NEUROMOLECULAR MEDICINE
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2022
·Vol. 25
·期 1
·53-63
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IF 4.103
Cheng Jing,Fan Yan-Qin,Zhang Wen-Fei,Zhang Guo,Zeng Kuo,Ye Zhang,Zhao Dan,Wu Li-Quan,Chen Zhi-Biao
Sirtuin-6 (SIRT6), a member of the sirtuins family of NAD ( +) dependent deacetylases, has been shown to have beneficial effects in ischemic stroke. However, the role of SIRT6 in intracerebral haemorrhage (ICH) has not reported. We observed that SIRT6 expression was down-regulated in human ICH patients and down-regulated in ICH-induced rat cortical neurons. We subsequently found that SIRT6 overexpression reduced brain tissue damage and increased neuronal survival in the ICH model of rats and hemin-induced cortical neurons. Our further study found that overexpression of SIRT6 can reduce inflammatory response by down-regulating the expression of NF-kB and thus promote the recovery of neurological function in ICH animals. In conclusion, SIRT6 can inhibit the expression of NF-kB and plays a neuroprotective role in ICH by inhibiting the NF-kB-mediated inflammatory response.SIRT6 could be a novel therapeutic target for ICH.
研究领域:
神经科学
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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
BIOMATERIALS
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2021
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IF 12.479
Shaojun Pan,Yuhui Zhang,Mark Huang,Zhoufeng Deng,Amin Zhang,Lijia Pei,Lirui Wang,Weiyong Zhao,Lijun Ma,Qian Zhang,Daxiang Cui
s Multi-functional nanovectors based on exosomes from cancer cell culture supernatants in vitro has been successfully utilized for tumor-specific targeting and immune escape. However, the labor-intensive purification procedures for rich-dose and high-purity homogeneous exosomes without using targeting ligands are still a challenging task. Herein, we developed a nanovector Exo-PMA/ [email protected] through cloaked by urinary exosome membrane as a chemo/chemodynamic theranostic nano-platform for targeted homologous prostate cancer therapy which pertain to the abrogation of Epidermal Growth Factor Receptor (EGFR) and its downstream AKT/NF-kB/IkB signaling instead of ERK signaling cascades. Urinary exosomes-based nanovectors own the same urological cancer cell membrane antigen inclusive of E-cadherin, CD 47 and are free from intracellular substance such as Histone 3 and COX Ⅳ. The targeting properties of the homologous cancer cell are well preserved in Exo-PMA/ [email protected] nanovectors in high purity. Meanwhile, the nanovectors based on urinary exosomes from prostate patients deeply penetrated into prostate cancer DU145 3D MCTS , and successfully achieve superior synergistic low-dose chemo/chemodynamic performance in vivo . In addition, the blockage of bypassing EGFR/AKT/NF-kB/IkB signaling pathway is greatly enhanced via elevated intracellular PMA/ [email protected] nanoparticles (NPs). It is expected that the rich source and high purity of urinary exosomes offer a reliable solution for mass production of such nanovectors in the future. The targeted homologous cancer therapy based on the urinary exosomes from cancer patients exemplifies a novel targeted anticancer scheme with efficient and facile method.
研究领域:
癌症生物学
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纳米技术
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药学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2017
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IF 8.402
Qin Wang,Hao Jiang,Yan Li,Wenfei Chen,Hanmei Li,Ke Peng,Zhirong Zhang,Xun Sun
The transcription factor NF-kB plays a pivotal role in the pathogenesis of rheumatoid arthritis. Here we attempt to slow arthritis progression by co-delivering the glucocorticoid dexamethasone (Dex) and small-interfering RNA targeting NF-kB p65 using our previously developed polymeric hybrid micelle system. These micelles contain two similar amphiphilic copolymers : polycaprolactone-polyethylenimine (PCL-PEI) and polycaprolactone-polyethyleneglycol (PCL-PEG). The hybrid micelles loaded with Dex and siRNA effectively inhibited NF-kB signaling in murine macrophages more efficiently than micelles containing either Dex or siRNA on their own. In addition, the co-delivery system was able to switch macrophages from the M1 to M2 state. Injecting hybrid micelles containing Dex and siRNA into mice with collagen-induced arthritis led the therapeutic agents to accumulate in inflamed joints and reduce inflammation, without damaging renal or liver function. Thus, blocking NF-kB activation in inflammatory tissue using micelle-based co-delivery may provide a new approach for treating inflammatory disease.
