MOLECULAR NEUROBIOLOGY
·
2024
·
IF 4.6
Yu Shan,Yang Jinghui,Zhang Rui,Guo Qian,Wang Lu
Systemic inflammatory stimulus is a risk factor for the incidence of ischemic stroke and contributes to poorer clinical outcomes. Solute carrier 15A3 (SLC15A3) is a peptide/histidine transporter that is implicated in regulating inflammatory responses. However, whether SLC15A3 affects the progression of ischemic stroke associated with systemic inflammation is unclear. The transient middle cerebral artery occlusion (tMCAO) mice with LPS administration (LPS/tMCAO) were prepared as an in vivo model, and LPS-induced BV2 cells under oxygen–glucose deprivation (OGD) exposure were utilized as an in vitro model. We found that SLC15A3 was highly expressed in the ischemic penumbra of LPS/tMCAO mice, and its inhibition reduced infarct area, attenuated neurological deficit, recovered motor function, and mitigated apoptotic neurons. Knockdown of SLC15A3 suppressed the proinflammatory M1-type markers and promoted the levels of M2-associated genes. The in vitro results confirmed that SLC15A3 overexpression promoted microglia polarizing towards M1 subtypes, while SLC15A3 inhibition exerted an opposite effect. In addition, we demonstrated that the p65 signaling pathway and HIF1α were activated by LPS/OGD. Luciferase reporter assay showed that inhibiting p65 using its specific inhibitor BAY 11–7082 or silencing HIF1α using siRNAs reduced the transcriptional activity of SLC15A3 in LPS/OGD-induced BV2 cells. Results in NIH 3T3 cells also confirmed that p65 and HIF1α directly bound to the SLC15A3 promoter to activate SLC15A3 transcription. In conclusion, this work shows that SLC15A3 , transcriptionally activated by p65 and HIF1α, contributes to poor outcomes in ischemic stroke associated with systemic inflammation by promoting microglial cells polarizing towards M1 types.
研究领域:
神经科学
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免疫学
·
分子生物学
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病理生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Chaofan Zhang,Erya Cai,Xiaoliang Qi,XinXin Ge,Yajing Xiang,Jiajia Wang,Ying Li,Lizhang Lv,Hui Zheng,Yuna Qian,Wei Dong,He Li,Jianliang Shen
Current approaches to treating infected pressure ulcers (IPUs) tend to lack specificity. Such injuries frequently exhibit extended inflammation and slow tissue regeneration, largely due to a surplus of M1 macrophages in the impacted regions. While immunomodulatory hydrogels offer potential for targeted IPU care, facilitating a safe and efficient shift from M1 to M2 macrophages continues to be a considerable challenge. The wound's harsh microenvironment—marked by unchecked infections and reactive oxygen species—often undermines the effectiveness of these hydrogels. We unveil a custom-engineered hydrogel dressing specifically designed to have immunomodulatory properties for expediting the healing of IPUs. Consisting of intertwined polymer networks, this hydrogel incorporates gallium (Ga) ions-triggered self-assembled glycyrrhizic acid (GA). Crucially, both in vitro and in vivo examinations, along with RNA sequencing assessments, demonstrate that the Ga/GA combination successfully reduces the M1/M2 macrophage ratio under inflamed circumstances, thereby contributing to improved IPU wound recovery. In summary, our proposed immunomodulatory strategy provides a simple, secure, and highly efficacious method for managing IPUs.
