INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Rong Huang,Wenyu Zhang,Yueqi Hu,Junjie Xu,Zhihui Dong,Jikai Liu,Li Zhou
Atopic dermatitis (AD), a prevalent inflammatory skin condition, significantly impacts patients' quality of life due to the multifaceted etiology and the lack of targeted therapeutic options. As the “Chinese herbal antibiotic”, Houttuynia cordata is renowned for its diverse pharmacological attributes. This study aims to investigate the therapeutic potential of Houttuynia cordata polysaccharides (HCP) in treating AD and to elucidate the mechanisms involved. HCP alleviated AD in MC903-induced mice by reducing epidermal thickness, skin lesions, mast cell infiltration, inflammatory cytokines, and restoring barrier proteins. It also suppressed inflammatory cytokines/chemokines via the mitogen-activated protein kinase (MAPK) pathway in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and tumor necrosis factor-alpha (TNF-α)/ interferon-γ(IFN-γ)-induced human keratinocytes cells (HaCaT). Moreover, HCP modulated inflammation-related metabolic pathways, especially restored lipid metabolic homeostasis through upregulating phosphatidylcholine (PC) and downregulating triglyceride (TG), lysophosphatidylcholine (LPC), potentially alleviating AD-like lesions and restoring barrier function. Our findings underscore the promising potential of HCP as a topical therapeutic candidate for AD treatment, offering a new direction for the development of targeted AD therapies.
研究领域:
皮肤病学
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药理学
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免疫学
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产品关联
DOI
PubMed
高影响因子
DEVELOPMENTAL CELL
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2025
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IF 8.7
Qi Zhang,Yezhen Tan,Qiyang Liang,Liangyou Gu,Yue Shi,Yan Huang,Xiubin Li,Jie Qi,Cheng Peng,Hanfeng Wang,Yaohui Wang,Kan Liu,Tianwei Cai,Yudan He,Qingbo Huang,Xu Zhang,Baojun Wang,Xin Ma,Weimin Ci
Preoperative downstaging of renal cell carcinoma with a tumor thrombus (RCC-TT) makes thrombectomy feasible. However, treatment resistance is common and may partly be attributed to the tumor-promoting role of the tumor microenvironment (TME). Herein, we sequenced, integrated, and comprehensively analyzed multi-center, multi-omics data from 164 RCC-TT patients and identified two clinically relevant RCC-TT subtypes. We find that the poor-prognosis subtype (TT1) exhibits enhanced extracellular-matrix (ECM) remodeling driven by epithelial LOX expression. Spatial transcriptomics (ST) shows the co-localization of GPNMB + macrophages, THBS2 + fibroblasts, and LOX + malignant cells around tumor nests in TT1 tumors, reinforcing tumor immune barriers (TIBs). Our extensive validations using cell lines, syngeneic mouse models, multiplex immunofluorescence staining, and large-scale RCC cohorts underscore the potential of LOX inhibition in disrupting TIBs, sensitizing RCC to immunotherapy, and overcoming treatment-induced phenotypic plasticity. This study provides insights into the biological underpinnings and prognosis assessment of RCC-TT, demonstrating targetable ECM-remodeling vulnerabilities.
研究领域:
肿瘤学
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分子生物学
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免疫学
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生物信息学
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病理学
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产品关联
DOI
PubMed
高影响因子
CELL RESEARCH
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2025
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IF 25.9
Hu Hui-Hui,Wang Xuefeng,Lan Bin,Cheng Haili,Wen Hong,Chen Fangfang,Wu Jianfeng,Li Mengqi,Chen Jiazhou,Zhang Jinhui,Chen Dongxu,Lin Shiyu,Lin Jieyu,Yang Mingyang,Wu Zhenhua,Zheng Zhong-Zheng,Chen Fuqing,Zhou Jianyin,Chen Gang,Chen Yu,Deng Xianming,Zhang Chen-Song,Liu Jingfeng,Lin Sheng-Cai
Dysregulated metabolism in tumor tissues and para-tumor tissues alike can lead to immunosuppression, which may underlie cancer development. However, metabolic intervention as a therapeutic strategy has been of no avail. In this study, we explored the anti-cancer therapeutic effect of aldometanib, which specifically targets lysosome-associated aldolase to mimic glucose starvation and thereby activates lysosomal AMP-activated protein kinase (AMPK), a master regulator of metabolic homeostasis. We show that aldometanib inhibits the growth of hepatocellular carcinoma (HCC) in an AMPK-dependent manner, allowing hepatoma-bearing mice to survive to mature ages, although aldometanib does not possess cytotoxicity toward HCC or normal cells. Intriguingly, aldometanib exerts anti-cancer effects only in immune-competent host mice, but not in immune-defective mice. We also found that HCC tissues in aldometanib-treated mice were massively infiltrated with CD8 + T cells, which was not seen in mice with liver-specific knockout of AMPKα . Our findings thus suggest that the metabolic regulator AMPK rebalances the tumor microenvironment to allow cytotoxic immune cells inside the body to eliminate cancer cells and effectively contain the tumor tissues. The finding that metabolic intervention can make cancer a lifelong manageable disease may usher in a new era of cancer therapy.