研究领域:
药理学
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纳米技术
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风湿病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2024
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IF 4.9
Maolin Li,Yuting Zhang,Xiuyuan Jiang,Jiao Jiang,Xina Gu,Hua Zhang
Transcription factors play crucial roles in governing gene expression and are implicated in various physiological and pathological processes. Here, we propose a novel electrochemiluminescence (ECL) biosensor for the sensitive and specific detection of the transcription factor NF-kB p50, utilizing CRISPR/Cas12a-assisted hyperbranched rolling circle amplification (HRCA) technology. The biosensor achieves a remarkable limit of detection (LOD) of 3.6 fM and demonstrates excellent specificity against interfering proteins. Optimization of experimental parameters further enhances the biosensor’s performance, ensuring its reliability and accuracy. In addition, validation in real biological samples confirms the feasibility of biosensor for practical applications, offering a promising tool for clinical trials and disease diagnosis.
研究领域:
生物技术
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分子生物学
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分析化学
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临床诊断
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产品关联
DOI
高影响因子
JOURNAL OF ARTHROPLASTY
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2024
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IF 3.4
Junqi Niu,Fanggang Bi,Qing Tian,Ke Tian
Background Aseptic loosening around the prosthesis is a common cause of failure in total joint arthroplasty. Polyethylene wear particles trigger the release of inflammatory factors by macrophages. Key mediators involved in osteoclastogenesis include interleukin-6, tumor necrosis factor-α, receptor activator of nuclear factor kappa B (RANK), RANK ligand (RANKL), and bone protection hormone (Osteoprotegerin [OPG]). The purpose of our experiment was to see whether melittin can slow down the release of inflammatory mediators through the NF-kB pathway, regulate the RANKL/OPG ratio, reduce osteoclast formation, and delay the onset of arthritis in rats. Methods A total of 20 male Sprague-Dawley rats (10 months, Specific Pathogen Free, 350 g ± 20 g) were randomly divided into 5 groups: sham group, model group, melittin concentration 1 group (0.2 mg/kg), concentration 2 group (0.4 mg/kg), and concentration 3 group (0.6 mg/kg). All rats were implanted with TA2 high-purity titanium rods. A drill was used to create a bone canal along the long axis of the femur in the intercondylar notch. The model group and experimental groups were exposed to polyethylene particles, while the sham group did not receive any particles. Results The melittin group exhibited significantly increased serum levels of serum P, calcium-phosphorus product, OPG, PINP, PINP/CTX-I, and OPG/RANKKL ( P < .05). In the experimental group, micro computed tomography scanning results revealed a decrease in the amount of bone defect around the prosthesis. Immunofluorescence analysis demonstrated a decrease in the expression of IKKα and P65, while the expression of OPG showed an upward trend. Both Hematoxylin-Eosin and Tartrate-Resistant Acid Phosphatase staining revealed less osteoclast and inflammatory cell infiltration in bone resorption pits. Conclusions Our study demonstrates that melittin has the ability to inhibit the NF-kB pathway in a rat model, and reduce the impact of RANKL/OPG, thereby delaying osteoclast activity and alleviating periprosthetic osteolysis.
研究领域:
骨科
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免疫学
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药理学
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DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
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2019
·Vol. 24
·期 5
·833-848
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IF 2.214
Gui-xin Zhang,Chen Zhan,Kai Wang,Jian Han,Dong Shang,Hai-long Chen
Acute biliary pancreatitis (ABP) is a potentially life-threatening disease that is induced by the common bile duct (CBD) sludge or stones. This study aimed to investigate protective effects of Qingyi Decoction (QYT) on deoxycholic-acid-sodium salt (DCA) induced ABP in rats. Gpbar1 is a G-protein coupled receptor that can be activated by DCA. Both Gpbar1 overexpression vector and Gpbar1 RNAi were constructed and transfected into ABP cell models. Functional assays reveal that DCA significantly induced AR42J apoptosis and triggered Gpbar1 expression. Gpbar1 significantly activated caspase 8 and caspase 9 as compared to LV5-NC and LV3-NC (p<0.05). Gpbar1 significantly triggered apoptosis associated inflammatory factors as compared to LV5-NC and LV3-NC (p<0.05). Gpbar1 significantly induced calcium flux as compared to LV5-NC and LV3-NC (p<0.05). Gpbar1 up-regulated caspases and inflammatory factors in DCA treated pancreatic acinar cells. QYT reversed DCA induced apoptosis and inflammatory response. QYT significantly reduced Gpbar1 levels compared to no-QTY treated cells (p<0.05). In conclusion, QYT protects against DCA induced pancreatic acinar cell damage in ABP by inhibiting Gpbar1/NF-kB/p-RIP signaling pathway.
