RSC Advances
·
2024
·Vol. 14
·期 49
·36804-36815
·
IF 3.9
Yi Zheng,Haochen Liu,Bingkun Lu,Muchen Dong,Xinhai Wang
Dry eye syndrome (DES) is a prevalent condition linked to oxidative stress from Orthokeratology (OK) lens use, causing significant discomfort and impacting quality of life. Herein, this study investigates the role of Reactive Oxygen Species (ROS) in modulating T cell responses, particularly Th17 cells and IL-17A production, which are central to DES pathogenesis. We propose a novel therapeutic strategy using ceria nanoparticles (CeNPs) for ocular ROS clearance, hypothesized to attenuate Th17 activation and IL-1β and IL-17A production, thereby reducing DES symptoms. We developed a hybrid coating for OK lenses using Schiff base reactions to link tannic acid with CeNPs, aiming to neutralize ROS and mitigate inflammation. This approach could offer a transformative treatment for DES, especially among OK lens users. In comparison to existing therapies, our approach demonstrated a 70% reduction in corneal inflammation markers and a 2.5-fold increase in tear secretion, offering a transformative treatment for DES, especially among OK lens users.
研究领域:
免疫学
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眼科
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纳米医学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR BIOTECHNOLOGY
·
2024
·
IF 2.4
Chen Ya,Zhu Congcong,Tai Zongguang,Lian Tianyan,Zhu Quangang,Chen Zhongjian
Apoptosis is a natural physiological process of programmed cell death. It is essential for maintaining the homeostasis of the body and the immune system. The dysfunction of apoptosis can lead to the development of autoimmune diseases. In psoriasis, the dysfunction of keratinocyte proliferation manifests as an impairment of apoptosis. Cordycepin is the major active component in cordyceps militaris and has pharmacological effects, including regulation of apoptosis. The pharmacological mechanism of Cordycepin in psoriasis remains unclear. In this study, bioinformatics analysis revealed that the mechanism may be associated with the p53 apoptotic pathway. Further, we confirmed in the experiments that cordycepin inhibited the interleukin (IL)-17A-induced proliferation of HaCaT cells and down-regulated the expression of proliferating cell nuclear antigen (PCNA) and Ki-67. Regulating the expression of apoptotic proteins BAX, Bcl-2, and p53 promote apoptosis. Further investigation of the upstream pathway of apoptosis revealed that cordycepin could normalize the abnormal p53-mouse double minute 2 (MDM2) feedback loop. In vivo results showed that the cordycepin gel could effectively improve imiquimod (IMQ)-induced psoriasis-like skin lesions in mice, and the p53-MDM2 pathway was verified at the protein level. In conclusion, the anti-psoriasis effect of Cordycepin and its potential mechanism have not been discussed in detail. However, our work supports the idea that Cordycepin can be further developed as an Active Pharmaceutical Ingredient (API) for the treatment of psoriasis.
研究领域:
药理学
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皮肤科
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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
Frontiers in Immunology
·
2020
·
IF 5.085
Ma Zhanchuan,Zhen Yu,Hu Cong,Yi Huanfa
Myeloid-derived suppressor cells (MDSC) play a crucial role in regulating the intestinal immune response during colitis. We previously revealed an essential role of MDSC in promoting TH17 cell polarization, which was found to be arginase-1 (Arg-1)-dependent; however, the underlying mechanism remains obscure. Here we report that percentage of MDSC decreased in ArgmyeKO mice during DSS-induced colitis. IL-17A levels reduced but IL-17F levels increased significantly in the colorectum of ArgmyeKO mice, leading to severe tissue damage and high risk of mortality rate. Activation of estrogen receptor (ESR) increased pSTAT3 level in MDSC and consequently led to elevated percentage of MDSC and more Arg-1 and inducible nitric oxide synthase expression in MDSC. Increased level of IL-17A and reduced level of IL-17F alleviated colitis in mice consequently. Together, these findings demonstrate a protective role of MDSC-derived Arg-1 during colitis after activates ESR/STAT3 signaling in MDSC. High level of Arg-1 favors accumulation of IL-17A, but reduced IL-17F expression in the colorectum of mice and ultimately leading to relief of colitis, indicating a potential clinical impact of MDSC-derived Arg-1 for controlling inflammatory bowel disease.
