Biomedical subjects

Jingjing Liu

Publications and source records attributed to Jingjing Liu.

7 recordsLinked to original sources

PubMed2026

ATX1-COMPASS-like complex participates in the bud dormancy release of tree peony by regulating H3K4me3 modification.

Bud dormancy release in woody plants is crucial for survival, regrowth, flowering, and fruiting. Tree peony (Paeonia suffruticosa), an important ornamental and economic plant, undergoes bud endodormancy in winter, and sufficient chilling duration and exogenous gibberellins (GAs) can effectively break the dormancy. However, the epigenetic regulation mechanism remains poorly understood. Here, immunoblotting revealed that H3K4me3, but not H3K4me1 or H3K4me2, was associated with chilling- and GA3-induced dormancy release. Chromatin immunoprecipitation sequencing (ChIP-seq) combined with RNA-seq results revealed that H3K4me3 enriched near transcription start sites (TSS). H3K4me3 enrichment genes (HEGs) and differentially expressed genes (DEGs) were commonly enriched in KEGG pathways, such as plant hormone signal transduction and MAPK signaling. The expression patterns of these marker genes, such as EARLY BUD-BREAK 3 (PsEBB3), CYCLIND3.1 (PsCYCD3.1), CYCLIND3.3 (PsCYCD3.3), and β-1,3-glucanase 6 (PsBG6), were correlated with their H3K4me3 enrichment and were validated by chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR). Four COMPASS-like component homologs and one histone methyltransferase were screened; among them, PsWDR5a, PsRBL, PsASH2R, and PsATX1 were upregulated by prolonged chilling and GA3 treatments. Yeast two-hybrid (Y2H), yeast three-hybrid (Y3H), luciferase complementation (LCA), and co-immunoprecipitation (Co-IP) analyses revealed that PsRBL interacts with PsWDR5a and PsASH2R as a bridge. PsATX1 was confirmed as an H3K4me3 methyltransferase and interacted with PsWDR5a and PsRBL to form the PsATX1-COMPASS-like complex using Y2H, LCA, and Co-IP assays. Functional analyses showed that PsWDR5a, PsRBL, PsASH2R, and PsATX1 significantly promoted budburst by elevating genomic H3K4me3 levels. Our findings provide insights into the epigenetic regulation of dormancy transitions in woody perennials.

Histones↗

PubMed2026

Intratumoral Sotigalimab with Pembrolizumab Induces Rapid Activation of Antigen-Presenting Cells and Drives Antitumor Responses in Non-injected Tumors in Metastatic Melanoma: A Phase I/II Study.

UNLABELLED: Immune checkpoint blockers (ICB) improve outcomes in metastatic melanoma (MM), but resistance limits benefit. This phase I/II (NCT02706353) study evaluated intratumoral sotigalimab (anti-CD40 agonist) with pembrolizumab in 32 patients with ICB-naïve MM. Primary endpoints were safety and objective response rate (ORR). Sotigalimab was well tolerated. At the recommended phase II dose, the ORR was 50%, and the disease control rate was 92%, with ORRs of 67% in injected and 50% in non-injected tumors. Multiomic analyses of tumor and blood showed that sotigalimab effectively engaged the CD40 pathway, boosting infiltration and activation of myeloid cells, including CD11c+DC-LAMP+ dendritic cells and macrophages. The combination therapy activated innate and adaptive immunity in injected tumors and cytotoxic responses in non-injected tumors. T-cell receptor sequencing showed increased T-cell clonality with expanded new clones shared across tumors. Clinical responses correlated with these immunologic changes but not with baseline features associated with response to anti-PD-1 monotherapy. SIGNIFICANCE: In this study, we provide compelling data that intratumoral sotigalimab combined with pembrolizumab is safe, activates antigen-presenting cells, and elicits broad innate and adaptive immune responses in both injected and non-injected tumors, supporting further randomized phase II trials to evaluate sotigalimab's potential to enhance anti-PD-1 therapy through "in situ" immunization.

Humans↗

PubMed2026

Decreased TXNRD1 is associated with resistance to tagraxofusp in blastic plasmacytoid dendritic cell neoplasms, as seen in phase II.

Tagraxofusp is a CD123-targeted therapy comprised of a recombinant human interleukin-3 (IL-3) fused to a truncated diphtheria toxin payload. It is the first approved treatment specifically for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). To identify biomarkers of response, bone marrow samples from 12 BPDCN patients who were treated with tagraxofusp in the pivotal phase II trial (NCT02113982) were profiled longitudinally using a gene panel and single-cell RNA sequencing. Residual tumor cells following tagraxofusp expressed lower levels of TXNRD1 that would reduce the efficacy of tagraxofusp. In support of this, enzymatic inhibition of TXNRD1 resulted in higher viability of CAL-1 BPDCN cells following tagraxofusp. Responders had either wild-type or missense TET2 mutations, while transient and non-responders had at least one truncating TET2 mutation. Examples of these mutations within the catalytic domain of TET2 were constructed and transduced into cells. Missense and truncating mutants displayed reduced sensitivities to hypomethylating agents and prolonged S-phase stasis. These results suggest that the levels of TXNRD1 interact with intrinsic TET2 truncating mutations within the bone marrow to modulate patient response to tagraxofusp.

