Food & Function
·
2024
·
IF 5.1
Yahui Wu,Mona Alrasheed Bashir,Changsheng Shao,Han Wang,Jianxia Zhu,Qing Huang
Numerous natural compounds are recognized for their anti-inflammatory properties attributed to antioxidant effects and modulation of key inflammatory factors. Among them, astaxanthin (AST), a potent carotenoid antioxidant, remains relatively underexplored regarding its anti-inflammatory mechanisms and specific molecular targets. In this study, human monocytic leukemia cell-derived macrophages (THP-1) were selected as experimental cells, and lipopolysaccharide (LPS) served as the inflammatory stimulus. Upon LPS treatment, the oxidative stress was significantly increased, accompanied by remarkable cellular damage. Moreover, LPS escalated the expression of inflammation-related molecules. Our results demonstrated that AST intervention could effectively allevate the LPS-induced oxidative stress, facilitate the cellular repair, and significantly attenuate the inflammation. Further exploration of anti-inflammatory mechanism revealed AST could substantially inhibit the NF-κB translocation and activation, and mitigate the inflammatory factor production by hindering NF-κB through the antioxidant mechanism. We further confirmed that AST exhibited protective effects against cell damage and reduced the injury from inflammatory cytokines by activating p53 and inhibiting STAT3. In addition, utilizing network pharmacology and in silico calculations based on molecular docking, molecular dynamics simulation, we identified interleukin-6 (IL-6) as a prominent core target of AST anti-inflammation, which was further validated by the RNA interference experiment. This IL-6 binding capacity actually enabled AST to curb the positive feedback loop of inflammatory factors, averting the onset of possible inflammatory storms. Therefore, this study offers a new possibility for the application and development of astaxanthin as an popular dietary supplement of anti-inflammatory or immunomodulatory function.
研究领域:
免疫学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 2
·483
·
IF 4.2
Linlin Cui,Li Zhao,Guanghuan Shen,Dahai Yu,Tian Yuan,Yingyu Zhang,Bo Yang
Cordycepin has good antitumor activity, but its clinical application is limited due to the easy deamination of N6 in structure. In this study, a large lipolysis group was introduced at the cordycepin N6 to improve the problem, cordycepin derivatives (3a–4c) were synthesized, and biological evaluation of compounds was studied. In this study, the vitro antitumor activity of the compounds against MCF7 cells, HepG2 cells and SGC-7901 cells was evaluated by MTT assay. In the results, compound4ashowed the most obvious inhibitory effect on MCF7 cells with an IC50value of 27.57 ± 0.52 μM, which was much lower than cordycepin. Compound4ashowed high selectivity between MCF7 and normal MCF-10A cells. Further biological evaluation showed that compound4apromoted apoptosis and blocked the cell cycle in the G0/G1 phase. Then, Western Blot was used to detect related apoptotic proteins. It was found that Compound4acould down-regulate the expression of Bcl-2 protein and up-regulate the expression of p53, Bax, Caspase-3 and Caspase-9 proteins. The mitochondrial membrane potential decreased continuously and the positive expression rate decreased. It was speculated that compound4ainduced the apoptosis of MCF7 cells through the mitochondrial pathway.Keywords:cordycepin derivatives;antitumor;structural modification
研究领域:
药理学
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2025
·
IF 2.8
Nian Liu,Shuchao Zhang,Yiliang Liu,Xing Lu,Xiaozhen He
Carbimazole, a first-line antithyroid agent, alleviates hyperthyroidism by inhibiting thyroid hormone synthesis. However, its clinical use is complicated by adverse effects such as cardiotoxicity and hepatotoxicity, underscoring the need to elucidate its mechanisms in model organisms. In this study, zebrafish embryos at 6-h postfertilization (hpf) were continuously exposed to increasing carbimazole concentrations, with systematic assessment of developmental and physiological parameters. Results demonstrated that concentrations above 3.5 μg/mL caused significant mortality and delayed hatching. Dose-dependent developmental abnormalities included shortened body length, reduced swim bladder area, and pericardial edema. Further analyses indicated carbimazole-induced cardiotoxicity characterized by impaired cardiac development, decreased heart rate, and dysregulation of apoptosis-related genes. A diminished fluorescence area suggested compromised cardiac tissue integrity. Concurrently, hepatotoxicity manifested as yolk sac enlargement and altered expression of liver-specific genes, indicating disrupted hepatic function. RNA sequencing (RNA-seq) analyses indicated that at 120 hpf, the 5-μg/mL carbimazole-treated group exhibited 158 upregulated genes and 562 downregulated genes compared with the wild-type (WT) group. GO and KEGG enrichment analyses revealed disruptions in several signaling pathways associated with liver metabolism and cardiac development, including metabolism, FoxO signaling, and the p53 signaling pathway. These findings demonstrate that carbimazole induces early embryonic developmental abnormalities, cardiotoxicity, and hepatotoxicity in zebrafish. This research provides new insights into carbimazole toxicity and valuable perspectives for optimizing its clinical dosing regimen.
