NEUROSCIENCE
·
2022
·
IF 3.708
Hanshu Zhao,Yushuang Liu,Nan Chen,Hongyi Yu,Sihan Liu,Meihe Qian,Zhongling Zhang
Cerebral ischemia/reperfusion injury is the main cause of neurological deficit following stroke. Pleckstrin homology-like domain, family A, member 1 (PHLDA1) is increasingly recognized as a critical determinant in immunological regulation and cell apoptosis, but its role in neuroinflammation during cerebral ischemia/reperfusion injury remains to be elucidated. In this study, middle cerebral artery occlusion/reperfusion (MCAO/R) in C57BL/6 mice and oxygen-glucose deprivation/reoxygenation (OGD/R) in BV-2 cells were used as models in vivo and in vitro , respectively. MACO/R mice and OGD/R cells were treated with scramble or PHLDA1 small interfering RNAs (siRNAs) to achieve the goal of PHLDA1 knockdown. The results showed that the expression of PHLDA1 was significantly increased in MCAO/R mice and OGD/R cells compared to their normal controls, respectively. Mice treated with PHLDA1 siRNA exhibited a lower degree of infarct volume and brain water content compared to the NC siRNA-treated mice. Notably, PHLDA1 knockdown switched the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype by decreasing the expression of M1 markers (i.e., CD16, TNF-α, IL-6 and IFN-γ, and iNOS) and elevating the expression of M2 markers (i.e., CD206, IL-4, IL-10, and Arg-1). Moreover, PHLDA1 knockdown suppressed the NLRP3 inflammasome activation by reducing NLRP3, ASC, cleaved caspase 1 and cleaved IL-1β expression. In summary, these results suggest that PHLDA1 blockade effectively alleviates the ischemia/reperfusion-induced cerebral injury by switching microglial M1/M2 polarization and inhibiting NLRP3 inflammasome activation. Targeting PHLDA1 could be considered as a novel strategy in the treatment against post-ischemic brain injury.
研究领域:
神经科学
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免疫学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2024
·
IF 7.1
Xiaowen Liu,Huamei Cai,Liang Peng,Hongli Ma,Yun Yan,Weixia Li,Jing Zhao
Remifentanil-induced hyperalgesia (RIH) represents a significant clinical challenge due to the widespread use of opioids in pain management. However, the molecular and cellular mechanisms underlying RIH remain elusive. This study aimed to unravel the role of spinal cord microglia, focusing on the Nrf2/HO-1 signaling pathway and TRPV4 channels in the development of RIH. We used both in vivo and in vitro models to investigate the activation state of spinal cord microglia, the expression of TRPV4 channels, and the modulation of the Nrf2/HO-1 pathway under remifentanil exposure. In addition, we evaluated the potential therapeutic effects of dexmedetomidine, a perioperative α2-adrenergic agonist, on RIH and its related molecular pathways. Our results revealed a prominent role of spinal cord microglia in RIH, demonstrating an apparent microglial M1 polarization and increased TRPV4 channel expression. A notable observation was the downregulation of the Nrf2/HO-1 pathway, which was associated with increased neuroinflammation and mechanical allodynia. By upregulating or overexpressing Nrf2, we confirmed its ability to inhibit TRPV4 and thereby attenuate RIH-associated mechanical allodynia, M1 polarization, and neuroinflammation. Encouragingly, dexmedetomidine demonstrated therapeutic potential by positively modulating the Nrf2-TRPV4 nexus, attenuating mechanical allodynia, and reducing microglial inflammation. Our research highlights the critical role of spinal cord microglia in RIH mediated by the Nrf2-TRPV4 axis. The ability of dexmedetomidine to modulate this axis suggests its potential as an adjunctive therapy to remifentanil in mitigating RIH. Further studies are imperative to explore the broader implications and practical applicability of our findings.
