Search

The exponentially increased use of gold nanoclusters in diagnosis and treatment has raised serious concern about their potential threat to living organisms. However, the mechanisms of toxicity of gold nanoclusters in vitro and in vivo remain poorly understood. In this work, comparative toxicity studies, including biodistribution and excretion, were carried out with mildly and chemically synthesized ultra-small L-histidine-protected and bovine serum albumin (BSA)-protected gold nanoclusters in an all-aqueous process. These nanoclusters did not induce a remarkable impact on cell viability, even at relatively high concentrations (100 μg/mL). The haemolytic assay demonstrated that the gold nanoclusters could not destroy blood cell at 600 μg/mL. After intravenous injection with mice, the biocompatibility, biodistribution, and excretion were determined. Quantitative analysis results showed that accumulation varied in the liver, spleen, kidney, and lung, though primarily in the liver and spleen. They were excreted in urine and faeces, but mainly excreted through urine. In our study, no obvious abnormalities were found in body weight, behavioral changes, blood and serum biochemical indicators, and histopathology. These findings suggested that both gold nanoclusters showed similar effects in vivo and were safe and biocompatible, laying the foundation for safe biomedical application in the future.

It is an urgent need to develop multifunctional agents with integrated accurate diagnostics and treatment for conquering intrinsic limitations of traditional cancer therapies. Herein, a small-size nanocomposite consisting of chlorine e6-integrated gold nanoclusters, hyaluronic acid, doxorubicin and folic acid was synthesized by a simple and mild method. The chlorine e6-integrated gold nanoclusters (Au:Ce6 NCs) were synthesized in an one-step for biological fluorescence imaging and photodynamic therapy. The hyaluronic acid-modified Au:Ce6 (Au:Ce6@HA) can not only act as drug carrier to delivery doxorubicin but increase the cellular selectively target. The folic acid-conjugated Au:Ce6@HA:DOX (Au:Ce6@HA:DOX@FA) was fabricated as a double targeted and pH-responsive drug delivery system for controlling the release of doxorubicin for tumor chemotherapy. The prepared Au:Ce6@HA:DOX@FA nanocomposite possessed small size and high drug encapsulation and loading efficiency. The nanocomposite exhibited good biocompatibility, colloidal stability and potostability, and high cumulative release rate in the acidic microenvironments. The fluorescence microscopy of in vitro confirmed the enhanced cellular uptake of Au:Ce6@HA:DOX@FA for fluorescence imaging. Importantly, the nanocomposite exhibited remarkable mortality of cancer cells under laser irradiation by synergistic chemotherapy and PDT. Together, this study demonstrates the designed small-sized nanocomposite could be used as a promising theranostic agent with dual-responsive tumor targeting capability.

Background: More than half of lymphoma patients are complicated with anemia. Anemia often indicates a poor prognosis, but the mechanism is still unclear. Erythroid progenitor cells (EPCs) are precursors of erythrocytes and play an important role in maintaining the homeostasis of erythrocytes. Here we investigated the role and mechanism of EPCs in promoting lymphoma progression.Materials and methods: Ki-67, CD31, P-AMPK and CPT1A expression was detected by immunohistochemical staining. CD45+ EPCs were detected and sorted by flow cytometry. Animal experiments were used to detect the effect of CD45+ EPCs on lymphoma.Results: Our study found that the proportion of CD45+ EPCs in diffuse large B-cell lymphoma (DLBCL) patients with anemia was significantly higher, which is positively correlated with the expressions of P-AMPK and CPT1A in lymphoma tissues. Interestingly, we found that in hypoxic conditions, CD45+ EPCs regulated lipid metabolism and enhanced energy metabolism of lymphoma cells through AMPK-ACC-CPT1A pathway, further promoted cell proliferation and inhibited apoptosis of lymphoma cells. Animal experiments showed that CD45+ EPCs transplantation significantly increased the resistance of antiangiogenic drugs. Reactive oxygen species (ROS) played a key role in these processes. Conclusion: CD45+ EPCs contributed to antiangiogenic drug resistance through ROS in lymphoma.

Background: More than half of lymphoma patients are complicated with anemia. Anemia often indicates a poor prognosis, but the mechanism is still unclear. Erythroid progenitor cells (EPCs) are precursors of erythrocytes and play an important role in maintaining the homeostasis of erythrocytes. Here we investigated the role and mechanism of EPCs in promoting lymphoma progression. Methods: Ki-67, CD31, P-AMPK and CPT1A expression was detected by immunohistochemical staining. CD45+ EPCs were detected by flow cytometry. Animal experiments were used to detect the effect of CD45+ EPCs on lymphoma. Results: Our study found that the proportion of CD45+ EPCs in anemic patients with diffuse large B-cell lymphoma (DLBCL) was significantly higher, which is positively correlated with the expressions of P-AMPK and CPT1A in lymphoma tissues. Interestingly, we found that in hypoxic conditions, CD45+ EPCs regulated lipid metabolism and enhanced energy metabolism of lymphoma cells through AMPK-ACC-CPT1A pathway, further promoted cell proliferation and inhibited apoptosis of lymphoma cells. Animal experiments showed that CD45+ EPCs combined transplantation significantly increased the resistance of antiangiogenic drugs. ROS played a key role in this process. Conclusion: CD45+ EPCs contributed to antiangiogenic drug resistance via regulating lipid metabolism in lymphoma.