研究领域:
药理学
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胃肠病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENT INTERNATIONAL
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2020
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IF 7.577
Wenhui Qiu,Jiaqi Hu,Jason T. Magnuson,Justin Greer,Ming Yang,Qiqing Chen,Meijuan Fang,Chunmiao Zheng,Daniel Schlenk
Low doses of antibiotics are ubiquitous in the marine environment and may exert negative effects on non-target aquatic organisms. Using primary macrophages of common carp, we investigated the mechanisms of action following exposure to several common antibiotics; cefotaxime, enrofloxacin, tetracycline, sulfamonomethoxine, and their mixtures, and explored the immunomodulatory effects associated with the nuclear factor-κB (NF-κB) signaling pathway. A KEGG pathway analysis was conducted using the sixty-six differentially expressed genes found in all treatments, and showed that exposure to 100 μg/L of antibiotics could affect regulation of the NF-κB signaling pathway, suggesting that activation of NF-κB is a common response in all four classes of antibiotics. In addition, the four antibiotics induced nf-κb and NF-κB-associated cytokines expression, as verified by qPCR, however, these induction responses by four antibiotics were minor when compared to the same concentration of LPS treatment (100 μg/L). Antagonists of NF-κB blocked many of the immune effects of the antibiotics, providing evidence that NF-κB pathways mediate the actions of all four antibiotics. Moreover, exposure to environmentally relevant, low levels (0.01–100 μg/L) of antibiotics induced a NF-κB-mediated immune response, including endogenous generation of ROS, activity of antioxidant enzymes, as well as expression of cytokine and apoptosis. Moreover, exposure to mixtures of antibiotics presented greater effects on most tested immunological parameters than exposure to a single antibiotic, suggesting additive effects from multiple antibiotics in the environment. This study demonstrates that exposure of fish primary macrophages to low doses of antibiotics activates the NF-kB pathway.
研究领域:
水生毒理学
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免疫学
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环境科学
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产品关联
DOI
PubMed
高影响因子
Bioengineered
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2022
·
IF 6.832
Wenjun Jiang,Xiaoying Wang,Siwei Su,Sen Du,Hongqiang Song
Osteoarthritis (OA) is a common chronic degenerative disease characterized by the loss of articular cartilage, which causes loss of joint function and reduce quality of life. Resolvin D1 (RvD1) has shown interesting anti-inflammatory effects; however, the mechanism of action of RvD1 in OA remains unclear. The aim of this study was to investigate the potential mechanism of RvD1 in OA by bioinformatics and partial in vitro mechanisms. Here, 106 shared differentially expressed genes (DEGs) were identified based on the GSE82107, GSE55235, GSE55457 dataset; 700 DEGs were identified based on GSE169077. Enrichment analyses of these genes were then successively conducted. RvD1-targeted genes and KEGG pathways are identified by STITCH. 27 shared KEGG pathways were identified among RvD1-targeted pathways and OA. Furthermore, cell apoptosis assay, western blotting, real-time fluorescent quantitative PCR (qRT-PCR), enzyme linked immunosorbent assay (ELISA) were used to confirm the expression levels of the key genes of shared Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between RvD1-targeted and OA in IL-1β treated rat knee chondrocytes. The results showed that RvD1-targeted pathways and the expression of nuclear p65, p53, and p-JNK were inhibited in the RvD1 group compared with the IL-1β group. Thus, the findings indicate that RvD1 may inhibit the development of OA through NF/kB, p53, MAPK/JNK, PI3K-AKT signaling pathways, and act as a treatment for OA.