研究领域:
疼痛管理
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神经科学
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药理学
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炎症生物学
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产品关联
DOI
PubMed
高影响因子
Food Additives and Contaminants Part A-Chemistry Analysis Control Exposure & Risk Assessment
·
2022
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IF 3.549
Amir Kiani,Kiomars Sharafi,Toraj Ahmadi Jouybari,Hadi Ahmadi Jouybari,Hamed Biglari,Gholamreza Ebrahimzadeh,Nazir Fattahi
In this study, solid-phase extraction (SPE) combined with the dispersive liquid–liquid microextraction based on novel hydrophobic deep eutectic solvent (DLLME − DES) has been developed as an ultra-pre-concentration technique for the extraction of aflatoxin M1 (AFM1) in milk-based baby food (MBBF) and infant formula milk (IFM) samples followed by HPLC combined with fluorescence detection (HPLC − FL). In addition, carcinogenic and non-carcinogenic risk assessment was performed by health-related risk factors including liver cancer risk (LCR), margin of exposure (MOE) and target hazard quotient (THQ) were calculated using the mean of AFM1 in different infant food samples. The results of the study showed that the mean of AFM1 was statistically significant different between various brands and types of IFM and MBBF. The results of the study showed that the percentage of positive samples higher than the allowable limit of AFM1 in 36 samples of domestic infant formula milk (DIFM), 24 samples of imported infant formula milk (IIFM), 36 samples of domestic milk-based baby food (DMBBF) and 18 samples of imported milk-based baby food (IMBBF) were 41.6, 12.5, 66.7 and 33.3%, respectively. In addition, estimated values for health risk-related factors including LCR, MOE and THQ indicated that for most infants less than one-year-old were higher than the acceptable levels. Based on the results, it can be concluded that the quality of IFM and MBBF consumed in Iran in terms of AFM1 is poor. Therefore, it is necessary to take appropriate measures to reduce the amount of AFM1 in DIFM and DMBBF, and in addition, the IIFM and IMBBF should be controlled qualitatively before supplying the market.
研究领域:
食品安全
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毒理学
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分析化学
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DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Chen-chen Wu,Jing-yao Ge,Xin-yue Huang,Xiao-ming Liu,Yan Liao,Shui-jing Zhang,Lin Wu,Xiao-fan Chen,Bo Yu
Rosacea is a chronic inflammatory skin disease, which is prone to flares and requires continuous management and treatment. However, long-term use of drugs can lead to additional adverse drug reactions. Based on the comorbid relationship between rosacea and Parkinson’s disease, bioinformatics and network pharmacology analysis were used to identify a safer drug for rosacea. It has been demonstrated that ISA has an ameliorative impact on the symptoms of Parkinson’s disease. The results demonstrated that ISA exhibited anti-inflammatory properties, including reducing erythema areas and inflammatory cell infiltration in rosacea-like mice models, and inhibiting the expression of inflammatory factors in cellular inflammation models. Furthermore, the anti-inflammatory effect of ISA was associated with inhibition of the Erk, p38 and NF-κB signaling pathways and inhibition of macrophage polarization to M1 type. In addition, molecular docking and drug affinity responsive target stability experiment results indicated that VEGFA and RELA were the direct targets of ISA in the treatment for rosacea. In conclusion, these results suggested that ISA may be a potential therapeutic agent for rosacea.
