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The Berry curvature dipole (BCD) serves as a one of the fundamental contributors to emergence of the nonlinear Hall effect (NLHE). Despite intense interest due to its potential for new technologies reaching beyond the quantum efficiency limit, the interplay between BCD and NLHE has been barely understood yet in the absence of a systematic study on the electronic band structure. Here, we report NLHE realized in NbIrTe4 that persists above room temperature coupled with a sign change in the Hall conductivity at 150 K. First-principles calculations combined with angle-resolved photoemission spectroscopy (ARPES) measurements show that BCD tuned by the partial occupancy of spin-orbit split bands via temperature is responsible for the temperature-dependent NLHE. Our findings highlight the correlation between BCD and the electronic band structure, providing a viable route to create and engineer the non-trivial Hall effect by tuning the geometric properties of quasiparticles in transition-metal chalcogen compounds.
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Cronkhite-Canada syndrome is a rare gastrointestinal polyposis syndrome with distinctive clinical features and endoscopic findings. Diagnosis can be challenging without suspicion, and the disease carries high mortality due to complications such as infection, gastrointestinal bleeding, and malignancies. This paper presents two cases of Cronkhite-Canada syndrome occurring after coronavirus disease 2019 (COVID-19) mRNA vaccination. Both cases exhibited typical clinical findings, including hypogeusia, onychodystrophy, alopecia, and weight loss. Typical polyposis in the gastrointestinal tract was confirmed through endoscopies. As symptomatic treatment did not improve the symptoms, corticosteroids were administered, and symptoms and laboratory test results improved immediately. The patients improved upon corticosteroids tapering. These cases illustrate typical presentations of Cronkhite-Canada syndrome and the course of the disease following corticosteroid treatment. Additionally, they suggest the possibility that Cronkhite-Canada syndrome may be triggered by COVID-19 mRNA vaccination.
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BACKGROUND: Double-strand break repair protein (RAD50) gene plays important roles in genomic integrity, DNA double-strand break repair, cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. The risk allele of RAD50 may negatively affect cancer by reducing the DNA repair capacity. Additionally, Sodium intake and Helicobacter pylori (H. pylori) infection are major risk factors for gastric cancer (GC). Our study investigated the association between polymorphisms in RAD50 gene and the risk of GC case-fatality. We evaluated whether the association differed with sodium intake or H. pylori infection. METHODS: We enrolled 490 patients from two hospitals between 2002 and 2006. Their survival or death was prospectively followed up until December 31, 2016, through a review of medical records and telephone surveys. The GC survival was assessed using the Cox proportional hazards regression analysis. RESULTS: In 319 GC cases, the total person-years were 1928.3, and the median survival years was 5.4 years. A total of 137 GC deaths were recorded. Our fully adjusted model showed that the GG type of RAD50 rs17772583 polymorphism is significantly associated with an increased risk of GC case-fatality (hazard ratio [HR] = 2.20, 95% confidence interval [CI] = 1.28-3.77) compared to that associated with the homozygous AA type. In the high sodium intake group, patients with the GG type of RAD50 rs17772583 showed a significantly higher GC case-fatality (HR = 8.61, 95% CI = 2.58-26.68) than that of patients with homozygous AA type. In the positive-H. pylori infection group, patients with GG-type RAD50 rs17772583 showed a significantly higher GC case-fatality (HR = 10.11, 95% CI = 2.81-36.35) than that of with AA homozygotes. CONCLUSIONS: Patients with GG-type RAD50 rs17772583, high sodium intake, or a positive-H. pylori infection are at a significantly increased risk of GC case-fatality compared to that associated with the absence of these risk factors.
