ENVIRONMENTAL TOXICOLOGY
·
2018
·Vol. 34
·期 2
·141-149
·
IF 2.491
Xia Wang,Baida Kong,Bingnan He,Lai Wei,Jianbo Zhu,Yuanxiang Jin,Yudong Shan,Weitao Wang,Chunqiang Pan,Zhengwei Fu
8:2 Fluorotelomer alcohol (8:2 FTOH) is widely used in houseware and industrial goods and is ubiquitous in the surrounding environment. 8:2 FTOH has been linked to hepatoxicity, nephrotoxicity, and reproductive toxicity, as well as endocrine-disrupting effects. However, as of yet, the research regarding immunotoxicity of 8:2 FTOH remains largely limited. In the present study, adult male C57BL/6 mice were administered with 10, 30, and 100 mg/kg/d 8:2 FTOH by gavage for 28 days to investigate its immunotoxicity in vivo. The results showed that exposure to 8:2 FTOH caused increases in liver weight and histological changes in the liver, including vacuolation, cell swelling, immune cell infiltration, karyopyknosis and nuclear swelling. No histological change in either the spleen or the thymus was observed after administration of 8:2 FTOH. In addition, exposure to 8:2 FTOH reduced the concentration of IL-1β in serum, and mRNA levels of IL-1β, IL-6 , and TNF-α in both the thymus and spleen. CXCL-1 mRNA expression was downregulated in both the liver and thymus after 8:2 FTOH administration, while only IL-1β mRNA expression was upregulated in the liver. Moreover, the exposure of primary cultured splenocytes to 8:2 FTOH inhibited the ConA-stimulated proliferation of splenocytes at concentrations of 30 and 100 μM, and the LPS-stimulated proliferation of splenocytes at 100 μM. Furthermore, 8:2 FTOH inhibited the level of secreted IFN-γ in ConA-stimulated splenocytes. The results obtained in the study demonstrated that 8:2 FTOH posed potential immunotoxicity and liver injury in mice. Our findings will provide novel data for the health risk assessment of 8:2 FTOH.
研究领域:
毒理学
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免疫学
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环境健康
✓ 已验证
DOI
PubMed
高影响因子
Cellular & Molecular Immunology
·
2025
·
IF 19.8
Bai Ying,Ren Hui,Leng Shuo,Yuan Mengqin,Jiang YiXin,Zhang Shenyang,Wang Yu,Ju Minzi,Wang Zhi,Xi Wen,Xu Lian,Zheng Bingjing,Li Daxing,Huo Xinchen,Zhu Tianhao,Zhang Beicheng,Shen Ling,Zhang Yuan,Jiang Wei,Zhang John H.,Han Bing,Yao Honghong
Splenic sympathetic activity critically modulates peripheral immunity after ischemic stroke, thus intervention in spleen sympathetic activity represents a promising therapeutic strategy for stroke. However, the mechanisms underlying spleen-brain-immune axis communication remain poorly understood. Here, we utilized a surgical denervation protocol to perform splenic sympathetic denervation (SDN), which significantly attenuated brain injury following stroke. Through single-cell RNA sequencing, we identified a novel GZMK + CD8 + CD27 + CCR7 + T-cell subset in patients with acute ischemic stroke (AIS), which we designated stroke-associated T (Tsa) cells. The expansion of Tsa cells was positively correlated with the severity of clinical symptoms and was driven by the splenic sympathetic nervous system. Stroke-induced sympathetic activation triggers the release of splenic norepinephrine (NE), which preferentially signals through ADRB2 on Tsa cells to promote their mobilization. Additionally, ischemic injury induces endothelial cell-specific expression of CCL19, which chemoattracts Tsa cells into the brain parenchyma via their cognate CCR7 receptor, exacerbating neuroinflammatory injury and neurological deficits in a transient middle cerebral artery occlusion (tMCAO) mouse model. We developed a CCR7-targeting peptide to disrupt this chemotactic axis and reduce T-cell infiltration, thereby mitigating brain injury. Our findings highlight SDN as a promising therapeutic strategy to attenuate ischemia‒reperfusion injury and suggest its potential as an adjunctive therapy for reperfusion treatment in AIS patients.