研究领域:
皮肤科
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药理学
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炎症研究
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神经学
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产品关联
DOI
PubMed
高影响因子
FOLIA NEUROPATHOLOGICA
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2020
·Vol. 58
·期 1
·70-82
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IF 1.278
Yanxiang Zhang,Qi Chen,Yu Nai,Chunni Cao
IntroductionThe polarization state of microglia affects the progress of neuropathic pain. MiR-155 modulates polarization of microglia, while its role in neuropathic pain has not been well studied.Material and methodsWe separately used lipopolysaccharide (LPS) and interleukin 4 (IL-4) for constructing an M1/M2 polarization model in BV-2 cells. The levels of CD86, iNOS, CD206, Arg and miR-155 were measured by western blot or qRT-PCR, as needed. Subsequently, BV-2 cells were transfected with miR-155 mimics or inhibitor to explore the effects of miR-155 on polarization states. We also constructed a neuropathic pain model by applying spinal nerve ligation (SNL) in Wistar rats with miR-155 agomir or antagomir injection. The withdrawal threshold was measured by Von Frey fibre needle. The levels of interleukin 1b (IL-1b), tumour necrosis factor a (TNF-a) and the proportion of M1-polarized microglia in primary microglia from rats were measured by ELISA and flow cytometry.ResultsLPS induced M1 polarization in BV-2 cells with increasing of CD86, iNOS and miR-155, while IL-4 induced M2 polarization in BV-2 cells with increasing of CD206, Arg and decreasing of miR-155. MiR-155 mimics upregulated CD86 and downregulated CD206, whereas miR-155 inhibitor downregulated CD86 and upregulated CD206. MiR-155 antagomir increased the withdrawal threshold, decreased the production of IL-1b, TNF-a and the proportion of M1-polarized microglia in primary microglia.ConclusionsResults demonstrate that suppression of miR-155 attenuates neuropathic pain by inducing an M1 to M2 switch in microglia. Our findings provide a new perspective to understand the function of miR-155 in microglia.
研究领域:
神经科学
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疼痛研究
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
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IF 7.7
Wanyu Li,Zhonghao Jiang,Zhuo Yan,Zhihao Chen,Lianhai Li,Dan Wang,Jilong Wang,Li Li,Huiling Yang,Junjie Deng,Jiantao Lin
Despite the monumental success of immunotherapy in treating melanoma clinically, it still confronts significant challenges, chiefly that singular immunomodulatory tactics are insufficient to suppress the recurrence and metastasis of melanoma. Herein, these challenges are addressed by a hydrogel based on M1 macrophage lysate and alginate (M1LMHA) loaded with oxaliplatin (OXA), named [email protected] results obtained from scanning electron microscopy and confocal microscopy indicate that the structure and morphology of M1LMHA@OXA remain unchanged. Flow cytometry results reveal that M1LMHA@OXA significantly promotes the maturation of dendritic cells (DCs) and enhances the proliferation of T lymphocytes. In a subcutaneous melanoma transplant model, M1LMHA@OXA effectively suppressed tumor growth in comparison to OXA alone and M1LMHA alone. Flow cytometry demonstrated that M1LMHA@OXA markedly increased the number of mature DCs and CD8 + T cells at the tumor site, while significantly reducing the quantity of M2-like tumor-associated macrophages (TAM) and enhancing the presence of M1 macrophages. Enzyme-linked immunosorbent assay (ELISA) results indicated that following treatment with M1LMHA@OXA, the levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the bloodstream of mice were significantly elevated, whereas interleukin-10 (IL-10) exhibited no significant difference. This outcome further corroborates the ability of M1LMHA@OXA to substantially bolster the immune capability of mice. Similar results have also been observed in a melanoma subcutaneous transplantation recurrence model, and optical imaging of the lungs of mice revealed that M1LMHA@OXA inhibited tumor metastasis to the lungs. Notably, M1LMHA@OXA exhibits an exceptional therapeutic effect on the growth, post-surgical recurrence, and metastasis of the B16F10 melanoma. Therefore, this study provides a straightforward strategy that leverages the cooperative regulation of multiple immune cells to thwart the proliferation, recurrence, and spread of melanoma.
