Origin of O2 Generation in Sulfide-Based All-Solid-State Batteries and its Impact on High Energy Density.

The cathode surface of sulfide-based all-solid-state batteries (SBs) is commonly coated with amorphous-LiNbO3 in order to stabilize charge-discharge reactions. However, high-voltage charging diminishes the advantages, which is caused by problems with the amorphous-LiNbO3 coating layer. This study has investigated the degradation of amorphous-LiNbO3 coating layer directly during the high-voltage charging of SBs. O2 generation via Li extraction from the amorphous-LiNbO3 coating layer is observed using electrochemical gas analysis and electrochemical X-ray photoelectron spectroscopy. This O2 leads to the formation of an oxidative solid electrolyte (SE) around the coating layer and degrades the battery performance. On the other hand, elemental substitution (i.e., amorphous-LiNbxP1- xO3) reduces O2 release, leading to stable high-voltage charge-discharge reactions of SBs. The results have emphasized that the suppression of O2 generation is a key factor in improving the energy density of SBs.

Takotsubo cardiomyopathy in Guillain-Barré syndrome.

BACKGROUND AND PURPOSE: Takotsubo cardiomyopathy (TCM) is a serious autonomic complication of Guillain-Barré syndrome (GBS). However, the association between TCM and GBS has not been investigated in detail. We investigated the characteristics of GBS patients with TCM (GBS-TCM). METHODS: Clinical features and anti-ganglioside antibody between the GBS-TCM patients and 62 classical GBS patients without TCM as control patients were compared. RESULTS: Eight GBS-TCM patients were identified, in whom TCM was diagnosed at a mean of 6.5 [range 3-42] days after the onset of GBS. The age at onset of GBS was elder in the GBS-TCM patients than in the control GBS patients (76.5 [56-87] vs. 52 [20-88] years, p < 0.01). Notably, cranial nerve deficits, particularly in the lower cranial nerves, were observed in all GBS-TCM patients (100% vs. 41.9%, p < 0.01). Additionally, the GBS-TCM patients showed a higher GBS disability score at nadir (5 [4-5] vs. 4 [1-5], p < 0.01), and lower Medical Research Council sum scores at admission and nadir (37 [30-44] vs. 48 [12-60] at admission, p < 0.05, and 20 [12-44] vs. 40 [0-60] at nadir, p < 0.05, respectively). Mechanical ventilation was more frequently required in the GBS-TCM patients (62.5% vs. 11.3%, p < 0.01). Three GBS-TCM patients were positive for anti-ganglioside antibodies. CONCLUSIONS: TCM occurred at a relatively early phase of GBS. The characteristics of GBS-TCM were the elder, lower cranial nerve involvements, severe limb weakness, and respiratory failure.

Long term administration of loquat leaves and their major component, ursolic acid, attenuated endogenous amyloid-ß burden and memory impairment.

Loquat (Eriobotrya japonica) leaves contain many bioactive components such as ursolic acid (UA) and amygdalin. We investigated the effects of loquat leaf powder and methanol extract in human neuroglioma H4 cells stably expressing the Swedish-type APP695 (APPNL-H4 cells) and C57BL/6 J mice. Surprisingly, the extract greatly enhanced cellular amyloid-beta peptide (Aß) 42 productions in APPNL-H4 cells. Administration of leaf powder increased Aß42 levels after 3 months and decreased levels after 12 months compared to control mice. Leaf powder had no effect on working memory after 3 months, but improved working memory after 12 months. Administration of UA decreased Aß42 and P-tau levels and improved working memory after 12 months, similar to the administration of leave powder for 12 months. Amygdalin enhanced cellular Aß42 production in APPNL-H4 cells, which was the same as the extract. Three-month administration of amygdalin increased Aß42 levels slightly but did not significantly increase them, which is similar to the trend observed with the administration of leaf powder for 3 months. UA was likely the main compound contained in loquat leaves responsible for the decrease in intracerebral Aß42 and P-tau levels. Also, amygdalin might be one of the compounds responsible for the transiently increased intracerebral Aß42 levels.

