RESUMEN
OBJECTIVE: To examine the association between rheumatoid arthritis (RA) and oral hypofunction (OHF) using propensity score matching (PSM) to adjust for differences between older adults with RA and the general older adult population. METHODS: We conducted a cross-sectional survey among 189 older adults with RA in 2019 (mean age, 71.9 ± 3.6) and 47 178 independent older adult residents in 2016 (mean age, 71.6 ± 4.0), respectively. The questionnaire covered information on socio-demographic characteristics and OHF for both groups. Age, sex, educational level and smoking history were used to determine PSM. Prevalence ratios (PRs) and 95% confidence intervals (CIs) of self-reported OHF (fewer remaining teeth, decreased masticatory function, deterioration of swallowing function and oral dryness) were estimated using Poisson regressions. RESULT: OHF was observed in 44.4% of patients with RA and 27.5% of residents. Before PSM, the prevalence of OHF among patients with RA was higher than that of residents (PR, 1.75; 95% CI, 1.50-2.05). After PSM, there were 189 patients with RA and residents, and the prevalence of OHF among patients with RA was still higher (PR, 1.61; 95% CI, 1.22-2.13). Poisson regression showed that the prevalence of 19 or fewer teeth (PR, 1.06; 95% CI, 0.82-1.36), difficulties eating tough foods (PR, 1.18; 95% CI, 0.90-1.55), difficulties swallowing tea or soup (PR, 1.77; 95% CI, 1.19-2.63), and dry mouth (PR, 2.79; 95% CI, 1.90-4.07) was higher among patients with RA than residents. CONCLUSION: Compared with the general older adult population, patients with RA have a higher prevalence of self-reported OHF.
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Artritis Reumatoide , Puntaje de Propensión , Autoinforme , Humanos , Estudios Transversales , Femenino , Masculino , Artritis Reumatoide/epidemiología , Artritis Reumatoide/fisiopatología , Artritis Reumatoide/complicaciones , Anciano , Prevalencia , Xerostomía/epidemiología , Anciano de 80 o más Años , Encuestas y CuestionariosRESUMEN
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder in the intestine, and the dysfunction of intestinal epithelial barrier (IEB) may trigger the onset of IBD. Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor that has been implicated in the tissue-protective effect in the skin and lung. We found that SLPI was induced in lipopolysaccharides-treated colon carcinoma cell line and in the colon of dextran sulfate sodium (DSS)-treated mice. SLPI-deficient mice were administered DSS to induce colitis and sustained severe inflammation compared with wild-type mice. The colonic mucosa of SLPI-deficient mice showed more severe inflammation with neutrophil infiltration and higher levels of proinflammatory cytokines compared with control mice. Moreover, neutrophil elastase (NE) activity in SLPI-deficient mice was increased and IEB function was severely impaired in the colon, accompanied with the increased number of apoptotic cells. Importantly, we demonstrated that DSS-induced colitis was ameliorated by administration of protease inhibitor SSR69071 and recombinant SLPI. These results suggest that the protease inhibitory activity of SLPI protects from colitis by preventing IEB dysfunction caused by excessive NE activity, which provides insight into the novel function of SLPI in the regulation of gut homeostasis and therapeutic approaches for IBD.
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Colitis , Inhibidor Secretorio de Peptidasas Leucocitarias , Animales , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Mucosa Intestinal , Ratones , Inhibidor Secretorio de Peptidasas Leucocitarias/genética , Inhibidores de Serina ProteinasaRESUMEN
Mutations in RAS or BRAF are associated with poor prognosis and resistance to epidermal growth factor receptor (EGFR)-targeted therapy in colorectal cancer (CRC). Despite their common ability to activate downstream genes such as MEK and ERK, the therapeutic benefit of MEK inhibitors for patients with RAS/BRAF mutant CRC is limited, highlighting the need for biomarkers to predict the efficacy of MEK inhibition. Previously, we reported that a change in phosphorylation of ribosomal protein S6 (pS6) after MEK inhibition was significantly associated with sensitivity to MEK inhibition in gastric cancer cells. Here, we investigated the value of the response in pS6 for predicting the efficacy of trametinib, a MEK inhibitor, in patients with RAS/BRAF mutant CRC using patient-derived CRC organoids. We found that a subset of CRC cell lines and organoids were sensitive to trametinib. The change in phosphorylated ERK, a downstream molecule of the RAS/RAF/MEK pathway, was not significantly associated with trametinib sensitivity. On the other hand, only those with sensitivity showed a reduction of pS6 levels in response to trametinib. The change in pS6 after trametinib treatment was detectable by Western blotting, immunohistochemistry or immunocytochemistry. We also demonstrated an impact of MEK inhibition on pS6 in vivo using a xenograft model. Our data suggest that, in combination with patient-derived organoids, immunostaining-based detection of pS6 could be useful for prediction of trametinib sensitivity.
