ADVANCED MATERIALS
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2025
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IF 26.8
Quanwei Sun,Huiyu Lu,Wenshuo Yang,Zhengwei Song,Chen Chen,Xu Ruan,Min Luo,Yunlong Li,Huihui Li,Zexin Yang,Kang Liu,Wencui Shang,Yujing Xu,Qinghua Wu,Wei Shen,Ye Yang,Dengke Yin
Humoral immunity-cancer crosstalk has gained attention recently owing to its impact on tumor immune responses and therapy responsiveness. Here, it is shown that epithelial breast cancer cells can directly bind with non-antigen-specific IgA, dependent on polymeric immunoglobulin receptor (PIGR)-mediated transcytosis function, modulating tumoral inflammatory genes and sensitizing antitumor response. To harness this biology, a hybrid tumor vaccine is designed by covering the adjuvant-loaded cancer cell vesicles with a calcium phosphate shell, which retains the antigen information of the original tumor cells and exhibits robust mucosal adhesion in nasal tissues. Following intranasal vaccination, such a hybrid vaccine preferentially activates germinal center responses in nasal-associated lymphoid tissues and drives the production of tumoral antigen-specific IgA-dominated humoral immunity in both serum and lung through the property of “common mucosal immune system”, thus coordinating cellular immune responses to prevent lung colonization of IgA-opsonized breast cancer. In the inoperable and postoperative breast cancer model, intranasal vaccination with the hybrid vaccine also enables the amplification of the therapeutic benefits of local/systemic therapies. In summary, this work presents insights into the antitumor biology of IgA in epithelial breast cancer and explores a highly effective vaccine strategy focused on governing IgA-dominated humoral immunity to combat breast cancer, especially lung metastasis.
研究领域:
肿瘤学
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免疫学
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微生物学
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药理学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF IMMUNOLOGY
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2024
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IF 4.5
Caiying Wang,Yue Zhang,Yabin Lu,Xin Huang,Huazheng Jiang,Guohui Chen,Yongheng Shao,Huub F.J. Savelkoul,Christine A. Jansen,Guangliang Liu
Secretory IgA is crucial for preventing the invasion of entero-pathogens via intestinal mucosa. While it is well-established that Transforming growth factor β1 (TGF-β1) regulates IgA production in human and mouse B cells, our previous investigation revealed different functions of TGF-β1 in IgA generation in pigs compared with humans and mice, with the underlying mechanism remaining elusive. In this study, IgM + B cells from porcine Peyer's patches (PPs) were isolated and stimulated with recombinant porcine TGF-β1 to evaluate the effect of TGF-β1 on pigs. The results showed that antibody production from B cells of PPs was impaired by TGF-β1 ex vivo. Furthermore, TGF-β1 treatment led to a decrease in the expression of germ-line transcript αand postswitch transcript α. Moreover, we observed that TGF-β1 predominantly inhibited the phosphorylation of p38-mitogen-activated protein kinases (MAPK), confirming the involvement of the p38-MAPK pathway in porcine IgA generation and IgA class switch recombination. The application of p38-MAPK inhibitor resulted in decreased B-cell differentiation levels. Collectively, this study demonstrates that exogenous TGF-β1 restrains the production and class switch recombination of IgA antibodies by inhibiting p38-MAPK signaling in porcine PPs B cells, which may constitute a component of TGF-β1-mediated inhibition of B-cell activation.
