Dodder-transmitted mobile systemic signals activate a salt-stress response characterized by a transcriptome change in Citrus sinensis.

Citrus is an essential horticultural fruit whose yield and quality are affected by salinity all over the world. The recognition and adaptive regulation of citrus against salt stress are important areas for cultivar improvement, but the vascular system signal transduction mechanism of the plant response to salt stress remains elusive. In this study, we constructed a dodder (Cuscuta spp.) linked Hamlin sweet orange (Citrus sinensis) plant community in which deliver a vascular signal through the dodder in response to salt stress. RNA-seq technology was used to analyze the gene expression profile of citrus leaves after salt treatment. The results showed that a vascular signal was transmitted to a dodder-linked host plant, triggering a transcriptional response to salt stress. However, the phenotypic and transudative ability of the dodder changed after 24 h. The salt treatment group (Group S) and the dodder-linked group (Group D) respectively contained 1,472 and 557 differentially expressed genes (DEGs). 454 of which were common to both groups. The results of our analysis revealed that the gene expression categories in Group D represented a highly consistent trend compared to the group S plants, indicating that the dodder-bridged vascular signals activated the stress-response of citrus leaves for transcriptomic reconfiguration. The KEGG pathway database and an analysis of key drivers revealed that phenylpropanoid biosynthesis, photosynthesis-antenna proteins, starch and sucrose metabolism, plant hormone signal transduction, circadian rhythm, and MAPK signaling pathways were significantly enriched as the critical genes during salt stress. A systemic signal in the dodder-bridged host significantly regulated abiotic stress-related secondary metabolic pathways, including those for phenylpropanoids, lignin, and lignans. The physiological indexes of photosynthetic intensity, respiration, and attractiveness among communities supported the transcriptional changes. Thus, our results indicate that salt stress-induced vascular system signals can be transmitted through the vascular system of a dodder linking citrus plants, revealing the genetic regulation and physiological changes of citrus leaves responding to plant stress signal transmission.

AKR1C3 regulated by NRF2/MAFG complex promotes proliferation via stabilizing PARP1 in hepatocellular carcinoma.

Aldo-keto reductase family 1 member C3 (AKR1C3) serves as a contributor to numerous kinds of tumors, and its expression is elevated in patients with hepatocellular carcinoma (HCC). However, the biological function of AKR1C3 in HCC remains unclear. Here we investigated the role of AKR1C3 in liver carcinogenesis using in vitro and in vivo models. We determined that AKR1C3 is frequently increased in HCC tissues with poor prognosis. Genetically manipulated cells with AKR1C3 construction were examined to highlight the pro-tumoral growth of both wild-type AKR1C3 and mutant in vitro and in vivo. We observed promising treatment effects of AKR1C3 shRNA by intratumoral injection in mice. Mechanically, we demonstrated that the transcription factor heterodimer NRF2/MAFG was able to bind directly to AKR1C3 promoter to activate its transcription. Further, AKR1C3 stabilized PARP1 by decreasing its ubiquitination, which resulted in HCC cell proliferation and low sensitivity of Cisplatin. Moreover, we discovered that the tumorigenic role of AKR1C3 was non-catalytic dependent and the NRF2/MAFG-AKR1C3-PARP1 axis might be one of the important proliferation pathways in HCC. In conclusion, blockage of AKR1C3 expression provides potential therapeutic benefits against HCC.

Panax notoginseng saponins prevent colitis-associated colorectal cancer via inhibition IDO1 mediated immune regulation.

Colorectal cancer (CRC) is the third most lethal cancer and leading cause of cancer mortality worldwide. A key driver of CRC development is colon inflammatory responses especially in patients with inflammatory bowl disease (IBD). It has been proved that Panax notoginseng saponins (PNS) have anti-inflammatory, anti-oxidant and anti-tumor effects. The chemopreventive and immunomodulatory functions of PNS on colitis-associated colorectal cancer (CAC) have not been evaluated.This present study was designed to study the potential protective effects of PNS on AOM/DSS-induced CAC mice to explore the possible mechanism of PNS against CAC. Our study showed that PNS significantly alleviated colitis severity and prevented the occurrence of CAC. Functional assays revealed that PNS relieved immunosuppression of Treg cells in the CAC microenvironment by inhibiting the expression of IDO1 mediated directly by signal transducer and activator of transcription 1 (STAT1) rather than phosphorylated STAT1. Ultimately, Rh1, one of the PNS metabolites, exhibited the best inhibitory effect on IDO1 enzyme activity. Our study showed that PNS exerted significant chemopreventive function and immunomodulatory properties on CAC. It could reduce macrophages accumulation and Treg cells differentiation to reshape the immune microenvironment of CAC. These findings provided a promising approach for CAC intervention.

