FISH & SHELLFISH IMMUNOLOGY
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2024
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IF 4.1
Qiulu Li,Kaixin Ping,Yannan Xiang,Ying Sun,Zunhan Hu,Shujuan Liu,Xinying Guan,Mian Fu
Avamectin (AVM), a macrolide antibiotic, is widely used in fisheries, agriculture, and animal husbandry, however, its irrational use poses a great danger to aquatic organisms. Ferulic acid (FA) is a natural chemical found in the cell walls of plants. It absorbs free radicals from the surrounding environment and acts as an antioxidant. However, the protective effect of FA against kidney injury caused by AVM has not been demonstrated. In this study, 60 carp were divided into the control group, AVM group (2.404 μg/L), FA+AVM group and FA group (400 mg/kg). Pathological examination, quantitative real-time PCR (qPCR), reactive oxygen species (ROS) and western blot were used to evaluate the preventive effect of FA on renal tissue injury after AVM exposure. Histological findings indicated that FA significantly reduced the swelling and infiltration of inflammatory cells in the kidney tissues of carp triggered by AVM. Dihydroethidium (DHE) fluorescent probe assay showed that FA inhibited the accumulation of kidney ROS. Biochemical results showed that FA significantly increased glutathione (GSH) content, total antioxidant capacity (T-AOC) and catalase (CAT) activity, and decreased intracellular malondialdehyde (MDA) content. In addition, western blot results revealed that the protein expression levels of Nrf2 and p-NF-κBp65 in the carp kidney were inhibited by AVM, but reversed by the FA. The qPCR results exhibited that FA significantly increased the mRNA levels of tgf-β1 and il-10 , while significantly down-regulated the gene expression levels of tnf-α , il-6 and il-1β . These data suggest that FA can reduce oxidative stress and renal tissue inflammation induced by AVM. At the same time, FA inhibited the apoptosis of renal cells induced by AVM by decreasing the transcription level and protein expression level of Bax, and increasing the transcription level and protein expression level of Bcl2, PI3K and AKT. This study provides preliminary evidence for the theory that FA reduces the level of oxidative stress, inflammation response and kidney tissue damage caused by apoptosis in carp, providing a theoretical basis for the prevention and treatment of the AVM.
研究领域:
水生毒理学
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药理学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
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2024
·
IF 5.4
Yuting Hou,Zhe Wang,Zhen Chen,Lan Shuai,Yifei Pei,Binbin Sun,Yuxin Jiang,Hongsheng Wang
It is difficult to obtain specific tumor antigens, which is one of the main obstacles in the development of tumor vaccines. The vaccines containing multivalent antigens are thought to be more effective in antitumor therapy. In this study, a mRNA encoding three neoantigens of melanoma were prepared and encapsulated into the mannosylated chitosan-modified ethosomes (EthsMC) to obtain a multivalent mRNA vaccine (MmRV) for transcutaneous immunization (TCI). MmRV can effectively induce maturation of dendritic cells, with a better performance than mRNA of a single neoantigen. TCI patches (TCIPs) loading MmRV or siRNA against PDL1 (siPDL1) were prepared and applied to the skin of melanoma-bearing mice. The results showed that TCIPs significantly increase the levels of TNF-α, IFN-γ, and IL-12 in both plasma and tumor tissues, inhibit tumor growth, as well as promote infiltration of CD4+ and CD8+ T cells in the tumor tissues. Furthermore, the combination of MmRV and siPDL1 showed much better antitumor effects than either monotherapy, suggesting a synergistic effect between the vaccine and PDL1 blocker. In addition, the treatment with the TCIPs did not cause damage to the skin, blood, and vital organs of the mice, showing good biosafety. To the best of our knowledge, this work is the first to construct a noninvasive TCI system containing MmRV and siPDL1, providing a convenient and promising approach for tumor treatment.
