INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yaozhong Lv,Yajun Yang,Ying Chen,Dongfan Wang,Yipeng Lei,Mingyue Pan,Zhenzhong Wang,Wei Xiao,Yujie Dai
In order to investigate the structural characteristics and immunomodulatory effects of Poria cocos polysaccharides , a water-soluble homogeneous polysaccharide (PCP-2) was isolated by water extraction and alcohol precipitation and further purified by Cellulose DEAE-52 and Sephacryl S-100HR column chromatography . PCP-2 is a heteropolysaccharide composed of glucose, galactose , mannose , and fucose in a molar ratio of 42.0: 35.0: 13.9: 9.1. It exhibits a narrow molecular weight distribution at 2.35 kDa with a branching degree of 37.1 %. The main chain types of PCP-2 include 1,3- β -D-Glc and 1,6- β -D-Glc as the backbone glucans and 1,6- α -D-Gal as the backbone heterogalactan. In vitro experiments demonstrate that PCP-2 directly stimulate RAW264.7 cell proliferation and secretion of inflammatory factors such as NO and TNF- α . In cyclophosphamide (CTX)-induced mice, it promotes the development of thymus and spleen immune organs, elevates the blood levels of IgG, IgA, IgM and CD3 + CD4 + T cells , increases the intestinal villus height/ crypt depth ratio and improves gut barrier dysfunctions. These findings suggest that PCP-2 is a natural fungal polysaccharide with broad spectrum of immunoenhancing effects, which can significantly ameliorate the immunocompromised state.
研究领域:
免疫学
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药理学
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生物化学
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真菌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
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2024
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IF 15.8
Zijin Luo,Yi Lin,Yanan Meng,Mengyao Li,Hongyu Ren,Haoping Shi,Qiang Cheng,Tuo Wei
The successful application of mRNA vaccines in preventing and treating infectious diseases highlights their potential as therapeutic vaccines for cancer treatment. However, unlike infectious diseases, effective antitumor therapy, particularly for solid tumors, necessitates the activation of more powerful cellular and humoral immunity to achieve clinical efficacy. Here, we report a spleen-targeted mRNA vaccine (Mn@mRNA-LNP) designed to deliver tumor antigen-encoding mRNA and manganese adjuvant (Mn2+) simultaneously to dendritic cells (DCs) in the spleen. This delivery system promotes DC maturation and surface antigen presentation and stimulates the production of cytotoxic T cells. Additionally, Mn2+ codelivered in the system serves as a safe and effective immune adjuvant, activating the stimulator of interferon genes (STING) signaling pathway and promoting the secretion of type I interferon, further enhancing the antigen-specific T cell responses. Mn@mRNA-LNP effectively inhibits tumor progression in established melanoma and colon tumor models as well as in a model of tumor recurrence after resection. Notably, the combination of Mn@mRNA-LNP with immune checkpoint inhibitors further enhances complete tumor suppression and prolonged the overall survival in mice. Overall, this “All-in-One” mRNA vaccine significantly boosts antitumor immunity responses by improving spleen targeting and immune activation, providing an attractive strategy for the future clinical translation of therapeutic mRNA vaccines.
研究领域:
癌症免疫治疗
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疫苗开发
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Yiming Wang,Chen Wang,Yuan Lu
Nucleic acids have attracted increasing attention as drugs due to their fascinating advantages, such as long-term efficacy and ease of preparation compared to proteins. The nucleic acid therapy relies heavily on delivery vectors, which can prevent the degradation of nucleic acids while assisting them in cellular internalization. However, commonly used nonviral vector liposomes easily accumulate in the liver, which can limit their application in extrahepatic diseases. Herein, a potential spleen targeting vector for nucleic acids is developed based on the metal–organic frameworks. The plasmids are encapsulated inside the nanoscale zeolitic imidazolate framework (ZIF) via coprecipitation. The co-encapsulation of the cationic polymer poly(ether imide) (PEI) and the stabilizer polyvinylpyrrolidone (PVP) can significantly improve particle dispersion and stability. The prepared nanoparticles allow efficient transfection in vitro, mainly through clathrin-mediated and caveolae-mediated endocytosis. The biodistribution in mice shows that 46% of the nanoparticles accumulate in the spleen, which is much higher than that of the liposomes. The vector can successfully deliver plasmids to extrahepatic organs for protein synthesis and even induce an immune response. The elaborate ZIF-based nanoparticle may offer a new route for extrahepatic, especially spleen targeting delivery for the nucleic acids.