Field-Deployable Candidatus Liberibacter asiaticus Detection Using Recombinase Polymerase Amplification Combined with CRISPR-Cas12a.

The early detection of Candidatus Liberibacter asiaticus (CLas) by citrus growers facilitates early intervention and prevents the spread of disease. A simple method for rapid and portable Huanglongbing (HLB) diagnosis is presented here that combines recombinase polymerase amplification and a fluorescent reporter utilizing the nuclease activity of the clustered regularly interspaced short palindromic repeats/CRISPR-associated 12a (CRISPR-Cas12a) system. The sensitivity of this technique is much higher than PCR. Furthermore, this method showed similar results to qPCR when leaf samples were used. Compared with conventional CLas detection methods, the detection method presented here can be completed in 90 min and works in an isothermal condition that does not require the use of PCR machines. In addition, the results can be visualized through a handheld fluorescent detection device in the field.

miR-1258 Attenuates Tumorigenesis Through Targeting E2F1 to Inhibit PCNA and MMP2 Transcription in Glioblastoma.

MicroRNAs are a group of endogenous small non-coding RNAs commonly dysregulated in tumorigenesis, including glioblastoma (GBM), the most malignant brain tumor with rapid proliferation, diffuse invasion, and therapeutic resistance. Accumulating evidence has manifested that miR-1258 exerts an inhibitory role in many human cancers. However, the expression pattern of miR-1258 and its potential function in GBM tumorigenesis remain unclear. In this study, we reported that miR-1258 expression decreased with the ascending pathological grade of glioma, which indicated an unfavorable prognosis of patients. Functional assays revealed an inhibitory effect of miR-1258 on malignant proliferation, therapeutic resistance, migration, and invasion of GBM in vitro. Moreover, xenograft models also suggested a repression effect of miR-1258 on gliomagenesis. Mechanistically, miR-1258 directly targeted E2F1 in 3'-untranslated regions and attenuated E2F1-mediated downstream gene PCNA and MMP2 transcriptions. Furthermore, restoration of E2F1 expression in GBM cells effectively rescued the tumor-suppressive effect of miR-1258. Our studies illustrated that miR-1258 functioned as a tumor suppressor in GBM by directly targeting E2F1, subsequently inhibiting PCNA and MMP2 transcriptions, which contributed to new potential targets for GBM therapy and other E2F1-driven cancers.

Oroxylin A reversed Fibronectin-induced glioma insensitivity to Temozolomide by suppressing IP3R1/AKT/ß-catenin pathway.

AIMS: Cell adhesion mediated-drug resistance (CAM-DR) is one of main reasons for. the limitation to chemotherapy, but the underlying mechanism remains unclear in glioma. In this study, we investigated the mechanism of CAM-DR induced by Fibronectin (Fn). Besides, we studied the reversal effect of Oroxylin A, a natural flavonoid extracted from Scutellaria radix, on Temozolomide (TMZ) insensitivity of glioma cells. MAIN METHODS: Human Fn protein was used to mimic cell adhesion model and investigate its effect on the insensitivity of glioma cells to TMZ. Moreover, Oroxylin A was studied regarding its reversal effect on TMZ insensitivity of glioma via multiple molecular biological methods such as MTT, cell apoptosis assay, siRNA transfection, western blot, immunofluorescence assay. KEY FINDINGS: Fn could decrease the apoptosis-inducing effect of TMZ and led to the CAM-DR in glioma cells. Further studies showed that up-regulations of IP3R1 and intracellular Ca2+ level induced the activation of AKT kinase which increased the phosphorylation of GSK-3ß and subsequently caused the entry of ß-catenin into the nucleus. Knocking down IP3R1 significantly improved the sensitivity of glioma cells to TMZ. Meanwhile, after treatment with low-toxic concentration of Oroxylin A, the apoptosis induced by TMZ under Fn condition increased dramatically. Furthermore, our results revealed that Oroxylin A markedly inhibited the expression of IP3R1 and the activation of AKT/ß-catenin pathway. SIGNIFICANCE: Oroxylin A could reverse the insensitivity of TMZ via suppressing IP3R1/AKT/ß-catenin pathway and it might be helpful for enhancing the anti-cancer effect of TMZ in glioma.