研究领域:
免疫学
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分子生物学
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消化病学
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DOI
PubMed
高影响因子
Pharmaceutics
·
2025
·Vol. 17
·期 8
·1058
·
IF 5.5
Zhuoya Qiu,Mengru Zhang,Haitao Du,Yi Wang,Xuekun Shao,Jialei Fu,Ping Wang,Cheng Wang
Objectives:Atopic dermatitis (AD) is a long-term, recurring inflammatory skin condition characterized by impaired epidermal barrier function and abnormal immune system regulation. Pine pollen has traditionally been used for dermatological treatments, though its active components remain unclear. The primary objective of this study was to pinpoint the active constituents of pine pollen and elucidate its therapeutic effects against AD.Methods:The safety concentration ranges and protective efficacy of nine pine pollen constituents against 2,4-dinitrochlorobenzene (DNCB)-induced HaCaT cell damage were evaluated using the CCK-8 assay. Furthermore, models of DNCB-induced damage were established both in vitro (HaCaT cells) and in vivo (BALB/c mice) to explore the protective effects of the key functional component.Results:Our findings identified pine pollen polysaccharides (PPPS) as the principal bioactive constituent, characterized by a unique infrared absorption spectral profile and a sponge-like architecture with three-dimensional interconnected porous networks. In vitro, PPPS inhibited DNCB-induced decreases in cell viability, morphological abnormalities, oxidative stress, and apoptosis. In vivo, PPPS alleviated DNCB-induced skin lesions by attenuating epidermal hyperplasia, suppressing mast cell infiltration, inhibiting cell apoptosis, and downregulating the expression of IL-4 and IL-17A.Conclusions:This study provides evidence that PPPS from pine pollen can alleviate epidermal damage in AD, offering a novel therapeutic strategy for AD treatment.
研究领域:
生药学
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免疫皮肤学
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天然产物化学
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炎症研究
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多糖生物化学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
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2022
·Vol. 30
·期 5
·13739-13754
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IF 5.19
Wu Hao,Bao Yuling,Yan Tongtong,Huang Hui,Jiang Ping,Zhang Zhan,Li Lei,Wu Qian
Epidemiological studies have shown that PAHs may exert adverse effects on childhood asthma. However, the underlying molecular mechanism remains to be fully elucidated. This study aimed to investigate this process in view of metabolic pathways, especially one-carbon metabolism and tryptophan metabolism. Fifty asthmatic children and 50 control subjects were recruited for this study. Serum IgE and IL-17A levels were detected by ELISA. Serum PAH concentrations were measured by GC-MS. One-carbon-related metabolites and tryptophan metabolites were determined by UPLC-Orbitrap-MS. DNA methylation was analyzed by bisulfite sequencing PCR. ChIP assays were used to examine H3K4me3 enrichment on IL-17A gene. Multivariable linear regression was performed to evaluate the association between PAHs and childhood asthma mediated by intermediators. HE staining in lung tissue, IgE and IL-17A in BALF, metabolic profiles in urine, and Ahr , Il-17a , and Cyp1a1 gene expression were determined in PAH-exposed mice. Serum Fla level was associated with childhood asthma (OR = 1.380, 95% CI: 1.063–1.792), and had a great effect on one-carbon metabolites, especially SAH, SAM, and Ser, which exerted significant mediation effects on the relationship between the Fla concentration and asthma. Moreover, we did find significant mediation effects between serum Fla and asthma by LINE-1 DNA methylation and H3K4me3 levels in the IL-17A promoter region. The differential Trp metabolites, such as Trp, tryptamine, IA, IAA, indole, IAld, and IAAld, indicated that asthmatic children had increased indole-AhR pathway. Mediation analysis failed to show a mediator effect of Trp metabolites in the association between PAHs and childhood asthma. An animal study confirmed that PAH exposure increased methylation levels, and altered Trp metabolite-AhR-IL-17A axis, which may be influenced by gender. PAHs disturbed one-carbon metabolism to influence the methyl group refilling DNA methylation and histone methylation, and disturbed tryptophan metabolism to regulate Th17-cell differentiation, which may elevate serum IL-17A concentration in asthmatic children.