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Neoplasias Colorrectales/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Fosforilación/efectos de los fármacos , Piridonas/farmacología , Pirimidinonas/farmacología , Proteína S6 Ribosómica , Anciano , Anciano de 80 o más Años , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Femenino , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos NOD , Persona de Mediana Edad , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Proteína S6 Ribosómica/química , Proteína S6 Ribosómica/metabolismoRESUMEN
BACKGROUND AND AIM: Improvement of atrophic gastritis and intestinal metaplasia (IM) is considered to reduce the gastric cancer risk, but whether it can be achieved by H. pylori eradication (HPE) remains controversial. To evaluate the effect of HPE, we observed the gastric mucosa for up to17 years after HPE and sex differences in gastric mucosa. METHODS: In total, 172 patients (94 males, 78 females) with HPE were enrolled. Annual histological evaluations were performed for up to 17 years. The grades of mononuclear cells, neutrophils, atrophy, IM in the antrum and corpus were evaluated using the updated Sydney system. RESULTS: Relative to the pre-HPE period, atrophy had improved significantly 1 year after HPE in the antrum (1.50 ± 0.75 vs. 1.21 ± 1.25, P < 0.01) and corpus (0.59 ± 0.75 vs. 0.18 ± 0.52, P < 0.05). IM showed no significant change during 17 years after HPE at either biopsy site. Atrophy scores did not differ significantly between males and females. IM scores were significantly higher in males than in females before eradication (antrum, 0.67 ± 0.94 vs. 0.44 ± 0.77, P = 0.003, corpus, 0.20 ± 0.62 vs. 0.047 ± 0.21, P = 0.0027) and at most observation timepoints. CONCLUSIONS: During 17 years after HPE, atrophy, but not IM, improved significantly at the greater curvatures of the antrum and corpus. IM was significantly more severe in males than in females. Careful follow-up after HPE based on sex differences in gastric mucosal characteristics is important.
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Antibacterianos/administración & dosificación , Mucosa Gástrica , Infecciones por Helicobacter , Helicobacter pylori , Inhibidores de la Bomba de Protones/administración & dosificación , Adulto , Anciano , Amoxicilina/administración & dosificación , Atrofia/tratamiento farmacológico , Atrofia/patología , Claritromicina/administración & dosificación , Femenino , Estudios de Seguimiento , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Gastritis Atrófica/tratamiento farmacológico , Gastritis Atrófica/patología , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/patología , Helicobacter pylori/aislamiento & purificación , Humanos , Lansoprazol/administración & dosificación , Masculino , Metaplasia/tratamiento farmacológico , Metaplasia/patología , Metronidazol/administración & dosificación , Persona de Mediana Edad , Omeprazol/administración & dosificación , Estudios Prospectivos , Rabeprazol/administración & dosificación , Factores Sexuales , Adulto JovenRESUMEN
Fluorescence microendoscopy is becoming a standard technique in neuroscience for visualizing neuronal activity in the deep brain. Gradient refractive index (GRIN) lenses are increasingly used for fluorescence microendoscopy; however, they inherently suffer from strong aberrations and distortion. Aspherical lenses change their radius of curvature with distance from the optical axis and can effectively eliminate spherical aberrations. The use of these lenses has not been fully explored in deep brain fluorescence microendoscopy due to technical difficulties in manufacturing miniature aspherical lenses. In this study, we fabricated a novel microendoscope lens assembly comprised two nested pairs of aspherical microlenses made by precision glass molding. This assembly, which was 0.6 mm in diameter and 7.06 mm in length, was assembled in a stainless steel tube of 0.7 mm outer diameter. This assembly exhibited marked improvements in monochromatic and chromatic aberrations compared with a conventional GRIN lens, and is useful for deep brain fluorescence microendoscopy, as demonstrated by two-photon microendoscopic calcium imaging of R-CaMP1.07-labeled mouse hippocampal CA1 neurons. Our aspherical-lens-based approach offers a non-GRIN-lens alternative for fabrication of microendoscopic lenses.