研究领域:
生物信息学
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分子生物学
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药理学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Qingqi Zhou,Xun Li,Decai Hou
Background Osteoarthritis (OA) is an age-related progressive joint disease characterized by loss of cartilage and subsequent inflammation. Perillaldehyde is a compound extracted from Perilla , which has multiple pharmacological activities including anti-inflammatory, and anti-apoptosis. However, it still remains unknown whether and how perillaldehyde could regulate chondrocyte apoptosis and inflammation in OA. Methods The interleukin-1beta (IL-1β)-treated chondrocytes and destabilized medial meniscus (DMM) -induced rats were used as in vitro and in vivo models of OA. Cell viability, proliferation, and apoptosis were investigated by cell counting kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays. The mitochondrial membrane potential was analyzed by 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining. Light chain 3 (LC3) location, and expression of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) and apoptosis-associated speck-like protein (ASC) were detected by immunofluorescence staining. Relative protein levels were measured via western blotting. Tumor necrosis factor-alpha (TNF-α), IL-6 and IL-8 levels were measured by enzyme-linked immunosorbent assay (ELISA). The cartilage injury in rats was investigated via hematoxylin-eosin (HE) staining. Results Perillaldehyde attenuated IL-1β-induced inhibition of viability (from 44.45 % to 92.72 %, p < 0.05) and proliferative potential of chondrocytes ( p < 0.05). Perillaldehyde mitigated mitophagy-associated apoptosis of chondrocytes by enhancing mitophagy ( p < 0.05) and reducing cell apoptosis (from 32.36 % to 8.00 %, p < 0.05). Perillaldehyde attenuated NLRP3-mediated inflammation through reducing NLRP3, ASC, TNF-α, IL-6 and IL-8 levels ( p < 0.05). ALOX5 expression was upregulated in OA (fold change: 2.61, p < 0.05), and decreased by perillaldehyde treatment (fold change: 1.34, p < 0.05). Perillaldehyde inhibits p65 nuclear factor kappa B (NF-κB) signaling activation (fold change: 3.19 to 1.33, p < 0.05) by regulating ALOX5 expression. ALOX5 overexpression reversed the effects of perillaldehyde on mitophagy-associated apoptosis and NLRP3-mediated inflammation ( p < 0.05), and these roles were mitigated due to NF-κB inactivation ( p < 0.05). Perillaldehyde attenuated cartilage injury in OA rats ( p < 0.05). Conclusion Perillaldehyde attenuated IL-1β-induced mitophagy-associated apoptosis and NLRP3-mediated inflammation through decreasing ALOX5 and inactivating NF-κB signaling, indicating the potentially protective potential of perillaldehyde in osteoarthritis.
研究领域:
医学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACOLOGICAL SCIENCES
·
2025
·
IF 2.9
Jingwei Liu,Cheng Qiu,Xiaoxiong Wang,Ziqian Xiang,Junyuan Sun,Mingzheng Chang,Qingliang Ma,Yan Zhuang,Yunpeng Zhao,Qiang Yang,Lianlei Wang,Xinyu Liu
Fracture is a common type of traumas and alternative therapies to boost bone fracture healing is necessary. The aim of this study is to elucidate the role of sulfasalazine in bone fracture healing by using MC3T3-E1 cells in vitro and murine femoral fracture model in vivo . Western blotting, flow cytometry, RNA sequencing, Calcein AM/PI staining, Alizarin-Red-S staining, ALP activity assay, transmission electron microscope, histological staining, immunohistochemistry, immunofluorescence and Surface plasmon resonance analysis were performed in this study. Sulfasalazine failed to elicit ferroptosis in osteoblasts within acceptable dose manner while promoted osteogenic differentiation. Furthermore, sulfasalazine was identified to inhibit inflammation by declination of inflammatory biomarkers. Besides, TNFα was verified as a potential downstream target for sulfasalazine and the adverse effect of TNFα on osteogenic differentiation could be largely salvaged by sulfasalazine due to direct binding between these two molecules. RNA-seq further implied decreased transcription of genes related to NF-κB pathway. Murine study showed sulfasalazine promotes fracture healing as evidenced by increased bone remodeling both histologically and radiologically. Overall, sulfasalazine accelerates osteogenic differentiation and promotes bone healing by direct binding to and thus inhibiting TNFα, which subsequently suppresses NF-κB signaling. Therefore, sulfasalazine shows a promising outcome for the treatment of bone fracture.
