BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2024
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IF 4.2
Dong-Jing Yang,Yang Bai,Min Wu,Yin-Ming Liang,Bin-Hui Zhou,Wenzhi Guo,Shui-Jun Zhang,Ji-Hua Shi
Vascular endothelial inflammation is crucial in hepatic ischemia–reperfusion injury (IRI). Our previous research has shown that connective tissue growth factor (CTGF), secreted by endothelial cells, protects against acute liver injury, but its upstream mechanism is unclear. We aimed to clarify the protective role of CTGF in endothelial cell inflammation during IRI and reveal the regulation between endoplasmic reticulum stress-induced activating transcription factor 6 (ATF6) and CTGF. Hypoxia/reoxygenation in endothelial cells, hepatic IRI in mice and clinical specimens were used to examine the relationships between CTGF and inflammatory factors and determine how ATF6 regulates CTGF and reduces damage. We found that activating ATF6 promoted CTGF expression and reduced liver damage in hepatic IRI. In vitro, activated ATF6 upregulated CTGF and downregulated inflammation, while ATF6 inhibition had the opposite effect. Dual-luciferase assays and chromatin immunoprecipitation confirmed that activated ATF6 binds to the CTGF promoter, enhancing its expression. Activated ATF6 increases CTGF and reduces extracellular regulated protein kinase 1/2 (ERK1/2) phosphorylation, decreasing inflammatory factors. Conversely, inhibiting ATF6 decreases CTGF and increases the phosphorylation of ERK1/2, increasing inflammatory factor levels. ERK1/2 inhibition reverses this effect. Clinical samples have shown that CTGF increases after IRI, inversely correlating with inflammatory cytokines. Therefore, ATF6 activation during liver IRI enhances CTGF expression and reduces endothelial inflammation via ERK1/2 inhibition, providing a novel target for diagnosing and treating liver IRI.
研究领域:
分子生物学
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肝病学
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炎症
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转录因子
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产品关联
DOI
PubMed
高影响因子
Natural Product Communications
·
2024
·
IF 1.5
Liu Tang,Tianshuai Wang,Ruzhen Peng,Jingyi Guo,Liping Li,Benhong Zhou,Guangwen Luo,Shasha Fang,Xiao Jiang
Background: Atopic dermatitis, often referred to as AD, is a common chronic and relapsing skin disease with few treatment options. Epigallocatechin 3-gallate (EGCG), the most abundant catechin derived from green tea, has gained widespread attention due to its excellent anti-inflammatory and anti-oxidative properties. This research aims to investigate the effect and mechanism of EGCG in alleviating AD by integrative approach of an in vivo AD mouse model, network pharmacology and molecular docking. Materials and Methods: EGCG was administered by intragastric administration at the dose of 100 mg/kg, once daily for 14 consecutive days to AD mice, a model established by repeated application of 2, 4-dinitrofluorobenzene (DNFB) to the mouse dorsal skin. Results: Macroscopical and histopathological examination showed that oral administration with EGCG could markedly relieve AD-like skin phenotypes, as evidenced by a substantial reduction in severity score, serum immunoglobulin E (IgE) level, epidermal thickness, and the infiltration of inflammatory cells and mast cells into the dermal layers. Mechanistically, the network pharmacology analysis indicated that the protective effects of EGCG against AD were mainly related to the regulation of AGE-RAGE signaling pathway in diabetic complications, Th17 cell differentiation, IL-17 signaling pathway, NF-κB signaling pathway, Toll-like receptor signaling pathway, TNF signaling pathway, etc. In silico molecular docking demonstrated the high binding affinity of EGCG to the core targets such as ABCB1, MMP2, MMP9, MAPK14 and STAT1. Furthermore, western blotting (WB) results showed that EGCG obviously downregulated the expression of RAGE and STAT1, thereby regulating the AGE-RAGE signaling pathway to improve AD. Conclusions: These findings indicated that EGCG can be a promising therapeutic candidate for AD.
