Cell Metabolism
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2025
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IF 30.9
Tiezhu Shi,Jialiang Shao,Yufeng Ding,Hong Tang,Xiangyin Tan,Sisi Zhou,Shaoqing Yu,Xiang Wang,Guanzhen Yu,Ninghan Feng,Xiongjun Wang
Metabolic adaptations involved in tumor metastasis and immune evasion merit investigation. Here, using in vivo metabolic CRISPR/Cas9 knockout screening, we identified xylulokinase (XYLB) as a tumor suppressor that impairs lung colonialization by producing xylulose 5-phosphate (Xu5P), which promotes CD8 + T cell cytotoxicity. Mechanistically, CD8 + T cells express relatively high levels of solute carrier family 35 member E2 (SLC35E2), a homolog of the plant Xu5P transporter, to facilitate Xu5P uptake and subsequently intensify the pentose phosphate pathway and glycolysis for energy/redox balance. Furthermore, we revealed that Xu5P potentiates CD8 + T cell response by promoting Xu5P-responsive progenitor-like SLC35E2 + CD8 + exhausted T cells via tet methylcytosine dioxygenase 3 (TET3)-mediated DNA demethylation of the Tcf7 promoter. Clinically, elevated XYLB or blood Xu5P correlates with enhanced CD8 + T cell efficacy and reduced metastasis. In murine models, Xu5P supplementation or adopting Xu5P-rich diets synergizes with anti-PD-1 therapy to enhance antitumor immunity. These findings offer insights into the potentiality of dietary interventions for metastatic cancer.
研究领域:
癌症生物学
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免疫学
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代谢工程
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分子生物学
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遗传学
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肿瘤免疫学
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营养科学
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细胞信号传导
✓ 已验证
DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2021
·
IF 9.078
Yu Chen,Long Chen,Yitong Wang,Kaili Lin,Jiaqiang Liu
The repair of bone defects in patients with diabetes mellitus (DM) is a challenge in clinical treatment mainly because of inhibited osteogenesis caused by stem cell dysfunction. Our research found that high glucose induced the activation of GSK-3β, which played an important role in this process. Inhibited GSK-3β induced an acceptable osteogenic effect of lithium ions . However, whether lithium-containing biomaterials can exert a good bone-repair effect under the pathological state of DM is still unclear. Therefore, we synthesized a type of lithium-containing mesoporous bioactive glasses (Li-MBG), and explored their in vitro roles in regulating the proliferation, migration and osteogenic differentiation of BMSCs under the high-glucose microenvironment , and the underlying mechanism. Meanwhile, Li-MBG/PLGA composite scaffolds were prepared by 3D printing , followed by investigating their in vivo effects on repairing critical skull defects of DM mice. We found that Li-MBG reversed high glucose-induced suppression in the proliferation, migration and osteogenic differentiation of BMSCs by upregulating Itga3 and activating the β-catenin/Tcf7/Ccn4 signaling pathway. Li-MBG/PLGA composite scaffolds could effectively repair skull defects of DM mice by recruiting stem cells, presenting an excellent osteogenesis effect. Our findings provide references for clinical bone defect repair in DM patients.
