Bioengineered
·
2021
·
IF 3.269
Chuanfeng Lv,Hui Li,Hongxia Cui,Qianyu Bi,Meng Wang
Allergic asthma is one of the most common chronic airway diseases, and there is still a lack of effective drugs for the treatment of allergic asthma. The purpose of this work is to formulate rhynchophylline (Rhy)-solid lipid nanoparticles (SLNs) to improve their therapeutic efficacy in a mice allergic model of asthma. A solvent injection method was employed to prepare the Rhy-SLNs. Physicochemical characterization of Rhy-SLNs was measured, and the release assessment was investigated, followed by the release kinetics. Next, a model of murine experimental asthma was established. Mice were subcutaneously injected with 20 μg ovalbumin mixed with 1 mg aluminum hydroxide on days 0, 14, 28, and 42 and administrated aerosolized 1% ovalbumin (w/v) by inhalation from day 21 to day 42. Mice were intraperitoneally injected with 20 mg/kg Rhy-SLNs or Rhy at one hour before the airway challenge with ovalbumin. The results showed that Rhy-SLNs revealed a mean particle size of 62.06 ± 1.62 nm with a zeta potential value of −6.53 ± 0.04 mV and 82.6 ± 1.8% drug entrapment efficiency. The release curve of Rhy-SLNs was much higher than the drug released in phosphate buffer saline at 0, 1, 1.5, 2, 4, or 6 h. Moreover, Rhy-SLNs exerted better effects on inhibiting ovalbumin-induced airway inflammation, oxidative stress, airway remodeling (including collagen deposition and mucus gland hyperplasia) than Rhy in murine experimental asthma. Subsequently, we found that Rhy-SLNs relieved allergic asthma via the upregulation of the suppressor of cytokine signaling 1 by repressing the p38 signaling pathway.
研究领域:
药学
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免疫学
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纳米技术
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呼吸医学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2017
·
IF 3.671
Wenjie Jiang,Yanna Cheng,Na Zhao,Lian Li,Yikang Shi,Aizhen Zong,Fengshan Wang
Previous studies demonstrated that SIP-SII, a sulfated derivative of SIP that is isolated from the ink of Sepiella maindroni , showed significant inhibition of tumor growth and metastasis. In this study, the effects of SIP-SII on the migration, invasion and molecular mechanism in ovarian cancer cell line, SKOV-3 cells, were investigated. The flow cytometry, confocal microscope observation, western blot and RT-PCR results indicated that SIP-SII located on cell membrane and inhibited the expression and activation of epidermal growth factor receptor (EGFR). Moreover, the binding capacity of SIP-SII with EGFR was confirmed by surface plasmon resonance (SPR) analysis and co-localization of EGFR and SIP-SII. Accordingly, SIP-SII was proved to attenuate the EGF-induced EGFR phosphorylation and migration by western blot and wound healing assay, respectively. Additionally, SIP-SII inhibited p38/MAPK and PI3K/Akt/mTOR signaling pathways in SKOV-3 cells significantly. What is more, SIP-SII showed amplified inhibitory activity on migration, invasion, and MMP-2 expression in combination with p38-specific inhibitor, PI3K-specific inhibitor or mTOR-specific inhibitor in SKOV-3 cells. Therefore, the mechanism that SIP-SII suppressed EGFR-mediated p38/MAPK and PI3K/Akt/mTOR signaling pathways to inhibit migration and invasion of SKOV-3 cells was demonstrated. These findings suggested that SIP-SII might be used as a potential inhibitor against tumor metastasis.