研究领域:
癌症研究
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免疫治疗
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生物医学工程
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药学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2020
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IF 7.1
Sobia Niazi,Imran Mahmood Khan,Ye Yu,Imran Pasha,Yan Lv,Ali Mohsin,Bilal Sajid Mushtaq,Zhouping Wang
Aflatoxin M 1 is a prevailing natural carcinogenic mycotoxin, found in milk. Herein, we reported a sensitive fluorescent aptasensor for AFM 1 , based on rolling circle amplification (RCA) technology to improve the sensitivity of the assay. The detection of AFM 1 was achieved using KYF 4 : Eu 3+ time-resolved fluorescent nanoparticles (KYF 4 : Eu 3+ TRFNPs) as signal probe and graphitic carbon nitride (g-C 3 N 4 ) nanosheet as a quencher. The AFM 1 aptamer act as a recognition element and as a primer for DNA synthesis. TRFNPs attached to complementary DNA (TRFNPs-cDNA) acts as a signal probe. In the absence of target, a rolling circle template (RCT) ligated to aptamer and RCA reaction initiated. The TRFNPs-cDNA was strengthened to amplified RCA product (RCAP) to make RCAP/TRFNPs-cDNA duplex. This duplex cannot be adsorbed onto g-C 3 N 4 , and ultimately no fluorescence quenched. In the presence of AFM 1 , aptamer recognized the target and aptamer-target complex was formed. Hence, no aptamer hybridized with RCT, therefore, no RCA and duplex formation. Consequently, free TRFNPs-cDNA adsorbed onto g-C 3 N 4 and resulted in quenched fluorescence. The assay provides a lower detection limit (0.0194 pg/mL) than the previously reported assays and has good recoveries between 92–99.8 %. Hence, the present method would be a suitable method for the quantification of small molecules.
研究领域:
食品安全
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分析化学
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毒理学
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生物传感器
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DOI
高影响因子
IMMUNOLOGY LETTERS
·
2025
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IF 2.8
Xing Chen,Lixiang Li,Yan Deng,Juan Liao,Hui Meng,Limei Liang,Jie Hu,Dongwei Xie,Guizi Liang
(1) Background Metabolic abnormalities and immune inflammation are key elements within pathogenesis of pulmonary arterial hypertension (PAH). And in PAH patients, aberrant glutamine metabolism has been observed; however, the function of glutaminase 1 (GLS1) in macrophage is still unknown. So we aims to investigate GLS1′s impact upon macrophages in PAH. (2) Methods We firstly constructed an monocrotaline (MCT)-induced PAH rat model. Briefly, the PAH rats were treated with the GLS1 inhibitor BPTES, and various index were evaluated, including hemodynamics, right ventricular function, pulmonary vascular remodeling, macrophage markers, and glutamine metabolism. After that, we polarized bone marrow-derived macrophages (BMDMs) into M1 phenotype and then subjected to BPTES intervention. Finally, we assessed macrophage phenotype, inflammatory markers, and glutamine metabolism indicators, along with the impact of BMDM supernatant on the behavior of pulmonary arterial smooth muscle cells (PASMCs). (3) Results : GLS1 was significantly upregulated in both PAH patients and rats. Treatment with the GLS1 inhibitor BPTES markedly improved pulmonary arterial pressure, right ventricular function, and pulmonary vascular remodeling in PAH rats, while inhibiting M1 macrophage polarization, NLRP3 activation, and the release of pro-inflammatory cytokines. This, in turn, alleviated the proliferation and migration of PASMCs induced by inflammatory stimuli. (4) Conclusion : We propose that targeting GLS1 to reduce M1 macrophage polarization and inflammatory responses may represent a promising therapeutic approach for PAH.