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Infecções por Helicobacter , Helicobacter pylori , Sódio na Dieta , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/complicações , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Fatores de Risco , República da Coreia/epidemiologia , Estudos de Casos e ControlesRESUMO
The recently discovered interlayer Dzyaloshinskii-Moriya interaction (IL-DMI) in multilayers with perpendicular magnetic anisotropy favors canting of spins in the in-plane direction. It could thus stabilize intriguing spin textures such as Hopfions. A key requirement for nucleation is to control the IL-DMI. Therefore, we investigate the influence of an electric current on a synthetic antiferromagnet with growth-induced IL-DMI. The IL-DMI is quantified by using out-of-plane hysteresis loops of the anomalous Hall effect while applying a static in-plane magnetic field at varied azimuthal angles. We observe a shift in the azimuthal dependence with an increasing current, which we conclude to originate from the additional in-plane symmetry breaking introduced by the current flow. Fitting the angular dependence, we demonstrate the presence of an additive current-induced term that linearly increases the IL-DMI in the direction of current flow. This opens the possibility of easily manipulating 3D spin textures by currents.
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BACKGROUND/OBJECTIVES: Consumption of certain protective foods may help inhibit Helicobacter pylori (H. pylori) associated gastric pathologies. However, studies conducted to assess the efficacy of protective foods in H. pylori-infected subjects are either limited or inconsistent. This study evaluated the association of individual or a combination of protective foods on the incidence of gastric cancer (GC) in H. pylori-positive subjects through a case-control study. MATERIALS/METHODS: Subjects aged 20-79 years were selected from 2 hospitals between December 2002 and September 2006. In total, 134 patients and 212 controls tested positive for H. pylori infection. Among these, we included 82 pairs of cases and controls matched by sex, age (± 5 years), enrollment period (± 1 years), and hospital. RESULTS: A higher intake of soy products was associated with a significantly lower risk of GC than a lower intake of soy products (odds ratio [OR] = 0.37, 95% confidence interval [CI] = 0.14-0.96). Additionally, a higher fruit intake resulted in a significantly lower risk of GC than a lower fruit intake (OR = 0.35, 95% CI = 0.13-0.94). A combination of food groups was evaluated, and a lower risk of GC was observed with a high intake of both soy products and fruits (OR = 0.20, 95% CI = 0.06-0.67), high intake of soy and dairy products (OR = 0.28, 95% CI = 0.10-0.78) and high intake of fruits and dairy products (OR = 0.28, 95% CI = 0.09-0.83). CONCLUSIONS: A high intake of soy products or fruits was associated with a lower risk of GC. A combination of soy products or fruits with dairy products was associated with a lower risk of GC. A balanced intake of soy products, fruits, and dairy products may help reduce GC risk.
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Background/Aims: To date, there is no prospective study that specifically investigated the efficacy of infliximab in intestinal Behçet's disease (BD). This study evaluated the efficacy of infliximab in patients with moderate-to-severe active intestinal BD that are refractory to conventional therapies. Methods: This phase 3, interventional, open-label, single-arm study evaluated clinical outcomes of infliximab treatment in patients with moderate-to-severe intestinal BD. The coprimary endpoints were clinical response, decrease in disease activity index for intestinal BD (DAIBD) score ≥20 from weeks 0 to 8 for the induction therapy and week 32 for the maintenance therapy. Results: A total of 33 patients entered the induction therapy and were treated with infliximab 5 mg/kg intravenously at weeks 0, 2, and 6. The mean DAIBD score changed from 90.8±40.1 at week 0 to 40.3±36.4 at week 8, with a significant mean change of 50.5±36.4 (95% confidence interval, 37.5 to 63.4; p<0.001). Thirty-one (93.9%) continued to receive 5 mg/kg infliximab every 8 weeks during the maintenance therapy. The mean change in the DAIBD score after the maintenance therapy was statistically significant (61.5±38.5; 95% confidence interval, 46.0 to 77.1; p<0.001, from weeks 0 to 32). The proportion of patients who maintained a clinical response was 92.3% at week 32. No severe adverse reactions occurred during the induction and maintenance therapies. Conclusions: This study provided evidence that infliximab 5 mg/kg induction and maintenance therapies are efficacious and well-tolerated in patients with moderate-to-severe active intestinal BD. (ClinicalTrials.gov identifier: NCT02505568).
