Article
Biochemistry & Molecular Biology
Qing Shi, Xiaofeng Jin, Pingzhao Zhang, Qian Li, Zeheng Lv, Yan Ding, Huiying He, Yijun Wang, Yuanlong He, Xiaying Zhao, Shi-Min Zhao, Yao Li, Kun Gao, Chenji Wang
Summary: This study reveals that SPOP mutations induce non-degradative ubiquitination of p62, leading to suppression of p62-dependent autophagy and decreased Nrf2-mediated transcriptional activation of antioxidant genes, thus promoting tumor formation in SPOP-mutated PCa.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Immunology
Su Zhang, Yaya Liu, Xuefeng Zhou, Min Ou, Guohui Xiao, Fang Li, Zhongyuan Wang, Zhaoqin Wang, Lei Liu, Guoliang Zhang
Summary: This study identified a SIRT7-mediated protective mechanism against Mycobacterial infection by regulating NO production and apoptosis, indicating the potential of SIRT7 as a novel effective target for HDT of TB.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Tomomi Kurane, Tetsuro Matsunaga, Tomoaki Ida, Kazuko Sawada, Akira Nishimura, Masayuki Fukui, Masayuki Umemura, Masaaki Nakayama, Naoya Ohara, Sohkichi Matsumoto, Takaaki Akaike, Goro Matsuzaki, Giichi Takaesu
Summary: The study reveals the previously unrecognized role of GRIM-19 as an essential regulator of NLRP3 inflammasome and a molecular mechanism underlying Zmp1-mediated suppression of IL-1 beta production during mycobacterial infection.
Article
Immunology
Wenying Gao, Yajuan Rui, Guangquan Li, Chenyang Zhai, Jiaming Su, Han Liu, Wenwen Zheng, Baisong Zheng, Wenyan Zhang, Yongjun Yang, Shucheng Hua, Xiaofang Yu
Summary: The study demonstrates that specific deubiquitinating enzymes (DUBs) can inhibit viral proteins from HIVs/SIVs, highlighting a previously unrecognized interplay between DUBs and viral replication. This suggests that enhancing the antiviral activity of DUBs represents a promising strategy against HIVs/SIVs.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Medicinal
Serah W. Kimani, Julie Owen, Stuart R. Green, Fengling Li, Yanjun Li, Aiping Dong, Peter J. Brown, Suzanne Ackloo, David Kuter, Cindy Yang, Miranda MacAskill, Stephen Scott MacKinnon, Cheryl H. Arrowsmith, Matthieu Schapira, Vijay Shahani, Levon Halabelian
Summary: DCAF1 serves as a subunit for RING-type CRL4(DCAF1) and HECT family EDVPDCAF1 E3 ubiquitin ligases in substrate recruitment. The WDR domain of DCAF1 acts as a binding platform for substrate proteins and is targeted by HIV and SIV lentiviral adaptors. This study used a proteome-scale drug-target interaction prediction model to identify ligands for the DCAF1 WDR domain through biophysical screening and X-ray crystallography, confirming the selective binding of a predicted ligand. The findings demonstrate the successful application of artificial intelligence-enabled virtual screening methods in the absence of previously known ligands.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Multidisciplinary Sciences
Shengli Ding, Jing Yang, Xuehuan Feng, Aseem Pandey, Rola Barhoumi, Dongmei Zhang, Samantha L. Bell, Yue Liu, Luciana Fachini da Costa, Allison Rice-Ficht, Robert O. Watson, Kristin L. Patrick, Qing-Ming Qin, Thomas A. Ficht, Paul de Figueiredo
Summary: This study reveals that the recruitment of host AIC proteins to forming phagosomes depends on the activity of CD44, which is crucial for the internalization of fungal pathogens into host cells.
Review
Pharmacology & Pharmacy
Andrey A. Rosenkranz, Tatiana A. Slastnikova
Summary: A large variety of proteins have been used successfully for the treatment of different diseases, especially cancer. While most drugs target cell surface proteins, the majority of therapeutic targets are actually located inside the cell. Traditional low molecular weight drugs can penetrate all cells, causing side effects. Recent studies focus on designing multifunctional proteins to overcome these challenges and deliver drugs to the desired intracellular compartment of target cells. This review discusses the application of artificial constructs for targeted delivery of protein-based and low molecular weight drugs, as well as the obstacles and means to overcome them.
Article
Biology
Arshad Khan, Kangling Zhang, Vipul K. Singh, Abhishek Mishra, Priyanka Kachroo, Tian Bing, Jong Hak Won, Arunmani Mani, Ramesha Papanna, Lovepreet K. Mann, Eder Ledezma-Campos, Genesis Aguillon-Duran, David H. Canaday, Sunil A. David, Blanca Restrepo, Nhung Nguyen Viet, Ha Phan, Edward A. Graviss, James M. Musser, Deepak Kaushal, Marie Claire Gauduin, Chinnaswamy Jagannath
Summary: This study investigates the role of human macrophages in tuberculosis (TB) immunity and finds that different types of macrophages exhibit distinct immune responses in dealing with Mycobacterium tuberculosis. The findings suggest potential therapeutic targets for the diagnosis and immunotherapy of TB.
