ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Xiaoliang Deng,Xianquan Feng,Xiaohui Tang,Zhihui Zheng,Da Zheng,Enqin Zheng,Lingjun Zeng,Shiying Xu,Boxin Chen,Qian Zhang,Zhihong Liu,Hongtao Song
The clinical efficacy of immunotherapy in triple-negative breast cancer (TNBC) faces dual barriers: poor immunogenicity and a suppressive tumor microenvironment. While low-temperature photothermal therapy (LTPTT) has emerged as a potential immunostimulatory strategy, its efficacy is counteracted by heat shock protein (HSP) induction and COX-2/PGE2-mediated immunosuppression. To address these challenges, we developed a multifunctional immunophotothermal nanoplatform (IAC NPs) through rational engineering of human serum albumin for combinatorial delivery of indocyanine green as a photothermal converter, atovaquone for HSP70-mediated thermoresistance blockade, and celecoxib for COX-2/PGE2 pathway inhibition. The IAC NPs achieved tumor-targeted delivery and NIR-activated immunogenic phototherapy while coinhibiting HSP70 (via atovaquone’s mitochondrial complex III blockade) and the COX-2/PGE2 immunosuppressive axis (via celecoxib). The triple medications’ synergistic action improved the expression of effector memory T cells, boosted the maturation of dendritic cells, encouraged the infiltration of CD4+ and CD8+ T cells, and reduced regulatory T cells. In vivo, the IAC NPs mediated profound suppression of both primary tumors and metastatic dissemination while exhibiting optimal biocompatibility for clinical translation. Our work validates a nanoenabled self-delivery system that augments the efficacy of LTPTT immunotherapy against TNBC by orchestrating coordinated inhibition of HSPs and inflammatory responses.
研究领域:
癌症免疫治疗
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纳米医学
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光热治疗
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分子靶向治疗
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肿瘤微环境
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Jiao Wu,Xiang-Tan Xu,Cheng Xing,Xin-Bao Hao,Xing-Yue Fang,Zhi-Hao Xie,Shan Zhao,Jing-Lin Gao,Lu Xu,Shi-Jie Wang
Honey has been recognized for its role in disease prevention through nutritional modulation. In this study, we comprehensively assessed the physicochemical parameters, metabolic profile, antioxidant and anti-inflammatory activities of multifloral honeys produced by Apis cerana cerana in Sansha City (SS), Hainan Province. Metabolomic analysis identified SS honey had multiple bioactive compounds known for antioxidant and anti-inflammatory properties. Compared to A. cerana cerana honey from central regions of Hainan Province, SS honey showed higher levels of TFC (113.80 mg RE/100 g) and TPC (45.86 mg GAE/100 g). Furthermore, SS honey demonstrated greater antioxidant activity, as evidenced by FRAP (1503.16 μmol TE/kg), DPPH IC 50 (36.13 mg/mL), and ABTS IC 50 (11.03 mg/mL). SS honey significantly reduced the levels of cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-induced RAW 264.7 cells, along with suppressing the mRNA expression of these inflammatory markers.
研究领域:
养蜂学
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生物化学
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药理学
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营养科学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2021
·
IF 9.028
Shixuan Cui,Yang Yu,Tingjie Zhan,Yuchen Gao,Jiachen Zhang,Liang Zhang,Zhiwei Ge,Weiping Liu,Chunlong Zhang,Shulin Zhuang
Thousands of contaminants are used worldwide and eventually released into the environment, presenting a challenge of health risk assessment. The identification of key toxic pathways and characterization of interactions with target biomacromolecules are essential for health risk assessments. The adverse outcome pathway (AOP) incorporates toxic mechanisms into health risk assessment by emphasizing the relationship among molecular initiating events (MIEs), key events (KEs), and adverse outcome (AO). Herein, we attempted the use of AOP to decipher the toxic effects of 2,6-di-tert-butylphenol (2,6-DTBP) and its para-quinone metabolite 2,6-di-tert-butyl-1,4-benzoquinone (2,6-DTBQ) based on integrated transcriptomics, molecular modeling, and cell-based assays. Through transcriptomics and quantitative real-time PCR validation, we identified retinoic acid receptor β (RARβ) as the key target biomacromolecule. The epigenetic analysis and molecular modeling revealed RARβ interference as one MIE, including DNA methylation and conformational changes. In vitro assays extended subsequent KEs, including altered protein expression of p-Erk1/2 and COX-2, and promoted cancer cell H4IIE proliferation and metastasis. These toxic effects altogether led to carcinogenic risk as the AO of 2,6-DTBP and 2,6-DTBQ, in line with chemical carcinogenesis identified from transcriptome profiling. Overall, our simplified AOP network of 2,6-DTBP and 2,6-DTBQ facilitates relevant health risk assessment.
