Acid ceramidase (AC), a pivotal enzyme in sphingolipid metabolism, has been associated with various cancers; however, its specific role in rectal cancer remains poorly understood. This study aimed to explore the clinical significance of AC gene and protein expression in rectal cancer. We analyzed the expression of ASAH1, BAX, and BCL2 through quantitative Real-Time PCR in paired tumor and non-tumor tissue samples obtained from patients with locally advanced rectal cancer (LARC) prior to neoadjuvant chemoradiotherapy. Additionally, serum AC levels and standard biochemical parameters were assessed. We further evaluated ASAH1 expression using RNA-seq data from publicly available TCGA-READ datasets accessed via the UCSC Xena Browser. Two approaches indicated a significant reduction in ASAH1 expression in tumor tissue (p=0.004 and p<0.001, respectively). Receiver operating characteristic curve analysis revealed a modest capacity for ASAH1 expression to differentiate between tumor and non-tumor tissue in LARC patients (AUC=0.652, p=0.042). No correlation was observed between ASAH1 expression and the BAX/BCL2 ratio in tumor tissue, nor with serum AC levels or the CRP-albumin-lymphocyte (CALLY) index. Conversely, serum AC levels exhibited a negative correlation with the BAX/BCL2 ratio (rs=−0.536, p=0.002, FDR-adjusted q=0.021). Furthermore, ASAH1 expression, AC levels, and the CALLY index were not linked to overall survival or treatment response. A key finding of this study is the inverse relationship between serum AC levels and the pro-apoptotic status of tumor tissue, suggesting that circulating AC may provide valuable insights into tumor apoptotic activity. Further large-scale studies are necessary to validate these preliminary findings and elucidate the biomarker potential of AC in rectal cancer.

Bacterial nanocellulose (BNC) stands out among polymers as a promising biomaterial due to its mechanical strength, hydrophilicity, biocompatibility, biodegradability, low toxicity and renewability. The use of scaffolds based on BNC for 3D cell culture has been previously demonstrated. The study exploited excellent properties of the BNC to develop an efficient and low-cost in vitro cell migration assay. The BNC scaffold was introduced into a cell culture 24 h after the SW480 cells were seeded, and cells were allowed to enter the scaffold within the next 24–48 h. The cells were stained with different fluorophores either before or after the introduction of the scaffold in the culture. Untreated cells were observed to enter the BNC scaffold in significant numbers, form clusters and retain a high viability after 48 h. To validate the assay’s usability for drug development, the treatments of SW480 cells were performed using aspirin, an agent known to reduce the migratory potential of this cell line in culture. This study demonstrates the application of BNC as a scaffold for cell migration testing as a low-cost alternative to commercial assays based on the Boyden chamber principle. The assay could be further developed for routine use in cancer research and anticancer drug development.

Transforming growth factor beta 1 (TGFB1) is a multifunctional cytokine with a key role in asthma airway inflammation and remodeling. Since elevated levels of this cytokine in airways might be associated with response to asthma therapy, the aim of this study was to investigate whether the presence of the polymorphism C-509T in the promoter of the TGFB1 gene is associated with response to montelukast. A group of 102 asthmatic patients was genotyped for the presence of the C-509T polymorphism by DNA sequencing and subjected to induced sputum sampling. Cells from sputum samples and BEAS 2B cells were treated with montelukast and endogenous TGFB1 expression was measured by quantitative real-time polymerase chain reaction. The promoter activity was analyzed by luciferase assays in BEAS 2B cells transfected with constructs carrying variants −509C and −509T of the TGFB1 gene promoter. After treatment with montelukast, the decrease in TGFB1 gene expression was greater for the −509TT genotype (58.9%) than for the −509CC and −509CT genotypes (49.6% and 31.8%, respectively) (P = 0.071). In BEAS 2B cells, expression of endogenous TGFB1 was reduced by about 27% after montelukast treatment, while luciferase activity of both promoter variants was increased after montelukast treatment (−509C allele: 48.3%, P = 0.060; and −509T allele: 100.5%, P = 0.062). A more intensive response was registered in the promoter containing the −509T allele, which had 135% higher activity than the −509C variant (P = 0.035). This study showed that the presence of the −509T allele in the TGFB1 promoter might modulate effects of montelukast on TGFB1 gene expression, but future studies are necessary, taking into consideration other genetic and nongenetic factors. It is of potential importance for clinical management of asthma to clarify the influence of the C-509T polymorphism on the response to treatment with montelukast.

Cardiovascular (CV) morbidity and mortality increase along with the progression of chronic kidney disease (CKD). The potential novel biomarkers of cardiotoxicity have been tested with the aim of the early detection of patients at high CV risk, and among them are markers of inflammation, oxidative stress, acute renal injury, and microRNAs. The study analyzed biomarkers in non-dialysis-dependent (NDD; stage 3a–4 CKD) and dialysis-dependent (DD) CKD patients. The prospective cohort study included 87 patients who were followed for 18 months, during which period newly occurred CV events were recorded. Cox regression analysis confirmed serum albumin, urea, interventricular septum thickness diameter (IVST), the use of calcium antagonist, and erythropoiesis-stimulating agent to be significant predictors of CV outcome. No significant difference was observed in biomarkers of inflammation, oxidative stress, acute kidney injury (IL-18, CRP, ferritin, IMA, SOD, NGAL, and KIM-1), and miR-133a, in regards to the presence/absence of CV event, CV death, and left ventricular hypertrophy. Serum albumin, urea, IVST, and the use of calcium antagonist and erythropoiesis-stimulating agents were confirmed to be factors associated with CV events in CKD patients. Apart from traditional risk factors, new research is needed to define novel and reliable biomarkers of cardiotoxicity in CKD patients.

Approximately 20% of patients with colorectal cancer (CRC) are diagnosed with a mucinous subtype of this tumor, have a worse prognosis, and often show resistance to available therapies. Molecules from the mucin family are involved in the regulation of epithelial–mesenchymal transition (EMT), which significantly determines the cancer aggressiveness. This study aimed to examine the diagnostic and prognostic significance of mucinous histology and EMT markers in patients with early-onset CRC and their association with disease severity and tumor characteristics. This study included tumor tissue samples from 106 patients diagnosed with CRC before the age of 45, 53 with mucinous and 53 with non-mucinous tumors. The EMT status was determined by immunohistochemical analysis of E-cadherin and Vimentin in tissue sections. Mucinous tumors had significantly higher Mucin-1 (p < 0.001) and cytoplasmic E-cadherin (p = 0.043) scores; they were significantly less differentiated (p = 0.007), more advanced (p = 0.027), and predominately affected right the colon (p = 0.039) compared to non-mucinous tumors. Epithelial tumors were significantly better differentiated (p = 0.034) and with less prominent tumor budding (p < 0.001) than mesenchymal tumors. Mucin-1 and Vimentin were independent predictors of tumor differentiation (p = 0.006) and budding (p = 0.001), respectively. Mucinous histology and EMT markers are significant predictors of disease severity and tumor characteristics in early-onset colorectal cancer.