研究领域:
药理学
·
毒理学
·
发育生物学
·
分子生物学
·
基因组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANNALS OF THE RHEUMATIC DISEASES
·
2024
·
IF 20.3
Fang Qiu,Duoli Xie,Hongzhen Chen,Zhuqian Wang,Jie Huang,Chunhao Cao,Yiying Liang,Xu Yang,Dong-Yi He,Xuekun Fu,Aiping Lu,Chao Liang
Objectives Rheumatoid arthritis (RA) is an autoimmune disease characterised by aggressive fibroblast-like synoviocytes (FLSs). Very few RA patients-derived FLSs (RA-FLSs)-specific surface signatures have been identified, and there is currently no approved targeted therapy for RA-FLSs. This study aimed to screen therapeutic aptamers with cell-targeting and cytotoxic properties against RA-FLSs and to uncover the molecular targets and mechanism of action of the screened aptamers. Methods We developed a cell-specific and cytotoxic systematic evolution of ligands by exponential enrichment (CSCT-SELEX) method to screen the therapeutic aptamers without prior knowledge of the surface signatures of RA-FLSs. The molecular targets and mechanisms of action of the screened aptamers were determined by pull-down assays and RNA sequencing. The therapeutic efficacy of the screened aptamers was examined in arthritic mouse models. Results We obtained an aptamer SAPT8 that selectively recognised and killed RA-FLSs. The molecular target of SAPT8 was nucleolin (NCL), a shuttling protein overexpressed on the surface and involved in the tumor-like transformation of RA-FLSs. Mechanistically, SAPT8 interacted with the surface NCL and was internalised to achieve lysosomal degradation of NCL, leading to the upregulation of proapoptotic p53 and downregulation of antiapoptotic B-cell lymphoma 2 (Bcl-2) in RA-FLSs. When administrated systemically to arthritic mice, SAPT8 accumulated in the inflamed FLSs of joints. SAPT8 monotherapy or its combination with tumour necrosis factor (TNF)-targeted biologics was shown to relieve arthritis in mouse models. Conclusions CSCT-SELEX could be a promising strategy for developing cell-targeting and cytotoxic aptamers. SAPT8 aptamer selectively ablates RA-FLSs via modulating NCL-p53/Bcl-2 signalling, representing a potential alternative or complementary therapy for RA.
研究领域:
免疫学
·
分子生物学
·
治疗学
·
自身免疫疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2024
·
IF 3.9
Ying Sun,Xiaohui Jin,Zuwang Yang,Zunhan Hu,Qiulu Li,Jingquan Dong,Mian Fu
Difenoconazole (DFZ) is a widely used triazole fungicide in agricultural production. However, the presence of DFZ residue in the environment poses a significant risk to non-target organisms. Ferulic acid (FA) is a phenolic compound known for its antioxidant and anti-inflammatory properties. This study aims to investigate the hepatic damage caused by DFZ in carp and explore the mechanism through which FA alleviates this damage. The findings revealed that FA enhanced the antioxidant capability of the carp's liver and reduced the accumulation of reactive oxygen species (ROS) in the liver tissue. Moreover, FA regulated the transcriptional levels of inflammation-related factors, effectively preventing the inflammatory response triggered by the NF-κB signaling pathway. Additionally, TUNEL results demonstrated that DFZ initiated apoptosis, while dietary supplementation with FA decreased the protein expression levels of Bax and Cytochrome C (Cyt c) and the transcriptional levels of bax , caspase3 , caspase9 , p53 genes. Furthermore, FA increased the protein expression and transcriptional levels of Bcl-2. In conclusion, FA protects against liver injury induced by DFZ exposure in carp by modulating oxidative damage, inflammation, and apoptosis.
