INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Huan Chen,Jin Liu,Jia Zhang,Yuqian Chen,Yan Wang,Yuanjie Qiu,Huizhong Hu,Limin Chai,Qianqian Zhang,Qingting Wang,Manxiang Li
Bromodomain-containing protein 4 (BRD4) is recognized as a member of the bromodomain and extraterminal (BET) family that is involved in the airway inflammation and airway remodeling of asthma. However, the underlying mechanisms of BRD4 in airway smooth muscle cells (ASMCs) proliferation and airway remodeling remain unclear. Primary cultured rat ASMCs and ovalbumin (OVA)-induced rat asthma models were applied to address these issues in the present study. We showed that transforming growth factor β1 (TGF-β1) increased the protein expression of ubiquitin specific peptidase 22 (USP22), which deubiquitinated BRD4 therefore increased its expression, and then resulted in the upregulation of glioma-associated oncogene homolog 1 (GLI1) and osteopontin (OPN) leading to ASMCs proliferation. We further confirmed that induction of TGF-β1 sequentially upregulated USP22, BRD4, GLI1 and OPN leading to airway remodeling in OVA-induced rat asthma models, targeting TGF-β1/USP22/BRD4/GLI1/OPN pathway axis effectively attenuated airway remodeling and asthma development. Our study provides novel sights to understand the role of TGF-β1/USP22/BRD4/GLI1/OPN axis in airway remodeling, and targeting this pathway might have potential value for the prevention and treatment of asthma.
研究领域:
医学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Lei Wang,Yufeng Bai,Dan Ma,Wenxiu Liu,Zhiyu Shi,Chunnan Liu,Meng Zhao,Huiying Wang,Liying Luo,Jinyu Chi
Hypertension is a risk factor for cardiovascular diseases, primarily through its induction of pathological vascular and ventricular remodeling. TEA domain transcription factor 3 (TEAD3) is a transcription factor highly expressed in myocardial tissues. PDZ domain-containing 1 (PDZK1) has been reported to protect blood vessels. This study discovered decreased expression of TEAD3 and PDZK1 in the aortic tissues of spontaneously hypertensive rats (SHRs). TEAD3 overexpression in SHR vascular smooth muscle cells (VSMCs) driven by the SM22α promoter was achieved through adeno-associated virus delivery. TEAD3 overexpression alleviated aortic remodeling by reducing elastic fiber and collagen deposition. This improvement in vascular structure attenuated hypertension. Subsequently, ventricular remodeling was alleviated by reducing periaortic myocardial fibrosis and left ventricular posterior wall thickness. To elucidate the underlying mechanisms, we overexpressed TEAD3 or PDZK1 in SHR-derived VSMCs via adenoviral infection. Both interventions suppressed VSMC proliferation and migration. Crucially, TEAD3 overexpression upregulated PDZK1 expression, and DNA pull-down assays confirmed direct binding of TEAD3 protein to the PDZK1 promoter. PDZK1 knockdown abolished the anti-proliferative and anti-migratory effects of TEAD3. Further analysis suggested that PDZK1 exerted its protective role by inhibiting the phosphoinositide-3-kinase adaptor protein 1-mediated PI3K/Akt pathway. In conclusion, this study reveals that TEAD3-PDZK1 axis attenuates the abnormal proliferation and migration of VSMCs, which ameliorates aortic and left ventricular remodeling in hypertensive conditions. These findings establish a molecular basis for developing targeted therapies against hypertension-induced cardiovascular remodeling.
