These results suggest that determining F. nucleatum levels may help predict clinical outcomes in colorectal cancer patients. Further confirmatory studies using independent datasets are required to confirm our findings.
Nonessential amino acid L-Ser plays an essential role in neuronal survival and differentiation, through preferential expression of the L-Ser biosynthetic enzyme 3-phosphoglycerate dehydrogenase (3PGDH), in particular in glial cells but not in neurons. To seek the molecular candidates responsible for glia-borne L-Ser transport, we performed histochemical analyses on amino acid transporter ASCT1, which prefers small neutral amino acids, such as Ala, Ser, Cys, and Thr, and mediates their obligatory exchange. At early developmental stages, neuroepithelial cells constituting the ventricular zone expressed ASCT1 mRNA and protein ubiquitously. Thereafter, ASCT1 expression was gradually downregulated in neuronal populations during the late embryonic and neonatal periods, whereas its high expression was transmitted to radial glial cells and then to astrocytes. High levels of ASCT1 were also detected in the olfactory ensheathing glia. The preferential glial expression of ASCT1 was consistent with that of 3PGDH, and their extensive colocalization was demonstrated at the cellular level. Moreover, high cellular contents of L-Ser were revealed in these glial cells by using a specific antibody to L-Ser. These results strongly suggest that a large amount of L-Ser is synthesized and stored in these glial cells and is released through ASCT1 in exchange for other extracellular substrates. In addition, we observed prominent expression of ASCT1 in capillary endothelial cells of embryonic and neonatal brains. Therefore, ASCT1 appears to be regulated to meet metabolic demands by differentiating and mature neurons through the transport of glia- and blood-borne small neutral amino acids.
Little is known about the cerebral distribution and clearance of guanidinoacetate (GAA), the accumulation of which induces convulsions. The purpose of the present study was to identify creatine transporter (CRT)‐mediated GAA transport and to clarify its cerebral expression and role in GAA efflux transport at the blood‐cerebrospinal fluid barrier (BCSFB). CRT mediated GAA transport with a Km value of 269 μM/412 μM which was approximately 10‐fold greater than that of CRT for creatine. There was wide and distinct cerebral expression of CRT and localization of CRT on the brush‐border membrane of choroid plexus epithelial cells. The in vivo elimination clearance of GAA from the CSF was 13‐fold greater than that of d‐mannitol reflecting bulk flow of the CSF. This process was partially inhibited by creatine. The characteristics of GAA uptake by isolated choroid plexus and an immortalized rat choroid plexus epithelial cell line (TR‐CSFB cells) used as an in vitro model of BCSFB are partially consistent with those of CRT. These results suggest that CRT plays a role in the cerebral distribution of GAA and GAA uptake by the choroid plexus. However, in the presence of endogenous creatine in the CSF, CRT may make only a limited contribution to the GAA efflux transport at the BCSFB.
Background Accumulating evidence shows an over-abundance of Fusobacterium nucleatum in colorectal tumour tissues. Although stool DNA testing of Fusobacterium nucleatum might be a potential marker for the detection of colorectal tumours, the difficulty in detecting Fusobacterium nucleatum in stool by conventional methods prevented further explorations. Therefore, we developed a droplet digital polymerase chain reaction (PCR) assay for detecting Fusobacterium nucleatum in stool and investigated its clinical utility in the management of colorectal tumours in a Japanese population. Methods Feces were collected from 60 healthy subjects (control group) and from 11 patients with colorectal non-advanced adenomas (non-advanced adenoma group), 19 patients with colorectal advanced adenoma/carcinoma in situ (advanced adenoma/carcinoma in situ (CIS) group) and 158 patients with colorectal cancer of stages I to IV (colorectal cancer group). Absolute copy numbers of Fusobacterium nucleatum were measured by droplet digital PCR. Results The median copy number of Fusobacterium nucleatum was 17.5 in the control group, 311 in the non-advanced adenoma group, 122 in the advanced adenoma/CIS group, and 317 in the colorectal cancer group. In comparison with that in the control group, the Fusobacterium nucleatum level was significantly higher in the non-advanced adenoma group, the advanced adenoma/CIS group and the colorectal cancer group. Conclusions This study illustrates the potential of stool DNA testing of Fusobacterium nucleatum by droplet digital PCR to detect individuals with colorectal tumours in a Japanese population.
