Review
Biochemistry & Molecular Biology
Yuko Ishida, Yumi Kuninaka, Naofumi Mukaida, Toshikazu Kondo
Summary: Fibrosis and structural remodeling of lung tissue can seriously impact lung function and have fatal consequences. The causes of pulmonary fibrosis (PF) vary, including allergens, chemicals, radiation, and environmental particles. The cause of idiopathic PF (IPF), one of the most common forms, is still unknown. The murine bleomycin (BLM) model has been extensively studied to understand the mechanisms of PF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Sara Lettieri, Tiberio Oggionni, Andrea Lancia, Chandra Bortolotto, Giulia Maria Stella
Summary: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease with unknown cause, associated with an increased risk of lung cancer. Recent research suggests that immune checkpoint inhibition could be a rational treatment approach for IPF. Understanding the immune microenvironment of lung cancer has diagnostic and therapeutic implications for IPF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Xinyu Li, Haozheng Cai, Yufeng Cai, Quyan Zhang, Yinghe Ding, Quan Zhuang
Summary: This study developed a hypoxia-immune-related prediction model for the prognosis of IPF, identifying high hypoxia and high immune status as risk factors for poor prognosis in IPF patients. Specific immune cells were found to play key roles in the hypoxia-immune-related microenvironment, and a prediction model based on one protective and nine risk genes was established. The model showed significant applicability in peripheral whole blood, peripheral blood mononuclear cell, and lung tissue of IPF patients in independent validation cohorts.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Yuanyuan Han, Mao Jiang, Rongling He, Xin Lv, Xiaohua Liao, Yijun He, Fan Zhang, Lingzhi Long, Guoliang Jiang, Zhangzhe Peng, Lijian Tao, Gaoyun Hu, Jie Meng
Summary: The study found that the newly synthesized drug MFD can alleviate lung fibrosis by suppressing TGF-beta/Smad2 and MAPK pathways, reducing cell apoptosis and EMT in the fibrotic process.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Plant Sciences
Shuyu Li, Qixin Yang, Feilong Chen, Linhua Tian, Jinhai Huo, Yanli Meng, Qingfa Tang, Weiming Wang
Summary: This study investigates the antipulmonary fibrosis mechanism of Pheretima protein and its possible cell signaling pathways. The results demonstrate that Pheretima protein can inhibit epithelial-mesenchymal transition, reduce inflammation, and alleviate BLM-induced pulmonary fibrosis in a mouse model. The preliminary mechanistic studies suggest that Pheretima protein exerts its biological activity by downregulating the TGF-β1/Smad2/3 pathway.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Hanjing Sheng, Gang Lin, Shengxian Zhao, Weibin Li, Zhaolin Zhang, Weidong Zhang, Li Yun, Xiaoyang Yan, Hongyu Hu
Summary: This study evaluated the anti-fibrotic role of Piceatannol (PIC) in a mouse model of pulmonary fibrosis and found that PIC reduces the number of activated myofibroblasts by promoting autophagy. The study demonstrates for the first time the protective effects of PIC against pulmonary fibrosis and suggests its potential as a candidate compound for pulmonary fibrosis therapy.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Ying-Qiu Yin, Feng Peng, Hui-Jing Situ, Jun-Ling Xie, Liming Tan, Jie Wei, Fang-fang Jiang, Shan-Qiang Zhang, Jun Liu
Summary: This study establishes a four-gene risk model for predicting the overall survival rate of inflammation-related idiopathic pulmonary fibrosis (IPF). The high-risk group has shorter survival time, and the model shows potential as an independent risk indicator for poor prognosis. In addition, immune infiltration analysis shows increased immune cell infiltration in the high-risk group.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Zhuo Pei, Yifei Qin, Xianghui Fu, Fengfan Yang, Fei Huo, Xue Liang, Shijie Wang, Hongyong Cui, Peng Lin, Gang Zhou, Jiangna Yan, Jiao Wu, Zhi-Nan Chen, Ping Zhu
Summary: This study investigated the role of ferroptosis and iron accumulation in the progression of pulmonary fibrosis. The findings suggest that inhibiting ferroptosis and reducing iron accumulation may be potential therapeutic strategies for treating pulmonary fibrosis. Additionally, TGF-0 was found to promote the transformation of fibroblasts into myofibroblasts by upregulating the expression of TFRC.