研究领域:
心血管研究
·
分子生物学
·
高血压
·
转录调控
·
血管生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC Pulmonary Medicine
·
2025
·Vol. 25
·期 1
·1-13
·
IF 2.8
Huang Zhiheng,Li Liangxian,Zhang Bingxi,Yao Dong,Xiao Bo,Mo Biwen
Background Bronchial asthma, a chronic inflammatory airway disease, is characterized by airway remodeling, including thickening of the airway smooth muscle layer, primarily due to abnormal proliferation of airway smooth muscle cells (ASMCs). CBL0137 (Curaxin-137 hydrochloride), a histone chaperone facilitate chromatin transcription (FACT) inhibitor, has demonstrated anti-tumor properties, including inhibition of proliferation, promotion of apoptosis, and increased autophagy. However, its effects on ASMCs and airway remodeling remain unexplored. Methods Asthma models were established using ovalbumin (OVA) in female C57BL/6 J mice, with therapeutic interventions using CBL0137 and budesonide. Lung tissues were analyzed using Hematoxylin and eosin (H&E), PAS, Masson’s trichrome, and α-SMA immunofluorescence staining. ASMCs extracted from Sprague–Dawley rats were cultured in vitro experiments, with phenotypic changes assessed via flow cytometry. Gene and protein expressions were analyzed using RT-PCR and Western blotting. Results CBL0137 significantly reduced airway resistance, goblet cell proliferation, alveolar collagen deposition, and airway smooth muscle layer thickening in asthmatic mice. In vitro, CBL0137 inhibited ASMC proliferation and induced apoptosis, downregulating cyclin-B1, Cdc2, and Bcl-2 while upregulating caspase-3. Conclusions CBL0137 mitigates airway remodeling of asthmatic mice by modulating ASMC proliferation and apoptosis, presenting a potential therapeutic strategy for asthma treatment.
研究领域:
药理学
·
呼吸病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry C
·
2019
·Vol. 8
·期 7
·2326-2335
·
IF 6.641
Tianyu Yang,Mian Wang,Fei Jia,Xiuyan Ren,Guanghui Gao
Recently, hydrogel-based sensors have been rapidly developed due to their excellent flexibility, stretchability and toughness. However, it is still necessary to develop a hydrogel sensor with shape memory and remolding performance for multi-field applications. Here, a dual physically cross-linked shape memory hydrogel sensor was fabricated via blending poly vinyl alcohol (PVA), cationic chitosan and graphene oxide in water and glycerol. The introduction of cationic chitosan endows the hydrogels with excellent electrical conductivity. Therefore, the hydrogel can be integrated as a strain sensor to repeatedly monitor human motions. Meanwhile, the hydrogel can be used as a thermo-responsive shape memory sensor by virtue of orientation of PVA molecular chains under force and disorientation after heating. Besides, the hydrogel possesses anti-freezing properties with mechanical flexibility at −20 °C. Due to the dual physical cross-linking, the hydrogels can effectively dissipate energy and reconstruct the network; thus, the hydrogels gain excellent strength and remolding properties. In a word, this strategy provides a feasible method to prepare multifunctional shape memory hydrogels applied as wearable strain sensors and shape memory sensors.
研究领域:
材料科学
·
生物医学工程
✓ 已验证
DOI
高影响因子
Frontiers in Cellular and Infection Microbiology
·
2025
·
IF 4.8
Xueyao Fang,Yanhui Chen,Longhua Hu,Shumin Gu,Junqi Zhu,Yaping Hang,Xingwei Cao,Yanping Xiao,Hong Luo,Chuwen Zhao,Lianhua Xiao,Qiaoshi Zhong
Indole, a crucial bacterial signaling molecule, plays a fundamental role in regulating various physiological processes within bacteria, including growth, acid tolerance, biofilm development, motility, and other cellular functions. Its regulatory influence extends beyond indole-producing bacteria, significantly impacting the physiological activities in non-indole-producing species. In this study, we demonstrate that indole enhances the pathogenicity and viability of Klebsiella pneumoniae using the Galleria mellonella infection model and serum killing assay. Concurrently, indole has varying effects on biofilm formation in K. pneumoniae, with some strains showing enhanced biofilm formation ability. To elucidate the underlying molecular mechanisms, transcriptome analysis revealed that indole exposure in K. pneumoniae led to the upregulation of genes associated with pili formation and iron acquisition systems, while simultaneously inducing oxidative stress responses. Additionally, our analysis uncovered extensive metabolic remodeling. Specifically, we observed significant upregulation of genes involved in simple carbohydrate utilization pathways, including those responsible for galactose, mannose, and maltose metabolism, as well as enhanced expression of genes associated with pyrimidine biosynthesis. These findings collectively indicate that indole enhances the intestinal colonization and pathogenicity of K. pneumoniae primarily by modulation of fimbriae expression and metabolic pathway regulation.
