BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2018
·
IF 2.559
Xin-Chun Zhang,Hong-Feng Liang,Xiao-Dong Luo,Hua-Jun Wang,Ai-Ping Gu,Chun-Ye Zheng,Qiao-Zhen Su,Jun Cai
Neuroinflammation plays a critical role in the process of neurodegenerative disorders, during which microglia , the principal resident immune cells in the central nervous system, are activated and produce proinflammatory mediators. Yin-Yang 1 (YY1), a multi-functional transcription factor, is widely expressed in cells of the immune system and participate in various cellular processes. However, whether YY1 is involved in the process of neuroinflammation is still unknown. In the present study, we found that YY1 was progressively up-regulated in BV2 microglial cells stimulated with lipopolysaccharide (LPS), which was dependent on the transactivation function of nuclear factor kappa B (NF-κB). Furthermore, YY1 knockdown notably inhibited LPS-induced the activation of NF-κB signaling and interleukin-6 (IL-6) expression in BV-2 cells, but not mitogen-activated protein kinase (MAPK) signaling. Moreover, YY1 strengthened p65 binding to IL-6 promoter by interacting with p65 but decreased H3K27ac modification on IL-6 promoter, eventually increasing IL-6 transcription. Taken together, these results for the first time uncover the regulatory mechanism of YY1 on IL-6 expression during neuroinflammation responses and provide new lights into neuroinflammation.
研究领域:
神经科学
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免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
IMMUNOBIOLOGY
·
2025
·
IF 2.3
Yu-yao Qin,Zi-yi Qin,Tao Liang,Dong-er Qin,Sheng-yi Hua,Ming-hui Tan,Shun Guo,Fan Yang,Le Shi,Yun Yu,Guang-ji Zhang
Background Phellodendrine, a primary bioactive constituent of Phellodendron chinense Schneid (PCS), is crucial in its pharmacological profile. Phellodendrine exhibits potent anti-nephritic properties and demonstrates a marked inhibitory effect on the cellular immune response. However, the effects of phellodendrine on proteoglycan depletion and cartilage degeneration in gouty arthritis remain insufficiently understood. Therefore, the objective of this study is to elucidate the therapeutic potential and underlying mechanisms of phellodendrine chloride (PC) in the treatment of gouty arthritis. Methods A monosodium urate (MSU)-induced arthritis model in rats, along with a peritonitis model in mice, was developed, in combination with a chondrocyte model. Neutrophil proportions were quantified using flow cytometry. The expression levels of MMP-3, STAT3, and phosphorylated STAT3 (p-STAT3) in chondrocytes were determined by Western blot analysis. Proteoglycan levels in chondrocytes were assessed using toluidine blue staining and quantitative reverse transcription PCR (qRT-PCR). Joint swelling rates were monitored at 0–24 h in rats, and histopathological changes in joint tissues were subsequently analyzed. Results Phellodendrine chloride mitigated the rise in neutrophil proportions within MSU-induced peritoneal lavage fluid in mice and decreased inflammatory cell infiltration in rat ankle tissues. Treatment with phellodendrine chloride led to a downregulation of MMP-3 protein levels and inhibited IL-1β-induced proteoglycan degradation in chondrocytes. Additionally, results from experiments combining IL-1β with AG490 or IL-6 demonstrated that phellodendrine chloride attenuated IL-1β-induced MMP-3 expression and proteoglycan degradation. Conclusion Our findings suggest that phellodendrine chloride mitigates gouty arthritis (GA) by modulating the IL-6/STAT3 signaling pathway.
研究领域:
药理学
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免疫学
·
风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Inflammation
·
2014
·
IF 0
Hang Yang,Haili Qi,Jingli Ren,Jing Cui,Zhenfeng Li,Helge L. Waldum,Guanglin Cui
Nuclear factor-kappaB (NF-κB)/interleukin (IL-6) pathway links chronic inflammation to colitis associated cancer (CAC). In this study, we examined the dynamic temporal changes of the NF-κB/IL-6 pathway during the procession of experimental CAC mouse model. Mice were sacrificed after induction for 14, 16, 18, and 22 weeks for the examination of tumor burden, inflammation degree, and protein level of NF-κB and IL-6 in bowel tissues. The results showed that tumor burden and inflammation severity in the bowels were gradually increased over the observed time-points. The expressions of IL-6 and NF-κB proteins were gradually increased after induction of dysplastic lesions over times. These data provide new information on the dynamic temporal changes of NF-κB/IL-6 pathway in relation to CAC development that may be relevant in the design of future investigations of therapeutic interventions to effectively target CAC processes.