研究领域:
药理学
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纳米技术
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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
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2021
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IF 4.221
Tingting Zhou,Yueyan He,Yujie Qin,Bing Wang,Hongmao Zhang,Shumao Ding
The large conjugated π bond in the molecular structure of carbon nanotubes (CNTs) interacts with the benzene ring structure in di (n-butyl) phthalates (DBP) through a π - π bond . Compounds of CNTs and DBP form easily, becoming another environmental pollutant of concern. We explore whether CNTs entering animals slow down the degradation of the DBP adsorbed in the CNT cavity, thereby prolonging the "hormonal activity" of DBP. In our study, male BALb/c mice were used as experimental subjects divided into four groups: the control group; the multi-walled carbon nanotubes (MWCNTs) exposure group (10mg/kg/d); the DBP exposure group (2.15 mg/kg/d); and the compound exposure group (MWCNTs + DBP). After 30 days of exposure, the mice were sacrificed and their spleens used for immunotoxicology study. The results showed that the exposure groups exhibited splenomegaly and suffered severe oxidative damage to the spleen. In the compound exposure group: levels of IgA and IgG in the serum of the mice changed, and were significantly different from levels in both the MWCNTs and DBP exposure groups (p <0.05); the pathological sections of the spleen showed that the boundary between the white pulp area (WP) and the red pulp area (RP) was blurred, that the cell arrangement was loose, and that more red blood cells were retained in the spleen. Proteomics mass spectrometry analysis showed that compared with the control group, 70 proteins were up-regulated and 27 proteins were down-regulated in the MWCNTs group, 36 proteins were up-regulated and 23 proteins were down-regulated in the DBP group, 87 proteins were up-regulated and 21 proteins were down-regulated in the compound exposure group. The results of GO enrichment analysis and KEGG enrichment analysis of the differentially expressed proteins showed that the compound exposure harmed the spleen antigen recognition, processing, and presentation, inhibited the activation and proliferation of B cells and T cells, and hindered the adaptive immune responses. Our results showed that MWCNTs and DBP compounds can damage the spleen, and impair the innate and adaptive immune functions of the body.
研究领域:
环境毒理学
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免疫学
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蛋白质组学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CELLULAR IMMUNOLOGY
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2024
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IF 3.7
Jingying Qin,Cheli Wang,Xiaoying Zhou
Reduced glutathione (GSH) is an antioxidant involved in redox homeostasis, and recently regarded as an inducer of Reductive stress. Its immune-regulatory effects on lymphocytes have not been extensively studied. This study is based on the finding that much increased GSH level in collagen-induced arthritis (CIA) rat spleen, and aimed to investigate the effects of GSH (0, 1, 10, 100 mM) on normal and immune-stimulated spleen lymphocytes respectively. The elevated GSH level is associated with the increased levels of inflammatory factors; especially the increased DPP1 activity indicated immune-granulocytes activation in CIA rat spleen. Exogenous GSH had different influences on normal and CIA lymphocytes, affecting intracellular levels of GSH, Glutathione-S-transferases (GSTs) and Reactive oxygen species (ROS); as well as the expressions of NF-κB, MMP-9, Bcl-2, GST, P38, PCNA and TLR4. The increased extracellular GSH level disturbed redox homeostasis and induces reductive stress to spleen lymphocytes, which decreased intracellular GSH concentration and influenced the MAPK/PCNA and NF-κB/MMP-9 signaling pathways, as well as cell cycles respectively, leading to cell senescence/ferroptosis/apoptosis. This study also revealed the multiple faces of GSH in regulating spleen lymphocytes, which depended on its levels in tissue or in cells, and the activation status of lymphocytes. These findings indicate the immune-regulatory role of GSH on spleen-lymphocytes, and the high level GSH in CIA rat spleens may contribute to CIA development.