Article
Immunology
Bowen Liu, Qiuyan Jiang, Ruxuan Chen, Shaoyan Gao, Qin Xia, Jingyan Zhu, Fangxia Zhang, Chi Shao, Xiangning Liu, Xiaohe Li, Honggang Zhou, Cheng Yang, Hui Huang
Summary: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by excessive proliferation of fibroblasts and the distortion of alveolar architecture. In this study, tacrolimus was found to suppress the polarization of M2 macrophages and alleviate fibrosis progression by inhibiting pro-fibrotic factors and targeting the JAK2/STAT3 signaling pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Genetics & Heredity
Yiyi Zhou, Chen Fang, Qinying Sun, Yuchao Dong
Summary: This study uncovers the important role of N6-methyladenosine (m6A) modification in chronic hypersensitivity pneumonitis (CHP) and idiopathic pulmonary fibrosis (IPF). Through differential gene analysis, several m6A regulators associated with the risk of pulmonary fibrosis were identified and used to divide treatment samples into two groups with distinct m6A patterns. The study suggests that m6A patterns can serve as biomarkers for the identification of CHP and IPF, facilitating the development of immunotherapy strategies for pulmonary fibrosis in the future.
FRONTIERS IN GENETICS
(2022)
Article
Food Science & Technology
Bei Liu, Jinyu Yang, Jiatong Hao, Haifeng Xie, Kuniyoshi Shimizu, Renshi Li, Chaofeng Zhang
Summary: Mogrol from Siratia grosvenorii demonstrated anti-fibrotic effects by suppressing TGF-beta 1 pathway, restoring NOX4 expression, and promoting AMPK phosphorylation. The protective effect against lung fibrosis may be attributed to the activation of AMPK and amelioration of TGF-beta 1 signalling pathway.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Plant Sciences
Dong Wang, Lili Gong, Zifa Li, Haihong Chen, Mengzhen Xu, Rong Rong, Yingying Zhang, Qingjun Zhu
Summary: Our study demonstrates that Gancao Ganjiang decoction positively affects IPF by regulating the PD-1/TGF-beta 1/IL-17A pathway, suggesting its potential as a therapeutic agent for idiopathic pulmonary fibrosis.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Xingping Su, Zui Tan, Guan Wang, Zhihao Liu, Cailing Gan, Lin Yue, Hongyao Liu, Yuting Xie, Yuqin Yao, Tinghong Ye
Summary: This study suggests that compounds 44 and 52 may serve as potential lead compounds for the treatment of idiopathic pulmonary fibrosis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Immunology
Shanshan Chen, Yuli Wei, Shimeng Li, Yang Miao, Jinying Gu, Yunyao Cui, Zhichao Liu, Jingjing Liang, Luqing Wei, Xiaohe Li, Honggang Zhou, Cheng Yang
Summary: The study demonstrates that zanubrutinib attenuates bleomycin-induced pulmonary fibrosis by inhibiting the TGF-beta 1 signaling pathway. This finding suggests a new potential treatment option for idiopathic pulmonary fibrosis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xiaohe Li, Ling Ma, Kai Huang, Yuli Wei, Shida Long, Qinyi Liu, Deqiang Zhang, Shuyang Wu, Wenrui Wang, Guang Yang, Honggang Zhou, Cheng Yang
Summary: Regorafenib is a novel drug that can alleviate bleomycin-induced pulmonary fibrosis in mice by suppressing the TGF-beta 1 signaling pathway, reducing collagen accumulation, and myofibroblast activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)