Human Cell
·
2022
·Vol. 35
·期 5
·1440-1452
·
IF 4.374
Song Guiyu,Jin Feng
Preeclampsia (PE) is a pregnancy-associated disease, which is the major cause of mortality on maternity and perinatal infants. It is hypothesized that PE is a consequence of the dysfunction of the trophoblast cells. Pleckstrin homology-like domain, family A, member 2 (PHLDA2) was shown to inhibit the proliferation, migration, and invasion of trophoblast cells in our previous studies. However, the mechanism by which PHLDA2 affects trophoblast cell function has not been clarified. In the current study, co-immunoprecipitation (Co-IP) with mass spectroscopy analysis was used to explore the proteins that interacted with PHLDA2. A total of 291 candidate proteins were found to be associated with PHLDA2. The interaction between PHLDA2 and Rho guanine nucleotide dissociation inhibitor (RhoGDI) 1 was identified by Co-IP and immunofluorescence staining. Western blot analysis indicated that overexpression of PHLDA2 resulted in upregulation of the RhoGDI1 protein levels, which were stabilized in the presence of cycloheximide. Similarly, overexpression of RhoGDI1 promoted PHLDA2 expression and its stability. Furthermore, pull-down and Co-IP results indicated that PHLDA2 repressed the activity of Rho guanosine triphosphate hydrolase family proteins by regulating RhoGDI1 expression. In addition, RhoGDI1 expression was upregulated in the placental tissues of patients with PE. The effects of the suppression of PHLDA2 expression on proliferation, migration, and invasion of trophoblast cells were partly abrogated following knockdown of RhoGDI1. Taken together, the data indicated that RhoGDI1 mediated regulation of PHLDA2 on the biological behavior of trophoblast cells and may participate in the pathophysiology of PE.
研究领域:
妇产科学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Changcan Li,Gang Xu,Yinhan Wang,Laixin Huang,Feiyan Cai,Long Meng,Bao Jin,Zhuoran Jiang,Hang Sun,Haitao Zhao,Xin Lu,Xingting Sang,Pengyu Huang,Fei Li,Huayu Yang,Yilei Mao,Hairong Zheng
Acoustic holography (AH), a promising approach for cell patterning, emerges as a powerful tool for constructing novel in vitro 3D models that mimic organs and cancers features. However, understanding changes in cell function post-AH remains limited. Furthermore, replicating complex physiological and pathological processes solely with cell lines proves challenging. Here, we employed acoustical holographic lattice to assemble primary hepatocytes directly isolated from mice into a cell cluster matrix to construct a liver-shaped tissue sample. For the first time, we evaluated the liver functions of AH-patterned primary hepatocytes. The patterned model exhibited large numbers of self-assembled spheroids and superior multifarious core hepatocyte functions compared to cells in 2D and traditional 3D culture models. AH offers a robust protocol for long-term in vitro culture of primary cells, underscoring its potential for future applications in disease pathogenesis research, drug testing, and organ replacement therapy.
CAS / MDL:
研究领域:
生物医学工程
·
组织工程
·
细胞生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2022
·
IF 4.831
Junjun Shao,Shuai Sun,Da Zhan,Lipeng Pan,Guangzong Min,Xiaobao Li,Kailun Huang,Wei Chen,Likun Yang,Xiang-Yang Liu,Naibo Lin
As a kind of reactive oxygen species, peroxynitrite is related to various diseases closely such as cancer and neurodegenerative diseases. Constructing probes with highly specific ability and a wide linear detection range for peroxynitrite detection is crucial for understanding the pathogenesis of related diseases and optimizing treatments. In this work, we developed a novel luminescent ratiometric fluorescence nanoprobe (PC-CDs) based on carbon dots and phycocyanin. PC-CDs are constructed by amidation reaction between carbon dots and phycocyanin. The nanoprobe we obtained has a good ability of distinguishing peroxynitrite from other reactive oxygen species and interfering substances. Moreover, the linear range of the nanoprobe is 0.5–100 μM and the limit of detection is 0.5 μM when detecting peroxynitrite. In the spiked recovery experiments under phosphate buffered saline (PBS) environment, our nanoprobe has a good recovery performance and the recovery is 99% − 104%, which will be beneficial to the further development of peroxynitrite testing and the research progress of related diseases. Finally, we discuss the quenching mechanism of peroxynitrite for nanoprobe, and found that there is the combination of dynamic and static quenching in the quenching process.
