CELL
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2025
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IF 42.5
Yaozhen Chen,Shouwen Chen,Zhixin Liu,Yafen Wang,Ning An,Yutong Chen,Yihao Peng,Zheng Liu,Qin Liu,Xingbin Hu
The canonical complement-mediated lysis of mature red blood cells (RBCs) leads to severe pathogenesis. However, inhibition strategies targeting complement are not always as efficient as expected, indicating that unknown mechanisms are awaiting elucidation. In this study, we investigate the intracellular events in mature RBCs following complement activation. The collected evidence demonstrates that complement-induced hemolysis is a caspase-8-dependent programmed RBC death. Furthermore, short NLRP3 (miniNLRP3) fragments in RBCs are identified to engage in the assembly of NLRP3-apoptosis-associated speck-like protein containing a CARD (ASC)-caspase-8 complex. Activated caspase-8 directly induces the proteolysis of β-spectrin, thereby disrupting the skeletal network of the RBC membrane, a process we refer to as spectosis. Spectosis signaling is also activated in autoimmune hemolytic anemia or paroxysmal nocturnal hemoglobinuria, and the inhibition of spectosis significantly reduced complement-induced hemolysis. These findings reveal a programmed death cascade in mature RBCs, which may have important implications for the treatment of hemolytic disorders.
研究领域:
免疫学
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血液学
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细胞生物学
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DOI
PubMed
高影响因子
Polymers
·
2022
·Vol. 14
·期 21
·4636
·
IF 4.967
Zhengyu Hu,Jiaming Wang,Long Jin,Tieqiang Zong,Yuanqi Duan,Jinfeng Sun,Wei Zhou,Gao Li
This investigation focuses on the three novel polysaccharides fromCordyceps militarisand then discusses their characterization and anti-complementary activity. The three polysaccharides fromC. militaris(CMP-1, CMP-2 and CMP-3) were prepared using a DEAE-52 cellulose column. The HPLC, HPGPC, FT-IR and Congo red analyses were used to characterize their monosaccharides, molecular weight and stereo conformation, which demonstrated that the three polysaccharides were homogenous polysaccharides with different molecular weights and were composed of at least ten monosaccharides with different molar ratios, and all had a triple-helix conformation. The evaluation of anti-complementary activity demonstrated that the three polysaccharides significantly inhibited complement activation through the classical pathway and alternative pathway. Preliminary mechanism studies indicated that CMP-1, CMP-2 and CMP-3 acted with C2, C5, C9, factor B, factor B, and P components in the overactivation cascade of the complement system. The analysis of the Pearson correlation and network confirmed that the ribose, glucuronic acid and galacturonic acid composition were negatively correlated with the anti-complementary activity of polysaccharides. These results suggested that the three novel polysaccharides are potential candidates for anti-complementary drugs.Keywords:Cordyceps militaris;anti-complementary activity;polysaccharides;structure-activity relationship
研究领域:
免疫学
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生物化学
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DOI
PubMed
高影响因子
Journal of Chemistry
·
2018
·
IF 1.726
Ruijun Wang,Yunfei Ji,Ying Peng,Xiaobo Li
Sijunzi decoction (SJZD) is a classical herbal prescription in traditional Chinese medicine (TCM) used for enhancing the function of immune system. In previous studies, a polysaccharide fraction S-3 was screened from SJZD by assessment of immune system regulation, intestinal microbiota, and SCFA in order to explore the immune active ingredients in SJZD. In the present study, S-3 was further purified, and a homogeneous polysaccharide S-3-1 with a molecular mass of 13.5 × 104 Da was obtained after further fractionation by Sephadex G-150 size-exclusion chromatography. The immunological activities of S-3-1 were assayed in vitro for the first time. The determination of the anticomplement activity showed that S-3-1 displayed inhibitory effects on classical pathway of the complement system, with CH50 values of 530 μg/mL. The FT-IR analysis showed that S-3-1 had absorptive peaks characteristic of polysaccharides. The methylation and GC-MS analysis showed that it is comprised of Rha, Ara, Xyl, Man, Gal, and Glc in a relative molar ratio of 0.35 : 0.37 : 1.4 : 0.31 : 3 : 0.8 and that it mainly contained 1,4-linked-Glc and 1,6-linked-Gal glycosidic bonds. The morphology of S-3-1 was observed by atomic force microscope (AFM). These results provided evidences for tracking the material basis of SJZD immune activity.