研究领域:
毒理学
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分子生物学
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癌症研究
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环境科学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2022
·Vol. 13
·期 22
·11676-11689
·
IF 6.317
Abel Wend-Soo Zongo,Daniel Zogona,Mahmoud Youssef,Shuxin Ye,Fuchao Zhan,Jing Li,Bin Li
The intestinal barrier dysfunction associated with chronic inflammation is a major health concern. This work aimed to investigate the protective effect and molecular mechanism of Senegalia macrostachya seed polysaccharide fraction (SMSP2) on inflammation-induced barrier dysfunction using Caco-2 cells and RAW264.7 macrophage co-culture model. The results showed that LPS stimulation of the basolateral RAW264.7 compromised the integrity of the apical differentiated Caco-2 cells monolayer, resulting in decreased transepithelial electrical resistance (TER) and increased inflammatory markers. SMSP2 apical treatment maintained a higher TER value and reduced the epithelial permeability to lucifer yellow (LY) dye. In addition, the SMSP2 group showed a significant decrease in the mRNA level of inflammatory factors such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin (IL)-8, and tumor necrosis factor-α (TNF-α) in the Caco-2 monolayer compared to the LPS group. Moreover, SMSP2 increased the expression of the tight junctions (TJ) zonula occludens (ZO-1), occludin, and claudin-1 at the mRNA and protein levels. Furthermore, the immunofluorescence assay showed that SMSP2 ameliorated the overall distribution of the TJ proteins in the Caco-2 monolayer. SMSP2 application also resulted in the downregulation of the nuclear factor kappa-B (NF-κB) phosphorylation and the myosin light chain kinase (MLCK) expression, which implies that SMSP2 preserved the monolayer integrity from the inflammation-induced barrier disruption through the inhibition of the NF-kB-mediated MLCK signaling pathway activation. Senegalia macrostachya seeds could therefore be a promising functional food that could be used to improve intestinal barrier function.
研究领域:
药理学
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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
·
胃肠病学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2022
·
IF 5.895
Fanghua Guo,Rong Tsao,Chuyao Li,Xiaoya Wang,Hua Zhang,Li Jiang,Yong Sun,Hua Xiong
Green pea hulls are a byproduct of the processing of green pea and are rich in phenolic substances. In the present study, in vitro digestion, human colonic adenocarcinoma cell line (Caco-2) monolayer, and the Caco-2/macrophage cell lines of the murine origin (Raw264.7) coculture model were established to investigate the release of polyphenols, absorption, and transport of digestive products and their effects on inflammation and intestinal barrier. During the digestive process, polyphenols were constantly released from the pea hulls, reaching the maximum amount in the small intestine (total phenolic content (TPC): 5.41 ± 0.04 mg gallic acid (GAE)/g dry weight (DW)), and the digestive products (800 μg/mL) could reduce the secretion of NO (50.9%), IL-6 (50.6%), and TNF-α (24.6%) and inhibit the mRNA expression of cyclooxygenase-2 (COX-2) (37.2%) and inducible nitric oxide synthase (iNOS) (91.1%) compared with the lipopolysaccharide (LPS) group. A total of 12 phenolic components were quantified by ultraperformance liquid chromatography-linear ion trap orbitrap tandem mass spectrometry (UHPLC-LTQ-OrbiTrap-MS) technology. Kaempferol trihexoside in digestive products could be absorbed and transported (1.25 ± 0.13 ng quercetin/mL). The digestive products could promote the expression of claudin-1 (210.8%), occludin (64.9%), and zonulin occludin-1 (ZO-1) (52.0%) compared with the LPS group and exert anti-inflammatory effects after being absorbed. The results indicated that pea hull polyphenols could be continuously released and absorbed to play a positive role in protecting the intestinal barrier and anti-inflammatory activity.
研究领域:
食品科学
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营养学
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药理学
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细胞生物学
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2024
·Vol. 53
·期 20
·8772-8780
·
IF 3.5
Kai Xie,Xing-Yun Lu,Hou Zhu,Lin-Yuan Zhu,Rong-Tao Li,Rui-Rong Ye
A series of Ir(III)–naproxen (NPX) conjugates with the molecular formula [Ir(C^N)2bpy(4-CH2ONPX-4′-CH2ONPX)](PF6) (Ir-NPX-1–3) were designed and synthesized, including C^N = 2-phenylpyridine (ppy, Ir-NPX-1), 2-(2-thienyl)pyridine (thpy, Ir-NPX-2) and 2-(2,4-difluorophenyl)pyridine (dfppy, Ir-NPX-3). Cytotoxicity tests showed that Ir-NPX-1–3 exhibited excellent antitumor activity, especially in A549R cells. The cellular uptake experiment showed that the complexes were mainly localized in mitochondria, and induced apoptosis in A549R cells by damaging the structure and function of mitochondria. The main manifestations are a decrease in the mitochondrial membrane potential (MMP), an increase in reactive oxygen species (ROS) levels, and cell cycle arrest. Furthermore, Ir-NPX-1–3 could inhibit the migration and colony formation of cancer cells, demonstrating potential anti-metastatic ability. Finally, the anti-inflammatory and immunological applications of Ir-NPX-1–3 were verified. The downregulation of cyclooxygenase-2 (COX-2) and programmed death-ligand 1 (PD-L1) expression levels and the release of immunogenic cell death (ICD) related signaling molecules such as damage-associated molecular patterns (DAMPs) (cell surface calreticulin (CRT), high mobility group box 1 (HMGB1), and adenosine triphosphate (ATP)) indicate that these Ir(III) –NPX conjugates are novel ICD inducers with synergistic effects in multiple anti-tumor pathways.
