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ENVIRONMENTAL TOXICOLOGY · 2022 ·Vol. 37 ·期 12 ·2844-2854 · IF 4.109

Molybdenum and cadmium co-exposure promotes M1 macrophage polarization through oxidative stress-mediated inflammatory response and induces pulmonary fibrosis in Shaoxing ducks (Anas platyrhyncha)

Gang Huang,Junrong Luo,Huiling Guo,Xueru Wang,Zhisheng Hu,Wenjing Pu,Xuesheng Chu,Caiying Zhang

High molybdenum (Mo) and cadmium (Cd) are harmful to the body, but pulmonary toxicity induced by Mo and Cd co-exposure is unknown. To assess the combined impacts of Mo and Cd on fibrosis through M1 polarization in the lung of ducks, 80 healthy 8-day-old Shaoxing ducks ( Anas platyrhyncha ) were randomly assigned to 4 groups and fed with containing unequal doses of Mo or/and Cd diet. Lung tissues were collected on the 16th week. Results indicated that Mo or/and Cd significantly increased their contents in the lungs, and led to trace elements disorder and histological abnormality, and oxidative stress accompanied by promoting contents of H 2 O 2 and MDA and decreasing activities of T-SOD, GSH-Px, and CAT, then activated the TLR4/NF-κB/NLRP3 pathway accompanied by upregulating Caspase-1, ASC, IL-18, IL-1β, TLR4, NF-κB, and NLRP3 expression levels, and disrupted M1/M2 balance to divert toward M1, which evoked the TGF-β/Smad2/3-mediated fibrosis by elevating TGF-β1, Smad2, Smad3, COL1A1, α-SMA, and MMP2 expression levels, and decreasing Smad7 and TIMP2 expression levels. The changes of the combined group were most obvious. To sum up, the research demonstrated that Mo or/and Cd may cause macrophages to polarize toward M1 by oxidative stress-mediated the TLR4/NF-κB/NLRP3 pathway, then result in fibrosis through the TGF-β1/Smad2/3 pathway in duck lungs. Mo and Cd may worsen lung damage.

研究领域: 毒理学 · 免疫学 · 肺科学 · 动物科学
✓ 已验证 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2024 · IF 8

Dendritically hybrid-DNA double fluorescence amplification technology ultra-sensitive detection of AFM1 in food

Yue Hou,Zensheng Liu,Shuyue Ren,Shuang Li,Kang Qin,Yuan Peng,Yu Wang,Dianpeng Han,Shiping Yang,Huanying Zhou,Zhixian Gao

Aflatoxins are highly carcinogenic and mutagenic. Among them, aflatoxin M1 (AFM1) is a hydroxylated metabolite that seriously poses threats to human health and safety, so there is a need to construct an efficient and sensitive detection system for AFM1. In this study, an analytical method was established for ultra-sensitive determination of AFM1 in food based on dendritic hybridization chain reaction (HCR) dual-amplification. The prepared carboxylated silica was modified with AFM1 antibody, dendritic (S) chain and initiator (H0) chain as fluorescent probes, the whole AFM1 antigen was coated on the microplate, and the antibody on the fluorescent probes competed with the AFM1 standard for binding to the whole antigen. Then the fluorescence response value of the supernatant was measured, which displayed a good linear relationship with the standard concentration. The detection range was 10 pg/mL-10 μg/mL, and the limit of detection was 5.41 fg/mL, which was in line with the limit value of China's national standard. In addition, the spiked recovery rate was between 84.77% and 115.70%. The method developed in this study displays an increase of three orders of magnitude in comparison with indirect competitive enzyme-linked immunosorbent assay (ic-ELISA), in the detection of AFM1, showing ultra-high sensitivity, which satisfies the needs of AFM1 analysis and detection in food. This biosensing method also has reference value for the detection of other toxins in food.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 食品科学 · 分析化学 · 毒理学 · 生物技术
✓ 已验证 产品关联 DOI 高影响因子
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PHYTOTHERAPY RESEARCH · 2022 ·Vol. 36 ·期 4 ·1678-1691 · IF 6.388

Kaempferol exerts a neuroprotective effect to reduce neuropathic pain through TLR4/NF-ĸB signaling pathway

Shiquan Chang,Xin Li,Yachun Zheng,Huimei Shi,Di Zhang,Bei Jing,Zhenni Chen,Guoqiang Qian,Guoping Zhao

