Due to their unique physicochemical properties, graphene-family nanomaterials (GFNs) are widely used in many fields, especially in biomedical applications. Currently, many studies have investigated the biocompatibility and toxicity of GFNs in vivo and in intro. Generally, GFNs may exert different degrees of toxicity in animals or cell models by following with different administration routes and penetrating through physiological barriers, subsequently being distributed in tissues or located in cells, eventually being excreted out of the bodies. This review collects studies on the toxic effects of GFNs in several organs and cell models. We also point out that various factors determine the toxicity of GFNs including the lateral size, surface structure, functionalization, charge, impurities, aggregations, and corona effect ect. In addition, several typical mechanisms underlying GFN toxicity have been revealed, for instance, physical destruction, oxidative stress, DNA damage, inflammatory response, apoptosis, autophagy, and necrosis. In these mechanisms, (toll-like receptors-) TLR-, transforming growth factor β- (TGF-β-) and tumor necrosis factor-alpha (TNF-α) dependent-pathways are involved in the signalling pathway network, and oxidative stress plays a crucial role in these pathways. In this review, we summarize the available information on regulating factors and the mechanisms of GFNs toxicity, and propose some challenges and suggestions for further investigations of GFNs, with the aim of completing the toxicology mechanisms, and providing suggestions to improve the biological safety of GFNs and facilitate their wide application.

No abstract

Oxidative stress plays a crucial role in the pathogenesis of acute pancreatitis (AP). Isoliquiritigenin (ISL) is a flavonoid monomer with confirmed antioxidant activity. However, the specific effects of ISL on AP have not been determined. In this study, we aimed to investigate the protective effect of ISL on AP using two mouse models. In the caerulein-induced mild acute pancreatitis (MAP) model, dynamic changes in oxidative stress injury of the pancreatic tissue were observed after AP onset. We found that ISL administration reduced serum amylase and lipase levels and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. Meanwhile, ISL decreased the oxidative stress injury and increased the protein expression of the Nrf2/HO-1 pathway. In addition, after administering a Nrf2 inhibitor (ML385) or HO-1 inhibitor (zinc protoporphyrin) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of ISL on AP in mice. Furthermore, we found that ISL mitigated the severity of pancreatic tissue injury and pancreatitis-associated lung injury in a severe acute pancreatitis model induced by L-arginine. Taken together, our data for the first time confirmed the protective effects of ISL on AP in mice via inhibition of oxidative stress and modulation of the Nrf2/HO-1 pathway.

Prostate stem cell antigen (PSCA), a member of the LY-6/Thy-1 family of glycosylphosphatidylinositol-anchored cell surface proteins, is considered to be involved in the cell-proliferation inhibition and/or cell-death induction activity. Two single nucleotide polymorphisms (SNPs) (rs2976392 and rs2294008) in the PSCA gene were recently identified as the susceptibility loci of gastric cancer, especially in diffuse type. Therefore, this study was to investigate whether these 2 SNPs were associated with the risk of gastric cancer in Chinese population. We genotyped rs2976392 and rs2294008 in PSCA in a case-control study including 1,053 incident gastric cancer patients and 1,100 cancer-free controls in a high-risk Chinese population. We found that variant genotypes of rs2976392 (GA/AA) were associated with a significantly 37% increased risk of gastric cancer (adjusted OR 51.37, 95% CI 5 1.15-1.62), compared with variant homozygote GG, and the associations were all consistently significant in both intestinal and diffuse subtypes, and among different subgroups stratified by age, sex, drinking or smoking status. Interestingly, a significant multiplicative interaction between rs2976392 (GA/AA) and alcohol drinking was detected on the development of intestinal-type gastric cancer (p 5 0.009). However, rs2294008 variant genotypes (CT/TT) were associated with a nonsignificant increased risk of gastric cancer (adjusted OR 5 1.14, 95% CI 5 0.96-1.36). A small meta-analysis including 5 case-control studies showed undoubtedly associations between PSCA rs2294008 and rs2976392 and gastric cancer risk (OR 5 1.83, 95% CI: 1.29-2.60 and OR 5 1.84, 95% CI: 1.33-2.56, respectively). These findings provide further evidence supporting that the genetic variants of PSCA gene may contribute to the gastric carcinogenesis.Approximately 40% gastric cancer cases occur in China, 1 which remains a huge burden for Chinese and is one of the key public health issues in cancer prevention and control for Chinese government. Gastric cancer, predominantly adenocarcinoma, could be further classified as intestinal and diffuse subtypes.2 Intestinal-type tumors are characterized by a corpus-dominated gastritis with gastric atrophy and intestinal metaplasia, whereas diffuse-type tumors are characterized by gastritis throughout the stomach.3 Intestinal-type tumors are found predominantly in geographic areas with a high incidence of gastric cancer, whereas diffuse-type tumors are found more uniformly throughout the world.The exact mechanism of gastric cancer development remains unclear. Although some exogenous factors, such as diet, tobacco smoke and Helicobacter pylori, have been proposed to play important role in gastric carcinogenesis, the genetic susceptibility factors may also contributed to gastric cancer development, especially to diffuse-type gastric cancer. 4,5 The prostate stem cell antigen (PSCA) gene encodes a 123-amino acid glycoprotein, which is a cell surface antigen. PSCA is highly expressed by a large proportion of human prostate tumors, incl...

Regulatory T cell (Treg)-mediated immunosuppression represents one of the crucial tumor immune evasion mechanisms and is a main obstacle for successful tumor immunotherapy. Hypoxia, a common feature of solid tumors, has been associated with potentiated immunosuppression, decreased therapeutic response, malignant progression and local invasion. Unfortunately, the link between hypoxia and Treg-mediated immune tolerance in gastric cancer remains poorly understood. In our study, Tregs and hypoxia inducible factor-1α were found to be positively correlated with each other and were increased with the tumor progression. A subsequent in vitro study indicated that supernatants derived from gastric cancer cells under hypoxic condition, could induce the expression of Foxp3 via TGF-β1. These findings confirmed the crucial role of Tregs as a therapeutic target in gastric cancer therapy and provided helpful thoughts for the design of immunotherapy for gastric cancer in the future.