β-Catenin Deletion in Regional Neural Progenitors Leads to Congenital Hydrocephalus in Mice / 神经科学通报·英文版

Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality; however, the underlying cellular and molecular mechanisms remain largely unknown. Reproducible animal models mirroring both embryonic and postnatal hydrocephalus are also limited. Here, we describe a new mouse model of congenital hydrocephalus through knockout of β-catenin in Nkx2.1-expressing regional neural progenitors. Progressive ventriculomegaly and an enlarged brain were consistently observed in knockout mice from embryonic day 12.5 through to adulthood. Transcriptome profiling revealed severe dysfunctions in progenitor maintenance in the ventricular zone and therefore in cilium biogenesis after β-catenin knockout. Histological analyses also revealed an aberrant neuronal layout in both the ventral and dorsal telencephalon in hydrocephalic mice at both embryonic and postnatal stages. Thus, knockout of β-catenin in regional neural progenitors leads to congenital hydrocephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.

A case of brain-lung-thyroid syndrome / 中南大学学报(医学版)

Brain-lung-thyroid syndrome is a rare autosomal dominant disorder. More than 100 cases have been reported worldwide, but few cases have been reported in China. In December 2018, a boy with brain-lung-thyroid syndrome, aged 3 years and 10 months, was admitted to Xiangya Hospital of Central South University due to repeated cough for more than 3 years. In infancy of the boy, psychomotor retardation, repeated cough, and hypothyroidism were found. Gene detection showed that there was c.927delc heterozygous variation in NKX2-1 gene (NM-001079668: exon3: c.927delC). The variation of this gene locus has not been reported in relevant literature so far, which indicates a new mutation. According to the above clinical manifestations and examination results, the boy was diagnosed as brain-lung-thyroid syndrome, which mainly characterized by nervous system disorders, accompanied by respiratory manifestations and hypothyroidism. The boy was treated with oral dopasehydrazine to relieve tremor and levothyroxine sodium tablets to relieve hypothyroidism. Anti-infection, atomization, rehabilitation training and other symptomatic supporting treatment were also administered. The boy's language and movement have improved, the thyroid hormone level is normal, and there are still repeated respiratory tract infections.

Effect of qingfei-yangyin-huoxue recipe on radiation-induced pulmonary injury via lncrna nanci-nkx2.1 pathway / 中国药学杂志

OBJECTIVE: To discuss the effect of Qingfei-yangyin-huoxue recipe on radiation-induced pulmonary injury by regulating the lncRNA NANCI-NKX2.1 pathway. METHODS: The C57BL/6 mice were randomly divided into normal control group (A group, n=16), drug only group (B group, n=16), model group (C group, n=16) and drug model group (D group, n=16). After exposure to Qingfei-yangyin-huoxue recipe for 10 w, the pathological change of lung tissue was examined by H&E and Masson staining. The expressions of lncRNA NANCI and NKX2.1 mRNA in lung tissues were detected by qRT-PCR. And the NKX2.1 protein expressions were detected by Western blot. RESULTS: The mean animal weight in D groups was less than A and B group, but more than C group after treatment of 7 d(P<0.05). There were marked interstitial edema and inflammatory cells, fibrocytes accumulation in C group but not in A and B groups by H&E and Masson stain. The alveolitis and fibrosis changes in D group were better than C group. And the mean radiation-induced pulmonary injury score in D group was (3.875±1.746), which was less than C group, but more than A and B groups (P<0.05). The expression of lncRNA NANCI and NKX2.1in D group was higher than C group, but lower than A and B groups (P<0.05). Besides, the radiation-induced pulmonary injury score was negative related with lncRNA NANCI and NKX2.1 (r=-0.510, -0.786, P<0.05). CONCLUSION: There are significant evidences that Qingfei-yangyin-huoxue recipe could protect radiation-induced pulmonary injury by up-regulation lncRNA NANCI-NKX2.1 pathway.

Bases moleculares del hipotiroidismo congénito / Molecular bases of congenital hypothyroidism

Las alteraciones endocrinológicas constituyen parte importante de la consulta pediátrica, la más frecuente es el hipotiroidismo congénito, grave problema de salud pública que requiere de diagnóstico neonatal. Los avances en el estudio molecular han permitido discernir las alteraciones en los procesos de organogénesis y hormonogénesis que lo producen. Se describen las principales alteraciones moleculares relacionadas con: diferenciación tiroidea, síntesis hormonal, hipotiroidismo central y con su acción periférica. El estudio de las alteraciones moleculares abre posibilidades interesantes, pues a partir del conocimiento preciso de los procesos fisiopatológicos y moleculares podrá realizarse en forma precoz el diagnóstico y manejo de estos pacientes, previniendo las secuelas que genera esta enfermedad.

The endocrinological disorders constitute an important percentage of the pediatric consultations. The most frequently endocrinopathy is congenital hypothyroidism, which is considered a public health problem. Newborn screening is mandatory in Mexico. The advances in the molecular field have allowed differentiating among the alterations caused by this disease with especial relevance in the organogénesis and homonogenesis. In this review, the main molecular alterations are analyzed, describing their relationship with thyroid cellular differentiation, hormonal synthesis, central origin hypothyroidism and peripheral tissues target. The study of the molecular abnormalities open new possibilities as to the precise knowledge of the physiopathological and molecular processes. A better and earlier diagnosis and management of this pathology may arise, which in turn will prevent the severe sequelae that congenital hypothyroidism causes.