研究领域:
药理学
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分子生物学
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免疫学
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骨科学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Hend Mohamed Anwar,Gad Elsayed Mohamed Salem,Hanan M. Abd El-Latief,Amany Abd Elhameid Osman,Sahar K. Ghanem,Haroon Khan,Suchana Chavanich,Alshaymaa Darwish
The COVID-19 pandemic has drawn attention to acute lung injury and respiratory distress syndrome as major causes of death, underscoring the urgent need for effective treatments. Protease enzymes possess a wide range of beneficial effects, including antioxidant, anti-inflammatory, antifibrotic, and fibrinolytic effects. This study aimed to evaluate the potential therapeutic effects of bacterial protease and chymotrypsin in rats in mitigating acute lung injury induced by lipopolysaccharide . Molecular docking was employed to investigate the inhibitory effect of bacterial protease and chymotrypsin on TLR-4, the receptor for lipopolysaccharide. Bacterial protease restored TLR-4, Nrf2 , p38 MAPK , NF-kB, and IKK-β levels to normal levels, while chymotrypsin normalized TLR-4, IKK-β, IL-6, and IL-17 levels. The expression of TGF-β, caspase-3, and VEGF in the bacterial protease- and chymotrypsin-treated groups was markedly reduced. Our results suggest that both therapies ameliorate LPS-induced acute lung injury and modulate the TLR4/Nrf2/NF-k signaling pathway. Each protease exhibited distinct mechanisms, with bacterial protease showing a better response to oxidative stress, edema, and fibrosis , whereas chymotrypsin provided a better response in the acute phase and innate immunity. These findings highlight the potential of each protease as a promising therapeutic option for acute lung injury and respiratory distress syndrome.
研究领域:
医学
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药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-22
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IF 10.6
Jiang Hua,Qin Hongyu,Yang Qinghua,Huang Longao,Liang Xiao,Wang Congyang,Moro Abu,Xu Sheng,Wei Qingjun
Background The use of gene therapy to deliver microRNAs (miRNAs) has gradually translated to preclinical application for the treatment of intervertebral disc degeneration (IDD). However, the effects of miRNAs are hindered by the short half-life time and the poor cellular uptake, owing to the lack of efficient delivery systems. Here, we investigated nucleus pulposus cell (NPC) specific aptamer-decorated polymeric nanoparticles that can load miR-150-5p for IDD treatment. Methods The role of miR-150-5p during disc development and degeneration was examined by miR-150-5p knockout (KO) mice. Histological analysis was undertaken in disc specimens. The functional mechanism of miR-150-5p in IDD development was investigated by qRT-PCR assay, Western blot, coimmunoprecipitation and immunofluorescence. NPC specific aptamer-decorated nanoparticles was designed, and its penetration, stability and safety were evaluated. IDD progression was assessed by radiological analysis including X-ray and MRI, after the annulus fibrosus needle puncture surgery with miR-150-5p manipulation by intradiscal injection of nanoparticles. The investigations into the interaction between aptamer and receptor were conducted using mass spectrometry, molecular docking and molecular dynamics simulations. Results We investigated NPC-specific aptamer-decorated polymeric nanoparticles that can bind to miR-150-5p for IDD treatment. Furthermore, we detected that nanoparticle-loaded miR-150-5p inhibitors alleviated NPC senescence in vitro, and the effects of the nanoparticles were sustained for more than 3 months in vivo. The microenvironment of NPCs improves the endo/lysosomal escape of miRNAs, greatly inhibiting the secretion of senescence-associated factors and the subsequent degeneration of NPCs. Importantly, nanoparticles delivering miR-150-5p inhibitors attenuated needle puncture-induced IDD in mouse models by targeting FBXW11 and inhibiting TAK1 ubiquitination, resulting in the downregulation of NF-kB signaling pathway activity. Conclusions NPC-targeting nanoparticles delivering miR-150-5p show favorable therapeutic efficacy and safety and may constitute a promising treatment for IDD. Graphical Abstract
研究领域:
骨科
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基因治疗
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纳米技术
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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