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Síndrome de Behçet , Enteropatias , Humanos , Síndrome de Behçet/tratamento farmacológico , Infliximab/efeitos adversos , Enteropatias/tratamento farmacológico , Intestinos , Estudos Prospectivos , Resultado do TratamentoRESUMO
Smoking is a risk factor for gastric cancer (GC) and causes oxidative stress. Antioxidant vitamins may protect against oxidative stress. This study aimed to determine the association between dietary antioxidant vitamin intake and GC risk according to smoking status and the histological subtype. This case-control study included 286 pairs of patients with GC and controls aged 20-79 years enrolled at two hospitals from 2002 to 2006, matched by age (± 2 years), sex, hospital, and participation period (± 1 years). Dietary information was collected using a quantitative food frequency questionnaire (FFQ). When stratified by smoking status, increased intake of vitamin C (OR = 0.38; 95% CI = 0.17-0.84 for highest vs. lowest; P for trend = 0.033) and folate (OR = 0.28; 95% CI = 0.12-0.64 for highest vs. lowest; P for trend = 0.003) decreased GC risk in nonsmokers. Vitamin C (P for interaction = 0.043) and folate (P for interaction =0.015) levels were significantly associated with smoking status. Similar results were observed in nonsmokers with diffuse and mixed types of GC, but not in those with intestinal type of GC. Therefore, we found an inverse association between higher intake of dietary vitamin C and folate with the risk of GC among nonsmokers. These protective associations were strong in nonsmokers with diffuse and mixed types of GC.
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Antioxidantes , Neoplasias Gástricas , Humanos , Vitaminas , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/prevenção & controle , Neoplasias Gástricas/etiologia , Estudos de Casos e Controles , Dieta , Ácido Ascórbico , Fatores de Risco , Ácido Fólico , Fumar/efeitos adversos , República da Coreia/epidemiologiaRESUMO
BACKGROUND: We aimed to compare trough infliximab levels and the development of antidrug antibody (ADA) for 1 year between Crohn's disease (CD) and ulcerative colitis (UC) patients who were biologic-naive, and to evaluate their impact on clinical outcomes. METHODS: This was a prospective, multicenter, observational study. Biologic-naive patients with moderate to severe CD or UC who started CT-P13, an infliximab biosimilar, therapy were enrolled. Trough drug and ADA levels were measured periodically for 1 year after CT-P13 initiation. RESULTS: A total of 267 patients who received CT-P13 treatment were included (CD 168, UC 99). The rates of clinical remission (72% vs. 32.3%, P <0.001) at week 54 were significantly higher in CD than in UC. The median trough drug level (µg/mL) was significantly higher in CD than in UC up to week 14 (week 2, 18.7 vs. 14.7, P <0.001; week 6, 12.5 vs. 8.6, P <0.001; week 14, 3.4 vs. 2.5, P =0.001). The median ADA level (AU/mL) was significantly lower in CD than in UC at week 2 (6.3 vs. 6.5, P =0.046), week 30 (7.9 vs. 11.8, P =0.007), and week 54 (9.3 vs. 12.3, P =0.032). Development of ADA at week 2 [adjusted odds ratio (aOR)=0.15, P =0.026], initial C-reactive protein level (aOR=0.87, P =0.032), and CD over UC (aOR=1.92, P <0.001) were independent predictors of clinical remission at week 54. CONCLUSION: Infliximab shows more favorable pharmacokinetics, including high drug trough and low ADA levels, in CD than in UC, which might result in better clinical outcomes for 1-year infliximab treatment in CD patients.
