Radiation-induced brain structural and functional abnormalities in presymptomatic phase and outcome prediction: Radiation-Induced Brain Abnormalities

Radiation therapy, a major method of treatment for brain cancer, may cause severe brain injuries after many years. We used a rare and unique cohort of nasopharyngeal carcinoma patients with normal-appearing brains to study possible early irradiation injury in its presymptomatic phase before severe, irreversible necrosis happens. The aim is to detect any structural or functional imaging biomarker that is sensitive to early irradiation injury, and to understand the recovery and progression of irradiation injury that can shed light on outcome prediction for early clinical intervention. We found an acute increase in local brain activity that is followed by extensive reductions in such activity in the temporal lobe and significant loss of functional connectivity in a distributed, large-scale, high-level cognitive function-related brain network. Intriguingly, these radiosensitive functional alterations were found to be fully or partially recoverable. In contrast, progressive late disruptions to the integrity of the related far-end white matter structure began to be significant after one year. Importantly, early increased local brain functional activity was predictive of severe later temporal lobe necrosis. Based on these findings, we proposed a dynamic, multifactorial model for radiation injury and another preventive model for timely clinical intervention. Hum Brain Mapp 39:407-427, 2018. © 2017 Wiley Periodicals, Inc

Elevated FOXC2 Expression Promotes Invasion of HCC Cell Lines and is Associated with Poor Prognosis in Hepatocellular Carcinoma

Background/Aims: Increasing evidence has indicated that Forkhead box protein C2 (FOXC2) plays an important role in carcinogenesis. However, the expression and the role of FOXC2 in hepatocellular carcinoma (HCC) have not been extensively studied. Methods: FOXC2 expression was analyzed by quantitative real-time polymerase chain reaction, Western blot analysis and immunohistochemistry in HCC tissue and cells. The relationship between FOXC2 expression and patient clinical significance and survival were assessed by Pearson’s correlation and Kaplan-Meier analysis, respectively. Cell proliferation assays, colony formation assays, flow cytometric analysis and Transwell assays were employed to measure the effects of FOXC2 on HCC cells in vitro. Results: The expression of FOXC2 was increased in HCC tissue, and high FOXC2 expression was associated with worse patient survival. Knockdown of FOXC2 inhibited HCC cell growth, migration, and invasion in vitro, as well as tumor growth. Furthermore, we found that activation of AKT-mediated MMP-2 and MMP-9 was involved in FOXC2 promoting an aggressive phenotype. Conclusions: Taken together, these findings demonstrate that FOXC2 is upregulated in HCC tissue and is associated with tumor size, vascular invasion and advanced TNM stage. Further investigation suggested that FOXC2 may play a vital role in promoting proliferation and invasion in HCC and serves as a novel therapeutic target in HCC

Mesoporous palladium–boron alloy nanospheres

Noble-metal-metalloid binary palladium-boron (Pd-B) nanoalloys are interesting because the smaller boron atoms enlarge the Pd-Pd interlattice spacings and modify the binding energy barriers of catalytic intermediates. Binary Pd-B nanoalloys with nanostructured morphologies are an emerging class of (electro)catalysts that leverage these properties to enhance their performance in various chemical reactions. We describe here the first synthesis of Pd-B alloy mesoporous nanospheres (MNSs) and evaluate their electrocatalytic performance in the ethanol oxidation reaction (EOR). This method uses dimethylamine borane and boric acid as both the reducing agents and boron sources and amphiphilic dioctadecyldimethylammonium chloride (DODAC) as the surfactant template. The cylindrical mesophase of DODAC inhibits the mobility of the Pd metal precursor and confines the crystalline growth to form binary Pd-B MNSs with three-dimensional dendritic center-radial mesochannels. We demonstrate that the synthetic protocol can be adopted to rationally tune the diameters of the Pd-B MNSs from 30 nm to 120 nm without destroying the mesoporous structure and elemental composition. The Pd-B MNSs combine high surface area with favorable electrocatalytic surface properties to generate exceptional electrocatalytic performance for the EOR under alkaline conditions, illustrating the potential of this method as a platform to yield a new type of highly efficient electrocatalyst

Mitofusin 2 protects hepatocyte mitochondrial function from damage induced by GCDCA.

Mitochondrial impairment is hypothesized to contribute to the pathogenesis of chronic cholestatic liver diseases. Mitofusin 2 (Mfn2) regulates mitochondrial morphology and signaling and is involved in the development of numerous mitochondrial-related diseases; however, a functional role for Mfn2 in chronic liver cholestasis which is characterized by increased levels of toxic bile acids remain unknown. Therefore, the aims of this study were to evaluate the expression levels of Mfn2 in liver samples from patients with extrahepatic cholestasis and to investigate the role Mfn2 during bile acid induced injury in vitro. Endogenous Mfn2 expression decreased in patients with extrahepatic cholestasis. Glycochenodeoxycholic acid (GCDCA) is the main toxic component of bile acid in patients with extrahepatic cholestasis. In human normal hepatocyte cells (L02), Mfn2 plays an important role in GCDCA-induced mitochondrial damage and changes in mitochondrial morphology. In line with the mitochondrial dysfunction, the expression of Mfn2 decreased significantly under GCDCA treatment conditions. Moreover, the overexpression of Mfn2 effectively attenuated mitochondrial fragmentation and reversed the mitochondrial damage observed in GCDCA-treated L02 cells. Notably, a truncated Mfn2 mutant that lacked the normal C-terminal domain lost the capacity to induce mitochondrial fusion. Increasing the expression of truncated Mfn2 also had a protective effect against the hepatotoxicity of GCDCA. Taken together, these findings indicate that the loss of Mfn2 may play a crucial role the pathogenesis of the liver damage that is observed in patients with extrahepatic cholestasis. The findings also indicate that Mfn2 may directly regulate mitochondrial metabolism independently of its primary fusion function. Therapeutic approaches that target Mfn2 may have protective effects against hepatotoxic of bile acids during cholestasis

Omentin-1 Ameliorated Free Fatty Acid-Induced Impairment in Proliferation, Migration, and Inflammatory States of HUVECs

Objectives. Endothelial cell injury is a critical pathological change during the development of atherosclerosis. Here, we explored the effect of omentin-1 on free fatty acid- (FFA-) induced endothelial cell injury. Methods. An FFA-induced endothelial cell injury model was established to investigate the role of omentin-1 in this process. Cell proliferation was analyzed with the Cell Counting Kit assay and flow cytometry. Scratch and transwell assays were used to evaluate cell migration. Factors secreted by endothelial cells after injury were detected by western blotting, reverse-transcription quantitative polymerase chain reaction, and cellular fluorescence assay. Results. Omentin-1 rescued the FFA-induced impaired proliferation and migration capabilities of human umbilical vein endothelial cells (HUVECs). It decreased the number of THP-1 cells attached to HUVECs in response to injury and inhibited the FFA-induced proinflammatory state of HUVECs. Conclusion. Omentin-1 could partly ameliorate FFA-induced endothelial cell injury

Plasmonic mesoporous AuAg nanospheres with controllable nanostructures

Three kinds of plasmonic mesoporous AuAg (mesoAuAg) nanospheres, including well-alloyed mesoAuAg, hollow mesoAuAg, and core-shell Ag-mesoAu nanospheres, were successfully synthesized by carefully controlling the reduction kinetics of metal precursors in the presence of a functional surfactant, C22H45N+(CH3)2-C3H6-SH(Cl-). The resulting mesoAuAg exhibited a remarkable structure-dependent electrocatalytic performance toward methanol oxidation reaction