研究领域:
生物材料
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组织工程
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糖尿病研究
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骨再生
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产品关联
DOI
高影响因子
HUMAN GENE THERAPY
·
2023
·
IF 4.2
Dr. Zhiguang Chen,Ms. Qi Zhao,Mr. Ran Zhang,Dr. Lianghong Chen,Mr. Songlan Gao,Dr. Yu Wang,Dr. Tiegang Li,Dr. Jinqi Xue
Substantial advances have been made in understanding the role of partial PDZ and LIM domain (PDLIM) family’s proteins in skeletal-related diseases. Yet, little is known about the effect of Pdlim1 on osteogenesis and fracture repair. This study aimed to investigate whether direct gene delivery using an adenovirus vector carrying Pdlim1 (Ad-oePdlim1) or encoding shRNA-Pdlim1 (Ad-shPdlim1) could affect the osteogenic activity of pre-osteoblastic MC3T3-E1 cells in vitro, and influence the fracture healing of mice in vivo. We found that Ad-shPdlim1 transfection contributed to the calcified nodule formation in MC3T3-E1 cells. Downregulation of Pdlim1 enhanced the alkaline phosphatase (ALP) activity and increased the expression of osteogenic markers (Runx2, Col1A1, osteocalcin and osteopontin). Further analysis indicated that Pdlim1 knockdown could activate β-catenin signaling, as evidenced by the accumulation of β-catenin in the nucleus and the increase levels of downstream regulators such as Lef1/Tcf7, Axin2, Cyclin D1 and Sox9. By contrast, Pdlim1 overexpression resulted in inhibition of the osteogenic activity of MC3T3-E1 cells. In vivo, at day 3 after fracture, Ad-shPdlim1 adenovirus particles were injected into the fracture site of the femur of mice, and the process of fracture healing was evaluated by X-ray, Micro-CT and histological examination. Local injection of Ad-shPdlim1 promoted the early cartilage callus formation, restored bone mineral density and accelerated cartilaginous ossification, with the upregulation of osteogenic gene (Runx2, Col1A1, osteocalcin and osteopontin) expression and activation of β-catenin signaling. Thus, we concluded that inhibition of Pdlim1 contributed to osteogenesis and fracture healing by activating the β-catenin signaling pathway.
研究领域:
分子生物学
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骨科
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再生医学
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基因治疗
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产品关联
DOI
PubMed
高影响因子
Lipids in Health and Disease
·
2024
·Vol. 23
·期 1
·1-17
·
IF 3.9
Tan Cuiyu,Huang Shuqiang,Xu Liying,Zhang Tongtong,Yuan Xiaojun,Li Zhihong,Chen Miaoqi,Chen Cairong,Yan Qiuxia
Background Changes in the oxidative stress and lipid metabolism (OSLM) pathways play important roles in polycystic ovarian syndrome (PCOS) pathogenesis and development. Consequently, a systematic analysis of genes related to OSLM was conducted to identify molecular clusters and explore new biomarkers that are helpful for the diagnostic of PCOS. Methods Gene expression and clinical data from 22 PCOS women and 14 normal women were obtained from the GEO database (GSE34526, GSE95728, and GSE106724). Consensus clustering identified OSLM-related molecular clusters, and WGCNA revealed co-expression patterns. The immune microenvironment was quantitatively assessed utilizing the CIBERSORT algorithm. Multiple machine learning models and connectivity map analyses were subsequently applied to explore potential biomarkers for PCOS, and nomograms were employed to develop a predictive multigene model of PCOS. Finally, the OSLM status of PCOS and the hub genes expression profiles were preliminarily verified using TUNEL, qRT‒PCR, western blot, and IHC assays in a PCOS mouse model. Results 19 differential expression genes (DEGs) related to OSLM were identified. Based on 19 DEGs that were strongly influenced by OSLM, PCOS patients were stratified into two distinct clusters, designated Cluster 1 and Cluster 2. Distinct differences in the immune cell proportions existed in normal and two PCOS clusters. The random forest showed the best results, with the least cross-entropy and the utmost AUC (cross-entropy: 0.111 AUC: 0.960). Among the 19 OSLM-related genes, CXCR1, ACP5, CEACAM3, S1PR4, and TCF7 were identified by a Bayesian network and had a good fit with PCOS disease risk by the nomogram (AUC: 0.990 CI: 0.968–1.000). TUNEL assays revealed more severe DNA damage within the ovarian granule cells of PCOS mice than in those of normal mice ( P < 0.001). The RNA and protein expression levels of the five hub genes were significantly elevated in PCOS mice, which was consistent with the results of the bioinformatics analyses. Conclusion A novel predictive model was constructed for PCOS patients and five hub genes were identified as potential biomarkers to offer novel insights into clinical diagnostic strategies for PCOS.
研究领域:
生殖医学
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分子生物学
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免疫学
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生物信息学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）