Gallbladder carcinoma (GBC) is one of the most aggressive malignancies, and frequently shows vascular invasion and lymph node metastasis. Our previous study has classified the wall-invasion pattern of GBC into two groups, i.e., infiltrative growth type (IG type) and destructive growth type (DG type). The DG type was significantly associated with poor clinical outcome. In this study, we analyzed the relationship between the wall-invasion pattern and the histological phenotype of GBC, using 61 surgically-resected primary gallbladder adenocarcinomas. Histologically, the 61 cases were classified into the biliary (44 cases, 72.1%), gastric foveolar (13 cases, 21.3%), and intestinal (4 cases, 6.6%) types. Biliary type frequently exhibited MUC1, but less frequently showed MUC2, MUC5AC, and MUC6. The biliary type and MUC1 expression were significantly correlated with DG type wall-invasion pattern (P = 0.020 and P < 0.001, respectively). In conclusion, histological phenotype and mucin expression were thought to be indicators of aggressiveness of GBC.
The intestinal microbiome might be an important contributor to the development of type 2 diabetes. This study was designed to test the hypothesis that oral administration of Bifidobacterium species (spp.) (including B. longum, B. bifidum, B. infantis, and B. animalis) may both ameliorate insulin resistance and reduce the expressions of inflammatory adipocytokines. Male Swiss-Webster mice fed a high-fat diet with or without oral administration of Bifidobacterium spp. for 5 weeks were subjected to an insulin tolerance test and an oral glucose tolerance test. Plasma levels of glucose at 30, 60, 90 and 120 min after insulin injection or glucose administration were significantly lower in the Bifidobacterium spp. than in the control group (P < 0.05), showing the beneficial effect of oral administration on insulin resistance in obese Swiss mice. In addition, Bifidobacterium spp. increased the adiponectin mRNA level and decreased those of monocyte chemoattractant protein 1 and interleukin 6 in non-diabetic C57BL/6J mice fed a normal diet, indicating a molecular mechanism which may ameliorate the inflammatory state, thereby reducing insulin resistance. In conclusion, oral administration of Bifidobacterium spp. improves insulin resistance and glucose tolerance in obese mice by reducing inflammation, as it does in the lean state.
Bonito extract, i.e., dried bonito broth (DBB), has been reported to counteract mental fatigue and to increase performance in a simple calculation task, but the mechanism by which DBB increases task performance is not known. The brain neurotransmitter histamine is biosynthesized only from histidine in the tuberomammillary nucleus. Histamine neurons are projected to almost all areas of the cerebral cortex, and histamine has various behavioral and neurobiological functions, particularly in recognition memory. Here we used a mouse model to investigate the effects of the oral ingestion of DBB, which contains abundant histidine, as well as the ingestion of histidine on cognitive function. In a retention trial of novel object recognition test, the administration of 1.6 g/kg of DBB and 500 mg/kg of histidine significantly increased the animals’ exploratory behavior toward a novel object, and that these agents significantly increased the spontaneous alternation behavior ratio in a Y-maze under conditions of scopolamine-induced amnesia, which induced learning and memory impairment. These results suggested the improvement of spatial short-term working memory in a scopolamine amnesia model, as well as the strengthening of visual cognitive function by a single ingestion of DBB and histidine. Interestingly, the administration of αFMH, which is an inhibitor of histamine biosynthesis, eliminated the increase in the spontaneous alternation behavior ratio by DBB ingestion in the scopolamine-induced amnesia model, suggesting that DBB may improve working memory impairment via activation of the histaminergic neuron system.
