ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Li Zhang,Shuai Cui,Ning Ding,Jing Zhang,Enna Cui,Qian Xiang,Zhenghao Zhou,Bo Sun,Yinan Wang,Hao Hong,Yunsu Ma,Dongzhi Yang
Tumor-associated macrophages (TAMs) play a critical role in tumor progression and metastasis. Modulation of TAM polarization is one of the most effective strategies to change the immunosuppressive tumor microenvironment (TME). In this study, organic polymer nanoparticles (CPHT) were prepared using hyaluronic acid (HA)-conjugated disulfide-bonded polyethylene imide (PEIS) as a carrier through a self-assembly strategy. These nanoparticles were modified by transferrin (Tf) and loaded with chlorin e6 (Ce6). The results showed that CPHT had good dispersion with a particle size of about 30 nm. CPHT gradually disintegrated under the exposure with a high concentration of glutathione (GSH) in tumor cells, proving the possibility for the controlled release of Ce6 and photodynamic therapy. An in vitro test showed that the uptake of CPHT in tumor cells was mediated by both HA and Tf, indicating the active tumor-targeting capacity of CPHT. CPHT significantly downregulated the ratio of CD206/CD86 and triggered the upregulation of immune factors such as TNF-α and iNOS, suggesting the repolarization of TAMs. We also found that CPHT effectively induced ferroptosis in tumor cells through lipid peroxide accumulation, GSH depletion, and downregulation of lipid peroxidase (GPX4) expression. Animal experiments confirmed that CPHT not only effectively inhibited the growth of tumors in situ but also significantly decelerated the growth of the distal tumor. Elevated levels of CD86 and IFN-γ and decreased expression of CD206 were observed at the tumor sites post CPHT treatment. These results confirmed the value of CPHT as a multifunctional nanoplatform that can tune the TME and provide new hope for tumor treatment.
研究领域:
癌症生物学
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纳米技术
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药学
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免疫学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2023
·
IF 3.1
Yang Ding,Shengyun Wan,Long Ma,Kaikai Wei,Kun Ye
Hindlimb ischemia (HLI) is an arterial occlusive disease that exposes the patients to the risk of limb gangrene and loss. Polarization of macrophages is related to HLI-induced inflammation. Period circadian regulator 1 (PER1) is a core component of the circadian clock. We first showed, based upon bioinformatics analysis of microarray data, that PER1 expression was reduced in monocytes from patients with critical limb ischemia. The proximal femoral artery in the left hindlimb of male mice was ligated and then the femoral artery and its collateral branches were removed to establish the HLI mouse model. After modeling, a single intramuscular injection of 1 × 10 9 pfu Ad-PER1 was performed at the adductor and gastrocnemius muscles. The gastrocnemius muscle tissues were collected at day 0, 3, 7, 14, 21 post-HLI. There was obvious pathological necrosis, accompanied with reduced expression of PER1 in the muscle tissues of HLI mice. Expression of CD68 and CD31 seemed to be corresponded to PER1 in gastrocnemius muscle, implying the potential of PER1 in regulating macrophage-related inflammation and angiogenesis . PER1 overexpression diminished myocyte damage, promoted blood flow restoration and improved behavioral scores of HLI mice. Immunostaining of CD31 and α-SMA revealed that PER1 upregulation reversed HLI-induced decreases in capillary and arteriole density. In vitro, RAW264.7 cells were cultured in hypoxia (1% O 2 ) for 24 h. The percentage of pro-inflammatory CD86 + macrophages (M1 type) was decreased and that of anti-inflammatory CD206+ macrophages (M2 type) was increased when PER1 was overexpressed. Moreover, the expression levels of TNF-α, IL-6 and M1-type marker iNOS were decreased, and levels of IL-10 and M2-type marker Arg-1 were increased by PER1 in gastrocnemius muscle of HLI mice and hypoxia-treated RAW264.7 cells. PER1 might reduce M1 macrophage polarization and promote M2 macrophage polarization, and thus exert anti-inflammatory and pro-angiogenic actions. Our findings suggest that PER1 overexpression promotes functional recovery of mice with HLI through regulating macrophage polarization.