研究领域:
肿瘤学
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免疫学
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药学
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生物技术
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Ximeng Lin,Wenxia Li,Hywel Yuen,Michael Yuen,Qiang Peng
Agaricus bitorquis (QuéL.) Sacc. Chaidam is a valuable edible fungus in Qinghai-Tibet plateau and ABSP is a novel intracellular polysaccharide from its mycelia. GC and NMR analysis determined ABSP is galactoglucomannan-like polysaccharide that may have immunomodulatory effect. This study used RAW264.7 as model cell to determine immunomodulatory effect of ABSP. After ABSP treatment, viability and phagocytic ability promoted, and NO, ROS, TNF-α levels also raised which proved ABSP had immune regulation to RAW264.7. WB and qRT-PCR determined the key proteins and genes expression of TLR4, MyD88, TRAF-6 and NF-κB significantly increased while protein and gene expression of TRAM had no significant increase. Also, TNF-α level extremely decreased by adding inhibitors of TLR4 and MyD88 which confirmed ABSP could immunologically regulate RAW264.7 byTLR4-MyD88 dependent pathway. This study would provide theoretical basis for further study on ABSP and be helpful for development of beneficial functionally foods and exploitation of this resource.
研究领域:
免疫学
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真菌学
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药理学
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生物化学
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产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
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2020
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IF 5.778
Jiafeng Zhou,Ruonan Shu,Chunan Yu,Ze Xiong,Qingfeng Xiao,Zezhi Li,Xiaoxian Xie,Zhengwei Fu
Trifluoromethanesulfonic acid (TFMS) is the shortest chain perfluorinated compound . Recently, it has been identified as a persistent and mobile organic chemical with a maximum concentration of 1 μg/L in the environment. However, its toxicological mechanism remains unclear. In this study, to evaluate the liver and intestinal toxicity of TFMS in mammals, male mice were orally exposed to 0, 1, 10 and 100 μg/kg for 12 weeks. Our results showed that TFMS exposure reduced the epididymal fat weight in mice, caused the decrease of serum and liver triglyceride (TG) level and the increase of serum low density lipoprotein (LDL) level. Also, we observed the inflammatory cell infiltration in the liver of mice exposed to 10 μg/kg and 100 μg/kg TFMS, which was coupled with the increased mRNA expression levels of inflammatory factors such as COX2 , TNF-α , IL-1β in the liver. In addition, the mRNA expression levels of lipid metabolism-related genes ( PPAR-α , ACOX , SCD1 , PPAR-γ , etc.) were significantly decreased in the liver of mice after exposure to both doses of TFMS. We also found TFMS exposure caused the imbalance of cecal gut microbiota and change of cecal microbiota diversity. KEGG pathway predictions showed that the exposure of 100 μg/kg TFMS changed the synthesis and degradation of ketone bodies, benzoate degradation and several other metabolic pathways. Our findings indicated that TFMS exposure disturbed the liver lipid metabolism possibly via altering the gut microbiota.
研究领域:
毒理学
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分子生物学
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微生物学
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环境科学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
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2022
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IF 6.59
Han Mengyao,Zhang Zhongshan,Li Xinyue,Tong Haibin,Xu Zhiguo,Ding Zikang,Yang Anquan,Xie Min,Wang Xiaomei
To investigate the protective effect of collagen peptide from Micropterus salmoides skin (CPMs) on oxidative damage induced by cyclophosphamide in mice. Balb/c female mice were divided into blank, model (cyclophosphamide, CTX), positive control (levamisole hydrochloride), and collagen peptide low-, medium-, and high-dose groups. The results showed that CPMs increase the body mass and immune-related organ indexes, such as liver and kidneys of immunosuppressed mice. The activities of ALT, AST, UA, BUN, and MDA in the liver and kidney tissues decreased significantly, while those of SOD and GSH-Px increased significantly. CPMs can relieve the pathological damage to immune organs. CPMs significantly increase the activities of IL-2, IgG, and TNF-α in serum and SOD activity, while the MDA content was decreased compared to the model group. CPMs can exert a protective effect on cyclophosphamide-induced oxidative damage and have application prospects in the field of health food.
研究领域:
药理学
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免疫学
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毒理学
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营养学
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产品关联
DOI
PubMed
高影响因子
Advanced Biology
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2023
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IF 3.7
Jingjia Ye,Zhengfa Wen,Tianxin Wu,Liangliang Chen,Lingchao Sheng,Chenhuan Wang,Chong Teng,Bingbing Wu,Jian Xu,Wei Wei
Though the occurrence of neuroinflammation after spinal cord injury (SCI) is essential for antigen clearance and tissue repair, excessive inflammation results in cell death and axon dieback. The effect of anti-inflammatory medicine used in clinical treatment remains debatable owing to the inappropriate therapeutic schedule that does not align with the biological process of immune reaction. A better understanding of the immunity process is critical to promote effective anti-inflammatory therapeutics. However, cellular heterogeneity, which results in complex cellular functions, is a major challenge. This study performs single-cell RNA sequencing by profiling the tissue proximity to the injury site at different time points after SCI. Depending on the analysis of single-cell data and histochemistry observation, an appropriate time window for anti-inflammatory medicine treatment is proposed. This work also verifies the mechanism of typical anti-inflammatory medicine methylprednisolone sodium succinate (MPSS), which is found attributable to the activation inhibition of cells with pro-inflammatory phenotype through the downregulation of pathways such as TNF, IL2, and MIF. These pathways can also be provided as targets for anti-inflammatory treatment. Collectively, this work provides a therapeutic schedule of 1–3 dpi (days post injury) to argue against classical early pulse therapy and provides some pathways for target therapy in the future.
