Journal of Biomedical Nanotechnology
·
2015
·Vol. 11
·期 3
·403-415
·
IF 5.338
Wang Jiao,Zhu Rongrong,Sun Dongmei,Sun Xiaoyu,Geng Zhengsong,Liu Hui,Wang Shi-Long
Curcumin (Cur) is a naturally derived, novel anti-inflammatory agent, but its poor solubility limits its clinical use. The aim of the present study was to encapsulate Cur into solid lipid nanoparticles (SLNs) to improve its anti-inflammatory activity. The Cur-loaded SLNs (Cur-SLNs)
were prepared using emulsification and low-temperature solidification methods. In contrast to free Cur, the particles were well dispersed in aqueous medium, showing a narrow size distribution with a range of 55 ± 1.2 nm, a zeta potential value of –26.2 ± 1.3 mV, and a high
drug loading efficiency of 37% ± 2.5%. The sustained release of Cur was observed for up to 6 days. The particles displayed enhanced stability in phosphate-buffered saline by protecting the encapsulated Cur against hydrolysis and biotransformation, as well as increasing biocompatibility.
Cur-SLNs were more effective than free Cur at reducing the expression levels of several proinflammatory mediators, including inflammatory cytokines (IL-6, TNF-α, and IL-1β) and nitric oxide (NO), under in vitro conditions. By Western blotting, we found that
Cur-SLNs were more active than free Cur in inhibiting the LPS-induced activation of the inflammatory transcription factor NF-κB through the suppression of IκB kinase activation. Compared to free Cur, Cur-SLNs had an increased intracellular uptake over time (observed
after 24 h) in RAW264.7 cells. Moreover, the Cur-SLNs (≥20 μM) significantly improved RAW264.7 cell viability by inhibiting apoptosis. Thus, these results demonstrated that SLNs could be used as potential anti-inflammatory drug carriers for the treatment of various chronic diseases.
研究领域:
药理学
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纳米技术
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免疫学
·
药物开发
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DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2024
·Vol. 104
·期 4
·e70003
·
IF 3.2
Xiang Yu,Di Zhang,Chengming Hu,Zejun Yu,Yang Li,Cheng Fang,Yinsheng Qiu,Zhinan Mei,Lingyun Xu
Hepatocellular carcinoma (HCC) is the sixth most prevalent malignant tumor. Hepatocellular carcinogenesis is closely linked to apoptosis, autophagy, and inflammation. Diosmetin and chrysin, are two flavonoid compounds, exhibit anti-inflammatory and anticancer properties. In this study, the TCGA database was utilized to identify differentially expressed genes between normal subjects and HCC patients. Molecular docking and molecular dynamics analyses were employed to assess the binding affinity of chrysin and diosmetin to key proteins in the PI3K/AKT/mTOR/NF-κB signaling pathway. Western blotting and RT-qPCR were used to measure the protein and gene expression within this pathway. The results indicated that HCC patients had elevated levels of PI3K, AKT, mTOR, and P65 proteins compared to normal subjects, which adversely affected patient survival. Molecular docking and dynamics studies demonstrated that diosmetin and chrysin are effectively bound to these four proteins. In vitro experiments revealed that the combination of diosmetin and chrysin could induce apoptosis, enhance autophagy, reduce inflammatory mediator production, and improve the tumor cell microenvironment by inhibiting the PI3K/AKT/mTOR/NF-κB signaling pathway. Notably, the synergy score for the combination of diosmetin (25 μM) and chrysin (10 μM) was 16. Thus, the diosmetin–chrysin combination shows promise as an effective therapeutic approach for hepatocellular carcinoma due to its strong synergistic effect.