研究领域:
肿瘤学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Lei Lei,Guoguo Wan,Xiaoyu Geng,Jianguo Sun,Yi Zhang,Jianwei Wang,Congwen Yang,Zheng Pan
Ethnopharmacological relevance Lamiophlomis rotata (Benth.) Kudo ( L . rotata ), a Tibetan medicinal plant , is used to treat “yellow-water diseases”, such as skin disease, jaundice and rheumatism . Our previous study showed that the iridoid glycoside extract of L. rotata (IGLR) is the major constituent of skin wound healing. However, the role of IGLR in the biological process of trauma repair and the probable mechanism of the action remain largely unknown. Aim of the study To investigate the role of IGLR in the biological process of trauma repair and the probable mechanism of the action. Materials and methods The role of IGLR in wound healing was investigated by overall skin wound in mice with Hematoxylin and Eosin (H&E) and Masson trichrome staining. The anti-inflammatory, angiogenesis-promoting and fibril formation effects of IGLR were visualized in wound skin tissue by immunofluorescence staining, and the proinflammatory factors and growth factors were assayed by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Macrophages, dermal fibroblasts, and endothelial cells were cultured to measure the direct/indirect interaction effects of IGLR on the proliferation and migration of cells, and flow cytometry was employed to assess the role of IGLR on macrophage phenotype. Network pharmacology combined with Western blot experiments were conducted to explore possible mechanisms of the actions. Results IGLR increased the expression of CD206 (M2 markers) through the RAS/p38 MAPK/NF-κB signaling pathway during wound injury in vivo and in vitro . IGLR suppressed the inflammatory cytokines iNOS, IL-1β and TNF-α in the early stage of wound healing . During the proliferation step of wound repair, IGLR promoted angiogenesis and fibril formation by increasing the expression of VEGF, CD31, TGF-β and α-SMA in wound tissue, and similar results were verified by RT-PCR and ELISA. In a paracrine mechanism, the extract promoted the proliferation of dermal fibroblasts, and endothelial cells were founded by the conditioned medium (CM). Conclusion IGLR induced M2 macrophage polarization in the early stage of wound healing; in turn, IGLR played a key role in the transition from inflammation to cell proliferation during the biological process of wound healing.
研究领域:
药理学
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免疫学
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伤口愈合
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植物科学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 46
·9639-9653
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IF 7.571
Xinyuan Yuan,Teliang Lu,Fupo He,Tingting Wu,Xiaolan Wang,Jiandong Ye
Biomaterials in combination with multiple bioactive ions could create a favorable microenvironment for bone remolding. Herein, zinc silicate/β-tricalcium phosphate (ZS/β-TCP) composite ceramic scaffolds with different amounts of ZS (5, 10, and 15 wt%) were constructed using a three-dimensional fiber deposition (3DF) technique. The physicochemical, osteogenic and angiogenic properties of these interconnected macroporous scaffolds were investigated systematically. Simultaneously, GeneChip, alkaline phosphatase (ALP), western blot (WB) and polymerase chain reaction (PCR) were utilized to elucidate the underlying mechanism of the enhancement in osteogenic differentiation. The results showed that the incorporation of ZS significantly improved the mechanical performance by more than 5 fold in comparison with the β-TCP ceramic scaffold (4.79 ± 0.99 MPa). The ZS modified β-TCP scaffolds greatly supported the cytoactivity, adhesion, proliferation of mouse bone marrow mesenchymal stem cells (mBMSCs) and human umbilical vein endothelial cells (HUVECs). The expression levels of osteogenic genes and proteins as well as angiogenic genes were markedly upregulated by the sustained release of bioactive ions (mainly Si and Zn) from the composite scaffolds. The 10ZS/β-TCP demonstrated the best overall performance in vitro. Moreover, the 10ZS/β-TCP displayed a high bone volume fraction, bone maturity and angiogenesis after implantation in the rat skull defects for 6 weeks. It was further verified that ZS/β-TCP scaffolds stimulated the osteogenic differentiation of mBMSCs by activating the p38 signaling pathway directly. The 10ZS/β-TCP ceramic scaffold holds great potential for the fast repair of bone defects, and deep understanding of the mechanism will facilitate the formulation of new strategies for bone repair.
研究领域:
生物材料
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组织工程
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骨再生
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH
·
2023
·Vol. 22
·期 3
·517-523
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IF 0.6
Shun Xu,Aili Wang,Zaoli Shen,Yu Chen,Qing Jia
Purpose: To investigate the mechanism of action involved in the treatment of severe burn injury with glycyrrhizinate (DG). Methods: Exosomes were purified from sera of patients with burn injury using an ultra-high-speed centrifuge, and verified by western blot. Cell proliferation and permeability were assessed using cell counting kit (CCK)-8, transepithelial-transendothelial electrical resistance (TEER), and Fluorescein Isothiocyanate (FITC) dextran assays, while immunoblotting was used for assay of the levels of p38, occluding, and zonula occludens 1 (ZO-1). Results: Serum-derived exosomes (serum-exo) significantly suppressed cell proliferation while causing hyperpermeability in HUVECs (p < 0.001). Furthermore, DG alleviated the hyperpermeability and inhibition of cell proliferation caused by serum-exo (p < 0.001). In addition, the upregulation of p-P38 induced by serum-exo decreased upon DG treatment. Interestingly, the effect of DG was blocked by anisomycin, a specific p38 activator, indicating that p38 signaling pathway may contribute to the function of DG. Conclusion: Glycyrrhizinate attenuates serum-exo-induced cell proliferation and permeability alteration via p38 signaling pathway, thereby making it a potential agent for the management of severe burn injury.
