MATERIALS & DESIGN
·
2023
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IF 8.4
Quanxiao Li,Wenzhe Fan,Yunyan Ling,Jie Wen,Jiaping Li,Zhenwei Peng,Meng Jin
Although radiotherapy has become indispensable for tumor treatment in recent years, the inevitable side effects of high-dose radiation on the normal tissue and deficiency of appropriate radiosensitizers without long-term body retention that do not cause potential toxicity limit further clinical applications to a certain extent. Herein, we rationally synthesized BiOI nanodots coated with M1 macrophage membrane ( [email protected] ) by utilizing their coordination interaction. With two high-atomic-number elements and ultrasmall size, the prepared BiOI nanodots not only enhanced radiosensitivity by reactive oxygen species under X-ray irradiation in vitro , but also could be excreted quickly by kidneys. Meanwhile, the M1 macrophage membrane functioned as a highly desirable carrier with long-circulating and tumor-targeting capability. As a result, treatment with as-prepared [email protected] could improve the therapeutic outcome of radiotherapy in a xenograft mouse model and reduce the potential toxicity of nanoparticles. Simultaneously, BiOI nanodots exhibited excellent CT imaging ability as contrast agents to visualize biodistribution in vivo and to monitor tumor growth. Therefore, our work demonstrated the preparation of a tumor targeting and renal clearable radiosensitizer and offered a potential approach to enhance the radiotherapy efficacy of hepatocellular carcinoma.
研究领域:
纳米技术
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肿瘤学
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放射学
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药学
✓ 已验证
产品关联
DOI
高影响因子
NEUROSCIENCE LETTERS
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2021
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IF 3.046
Hui Tian,Yahong Cheng,Yiyuan Zhang,Xinying Bai,Yuan Jiang,Jinjin Li,Shiqi Fan,Hong Ding
This research aimed to examine the nutritious supplementary function of 18β-Glycyrrhetinic acid (18β-GA) in moderating the myelin sheath destruction and behavioral impairments observed in the cuprizone model of demyelination. Mice were fed daily on food containing cuprizone (0.3 %) and given doses of 18β-GA (5 or 1 mg/kg) for a period of five weeks. The groups treated with 18β-GA exhibited improvements in exploratory behavior, locomotive activity, and weight. As assessed using luxol-fast blue and myelin basic protein (MBP) staining, which were used to detect demyelination in the brain, 18β-GA both reduced and prevented instances of cuprizone-induced demyelinating lesions; treatment with 18β-GA also caused the MBP level in the corpus callosum to increase. Furthermore, alongside these positive results following 18β-GA treatment, microglial polarisation was also observed to shift towards the beneficial M2 phenotype. The results of this research thus indicate the potential clinical application of 18β-GA for the prevention of myelin damage and behavioral dysfunction.
研究领域:
神经科学
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药理学
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免疫学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
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2024
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IF 3.4
Wenjia Tong,Conglei Song,Danqun Jin,Min Li,Zimei Cheng,Guoping Lu,Bin Yang,Fang Deng
Sepsis is a systemic inflammatory response caused by an infection, which can easily lead to acute lung injury. Quiescin Q6 sulfhydryl oxidase 1 (QSOX1) is a sulfhydryl oxidase involved in oxidative stress and the inflammatory response. However, there are few reports on the role of QSOX1 in sepsis-induced acute lung injury (SALI). In this study, mice model of SALI was constructed by intraperitoneal injection with lipopolysaccharide (LPS). The increased inflammatory response and lactate dehydrogenase activity in bronchoalveolar lavage fluid (BALF) indicated successful modeling. Increased QSOX1 expression was both observed in lung tissues and lung macrophages of sepsis mice accompanied by increased polarization of M1-type macrophages. To explore the role of QSOX1 in the SALI, lentivirus containing QSOX1-specific overexpression or knockdown vectors were used to change QSOX1 expression in LPS-treated RAW264.7 cells. QSOX1 suppressed LPS-induced M1 polarization and further inhibited inflammatory response in RAW264.7 cells. Interestingly, the phosphorylation of epidermal growth factor receptor (EGFR), the promoter of M1 polarization in macrophages, was found to be downregulated upon QSOX1 overexpression in RAW264.7 cells. Mechanically, the binding of QSOX1 to EGFR protein promoted EGFR ubiquitination and degradation, thereby down-regulating EGFR phosphorylation. Moreover, inhibiting EGFR expression or its phosphorylation restored the impact of QSOX1 silencing on M1 polarization and inflammation in the LPS-treated RAW264.7 cells. In summary, QSOX1 may exert anti-inflammatory effects in SALI by inhibiting EGFR phosphorylation-mediated M1 macrophage polarization. This presented a potential target for the treatment and prevention of SALI.
