FISH & SHELLFISH IMMUNOLOGY
·
2020
·
IF 0
Liting Wu,Along Gao,Yang Lei,Jun Li,Kangsen Mai,Jianmin Ye
Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1), a kind of protein tyrosine phosphatases (PTPs), is a critical regulator of antigen receptor signal transduction . Signal transduction of BCR is regulated by phosphatases in teleost as in mammals. In this study, SHP1 from Nile tilapia ( Oreochromis niloticus ) (OnSHP1) was identified and characterized, including the expression pattern against bacterial infection and regulation function in BCR signaling pathway. The open reading frame of OnSHP1 contains 1749 bp of nucleotide sequence , encoding a protein of 582 amino acids. The OnSHP1 protein was highly conversed compared to that of other species, including two amino-terminal SH2 domains at the N terminus and a PTP catalytic domain . Transcriptional expression analysis revealed that OnSHP1 was detected in all examined tissues and highly expressed in spleen . The up-regulated OnSHP1 expression was observed in peripheral blood, spleen and anterior kidney following challenge with Streptococcus agalactiae or lipopolysaccharide (LPS) in vivo , as well as that displayed in leukocytes stimulated with S. agalactiae or LPS in vitro . Further, after induction with mouse anti-tilapia IgM monoclonal antibody in vitro , OnSHP1 was significantly up-regulated in leukocytes. When spleen leukocytes treated with PTP Inhibitor II in vitro , the phosphorylation level of OnSHP1 at the phosphorylation sites (Y 535 and Y 557 ) and the cytoplasmic free Ca 2+ concentration were up-regulated significantly. Overall, the findings of this study indicate that SHP1 gets involved in host defense against bacterial infection and BCR signaling pathway in Nile tilapia .
研究领域:
免疫学
·
分子生物学
·
鱼类生物学
·
病原-宿主互作
✓ 已验证
产品关联
DOI
PubMed
Food Chemistry-X
·
2022
·
IF 6.443
Hualing Xie,Jingyu Fang,Mohamed A. Farag,Zhenhao Li,Peilong Sun,Ping Shao
In this study, the polysaccharides extracted from Dendrobium officinale leaf (DOLP) was used in immune deficiency mice to evaluate the bioactivity. Thymus and spleen indices were calculated while the alleviation of the colon and liver histopathological progression was evaluated by H&E staining. The data indicated that DOLP improved immunity status by restoring the gut barrier and atrophy of immune organs. Cytokines levels as marker of inflammation were determined using ELISA in serum and colon. Which proved that DOLP inhibited the expression of pro-inflammatory cytokines (TNF- α , TGF- β 1, IL-6, IL-1 β ) and promoted the expression of anti-inflammatory cytokines (IL-10). Short chain fatty acids (SCFAs) levels and microbial composition in feces were determined using GS and high-throughput sequencing. DOLP improved gut microbiota by increasing the relative abundance of total bacteria and probiotics such as Bacteroides , Lactobacillus and Lachnospiraceae. Therefore, DOLP has potential effect for the treatment of chronic immune diseases.
研究领域:
免疫学
·
微生物学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Cellular and Infection Microbiology
·
2022
·
IF 6.073
Yi Yan-ling,Li Yao,Guo Sheng,Yan Hui,Ma Xin-fei,Tao Wei-wei,Shang Er-xin,Niu Yang,Qian Da-wei,Duan Jin-ao
Jujube (Ziziphus jujuba Mill.) fruit (JF) is widely consumed as food in Asian countries due to its potential effects for human health. As a traditional Chinese medicine, JF is often used to treat anorexia, fatigue and loose stools caused by spleen deficiency syndromes in China, but the mechanism underlying this effect has not been thoroughly elucidated. In this study, a rat model of spleen deficiency syndromes was adopted to investigate the therapeutic effect of JF extract and its possible mechanism by metabolomics analyses of plasma and urine as well as the intestinal flora analysis. The results showed that the changes in plasma and urine metabolites caused by spleen deficiency were reversed after administration of JF, and these changed endogenous metabolites were mainly involved in retinol metabolism, pentose and glucuronate interconversions, nicotinate and niacinamide metabolism pathways. The 16S rDNA sequencing results showed that JF could regulate intestinal flora imbalance caused by spleen deficiency. The covariance analysis of intestinal flora structure and metabolome indicated that Aerococcus may be a candidate strain for predicting and treating the metabolic pathways of spleen deficiency and related disorders. In summary, it can be revealed that spleen deficiency, which alters metabolic profiles and the intestinal flora, could be alleviated effectively by JF extract.