研究领域:
药理学
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细胞生物学
·
烧伤与创伤
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DOI
高影响因子
Journal of Healthcare Engineering
·
2022
·
IF 3.822
Canhong Yang,Sisi Qin,Jiafa Zhang,Yuanyuan Wang,Huan Li,Tianming Lü
Protein misfolding and/or aggregation are common pathological features associated with a number of neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson disease (PD). Abnormal protein aggregation may be caused by misfolding of the protein and/or dysfunction of the protein clearance system. Recent studies have demonstrated that the specific water channel protein, aquaporin-4 (AQP4), plays a role in the pathogenesis of neurodegenerative diseases involving protein clearance system. In this study, we aimed to investigate the role of sulforaphane (SFN) in the upregulation of AQP4 expression, along with its underlying mechanism using cultured mouse astrocytes as a model system. At low concentrations, SFN was found to increase cell proliferation and result in the activation of astrocytes. However, high SFN concentrations were found to suppress cell proliferation of astrocytes. In addition, our study found that a 1 μM concentration of SFN resulted in the upregulation of AQP4 expression and p38 MAPK phosphorylation in cultured mouse astrocytes. Moreover, we demonstrated that the upregulation of AQP4 expression was significantly attenuated when cells were pretreated with SB203580, a p38 MAPK inhibitor. In conclusion, our findings from this study revealed that SFN exerts hormesis effect on cultured mouse astrocytes and can upregulate astrocytic AQP4 expression by targeting the p38 MAPK pathway.
研究领域:
神经科学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
International Journal of Polymeric Materials and Polymeric Biomaterials
·
2024
·
IF 2.5
Sizhen Huang,Haodi Kou,Zhichao Zheng,Ming Lu,Lihong Wu,Huade Zheng
Angiogenesis within the wound site is a necessary prerequisite for skin tissue regeneration during the process of wound healing. Skin vessels provide adequate nutrients and soluble bioactive factors to the wounded area and remove metabolites. In this study, we prepared a double-cross-linked hydrogel based on GelMA and PVAMA to load Myeloid-derived growth factor (MYDGF). Additionally, we evaluated the healing-promoting effect of the hydrogel using a full-thickness skin injury mouse model. Compared with the control and MYDGF-free hydrogels, the MYDGF-loaded hydrogels significantly increased the percentage of wound healing and promoted granulation tissue proliferation and epidermization. In vitro experiments have shown that MYDGF may augment the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) by upregulating the expression of phosphorylated ERK and phosphorylated P38. These findings indicate that MYDGF-loaded hydrogels promote wound healing by accelerating angiogenesis.