研究领域:
心脏病学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yu Liu,Meng Zhu,Jinzhao Ou,KeJia Li,Xiaoyan Ju,Ye Tian,Zhongwei Niu
Oxidative stress caused by excessive reactive oxygen species (ROS) accumulation significantly hinders wound healing in patients with diabetes. Scavenging ROS and reducing inflammation are crucial for rapid healing. In this work, a multi-responsive sodium hyaluronate (HA)/tannic acid (TA) hydrogel was developed based on boronate ester bonds. Sodium hyaluronate with 3-aminophenyl boronic acid modification (HA-APBA) was mixed and crosslinked with TA to form HA-APBA/TA hydrogels. These hydrogels are injectable, self-healing, and biocompatible. The HA-APBA/TA hydrogels could release free TA through the collapse of the structure at low pH, high H 2 O 2 concentration, and high glucose concentration, thus possessing good ROS scavenging ability. In full-thickness skin wounds of db/db mice, the HA-APBA/TA hydrogels promoted wound healing, collagen deposition, and significant angiogenesis. Furthermore, they have been shown to effectively reduce the levels of inflammatory factors in wounds and lower the expression of CD86, a pro-inflammatory macrophage surface marker. This resulted in a more effective transition of wound healing from the inflammatory phase to the proliferative phase. This study provides an optional strategy for alleviating oxidative stress and controlling excessive inflammation, thereby promoting diabetic wound healing.
研究领域:
材料科学
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生物材料
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药学
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伤口愈合
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糖尿病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Qingxia Yuan,Rongyi Liang,Kunling Lv,Xiaohuo Shi,Jing Leng,Yonghong Liu,Jian Xiao,Lifeng Zhang,Longyan Zhao
Chlorella polysaccharides have been gaining increasing attention because of their high yield from dried Chlorella powder and their remarkable immunomodulatory activity. In this study, the major polysaccharide fraction, CPP-3a, in Chlorella pyrenoidosa , was isolated, and its detailed structure was investigated by analyzing the low-molecular-weight product prepared via free radical depolymerization. The results indicated that CPP-3a with a molecular weight of 195.2 kDa was formed by →2)-α-L-Ara f -(1→, →2)-α-D-Rha p -(1→, →5)-α-L-Ara f -(1→, →3)-β-D-Glc p- (1→, →4)-α-D-Glc p- (1→, →4)-α-D-Glc p A-(1→, →2,3)-α-D-Man p- (1→, →3,4)-α-D-Man p- (1→, →3,4)-β-D-Gal p- (1→, →3,6)-β-D-Gal p- (1→, and →2,3,6)-α-D-Gal p- (1→ residues, branched at C2, C3, C4, or C6 of α/β-D-Gal p and α-D-Man p , and terminated by α/β-L-Ara f , α-L-Ara p , α-D-Gal p , and β-D-Glc p . Biological assays showed that CPP-3a significantly altered the dendritic morphology of immature dendritic cells (DCs). Enhanced CD80, CD86, and MHC I expression on the cell surface and decreased phagocytic ability indicated that CPP-3a could induce the maturation of DCs. Furthermore, CPP-3a-stimulated DCs not only stimulated the proliferation of allogeneic naïve CD4 + T cells and the secretion of IFN-γ, but also directly stimulated the activation and proliferation of CD8 + T cells through cross-antigen presentation. These findings indicate that CPP-3a can promote human DC maturation and T-cell stimulation and may be a novel DC maturation inducer with potential developmental value in DC immunotherapy.
