Hsa_circRNA_007630 knockdown delays colon cancer progression by modulation of ferroptosis via miR-506-3p/AURKA axis.

Colon cancer contributes to high mortality rates internationally that has seriously endangered human health. Aurora kinase A (AURKA) served as a key molecule in colon cancer. However, its role of AURKA on regulating ferroptosis in colon cancer and their possible interactions with miRNAs and circRNAs remain still elusive. Comprehensive bioinformatics analysis after RNA-sequencing was conducted to determine the differentially expressed genes (DEGs), ferroptosis-related DEGs and hub genes. The direct relationship between miR-506-3p and hsa_circRNA_007630 or AURKA was predicted, then verified by dual luciferase reporter and quantitative real-time polymerase chain reaction. The rescue experiments were conducted by cotransfection with si-hsa_circRNA_007630, miR-506-3p inhibitor or pcDNA-AURKA in HT29 cells. Erastin was used to induce ferroptosis in HT29 cells and validated by detecting levels of intracellular Fe2+, lipid reactive oxygen species, glutathione, malondialdehyde and ferroptosis markers expression. We screened a total of 331 DEGs, 26 ferroptosis-related genes, among which 3 hub genes were identified through PPI network analysis. Therein, AURKA expression was elevated in colon cancer cells. Moreover, AURKA was targeted by miR-506-3p, and hsa_circRNA_007630 operated as miR-506-3p sponge. The effect of hsa_circRNA_007630 depletion on the inhibiting malignant phenotypes of HT29 cells was rescued by inhibition of miR-506-3p or AURKA overexpression. Additionally, AURKA reduced erastin-induced ferroptosis in HT29 cells. Depletion of circRNA_007630 exerts as a suppressive role in colon cancer through a novel miR-506-3p/AURKA pathway related to ferroptosis, and might become a novel marker for colon cancer.

Thymoquinone Increases the Sensitivity of SW-480 Colon Cancer Cells to 5-Fluorouracil.

Background: Studies have concentrated on the therapeutic potential of thymoquinone (TQ), a natural polyphenol, in diverse malignancies, such as colorectal cancer. Nevertheless, the precise mechanisms of TQ-mediated anticancer properties are not yet fully elucidated. Objective: The present study has been designed to scrutinize the impact of TQ on 5-fluorouracil (5-FU)-mediated apoptosis in SW-480 cells. Materials and Methods: SW-480 cells were treated with TQ, 5-FU, and a combination of TQ + 5-FU. MTT assay was employed to assess cell viability. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to evaluate apoptotic markers comprising Bcl-2, Bax, and caspase-9 expression levels. The γ-H2AX protein expression was assessed by western blotting, and Annexin V flow cytometry was implemented to determine the apoptosis rate. Results: 5-FU significantly reversed the cell proliferation in a dose-dependent circumstance. The concurrent administration of TQ and 5-FU led to a substantial inhibition of cell growth in comparison to single treatments (p < 0.05). TQ also facilitated apoptosis via upregulating Bax and caspase-9 proapoptotic markers and suppressing antiapoptotic mediators, like Bcl-2. In addition, TQ augmented 5-FU-induced apoptosis in SW-480 cells. 5-FU, combined with TQ, increased the protein expression of γ-H2AX in SW-480 cells compared with groups treated with TQ and 5-FU alone. Conclusion: The present study's findings unveil the significance of TQ as a potential therapeutic substance in colorectal cancer, particularly through enhancing 5-FU-induced apoptosis.

The expression and clinical significance of CFAP65 in colon cancer.

