International Journal of Nanomedicine
·
2024
·
IF 6.6
Xu Zuo,Yinuo Gu,Xiaoping Guo,Wenxue Zheng,Haoyu Zheng,Yiming An,Caina Xu,Fang Wang
Purpose Inhaled corticosteroids, including budesonide (BUD), are widely employed for the treatment of asthma. However, the frequent use of corticosteroids is associated with numerous adverse effects and poses challenges to ongoing drug therapy and patient adherence. Budesonide liposomal nanoparticles (BUD-LNPs) were developed to improve the bioavailability of the drug and thereby improve the effectiveness of asthma treatment.Methods BUD-LNPs were prepared via thin-film hydration, and the characterizations, stability, and in vitro release of BUD-LNPs were studied. In vitro cellular uptake was observed by laser-scanning confocal microscope (LSCM) and flow cytometry. And the in vitro anti-inflammatory activity of BUD-LNPs was evaluated by measuring the expression of pro-inflammatory cytokines in activated macrophages. Besides, the accumulation time in the lung of drugs delivered via liposomal carriers and free drugs was compared in vivo. And the in vivo therapeutic efficacy of BUD-LNPs was assessed in OVA-induced asthmatic mice. Finally, in vivo biosafety assessment was performed.Results The particle size, PDI, and zeta potential of BUD-LNPs were 127.63±1.33 nm, 0.27±0.02, and 3.33±0.13 mV, respectively. BUD-LNPs exhibited excellent biosafety and anti-inflammatory activity in vitro. Furthermore, compared with the free drugs, the utilization of liposomal nano-vehicles for drugs delivery could effectively extend the duration of drugs accumulation in the pulmonary system. Additionally, treatment with BUD-LNPs alleviated airway hyperresponsiveness, reduced airway mucus secretion, and mitigated pulmonary inflammation in OVA-induced asthmatic mice. And the BUD-LNPs demonstrated superior therapeutic efficacy compared to free BUD.Conclusion BUD-LNPs was successfully prepared with excellent stability and sustained release for 24 h in vitro. The data of anti-inflammatory activity, asthma therapeutic effects and safety studies indicated that drug delivery mediated by liposomal nano-vehicles was a feasible and desirable strategy for medical strategy and showed great promise in the clinical therapy of asthma.
研究领域:
药剂学
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药理学
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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
Frontiers in Microbiology
·
2025
·
IF 4.5
Lin Lin,Siyuan Li,Que Liu,Xingxing Zhang,Ying Xiong,Shaoyun Zhao,Liyue Cao,Jiaxuan Gong,Yaping Liu,Rong Wu
Objective: This study aimed to investigate the potential relation between the retarded growth of skeletal muscle (SM) and dysbiosis of gut microbiota (GM) in children with asthma, and to explore the potential action mechanisms of traditional pediatric massage (TPM) from the perspective of regulating GM and short-chain fatty acids (SCFAs) production by using an adolescent rat model of asthma.Methods: Male Sprague-Dawley rats aged 3weeks were divided randomly into the 5 groups (n=6~7) of control, ovalbumin (OVA), OVA + TPM, OVA + methylprednisolone sodium succinate (MP) and OVA + SCFAs. Pulmonary function (PF) was detected by whole body plethysmograph, including enhanced pause and minute ventilation. Airway allergic inflammation (AAI) status was assessed by concentrations of OVA-specific immunoglobulin E in plasma, interleukin (IL)-4 and IL-1β in bronchoalveolar lavage fluid via ELISA assay. SM mass was assessed by using cross-sectional areas of diaphragm muscle and gastrocnemius via hematoxylin and eosin staining. GM and SCFAs production were detected by 16S rDNA sequencing and GC-MS, respectively. The protein and gene expressions of free fatty acid receptor 2 in SM were detected by using immunohistochemical staining and qRT-PCR, respectively. qRT-PCR was used to detect other relative gene expressions that were closely related with SM mass. The activity of insulin-like growth factor-1 (IGF-1)/protein kinase B (PKB/AKT) pathway in SM was detected by western blotting test.Results: OVA exposure caused obvious AAI and poor PF in adolescent rats. OVA-exposed adolescent rats had a retarded growth of SM mass and inhibited activity of IGF-1/AKT pathway, which was related with GM dysbiosis, reduced SCFAs production and FFAR2 expressions in SM. TPM efficiently enhanced the SM mass, along with alleviating AAI and improving PF. TPM activated IGF-1/AKT pathway in SM, which was closely related with correcting GM dysbiosis, enhanced SCFAs production and FFAR2 expressions.Conclusion: The retarded growth of SM mass and inhibition of IGF-1/AKT pathway existed in OVA-exposed adolescent rats, which was related with GM dysbiosis, reduced SCFAs production and FFAR2 expressions in SM. TPM efficiently enhanced the SM mass, at least, partially via regulating GM, enhancing SCFAs production and activating FFAR2-IGF-1/AKT pathway.