研究领域:
免疫学
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生物化学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EMBO Molecular Medicine
·
2025
·
IF 8.3
FengShengyong,MaEnhao,NaXiaona,WangZongmei,TaiWanbo,BaoXinhui,WangMao,ChangHan,WuBaolei,LiuMiaoxi,LiJuzhen,ShiHuicheng,YangCeli,XiMenglu,YangHaibing,LiYuhan,ZhuYibin,WangPenghua,ZhaoLing,ZhaoAi,ChengGong
Vaccination offers the most effective protection against contagious infectious diseases primarily by inducing humoral immunity. Vaccination efficacy is influenced by various factors. We report that dietary administration of arachidonic acid (ARA) significantly boosts rabies vaccine-induced production of neutralizing antibodies and protection against lethal rabies virus (RABV) infection in mice. In human volunteers, oral supplementation of ARA accelerates the expression of neutralizing antibodies to the levels sufficient for protection against RABV as early as one week after primary immunization. Mechanistically, ARA is enriched in lymph nodes and metabolized into immune modulators there. One of the ARA metabolites, prostaglandin I2 (PGI2), via the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) axis, upregulates the expression of costimulatory molecule CD86, and activates activation-induced cytidine deaminase (AID) in B cells. These results suggest that ARA can be a potent dietary adjuvant to foster germinal center (GC) B cell response and humoral immunity.
研究领域:
免疫学
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营养科学
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病毒学
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疫苗研究
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产品关联
DOI
PubMed
高影响因子
MOLECULAR MEDICINE
·
2025
·Vol. 31
·期 1
·1-11
·
IF 6.4
Liu Miao,Xie Wen-jie,Zhang Xu,Wu Wei,Li Guang,Wang Lu
Background Macrophages play an important role in the pathogenesis of ulcerative colitis (UC). We will explore the effects of sodium butyrate (SB) on macrophage function.Methods The targets of butyric acid were identified using SwissTargetPrediction database and surface plasmon resonance (SPR). Limited proteolysis mass spectrometry (Lip-MS) was used to further investigate the binding sites of butyric acid with its targets and molecular docking was employed to simulate their binding modes. Macrophage polarization model was established with lipopolysaccharide (LPS) in vitro. Takeda G protein-coupled receptor 5 (TGR5) and β-arrestin2 expression and macrophage polarization markers were detected with or without SB.Results TGR5 was identified as the target of butyric acid. Moreover, the amino acid regions 275–286 and 321–330 of TGR5 (GPBAR1 [275–286] and GPBAR1 [321–330]) were the potential binding regions for butyric acid. Based on molecular docking analysis, butyric acid formed effective hydrogen-bonding interactions with ASP-284 and TYR-287 of TGR5. In cell experiments, LPS inhibited the expression of TGR5, β-arrestin2, IL-10, ARG1, and CD206 and increased the expression of IL-1β, iNOS, and CD86, while SB reversed the effect of LPS. SBI-115, a TGR5 antagonist, and knockdown of β-arrestin2 inhibited the effect of sodium butyrate. INT-777, a TGR5 agonist, reversed the inhibitory effect of knockdown of β-arrestin2.Conclusion SB inhibited M1-like polarization and promoted M2-like polarization induced by LPS via TGR5/β-arrestin2 in RAW264.7 cells and TGR5 was the target of SB.
研究领域:
免疫学
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药理学
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胃肠病学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2020
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IF 8.724
Xiaoge Zhang,Junjie Tang,Chao Li,Yao Lu,Lili Cheng,Jie Liu
Photo-immunotherapy is a novel therapeutic approach against malignant tumors with minimal invasiveness. Herein, a targeting multifunctional black phosphorus (BP) nanoparticle, modified by PEGylated hyaluronic acid (HA), was designed for photothermal/photodynamic/photo-immunotherapy. In vitro and in vivo assays indicated that HA-BP nanoparticles possess excellent biocompatibility, stability, and sufficient therapeutic efficacy in the combined therapy of photothermal therapy (PTT) and photodynamic therapy (PDT) for cancer therapy. Moreover, the results of in vitro showed that HA-BP down-regulated the expression of CD206 (M2 macrophage marker) by 42.3% and up-regulated the ratio of CD86（M1 macrophage marker）by 59.6%, indicating that HA-BP nanoparticles have functions in remodeling tumor associated macrophages (TAMs) phenotype (from pro-tumor M2 TAMs to anti-tumor M1 macrophages). Fluorescence (FL) and photoacoustic (PA) multimodal imaging confirmed the selective accumulation of HA-BP in tumor site via both CD44 + mediated active targeting and passive EPR effect. In vitro and in vivo studies suggested that the combined therapy of PDT, PTT and immunotherapy using HA-BP could not only significantly inhibit original tumor but also induce immunogenic cell death (ICD) and release Damage-associated molecular patterns (DAMPs), which could induce maturation of dendritic cells (DCs) and activate effector cells that robustly evoke the antitumor immune responses for cancer treatment. This study expands the biomedical application of BP nanoparticles and displays the potential of modified BP as a multifunctional therapeutic platform for the future cancer therapy.