Memantine administration prevented chorea movement in Huntington's disease: a case report.

BACKGROUND: Huntington's disease is an autosomal dominant inherited disorder characterized by personality changes (such as irritability and restlessness) and psychotic symptoms (such as hallucinations and delusions). When the personality changes become noticeable, involuntary movements (chorea) also develop. The disease is caused by the CAG repeat expansion in the coding region of the HTT gene, and the diagnosis is based on the presence of this expansion. However, there is currently no effective treatment for the progression of Huntington's disease and its involuntary motor symptoms. Herein, we present a case in which memantine was effective in treating the chorea movements of Huntington's disease. CASE PRESENTATION: A 75-year-old Japanese woman presented to the hospital with involuntary movements of Huntington's disease that began when she was 73 years old. In a cerebral blood flow test (N-isopropyl-p-iodoamphetamine-single-photon emission computed tomography), decreased blood flow was observed in the precuneus (anterior wedge) and posterior cingulate gyrus. Usually, such areas of decreased blood flow are observed in patients with Alzheimer's-type dementia. So, we administered memantine for Alzheimer's-type dementia, and this treatment suppressed the involuntary movements of Huntington's disease, and the symptoms progressed slowly for 7 years after the onset of senility. In contrast, her brother died of complications of pneumonia during the course of Huntington's disease. CONCLUSIONS: We recorded changes in parameters such as the results of the N-isopropyl-p-iodoamphetamine-single-photon emission computed tomography and gait videos over 7 years. Treatment with memantine prevented the chorea movement and the progression of Huntington's disease. We believe this record will provide clinicians with valuable information in diagnosing and treating Huntington's disease.

Microglial depletion exacerbates axonal damage and motor dysfunction in mice with cuprizone-induced demyelination.

The cuprizone (CPZ)-induced demyelination model, an animal model of Multiple sclerosis (MS), is characterized by demyelination and motor dysfunction due to microglial-mediated neuroinflammation. To determine the contribution of microglia to motor function during CPZ-induced demyelination, the microglia of mice in the CPZ-model were depleted using PLX3397 (PLX), an orally bioavailable selective colony stimulating factor 1 receptor inhibitor. PLX treatment aggravated motor dysfunction as shown by the pole, beam walk, ladder walk, and rotarod tests. PLX treatment removed microglia from the superior cerebellar peduncle (SCP), but not from the corpus callosum (CC). Although PLX treatment did not affect the degree of demyelination in both of CC and SCP, the expression of axonal damage marker APP (amyloid precursor protein) was increased. Increased TNF-α, IL-1ß, and iNOS expressions were observed in PLX-treated mice. These results suggest that microglial depletion exacerbates axonal damage and motor dysfunction in CPZ model mice. In this study, we found that microglia contribute to motor function and axon-protective effects in CPZ-induced demyelination.

A case of thymoma-associated myasthenia gravis accompanied with myositis showing the clusters of histiocyte along the fascicles in perimysium.

Patients with myasthenia gravis (MG) often have other autoimmune disorders. However, the coexistence of MG and myositis is rare. Here, we report a case of a 77-year-old woman who developed mild fatigable muscle weakness and diplopia in 3 months. Serum creatine kinase was elevated to 1385 IU/L. Antibodies to acetylcholine receptor (AChR), titin and voltage-gated potassium channel 1.4 (Kv 1.4) were all positive while all tested myositis-specific autoantibodies were negative. Standard needle electromyography showed fibrillation potential and early recruitment of motor units. The repetitive nerve stimulations were consistent with a disorder of the neuromuscular junction. Muscle biopsy showed that the clusters of histiocyte were present along the fascicles in perimysium and some of them invaded into endomysium.

Characteristics of Guillain-Barré syndrome in super-elderly individuals.