研究领域:
中药学
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药理学
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免疫学
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生物化学
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
·
IF 13.2
Zhonghao Liao,Jiang Yu,Fangming Liang,Yubo Liu,Zhenyang Zhao,Yue Wang,Xianbao Shi,Yongjun Wang,Hongzhuo Liu
Adeno-associated virus (AAV) has been extensively employed in gene therapy owing to its outstanding safety profile and low immunogenicity. AAV vector-mediated gene therapy necessitates repeated administrations to achieve prolonged therapeutic efficacy. However, clinical trials have demonstrated that subsequent to the initial administration of AAV, the host mounts an immune response against the vectors, thereby hindering the clinical feasibility of repeated AAV administration. Moreover, when the AAV dosage exceeds 1.0 × 10 13 vg/kg, there is a significant risk of excessive activation of the complement system, which can result in severe adverse reactions. Notably, research indicates that merely depleting IgG antibodies does not enable high-dose re-administration of AAV or alleviate excessive complement activation; IgM antibodies also play a pivotal role in both the immune response against AAV and complement system activation. In this study, we synthesized a series of rapamycin lipid prodrugs utilizing succinic anhydride as a chemical linker and co-assembled them with dexamethasone palmitate to produce co-assembled nanoparticles ranging from 100 to 180 nm in size. These co-assembled nanoparticles are capable of inducing regulatory T cell (Treg) generation while inhibiting T follicular helper (Tfh) cell formation, thus reducing germinal center B (GC B) cell production and consequently suppressing anti-AAV IgG and IgM antibody responses along with complement system activation. The findings suggest that these rapamycin lipid prodrug co-assembled nanoparticles facilitate high-dose re-administration of AAV while enhancing gene expression delivered by the vector.
研究领域:
生物医学工程
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免疫学
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基因治疗
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DOI
高影响因子
JOURNAL OF BIOACTIVE AND COMPATIBLE POLYMERS
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2015
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IF 2.352
Yeyun Fu,Xiaoyan Wang,Yu Zhang,Zonghua Liu,Wei Xue
Cyclodextrins have been extensively used in various biomedical and pharmaceutical applications. In these applications, cyclodextrins administered in vivo would inevitably enter blood stream. However, there is not enough information on the hemocompatibility of cyclodextrins until now. In this study, we investigated the influences of cyclodextrins (α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin) on human blood components and functions in vitro, that is, morphology and lysis of red blood cells, structure and conformation of fibrinogen, complement activation, and blood coagulation. It was found that 10 mg/mL of α- or β-cyclodextrins caused abnormal red blood cell morphology and serious hemolysis, while γ-cyclodextrin at 10 mg/mL did not impair red blood cell membrane morphology and integrity. The three cyclodextrins at up to 10 mg/mL affected the local microstructure but did not change the conformation of fibrinogen. The three cyclodextrins from 0.01 to 1 mg/mL all significantly activated the complement system in a concentration-dependent way. The three cyclodextrins at up to 5 mg/mL in blood plasma did not cause significantly different coagulation times compared with the negative control. In addition, the three cyclodextrins at up to 5 mg/mL in whole blood did not cause abnormal coagulation parameters. These results provide significant information on blood safety of the three cyclodextrins for their biomedical and pharmaceutical applications.