研究领域:
生物医学工程
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药剂学
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伤口愈合
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免疫学
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传染病
✓ 已验证
产品关联
DOI
高影响因子
Cell Death Discovery
·
2023
·Vol. 9
·期 1
·1-11
·
IF 7
Zhang Libo,Ren Zhen,Lü Jinhui,Mo Xinhai,Lin Jie,Li Ya,Ma Wenjing,Liu Pengfei,Shen Yajing,Zhao Qian,Qian Lu,Cheng Xiaoxin,Yu Zuoren,Zhang Bo
Nanomaterials have been well demonstrated to have the potential to be used for tumor cell-targeted drug delivery. Targeted inhibition of miR-221 was proved to promote the sensitivity of triple genitive breast cancer (TNBC) cells to chemo-drugs. In order to improve the chemotherapeutic effect in TNBC, herein, we developed a novel kind of nanoparticles shelled with PLGA and loaded with perfluoropentane (PFP), paclitaxel (PTX), and anti-miR-221 inhibitor, which was named PANP. Ultrasound-triggered vaporization of PFP in PANPs was utilized for real-time imaging track of the nanoparticles in vivo. In addition, macrophages were applied for the internalization of PANPs to form RAW-PANP with strong chemotaxis to accumulate around cancer cells. Nanoparticles with different contents did not cause M2 polarization compared with the control group but caused polarization toward M1. We compared the inherent tumor-homing behavior of macrophages containing different contents with that of normal macrophages and no significant abnormalities were observed. After injection into the tumor-burden mice, RAW-PANPs showed enrichment within tumor tissues. Upon the ultrasound cavitation-triggered burst, PTX was released in the tumor. Meanwhile, the release of anti-miR-221 improved the sensitivity of tumor cells to PTX. As a result, RAW-PANPs showed high efficiency in suppressing TNBC cell proliferation in vitro and inhibiting tumor growth and progression in vivo. The treatments did not induce liver, heart, or kidney injury. In conclusion, the current study not only developed a macrophage-carried, ultrasound-triggered, cancer cell-targeted chemotherapeutic system, but also demonstrated a miRNA-based technique to promote drug sensitivity of cancer cells, which holds strong potential to treat patients with TNBC, especially for those suffering drug-resistance. The innovation of this study is to use macrophages to deliver nanoparticles to the tumors and then use ultrasound locally to burst the nanoparticles to release the miRNA and PTX.
研究领域:
癌症生物学
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药学
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生物医学工程
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纳米技术
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治疗诊断学
✓ 已验证
DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2024
·Vol. 30
·期 7
·e14791
·
IF 4.8
Guangcai Shao,Xiangguo Cui,Yiliang Wang,Shuyan Luo,Chuanyu Li,Yu Jiang,Dasheng Cai,Nu Li,Xiang Li
Introduction Glioblastoma (GBM) remains a challenging brain tumor to treat, with limited response to PD-1 immunotherapy due to tumor-associated macrophages (TAMs), specifically the M2 phenotype. This study explores the potential of MS4A4A (membrane spanning four domains, subfamily A, member 4A) inhibition in driving M2 macrophage polarization toward the M1 phenotype via the ferroptosis pathway to enhance the effectiveness of immunotherapy in GBM. Methods Single-cell RNA sequencing and spatial transcriptomic analyses were employed to characterize M2 macrophages and MS4A4A expression in GBM. In vitro studies utilizing TAM cultures, flow cytometry, and western blot validations were conducted to assess the impact of MS4A4A on the tumor immune microenvironment and M2 macrophage polarization. In vivo models, including subcutaneous and orthotopic transplantation in mice, were utilized to evaluate the effects of MS4A4A knockout and combined immune checkpoint blockade (ICB) therapy on tumor growth and response to PD-1 immunotherapy. Results Distinct subsets of GBM-associated macrophages were identified, with spatial distribution in tumor tissue elucidated. In vivo experiments demonstrated that inhibiting MS4A4A and combining ICB therapy effectively inhibited tumor growth, reshaped the tumor immune microenvironment by reducing M2 TAM infiltration and enhancing CD8 + T-cell infiltration, ultimately leading to complete tumor eradication. Conclusion MS4A4A inhibition shows promise in converting M2 macrophages to M1 phenotype via ferroptosis, decreasing M2-TAM infiltration, and enhancing GBM response to PD-1 immunotherapy. These findings offer a novel approach to developing more effective immunotherapeutic strategies for GBM.