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Encéfalo/diagnóstico por imagen , Calcio/análisis , Endoscopía/instrumentación , Imagen Óptica/instrumentación , Animales , Química Encefálica , Endoscopios , Diseño de Equipo , Fluorescencia , RatonesRESUMEN
BACKGROUND: Persistent Helicobacter pylori infection induces gastric mucosal atrophy, which is a precancerous condition. Hydrogen sulfide (H2 S), a gaseous biological transmitter, has been implicated in both the physiological functions of the gastrointestinal tract and its diseases. To understand gastric epithelial cell response against H pylori infection, we investigated the metabolic changes of gastric cancer cells co-cultured with H pylori and observed the modulation of endogenous H2 S production. MATERIALS AND METHODS: Gastric cancer AGS cells were co-cultured with an H pylori standard strain possessing bacterial virulence factor CagA (ATCC 43504) and a strain without CagA (ATCC 51932). Three hours after inoculation, the cells were subjected to metabolomics analysis using gas chromatography-tandem mass spectrometry (GC-MS/MS). Orthogonal projections to latent structures discriminant analysis (OPLS-DA) and pathway analysis were performed. In addition, intracellular H2 S levels were measured by using HSip-1 fluorescent probe. RESULTS: Results of OPLS-DA showed a significant difference between the metabolism of untreated control cells and cells inoculated with the H pylori strains ATCC 51932 or ATCC 43504, mainly due to 45 metabolites. Pathway analysis with the selected metabolites indicated that methionine metabolism, which is related to H2 S production, was the most frequently altered pathway. H pylori-inoculated cells produced more endogenous H2 S than control cells. Moreover, ATCC 43504-inoculated cells produced less H2 S than ATCC 51932-inoculated cells. CONCLUSIONS: H pylori infection modulates endogenous H2 S production in AGS cells, suggesting that H2 S might be one of the bioactive molecules involved in the biological mechanisms of gastric mucosal disease including mucosal atrophy.
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Mucosa Gástrica/metabolismo , Infecciones por Helicobacter/metabolismo , Helicobacter pylori/metabolismo , Sulfuro de Hidrógeno/metabolismo , Neoplasias Gástricas/metabolismo , Antígenos Bacterianos/metabolismo , Proteínas Bacterianas/metabolismo , Línea Celular Tumoral , Técnicas de Cocultivo , Mucosa Gástrica/patología , Humanos , Neoplasias Gástricas/patologíaRESUMEN
High-fat diet (HFD)-induced alteration in the gut microbial composition, known as dysbiosis, is increasingly recognized as a major risk factor for various diseases, including colon cancer. This report describes a comprehensive investigation of the effect of agaro-oligosaccharides (AGO) on HFD-induced gut dysbiosis, including alterations in short-chain fatty acid contents and bile acid metabolism in mice. C57BL/6N mice were fed a control diet or HFD, with or without AGO. Terminal restriction fragment-length polymorphism (T-RFLP) analysis produced their fecal microbiota profiles. Profiles of cecal organic acids and serum bile acids were determined, respectively, using HPLC and liquid chromatography-tandem mass spectrometry systems. T-RFLP analyses showed that an HFD changed the gut microbiota significantly. Changes in the microbiota composition induced by an HFD were characterized by a decrease in the order Lactobacillales and by an increase in the Clostridium subcluster XIVa. These changes of the microbiota community generated by HFD treatment were suppressed by AGO supplementation. As supported by the data of the proportion of Lactobacillales order, the concentration of lactic acid increased in the HFD + AGO group. Data from the serum bile acid profile showed that the level of deoxycholic acid, a carcinogenic secondary bile acid produced by gut bacteria, was increased in HFD-receiving mice. The upregulation tended to be suppressed by AGO supplementation. Finally, results show that AGO supplementation suppressed the azoxymethane-induced generation of aberrant crypt foci in the colon derived from HFD-treated mice. Our results suggest that oral intake of AGO prevents HFD-induced gut dysbiosis, thereby inhibiting colon carcinogenesis.
