Ischemia-reperfusion injury (IRI) is a common complication in liver surgeries. It is a focus to discover effective treatments to reduce ischemia-reperfusion injury. Previous studies show that oxidative stress and inflammation response contribute to the liver damage during IRI. SS-31 is an innovated mitochondrial-targeted antioxidant peptide shown to scavenge reactive oxygen species and decrease oxidative stress, but the protective effects of SS-31 against hepatic IRI are not well understood. The aim of our study is to investigate whether SS-31 could protect the liver from damages induced by IRI and understand the protective mechanism. The results showed that SS-31 treatment can significantly attenuate liver injury during IRI, proved by HE staining, serum ALT/AST, and TUNEL staining which can assess the degree of liver damage. Meanwhile, we find that oxidative stress and inflammation were significantly suppressed after SS-31 administration. Furthermore, the mechanism revealed that SS-31 can directly decrease ROS production and regulate STAT1/STAT3 signaling in macrophages, thus inhibiting macrophage M1 polarization. The proinflammation cytokines are then significantly reduced, which suppress inflammation response in the liver. Taken together, our study discovered that SS-31 can regulate macrophage polarization through ROS scavenging and STAT1/STAT3 signaling to ameliorate liver injury; the protective effects against hepatic IRI suggest that SS-31 may be an appropriate treatment for liver IRI in the clinic.
Background
Heterozygous mutations in the AT‐hook DNA‐binding motif containing one (AHDC1, OMIM * 615790) gene cause an autosomal dominant multisystem developmental disorder known as Xia‐Gibbs syndrome (OMIM #615829). Xia‐Gibbs syndrome typically presented with global developmental delay, hypotonia, obstructive sleep apnea, seizures, delayed myelination, micrognathia, and other mild dysmorphic features.
Methods
Description of the clinical materials of two Chinese boys who were diagnosed with Xia‐Gibbs syndrome based on clinical presentations and next generation sequencing. Review of clinical features and AHDC1 mutations in previously reported Xia‐Gibbs syndrome patients together with our two new patients.
Results
The Xia‐Gibbs syndrome patients exhibited short stature, hypotonia, global developmental delay, speech delay, simian crease, and mild dysmorphic features. Next generation sequencing revealed de novo heterozygous variants in AHDC1 gene. In addition, laboratory test revealed partial growth hormone deficiency. Both patients underwent growth hormone replacement therapy for 24 and 9 months, respectively, and exhibited good response to the treatment.
Conclusion
This is the first report of Xia‐Gibbs syndrome patients to be treated with growth hormone. Review of previously reported Xia‐Gibbs syndrome patient indicated that short stature is a frequent feature of this condition, but its underlying cause needs to be further investigated.
The pathogenesis of non-alcoholic fatty liver disease is currently unclear, however, lipid accumulation leading to endoplasmic reticulum stress appears to be pivotal in the process. At present, FOXO1 is known to be involved in NAFLD progression. The relationship between necroptosis and non-alcoholic steatohepatitis has been of great research interest more recently. However, whether FOXO1 regulates ER stress and necroptosis in mice fed with a high fat diet is not clear. Therefore, in this study we analyzed the relationship between non-alcoholic steatohepatitis, ER stress, and necroptosis. Main Methods: Male C57BL/6J mice were fed with an HFD for 14 weeks to induce non-alcoholic steatohepatitis. ER stress and activation of necroptosis in AML12 cells were evaluated after inhibition of FOXO1 in AML12 cells. In addition, mice were fed with AS1842856 for 14 weeks. Liver function and lipid accumulation were measured, and further, ER stress and necroptosis were evaluated by Western Blot and Transmission Electron Microscopy.
ObjectiveThis article analyzes the data of four families with mutations of the GLA (galactosidase) gene with a special focus on the clinical presentation, diagnosis, and interdisciplinary clinical management of Fabry disease (FD) and enzyme replacement therapy (ERT) treatment, and has the aim to assess more accurate prevention and treatment strategy.MethodsThe MSSI (Mainz Severity Score Index) scale was used to evaluate the clinical data of five children diagnosed in our hospital, and the genotypes of all the patients with FD were collected. Two of the male children started ERT. We summarize the clinical effect and the evaluation of globotriaosylsphingosine (Lyso-GL-3) before and after treatment.ResultsFive children were confirmed as having FD using the family histories, clinical manifestations, α-galactosidase A (a-Gal A) activity, and genetic test results. Two children used agalsidase α every 2 weeks regularly, after ERT. Their clinical symptoms improved, their pain intensity was significantly relieved, and upon re-examination their Lyso-GL-3 decreased conspicuously and no serious adverse reactions occurred. We report for the first time four families with children with FD. The youngest child was only 1 year old. The four families included one girl which is rare in X-linked lysosomal storage diseases.ConclusionThe clinical phenotype of FD in childhood is nonspecific, and the misdiagnosis rate is high. Most children with FD have a delayed diagnosis, and their organs are often seriously damaged in adulthood. Pediatricians must improve their diagnosis and treatment awareness, screen high-risk groups, and emphasize multidisciplinary cooperation and holistic lifestyle management after diagnosis. The diagnosis of the proband is also conducive to the mining of other cases of FD families and has important guiding significance for prenatal diagnosis.
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