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Medicamentos Biossimilares , Colite Ulcerativa , Doença de Crohn , Humanos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Doença de Crohn/tratamento farmacológico , Infliximab/uso terapêutico , Estudos Prospectivos , Fármacos Gastrointestinais/uso terapêutico , Resultado do Tratamento , Indução de Remissão , Medicamentos Biossimilares/uso terapêuticoRESUMO
BACKGROUND/OBJECTIVES: The hormone-dependent effect of MAP3K1 gene polymorphisms may explain sex-specific differences in gastric cancer (GC) risk. Phytoestrogens have been shown to interact with this genetic factor. Here, we investigated the association between MAP3K1 gene polymorphisms and GC risk by sex and whether these associations differ depending on soy products intake. METHODS: Participants aged 20-79 years were recruited from two hospitals between December 2002 and September 2006. In all, 440 cases and 485 controls were recruited, among, 246 pairs of cases and controls, matched by sex, age (± 5 years), study admission period (± 1 years), and hospital, were included for the analysis. RESULTS: In dominant model, men with the A allele of rs252902 showed significantly increased GC risk (odd ratio; OR=2.19, 95% confidence interval; CI=1.31-3.64) compared to GG homozygotes. When stratified by intake of soy products, men with the A allele of rs252902 and low intake of soy products showed significantly higher GC risk (OR=3.29, 95% CI=1.55-6.78) than that in GG homozygotes. CONCLUSIONS: Men with the risk allele of MAP3K1 had a significantly increased GC risk compared to GG homozygotes; this trend was more pronounced in those with low intake of soy products.
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MAP Quinase Quinase Quinase 1 , Neoplasias Gástricas , Masculino , Feminino , Humanos , Neoplasias Gástricas/genética , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único , Alelos , Razão de Chances , Fatores de Risco , Predisposição Genética para Doença , MAP Quinase Quinase Quinase 1/genéticaRESUMO
Purpose: Current evidence regarding the association between zinc intake and gastric cancer (GC)-specific survival in patients with intestinal-type GC is lacking. Therefore, this cohort study investigated the association between zinc intake and GC mortality through follow-up on GC death among patients with intestinal-type GC and whether these effects differ according to the source of zinc intake. Methods: A total of 185 patients with intestinal-type GC were enrolled from two hospitals between 2002 and 2006. Their survival or death was prospectively followed up until December 31, 2016, through a review of medical records and telephone surveys. Results: A total of 178 patients were included and analyzed. The median follow-up period was 7.3 years. In the fully adjusted models, the highest tertile of total zinc intake showed a significantly lower GC mortality than the lowest tertile (hazard ratio, 0.22; 95% confidence interval: 0.08-0.64). In addition, the tertile of total zinc intake showed a dose-response association with GC mortality (p=0.015). Analysis of the source of zinc intake revealed that when zinc intake from staples (rice and noodles), animal, and plant food sources were combined, the results were similar to those of total zinc intake and GC mortality. Conclusion: Zinc intake through various foods may be effective in reducing GC mortality by achieving balance with other nutrients. Our results suggest that zinc improves the survival of patients with intestinal-type GC in Korea.
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BACKGROUND/AIMS: In ulcerative colitis (UC) patients, Escherichia coli Nissle 1917 (EcN) is equivalent to mesalazine for preventing disease relapse; however, evidence of the ability of EcN to increase health-related quality of life or induce remission remains scarce. We investigated the efficacy of EcN as an add-on therapy for UC. METHODS: In this multicentre, double-blind, randomised, placebo-controlled study, a total of 133 UC patients were randomly assigned to receive either EcN or placebo once daily for 8 weeks. Inflammatory bowel disease questionnaire (IBDQ) scores (primary endpoint) and clinical remission and response rates (secondary endpoints) were compared (Clinical trial registration number: NCT04969679). RESULTS: In total, 118 patients (EcN, 58; placebo, 60) completed the study. The number of patients reaching the primary endpoint did not differ between the EcN and placebo groups (30 [51.7%] vs. 31 [51.7%]; per-protocol analysis, p = 1.0; intention-to-treat analysis, p = 0.86). However, significantly fewer patients in the EcN group exhibited a decreased IBDQ score (1 [1.7%] vs. 8 [13.3%]; per-protocol analysis, p = 0.03; intention- to-treat analysis, p = 0.02). Moreover, a significantly higher number of patients in the EcN group displayed clinical response at 4 weeks (23 [39.7%] vs. 13 [21.7%], p = 0.04) and endoscopic remission at 8 weeks (26 [46.4%] vs. 16 [27.1%], p = 0.03). CONCLUSION: Although the number of patients reaching the primary endpoint did not differ between the EcN and placebo groups, EcN was found to be safe and effective in preventing the exacerbation of IBDQ scores and achieving clinical responses and endoscopic remission in patients with mild-to-moderate UC.
