In vivo最新文献

Background/aim: Inflammatory bowel diseases and colorectal cancer are a major cause of morbidity and mortality. Amine oxidase, copper-containing 3 (AOC3) is a critical enzyme in the physiological trafficking of leukocytes and the regulation of inflammation. This study aimed to examine the effects of Aoc3 deficiency in mice models of colitis and colorectal tumorigenesis.

Materials and methods: C57BL/6 and Aoc3 knockout mice were used for Dextran Sodium Sulfate (DSS) induced acute colitis and the Azoxymethane (AOM)/DSS model of inflammation-related colon cancer. We also evaluated the effect of Aoc3 in an Apc mutant mice model of intestinal and colonic tumorigenesis.

Results: We observed that Aoc3 deficient mice were more prone to colitis induced by DSS in early phases and their survival was shorter. We also showed that Aoc3 deficient mice developed more tumors both in AOM/DSS and Apc mutant mice models. Furthermore, colonic tumors in the AOM/DSS groups in Aoc3 mutant mice were generally invasive type adenocarcinomas.

Conclusion: Aoc3 deficiency promotes colitis and colonic tumorigenesis in mouse models.

Background/aim: Benign and tumor-like lesions of the hindfoot and ankle are common, whereas malignant entities are rare. Accurate evaluation and timely management of these lesions can be challenging, making it crucial to understand their incidence and anatomic localization. This study retrospectively analyzed the distribution of benign and malignant bone and soft tissue tumors in the hindfoot and ankle.

Patients and methods: This study included patient data from a single center, such as age, sex, histologic diagnosis, and anatomic location over a 12.5 year period.

Results: Of the 105 cases reviewed, 19 cases (18.1%) were osseous lesions and 86 cases (81.9%) were soft tissue lesions. The latter were divided into 77 benign and 9 malignant cases, resulting in an overall malignancy rate of 8.6%. The most common osseous lesion was the intraosseous ganglion (n=12). The majority of benign soft tissue lesions (75.3%) were located in the hindfoot, with TGCT, schwannoma, and ganglion cysts being the most common types. The nine malignant cases were distributed among seven entities and were evenly distributed among both regions and sexes. Malignant cases had a higher mean age (59.2 years) compared to benign cases (40.8 years; p=0.001).

Conclusion: Tumors, tumor-like lesions, and pseudotumors represent an important aspect of ankle pathology. The majority of focal masses and swellings are benign soft tissue or osseous lesions, but malignant entities can occur and may be mistaken for benign conditions. Preoperative imaging and histopathologic examination are essential, and preoperative presentation to a multidisciplinary tumor board is recommended in unclear cases.

Background/aim: We hypothesized that the hemoglobin, albumin, lymphocyte, and platelet (HALP) score may be a promising marker for the treatment and management of gastric cancer (GC). To test this hypothesis, we evaluated the clinical impact of the HALP score in patients with GC who received curative treatment.

Patients and methods: Consecutive patients who underwent curative resection for GC at the Yokohama City University between 2005 and 2020 were selected based on their medical records. The HALP score was calculated as follows: HALP=Hemoglobin (g/l) × albumin (g/l) × lymphocytes (10⁹/l)/platelets (10⁹/l).

Results: The 3-year and 5-year overall survival (OS) rates were 88.6% and 85.8%, respectively, in patients with HALP scores of >40, and 70.3% and 57.2% in patients with HALP scores of ≤40. There were significant differences between the groups analyzed (p<0.001). In univariate analysis, age, T status, lymph node metastasis status, HALP score, lymphovascular invasion status, pathological type, and postoperative complication status were identified as significant prognostic factors for OS. In multivariate analysis, the HALP score remained a significant prognostic factor for OS [hazard ratio (HR)=2.679; 95% confidence interval (CI)=1.455-4.934, p=0.002]. Similar results were observed in the analysis of recurrence-free survival. In addition, the HALP score status affects the postoperative clinical course, including the occurrence of postoperative anastomotic leakage and the introduction of postoperative adjuvant chemotherapy.

Conclusion: The HALP score affects both short- and long-term oncological outcomes. Thus, the HALP score may be a promising prognostic factor for the treatment and management of GC.

Background/aim: The aim of the study was to investigate whether it is possible to evaluate the axilla after treatment without performing sentinel lymph node biopsy (SLNB) in breast cancer patients with biopsy-proven axillary lymph node metastases who received neoadjuvant chemotherapy (NAC).