研究领域:
肿瘤学
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分子生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Ruijie Wang,Quan Li,Pengxin Wu,Ke Ren,Yan Li,Yang Wang,Huadong Zhu,Chuanzhu Lv
Background In sepsis, the lungs are one of the most severely affected organs, usually resulting in acute lung injury (ALI). Capsaicin (CAP) is a natural compound found in chili peppers that has pain-relieving and anti-inflammatory properties. Here, we report that nanoparticles containing capsaicin and iron (Fe-CAP NPs) exhibited anti-inflammatory effects in the treatment of ALI. Methods The morphological characteristics of nanozymes were detected. RAW 264.7 cells were divided into four groups: control, lipopolysaccharide (LPS), CAP+LPS and Fe-CAP+LPS groups. The expression of inducible nitric oxide synthase (iNOS), transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α) was assessed by immunofluorescence, Western blot, and enzyme-linked immunosorbent assay (ELISA). Nuclear factor kappa-B (NF-κB) expression was determined by Western blot. C57 mice were divided into control, LPS, CAP+LPS and Fe-CAP+LPS groups. Interleukin-6 (IL-6) and iNOS expression in the lung was detected by Western Blot. IL-6 and TNF-α expression in serum was detected by ELISA. Extravasated Evans blue, histopathological evaluation and wet-to-dry (W/D) weight ratio were used to assess pulmonary capillary permeability. The blood and major organs (heart, liver, spleen, lung and kidney) of mice were tested for the toxicity of Fe-CAP NPs. Results In the LPS group, TNF-α, iNOS, p-NF-κB and p-IKBα expression increased. However, their expression was significantly decreased in the Fe-CAP+LPS group. TGF-β expression showed the opposite trend. In vivo, IL-6 and iNOS expression was notably increased in the lungs of LPS group of mice but decreased with Fe-CAP pretreatment. Fe-CAP significantly ameliorated lung EB leakage, improved the histopathology of lung tissue and reduced the W/D weight ratio. The nanoparticles showed non-cytotoxicity, when studying these biological activities. Conclusion Fe-CAP NPs could alleviated inflammation by inhibiting the expression of pro-inflammatory factors in macrophages, increasing the expression of anti-inflammatory factors, and alleviating lung tissue damage.
研究领域:
药理学
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免疫学
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纳米技术
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2023
·Vol. 46
·期 2
·209-218
·
IF 2
Chenhao Li,Cuizhi Geng
Triple-negative breast cancer (TNBC) puts a great threat to women’s health. GLIS family zinc finger 3 (GLIS3) belongs to the GLI transcription factor family and acts as a critical factor in cancer progression. Nevertheless, the part of GLIS3 played in TNBC is not known. Immunohistochemical (IHC) staining analysis displayed that GLIS3 was highly expressed in TNBC tissues. The effect of GLIS3 on the malignant phenotype of TNBC was tested in two different cell lines according to GLIS3 regulation. Upregulation of GLIS3 promoted the proliferation, migration, and invasion of TNBC cell lines, whereas the knockdown of GLIS3 suppressed these tumor activities. Inhibition of GLIS3 induced TNBC cell apoptosis. Furthermore, study as immunofluorescence and electrophoretic mobility shift assay confirmed that the nuclear factor-κB (NF-κB) signaling pathway activated by GLIS3 played an important role in TNBC cells’ malignant phenotype. In conclusion, the present work demonstrated that GLIS3 acts as a crucial element in TNBC progression via activating the NF-κB signaling pathway. Accordingly, above mentioned findings indicated that modulation of GLIS3 expression is a potential tactic to interfere with the progression of TNBC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Guo-Dong Zhuang,Si-Min Deng,Meng-Di Chen,Chao-Fan Deng,Wen-Ting Gu,Shu-Mei Wang,Dan Tang
Ethnopharmacological relevance Cognitive dysfunction associated with diabetes, known as diabetic encephalopathy (DE), is a grave neurodegenerative condition triggered by diabetes, and persistent inflammation plays a vital role in its development. The renowned traditional Chinese medicine Huang-Lian-Jie-Du Decoction (HLJDD) is clinically proven to manage diabetes mellitus and Alzheimer's disease and is famous for its heat-clearing and detoxifying effects. However, the underlying mechanisms through which HLJDD affects DE remain to be elucidated. Aim of the study To explore the beneficial effects of HLJDD on improving cognitive dysfunction in DE mice. Study design and methods A diabetic mouse was established through a high-fat diet and subsequent administration of streptozotocin over five consecutive days. After the animals were confirmed to have diabetes, they were treated with HLJDD. After oral administration of HLJDD or metformin for 14 weeks, behavioral tests were used to assess their cognitive capacity. Biochemical analyses were then performed to detect levels of glucose metabolism, followed by histological analyses to assess pathological damage. Furthermore, AGEs/RAGE/NF-κB axis related proteins were detected by Western blot or immunofluorescence techniques. An advanced UPLC-Q-Orbitrap HRMS/MS analytical technique utilizing a chemical derivatization strategy was employed for comprehensive metabolic profiling of carbonyl compounds in the plasma of DE mice. Results Pharmacological assessment revealed that HLJDD effectively mitigated cognitive dysfunction, normalized glucose metabolic imbalances, and repaired neuronal damage in DE mice. It reduced neuroinflammation by attenuating carbonyl stress, deactivating astrocytes and microglia, and preserving dopaminergic neurons. Additionally, metabolomics analysis revealed 18 carbonyl compounds with marked disparities between DE and control mice, with 12 metabolites approaching normal levels post-HLJDD intervention. Further investigations showed that HLJDD regulated inflammation and pyroptosis through suppressing AGEs/RAGE/NF-κB pathways. Conclusion Our study indicated that HLJDD could ameliorate carbonyl stress via the regulation of carbonyl compound metabolism profiling, and inhibiting the AGEs/RAGE/NF-κB pathway, thereby alleviating inflammation and pyroptosis to exert beneficial effects on DE.