研究领域:
免疫学
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分子生物学
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兽医学
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PubMed
高影响因子
Drug Design Development and Therapy
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2023
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IF 4.8
Wei-guang Yang,Ao Sun,Rong Zhu,Nan Liu,Wei-jie He,Lin-lin Liu
Background Artemisinin (ART) is a safe and effective antimalarial drug. In recent years, antimalarial drugs have demonstrated a good therapeutic efficacy in IgA nephropathy, suggesting that this may become a new treatment option.Purpose We aimed to evaluate the effect and mechanism of artemisinin in IgA nephropathy.Methods In this study, CMap database was used to predict the artemisinin therapeutic effect for IgA nephropathy. A network pharmacology approach was applied to explore the unknown mechanism of artemisinin in IgA nephropathy. We used molecular docking to predict the binding affinity of artemisinin with the targets. A mouse model of IgA nephropathy was established to investigate the therapeutic effect of artemisinin on IgA nephropathy. In vitro, the cell counting Kit-8 assay was used to evaluate the cytotoxicity of artemisinin. Flow cytometry and PCR assays were used to detect the effects of artemisinin on oxidative stress and fibrosis in lipopolysaccharide (LPS)-stimulated mesangial cells. Western blot and immunofluorescence were used to detect the expression of pathway proteins.Results CMap analysis showed artemisinin may reverse the expression levels of differentially expressed genes in IgA nephropathy. Eighty-seven potential targets of artemisinin in the treatment of IgA nephropathy were screened. Among them, 15 hub targets were identified. Enrichment analysis and GSEA analysis indicated that response to reactive oxygen species is the core biological process. AKT1 and EGFR had the highest docking affinity with artemisinin. In vivo, artemisinin could improve renal injury and fibrosis in mice. In vitro, artemisinin attenuated LPS-induced oxidative stress and fibrosis promoted AKT phosphorylation and Nrf2 nuclear translocation.Conclusion Artemisinin reduced the level of fibrosis and oxidative stress with IgA nephropathy through the AKT/Nrf2 pathway, which provided an alternative treatment for IgAN.
研究领域:
药理学
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肾病学
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分子生物学
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生物信息学
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DOI
PubMed
高影响因子
MICROBIOLOGICAL RESEARCH
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2025
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IF 6.9
Jing Xu,Haoming Xu,Jianhong Li,Wenqi Huang,Yingfei Li,Xue Guo,Minzheng Zhu,Yao Peng,Youlian Zhou,Yuqiang Nie
Gut microbiota and their metabolites play a significant role in inflammatory bowel disease. Here, we attempted to determine the anti-inflammatory role of the probiotic Clostridium. butyricum (CB) in inflammatory bowel disease and identify the exact immune mechanism. The clinical significance of Clostridiales and CB was explored in patients with ulcerative colitis. The inflammation-suppressive role of CB was evaluated in mice with DSS-induced colitis. 16S rRNA sequencing was performed to assess changes in the gut microbiota. Altered transcription levels were detected by RNA sequencing. Flow cytometry was performed to assess the frequency of IgA responses to gut microbiota. Clostridiales and CB were depleted in ulcerative colitis. Oral gavage with CB significantly suppressed weight loss and colon shortening in the dextran sulfate sodium-induced colitis mouse model. Intestinal barrier injury was reversed and the gut microbiota was restored upon treatment with CB administration. The mucosal immune response to gut microbiota was reversed upon treatment with CB. CB conditional medium was more effective than heat-killed CB in alleviating inflammation. Mechanistically, retinol metabolism and retinoic acid levels were higher in groups treated with CB and butyrate. CB and the metabolite butyrate exerted a suppressive role on the abundance of Immunoglobulin A-coated gut microbiota by inhibiting retinoic acid synthesis. In summary, CB protects against inflammation and intestinal barrier injury by producing anti-inflammatory metabolites that can regulate the mucosal immune response to gut microbiota by increasing retinoic acid levels in the colon.
研究领域:
微生物学
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免疫学
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肠道疾病研究
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Huan Song,Guo-Qiang Liang,Man-Shu Yu,Yun Shan,Jun Shi,Chun-Bo Jiang,Dao-Lei Ni,Mei-Xiao Sheng
Ethnopharmacological relevance Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis in the world, it is one of the most common causes of kidney disease and can lead to end-stage kidney disease, however, its pathogenesis is still complicated. The Shen-yan-yi-hao oral solution (SOLI) is an effective prescription for the clinical treatment of IgAN while its specific mechanism remains to be further elucidated. Aim of the study This study investigates SOLI's effects on IgAN in rats, particularly on the intestinal mucosal barrier, and identifies potential therapeutic targets through network pharmacology and molecular docking, validated experimentally. Materials and methods Target genes for SOLI in IgAN were identified and analysed through molecular docking and KEGG pathway enrichment. An IgAN rat model examined SOLI's effect on renal biomarkers and cytokines involved in specific pathways, ileum mucosal lesions, and the intestinal immune system. The IL-17 pathway's role was studied in IEC-6 cells with SOLI in vitro. Result Rats developed increased proteinuria and kidney damage marked by IgA deposition and inflammation. SOLI treatment significantly ameliorated these symptoms, reduced galactose-deficient Ig A1 (Gd-IgA1), and decreased cytokines like IL-17, TNF-α, IL-6 and IL-1β etc. SOLI also normalized intestinal tight junction protein expression, ameliorated intestinal damage, and regulated intestinal immune response (focused on IL-17/NF-κB signal pathway). SOLI moderated the abnormally activated IL-17 pathway, which damages intestinal epithelial cells, suggesting IgAN treatment potential. Conclusion SOLI reduces proteinuria and enhances intestinal mucosal function in IgAN rats, kidney protection in the IgAN rat model may initiate from modulating the intestinal IL-17/NF-κB pathway and subsequent Gd-IgA1 accumulation.
