Human tissue kallikrein-binding protein (Kallistatin, KAL), a secretory protein that participates in the regulation of multiple signaling pathways by binding to the extracellular receptor, however, at present has not been reported about the intracellular activity, and whether it has the similar biological activity with extracellular activity. Here we constructed no signal peptide KAL (NSK) into the adeno-associated virus vector to explore the intracellular activity of KAL. Both the endothelial cell and lung cancer cells could express KAL, but not secreted after rAAV2-NSK transfection. The proliferation and migration of human umbilical vein endothelial cells (HUVECs) were inhibited, but the apoptosis rate was not affected. The proliferation rates, mobility and tubule formation of all the three tested lung cancer cells, such as NCI-H446, NCI-H460 and A549, were inhibited to different extents. This cellular study not only confirmed the intracellular activity, but also suggested it may serve as a kind of "balance factor" in multi-targeted controlling, which may provide a new train of thoughts to explain the regulatory contradiction in PI3K-Akt signaling pathways by KAL.
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Bioresour Bioprocess
January 2025
Qingdao Innovation Institute of East China University of Science and Technology, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, People's Republic of China.
Cephalosporin C (CPC) is a critical raw material for cephalosporin antibiotics produced by Acremonium chrysogenum. During fermentation, the oxygen supply is a crucial factor limiting the efficient biosynthesis of CPC. This study demonstrated that the addition of exogenous surfactants significantly increased the dissolved oxygen (DO) level, extracellular catalase content, and final CPC titer.
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January 2025
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Fenglin Road, Shanghai 200032, China; State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, China; Key Laboratory of Viral Heart Diseases, National Health Commission, Shanghai, China; Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai, China; Institutes of Biomedical Sciences, Fudan University, Shanghai, China. Electronic address:
Angiogenesis plays a pivotal role in ischemic cardiovascular disease, accompanied by epigenetic regulation during this process. Sirtuin 6 (SIRT6) has been implicated in the regulation of DNA repair, transcription and aging, with its deacetylase activity fully studied. However, the role of SIRT6 demyristoylase activity remains less clear, with even less attention given to its myristoylated substrates.
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December 2024
School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112102, Israel; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA. Electronic address:
Alzheimer's disease (AD) diagnosis relies on the presence of extracellular β-amyloid (Aβ) and intracellular hyperphosphorylated tau (p-tau). Emerging evidence suggests a potential link between AD pathologies and infectious agents, with herpes simplex virus 1 (HSV-1) being a leading candidate. Our investigation, using metagenomics, mass spectrometry, western blotting, and decrowding expansion pathology, detects HSV-1-associated proteins in human brain samples.
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Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Centre for Cancer Research, University of Melbourne, Melbourne, VIC, Australia. Electronic address:
Several transcription inhibitors have been developed as cancer therapies. However, they show modest clinical activity, highlighting that our understanding of the cellular response to transcriptional inhibition remains incomplete. Here we report that potent inhibitors of transcription not only impact mRNA output but also markedly impair mRNA transcript localization and nuclear export.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
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Darmstadt University of Technology: Technische Universitat Darmstadt, Clemens-Schöpf-Institute of Organic Chemistry and Biochemistry, Alarich-Weiss-Strasse 4, 64287, Darmstadt, GERMANY.
Macrocycles are increasingly considered as promising modalities to target challenging intracellular proteins. However, strategies for transitioning from active linear starting points to improved macrocycles are still underdeveloped. Here we explored the derivatization of linkers as an approach for macrocycle optimization.
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