Novel XIAP mutation with early-onset Crohn's disease complicated with acute heart failure: a case report.

BACKGROUND: The X-linked inhibitor of apoptosis (XIAP) protein is encoded by the XIAP gene and is critical for multiple cell responses and plays a role in preventing cell death. XIAP mutations are associated with several diseases, primarily including hemophagocytic lymphohistiocytosis and inflammatory bowel disease (IBD). We report the clinical features and results associated with hemizygous mutation of the XIAP gene in a young male with Crohn's disease complicated with acute heart failure.This 16-year-old patient ultimately died of heart failure. CASE PRESENTATION: A young male of 16 years of age was initially diagnosed with Crohn's disease based on evidences from endoscopic and histological findings. Although supportive care, anti-infective drugs and biologics were administered consecutively for 11 months, his clinical manifestations and laboratory indices (patient's condition) did not improved. Additionally, the patient exhibited a poor nutritional status and sustained weight loss. Subsequently, acute heart failure led to the exacerbation of the patient's condition. He was diagnosed with wet beriberi according to thiamine deficiency, but the standard medical therapy for heart failure and thiamine supplementation did not reverse the adverse outcomes. Comprehensive genetic analysis of peripheral blood-derived DNA revealed a novel hemizygous mutation of the XIAP gene (c.1259_1262 delACAG), which was inherited from his mother. CONCLUSION: A novel XIAP mutation (c.1259_1262 delACAG) was identified in this study. It may be one of the potential pathogenic factors in Crohn's disease and plays an important role in the progression of heart failure. Additionally, thiamine deficiency triggers a vicious cycle.

Betaine supplementation is associated with the resilience in mice after chronic social defeat stress: a role of brain-gut-microbiota axis.

BACKGROUND: The brain-gut-microbiota axis plays a role in the pathogenesis of stress-related psychiatric disorders; however, its role in the resilience versus susceptibility after stress remains unclear. Dietary nutrient betaine is suggested to affect the gut microbiome. Here, we examined whether betaine supplementation can affect anhedonia-like phenotype in mice subjected to chronic social defeat stress (CSDS). METHODS: CSDS was performed during betaine supplementation. Sucrose preference test and 16S rRNA analysis of fecal samples were performed. RESULTS: CSDS did not produce an anhedonia-like phenotype in the betaine-treated mice, but did induce an anhedonia-like phenotype in water-treated mice. Furthermore, CSDS treatment did not alter the plasma levels of interleukin-6 (IL-6) of betaine-treated mice whereas CSDS caused higher plasma levels of IL-6 in water-treated mice. Betaine supplementation ameliorated the abnormal diversity and composition of the microbiota in the host gut after CSDS. At the genus level, CSDS caused marked increases in the several bacteria of water-treated mice, but not betaine-treated mice. CSDS increased levels of short-chain fatty acids (i.e., succinic acid and acetic acid) in feces from water-treated mice, but not betaine-treated mice. Interestingly, there are positive correlations between short-chain fatty acids (i.e., succinic acid, acetic acid, butyric acid) and several bacteria among the groups. LIMITATIONS: Specific microbiome were not determined. CONCLUSIONS: These findings suggest that betaine supplementation contributed to resilience to anhedonia in mice subjected to CSDS through anti-inflammation action. Therefore, it is likely that betaine could be a prophylactic nutrient to prevent stress-related psychiatric disorders.

Dietary intake of glucoraphanin prevents the reduction of dopamine transporter in the mouse striatum after repeated administration of MPTP.

AIMS: Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder. Although diet may influence the development of PD, the precise mechanisms underlying relationship between diet and PD pathology are unknown. Here, we examined whether dietary intake of glucoraphanin (GF), the precursor of a natural antioxidant sulforaphane in cruciferous vegetables, can affect the reduction of dopamine transporter (DAT) in the mouse striatum after repeated administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). METHODS: Normal food pellet or 0.1% GF food pellet was given into male mice for 28 days from 8-week-old. Subsequently, saline (5 mL/kg × 3, 2-hour interval) or MPTP (10 mg/kg × 3, 2-hour interval) was injected into mice. Immunohistochemistry of DAT in the striatum was performed 7 days after MPTP injection. RESULTS: Repeated injections of MPTP significantly decreased the density of DAT-immunoreactivity in the mouse striatum. In contrast, dietary intake of 0.1% GF food pellet significantly protected against MPTP-induced reduction of DAT-immunoreactivity in the striatum. CONCLUSION: This study suggests that dietary intake of GF food pellet could prevent MPTP-induced dopaminergic neurotoxicity in the striatum of adult mice. Therefore, dietary intake of GF-rich cruciferous vegetables may have beneficial effects on prevention for development of PD.