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Abstract Glutamate dehydrogenase 1 (GLUD1) is an important enzyme in glutamine metabolism. Previously, we found GLUD1 was down-regulated in tumor tissues of hepatocellular carcinoma (HCC) patients by proteomics study. To explore its role in the progression of HCC, the expressional level of GLUD1 was firstly examined and presented as that both the protein and mRNA levels were down-regulated in tumor tissues compared to the normal liver tissues. GLUD1 overexpression significantly inhibited HCC cells proliferation, migration, invasion and tumor growth both in vitro and in vivo, while GLUD1 knocking-down promoted HCC progression. Metabolomics study of GLUD1 overexpressing and control HCC cells showed that 129 differentially expressed metabolites were identified, which mainly included amino acids, bases, and phospholipids. Moreover, metabolites in mitochondrial oxidative phosphorylation system (OXPHOS) were differentially expressed in GLUD1 overexpressing cells. Mechanistic studies showed that GLUD1 overexpression enhanced mitochondrial respiration activity and reactive oxygen species (ROS) production. Excessive ROS lead to mitochondrial apoptosis that was characterized by increased expression levels of p53, Cytochrome C, Bax, Caspase 3 and decreased expression level of Bcl-2. Furthermore, we found that the p38/JNK MAPK pathway was activated in GLUD1 overexpressing cells. N-acetylcysteine (NAC) treatment eliminated cellular ROS and blocked p38/JNK MAPK pathway activation, as well as cell apoptosis induced by GLUD1 overexpression. Taken together, our findings suggest that GLUD1 inhibits HCC progression through regulating cellular metabolism and oxidative stress state, and provide that ROS generation and p38/JNK MAPK pathway activation as promising methods for HCC treatment.

Abstract Background Diabetic retinopathy (DR) is a common and potentially devastating microvascular complication of diabetes mellitus (DM). The main features of DR are inflammation and oxidative damage. Gliquidone (GLI) is confirmed to be a hypoglycemic drug by oral administration. The current study is aimed to investigate the role and mechanism of GLI on the pathogenesis of DR. Methods High glucose (HG)-induced human retinal endothelial cells (HRECs) were used to explore the anti-inflammatory and anti-oxidant effects of GLI on DR in vitro. Streptozotocin (STZ)-induced DM rats were used to investigate the effects of GLI on retinal structures, inflammation, and oxidative stress. The levels of SIRT1/Notch1 pathway-related proteins were determined by western blotting. Results GLI treatment promoted the viability and inhibited the apoptosis of HG-induced HRECs. Meanwhile, the levels of interleukin (IL)-6, IL-1β, tumour necrosis factor alpha and reactive oxygen species were suppressed, while both catalase and superoxide dismutase were elevated after GLI treatment in HG-induced HRECs. Furthermore, we found that Silencing information regulator 2 related enzyme 1 (SIRT1) silencing reversed the inhibiting effects of GLI on the levels of protein Notch1 and effector genes Hes1 and Hey2. Similar anti-inflammatory and anti-oxidant effects of GLI in STZ-induced DM rats were observed. Additionally, GLI administration also repressed vascular hyperpermeability in vivo. Conclusion GLI may be an effective agent to improve DR through repression of inflammation and oxidative stress via SIRT1/Notch1 pathway.

The unique bicontinuous porous structure and superior electrical conductivity of nanoporous gold (NPG) make it a highly promising material for energy storage and conversion. Although the number of articles on the study of NPG-based materials in energy fields has increased significantly in recent years, the collation and review of these articles are still lacking. Herein, we address this gap by reviewing recent research activities on dealloyed NPG for energy storage and conversion applications. Firstly, the typical dealloying process for forming NPG is introduced. Subsequently, NPG-based composite catalysts used to catalyze water splitting and fuel cells electrode reactions are presented. Afterward, the applications of NPG for different types of electrodes of supercapacitors (SCs) and batteries are discussed. Finally, the studies on NPG for catalyzing CO2 reduction reaction (CO2RR) are reviewed. In a word, the recent research progress of NPG-based materials is reviewed and the future research directions are outlined, laying the cornerstone for the preparation of more advanced energy storage and conversion devices in the future.

Primary pleural angiosarcoma is an exceptionally rare malignancy of pleura originating from the vascular endothelial cells. Here, we present a 70-year-old African-American female who presented with 1-month history of dyspnea on exertion, loss of appetite, and loss of weight along with left-sided pleuritic chest pain. Evaluation revealed hemorrhagic pleural effusion in the left pleural cavity. Computed tomography of the chest performed after therapeutic thoracocentesis revealed left upper lobe lung mass along with multiple nodules in right lung. Mass was biopsied at video-assisted thoracoscopy. Histopathology was consistent with high-grade angiosarcoma. Endothelial origin of the tumor cells was confirmed with positive immunohistochemical staining with CD31 antibodies. Our patient was diagnosed with primary pleural angiosarcoma metastatic to the lung. She opted for palliative care and had a rapidly declining clinical course and expired within 5 weeks of the diagnosis. Here, we present a case report and review the relevant literature.