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Resumen La enfermedad inflamatoria intestinal de inicio muy temprano (VEOIBD) es una entidad rara en pediatría. Es conocida su asociación con inmunodeficiencias prima rias de origen monogénico. Presentamos el caso de una paciente con diagnóstico de VEOIBD a quien se le realizó una secuenciación masiva del exoma. El resultado del estudio permitió identificar una variante patogénica en el proto oncogen RET, asociada con enfermedad neoplasia endocrina múltiple tipo 2A. No hay reportes de asociación de variantes en el proto oncogen RET con VEOIBD. No se puede adjudicar la presencia de estas dos entidades clínicas a una única causa genética.
Abstract Very early onset inflammatory bowel disease (VEOI BD) is a rare entity in pediatrics. Its association with pri mary immunodeficiencies of monogenic origin is known. We present the case of a patient diagnosed with VEOIBD who underwent massive paralleled exome sequencing. The result of the study showed a pathogenic variant in the RET proto-oncogene, associated with multiple endo crine neoplasia type 2A disease. There are no previous reports of association of RET proto-oncogene variants with VEOIBD. The presence of these two clinical entities cannot be attributed to a single genetic cause.
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AIM:To detect the expression of CBir1 in the serum and colon tissue and mast cell degranulation in the tissue of 2,4,6-trinito-benzene-sulfonic acid ( TNBS)-induced colitis in mice with different interventions. ME-THODS:SPF male BALB/c mice were randomized into 6 groups (12 mice in each group):normal control group, normal saline group, 50% alcohol group, 50% alcohol+TNBS group, 50% alcohol+TNBS+lipopolysaccharide (LPS) +ovalbu-min (OVA) group and 50% alcohol+TNBS+ketotifen group. Corresponding treatment was given to each group, and the disease activity index (DAI) of the mice was evaluated. The mice were sacrificed on day 22 after treatment. The colon tis-sues were evaluated by histological index (HI) scoring. Serum concentrations of anti-CBir1, mast cell tryptase (MCT) and histamine were measured by ELISA. The expression of CBir1, toll-like receptor 5 (TLR5) and MCT in the colon tissues was detected by immunohistochemistry. RESULTS:Compared with the normal control group, the DAI score, HI score and CBir1, anti-CBir1, MCT, TLR5, histamine concentrations in colon tissues and serum were all significantly higher in 50% alcohol+TNBS group, 50% alcohol+TNBS+ketotifen group and 50% alcohol+TNBS+LPS+OVA group (P<0.05). The DAI score, HI score and anti-CBir1, CBir1, MCT, histamine levels in 50% alcohol+TNBS group were lower than those in 50% alcohol+TNBS+LPS+OVA group (P<0.05). The DAI score, HI score and anti-CBir1, TLR5, hista-mine, CBir1 Levels in 50% alcohol+TNBS group were higher than those in 50% alcohol+TNBS+ketotifen group ( P<0.05). Normal saline group and 50% alcohol group had no statistically significant difference in comparison with normal control group. In TNBS model group, serum concentration of anti-CBir1 was positively correlated with MCT concentration (r=0.648, P<0.01) and histamine concentration (r=0.751, P<0.01). CONCLUSION:The heavier degree of in-flammation in TNBS-induced colitis, the higher levels of the CBir1 and the degranulation of mast cells. There is a positive correlation between the expression of CBir1 and the degranulation of mast cells in TNBS-induced colitic mice.
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Aim To investigate whether Hcy influenced the intestinal mucosal permeability by regulating MEK-ERK-MLCK pathway. Methods SD rats were divided into 4 groups:normal group, normal+Hcy group, TN-BS/ethanol group, TNBS/ethanol+Hcy group. Experi-mental colitis model with hyperhomocystinemia was es-tablished in rats with intracolonic administration of TN-BS and subcutaneous injection of Hcy. The colonic mucosal tissue was collected for histopathological exam-ination and activity of myeloperoxidase ( MPO ) . The protein expression of MLCK, p-MLCK, MEK, ERK and p-ERK in intestinal mucosal tissues was examined by Western blot method. The mRNA expression of ML-CK was examined by RT-qPCR method. Result Com-pared with the normal group and TNBS group, the DAI and HI scores and the MPO activity were increased in TNBS/ethanol+Hcy group ( P <0. 01 ) . Western blot and RT-qPCR showed that expression of MLCK, p-ML-CK, MEK, ERK and p-ERK increased in small intes-tine in TNBS/ethanol+Hcy group. Conclusion Hcy can increase intestinal permeability in TNBS-induced colitis rats by regulating the expression of MEK-ERK-MLCK signal pathway.