研究领域:
药理学
·
神经科学
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传统中医
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分子生物学
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代谢组学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF HYDROGEN ENERGY
·
2024
·
IF 8.1
Jiejie Feng,Changshun Chu,Jianting Liu,Liling Wei,Huayi Li,Jianquan Shen
To push forward the hydrogen energy technology, it is crucial to develop a highly active catalyst for the application of water splitting. Nevertheless, many electrocatalysts suffer from functional limitations, making them unsuitable for both anode and cathode applications. Therefore, the utilization of bifunctional electrocatalysts is necessary to overcome this limitation. In this study, we have reported a bifunctional CoMoP-Fe x P/NF catalyst with favorable electrocatalytic performance toward hydrogen evolution reaction/oxygen evolution reaction (HER/OER). Balanced amorphous/crystalline heterophase endows CoMoP-Fe x P/NF with more exposed active sites. In addition, the superhydrophobic nature of CoMoP-Fe x P/NF helps to improve the contact with electrolyte. Following conditional optimization, CoMoP-Fe x P/NF requires only an overpotential of 85.6 mV to achieve a current density of 10 mA cm −2 for HER, and 249.6 mV for a current density of 20 mA cm −2 for OER. A water-splitting electrolyzer comprising CoMoP-Fe x P/NF requires a low cell voltage of 1.56 V to achieve a current density of 10 mA cm −2 . This study provides valuable insights into designing bifunctional electrocatalysts and replacing noble metallic materials to enhance hydrogen production from water splitting.
研究领域:
材料科学
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电化学
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能源材料
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催化
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产品关联
DOI
高影响因子
ENVIRONMENT INTERNATIONAL
·
2025
·
IF 9.7
Chengwei Zhou,Wei Chen,Rongrong Xuan,Xinyuan Kang,Jiazhen Wang,Jason T. Magnuson,Jialin Li,Di Fang,Wenhui Qiu
Perfluorodecanesulfonate (PFDS), a long-chain polyfluoroalkyl substance (PFAS), is widely detected in aquatic environments and increasingly recognized for its environmental persistence and bioaccumulative potential; however, its immunotoxicity remains poorly understood in aquatic biota. In this study, early life stage zebrafish ( Danio rerio ) were exposed to environmentally relevant concentrations of PFDS and PFOS for 120 h to better characterize the adverse effects of PFDS on aquatic organisms. Additionally, the toxicological differences between PFDS and PFOS at the same exposure concentrations were compared, as PFDS is a known substitute for PFOS. PFDS bioaccumulated in zebrafish larvae at environmentally relevant concentrations, which disrupted immune function by altering the number of macrophages and neutrophils, inducing oxidative stress, and dysregulating immune markers such as interleukins and immunoglobulins. Mechanistically, PFDS activated the nuclear factor kappa B (NF-κB) signaling pathway, driving pro-inflammatory cytokine expression and immune dysfunction. Furthermore, the use of a NF-κB morpholino knockdown confirmed the role of the NF-κB pathway in mediating PFDS-induced immunotoxicity. These findings provide the first comprehensive evidence of PFDS-induced immunotoxicity being mediated through NF-κB activation, offering novel insights into the ecological risks of long-chain perfluorosulfonic acids. Notably, PFDS exhibited a stronger immunotoxic response relative to PFOS, indicating that its adverse effects may be more severe. Overall, these findings provide valuable insights for the ecological risk assessment of PFDS and the toxic potential that unregulated PFAS can have to aquatic systems.