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Neoplasias del Colon/microbiología , Dieta Alta en Grasa/efectos adversos , Disbiosis/microbiología , Oligosacáridos/farmacología , Sefarosa/farmacología , Animales , Ácidos y Sales Biliares/metabolismo , Clostridium , Fibras de la Dieta , Disbiosis/inducido químicamente , Endotoxinas/sangre , Ácidos Grasos/metabolismo , Heces/microbiología , Lactobacillales , Masculino , Ratones , Ratones Endogámicos C57BL , Microbiota , Obesidad/prevención & control , Oligosacáridos/química , Sefarosa/químicaRESUMEN
BACKGROUND/AIMS: Although undifferentiated gastric cancer (UGC) diagnosed after Helicobacter pylori eradication (HPE) carries a poor prognosis, characteristics of post-HPE UGC have not been evaluated in detail because of its low incidence. Therefore, we compared the clinicopathologic characteristics of UGC and differentiated gastric cancers (DGC) diagnosed after successful HPE. METHODS: GC lesions from patients who had successfully completed HPE and who had undergone upper gastrointestinal endoscopy between January 2004 and March 2016 were analyzed. Tumors were divided into DGC and UGC groups. Clinicopathologic factors of background and tumor characteristics were compared using univariate and multiple logistic analyses. RESULTS: A total of 129 tumors from 115 patients were evaluated; 113 tumors were in the DGC group and 16 in the UGC group. Depressed-type tumors (P = 0.024) and sub-submucosal invasion (P<0.001) were significantly higher in the UGC group. The UGC group had larger tumor diameters (25.9±7.3 mm) than the DGC group (13.2±10.2 mm) (P<0.001). Multivariate analysis showed that female sex (odds ratio [OR] 3.24, 95%CI:1.02-10.37; P = 0.047) and absent follow-up (OR 4.99, 95%CI:1.60-15.57; P = 0.006) were significant independent risk factors for UGC. The DGC group showed a gradually decreasing temporal trend by trend test (P = 0.015), while the UGC group showed a relatively constant incidence over time, although the number of cases was small. CONCLUSION: UGC was diagnosed even after long time spans following HPE, although the number of cases was small. Female sex, and especially absent follow-up, were risks for post-HPE UGC, suggesting that diligent long-term follow-up after HPE is essential.
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Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Femenino , Neoplasias Gástricas/patología , Estudios Retrospectivos , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/diagnóstico , Factores de RiesgoRESUMEN
The activation of renin-angiotensin system contributes to the development of metabolic syndrome and diabetes as well as hypertension. However, it remains undetermined how renin-angiotensin system is implicated in feeding behavior. Here, we show that angiotensin II type 1 (AT(1)) receptor signaling regulates the hypothalamic neurocircuit that is involved in the control of food intake. Compared with wild-type Agtr1a(+/+) mice, AT(1) receptor knock-out (Agtr1a(-/-)) mice were hyperphagic and obese with increased adiposity on an ad libitum diet, whereas Agtr1a(-/-) mice were lean with decreased adiposity on a pair-fed diet. In the hypothalamus, mRNA levels of anorexigenic neuropeptide corticotropin-releasing hormone (Crh) were lower in Agtr1a(-/-) mice than in Agtr1a(+/+) mice both on an ad libitum and pair-fed diet. Furthermore, intracerebroventricular administration of CRH suppressed food intake both in Agtr1a(+/+) and Agtr1a(-/-) mice. In addition, the Crh gene promoter was significantly transactivated via the cAMP-responsive element by angiotensin II stimulation. These results thus demonstrate that central AT(1) receptor signaling plays a homeostatic role in the regulation of food intake by maintaining gene expression of Crh in hypothalamus and suggest a therapeutic potential of central AT(1) receptor blockade in feeding disorders.