研究领域:
药理学
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皮肤病学
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分子生物学
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DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
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IF 4.7
Wenkai Nie,Xuan Zhao,Yan Zhang,Cheng Zeng,Huiwen Yang,Bing Liu
Objective Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease that significantly impacts patients' quality of life. Chlorogenic acid (CGA), a polyphenol present in various dietary sources and plants, has been shown to reduce skin inflammation. However, its efficacy and mechanisms of action in AD have not been thoroughly investigated. This study aimed to evaluate the therapeutic effect of CGA on AD in mice and explored its mechanism. Methods To establish a BALB/c mouse model of AD induced by 2,4-dinitrochlorobenzene (DNCB) to evaluate the therapeutic potential of CGA. The anti-inflammatory effects of CGA were assessed by measuring IL-1β and IL-6 levels in TNF-α-stimulated HaCaT cells. The phosphorylation levels of PI3K, Akt, Akt1, NF-κB, and IκB-α were analyzed using Western blotting. Molecular docking was conducted to evaluate the binding affinity of CGA to Akt1. Results Topical application of CGA significantly reduced dermatitis scores, spleen index, epidermal thickness, mast cell infiltration, and skin fibrosis. CGA reversed DNCB-induced increases in IgE, histamine, TNF-α, IL-1β, IL-6, and IL-8 levels. Western blot analysis showed that CGA inhibited the PI3K/Akt and NF-κB signaling pathways. In vitro , CGA exerts its anti-inflammatory effects by inhibiting the Akt1/NF-κB pathway, and the Akt activator (SC79) can counteract this effect. Molecular docking and dynamics simulations suggest that CGA may inhibit Akt1 activity by interacting with specific residues (ALA-50, GLY-37, TYR-326, ASP-323). Conclusions CGA improves AD by inhibiting the Akt1/NF-κB pathway, suggesting its potential as a natural treatment for AD.
研究领域:
皮肤病学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-12
·
IF 10.2
Qiu Lirong,Ouyang Chengcheng,Zhang Wei,Liu Jia,Yu Luting,Chen Guoguang,Ren Lili
Atopic dermatitis (AD) is a chronic and recurrent inflammation disease associated with immune dysfunction. The high level of reactive oxygen species (ROS) causes high oxidative stress and further results in the deterioration of AD. At the same time, the ROS produced by bacterial infection can further aggravate AD. Here, the prepared PVA-based hydrogel (Gel) has a high ROS scavenging ability, and the antibacterial agent Zn-MOF(ZIF-8) loaded into the hydrogel shows a lasting and effective antibacterial activity. Thus, a Zn-MOF hydrogel (Gel@ZIF-8) is prepared to regulate ROS-mediated inflammatory microenvironment. In vitro experiments show that Gel@ZIF-8 has good antibacterial effect and cell biocompatibility. In the AD-induced mouse model, Gel@ZIF-8 can significantly enhance the therapeutic effect, such as reduce the thickness of epidermis, the number of mast cells and IgE antibodies. The results indicate that the ROS-scavenging hydrogel could treat the AD by regulating the inflammatory microenvironment, providing a promising treatment for managing AD.
研究领域:
生物材料学
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免疫学
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皮肤病学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Rong Huang,Wenyu Zhang,Yueqi Hu,Junjie Xu,Zhihui Dong,Jikai Liu,Li Zhou
Atopic dermatitis (AD), a prevalent inflammatory skin condition, significantly impacts patients' quality of life due to the multifaceted etiology and the lack of targeted therapeutic options. As the “Chinese herbal antibiotic”, Houttuynia cordata is renowned for its diverse pharmacological attributes. This study aims to investigate the therapeutic potential of Houttuynia cordata polysaccharides (HCP) in treating AD and to elucidate the mechanisms involved. HCP alleviated AD in MC903-induced mice by reducing epidermal thickness, skin lesions, mast cell infiltration, inflammatory cytokines, and restoring barrier proteins. It also suppressed inflammatory cytokines/chemokines via the mitogen-activated protein kinase (MAPK) pathway in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and tumor necrosis factor-alpha (TNF-α)/ interferon-γ(IFN-γ)-induced human keratinocytes cells (HaCaT). Moreover, HCP modulated inflammation-related metabolic pathways, especially restored lipid metabolic homeostasis through upregulating phosphatidylcholine (PC) and downregulating triglyceride (TG), lysophosphatidylcholine (LPC), potentially alleviating AD-like lesions and restoring barrier function. Our findings underscore the promising potential of HCP as a topical therapeutic candidate for AD treatment, offering a new direction for the development of targeted AD therapies.
研究领域:
皮肤病学
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药理学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·Vol. 12
·期 28
·6927-6939
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IF 6.1
Xue Luo,Huan Liu,Jing Wen,Jiaxin Hu,Yongzhi Li,Guangjun Li,Guyu Dai,Yubao Li,Jidong Li
Radiotherapy is a pivotal means of cancer treatment, but it often leads to radiation dermatitis, a skin injury caused by radiation-induced excess reactive oxygen species (ROS). Scavenging free radicals in the course of radiation therapy will be an effective means to prevent radiation dermatitis. This study demonstrates a novel double network hydrogel doped with MoS2 nanosheets for the prevention of radiation-induced dermatitis. The resultant SPM hydrogel constructed from polyacrylamide (PAM) and sodium alginate (SA) nanofiber presented favorable mechanical and adhesion properties. It could conform well to the human body's irregular contours without secondary dressing fixation, making it suitable for skin protection applications. The in vitro and in vivo experiments showed that the antioxidant properties conferred by MoS2 nanosheets enable SPM to effectively mitigate excessive ROS and reduce oxidative stress, thereby preventing radiation dermatitis caused by oxidative damage. Biosafety assessments indicated good biocompatibility of the composite hydrogel, suggesting SPM's practicality and potential as an external dressing for skin radiation protection.