研究领域:
环境毒理学
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免疫毒理学
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水生毒理学
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分子生物学
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生态毒理学
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发育生物学
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产品关联
DOI
PubMed
高影响因子
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2025
·Vol. 52
·期 3
·e70025
·
IF 2.5
Suqin Sun,Rong Fan,Li Chang,Lei Gao,Chunting Liu,Dongying Liu,Shiyu Niu
Isoferulic acid (IA), a derivative of cinnamic acid, is derived from Danshen and exhibits anticancer properties by disrupting cancer cell activities. However, its role in pancreatic cancer, the “king of cancer”, was unknown. In this study, pancreatic cancer cells were subjected to treatment with IA (6.25, 12.5, 25 μM), and nude mice injected with pancreatic cancer cells were received IA at doses of 7.5 mg/kg/day or 30 mg/kg/day by oral administration. CCK8, Annexin V-FITC/propidium iodide (PI) double staining and TUNEL assay were conducted to evaluate the cell viability and apoptosis. Hoechst staining and comet assay was employed to measure DNA damage. Mitochondrial membrane potential (MMP) analysis was carried out to explain the mitochondrial damage. EdU and wound healing assay were performed for cell proliferation and migration detection. Immunofluorescence and western blot were used to explore the mechanism. We found that IA reduced cell viability and induced apoptosis, as evidenced by an increase in Annexin V-FITC + PI − and Annexin V-FITC + PI + cell populations, brighter TUNEL and Hoechst staining, and more percentage of tail DNA. Furthermore, IA decreased MMP and changed levels of apoptosis-related proteins. The cell proliferation and migration were inhibited by IA treatment. Mechanically, IA downregulated the phosphorylation of IĸBα and inhibited p65 nuclear translocation, consequently suppressing NF-κB pathway. In general, IA suppressed the cell proliferation and migration, and caused apoptosis of pancreatic cancer cells in a mitochondria-dependent manner through blocking NF-κB signalling pathway, indicating that IA may be a potential therapeutic strategy for pancreatic cancer.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Cell Communication and Signaling
·
2024
·
IF 3.6
Le Cao,Weilu Gao,Haitao Yang,Ran Zeng,Zongsheng Yin
Inflammation promotes the degradation of the extracellular matrix, which contributes to the development of osteoarthritis (OA). Adipocyte enhancer binding protein 1 (AEBP1) participates in multiple pathological processes related to inflammatory diseases. However, the role of AEBP1 in OA development is unknown. We found a higher AEBP1 expression in articular cartilage of OA patients ( n = 20) compared to their normal controls ( n = 10). Thus, we inferred that AEBP1 might affect OA progression. Then mice with destabilization of the medial meniscus (DMM) surgery and chondrocytes with IL-1β treatment (10 ng/mL) were used to mimic OA. The increased AEBP1 expression was observed in models of OA. AEBP1 knockdown in chondrocytes reversed IL-1β-induced inflammation and extracellular matrix degradation, which was mediated by the inactivation of NF-κB signaling pathway and the increased IκBα activity. Co-immunoprecipitation assay indicated the interaction between AEBP1 and IκBα. Importantly, IκBα knockdown depleted the protective role of AEBP1 knockdown in OA. Moreover, AEBP1 knockdown in mice with OA showed similar results to those in chondrocytes. Collectively, our findings suggest that AEBP1 knockdown alleviates the development of OA, providing a novel strategy for OA treatment.
研究领域:
风湿病学
·
分子生物学
·
细胞生物学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
CELLULAR IMMUNOLOGY
·
2024
·
IF 3.7
Jingying Qin,Cheli Wang,Xiaoying Zhou
Reduced glutathione (GSH) is an antioxidant involved in redox homeostasis, and recently regarded as an inducer of Reductive stress. Its immune-regulatory effects on lymphocytes have not been extensively studied. This study is based on the finding that much increased GSH level in collagen-induced arthritis (CIA) rat spleen, and aimed to investigate the effects of GSH (0, 1, 10, 100 mM) on normal and immune-stimulated spleen lymphocytes respectively. The elevated GSH level is associated with the increased levels of inflammatory factors; especially the increased DPP1 activity indicated immune-granulocytes activation in CIA rat spleen. Exogenous GSH had different influences on normal and CIA lymphocytes, affecting intracellular levels of GSH, Glutathione-S-transferases (GSTs) and Reactive oxygen species (ROS); as well as the expressions of NF-κB, MMP-9, Bcl-2, GST, P38, PCNA and TLR4. The increased extracellular GSH level disturbed redox homeostasis and induces reductive stress to spleen lymphocytes, which decreased intracellular GSH concentration and influenced the MAPK/PCNA and NF-κB/MMP-9 signaling pathways, as well as cell cycles respectively, leading to cell senescence/ferroptosis/apoptosis. This study also revealed the multiple faces of GSH in regulating spleen lymphocytes, which depended on its levels in tissue or in cells, and the activation status of lymphocytes. These findings indicate the immune-regulatory role of GSH on spleen-lymphocytes, and the high level GSH in CIA rat spleens may contribute to CIA development.