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Hormona Liberadora de Corticotropina/metabolismo , Conducta Alimentaria , Regulación de la Expresión Génica , Hipotálamo/fisiología , Receptor de Angiotensina Tipo 1/metabolismo , Tejido Adiposo/metabolismo , Animales , Células HEK293 , Humanos , Masculino , Ratones , Ratones Noqueados , Neuropéptidos/química , Obesidad/metabolismo , Oligopéptidos/química , Ácido Pirrolidona Carboxílico/análogos & derivados , Ácido Pirrolidona Carboxílico/químicaRESUMEN
Angelica keiskei is a traditional herb peculiar to Japan and abundantly contains vitamins, dietary fiber and such polyphenols as chalcone. We investigated in the present study the effect of A. keiskei on insulin resistance and hypertriglyceridemia in fructose-drinking rats as a model for the metabolic syndrome. Male Wistar rats were given a 15% fructose solution as drinking water for 11 weeks. Fructose significantly increased the levels of serum insulin and triglyceride (TG) compared with the control level. Treatment with an ethanol extract of A. keiskei (AE) significantly reduced the levels of blood glucose (-16.5%), serum insulin (-47.3%), HOMA-R (-56.4%) and TG (-24.2%). A hepatic gene analysis showed that fructose reduced the expression of the genes related to fatty acid ß-oxidation and high-density lipoprotein (HDL) production. Treatment with AE enhanced the expression of the acyl-CoA oxidase 1 (ACO1), medium-chain acyl-CoA dehydrogenase (MCAD), ATP-binding membrane cassette transporter A1 (ABCA1) and apolipoprotein A1 (Apo-A1) genes. These results suggest that AE improved the insulin resistance and hypertriglyceridemia of the fructose-drinking rats.
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Angelica/química , Hipertrigliceridemia/tratamiento farmacológico , Hipolipemiantes/farmacología , Resistencia a la Insulina , Síndrome Metabólico/tratamiento farmacológico , Extractos Vegetales/farmacología , Transportador 1 de Casete de Unión a ATP , Transportadoras de Casetes de Unión a ATP/metabolismo , Acil-CoA Deshidrogenasa/metabolismo , Acil-CoA Oxidasa/metabolismo , Animales , Apolipoproteína A-I/metabolismo , Glucemia/análisis , Agua Potable/administración & dosificación , Fructosa/administración & dosificación , Expresión Génica/efectos de los fármacos , Hipertrigliceridemia/sangre , Hipertrigliceridemia/inducido químicamente , Hipolipemiantes/aislamiento & purificación , Insulina/sangre , Lipoproteínas HDL/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/inducido químicamente , Extractos Vegetales/química , Ratas , Ratas Wistar , Triglicéridos/sangreRESUMEN
Angelica keiskei (Ashitaba in Japanese), a traditional herb in Japan, contains abundant prenylated chalcones. It has been reported that the chalcones from A. keiskei showed such bioactivities as anti-bacterial, anti-cancer and anti-diabetic effects. Xanthoangelol, 4-hydroxyderricin and six new chalcones were isolated in this study from an ethanol extract of A. keiskei by octadecyl silyl (ODS) and silica gel chromatography, and identified by 1D- and 2D-nuclear magnetic resonance (NMR) and high-resolution mass spectrometric analyses. The chalcones from A. keiskei markedly increased the expression of the adiponectin gene and the production of adiponectin in 3T3-L1 adipocytes. These results suggest that the chalcones from A. keiskei might be useful for preventing the metabolic syndrome.
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Adipocitos/efectos de los fármacos , Adiponectina/biosíntesis , Angelica/química , Chalcona/análogos & derivados , Hipoglucemiantes/aislamiento & purificación , Raíces de Plantas/química , Adipocitos/citología , Adipocitos/metabolismo , Adiponectina/genética , Animales , Línea Celular , Chalcona/aislamiento & purificación , Chalcona/farmacología , Cromatografía , Etanol/química , Expresión Génica/efectos de los fármacos , Hipoglucemiantes/farmacología , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , RatonesRESUMEN
The 3-phosphoinositide-dependent kinase-1 (PDK1) plays an important role in the regulation of cellular responses in multiple organs by mediating the phosphoinositide 3-kinase (PI3-K) signaling pathway through activating AGC kinases. Here we defined the role of PDK1 in controlling cardiac homeostasis. Cardiac expression of PDK1 was significantly decreased in murine models of heart failure. Tamoxifen-inducible and heart-specific disruption of Pdk1 in adult mice caused severe and lethal heart failure, which was associated with apoptotic death of cardiomyocytes and beta(1)-adrenergic receptor (AR) down-regulation. Overexpression of Bcl-2 protein prevented cardiomyocyte apoptosis and improved cardiac function. In addition, PDK1-deficient hearts showed enhanced activity of PI3-Kgamma, leading to robust beta(1)-AR internalization by forming complex with beta-AR kinase 1 (betaARK1). Interference of betaARK1/PI3-Kgamma complex formation by transgenic overexpression of phosphoinositide kinase domain normalized beta(1)-AR trafficking and improved cardiac function. Taken together, these results suggest that PDK1 plays a critical role in cardiac homeostasis in vivo by serving as a dual effector for cell survival and beta-adrenergic response.
