian human cadavers. The expression profiles of BDnF, GDnF, and GAP-43 were determined by enzyme-linked immunosorbent assay (ELISA). Results: Our statistical analysis confirmed that patients who were overweight/obese, smoked tobacco, consumed alcohol, or had diabetes had a higher risk of IVDD (OR>1). Statistical analysis showed that BDnF, GAP-43, and GDnF concentrations were significantly higher in the IVDs obtained from the study group compared with the control group (p<0.05). In addition, higher levels of BDnF, GDnF, and GAP-43 were noted in IVDD patients who consumed alcohol, smoked tobacco, were overweight/obese, or had comorbid diabetes compared with patients without these risk factors (p<0.05). Conclusions: We showed that changes in energy metabolism, habits, and lifestyle as well as the degenerative process of IVD in the lumbosacral spine contribute to changing the concentration profile of the analyzed neurotrophic factors. [ABSTRACT FROM AUTHOR]

Introduction: Endometrioid endometrial cancer ranks among the most prevalent malignant tumors affecting women in developed nations, with its incidence steadily rising. Over the past decade, its frequency currently reaching 79 cases per 100,000 women in Europe. Histamine, a biogenic amine, exhibits immunomodulatory properties and serves as the primary mediator of severe and acute inflammatory reactions, as well as immediate hypersensitivity reactions. Histamine operates via four distinct receptor subtypes: HRH1, HRH2, HRH3, and HRH4, with its expression documented across various cancer types. Aim: This study aimed to assess alterations in the expression pattern of genes associated with the histaminergic system in boThendometrial tissue samples and whole blood derived from women diagnosed wiThendometrioid endometrial cancer. Material and methods: The study cohort comprised 30 women diagnosed wiThendometrioid endometrial cancer who underwent hysterectomy. Within this group, 15 cases were classified as G1 (well-differentiated), 8 cases as G2 (moderately differentiated), and 7 cases as G3 (poorly differentiated). The control cohort comprised 30 women with no neoplastic changes during routine gynecological examinations. Molecular analysis encompassed microarray analysis of mRnAs associated with the histaminergic system, reverse-transcription quantitative polymerase chain reaction (RT-qPCR), and enzymelinked immunosorbent assay (ELISA). Results: Among 65 mRnAs associated with the histaminergic system, 10 exhibited differentiations between tissue and blood samples obtained from endometrioid endometrial cancer patients compared to the control group (p<0.05). mRnA histamine receptor 1,3 (HRH1, HRH3), and solute carrier family 22 member 3 (SLC23A2) showed differentiation in endometrioid endometrial cancer samples irrespective of their comparison to the control or G group. Conclusions: The findings reveal a complex architecture of the histaminergic system. The identified mRnA targets hold promise for molecularly targeted therapies in the context of endometrioid endometrial cancer. Furthermore, these results may offer insights into assessing the severity of endometrioid endometrial cancer. [ABSTRACT FROM AUTHOR]