研究领域:
神经科学
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免疫学
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卒中研究
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神经免疫学
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分子生物学
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细胞生物学
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生物医学研究
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药理学
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系统生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Jing Li,Rui Hu,Xingning Liu,Lanfen Peng,Jinyu Yi,Xin Zhong,Qi Huang,Jialing Sun,Wenxing Feng,Wenfeng Ma,Xiaozhou Zhou
Ethnopharmacological relevance Mitophagy regulates cellular homeostasis and liver inflammation; however, it is inhibited in acute-on-chronic liver failure (ACLF), which drives disease progression. The JianPi LiShi YangGan formula (YGF) has the potential to improve inflammatory responses and reduce mortality in patients with ACLF. However, the precise mechanisms underlying these effects remain unknown. Aim of the study We investigated the role of S100A9/RAGE signaling in mitophagy and the protective effects of traditional Chinese medicinal compounds on ACLF. Materials and methods An ACLF mouse model was established using carbon tetrachloride, lipopolysaccharide, and d-galactose. Hematoxylin and eosin staining and enzyme-linked immunosorbent assay were employed to evaluate the hepatoprotective effect of YGF in ACLF mice. Mitochondrial damage was assessed using transmission electron microscopy. Protein levels of mitophagy-related indicators were assessed through immunohistochemistry and western blotting, and immunofluorescence staining was performed to observe Lamp2 and COX-IV co-localization. Results The hepatocytes of ACLF mice contained damaged mitochondria, decreased mitophagy-related protein (Pink1, Parkin, and LC3B) expression and activated S100A9/RAGE signaling. Inhibiting S100A9 or RAGE improved liver injury in ACLF mice and enhanced Lamp2-COX-IV co-localization. In alpha mouse liver 12 (AML12) cells overexpressing RAGE, recombinant S100A9 protein inhibited mitophagy induced by 3-chlorocarbonyl benzoyl chloride. YGF reduced mitochondrial damage, increased Pink1, Parkin, and LC3B levels, and enhanced mitophagy while inhibiting S100A9/RAGE activation in the hepatocytes of ACLF mice. Conclusions This study found that S100A9/RAGE pathway activation impairs mitophagy, and YGF alleviates liver injury by downregulating S100A9 and RAGE signaling, which may be a novel therapeutic strategy for ACLF.
研究领域:
药理学
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肝脏病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Environmental Sciences
·
2024
·
IF 5.9
Hanyu Wang,Shenye Feng,Enzhuang Pan,Xiaomeng Ji,Mengyuan Zhou,Shuai Zhang,Baoshi Xu,Huimiao Feng,Jilei Yin,Zibo Dong
Extensive use of avermectin (AVM) in agriculture can seriously contaminate fish in aquaculture. Ferulic acid (FA) is a strong antioxidant sourced from plants and is widely applied in food and medicine, but its protective function on the immunological damage caused by AVM is still lacking. In this study, carp were chronically exposed to (1/10 96 hr LC 50 ) AVM for 30 day(s), with a dietary supplement of FA (400 mg/kg) to assess its effects on carp spleen. The experimental groups ( n = 10) included: control, AVM-exposed (2.404 µg/L), FA + AVM co-treated, and FA alone. Long-term AVM exposure altered spleen tissue, reducing serum complement C3 ( p < 0.01) and immunoglobulin M levels ( p < 0.001), and increasing pro-inflammatory tnf-α ( p < 0.001), il-6 ( p < 0.001), il-1β ( p < 0.001), and inos mRNA levels, whilst down-regulating the anti-inflammatory tgf-β ( p < 0.05). Additionally, it disrupted the balance of oxidative stress indicators such as MDA ( p < 0.001), T-AOC, GSH, and CAT, leading to spleen tissue apoptosis (42.4%). However, the addition of FA reversed these conditions, elevated the anti-inflammatory factor, and improved spleen immune function following chronic exposure to AVM in carp. Moreover, the ability to restore oxidative homeostasis in carp by adjusting the Nrf2/NQO-1 axis protected the health of spleen tissues. This discovery also supports the development of fish feed for aquaculture.