研究领域:
医学
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药理学
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DOI
高影响因子
Frontiers in Sustainable Food Systems
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2025
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IF 3.1
Yuanqi Duan,Yuxin Jiang,Jiayu Gu,Chenxi Sun,Boshi Sun,Yue Xu,Long Jin,Mei Jin,Jinfeng Sun,Wei Zhou,Zhengyu Hu,Gao Li
This study employed ultrasound-assisted extraction to obtain polysaccharides from Albizia julibrissin Durazz. leaf and pod agricultural by-products, with subsequent process optimization. A comparative analysis was then conducted on the physicochemical properties and anticomplementary activity of the isolated polysaccharides derived from two parts. The investigation identified different extraction conditions for leaf and pod, leaf demonstrated maximum polysaccharide yield (1.07 ± 0.20%) at 70°C, 40 mL/g, 50 min and 249 W, contrasting with pod which achieved 8.32 ± 0.27% yield at 70°C, 28 mL/g, 40 min and 201 W. Besides, physicochemical characterization demonstrated distinct molecular weights between leaf (AJLP) and pod (AJPP) polysaccharides (62.55–232.30 kDa) despite shared functional groups. Both polysaccharides contained mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, xylose, and arabinose in varying ratios, while displaying divergent microstructures and excellent thermal stability. In vitro, leaf (AJLP) and pod (AJPP) polysaccharides exhibited potent anticomplementary activity in alternative and classical pathways, respectively. This study established a foundation for developing and utilizing polysaccharide resources from A. julibrissin agro-byproducts, while providing a theoretical basis for their application in complement system overactivation.
研究领域:
植物化学
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免疫学
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食品科学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2018
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IF 3.909
Tong Sun,Xi Guo,Rui Zhong,Lu Ma,Hao Li,Zhipeng Gu,Junwen Guan,Hong Tan,Chao You,Meng Tian
Oligochitosan (OCHI) is known to have some specific biological activities. However, its interactions with blood components and related correlation with molecular structures remains to be clarified due to its growing use in biomedical areas. Herein, a series of OCHI were prepared by hydrogen peroxide induced degradation combined fractionation in ethanol solutions and their molecular structures were characterized by GPC, FTIR, 1 H and 13 C NMR, and then the interactions of the prepared OCHI with blood components, including red blood cells (hemolysis, deformability, and aggregation), coagulation system, complement (C3a, and C5a activation), and platelet (activation, and aggregation), were investigated. For red blood cells, OCHI has a quite low risk of hemolysis in a dose- and MW-dependent manner and the deformability and aggregation were observed in its high MW fraction. The coagulation tests revealed that OCHI is capable of a mild anticoagulation through blocking the intrinsic pathway and the anticoagulation corresponding MW was identified. In terms of complement, OCHI could inhibit C3a in a dose-dependent manner and activate C5a with its high MW fraction. In addition, there is no significant effect of OCHI on platelet activation and aggregation. Based on above results, the interactions related mechanism was discussed and proposed.
研究领域:
生物医学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Nana Meng,Jiasheng Lu,Jianfen Zhou,Shengmin Yang,Chen Zhang,Ruiyi Jia,Yuan Ding,Yanning Bao,Jun Wang,Xiaopei Ma,Ruohan Chen,Zhixuan Jiang,Cao Xie,Linwei Lu,Weiyue Lu
One of the challenges for the clinical translation of active targeting nanomedicines is the adverse interactions between targeting ligands and blood components. Herein, a novel regularity, which reveals the interactions between cyclic RGD (Arg-Gly-Asp) peptide-modified liposomes and complement components in blood, is reported. As the nucleophilicity of arginine guanidine group within the cyclic RGD-like peptide increases, targeting liposomes potentiate complement cascade via the amplification loop of complement 3 (C3), ultimately leading to accelerated blood clearance, increased deposition in the reticuloendothelial system (RES) organs, enhanced immune responses, and potential side effects. By appropriately reducing the nucleophilicity of guanidine group, cyclic R2 peptide is designed for modification of liposomes to target integrin α v β 3 . Compared to the widely used targeting molecule c(RGDyK), R2 eliminates the negative effects of C3 opsonization and specific antibody production, significantly improves the in vivo immunocompatibility of targeting liposomes, and demonstrates superior anti-tumor efficacy in mouse models of orthotopic breast cancer and glioma. Thus, the proposed regularity of interactions between guanidine nucleophilicity and C3, along with the successful application of the low complement activation capacity targeting ligand R2, provides new insights for addressing challenges related to complement activation in the clinical translation of active targeting nanomedicines.