研究领域:
心血管疾病
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免疫学
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药理学
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细胞生物学
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代谢
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产品关联
DOI
PubMed
高影响因子
Redox Biology
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2024
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IF 10.7
Wei Li,Qingwen Zeng,Bing Wang,Chao Lv,Haoan He,Xi Yang,Bin Cheng,Xiaoan Tao
Although oxidative stress is closely associated with tumor invasion and metastasis, its’ exact role and mechanism in the initial stage of oral cancer remain ambiguous. Glutamine uptake mediated by alanine-serine-cysteine transporter 2 (ASCT2) participates in glutathione synthesis to resolve oxidative stress. Currently, we firstly found that ASCT2 deletion caused oxidative stress in oral mucosa and promoted oral carcinogenesis induced by 4-Nitroquinoline-1-oxide (4-NQO) using transgenic mice of ASCT2 knockout in oral epithelium. Subsequently, we identified an upregulated gene Thbs1 linked to macrophage infiltration by mRNA sequencing and immunohistochemistry. Importantly, multiplex immunohistochemistry showed M1-like tumor-associated macrophages (TAMs) were enriched in cancerous area. Mechanically, targeted ASCT2 effectively curbed glutamine uptake and caused intracellular reactive oxygen species (ROS) accumulation, which upregulated Thbs1 in oral keratinocytes and then activated p38, Akt and SAPK/JNK signaling to polarize M1-like TAMs via exosome-transferred pathway. Moreover, we demonstrated M1-like TAMs promoted malignant progression of oral squamous cell carcinoma (OSCC) both in vitro and in vivo by a DOK transformed cell line induced by 4-NQO. All these results establish that oxidative stress triggered by ASCT2 deletion promotes oral carcinogenesis through Thbs1-mediated M1 polarization, and indicate that restore redox homeostasis is a new approach to prevent malignant progression of oral potentially malignant disorders.
研究领域:
癌症生物学
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免疫学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
·
IF 6.2
Xueru Wang,Waseem Ali,Kanglei Zhang,Yonggang Ma,Hui Zou,Xishuai Tong,Jiaqiao Zhu,Ruilong Song,Hongyan Zhao,Zongping Liu,Wenxuan Dong
Cadmium (Cd) has adverse effects on organisms. Serine is an essential nutritional factor and its nutritional value is extremely high for body. To explore the effects of serine on spleen toxicity induced by Cd in mice, cadmium chloride (CdCl 2 , 50 mg/L) and serine (50 g/L) were individually administered or co-administrated in drinking water of mice for 18 weeks. Results demonstrated that Cd exposure induced splenic toxicity and serine against the toxicity damage caused by Cd in mice. Under Cd stress, trace element homeostasis was disturbed, the mice's body weight and spleen index were increased, and splenic morphology and ultrastructure were altered. Furthermore, Cd exposure led to the cell populations disorder, which in turn triggers cell death. Notably, Cd treatment induced oxidative stress and inflammation, increased M1/M2 (iNOS, CD68) and Th1/Th2 (T-bet, CD4) levels, decreased M1/M2 (Arg1) and Th1/Th2 (GATA3) levels, while disrupted the macrophages and lymphocytes homeostasis, which trigged apoptosis and pyroptosis in spleen. In contrast, serine supplementation changed the levels of Cd and other elements, weakened Cd-induced tissue damage and inflammation, enhanced antioxidant capacity, significantly restored cell homeostasis, and effectively inhibited Cd-induced apoptosis and pyroptosis in the spleen. Shortly, the results verified that serine had an ameliorating toxicity effect and restored the M1/M2 and Th1/Th2 balance, restrained apoptosis and pyroptosis induced by Cd.