研究领域:
药理学
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中医中药
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微生物学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
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
·
药理学
·
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
FASEB JOURNAL
·
2018
·Vol. 32
·期 6
·3398-3410
·
IF 5.595
Yugai Jia,Yumeng Miao,Mengfan Yue,Mei Shu,Zhifeng Wei,Yue Dai
Tetrandrine, a bisbenzylisoquinoline alkaloid, was previously demonstrated to attenuate inflammation and cartilage destruction in the ankles of mice with collagen-induced arthritis (CIA). Here, we explored the underlying mechanism by which tetrandrine prevented arthritis-induced bone erosion by focusing on the differentiation and function of osteoclasts. We found that daily administration of tetrandrine (30 mg/kg) markedly reduced the bone damage and decreased the number of osteoclasts in CIA rats. In vitro , tetrandrine inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis at the early stage and reduced the expressions of osteoclast-related marker genes. In bone marrow-derived macrophages and RAW264.7 cells, tetrandrine inhibited RANKL-induced translocation of NF-κB-p65 and nuclear factor of activated T cell 1 (NFATc1) through suppressing spleen tyrosine kinase (Syk)-Bruton's tyrosine kinase-PLCγ2-Ca 2+ signaling. Of interest, tetrandrine did not affect the phosphorylation of immunoreceptor tyrosine-based activation motifs, the conventional upstream of Syk, but it inhibited the activity of Syk by enhancing its ubiquitination and degradation. The anti–osteoclastogenesis effect of tetrandrine nearly disappeared when it was used in combination with the Syk inhibitor piceatannol or in constitutively activated Syk-overexpressing cells. Taken together, tetrandrine attenuated CIA-induced bone destruction by inhibiting osteoclastogenesis through hindering the translocation of NF-κB-p65 and NFATc1 via reducing the activation of Syk.—Jia Y., Miao, Y., Yue, M., Shu, M., Wei, Z., Dai Y. Tetrandrine attenuates the bone erosion in collagen-induced arthritis rats by inhibiting osteoclastogenesis via spleen tyrosine kinase. FASEB J. 32, 3398–3410 (2018). www.fasebj.org
研究领域:
药理学
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免疫学
·
风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Chunlian Liu,Chengcheng Song,Yan Wang,Yangxin Xiao,Zhongshi Zhou,Guosheng Cao,Xiongjie Sun,Yanju Liu
Ethnopharmacological relevance Atractylodes lancea (Thunb.) DC. is a Chinese herb that has been commonly used to treat spleen-deficiency diarrhea (SDD) in China for over a thousand years. However, the underlying mechanism of its antidiarrheal activity is not fully understood. Aim of the study The antidiarrheal effects of the ethanol extract of deep-fried A. lancea rhizome (EEDAR) due to spleen deficiency induced by folium sennae (SE) were determined on the regulation of the short-chain fatty acid (SCFA) metabonomics induced by the intestinal flora . Materials and methods The effects of EEDAR on a SE-induced mouse model of SDD were evaluated by monitoring the animal weight, fecal water content, diarrhea-grade rating, goblet cell loss, and pathological changes in the colon. The expression of inflammatory factors (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-6, IL-10), aquaporins (AQP3, AQP4, and AQP8), and tight junction markers (ZO-1, occludin , claudin-1) in colon tissues were determined using quantitative polymerase chain reaction and western blotting . SCFA metabonomics in the feces of mice treated with EEDAR was evaluated using gas chromatography–mass spectrometry. Furthermore, 16S rDNA sequencing was used to determine the effect of EEDAR on the intestinal flora of SDD mice, and fecal microbiota transplantation (FMT) was used to confirm whether the intestinal flora was essential for the anti-SDD effect of EEDAR. Results Treatment with EEDAR significantly improved the symptoms of mice with SDD by inhibiting the loss of colonic cup cells, alleviating colitis , and promoting the expression of AQPs and tight junction markers. More importantly, the effect of EEDAR on the increase of SCFA content in mice with SDD was closely related to the gut microbiota composition. EEDAR intervention did not significantly improve intestinal inflammation or the barrier of germ-free SDD mice, but FMT was effective. Conclusion EEDAR alleviated SE-induced SDD in mice, as well as the induced SCFA disorder by regulating the imbalance of the intestinal microbiota.