研究领域:
肿瘤学
·
药物化学
·
细胞生物学
·
免疫学
✓ 已验证
DOI
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Yan Chen,Ming Zhang,Zhifang Liu,Ning Zhang,Qingpeng Wang
Tumor microenvironment (TME) is a pivotal factor driving the tumor metastasis and leading to the failure of tumor therapy. Here, a series of ursodeoxycholic acid platinum(IV) conjugates with potency in remodeling the TME through suppressing JAK2/STAT3 signaling was developed. A candidate was screened out, which displayed potent antiproliferative and antimetastatic performance both in vitro and in vivo. It displayed superior pharmacokinetic properties compared to cisplatin. Serious DNA injury was induced, and then mitochondria-mediated apoptosis was initiated through the Bcl-2/Bax/Caspase3 pathway. The JAK2/STAT3 and TGF-β1 signaling pathways were remarkably inhibited, and pro-death autophagy was subsequently promoted. The inflammatory and hypoxic TME was suppressed by downregulating COX-2, MMP9, and HIF-1α, which resulted in inhibited angiogenesis in tumors by inhibiting the HIF-1α/VEGFA axis. Additionally, the immunosuppressive TME was reversed by blocking the immune checkpoint PD-L1, further improving the density of CD3+ and CD8+ tumor-infiltrating lymphocytes, and promoting macrophage polarization from M2- to M1-type.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Hang Qu,Xin Gao,Zhen-Yu Wang,Juan-Juan Yi
A novel polysaccharide (PNP80b-2) was obtained from Pinus koraiensis pine nut, which has been proved to possess good hepatoprotective effects in vitro . This study comprehensively investigated its hepatoprotective activities against different types of chemical-induced liver injury in vivo . Carbon tetrachloride, alcohol and acetaminophen were used as hepatic toxicants to establish chemical pollutant-induced liver injury (CILI) model, alcohol induced-liver injury (AILI) model and drug-induced liver injury (DILI) model, respectively. The results showed that PNP80b-2 prevented elevation of biomarkers for liver injury in each model, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (TBIL). The expression of cytochrome P450 in damaged hepatocytes was also downregulated. Additionally, PNP80b-2 enhanced hepatic antioxidant capacity through upregulating the expression of NRF2 and HO-1, thereby increasing superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities and decreasing malondialdehyde (MDA) levels. The uncontrolled production of inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) in CILI, AILI and DILI models was also suppressed by PNP80b-2. By contrast, PNP80b-2 exerted the strongest hepatoprotection against AILI model, through improving hepatic antioxidant capacity via NRF2/ARE pathway and regulating inflammation response. Thus, PNP80b-2 is a promising functional food to prevent AILI.
研究领域:
药理学
·
肝病学
·
功能性食品
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2021
·
IF 4.432
Yao Hua,Limei Zhou,Weidong Yang,Wenji An,Xiaolin Kou,Jian Ren,Hailang Su,Rong Chen,Zhengping Zhang,Jianjun Zou,Zhihong Zhao
Intracerebral hemorrhage (ICH) is a devastating disease, and there is currently no specific pharmacological treatment that can improve clinical outcomes. Y-2 sublingual tablets, each containing 30 mg edaravone and 6 mg (+) - borneol , is undergoing a phase III clinical trial for treatment of ischemic stroke in China. The purpose of the present study is to investigate the efficacy and potential mechanism of Y-2 in a rat model of collagenase IV injection induced ICH. Sublingual administration of Y-2 at the dose of 1, 3 and 6 mg/kg improved ICH-induced sensorimotor dysfunction, alleviated cell death and histopathological change, restored the hippocampal long-term potentiation (LTP), reduced brain edema and maintained blood-brain barrier (BBB) integrality in ICH rats. Further study demonstrated that Y-2 could reduce inflammatory response and oxidative stress by decreasing the levels of myeloperoxidase (MPO), ionized calcium-binding adaptor protein-1 (Iba-1), inflammatory cytokines and oxidative products, inhibit transcription factor nuclear factor-κB (NF-κB) activation, cyclooxygenase-2 (COX-2) and matrix metallopeptidase 9 (MMP-9) expression in brain tissue around in the core regions of hematoma . Importantly, the protective efficacy of Y-2 from ICH-induced injury was superior to edaravone. In conclusion, Y-2 sublingual tablets might be a promising therapeutic agent for the treatment of ICH.
研究领域:
神经病学
·
药理学
·
实验性卒中研究
✓ 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）