INFLAMMATION
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2019
·Vol. 42
·期 4
·1179-1189
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IF 2.939
Xue Yu-Long,Zhang Sheng-Xiao,Zheng Chao-Feng,Li Yu-Feng,Zhang Li-Hui,Hao Yu-Fei,Wang Shu,Li Xue-Wen
Signal transducer and activator of transcription 4 (STAT4) has been implicated in the progression of myocarditis. The aim of the current study was to investigate the role by which STAT4 influences autoimmune myocarditis in an attempt to identify a theoretical therapeutic perspective for the condition. After successful establishment of an autoimmune myocarditis rat model, the expression patterns of STAT4, NF-κB pathway–related genes, Th1 inflammatory cytokines (IFN-γ and IL-2), and Th2 inflammatory cytokines (IL-6 and IL-10) were subsequently determined. The rats with autoimmune myocarditis were treated with oe-STAT4 or sh-STAT4 lentiviral vectors to evaluate the role of STAT4 in autoimmune myocarditis, or administrated with 1 mL 10 μmol/L of BAY11-7082 (the NF-κB pathway inhibitor) via tail vein to investigate the effect of the NF-κB pathway on autoimmune myocarditis. Finally, cell apoptosis was evaluated. The serum levels of IFN-γ and IL-2, extent of IκBα and P65 phosphorylation, and the expression of STAT4 were elevated, while the serum levels of IL-6 and IL-10 as well as the expression of IκBα were reduced among the rats with autoimmune myocarditis, which was accompanied by an increase in the apoptotic cells. More importantly, the silencing of STAT4 or the inhibition of the NF-κB pathway was detected to result in a decrease in the serum levels of IFN-γ and IL-2 and an elevation of the serum levels of IL-6 and IL-10, and inhibited myocardial cell apoptosis in rats with autoimmune myocarditis. Moreover, STAT4 silencing was also observed to decrease the extent of IκBα and P65 phosphorylation while acting to elevate the expression of IκBα. Taken together, silencing of STAT4 could hinder the progression of autoimmune myocarditis by balancing the expression of Th1/Th2 inflammatory cytokines via the NF-κB pathway, which may provide a novel target for experimental autoimmune myocarditis (EAM) treatment.
研究领域:
免疫学
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心脏病学
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分子生物学
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DOI
PubMed
高影响因子
ACS Nano
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2025
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IF 16
Yichao Lu,Xinyu Shan,Jiaxin Huang,Huanli Zhou,Ying Zhu,Sijie Wang,Zhenyu Luo,Xu Liu,Xuemeng Guo,Yingying Shi,Yilong Hu,Huihui Liu,Junlei Zhang,Ping Huang,Lihua Luo,Jian You
Atopic dermatitis (AD) is a recurrent and chronic inflammatory skin condition characterized by a high lifetime prevalence and significant impairment of patients’ quality of life, primarily due to intense itching and discomfort. However, current pharmacological interventions provide only moderate efficacy and are frequently accompanied by adverse side effects. The immune-pathogenesis of AD involves dysregulation of the Th2 immune response and exacerbation of inflammation related to excessive reactive oxygen species (ROS). Therefore, to address these issues, in this study, we targeted the upstream pathogenesis by designing a pro-Th1 adjuvant nanoemulsion loaded with poly(I:C) and encapsulated with the ROS-scavenger vitamin E, termed PV-NE. PV-NE effectively rebalanced the Th1/Th2 immune response and reduced ROS levels both in vivo and ex vivo, leading to the restoration of immune balance in AD-affected skin and alleviation of symptoms such as lichenification and erythematous patches. In conclusion, our development of the reductive adjuvant nanosystem PV-NE demonstrates its biocompatibility and efficacy in combating AD progression without the use of immunosuppressant glucocorticoids. This has the potential to significantly impact the design and enhancement of pharmacotherapy in future clinical research aimed at curing AD.