研究领域:
环境卫生
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免疫学
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分子生物学
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儿科
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2025
·
IF 4.3
Mali Dai,Pengyuan Du,Yijing Li,Xiaiting Wang,Jinrun Chen,Hui Liu,Wenqiao Zhang,Jianhong Zhou,Xingyi Li,Yuqin Wang
Effective treatment of chronic posterior ocular diseases such as uveitis, diabetic retinopathy, and age-related macular degeneration requires improvements in targeted drug delivery strategies. This study introduces a novel injectable drug delivery system co-assembled with a peptide-based hydrogel and secukinumab (SEK), an IL-17A neutralising monoclonal antibody, targeting retinal pigmented epithelium (RPE) cells. Compared to a SEK solution, the SEK loaded hydrogel significantly enhanced the protein uptake (3.7 times higher) by RPE cells in an inflammatory state after 24 h of treatment and increased the drug concentration in retinal tissues during 20 d of treatment. A single intravitreal injection of the SEK loaded hydrogel effectively suppressed inflammation in a uveitis model. It also reduced the immunoreactivity of microglia and T helper 17 cells, preserved the integrity of the blood-retina barrier, mitigated retinal cell apoptosis, and facilitated the recovery of the retinal function. This delivery system comprising an antibody-drug co-assembled with a peptide-based hydrogel shows promising potential for targeting the retina and treating complex chronic posterior ocular diseases.
研究领域:
药学
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眼科学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Chen Mingjun,Feng Yang,Luo Dan,Zhang Chen,Zhou Jing,Dai Hengheng,Lin Mingxiong,Tong ZhanQi
Purpose: Wuwei Kushen Changrong capsule (Composite Sophora Colon-soluble Capsule, CSCC) is a Chinese patent medicine developed to treat ulcerative colitis. Studies highlight CSCC potential efficacy for ulcerative colitis (UC) but unclear mechanism limits its widely treatment for patients. We aimed to investigate the anti-colitis efficacy of CSCC and explore the mechanism by which GPR43 inhibits the NLRP3/STAT3 signaling pathway, thereby mediating the protective effects of CSCC on the intestinal barrier.Methods: The protective effects of CSCC were evaluated in a murine ulcerative colitis model induced by 3% DSS. Assessments included body weight, Disease Activity Index (DAI) score, colon length, and histopathological score. Colon tissue, cell function, and immune-inflammatory status were evaluated using immunohistochemistry, immunofluorescence, ELISA, and real-time fluorescence quantitative PCR (RT-PCR). Protein expression levels of relevant pathways and receptors were measured using Western blot. All experiments were repeated.Results: CSCC protected mice from DSS-induced colitis by upregulating Gpr43, promoting the expression of ZO-1 and Occludin tight junction proteins. Mechanistically, CSCC inhibits the MEK4/JNK1/STAT3 activation pathway, consequently suppressing the STAT3/NLRP3/IL-1β pathway and inhibiting the production of inflammatory factors such as IL-17A.Conclusion: The mechanisms through which CSCC protects against DSS-induced colitis may include upregulating Gpr43, inhibiting the STAT3/NLRP3 pathway, and suppressing inflammation factors like IL-17A. These findings highlight the mechanisms underlying CSCC’s anti-colitis effects and suggest its potential as a therapeutic candidate for managing the progression of UC.