研究领域:
环境毒理学
·
水生生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
·
IF 8.786
Liu Senyue,Luo Lin,Zuo Fengyuan,Geng Yi,Ou Yangping,Chen Defang,Yang Shiyong,Luo Wei,Wang Yan,Wang Jun,Huang Xiaoli
Myxobolus, a major harmful type of myxospora, is one of the main parasitic pathogens of freshwater fish. Once myxoboliosis occurs, treatment can be extremely difficult. Therefore, clear understandings of the etiology of myxoboliosis and its pathological mechanism are keys for prevention and control. Here, histology, transmission electron microscopy, transcriptome study, tunel assay, and immunohistochemistry were carried out, revealing the morphology, pathological effects as well as host response mechanism of goldfish gill to Myxobolus ampullicapsulatus. Histological studies showed that the mature spores of Myxobolus ampullicapsulatus were composed of three parts, the spore shell, sporoplasm and bottle shaped polar capsule containing double S-shaped polar filaments. Transcriptome analysis revealed that Myxobolus ampullicapsulatus -infected (Myx) goldfish gills were characterized by apoptosis activation mediated by “p53 signaling pathway” with significantly up-regulated apoptosis-related differential genes dominated by p53-Bcl2/Bax signaling pathway. In addition, tunel assay revealed severe gill apoptosis in the Myx group. Transcriptome analysis also revealed that Myx group showed changes in immune response and significantly down-regulated immune-related differential genes. Beyond that, immunohistochemistry showed that there was no significant increase in the number of gill lymphocyte after parasite infection. These results suggest that the pathological mechanism of Myxobolus ampullicapsulatus infection on gills of goldfish may be related to apoptosis and immunosuppression. Subsequent qRT-PCR showed that apoptosis-related genes (Caspase3,Bad, Bax) and anti-inflammatory gene IL-10 were significantly increased, while immune-related pro-inflammatory genes (IL-1β, IL-8) were markedly down-regulated, further verifying the transcriptome results. Based on the above results, we concluded that p53-Bcl2/Bax related networks that dominant the expression of apoptosis genes were activated while immunity was suppressed in the gills of Myxobolus ampullicapsulatus infected goldfish. Our study is not only of benefit to enrich the taxonomy of Myxobolus but also clarifies its pathogenic mechanism, thus providing targets for prevention and control of myxoboliosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Xiong Jinfeng,Li Guannan,Mei Xinyu,Ding Jiahui,Shen Hui,Zhu Da,Wang Hui
The p53 gene has the highest mutation frequency in tumors, and its inactivation can lead to malignant transformation, such as cell cycle arrest and apoptotic inhibition. Persistent high-risk human papillomavirus (HR-HPV) infection is the leading cause of cervical cancer. P53 was inactivated by HPV oncoprotein E6, promoting abnormal cell proliferation and carcinogenesis. To study the treatment of cervical intraepithelial neoplasia (CIN) and cervical cancer by restoring p53 expression and inactivating HPV oncoprotein, and to verify the effectiveness of nano drugs based on nucleic acid delivery in cancer treatment, we developed poly (beta-amino ester)537, to form biocompatible and degradable nanoparticles with plasmids (expressing p53 and targeting E7). In vitro and in vivo experiments show that nanoparticles have low toxicity and high transfection efficiency. Nanoparticles inhibited the growth of xenograft tumors and successfully reversed HPV transgenic mice’s cervical intraepithelial neoplasia. Our work suggests that the restoration of p53 expression and the inactivation of HPV16 E7 are essential for blocking the development of cervical cancer. This study provides new insights into the precise treatment of HPV-related cervical lesions.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2020
·
IF 9.038
Junke Wang,Tianxin Zhao,Jiadong Chen,Lian Kang,Yuexin Wei,Yuhao Wu,Lindong Han,Lianju Shen,Chunlan Long,Shengde Wu,Guanghui Wei