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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免疫学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Yang Gao,Shi-Qiao Liu,Jia-Long Wang,Han-Ming Cui,Qiu-Yan Zhang,Lei Wang,Yi-Xin Zhang,Jian Li,Yu Dong,Yuan-Hui Hu
Ethnopharmacological relevance Sanhuang Xiexin Decoction (SHXD), consisting of Coptis chinensis Franch., Scutellaria baicalensis Georgi and Rheum palmatum L. , is t raditionally used for relieving fever, purging fire for removing toxins, eliminating phlegm and haemostasis, eliminating the wetness-evil from the upper warmer, clearing away the heat-evil and expelling superficial evils. Each of the three herbs contained in SHXD has been indicated to have anti-inflammatory effects in vivo , but its effects on rat NK-cell phenotypes remain unexplored, and the comprehensive mechanism of this compound SHXD in curing the inflammation induced by lipopolysaccharides (LPS) remains to be revealed. Aim of the study The study aim was to assess the effect of SHXD on LPS-induced fever and inflammation in a rat model, reduce NLRP3 activation in NK cells expressing specific cell phenotype antibodies and determine the therapeutic value of this approach in vivo . Materials and methods SHXD extract was prepared and analysed by the developed ultra-performance liquid chromatography (UPLC) method for the simultaneous detection of 14 compounds. The main peaks were firstly identified on an Orbitrap via high resolution tandem mass spectrometry (MS). Then, the extract was used in the rat model of LPS-induced inflammation and fever for pharmacologically study the effects of drug treatment. Peripheral blood lymphocyte cells were isolated from the animals, including those subjected to the SHXD extract treatment, and the cell phenotype was determined prior to cell culture and after treating the cell cultures with the extract. The phenotypes of cells harvested using CD3, CD4, CD8a, CD81, CD161 and CD86 antibodies were used to verify the enhanced memory of the peripheral blood lymphocytes cells (PBMC) that were induced into nature killer (NK) cells. Results The SHXD extract was prepared, analysed and identified via quality control equipment and was observed to have pharmacological effects that reduced NLRP3 activation and fever in rats. The production of NK cells and peripheral blood lymphocytes was induced by the SHXD extract, which manifested as increased levels of CD4 + , CD8a+, CD81 + , CD161+ and CD86 + cells. The levels of CD3 + cells were significantly different between the model group and the drug-treated or control groups (p < 0.01) with dose independence, while the levels of CD4 + cells were not significantly different between the drug-treated and control groups, with a trend towards lower levels in the model group with dose independence. The levels of CD4 + cells was significantly different between the drug-treated group and the model groups with dose independence (p < 0.05). The levels of CD86 + cells were not significantly different between the drug-treated group and the model and control groups. The levels of CD8a + cells was significantly different between the model group and the drug and control groups (p < 0.05, dose 2.0 μg/ml), with higher levels in the drug-treated group. The levels of CD3 + , CD4 + , CD8a + cells in the drug treated group have dose dependence with SHXD. Conclusions This experiment revealed that SHXD reduced NLRP3 activation in the blood of LPS-treated rats, which occurred through the activation of NK cells that expressed CD3, CD8a and CD161. SHXD may possess anti-inflammatory effect via activacting the one of major pharmacology effcet of NK cells that expressed CD3, CD8a and CD161 phenotypes expression. This result demonstrates that SHXD may possess ability to enhance the memory of peripheral blood lymphocytes and natural killer cells.
