FASEB JOURNAL
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2020
·Vol. 34
·期 6
·8671-8685
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IF 4.966
Jie Cai,Diming Wang,Shulin Liang,Jinrong Peng,Fengqi Zhao,Jianxin Liu
During lactation, an improper glucose supply often threatens mammary gland (MG) health. However, information is limited on the metabolic trajectories and molecules that regulate lactating MGs with an excessive glucose supply. Based on the network analysis of transcriptome and microRNAs, we found that the oversupply of glucose-induced severe glucose metabolic disorders in MGs of lactating goats, shifting lactose synthesis to acute fermentative glycolysis which caused increased flux of glucose metabolism into lactate. Moreover, NF-κB2 played a key role in regulating glycolysis, exhibiting a metabolic shift when MGs had an excessive supply of glucose. In primary mammary epithelial cells, fermentative glycolysis, and intracellular concentration of reactive oxygen species (ROS) were reduced by ganoderic acid A through blocking NF-κB2, while activation of NF-κB2 with phorbol myristate acetate (PMA) upregulated fermentative glycolysis and increased cellular ROS accumulation under excessive glucose. Thus, we established an NF-κB2-targeting method to reform the metabolic shift toward glycolysis caused by glucose oversupply by integrating NF-κB2 blockade and intracellular ROS scavenging.
研究领域:
动物生理学
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分子生物学
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营养学
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DOI
PubMed
高影响因子
RSC Advances
·
2024
·Vol. 14
·期 18
·12864-12872
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IF 3.9
Lili Zhong,Datian Fu,Jin Xu,Linyan Tan,Haimei Wu,Min Wang
Ferroptosis is a newly discovered iron-dependent form of regulated cell death associated with high levels of hydroxyl radical (˙OH) production. Meanwhile, lysosome dysfunction has been shown to be one of the causes of ferroptosis. Although a variety of ˙OH-responsive fluorescent probes have been developed for detecting intracellular ˙OH in living cells, there are still only few lysosome-targeted probes to monitor the variation in lysosomal ˙OH levels during ferroptosis. Herein, we report a novel ˙OH-specific fluorescent probe HCy-Lyso, which is composed of the hydrocyanine and morpholine moiety. Upon treatment with ˙OH, its hydrocyanine unit was converted to the corresponding cyanine group, thus leading to a large π-conjugation extension of HCy-Lyso, accompanied by a significant fluorescence off–on response. Moreover, after reacting with ˙OH in an acidic environment, the protonation product of HCy-Lyso exhibits a higher fluorescence enhancement, which is suitable for detecting lysosomal ˙OH variation. HCy-Lyso has been utilized for imaging endogenous ˙OH in living cells under phorbol myristate acetate (PMA) stimuli and monitoring the changes in lysosomal ˙OH levels during ferroptosis. Thus, our study proposes a new strategy to design lysosome-targeted and ˙OH-responsive fluorescent probes to investigate the relationship between lysosomes and ferroptosis.
研究领域:
细胞生物学
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化学
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生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
·
2023
·
IF 1.6
Fang Wang,Xiu-Li Zhang,Jing-Ya Yang,Gang Zhou
ObjectiveOral lichen planus (OLP) is a T cell-mediated inflammatory condition in the oral cavity. Mucosal-associated invariant T (MAIT) cells are gaining more relevance in immune diseases because they can be activated by cytokines without T cell receptor stimulation. Herein, we tested the effect of interleukin-23 (IL-23) on the activation status of OLP MAIT cells.MethodsPeripheral blood mononuclear cells (PBMCs) isolated from OLP patients were stimulated by IL-23 in the absence or presence of phorbol myristate acetate (PMA) and ionomycin. The activation status of MAIT cells was analyzed by flow cytometry after staining for CD3, CD4, CD8, CD161, TCR Vα7.2, and CD69.ResultsThe fraction of MAIT cells in OLP peripheral blood was approximately 0.38% to 3.97%, and CD8+ subpopulations overwhelmed CD4+ cells. The mean percentages of OLP MAIT cells in PBMCs and CD8+MAIT cells in MAIT cells were approximately 40%. PMA and ionomycin significantly increased CD69 expression on OLP T cells, MAIT cells, and CD8+MAIT cells. Cells with enhanced activation had different responsiveness to exogenous IL-23, showing increased CD69 expression on OLP T cells, decreased CD69 on OLP CD8+MAIT cells, and no significant change on OLP MAIT cells.ConclusionsIL-23 showed different effects on the activation status of OLP MAIT cells and CD8+MAIT cells.