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Corazón/efectos de los fármacos , Miocardio/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Receptores Adrenérgicos beta/metabolismo , Proteínas Quinasas Dependientes de 3-Fosfoinosítido , Animales , Apoptosis , Quinasa 2 del Receptor Acoplado a Proteína-G/metabolismo , Regulación de la Expresión Génica , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/enzimología , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/patología , Ratones , Ratones Noqueados , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/deficiencia , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Tasa de Supervivencia , Tamoxifeno/farmacologíaRESUMEN
Antibiotics disrupt normal gut microbiota and cause dysbiosis, leading to a reduction in intestinal epithelial barrier function. Disruption of the intestinal epithelial barrier, which is known as "leaky gut", results in increased intestinal permeability and contributes to the development or exacerbation of gastrointestinal diseases such as inflammatory bowel disease and irritable bowel syndrome. We have previously reported on a murine model of intestinal epithelial barrier dysfunction associated with dysbiosis induced by the administration of ampicillin and vancomycin. Saireito, a traditional Japanese herbal medicine, is often used to treat autoimmune disorders including ulcerative colitis; the possible mechanism of action and its efficacy, however, remains unclear. In this study, we examined the efficacy of Saireito in our animal model for leaky gut associated with dysbiosis. C57BL/6 mice were fed a Saireito diet for the entirety of the protocol (day1-28). To induce colitis, ampicillin and vancomycin were administered in drinking water for the last seven consecutive days (day22-28). As previously demonstrated, treatment with antibiotics caused fecal occult bleeding, cecum enlargement with black discoloration, colon inflammation with epithelial cell apoptosis, and upregulation of pro-inflammatory cytokines. Oral administration of Saireito significantly improved antibiotics-induced fecal occult bleeding and cecum enlargement by suppressing inflammation in the colon. Furthermore, Saireito treatment ensured the integrity of the intestinal epithelial barrier by suppressing apoptosis and inducing cell adhesion proteins including ZO-1, occludin, and E-cadherin in intestinal epithelial cells, which in turn decreased intestinal epithelial permeability. Moreover, the reduced microbial diversity seen in the gut of mice treated with antibiotics was remarkably improved with the administration of Saireito. In addition, Saireito altered the composition of gut microbiota in these mice. These results suggest that Saireito alleviates leaky gut caused by antibiotic-induced dysbiosis. Our findings provide a potentially new therapeutic strategy for antibiotic-related gastrointestinal disorders.
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Colitis Ulcerosa , Colitis , Ampicilina/metabolismo , Animales , Antibacterianos , Colitis/metabolismo , Colitis Ulcerosa/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Disbiosis/inducido químicamente , Disbiosis/tratamiento farmacológico , Disbiosis/metabolismo , Medicina de Hierbas , Inflamación/metabolismo , Mucosa Intestinal/metabolismo , Japón , Ratones , Ratones Endogámicos C57BL , Vancomicina/efectos adversosRESUMEN
OBJECTIVES: We aimed to evaluate the clinical value of an entire-circumferential intraoperative frozen section analysis (e-IFSA) for the complete resection of superficial squamous cell carcinoma (SCC) of the tongue. MATERIALS AND METHODS: A total 276 specimens from 51 patients with pT1-2, N0, mucosal or submucosal invasion SCC were analyzed to evaluate the diagnostic accuracy of the e-IFSA and the added value of the e-IFSA to iodine staining. The e-IFSA results were compared with the final histologic results obtained using permanent sections. All specimens for the e-IFSA were taken over the entire circumference 5 mm outside from the iodine unstained areas. The outline of the main resected specimen after taking these outer mucosal specimens were defined as the surgical margins determined by iodine staining alone. RESULTS: The e-IFSA results were in excellent agreement with final histological results (Cohen's kappa value: 0.85) and the e-IFSA showed high sensitivity (100%) and high negative predictive value (100%). The actual complete resection rate with an e-IFSA was 100% (51/51), and no patient required additional resection after surgery. In contrast, 10/51 patients (20%) patients showed residual atypical mucosal epithelium at or beyond the margin determined by iodine staining alone; this difference was statistically significant (P = 0.002). The 5-year local control rate and 5-year overall survival rate after this procedure were both 100%. CONCLUSION: An e-IFSA has additional value when performed in conjunction with iodine staining. An e-IFSA would be useful for achieving complete resection of superficial SCC of the tongue.