Female↗

PubMed2026

Multi-omics reveal molecular changes during suspension adaptation of HEK293 cells.

Human embryonic kidney 293 (HEK293) cells have been successfully adapted from adherent to suspension culture and widely applied in both scientific research and the pharmaceutical industry. Although some studies investigated the variances between established adherent and suspension HEK293 cells of different strains, specific alterations in the cells during this consecutive process of suspension adaptation and possible factors driving this process have not been well described. Here, we adapted adherent HEK293 to suspension with desirable cell growth and high productivity for recombinant adenoviral vectors, and cells at several stages throughout the process were characterized. Slower cell growth, lower glucose uptake, increased lactate production, and weaker cell-surface adhesion were observed in suspension cells compared to their adherent counterparts. We further performed transcriptomics, proteomics, and metabolomics analysis to identify key cellular switches. A total of 2476 differentially expressed genes were found, including 1218 upregulated and 1258 downregulated genes in suspension cells. A similar and correlated pattern was observed in the proteomic study, and 702 differentially expressed metabolites were identified by untargeted metabolomics. In light of enrichment analysis, we summarized that HEK293 adherent cells survived and adapted to suspension culture via structural remodeling, metabolic shift and stress resistance. Our results provide a molecular enlightenment for suspension adaptation and potential directions for rational modification of HEK293 cell lines for future use. KEY POINTS: • Suspension adaptation reduced adhesion and reshaped the HEK293 cytoskeleton. • Multi-omics revealed metabolic rewiring and enhanced stress resistance. • An optimized suspension line outperformed an internal HEK293 suspension reference.

Humans↗

PubMed2026

Causal effect of chloride intracellular channel protein 5 on chronic periodontitis: A Mendelian randomization study.

This study aimed to evaluate the potential causal effect of chloride intracellular channel protein 5 (CLIC5) on the risk of chronic periodontitis (CP) using a Mendelian randomization (MR) approach. MR analysis was conducted utilizing publicly available summary statistics from genome-wide association studies summary statistics for CLIC5 and CP. Multiple MR methods, including inverse variance weighted, MR Egger, weighted median and weighted mode, were employed to estimate the causal effects. Sensitivity analyses, comprising leave-one-out and heterogeneity assessments were performed to evaluate the robustness of our findings. This MR analysis consistently revealed a negative association between CLIC5 and CP, with statistical significance achieved using the inverse variance weighted and weighted median methods. The concordant effect estimates obtained from all methodological approaches collectively indicated a potential protective effect of CLIC5 against CP. The sensitivity analyses further confirmed the robustness of these findings. This study provides genetic evidence suggesting a potential causal association between increased CLIC5 levels and decreased risk of CP. These findings augment the existing literature implicating chloride channel proteins in modulating the inflammatory processes pertinent to periodontal health. Further investigation is warranted to decipher the underlying biological mechanisms and to explore the potential of CLIC5 as a therapeutic target for CP.

Chloride Channels↗

PubMed2025

Translation Co-factor PABP-interacting protein 11 moonlights as a transcriptional activator to modulate callose synthesis gene expression.

The development of rice fertility is a complex process, which is precisely regulated by numerous genes. In this study, we cloned and characterized OsPAIP11, a PABP-interacting protein that functions as an auxiliary factor in translation initiation. The ospaip11 exhibited multiple defects, including impaired callose synthesis, delayed tapetum apoptosis, and abnormal pollen wall development, which are essentially consistent with the phenotype of the allelic mutant dcet1. Subcellular localization analysis revealed that OsPAIP11 is localized in both the cytoplasm and nucleus. Interestingly, further investigation demonstrated that the RRM2 domain of OsPAIP11 exhibits transcriptional activation activity. Moreover, OsPAIP11 directly binds to the promoter of the callose synthesis-related genes GLUCAN SYNTHASE-LIKE 5 (OsGSL5) and OsGAMYB, thereby regulating their transcription and influencing callose biosynthesis during pollen development. Additionally, OsPAIP11 also interacts with the translation initiation factor and auxiliary factors. These findings suggest that OsPAIP11 modulates male fertility primarily by regulating the transcription of callose synthesis-related genes and may also participate in the translation process.

Glucans↗

PubMed2023

Photoaffinity labeling coupled with proteomics identify PDI-ADAM17 module is targeted by (-)-vinigrol to induce TNFR1 shedding and ameliorate rheumatoid arthritis in mice.

Various biological agents have been developed to target tumor necrosis factor alpha (TNF-α) and its receptor TNFR1 for the rheumatoid arthritis (RA) treatment, whereas small molecules modulating such cytokine receptors are rarely reported in comparison to the biologicals. Here, by revealing the mechanism of action of vinigrol, a diterpenoid natural product, we show that inhibition of the protein disulfide isomerase (PDI, PDIA1) by small molecules activates A disintegrin and metalloprotease 17 (ADAM17) and then leads to the TNFR1 shedding on mouse and human cell membranes. This small-molecule-induced receptor shedding not only effectively blocks the inflammatory response caused by TNF-α in cells, but also reduces the arthritic score and joint damage in the collagen-induced arthritis mouse model. Our study indicates that targeting the PDI-ADAM17 signaling module to regulate the shedding of cytokine receptors by the chemical approach constitutes a promising strategy for alleviating RA.

Mice↗