COMMUNICATIONS BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Monica Varela, Annemarie H. Meijer
Summary: The zebrafish model is valuable for studying tuberculosis and granulomas, providing insights into the role of innate immunity. Techniques like fluorescent dyes and transgenic markers allow real-time visualization of innate immune mechanisms like autophagy and inflammasomes in infected macrophages. Interactions between macrophages and mycobacteria drive tissue dissemination and granuloma formation, while chemokine signaling pathways recruit macrophages and influence microbicidal capacity and granuloma vascularization.
MOLECULAR MICROBIOLOGY
(2022)
Article
Medicine, Research & Experimental
Guoli Shi, Abhilash I. Chiramel, Tiansheng Li, Kin Kui Lai, Adam D. Kenney, Ashley Zani, Adrian C. Eddy, Saliha Majdoul, Lizhi Zhang, Tirhas Dempsey, Paul A. Beare, Swagata Kar, Jonathan W. Yewdell, Sonja M. Best, Jacob S. Yount, Alex A. Compton
Summary: The use of rapalog drugs increases susceptibility to SARS-CoV-2 infection in immunocompromised individuals by promoting virus entry into cells and inhibiting the cell-intrinsic immune response.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Chemistry, Multidisciplinary
Pengyu Wang, Manman Li, Tielei Gao, Jiaying Fan, Dengfeng Zhang, Ying Zhao, Yajie Zhao, Yuqin Wang, Tianwei Guo, Xi Gao, Yujun Liu, Yang Gao, Xue Guan, Xinyong Sun, Jiyi Zhao, Hong Li, Liming Yang
Summary: Electrical stimulation (ES) is a safe and effective clinical rehabilitation procedure for atherosclerosis (AS). In this study, ES was applied to the abdominal aorta of high-fat-fed Apolipoprotein E (ApoE(-/-)) mice to observe the effects on atherosclerotic plaques. Results showed that ES reduced plaque growth and increased autophagy-related gene activity. ES also restored cholesterol efflux and alleviated atherosclerotic lesion formation through the Sirt1/Atg5 pathway.
Article
Cell Biology
Chang-Jun Li, Ye Xiao, Yu-Chen Sun, Wen-Zhen He, Ling Liu, Mei Huang, Chen He, Min Huang, Kai-Xuan Chen, Jing Hou, Xu Feng, Tian Su, Qi Guo, Yan Huang, Hui Peng, Mi Yang, Guang-Hui Liu, Xiang-Hang Luo
Summary: The study reveals that during skeletal aging, proinflammatory and senescent immune cells accumulate in the bone marrow and secrete grancalcin, leading to low bone turnover and marrow fat accumulation. Grancalcin binds to plexin-b2 receptor, inhibiting its downstream signaling pathways and promoting adipogenesis over osteogenesis. Developing a grancalcin-neutralizing antibody could potentially be a targeted treatment for age-related osteoporosis.
Article
Oncology
Ashu Singh, Saumitra Dey Choudhury, Prabhjot Singh, Vishwendra Vikram Singh, Som Nath Singh, Alpana Sharma
Summary: In RCC, procedures like surgery and chemo-radiation therapy increase the risk of comorbidities. Immune-based checkpoint inhibitor therapies have limited efficacy. This study identifies KCMF1 as a potential therapeutic target in RCC due to the presence of persistent hypoxia.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Tong Zhang, Yifan Li, Chengyang Li, Jingze Zang, Erlin Gao, Johan T. Kroon, Xiaolu Qu, Patrick J. Hussey, Pengwei Wang
Summary: The study reveals a connection between the exocyst complex and the ER network in regulating the degradation of exocytic compartments, stigma senescence, and flower receptivity in plants. This research provides insights into the internal degradation mechanism in plant cells, which is essential for plant development and reproduction.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Shakuntala Surender Kumar Saraswati, Ankush Kumar Rana, Aayushi Singh, Vandana Anang, Aarti Singh, Krishnamurthy Natarajan
Summary: Mycobacterium tuberculosis suppresses defence responses in alveolar macrophages to establish a favorable environment in the human lung during infection. Heat Shock Proteins (HSPs) show significantly higher expression in active TB patients compared to those with latent infection. Inhibiting HSP-27 and HSP-70 prior to mycobacterial infection leads to a significant decrease in mycobacterial growth within macrophages. Inhibiting HSPs also increases intracellular oxidative burst levels and enhances T cell activation while inhibiting T cell inhibitory molecules. Additionally, inhibiting HSPs promotes autophagy pathway and pro-inflammatory transcription factors. HSP-27 and HSP-70 are associated with anti-apoptotic proteins Bcl-2 and Beclin-1. These findings suggest a suppressive role of host HSP-27 and HSP-70 during mycobacterial infection.
MICROBES AND INFECTION
(2023)