研究领域:
生物材料学
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再生医学
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细胞生物学
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产品关联
DOI
高影响因子
Cell Death & Disease
·
2026
·Vol. 17
·期 1
·198
·
IF 12.2
Guo Chipeng,Luo Siweier,Luo Jigang,Lu Siyao,You Xiaomei,Cao Junlin,Du Yufei,Lv Haoran,Liang Hanzhi,Wang Le,Wang Liangchun,Liu Tao,Zhou Yiming
Ultraviolet B (UVB) is a well-recognized trigger of cutaneous lupus erythematosus (CLE), yet its molecular basis remains largely undefined. Here, using single-cell transcriptomics and a lupus-prone mouse model, we identify keratinocyte-derived macrophage migration inhibitory factor (MIF) as a key amplifier of cutaneous inflammation through a self-sustaining feedback loop. Single-cell RNA sequencing reveals elevated MIF expression specifically within pathogenic, interferon-high keratinocyte subclusters associated with CLE, which is further validated across major CLE subtypes in clinical skin samples. In vitro, UVB irradiation dose-dependently induces the release of MIF from keratinocytes, which in turn promotes inflammatory signaling and matrix remodeling in both keratinocytes and fibroblasts. Mechanistically, we demonstrate that UVB irradiation activates the ribotoxic stress response (RSR), leading to the p38-C/EBPβ-mediated transcriptional upregulation of NLRP3 and GSDMD cleavage in keratinocytes. The ensuing GSDMD-dependent pyroptosis facilitates the release of MIF, primarily through GSDMD pores rather than vesicular secretion, which in turn amplifies the p38-C/EBPβ signaling pathway. Therapeutic disruption of this loop either by gene silencing via AAVs or pharmacological inhibition via microneedles, markedly attenuates epidermal hyperplasia and cytokine imbalance in lupus-prone mice. These findings uncover a previously unrecognized MIF-p38-GSDMD inflammatory loop contributes to the UVB-induced cutaneous lupus, offering both mechanistic insights and translational opportunities for CLE.
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DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2026
·Vol. 58
·期 1
·1-25
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IF 8.5
Hui Fang,Min Shu,Jiaju Wang,Heng Tian,Jianguo Zhang,Ying Hu,He Li,Huan Zhou,Kangsheng Gu,Zhenhua Ren
International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.
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DOI
PubMed
高影响因子
Cell and Bioscience
·
2021
·Vol. 11
·期 1
·1-13
·
IF 7.133
Tang Ying,Zhou Mengchun,Huang Rongrong,Shen Ling,Yang Li,Zhou Zhongqiu,Ren Hui,Bai Ying
Background Astrocytes participate in innate inflammatory responses within the mammalian central nervous system (CNS). HECT domain E3 ubiquitin protein ligase 1 (HECTD1) functions during microglial activation, suggesting a connection with neuroinflammation. However, the potential role of HECTD1 in astrocytes remains largely unknown. Results Here, we demonstrated that HECTD1 was upregulated in primary mouse astrocytes after 100 ng/ml lipopolysaccharide (LPS) treatment. Genetic knockdown of HECTD1 in vitro or astrocyte-specific knockdown of HECTD1 in vivo suppressed LPS-induced astrocyte activation, whereas overexpression of HECTD1 in vitro facilitated LPS-induced astrocyte activation. Mechanistically, we established that LPS activated σ-1R-JNK/p38 pathway, and σ-1R antagonist BD1047, JNK inhibitor SP600125, or p38 inhibitor SB203580 reversed LPS-induced expression of HECTD1, thus restored LPS-induced astrocyte activation. In addition, FOXJ2 functioned as a transcription factor of HECTD1, and pretreatment of primary mouse astrocytes with BD1047, SB203580, and SP600125 significantly inhibited LPS-mediated translocation of FOXJ2 into the nucleus. Conclusions Overall, our present findings suggest that HECTD1 participates in LPS-induced astrocyte activation by activation of σ-1R-JNK/p38-FOXJ2 pathway and provide a potential therapeutic strategy for neuroinflammation induced by LPS or any other neuroinflammatory disorders.
研究领域:
神经科学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL DENTAL JOURNAL
·
2026
·Vol. 76
·期 5
·109799
·
IF 5.2
Xinda Li,Zhijia Liu,Xinzhu Liu,Jianing Wang,Jinlai Bao,Wuwei Li
Background To explore the osteogenic promotion of carboxymethyl chitosan (CMCS), clarify the signalling pathways involved and preliminarily evaluate the translational potential of CMCS in transcrestal sinus floor elevation. Methods Overlapping targets were identified by integrating potential CMCS targets and bone regeneration-related genes, and protein-protein interaction and GO/KEGG enrichment analyses were conducted. The GEO dataset GSE50743 was externally validated. Bone marrow-derived mesenchymal stem cells from mice were induced to osteogenic differentiation in vitro and treated with CMCS alone or in combination with the p38 inhibitor SB203580 or the VEGFR2 inhibitor SU5416. The osteogenic phenotypes and mechanism-related changes were determined by ALP, Alizarin Red S staining, RUNX2 immunofluorescence, qPCR and Western blotting. A retrospective comparative clinical study further evaluated radiographic, functional and patient-reported outcomes after transcrestal sinus floor elevation. Results We identified 187 common targets of CMCS-bone regeneration. Enrichment analyses revealed that these targets were primarily involved in cell adhesion, inflammatory and immune regulation, extracellular matrix remodelling, and osteogenesis-related pathways, including MAPK and VEGF signalling. Validation with GSE50743 confirmed significant positive enrichment of candidate gene set under osteogenic conditions. In vitro, CMCS increased ALP activity, mineralised nodule formation and the expression of RUNX2, ALP and OPN, whereas inhibition of p38 or VEGFR2 partially reduced these effects. Clinical findings showed that the two groups were generally similar in terms of safety, implant stability and patient-reported outcomes, whereas the CMCS group had better volume maintenance. Conclusions CMCS promotes osteogenesis and mineralisation, at least partly via p38 MAPK and VEGF–VEGFR2 signalling. Retrospective clinical findings also indicate its potential utility in transcrestal sinus floor elevation.