研究领域:
分子生物学
·
肿瘤学
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免疫学
✓ 已验证
DOI
PubMed
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
·
2025
·
IF 3.1
Jiahui Sun,Luyao Shi,Fan Xu,Hanyan Sun,Yitong Liu,Jiangyun Sun,Qingxin Zhou
Colorectal cancer (CRC) is a worldwide health issue. It causes illness and death in millions of people each year. A positive correlation has been observed between the intake of dietary fat and the development of CRC. The composition of gut microbiota exhibits a significant correlation with pathophysiologic processes in intestine. Clinical treatment remains inadequate due to the complex pathogenic mechanisms of CRC triggered by a high-fat diet (HFD). Naringenin, a flavonoid from grapefruit, has anti-cancer activity. Our findings suggest that naringenin enhances gut microbiota diversity by increasing the abundance of beneficial bacterial species while reducing opportunistic pathogenic bacteria. The fecal microbiota transplantation assay (FMT) demonstrated that the anti-HFD-CRC activity of naringenin depended on the gut microbiota. Furthermore, naringenin antagonized the IL-6/STAT3 pathway. These results suggest that naringenin may be a potential treatment for HFD-CRC.
研究领域:
肿瘤学
·
营养学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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
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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
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xiangrui Meng,Xue Zhan,Hang Xiao,Songtao Li,Xuelian Zhang,Li Ma,Yiyao Liu,Jianyuan Tang
Natural killer (NK) cell-based immunotherapy is a promising approach for treating solid tumors and hematological malignancies. However, its therapeutic efficacy is limited by poor tumor infiltration and suppressive tumor microenvironment. Here, we introduce a rapid, simple, and efficient solution: bovine serum albumin-stabilized ultra-small (4 nm) NK cell nano-engagers, termed Bi 2 Se 3 @BSA nanodots (Nds). These Nds, responsive to high H 2 O 2 levels in tumor cell environments, enhance near-infrared (NIR)-II photothermic immunotherapy. In vitro and in vivo experiments demonstrate their effectiveness in activating photothermal therapy (PTT)-induced immunogenic cell death (ICD), initiating immune cascade reactions, and stimulating immune response activation. By upregulating NKG2D, RAE-1, and secreting cytokines such as IFN-γ and TNF-α, targeted NK cell infiltration is achieved, reversing the immunosuppressive tumor microenvironment and optimizing NK cell cytotoxicity. Transcriptomic analysis confirms the association of immune response activation with the IL-6/JAK2/STAT3 signaling pathway. Notably, combining these nano-engagers with immune checkpoint inhibitors (aPD-1) significantly enhances therapeutic efficacy, facilitating tumor eradication and reducing recurrence risk. Taken together, NK cell nano-engagers inhibit the IL-6/JAK2/STAT3 signaling pathway, target NK cell activation, stimulate immune functions, and improve the immunosuppressive microenvironment. This study presents an alternative strategy for NK cell-based immunotherapy and highlights this promising tool for cancer immunotherapy.
研究领域:
肿瘤免疫学
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纳米医学
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细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-11
·
IF 3.9
Li Wenlan,Zhang Zijie,Jiang Zixiao,Barasarathi Jayanthi,Zhou Ying,Liu Sui,Lee Shiou Yih,Liu Yangyang
Psychotria rubra Herbal Tea (PRHT) is a traditional Chinese folk medicine used to treat in-flammation induced by respiratory infections. Its specific mechanisms of action, however, remain unclear. The study combined ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), network pharmacology, and in vitro cell experiments to systematically analyze the chemical composition and validate the biological activity of PRHT. Protein-protein interaction (PPI) network analysis and molecular docking were used to identify key targets and mechanisms. PRHT was found to contain 128 active compounds, including alkaloids, amino acids and their derivatives, and flavonoids. Key targets such as STAT3, IL-6, and TP53 were identified through PPI network analysis. PRHT exhibited significant anti-inflammatory effects by modulating the STAT3/IL-6/TNF-α signaling pathway. Experimental results demonstrated that PRHT inhibited the release of inflammatory cytokines in a dose-dependent manner. Molecular docking confirmed strong interactions between PRHT components and core targets. The study reveals that PRHT exerts anti-inflammatory effects by regulating the STAT3/IL-6/TNF-α signaling pathway, contributing to inflammation balance and tis-sue repair. These findings provide scientific evidence for the development of PRHT as a functional anti-inflammatory agent and offer new insights into treatment strategies for respiratory infections.