研究领域:
药理学
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免疫学
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肾病学
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分子生物学
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2019
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IF 4.825
Lixia Bai,Jicheng Li,Honglian Li,Jianping Song,Yuan Zhou,Ruirui Lu,Bihao Liu,Yu Pang,Peichun Zhang,Junqi Chen,Xusheng Liu,Junbiao Wu,Chunling Liang,Jiuyao Zhou
Immunoglobulin A nephropathy (IgAN) is an autoimmune kidney disease with complex pathogenesis leading to end-stage renal damage . The prime pathological characteristics of IgAN are IgA immune complexes deposition accompany with mesangial cell proliferation and urine protein elevation. Artemisinin (ART) is extracted from traditional Chinese medicine Artemisia annua L. Hydroxychloroquine (HCQ) is a classical antimalarial drug applied in the treatment of autoimmune diseases. Both of them possess anti-inflammatory and immunomodulatory properties. The purpose of this research was to investigate the pharmacological effects of ART combined with HCQ (AH) and discuss thoroughly the potential molecular mechanisms in IgAN. In vivo , our results demonstrated that AH could efficiently ameliorate kidney damage by improving kidney dysfunction and reducing the levels of 24 h urine protein, IgA and IgG immune complexes deposition in glomerulus of IgAN rats. Interestingly, AH obviously promoted the secretion of exosomes in renal tissues, inhibited the expressions of nuclear factor- κ B (NF- κ B) signaling and NLRP3 inflammasome-related proteins, including I κ B- α , p-p65, NLRP3, ASC, IL-1 β and caspase-1 in IgAN rats. In vitro , further mechanistic study illustrated that exosomes derived from human renal tubular epithelial cells (HK-2) were significantly enhanced by AH, which could be utterly taken up in human mesangial cells (HMCs) and inhibited the activation of NF- κ B pathway and NLRP3 inflammasome after AH intervention. However, GW4869 interdicted the promotive effect of AH on exosomes from HK-2 cells and the suppression of exosomes on NF- κ B/NLRP3 activation in HMCs. Taken together, this study demonstrated that there was an inhibitory effect of AH therapy on NF- κ B/NLRP3 signaling via mediating exosomes release in IgAN rats, which provided an alternative approach for IgAN treatment.
研究领域:
药理学
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免疫学
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肾病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Heliyon
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2023
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IF 4
Huaxi Liu,Weijie Chen,Chunyang Tian,Yijian Deng,Liangwo Xu,Wenkun Ouyang,Renjie Qiu,Yanting You,Pingping Jiang,Lin Zhou,Jingru Cheng,Hiu Yee Kwan,Xiaoshan Zhao,Xiaomin Sun
Background IgA nephropathy (IgAN) is a major and growing public health problem. Renal fibrosis plays a vital role in the progression of IgAN. This study is to investigate the mechanisms of action underlying the therapeutic effects of Shenbing Decoction II (SBDII) in IgAN renal fibrosis treatment based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), network pharmacology and experimental verification. Method We first used UPLC-MS/MS to explore the main compounds of SBDII, and then used network pharmacology to predict the targets and key pathways of SBDII in the treatment of IgAN renal fibrosis. Next, bovine serum albumin (BSA), lipopolysaccharide (LPS), and carbon tetrachloride (CCL4) were used to induce IgAN in rats, and then biochemical indicators, renal tissue pathology, and renal fibrosis-related indicators were examined. At the same time, part of the results predicted by network pharmacology were also verified. Result A total of 105 compounds were identified in SBDII by UPLC-MS/MS. Network pharmacology results showed that the active compounds such as acacetin, eupatilin, and galangin may mediate the therapeutic effects of SBDII in treating IgAN by targeting tumor protein p53 (TP53) and regulating phosphatidylinositol 3-kinase (PI3K)-Akt kinase (Akt) signaling pathway. Animal experiments showed that SBDII not only significantly improved renal function and fibrosis in IgAN rats, but also significantly downregulated the expressions of p53, p-PI3K and p -Akt. Conclusion This UPLC-MS/MS, network pharmacological and experimental study highlights that the TP53 as a target, and PI3K-Akt signaling pathway are the potential mechanism by which SBDII is involved in IgAN renal fibrosis treatment. Acacetin, eupatilin, and galangin are probable active compounds in SBDII, these results might provide valuable guidance for further studies of IgAN renal fibrosis treatment.