研究领域:
药理学
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免疫学
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分析化学
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中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2023
·Vol. 51
·期 08
·2157-2173
·
IF 5.7
Zhenfeng Liu,Wuming Zhou,Qingyang Liu,Zhirong Huan,Qiubo Wang,Xin Ge
Hemorrhagic shock (HS) is the leading cause of death in trauma patients. Inflammation following HS can lead to cardiac damage. Pachymic acid (PA), a triterpenoid extracted from Poria cocos , has been found to possess various biological activities, including anti-inflammatory and anti-apoptotic properties. Our research aims to investigate the protective effects of PA against HS-induced heart damage and the underlying mechanisms involved. Male Sprague-Dawley rats were intraperitoneally injected with PA (7.5 or 15 mg/kg) daily for three days. Subsequently, we created a rat model of HS by drawing blood through a catheter inserted into the femoral artery followed by resuscitation. The results revealed that HS led to abnormalities in hemodynamics, serum cardiac enzyme levels, and cardiac structure, as well as induced cardiac apoptosis. However, pretreatment with PA effectively alleviated these effects. PA-pretreatment also suppressed mRNA and protein levels of interleukin (IL)-1 β , IL-6, and tumor necrosis factor α (TNF- α ) in the heart tissues of HS rats. Additionally, PA-pretreatment reduced inflammatory cell infiltration and M1 macrophage polarization while exaggerating M2 polarization in HS rat hearts. The study observed a decreased proportion of the expression of of M1 macrophages (CD86 + ) and their marker (iNOS), along with an increased proportion of the expression of M2 macrophages (CD206 + ) and their marker (Arg-1). Notably, PA-pretreatment suppressed NF- κ B pathway activation via inhibiting NF- κ B p65 phosphorylation and its nuclear translocation. In conclusion, PA-pretreatment ameliorates HS-induced cardiac injury, potentially through its inhibition of the NF- κ B pathway. Therefore, PA treatment holds promise as a strategy for mitigating cardiac damage in HS.
研究领域:
药理学
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免疫学
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心脏病学
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病理生理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Liqun Jiang,Ziyao Wang,Yan Wang,Shuo Liu,Ya Xu,Cong Zhang,Lei Li,Sujia Si,Bingmei Yao,Wenjin Dai,Huiyang Li
The re-education of tumor-associated macrophages (TAMs) is an effective strategy to inhibit the growth and metastasis of lung cancer. We have reported that chitosan could re-educate the TAMs and then inhibit cancer metastasis; however, the re-exposure of chitosan from the chemical corona on their surface is critical for this effect. In this study, a strategy was proposed to re-expose the chitosan from chemical corona, and a sustained H 2 S generation was applied to enhance the immunotherapy of chitosan. To achieve this objective, an inhalable microsphere (namely F/Fm) was designed, which could be degraded by the matrix metalloproteinase in lung cancer, releasing two kinds of nanoparticles ; in an external magnetic field, these nanoparticles can aggregate with each other, and β-cyclodextrin on the surface of one nanoparticle can be hydrolyzed by amylase on the surface of another nanoparticle, leading to the re-exposure of chitosan in the inner layer of β-cyclodextrin and the release of diallyl trisulfide for H 2 S generation. In vitro , the expression of CD86 and secretion of TNF-α by TAMs was increased by F/Fm, proving the re-education of TAMs, and the apoptosis of A549 cells was promoted with the migration and invasion being inhibited. In the Lewis lung carcinoma-bearing mouse, the F/Fm re-educated the TAMs and provided a sustained generation of H 2 S in the region of lung cancer, effectively inhibiting the growth and metastasis of lung cancer cells. This work provides a new strategy for the treatment of lung cancer in combination of re-education of TAMs by chitosan and the adjuvant chemotherapy by H 2 S.