研究领域:
微生物学
·
分子生物学
·
感染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Current Protocols
·
2025
·Vol. 5
·期 5
·e70151
·
IF 2.2
Yue Liu,Wansen Tan,Jingjun Hong
Chromatin remodeling serves as a critical mechanism for gene regulation, enabling the replacement of canonical histones with their variants through the assistance of histone chaperones. Our study focused on the process by which the histone variant H2A.Z replaces H2A, mediated by the mammalian SRCAP chromatin remodeling complex subunit hYL1. Previous approaches typically involved separately expressing the two proteins and validating their interaction in vitro . In contrast, we designed an artificial single-chain hH2B-hH2A.Z (hTBZ) construct, co-transformed the hYL1 gene with hTBZ, and co-expressed the proteins in E. coli BL21(DE3). We then performed purification, fast protein liquid chromatography (FPLC), and SDS-PAGE analysis. This approach successfully yielded the complexed proteins, confirming the in vivo interaction between hYL1 and hTBZ. © 2025 Wiley Periodicals LLC. Basic Protocol : Co-transformation of hTBZ/YL1 into BL21 (DE3) competent cells, followed by induction and acquisition of protein
研究领域:
生物化学
·
分子生物学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2025
·
IF 5.9
DongXue Ma,YuXin Zhang,Jia Zhang,Jun Shi,ShanHu Gao,Fei Long,Xin Wang,XingYu Pu,Jiayao Sun,Shuang Liang,Richard D. Cannon,Silas Villas-Boas,Ting-Li Han
Introduction: Escherichia coli Nissle 1917 (EcN) is one of the most extensively studied nonpathogenic Gram-negative probiotic strains worldwide. Recent research has highlighted the ability of EcN outer membrane vesicles (OMVs) to enhance the phagocytosis and proliferation of RAW264.7 macrophages. However, the impact of EcN-OMVs on M1/M2 polarization and metabolic modulation remains unknown.Methods: In this study, we evaluated the metabolic effects of EcN-OMVs on RAW264.7 macrophage polarization using metabolomic, transcriptomic, and fluxomic approaches.Reuslts: We found that the RAW264.7 macrophages phagocytosed EcN-OMVs, triggering upregulation of the HIF-1, mTORC1, and NF-κB signaling pathways. This metabolic reprogramming enhanced glycolysis, suppressed the TCA cycle, elevated intracellular reactive oxygen species (ROS), TNF-α, IL-6, IL-1β, ATP, and nitric oxide (NO) production, and promoted macrophage proliferation, migration, invasion, and M1-type polarization.Discussion: In summary, this research establishes a theoretical foundation for utilizing probiotic OMVs in immunomodulatory therapeutic applications.