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Colite Ulcerativa , Infecções por Escherichia coli , Probióticos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Método Duplo-Cego , Escherichia coli , Infecções por Escherichia coli/tratamento farmacológico , Humanos , Mesalamina/efeitos adversos , Probióticos/efeitos adversos , Qualidade de Vida , Indução de RemissãoRESUMO
Diet is a critical risk factor for gastric cancer, and Koreans consume significantly high amounts of carbohydrates. This study examined the association between carbohydrate intake, glycemic index, and glycemic load and the risk of gastric cancer and whether the association varied based on the general risk factors for gastric cancer. We hypothesized that carbohydrate intake, glycemic index, and glycemic load elevated gastric cancer risk and the relationship differed by the gastric cancer risk factors. This was a case-control study with a total of 307 matched pairs aged 20 to 79 years. Data collection was completed at two hospitals from December 2002 to September 2006. A food frequency questionnaire was applied for dietary assessment. Carbohydrate intake was not related to gastric cancer risk. However, a high glycemic index (odds ratio [OR], 1.88; 95% confidence interval (95% CI), 1.18-2.97) and glycemic load (OR, 2.51; 95% CI, 1.53-4.12) were significantly associated with the elevated risk of gastric cancer. When the relationship between glycemic load and gastric cancer risk was stratified by risk factors for gastric cancer, the gastric cancer risk especially increased among men, ≥65 years, smokers, drinkers, and people with Helicobacter pylori infection. Although there was no association between carbohydrate consumption and gastric cancer, high glycemic index and glycemic load were associated with the increased gastric cancer risk.
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Carga Glicêmica , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Estudos de Casos e Controles , Dieta/efeitos adversos , Carboidratos da Dieta/efeitos adversos , Índice Glicêmico , Infecções por Helicobacter/complicações , Humanos , Masculino , República da Coreia/epidemiologia , Fatores de Risco , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/etiologiaRESUMO
The incidence of gastric cancer is high in Korea, and dietary factors are important risk factors for gastric cancer. This study examined whether gastric cancer risk was related to dietary factors that directly irritate the stomach wall. This case−control study consisted of 308 matched pairs of gastric cancer cases and controls recruited from 2002 to 2006 at two hospitals in Korea. Dietary assessments were completed using a food frequency questionnaire and a dietary habit questionnaire. Gastric cancer risk was increased for high meal frequency of >3 vs. low meal frequency of ≤3 times per day, overeating vs. not overeating, and preferred vs. not preferred spicy or salty foods. Furthermore, participants with dietary factors of high meal frequency, overeating, and preference for spicy or salty foods elevated the risk of gastric cancer compared to those with low meal frequency, not overeating, and not preferring spicy or salty foods, simultaneously. In conclusion, gastric cancer risk was significantly increased in people with dietary factors that irritate the stomach wall, such as high meal frequency, overeating, and preference for spicy or salty foods.