BACKGROUND: CFAP65 (cilia and flagella associated protein 65) is a fundamental protein in the development and formation of ciliated flagella, but few studies have focused on its role in cancer. This study aimed to investigate the prognostic significance of CFAP65 in colon cancer. METHODS: The functionally enriched genes related to CFAP65 were analyzed through the Gene Ontology (GO) database. Subsequently, CFAP65 expression levels in colon cancer were evaluated by reverse transcription and quantitative polymerase chain reaction (RT-qPCR) and immunoblotting in 20 pairs of frozen samples, including tumors and their matched paratumor tissue. Furthermore, protein expression of CFAP65 in 189 colon cancer patients were assessed via immunohistochemical staining. The correlations between CFAP65 expression and clinical features as well as long-term survival were statistically analyzed. RESULTS: CFAP65-related genes are significantly enriched on cellular processes of cell motility, ion channels, and GTPase-associated signaling. The expression of CFAP65 was significantly higher in colon cancer tissue compared to paratumor tissue. The proportion of high expression and low expression of CFAP65 in the clinical samples of colon cancer were 61.9% and 38.1%, respectively, and its expression level was not associated with the clinical parameters including gender, age, tumor location, histological differentiation, tumor stage, vascular invasion and mismatch repair deficiency. The five-year disease-free survival rate of the patients with CFAP65 low expression tumors was significantly lower than that those with high expression tumors (56.9% vs. 72.6%, P = 0.03), but the overall survival rate has no significant difference (69% vs. 78.6%, P = 0.171). The cox hazard regression analysis model showed that CFAP65 expression, tumor stage and tumor location were independent prognostic factors. CONCLUSIONS: In conclusion, we demonstrate CFAP65 is a potential predictive marker for tumor progression in colon cancer.

Evolution of Surgical Management of Complicated Left Colon Cancer.

Complicated colon cancer accounts for up to 40% of colon cancer patients. While the management of complicated right colon cancer has some standard recommendations, for complicated left colon cancer single stage or two-stage procedures are subject to controversies. AIM: To study the types of procedures and postoperative morbidity and mortality for complicated left colon cancer patients admitted to the 1st Surgical Clinic of the County Clinical Emergency Hospital of Craiova during the past 23 years. We aimed to present the evolution of the surgical management in the emergency procedures for complicated left colon. MATERIAL AND METHOD: retrospective study of patients with complicated left colon cancer admitted to our clinic between 2001 and 2023. We analyzed the postoperative morbidity and mortality of each type of emergency procedure (single stage or two-stage) and compared them throughout three periods of time. Results: Three groups observed: G1 â?" 2001-2010, (96 patients); G2 â?" 2011-2016, (65 patients); G3 â?" 2017-2023, (77 patients). We registered significant increase in single stage procedures from G1 to G2 (11.2% vs. 33.8%). In G3, single stage procedure rate decreased significantly (20.8% vs. 33.8%). Postoperative morbidity and mortality was significantly lower in G2 compared to G1 in both single stage and two-stage procedures. G3 compared to G2 registered significant decrease for single stage procedures but similar for two-stage procedures. CONCLUSION: For left colon emergencies, two-stage procedures seem safer, as resections with primary anastomosis, even with selected cases and experienced surgeons, still associate higher postoperative morbidity and mortality.

Effects of photobiomodulation on colon cancer cell line HT29 according to mitochondria.

BACKGROUND/AIM: Although photobiomodulation therapy (PBMt) is available to alleviate post-operative side effects of malignant diseases, its application is still controversial due to some potential of cancer recurrence and occurrence of a secondary malignancy. We investigated effect of PBMt on mitochondrial function in HT29 colon cancer cells. METHODS: HT29 cell proliferation was determined with MTT assay after PBMt. Immunofluorescent staining was performed to determine mitochondrial biogenesis and reactive oxygen species (ROS). Mitochondrial membrane potential was measured with Mitotracker. Western blotting was executed to determine expression of fission, fusion, UCP2, and cyclin B1 and D1 proteins. In vivo study was performed by subcutaneously inoculating cancer cells into nude mice and immunohistochemistry was done to determine expression of FIS1, MFN2, UCP2, and p-AKT. RESULTS: The proliferation and migration of HT29 cells reached maximum with PBMt (670 nm, light emitting diode, LED) at 2.0 J/cm2 compared to control (P < 0.05) with more expression of cyclin B1 and cyclin D1 (P < 0.05). Immunofluorescent staining showed that ROS and mitochondrial membrane potential were enhanced after PBMt compared to control. ATP synthesis of mitochondria was also higher in the PBMt group than in the control (P < 0.05). Expression levels of fission and fusion proteins were significantly increased in the PBMt group than in the control (P < 0.05). Electron microscopy revealed that the percentage of mitochondria showing fission was not significantly different between the two groups. Oncometabolites including D-2-hydoxyglutamate in the supernatant of cell culture were higher in the PBMt group than in the control with increased UCP2 expression (P < 0.05). Both tumor size and weight of xenograft in nude mice model were bigger and heavier in the PBMt group than in the control (P < 0.05). Immunohistologically, mitochondrial biogenesis proteins UCP2 and p-AKT in xenograft of nude mice were expressed more in the PBMt group than in the control (P < 0.05). CONCLUSIONS: Treatment with PBM using red light LED may induce proliferation and progression of HT29 cancer cells by increasing mitochondrial activity and fission.