研究领域:
神经科学
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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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产品关联
DOI
PubMed
高影响因子
Frontiers in Physiology
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2023
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IF 4
Senyue Liu,Lin Luo,Fengyuan Zuo,Xiaoli Huang,Liang Zhong,Sha Liu,Yi Geng,Yangping Ou,Defang Chen,Wenlong Cai,Yongqiang Deng
Nitrogen from ammonia is one of the most common pollutants toxics to aquatic species in aquatic environment. The intestinal mucosa is one of the key mucosal defenses of aquatic species, and the accumulation of ammonia nitrogen in water environment will cause irreversible damage to intestinal function. In this study, histology, immunohistochemistry, ultrastructural pathology, enzyme activity analysis and qRT-PCR were performed to reveal the toxic effect of ammonia nitrogen stress on the intestine of Pelteobagrus fulvidraco . According to histological findings, ammonia nitrogen stress caused structural damage to the intestine and reduced the number of mucous cells. Enzyme activity analysis revealed that the activity of bactericidal substances (Lysozyme, alkaline phosphatase, and ACP) had decreased. The ultrastructure revealed sparse and shortened microvilli as well as badly degraded tight junctions. Immunohistochemistry for ZO-1 demonstrated an impaired intestinal mucosal barrier. Furthermore, qRT-PCR revealed that tight junction related genes ( ZO-1, Occludin, Claudin-1 ) were downregulated, while the pore-forming protein Claudin-2 was upregulated. Furthermore, as ammonia nitrogen concentration grew, so did the positive signal of Zap-70 (T/NK cell) and the expression of inflammation-related genes ( TNF , IL-1β , IL-8, IL-10) . In light of the above findings, we conclude that ammonia nitrogen stress damages intestinal mucosal barrier of Pelteobagrus fulvidraco and induces intestinal inflammation.
研究领域:
水生毒理学
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环境科学
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鱼类生理学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Jianhao Xie,Juan Su,Wanqi Zhou,Simin Cai,Wenfeng Liao,Jianing Zong,Junfeng Peng,Huanhuan Qu,Fei He,Kan Ding
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with limited treatment options. Recent pharmacological studies suggested that Lamiophlomis rotata might contain components with antitumor activities. In this study, we aimed to investigate the potential of polysaccharides as active components in Lamiophlomis rotata . Our findings suggest that a polysaccharide, LRP01B, from Lamiophlomis rotata induces PDAC cells apoptosis by causing mitochondrial dysfunction and oxidative stress in vitro and in vivo . LRP01B is a homogeneous polysaccharide with a molecular weight of 15.9 kDa, composed of galactose, glucose, xylose, arabinose, rhamnose, and galacturonic acid in a molar ratio of 0.7: 0.3: 0.1: 1.1: 1.0: 4.3. The backbone of LRP01B mainly consists of 1,4-linked α-Gal p A, 1,2-linked α-Rha p , and 1,3-linked α-Gal p A, with existence of arabinose and xylose on the side chain. In vivo experiments demonstrate that LRP01B significantly inhibits pancreatic tumor growth in a patient-derived xenograft nude mouse model. Mechanism studies uncover that LRP01B induces apoptosis of PDAC cells through mitochondrial dysfunction and oxidative stress by recruiting TNF-related apoptosis-inducing ligand (TRAIL) to TRAIL-R1, which leads to the binding of LRP01B to both TRAIL and TRAIL-R1. Our results demonstrate that LRP01B is a dual-targeting polysaccharide with anti-PDAC activity and may be a promising anti-PDAC drug candidate.