研究领域:
肿瘤学
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免疫学
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神经科学
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分子生物学
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癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Wanru Tian,Xin Zhao,Yao Li,Xuan Cheng,Zheng Yang,Peisen Zhang,Mingxia Jiao,Xiliang Luo
Encephalitis, a severe inflammatory brain condition, poses significant diagnostic challenges due to its heterogeneous symptoms and the limitations of conventional imaging techniques, such as magnetic resonance imaging (MRI), which often fail to detect early or subtle lesions. To address this clinical need, herein, a near-infrared (NIR) optical imaging strategy using engineered silver indium selenide quantum dots (QDs) was developed for precise and early detection of microencephalitic lesions. The QDs were synthesized via a robust aqueous-phase method with optimized NIR emission intensity through suppression of nonradiative recombination pathways. Surface modification with carboxyl-terminated poly(ethylene glycol) (carboxyl-PEG) enhanced colloidal stability, biocompatibility, and selective uptake capabilities by disease-associated M1 macrophages, improving localization at inflammatory sites. In vivo studies demonstrated the outstanding imaging performance of QDs, with encephalitis lesions clearly delineated at ultrahigh spatial resolution, enabling reliable detection of microinflammatory foci as small as 4.6 mm × 5.3 mm. This breakthrough capability facilitates early diagnosis by resolving sub-5 mm lesions, surpassing the sensitivity and resolution of conventional methods for the first time. By providing a noninvasive, high-resolution diagnostic tool, this technology holds potential for improving clinical decision-making and patient outcomes in encephalitis and other neuroinflammatory disorders, particularly in resource-limited settings where early diagnosis remains challenging.
研究领域:
神经免疫学
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分子影像学
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纳米医学
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转化医学
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生物材料
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神经病学
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炎症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CANCER LETTERS
·
2016
·
IF 5.992
Renyu Lin,Ziheng Zhang,Lingfeng Chen,Yunfang Zhou,Peng Zou,Chen Feng,Li Wang,Guang Liang
Head and neck cancer is the sixth most common cancer worldwide. Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, exhibits a wide range of biological roles including a highly efficient and specific anti-tumor activity. Here, we aimed to examine the effect of DHA on head and neck carcinoma cells and elucidate the potential mechanisms. We used five head and neck carcinoma cell lines and two non-tumorigenic normal epithelial cell lines to achieve our goals. Cells were exposed to DHA and subjected to cellular activity assays including viability, cell cycle analysis, cell death, and angiogenic phenotype. Our results show that DHA causes cell cycle arrest which is mediated through Forkhead box protein M1 (FOXM1). We also demonstrate that DHA induces ferroptosis and apoptosis in head and neck carcinoma cells. Lastly, our results show that DHA alters the angiogenic phenotype of cancer cells by reducing the expression of angiogenic factors and the ability of cancer cells to support endothelial cell tubule formation. Our study suggests that DHA specifically causes head and neck cancer cell death through contribution from both ferroptosis and apoptosis. DHA may represent an effective strategy in head and neck cancer treatment.
研究领域:
肿瘤学
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药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2024
·
IF 3.8
Linglian Kong,Peng Sun,Xue Pan,Chuanpi Xiao,Bochen Song,Zhigang Song
ABSTRACT Macrophages play a crucial role in both innate and adaptive immunity. However, their abnormal activation can lead to undesirable inflammatory reactions. This study aimed to investigate the effects of glycerol monolaurate (GML), a natural monoester known for its anti-inflammatory and immunoregulatory properties, on avian macrophages using the HD11 cell line. The results indicated that a concentration of 10 μg/mL of GML enhanced the phagocytic activity of HD11 cells ( P < 0.05) without affecting cell viability ( P > 0.05). GML decreased the expression of M1 macrophage polarization markers, such as CD86 and TNF-α genes ( P < 0.05), while increasing the expression of M2 macrophage polarization markers, such as TGF-β1 and IL-10 genes ( P < 0.05). GML suppressed ROS production, apoptosis, and the expression of proinflammatory genes (IL-1β and IL-6) induced by LPS ( P < 0.05). GML also promoted the expression of TGF-β1 and IL-10 ( P < 0.05), both in the presence and absence of LPS exposure. Moreover, GML suppressed the gene expression of TLR4 and NF-κB p65 induced by LPS ( P < 0.05), as well as the phosphorylation of NF-κB p65 ( P < 0.05). In conclusion, GML exhibited regulatory effects on the polarized state of avian macrophages and demonstrated significant anti-apoptotic and anti-inflammatory properties by suppressing intracellular ROS and the NF-κB signaling pathway.