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产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Jingjing Xia,Jiawei Huang,Xiaobing Hou,Haibing Hua,Ming Chen
TMF was prioritized from Wendan Decoction by network analysis. • TMF reduced cochlear inflammation and injury in experimental EH. • TMF suppressed p38 MAPK/AQP2 signaling and restored DUSP3/ZO-1. • DUSP3 knockdown weakened TMF regulation in vitro and in vivo. Ethnopharmacological relevance Wendan Decoction is a classical traditional Chinese medicine formula historically used for phlegm-related dizziness and vertigo. Recent studies have shown that Wendan Decoction can ameliorate experimental endolymphatic hydrops (EH), a characteristic pathological correlate of Ménière's disease. However, the bioactive constituents responsible for these effects and their molecular targets remain incompletely defined. Aim of the study This study aimed to identify and quantify a pharmacologically relevant constituent of Wendan Decoction and to investigate its molecular target and mechanism of action in experimental EH. Materials and methods Candidate constituents and regulatory targets were prioritized through ADME-guided screening, target prediction, MD-associated transcriptomic analysis, protein–protein interaction network analysis, pathway enrichment, MAPK pathway mapping, and molecular docking. Targeted UPLC-ESI-MS/MS was used to verify and quantify 5,6,7,4′-tetramethoxyflavone (TMF) in Wendan Decoction granules. The interaction between TMF and DUSP3 was examined using surface plasmon resonance (SPR) and a cell lysate-based cellular thermal shift assay (CETSA). The effects of TMF were evaluated in LPS-stimulated HEI-OC1 cells and a DDAVP-induced guinea pig model of EH. DUSP3 knockdown and pharmacological inhibition of p38 MAPK with SB203580 were used to investigate the functional relationships among DUSP3, p38 MAPK, AQP2, and ZO-1. Results TMF was detected in Wendan Decoction granules at 0.0379% (w/w). SPR showed micromolar binding between TMF and recombinant DUSP3, while CETSA showed that TMF increased the thermal stability of DUSP3. In LPS-stimulated HEI-OC1 cells, TMF reduced inflammatory mediator production, increased DUSP3 and ZO-1 expression, inhibited p38 MAPK activation, and decreased AQP2 expression. SB203580 attenuated AQP2 upregulation, ZO-1 reduction, and pro-inflammatory cytokine production, including after DUSP3 silencing, supporting p38 MAPK as a downstream component of DUSP3-associated signaling. In DDAVP-treated guinea pigs, TMF reduced morphometrically quantified cochlear hydrops, alleviated cochlear ultrastructural injury and vestibular-associated behavioral impairment, and decreased cochlear inflammatory cytokine levels. Cochlear DUSP3 knockdown was confirmed at both the mRNA and protein levels and partially weakened TMF-mediated regulation of the p38 MAPK/AQP2 axis. Conclusions TMF is a quantified Wendan Decoction-derived constituent with protective activity against experimental EH. The findings support a direct interaction between TMF and DUSP3 and suggest that TMF alleviates EH-associated pathological changes, at least in part, through DUSP3-associated regulation of p38 MAPK activation and downstream AQP2 and ZO-1 expression. Download: Download high-res image (263KB) Download: Download full-size image
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DOI
高影响因子
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