BACKGROUND: Japan has the world's largest super-aging population, and the number of elderly patients with various diseases is increasing. Herein, we reported the characteristics of super-elderly patients, aged over 80 years, with Guillain-Barré syndrome (GBS), a typical neuroimmune disease. METHODS: During the period 2019-2021, 74 patients over the age of 80 years diagnosed with GBS at Kindai university were analyzed as the super-elderly group patients. The control group comprised 74 consecutive patients aged < 79 years, under the same conditions. GBS was diagnosed using Brighton diagnostic criteria. Electrophysiology was assessed using the Ho criteria. RESULTS: The mean age was 83.5 years in the super-elderly group and 51.7 years in the control group. Prior infection was recognized in 50% of cases in the super-elderly group and 77% of cases in the control group with fewer cases in the super-elderly group. The mean number of days until peak symptom presentation was longer in the super-elderly group. The percentage who required a ventilator was significantly higher among the super-elderly group than among the control group. Hughes functional grading scale was more severe in the super-elderly group. Electrophysiological examination revealed the demyelinating form was particularly common in the super-elderly group. Intravenous immunoglobulin was the most common treatment in both the groups, with no difference in efficacy. CONCLUSIONS: Super-elderly onset GBS tends to be severe, therefore it is important to diagnose and treat appropriately, even in the absence of prior episodes of infection.

GPR137 Inhibits Cell Proliferation and Promotes Neuronal Differentiation in the Neuro2a Cells.

The orphan receptor, G protein-coupled receptor 137 (GPR137), is an integral membrane protein involved in several types of cancer. GPR137 is expressed ubiquitously, including in the central nervous system (CNS). We established a GPR137 knockout (KO) neuro2A cell line to analyze GPR137 function in neuronal cells. KO cells were generated by genome editing using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 and cultured as single cells by limited dilution. Rescue cells were then constructed to re-express GPR137 in GPR137 KO neuro2A cells using an expression vector with an EF1-alpha promoter. GPR137 KO cells increased cellular proliferation and decreased neurite outgrowth (i.e., a lower level of neuronal differentiation). Furthermore, GPR137 KO cells exhibited increased expression of a cell cycle regulator, cyclin D1, and decreased expression of a neuronal differentiation marker, NeuroD1. Additionally, GPR137 KO cells exhibited lower expression levels of the neurite outgrowth markers STAT3 and GAP43. These phenotypes were all abrogated in the rescue cells. In conclusion, GPR137 deletion increased cellular proliferation and decreased neuronal differentiation, suggesting that GPR137 promotes cell cycle exit and neuronal differentiation in neuro2A cells. Regulation of neuronal differentiation by GPR137 could be vital to constructing neuronal structure during brain development.

Electronic properties of lithium-ion conductive amorphous lithium phosphorus oxynitride.

The valence band maxima of Li+ conductive amorphous lithium phosphorus oxynitride (LiPON) electrolyte depend on the chemical bonding states, and isolated nonbonding oxygen raises them. In contrast, the conduction band minima of the LiPON are independent of the composition and the values are less than the work function of Li.

Suppressive Effect of Fruiting Bodies of Medicinal Mushrooms on Demyelination and Motor Dysfunction in a Cuprizone-Induced Multiple Sclerosis Mouse Model.

Epidemiologic studies have shown a high prevalence of multiple sclerosis (MS) in Europe and North America, and a low prevalence in East Asia. Mushrooms contain various biological response modifiers (BRMs) and are widely used in traditional Chinese medicine in East Asian countries. To investigate whether mushrooms have potential beneficial effects on MS, we administered mushrooms to cuprizone (bis-cyclohexanone-oxalyldihydrazone, CPZ)-induced MS model mice. This model is used to study the processes of demyelination in the CNS. The CPZ-induced demyelination is involved in the apoptotic death of mature oligodendrocytes, neuroinflammation, and motor dysfunction. Mice were fed a powdered diet containing 5% each mushroom and CPZ diet for 5 weeks, which coincides with peak demyelination. We measured the body weight of the mice, evaluated their motor function using a rotarod, and quantified the myelin levels using Black-Gold II staining. Ganoderma lucidum and Hericium erinaceus treatments showed recovery from weight loss. Pleurotus eryngii, G. lucidum, and Flammulina velutipes treatments significantly improved CPZ-induced motor dysfunction. P. eryngii, G. lucidum, F. velutipes, and H. erinaceus treatments effectively suppressed CPZ-induced demyelination. The four medicinal mushrooms may be promising BRMs for prevention and alleviation of the symptoms of MS.