Di(2-ethylhexyl) phthalate (DEHP) is a widely-used plasticizer and has long been recognized as an endocrine-disrupting chemical with male reproductive toxicities. DEHP exposure at the prepubertal stage may lead to extensive testicular injury. However, the underlying mechanisms remain to be elucidated. In the present study, we gavaged male C57BL/6 mice with different concentrations of DEHP (0, 250, and 500 mg/kg-bw·d) from postnatal day 22–35, and exposed TM3 Leydig cells with 0, 100, 200, 300, and 400 μM of MEHP (bioactive metabolite of DEHP) for 12–48 h. RNA sequencing was performed both in testicular tissue and TM3 cells. The results showed that DEHP disrupts testicular development and reduces serum testosterone levels in male prepubertal mice. Bioinformatic analysis and experimental verification have revealed that DEHP/MEHP induces cell cycle arrest in TM3 cells and increases apoptosis both in vivo and in vitro. Furthermore, the p53 signaling pathway was found to be activated upon DEHP/MEHP treatment. The inhibition of p53 by pifithrin-α significantly reduced MEHP-induced injuries in TM3 cells. Cumulatively, these findings revealed the involvement of the p53 signaling pathway in DEHP-induced prepubertal testicular injury by promoting cell apoptosis and inhibiting cell proliferation of Leydig cells.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2020
·
IF 5.162
Linlin Hou,Yaliang Huang,Weilin Hou,Yurou Yan,Jinlin Liu,Ning Xia
Sensitive and accurate quantification of wild-type p53 protein is of great importance for biological research and clinical diagnosis. Herein, a modification-free amperometric biosensor was proposed for sensitive detection of wild-type p53 protein by the signal amplification of silver nanoparticles (AgNPs) networks formed in situ on electrode surface. Double-stranded DNA (dsDNA) probe containing two consensus sites was immobilized on gold electrode surface to capture wild-type p53 protein. The cysteine thiol and amine groups on the exterior of the protein allowed for the attachment of bare AgNPs through the Ag S or Ag N interactions. Meanwhile, benzene-1,4-dithiol (BDT) molecules in solution triggered the assembly of more AgNPs on electrode surface through the Ag S interactions, thus leading to the in situ formation of AgNPs networks for signal amplification. The target at the concentration as low as 0.1 pM can be readily determined. This method was further applied to determine wild-type p53 protein in spiked human serum and cell lysates with satisfactory results. Moreover, the biosensor is regenerative and does not require the modification of AgNPs with recognition element for signal readout. The modification-free strategy can potentially be applied to develop novel biosensors for detection of other biological macromolecules.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Abdul Mueed,He Ma,Abdul Basit,Philippe Madjirebaye,Akhtar Ali,Shoaib Khan,Jing Li,Ze-yuan Deng
Flaxseed cyclolinopeptides (CLs) inhibit the lipid oxidation during in vitro digestion of high-fat meat. However, the effect of CLs on high-fat diet (HFD) induced lipid impairment metabolism remains unclear. Therefore, this study aimed to investigate the impact of CLs on HFD-induced lipid metabolism in the liver and pancreas of mice. The results demonstrated that the CLs administration significantly improved serum lipids (TG, TC, and LDL-C) in the HFD-induced model ( p < 0.05). Histological analysis using H&E and immunofluorescence staining revealed that CLs significantly restored pancreatic structure, and enhanced the secretion of insulin and glucagon. Furthermore, CLs intervention significantly improved antioxidant capacity in both the liver and pancrease by increasing the level of GSH-Px, T-GSH and GSH while decreasing GSSG and MDA levels in HFD-induced model. Lipidomic analysis further revealed that CLs treatment significantly reduced the levels of several lipid metabolites, including lysophosphatidylcholines (LPC), phosphatidylinositols (PI), lysophosphatidylethanolamines (LPE), phosphatidylethanolamines (PE), fatty acyls (FA), and diacylglycerols (DG), while increasing the levels of sphingomyelins (SM) and phosphatidylcholines (PC) compared to the model group. Pathway enrichment analysis indicated that CLs promoted the fatty acids metabolism and biosynthesis of unsaturated fatty acid, as supported by the upregulated expression of lipid metabolism gene/protien (CPT1, SLC7A11 and GPX4) and downregulated expression of lipid tranporter gene/protien (CD36, ACSL4, LPCAT3, and P35). Collectively, these findings suggest that CLs effectively enhance hepatic and pancreatic functiona and inhibit lipid accumulation in liver and pancreas through modulation of the CD36/p53/ACSL4 signalling pathway.
