International Journal of Nanomedicine
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2015
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IF 4.383
Dong Dong,Xiao Wang,Huailing Wang,Xingwang Zhang,Yifei Wang,Baojian Wu
Introduction SNX-2112 is a promising anticancer agent but has poor solubility in both water and oil. In the study reported here, we aimed to develop a nanocrystal formulation for SNX-2112 and to determine the pharmacokinetic behaviors of the prepared nanocrystals.Methods Nanocrystals of SNX-2112 were prepared using the wet-media milling technique and characterized by particle size, differential scanning calorimetry, drug release, etc. Physiologically based pharmacokinetic (PBPK) modeling was undertaken to evaluate the drug’s disposition in rats following administration of drug cosolvent or nanocrystals.Results The optimized SNX-2112 nanocrystals (with poloxamer 188 as the stabilizer) were 203 nm in size with a zeta potential of −11.6 mV. In addition, the nanocrystals showed a comparable release profile to the control (drug cosolvent). Further, the rat PBPK model incorporating the parameters of particulate uptake (into the liver and spleen) and of in vivo drug release was well fitted to the experimental data following administration of the drug nanocrystals. The results reveal that the nanocrystals rapidly released drug molecules in vivo, accounting for their cosolvent-like pharmacokinetic behaviors. Due to particulate uptake, drug accumulation in the liver and spleen was significant at the initial time points (within 1 hour).Conclusion The nanocrystals should be a good choice for the systemic delivery of the poorly soluble drug SNX-2112. Also, our study contributes to an improved understanding of the in vivo fate of nanocrystals.
研究领域:
药理学
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纳米医学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2022
·
IF 4.966
Tianmeng Zhang,Zhuhua Dong,Feixue Liu,Enzhuang Pan,Nana He,Fenfen Ma,Xinyu Wu,Yan Wang,Jingquan Dong
Avermectin is one of the most widely used pesticides, but its toxicity to non-target organisms, especially aquatic organisms , has been ignored. Therefore, an acute spleen injury model of avermectin in carp was established to assess the non-target toxicity of avermectin to carp. In this study, 3.005 μg/L and 12.02 μg/L were set as the low and high dose groups of avermectin, respectively, and a four days acute exposure experiment was conducted. Pathological structure observation showed that avermectin damaged spleen tissue structure and produced inflammatory cell infiltration . Biochemical analysis showed that avermectin significantly reduced the activities of antioxidant enzymes CAT, SOD, and GSH-px, but increased the content of MDA, a marker of oxidative damage. Avermectin exposure also significantly increased the transcription levels of inflammatory cytokines such as IL-1β, IL-6, TNF-α, and INOS, and also significantly enhanced the activity of the inflammatory mediator iNOS, but suppressed the transcription levels of anti-inflammatory factors TGF-β1 and IL-10. In addition, TUNEL detected that the apoptosis rate increased significantly with the increase of avermectin dosage, and the transcription levels of apoptosis-related genes BAX, P53, and Caspase 3/9 also increased in a dose-dependent manner. This study is preliminary evidence that avermectin induces spleen injury in carp through oxidative stress , inflammation, and apoptosis, which has important implications for subsequent studies on the effects of avermectin on non-target organisms.