Patients and methods: This prospective, randomized, clinically designed study included patients with clinical T_1-3 and biopsy-proven N₁ breast cancer. Prior to the surgery scheduled after NAC, the patients were randomized into two groups. A biopsy sample was obtained from the clipped axillary lymph node, which was preoperatively known to be metastatic, using fine needle aspiration (FNAB) in the first group and core needle biopsy (CNB) in the second group. The predictive ability of the two biopsy methods for the SLNB results was evaluated.

Results: The study included 50 female patients with breast cancer, with a mean age of 48.4±10.72 years. In both groups, metastasis was detected in nine patients, and no metastasis was seen in 14 patients. In intergroup comparisons, all patients with metastasis in the FNAB group also had metastasis according to SLNB, while 21.4% of the cases without metastasis in this group were metastatic according to SLNB. In the CNB group, metastasis was observed in all patients with metastasis according to SLNB, while no metastasis was detected in those who were reported to have no metastasis by SLNB. The accuracy, specificity, and sensitivity values for the prediction of SLNB results were all found to be 100% for CNB, whereas they were 87%, 100%, and 75%, respectively, for FNAB.

Conclusion: Both CNB and FNAB could potentially replace SLNB due to their high accuracy rates in evaluating the axilla after NAC. The sensitivity and accuracy of CNB were determined to be higher.

Background/aim: Bone marrow cells contain nonhematopoietic cells with the ability to differentiate into osteogenic, chondrogenic, and adipogenic lineages. Mechanical stress influences osteoblast differentiation of bone marrow cells into osteogenic, chondrogenic, and adipogenic lineages, measurable as the abundance of alkaline phosphatase-positive (ALP⁺) colony-forming unit-fibroblasts (CFU-F); however, the effect of diode laser irradiation on osteoblast differentiation is unknown. The aim of this study was to analyze the effects of photobiomodulation on the osteogenic differentiation of mesenchymal stem cells in the bone marrow, using the CFU-F assay.

Materials and methods: Bone marrow cells isolated from rat tibiae were cultured and irradiated with a diode laser (wavelength 808 nm) at a total energy of 0 J (control), 50 J, and 150 J.

Results: On day 7 after irradiation, ALP⁺ CFU-F were most abundant in the 50 J group and the least abundant in the 150 J group. Mineralized nodule formation was observed after long-term culture (21 days). Compared with the control group, there were significantly more nodules in the 50 J group and significantly fewer nodules in the 150 J group. Osteocalcin mRNA expression was highest in the 50 J group, and there was no difference between the control and 150 J groups.

Conclusion: Irradiation with 50 J was effective in stimulating osteogenesis in bone marrow stem cells. These findings suggest that diode laser irradiation can induce osteogenesis in rat bone marrow cells in an energy-dependent manner, and appears suitable for application in bone regeneration therapy.

Background/aim: In a previous report, our group showed that oral administration of lipopolysaccharides (LPS) from Pantoea agglomerans can prevent the progression of streptozotocin (STZ)-induced diabetes-related cognitive dysfunction (DRCD) in mice without causing significant side-effects. However, the treatment effects of oral administration of LPS to DRCD remain unknown.

Materials and methods: We modified our previous animal experimental model to investigate whether oral administration of LPS can recover cognitive function after DRCD onset.

Results: The Morris water maze (MWM) revealed a significant decrease in learning and memory abilities at 13 days after intracerebroventricular administration of STZ, thereby providing evidence of the occurrence of DRCD in the animal model. Oral administration of LPS (1 mg/kg per day) started after cognitive impairment was observed. After 28 days of treatment, mice receiving LPS via the oral route showed significant recovery of spatial learning ability, a symptom of early dementia, while only a trend toward recovery was seen for spatial memory compared to the untreated group.

Conclusion: These results, limited to MWM, suggest that oral administration of LPS is a promising therapeutic strategy for restoring decreased spatial learning ability.

Background/aim: Cigarette smoke has been shown to induce a phenotype in humans known as "acquired cystic fibrosis". This occurs because the cystic fibrosis transmembrane conductance regulator (CFTR) functions are impaired systemically due to the deleterious effects of smoke components. Elucidation of cigarette smoke effects on the tracheal epithelium is important. The aim of this study was to develop an ex vivo sheep tracheal model to investigate tracheal ion function. In this model, the epithelial sodium channel (ENaC) is inhibited after exposure to cigarette smoke extract (CSE) as a proof of principle.

Materials and methods: Tracheas were isolated from healthy sheep and the tracheal epithelium was surgically excised. Tissues were mounted in Ussing chambers and the short circuit current (I_sc) was measured after incubation with 5% CSE in PBS or PBS alone for 30 min. The function of ENaC was investigated by the addition of amiloride (10^-5M) apically. Western blot analysis was performed to assess differences in ENaC quantity after CSE exposure. Some specimens were stained with H&E for detection of histological alterations.