研究领域:
癌症生物学
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药学
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纳米技术
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
·
2024
·
IF 4.3
Can Wang,Yihang Yang,Ruming Liang,Shikui Wu,Chengrui Xuan,Wei Lv,Jian Li
We successfully prepared mercury sulphide nanoparticle hydrogels by physical encapsulation method. The successfully prepared mercuric sulphide nanoparticle hydrogel was a zinc folate hydrogel, which showed an obvious porous structure with interconnected and uniformly distributed pores and a pore size range of about 20 μm. The maximum drug loading of the hydrogels was 3%, and the in vitro cumulative release degree was in accordance with the first-order kinetic equation Mt = 149.529 (1 − e−0.026t). The particles in mercuric sulphide nanoparticle hydrogels significantly down-regulated the expression of the cell surface co-stimulatory molecule CD86 (p < .0001). Meanwhile, the inflammatory response was regulated through the NF-κB pathway in LPS-induced inflammatory cells. Later, it was observed that mercuric sulphide nanoparticle hydrogels could significantly counteract the inflammatory and immune models through a mouse ear swelling model, a rat foot-plantar swelling model and a rheumatoid arthritis model. This design targets the immunomodulatory, and anti-inflammatory effects through nanocomposite hydrogel technology. It reduces the drawbacks of low mercury utilisation and susceptibility to accumulation of toxicity. It aims to provide an experimental basis for the development of mercuric sulphide and the treatment of inflammatory and immune-related diseases.
HighlightsMercury sulphide nanoparticle hydrogel has an optimal mercury sulphide nanoparticle content of 2%, is structurally homogeneous and stable, and does not exhibit significant liver or kidney toxicity.Mercuric sulphide nanoparticle hydrogel exerts anti-inflammatory effects in cells and rats, and regulates the expression of macrophage surface molecules and factors related to the NF-κB pathway.Mercuric sulphide nanoparticle hydrogel improves the condition of ankle synovial joints in a rat model of rheumatoid arthritis.
研究领域:
纳米技术
·
药学
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免疫学
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PeerJ
·
2024
·
IF 2.3
Junli Du,Chao Chen,Jie Chen
Background Cirsilineol is a trimethoxy and dihydroxy flavonoid isolated from plant species such as Artemisia vestita and has a variety of pharmacological properties. This study analyzed whether cirsilineol could prevent postoperative cognitive dysfunction (POCD). Methods A POCD mouse model induced by anesthesia/surgery induction and a cell model established with hydrogen peroxide (H 2 O 2 )-induced microglia BV-2 were employed to explore the efficacy of cirsilineol on POCD. The cognition function of the mice were assessed by carrying out behavioral tests (Morris water maze test and Y-maze test). We assessed the activation and polarization status of microglia using immunofluorescence analysis and detected the expression levels of CD86 and CD206 using the quantitative PCR (qPCR). Subsequently, cell viability was determined by CCK-8 assay and apoptosis was assessed using Calcein-AM/PI staining. Meanwhile, superoxide dismutase (SOD) and malondialdehyde (MDA) levels in plasma and cell culture medium were detected using chemiluminescence. Finally, the phosphorylation levels of JAK/STAT signaling pathway-related proteins were analyzed by Western blot. Results Cirsilineol reduced the escape latency and times of crossing island and increased spontaneous alternation (SA) rate, restoring the cognitive dysfunctions of POCD-modeled mice. Meanwhile, POCD elevated CD86 expression and malondialdehyde content and lowered the level of SOD; however, cirsilineol promoted CD206 expression and generation of SOD and inhibited malondialdehyde production. In H 2 O 2 -induced microglia BV-2, cirsilineol treatment increased SOD content and suppressed the generation of reactive oxygen species (ROS) and malondialdehyde, modulating microglia M1/M2 polarization and JAK/STAT pathway. Conclusion Cirsilineol prevented against POCD by attenuating oxidative stress and modulating microglia M1/M2 polarization, providing novel insights for the management of POCD.
研究领域:
药理学
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神经科学
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外科手术
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分子生物学
✓ 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）