研究领域:
免疫学
·
微生物学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Systems Microbiology and Biomanufacturing
·
2022
·
IF 0
Shen Yi,Ke Xia,Pan Zi-Hao,Cao Li-Sha,Liu Zhi-Qiang,Zheng Yu-Guo
With staggering progress on genetic manipulation strategies, Saccharomyces cerevisiae is becoming an ideal cell factory for the de novo biosynthesis of lipid compounds. However, due to their hydrophobicity, lipids tend to be accumulated within intracellular spaces and cause a high burden on cell activity and induce product inhibition effect, which ultimately restricted the lipids biomanufacturing for industrial application. Herein, an oleic acid stress (OAS) model was applied for the long-time domestication of BY4741 cells, and a subclone of A-22 was obtained through a series of acclimation (0.1% glucose and 0.2% oleic acid), showing increased accumulation of both biomass and intracellular lipid droplets compared to WT. Comparative transcriptome analysis indicated that compared to fatty acid metabolism, most transcripts enriched in the pathways of glucose catabolism (glycolysis and citrate cycle) and lipid synthesis (phospholipid and sterol) were down-regulated under OAS. While interestingly, most the above transcripts tended to be ‘restored’ in adapted strain A-22. In addition, for physical adaptation, significant increase of phosphatidylcholines was identified by lipidomic analysis, which probably caused the subsequent subcellular expansion of peroxisomes and lipid droplets as observed in the adapted strain, since phosphatidylcholines are the major constituent of their membranes. The present study systematically investigated both the phenotype change and molecular mechanism on adaptation of S. cerevisiae towards oily environment. Detailed information on functional transcripts may provide novel rational modification targets to reinforce the hydrophobic lipids biosynthesis within S. cerevisiae engineered cell factory.
研究领域:
微生物学
·
生物化学与分子生物学
·
系统生物学
✓ 已验证
DOI
Journal of Genetics and Genomics
·
2025
·
IF 7.1
Wuming Qin,Xiaobo Yang,Lu Zhang,Linghui Cao,Shi Ouyang,Dafeng Yang,Yangzhao Zhou,Anji Chen,Tao Liao,Xinyu Zhu,Yuting Liu,Wei Tang,Tongtong Ma,Yiyue Tang,Yonghe Ding,Yun Deng
LIM zinc finger domain containing 1 (LIMS1), an evolutionally conserved LIM domain adaptor protein, is implicated in diverse pathologies, including cancer and neurological disorders. However, its roles in cardiac diseases and the underlying mechanisms remain unclear. Here, we explore the functions and mechanisms of LIMS1 in cardiac remodeling and heart failure. We identify the elevated LIMS1 expression in patients with dilated cardiomyopathy (DCM) and murine cardiomyocytes, suggesting that LIMS1 dysregulation contributes to cardiac pathology. Using CRISPR/Cas9 technology, we generate a zebrafish model of lims1 loss-of-function mutant, which exhibits severe cardiac chamber remodeling, systolic dysfunction, and premature mortality, demonstrating the essential role of lims1 in maintaining cardiac integrity. Transcriptomic profiling reveals the activation of the gp130/Jak1/Stat3 signaling in the lims1 -deficient hearts. Strikingly, pharmacological inhibition of Stat3 or c-Fos partially rescues cardiomyopathy phenotypes. Our findings reveal the underlying mechanism of lims1 deficiency-caused heart failure through gp130/Jak1/Stat3 hyperactivation, offering insights into cardiac remodeling and potential therapeutic strategies.
研究领域:
心血管病学
·
分子生物学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR MEDICINE-JMM
·
2025
·
IF 4.2
Wen Xin,Peng Yuefeng,Yang Wenqing,Zhu Yuzhong,Yu Fan,Geng Li,Wang Xianfeng,Wang Xiaoyan,Zhang Xiaodong,Tang Yi,Feng Lei,Zhou Tingting,Jia Hongliang,Yang Liu
Transient receptor potential canonical 1 (TRPC1) channel, a Ca 2+ -permeable ion channel widely expressed in vasculature, has been reported to be involved in various cardiovascular disorders. However, the pathophysiological function of vascular smooth muscle cell (VSMC)-derived TRPC1 in hypertension and hypertensive cardiovascular remodeling remains to be defined. In this study, we found increased TRPC1 expression in both angiotensin II (AngII)-treated VSMCs and aortas from AngII-infused mice. VSMC-specific TRPC1 deficiency strikingly attenuated AngII-induced vasoconstriction, hypertension, vascular remodeling, and cardiac hypertrophy. Mechanistically, AngII activated enhancer of zeste homolog 2 (EZH2) to stimulate TRPC1 expression, induced calcium influx and phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK-ERK), which in turn triggered VSMC proliferation and migration and exacerbated hypertension and cardiovascular remodeling. Treatment with EZH2 inhibitor reduced VSMC proliferation and migration and alleviated vasoconstriction and hypertension in AngII-infused mice. Together, we revealed the pathogenic role of the EZH2-TRPC1-MEK/ERK pathway in AngII-induced hypertension and cardiovascular damage. TRPC1 or EZH2 inhibition may represent a desirable therapeutic target for the treatment of hypertension. Key messages
AngII activates AT1R-EZH2-TRPC1 pathway in VSMCs and aortas of hypertensive mice.