Uncovering Metabolic Alterations in HCT-116 Colon Cancer Cells upon Exposure to Bamboo Leaf Extract Obtained from Guadua incana Londoño.

Metabolic alterations are increasingly recognized as important aspects of colorectal cancer (CRC), offering potential avenues for identifying therapeutic targets. Previous studies have demonstrated the cytotoxic potential of bamboo leaf extract obtained from Guadua incana (BLEGI) against HCT-116 colon cancer cells. However, the altered metabolic pathways in these tumor cells remain unknown. Therefore, this study aimed to employ an untargeted metabolomic approach to reveal the metabolic alterations of the endometabolome and exometabolome of HCT-116 cells upon exposure to BLEGI treatment. First, a chemical characterization of the BLEGI was conducted through liquid chromatography coupled with mass spectrometry (LC-MS). Next, we assessed cell viability via MTT and morphological analysis using an immunofluorescence assay against colon cancer cells, and anti-inflammatory activity using an LPS-stimulated macrophage model. Subsequently, we employed LC-MS and proton nuclear magnetic resonance (1H-NMR) to investigate intra- and extracellular changes. Chemical characterization primarily revealed the presence of compounds with a flavone glycoside scaffold. Immunofluorescence analysis showed condensed chromatin and subsequent formation of apoptotic bodies, suggesting cell death by apoptosis. The results of the metabolomic analysis showed 98 differential metabolites, involved in glutathione, tricarboxylic acid cycle, and lipoic acid metabolism, among others. Additionally, BLEGI demonstrated significant nitric oxide (NO) inhibitory capacity in macrophage cells. This study enhances our understanding of BLEGI's possible mechanism of action and provides fresh insights into therapeutic targets for treating this disease.

Comprehensive Analysis of the Function and Prognostic Value of TAS2Rs Family-Related Genes in Colon Cancer.

In the realm of colon carcinoma, significant genetic and epigenetic diversity is observed, underscoring the necessity for tailored prognostic features that can guide personalized therapeutic strategies. In this study, we explored the association between the type 2 bitter taste receptor (TAS2Rs) family-related genes and colon cancer using RNA-sequencing and clinical datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Our preliminary analysis identified seven TAS2Rs genes associated with survival using univariate Cox regression analysis, all of which were observed to be overexpressed in colon cancer. Subsequently, based on these seven TAS2Rs prognostic genes, two colon cancer molecular subtypes (Cluster A and Cluster B) were defined. These subtypes exhibited distinct prognostic and immune characteristics, with Cluster A characterized by low immune cell infiltration and less favorable outcomes, while Cluster B was associated with high immune cell infiltration and better prognosis. Finally, we developed a robust scoring system using a gradient boosting machine (GBM) approach, integrated with the gene-pairing method, to predict the prognosis of colon cancer patients. This machine learning model could improve our predictive accuracy for colon cancer outcomes, underscoring its value in the precision oncology framework.

Far-Ultraviolet Light at 222 nm Affects Membrane Integrity in Monolayered DLD1 Colon Cancer Cells.

222 nm far-ultraviolet (F-UV) light has a bactericidal effect similar to deep-ultraviolet (D-UV) light of about a 260 nm wavelength. The cytotoxic effect of 222 nm F-UV has not been fully investigated. DLD-1 cells were cultured in a monolayer and irradiated with 222 nm F-UV or 254 nm D-UV. The cytotoxicity of the two different wavelengths of UV light was compared. Changes in cell morphology after F-UV irradiation were observed by time-lapse imaging. Differences in the staining images of DNA-binding agents Syto9 and propidium iodide (PI) and the amount of cyclobutane pyrimidine dimer (CPD) were examined after UV irradiation. F-UV was cytotoxic to the monolayer culture of DLD-1 cells in a radiant energy-dependent manner. When radiant energy was set to 30 mJ/cm2, F-UV and D-UV showed comparable cytotoxicity. DLD-1 cells began to expand immediately after 222 nm F-UV light irradiation, and many cells incorporated PI; in contrast, PI uptake was at a low level after D-UV irradiation. The amount of CPD, an indicator of DNA damage, was higher in cells irradiated with D-UV than in cells irradiated with F-UV. This study proved that D-UV induced apoptosis from DNA damage, whereas F-UV affected membrane integrity in monolayer cells.