研究领域:
药理学
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免疫学
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胃肠病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF CHEMISTRY
·
2022
·Vol. 41
·期 2
·199-206
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IF 5.56
Linzi Chen,Zhenqi Jiang,Lifei Yang,Ye Fang,Shuwei Lu,Ozioma U. Akakuru,Shuaishuai Huang,Juan Li,Suya Ma,Aiguo Wu
Comprehensive Summary Thrombosis, secondary to rupture of unstable plaque, is a fatal risk factor for myocardial infarction and ischemic stroke. At present, more novel methods are needed for the diagnosis and treatment of vulnerable plaque. Here, we report a hollow polydopamine/Zn (HPDA/Zn) ultrasound contrast agent. Through western-blot, Elisa, and other experiments, we found that in addition to having a good contrast-enhancement capability in ultrasound imaging in vitro and in vivo , HPDA/Zn also has the effect of reducing the expression of CREB. CREB protein and its downstream-regulated proteins and factors are closely related to the stability of plaque. HPDA/Zn has the effect of reducing the expression of CREB protein, which leads to the decrease of expression of MMP-9, the regulatory protein downstream of the CREB protein. In addition, it also reduces the secretion of inflammatory factors hs-CRP and IL-17A. Thus, HPDA/Zn can stabilize plaque by inhibiting CREB and reducing plaque vulnerable markers and inflammatory factors. In a word, HPDA/Zn is a kind of ultrasound contrast agent, which can stabilize plaques by inhibiting CREB protein.
研究领域:
医学影像
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心血管疾病
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药理学
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生物医学工程
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产品关联
DOI
高影响因子
Cellular & Molecular Immunology
·
2023
·
IF 24.1
Luo Ya,Liu Cheng,Luo Yuan,Zhang Xianglian,Li Jing,Hu Changjiang,Yang Shiming
Thiostrepton (TST) is a natural antibiotic with pleiotropic properties. This study aimed to elucidate the therapeutic effect of TST on experimental colitis and identify its targets. The effect of TST on colon inflammation was evaluated in a dextran sulfate sodium (DSS)-induced colitis model and a T-cell transfer colitis model. The therapeutic targets of TST were investigated by cytokine profiling, immunophenotyping and biochemical approaches. The effect of TST on the gut microbiota and its contribution to colitis were evaluated in mice with DSS-induced colitis that were subjected to gut microbiota depletion and fecal microbiota transplantation (FMT). Alterations in the gut microbiota caused by TST were determined by 16S rDNA and metagenomic sequencing. Here, we showed that TST treatment significantly ameliorated colitis in the DSS-induced and T-cell transfer models. Specifically, TST targeted the retinoic acid-related orphan nuclear receptor RORγt to reduce the production of IL-17A by γδ T cells, type 3 innate lymphoid cells (ILC3s) and Th17 cells in mice with DSS-induced colitis. Similarly, TST selectively prevented the development of Th17 cells in the T-cell transfer colitis model and the differentiation of naïve CD4 + T cells into Th17 cells in vitro. Mechanistically, TST induced the ubiquitination and degradation of RORγt by promoting the binding of Itch to RORγt. Moreover, TST also reversed dysbiosis to control colonic inflammation. Taken together, these results from our study describe the previously unexplored role of TST in alleviating colonic inflammation by reducing IL-17A production and modulating dysbiosis, suggesting that TST is a promising candidate drug for the treatment of IBD.
研究领域:
免疫学
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胃肠病学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2022
·
IF 6.556
Xueyu Zhang,Mingyan Liu,Minghui Yang,Wangqing Cheng,Juan Xiang,Wu Zhu,Xiang Chen
Nanoparticles are usually used as carrier to load more antibody and enzyme to improve the sensitivity of enzyme-linked immunosorbent assay (ELISA). However, limited by high density and complicated modification procedure, the traditional nanoparticles such as Au nanoparticles (AuNPs) usually induce large background signal and poor reproducibility in ELISA. In this work, functional lightweigh nanoparticle [email protected] ( [email protected] ) was prepared and induced as the carrier of detection antibody and horseradish peroxidase (HRP) to form [email protected] @Ab 2 /HRP biojungates. The appropriate density (close to water) and good hydropilicity ensure the good dispersion of [email protected] @Ab 2 /HRP in solution, preventing the physical sedimention and decreasing the background signal even though the bioconjugate's size is close to 200 nm. The large surface area and abundant active group from PDA facilitate the loading of detection antibody and HRP, improving the loading efficiency and stability of biojungates. Based on it, taking interleukin-17A (IL-17A, a biomarker of psoriasis) as the detection target, we developed a [email protected] sandwich ELISA, achieving a sensitive dynamic range from 0.3 to 80 pg/mL and a detection limit of 0.2 pg/mL. Furthermore, the contents of IL-17A were assayed successfully in 10-fold diluted serum samples from psoriasis patients. Compared with those commercial or AuNP-based ELISA, our [email protected] ELISA method exhibits higher sensitivity, lower background interference, and higher stability, which will significantly improve the application of ELISA in the low-abundant biomolecule assays.