研究领域:
皮肤病学
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免疫学
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纳米医学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Wushi Chen,Yunqin Shen,Hongyun Jia,Shanshan Hou,Lingjie Li,Lixia Huang,Jiyi Cai,Yuhan Xing,Yanqiu Chen,Yan Yang
Ethnopharmacological relevance Humulus lupulus L. , an herb traditionally employed in medicinal practices across North America, Egypt, India, and China, demonstrates broad therapeutic properties, including anti-inflammatory, antioxidant, hepatoprotective, and diuretic effects. Xanthohumol (XN), a prenylated flavonoid derived from Humulus lupulus L., retains these anti-inflammatory and antioxidant activities. However, its potential efficacy in allergic asthma remains largely unexplored. Aim of the study This study aimed to investigate the protective properties of XN against allergic asthma and to elucidate the underlying mechanisms, particularly the role of Absent in Melanoma 2 (AIM2), an innate immune sensor, in allergic asthma and its modulation by XN. Materials and methods The OVA-induced murine model of allergic asthma with XN administration in different dosages was constructed to evaluate the regulatory effects of XN on allergic asthma, particularly during the period of acute attack. Pathological alterations, T-cell polarization, inflammatory cytokine profiles, and oxidative stress markers were systematically assessed. Bioinformatic analysis, clinical case-control, and molecular docking combined with cellular thermal shift assay (CETSA) were applied to identify the specific target of XN to execute its effects. Human bronchial epithelial (16HBE) cell models with various stimulations and treatments were used in this study to verify the mechanistic exploration. Results In allergic asthmatic mice, the results demonstrated that XN dose-dependently attenuated airway inflammation and immune balance, characterized by reduced inflammatory cell infiltration, cytokine production, IgE secretion, and Th2 immune response. AIM2 was recognized as a critical binding target of xanthohumol through database analysis, molecular docking, and CETSA. Clinically, elevated serum AIM2 levels in asthma patients correlated positively with eosinophil percentage, IgE levels, and systemic immune inflammation index (SII). Mechanistically, both in vivo and in vitro studies revealed that XN mitigated oxidative stress and mitochondrial dysfunction, thereby reducing double-stranded DNA release, a key activator of the AIM2 inflammasome. Moreover, XN dose-dependently suppressed AIM2 inflammasome activation, an effect further validated in Poly (dA:dT)-stimulated and AIM2-silenced 16HBE cells. Conclusion This study provides the first evidence implicating XN can improve OVA-induced allergic asthma by suppressing AIM2 inflammasome activation, highlighting XN as a promising therapeutic candidate for allergic asthma.
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Donghui Li,Wenbo Li,Sheng Li,Yangyang Zhang,Xianwen Hu,Shilin Liu,Yan Li
Nasal vaccine is a non-invasive vaccine that activates systemic and mucosal immunity in the presence of an adjuvant, thereby enhancing immune function. In this work, chitosan/oligochitosan/tween 80 (CS-COS-T80) co-stabilized emulsion was designed and further used as the nasal adjuvant. CS-COS-T80 emulsion exhibited outstanding stability under pH 6–8 with uniformly dispersed droplets and nano-scale particle size (<0.25 μm), and maintained stable at 4 °C for 150-day storage. Addition of model antigen ovalbumin (OVA) had no effect on the stability of CS-COS-T80 emulsion. In vivo nasal immunity indicated that CS-COS-T80 emulsion prolonged the retention time of OVA in the nasal cavity (from 4 to 8 h to >12 h), as compared to T80-emulsion. CS-COS-T80 emulsion produced a stronger mucosal immune response to OVA, with secretory IgA levels 5-fold and 2-fold higher than those of bare OVA and commercial adjuvant MF59, respectively. Compared to MF59, CS-COS-T80 induced a stronger humoral immune response and a mixed Th1/Th2 immune response of OVA after immunization. Furthermore, in the presence of CS-COS-T80 emulsion, the secretion of IL-4 and IFN-γ and the activation of splenocyte memory T-cell differentiation increased from 173.98 to 210.21 pg/mL and from 75.46 to 104.01 pg/mL, respectively. Therefore, CS-COS-T80 emulsion may serve as a promising adjuvant platform.