Memory effects of prior subculture may impact the quality of multiomic perturbation profiles.

Mass spectrometry-based omics technologies are increasingly used in perturbation studies to map drug effects to biological pathways by identifying significant molecular events. Significance is influenced by fold change and variation of each molecular parameter, but also by multiple testing corrections. While the fold change is largely determined by the biological system, the variation is determined by experimental workflows. Here, it is shown that memory effects of prior subculture can influence the variation of perturbation profiles using the two colon carcinoma cell lines SW480 and HCT116. These memory effects are largely driven by differences in growth states that persist into the perturbation experiment. In SW480 cells, memory effects combined with moderate treatment effects amplify the variation in multiple omics levels, including eicosadomics, proteomics, and phosphoproteomics. With stronger treatment effects, the memory effect was less pronounced, as demonstrated in HCT116 cells. Subculture homogeneity was controlled by real-time monitoring of cell growth. Controlled homogeneous subculture resulted in a perturbation network of 321 causal conjectures based on combined proteomic and phosphoproteomic data, compared to only 58 causal conjectures without controlling subculture homogeneity in SW480 cells. Some cellular responses and regulatory events were identified that extend the mode of action of arsenic trioxide (ATO) only when accounting for these memory effects. Controlled prior subculture led to the finding of a synergistic combination treatment of ATO with the thioredoxin reductase 1 inhibitor auranofin, which may prove useful in the management of NRF2-mediated resistance mechanisms.

The effect of ileal resection length on postoperative complications and prognosis in right colon cancer.

BACKGROUND: There is a lack of literature on the length of the terminal ileum to be resected in right hemicolectomy for colon cancer. Therefore, we aimed to determine the mean ileal loop length and the effect of this variation on postoperative complications and long-term oncological outcomes in patients who underwent right hemicolectomy. METHODS: Right hemicolectomy surgeries performed for colon cancer in a tertiary care hospital between January 2011 and December 2018 were retrospectively analyzed from a prospective database. Two patient groups were established based on the mean length of the resected ileum above and below 7 cm. The two groups were compared for clinicopathological data, postoperative complications, mortality, long-term overall survival (OS) and disease-free survival (DFS). The factors contributing to OS and DFS were analyzed. RESULTS: The study included 217 patients. Body mass index (BMI) values were significantly higher in the ileum resection length > 7 cm group (p = 0.009). Pathological N stage, tumor diameter, and number of metastatic lymph nodes were significantly higher in the ileum resection length > 7 cm group (p = 0.001, p = 0.001, and p = 0.026, respectively). There was no significant difference for postoperative complication and mortality rates between the two groups. The mean follow-up period was 61.2 months (2-120) in all patients. The total number of deaths was 29 (11.7%) while the 60-month OS was 83.5% and 50-month DFS was 81.8%. There was no significant difference between the groups in terms of OS and DFS rates (p > 0.05). CONCLUSIONS: Excessive resection of the distal ileum in right hemicolectomy does not provide any benefit in terms of prognosis and complications.The ileum resection length and values close to it in our study appear to be sufficient.

Comparison of D2 vs D3 lymph node dissection for RIght COloN cancer (RICON): study protocol for an international multicenter open-label randomized controlled trial.

BACKGROUND: Colon cancer is a global health concern, ranking fifth in both new diagnoses and deaths among tumors worldwide. Surgical intervention remains the primary treatment for localized cases, with a historical evolution marked by a focus on short-term outcomes. While Japan pioneered radical tumor removal with a systematic categorization of lymph nodes (D1, D2, D3), the dissemination of Japanese practices to the West was delayed until 90th of last century. Discrepancies between Japanese D3 dissection and the CME with CVL principle persist, with variations in longitudinal margins and recommended procedures. Non-randomized trials indicate the superiority of D3 over D2, but a consensus is lacking. METHODS: This prospective, international, multicenter, randomized controlled trial employs a two-arm, parallel-group, open-label design to rigorously compare the 5-year overall survival outcomes between D2 and D3 lymph node dissection in stage II-III right colon cancer. Building on prior studies, the trial aims to address existing knowledge gaps and provide a comprehensive evaluation of the outcomes associated with D3 dissection. The study population comprises patients with right colon cancer, ensuring a focused investigation into the specific context of this disease. The trial design emphasizes its global scope and collaboration across multiple centers, enhancing the generalizability of the findings. DISCUSSION: This study's primary objective is to elucidate the potential superiority in 5-year overall survival benefits of D3 lymph node dissection compared to the conventional D2 approach in patients with stage II-III right colon cancer. By examining this specific subset of patients, the research aims to contribute valuable insights into optimizing surgical strategies for improved long-term outcomes. The trial's international and multicenter nature enhances its applicability across diverse populations. The outcomes of this study may inform future guidelines and contribute to the ongoing discourse surrounding the standardization of colon cancer surgery, particularly in the context of right colon cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT03200834. Registered on June 27, 2017.

