Background:Head and neck squamous cell carcinomas (HNSCCs) display cellular heterogeneity and contain cancer stem cells (CSCs). Sex-determining region Y [SRY]-box (SOX)2 is an important regulator of embryonic stem cell fate and is aberrantly expressed in several types of human tumours. Nonetheless, the role of SOX2 in HNSCC remains unclear.Methods:We created cells ectopically expressing SOX2 from previously established HNSCC cells and examined the cell proliferation, self-renewal capacity, and chemoresistance of these cells compared with control cells. In addition, we knocked down SOX2 in primary spheres obtained from HNSCC tumour tissue and assessed the attenuation of stemness-associated traits in these cells in vitro and in vivo. Furthermore, we examined the clinical relevance of SOX2 expression in HNSCC patients.Results:SOX2 is aberrantly expressed in primary tissue of HNSCC patients but not in healthy tissue. SOX2 expression correlated with tumour recurrence and poor prognosis of HNSCC patients. Ectopic expression of SOX2 induced cell proliferation via cyclin B1 expression and stemness-associated features, such as self-renewal and chemoresistance. In addition, a knockdown of SOX2 in HNSCC CSCs attenuated their self-renewal capacity, chemoresistance (through ABCG2 suppression), invasion capacity (via snail downregulation), and in vivo tumorigenicity.Conclusions:These results suggest that SOX2 may have important roles in the ‘stemness' and progression of HNSCC. Targeting SOX2-positive tumour cells (CSCs) could be a new therapeutic strategy in HNSCCs.
Objective: This study examined household food insecurity of urban low-income families in Korea and the associations of the food insecurity with children's dietary intake and body size. Design: Cross-sectional study. Setting: Low-income neighborhoods in large cities. Subjects: Included 370 children aged 4-12 y, who had all records on dietary intake and anthropometry as well as household food insecurity measures. Results: Using the 10-item Radimer/Cornell Scale, 62.7% of the households showed some degree of food insecurity (8.6% for food insecure for family, 28.4% for food insecure for adults and 25.7% for child hunger households). Food insecurity was linearly and negatively associated with household economic conditions as well as the caretaker's use of nutrition knowledge. There were also significant associations of food insecurity with the children's dietary intakes, indicating the largest amount of nutrients for the children from the household food insecure, followed by those from the food secure, adult food insecure and child hunger groups. The household food insecure children were fatter than the food secure children. The fatter condition of the former children appeared to be related to more frequent intakes of low-quality foods.
Background and aims: Overproduction of nitric oxide via inducible nitric oxide synthase (iNOS) is suggested to be a significant pathogenic factor in Helicobacter pylori induced gastritis. The purpose of this study was to examine the role of iNOS in H pylori associated gastric carcinogenesis. Methods: Two types of mice were used in this study: iNOS deficient mice (iNOS2/2) and wild-type littermates. Gastric cancer was generated in mice using a combination treatment comprising N-methyl-Nnitrosourea administration and H pylori infection. Fifty weeks after treatment, tumours in gastric tissues from both types of mice were examined using histopathology, immunohistochemistry, and immunoblotting for iNOS and 3-nitrotyrosine. Results: The overall incidence of gastric cancer at week 50 was significantly lower in iNOS2/2 compared with iNOS wild-type mice (p,0.05). When analysed according to tumour pathology, the incidence of gastric adenocarcinoma was significantly lower in iNOS2/2 compared with iNOS wild-type mice (p,0.05). Immunostaining for iNOS was clearly observed in adenocarcinoma cells of iNOS wild-type mice, and was characterised by a strong cytoplasmic expression pattern. 3-Nitrotyrosine was expressed mostly in the area of the lamina propria of gastritis and adenoma lesions in iNOS wild-type mice. Immunoblotting analyses showed that iNOS and 3-nitrotyrosine were also expressed in both adenoma and adenocarcinoma tissues from iNOS wild-type mice. iNOS and 3-nitrotyrosine expression was greater in tumour tissues than in non-tumour tissues. Conclusions: These findings suggest that iNOS contributes to H pylori associated gastric carcinogenesis in mice.
Acute ophthalmoplegia (AO) commonly occurs in anti-GQ1b antibody syndrome and manifests as various combinations of external and internal ophthalmoplegia. Internal ophthalmoplegia is fairly common and unilateral involvement may occur in AO.