研究领域:
免疫学
·
细胞生物学
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兽医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-23
·
IF 10.6
Deng Zihan,Yang Chuan,Xiang Tingwen,Dou Ce,Sun Dong,Dai Qijie,Ling Zhiguo,Xu Jianzhong,Luo Fei,Chen Yueqi
Osteoarthritis (OA) is a common degenerative joint disease that can cause severe pain, motor dysfunction, and even disability. A growing body of research indicates that gut microbiota and their associated metabolites are key players in maintaining bone health and in the progression of OA. Short-chain fatty acids (SCFAs) are a series of active metabolites that widely participate in bone homeostasis. Gold nanoparticles (GNPs) with outstanding anti-bacterial and anti-inflammatory properties, have been demonstrated to ameliorate excessive bone loss during the progression of osteoporosis (OP) and rheumatoid arthritis (RA). However, the protective effects of GNPs on OA progression are not clear. Here, we observed that GNPs significantly alleviated anterior cruciate ligament transection (ACLT)-induced OA in a gut microbiota-dependent manner. 16S rDNA gene sequencing showed that GNPs changed gut microbial diversity and structure, which manifested as an increase in the abundance of Akkermansia and Lactobacillus . Additionally, GNPs increased levels of SCFAs (such as butyric acid), which could have improved bone destruction by reducing the inflammatory response. Notably, GNPs modulated the dynamic balance of M1/M2 macrophages, and increased the serum levels of anti-inflammatory cytokines such as IL-10. To sum up, our study indicated that GNPs exhibited anti-osteoarthritis effects via modulating the interaction of “microbiota-gut-joint” axis, which might provide promising therapeutic strategies for OA.
研究领域:
纳米技术
·
风湿病学
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微生物学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Huan Cao,Jianhua Zhang,Lei Yang,Haotian Li,Rong Tian,Haoxing Wu,Yiwen Li,Zhipeng Gu
Apart from bacterial growth and endotoxin generation, the excessive production of reactive radicals linked with sepsis also has a substantial impact on triggering an inflammatory response and further treatment failure. Hence, the rational design and fabrication of robust and multifunctional nanoparticles (NPs) present a viable means of overcoming this dilemma. In this study, we used antibiotic polymyxin B (PMB) and antioxidant natural polyphenolic protocatechualdehyde (PCA) to construct robust and multifunctional NPs for sepsis treatment, leveraging the rich chemistries of PCA. The PMB release profile from the NPs demonstrated pH-responsive behavior, which allowed the NPs to exhibit effective bacterial killing and radical scavenging properties. Data from in vitro cells stimulated with H2O2 and lipopolysaccharide (LPS) showed the multifunctionalities of NPs, including intracellular reactive oxygen species (ROS) scavenging, elimination of the bacterial toxin LPS, inhibiting macrophage M1 polarization, and anti-inflammation capabilities. Additionally, in vivo studies further demonstrated that NPs could increase the effectiveness of sepsis treatment by lowering the bacterial survival ratio, the expression of the oxidative marker malondialdehyde (MDA), and the expression of inflammatory cytokine TNF-α. Overall, this work provides ideas of using those robust and multifunctional therapeutic NPs toward enhanced sepsis therapy efficiency.
研究领域:
纳米技术
·
药学
·
传染病学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Materials
·
2022
·
IF 3.985
Zhu Peijun,Lai Chunhua,Cheng Mingwei,He Yiheng,Xu Yan,Chen Jiahao,Zhou Zhengnan,Li Ping,Xu Shulan
A biomaterial-mediated immune response is a critical factor to determine the cell fate as well as the tissue-regenerative outcome. Although piezoelectric-membranes have attracted considerable interest in the field of guided bone regeneration thanks to their biomimetic electroactivity, the influence of their different surface-charge polarities on the immune-osteogenic microenvironment remains obscure. The present study aimed at investigating the interaction between piezoelectric poly (vinylidene fluoridetrifluoroethylene) [P (VDF-TrFE)] membranes with different surface polarities (negative or positive) and macrophage response, as well as their subsequent influence on osteogenesis from an immunomodulating perspective. Specifically, the morphology, wettability, crystal phase, piezoelectric performance, and surface potential of the synthetic P (VDF-TrFE) samples were systematically characterized. In addition, RAW 264.7 macrophages were seeded onto differently charged P (VDF-TrFE) surfaces, and the culture supernatants were used to supplement cultures of rat bone marrow mesenchymal stem cells (rBMSCs) on the corresponding P (VDF-TrFE) surfaces. Our results revealed that oppositely charged surfaces had different abilities in modulating the macrophage-immune-osteogenic microenvironment. Negatively charged P (VDF-TrFE), characterized by the highest macrophage elongation effect, induced a switch in the phenotype of macrophages from M0 (inactivated) to M2 (anti-inflammatory), thus promoting the osteogenic differentiation of rBMSCs by releasing anti-inflammatory cytokine IL-10. Interestingly, positively charged P (VDF-TrFE) possessed pro-inflammatory properties to induce an M1 (pro-inflammatory) macrophage-dominated reaction, without compromising the subsequent osteogenesis as expected. In conclusion, these findings highlighted the distinct modulatory effect of piezoelectric-P (VDF-TrFE) membranes on the macrophage phenotype, inflammatory reaction, and consequent immune-osteogenic microenvironment depending on their surface-charge polarity. This study provides significant insight into the design of effective immunoregulatory materials for the guided bone regeneration application.