研究领域:
水产养殖
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免疫学
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毒理学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 7
·2914-2924
·
IF 5.396
Li Tao,Wei Zhang,Yaxin Zhang,Mei Zhang,Yueying Zhang,Xing Niu,Qing Zhao,Zhenxing Liu,Yuyin Li,Aipo Diao
Telomere shortening is one of the main causes of cellular senescence. Caffeine is a natural stimulant most commonly found in coffee and tea. In this study, caffeine was found to promote the expression of telomerase reverse transcriptase (TERT) at both mRNA and protein levels, and consequently extended the telomere length and prevented cellular senescence. Knockdown of TERT eliminated the effect of caffeine on telomere elongation. Moreover, animal studies indicated that caffeine promoted the expression of TERT and extended the telomere length in the thymus and spleen of mice treated with caffeine for a long period of eight months. In addition, caffeine restored the decline of organ index and improved the histological structural change of the thymus, spleen and liver of mice due to aging. These results suggest that caffeine promotes the expression of TERT to delay cellular senescence and aging, which help to understand the mechanism for the beneficial effects of caffeine containing foods on health.
研究领域:
分子生物学
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老年学
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营养学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Shiru Huang,Han He,Hanxi Li,Chongyang Li,Fu Wang,Yuan Hu,Youping Liu,Lin Chen,Hongping Chen
Atractylodis macrocephalae Rhizoma (AM), a widely used Chinese herb for treating spleen deficiency diarrhea (SDD), is rich in polysaccharides. However, the precise mechanism underlying the antidiarrheal effects of Atractylodis macrocephalae Rhizoma polysaccharide (AMP) remains unclear. In this study, AMP, with a molecular weight of 69 kDa, is isolated from AM and consists of Glc, Gal, and Ara in a molar ratio of 84.16:6.51:9.33. FTIR and NMR analyses indicate that AMP features a linear backbone of →4,6)-α-D-Glc p -(1→ with branches of →3)-β-D-Glc p -(1→, terminating in →2,4)-β-D-Gal p -(1→. Animal models of SDD induced by Folium sennae demonstrate that AMP alleviates diarrhea symptoms, mitigates colon damage, and enhances spleen index, thymus index, and the expression of CD4 + CD25 + Foxp3 + Treg cells. Further, the potential mechanisms for AMP's antidiarrheal action are explored through the comprehensive approach integrating intestinal flora, polysaccharide utilization loci, short-chain fatty acids (SCFAs), and metabolomics. AMP reduces the abundance of pathogenic c_ Clostridia while promoting beneficial o_Bacteroidales and f_Muribaculaceae, influencing SCFAs production via its strong binding affinities with SusD, GH2, and GH43. This modulation is linked to alterations in linoleic acid metabolism, alpha-linolenic acid metabolism, and primary bile acid biosynthesis. In conclusion, AMP demonstrates significant potential as a therapeutic agent for SDD.
研究领域:
药理学
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微生物学
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免疫学
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代谢组学
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中医药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Analytical Chemistry
·
2020
·
IF 1.678
Fang Zhao,Yuan Wei,Yiming Yan,Han Liu,Sitong Zhou,Bo Ren,Ruijuan Liu
Toxicity induced by crizotinib, a small-molecule tyrosine kinase inhibitor, is a significant clinical issue during treatment. A tissue distribution study is required to explore the organs affected by this molecule. In this study, a simple liquid chromatography tandem mass spectrometry method was developed and validated for the determination of crizotinib in various mouse tissues. Mouse tissue homogenates were processed by protein precipitation with methanol, and apatinib was chosen as the internal standard. The analytes were separated on a Phenomenex Kinetex C18 (50 mm × 2.1 mm, 2.6 μm) column with gradient elution using methanol and 0.3% formic acid water solution. Tandem mass spectrometric detection was conducted using multiple reaction monitoring via an electrospray ionization source in the positive mode. The monitored ion transitions were m/z 450.1 ⟶ 260.2 for crizotinib and m/z 398.2 ⟶ 212.0 for apatinib. The problem of the severe carryover effect was successfully resolved. The method was validated and applied to a tissue distribution study of crizotinib in mice, which was reported for the first time. The results of the study showed that the main target organs of crizotinib were the lung, liver, and spleen, and a high concentration of crizotinib was found in the gastrointestinal tract. This study offers a reliable method for quantifying crizotinib and provides a basis for further research on crizotinib toxicity.