研究领域:
免疫学
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药理学
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细胞生物学
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风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Jinzhi Shi,Kai Shi,Qi Dong,Junfeng Yang,Yingshan Zhou,Peng Ma,Sha She,Fan Yang,Zuojiong Gong
Enriching erythrocytes and platelets in seconds and providing a fast seal in bleeding sites is vital to fatal hemorrhage control. Herein, hydrophilic chitosan fibrous mats (CECS-D mats) are fabricated by introducing hydrophilic carboxyethyl groups and subsequent catechol groups onto chitosan fibers. Due to strong hydrophilicity, CECS-D mats exhibit rapid liquid-absorption capacity, especially instantaneous absorptivity to the rabbit blood, which can achieve erythrocyte and platelet aggregations quickly by concentrating blood, thus promoting the formation of blood clots. Furthermore, the mats are self-oxidated to form quinone-amine adducts or quinone multimers by adjusting pH conditions, which not only provides tissue adhesion but also induces erythrocyte aggregation and platelet adhesion, further enhancing the seal and triggering quick closure to achieve fast hemostasis. Therefore, the mats reveal superior hemostatic performance in rabbit liver and spleen models over CECS mats and gauze. Especially in the fatal femoral artery injury model of rabbits, the mats reduce the blood loss by ∼75% and shortened the bleeding time by ∼50% compared with CECS mats, which have been reported to have the same hemostatic effect as commercialized Celox products in a swine femoral artery injury model. Besides, the mats are cytocompatible and degradable as well as antibacterial. This chitosan mat is a promising hemostatic material for fatal hemorrhage control.
研究领域:
生物材料
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止血
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组织工程
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
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2024
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IF 13.2
Jinghui Wang,Rongrong Jia,Wei Wei,Mingli Hu,Feng Li,Wenjing Wang,Peng Ye,Jiawei Zhao,Ling Xu,Shuang Wang,Yugang Wang,Min Shi,Guanghui Ma
Liver fibrosis (LF) afflicts millions of patients worldwide, yet a universally accepted standard therapy remains elusive. Notably, an elevation of profibrotic monocytes is observed in peripheral blood of LF patients. Inspired by the spleen’s reported “accomplice” role in LF development and its monocyte reservoir function, the mechanism of spleen-liver co-morbidity is further explored, unveiling an innovative therapy strategy for LF. In detail, exosomes are prepared from macrophages with low expression of lymphocyte antigen 6 complex locus C (ly6c low Exo), showcasing a distinctive ability to accumulate simultaneously in both spleen and liver. The ly6c low Exo treatment reduces profibrotic monocyte proportion in spleen, decreases the circulating profibrotic monocytes, and reshapes hepatic immune microenvironment including macrophages, T cells, and natural killer cells. Such synergistic modulation culminates in the reduction of extracellular matrix, achieving satisfying therapeutic outcomes in LF model. Furthermore, the exosome therapeutic is iterated via loading pirfenidone into ly6c low Exo. A cooperation of two distinct mechanisms is thus achieved by combining the ly6c low Exo immunoregulation with pirfenidone-mediated transforming growth factor-β pathway inhibition, resulting in an enhanced antifibrotic effect in severe LF model. The ly6c low Exo platform described, with its remarkable capacity for dual-accumulation, multifunctional immunoregulatory capabilities, and drug-loading property, presents extensive clinical application prospects for LF treatment.