研究领域:
免疫学
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药理学
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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 HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Yue Zhang,Hongmin Lu,Lulu Hou,Xin Zhang,Tiantian Guo,Ruoqi Wang,Qi Wang,Mingwei Xing
Acetochlor is a widely used and highly effective herbicide. Its overuse poses significant threats to biosecurity and ecological integrity, particularly affecting free-ranging birds. Data on its impact, especially mechanisms of liver toxicity in chickens, are lacking. Thus, we established an animal-cell-animal model to explore intrinsic mechanisms at multiple levels. We found that acetochlor exposure caused liver cell swelling, inflammatory cell accumulation, and lipid deposition. Transcriptomic analyses revealed that differential gene were mainly enriched in hepatic immune, inflammatory, and programmed cell death pathways. We next focused on the gene GPR120, conducting transfection and agonism experiments in LMH, HD11, and co-cultured cells. Acetochlor significantly increased ROS accumulation, activated the NLRP3 inflammasome, and which induced PANoptosis. HD11 cells exhibited M1 polarization with upregulated pro-inflammatory factors. Silencing GPR120 exacerbated cellular damage and immune responses, whereas its agonist, GSK7A, dramatically reduced macrophage M1 polarization and mitigated immune damage to LMH cells. Finally, we returned to animal studies, adding Omega-3-a known GPR120 agonist-to the diet. Omega-3 effectively reversed acetochlor-induced hepatitis and PANoptosis. Given that acetochlor residues pose potential threats to ecosystems and avian health, it is crucial to strengthen residue control, conduct risk assessments, and explore targeted pathways and nutritional supplementation to counteract these negative impacts.
研究领域:
毒理学
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免疫学
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分子生物学
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兽医学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Medical Sciences
·
2024
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IF 3.2
Mi Tang,Min Wang,Zhirong Wang,Bo Jiang
Aortic aneurysm and dissection (AD) represent a critical cardiovascular emergency with an alarmingly high mortality rate. Recent research has spotlighted the overexpression of genes associated with the m6A modification in AD patients, linking them to the presence of inflammatory M1-type macrophages. Moreover, glycolysis is widely recognized as a key feature of inflammatory M1-type macrophages, but biomarkers linking glycolysis and macrophage function to promote disease progression in AD have not been reported. We conducted an analysis of aortic immune cell infiltration, macrophages, and m6A-related biomarkers in AD patients using bioinformatics techniques. Subsequently, we employed a combination of RT-PCR, WB, and immunofluorescence assays to elucidate the alterations in the expression of M1- and M2-type macrophages, as well as markers of glycolysis, following the overexpression of key biomarkers. These findings were further validated in vivo through the creation of a rat model of AD with knockdown of the aforementioned key biomarkers. The findings revealed that the m6A-modified related gene RBM15 exhibited heightened expression in AD samples and was correlated with macrophage polarization. Upon overexpression of RBM15 in macrophages, there was an observed increase in the expression of M1-type macrophage markers CXCL9 and CXCL10, alongside a decrease in the expression of M2-type macrophage markers CCL13 and MRC1. Furthermore, there was an elevation in the expression of glycolytic enzymes GLUT1 and Hexokinase, as well as HIF1α, GAPDH, and PFKFB3 after RBM15 overexpression. Moreover, in vivo knockdown of RBM15 led to an amelioration of aortic aneurysm in the rat AD model. This knockdown also resulted in a reduction of the M1-type macrophage marker iNOS, while significantly increasing the expression of the M2-type macrophage marker CD206. In conclusion, our findings demonstrate that RBM15 upregulates glycolysis in macrophages, thus contributing to the progression of AD through the promotion of M1-type macrophage polarization. Conversely, downregulation of RBM15 suppresses M1-type macrophage polarization, thereby decelerating the advancement of AD. These results unveil potential novel targets for the treatment of AD.
