21 research outputs found

    Amphiphilic peptide-tagged N-cadherin forms radial glial-like fibers that enhance neuronal migration in injured brain and promote sensorimotor recovery

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    The mammalian brain has very limited ability to regenerate lost neurons and recover function after injury. Promoting the migration of young neurons (neuroblasts) derived from endogenous neural stem cells using biomaterials is a new and promising approach to aid recovery of the brain after injury. However, the delivery of sufficient neuroblasts to distant injured sites is a major challenge because of the limited number of scaffold cells that are available to guide neuroblast migration. To address this issue, we have developed an amphiphilic peptide [(RADA)3-(RADG)] (mRADA)-tagged N-cadherin extracellular domain (Ncad-mRADA), which can remain in mRADA hydrogels and be injected into deep brain tissue to facilitate neuroblast migration. Migrating neuroblasts directly contacted the fiber-like Ncad-mRADA hydrogel and efficiently migrated toward an injured site in the striatum, a deep brain area. Furthermore, application of Ncad-mRADA to neonatal cortical brain injury efficiently promoted neuronal regeneration and functional recovery. These results demonstrate that self- assembling Ncad-mRADA peptides mimic both the function and structure of endogenous scaffold cells and provide a novel strategy for regenerative therapy

    The Sulfur Microbial Diet and Risk of Colorectal Cancer by Molecular Subtypes and Intratumoral Microbial Species in Adult Men

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    INTRODUCTION: We recently described the sulfur microbial diet, a pattern of intake associated with increased gut sulfur-metabolizing bacteria and incidence of distal colorectal cancer (CRC). We assessed whether this risk differed by CRC molecular subtypes or presence of intratumoral microbes involved in CRC pathogenesis (Fusobacterium nucleatum and Bifidobacterium spp.). METHODS: We performed Cox proportional hazards modeling to examine the association between the sulfur microbial diet and incidence of overall and distal CRC by molecular and microbial subtype in the Health Professionals Follow-Up Study (1986-2012). RESULTS: We documented 1,264 incident CRC cases among 48,246 men, approximately 40% of whom had available tissue data. After accounting for multiple hypothesis testing, the relationship between the sulfur microbial diet and CRC incidence did not differ by subtype. However, there was a suggestion of an association by prostaglandin synthase 2 (PTGS2) status with a multivariable adjusted hazard ratio for highest vs lowest tertile of sulfur microbial diet scores of 1.31 (95% confidence interval: 0.99-1.74, Ptrend = 0.07, Pheterogeneity = 0.04) for PTGS2-high CRC. The association of the sulfur microbial diet with distal CRC seemed to differ by the presence of intratumoral Bifidobacterium spp. with an adjusted hazard ratio for highest vs lowest tertile of sulfur microbial diet scores of 1.65 (95% confidence interval: 1.14-2.39, Ptrend = 0.01, Pheterogeneity = 0.03) for Bifidobacterium-negative distal CRC. We observed no apparent heterogeneity by other tested molecular markers. DISCUSSION: Greater long-term adherence to the sulfur microbial diet could be associated with PTGS2-high and Bifidobacterium-negative distal CRC in men. Additional studies are needed to further characterize the role of gut microbial sulfur metabolism and CRC

    Characteristics of non-neoplastic epithelium that appears within gastric cancer with and without Helicobacter pylori eradication: A retrospective study.

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    A non-neoplastic epithelium (NE) often appears in gastric cancer (GC). We explored the histological features of NE in comparison between HP-eradicated and HP-infected GCs. We enrolled 40 HP-eradicated and 40 HP-infected GCs matched by size, macroscopic and histological type. NE was classified into full gland type and surface type; the former was a non-neoplastic gland isolated within cancer, and the latter was NE on the surface of the cancer. Surface type was additionally divided into NE at the cancer margin (marginal surface type) and NE inside cancer (internal surface type). The primary endpoints were the frequency and the length ratio (the ratio to cancer length) of NE. The secondary endpoints were the relationships between NE and clinicopathological factors, including endoscopic findings of a gastritis-like appearance (GLA), reddish depressed lesion (RDL), and white nodular mucosa (WNM). The frequency and length ratio of the internal surface type in HP-eradicated GCs were significantly higher (82.5% vs 50%, P = 0.005) and larger (11.6 ± 10.6 vs 4.2 ± 9.9, P < 0.001) than those in HP-infected GCs, and the increase was more significant according to the passage of time since HP eradication. The frequency and length ratio of marginal surface type and full gland type were not significantly different between the two groups, but the coexistence of internal surface and full gland types was statistically significant (p < 0.001). The frequencies of GLA, RDLs, and WNM in HP-eradicated GCs were significantly higher than those in HP-infected GCs. GLA-positive GCs were covered more widely by internal surface type than GLA-negative GCs (13.3% vs. 6.6%, P = 0.003). Various types of NE were noted in gastric cancer, and the internal surface type of NE was shown to be significantly linked to HP-eradicated cancer and GLA

    Comparison of clinical symptoms, gastric motility and fat intake in the early chronic pancreatitis patients with anti-acid therapy-resistant functional dyspepsia patients.

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    BACKGROUND:There was no available data concerning the clinical differentiation between the updated definition of early chronic pancreatitis (ECP) and anti-acid therapy-resistant functional dyspepsia (RFD). AIMS:We aimed to determine whether clinical symptoms, gastric motility, psychogenic factors and fat intake can help distinguish early chronic pancreatitis (ECP) from anti-acid therapy-resistant functional dyspepsia patients with pancreatic enzyme abnormalities (RFD-P) and anti-acid therapy-resistant functional dyspepsia (RFD) patients using endosonography. METHODS:We enrolled 102 consecutive patients presenting with typical symptoms of RFD patients (n = 52), ECP patients (n = 25) and RFD-P patients (n = 25). ECP patients were diagnosed based on the criteria recommended by the Japan Pancreatic Association. Gastric motility was evaluated by 13C-acetate breath tests. Severity of duodenal inflammation was examined. RESULTS:24.5% of RFD patients were determined as ECP using endosonography. Abdominal pain score in Gastrointestinal Symptom Rating Scale (GSRS) in the patients with ECP was significantly lower compared to that in the patients with RFD-P. There were no significant differences in State-Trait Inventory (STAI)-state/-trait scores, Self-Rating Questionnaire for Depression (SRQ-D) scores and clinical symptoms for fat intake among three groups. The early phase of gastric emptying (AUC5; AUC15) in ECP and RFD-P patients were significantly disturbed compared to those in RFD patients. CONCLUSIONS:Evaluation of severity of abdominal pain and measurement of the early phase of gastric emptying will be useful tools to distinguish ECP patients from RFD patients. Accurate diagnosis of ECP patients may contribute to the prevention from advancing of chronic pancreatitis
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