A Fusion Protein of RGD4C and ß-Lactamase Has a Favorable Targeting Effect in Its Use in Antibody Directed Enzyme Prodrug Therapy.

Antibody directed enzyme prodrug therapy (ADEPT) utilizing ß-lactamase is a promising treatment strategy to enhance the therapeutic effect and safety of cytotoxic agents. In this method, a conjugate (antibody-ß-lactamase fusion protein) is employed to precisely activate nontoxic cephalosporin prodrugs at the tumor site. A major obstacle to the clinical translation of this method, however, is the low catalytic activity and high immunogenicity of the wild-type enzymes. To overcome this challenge, we fused a cyclic decapeptide (RGD4C) targeting to the integrin with a ß-lactamase variant with reduced immunogenicity which retains acceptable catalytic activity for prodrug hydrolysis. Here, we made a further investigation on its targeting effect and pharmacokinetic properties, the results demonstrated that the fusion protein retains a targeting effect on integrin positive cells and has acceptable pharmacokinetic characteristics, which benefits its use in ADEPT.

The respiratory burst activity and expression of catalase in white shrimp, Litopenaeus vannamei, during long-term exposure to pH stress.

In this study, changes of reactive oxygen species (ROS) and the mRNA expression of catalase of the Pacific white shrimp, Litopenaeus vannamei, exposed to pH (5.4, 6.7, 8.0, and 9.3) stress was investigated at different stress time (24, 48, 72, 96, and 120 h). Level of malondialdehyde (MDA) in shrimp also were assessed. The results revealed that acidic (pH 5.4 and 6.7) or alkaline exposure (pH 9.3) induced production of ROS hemocytes and increase of MDA level in shrimp. Moreover, the catalase mRNA expression in hepatopancreas of L. vannamei was up-regulated in 24 h at pH 5.4, in 72 h at pH 6.7 and in 48 h at pH 9.3, whereas was down-regulated significantly after 72 h acidic (pH 5.4 and 6.7) or alkaline (pH 9.4) exposure. In the present study, there was the relationship between ROS and catalase mRNA expression under normal acidic and alkaline conditions. At pH 8, the increase of catalase transcripts due to up-regulation by ROS, whereas MDA level did not significantly change, suggesting activation of corresponding protective mechanisms of detoxifying ROS is essential for the proper functioning of cells and the survival of shrimps.

Bioinformatics analysis of the prognosis and biological significance of VCAN in gastric cancer.

Gastric cancer (GC) is one of the most common cancers in the world, and the tumor microenvironment (TME) plays a vital role in the occurrence and development of GC. In this study, we obtained differential expressed genes in GC tissues from The Cancer Genome Atlas. After ESTIMATE and weighted correlation network analysis, we obtained differentially expressed genes (DEGs). With further screening DEGs of immune infiltration and then through Kaplan-Meier survival analysis, least absolute shrinkage and selection operator regression analysis and COX analysis, we found that VCAN was a gene positively correlated with high immune infiltration and poor prognosis of patients in GC. In addition, we selected a Gene Expression Omnibus dataset (GSE84433) to verify the effect of VCAN on the patient's prognosis, and analyzed the value of VCAN in immunotherapy through TIMER database and TISIDB. In conclusion, we hold the view that VCAN may affect the development of GC by regulating the TME, which may act as a potential therapeutic target for GC.

Targeting assay of a fusion protein applied in enzyme prodrug therapy.

Tumor growth and metastasis are dependent on angiogenesis. The overexpression of integrin αvß3 on angiogenic vessels and on numerous malignant human tumor cells suggests that these labeled ligands of integrin are potentially suitable for molecular imaging and in targeted therapy of tumors. In previous studies, we added a ß-lactamase variant with reduced immunogenicity to the cyclic peptide RGD4C, resulting in the fusion protein RGD4CßL, which is suitable for use in targeted enzyme prodrug therapy (TEPT), a promising treatment for tumors. The targeting of the aforementioned fusion protein serves an important role in TEPT. In the present study, RGD4CßL was labeled with 125I and the targeting effect on integrin-positive tumors was evaluated. The results demonstrated that the 125I-RGD4CßL protein exhibited high levels of accumulation at the tumor site and rapid renal clearance, which revealed the potency and efficiency of RGD4CßL in TEPT.

Dual-frequency (20/40 kHz) ultrasonic assisted photocatalysis for degradation of methylene blue effluent: synergistic effect and kinetic study.

Dual-frequency ultrasonic assisted photocatalysis (DUAP) was proposed to enhance the degradation efficiency of methylene blue (MB) solution. The influence of operational parameters, i.e., irradiation time, ultrasonic arrangement, TiO(2) concentration and power density, was studied. The results implied that the rapid degradation of MB solution was achieved in 18 min under DUAP with the dual frequencies of 20/40 kHz. Kinetic investigation of MB degradation for the DUAP process was conducted on the basis of first-order kinetic equation and the synergistic effect was assessed by examination of the apparent rate constant. The effect of ultrasonic arrangement was analyzed by comparison of the pressure amplitude of ultrasonic superposition field. The evolvement of intermediate products and the role of active species during DUAP were distinguished by UV-Vis spectra and the free radical scavenging experiment.