Changes in the frequency of myeloid-derived suppressor cells after transarterial chemoembolization with gelatin sponge microparticles for hepatocellular carcinoma

Purpose: A series of clinical studies have established the safety and efficacy of transcatheter arterial chemoembolization(TACE) with gelatin sponge microparticles(GSMs) in treating hepatocellular carcinoma(HCC). HCC can lead to obvious necrosis inside tumors, especially larger ones, although it is unclear whether such necrotic tumor tissue can induce favorable immune reactions against the tumor. Myeloid-derived suppressor cells(MDSCs)have immunosuppressive functions and are currently considered a very important cell type affecting tumor immunity. This study observed changes in MDSC frequency in peripheral blood before and after GSM–TACE to evaluate the effect on the immune function of HCC patients.Methods: Eight patients diagnosed with HCC underwent GSM–TACE treatment in the Hepatobiliary Interventional Department of Beijing Tsinghua Chang Gung Hospital, Beijing, China;we followed up with the patients over a period of 30 days post-surgery. We used flow cytometry(FCM) to quantify the frequency of MDSCs in peripheral blood before TACE, 10 days after surgery and 30 days after surgery.Results: MDSC frequency after GSM–TACE had a significant downward trend. Pre-TACE, it was 30.73% ? 11.93%,decreasing to 18.60% ? 11.37% at 10 days after operation. This decrease was not statistically significant(P > 0.05). MDSC frequency was even lower 30 days after TACE(7.63% ? 7.32%) than at 10 days after TACE(P < 0.05), and there was a significant difference compared with pre-TACE(P < 0.001). We evaluated tumor response at 30 days after GSM–TACE according to the Modified Response Evaluation Criteria in Solid Tumors(mRECIST), and all eight patients showed partial response(PR).Conclusion: Our results confirmed that GSM–TACE was beneficial for improving anti-tumor immunity in the treatment of HCC.

The Flowering Repressor SVP Confers Drought Resistance in Arabidopsis by Regulating Abscisic Acid Catabolism

Terrestrial plants must cope with drought stress to survive. Under drought stress, plants accumulate the phytohormone abscisic acid （ABA） by increasing its biosynthesis and decreasing its catabolism. However, the regulatory pathways controlling ABA catabolism in response to drought remain largely unclear. Here, we report that the flowering repressor SHORT VEGETATIVE PHASE （SVP） is induced by drought stress and associates with the promoter regions of the ABA catabolism pathway genes CYP707A 1, CYP707A3 and AtBG1, causing decreased expression of CYP7OTA 1 and CYP707A3 but enhanced expression ofAtBG1 inArabidopsis leaves. Loss-of-function mutations in CYP707A 1 and CYP707A3 or overexpression of AtBG1 could rescue the drought-hypersensitive phenotype of svp mutant plants by increasing cellular ABA levels. Collectively, our results suggest that SVP is a central regulator of ABA catabolism and that a regulatory pathway involving SVP, CYP707A1/3, and AtBG1 plays a critical role in plant response to water deficit and plant drought resistance.

Genome-wide distribution and functions of the AAE complex in epigenetic regulation in Arabidopsis

Heterochromatin is widespread in eukaryotic genomes and has diverse impacts depending on its genomic context.Previous studies have shown that a protein complex,the ASI1-AIPP1-EDM2(AAE)complex,participates in polyadenylation regulation of several intronic heterochromatin-containing genes.However,the genome-wide functions of AAE are still unknown.Here,we show that the ASI1 and EDM2 mostly target the common genomic regions on a genome-wide level and preferentially interacts with genetic heterochromatin.Polyadenylation(poly(A)sequencing reveals that AAE complex has a substantial influence on poly(A)site usage of heterochromatin-containing genes,includingnotonlyintronicheterochromatincontaining genes but also the genes showing overlap with heterochromatin.Intriguingly,AAE is also involved in the alternative splicing regulation of a number of heterochromatin-overlapping genes,such as the disease resistance gene RPP4.We provided evidence that genic heterochromatin is indispensable for the recruitment of AAE in polyadenylation and splicing regulation.In addition to conferring RNA processing regulation at genic heterochromatin-containing genes,AAE also targets some transposable elements(TEs)outside of genes(including TEs sandwiched by genes and island TEs)for epigenetic silencing.Our results reveal new functions of AAE in RNA processing and epigenetic silencing,and thus representimportantadvancesinepigenetic regulation.