研究领域:
癌症生物学
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药理学
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生物化学
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分子生物学
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药物化学
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2021
·Vol. 31
·期 21
·2008960
·
IF 18.808
Jiandong Yang,Shanzhou Duan,Huan Ye,Chenglong Ge,Chunxian Piao,Yongbing Chen,Minhyung Lee,Lichen Yin
Pulmonary delivery of anti-inflammatory siRNA holds great potential in mitigating the cytokine storm during severe pneumonia. However, commonly utilized polycationic siRNA delivery vehicles can hardly penetrate the mucus barrier, thus greatly hurdling their therapeutic efficacy. Herein, TNF-α siRNA (siTNF-α) delivery nanocomplexes (NCs) are engineered with mucus/cytomembrane dual-penetration capabilities, realized via surface-coating of NCs with RC, an inflammation-sheddable, charge-reversal pro-peptide of RAGE-binding peptide (RBP). RC-coated dendritic poly- L -lysine/siTNF-α (DsT) NCs possess negative surface charges, and can thus efficiently penetrate the mucus layer after intratracheal administration. In the inflamed alveolar space with mild acidity, RC recovers to the cationic RBP and shed off, re-exposing the DsT NCs that efficiently transfect the alveolar macrophages and provokes TNF-α silencing. Thus, siTNF-α and RBP cooperatively alleviate the uncontrolled inflammation during acute lung injury. This study renders a unique approach for mediating trans-mucus nucleic acid delivery, and will find promising utilities for the treatment of severe pneumonia.
研究领域:
药剂学
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纳米技术
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肺科学
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分子生物学
✓ 已验证
DOI
高影响因子
PHYTOMEDICINE
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2025
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IF 8.3
Jie Gao,Jin Yan,Xingwang Zu,Yanyan Xu,Shilong Wang,Yue Li,Zhenying Zhao,Yuanyuan Hou,Gang Bai
Background In the innate immune system, damage-associated molecular patterns (DAMPs) released by damaged cells, such as peroxiredoxin 1 (PRDX1), interact with Toll-like receptor 4 (TLR4), exacerbating inflammation and tissue injury. Ferulic acid (FA), a dietary and herbal phenolic compound, exhibits notable anti-inflammatory properties. However, the precise anti-inflammatory mechanisms of FA are not fully understood. Purpose The objective of this study was to elucidate mechanisms underlying the anti-inflammatory effects of FA. Methods Lipopolysaccharide (LPS) was intratracheally instilled to establish a mouse model of LPS-induced pneumonia. Different doses of FA were injected intraperitoneally, and their anti-inflammatory effects were evaluated. An alkynyl-modified FA probe was used in conjunction with various chemobiological strategies to explore the localization, capture, and identification of FA targets. The pharmacophore of FA and its mechanisms of interaction with its target or pathway were further validated using rigorous biochemical assays and comprehensive transcriptomic profiling. The proposed mechanism of FA against systemic inflammation was validated in mice administered LPS intraperitoneally. Results FA alleviated LPS-induced pulmonary inflammation in mice by selectively targeting macrophages. Subsequently, PRDX1 was identified as an irreversible FA-binding target. Mechanistic investigations revealed that α,β-unsaturated ketone in FA serves as a critical pharmacophore that covalently binds to the Cys173 residue of PRDX1. This covalent binding event effectively suppressed PRDX1 dimerization, resulting in reduced PRDX1 secretion. The co-localization assay demonstrated that FA reduced TLR4-binding PRDX1 in LPS-treated RAW264.7 cells. Transcriptomic analysis indicated that NF-κB and TNF signaling pathways, downstream of TLR4 signaling, were involved in the FA-mediated anti-inflammatory effects. Reduction of TLR4 activation caused by FA treatment decreased levels of downstream inflammatory cytokines in LPS-treated RAW264.7 cells. Finally, reduced co-localization of TLR4 and PRDX1 by FA was confirmed in the lung slices of mice with LPS-induced intratracheal inflammation. FA also reduced PRDX1 dimerization and mitigated inflammation in mice administered LPS intraperitoneally. Conclusion Our study elucidated a novel mechanism in which FA covalently binds to the Cys173 residue of PRDX1, suppressing its dimerization and secretion and thereby alleviating inflammation by modulating the PRDX1/TLR4 signaling pathway. Our findings redefine plant phenylacrylic acids as covalent modulators of DAMPs, with therapeutic potential for ameliorating inflammation beyond conventional antioxidants.