研究领域:
免疫学
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皮肤科
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口腔医学
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DOI
PubMed
高影响因子
Biomarker Research
·
2024
·Vol. 12
·期 1
·1-16
·
IF 9.5
Wang Zhen,Liu Zhongwen,Zhou Pan,Niu Xiaona,Sun Zhengdao,He Huan,Zhu Zunmin
Background Megakaryocytic differentiation is a complicated process regulated by a series of transcription factors in a context- and stage-dependent manner. Recent studies have suggested that krüppel-like transcription factor 2 (KLF2) is involved in the control of embryonic erythroid precursor cell differentiation and maturation. However, the function and mechanism of KLF2 in regulating megakaryocytic differentiation remain unclear. Methods The expression patterns of krüppel-like transcription factors (KLFs) during megakaryocytic differentiation were identified from public databases. Phorbol 12-myristate 13-acetate (PMA) treatment of the myeloid-erythroid-leukemic cell lines K562 and HEL were used as cellular megakaryocytic differentiation models. A lentiviral transduction system was utilized to achieve the goal of amplifying or reducing KLF2. The expression of KLF2 was examined using real-time PCR and western blot. The impact of KLF2 on the megakaryocytic differentiation of K562 cells was examined by flow cytometry, Giemsa staining, Phalloidin staining and western blot. RNA-sequencing (RNA-seq) and chromatin immunoprecipitation-sequencing (ChIP-seq) technologies were used to identify the KLF2-regulated targets. Results KLF2 is increased in the maturation process of megakaryocytes. KLF2 overexpression accelerated the PMA-induced megakaryocytic differentiation, as reflected by an increased percentage of CD41/CD61 cells, an increased number of polyploid cells, and an elevated expression of P21 and P27. KLF2 knockdown exhibited the opposite results, indicating that KLF2 knockdown suppressed the megakaryocytic differentiation. Further, combination of the RNA-seq and ChIP-seq results suggested that chimerin 1 (CHN1) and potassium voltage-gated channel subfamily Q member 5 (KCNQ5) may be target genes regulated of KLF2. Both CHN1 and KCNQ5 knockdown could block the megakaryocytic differentiation to some content. Conclusion This study implicated a regulatory role of KLF2 in megakaryocytic differentiation, which may suggest KLF2 as a target for illness with abnormal megakaryocytic differentiation.
研究领域:
血液学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Natural Product Communications
·
2020
·
IF 0.468
Dongli Li,Xiaodan Tang,Chang Liu,Huifang Li,Shuzhen Li,Shili Sun,Xi Zheng,Panpan Wu,Xuetao Xu,Kun Zhang,Hang Ma
Published data from in vitro assays support the anti-inflammatory effects of jasmine (Jasminum grandiflorum Linn.) but limited studies are reported in animal models. Herein, the anti-inflammatory effects of jasmine flower extracts (JFEs) including ethanol extract (JF-EE), petroleum ether extract (JF-PEE), ethyl acetate extract (JF-EAE), and n-butanol extract (JF-BE) were evaluated in a mouse ear edema model. Acute mouse ear skin inflammation was induced by tetradecanoylphorbol acetate (TPA; 125 µg/mL) and then treated with JFEs (100 mg/mL) or dexamethasone (DEX; 6.25 mg/mL; as a positive control). Jasmine flower extracts alleviated ear edema by reducing TPA-increased ear thickness and ear weight by 30.8% to 64.1% and 24.0% to 47.1%, respectively, whereas DEX showed comparable activity (by 71.8% and 49.1%, respectively). Their anti-inflammatory effects were supported by data from the immunohistochemical assays. Jasmine flower extracts reduced the inflammatory cells (from 5.5- to 9.5-fold) and the expressions of inflammation related enzymes including cyclooxygenase-2 and inhibitor of kappa-B kinase (from 1.9- to 2.8-fold and from 7.1- to 11.0-fold, respectively). Findings from this study showed that JFEs were able to ameliorate TPA-induced mouse skin inflammation. However, future studies on the underlying mechanisms of jasmine flower’s anti-inflammatory effects are warranted.
研究领域:
药理学
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炎症研究
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天然产物
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产品关联
DOI
高影响因子
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