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Neoplasias Gástricas , Estudos de Casos e Controles , Dieta/efeitos adversos , Humanos , Hiperfagia/complicações , República da Coreia/epidemiologia , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologiaRESUMO
Sodium and zinc display opposite effects on immune cells, such as regulatory T cells (Tregs) and T helper 17 cells (Th17), resulting in an altered immune response. Immune cells have a pivotal role in regulating tumor progression, which may affect gastric cancer (GC) mortality. Thus, this cohort study investigated the associations between the combination of sodium and zinc intake and GC mortality and whether these associations differ by histological type by following up deaths of GC cases in Korea. A total of 490 patients with GC were enrolled between 2002 and 2006. Survival or death was prospectively followed up until December 31, 2016. Finally, 300 patients with the two main histological types of GC were included; 99 GC deaths occurred during a median follow-up period of 7.1 years. Patients with high sodium and low zinc intake had a significantly higher GC mortality than those with low sodium and high zinc intake (hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.09-3.93). However, no significant association was found between the histological types of GC. In conclusion, we found that high sodium and low zinc intake may worsen the survival rate of patients with GC.
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Neoplasias Gástricas , Estudos de Coortes , Ingestão de Alimentos , Humanos , Estudos Prospectivos , República da Coreia/epidemiologia , Sódio , Neoplasias Gástricas/patologia , ZincoRESUMO
[This corrects the article on p. 403 in vol. 21, PMID: 35079442.].
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Background/Aims: The prospective Crohn's Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn's disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD. Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019). Results: A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35; 95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection. Conclusions: The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.
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Doença de Crohn , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/cirurgia , Estudos de Coortes , Estudos Prospectivos , Seguimentos , Prognóstico , Estudos RetrospectivosRESUMO
Short-chain fatty acids (SCFAs) play a pivotal role in maintaining intestinal homeostasis. We aimed to investigate the effects of SCFA supplementation on gut inflammation and microbiota composition in a murine colitis model. Mice were fed with sodium butyrate or a mixture of SCFAs in the drinking water for 2 weeks, followed by 2% dextran sulfate sodium (DSS) for 7 d. After euthanasia, mouse colons were extracted to examine histological findings. Flow cytometry of the mouse colon tissues was performed to assess T cell differentiation. Changes in gut microbiota were assessed by high-throughput sequencing of the mouse feces. There were no significant differences in weight change, colonic length, or histologic inflammation score between the DSS, butyrate, and SCFA mix groups. However, flow cytometry revealed that both the expression of CD4+Foxp3+ regulatory T cells and of IL-17-producing T cells were increased in the butyrate and SCFA mix groups. Microbial compositions of the butyrate and SCFA mix groups were significantly different from those of the control and DSS groups in principal coordinate analysis. Relative abundances of the phyla Verrucomicrobia and Proteobacteria, species Akkermansia muciniphila and Escherichia fergusonii were increased in the butyrate and SCFA mix groups. Genera Roseburia and Lactobacillus showed a negative correlation with the degree of colitis, whereas genera Escherichia and Mucispirillum showed a positive correlation. SCFA supplementation did not result in a significant reduction in colon inflammation, but it promoted both regulatory T cell and IL-17-producing T cell expression, and increased both protective and aggressive gut microbiota.
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Butiratos/administração & dosagem , Suplementos Nutricionais , Ácidos Graxos Voláteis/administração & dosagem , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Animais , Diferenciação Celular , Colite/imunologia , Colite/microbiologia , Colite/patologia , Colo/patologia , Modelos Animais de Doenças , Fezes/microbiologia , Feminino , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/patologia , Doenças Inflamatórias Intestinais/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologiaRESUMO
INTRODUCTION: Syndecan-2 expression is elevated during chronic inflammation and cancer development, and its shedding is observed in cancer patients. However, it remained unknown whether inflammation triggers syndecan-2 shedding. METHODS: The colitis model was produced in C57BL/6 mice by oral administration of 2-3% dextran sulfate sodium (DSS) in the drinking water. Syndecan-2 and MMP-7 expression levels in tissues and cells were detected by real-time PCR, Western blotting, and immunohistochemistry. Shed syndecan-2 levels were detected by slot blotting. For tissue culture, colon tissues were divided into proximal, transverse, and distal parts, and incubated in culture media. RESULTS: In C57BL/6 mice with DSS-induced colitis, syndecan-2 shedding began to increase after week 12 of chronic inflammation and continued to increase at week 15. The level of shed syndecan-2 correlated with the colocalization of syndecan-2 and MMP-7 in distal colon tissues. The mRNA expression of IL-6 was increased specifically in trans-distal colon tissues from weeks 9 to 15. IL-6 induced syndecan-2 expression and shedding and MMP-7 expression in ex vivo-cultured distal colon tissues and adenoma cell lines derived from the distal colon. IL-6 treatment induced STAT3 phosphorylation and MMP-7 expression in DLD-1 cells. The application of MMP-7 to ex vivo-cultured colon tissues increased the shedding of syndecan-2 to the culture medium. CONCLUSION: Our findings suggest that chronic inflammation induces syndecan-2 shedding via the site-specific colocalization of syndecan-2 with MMP-7 in the distal colon.