Switching microglial polarization from the M1 to M2 phenotype is a promising therapeutic strategy for neuropathic pain (NP). Toll-like receptor 4 (TLR4) is activated by lipopolysaccharide (LPS). Uncontrolled activation of TLR4 has been proven to trigger chronic inflammation. Kaempferol, a dietary flavonoid, is known to have anti-inflammatory properties. This study is aimed to investigate the analgesic and anti-inflammatory effects and the underlying mechanisms of kaempferol, which were explored with an NP model in vivo and LPS-induced injury in microglial BV2 cells in vitro. The levels of proinflammatory cytokines were evaluated. H&E staining and immunohistochemistry were used to assess the sciatic nerve condition after chronic constriction injury surgery. Western blotting and immunofluorescence were used to determine whether TLR4/NF-ĸB signaling pathway plays a major role in kaempferol-mediated alleviation of neuroinflammation. Quantitative real-time polymerase chain reaction and flow cytometry were used to examine the modulator effect of kaempferol on microglial M1/M2 polarization. We found that kaempferol treatment can significantly reduce NP and proinflammatory cytokine production. Kaempferol attenuated the activation of TLR4/NF-κB pathways in LPS-activated BV2 cells. The analgesic effects of kaempferol on NP may be due to inhibition of microglia activation and switching the M1 to M2 phenotype.

CAS / MDL: 520-18-3
研究领域: 神经科学 · 药理学 · 炎症 · 疼痛管理
✓ 已验证 产品关联 DOI PubMed 高影响因子
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GENES AND IMMUNITY · 2024 · IF 5

Neu5Gc regulates decidual macrophages leading to abnormal embryo implantation

Yue Wu,Huiling Zhou,Yuxin Liu,Ling Wang,Feng Gao,Qicai Liu

Repeated implantation failure (RIF) is one of the most prominent problems in the field of assisted reproduction. Neu5Gc on the surface of decidual macrophages (dMΦ) leads to different activation patterns of dMΦ, which affects embryo implantation and development. Cmah −/− (Neu5Gc-deficient) mice induced to produce anti-Neu5Gc antibodies in vivo were given a special diet rich in Neu5Gc and their fertility was monitored. The long-term diet rich in Neu5Gc induced the decrease of endometrial receptivity of female mice. The pregnancy rate of female mice fed the normal diet was 63.6% ( n  = 11) and the average number of embryos was 9.571 ± 1.272, while the pregnancy rate of female mice fed the diet rich in Neu5Gc was 36.4% ( n  = 11) and the average number of embryos in pregnant mice was 5.750 ± 3.304. The intake of Neu5Gc and the production of anti-Neu5Gc antibody led to M1 polarization of endometrial dMΦ and abnormal embryo implantation.

CAS / MDL: 1113-83-3
研究领域: 生殖生物学 · 免疫学 · 胚胎学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2019 · IF 3.973

Titania nanotubes promote osteogenesis via mediating crosstalk between macrophages and MSCs under oxidative stress

Xinkun Shen,Yonglin Yu,Pingping Ma,Zhong Luo,Yan Hu,Menghuan Li,Ye He,Yangyang Zhang,Zhihong Peng,Guanbin Song,Kaiyong Cai

Before mesenchymal stem cells (MSCs) adhere to the surface of an implant and differentiate into osteoblasts, monocytes (especially macrophages) arrive at the bone injury site and interact with the implant and subsequent MSCs. In our previous study, large titania nanotubes (TNT 110 ) had been verified to endow superior oxidation resistance to osteoblasts. The early regulation between macrophages and MSCs by surface nanotubes under oxidative stress (OS) was evaluated further in this study. Cellular and molecular results show that TNT 110 greatly increased early inflammation of macrophages by activating integrin/FAK-mediated MAPK and NFκB signals and simultaneously promoted their gene expression of SDF1, IL-8, and CCL2 (chemokines) compared with 30 nm nanotubes and titanium substrates. Co-culture results show that more MSCs were recruited by those chemokines and may promote osteogenic self-differentiation, reducing early inflammation of macrophages by accelerating their M1-to-M2 transition in the TNT 110 group. All findings reveal that the early cellular behavior of macrophages and MSCs was effectively regulated by TNT 110 , indicating large nanotubes would be more suitable to prevent oxidative damages.