The present study was designed to investigate effects and molecular mechanisms of Coptidis Rhizoma extracts (CRE) on the improvement of insulin resistance induced by tumor necrosis factor-α (TNF-α) in adipocytes. We examined whether CRE administration could directly influence the insulin resistance in 3T3-L1 adipocytes. Potential roles of CRE in glucose consumption, mRNA expression of peroxisome proliferators activated receptor (PPAR-γ), expression of insulin receptor substrate-1 (IRS-1) protein, and phosphorylation of IRS-1 Ser307 were also investigated in the present study. Our data demonstrated that TNF-α significantly reduced levels of glucose consumption and IRS-1 protein expression, while TNF-α increased the phosphorylation of IRS-1 Ser307 in adipocytes 24 h after the challenge, suggesting that TNF-α induced a condition with the occurrence of insulin resistance. Those alterations induced by TNF-α were prevented and the mRNA expression of PPAR-γ was up-regulated by the administration of CRE. Thus, our results indicate that CRE can be used to prevent from the TNF-α-induced insulin resistance through PPAR-γ pathways.
GP2, a GPI-anchored glycoprotein, is a useful marker of M cells in Peyer’s patches. Our immunostaining of the paranasal sinuses in mice detected a condensed distribution of GP2-immunoreactive cells within the epithelium, apart from lymphoid tissues. In the paranasal sinuses, the cells exhibited a unique morphology characterized by a slender neck portion and huge terminal bulb, quite different from M cells. Electron microscopically, the GP2 immunoreactivity centered on the luminal plasma membrane of the terminal bulb, being less intense in the baso-lateral plasma membrane and not visible at all in the cytoplasm. The cells frequently came in contact with nerve fibers containing small synaptic vesicles. These nerve fibers contained neither CGRP nor substance P—indicators of sensory neurons; moreover, no signal molecules used for a sensory function were expressed in the GP2-immunoreactive cells, implying that these nerves are efferent in nature. A weak but significant stainability in PAS reaction and an intense GP2 immunoreactivity for typical goblet cells in the tunica conjunctiva suggest that the GP2-expressing cells in paranasal sinuses are in the lineage of goblet cells.
This study investigated biomechanical mechanisms of acute subdural hematoma caused by judo and sought preventive measures to reduce injury. A Japanese judo expert repeatedly threw an anthropometric test device using two throwing techniques, Osoto-gari and Ouchi-gari. Linear and angular accelerations of the head were measured. Both throwing techniques resulted in the dummy falling backwards, with the occipital area of the head contacting the mat, and peak linear and angular accelerations being observed when the head contacted the mat. For linear acceleration, the posterior–anterior direction showed the greatest force (41.0 ± 2.6 G using Osoto-gari, and 86.5 ±4.3 G using Ouchi-gari). For angular acceleration, values for sagittal plane rotation were greatest among the three directions measured (3315 ± 168 rad/s2 using Osoto-gari, and 1328 ± 201 rad/s2 using Ouchi-gari). We concluded that occipital head contact produced the most forceful longitudinal linear and sagittal plane angular accelerations; subsequent stretches and ruptures of parasagittal bridging veins resulting in acute subdural hematoma. As severe head injuries can result if a person’s head comes into contact with the mat, offensive throwing techniques should be restricted to participants able to sufficiently demonstrate the Ukemi technique.
Alport syndrome (AS) and thin basement membrane nephropathy (TBMN) are genetic disorders caused by mutations of the type IV collagen genes COL4A3, COL4A4, and/or COL4A5. We here aimed to investigate the three-dimensional ultrastructure of the glomerular basement membrane (GBM) in order to introduce a novel method of diagnosing AS and TBMN. The subjects were 4 patients with AS and 6 patients with TBMN. Conventional renal biopsy paraffin sections from AS and TBMN patients were stained with periodic acid methenamine silver (PAM) and observed directly under low vacuum scanning electron microscopy (LVSEM). The PAM-positive GBMs were clearly visible under LVSEM through the overlying cellular components. The GBMs showed characteristic coarse meshwork appearances in AS, and thin and sheet-like appearances in TBMN. At the cut side view of the capillary wall, the GBMs in AS appeared as fibrous inclusions between a podocyte and an endothelial cell, while the GBMs in TBMN showed thin linear appearances. These different findings of GBMs between AS and TBMN were easily observed under LVSEM. Thus, we conclude that three-dimensional morphological evaluation by LVSEM using conventional renal biopsy paraffin sections will likely be useful for the diagnosis of AS and TBMN, including for retrospective investigations.