研究领域:
药理学
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肾病学
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分子生物学
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中医药
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DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2024
·Vol. 38
·期 6
·e5866
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IF 1.8
Zhijian Zha,Ruihua Wang,Qian Wang,Fahui Chen,Ziyang Ye,Yafeng Li
Immunoglobulin nephropathy (IgAN) stands as the most prevalent primary glomerular nephropathy globally, typically diagnosed through an invasive renal biopsy. Emerging research suggests the significant involvement of chiral amino acids in kidney disease progression. This study introduces a nonderivative LC–tandem mass spectrometry approach, offering efficient separation outcomes within 15 min for identifying chiral amino acids in human urine samples. Subsequently, using this method, the analysis of l - and d -amino acids in the urine of both patients with IgAN and healthy individuals was conducted. Fourteen d -amino acids and 20 l -amino acids were identified in the urine samples obtained from 17 patients with IgAN and 21 healthy individuals. The results indicated notable variances in the concentrations of both l - and d -amino acids between the IgAN and healthy control groups. In contrast to the healthy group, the IgAN group exhibited higher mean urine concentrations of most l -amino acids and lower concentrations of d -amino acids. Furthermore, correlations between amino acids and clinical markers were investigated. These results propose a novel method for monitoring trace amino acids in urine samples and introduce a new concept for potential markers of IgAN.
研究领域:
医学
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分析化学
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肾脏病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 5.4
Xing-lan Ye,Ling-shuai Zeng,Qiang Liu,Wen-cheng Xu,Hong Liu,Hong Cheng,Wen-xiao Zheng,Xiao-qin Wang,Xue Xue
Ethnopharmacological relevance Huaiqihuang granule (HQH) is a traditional Chinese herbal formula comprising Trametes robiniophila Murr. , Lycii Fructus ., and Polygonatum sibiricum Red. This granule can nourish Qi and Yin, improve blood circulation and remove blood stasis. HQH has been extensively used to improve immune-mediated kidney diseases, such as IgA vasculitis nephritis (IgAVN). However, its renal protective mechanism remains elusive. Aim of the study This study investigated whether HQH ameliorates IgAVN by modulating the AMPK/mTOR-mediated autophagy pathway. Materials and methods The IgAVN mouse model was established using gliadin sensitization and India ink-mediated reticuloendothelial blockade (n = 10/group). The model mice were then treated for 4 weeks with low/high-dose HQH (4/8 g/kg/day) or dexamethasone (2.5 mg/kg/day). For in vitro analyses, human mesangial cells (HMCs) were first stimulated with aggregated IgA1 (aIgA1, 25 μg/mL) and then treated with the optimal concentration of HQH-containing serum (40 %). Furthermore, biochemical indices assays, renal histopathology, and immunofluorescence analysis of IgA deposition were performed. Moreover, autophagy levels were evaluated by assessing the expression of autophagy-related proteins, MDC staining, and mCherry-EGFP-LC3 transfection. Western blot and immunofluorescence were carried out to assess the levels of the AMPK/mTOR pathway proteins and proliferation markers. Results The results showed that HQH treatment significantly reduced 24-h urinary protein and serum IgA levels, but improved renal histopathology in IgAVN mice. Furthermore, HQH activated autophagy by upregulating p-AMPKα, LC3-Ⅱ/LC3-Ⅰ, and Beclin1, while inhibiting p-mTOR/mTOR and p62. Moreover, in HMCs, 40 % HQH-containing serum optimally inhibited aIgA1-induced mesangial proliferation and increased autophagic levels, as evidenced by the quantitative increase in autophagy activity and mean fluorescence intensity of MDC. However, these effects were blocked by AMPK inhibition. Conclusion This study showed that HQH alleviates IgAVN by upregulating AMPK/mTOR-mediated autophagy, inhibiting mesangial cell proliferation, and mitigating renal injury. These findings suggest that HQH has therapeutic potential for IgAVN and link autophagy modulation to IgAVN treatment.
