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Cell Biology
Dong Guo, Yingying Tong, Xiaoming Jiang, Ying Meng, Hongfei Jiang, Linyong Du, Qingang Wu, Shan Li, Shudi Luo, Min Li, Liwei Xiao, Haiyan He, Xuxiao He, Qiujing Yu, Jing Fang, Zhimin Lu
Summary: High glucose promotes PD-L1 expression in tumor cells, leading to tumor immune evasion. Inhibition of HK2 and PD-1 can eliminate tumor immune evasion and enhance the anti-tumor effect of immune checkpoint blockade.
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Multidisciplinary Sciences
Jian-shuai Yu, Tao Huang, Yu Zhang, Xin-tao Mao, Ling-jie Huang, Yi-ning Li, Ting-ting Wu, Jiang-yan Zhong, Qian Cao, Yi-yuan Li, Jin Jin
Summary: The classic NF-kappa B pathway is crucial in immune responses and inflammatory diseases. This study showed that IKK beta ubiquitination on lysine-238 increases during inflammation, with USP16 identified as a key regulator affecting p105 phosphorylation. Elevated expression of USP16 in colon macrophages of IBD patients and conditional knockout of USP16 in myeloid cells resulted in reduced severity of IBD, providing insights for targeted intervention therapy.
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Biochemistry & Molecular Biology
Lei Xu, Yangfan Ye, Zeqiang Tao, Tian Wang, Yutian Wei, Wanzhi Cai, Xin Wan, Pengzhan Zhao, Wei Gu, Bin Gu, Liuchao Zhang, Yufei Tian, Ning Liu, Yiming Tu, Jing Ji
Summary: This study elucidated the role of MLPH in GBM radiation resistance, showing that MLPH promotes radiotherapy resistance by regulating the NF-kappa B pathway. Additionally, O-GlcNAcylation of MLPH protects it from degradation and stabilizes its presence in cells. These findings provide insights into a potential mechanism of GBM radiation resistance and suggest a therapeutic strategy for GBM treatment.
Article
Oncology
Thomas A. Burley, Emma Kennedy, Georgia Broad, Melanie Boyd, David Li, Timothy Woo, Christopher West, Eleni E. Ladikou, Iona Ashworth, Christopher Fegan, Rosalynd Johnston, Simon Mitchell, Simon P. Mackay, Andrea G. S. Pepper, Chris Pepper
Summary: In this study, the researchers evaluated the effects of an NF-kappa B inducing kinase (NIK) inhibitor, CW15337, on primary chronic lymphocytic leukemia (CLL) cells, CLL and multiple myeloma (MM) cell lines, and normal B- and T-lymphocytes. They found that CW15337 induced apoptosis and inhibited the non-canonical NF-kappa B signaling pathway, reversing BCL2 family-mediated resistance. The combination of CW15337 with fludarabine or ABT-199 showed synergistic cytotoxic effects.
Review
Biochemistry & Molecular Biology
Li Tao, Xiaomeng Ren, Wenhui Zhai, Zheng Chen
Summary: The non-canonical NF-kappa B signaling pathway plays a crucial role in liver diseases by regulating liver homeostasis and participating in various pathological processes. Small-molecule inhibitors targeting this pathway have shown potential in the treatment of liver injuries.
Article
Immunology
Kunihiko Moriya, Tomohiro Nakano, Yoshitaka Honda, Miyuki Tsumura, Masato Ogishi, Motoshi Sonoda, Masahiko Nishitani-Isa, Takashi Uchida, Mohamed Hbibi, Yoko Mizoguchi, Masataka Ishimura, Kazushi Izawa, Takaki Asano, Fumihiko Kakuta, Daiki Abukawa, Darawan Rinchai, Peng Zhang, Naotomo Kambe, Aziz Bousfiha, Takahiro Yasumi, Bertrand Boisson, Anne Puel, Jean-Laurent Casanova, Ryuta Nishikomori, Shouichi Ohga, Satoshi Okada, Yoji Sasahara, Shigeo Kure
Summary: This study reports six patients from five families with RELA mutations, leading to autoinflammatory and autoimmune manifestations. The mutations result in loss of function of RelA protein, leading to excessive IFN expression and autoimmune response. The DN RELA mutations are identified as a novel cause of chronic mucocutaneous ulcerations with autoinflammatory and autoimmune manifestations.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Wei Xiao, Zehui He, Weikang Luo, Dandan Feng, Yang Wang, Tao Tang, Ali Yang, Jiekun Luo
Summary: Intracerebral hemorrhage (ICH) induces inflammatory response that affects brain repair and organism recovery. Research suggests that Buyang Huanwu Decoction (BYHWD) can attenuate the inflammatory response during ICH recovery in rats by inhibiting the NIK-mediated noncanonical NF-kappa B signaling pathway, improving neurological function in rats.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Qian Li, Yu-Heng Zhao, Cheng Xu, Ye-Lin Liang, Yin Zhao, Qing-Mei He, Jun-Yan Li, Kai-Lin Chen, Han Qiao, Na Liu, Jun Ma, Lei Chen, Ying-Qin Li
Summary: This study reveals that circWDR37 deficiency limits the proliferation, migration, and invasion of senescent NPC cells induced by cisplatin or gemcitabine. Mechanistically, circWDR37 binds and dimerizes PKR, leading to PKR autophosphorylation and activation. Activated PKR phosphorylates IKKβ, releasing RELA from IκBα and activating NF-κB, thus promoting the transcription of CCND1 and senescence-associated secretory phenotype component genes in a circWDR37-dependent manner. Low circWDR37 levels are associated with favorable survival and chemotherapy response in NPC patients treated with gemcitabine or cisplatin induction chemotherapy.
