Bionic natural small molecule co-assemblies towards targeted and synergistic Chemo/PDT/CDT

Abstract Background Multi-component nano-delivery systems based on chemotherapy (chemo)- photodynamic therapy (PDT)- chemodynamic therapy (CDT) have gained increased attention as a promising strategy to improve clinical outcomes in cancer treatment. However, there remains a challenge in developing biodegradable, biocompatible, less toxic, yet highly efficient multicomponent nanobased drug delivery systems (DDS). Here, our study presents the screening and development of a novel DDS based on co-assemblies natural small molecule (NSMs). These molecules (oleanolic acid, and betulinic acid) are combined with photosensitizers Chlorine6 (Ce6) and Cu2+ that are encapsulated by tumor cell membranes. This nanocarrier encapsulated in tumor cell membranes achieved good tumor targeting and a significant improvement in tumor accumulation. Methods A reprecipitation method was used to prepare the co-assembled nanocarrier, followed by the introduction of Cu2 + into the DDS (OABACe6 NPs). Then, by wrapping the surface of NPs with the cell membranes of 4T1 which is a kind of mouse breast cancer cells (CM@OABACe6/Cu NPs). and analysis of its structure and size distribution with UV–Vis, XPS, FT-IR, SEM, TEM, and DLS. The synergistic effects of in vitro chemotherapy, CDT and PDT and targeting were also validated by cellular and animal studies. Results It was shown that CM@OABACe6/Cu NPs achieved good tumor targeting and a significant improvement in tumor accumulation. In the composite nano-assembly, the NSMs work together with the Ce6 to provide effective and safe chemo and PDT. Moreover, the effect of reduced PDT due to the depletion of reactive oxygen species (ROS) by excess glutathione (GSH) in the tumor can be counteracted when Cu2 + is introduced. More importantly, it also confers CDT through a Fenton-like catalytic reaction with H2O overexpressed at the tumor site. Conclusions By constructing CM@OABACe6/Cu NPs with homologous targeting, we create a triple synergistic platform for cancer therapy using PDT, chemo, and CDT. We propose here a novel combinatorial strategy for designing more naturally co-assembled small molecules, especially for the development of multifunctional synergistic therapies that utilize NSMs

QTL Analysis and Heterosis Loci of Effective Tiller Using Three Genetic Populations Derived from <i>Indica</i>-<i>Japonica</i> Crosses in Rice

Effective panicle numbers (PNs) and Tiller numbers (TNs) are important traits affecting rice (Oryza sativa L.) architecture and grain yield. However, the molecular mechanisms underlying PN and TN heterosis remain unknown in rice. In addition, new PN- or TN-related genes need to be detected and discovered. In this study, in order to detect rice quantitative trait loci (QTLs) and the heterosis-related loci of PN or TN in rice, we developed a high generation recombinant inbred line (RIL) population from a cross of two elite cultivars, Luohui9 (Xian/Indica) and RPY geng (Geng/Japonica), and two testcross hybrid populations derived from the crosses of RILs and two cytoplasmic male sterile lines, YTA (Xian/Indica) and Z7A (Geng/Japonica). Finally, nine QTLs of PN across four seasons were identified, and two QTLs of TN in 191HB were mapped. Besides this, six heterosis-related QTLs of PN and five heterosis-related QTLs of TN were located. We found that heterosis-related QTLs of PN or TN covered multiple known genes, such as MOC1, TAC1 and OsETR2. Furthermore, homologous gene analysis identified one candidate gene of PN (LOC_10g25720). Together, these findings uncover multiple heterosis-related loci, and provide a new insight into the heterosis mechanism of PN and TN in rice

QTL Analysis and Heterosis Loci of Effective Tiller Using Three Genetic Populations Derived from Indica-Japonica Crosses in Rice

Effective panicle numbers (PNs) and Tiller numbers (TNs) are important traits affecting rice (Oryza sativa L.) architecture and grain yield. However, the molecular mechanisms underlying PN and TN heterosis remain unknown in rice. In addition, new PN- or TN-related genes need to be detected and discovered. In this study, in order to detect rice quantitative trait loci (QTLs) and the heterosis-related loci of PN or TN in rice, we developed a high generation recombinant inbred line (RIL) population from a cross of two elite cultivars, Luohui9 (Xian/Indica) and RPY geng (Geng/Japonica), and two testcross hybrid populations derived from the crosses of RILs and two cytoplasmic male sterile lines, YTA (Xian/Indica) and Z7A (Geng/Japonica). Finally, nine QTLs of PN across four seasons were identified, and two QTLs of TN in 191HB were mapped. Besides this, six heterosis-related QTLs of PN and five heterosis-related QTLs of TN were located. We found that heterosis-related QTLs of PN or TN covered multiple known genes, such as MOC1, TAC1 and OsETR2. Furthermore, homologous gene analysis identified one candidate gene of PN (LOC_10g25720). Together, these findings uncover multiple heterosis-related loci, and provide a new insight into the heterosis mechanism of PN and TN in rice

PS341 inhibits hepatocellular and colorectal cancer cells through the FOXO3/CTNNB1 signaling pathway

Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are among the most common cancers across the world. Particularly, a large number of patients with CRC also have liver metastasis. Currently, there are just a few targeted drugs against these two kinds of tumors which can only benefit a very small population of patients. Therefore, the need of more effective therapeutic drugs or strategies for these two types of cancers is urgent. PS341 (Bortezomib) is the first proteasome inhibitor drug which has been approved in clinical treatment for multiple myeloma. Here we demonstrated that PS341 negatively regulated HCC and CRC both in vitro and in vivo, including the inhibition of cell proliferation, epithelial-mesenchymal transition (EMT), the expression of stemness-related genes, cell migration and invasiveness. Mechanically, PS341 upregulated the expression of FOXO3, which inhibited the transcriptional activation of CTNNB1. The downregualtion of CTNNB1 led to apoptosis, cell cycle arrest, and the inhibition of migration, invasion, self-renewal and tumor formation of these two cancer types. In sum, our findings shed light on the PS341 mediated targeted therapy against both HCC and CRC in the future