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Carcinoma de Células Escamosas , Márgenes de Escisión , Neoplasias de la Lengua , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Epitelio/patología , Secciones por Congelación , Humanos , Estudios Retrospectivos , Lengua/patología , Lengua/cirugía , Neoplasias de la Lengua/patología , Neoplasias de la Lengua/cirugíaRESUMEN
AIM: Antioxidant therapy for with vitamin E appears to be effective for the treatment of nonalcoholic fatty liver diseaseã(NAFLD). However, the mechanism of action and optimal therapeutic dosage is unclear. The present study was undertaken to examine whether the effects of α-tocopherol (α-Toc) on NAFLD are dose-dependent in a diet-induced obese model. METHODS: Male mice were fed standard chow, high-fat (HF) diet, HF diet with low-dose, or with high dose of α-Toc supplementation. Histological findings, triglyceride content, and the levels of protein expression related to fatty acid synthesis/oxidation such as carnitine palmitoyltransferase I (CPT-1) of liver were evaluated. In addition, 2-tetradecylglycidic acid (TDGA), a CPT-1 inhibitor, was administered to mice fed HF diet with low-dose of α-Toc. Finally, HepG2 cells in fat-loaded environment were treated with 0-50 µM α-Toc. RESULTS: Treatment of low-dose of α-Toc decreased HF-induced hepatic fat accumulation, but this finding was not observed in treatment of high dose of α-Toc. HF-induced reduction of CPT-1 was attenuated with low-dose of α-Toc but not with high dose of α-Toc. TDGA suppressed the improvement of histological findings in liver induced by low-dose of α-Toc treatment. CPT-1 expression in HepG2 cells increased in response to low-dose of α-Toc, but not in high dose. CONCLUSIONS: Dual action of α-Toc on CPT-1 protein levels was observed. The effect of vitamin E on NAFLD may be not be dose-dependent.
RESUMEN
We investigated whether agaro-oligosaccharides have any immunological effects on RAW264.7 mouse macrophages and human monocytes in vitro. We demonstrate that agaro-oligosaccharides suppressed the elevated levels of nitric oxide, prostaglandin E(2), and such pro-inflammatory cytokines as tumor necrosis factor-alpha, interleukin-1beta and interleukin-6 in lipopolysaccharide-stimulated monocytes and macrophages. We also demonstrate that those effects of agaro-oligosaccharides on activated monocytes and macrophages may have been caused by heme oxygenase-1 induction. It is therefore proposed that agaro-oligosaccharides might be a good candidate for a functional food to prevent inflammatory diseases.
Asunto(s)
Agar/farmacología , Oligosacáridos/farmacología , Animales , Citocinas/inmunología , Citocinas/farmacología , Alimentos Funcionales , Hemo-Oxigenasa 1/antagonistas & inhibidores , Hemo-Oxigenasa 1/inmunología , Hemo-Oxigenasa 1/farmacología , Humanos , Inflamación/inmunología , Mediadores de Inflamación/inmunología , Interleucina-1beta/inmunología , Interleucina-6/inmunología , Lipopolisacáridos/inmunología , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones , Monocitos/efectos de los fármacos , Monocitos/inmunología , Óxido Nítrico/inmunología , Oligosacáridos/inmunología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
BACKGROUND: Helicobacter pylori CagA has been found to be immuno-dominant protein and utilized for the diagnosis of the infection with cagA-positive strains. It is important to characterize the peptide epitopes capable of detecting serum anti-CagA antibodies to understand CagA immunogenicity. METHODS: Sera from 171 Japanese patients were subjected for the epitope mapping study. Eighty seven peptides were designed from the CagA consensus sequence and were used for ELISA protocol to test the serum samples. The reacting anti-CagA IgG amounts to specific peptides were measured and compared. RESULTS: The study revealed a strong reactivity of two peptides (c7-NNTEPIYAQVNKKKAGQAT and c8-AGQATSPEEPIYAQVAKKV) in H. pylori-infected group. Interestingly, these two peptides contained the well-known EPIYA-A and EPIYA-B region, respectively, which are two out of three CagA phosphorylation domains. Tyrosine-phosphorylation of these peptides reduced their reactivity in most sera. Moreover, additional peptides' mapping and chimeric-peptides' experiments indicated that the amino acids (QV and KK) accommodated in right-side flanking regions of both EPIYA-motifs were essential for their strong reactivity, whereas the third EPIYA-motif containing peptide (c12-GRSASPEPIYATIDFDEA) with differing flanking amino acids was not reactive in most cases. CONCLUSIONS: Our results suggest that the amino acid sequences constituted in the two reactive peptides are the important immunogenic regions of CagA which would be useful to develop next-generation peptide-based diagnostic assays.