研究领域:
肿瘤学
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免疫代谢
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癌症免疫治疗
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分子生物学
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代谢调控
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产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
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2025
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IF 4.1
Jiaxin Di,Meifang Guo,Maijiao Peng,Leyao Fang,Junxi Shen,Nenqun Xiao,Zhoujin Tan
Purpose To investigate the therapeutic mechanisms of sodium butyrate combined with SSP in treating diarrhea with kidney-yang deficiency syndrome, providing experimental evidence for the modern application of classical Chinese medicine formulas.Methods A mouse model of diarrhea with kidney-yang deficiency syndrome was established via adenine combined with Folium sennae gavage. After successful model establishment, the drug intervention groups were administered by gavage with 100% SSP decoction, 300 mg/mL sodium butyrate, and 100 mg/kg sodium butyrate + 50% SSP decoction, respectively. General physical conditions and organ indices were assessed. Serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, as well as colonic immunoglobulin A (sIgA) and mucin 2 (MUC2) levels, were determined via ELISA. Kidney and intestinal histology were evaluated via hematoxylin‒eosin (HE) staining. The characteristics of the small intestinal mucosal microbiota under different interventions were analysed via 16S rRNA sequencing.Results Compared with natural recovery, the combination of 100 mg/kg sodium butyrate + 50% SSP significantly restored colonic sIgA levels (p< 0.05) and MUC2 levels, indicating an improvement in intestinal mucosal barrier function. Histological analysis revealed that the combination of 100 mg/kg sodium butyrate + 50% SSP improved renal inflammation and restored intestinal villus length and crypt depth. The combination therapy controlled the relative abundance of Corynebacterium while restoring Dwaynesavagella and Megasphaera_A. Correlation analysis indicated that Mammaliicoccus and Corynebacterium were significantly negatively correlated with sIgA and MUC2 levels and that their relative abundances were inhibited by the combination therapy.Conclusion Sodium butyrate enhanced the therapeutic efficacy of SSP. The combination therapy effectively repaired damaged kidneys and intestines and alleviated diarrhea with kidney-Yang deficiency syndrome by modulating the relative abundance of intestinal microbiota and enhancing intestinal immunity as well as mucosal barrier function. The interaction between the intestinal microbiota and intestinal mucosal protective factors may be a key mechanism in the combined treatment of diarrhea with kidney-yang deficiency syndrome.
研究领域:
药理学
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中医学
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微生物学
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免疫学
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胃肠病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2022
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IF 15.304
Pai Liu,Fei Ren,Subin Son,Myung Sun Ji,Peng Li,Zhengxu Cai,Jianbing Shi,Yi Liu,Yuping Dong,Jong Seung Kim
Photodynamic therapy combined with immunogenic cell death has been proposed to overcome the unsolvable problems of single therapy, such as high levels of tumor recurrence and treatment resistance of tumors. Previous works on this theme have mostly concentrated on endoplasmic reticulum (ER)-stressed damage-associated molecular patterns (DAMPs), ignoring the secretion and function of mitochondria-related DAMPs. Herein, our work reports two intersystem crossing photosensitizers based on well-designed multiarylpyrrole structures and draws valuable attention to mitochondria-related DAMP-TFAM (mitochondrial transcription factor) when cancer cells are under forceful oxidative stress . The tumors vanished, and immunogenic experiments were applied to illuminate the advantages of double treatment. Our discovery of new mitochondria-related DAMPs compensates for the lack of ER-stressed DAMPs and offers an innovative target for immunity therapy.
研究领域:
癌症治疗
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免疫疗法
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光动力疗法
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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
危险品化学品经营许可证（带存储）