研究领域:
免疫学
·
药理学
·
细胞生物学
·
风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL AND MOLECULAR MEDICINE
·
2025
·
IF 12.9
Yang Qihao,Wu Jianqun,Huang Songqiang,Zeng Jing,Jing Yihan,Wang Zhiyong,Zhang Chi,Wu Zenghui,Liu Song,Wang Zhao
Here we investigate the effects and mechanisms of eicosapentaenoic acid (EPA) in regulating chondrocyte mechanics during inflammation in the progression of osteoarthritis (OA). Primary porcine chondrocytes and human OA chondrocytes were isolated and cultured. Cell mechanical properties were measured using atomic force microscopy. RNA sequencing, immunocytochemistry, quantitative PCR and western blotting were used to elucidate associated signaling mechanisms. Porcine cartilage and human OA cartilage explants were collected. Human articular cartilage samples were obtained from ten donors. Anterior cruciate ligament transection surgery was performed to induce OA in male C57BL/6J mice. The therapeutic effects of EPA and activation of associated signaling were evaluated using histology, immunohistochemistry and micro-computed tomography. EPA reduced F-actin intensity and Young’s modulus in IL-1α-treated porcine chondrocytes and in human OA chondrocytes. Mechanistically, EPA inhibited IL-1α-induced increase in CD44 expression in porcine chondrocytes by suppressing phosphorylation of NF-κB subunits p65. In addition, EPA alleviated articular cartilage degeneration and decreased the expression of p-p65 and CD44 in IL-1α-treated porcine and human OA cartilage explants. Moreover, EPA suppressed the increase in Young’s modulus induced by CD44 ligands (A6 peptide and low-molecular-weight hyaluronic acid) in porcine chondrocytes. Finally, intraarticular injection of EPA emulsion-integrated hyaluronic acid injection attenuated OA-associated alterations in articular cartilage and subchondral bone and decreased CD44 expression in mice. Our data not only provide new insights into EPA’s chondroprotective actions and underlying mechanisms but also offer new evidence supporting the therapeutic efficacy of a novel EPA emulsion-integrated hyaluronic acid injection for OA treatment.
研究领域:
风湿病学
·
分子生物学
·
生物力学
·
骨科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROREPORT
·
2024
·
IF 1.6
Bian Jing,Liu Chunxu,Li Xiang,Qin Xiaoye,Wang Feng,Xuan Lina,Zhang Weimin
This study aims to investigate how electroacupuncture regulates the learning and memory abilities of poststroke cognitive impairment (PSCI) rats through the TLR4/NF-κB/NLRP3 signaling pathway on the hippocampal microglia. Thirty male rats were randomly divided into three groups: sham surgery group, PSCI model group, and electroacupuncture group, with 10 rats in each group. Middle cerebral artery occlusion was used to establish the PSCI model. The Zea Longa method was used to score the rats’ neurological function. Electroacupuncture was utilized for 21 days to improve PSCI. The learning and memory abilities of rats were tested using the Morris water maze. Hematoxylin–eosin staining and immunofluorescence were used to find the hippocampus’ pathological changes. The concentration of interleukin-1β, interleukin-6, tumor necrosis factor-α, and interleukin-18 were detected by ELISA. The mRNA expression levels of associated inflammatory corpuscles were measured by quantitative real-time PCR. The protein expression levels of TLR4, MyD88, NF-κB, and NLRP3 were measured using western blotting. Electroacupuncture improved not only the learning and memory abilities of PSCI rats but also hippocampal morphology. Electroacupuncture inhibited the activation of microglia and the TLR4/NF-κB/NLRP3 signaling pathway. Electroacupuncture also reduced proinflammatory factors and restrained the mRNA levels of NLRP3-associated inflammatory cytokines. Its mechanism was related to inhibiting the expression of the TLR4/NF-κB/NLRP3 signaling pathway, attenuating the release of inflammatory factors, and regulating the activation of hippocampal microglia in the brain.
研究领域:
神经科学
·
针灸
·
认知障碍
·
炎症
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）