The Epstein-Barr virus (EBV) is detected in about 10% of gastric carcinoma cases throughout the world. In EBV-associated gastric carcinoma, all tumor cells harbor the clonal EBV genome. Gastric carcinoma associated with EBV has distinct clinicopathological features, occurs predominately in men and in younger-aged individuals, and presents a generally diffuse histological type. Most cases of EBV-associated gastric carcinoma exhibit a histology rich in lymphocyte infiltration. The immunological reactiveness in the host may represent a relatively preferable prognosis in EBV-positive cases. This fact highlights the important role of EBV in the development of EBV-associated gastric carcinoma. We have clearly proved direct infection of human gastric epithelialcells by EBV. The infection was achieved by using a recombinant EBV. Promotion of growth by EBV infection was observed in the cells. Considerable data suggest that EBV may directly contribute to the development of EBV-associated GC. This tumor-promoting effect seems to involve multiple mechanisms, because EBV affects several host proteins and pathways that normally promote apoptosis and regulate cell proliferation.
Autism spectrum disorder (ASD) is a multifactorial disorder with characteristic synaptic and gene expression changes. Early intervention during childhood is thought to benefit prognosis. Here, we examined the changes in cortical synaptogenesis, synaptic function, and gene expression from birth to the juvenile stage in a marmoset model of ASD induced by valproic acid (VPA) treatment. Early postnatally, synaptogenesis was reduced in this model, while juvenile-age VPA-treated marmosets showed increased synaptogenesis, similar to observations in human tissue. During infancy, synaptic plasticity transiently increased and was associated with altered vocalization. Synaptogenesis-related genes were downregulated early postnatally. At three months of age, the differentially expressed genes were associated with circuit remodeling, similar to the expression changes observed in humans. In summary, we provide a functional and molecular characterization of a non-human primate model of ASD, highlighting its similarity to features observed in human ASD.
The rodent granular retrosplenial cortex (GRS) is reciprocally connected with the hippocampus. It is part of several networks implicated in spatial learning and memory, and is known to contain head-direction cells. There are, however, few specifics concerning the mechanisms and microcircuitry underlying its involvement in spatial and mnemonic functions. In this report, we set out to characterize intrinsic properties of a distinctive population of small pyramidal neurons in layer 2 of rat GRS. These neurons, as well as those in adjoining layer 3, were found to exhibit a late-spiking (LS) firing property. We established by multiple criteria that the LS property is a consequence of delayed rectifier and A-type potassium channels. These were identified as Kv1.1, Kv1.4 and Kv4.3 by Genechip analysis, in situ hybridization, single-cell reverse transcriptase-polymerase chain reaction, and pharmacological blockade. The LS property might facilitate comparison or integration of synaptic inputs during an interval delay, consistent with the proposed role of the GRS in memory-related processes.
Although growing evidence demonstrates that TWIST1 is an interesting tumor biomarker, little is known about the clinical significance of TWIST1 expression and TWIST1 methylation in human primary colorectal cancer. In this study, we examined the association of TWIST1 expression and TWIST1 methylation with clinicopathologic features in human primary colorectal tumors. Primary colorectal cancer (CRC) specimens from 319 patients, corresponding normal colorectal nontumorous mucosa from 251 patients with cancer, and colorectal adenomas from 189 patients were used. Methylation and expression levels of TWIST1 were compared with clinicopathologic features. The TWIST1 methylation level was higher in colorectal adenoma and cancer than in normal colorectal mucosa. Elevated TWIST1 mRNA expression in normal colorectal mucosa in patients with CRC as well as in primary CRC specimens was associated with unfavorable outcomes. There was no correlation between TWIST1 methylation and TWIST1 expression. Our results suggest that TWIST1 methylation may be a useful biomarker for screening colorectal tumors. In addition, TWIST1 mRNA expression is a possible molecular marker for predicting the outcome in patients with CRC. Confirmatory studies using independent data sets are needed to confirm our findings.
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