Article
Fisheries
Rodrigo Guabiraba, Damaris Ribeiro Rodrigues, Paul T. Manna, Melanie Chollot, Vincent Saint-Martin, Sascha Trapp, Marisa Oliveira, Clare E. Bryant, Brian J. Ferguson
Summary: The innate immune response relies on the ability of host cells to detect and respond to microbial nucleic acids. Toll-like receptors (TLRs) play a crucial role in this process by distinguishing self from non-self. This study focused on TLR21, an avian TLR that recognizes bacterial DNA motifs. The findings suggest that avian TLR21 shares similar activation mechanisms to mammalian TLR9, highlighting the conservation of nucleic acid sensing mechanisms across species.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2024)
Article
Cell Biology
Wenfei Pan, Limei Deng, Haitao Wang, Vivien Ya-Fan Wang
Summary: The NF-kappa B family of dimeric transcription factors regulate various biological functions. A study has revealed that the atypical I kappa B protein, Bcl3, plays a crucial role in enhancing the population of the p52:p52 homodimer within the NF-kappa B family. Bcl3 competes with other NF-kappa B subunits for efficient p52:p52 homodimer formation, leading to the upregulation of target genes involved in cell proliferation, migration, and inflammation. The aberrant activation of Bcl3 and p52 contributes to cancer.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Lijie Yao, Liqing Xu, Lijuan Zhou, Shuizhen Wu, Weihao Zou, Min Chen, Jiating Chen, Hongjuan Peng
Summary: Toxoplasma gondii evades host innate immune responses by promoting the degradation of TRIM21 through interacting with its virulence factor ROP18, TRIM21 plays a significant role in combating T. gondii infection, and its function can modulate parasitophorous vacuole membrane acidification through ubiquitin labeling, affecting the parasite's growth.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Microbiology
Wai-Yin Lui, Aradhana Bharti, Nok-Hei Mickey Wong, Sonia Jangra, Michael Botelho, Kit-San Yuen, Dong-Yan Jin
Summary: This study identifies BPLF1 as a virulence factor of EBV that evades human innate immune responses by removing polyubiquitin marks on critical effector proteins. The study demonstrates the importance of the DUB activity of BPLF1 in suppressing antiviral responses and provides insights into the pathogenesis of EBV and potential antiviral strategies.
Article
Cell Biology
Dianbo Long, Yiyang Xu, Guping Mao, Ruobing Xin, Zengfa Deng, Hongyi Liao, Zhiwen Li, Zhi Yang, Baoxi Yu, Zhijian Yang, Aishan He, Ziji Zhang, Yan Kang
Summary: tRNA-derived fragments (tRFs) have been shown to play important roles in cell metabolism by regulating gene expression. This study investigates the role of tRFs in the cellular metabolism of the anterior cruciate ligament (ACL). The findings reveal that TRF365 regulates ACL cell metabolism by targeting IKBKB.
CELL DEATH DISCOVERY
(2022)
Article
Cell Biology
Juan Antonio Fafian-Labora, Ana O'Loghlen
Summary: The study showed that IKK epsilon, IKK alpha, and IKK beta play crucial roles in EV-mediated senescence, while siRNA targeting p65 can prevent senescence activation. Additionally, the IKK pathways are also relevant to aging, as knockout of IKKA, IKKB, and IKKE can avoid the activation of senescence.
Article
Multidisciplinary Sciences
Dai Kusumoto, Tomohisa Seki, Hiromune Sawada, Akira Kunitomi, Toshiomi Katsuki, Mai Kimura, Shogo Ito, Jin Komuro, Hisayuki Hashimoto, Keiichi Fukuda, Shinsuke Yuasa
Summary: The paper presents a morphology-based deep learning system to identify senescent cells and evaluate the effects of anti-senescent reagents. The system uses convolutional neural networks (CNN) to classify cellular senescence and successfully identifies anti-senescent drugs through morphology-based drug screening.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)