研究领域:
中药学
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分子生物学
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网络药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2019
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IF 4.328
Dandan Chen,Zhe Li,Peiqing Bao,Miao Chen,Miao Zhang,Fangrong Yan,Yitao Xu,Caoyu Ji,Xinyue Hu,Daniel Sanchis,Yubin Zhang,Junmei Ye
Background NF-E2-related factor 2 (Nrf2) is a transcription factor playing cytoprotective effects in various pathological processes including oxidative stress and cardiac hypertrophy. Despite being a potential therapeutic target to treat several cardiomyopathies, the signaling underlying Nrf2-dependent cardioprotective action remains largely uncharacterized. Aim This study aimed to explore the signaling mediating the role of Nrf2 in the development of hypertensive cardiac pathogenesis by analyzing the response to Angiotensin II (Ang II) in the presence or absence of Nrf2 expression, both in vivo and in vitro. Results Our results indicated that Nrf2 deficiency exacerbated cardiac damage triggered by Ang II infusion. Mechanistically, our study shows that Ang II-triggered hypertrophy and inflammation is exacerbated in the absence of Nrf2 expression and points to the involvement of the IL-6/STAT3 signaling pathway in this event. Indeed, our results show that IL-6 abundance triggered by Ang II is increased in the absence of Nrf2 and demonstrate the requirement of IL-6 in STAT3 activation and cardiac inflammation induced by Ang II. Conclusion Our results show that Nrf2 is important for the protection of the heart against Ang II-induced cardiac hypertrophy and inflammation by mechanisms involving the regulation of IL-6/STAT3-dependent signaling.
研究领域:
心脏病学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD SCIENCE AND BIOTECHNOLOGY
·
2019
·Vol. 28
·期 4
·1235-1240
·
IF 0.888
Kwon Yeji,Yu Seungmin,Choi Gwang Su,Kim Jang Hwan,Baik Mooyeol,Su Seung Tae,Kim Wooki
The roots of Rehmannia glutinosa (RG) have been widely used for medicinal purposes in Asia. The traditional processing of RG involves repetitive steaming and drying, and 9-time-steamed RG (NSRG) is the most commonly consumed form. For a development of a convenient processing method, RG was puffed at various pressures resulting in significantly increased solid extraction yield by up to 14%. The amount of the Maillard reaction product 5-hydroxymethylfurfural and the antioxidant capacities determined by the ABTS and DPPH radical scavenging assays were enhanced at increasing puffing pressure. Treatment of lipopolysaccharide-stimulated RAW 264.7 macrophages with RG extracts revealed that puffing of RG enhanced its suppression of the pro-inflammatory cytokine IL-6 by up to 37%. The 5-hydroxymethylfurfural contents, ABTS/DPPH radical scavenging capacities, and IL-6 regulatory effects of puffed RG samples were greater than those of the NSRG control, indicating that puffing is a desirable processing technique for development of nutraceuticals using RG.