The Contribution of Chest X-Ray to Predict Extubation Failure in Mechanically Ventilated Patients Using Machine Learning-Based Algorithms.

OBJECTIVES: To evaluate the contribution of a preextubation chest X-ray (CXR) to identify the risk of extubation failure in mechanically ventilated patients. DESIGN: Retrospective cohort study. SETTINGS: ICUs in a tertiary center (the Medical Information Mart for Intensive Care IV database). PATIENTS: Patients greater than or equal to 18 years old who were mechanically ventilated and extubated after a spontaneous breathing trial. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 1,066 mechanically ventilated patients, 132 patients (12%) experienced extubation failure, defined as reintubation or death within 48 hours of extubation. To predict extubation failure, we developed the following models based on deep learning (EfficientNet) and machine learning (LightGBM) with the training data: 1) model using only the rapid-shallow breathing index (RSBI), 2) model using RSBI and CXR, 3) model using all candidate clinical predictors (i.e., patient demographics, vital signs, laboratory values, and ventilator settings) other than CXR, and 4) model using all candidate clinical predictors with CXR. We compared the predictive abilities between models with the test data to investigate the predictive contribution of CXR. The predictive ability of the model using CXR as well as RSBI was not significantly higher than that of the model using only RSBI (c-statistics, 0.56 vs 0.56; p = 0.95). The predictive ability of the model using clinical predictors with CXR was not significantly higher than that of the model using all clinical predictors other than CXR (c-statistics, 0.71 vs 0.70; p = 0.12). Based on SHapley Additive exPlanations values to interpret the model using all clinical predictors with CXR, CXR was less likely to contribute to the predictive ability than other predictors (e.g., duration of mechanical ventilation, inability to follow commands, and heart rate). CONCLUSIONS: Adding CXR to a set of other clinical predictors in our prediction model did not significantly improve the predictive ability of extubation failure in mechanically ventilated patients.

Acute eye movement-retained internal ophthalmoplegia in atypical Miller Fisher syndrome variants are associated with IgG anti-GQ1b antibodies.

Ophthalmoplegia is a common neurological finding in Miller Fisher syndrome (MFS), but acute eye movement-retained internal ophthalmoplegia is a rare variant of MFS. In this report, we present three cases of acute eye movement-retained internal ophthalmoplegia; IgG anti-GQ1b antibodies were detected in all patients. We reviewed a total of 13 cases, including 10 previously reported cases, and revealed that IgG anti-GQ1b antibodies were identified in all but one patient. In addition, we investigated the correlation between acute eye movement-retained internal ophthalmoplegia and antibodies against ganglioside complexes. We found that anti-GQ1b antibodies in our patients reacted with GQ1b or GT1a but not GQ1b/GM1 or GQ1b/GD1a complexes, indicating that antibodies against disialosyl residues have a pathogenetic role in acute eye movement-retained internal ophthalmoplegia. This is the first study describing that acute eye movement-retained internal ophthalmoplegia is associated with IgG antibodies specific to GQ1b or GT1a.

Dietary oleic acid contributes to the regulation of food intake through the synthesis of intestinal oleoylethanolamide.