研究领域:
生物材料
·
组织工程
·
免疫学
·
再生医学
·
骨科
✓ 已验证
DOI
高影响因子
Journal of Materials Chemistry B
·
2023
·
IF 7
Yongli Gao,Wenling Dai,Shikui Li,Xingchen Zhao,Jing Wang,Weili Fu,Likun Guo,Yujiang Fan,Xingdong Zhang
Collagen and hyaluronic acid are commonly applied in cartilage tissue engineering, yet there has been limited investigation into their inflammatory response, a crucial factor in articular cartilage repair. This study aimed to evaluate the impact of components and physical properties of hydrogels on inflammatory response and cartilage repair. Three kinds of hydrogels with comparable storage modulus at low frequencies were designed and fabricated, namely methacrylic anhydride modified hyaluronic acid hydrogel (HAMA), methacrylic anhydride modified type I collagen hydrogel (CMA) and unmodified type I collagen hydrogel (Col). HAMA hydrogel was unfavorable for adhesion and spreading of BMSCs. Furthermore, HAMA hydrogel stimulated rapid migration and pro-inflammatory M1 polarization of macrophages, leading to persistent and intense inflammation, which was unfavorable for cartilage repair. CMA and Col hydrogels possessed the same component and facilitated the adhesion, spreading and proliferation of BMSCs. Compared with CMA hydrogel, Col hydrogel induced rapid migration and moderate M1 polarization of macrophages at the early stage of injury, which was mainly influenced by its fast dissolution rate, small pore size fiber network structure and rapid stress relaxation. In addition, phenotype of macrophages timely transformed to anti-inflammatory M2 due to the property of collagen component, which shortened the duration of inflammation and enhanced cartilage repair. The results indicated that moderate macrophage activation modulated by hydrogel components and physical properties was critical in modulating inflammation and cartilage regeneration.
研究领域:
组织工程
·
生物材料
·
炎症
·
软骨再生
✓ 已验证
DOI
PubMed
高影响因子
BIOCONJUGATE CHEMISTRY
·
2024
·
IF 4
Yanian Xiong,Yingtung Lo,Huizhu Song,Jianzhong Lu
The penetration ability of visible light (<2 mm) and near-infrared (NIR) light (∼1 cm) remarkably impairs the therapeutic efficacy and clinical applications of photodynamic therapy (PDT). To address the limitation of light penetration depth, a novel self-luminescent bacterium, teLuc.FP-EcN, has been engineered through transfection of a fusion expression plasmid containing the luciferase gene teLuc and bright red fluorescent protein mScarlet-I into Escherichia coli Nissle 1917 (EcN). The engineered teLuc.FP-EcN can specifically target and colonize tumors without significant toxicity to the host. Acting as a continuous internal light source, teLuc.FP-EcN can activate the photosensitizer chlorin e6 (Ce6) to generate reactive oxygen species (ROS) and then effectively destroy tumor tissue from the inside. As a result, a significant reduction in tumor proliferation and extension of the overall survival in mouse tumor models has been observed. Furthermore, teLuc.FP-EcN-boosted PDT amplified its therapeutic effect by activating antitumor immune response, including the conversion of M2 macrophages into pro-inflammatory M1 macrophages, as well as an increase in the proportion of CD3+ T cells and a decrease in T-cell exhaustion. In conclusion, teLuc.FP-EcN can be used as an implantable light source for tumor phototherapy, which simultaneously possesses ROS generation and immune regulation.
研究领域:
生物技术
·
癌症研究
·
治疗学
·
免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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