Results: The amiloride effect on normal epithelium led to a significant decrease in I_sc [ΔI=33±5.92 μA/cm²; p<0.001 versus control experiments (ΔI=1.44±0.71 μA/cm²)]. After incubation with CSE, ENaC I_sc was significantly reduced (ΔI=14.80±1.96 μA/cm²; p<0.001). No differences in αENaC expression were observed between CSE-exposed and normal tracheal epithelium. Histological images post CSE incubation revealed decreases in the height of the epithelium, with basal cell hyperplasia and loss of ciliated cells.

Conclusion: Reduced ENaC inhibition by amiloride after CSE incubation could be due to alterations in the tracheal epithelium.

Background/aim: Cardiovascular diseases (CVD) are the leading cause of death worldwide. In 2019, 523 million people were diagnosed with CVD, with 18.6 million deaths. Improved treatment and diagnostics could reduce CVD's impact. Irisin (Ir) is crucial for heart function and may be a biomarker for heart attack. Ir is a glycoprotein with sugar residues attached to its protein structure. This glycosylation affects Ir stability, solubility, and receptor interactions on target cells. Its secondary structure includes a fibronectin type III domain, essential for its biological functions. Ir helps cardiomyocytes to respond to hypoxia and protects mitochondria. The aim of the study was to determine the FNDC5 gene expression level and the Ir level in HL-1 cardiomyocytes subjected to hypoxia.

Materials and methods: We examined the effect of hypoxia on the expression levels of the FNDC5 gene and those of Ir in mouse cardiomyocytes of the HL-1 cell line. Real-time PCR (RT-PCR) was used to estimate the expression levels of the FNDC5 gene. Western blot and immunofluorescence methods were used to analyze the Ir protein levels.

Results: Analyses showed an increased Ir level in HL-1 cardiomyocytes in response to hypoxia. This is the first study to confirm the presence of Ir in HL-1 cells.

Conclusion: The observed increase in Ir expression in murine cardiomyocytes is associated with the hypoxic environment and can be potentially used to diagnose hypoxia and CVD.

Background/aim: Hashimoto thyroiditis (HT) association with thyroid lymphoma is well established; however, the association with papillary thyroid cancer (PTC) is still unclear. Thyroid cancer incidence has shown an increasing trend in recent years. It is characterized by slow growth, making it generally amenable to successful treatment.

Materials and methods: We aimed to identify genes considered as promising biomarkers of the progression from thyroiditis to thyroid cancer in public gene expression datasets.

Results: We identified 70 differentially expressed genes (DEGs) and used them to prioritize biological risk genes for thyroiditis and thyroid cancer. Statistics and a scoring system based on six functional annotations of significant biological impact identified four genes of interest: CXCR4, IL6ST, PPARG and TP53. Kaplan-Meier plots were used to assess the expression levels related to overall survival. Furthermore, a manual bibliographic search was carried out for each gene, and a protein-protein interaction (PPI) network was built to verify their known associations.

Conclusion: The results showed that all four genes (CXCR4, IL6ST, PPARG, TP53) were highly relevant to thyroiditis and thyroid cancer, thus making them worthy of further investigation to understand their relationship with these two diseases.

Background/aim: Cemiplimab in patients with non-small cell lung cancer (NSCLC) with PD-L1 (programmed death ligand type 1) expression ≥50% showed a significant improved overall survival (OS) with increasing expression of PD-L1. To our knowledge there exist no similar data published for pembrolizumab regarding the increased OS in relation to the PD-L1 expression. Therefore, the objective of our study was to determine whether improvement in OS reflects increased expression levels of PD-L1 (≥50%) in patients with NSCLC.

Patients and methods: Retrospective data from 9 Czech and 1 Polish comprehensive oncology Centers were used. All patients with stage IV NSCLC and PD-L1 expression ≥50% treated with pembrolizumab in daily practice were included. The groups of patients according to the expression of PD-L1 were determined as follows: PD-L1 50-59%, 60-69%, 70-79%, 80-89% and 90-100%. The log-rank test and the Cox regression model were used to compare survival between study groups.

Results: A total of 617 patients were included in the study. We did not observe a statistically significant difference in OS between groups of patients with different levels of PD-L1 expression in the pooled comparison (p=0.445). Furthermore, we did not observe a statistically significant difference even when comparing OS in patients with PD-L1expression of 50-59% (reference) with the group of other patients according to the level of expression of PD-L1 in the Cox regression model including the effect covariates.

Conclusion: PD-L1 expression showed no significant effect on OS in patients with NSCLC with PD-L1≥50% treated with pembrolizumab.