研究领域:
分析化学
·
生物医学工程
·
纳米技术
·
疾病诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Manqi Xia,Jing Zhang,Yang Hu,Ziyan Chen,Yanan Ke,Shujuan Zhang,Zeen Yang,Xin Tian,Jingyao Liang,Yumei Liu
Background: Acne vulgaris is a prevalent chronic inflammatory disorderof the skin and oral isotretinoin is one of the most effective treatments forsevere acne with incompletely understood mechanisms. The aim of thisstudy was to investigate the pathogenesis of acne and the therapeuticmechanisms underlying isotretinoin treatment from integrated human plasma metabolomics and proteomics.Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) full-spectrum metabolomics and four-dimensional data-independent acquisition (4D-DIA) quantitative proteomics were employed to analyze plasma samples from patients with group AG (severe acne group), group AG1 (severe acne group1, before isotretinoin treatment), group TG (isotretinoin treatment group) and group CG (control group). Bioinformatics statistical analysis were employed to analyze the metabolomic and proteomic data.Results: 489 differentially expressed metabolites (DEMs) were detected in the plasma from patients with severe acne compared to controls. Isotretinoin treatment normalized the dysregulation of 94 metabolites, including inositol 1,3,4-trisphosphate (Ins(1,3,4)P3), 11-cis-retinol, thyroxine (T4), androstenediol, estrone 3-sulfate, bovinicacid, n-oleoylethanolamine, LPS(20:1), Cer(d16:1/23:0) and TG(17:1 18:2 18:3). Additionally, 36 differentially expressed proteins (DEPs) were identified in patients before and after isotretinoin treatment. Notably, downregulation of acyl-CoA synthetase long-chain family member 4 (ACSL4) suggests a potential therapeutic mechanism for isotretinoin, while upregulation of monoacylglycerol O-acyltransferase 2 (MOGAT2) may mediate the elevation of blood lipids and the correction of some abnormal lipids. Isotretinoin modulates multiple pathways, including inositol phosphatemetabolism, glycerolipid metabolism, thyroid hormone synthesis and insulin resistance.Conclusion: Important DEMs, DEPs and metabolic pathways were identified in this study, which will help clarify the pathogenesis of acneand the potential mechanisms of isotretinoin in the treatment of acne, andidentify novel targets for severe acne treatment and side effect reduction.
研究领域:
皮肤病学
·
药理学
·
生物信息学
·
系统生物学
·
代谢紊乱
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RESEARCH IN MICROBIOLOGY
·
2025
·
IF 3.4
Ping Lu,Juan Xue,Xuemeng Ji
Klebsiella pneumoniae is a major cause of endogenous endophthalmitis, a rapidly progressing intraocular infection associated with severe inflammation and vision loss. The vitreous body presents a hypoxic and iron-restricted environment, yet the bacterial metabolic adaptations that enable persistence in this niche remain largely unknown. Here, we show that K. pneumoniae undergoes metabolic reprogramming to facilitate intraocular survival, characterized by enhanced glycolysis and siderophore-mediated iron acquisition. Proteomic profiling under vitreous-mimicking conditions revealed significant upregulation of PfkA, PykF, and EntB. Targeted deletion of these genes impaired bacterial growth under hypoxia and iron limitation, and significantly reduced intraocular colonization, proinflammatory cytokine production, and visual impairment in a murine model. Double mutants lacking both glycolytic and iron acquisition pathways were nearly avirulent. Correspondingly, infected eyes exhibited lower levels of lactate and iron, reflecting reduced bacterial metabolic activity. These findings establish glycolysis and iron acquisition as critical determinants of K. pneumoniae virulence in the eye and provide insight into the metabolic strategies underpinning bacterial persistence in nutrient-limited host environments.