研究领域:
药理学
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营养保健品
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免疫学
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食品科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2024
·
IF 5.6
Hong He,Xiaoli Wang,Haolan Tan,Songtao Xiang,Yi Xu
A multifunctional microfluidic chip integrated with perfusion cell culture and in situ SERS detection of cell secretion was designed and developed for the detection of IL-6 secretion from LPS-stimulation of A549 cells in this paper. Researching works were focused on A549 cell activity and secretion in the constructed LPS-stimulated A549 cells model. On the designed microchip, a bubble trap chamber was designed to remove the bubbles in the culture medium which could also be simultaneously preheated by a split hot plate. Then, a long-time perfusion culture process of 549 cells could be realized. Under the optimized conditions the A549 cells could be cultured and kept in good activity for more than 36 h. Subsequently, the model of interaction between LPS and A549 cells was established on the designed microchip. When LPS-stimulated A549 cells, the IL-6 which was one of the secretions formed in this process was detected quantitatively by SERS spectral technique. The silver-coated gold nano-stars were prepared and taken as a sensitive enhancing probe for the SERS detection of IL-6 secreted from LPS-stimulated A549 cells. The immunomagnetic beads, IL-6 antigen, and SERS probes were mixed and incubated in the microchip and form a sandwich structure which was captured by the permanent magnet in the detection zone for SERS detection. The reference material of IL-6 was used to establish the calibration curve, and the linear range and detection limit were 1–10000 pg/mL and 0.75 pg/mL, respectively. Then, the IL-6 secretion from LPS-stimulated A549 cells was detected hourly for 7 h by this established method. The process of LPS stimulation of A594 cells did not lead to a sustained increase in the SERS spectral signature of IL-6. Instead, IL6 secretion initially increased sharply, then decreased and eventually stabilized. It could be due to a potential mechanism that the cells self-regulated to mitigate the inflammatory effects in response to sustained stimulation. The proposed multifunctional microfluidic chip, characterized by high sensitivity and the ability to perform continuous hourly detection, exhibited significant application prospects in the study of external stimulation on cells.
研究领域:
生物医学工程
·
细胞生物学
·
分析化学
·
微流控技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 26
·15346-15353
·
IF 3.119
Huaqiang Mo,Chenxing Fu,Zhiye Wu,Peng Liu,Zhibo Wen,Qingqing Hong,Yanbin Cai,Gongxin Li
Vulnerable plaques of atherosclerosis (AS) are the main culprit lesion for the serious risk of acute cardiovascular disease (CVD). Therefore, developing new non-invasive methods to detect vulnerable plaques and to evaluate their stability effectively is of great value in the early diagnosis of CVD. IL-6 plays a vital role in the development and rupture of AS. In this study, IL-6-targeted superparamagnetic iron oxide nanoparticles (Anti-IL-6-USPIO) are synthesized by a chemical condensation reaction. An AS model was established by damaging rabbit abdominal aortic intima with Foley's tube in combination with a high cholesterol diet. The results confirm that Anti-IL-6-USPIO have excellent IL-6-targeting ability and usefulness in detecting vulnerable plaques in vitro and in vivo, which may provide a novel, non-invasive strategy for evaluating acute cardiovascular risk or exploiting anti-atherosclerotic drugs.
研究领域:
医学影像学
·
纳米技术
·
心脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Chenxi Zhao,Ruihui Xie,Qiuhui Qian,Jin Yan,Huili Wang,Xuedong Wang
As a broad-spectrum antibacterial agent, triclosan (TCS) has been confirmed to possess potential immunotoxicity to organisms, but the underlying mechanisms remains unclear. Herein, with the aid of transgenic zebrafish strains Tg ( coro 1A: EGFP) and Tg ( rag 2: DsRed), we intuitively observed acute TCS exposure caused the drastic differentiation, abnormal development and distribution of innate immune cells, as well as barriers to formation of adaptive immune T cells. These abnormalities implied occurrence of the cytokine storm, which was further evidenced by expression changes of immune-related genes, and functional biomarkers. Based on transcriptome deep sequencing, target gene prediction and dual luciferase validation, the highly conservative and up-regulated miR-19a was chosen as the research target. Under TCS exposure, miR-19a up-regulation triggered down-regulation of its target gene socs3b , and simultaneously activated the downstream IL-6/STAT3 signaling pathway. Artificial over-expression and knock-down of miR-19a was realized by microinjecting agomir and antagomir, respectively, in 1–2-cell embryos. The miR-19a up-regulation inhibited socs3b expression to activate IL-6/STAT3 pathway, and yielded abnormal changes in the functional cytokine biomarkers, along with the sharp activation of immune responses. These findings disclose the molecular mechanisms regarding TCS-induced immunotoxicity, and offer important theoretical guidance for healthy safety evaluation and disease early warning from TCS pollution.
研究领域:
毒理学
·
分子生物学
·
免疫学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）