Osteosarcoma (OS) is the most common primary malignant bone tumour among adolescents and young adults; however, its molecular pathogenesis has not been completely elucidated. Ubiquitin‑specific protease 7 (USP7), a member of the deubiquitinating enzyme family, plays a role in the malignancy process of various cancer types by targeting the key oncoprotein; however, its biological function and mechanism in OS have not been elucidated. The present study demonstrated that USP7 expression in OS tumour tissues was markedly higher than that in the paired surrounding tissues, and high USP7 expression was positively correlated with the TNM stage and metastasis in patients with OS. Next, biological function assays demonstrated that USP7 knockdown markedly inhibited OS cell migration and invasion, whereas USP7 overexpression enhanced it. Notably, USP7 can directly bind with β‑catenin to activate the Wnt/β‑catenin signalling pathway and induce epithelial‑mesenchymal transition (EMT) of OS cells. Overall, USP7 overexpression could promote OS cell metastasis by activating the Wnt/β‑catenin signalling pathway by inducing EMT, suggesting that USP7 is a potential therapeutic target for OS.
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http://dx.doi.org/10.3892/or.2018.6835 | DOI Listing |
Biochemistry
January 2025
Department of Biochemistry, Genetics and Microbiology, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria 0002, South Africa.
C-terminal amidation of antimicrobial peptides (AMPs) is a frequent minor modification used to improve antibacterial potency, commonly ascribed to increased positive charge, protection from proteases, and a stabilized secondary structure. Although the activity of AMPs is primarily associated with the ability to penetrate bacterial membranes, hitherto the effect of amidation on this interaction has not been understood in detail. Here, we show that amidation of the scorpion-derived membranolytic peptide AamAP1-Lys produces a potent analog with faster bactericidal activity, increased membrane permeabilization, and greater Gram-negative membrane penetration associated with greater conformational flexibility.
View Article and Find Full Text PDFMicrobiol Spectr
January 2025
Office of Vaccine Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Although much has been learned about the entry mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many details of the entry mechanisms of seasonal human coronaviruses (HCoVs) remain less well understood. In the present study, we used 293T cell lines stably expressing angiotensin converting enzyme (ACE2), aminopeptidase N (APN), or transmembrane serine protease 2 (TMPRSS2), which support high-level transduction of lentiviral pseudoviruses bearing spike proteins of seasonal HCoVs, HCoV-NL63, -229E, or -HKU1, respectively, to compare spike processing and virus entry pathways among these viruses. Our results showed that the entry of HCoV-NL63, -229E, and -HKU1 pseudoviruses into cells is sensitive to endosomal acidification inhibitors (chloroquine and NHCl), indicating entry via the endocytosis route.
View Article and Find Full Text PDFJ Virol
January 2025
Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, Texas, USA.
Unlabelled: Human norovirus (HuNoV) is a leading cause of gastroenteritis worldwide and is associated with significant morbidity, mortality, and economic impact. There are currently no licensed antiviral drugs for the treatment of HuNoV-associated gastroenteritis. The HuNoV protease plays a critical role in the initiation of virus replication by cleaving the polyprotein.
View Article and Find Full Text PDFJ Infect Dis
January 2025
Gilead Sciences, Inc., 333 Lakeside Dr., Foster City, CA, 94404 USA.
Background: Lenacapavir is a highly potent first-in-class inhibitor of HIV-1 capsid approved for the treatment of heavily treatment-experienced (HTE) people with HIV-1 (PWH) harboring multidrug resistant (MDR) virus, in combination with an optimized background regimen (OBR). Resistance analyses conducted after 2 years of lenacapavir treatment in the phase 2/3 CAPELLA study are described.
Methods: CAPELLA enrolled viremic HTE PWH with resistance to 2 or more drugs per class in at least 3 of the 4 main drug classes.
Chem Biodivers
January 2025
Zhengzhou University, College of Chemistry, Kexue Road 100, 450001, Zhengzhou, CHINA.
The main protease (Mpro) is a cysteine enzyme and represents a vital target for antiviral drug screening. In this work, Twenty-five pyrrole derivatives were synthesized and screened by enzyme activity experiments. Results indicate that six pyrrole derivatives can bind to Mpro and have inhibitory effect on Mpro.
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