Tumor-associated macrophages (TAMs) are closely related to the occurrence and development of lymphoma, but their mechanism is still unclear. Here we collected peripheral blood and lymphoma tissue from patients with diffuse large B lymphoma. Results showed that the proportion of TAMs in high-risk group was significantly higher than that in low-risk group. Moreover, the expressions of pleiotrophin (PTN), PTPRZ1 (PTN receptor) and β-catenin in lymphoma tissues of high-risk group were also significantly higher than those in low-risk group. Correlation analysis showed that the proportion of TAMs in lymphocyte was positively correlated with the expression of PTN and PTPRZ1 in lymphoma tissue. In vitro experimental results showed that TAM promoted the invasion and proliferation of lymphoma cells by secreting PTN. We also found that TAMs increased the proportion of cancer stem cells in lymphoma. Animal experiments showed that TAMs promoted lymphoma growth. Both Ki-67 proliferation index and CD44+cancer stem cells increased significantly in TAM group. Blocking PTN or β-catenin partly inhibited these effects of TAMs. In conclusion, TAMs increased the proportion of cancer stem cells through PTN/β-catenin pathway in lymphoma.

In this paper, the system with impulsive state feedback control corresponding to the sulphitation reaction in process of manufacture of sugar is considered. By means of square approximation and a series of switched systems, the periodic solution is approximated by a series of continuous hybrid limit cycles. Similar to the analysis of limit cycles of continuous systems, the existence and stability criteria of the order-1 periodic solution are obtained. Further, numerical analysis and discussion are given.

Due to extensive metastasis, poor blood supply, and drug-resistant, there is still no effective clinical means to treat peritoneal dissemination of gastric cancer. Here, an aptamer-siRNA chimera (Chim)/polyethyleneimine (PEI)/5-fluorouracil (5-FU)/carbon nanotube (CNT)/collagen membrane is constructed, which could be divided into 15 layers with a thickness of 70-100 µm. Sustained release experiments show that the collagen membranes can control 5-FU release for more than 2 weeks. Aptamer-siRNA chimera can specifically bind to gastric cancer cells, enabling targeted delivery of 5-FU and silencing drug-resistant gene. In vitro experiments demonstrated that Chim/PEI/5-FU/CNT nanoparticles promoted the apoptosis of 5-FU-resistant gastric cancer cells, inhibited their invasion and proliferation. Animal experiments show that Chim/PEI/5-FU/CNT/collagen membrane significantly inhibits the expression of mitogen-activated protein kinase (MAPK), and effectively treats peritoneal dissemination of 5-FU-resistant gastric cancer. Compared with siRNA/PEI/5-FU/CNT group, ki-67 proliferation index, and matrix metallopeptidase 9 (MMP9) expression are significantly decreased in the Chim/PEI/5-FU/CNT group, while the proportion of apoptotic cells is markly increased. In conclusion, a chimera/PEI/5-FU/CNT/collagen membrane is constructed, which can effectively treat peritoneal dissemination of drug-resistant gastric cancer. The study provides a new therapeutic approach for relevant clinical treatment.

Protein hydrolysis of underutilized marine organisms is a method to improve added value. In the present article, anchovy protein was autolyzed at pH 8.5 and 50°C. After autolysis processing for 24 h, total nitrogen recovery reached 92.1%. The protein hydrolysates had antioxidant properties on reducing power, 1, 1-diphenyl-2-picryhydrazyl radical, and hydroxyl radical scavenging activity. More than 79% of the peptides in the hydrolysates had a molecular weight of lower than 3 kDa. Protein hydrolysates had balanced amino acid compositions, and total content of essential amino acids had no significant difference after hydrolysis. Protein hydrolysates from anchovy autolysis have potential in nutritional and functional foods.

Anchovy protein hydrolysates with high free radical-scavenging activity were prepared by endogenous and commercial enzymes. Various hydrolytic factors (commercial protease composition, protease concentration, temperature, and reaction time) were optimized. Using a single-factor experiment, three commercial proteases (Protamex, Flavourzyme 500 MG, and Alcalase 2.4 L) were selected for further optimization using a simplex lattice design. The optimum composition of Protamex:Flavourzyme 500 MG:Alcalase 2.4 L was found to be 1.1:1.0:0.9. The hydrolytic conditions (commercial protease concentration, temperature, and reaction time) for the optimum protease composition were optimized using a Box-Behnken design. The optimum hydrolytic conditions were as follows: total commercial protease concentration of 3.27%, pH of 7.5, temperature of 55.4℃, and reaction time of 2.7 h. Under these conditions, hydrolysate with a 1, 1-diphenyl-2-picryhydrazyl scavenging activity of 84.7% was obtained. Meanwhile, a degree of hydrolysis of 33.2% and high protein nitrogen recovery of 87.5% were achieved. The amino acid composition of the hydrolysates demonstrated that they have high nutritional value, thereby suggesting that the hydrolysates have potential to be used as raw material for functional food.