Antitumor Activity of cGAMP via Stimulation of cGAS-cGAMP-STING-IRF3 Mediated Innate Immune Response

Immunotherapy is one of the key strategies for cancer treatment. The cGAS-cGAMP-STING-IRF3 pathway of cytosolic DNA sensing plays a pivotal role in antiviral defense. We report that the STING activator cGAMP possesses significant antitumor activity in mice by triggering the STING-dependent pathway directly. cGAMP enhances innate immune responses by inducing production of cytokines such as interferon-β, interferon-γ, and stimulating dendritic cells activation, which induces the cross-priming of CD8(+) T cells. The antitumor mechanism of cGAMP was verified by STING and IRF3, which were up-regulated upon cGAMP treatment. STING-deficiency dramatically reduced the antitumor effect of cGAMP. Furthermore, cGAMP improved the antitumor activity of 5-FU, and clearly reduced the toxicity of 5-FU. These results demonstrated that cGAMP is a novel antitumor agent and has potential applications in cancer immunotherapy

Effect of Precipitate Embryo Induced by Strain on Natural Aging and Corrosion Behavior of 2024 Al Alloy

Pre-aging precipitates in 2024 Al alloy re-dissolved during rolling, and Mg and Cu atoms were enriched in the dislocation structure to form “precipitate embryo”, which is beneficial for the formation of second phase during the subsequent natural aging process. Due to the solubility of the large precipitate particles during deformation, the precipitates in the natural aging 2024 Al alloy were consist of two parts: The undissolved pre-precipitates and the natural aging precipitates derived from the embryos. The electrochemical corrosion behavior and passive film of the samples with different pre-aging time and strain were investigated by electrochemical tests and SEM. The results showed that the corrosion resistance and the passive film performance were deteriorated with the increase of pre-aging time due to the simultaneous increase of the quantity of the two-parts precipitates. The corrosion resistance can be improved by the increase of strain, because there will be smaller grain size and the existence of large undissolved precipitates in smaller strain samples

Stable Stacking Faults Bounded by Frank Partial Dislocations in Al7075 Formed through Precipitate and Dislocation Interactions

Through high-resolution electron microscopy, stacking faults (SFs) due to Frank partial dislocations were found in an aluminum alloy following deformation with low strain and strain rate, while also remaining stable during artificial aging. Extrinsic stacking faults were found surrounded by dislocation areas and precipitates. An intrinsic stacking fault was found between two Guinier-Preston II (GP II) zones when the distance of the two GP II zones was 2 nm. Defects (precipitates and dislocations) are considered to have an influence on the formation of the SFs, as their appearance may cause local strain and promote the gathering of vacancies to lower the energy

Serum IL-33 Levels Are Associated with Liver Damage in Patients with Chronic Hepatitis C

Interleukin-33 (IL-33) is associated with the development of Th2 responses. This study examined the potential role of IL-33 in the pathogenic process of chronic hepatitis C (CHC) in Chinese patients. The levels of serum IL-33 and sST2 in 154 patients with CHC, 24 with spontaneously resolved HCV (SR-HCV) infection and 20 healthy controls (HC), were analyzed by ELISA. The concentrations of serum IL-2, IFN-γ, TNF-α, IL-4, IL-6, and IL-10, HCV loads, ALT, AST, and HCV-Ab were measured. We found that the levels of serum IL-33 in CHC patients were significantly higher than those of SR-HCV and HC but decreased after treatment with interferon for 12 weeks. More importantly, the levels of serum IL-33 were correlated with the concentrations of ALT and AST in CHC patients. The levels of serum sST2, as a decoy receptor of IL-33, were significantly higher in CHC and SR-CHC patients than those in HC, and there was no correlation between the levels of serum sST2 and IL-33. The concentrations of serum IFN-γ and IL-6 in CHC patients were significantly lower than those of SR-HCV. These data suggest that IL-33 may be a pathogenic factor contributing to CHC-related liver injury

Application of tumor microparticles in tumor prevention and treatment

Abstract Tumor microparticles (T-MPs) are vesicles released from tumor cells when they receive apoptotic or stimuli signals. T-MPs, which contain some proteins, lipids and nucleic acids from tumor cells, contribute to the exchange of material, energy and information between cells. T-MPs contain both tumor antigens and innate immunostimulatory signals, making T-MPs as a new form of tumor vaccine. Meanwhile, T-MPs can be used as natural carriers to transport ‘‘cargoes’’, such as chemotherapy drugs, oncolytic viruses, nucleic acids, and metal nanoparticles to treat tumors. In addition, T-MPs enhance the effect of chemotherapy. This review introduces the application of T-MPs as vaccines, delivery systems and chemosensitizers in tumor prevention and treatment, with a focus on the mechanisms, clinical applications, and influencing factors of drug-loaded T-MPs in tumor treatment

Th1 and Th2 Immune Response in Chronic Hepatitis B Patients during a Long-Term Treatment with Adefovir Dipivoxil

Adefovir dipivoxil treatment has significantly improved the outcome of chronic hepatitis B virus (HBV) infection. However, it remains largely unknown how immune system responds to the treatment. Chronic HBV patients were treated with adefovir dipivoxil and examined for serum HBV DNA loads, cytokines, and T helper (Th1) and 2 (Th2) cytokine producing T cells during 104 weeks of the treatment. Th1/Th2 cytokines producing T cells were significantly lower in chronic HBV patients as compared to normal individuals. Adefovir dipivoxil treatment led to the increase of Th1/Th2 cytokines producing T cells and serum cytokine levels in association with the decline of HVB DNA load. In contrast, Th1/Th2 cytokines producing T cells remained lower in one patient detected with adefovir dipivoxil resistant HBV A181T/V mutation. This study has established inverse correlation of the increase of Th1/Th2 immunity and the decline of HBV DNA load in chronic HBV patients during adefovir dipivoxil treatment

Enhanced strength of dual-phase Ti6242 alloy via a heterogeneous microstructure

In α + β titanium alloys, increasing the amount of α/β phase boundaries via conventional heat treatment usually improves the strength but significantly deteriorates the alloy’s ductility. Instead of homogeneous β transformation microstructure (βt) in conventional equiaxed microstructure (EM), two types of microstructures with heterogeneous βt are obtained via insufficient diffusion of alloying elements induced by rapid heat treatment (RHT), forming a unique semi-equiaxed structure (S-ES) in the Ti6242 alloy. Such microstructural characteristics, including the Type Ⅰ microstructure characterized by a wavy interface between primary α phase (αp) and heterogeneous βt, and the Type Ⅱ microstructure, featuring heterogeneous βt embedded in the surrounding homogeneous βt structures, exhibit an enhanced strength with an insignificant loss of ductility. The enhanced strength is attributed to the increased fraction of α/β phase boundaries and precipitated residual β (βr) nanoparticles, whereas good ductility is obtained due to the soft αp, coherent β nanoparticles, and deformable β lamellae in the heterogeneous βt. However, the excessive presence of the Type Ⅱ microstructure can deteriorate ductility to some extent. This work provides a novel approach to achieving high-performance dual-phase titanium alloys and being potentially applicable to other α + β titanium alloys