研究领域:
儿科学
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免疫学
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药理学
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微生物学
·
肌肉骨骼系统
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DOI
PubMed
高影响因子
Food Chemistry-X
·
2024
·
IF 6.5
Xiefei Li,Yingmei Wu,Wenshan Duan,Lei Chen,Lujie Cheng,Junmei Liu,Yan Zhou,Chao Ai,Xin Li,Qun Huang
The poor thermal stability and emulsifying properties of ovalbumin (OVA) limit its functional performance, but these limitations may be overcome by forming binary complexes. We prepared binary complexes of OVA and fucoidan (FUC) through electrostatic self-assembly and investigated the emulsifying properties of the complex by measuring the particle size, interfacial membrane thickness, zeta potential, and stability of the emulsion prepared with camellia oil and the complex. The OVA-FUC emulsions have a thicker interfacial membrane, lower mobility, higher viscosity, and better stability compared with the OVA emulsions. The emulsion prepared with 1.5 % OVA-FUC remained stable and homogeneous during storage. They tended to become unstable with freeze–thaw, but the oil encapsulated did not leak after coalescence occurred. With the addition of Ca 2+ , the OVA-FUC emulsion will be converted into a gel state. These findings indicate that OVA-FUC binary complexes can be used to prepare high-performance emulsions with great potential for development.
研究领域:
食品科学
·
胶体与表面化学
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DOI
PubMed
高影响因子
Science China-Chemistry
·
2015
·Vol. 58
·期 9
·1508-1514
·
IF 1.695
Wang Lu-Liang,Qiao Juan,Qi Li,Xu Xiao-Zhe,Li Dan
Protein protected gold nanoclusters have outstanding physical and chemical properties that make them excellent scaffolds for the construction of novel chemical and biological probes. In this study, a simple one-pot synthesis method was proposed for the preparation of fluorescent probes based on ovalbumin-stabilized gold nanoclusters. This strategy allowed the generation of water-soluble gold nanoclusters within 5 min. The as-prepared fluorescent probe exhibited a red fluorescence emission at 625 nm, and good thermostability. The fluorescent probe was applied to measure glucose concentrations based on the hydrogen peroxide-induced fluorescence quenching principle, and showed favorable biocompatibility, high sensitivity and good selectivity. As a result of the advantageous properties and performance of this fluorescent probe, the present assay allowed for the selective determination of glucose in the range of 5.0×10 −6 to 10.0×10 −3 mol/L with a detection limit of 1.0×10 −6 mol/L. Moreover, the glucose content in urinary samples was analyzed using the constructed fluorescent probe: this indicated the potential of the fluorescent gold nanoclusters for applications in biological and clinical diagnosis and therapy.
