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Background: Thyroid dysfunction plays an important role in the pathology of diabetes-associated cognitive dysfunction (DACD). However, thyroid hormone (TH) signaling and action changes in DACD brains remain unknown. This study evaluated the alternations in TH signaling and action in the brains of DACD mice and explored the beneficial effects of levothyroxine (L-T4) treatment. Methods: KK-Ay mice, serving as a spontaneous type 2 diabetes mellitus model, underwent intragastric administration of 10 ng/g and 20 ng/g of L-T4 solution or normal saline for 8 weeks. Age-matched C57BL/6J mice were used as normal controls. Cognitive and memory functions were examined through the open field and Morris water maze tests. Hippocampal TH signaling and pathogenic status were evaluated. The potential signaling pathways involved in the neuroprotective action of L-T4 were investigated through RNA sequencing and further verified through quantitative real-time PCR (qPCR), Western blotting (WB), immunofluorescence (IF), and fluorescent multiplex immunohistochemistry (mIHC) in vivo and vitro. Results: The expressions of hippocampal TH transporters (Mct8 and Oatp1c1), Dio2, and TH receptor were upregulated, whereas Dio3 as well as the TH-positive regulated genes MBP, Enpp2, and Klf9 were downregulated in DACD mice. Exogenous L-T4 partially alleviated cognitive and memory dysfunction and restored hippocampal neuronal activity by optimizing TH signaling. RNA sequencing provided insights into the role of type I interferon (IFN-I) signaling and necroptosis on the amelioration of hippocampal damage after L-T4 treatment. WB and qPCR further confirmed that the levels of key proteins for IFN-I signaling and necroptosis (p-STAT1, p-STAT2, IRF9, ZBP1, p-RIP3, and p-MLKL) were increased, but largely returned after L-T4 administration in vivo and T3 treatment in vitro. IF and mIHC revealed that IRF9 and p-MLKL colocalized in neurons, but not in astrocytes or microglia, of the hippocampus in DACD mice. The diabetes mellitus group had an increased number of IRF9+ p-MLKL+ NeuN+ cells, which decreased after L-T4 treatment. The elevated IFN-I signaling-mediated necroptosis in HT22 cells was also decreased by T3. Conclusion: We demonstrated abnormal hippocampal TH signaling and action in DACD. Promoting TH action with exogenous L-T4 ameliorated hippocampal impairment through inhibiting IFN-I signaling-induced necroptosis. [ABSTRACT FROM AUTHOR]

Cerium oxide nanoparticles (NPs) due to their advanced catalytic performance have been widely used to treat oxidative damage. However, Ce2O3 NPs have not been further investigated in the treatment of acute oxidative injury in vivo. It is meaningful to improve the efficiency for treatment of acute oxidative injury with NPs in vivo. In this report, we designed Er3+-doped Ce2O3 (Er/Ce2O3) NPs with a size of 7.9 nm, which were used to treat acute liver injury. Er/Ce2O3 NPs realized high-efficiency catalysis of hydrogen peroxide (H2O2) at room temperature. An acute liver damage model was established through intraperitoneal injection of lipopolysaccharide (LPS) in C57 mice. By analyzing histopathological and biochemical indexes, Er/Ce2O3 NPs showed a significant improvement in LPS-induced acute liver injury. Acute liver oxidative damage can be treated within 24 hours, which proved the high catalytic efficiency of Er/Ce2O3 NPs in vivo. The activities of SOD, GPx and CTA increased and production of ROS decreased with Er/Ce2O3 NP treatment in comparison with LPS-induced injury, indicating that the mechanism of Er/Ce2O3 NPs in the treatment of acute oxidative damage of liver was mainly via catalysis of ROS products. Moreover, the protein expression levels of TNF-α, CD45 and IL-1β in liver decreased in the Er/Ce2O3 NPs-treated group, which indicated that Er/Ce2O3 NPs have the function of anti-inflammation property. Therefore, Er/Ce2O3 NPs can be applied to treat and prevent diseases caused by acute oxidative damage. [ABSTRACT FROM AUTHOR]

Objective To assess the validity of urinary iodine excretion ( UIE) estimated by urinary iodine/creatinine ratio ( UI/Cr) from spot urines in Chinese school-age children. Design A cross-sectional survey was performed in which twice-repeated collections of 24-h urine, and spot urine samples were obtained within 1 month. Measurements Urinary iodine concentration ( UIC), urinary creatinine concentration ( UCr), urine volume (Uvol) of spot and 24-h urine samples were measured. Measured 24-h UIE was calculated from 24-h UIC multiplied by 24-h Uvol, while the estimated 24-h UIE was calculated from spot UI/Cr multiplied by 24-h urinary creatinine excretion (24-h UCrE). Results No significant difference was observed in 24-h Uvol between two repeated collections ( P = 0·70), while spot UIC, 24-h UIC, spot UI/Cr and measured 24-h UIE were significantly different ( P < 0·05). The estimated 24-h UIE was 247 (136-431) μg/day in the first collection, lower than the measured 24-h UIE of 329 (183-536) μg/day ( P < 0·001), while no significant difference was observed ( P = 0·30) in the second sampling as the estimated 24-h UIE was 355 (168-624) μg/day and the measured 24-h UIE 350 (181-615) μg/day. The spot UIC ( r = 0·57, P < 0·001), spot UI/Cr ( r = 0·63, P < 0·001) and the estimated 24-h UIE ( r = 0·83, P < 0·001) were strongly correlated with the measured 24-h UIE in the first collection. Likewise, in the second sampling, spot UIC ( r = 0·60, P < 0·001), spot UI/Cr ( r = 0·72, P < 0·001) and the estimated 24-h UIE ( r = 0·89, P < 0·001) were also correlated with measured 24-h UIE. The Bland-Altman results indicated 95% of subjects were expected to locate within the limits of agreement ( LOA), but showed an underestimation of the urinary iodine excretion by the estimated 24-h UIE. In addition, moderate-to-good agreement was found for the estimated and measured 24-h UIE, with kappa values of 0·55 and 0·66. Conclusions Estimated 24-h UIE by UI/Cr ratio from spot urine could represent a valid and reliable alternative for measured 24-h UIE in estimating iodine excretion in children. [ABSTRACT FROM AUTHOR]

