Inhibition of AIM2 expression enhance treatment effect of osimertinib in treatment of glioma.

INTRODUCTION: Glioma is one of the most commonly tumours which occurs in the central nervous system and accounts for nearly 80% of brain tumours, with a significantly high mortality and morbidity. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are used as EGFR targeted therapy in various types of solid tumours; however, effective treatment for glioma is still limited. Osimertinib is an irreversible, oral third-generation TKI that targets the mutation at T790M, which causes cancer cells to acquire resistance to drugs. Osimertinib could be effective in the treatment of EGFR mutations with minimal effects on the activity of wild-type EGFR. Absent in melanoma 2 (AIM2) is highly expressed in glioma cells, promoting the maturation of pro-cancer cytokines and contributing to progression of glioma. However, the secretion of pro-cancer cytokines of tumour cells has been regarded as the resistance mechanism to EGFR-TKIs, including osimertinib. A high level of these cytokines also indicates a shorter progression-free survival (PFS). As AIM2 regulates the secretion of pro-cancer cytokines, we thought inhibition of AIM2 may contribute to the therapeutic effect of EGFR-TKIs. MATERIAL AND METHODS: We first established AIM2 inhibition and overexpression in cells. Then, the viability rate of cells was calculated by cell counting kit-8 (CCK-8) method, and apoptotic ratio of cells were measured by flow cytometry. The expression of inflammatory-related genes was detected using quantitative polymerase chain reaction (qPCR), concentrations of inflammatory-related factors were measured using enzyme-linked immunosorbent assay (ELISA). The expression of Wnt/b-catenin and EGFR/Ras/Mitogen-activated protein kinase kinase 1 (MEK) signalling pathway components was detected using western blotting. RESULTS: We found that inhibition of AIM2 enlarged the effect of osimertinib on the upregulation of inflammatory gene expression and secretion of these genes, increasing apoptosis. In addition, we also found that AIM2 could enhance the effect of osimertinib on reducing the expression of the Wnt/b-catenin and EGFR/Ras/MEK signalling pathways, resulting in the inhibition of cellular proliferation, and exerting an anti-tumour effect. These effects were also observed using in vivo experiments. CONCLUSIONS: AIM2 presents a potential therapeutic target in treatment of glioma.

Heat-sealable, transparent, and degradable arabinogalactan/polyvinyl alcohol films with UV-shielding, antibacterial, and antioxidant properties.

Petroleum-based packaging materials are nondegradable and unsustainable and thus are harmful to the environment. Renewable packaging films prepared from bio-based raw materials are promising alternatives to petroleum-based packaging materials. In this study, colorless and transparent bio-based films were successfully cast using a solution containing a mixture of arabinogalactan (AG) and poly (vinyl alcohol) (PVA). Vanillin was incorporated into the mixture to endow the films with UV-shielding, antioxidant, and antibacterial properties. The morphological, physical, antioxidant, and antibacterial properties of the blend films were then characterized. At an AG:PVA weight ratio of 1:3, and the vanillin content was 0.15 %, the tensile strength of the AG/PVA/Vanillin (APV) films reached ~28 MPa, while their elongation at break reached ~475 %. The addition of vanillin significantly affected the antioxidant and antibacterial properties of the blend films, which exhibited superb UV barrier capacity. The APV films exhibited extremely low oxygen transmittance, delaying the onset of mold/rot in strawberries and reducing their weight loss. Because of the heat sealability of the blend films, they can be used for encapsulating various substances, such as concentrated laundry liquid. Moreover, the blend films were recyclable and biodegradable. Thus, these films have great potential for applications that require sustainable packaging.

Green, recyclable, mechanically robust, wet-adhesive and ionically conductive cellulose-based bioplastics enabled by supramolecular covalent hydrophobic eutectic networks.

The development of novel cellulose-based bioplastics (CBPs) is highly desirable because CBPs are green, rationally use resources, and lead to a reduction in environmental pollution compared to alternative materials. However, incorporating high transparency, water resistance, mechanical robustness, wet-adhesion, ionic conductivity and recyclability into CBP remains a challenge. In this paper, novel CBPs with supramolecular covalent networks are fabricated by introducing polymerizable hydrophobic deep eutectic solvents (HDES) into ethylcellulose (EC) networks through in situ plasticization followed by a rapid photopolymerization process. The excellent molecular interfacial compatibility enables EC to be loaded with a high content of poly(HDES), while allowing high transparency (more than 90 %) of the prepared CBPs. Multiple intermolecular interactions provide CBPs with mechanical robustness, water resistance, and underwater adhesion, and CBPs can be readily recovered by the solvent in a closed loop. Moreover, CBPs possess inherent ionic conductivities, and using them as green substrates, personalized electroluminescent devices can be successfully constructed. The method proposed in this paper provides a new strategy for the preparation of multifunctional CBPs, which will greatly enrich their applications in self-adhesive materials, green flexible electronics and other package materials.

Overexpression of TRPM7 promotes the therapeutic effect of curcumin in wound healing through the STAT3/SMAD3 signaling pathway in human fibroblasts.

OBJECTIVE: Curcumin, a natural extract from the rhizomes of Curcuma longa, is also known as a curcuminoid. Curcumin has been studied as a therapeutic drug for wound healing because of its anti-inflammatory, anti-oxidant, and anti-bacterial activities. However, the detailed mechanism of curcumin in wound healing is not clear. It is well-known that the skin is the largest organ in humans and prevents tissues from damage, including infection, radiation, and mechanical damage. Wound healing of the skin is a complex physiological regulation process requiring various cell types and cytokines; hence, wound healing, including surgery and care, incurs a huge expenditure each year. Transient receptor potential cation channel subfamily M member 7 (TRPM7) regulates multiple physiological and pharmacological processes through its channel and kinase activities. In addition, TRPM7 regulates cell adhesion, migration, and anti-oxidative activity, thereby playing a regulatory role in the wound healing process. This study aimed to explore the function of curcumin in the wound healing process. METHODS: We first established TRPM7 overexpression and knockdown models in fibroblasts using lentivirus. CCK-8 and wound healing assays were used to clarify whether overexpression of TRPM7 promoted proliferation and migration in fibroblasts. Expression of target genes and proteins was detected using qPCR and western blotting. Concentrations of migration-related cytokines were measured using ELISA. RESULTS: Proliferation and migration of fibroblasts increased after curcumin treatment and was further enhanced after overexpression of TRPM7. In addition, expression of proliferation-related genes and proteins was elevated after TRPM7 overexpression. Further, the secretion of migration-related cytokines was elevated after TRPM7 overexpression. CONCLUSION: Curcumin treatment promoted proliferation and migration of fibroblasts, and these effects were mediated by the signal transducer and activator of transcription 3 (STAT3)/SMAD family member 3/hypoxia-inducible factor 1 subunit alpha signaling pathway. Thus, we conclude that overexpression of TRPM7 might contribute to wound healing.