研究领域:
心血管疾病
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免疫学
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分子生物学
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生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Aihua Xu,Yang Yang,Yang Shao,Manyu Jiang,Yongxin Sun,Bo Feng
Neuronal apoptosis and inflammation exacerbate the secondary injury after spinal cord injury (SCI). Four and a half domains 2 (FHL2) is a multifunctional scaffold protein with tissue- and cell-type specific effects on the regulation of inflammation, but its role in SCI remains unclear. The T10 mouse spinal cord contusion model was established, and the mice were immediately injected with lentiviruses carrying FHL2 shRNA after SCI. The results showed that FHL2 expression was increased following SCI, and then gradually decreased. Moreover, FHL2 depletion aggravated functional impairment, neuronal necrosis, and enlarged lesion cavity areas in the injured spinal cord. FHL2 deficiency facilitated neuronal apoptosis by elevating cleaved caspase 3/9 expression, neuroinflammation by regulating microglia polarization, and bone loss. Indeed, FHL2 deficiency increased the secretion of TNF-α and IL-6, M1 microglia polarization, and the activation of STAT1 pathway but decreased the secretion of IL-10 and IL-4, M2 microglia polarization, and the activation of the STAT6 pathway in the spinal cord. In vitro , FHL2 silencing promoted LPS + IFN-γ-induced microglia M1 polarization through activating the STAT1 pathway and alleviated IL-4-induced microglia M2 polarization via inhibiting the STAT6 pathway. FHL2 positively regulated the expression of poly (ADP-ribose) polymerase family member 14 (PARP14) by promoting its transcription. PARP14 overexpression inhibited FHL2 silencing-induced microglia M1 polarization and relieved the inhibitory effect of FHL2 silencing on microglia M2 polarization. Collectively, the study suggests that FHL2 reduces the microglia M1/M2 polarization-mediated inflammation via PARP14-dependent STAT1/6 pathway and thereby improves functional recovery after SCI.
研究领域:
神经科学
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炎症
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2024
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IF 3.1
Liu Junhao,Yong Shuangshuang,Yin Sisi,Feng Jinhong,Lian Caihua,Chen Jie
Background Psoriasis is a common immune-related chronic inflammatory skin disease, often accompanied by significant itching, and once diseased, the course of the disease lasts for most of the lifetime. Tanshinol (TAN) is an active ingredient of Salvia miltiorrhiza , which possesses pharmacological effects such as anti-inflammatory and antioxidant properties. However, the effects of TAN on psoriasis have not been widely reported. Therefore, the aim of this study was to investigate the therapeutic effects and mechanisms of TAN in psoriasis. Methods An imiquimod (IMQ)-induced psoriasis mouse model was constructed and treated with different doses of TAN to observe the changes in skin lesion phenotype, macrophage polarization, inflammation and Notch signaling pathway in mice. Further removal of macrophages or inhibition or activation of Notch signaling pathway was performed to examine the changes in skin lesion phenotype, macrophage polarization, inflammation and Notch signaling pathway in mice. In addition, in vitro experiments verified that TAN regulates RAW264.7 macrophage polarization and cytokine secretion through the Notch pathway. Results The results showed that TAN alleviated IMQ-induced skin lesions and pathological phenotypes in psoriasis mice and inhibited Notch signaling pathway and M1-type macrophage polarization. Moreover, macrophage clearance and Notch signaling pathway activation inhibited the effect of TAN on psoriasis. Further in vitro experiments showed that Notch agonists reversed the effects of TAN on macrophage polarization and inflammatory cytokines. Conclusions Collectively, these findings suggest that TAN may exert a therapeutic effect on psoriasis by inhibiting the Notch signaling pathway and thus M1-type macrophage polarization.
