Frontiers in Cell and Developmental Biology
·
2022
·
IF 6.081
Zhou Tong,Chen Guobin,Chen Meng,Wang Yubin,Zou Guiwei,Liang Hongwei
Sex dimorphism is a key feature of Chinese soft-shelled turtle (Pelodiscus sinensis). The males (M) have higher econosmic value than females (F) due to wider calipash and faster growth. Exogenous hormones like estradiol and methyltestosterone can induce sexual reversal to form new phenotypes (pseudo-female, PF; pseudo-male, PM) without changing the genotype. The possibility of inducing sexual reversal is particularly important in aquaculture breeding, but the underlying biological mechanisms remain unclear. Here we applied a direct RNA sequencing method with ultralong reads using Oxford Nanopore Technologies to study the transcriptome complexity in P. sinensis. Nanopore sequencing of the four gender types (M, F, PF, and PM) showed that the distribution of read length and gene expression was more similar between same-sex phenotypes than same-sex genotypes. Compared to turtles with an M phenotype, alternative splicing was more pronounced in F turtles, especially at alternative 3′ splice sites, alternative 5′ splice sites, and alternative first exons. Furthermore, the two RNA methylation modifications m5C and m6A were differentially distributed across gender phenotypes, with the M type having more modification sites in coding sequence regions, but fewer modification sites in 3′UTR regions. Quantitative analysis of enriched m6A RNAs revealed that the N6-methylated levels of Odf2, Pacs2, and Ak1 were significantly higher in M phenotype individuals, while the N6-methylated levels of Ube2o were reduced after sexual reversal from both M and F phenotypes. Taken together, these findings reveal an important role of epigenetics during sexual reversal in Chinese soft-shelled turtles.
研究领域:
发育生物学
·
分子生物学
·
水产养殖学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2021
·
IF 9.776
Lina Liang,Yan Peng,Liyan Qiu
Inducing mitochondrial malfunction is an appealing strategy to overcome tumor multidrug resistance (MDR). Reported here a versatile mitochondrial-damaging molecule, vitamin E succinate (VES), is creatively utilized to assist MDR reversal of doxorubicin hydrochloride (DOX·HCl) via a nanovesicle platform self-assembled from amphiphilic polyphosphazenes containing pH-sensitive 1H-benzo-[d]imidazol-2-yl) methanamine (BIMA) groups. Driven by multiple non-covalent interactions, VES is fully introduced into the hydrophobic membrane of DOX·HCl-loaded nanovesicles with loading content of 23.5%. The incorporated VES also offers robust anti-leakage property toward DOX·HCl under normal physiological conditions. More importantly, upon release within acidic tumor cells, VES can target mitochondria and result in various dysfunctions including excessive generation of reactive oxygen species (ROS), mitochondrial membrane potential (Δ Ψ m ) loss, and inhibited adenosine triphosphate (ATP) synthesis, which contribute to cell apoptosis and insufficient energy supply for drug efflux pumps . Consequently, the killing-effect of DOX·HCl is significantly enhanced toward drug resistant cancer cells at the optimal mass ratio of DOX·HCl to VES. Further in vivo antitumor investigation on nude mice bearing xenograft drug-resistant human chronic myelogenous leukemia K562/ADR tumors verifies the extremely enhanced anti-tumor efficacy of the dual drug-loaded nanovesicle with the tumor inhibition rate (TIR) of 82.38%. Collectively, this study provides a s safe, facile and promising strategy for both precise drug delivery and MDR eradication to improve cancer therapy.
研究领域:
肿瘤学
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药物递送系统
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2019
·Vol. 42
·期 24
·3611-3620
·
IF 2.516
Renxing Yi,Renjie Fu,Dapeng Li,Jin Qi,Haichun Liu
Multidrug resistance is recognized as one of the main reasons leading to the failure of chemotherapy. Studies have shown that glutathione S-transferase inhibitors could be regarded as multidrug resistance reversal agents. Herein, a method of applying enzyme immobilization, molecular docking, and high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was employed to screen glutathione S-transferase inhibitors from natural products. Magnetic mesoporous silica microspheres were synthesized and modified with a poly(dopamine) layer, which has a large quantity of amino, enabling further non-covalent binding with glutathione S-transferase. Moreover, the immobilization conditions, namely, potential of hydrogen, catalase concentration, reaction temperature and reaction time, were optimized. In total, six potential compounds were isolated and identified from Perilla frutescens (L.) Britt leaves and green tea and molecular docking was applied to identify the binding site. Rosmarinic acid, (−)-epigallocatechin-3- O -gallate and (−)-epicatechin-3-gallate showed higher binding affinity than the compounds, and their half maximal inhibitory concentration values were further determined. The results suggested that this proposed method was effective and convenient for identifying glutathione S-transferase inhibitors from natural products.
研究领域:
药物化学
·
分析化学
·
生物信息学
✓ 已验证
DOI
高影响因子
Cancer Immunology Research
·
2022
·Vol. 10
·期 4
·525-539
·
IF 12.02
Chen Yu,Cai Qiaomei,Pan Chaohu,Liu Wancheng,Li Lili,Liu Junxiao,Gao Meiling,Li Xiaorong,Wang Liguo,Rao Yu,Yang Heng,Cheng Genhong
Inhibitors of cyclin-dependent kinase-2 (CDK2) are commonly used against several solid tumors, and their primary mechanisms of action were thought to include cell proliferation arrest, induction of cancer cell apoptosis and induction of differentiation. Here, we found that CDK2 inhibition by either small molecular inhibitors or genetic Cdk2 deficiency promoted antitumor immunity in murine models of fibrosarcoma and lung carcinoma. Mechanistically, CDK2 inhibition reduced phosphorylation of RB protein and transcription of E2F-mediated DNA methyltransferase 1 (DNMT1), which resulted in increased expression of endogenous retroviral RNA and type I IFN (IFN-I) response. The increased IFN-I response subsequently promoted antitumor immunity by enhancing tumor antigen presentation and CD8 + T-cell infiltration. Our studies provide evidence that inhibition of CDK2 in cancer cells suppresses tumor growth by enhancing antitumor immune responses in the tumor microenvironment, suggesting a new mechanism to enhance antitumor immunity by CDK2 inhibitors.
研究领域:
肿瘤学
·
免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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