研究领域:
分析化学
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生物医学工程
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纳米技术
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DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
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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PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-13
·
IF 4.259
Li Kai,Zhang Yue,Liang Kang Yan,Xu Song,Zhou Xue Juan,Tan Kang,Lin Jun,Bai Xiao Chun,Yang Cui Lan
The small GTPase ras homolog enriched in brain ( Rheb ) is a downstream target of tuberous sclerosis complex 1/2 ( TSC1/2 ) and an upstream activator of the mechanistic target of rapamycin complex 1 (mTORC1), the emerging essential modulator of M1/M2 balance in macrophages. However, the role and regulatory mechanisms of Rheb in macrophage polarization and allergic asthma are not known. In the present study, we utilized a mouse model with myeloid cell-specific deletion of the Rheb1 gene and an ovalbumin (OVA)-induced allergic asthma model to investigate the role of Rheb1 in allergic asthma and macrophage polarization. Increased activity of Rheb1 and mTORC1 was observed in myeloid cells of C57BL/6 mice with OVA-induced asthma. In an OVA-induced asthma model, Rheb1 -KO mice demonstrated a more serious inflammatory response, more mucus production, enhanced airway hyper-responsiveness, and greater eosinophil numbers in bronchoalveolar lavage fluid (BALF). They also showed increased numbers of bone marrow macrophages and BALF myeloid cells, elevated M2 polarization and reduced M1 polarization of macrophages. Thus, we have established that Rheb1 is critical for the polarization of macrophages and inhibition of allergic asthma. Deletion of Rheb1 enhances M2 polarization but decreases M1 polarization in alveolar macrophages, leading to the aggravation of OVA-induced allergic asthma.
研究领域:
免疫学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Minyi Yang,Rongye Jia,Yuxuan Liu,Hengkun Tang,Huijuan Wu,Jun Yuan,Rongzhi Wang
Furosine, a hazardous compound mainly produced by the Maillard reaction in food at high temperatures, has been shown to exert cytotoxic effects on cells and cause liver damage after excessive consumption. Hence, it is desirable to develop correlative sensitive and robust immunoassays for furosine detection in real-world samples. In this study, Ovalbumin-furosine (OVA-furo) conjugates were employed as the immunogens for animal immunization, and a hybridoma (1C3) secreting an anti-furosine monoclonal antibody (mAb) was successfully screened. The purified 1C3 mAb exhibited high specificity and affinity (7.4 × 10 8 L/mol), and an indirect competitive ELISA (ic-ELISA) based on the 1C3 mAb was developed for the detection of furosine. The linear detection range of the ic-ELISA was 6.03–817.85 ng/mL, with a limit of detection (LOD) value of 2 ng/mL. Colloid gold nanospheres(AuNP-) and nanoflower gold-particles(AuNF)-based strips were also established based on this antibody, which had qLOD values and linear ranges of 40 and 20 ng/mL and 40–140 and 20–90 ng/mL, respectively. All the immunoassays showed good detection performance, indicating that these immunoassays have the potential for practical application for the inexpensive detection of furosine in real-world samples.
研究领域:
食品科学
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免疫学
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Wen Guo,Zhiqi Wang,Rubing Xue,Xinyue Zhang,Qinfu Zhao,Yikun Gao,Siling Wang,Yuling Mao
Weak response is the bottleneck for subunit prophylactic vaccines to trigger efficient immunization. The emergence of highly effective adjuvants will revolutionize. Considering that genomic epigenetic reprogramming plays an important role in the immune response, we herein present an minimalist epigenetic nano-adjuvant gMSN constructed of β-glucan-modified functional mesoporous silica (MSN), which we term as OVA/gMSN after loaded with the model antigen ovalbumin (OVA). Oral administration of OVA/gMSN ensures that enough antigen reach dendritic cells (DCs) in intestinal mucosal lymphoid follicles via intestinal M cells while relying on gMSN to exhibit good adjuvant properties to trigger an effective systemic co-mucosal immune response. gMSN upregulates genes associated with aerobic glycolysis, promoting metabolic reprogramming in DCs and enhancing the expression of genes related to DC activation, cross-presentation, maturation, and migration. Simultaneously, it increases the accumulation of key epigenetic markers H3K27ac, H3K4me1, and H3K4me3. ATAC-seq results reveal enhanced chromatin accessibility of key immune genes, such as Il2rα1, Il18r1, and Cd83, in gMSN-treated DCs. This integrative molecular mechanism demonstrates that gMSN induces epigenomic remodeling in DCs after oral administration, showcasing the potential of combining epigenetic adjuvants and nanotechnology in oral vaccine design, and providing new directions and a theoretical basis for vaccine adjuvant development.