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Studies on the association between gastric cancer (GC) and the intake of soup-based dish groups (noodles and dumplings, soups, and stews), which are sodium-contributing foods, in Korea are insufficient, and the results of studies on the intake of pickled vegetables such as kimchi are inconsistent. This study aimed to determine the association between the incidence of GC and the daily intake of high-sodium dish groups (noodles and dumplings, soups, stews, and pickled vegetables) and whether these associations differ depending on behavioral risk factors for GC. In this case-control study, subjects aged 20-79 years were recruited from two hospitals between December 2002 and September 2006. A total of 440 cases and 485 controls were recruited, of which 307 pairs were matched and included for the analysis. In our results, a higher intake of noodles and dumplings was associated with a significantly increased incidence of GC. In the participants who consumed past or current alcohol, a higher intake of noodles and dumplings was associated with a significantly increased incidence of GC. Our results suggest that efforts to reduce the daily sodium intake from noodles and dumplings are needed to prevent and reduce the incidence of GC.
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Dieta/estatística & dados numéricos , Sódio na Dieta/análise , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Dieta/efeitos adversos , Dieta/métodos , Inquéritos sobre Dietas , Ingestão de Alimentos , Comportamento Alimentar , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores de Risco , Neoplasias Gástricas/etiologia , Adulto JovemRESUMO
The gut microbiota has been implicated in the development of colitis-associated cancer (CAC). We investigated how the gut microbiota affects the development of CAC when the composition of the microbial community is altered by the administration of various antibiotics in a murine model. C57BL/6 mice were given intraperitoneal injection of 12.5 mg/kg azoxymethane (AOM), followed by two rounds of 2.0 % dextran sodium sulfate (DSS) exposure. Antibiotics, including ampicillin, neomycin, metronidazole, and/or vancomycin, were administered 14 days prior to AOM injection until the end of the experiment. High-throughput sequencing of mice feces was conducted to evaluate alterations of the gut microbiota. Tumorigenesis and inflammation were most markedly suppressed in the mice treated with an antibiotic cocktail therapy consisting of ampicillin, neomycin, metronidazole, and vancomycin. Individual antibiotic treatments had different effects on tumorigenesis and inflammation. Metronidazole attenuated both tumorigenesis and inflammation. Neomycin suppressed tumorigenesis but did not alleviate inflammation. Ampicillin and vancomycin did not significantly attenuate either tumorigenesis or inflammation. Antimicrobial therapy differentially altered the diversity and composition of the gut microbiota depending on antibiotic type. The phyla Proteobacteria and Tenericutes were positively correlated with tumor burden. Colon tumorigenesis was attenuated through various antibiotics in the AOM/DSS-induced CAC model. Individual antibiotics differentially altered the gut microbial composition and showed different effects on tumor suppression; however, the degree of tumor suppression was less pronounced than that relative to the antibiotic cocktail therapy, suggesting that the global gut microbial community plays an important role in the development of CAC.