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PubMed
高影响因子
Frontiers in Immunology
·
2026
·
IF 7
Zdenek Novak,Milan Raška,Jiri Mestecky
IgA nephropathy (IgAN) is an autoimmune disease in which polymeric IgA1, with joining (J) chain and altered glycosylation of the hinge region (HR), acts as an autoantigen recognized by naturally occurring IgG antibodies, resulting in generation of nephritogenic immune complexes (IC) that deposit in the kidney mesangium. By these criteria, IgA in IC and mesangial deposits displays properties identical to those of IgA produced by plasma cells infected by Epstein-Barr virus (EBV). Although ~95% of adults worldwide are EBV infected, there are important differences in the timing of infection in countries and areas with marked dissimilarities in socio-economic conditions. Epidemiological data convincingly documented that early EBV infection in children who live in developing countries, or in economically disadvantaged areas, display a significantly reduced frequency of IgAN compared to individuals from economically developed countries in which IgAN has been recognized as the leading cause of glomerulonephritis. Because physiological maturation of the IgA system is normally delayed until adolescence, in young children EBV infects B cells of Ig isotypes other than IgA, as these are relatively sparse. This early infection induces EBV-specific immune responses that prevent later infection of IgA-producing cells at older ages when these cells are more plentiful.
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DOI
PubMed
高影响因子
VACCINE
·
2014
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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
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药剂学
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产品关联
DOI
PubMed
高影响因子
Clinical Proteomics
·
2022
·Vol. 19
·期 1
·1-14
·
IF 5
Zhang Di,Li Yaohan,Liang Mingzhu,Liang Yan,Tian Jingkui,He Qiang,Yang Bingxian,Jin Juan,Zhu Wei
Background Immunoglobulin A nephropathy (IgAN), a globally common primary chronic glomerulopathy, is one of the leading causes of end-stage renal disease. However, the underlying mechanisms of IgAN have yet to be demonstrated. There were no adequate and reliable plasma biomarkers for clinical diagnosis, especially at the early stage. In the present study, integrative proteomics and metabolomics were aimed at exploring the mechanism of IgAN and identifying potential biomarkers.Methods Plasma from IgAN and healthy individuals were collected and analyzed in a randomized controlled manner. Data-independent acquisition quantification proteomics and mass spectrometry based untargeted metabolomics techniques were used to profile the differentially expressed proteins (DEPs) and differentially abundant metabolites (DAMs) between two groups and identify potential biomarkers for IgAN from health at the early stage. Disease-related pathways were screened out by clustering and function enrichment analyses of DEPs and DAMs. And the potential biomarkers for IgAN were identified through the machine learning approach. Additionally, an independent cohort was used to validate the priority candidates by enzyme-linked immunosorbent assay (ELISA).Results Proteomic and metabolomic analyses of IgAN plasma showed that the complement and the immune system were activated, while the energy and amino acid metabolism were disordered in the IgAN patients. PRKAR2A, IL6ST, SOS1, and palmitoleic acid have been identified as potential biomarkers. Based on the AUC value for the training and test sets, the classification performance was 0.994 and 0.977, respectively. The AUC of the external validation of the four biomarkers was 0.91.Conclusion In this study, we combined proteomics and metabolomics techniques to analyze the plasma of IgAN patients and healthy individuals, constructing a biomarker panel, which could provide new insights and provide potential novel molecular diagnoses for IgAN.
研究领域:
肾病学
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蛋白质组学
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代谢组学
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生物标志物发现
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系统生物学
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机器学习
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）