Radiotherapy (RT) is one of the most common treatments for cancer. However, intracellular glutathione (GSH) plays a key role in protecting cancer from radiation damage. Herein, we have developed a platelet membrane biomimetic nanomedicine (PMD) that induces double GSH consumption to enhance tumor radioimmunotherapy. This biomimetic nanomedicine consists of an external platelet membrane and internal organic mesoporous silica nanoparticles (MON) loaded with 2-deoxy-D-glucose (2-DG). Thanks to the tumor-targeting ability of the platelet membranes, PMD can target and aggregate to the tumor site, which is internalized by tumor cells. Within tumor cells overexpressing GSH, MON reacts with GSH to degrade and release 2-DG. This step initially depletes the intracellular GSH content. The subsequent release of 2-DG inhibits glycolysis and adenosine triphosphate (ATP) production, ultimately leading to secondary GSH consumption. This nanodrug combines dual GSH depletion, starvation therapy, and RT to promote immunogenic cell death and stimulate the systemic immune response. In the bilateral tumor model in vivo, distal tumor growth was also well suppressed. The proportion of mature dendritic cells (DC) and CD8⁺ T cells in the mice was increased. This indicates that PMD can promote anti-tumor radioimmunotherapy and has good prospects for clinical application.

Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure. The study aimed to investigate the protective effect of carnosic acid (CA) on APAP-induced acute hepatotoxicity and its underlying mechanism in mice. To induce hepatotoxicity, APAP solution (400 mg/kg) was administered into mice by intraperitoneal injection. Histological analysis revealed that CA treatment significantly ameliorated APAP-induced hepatic necrosis. The levels of both alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were reduced by CA treatment. Moreover, CA treatment significantly inhibited APAP-induced hepatocytes necrosis and lactate dehydrogenase (LDH) releasing. Western blot analysis showed that CA abrogated APAP-induced cleaved caspase-3, Bax and phosphorylated JNK protein expression. Further results showed that CA treatment markedly inhibited APAP-induced pro-inflammatory cytokines TNF-alpha, IL-1beta, IL-6 and MCP-1 mRNA expression and the levels of phosphorylated IkappaBalpha and p65 protein in the liver. In addition, CA treatment reduced APAP- induced hepatic malondialdehyde (MDA) contents and reactive oxygen species (ROS) accumulation. Conversely, hepatic glutathione (GSH) level was increased by administration of CA in APAP-treated mice. Mechanistically, CA facilitated Nrf2 translocation into nuclear through blocking the interaction between Nrf2 and Keap1, which, in turn, upregulated anti-oxidant genes mRNA expression. Taken together, our results indicate that CA facilitates Nrf2 nuclear translocation, causing induction of Nrf2-dependent genes, which contributes to protection from acetaminophen hepatotoxicity.
Acetaminophen ; Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Blotting, Western ; Caspase 3 ; Cytokines ; Glutathione ; Hepatocytes ; Injections, Intraperitoneal ; Interleukin-6 ; L-Lactate Dehydrogenase ; Liver ; Liver Failure, Acute ; Malondialdehyde ; Mice* ; Necrosis ; Reactive Oxygen Species ; RNA, Messenger ; Tumor Necrosis Factor-alpha

Objective To probe the changes of plasma albumin concentration and its correlation with that of blood inflammatory factors at the postoperative early stage in patients undergoing intraabdominal surgery. Methods From August 2008 to March 2009, 45 patients undergoing abdominal surgery were divided into three groups according to different types of operation with 15 cases in each group, cholecystectomy group( A), chole cystectomy plus common bile duct exploration group(B) and radical resection of alimentary duct maliguance group (C). Before the surgery and 12,24,48,72 h after operation, plasma albumin contentserum IL-6 and TNF-α concentration were measured. Results Postoperatively the content of plasma albumin did not change significantly in group A ( P ＞ 0.05 ), while that decreased after operation in group B and group C(P ＜0.01 ). The postoperative concentration of serum IL-6 and TNF-α increased in group A at 12, 24 h and 48 h after operation(P ＜0.01 ). In group B and group C IL-6 and TNF-α increased at all tested time point after operation ( P ＜ 0.01 ). The postoperative alterations of IL-6 and TNF-α were statistically different between the three groups at all time points(P ＜0.01 ). The content of plasma albumin was in a negative correlation with the concentration of IL-6 and TNF-α; ( r = - 0.376, P = 0.000; r =-0.772,P = 0.000). Conclusions The content of plasma albumin decreased at the early stage after major and moderate abdominal surgery. The content of plasma albumin was in a negative correlation with the concentration of inflammatory factors at the early stage after abdominal surgery.

Objective: To investigate the effects of trentment with hydroxythy starch(130/0.4) on the serum albumin and immunologic function in postoperative patients with obstructive jaundice.Methods: 24 patients with obstructive jaundice were randomly divided into the control group(n=12) and hydroxythy starch(130/0.4) (HS) group(n=12). The serum ALB was detected 1d, 3d, 5d, 7d after the operation,and the immunologic index were detected 1d and 7d after the operation.Results: The ALB content of control group and HS group were not significantly different in the postoperative 1d and 7 d(P>0.05) and had significant differences in the postoperative 3 d, 5 d (P<0.05).All immunologic index had no significant differences in the postoperative 1d, 7d (P>0.05).Conclusion: The ALB content of patients with obstructive jaundice may decrease postoperatively. Treatment with hydroxylthy starch(130/0.4) can alleviate the drop of the ALB content. But it has no effects on immunologic function.