研究领域:
营养科学
·
生物化学
·
分子生物学
·
药理学
·
代谢性疾病
✓ 已验证
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-16
·
IF 9.429
Wang Yang,Chen Jun,Tian Jiekang,Wang Guanchen,Luo Weikang,Huang Zebing,Huang Yan,Li Ning,Guo Mingming,Fan Xuegong
Background Despite novel advances in screening, targeting and immunotherapies, early diagnosis and satisfactory treatments against hepatocellular carcinoma (HCC) remain formidable challenges. Given the unique advantages, carbon quantum dots (CQDs) become a smart theranostic nanomaterial for cancer diagnosis and therapy. Results In this work, a type of bio-friendly CQDs, trichrome-tryptophan-sorbitol CQDs (TC-WS-CQDs), is synthesized from natural biocompatible tryptophan via the one-pot hydrothermal method. Compared with normal hepatocytes, a much stronger green fluorescence is detected in HCC cells, indicating the ability of TC-WS-CQDs to target HCC cells. Furthermore, green-emitting TC-WS-CQDs generate large amounts of reactive oxygen species (ROS), leading to autophagy of HCC cells. Additionally, the green-emitting TC-WS-CQDs perform significant tumor inhibition by inducing autophagy via p53-AMPK pathway in vitro and in vivo studies with almost no systemic toxicity. Conclusions The results may highlight a promising anticancer nanotheranostic strategy with integration of diagnosis, targeting, and therapy. Graphical Abstract
研究领域:
纳米技术
·
癌症研究
·
生物医学工程
·
分子生物学
·
治疗学
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2022
·
IF 6.911
Jieyu Hu,Xingxing Yu,Xiumei Zhuang,Yan Sun,Junjie Wang,Haiting Ren,Shenghao Zhang,Yueshou Zhang,Hongxing Qiu,Yongjun Hu
The p53 gene is a known cancer marker. We report a novel protocol for the SERS tandem strategy to detect the p53 gene with high sensitivity. Herein, the click reaction between azide and alkyne was catalyzed by utilizing copper oxide nanoparticles (CuONPs), which were enriched by a T-DNA-triggered hybridization chain reaction (HCR). The T-DNA signal was amplified by establishing the correlation between the T-DNA signal and the concentration of CuONPs in a nonenzymatic isothermal environment. In contrast to other Raman reporters, we used alkynyl compounds as Raman reporters, which showed excellent characteristics in the Raman-silent region (1800–2800 cm −1 ). Therefore, the highly sensitive and highly selective SERS signals could be obtained in complex biological matrices. Due to utilizing multistep amplification strategies, including the nanoparticle-modified HCR polymer and “click” reaction, the limit of detection (LOD) and the limit of quantification (LOQ) of this sensor could be as low as 0.0174 pM and 0.0583 pM, respectively. The accuracy of the strategy expressed as the RSD was in the range of 3.14%–6.21%. The results indicated that the constructed sensor has excellent performance for the detection of the p53 gene in serum samples in a low concentration range, which suggests that the proposed enzyme-free SERS analytical sensor has good clinical application prospects.
✓ 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）