研究领域:
药学
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免疫学
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生物技术
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产品关联
DOI
PubMed
高影响因子
Materials Horizons
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2024
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IF 12.2
Wenzhu Yin,Zeyu Xu,Chen Chang,Yanhong Zhao,Haiyan Wang,Jinqiu Zhang,Fang Ma,Xiaoxin Zuo,Bo Tang,Yu Lu
Pseudorabies virus (PRV) is a highly contagious viral disease, and leads to severe financial losses to the breeding industry worldwide. The PRV is mainly controlled using live attenuated and inactivated vaccines today. However, these vaccines have an innate tendency to lose their structural conformation upon environmental and chemical stressors, and can’t provide full protection against the prevalent variant PRV recently. In this work, we firstly synthesized aminated ZIF-7/8 nanoparticles (NPs), and then chemical bond coated alginate dialdehyde (ADA, a kind of dioxide alginate saccharides) on its surface via Schiff base reaction to get ZIF-7/8-ADA NPs. The as-fabricated ZIF-7/8-ADA NPs exhibited high stability, monodispersity and a high loading ratio of antigen. Furthermore, ZIF-7/8-ADA NPs showed good biocompatibility in vitro and in vivo. Using ZIF-7/8-ADA NPs as an adjuvant and inactivated PRV as the model antigen, we constructed a PR vaccine through a simple mixture. Immunity studies indicated that ZIF-7/8-ADA induced an enhancing Th1/Th2 immune response, which was superior to that of commercial ISA201, Alum adjuvant as well as ZIF-7/8. Due to the pH-sensitive release of the antigen in lysosomes, the as prepared PR vaccine subsequently accelerated antigen presentation and improved immune responses in vitro and in vivo. The results of challenge against PRV using mice as model proclaimed that ZIF-7/8-ADA could obtain the same preventive effect as commercial ISA201, and was much better than that of alum adjuvant, which could serve as a promising delivery and adjuvant to enhance humoral and cellular responses against PRV infection.
研究领域:
病毒学
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免疫学
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纳米技术
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药学
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产品关联
DOI
PubMed
高影响因子
Small
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2024
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IF 13
Yapeng Wang,Jing Yang,Yunhong Ma,Jun Liu,Peng Wang,Junhao Luo,Yongjun Rui,Yongwei Wu
The accumulation of excessive reactive oxygen species (ROS) and recurrent infections with drug-resistant bacteria pose significant challenges in diabetic wound infections, often leading to impediments in wound healing. Addressing this, there is a critical demand for novel strategies dedicated to treating and preventing diabetic wounds infected with drug-resistant bacteria. Herein, 2D tantalum carbide nanosheets (Ta 4 C 3 NSs) have been synthesized through an efficient and straightforward approach, leading to the development of a new, effective nanoplatform endowed with notable photothermal properties, biosafety, and diverse ROS scavenging capabilities, alongside immunogenic attributes for diabetic wound treatment and prevention of recurrent drug-resistant bacterial infections. The Ta 4 C 3 NSs exhibit remarkable photothermal performance, effectively eliminating methicillin-resistant Staphylococcus aureus ( MRSA ) and excessive ROS, thus promoting diabetic wound healing. Furthermore, Ta 4 C 3 NSs enhance dendritic cell activation, further triggering T helper 1 (T H 1)/T H 2 immune responses, leading to pathogen-specific immune memory against recurrent MRSA infections. This nanoplatform, with its significant photothermal and immunomodulatory effects, holds vast potential in the treatment and prevention of drug-resistant bacterial infections in diabetic wounds.