Background: Variation in different urinary measurements for evaluation of iodine status is of concern to clinicians and researchers.Objective: This study evaluated variations between urine iodine concentration (UIC), spot and 24-h urine sample creatinine concentrations, and 24-h urine iodine excretion (24-h UIE) in repeated samples from school-age children.Methods: Urine samples (24 h and morning spot) were collected on 2 occasions from 981 children in Ningjin and Lingxian counties, China. Samples from Ningjin were collected in October and November 2013, and samples from Lingxian were collected in April and May 2014. Morning spot urine iodine concentration (MUIC), morning spot urine creatinine, 24-h UIC, and 24-h urine creatinine were measured in all samples. The 24-h UIE was calculated by multiplying the 24-h UIC by the 24-h urine volume.Results: In Ningjin County, the 24-h UIC and 24-h UIE did not differ between repeated collections [192 and 172 μg/L, respectively, for 24-h UIC (P = 0.08); 123 and 120 μg/L, respectively, for 24-h UIE (P = 0.56)], whereas the MUIC was lower in November 2013 than in October 2013 (170 and 190 μg/L, respectively; P = 0.034). In Lingxian County, no significant differences were observed in 24-h UIC between the repeated collections (230 and 218 μg/L, respectively; P = 0.79), whereas the 24-h UIE and MUIC were higher in the samples collected in May 2014 than in April 2014 [161 and 155 μg/L, respectively, for 24-h UIE (P = 0.002); 244 and 203 μg/L, respectively, for MUIC (P < 0.001)]. When data from both counties were combined, no difference was observed between repeated 24-h UIC (214 compared with 196 μg/L; P = 0.17) and 24-h UIE (143 compared with 143 μg/d; P = 0.06), but MUICs were lower in the first collection than in the second collection (199 and 207 μg/L, respectively; P = 0.002). The κ values were >0.4 for 24-h UIC and mean UIE, whereas relatively low κ values were observed for MUIC and mean UIE.Conclusion: The 24-h UIC was more accurate and reproducible than the MUIC in evaluating iodine status in a large-scale population study of school-age children. [ABSTRACT FROM AUTHOR]

Objective To investigate the activation of β-sheet breaker peptide H102 on ERK signal transduction pathway in brain of PAP double transgenic mice. Methods PAP double transgenic mice were randomly divided into model group and H102 treatment group (n=10 for each group). A group of C57BL/6J mice with the same genetic background was served as controls. H102 (5.8 mg/kg) 5 µL was infused by intranasal administration to mice in H102 treatment group, and equal volume of blank solution of H102 (chitosan, BSA) was given to mice in control group and model group. The ability of spatial reference memory was tested by Morris water maze after 30 days of treatment. Then immunohistochemistry tests and Western blot technique were used to detect the content of RAS, P-MEK and P-ERK proteins in mouse brain. Results (1) The ability of learning and memory was significantly lower in model group than that of control group. The ability of learning and memory was significantly improved in treatment group than that in model group (P < 0.05). (2) The contents of RAS, P-MEK and P-ERK in mouse brain were significantly lower in model group than those of control group, and these protein expressions were significantly increased in treatment group than those in model group (P < 0.01). Conclusion β-sheet breaker peptide H102 can activate ERK signal transduction pathway in brain of PAP double transgenic mice, increase PAS, P-MEK and P-ERK levels in nerve cells, and improve the ability of learning and memory in PAP mice. [ABSTRACT FROM AUTHOR]

Cerium oxide nanoparticles (NPs) due to their advanced catalytic performance have been widely used to treat oxidative damage. However, Ce2O3 NPs have not been further investigated in the treatment of acute oxidative injury in vivo. It is meaningful to improve the efficiency for treatment of acute oxidative injury with NPs in vivo. In this report, we designed Er3+-doped Ce2O3 (Er/Ce2O3) NPs with a size of 7.9 nm, which were used to treat acute liver injury. Er/Ce2O3 NPs realized high-efficiency catalysis of hydrogen peroxide (H2O2) at room temperature. An acute liver damage model was established through intraperitoneal injection of lipopolysaccharide (LPS) in C57 mice. By analyzing histopathological and biochemical indexes, Er/Ce2O3 NPs showed a significant improvement in LPS-induced acute liver injury. Acute liver oxidative damage can be treated within 24 hours, which proved the high catalytic efficiency of Er/Ce2O3 NPs in vivo. The activities of SOD, GPx and CTA increased and production of ROS decreased with Er/Ce2O3 NP treatment in comparison with LPS-induced injury, indicating that the mechanism of Er/Ce2O3 NPs in the treatment of acute oxidative damage of liver was mainly via catalysis of ROS products. Moreover, the protein expression levels of TNF-α, CD45 and IL-1β in liver decreased in the Er/Ce2O3 NPs-treated group, which indicated that Er/Ce2O3 NPs have the function of anti-inflammation property. Therefore, Er/Ce2O3 NPs can be applied to treat and prevent diseases caused by acute oxidative damage.