研究领域:
药理学
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分析化学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Ping Chen,Xi He,Yue Hu,Xiao-Li Tian,Xiao-Qi Yu,Ji Zhang
In recent years, the application of mRNA vaccine-based tumor immunotherapy invigorated anti-tumor therapy. However, the low efficiency of mRNA delivery and the lack of targeting ability in vivo are the major obstacles to achieving highly efficient immunotherapy. In this work, we report a chemical library of amphiphilic carbon dots (ACDs) and the synthesized ACDs were applied to mRNA delivery, bio-imaging, and tumor immunotherapy. The ACDs can smoothly bind with mRNA to form ACDs@mRNA nanocomplexes, and the fluorescent properties of the ACDs afforded the nanoparticles with bio-imaging ability. By screening of the ACDs, O12-Tta-CDs were found to have optimal mRNA transfection efficiency and the ability of spleen-targeted delivery. In addition, O12-Tta-CDs can well transfect the immune cells and promote the maturation and antigen presentation of bone marrow-derived dendritic cells (BMDCs). Furthermore, O12-Tta-CDs@OVA-mRNA was successfully applied to inhibit tumor growth, and more specific T-cell infiltration was observed in spleen and tumors of mice after treatment in the E.G7-OVA tumor model. Besides, O12-Tta-CDs@OVA-mRNA also achieved a good therapeutic effect in tumor recurrence inhibition and tumor prophylactic experiments. This study provided a new direction for the design of mRNA vectors, which is promising in tumor immunotherapy.
研究领域:
生物医学工程
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免疫学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
·
2025
·
IF 4.7
Jianing Li,Letian He,Wenling Wang,Siyu Wang,Dan Zhang,Liyun Liang,Guangping Song,Yijian Zhang,Shaoqing Yu,Lei Wang,Qiuying Han,Shaoyi Huang,Sen Li,Haiqing Tu,Zengqing Song,Huaibin Hu,Huiyan Li,Yang Yang,Min Wu
As the largest secondary lymphoid organ, the spleen plays a crucial role in initiating and sustaining immune responses against blood-borne pathogens through antigen capture and delivery. It is innervated by both autonomic and sensory nerves, which allows for neural modulation of its immune responses. The intricate spatial structure and precise coordination between immune and neural components is essential for proper splenic function, necessitating three-dimensional (3D) imaging to reveal its architecture. However, the dense fibrous capsule and exceptionally rich vasculature of the spleen pose significant challenges for achieving comprehensive 3D visualization of the entire organ. Here, we systematically evaluated and compared five cutting-edge tissue clearing approaches—ImmuView, FLASH, SHANEL, advanced CUBIC, and Ce3D—for their effectiveness in rendering the spleen transparent for multiplexed antibody staining and high-resolution 3D imaging. Our results indicated that SHANEL provided the clearest visualization of essential splenic neural and immune components. Meanwhile, advanced CUBIC achieved the greatest labeling efficacy for immune cells, albeit with slightly reduced transparency. Importantly, our study marked the first application of these optimized protocols to human spleen tissue, successfully revealing the highly organized immune cell zones and neural networks with enhanced clarity. Notably, we identified the nociceptive sensory innervation within human spleen tissue for the first time. Collectively, these findings establish optimal imaging strategies for visualizing splenic immune cells and neural structure in both murine and human tissues, providing profound insights into the intricate neuroimmune interactions and their pivotal roles in the immune functions of the spleen.
研究领域:
免疫学
·
神经科学
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医学影像学
✓ 已验证
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2025
·
IF 2.5
Yanru Liu,Ya Hu,Xiaoxia Xie,Gongjun Yang,Fang Feng
Wen-Pi-Tang (WPT), a Traditional Chinese Medicine (TCM) prescription, is commonly used to treat chronic renal failure. However, the material basis and potential mechanisms of WPT against chronic renal failure have not been clarified. UHPLC-Q-Exactive Orbitrap-MS was utilized in this work to investigate the chemical components of WPT and their prototypes or metabolites in vivo. 227 chemical compounds were identified in the WPT. Meanwhile, 56 exogenous components (24 prototype components and 32 metabolic components) were examined in rat plasma. Meanwhile, network pharmacology revealed that liquiritigenin-O-sulfate, 3-keto-18β-glycyrrhetinic acid, 22-hydroxy-18-β-glycyrrhetinic acid, and hydroxyliquiritigenin (B ring)-O-sulfate with related targets AKT1, EGFR, STAT3, ESR1, SRC, MAPK3, MTOR, and PIK3CA were considered as the effective components and core targets. Furthermore, the findings suggested that the therapeutic effects of WPT on chronic renal failure may be substantially influenced by the PI3K-Akt, HIF-1, and FoxO signaling pathways. The outcomes of molecular docking and molecular dynamics simulations indicate that the key targets have strong binding capacities with effective components. Our study offers a comprehensive method for examining the molecular foundation and underlying mechanisms of WPT against chronic renal failure, opening up new therapeutic opportunities.