研究领域:
药学
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免疫学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2025
·
IF 3
Jiaxin Peng,Jing Chen,Mengran Wu,Tao He,Xiaojuan Guo,Qiangguo Ao,Ling Chen
Acute kidney injury (AKI) is widely recognized as an important risk factor for chronic kidney disease (CKD), and preventing or delaying the AKI-CKD transition represents a critical therapeutic priority. Ergothioneine (EGT), a natural antioxidant, has demonstrated renal protective potential, but its role in attenuating the AKI-CKD transition remains unclear. To investigate this, an AKI-CKD mouse model was constructed by administering multiple small-dose injections of cisplatin. Mice were divided into control, AKI-CKD, and AKI-CKD + EGT groups. The protective function of EGT was assessed using biochemical indexes and histopathology. Proteomic analysis and network pharmacology were applied to identify potential EGT targets, which were further verified by molecular docking and Western blot. Results showed that EGT significantly mitigated renal damage in AKI-CKD mice. Proteomic analysis identified 35 differentially expressed proteins (DEPs) potentially associated with EGT treatment, with GO and KEGG enrichment implicating complement activation as a key pathway. Protein-protein interaction (PPI) network analysis, topology analyses, and molecular docking identified C4B and PON1 as potential core EGT targets. In conclusion, EGT attenuates AKI-CKD progression by targeting C4B and PON1, modulating complement activation and oxidative stress. These findings highlight the therapeutic potential of EGT and provide novel insights for drug development targeting the AKI-CKD transition.
研究领域:
生物学
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医学
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药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Sha Li,Si-Ming Yan,Li-Wei Zhang,Xiao-Yan Yang,Zhong Guo
Introduction: Polydopamine nanoparticles (PDA NPs) exhibit numerous outstanding characteristics, including simple preparation, broad light absorption, drug binding ability, excellent biocompatibility and adhesive properties, making them suitable for biomedical application. However, the limited information on their hemocompatibility may hinder their progression from laboratory research to clinical application.Methods: In this study, we investigated comprehensively the hemocompatibility of PDA NPs, assessed the effects of PDA NPs on red blood cells (RBCs) morphology and lysis, fibrinogen structure and conformation, blood coagulation, platelet activation, complement system activation, and organ toxicity.Results: The results indicated that PDA NPs can induce morphological changes and hemolysis in RBCs in a concentration-dependent manner. Interactions with fibrinogen suggested a disturbance in the protein’s microenvironment without significantly altering its secondary structure. This study also revealed that PDA NPs have a concentration-dependent effect on blood coagulation, platelet activation, and complement system activation. Additionally, PDA NPs showed no significant acute toxicity after intravenous injection.Conclusion: The findings offer important insights into the hemocompatibility of PDA NPs, which is essential for their safe and effective clinical use. Understanding their interactions with blood components is key to ensuring their compatibility in biomedical applications. These results are vital for guiding the development of PDA NPs for medical use, particularly in blood-contacting applications.