CAS / MDL: 12125-01-8 56-81-5
研究领域: 生物材料 · 细胞生物学 · 组织工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food & Function · 2022 ·Vol. 13 ·期 7 ·3946-3956 · IF 6.317

Platycodon grandiflorum root fermentation broth reduces inflammation in a mouse IBD model through the AMPK/NF-κB/NLRP3 pathway

Zhe Wang,Chunhai Li,Xi He,Kang Xu,Zhipeng Xue,Ting Wang,Zhenshang Xu,Xinli Liu

The effect of Platycodon grandiflorum (PG) on colitis and its underlying mechanism were rarely studied. In this study, Lactobacillus rhamnosus 217-1 was used to ferment PG roots, and the concentrations of platycodin-D, flavonoids, and polyphenols and the DPPH free radical scavenging rate were significantly increased. Treatment with a PG root fermentation broth (PGRFB) could reduce dextran sulfate sodium (DSS) induced ulcerative colitis (UC) in mice. Meanwhile, the PGRFB significantly reduced the content of inflammatory factors in mouse serum and the expression of inflammatory factor mRNA in the intestinal tract, regulated the polarization of M1/M2 macrophages, and increased the expression of tight junction protein mRNA in intestinal epithelial cells. In summary, it was proved that the PGRFB could inhibit the nuclear factor kappa B (NF-κB) signaling pathway and the expression of Nod-like receptor protein 3 (NLRP3) inflammasomes by activating AMP-activated protein kinase (AMPK) and lowering the release of pro-inflammatory cytokines.

CAS / MDL: 1898-66-4
研究领域: 药理学 · 免疫学 · 微生物学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MEDICAL ONCOLOGY · 2022 ·Vol. 39 ·期 7 ·1-12 · IF 3.738

Tumor-associated macrophages of the M1/M2 phenotype are involved in the regulation of malignant biological behavior of breast cancer cells through the EMT pathway

Chen Zhuo,Wu Jing,Wang Liang,Zhao Hua,He Jie

Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. More and more studies have shown that the tumor immune microenvironment (TME) of TNBC is closely related to its poor prognosis and early metastasis. We try to explain how tumor-associate macrophages (TAMs), an important component of the TME, function in the matrix of TNBC. Therefore, we induced THP-1 cells to become M1-TAMs and M2-TAMs, investigated their influence on breast cancer cells. 82 TNBC paraffin samples were made into tissue microarrays. The expression of macrophages makers were measured by immunohistochemistry. Scratch assay, Transwell assay, CCK-8 cell proliferation assay were performed in the co-culture system of breast cancer cells lines and macrophages to observe the invasion and proliferation ability of breast cancer cell lines. Western Blot (WB) was performed to detect the expression of E-cadherin (CDH1) and N-cadherin (CDH2). M2-TAMs were more numerous than M1-TAMs in the matrix of TNBC cancer nests and associated with poor prognosis. M2-TAMs promoted the invasion, migration, and proliferation of TNBC cells. M1-TAMs had inhibitory effects. In MCF-7 cells, WB showed a decrease in CDH1 and an increase in CDH2. In MDA-MB-231 cells and BT549 cells, CDH2 expression was reduced and CDH1 expression was increased. All of the above results were statistically significant, p  < 0.001. M2-TAMs were more numerous in TNBC and associated with poor prognosis. M2-TAMs promoted the invasion, migration, and proliferation of breast cancer cells. The mechanism may be related to the epithelial-mesenchymal transition.

研究领域: 肿瘤学 · 免疫学 · 细胞生物学 · 病理学
✓ 已验证 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2026 · IF 8.7

Efficacious removal of aflatoxin M1 from milk and environmental samples using green spinel manganese ferrite-rice hull embedded by L-cysteine/cellulose-based nanocomposite biosorbent

N. Zabeti,A.R. Faraji,A.K. Kayhanizadeh,Y. Ramezan,M. Soltani

Aflatoxin M 1 (AFM 1 ) contamination is a significant factor contributing to economic losses in the dairy industry, and it can also pose human health risks. AFM 1 can be transported easily to aquatic environments from agricultural fields by rain or re-enter the food cycle through sewage. Here, a facile wet co-participation/impregnation method was applied to fabricate rice hull-spinel manganese ferrite embedded in a porous L -cysteine-trichloro- s -triazine-cellulose scaffold (CTCR-MCF) to develop a bio-adsorbent for AFM 1 . The rice hull waste was deaggregated with spinel ferrite beads and bound to the S/N/O-H conjugates-cellulose template to synthesize an amphiphilic and pH-responsive nano-biosorbent. The modified cellulosic polymer was comprehensively characterized using structural and morphological techniques. The adsorption capacity of engineered CTCR-MCF was 0.18520 mg g −1 , and it effectively removed 99.3% (and ∼ 75.2%) of AFM 1 from 50.0 μg mL −1 AFM 1 solution (and spiked cow milk) within 45.0 min under neutral pH. The Freundlich adsorption isothermal model (R 2  = 0.982) and pseudo-2st-order kinetic model (R 2  = 0.984) demonstrated that the removal occurs as a multi-layer on a non-uniform surface without chemical/physical interactions between molecules in a spontaneous/endothermic entropy-increasing process. Additionally, environmental compatibility, chemical/thermal stability, and regeneration were assessed in detail. The results showed that the durable bio-adsorbent had no significant effects on milk nutritional qualities and was successful in removing unsafe heavy metals from milk by using a less energy-intensive isolation method. These findings offer an efficient platform for “ treating toxins with biosorbent ” to mitigate their hazardous effects in environmental and food samples.