研究领域:
药理学
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微生物学
·
代谢组学
·
胃肠病学
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民族药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Liufang Hu,Jiali Chen,Huifang Duan,Zhenyu Zou,Yuan Qiu,Jing Du,Jiaxu Chen,Xinsheng Yao,Hiroaki Kiyohara,Takayuki Nagai,Zhihong Yao
Ethnopharmacological relevance Bu-Zhong-Yi-Qi-Tang is a famous traditional Chinese medicine formula that has been prevalent in China for over 700 years to treat spleen-qi deficiency related diseases, such as gastrointestinal and respiratory disorders . However, the bioactive components responsible for regulating spleen-qi deficiency remain unclear and have puzzled many researchers. Aim of the study The current study focuses on efficacy evaluation of regulating spleen-qi deficiency and screening the bioactive components of Bu-Zhong-Yi-Qi-Tang. Materials and methods The effects of Bu-Zhong-Yi-Qi-Tang were evaluated through blood routine examination, immune organ index, and biochemical analysis. Metabolomics was utilized to analyze the potential endogenous biomarkers (endobiotics) in the plasma, and the prototypes (xenobiotics) of Bu-Zhong-Yi-Qi-Tang in the bio-samples were characterized using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Then, these endobiotics were used as “bait” to predict targets based on network pharmacology and to screen potential bioactive components from the absorbed prototypes in the plasma by constructing an “endobiotics-targets-xenobiotics” association network. Further, the anti-inflammatory activities of representative compounds (calycosin and nobiletin) were validated through poly(I:C)-induced pulmonary inflammation mice model. Results Bu-Zhong-Yi-Qi-Tang exhibited immunomodulatory and anti-inflammatory activities in spleen-qi deficiency rat, as supported by the observation of increased levels of D-xylose and gastrin in serum, an increase in the thymus index and number of lymphocytes in blood, as well as a reduction in the level of IL-6 in bronchoalveolar lavage fluid. Furthermore, plasma metabolomic analysis revealed a total of 36 Bu-Zhong-Yi-Qi-Tang related endobiotics, which were mainly enriched in primary bile acids biosynthesis, the metabolism of linoleic acid , and the metabolism of phenylalanine pathways. Meanwhile, 95 xenobiotics were characterized in plasma, urine, small intestinal contents, and tissues of spleen-qi deficiency rat after Bu-Zhong-Yi-Qi-Tang treatment. Using an integrated association network, six potential bioactive components of Bu-Zhong-Yi-Qi-Tang were screened. Among them, calycosin was found to significantly reduce the levels of IL-6 and TNF-α in the bronchoalveolar lavage fluid, increase the number of lymphocytes, while nobiletin dramatically decreased the levels of CXCL10, TNF-α, GM-CSF, and IL-6. Conclusion Our study proposed an available strategy for screening bioactive components of BYZQT regulating spleen-qi deficiency based on “endobiotics-targets-xenobiotics” association network.
研究领域:
民族药理学
·
药理学
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中医
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代谢组学
·
免疫学
·
炎症研究
✓ 已验证
DOI
PubMed
高影响因子
TOXICOLOGY
·
2021
·
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
·
免疫学
·
蛋白质组学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
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
·
疫苗开发
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
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
·
纳米技术
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Pharmacology & Translational Science
·
2021
·
IF 0
Xue-Yan Dai,Shi-Yong Zhu,Mu-Zi Li,Milton Talukder,Yi Zhao,Jin-Long Li
Di(2-ethylhexyl) phthalate (DEHP) is a synthetic chemical and widely used as a plasticizer. Humans can be exposed to DEHP through direct contact or environmental contamination. Lycopene (Lyc) has been discussed as a potential effector in the prevention and therapy of various diseases. 140 male mice were assigned into control, vehicle control, Lyc (5 mg/kg BW/d), DEHP (500 and 1000 mg/kg BW/d, respectively), and DEHP + Lyc groups and treated with an oral gavage that lasted 28 d. The ultrastructural results showed that DEHP induced pathological changes and mitochondrial injuries. We further revealed that DEHP exposure destroyed the Fe2+ imbalance homeostasis and, consequently, increases of lipid peroxidation and inhibition of cysteine/glutamate antiporter, all of which were involved in the process of ferroptsis. Moreover, the supplementation of Lyc significantly inhibited the ferroptsis changes mentioned above. Altogether, these results indicated that DEHP exposure triggered splenic cell death via ferroptosis; meanwhile, they also shed new evidence on a potential clue for the intervention and prevention of DEHP-related diseases.
研究领域:
毒理学
·
药理学
·
细胞生物学
·
环境健康
✓ 已验证
产品关联
DOI
PubMed
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-9
·
IF 5.228
Gao Ningning,Zhong Jingjing,Wang Xiaodong,Jin Zhenchao,Li Wang,Liu Yu,Diao Yuwen,Wang Zhulin,Jiang Wenqi,Jin Guangyi
As new treatment approaches, both immunotherapy and targeted treatments have been used in the clinical treatment of cancers. These therapies are different from traditional surgery, chemotherapy and radiotherapy. Use of a combination of immunotherapy and targeted treatments may improve tumor clearance. We investigated the feasibility of combining tyrosine kinase inhibitors (TKIs, targeted drugs) and SZU-101 (a novel TLR7 agonist synthesized by our laboratory). Thirteen different TKIs were combined with or without SZU-101 and studied to determine their effects on immunocytes. On the basis of the distinctive results, lapatinib and sunitinib were selected for further tumor-inhibition investigation and determination of the underlying mechanism. Interestingly, we found lapatinib to work better with SZU-101, enhancing tumor clearance in vivo , without affecting the TLR7-NF-κB pathway activated by the TLR7 agonist in mouse spleen lymphocytes and bone marrow dendritic cells (BMDCs).
研究领域:
肿瘤学
·
免疫学
·
药理学
✓ 已验证
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）