研究领域:
中药学
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药理学
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代谢组学
✓ 已验证
产品关联
DOI
高影响因子
NEUROGASTROENTEROLOGY AND MOTILITY
·
2024
·
IF 3.5
Lei Chen,Xiangbing Chang,Chuntao Wu,Guofu Luo,Peifeng Zhang,Wei Tian
Background The traditional herbal medicine Atractylodes macrocephala Koidz. ( A. macrocephala ) is commonly utilized for alleviating symptoms associated with spleen deficiency, abdominal distension, diarrhea, and constipation. These pharmacological effects are attributed to a variety of active constituents. However, the specific bioactive compounds responsible for promoting defecation and gastrointestinal transit in A. macrocephala remain unidentified. Methods The primary polysaccharide characteristics of PAMK was elucidated by HPLC, FT-IR, and HGPGC. Efficacy of PAMK (0.07, 0.14, and 0.28 mg/g) on mice was evaluated in a spleen deficiency constipation mouse model by analyzing stool parameters, constipation-related physiological indexes, and SCFAs. The expression levels of 5-HT 3 R, 5-HT 4 R, and related receptor genes were examined by RT-qPCR, and neurotransmitters were examined using ELISA. Finally, the diversity of gut microbiota was analyzed with 16S rDNA sequencing. Key Results The results showed that PAMK significantly reduced the gastrointestinal transport time and increased the number of fecal pellets and fecal water content in spleen deficiency constipation model mice. PAMK kept the balance of 5-HT, SCFAs, TPH-1, SERT, CgA, and neurotransmitter levels (VIP, SP, MTL) in mice colon. In addition, PAMK could regulate the abundance of gut microbiota such as Alistopes , Bacteroides , and Odoribacter in spleen deficiency constipation model mice gut. Conclusions and Inferences It can be concluded that PAMK effectively ameliorated the symptoms of spleen deficiency constipation in mice by modulating the expression of 5-HT and its associated receptors. The underlying mechanism was elucidated, providing a solid theoretical foundation for the therapeutic application of A. macrocephala in treating spleen deficiency constipation and offering potential for developing novel approaches to address this condition.
研究领域:
药理学
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胃肠病学
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微生物学
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中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2025
·
IF 11.3
Ru-Yang Zhao,Mu-Zi Li,Qi-Qian Wang,Fu-Wei Jiang,Yi Zhao,Jin-Long Li
Butachlor (BTR), a globally prevalent amide herbicide, poses significant environmental health risks due to its bioaccumulation potential and documented chronic toxicity in mammalian systems. Given the spleen's pivotal role in orchestrating systemic immune homeostasis, this study investigated BTR-induced immunopathological mechanisms in ICR mice following 28-day subacute exposure (10 mg/kg). Histopathological examination revealed significant disorganization of the splenic marginal zone architecture, concomitant with ultrastructural mitochondrial abnormalities and a reduction in mitochondrial membrane potential (ΔΨm). Mitochondrial permeability transition pore opening triggered cytoplasmic translocation of mitochondrial DNA (mtDNA), activating the stimulator of interferon genes (STING) pathway—a master regulator of innate immunity. STING activation initiated bifurcated downstream signaling, evidenced by TBK1 phosphorylation and subsequent IRF3 / NF-κB nuclear translocation. This dual signaling cascade simultaneously executed immunogenic cell death via Gasdermin D-dependent pyroptosis (cleaved GSDMD-NT) and drove macrophage polarization (IFN-α / β, IL-1β, TNF-α). Crucially, pharmacological STING inhibition with C-176 attenuated both pyroptosis (GSDMD cleavage reduced) and inflammatory cytokine surge. Our findings not only pioneer the identification of the mtDNA-STING axis as the central mechanism underlying BTR-induced splenic immunotoxicity but also validate STING inactivation as a targeted strategy to mitigate herbicide-associated immune dysfunction. This work provides critical insights for environmental toxicant risk assessment and immunomodulatory.
研究领域:
环境毒理学
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免疫学
·
分子生物学
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药理学
·
细胞生物学
✓ 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）