研究领域:
微生物学
·
免疫学
·
眼科学
·
代谢
·
发病机制
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Aiying Shi,Juan Xue,Yongshuai Liu,Jianhui Wang,Xiaofei Liu,Lianqiang Song,Shanming Sun
Cronobacter sakazakii is a Gram-negative, foodborne pathogen associated with severe infections, particularly in infants and immunocompromised individuals. Given its significant public health implications and its remarkable resilience in powdered infant formula, understanding the genetic factors that contribute to its virulence and environmental tolerance is crucial. This study focuses on the kdpE gene in Cronobacter sakazakii , part of a two-component regulatory system known for its role in adaptation to environmental stress. A kdpE knockout mutant of Cronobacter sakazakii was constructed to evaluate its effects on bacterial growth, virulence, biofilm formation, and desiccation tolerance. The results revealed that kdpE deletion reduced bacterial growth and virulence, as evidenced by higher survival rates in rats infected with the Δ kdpE mutant compared to the wild-type strain. Notably, the Δ kdpE mutant showed significant downregulation of proteins involved in carbon metabolism and respiratory activity, while proteomic analysis revealed increased deamidation of proteins related to glycolysis. Furthermore, biofilm formation was significantly impaired in the mutant, although its desiccation tolerance was enhanced, attributed to the upregulation of the molecular chaperone GrpE. These findings suggest that kdpE plays a crucial role in regulating the virulence and environmental adaptability of Cronobacter sakazakii , with implications for understanding its pathogenic mechanisms and developing preventive measures.
研究领域:
微生物学
·
分子生物学
·
遗传学
·
发病机制
·
食品微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC Nephrology
·
2025
·Vol. 26
·期 1
·1-14
·
IF 2.4
Wang Yu,Zhang Jingjing,Tang Qian
Background Diabetic nephropathy (DN) is a primary contributor to end-stage renal disease, yet the underlying molecular mechanisms remain incompletely understood. This study aims to elucidate the role of RNA-binding proteins (RBPs) and RBP-alternative splicing (AS) regulatory networks in the pathogenesis of DN. Methods Two RNA-seq datasets (GSE117085 and GSE142025) were retrieved from the Sequence Read Archive (SRA) database. Regulated alternative splicing events (RASEs) and genes (RASGs) of RASEs, along with differentiated RBPs, were identified. Validated differentiated RBPs were correlated with clinical features using the Nephroseq v5 online platform. Using the DN mouse model and RT-qPCR, validated the alternative splicing of RNA. Results Our analysis revealed 15 differentiated RBP genes and 423 RASEs in the kidney cortex of DN rats compared to controls. Enrichment analysis highlighted lipid metabolism pathways for RASGs. Seven of the identified RBPs were validated in kidney biopsy samples from DN patients versus controls. A co-deregulatory network was constructed based on dysregulated RBPs and RASEs, with select RASGs identified. In vivo experiments, compared to normal mice, the mRNA levels of RPS19 were significantly elevated in the renal tissues of DN mice, while the levels of CPEB4 and CRYZ were markedly decreased. Conclusion In conclusion, this study provides evidence implicating dysregulated RBPs and RBP-AS regulatory networks in the development of diabetic nephropathy. The validated RBPs exhibited close associations with clinical biomarkers, reinforcing their potential as therapeutic targets for DN. These findings enhance our understanding of the molecular basis of DN and offer new insights for future research and intervention strategies. Clinical trial Not applicable.
研究领域:
分子生物学
·
基因组学
·
肾脏病学
·
生物信息学
·
发病机制
✓ 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）