TRPC1 promotes VSMC proliferation and migration via MEK/ERK signaling.
Inhibition of TRPC1 or EZH2 alleviates hypertension and cardiovascular remodeling.
研究领域:
心血管病学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2024
·
IF 12.7
Xiaohui Liu,Haojie Wang,Birong Zeng,Xindan Yi,Weiang Luo,Guorong Chen,Yiting Xu,Conghui Yuan,Lizong Dai
To prepare epoxy resins (EP) with flame retardancy and remolding capability, novel amine curing agents (DDPM and DDPS), which incorporate phosphonates and bis-Schiff bases, were used to replace DDM partially or completely for EP curing. Curing kinetics based on a dual-parameter autocatalytic model showed that DDPM and DDPS had higher reactivity of than DDM. EP/DDPM and EP/DDPS vitrimers demonstrated excellent flame retardancy and remolding capability (up to 60.8%). EP/DDPS with disulfide bonds could not effectively improve the dynamic bond exchange. The molecular weight , dynamic bond stability, and viscosity were analyzed to investigate the underlying mechanisms. This study endows the dynamic properties of EP using novel curing agents and achieves flame-retardant and sustainable epoxy thermosets .
研究领域:
材料科学
·
化学工程
✓ 已验证
产品关联
DOI
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Heng Tang,Ke Ning,Boji Wu,Xuhong Wang,Jingyu He,Pingping Li,Lina Pan,Jiawen Zhang,Yi He,Shizhu Bian,Xingyu Ma,Jihang Zhang,Chuan Liu,Zhexue Qin,Houyuan Hu
Scutellarein (Sc), a natural flavonoid, holds potential for treating pulmonary arterial hypertension (PAH), yet its mechanisms remain unexplored. This study investigated Sc’s therapeutic effects and underlying pathways in PAH. In vivo experiments demonstrated that Sc significantly attenuated right ventricular hypertension, pulmonary arterial remodeling, αSMA expression, and vascular inflammation in PAH models. In vitro, Sc suppressed hypoxia-induced proliferation, migration, inflammation, and pyroptosis in human pulmonary artery smooth muscle cells (HPASMCs). Mechanistically, Sc activated the SIRT1/NAD + axis to restore mitochondrial homeostasis: it upregulated SIRT1 expression and elevated NAD + levels by promoting SIRT1-mediated deacetylation of nicotinamide nucleotide transhydrogenase (NNT), thereby enhancing NNT activity. Elevated NAD + further activated SIRT1, forming a self-reinforcing SIRT1/NNT/NAD + feedback loop that mitigated hypoxia-induced mitochondrial dysfunction. This study identifies Sc as a novel regulator of the SIRT1-dependent NNT deacetylation pathway, which stabilizes NAD + homeostasis to counteract HPASMCs dysregulation in PAH. These findings highlight Sc’s potential as a therapeutic candidate for PAH, offering insights into targeting mitochondrial-metabolic pathways for vascular remodeling diseases.
研究领域:
药理学
·
心血管疾病
·
分子生物学
✓ 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）