CT enterography-based radiomics combined with body composition to predict infliximab treatment failure in Crohn's disease.

PURPOSE: Accurately predicting the treatment response in patients with Crohn's disease (CD) receiving infliximab therapy is crucial for clinical decision-making. We aimed to construct a prediction model incorporating radiomics and body composition features derived from computed tomography (CT) enterography for identifying individuals at high risk for infliximab treatment failure. METHODS: This retrospective study included 137 patients with CD between 2015 and 2021, who were divided into a training cohort and a validation cohort with a ratio of 7:3. Patients underwent CT enterography examinations within 1 month before infliximab initiation. Radiomic features of the intestinal segments involved were extracted, and body composition features were measured at the level of the L3 lumbar vertebra. A model that combined radiomics with body composition was constructed. The primary outcome was the occurrence of infliximab treatment failure within 1 year. The model performance was evaluated using discrimination, calibration, and decision curves. RESULTS: Fifty-two patients (38.0%) showed infliximab treatment failure. Eight significant radiomic features were used to develop the radiomics model. The model incorporating radiomics model score, skeletal muscle index (SMI), and creeping fat showed good discrimination for predicting infliximab treatment failure, with an area under the curve (AUC) of 0.88 (95% CI 0.81, 0.95) in the training cohort and 0.83 (95% CI 0.66, 1.00) in the validation cohort. The favorable clinical application was observed using decision curve analysis. CONCLUSIONS: We constructed a comprehensive model incorporating radiomics and muscle volume, which could potentially be used to facilitate the individualized prediction of infliximab treatment response in patients with CD.

UV filter ethylhexyl salicylate affects cardiovascular development by disrupting lipid metabolism in zebrafish embryos.

Ethylhexyl salicylate (EHS) is an organic UV filter commonly used in sunscreens to protect people from the UV radiation. The widespread use of EHS will enter the aquatic environment along with human activities. EHS readily accumulates in adipose tissue as a lipophilic compound, but its toxic effects on lipid metabolism and cardiovascular system of aquatic organisms have not been studied. This study investigated the effects of EHS on lipid metabolism and cardiovascular development during zebrafish embryogenesis. The results showed that EHS caused defects such as pericardial edema, cardiovascular dysplasia, lipid deposition, ischemia, and apoptosis in zebrafish embryos. In addition, qPCR and whole-mount in situ hybridization (WISH) results indicated that EHS treatment significantly altered the expression of genes related to cardiovascular development, lipid metabolism, erythropoiesis, and apoptosis. The hypolipidemic drug rosiglitazone was able to alleviate the cardiovascular defects caused by EHS, indicating that EHS affected cardiovascular development by disrupting lipid metabolism. In addition, severe ischemia caused by cardiovascular abnormalities and apoptosis were observed in the EHS-treated embryos, which was likely to be the main cause of embryonic mortality. In conclusion, this study shows that EHS has toxic effects on lipid metabolism and cardiovascular formation. Our findings provide new evidence for assessing UV filter EHS toxicity and contribute to raising awareness of the safety risks of EHS.

L-selenomethionine affects liver development and glucolipid metabolism by inhibiting autophagy in zebrafish embryos.

Selenium plays a vital role in cancer prevention, antioxidation, and the growth of humans and other vertebrates. Excessive selenium can cause liver injury and metabolic disorders, which can lead to hepatic disease, but few studies have shown the effects of excessive selenium on liver development and its mechanism in zebrafish embryos. In this study, liver development and glucolipid metabolism were investigated in selenium-stressed zebrafish embryos. Under selenium treatment, transgenic fabp10a-eGFP zebrafish embryos showed reduced liver size, and wild-type zebrafish embryos exhibited steatosis and altered lipid metabolism-related indexes and glucose metabolism-related enzyme activities. In addition, selenium-stressed embryos exhibited damaged mitochondria and inhibited autophagy in the liver. An autophagy inducer (rapamycin) alleviated selenium-induced liver injury and restored the expression of some genes related to liver development and glucolipid metabolism. In summary, our research evaluated liver developmental toxicity and metabolic disorders under selenium stress, and confirmed that autophagy and oxidative stress might involve in the selenium-induced hepatic defects.

Characterization of a novel marine microbial uricase from Priestia flexa and evaluation of the effects of CMCS conjugation on its enzymatic properties.

A novel uricase producing marine bacterium Priestia flexa alkaAU was isolated and identified. The 16S rDNA and the uricase coding gene were sequenced, analyzed and submitted to GenBank. The uricase from Priestia flexa alkaAU (PFU) was purified, determined to be 58.87 kDa, and conjugated with carboxymethyl chitosan (CMCS) by ionic gelation. CMCS conjugation had no effect on the optimum pH of PFU but decreased the optimum temperature by 10 °C. CMCS conjugation increased the specific activity of PFU by 53% at the human body temperature (37 °C) and small intestine's pH (pH 6.8). Uricase thermostabilizing ability of CMCS was significant in the range of 37-80 °C but not at lower temperatures. For improvement of the pH stability of PFU, CMCS was more effective at pHs 3-5 than pHs 6-11. CMCS increased the half-life of PFU against artificial intestinal fluid by 1.5 folds, which demonstrated the potential capability of CMCS-PFU for oral administration.

Ferroptosis and Apoptosis Are Involved in the Formation of L-Selenomethionine-Induced Ocular Defects in Zebrafish Embryos.

Selenium is an essential trace element for humans and other vertebrates, playing an important role in antioxidant defense, neurobiology and reproduction. However, the toxicity of excessive selenium has not been thoroughly evaluated, especially for the visual system of vertebrates. In this study, fertilized zebrafish embryos were treated with 0.5 µM L-selenomethionine to investigate how excessive selenium alters zebrafish eye development. Selenium-stressed zebrafish embryos showed microphthalmia and altered expression of genes required for retinal neurogenesis. Moreover, ectopic proliferation, disrupted mitochondrial morphology, elevated ROS-induced oxidative stress, apoptosis and ferroptosis were observed in selenium-stressed embryos. Two antioxidants-reduced glutathione (GSH) and N-acetylcysteine (NAC)-and the ferroptosis inhibitor ferrostatin (Fer-1) were unable to rescue selenium-induced eye defects, but the ferroptosis and apoptosis activator cisplatin (CDDP) was able to improve microphthalmia and the expression of retina-specific genes in selenium-stressed embryos. In summary, our results reveal that ferroptosis and apoptosis might play a key role in selenium-induced defects of embryonic eye development. The findings not only provide new insights into selenium-induced cellular damage and death, but also important implications for studying the association between excessive selenium and ocular diseases in the future.