研究领域:
免疫学
·
纳米医学
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疫苗学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2021
·
IF 5.34
Yisa Liu,Juan Wang,Xiao Guan,Dan Yu,Mengjie Huangfu,Tong Dou,Luwei Zhou,Lin Wang,Guoxiang Liu,Xiaojuan Li,Zhaokun Zhai,Mengjie Han,Haiping Liu,Xu Chen
Background Mogroside V, the main ingredient of Siraitia grosvenorii , has been proved to have therapeutic effects on pulmonary diseases . The specific mechanism still remains to be clarified, which hinders the potence of its medicinal value. Purpose Serum and lung metabolomics based on LC-MS analysis were applied to explore the mechanism of mogroside V against lung inflammation. Method In this study, balb/c mice were divided into control, model, mogeoside V and SH groups. We evaluated the protective effects of mogroside V on lung inflammation in asthmatic mice. Suhuang Zhike Jiaonang was used as positive drug . Metabolic profiles of serum and lung samples of mice in control, model and mogroside V groups were analyzed by LC-MS. Results Administration of mogroside V effectively relieved the expression of biochemical cytokines and lung inflammatory infiltration of asthmatic mice caused by ovalbumin (OVA). And visceral index of mice treated with mogroside V was close to control group. These results indicated that mogroside V ameliorated OVA-induced lung inflammation. LC-MS based metabolomics analysis demonstrated 6 main pathways in asthmatic mice including Vitamin B6 metabolism, Taurine and hypotaurine metabolism, Ascorbate and aldarate metabolism, Histidine metabolism, Pentose and glucuronate interconversions, Citrate cycle (TCA cycle) were regulated after using mogroside V. Conclusion The study firstly elucidates the metabolic pathways regulated by mogroside V on lung inflammation through metabolomics, providing a theoretical basis for more sufficient utilization and compatibility of mogroside V.
研究领域:
药理学
·
免疫学
·
代谢组学
·
呼吸医学
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DOI
PubMed
高影响因子
VACCINE
·
2014
·
IF 3.485
Qingfeng Liu,Chi Zhang,Xiaoyao Zheng,Xiayan Shao,Xi Zhang,Qizhi Zhang,Xinguo Jiang
The frequent outbreak of respiratory infectious diseases such as influenza and pulmonary tuberculosis calls for new immunization strategies with high effectiveness. Nasal immunization is one of the most potential methods to prevent the diseases infected through the respiratory tract. In this study, we designed a water-soluble system based on antigen/ N -trimethylaminoethylmethacrylate chitosan conjugates for nasal immunization. N -trimethylaminoethylmethacrylate chitosan (TMC) was synthesized by free radical polymerization of chitosan and N -trimethylaminoethylmethacrylate chloride and identified by 1 H NMR and FT-IR. Thiolated ovalbumin (OVA) was covalently conjugated to maleimide modified TMC with high conjugation efficiency. OVA conjugated TMC (OVA–TMC) significantly increased uptake of OVA by Raw 264.7 cells, which was 2.38 times higher than that of OVA/TMC physical mixture (OVA + TMC) at 4 h. After nasal administration, OVA–TMC showed higher transport efficiency to superficial and deep cervical lymph nodes than OVA + TMC or OVA alone. Balb/ C mice were intranasally given with OVA–TMC three times at 2-week internals to evaluate the immunological effect. The serum IgG, IgG1 and IgG2a levels of the OVA–TMC group were 17.9–87.9 times higher than that of the OVA + TMC group and comparable to that of the intramuscular group. The secretory IgA levels in nasal wash and saliva of the OVA–TMC group were 5.2–7.1 times higher than that of the OVA + TMC group while the secretory IgA levels of the intramuscular alum-precipitated OVA group were not increased. After immunofluorescence staining of nasal cavity, IgA antibody secreting cells were mainly observed in the lamina propria regions and glands of nasal mucosa. OVA–TMC showed little toxicity to the nasal epithelia or cilia of rats after nasal administration for three consecutive days. These results demonstrated that antigen conjugated TMC can induce both systemic and mucosal immune responses after nasal administration and may serve as a convenient, safe and effective vaccine for preventing respiratory infectious diseases.