研究领域:
肝病学
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免疫学
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药理学
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细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Functional Foods
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2021
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IF 4.451
Xiaoyan Su,Ming Zhao,Xinyu Fu,Xiaodan Ma,Wei Xu,Songhua Hu
Polysaccharides from Rubus chingii Hu fruits (RFPs) were extracted, purified, characterized and investigated for immunomodulatory activity. Results indicated that RFPs were heteropolysaccharides with molecular weight of 51.7 kDa and contained carbohydrate contents of 96.83%. RFPs with characteristic absorptive peaks of polysaccharide structure and α-configuration were composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose and fucose with a molecular ratio of 0.08:0.17:0.16:0.48:5.73:1.00:1.79:0.03. RFPs promoted splenocyte proliferation, NO release, cytokine production and intracellular Ca 2+ concentration. The mechanism underlying splenocyte activation by RFPs was elucidated by RNA-Seq, in which 2214 differentially expressed genes (DEGs), 2030 GO terms and 92 KEGG pathways were identified. RFPs were further proved to induce a balanced Th1/Th2/Th17 response pattern through MAPK, NF-κB, Jak-STAT and Calcium signaling pathways in splenocytes. These findings provided a fundamental basis for the further application of RFPs as immunomodulators in food and medicine.
研究领域:
免疫学
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药理学
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分子生物学
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生物化学
✓ 已验证
DOI
高影响因子
Science China-Life Sciences
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2024
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IF 8
Zhang Zhen,Huang Weijun,Zhang Xiaoran,Wang Zhecun,Xie Manting,Xie Bingbing,Wang Yiling,Chen Xiaoyong,Xiang Andy Peng,Xiang Qiuling
Despite substantial advancements in modern medicine, the management of hypertension remains a major challenge. Stem cell-based therapies have recently demonstrated remarkable efficacy in treating cardiovascular diseases, including hypertension. However, the antihypertensive mechanism of mesenchymal stem cells (MSCs) has not been extensively explored. This study aimed to investigate the role of injected MSCs in regulating blood pressure homeostasis. Our previous study demonstrated that human induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC-MSCs) are functional and homogeneous sources for MSC-based therapy. After the injection of hiPSC-MSCs, a significant reduction in blood pressure and end target organ inflammation were observed in spontaneously hypertensive rats (SHRs). Cell tracking assays demonstrated that the injected hiPSC-MSCs accumulated in the spleens of the SHRs. The injected hiPSC-MSCs accumulated adjacent to the splenic nerve, potentially contributing to the antihypertensive effects. Furthermore, the hiPSC-MSCs released abundant glutamate, which acts as a neuromodulator to activate the splenic sympathetic nerve. After inhibition of glutamate synthesis by siRNA, the ability of hiPSC-MSCs to activate sympathetic nerves was significantly diminished. In addition, the antihypertensive effects of hiPSC-MSCs were eliminated after splenic nerve denervation (SND), underscoring the critical role of the splenic nerve. Moreover, activation of the splenic nerve resulted in increased release of norepinephrine (NE), which increased the number of choline acetyltransferase-positive (ChAT + ) cells in the spleen and peripheral blood. Consequently, the acetylcholine (ACh) produced by elevated ChAT + cells could act as a vasodilator, lowering blood pressure and mitigating inflammation in end target organs. In summary, our findings indicate that hiPSC-MSCs effectively lower blood pressure in hypertension by influencing the splenic nerves and regulating ChAT + cells. The connection between blood pressure regulation and the splenic nerve may offer new insights into the treatment of hypertension.
研究领域:
干细胞治疗
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心血管疾病
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高血压
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神经科学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
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2024
·
IF 3.7
Menghan Yuan,Xinyue Huang,Shuang Tian,Shixuan Ma,Yuxing Guo,Mingxuan Tao
The selenized modification of purified Pleurotus eryngii polysaccharides (PPEP) were carried out in a nitric acid-sodium selenite system, and the preliminary structural characterization of PPEP and selenized PPEP (613.87 μg/g of selenium) (SPPEP) were carried out by advanced instrumentation techniques. It was found that the selenization modification did not seriously affect the structure of the PPEP. However, the SPPEP exhibited a lower molecular weight, more glycosidic bonds, reduced crystallinity, and improved thermal stability. Through in vivo animal experiments, the study found that PPEP and SPPEP were non-toxic to macrophages. Furthermore, they markedly increased the thymus and spleen indices of immunocompromised mice and improved the histomorphology of these organs. Moreover, PPEP and SPPEP enhanced the mice’s immune ability by markedly increasing the level of immune factor secretion, bone marrow hematopoietic function, and macrophage phagocytic capacity. In addition, the immune activity of SPPEP was better than PPEP’s activity.