Asunto(s)
Anticuerpos Antibacterianos/inmunología , Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Adulto , Secuencia de Aminoácidos , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/genética , Pueblo Asiatico , Proteínas Bacterianas/genética , Epítopos/genética , Infecciones por Helicobacter/microbiología , Helicobacter pylori/aislamiento & purificación , Humanos , Mapeo PeptídicoRESUMEN
Diabetes mellitus is a chronic disease that is characterized by hyperglycemia caused by insufficient insulin action. We have explored the edible ingredients from folk medicines in Japan that contain substances complementing insulin action, such as the induction of adipocyte differentiation and the enhancement of glucose uptake. We eventually found that the ethanol extract from a Japanese herb "Ashitaba", Angelica keiskei, contained two major chalcones of 4-hydroxyderricin (4-HD) and xanthoangelol that showed strong insulin-like activities via a pathway independent of the peroxisome proliferator-activated receptor-gamma activation. The 4-HD especially showed the preventive effects on the progression of diabetes in genetically diabetic KK-Ay mice.
Asunto(s)
Angelica/química , Chalconas/aislamiento & purificación , Chalconas/uso terapéutico , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/uso terapéutico , Animales , Diabetes Mellitus/prevención & control , Insulina/farmacología , Masculino , Ratones , PPAR gamma/efectos de los fármacos , Extractos Vegetales/químicaRESUMEN
OBJECTIVE: Steroid pulse therapy is used to relieve pancytopenias in our hospital and is effective in some patients. However, it is unclear which patients will benefit from such therapy. Thus, we retrospectively analyzed the clinical features of patients undergoing allogeneic hematopoietic stem cell transplantation who received steroid pulse therapy to facilitate recovery in their blood cell counts. METHODS: Between 2004 and 2012, 24 patients underwent steroid pulse therapy and the medical records of 17 of these evaluable patients (11 men, 6 women) were retrospectively reviewed. Bone marrow smears were assessed to calculate the proportion of hemophagocytic macrophages just prior to receiving pulse therapy. RESULTS: Steroid pulse therapy was started at a median of 15 days after transplantation (range, 10-28 days). The median white blood cell count was 0.02×10(3)/µL (range, 0.01-0.4×10(3)/µL). Eight patients responded to pulse therapy and subsequent engraftment was achieved in all responders. None of the patients who underwent cord blood transplantation responded to the pulse therapy. Among the non-responders, only two patients achieved engraftment and four of nine non-responders died within one month. When evaluating the efficacy of steroid pulse therapy according to the ferritin level and proportion of hemophagocytic macrophages among patients undergoing bone marrow or peripheral blood stem cell transplantation, both values were higher in responders than in non-responders. CONCLUSION: We speculate that responders have a hemophagocytic syndrome which is responsive to steroid pulse therapy. Thus, our results imply that the use of ferritin levels in combination with the proportion of hemophagocytic macrophages may be useful for the early detection of potential hemophagocytic syndrome after hematopoietic stem cell transplantation.
Asunto(s)
Células Sanguíneas/inmunología , Glucocorticoides/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/métodos , Pancitopenia/terapia , Adulto , Anciano , Recuento de Células Sanguíneas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pancitopenia/inmunología , Trasplante de Células Madre de Sangre Periférica/métodos , Quimioterapia por Pulso , Estudios RetrospectivosRESUMEN
Dietary factors that influence platelet aggregation have not been fully clarified in humans. 63 Japanese women, aged 40-70 years old, completed one-day weighted dietary records, and received physical and laboratory examinations. Platelet aggregation was measured by 1.0 and 3.0 microM ADP induction. The results were analyzed with special reference to fatty acids. The short and medium chain fatty acid intake showed negative correlation with maximum percent of platelet aggregation induced by 1.0 microM ADP. Short and medium chain fatty acids in this study were mostly derived from milk and dairy products. Importance of short and medium chain fatty acid intake on platelet aggregation requires further study for prevention of cardiovascular diseases.