研究领域:
免疫学
·
药剂学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2026
·Vol. 31
·期 16
·2768
·
IF 5.1
Chenliang Li,Lijin Xiao,Wei Wu,Lingyang Kong,Shuyuan Yue,Zhijie Zhan,Jiao Xu,Wei Ma
Apigenin (API) is a flavonoid compound widely distributed in nature. The global prevalence of asthma is increasing year by year, influenced by various factors and difficult to cure completely, and new drugs and therapies are constantly emerging. Although API is a low-toxicity flavonoid compound, its poor water solubility and low bioavailability present limitations in the treatment of asthma. In this study, the structure of API was chemically modified by introducing acyl and alkyl groups while preserving its original structure. The structures were identified using FT-IR,1H-NMR and13C-NMR spectroscopy, yielding derivatives (A–J). To further investigate the effects of structural modifications on API’s biological activity, an ovalbumin (OVA)-induced asthma model was established in mice to evaluate the antioxidants’ activity. Hematoxylin-eosin staining was used to observe pathological changes in lung tissue, and oxidative stress-related parameters, including ROS, SOD, and MDA, were measured to assess the derivatives’ protective effects against oxidative damage. The results showed that the 10 synthetic derivatives exhibited varying degrees of oxidative stress during treatment. Compared with the model group, the API derivative treatment group significantly reduced ROS and MDA levels and increased SOD activity. Moreover, treatment with the compounds reduced the levels of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased serum IgE levels. Histopathological examination further demonstrated that the compounds alleviated inflammatory cell infiltration and tissue damage in the lungs. Structure-activity analysis indicated that, among the 10 derivatives, the tri-substituted API derivatives exhibited superior antioxidant activity compared to the di-substituted API derivatives. By modifying the chemical structure of API, its antioxidant activity in OVA-induced bronchial asthma was significantly enhanced. 5,7,4′-O-triethyl API and 5,7,4′-O-triacetyl API demonstrated therapeutic effects comparable to those of dexamethasone and show promise as lead compounds for the development of novel asthma treatments.
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高影响因子
PLoS One
·
2016
·Vol. 11
·期 3
·e0149257
·
IF 3.057
Chao Fang,Weihong Lu,Chengyan Li,Xi Peng,Yang Wang,Xiulan Huang,Zhihong Yao,Nali Cai,Yuge Huang,Xingliang Zhang,Jianxin Tan
Asthma is a common chronic respiratory disease. In a previous study, we found several circulating microRNA signatures associated with childhood asthma and selected miR-3162-3p for subsequent studies. Since the target proteins and underlying molecular mechanisms of miR-3162-3p in asthma etiopathogenesis are not well characterized, we designed this study to clarify its role. We employed bioinformatics and quantitative PCR methods as a first step to determine the target of miR-3162-3p, and we elucidated β-catenin. Luciferase assays and western blot analysis confirmed β-catenin as a direct target of miR-3162-3p as the 3’-untranslated region of β-catenin mRNA possesses a specific miR-3162-3p pairing site. The correlation between the expression levels of miR-3162-3p and β-catenin is confirmed by quantitative PCR and western blot studies in A549, Beas-2B and H1299 cell lines and OVA-induced asthma mouse model. Of note, upregulation of the endogenous miR-3162-3p level is concomitant with the reduction of β-catenin mRNA and protein expression levels. MiR-3162-3p antagomir treatment antagonizes the endogenous miR-3162-3p and effectively rescues the attenuation of endogenous β-catenin in OVA-induced asthmatic mice, which alleviates airway hyperresponsiveness and ameliorates airway inflammation. Collectively, our findings suggest a novel relationship between miR-3162-3p and β-catenin and clarify their mechanistic role in asthma etiopathogenesis.
研究领域:
分子生物学
·
呼吸病学
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免疫学
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产品关联
DOI
PubMed
高影响因子
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