Results 141 to 150 of about 268,002 (359)

Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication

Viruses, 2018
Viruses must parasitize host cell translational machinery in order to make proteins for viral progeny. In this study, we sought to use this signal transduction conduit against them by inhibiting multiple kinases that influence translation.
Todd M. Bell, Virginia Espina, Lindsay Lundberg, Chelsea Pinkham, Ashwini Brahms, Brian D. Carey, Shih-Chao Lin, Bibha Dahal, Caitlin Woodson, Cynthia de la Fuente, Lance A. Liotta, Charles L. Bailey, Kylene Kehn-Hall   +12 more
doaj   +1 more source

Inhibition of the Mechanistic Target of Rapamycin (mTOR)–Rapamycin and Beyond [PDF]

Cold Spring Harbor Perspectives in Medicine, 2016
Rapamycin is a Food and Drug Administration (FDA)-approved immunosuppressant and anticancer agent discovered in the soil of Easter Island in the early 1970s. Rapamycin is a potent and selective inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, which acts as a central integrator of nutrient signaling pathways.
openaire   +2 more sources

FSTL1 Orchestrates Metabolic‐Epigenetic Crosstalk: Glycolysis‐Dependent H3K18 Lactylation Drives Cartilage Fibrosis in Osteoarthritis

Advanced Science, EarlyView.
FSTL1 promotes glycolysis during chondrocyte fibrosis by triggering the HIF‐1 signaling pathway, which causes lactate to accumulate. The buildup of lactate leads to changes in histone lysine lactylation, which in turn enhances the expression of genes associated with fibrosis.
Feng Lu, Yunyuan Yu, Guangrong Yin, Huiqun Hu, Shishuo Li, Yuting Tang, Yimin Liu, Maoyuan Li, Liang liang Wang, Chao Xu, Gongyin Zhao, Baojun Zhou, Yuji Wang   +12 more
wiley   +1 more source

Innovative Approaches for Immune Tolerance to Factor VIII in the Treatment of Hemophilia A

Frontiers in Immunology, 2017
Hemophilia A (coagulation factor VIII deficiency) is a debilitating genetic disorder that is primarily treated with intravenous replacement therapy.
Alexandra Sherman, Moanaro Biswas, Roland W. Herzog   +2 more
doaj   +1 more source

TRIM38 Suppresses Breast Cancer Progression via Modulating SQSTM1 Ubiquitination and Autophagic Flux

Advanced Science, EarlyView.
TRIM38, an E3 ubiquitin ligase, suppresses breast cancer progression by inhibiting proliferation, migration, and invasion. Downregulated in breast tumor, its loss correlates with poor prognosis. Mechanistically, TRIM38 mediates K63‐linked ubiquitination of SQSTM1/p62 at K420, disrupting SQSTM1‐LC3 interaction and blocking autophagic flux.
Shan Jiang, Lijuan Wang, Dianwen Han, Peng Su, Bing Chen, Wenjing Zhao, Tong Chen, Ning Zhang, Xiaolong Wang, Yiran Liang, Yaming Li, Chen Li, Xi Chen, Dan Luo, Qifeng Yang   +14 more
wiley   +1 more source

Multifaceted aging and rapamycin

Aging, 2013
Aging is commonly defined as a time-dependent loss of physiological integrity, leading to the decline and impair in organism functions and to the increase of risk for cancer and other major age-associated diseases, finally increasing vulnerability to death [1].
openaire   +2 more sources

Metabolic Reprogramming of T Cells by Dual UCP2 and IL‐17 Blockade Enhances Immunity Against Pancreatic Cancer

Advanced Science, EarlyView.
This study demonstrates that dual UCP2/IL‐17 blockade reprograms T‐cell metabolism to overcome PDAC immunosuppression. Genipin‐mediated UCP2 inhibition enhances CD8⁺ T‐cell IFN‐γ via IL‐12R/STAT4/mTOR signaling and mitochondrial OXPHOS. Combined IL‐17 depletion amplifies Tc1/Th1 responses, reduces MDSCs, and prolongs survival in PDAC models ...
Chuan‐Teng Liu, Chun‐Chieh Yeh, Tsai‐Chen Wu, Chia‐Hsin Lin, Yi‐Ting Kuo, Yoichiro Iwakura, Yuan‐Ji Day, Charles Drake, Vedran Radojcic, Ying‐Chyi Song, Heng‐Hsiung Wu, Hung‐Rong Yen   +11 more
wiley   +1 more source

Flipping the Switch: MeCP2‐Mediated Lactylation Rewires Microglial Metabolism and Inflammation via the HK2/mTOR Axis in Poststroke Neuroinflammation

Advanced Science, EarlyView.
Stroke‐induced lactate accumulation promotes p300‐mediated lactylation of methyl‐CpG binding protein 2 (MeCP2) at lysine 210, which reprograms microglial metabolism toward glycolysis and activates the hexokinase 2 (HK2)/mTOR axis. This cascade promotes proinflammatory responses and impairs neurofunctional outcomes.
Zengyu Zhang, Shanshan Huang, Yong Wang, Zhiwen Jiang, Zhuohang Liu, Chenran Wang, Rong Ji, Yiwen Yuan, Xueyu Mao, Kaicheng Yang, Huicong Niu, Yanqin Gao, Jing Zhao   +12 more
wiley   +1 more source

IL4I1⁺ Macrophages and TDO2⁺ Myofibroblasts Drive AhR‐Mediated Immunosuppression and Ferroptosis Resistance in Solid Predominant Lung Adenocarcinoma

Advanced Science, EarlyView.
Solid predominant lung adenocarcinoma exhibits an immune‐excluded, ferroptosis‐resistant niche enriched with IL4I1⁺ TAMs and TDO2⁺ myCAFs. Spatial and multi‐omics analyses reveal AhR‐driven crosstalk that promotes T cell exhaustion and therapy resistance. Blocking AhR with CH‐223191 restores ferroptosis sensitivity, and its combination with ferroptosis
Zhaoxuan Wang, Weijiao Xu, Lei Zhao, Lin Zhong, Wendan Yu, Shengmin Wang, Lu Sun, Tao Guo, Fengzhou Li, Zhuoshi Li, Lei Fang, Shiqing Wang, Guohui Zhang, Guoqing Xue, Wei Guo, Shilei Zhao, Chundong Gu   +16 more
wiley   +1 more source

PDIA3 Inhibition Facilitates Sensitivity of IKE‐Induced Ferroptosis via STAT3/LCN2 Axis to Improve Glioblastoma Therapy

Advanced Science, EarlyView.
In this manuscript, protein disulfide isomerase A3 (PDIA3) is identified as a key factor mediating the susceptibility of ferroptosis in GBM. Inhibition of PDIA3 enhances IKE or cystine starvation‐induced ferroptosis in GBM cells by resulting in the accumulation of lipid peroxidation and a reduction in GSH level.
Jie Zhang, Wei Wang, Xin Liu, Peifen Lu, Xinjing Liu, Qiucheng Nie, Siyuan Xin, Hong Li, Donglin Yu, Xinyue Zhang, Kailong Li, Xiaomin Han, Shuping Zhang, Wei Chong, Lili Sun, Wei Li, Tao Xin, Jin Jiao, Qiang Ma, Yiju Wei   +19 more
wiley   +1 more source