✓ 已验证 DOI PubMed 高影响因子
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FOLIA HISTOCHEMICA ET CYTOBIOLOGICA · 2022 ·Vol. 61 ·期 1 ·34-46 · IF 1.49

Overexpressing six-transmembrane protein of prostate 2 (STAMP2) alleviates sepsis-induced acute lung injury probably by hindering M1 macrophage polarization via the NF-κB pathway

Lili Ji Xiaojing Shi Gaopin Wang Huiping Wu Zhansheng Hu

Introduction. Acute lung injury (ALI) is a major cause of death in sepsis patients. The Six-transmembrane protein of prostate 2 (STAMP2) is a key regulator of inflammation, while its role in septic ALI remains unclear. Material and methods. Male C57BL/6 mice were subjected to cecal ligation puncture (CLP) to induce experimental sepsis whereas lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were used as the models of septic ALI in vivo and in vitro , respectively. Overexpression of STAMP2 in mouse lungs and RAW264.7 cells was performed with an adenoviral vector. We measured histological lung injury, lung wet/dry weight (W/D) ratio, and pulmonary myeloperoxidase (MPO) activity to assess lung injury extent. Cell counts in bronchoalveolar lavage fluid (BALF) were measured using Giemsa staining. The concentration of inflammatory factors was detected by enzyme-linked immunosorbent assay. The polarization of macrophages was evaluated by inducible nitric oxide synthase (iNOS) and F4/80 staining. The activation of cell apoptosis and NF-κB pathway was evaluated using Western blot, TUNEL staining, immunofluorescence, and immunohistochemistry. Results. Overexpression of STAMP2 alleviated CLP-induced lung injury of mice with decreased W/D ratio of the lung, and MPO activity in lung tissue. STAMP2 overexpression reduced the lung infiltration of inflammatory cells, and the levels of TNF-a, IL-6, and macrophage chemoattractant protein-1 (MCP-1) in BALF. Overexpressed STAMP2 inhibited macrophage M1 polarization in lung tissues as indicated by F4/80 and iNOS stainings in lung tissue. STAMP2 overexpression inhibited RAW 264.7 cell apoptosis by increasing Bcl-2 and decreasing Bax and cleaved-caspase 3 expression. Besides, STAMP2 overexpression suppressed nuclear factor κB (NF-κB) p65 pathway activation, as evidenced by reduced phosphorylation of IκBα, and phosphorylation and translocation of NF-κB p65. In vitro study further proved that STAMP2 overexpression suppressed the NF-κB pathway (IκBα/p65) in macrophages and decreased macrophage M1 polarization and M1-associated inflammatory factor production (TNF-a, IL-6, and MCP-1). Conclusions. Our study for the first time demonstrated that STAMP2 might be able to reduce inflammation in sepsis-induced ALI by inhibiting macrophage M1 polarization through repressing NF-κB signaling activation.

CAS / MDL: 47165-04-8
研究领域: 免疫学 · 病理生理学 · 分子生物学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Biomimetic carrier-free nanoplatform based on natural polyphenols and siRNA for targeted therapy in rheumatoid arthritis

Han Yang,Min Liu,Jingwen Jia,XiaoFang Li,Siyi Liu,Jingya Xiu,Jiulong Zhang,Xiuli Zhao