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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炎症研究
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药物化学
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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 ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Yanjun Yang,Zhouyang Qian,Chenhui Wu,Yue Cheng,Bing Yang,Jianguo Shao,Jing Zhao,Xiangjun Zhu,Xiaobin Jia,Liang Feng
Ethnopharmacological relevance Pudilan Xiaoyan Oral Liquid (PDL) is a proprietary Chinese medicinal preparation approved by the State for treating acute pharyngitis in both adults and children (Approval No. Z20030095). It is worth noting that children exhibit unique physiopathological characteristics compared to adults. However, the in vivo regulatory characteristics of PDL in treating acute pharyngitis in children remain incompletely understood. Aim of the study The differential absorption and metabolism characteristics of the main pharmacological components in PDL in young and adult rats were investigated with a view to providing a reference for preclinical data of PDL in medication for children. Materials and Methods This study utilized UPLC-Q-TOF-MS to investigate the pharmacodynamic material basis of PDL. The focus was on the gastrointestinal digestion and absorption characteristics of organic acid components in PDL (PDL-OAC), known as the primary pharmacodynamic components in this formulation. The research combined in vitro dynamic simulation and a Quadruple single-pass intestinal perfusion model to examine these characteristics. The permeability properties of PDL-OAC were evaluated using an artificial parallel membrane model. Additionally, an acute pharyngitis model was established to evaluate the histopathological condition of the pharynx in young rats using H&E staining. The levels of IL-1 β , TNF- α , IL-6, and IL-10 in blood and pharyngeal tissue homogenates of young rats were quantified using ELISA kits. Results A total of 91 components were identified in PDL, including 33 organic acids, 24 flavonoids, 14 alkaloids, 5 terpenoids and coumarins, 3 sugars, and 12 amino acids. The PDL-OAC exhibited a significant reduction in IL-1 β , TNF- α , IL-6, and IL-10 levels in the pharyngeal tissues of young rats with acute pharyngitis. Results from dynamic simulation studies of gastrointestinal fluids revealed that the PDL-OAC (Specifically chlorogenic acid (CGA), gallic acid (GA), chicoric acid (CRA), and caffeic acid (CA)) were effectively stabilized in the gastrointestinal fluids of both children and adults in vitro . Young rats, characterized by thinner intestinal walls and higher permeability, efficiently absorbed the four organic acids across the entire intestinal segment. The absorption of CGA, GA, and CRA followed a concentration-dependent pattern, with CGA and GA absorption being influenced by exocytosis. Conclusion The efficacy of the PDL-OAC in treating acute pharyngitis was demonstrated in young rats. The absorption rate of these components was observed to be faster in young rats compared to adult rats, underscoring the need for dedicated studies on the drug's usage in children. This research provides valuable insights for the appropriate clinical use of PDL in pediatric patients.
研究领域:
药理学
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民族药理学
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儿科
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药学
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产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Huan Cao,Jianhua Zhang,Lei Yang,Haotian Li,Rong Tian,Haoxing Wu,Yiwen Li,Zhipeng Gu
Apart from bacterial growth and endotoxin generation, the excessive production of reactive radicals linked with sepsis also has a substantial impact on triggering an inflammatory response and further treatment failure. Hence, the rational design and fabrication of robust and multifunctional nanoparticles (NPs) present a viable means of overcoming this dilemma. In this study, we used antibiotic polymyxin B (PMB) and antioxidant natural polyphenolic protocatechualdehyde (PCA) to construct robust and multifunctional NPs for sepsis treatment, leveraging the rich chemistries of PCA. The PMB release profile from the NPs demonstrated pH-responsive behavior, which allowed the NPs to exhibit effective bacterial killing and radical scavenging properties. Data from in vitro cells stimulated with H2O2 and lipopolysaccharide (LPS) showed the multifunctionalities of NPs, including intracellular reactive oxygen species (ROS) scavenging, elimination of the bacterial toxin LPS, inhibiting macrophage M1 polarization, and anti-inflammation capabilities. Additionally, in vivo studies further demonstrated that NPs could increase the effectiveness of sepsis treatment by lowering the bacterial survival ratio, the expression of the oxidative marker malondialdehyde (MDA), and the expression of inflammatory cytokine TNF-α. Overall, this work provides ideas of using those robust and multifunctional therapeutic NPs toward enhanced sepsis therapy efficiency.
研究领域:
纳米技术
·
药学
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传染病学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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