Introduction: Among the fatty acid ethanolamides (FAEs), oleoylethanolamide (OEA), linoleoylethanolamide (LEA), and palmitoylethanolamide (PEA) are reported to be involved in feeding regulation. In particular, OEA is well characterized as a satiety signal. Following food consumption, OEA is synthesized from oleic acid (OA) via an N-acyl phosphatidylethanolamine-specific phospholipase D-dependent pathway in the gastroenterocytes, and OEA induces satiety by recruiting sensory fibers. Thus, we hypothesized that dietary OA is an important satiety-inducing molecule. However, there has been no direct demonstration of the effect of dietary OA on satiety induction without the influence of the endogenous biosynthesis of OA from stearic acid (SA) or other FAEs. Methods: In this study, we used two experimental diets to test our hypothesis: (i) an OA diet (OAD; 38.4 mg of OA/g and 7.2 mg of SA/g) and (ii) a low OA diet (LOAD; 3.1 mg of OA/g and 42.4 mg of SA/g). Results: Relative to mice fed the OAD, mice fed the LOAD for two weeks exhibited reduced levels of jejunal OEA but not jejunal LEA and PEA. The LOAD-fed mice showed an increase in food intake and body weight gain. Moreover, LOAD-induced increase in food intake was immediately observed after the switch from the OAD, whereas these effects were diminished by the switch back to the OAD. Furthermore, treatment with OA and OEA diminished the effects of LOAD on food intake. Conclusion: Collectively, these results show that dietary OA is a key factor in the reduction of food intake and increase in satiety mediated by OEA signaling.

A peripheral lipid sensor GPR120 remotely contributes to suppression of PGD2-microglia-provoked neuroinflammation and neurodegeneration in the mouse hippocampus.

BACKGROUND: Neuroinflammation is a key pathological component of neurodegenerative disease and is characterized by microglial activation and the secretion of proinflammatory mediators. We previously reported that a surge in prostaglandin D2 (PGD2) production and PGD2-induced microglial activation could provoke neuroinflammation. We also reported that a lipid sensor GPR120 (free fatty acid receptor 4), which is expressed in intestine, could be activated by polyunsaturated fatty acids (PUFA), thereby mediating secretion of glucagon-like peptide-1 (GLP-1). Dysfunction of GPR120 results in obesity in both mice and humans. METHODS: To reveal the relationship between PGD2-microglia-provoked neuroinflammation and intestinal PUFA/GPR120 signaling, we investigated neuroinflammation and neuronal function with gene and protein expression, histological, and behavioral analysis in GPR120 knockout (KO) mice. RESULTS: In the current study, we discovered notable neuroinflammation (increased PGD2 production and microglial activation) and neurodegeneration (declines in neurogenesis, hippocampal volume, and cognitive function) in GPR120 KO mice. We also found that Hematopoietic-prostaglandin D synthase (H-PGDS) was expressed in microglia, microglia were activated by PGD2, H-PGDS expression was upregulated in GPR120 KO hippocampus, and inhibition of PGD2 production attenuated this neuroinflammation. GPR120 KO mice exhibited reduced intestinal, plasma, and intracerebral GLP-1 contents. Peripheral administration of a GLP-1 analogue, liraglutide, reduced PGD2-microglia-provoked neuroinflammation and further neurodegeneration in GPR120 KO mice. CONCLUSIONS: Our results suggest that neurological phenotypes in GPR120 KO mice are probably caused by dysfunction of intestinal GPR120. These observations raise the possibility that intestinal GLP-1 secretion, stimulated by intestinal GPR120, may remotely contributed to suppress PGD2-microglia-provoked neuroinflammation in the hippocampus.

2-Carba-lysophosphatidic acid is a novel ß-lysophosphatidic acid analogue with high potential for lysophosphatidic acid receptor activation and autotaxin inhibition.

Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator that, along with its chemically stabilized analogue 2-carba-cyclic phosphatidic acid (2ccPA), induces various biological activities in vitro and in vivo. Although cPA is similar to lysophosphatidic acid (LPA) in structure and synthetic pathway, some of cPA biological functions apparently differ from those reported for LPA. We previously investigated the pharmacokinetic profile of 2ccPA, which was found to be rapidly degraded, especially in acidic conditions, yielding an unidentified compound. Thus, not only cPA but also its degradation compound may contribute to the biological activity of cPA, at least for 2ccPA. In this study, we determined the structure and examined the biological activities of 2-carba-lysophosphatidic acid (2carbaLPA) as a 2ccPA degradation compound, which is a type of ß-LPA analogue. Similar to LPA and cPA, 2carbaLPA induced the phosphorylation of the extracellular signal-regulated kinase and showed potent agonism for all known LPA receptors (LPA1-6) in the transforming growth factor-α (TGFα) shedding assay, in particular for LPA3 and LPA4. 2carbaLPA inhibited the lysophospholipase D activity of autotaxin (ATX) in vitro similar to other cPA analogues, such as 2ccPA, 3-carba-cPA, and 3-carba-LPA (α-LPA analogue). Our study shows that 2carbaLPA is a novel ß-LPA analogue with high potential for the activation of some LPA receptors and ATX inhibition.

Case Report: Regulatory T Cell-Independent Induction of Remission in a Patient With Collagenous Colitis.

Collagenous colitis (CC), a prototypical microscopic colitis, is a chronic inflammatory disorder of the colon. The diagnosis of CC depends on the pathological examination. The colonic mucosa of patients with CC is characterized by the presence of a substantially thickened collagen band (>10µm) under the surface epithelium. In addition, intraepithelial and lamina propria lymphocytes are markedly increased in patients with CC. However, the roles played by the lymphocytes accumulating in the colonic mucosa of patients with CC are poorly defined. Recent studies indicate that T cells infiltrating the colonic mucosa of patients with CC are mainly represented by CD4+ T cells, CD8+ T cells, and forkhead box P3 (FOXP3)+ regulatory T cells (Tregs). Given that activation of CD4+/CD8+ T cells and FOXP3+ Tregs usually mediates pro-inflammatory and anti-inflammatory responses, respectively, alterations in the colonic numbers of these adaptive T cells might be related to the resolution of colitis in patients with CC. We determined alterations in the composition of colonic T cells by extensive immunohistochemical (IHC) analyses in a case of CC successfully treated with budesonide and metronidazole. Colonic lamina propria immune cells mainly comprised CD3+ T cells, CD4+ T cells, CD8+ T cells, CD68+ macrophages, and FOXP3+ Tregs, but not CD20+ B cells or myeloperoxidase (MPO)+ granulocytes in the active phase. During remission, the numbers of CD3+ T cells, CD4+ T cells, CD8+ T cells, and CD68+ macrophages did not change significantly in the colonic lamina propria, whereas FOXP3+ Tregs were markedly decreased, suggesting that induction of remission was achieved in a Treg-independent manner. Thus, our study indicates that accumulation of FOXP3+ Tregs in the colonic mucosa of patients with CC might be a counter-regulatory mechanism reflecting persistent inflammation and that induction of remission might be achieved without activation of Tregs.

Immunohistochemical characterization of granulomatosis with polyangiitis exhibiting spontaneous regression.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is characterized by granulomatous inflammation, vasculitis, and elevated levels of serum proteinase 3 (PR3)-anti-neutrophil cytoplasmic antibody (PR3-ANCA). OBJECTIVE: We tried to characterize immune cells accumulated into the lung lesions of a GPA patient exhibiting spontaneous regression. METHODS: Transbronchial lung biopsy (TBLB) samples were subjected to immunohistochemical analyses. RESULTS: Multiple lung nodules were detected by CT. TBLB showed granulomatous inflammation and small vessel vasculitis. This case was diagnosed as GPA based on pathological findings and elevation of PR-3 ANCA levels. Spontaneous disappearance of multiple lung nodules was observed in CT. CD3+ T cells and CD20+ B cells accumulated in the inflammatory lesions surrounding the vessels whereas granulomatous inflammation was mainly comprised of CD3+ T cells and CD68+ macrophages, but not B cells or myeloperoxidase+ neutrophils. CONCLUSIONS: We characterized immune cell compositions of the lung lesions of a patient with GPA exhibiting spontaneous regression.

Case Report: Concurrent Occurrence of Abdominal Double Expressor Lymphoma and Jejunum Follicular Lymphoma.