研究领域:
生物医学工程
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材料科学
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血液学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yuanqi Duan,Zhengyu Hu,Long Jin,Tieqiang Zong,Xiaohui Zhang,Yanan Liu,Pengcheng Yang,Jinfeng Sun,Wei Zhou,Gao Li
The degradation of Belamcanda chinensis (L.) DC. polysaccharides was carried out by five concentrations of trifluoroacetic acid (TFA) (1–5 mol/L), and their physicochemical properties, degradation kinetics and anticomplementary activity were investigated. The findings revealed a notable reduction in the molecular weight of BCP, from an initial value of 2.622 × 10 5 g/mol to a final value of 6.255 × 10 4 g/mol, and the water solubility index increased from 90.66 ± 0.42 % to 97.78 ± 0.43 %. The degraded polysaccharides of B. chinensis exhibited a comparable monosaccharide composition comprising Man, GalA, Glc, Gal, and Ara. As the concentration of TFA increased, the degradation rate constant increased from 1.468 × 10 −3 to 5.943 × 10 −3 , and the process followed the first-order degradation kinetic model (R 2 > 0.97) and the random fracture model (R 2 > 0.96). Furthermore, the five degraded polysaccharides still exhibit good thermal stability. In vitro experiments showed that DBCP-3 exhibited more potent anticomplementary activity than the original polysaccharides and positive drugs, which was strongly correlated with its Mw ( r = 0.6–0.8), inhibiting complement activation by blocking C2 and C4. These results indicated that TFA degradation has a positive effect on polysaccharides, of which DBCP-3 is expected to treat diseases involving hyperactivation of the complement system.
研究领域:
植物化学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
BMC Pulmonary Medicine
·
2020
·Vol. 20
·期 1
·1-12
·
IF 2.813
Guo Jing,Li Min,Yang Yi,Zhang Lin,Zhang Li-wei,Sun Qian-yun
Background The complement system plays a critical role as the pathogenic factor in the models of acute lung injury due to various causes. Cobra venom factor (CVF) is a commonly used complement research tool. The CVF can cause acute inflammation in the lung by producing complement activation components. Atorvastatin (ATR) is a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor approved for control of plasma cholesterol levels. This inhibitor can reduce the acute pulmonary inflammatory response. However, the ability of ATR in treating acute lung inflammation caused by complement activation is still unknown. Therefore, we investigated the effect of ATR on lung inflammation in mice induced by activation of the complement alternative pathway in this study.Methods ATR (10 mg/kg/day via oral gavage) was administered for 7 days before tail vein injection of CVF (25 μg/kg). On the seventh day, all mice were sacrificed 1 h after injection. The lung lobe, bronchoalveolar lavage fluid (BALF), and blood samples were collected. The myeloperoxidase (MPO) activity of the lung homogenate, the leukocyte cell count, and the protein content of BALF were measured. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), P-selectin, and Intercellular cell adhesion molecule-1 (ICAM-1) in BALF and serum were determined by enzyme-linked immunosorbent assay. The pathological change of the lung tissue was observed by hematoxylin and eosin staining. The deposition of C5b-9 in the lung tissue was detected by immunohistochemistry. The phosphorylation of NF-κB p65 in the lung tissues was examined by immunohistochemistry and western blotting.Results The lung inflammation levels were determined by measuring the leukocyte cell numbers and protein content of BALF, the lung MPO activity, and expression and staining of the inflammatory mediators (IL-6 and TNF-α), and adhesion molecules (P-selectin and ICAM-1) for lung lesion. A significant reduction in the lung inflammation levels was observed after 7 days in ATR pre-treated mice with a CVF-induced lung disease. Deposition of C5b-9 was significantly alleviated by ATR pretreatment. Early intervention with ATR significantly reduced the development of acute lung inflammation on the basis of phosphorylation of NF-κB p65 in the lung.Conclusion These findings suggest the identification of ATR treatment for the lung inflammation induced by activating the complement system on the basis of its anti-inflammatory response. Together with the model replicating the complement activating characteristics of acute lung injury, the results may be translatable to the overactivated complement relevant diseases.
研究领域:
药理学
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免疫学
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病理学
·
呼吸医学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）