研究领域:
纳米技术
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生物医学工程
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传染病学
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免疫学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
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2022
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IF 8.786
ZhengQing Yu,Ke He,WanDi Cao,Muhammad Tahir Aleem,RuoFeng Yan,LiXin Xu,XiaoKai Song,XiangRui Li
Caused by Toxoplasma gondii , toxoplasmosis has aroused great threats to public health around the world. So far, no effective vaccine or drug is commercially available, and the demands for a safe and effective therapeutic strategy have become more and more urgent. In the current study, we constructed a DNA vaccine encoding T. gondii ribosomal P2 protein (TgP2) and denoted as TgP2-pVAX1 plasmid. To improve the immunoprotection, nanomaterial poly-lactic- co -glycolic acid (PLGA) and chitosan were used as the delivery vehicle to construct TgP2-pVAX1/PLGA and TgP2-pVAX1/CS nanospheres. Before vaccinations in BALB/c mice, TgP2-pVAX1 plasmids were transiently transfected into Human Embryonic Kidney (HEK) 293-T cells, and the expression of the eukaryotic plasmids was detected by laser confocal microscopy and Western blotting. Then the immunoprotection of naked DNA plasmids and their two nano-encapsulations were evaluated in the laboratory animal model. According to the investigations of antibody, cytokine, dendritic cell (DC) maturation, molecule expression, splenocyte proliferation, and T lymphocyte proportion, TgP2-pVAX1 plasmid delivered by two types of nanospheres could elicit a mixed Th1/Th2 immune response and Th1 immunity as the dominant. In addition, TgP2-pVAX1/PLGA and TgP2-pVAX1/CS nanospheres have great advantages in enhancing immunity against a lethal dose of T. gondii RH strain challenge. All these results suggested that TgP2-pVAX1 plasmids delivered by PLGA or chitosan nanomaterial could be promising vaccines in resisting toxoplasmosis and deserve further investigations and applications.
研究领域:
免疫学
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分子生物学
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纳米技术
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寄生虫学
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疫苗学
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产品关联
DOI
PubMed
高影响因子
TALANTA
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2024
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IF 5.6
Chengchen Pang,Bei Yuan,Keyun Ren,Haitao Xu,Kunying Nie,Chunlei Yu,Zhanli Liu,Yanyan Zhang,Sibel A. Ozkan,Qingqing Yang
In preparing monoclonal antibodies by hybridoma cell technology, the quality of B lymphocytes used for cell fusion directly affects the sensitivity of monoclonal antibodies. To obtain B-lymphocytes producing high-quality specific antibodies for cell fusion during the immunization phase of the antigen, we prepared a TH2-Cell stimulatory delivery system as a novel adjuvant. Astragalus polysaccharide has a good ability to enhance antigenic immune response, and it was encapsulated in biocompatible materials PLGA as an immunostimulatory factor to form the delivery system (APS-PLGA). The preparation conditions of APSP were optimized using RSM to attain the highest utilization of APS. Immunization against ZEN-BSA antigen using APSP as an adjuvant to obtain B lymphocytes producing ZEN-specific antibodies for cell fusion. As results present, APSP could induce a stronger TH2 immune response through differentiating CD4 T cells and promoting IL-4 and IL-6 cytokines. Moreover, it could slow down the release efficiency of ZEN-BSA and enhance the targeting of ZEN-BSA to lymph nodes in vivo experiments. Ultimately, the sensitivity of mouse serum ZEN-specific antibodies was enhanced upon completion of immunization, indicating a significant upregulation of high-quality B lymphocyte expression. In the preparation of monoclonal antibodies, the proportion of positive wells for the first screening was 60%, and the inhibition rates of the antibodies were all similar (>50%). Then we obtained the ZEN monoclonal antibody with IC50 of 0.049 ng/mL, which was more sensitive than most antibodies prepared under conventional adjuvants. Finally, a TRFIAS strip assay was preliminarily established with a LOD value of 0.246 ng/mL.
研究领域:
免疫学
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生物技术
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纳米技术
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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