研究领域:
水生生物学
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毒理学
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环境科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
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IF 3.1
Ranqi Yao,Wenqi Cui,Weidi Wang,Chenlu Feng,Ying Chen,Xiujuan Zhao
Perimenopausal depression is a subtype of depression that seriously harms women's health. The pathogenesis of perimenopausal depression remains unclear, which limits its prevention and therapy. Quercetin is a flavonoid with antidepressant and estrogen-like effects. This study aimed to explore the effects of quercetin on spleen metabolism in rats with perimenopausal depression and its potential mechanism. Untargeted metabolomics was employed to obtain splenic metabolite profiles, and 21 differential metabolites were identified. Pathway analysis revealed that glycerophospholipid metabolism, retinol metabolism, steroid hormone biosynthesis, and linoleic acid metabolism were disturbed. Notably, Spearman’s rank correlation analysis revealed that differential metabolites were significantly correlated with behavioral test results (p < 0.01). After treatment with quercetin, the intensities of the above differential metabolites were restored (p < 0.01), indicating that quercetin can improve the spleen metabolic disorder induced by the perimenopausal depression model. Further study showed that quercetin can increase the expression of PPAR-α in the hippocampus and spleen, reduce the expression of NF-κB and the levels of TNF-α and IL-6 in the spleen, and restore the expression of CREB and BDNF in the hippocampus (p < 0.05 or p < 0.01). Our study is the first to explore the effect of quercetin on spleen metabolism disorders in perimenopausal depression model rats using untargeted metabolomics. Quercetin can improve spleen metabolism disorders through multiple pathways, which may be related to the restoration of hippocampal neuroplasticity and reduction of spleen inflammation by regulating the brain-spleen axis. Our study provides a potential strategy for preventing and treating perimenopausal depression.
研究领域:
药理学
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神经科学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Yichen Li,Yi Cao,Hao Bai,Luwei Zhang,Baiqiu Chen,Chengfan Wu,Qi Shuai,Yunfeng Yan
The application of mRNA-based therapies has gained significant attention in recent years, with lipid nanoparticles (LNPs) emerging as key delivery vehicles. However, challenges remain in optimizing delivery efficiency and targeting tissues beyond the liver, particularly for immunotherapy. In this study, we constructed novel lipids with disulfide bonds in the linkers and utilized the redox responsiveness of these bonds in the reductive microenvironment of tumor or immune cells to enable robust splenic mRNA delivery and potent cancer immunotherapy. A library of 119 lipids was synthesized by conjugating hydrophilic amines, disulfide-containing linkers, and hydrophobic amines via sequential aza-Michael addition. In vitro screening identified lipids with longer, branched hydrophobic tails, particularly 2C10, as leading carriers for mRNA delivery. Compared to conventional LNPs without disulfide linkers, disulfide-containing LNPs showed smaller size, higher mRNA binding, and enhanced mRNA release in the presence of GSH, with predominantly spleen-targeted in vivo delivery. Encapsulation with OVA mRNA promoted CD4 + and CD8 + T cell differentiation, leading to significant tumor regression in a melanoma mouse model. These findings highlight the potential of redox-responsive LNPs for targeted mRNA delivery and cancer immunotherapies.
研究领域:
生物技术
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药理学
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免疫学
✓ 已验证
产品关联
DOI
高影响因子
Redox Biology
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2025
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IF 11.9
Chuanlin Feng,Lei Zhang,Xiaoyuan Zhou,Shiyu Lu,Ruowen Guo,Chao Song,Xin Zhang
The magnetic properties of substances directly determine their response to an externally applied magnetic field, which are closely associated with magnetoreception, magnetic resonance imaging (MRI), and magnetic bioeffects. However, people understanding of the magnetic properties of living organisms remains limited. In this study, we utilized NRF2 (nuclear factor erythroid 2-related factor 2) deficiency mice to investigate the contribution of redox (oxidation–reduction) homeostasis, in which the key process is the transfer of electron, a direct target of magnetic field and origin of paramagnetism. Our results show that the NRF2 -/- mice exhibit significantly altered systemic redox state, accompanied by increased magnetic susceptibility, particularly in the liver and spleen. Further analyses reveal that the levels of paramagnetic reactive oxygen species (ROS) in these tissues are markedly elevated compared to wild-type mice. Moreover, the concentrations of Fe 2+ and Fe 3+ are significantly elevated in NRF2 -/- mice, which are directly correlated with the increased magnetic susceptibility. The disrupted redox balance in NRF2 -/- mice not only exacerbates oxidative stress and iron deposition, but also induces impairs to the liver and spleen. The findings highlight the combined effects of ROS and iron metabolism in driving magnetic susceptibility changes, providing valuable theoretical insights for further research into magnetic bioeffects effects and organ-specific sensitivity to magnetic fields.