Double expressor lymphoma (DEL), defined as overexpression of BCL2 and MYC, is an aggressive subtype of diffuse large B cell lymphoma (DLBCL). Here we report a case of a 64-year-old female diagnosed with abdominal DEL transformed from jejunum follicular lymphoma (FL). 18F-fluorodeoxyglucose (FDG)-positron emission tomography showed diffuse accumulation of FDG into the peritoneum and small bowel wall. Double balloon-assisted enteroscopy revealed whitish submucosal tumors in the proximal jejunum. Aggregation of atypical lymphocytes positive for CD20, CD79a, and BCL2 was seen in the jejunal biopsy samples. These atypical lymphocytes were monoclonal since cell surface expression of Ig light chains was limited to κ chain by flow-cytometry. Thus, immunohistochemical and flowcytometric analyses data were consistent with FL of the jejunum. Neoplastic lymphocytes obtained from ascites were positive for CD10, CD20, CD79a, BCL2, and BCL6. Fluorescence in situ hybridization (FISH) showed formation of BCL2/IgH fusion gene and extra copies of MYC, the former of which is a characteristic chromosomal abnormality of FL. These genetic alterations and protein expression profiles of ascitic fluid cells were consistent with those of DEL transformed from FL. Given that a significant population of patients with indolent FL of the gastrointestinal tract developed into aggressive DLBCL, it is likely that primary FL of the jejunum transformed into the abdominal aggressive DEL in this case. This case is unique in that concurrent occurrence of FL and DEL was confirmed by immunohistochemical and FISH analyses and that abdominal DEL transformed from jejunal FL was highly suspected.

Case Report: A Case of Intestinal Behçet's Disease Exhibiting Enhanced Expression of IL-6 and Forkhead Box P3 mRNA After Treatment With Infliximab.

Behçet's disease (BD) is a rare inflammatory condition characterized by oral and genital ulcers, skin lesions, as well as ophthalmological, neurological, and gastrointestinal manifestations. BD involving the gastrointestinal tract is known as intestinal BD. The mucosa of the gastrointestinal tract of patients with intestinal BD exhibits enhanced levels of proinflammatory cytokines, such as IL-1ß, IL-6, and TNF-α. These proinflammatory cytokines play pathogenic roles in the development of BD, as evidenced by the fact that biologics targeting these cytokines effectively induce BD remission. It should be noted, however, that the molecular mechanisms by which the blockade of these cytokines suppresses chronic inflammatory responses in BD are poorly understood. Herein, we report a case of intestinal BD resistant to prednisolone that was successfully treated with infliximab (IFX). The induction of remission by IFX was accompanied by a marked elevation of IL-6 and forkhead box P3 (FOXP3) at mRNA level. This case suggests that induction of remission by IFX is mediated not only by the suppression of TNF-α-mediated signaling pathways, but also by the promotion of IL-6 expression and accumulation of regulatory T cells expressing FOXP3.

Testosterone interrupts binding of Neurexin and Neuroligin that are expressed in a highly socialized rodent, Octodon degus.

Octodon degus is said to be one of the most human-like rodents because of its improved cognitive function. Focusing on its high sociality, we cloned and characterized some sociality-related genes of degus, in order to establish degus as a highly socialized animal model in molecular biology. We cloned degus Neurexin and Neuroligin as sociality-related genes, which are genetically related to autism spectrum disorder in human. According to our results, amino acid sequences of Neurexin and Neuroligin expressed in degus brain, are highly conserved to that of human sequences. Most notably, degus Neuroligin4 is highly similar to human Neuroligin4X, which is one of the most important autism-related genes, whereas mouse Neuroligin4 is known to be poorly similar to human Neuroligin4X. Furthermore, our work also indicated that testosterone directly binds to degus Neurexin and intercepts intercellular Neurexin-Neuroligin binding. Moreover, it is of high interest that testosterone is another key molecule of the higher incidence of autism in male. These results indicated that degus has the potential for animal model of sociality, and furthermore may promote understanding toward the pathogenic mechanism of autism.