Rheumatoid arthritis (RA) is an auto-immune disease characterized by the excessive production of pro-inflammatory factors siRNA-mediated RNA interference offers a promising alternative owing to its high specificity and minimal side effects. However, the current cationic gene delivery system has always suffers from systematic toxicity due to excess cationic groups in the carrier. To overcome this drawback, we introduced a biomimetic siRNA delivery system with no cationic moiety, EHPS, using epigallocatechin gallate (EGCG) to condense TNF-α siRNA through hydrogen bonding, electrostatic interactions, and hydrophobic forces for the treatment of RA. Additionally, we enhanced this system with M1 macrophage membrane (M1m)-coated nanoparticles (termed M−EHPS) to evade the immune system and selectively target inflammatory cells. This design improved nanoparticle stability through additional hydrogen and hydrophobic bonding and reduced toxicity caused by conventional cationic carriers. M−EHPS could respond to high concentration of reactive oxygen species (ROS) in RA, facilitating rapid siRNA release from lysosomes via the proton sponge effect. Critically, this nanosystem also released EGCG, which mitigated a broad spectrum of reactive oxygen and nitrogen species (RONS), thereby creating a synergistic effect with siRNA. In RA mice model, intravenous administration of M−EHPS achieved targeted accumulation in inflamed joints and demonstrated potent anti-RA efficacy. This novel siRNA delivery system, integrating triple-interaction stability and intrinsic self-destructive release capability, presents a robust and efficient approach for targeted RA therapy and has significant potential for advancing RNA interference therapeutics in other diseases.

研究领域: 医学 · 生物技术 · 纳米医学 · 免疫学
✓ 已验证 产品关联 DOI 高影响因子
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JOURNAL OF CONTROLLED RELEASE · 2025 · IF 11.5

Microneedle patch-involved local therapy synergized with immune checkpoint inhibitor for pre- and post-operative cancer treatment

Yue Yin,Lu Tang,Yuqi Cao,Hening Liu,Cong Fu,Jingwen Feng,Houhua Zhu,Wei Wang

The metastasis and recurrence of cancer post-surgery remain the major reasons for treatment failures. Herein, a photo-immune nanoparticle decorating with M1 macrophage membrane (BD@LM) is designed based on the inflammatory environment after surgical resection. By loading photosensitizer black phosphorus quantum dots (BPQDs) and chemotherapeutics doxorubicin (DOX) in BD@LM nanoparticles, an effective chemophototherapy-mediated immunogenic cell death of tumor cells is triggered, subsequently leading to the maturation of dendritic cells for further immune cascade. Moreover, by accommodating BD@LM in a dissolvable microneedle patch, the skin barrier is directly broken for efficacious delivery of BD@LM into solid tumors, which boosts the effectiveness of aPD-L1-based checkpoint blockade therapy. Consequently, the growth of both orthotopic and post-surgical breast tumor and melanoma is significantly inhibited. Specifically, an effective T cell activation accompanied with dramatic inhibition of immunosuppressive cells is observed. Meanwhile, the proportion of memory T cells remarkably grows after proposed treatment, indicating the establishment of a long-term immune memory effect for prevention of second tumor attack. Altogether, this work offers a meaningful strategy by combining photo-immune-inspired nanoparticles with microneedle patches for boosting aPD-L1-based tumor immunotherapy.

研究领域: 肿瘤学 · 免疫学 · 纳米医学 · 生物材料学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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PHARMACOLOGICAL RESEARCH · 2020 · IF 5.893

HYR-2 plays an anti-lung cancer role by regulating PD-L1 and Akkermansia muciniphila

Linxin Teng,Kaiyuan Wang,Weiping Chen,Yun-shan Wang,Lei Bi

Traditional Chinese medicine (TCM) plays a vital part in cancer treatment due to its unique superiority. Huoxue Yiqi Recipe-2 (HYR-2) was supposed to have therapeutic effect on lung cancer, which came from Ze Qi Decoction in one of the four great classics of TCM called "Synopsis of Prescriptions of the Golden Chamber". Network pharmacology demonstrated that the targets of active components from HYR-2 were significantly enriched in the signaling pathways, which were closely associated with non-small cell lung cancer (NSCLC) and programmed death ligand 1 (PD-L1). Then, data about NSCLC was downloaded from Gene Expression Omnibus database (GEO). The Cancer Genome Atlas (TCGA) and DisGeNET was analyzed by bioinformatics, and 214 biomarkers for NSCLC were obtained, containing 14 targets of active components from HYR-2 (which were significantly enriched in the PD-L1 related signaling pathway). In vivo and in vitro experiments showed that HYR and HYR-2 could inhibit the growth of lung cancer and down-regulate the expression of PD-L1, which might be related to the blocking effect of HYR-2 on the PI3K/Akt signaling pathway. Furthermore, HYR-2 promoted the transformation of M2 macrophages into M1 macrophages as well. It is deserved to be mentioned that the level of Akkermansia muciniphila was also significantly elevated by HYR-2, which was believed to enhance the therapeutic effect of PD-L1 antibodies. To sum up, HYR-2 might play an anti-lung cancer effect by down-regulating PD-L1 together with up-regulating Akkermansia muciniphila.

CAS / MDL: 98-10-2
研究领域: 药理学 · 肿瘤学 · 微生物学 · 生物信息学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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