研究领域:
生物物理学
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分子生物学
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医学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2021
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IF 6.025
Rili Hao,Yang Jiang,Feng Li,Dongxiao Sun-Waterhouse,Dapeng Li
Cadmium (Cd) is a toxic heavy metal pollutant that can be accumulated in organs including the spleen, thereby threatening human health. In this study, the effect of caffeic acid phenethyl ester (CAPE, a bioactive component of honeybee propolis) on CdCl 2 -induced spleen toxicity and underlying mechanisms were examined in mice. Histological examinations revealed that CAPE (10 μmol/kg/day b.w.) could mitigate spleen damage induced by CdCl 2 (1.5 mg/kg/day b.w.) in mice. Compared to the mice treated only by CdCl 2 , CAPE administration increased the body weight while decreasing the spleen weight, spleen Cd content and spleen to body ratio of the CdCl 2 -treated mice. Western blot and ELISA tests revealed that CAPE suppressed CdCl 2 -induced inflammation (indicated by the decreases in the levels of inflammatory indictors). TUNEL and Western blot results showed that CAPE suppressed CdCl 2 -induced apoptosis through reducing the percentage of TUNEL-positive cells and regulating apoptosis factors. The antagonistic effect of CAPE against CdCl 2 -induced spleen toxicity was realized by increasing miR-182–5p expression to regulate the TLR4/NF-κB pathway. Therefore, CAPE could be a food-derived spleen protector to counteract Cd-induced spleen toxicity through alleviating apoptosis and inflammation via the miR-182–5p/TLR4/NF-κB axis.
研究领域:
毒理学
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药理学
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分子生物学
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Environmental Sciences
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2024
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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
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2021
·Vol. 12
·期 7
·2914-2924
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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
ACS Applied Materials & Interfaces
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2023
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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
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产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
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2025
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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
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神经科学
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医学影像学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2025
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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
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分子生物学
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药理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2025
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IF 4.2
Yu Xia,Yidan Wang,Jiahui Xue,Jiahong Chu,Yanhe Zhang,Fuze She,Huijie Chen,Shu Li
Naringenin (Nar) is known to maintain mitochondrial homeostasis, antioxidation and anti-inflammation. Damaged mitochondria can promote excessive Reactive oxygen species (ROS) production, triggering pyroptosis and inflammation process in immune tissues. PTEN induced putative kinase 1 (PINK1)/E3 ubiquitin ligase PARK2 (Parkin)-mediated mitophagy contributes to removing damaged mitochondria. This study aims to investigate detailed mechanism of Nar against Lipopolysaccharide (LPS)-induced injury in broiler spleens and the role of mitophagy in this process. We used LPS as a stimulus and treated with Nar to establish relevant models in vivo and in vitro . Our findings demonstrated Nar increased the expression levels of Phospho-Adenosine 5 ’ -monophosphate (AMP)-activated protein kinase (p-AMPK)/AMPK, PINK1, Parkin and Microtubule-Associated Protein 1A/1B Light Chain 3 (LC3), and reduced the level of Sequestosome 1 (P62), leading to a reduction in levels of factors associated with mitochondrial fission, mtDNA release, pyroptosis, and inflammation. Conversely, Nar treatment enhanced the levels of factors related to mitochondrial fusion, energy metabolism, and anti-inflammatory response. Moreover, an increase was observed in ΔΨm, ATP content, and ATPase activity. Molecular docking analysis and cellular thermal shift assay (CETSA) supported the interaction between Nar and AMPK. In summary, Nar enhanced LPS-induced mitophagy and alleviated mitochondrial homeostasis imbalance and oxidative stress in broiler spleens through its interaction with AMPK, resulting in alleviating pyroptosis and inflammation.
研究领域:
兽医学
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免疫学
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分子生物学
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线粒体生物学
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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）