CT-derived body composition and differential association with age, TNM stage and systemic inflammation in patients with colon cancer.

Low skeletal muscle index/density (SMI/SMD) is prevalent in cancer, adversely prognostic and associated with tumour stage and the systemic inflammatory response (SIR). Age and SMI/SMD has not been widely studied. The present study analyses the association between age and SMI/SMD after adjustment for other clinicopathological factors. Patients undergoing resectional surgery for TNM Stage I-III disease within the West of Scotland between 2011 and 2014 were identified. A single CT slice was obtained from each patients staging CT scan. SMI and SMD were stratified normal/abnormal. The SIR was stratified using Systemic Inflammatory Grade (SIG). When stratified by age (< 50/50s/60s/70s/80+), 39%/38%/48%/62%/74% and 27%/48%/64%/82%/92% of patients had a low SMI and SMD respectively (both p < 0.001). Older age (OR 1.47, p < 0.001), female sex (OR 1.32, p = 0.032), lower socioeconomic deprivation (OR 1.15, p = 0.004), higher ASA (OR 1.30, p = 0.019), emergency presentation (OR 1.82, p = 0.003), lower BMI (OR 0.67, p < 0.002) and higher SIG (OR 1.23, p < 0.001) were independently associated with low SMI. Older age (OR 2.28, p < 0.001), female sex (OR 1.38, p = 0.038), higher ASA (OR 1.92, p < 0.001), emergency presentation (OR 1.71, p = 0.023), and higher SIG (OR 1.37, p < 0.001) were independently associated with lower SMD. Tumour factors were not independently associated with either SMI/SMD. Age was a major factor associated with low SMI/SMD in patients with colon cancer. Therefore, in these patients it is likely that this represents largely constitutional body composition as opposed to being a disease mediated effect. Adjustment for age is required when considering the cancer mediated effect on SMI/SMD in patients with colon cancer.

Identification and validation of calcium extrusion-related genes prognostic signature in colon adenocarcinoma.

Background: Disruptions in calcium homeostasis are associated with a wide range of diseases, and play a pivotal role in the development of cancer. However, the construction of prognostic models using calcium extrusion-related genes in colon adenocarcinoma (COAD) has not been well studied. We aimed to identify whether calcium extrusion-related genes serve as a potential prognostic biomarker in the COAD progression. Methods: We constructed a prognostic model based on the expression of calcium extrusion-related genes (SLC8A1, SLC8A2, SLC8A3, SLC8B1, SLC24A2, SLC24A3 and SLC24A4) in COAD. Subsequently, we evaluated the associations between the risk score calculated by calcium extrusion-related genes and mutation signature, immune cell infiltration, and immune checkpoint molecules. Then we calculated the immune score, stromal score, tumor purity and estimate score using the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm. The response to immunotherapy was assessed using tumor immune dysfunction and exclusion (TIDE). Finally, colorectal cancer cells migration, growth and colony formation assays were performed in RKO cells with the overexpression or knockdown SLC8A3, SLC24A2, SLC24A3, or SLC24A4. Results: We found that patients with high risk score of calcium extrusion-related genes tend to have a poorer prognosis than those in the low-risk group. Additionally, patients in high-risk group had higher rates of KRAS mutations and lower MUC16 mutations, implying a strong correlation between KRAS and MUC16 mutations and calcium homeostasis in COAD. Moreover, the high-risk group showed a higher infiltration of regulatory T cells (Tregs) in the tumor microenvironment. Finally, our study identified two previously unreported model genes (SLC8A3 and SLC24A4) that contribute to the growth and migration of colorectal cancer RKO cells. Conclusions: Altogether, we developed a prognostic risk model for predicting the prognosis of COAD patients based on the expression profiles of calcium extrusion-related genes, Furthermore, we validated two previously unreported tumor suppressor genes (SLC8A3 and SLC24A4) involved in colorectal cancer progression.