研究领域:
药理学
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免疫学
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皮肤科
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炎症
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
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IF 5.6
Ruixi Li,Qiang Tao,Jiandong Zha,Shikai Wang,Xiaozhun Huang,Jicai Wang,Hang Zhai,Shengjie Hong,Guangquan Zhang
Currently, suppressing macrophage M1 polarization and HSC activation are recognized as potential therapeutic strategies for liver cirrhosis. Ubiquitin-like with PHD and RING Finger Domains 1 (UHRF1) is a crucial epigenetic modulator implicated in maintaining DNA methylation and chromatin structure. Knockdown of high mobility group A protein 2 (HMGA2) was reported to ameliorate hepatic inflammation and fibrosis in nonalcoholic fatty liver disease. Here, the elaborate effect of UHRF1-mediated HMGA2 promoter methylation was investigated during the progression of liver cirrhosis. Transcriptomic sequencing of liver tissues of cirrhotic patients was carried out and a mouse model with liver cirrhosis was established by intraperitoneal injection of carbon tetrachloride (CCl 4 ) twice weekly for four consecutive weeks. Lipopolysaccharide (LPS)-induced RAW264.7 were transduced with overexpressed UHRF1 adenovirus and cell supernatant was applied as the conditional medium to cultivate hepatic stellate cells (HSCs). Notably, in vivo experiments, enhanced UHRF1 expression alleviated fibrosis and inflammation of mouse livers. In vitro experiments, upregulated UHRF1 suppressed CCl 4 -stimulated macrophage M1 polarization and HSC activation. Moreover, MSP assay revealed that methylation was enhanced on HMGA2 promoter at −599/2−450 site after UHRF1 overexpression. More intriguingly, ChIP and Co-IP results clarified that UHRF1 interacted with DNA methyltransferase 1 (DNMT1), thereby bound to HMGA2 promoter and facilitated its methylation. Furthermore, increased HMGA2 level abolished the inhibitory effects of UHRF1 upregulation on the mRNA expression of pro-inflammatory genes of macrophages and genes encoding collagen of HSCs. Collectively, UHRF1 weakened HMGA2 expression by catalyzing its promoter methylation, thereby blocked macrophage M1 polarization and mitigated liver cirrhosis.
研究领域:
分子生物学
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表观遗传学
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肝脏病学
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免疫学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ELECTROANALYTICAL CHEMISTRY
·
2020
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IF 3.807
Lu-Lu Guo,Yi-Ying Wang,Yue-Hong Pang,Xiao-Fang Shen,Nian-Ci Yang,Yun Ma,Yi Zhang
An in situ growth strategy for construction of covalent organic frameworks (COFs) TpBD on glassy carbon electrode using p-aminobenzoic acid and ethylenediamine as connector is introduced. The fabricated electrode was used for electrochemical biosensing of aflatoxin M1 in milk samples combined with magnetic nanoparticles , which acted as probe carriers. The developed electrochemical biosensor exhibited high selectivity and sensitivity toward aflatoxin M1 with a detection limit of 0.15 ng/mL (S/N = 3). Moreover, the covalent bonding of TpBD on the glassy carbon electrode has good stability, which retained 76% of the initial signal after 15 days storage at room temperature . This work provides a valuable case for in situ growth of COFs TpBD on the electrode, and the proposed synthetic route is expected to provide a powerful tool for the wide application of other functional COFs in electrochemical biosensor.
研究领域:
分析化学
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食品科学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR MEDICINE
·
2025
·Vol. 31
·期 1
·1-20
·
IF 6.4
Peng Shuaijun,Su Pan,Liu Liming,Li Zibo,Liu Yuan,Tian Lei,Bai Ming,Xu Erping,Li Yucheng
Background The dysregulation of neuroinflammation triggered by imbalance of microglia M1/M2 polarization is a key pathogenic factor and closely associated with occurrence of depression. Formononetin (FMN), a natural non-steroidal isoflavonoid, has been confirmed to exhibit remarkable anti-inflammatory efficacy, but the impact of FMN on depression and the underlying antidepressant mechanisms are still not fully understood. This study aimed to investigate whether the antidepressant effect of FMN is involved in modulating microglia polarization, and if so, what are the underlying mechanisms.Methods Lipopolysaccharide (LPS)-induced depressive mice were used to study antidepressant mechanisms of FMN. Microglia cell line BV2 stimulated by LPS was employed to investigate pharmacological mechanisms of FMN. Effects of FMN on neuronal damage were detected by H&E, Nissl and Golgi staining. The efficacy of FMN were evaluated by immunostaining and western blots in vivo and vitro. In addition, molecular docking, luciferase reporter assay, cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to confirm the direct target of FMN.Results Our results showed that FMN significantly reverses depression-like behaviors, alleviates neuroinflammation and neuronal damage, rebalances M1/M2 polarization, inhibits NLRP3 inflammasome and enhances microglial autophagy level in prefrontal cortex of LPS-induced depressive mice. In vitro assays, results unraveled that autophagy inhibitor chloroquine (CQ) blocks effects of FMN on inhibiting NLRP3 inflammasome and rebalancing M1/M2 polarization. Moreover, PPARα is identified as a direct target of FMN and FMN can activate PPARα-mediated autophagy. Furtherly, combination PPARα agonist (WY14643) with FMN had no significant additive effects on inhibiting NLRP3 inflammasome and rebalancing M1/M2 polarization, whereas PPARα antagonist (GW6471) abrogated these pharmacologic effects of FMN in BV2. Importantly, GW6471 exhibited similar pharmacologic effects to abolish antidepressant effect of FMN in LPS-induced depressive mice.Conclusion Our study firstly demonstrated that FMN can rebalance microglia M1/M2 polarization and inhibit NLRP3 inflammasome, with the involvement of activating PPARα-mediated autophagy to ameliorate depression-like behaviors, which provides a novel view to elucidate antidepressant mechanisms of FMN and also offers a potential therapeutic target for depression.