研究领域:
生物医学工程
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皮肤病学
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放射治疗学
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产品关联
DOI
PubMed
高影响因子
Smart Medicine
·
2025
·Vol. 4
·期 1
·e136
·
IF 11.6
Yuwei Wang,Lijun Cai,Yuanyuan Zhang,Yan Cong,Yuanjin Zhao
Allergic contact dermatitis (ACD) is an inflammatory dermatitis with a high morbidity and recurrence rate. Scientific attention is focused on the development of safe and comfortable therapeutics of ACD. Herein, we propose a natural matrine-integrated pollen delivery system for the ACD treatment. Sunflower pollens were collected and defatted to serve as adhesive drug carriers for matrine. Specifically, the exquisite porous and hollow structures of the pollen shells can absorb matrine and realize the sustained drug release. Besides, the prickly surface morphology can strongly adhere to the inflamed skin sites, which can prolong the duration of the drug. By utilizing them in an ACD model and an acute pruritus model of mice, we have demonstrated that these matrine-integrated pollen shells can decrease the swelling degree of mice ears and weight loss, down-regulate inflammatory response, and improve the scratching times. These results indicate that our matrine-integrated pollen delivery systems have great potential to serve as natural topical preparations for skin disease therapy.
研究领域:
皮肤病学
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药物递送
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生物材料
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天然产物
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Jin Wang,Liwen Zhang,Zhelin Kuang,Ye Ge,Yingqing Zhang
The health benefits of natto, a fermented soy product, have gained attention, but its effects on atopic dermatitis are not well-studied. This study aims to investigate the effects of natto extract on atopic dermatitis and to understand its underlying mechanisms. A mouse model of DNCB-induced atopic dermatitis was utilized to evaluate the intervention effects. Results showed that natto extract could significantly ameliorate the symptoms of atopic dermatitis, reduce the spleen index, attenuate dorsal skin lesions, and reduce the levels of IgE, IL-4, and IFN-γ in the serum. A total of 865 components were identified by UPLC-MS/MS-based untargeted metabolomics. Glycitein, hispidulin, and aurantiamide acetate were identified as key active components by network pharmacology. Interleukin-6, tumor necrosis factor, and prostaglandin endoperoxide synthase 2 were the core targets. Crucial signaling pathways involved Th17 cell differentiation, tumor necrosis factor signaling, and toll-like receptor signaling pathways. Molecular docking and dynamics simulation results demonstrated stable interactions between most active ingredients and core targets via hydrogen bond and hydrophobic interactions. These findings suggest that natto extract can ameliorate atopic dermatitis, enhance the understanding of the actions and mechanisms of its active ingredients, and provide a theoretical foundation for future research.
研究领域:
药理学
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免疫学
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生物信息学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
·
IF 3.649
Jiao Yu,Kawai Wan,Xun Sun
The skin is an important site for local or systemic application of drugs. However, most of the drugs have poor permeability through the skin’s outermost layer, stratum corneum. The aim of this study was to develop a method to enable transdermal delivery of morin (3, 5, 7, 2, 4-pentahydroxyflavone), which is a poorly water-soluble drug with anti-inflammatory properties obtained from natural products. Morin phospholipid complex (MPC) was prepared and then loaded in Carbopol 940 hydrogel (MPC-gel), which can significantly increase the transdermal flux of morin based on the in vitro skin penetration data presented in this paper. To further enhance permeation, different compositions of penetration enhancers were dispersed in the gel and screened. After applied onto the mouse skin, MPC-gel showed apparent reduction of ear swelling in 2, 4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis (ACD). Further determination of cytokines levels, histopathological analysis and T lymphocytes proliferation indicates that the MPC-gel is potent enough to reduce the inflammatory response mediated by the DNFB in ACD mice model. Collectively, we anticipate that such an approach may provide a new treatment for topical ACD.