Tumor Budding as a Prognostic Marker in Primary Colon Cancer - A Single Center Experience.

Introduction: Tumor budding (TB) is considered to be a morphological and prognostic factor relevant to colon cancer (CC). The aim of our study is to assess the TB and to evaluate its relationship to clinicopathological findings within stage II and III CC patients as a single center experience. Materials and methods: A total of 120 CC patients operated between 2018 and 2021 at the University Clinic of Digestive Surgery in Skopje, the Republic of North Macedonia were included in this retrospective, single center study. TB was evaluated by the magnification of 200x along the invasive front of the primary tumor on H&E and CKAE1/AE3 immunohistochemically stained sections. Two grades were used: low grade (TB1, 0-4 TBs) and high-grade, which includes intermediate (TB2, 5-9 TBs) and high grade (TB3 ≥10TBs) of TBs. Results: A statistically significant correlation has been identified between high-grade TB and age (p=0.05) of the patients. There was also a significantly higher occurrence of high-grade TB in patients within stage III CC. Statistically significant correlations were also found in lymph node status (p<0.01), vascular invasion (p<0.05), lymphatic invasion (p<0.01), postoperative relapse (p<0.01), and death (p<0.01). Tumor relapse and death were significantly more frequent in patients with high-grade TB than those with low-grade TB. Patients with registered high-grade TB demonstrated significantly lower relapse-free survival (RFS) and overall survival (OS) rates than patients with low-grade TB over the observation period (RFS: 53.8% vs. 98.5%, p<0.001; OS: 65.4% vs. 97.1%, p<0.001, respectively). Patients with lung and liver postoperative relapses had higher percentage of cases with high-grade TB (94.1%). Conclusion: Our results are highly suggestive that TB should be included as a histological biomarker in the pathology report of patients with stage II and stage III CC, because of its prognostic value.

[D2 and D3 lymph node dissection for colon cancer]. / Rezul'taty limfodissektsii d2 i d3 pri rake obodochnoi kishki.

OBJECTIVE: To evaluate surgical and oncological results of standard and extended lymph node dissection (D2 and D3) in patients with colon cancer. MATERIAL AND METHODS: We analyzed treatment outcomes in 74 patients with colon cancer stage T1-4aN0-2M0 who underwent right- and left-sided hemicolectomy, resection of sigmoid colon with standard and extended lymph node dissection (D2 and D3). RESULTS: Surgical approach and level of D3 lymph node dissection did not increase intra- and postoperative morbidity. Laparoscopic interventions were followed by significantly lower intraoperative blood loss and earlier gas discharge. Metastatic lesion of apical lymph nodes was observed in 5 out of 36 patients who underwent D3 lymph node dissection (13.8%), and metastases in regional lymph nodes rN1-2 were found in all these patients. Overall 5-year survival was 86%. Disease-free and overall 5-year survival were similar after D2 and D3 lymph node dissection. CONCLUSION: D3 lymph node dissection is safe for colon cancer. Metastatic lesions of apical lymph nodes during D3 lymph node dissection were detected only in patients with lesions of regional lymph nodes (rN1-2). Disease-free and overall 5-year survival were similar after D2 and D3 lymph node dissection.

Morphological Characteristics of Colon Tumors in Mice with Different Tolerance to Hypoxia.

In adult male C57BL/6 mice with high (HR) and low (LR) resistance to hypoxia, morphological features of colon tumors and blood parameters were evaluated 70 days after intraperitoneal injection of azoxymethane and subsequent consumption of 3 cycles of dextran sulfate sodium. On macroscopic analysis, tumors were found in the distal colon in 35% (7 of 20 animals) of HR and 31% (4 of 13 animals) of LR animals. Microscopic analysis of the distal colon revealed tumors in 75% (15 of 20 animals) of HR and 69% (9 of 13 animals) of LR mice. The tumors were presented by areas of glandular intraepithelial neoplasia and adenocarcinomas; the incidence and the area of the tumors did not differ in groups of HR and LR mice. The number of neuroendocrine and goblet cells in the distal colon mucosa in the areas of tumors was similar in the compared groups. However, in both HR and LR mice of the experimental groups, the content of goblet cells in tumors was lower and the content of endocrine cells was higher than in the corresponding control groups. In the peripheral blood, the erythrocyte count and hemoglobin content decreased in HR and LR mice of the experimental groups; the relative number of monocytes increased only in HR mice and the absolute number of lymphocytes and monocytes decreased in LR mice. Thus, 70 days after azoxymethane administration and dextran sulfate sodium consumption, the tumors in mice were presented by glandular intraepithelial neoplasia and adenocarcinomas, and their incidence and area did not differ between animals with different tolerance to hypoxia.