研究领域:
神经科学
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药理学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2023
·
IF 18.9
Chunchun Xue,Jia Tian,Zepeng Cui,Yang Liu,Dawei Sun,Mengting Xiong,Nanxing Yi,Kaiqiang Wang,Xiaofeng Li,Yongjun Wang,Hao Xu,Weian Zhang,Qianqian Liang
Osteoarthritis (OA) is a common chronic inflammatory disorder. Effective remodeling of inflammatory microenvironment in the joint is a promising strategy to prevent OA. However, current drugs remain unsatisfactory due to a lack of targeted and effective ways for relieving inflammatory conditions in OA joints. Bortezomib (BTZ), a proteasome inhibitor, could effectively inhibit proinflammatory cytokines but with poor accumulation in the inflammatory tissues. To overcome the shortcomings of BTZ delivery and to improve the efficacy of OA therapy, herein, we designed a novel nanomedicine (denoted as BTZ@PTK) by the co-assembly of BTZ and an amphiphilic copolymer (denoted as PTK) with ROS-cleaved thioketal (TK) linkages. The TK units in BTZ@PTK are first cleaved by the excessive ROS at OA sites, and then triggered the controlled release of BTZ, resulting in the accurate delivery and the inflammatory microenvironment remodeling. Accordingly, BTZ@PTK suppressed ROS generation and proinflammatory cytokines while promoting M1 macrophage apoptosis in lipopolysaccharide (LPS)-activated RAW264.7 macrophages or LPS/IFN-γ-treated primary macrophages, which leads to a better effect than BTZ. In OA mice, BTZ@PTK passively accumulates into inflamed joints to attenuate pain sensitivity and gait abnormality. Importantly, BTZ@PTK treatment successfully ameliorates synovitis with the reduction of synovial hyperplasia and synovitis scores by suppressing M1 macrophage polarization and promoting M1 macrophage apoptosis in the synovium, thereby delaying cartilage damage. Collectively, BTZ@PTK can effectively modulate inflammatory microenvironment for OA recession by activating M1 macrophage apoptosis and inhibiting M1macrophage-mediated inflammatory response.
研究领域:
药理学
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纳米技术
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免疫学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2022
·
IF 5.223
Suwen Liu,Zhang Lu,Chang Liu,Xuedong Chang,Buhailiqiemu Apudureheman,Shiguo Chen,Xingqian Ye
Castanea mollissima shells are a by-product of Chinese chestnut processing and contain many polyphenols. Macrophage polarization plays an important role in the progression of atherosclerosis (AS). We investigated the action of Castanea mollissima shell polyphenols (CSPs), with proanthocyanidin C1 and proanthocyanidin B1 as the main phenolic components, on macrophages. CSPs (40 μg/mL) significantly decreased inflammatory cytokines secretion in M1-type macrophages (p < 0.01). The addition of AG490, a JAK2 inhibitor, enhanced the regulatory effect of CSPs. CSPs also significantly upregulated the protein expressions of PPARγ, LXRα, and ABCA1/G1 (p < 0.01); however, this effect was inhibited by adding the PPARγ blocker GW9662. Therefore, CSPs possibly inhibit M1 type macrophage polarization to reduce inflammation by inhibiting the JAK2/STAT3 signaling pathway; however, it is not dependent on this. Furthermore, the activation of the PPARγ-LXRα-ABCA1/G1 pathway increases cholesterol efflux. Our study suggests that CSPs may act as functional food agents in the prevention of and adjuvant therapy for atherosclerosis.
研究领域:
药理学
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免疫学
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分子生物学
·
心血管疾病
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）