研究领域:
纳米技术
·
生物化学
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分析化学
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免疫学
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诊断学
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产品关联
DOI
PubMed
高影响因子
Nutrients
·
2024
·Vol. 16
·期 4
·519
·
IF 4.8
Xiao Li,Xingru Lu,Ming Liu,Yu Zhang,Yujun Jiang,Xinyan Yang,Chaoxin Man
The aim of this study was to investigate the immunomodulatory effects of A2 β-casein (β-CN) in cyclophosphamide-induced immunosuppressed BALB/c mice. Experiments conducted in vitro revealed that A2 β-CN digestive products have potent immunostimulatory activities. Animal studies demonstrated that A2 β-CN improved the immunological organ index reduction trend caused by cyclophosphamide, reduced the pathological damage to the spleen tissue in immunosuppressed mice, increased the release of IL-17A, IgG, and IgA, and reduced the production of IL-4. By regulating the relative abundance of advantageous bacteria likeOscillospira,Lactobacillus, andBifidobacteriaand harmful bacteria likeCoprococcusandDesulfovibrionaceae, A2 β-CN improved gut microbiota disorders in immunosuppressed mice. Moreover, A2 β-CN promoted the production of short-chain fatty acids and increased the diversity of the gut microbiota. Therefore, ingestion of A2 β-CN is beneficial to the host’s immune system and gut health. These findings provide insights for the future application of A2 β-CN-related dairy products.
研究领域:
免疫学
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微生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
·
2023
·
IF 3.3
Xiulian Zhang,Xueliang Li,Wei Ma,Fangying Liu,Pinxian Huang,Lei Wei,Li Li,Yechang Qian
Background Chronic obstructive pulmonary disease (COPD) has a high fatality rate and poses a great threat to human health. Astragaloside IV (AS-IV) is proven to attenuate cigarette smoke (CS)-induced pulmonary inflammation, based on which this research focuses on the mechanism of AS-IV in COPD.Methods To evaluate the effects of AS-IV, CD4+ T cells received different concentrations of AS-IV. CD4+ T cell viability, T helper 17 (Th17)/regulatory T (Treg) markers and CXCR4 expressions in CD4+ T cells or spleen/lung tissues were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, quantitative real-time polymerase chain reaction and Western blot. The proportions of Treg and Th17 cells were assessed by flow cytometry. Enzyme-linked immune sorbent assay was employed to determine cytokine contents in serum and lung tissues.Results AS-IV with concentration exceeding 40 µM inhibited CD4+ T cell viability. In vitro, AS-IV suppressed the expressions of CXCR4, retinoid-related orphan receptor γt (RORγt), and interleukin (IL)-17A as well as Th17 cells but promoted the expressions of forkhead box p3 (Foxp3) and IL-10 as well as Treg cells, while CXCR4 overexpression reversed the effects of AS-IV. In vivo, AS-IV alleviated COPD, and CS-induced Th17/Treg imbalance in mice and reduced CS-induced down-regulation of IL-10 in serum and lung tissues and Foxp3 and up-regulation of IL-1β, tumor necrosis factor alpha (TNF-α), IL-6, and IL-17A in serum and lung tissues and RORγt. AS-IV mitigated CS-induced CXCR4 up-regulation. Above effects of AS-IV on mice were offset by CXCR4 overexpression.Conclusions AS-IV restores Th17/Treg balance via impeding CXCR4 to ameliorate COPD.
研究领域:
免疫学
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肺科学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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