Geese as reservoirs of human colon cancer-associated Streptococcus gallolyticus.

Recently, an increased number of reports have described pathogens of animal origin that cause a variety of infections and a rise in their transmission to humans. Streptococcus gallolyticus, a member of the Streptococcus bovis/Streptococcus equinus complex (SBSEC), is one of these pathogens and infects a wide range of hosts from mammals to poultry and has a broad functionality ranging from pathogenicity to food fermentation. As S. gallolyticus causes complications including bacteremia, infective endocarditis, and colorectal malignancy in humans, it is important to investigate its occurrence in various hosts, including geese, to prevent potential zoonotic transmissions. This study aimed to investigate the presence of S. gallolyticus in the droppings of clinically healthy and diarrheic geese, which were raised intensively and semi-intensively, by the in vitro culture method, characterize the isolates recovered by PCR and sequence-based molecular methods and determine their antibiotic susceptibility by the disk diffusion and gradient test methods. For this purpose, 150 samples of fresh goose droppings were used. Culture positivity for S. gallolyticus was determined as 8% (12/150). PCR analysis identified 54.55% (n = 6) of the isolates as S. gallolyticus subsp. gallolyticus and 45.45% (n = 5) as S. gallolyticus subsp. pasteurianus. Following the 16S rRNA sequence and ERIC-PCR analyses, S. gallolyticus subspecies exhibited identical cluster and band profiles that could be easily distinguished from each other and were clonally identified. High rates of susceptibility to florfenicol, penicillin, rifampicin, and vancomycin were detected among the isolates, regardless of the subspecies diversity. Both subspecies showed high levels of resistance to bacitracin, clindamycin, doxycycline, tetracycline, trimethoprim-sulfamethoxazole, and erythromycin and multiple MDR profiles, indicating their potential to become superbugs. This first report from Türkiye demonstrates the occurrence of the S. gallolyticus subspecies in geese. In view of the recent increase of geese production and the consumption of goose meat in Türkiye, the occurrence of S. gallolyticus in geese should not be ignored to prevent zoonotic transmission.

Two spurge species, Euphorbia resinifera O. Berg and Euphorbia officinarum subsp. echinus (Hook.f. & Coss.) Vindt inhibit colon cancer.

BACKGROUND: Colon cancer, a prominent contributor to global cancer-related deaths, prompts the need for innovative treatment strategies. Euphorbia resinifera O. Berg (E. resinifera) and Euphorbia officinarum subsp. echinus Hook. f. & Coss Vindt (E. echinus) and their bee-derived products have been integral to traditional Moroccan medicine due to their potential health benefits. These plants have historical use in addressing various health issues, including cancer. However, their effects against colon cancer remain unclear, and the specific mechanisms underlying their anti-cancer effects lack comprehensive investigation. METHODS: The study aimed to assess the potential anti-cancer effects of Euphorbia extract on colon cancer cell lines (DLD-1) through various techniques. The apoptosis, migration, and proliferation of DLD-1 cells were measured in DLD-1 cells. In addition, we conducted High-Performance Liquid Chromatography (HPLC) analysis to identify the profile of phenolic compounds present in the studied extracts. RESULTS: The extracts demonstrated inhibition of colon cancer cell migration. E. resinifera flower and E. echinus stem extracts show significant anti-migratory effects. Regarding anti-proliferative activity, E. resinifera flower extract hindered proliferation, whereas E. echinus flower extract exhibited dose-dependent inhibition. Apoptosis assays revealed E. resinifera flower extract inducing early-stage apoptosis and E. echinus flower extract promoting late-stage apoptosis. While apoptotic protein expression indicated, E. resinifera stem and propolis extracts had minimal impact on apoptosis. CONCLUSION: The findings provide evidence supporting the beneficial effects of E resinifera and E. echinus extracts on colon cancer and exerting anti-cancer properties.