The Gram-negative bacterium Vibrio vulnificus produces hemolysin (VvhA), which induces cytotoxicity in mammalian cells. However, our understanding of the cytotoxic mechanism and the modes of action of VvhA are still fragmentary and incomplete. The recombinant protein (r) VvhA (50 pg/ml) significantly induces necrotic cell death and apoptosis in human intestinal epithelial (INT-407) cells. The apoptotic cell death induced by rVvhA is highly susceptible to the sequestration of cholesterol by methyl-β-cyclodextrin, whereas for necrotic cell death, this shows a marginal effect. We found that rVvhA induces the aggregation of lipid raft components coupled with NADPH oxidase enzymes, in which rVvhA increased the interaction of NADPH oxidase 2 (NOX2, gp91phox) with a cytosolic protein NCF1 (p47phox) to facilitate the production of reactive oxygen species (ROS). rVvhA uniquely stimulated a conventional PKC isoform PKCα and induced the phosphorylation of both ERK and JNK, which are responsible for the activation of transcription factor NF-κB. rVvhA induced an NF-κB-dependent imbalance of the Bcl-2/Bax ratio, the release of mitochondrial cytochrome c, and caspase-3/-9 activation during its promotion of apoptotic cell death. In addition, rVvhA has the ability to inhibit the expression of cell cycle-related proteins, such as CDK2, CDK4, cyclin D1, and cyclin E. These results demonstrate that rVvhA induces NF-κB-dependent mitochondrial cell death via lipid raft-mediated ROS production by the distinct activation of PKCα and ERK/JNK in intestinal epithelial cells.
Objectives: (i) To examine the components of variation in nutrient intakes for older Korean adults; (ii) To calculate the level of accuracy with varying degree of precision in order to achieve estimates of usual nutrient intakes. Design: Five or six 24 h recalls were made over a four month period on each individual. Setting: A senior school from a middle-income, urban community in Inchon, Korea. Subjects: Forty-seven males and 36 females over 60 y old with complete records for at least ®ve dietary recalls. Results: The within-person variation of nutrient intakes (21.8 ± 103.2%) was higher and differed more markedly by nutrients than the between-person variation (9.4 ± 63.7%). Males (2.26 ± 11.28) showed larger within-tobetween person variance ratios than females (1.73 ± 5.86). The variance ratios were different by nutrients for males, but no such pattern was observed for females. Depending on nutrients, 5 ± 6 recalls over a four month period gave estimates of nutrient intakes within 30 ± 50% of usual intakes. For most nutrients, 100 ± 200 subjects were suf®cient to obtain estimates with 10% deviation of group usual intakes. Achieving r 0.9 between observed and usual intakes required 24 ± 54 recalls for males and 8 ± 23 recalls for females. Conclusions: The degree of precision achieved during assessment of older Korean adults' usual nutrient intakes changes with gender and by the type of nutrients. Achieving similar level of accuracy of the estimates, older Korean adults may require more dietary recalls than the adults in western countries. Sponsorship: Supported by the Korean Research Foundation and the Kyung Hee University Research Center.
Endotoxin or lipopolysaccharide (LPS) is a cell wall component of Gram-negative bacteria. Like aeroallergens, LPS is ubiquitous in our living environment. Epidemiology studies in young children have found that LPS exposure at home is inversely correlated with the development of atopic diseases, thus the 'hygiene hypothesis' for allergic diseases. However, positive association has also been found between indoor LPS exposure and the development of wheezing or asthma in children. In humans, experimental exposure to LPS in the airways can cause inflammatory responses and lung function changes directly or modulate responses to allergens indirectly, particularly in those with asthma. In animal studies, experimental exposure to LPS has generated some conflicting, sometimes opposite, results in host responses to allergen stimulation. In this article, we will review recent advances in our understanding of the immunomodulating effects of LPS on allergen-induced responses and analyse some of the possible reasons for the inconsistent findings.
Purpose To compare retinal nerve fiber layer (RNFL) thickness profiles between preterm and full-term children and to investigate factors affecting the RNFL distribution in preterm children.Methods We performed Spectral domain optical coherence tomography (SD-OCT) peripapillary RNFL circular scan centered on the optic disc in 50 premature and 58 full-term children. RNFL thickness profiles were compared between preterm and fullterm children using a linear regression model. Among preterm patients in this study, 20 patients previously received laser treatment for severe retinopathy of prematurity (ROP).Results Global average, nasal, and superior disc RNFL thickness profiles were significantly smaller in preterm children (92.70 ± 16.57 μm, 56.02 ± 17.04 μm, and 108.74 ± 27.36 μm, respectively) compared with full-term children (101.63 ± 9.21 μm, P = 0.006, 69.14 ± 14.15 μm, Po0.001, and superior, 129.11 ± 18.14 μm, Po0.001, respectively). Multivariable analysis revealed that ROP stage was inversely correlated with nasal RNFL thickness (P = 0.010).Conclusions Our SD-OCT data demonstrate decreased global average, nasal, and superior disc RNFL thicknesses in preterm children. ROP stage was inversely correlated with nasal RNFL thickness. Further studies are needed to better understand the association between these structural changes and visual functions in preterm children.
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