研究领域:
毒理学
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免疫学
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营养科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Jiarui Liu,Siqi Chen,Zijing Zhang,Xitong Song,Zhiquan Hou,Ziyi Wang,Tao Liu,Liqun Yang,Yunen Liu,Zhonghua Luo
Controlling excessive inflammation of acute wound is an effective means to shorten the healing time. Therefore, targeted control of the inflammatory response of the wound is a promising therapeutic strategy. In this study, paeoniflorin (Pae) was encapsulated in microspheres and combined with oxidized hyaluronic acid hydrogels to prepare the hydrogel loaded with Pae microspheres (Pae-MPs@OHA) to promote the healing of acute wounds in rats. The results demonstrated that the particle size of the Pae-MPs was 6.84 ± 0.51 μm, and the positive charge was 26.87 ± 1.51 mV. The uniform spherical structure of the Pae-MPs was observed by TEM. The Pae-MPs@OHA can maintain colloidal state in the range of 0.1–3.16 Hz. FTIR suggested that Pae could be effectively wrapped in MPs, and SEM indicated that the Pae-MPs@OHA had a uniform network pore structure. The Pae-MPs@OHA can realize the sustained release of Pae for 96 h. Biocompatibility experiments showed that the Pae-MPs@OHA hydrogels were safe and available. The Pae-MPs@OHA hydrogels can accelerate wound healing in rats. HE and masson staining suggested that the Pae-MPs@OHA could reduce inflammatory cell infiltration, promote re-epithelialization and collagen formation. The Pae-MPs@OHA could decrease the number of M1 and increase the number of M2 in macrophages, thus regulating the release of inflammatory factor TNF-α and IL-1β. The results of molecular docking and western blot results also confirmed that the Pae-MPs@OHA could reduce the expression of NF-κB, p NF-κB, NLRP3, ASC and pro-caspase-1. These findings suggest that the Pae-MPs@OHA has great potential for application in the treatment of inflammatory wound.
研究领域:
药理学
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生物医学工程
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伤口愈合
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炎症
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2025
·
IF 7.3
Liang Chen,Yuanqing Liu,Chenhao Yu,Pei Cao,Yiming Ma,Yiran Geng,Yu Cai,Yong Zhang,Jia Liu,Yang Li,Qingxian Luan
Background Periodontitis is a chronic inflammatory disease and macrophages play a pivotal role in the progression of periodontitis. Mesenchymal stem cells (MSCs) have emerged as potential therapeutic agents for the treatment of periodontitis due to their immunomodulatory properties and capacity for tissue regeneration. Compared to conventionally derived MSCs, induced pluripotent stem cell-derived MSCs (iMSCs) offer distinct advantages as promising candidates for MSC-based therapies, owing to their non-invasive acquisition methods and virtually unlimited availability. This study aims to investigate the effects and mechanisms of iMSCs in modulating macrophage polarization and alleviating periodontitis-related alveolar bone loss. Methods iMSCs were generated from iPSCs and characterized for differentiation potential. The effects of iMSCs on macrophage polarization were evaluated using THP-1-derived macrophages under inflammatory conditions (LPS and IFN-γ stimulation). Co-culture assays, cytokine analysis, reactive oxygen species (ROS) detection, transcriptomic analysis, flow cytometry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blot analysis were performed to elucidate the underlying mechanisms. The therapeutic potential of iMSCs was assessed in a ligature-induced periodontitis mouse model using micro-CT, histological analysis, and immunofluorescence staining. Results iMSCs inhibit M1 macrophage polarization through the suppression of the NF-κB signaling pathway. Additionally, iMSCs reduce the production of pro-inflammatory cytokines (IL-1β, IL-17) and reactive oxygen species (ROS), while enhancing the secretion of anti-inflammatory cytokines (IL-10) and growth factors (VEGF), thereby improving the inflammatory microenvironment. Under inflammatory conditions, iMSCs preserve the osteogenic potential of periodontal ligament stem cells (PDLSCs) and alleviate alveolar bone loss in mice with periodontitis. In vivo, iMSCs reduce the number of M1 macrophages and inhibit the activation of NF-κB in periodontal tissues, supporting their anti-inflammatory and immunomodulatory effects. Conclusion iMSCs demonstrate significant therapeutic potential in periodontitis by modulating macrophage polarization, reducing oxidative stress, and mitigating alveolar bone loss associated with the disease. These findings provide new insights into the mechanisms of iMSCs and their application as cell-based therapies for periodontal diseases. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-025-04327-0.
研究领域:
口腔医学
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免疫学
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再生医学
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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）