研究领域:
生物技术
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免疫学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Immunology
·
2024
·
IF 5.7
Qi WeiYu,Yu YouLi,Yang ChenChen,Wang XiaoJuan,Jiang YuChen,Zhang Li,Yu ZhengQing
Toxoplasma gondii (T. gondii) is a zoonotic disease that poses great harm to humans and animals. So far, no effective T. gondii vaccine has been developed to provide fully protection against such parasites. Recently, numerous researches have focused on the use of poly-lactic-co-glycolic acid (PLGA) and chitosan (CS) for the vaccines against T. gondii infections. In this study, we employed PLGA and CS as the vehicles for T. gondii ribosome protein (TgRPS2) delivery. TgRPS2-PLGA and TgRPS2-CS nanospheres were synthesized by double emulsion solvent evaporation and ionic gelation technique as the nano vaccines. Before immunization in animals, the release efficacy and toxicity of the synthesized nanospheres were evaluated in vitro. Then, ICR mice were immunized intramuscularly, and immune protections of the synthesized nanospheres were assessed. The results showed that TgRPS2-PLGA and TgRPS2-CS nanospheres could induce higher levels of IgG and cytokines, activate dendritic cells, and promote the expression of histocompatibility complexes. The splenic lymphocyte proliferation and the enhancement in the proportion of CD4+ and CD8+ T lymphocytes were also observed in immunized animals. In addition, two types of nanospheres could significantly inhabit the replications of T. gondii in cardiac muscles and spleen tissues. All these obtained results in this study demonstrated that the TgRPS2 protein delivered by PLGA or CS nanospheres provided satisfactory immunoprotective effects in resisting T. gondii, and such formulations illustrated potential as prospective preventive agents for toxoplasmosis.
研究领域:
药剂学
·
免疫学
·
寄生虫学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
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2019
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IF 3.298
Shengli Fu,Mingmei Ding,Qingjian Liang,Yanjian Yang,Meng Chen,Xiufang Wei,Anli Wang,Shaoan Liao,Jianmin Ye
The immune mechanism elicited in pufferfish ( Takifugu obscurus ) against the invasion of Aeromonas hydrophila is still poorly understood. We examined the spleen of pufferfish at the transcriptome and proteome levels by using Illumina-seq and TMT coupled mass spectrometry after 12 h infection by A. hydrophila , respectively. A total of 2,339 genes (1,512 up-regulated and 827 down-regulated) and 537 (237 up-regulated and 300 down-regulated) proteins were identified. GO and KEGG analyses revealed that the responses to stimulus were the main biological processes , intestinal immune network for IgT production and calcium signaling pathway . Fourteen genes (8 up-regulated and 6 down-regulated) and proteins (5 up-regulated and 9 down-regulated) involved immune responses or signal transduction were validated by qRT-PCR and parallel reaction monitoring to confirm the reliability of the transcriptomic and proteomic analyses, respectively. Moreover, qRT-PCR and flow cytometry were used to detect dynamics of the genes in calcium signaling pathway and changes of concentration of cytoplasm Ca 2+ in spleen cells within a 72 h challenge. This study provides the findings regarding immune response, especially intestinal immune network for IgT production pathway and calcium signaling pathway at the molecular, protein and cellular in pufferfish after infection by A. hydrophila . These results would provide a new insight and molecular targets into the response to pathogenic infection in pufferfish.
研究领域:
免疫学
·
分子生物学
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水产养殖
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鱼类病理学
✓ 已验证
DOI
PubMed
高影响因子
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