研究领域:
药剂学
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免疫学
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皮肤病学
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产品关联
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2024
·Vol. 15
·期 1
·1-15
·
IF 7.1
Zhu Yufan,Liu Xu,Chen Xihang,Liao Yunjun
Background Chronic radiation dermatitis (CRD) is a late consequence of radiation with high incidence in patients receiving radiotherapy. Conventional therapies often yield unsatisfactory results. Therefore, this study aimed to explore the therapeutic potential and mechanism of adipose-derived stem cells (ADSCs) for CRD, paving the way for novel regenerative therapies in clinical practice.Methods Clinical CRD skin biopsies were analyzed to character the pathological changes of CRD skin and guided the animal modeling scheme. Subsequently, an in vivo analysisusing mouse CRD models was conducted to explore their effects of ADSCs on CRD, monitoring therapeutic impact for up to 8 weeks. Transcriptome sequencing and histologic sections analysis were performed to explore the potential therapeutic mechanism of ADSCs. Following observing extensive apoptosis of transplanted ADSCs, the therapeutic effect of ADSCs were compared with those of apoptosis-inhibited ADSCs. Multiphoton imaging and analysis of collagen morphologic features were employed to explain how translated ADSCs promote collagen remodeling at the microscopic level based on the contrast of morphology of collagen fibers.Results Following injection into CRD-afflicted skin, ADSCs therapy effectively mitigated symptoms of CRD, including acanthosis of the epidermis, fibrosis, and irregular collagen deposition, consistent with the possible therapeutic mechanism suggested by transcriptome sequencing. Notably, in vivo tracking revealed a significant reduction in ADSCs number due to extensive apoptosis. Inhibiting apoptosis in ADSCs partially tempered their therapeutic effects. Mechanically, analysis of collagen morphologic features indicated that translated ADSCs might promote dermal extracellular matrix remodeling through enlarging, lengthening, crimping, and evening collagen, counteracting the atrophy and rupture caused by irradiation.Conclusion sThis study demonstrated that ADSCs underwent substantial apoptosis upon local skin transplantation, and paradoxically, this apoptosis is essential for their efficacy in promoting the regeneration of late radiation-impaired skin. Mechanically, transplanted ADSCs could promote the remodeling and rearrangement of radiation-damaged dermal collagen matrix.
研究领域:
再生医学
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放射生物学
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干细胞生物学
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皮肤科
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2025
·
IF 3.5
Xiaoxue Wang,Zexin Zhu
Mosquito bites are prevalent occurrences among various populations worldwide, mosquito repellent chemical components (MRCCs) have been extensively utilized. MRCCs have been frequently identified in environmental settings nowadays. However, the implications of these compounds on skin conditions, particularly Atopic Dermatitis (AD), are not well understood. In this investigation, we analyzed three commercially available MRCCs: DEET (N,N-diethyl-3-methylbenzamide), IR3535 (ethyl butylacetylaminopropionate), and picaridin (2-(2-hydroxyethyl)-piperidinecarboxylic acid 1-methyl ester). A comprehensive analysis was conducted utilizing various databases to identify potential targets associated with exposure to these MRCCs and their correlation with AD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that exposure to these MRCCs influences inflammation-related pathways. Additionally, molecular docking studies indicated significant binding affinities of DEET, IR3535, and picaridin to critical core targets and receptor proteins. Furthermore, a series of cellular assays were conducted to empirically evaluate the actual effects of these three MRCCs on the induction of AD. The results suggest that MRCCs may facilitate the progression of AD by influencing inflammatory processes. This study provides a conceptual framework for understanding the association between MRCCs and the risk of AD, thereby contributing to the formulation of strategies aimed at mitigating their effects on dermatological disorders.
研究领域:
皮肤病学
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免疫学
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环境健康科学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2020
·
IF 3.701
Liu Tang,Xiaolei Li,Liping Wan,Huiling Wang,Qianting Mai,Zixin Deng,Hong Ding
The present research was designed to evaluate the protective effects and underlying mechanisms of different ratios of linoleic acid (LA) and α-linolenic acid (ALA), two essential polyunsaturated fatty acids (PUFAs) fatty acids, on atopic dermatitis (AD)-like skin lesions induced by 2, 4-dinitrofluorobenzene (DNFB). The dorsal flank and ear pinnas of mice were sensitized and challenged with DNFB for four weeks in order to establish AD model. Simultaneously, the mice were orally administered different ratios of LA/ALA (v/v; 4:1 or 1:1), or dexamethasone (Dex; 0.1 mg/kg). Results showed that different LA/ALA ratios, especially a ratio of 4:1 treatment, could effectively ameliorate DNFB-induced skin lesions, ear edema, scratching behavior and skin inflammation, as reflected by the reduced inflammatory blood cells, IgE serum levels, and skin levels of the pro-inflammatory lipid mediators, including PGE 2 and LTB 4 . These findings were further confirmed by skin pathological examination. Moreover, LA/ALA administration markedly suppressed the proliferation and infiltration of T cells, the production of T helper cell type 1 (Th1), Th2 and Th17 cytokines in dorsal skin and serum of DNFB-treated mice. Western blotting and immunohistochemistry staining revealed that LA/ALA downregulated the protein expressions of JAK2 and STAT4, and thus reducing the synthesis of type Th1 cytokine IFN-γ. Taken together, these results suggest that optimal nutrition ratio of LA/ALA has beneficial effects on AD-like symptoms, which provide theoretical basis for its therapeutic potential in the clinical prevention and treatment of AD.
研究领域:
免疫学
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营养学
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皮肤病学
✓ 已验证
DOI
高影响因子
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