Casticin (CAS), a natural flavonoid found in Viticis Fructus, Viticis Cannabifoliae Fructus, and Semen Euphorbiae, shows anti-inflammatory activity and efficacy against various cancers. However, its effect on stemness associated with self-renewal in cervical cancer (CC) cells remains unclear, as well as the underlying mechanism.

PURPOSE:

The primary objective of this study was to examine the effect of CAS on CC stemness and to explore the underpinning regulatory mechanism.

METHODS:

HeLa cells underwent treatment with varying concentrations of CAS (0, 10, 30, 100 nM). To evaluate the impacts of CAS on CC stemness and tumorigenicity, sphere- and colony-formation assays and a xenograft model were employed. The study involved screening for changes in miRNAs and their target genes. The miRNA array identified an upregulation in miRNAs, whereas the mRNA array detected a downregulation of specific target genes. The latter genes were found to regulate stem cell-related genes through miR-342-3p in HeLa cells administered CAS. Next, whether miR-342-3p directly targets FOXM1 when upregulated by CAS was assessed by the luciferase reporter assay. qRT-PCR was performed to analyze miR-342-3p expression. Additionally, immunoblotting was conducted to assess the protein amounts of FoxM1 and stemness-related factors (CD133, CD49f, Nanog, and Sox2). Function rescue experiments were conducted to determine the mechanism of CAS in stemness regulation. These experiments involved utilizing a miR-342-3p inhibitor and overexpressing FOXM1 in HeLa cells.

RESULTS:

CAS decreased in vitro stemness, suppressing sphere- and colony-formation capabilities of CC. It also dose-dependently downregulated the expression of stemness-associated proteins, including CD133, CD49f, Nanog, and Sox2. Moreover, CAS inhibited in vivo carcinogenesis, remarkably reducing tumor growth in mice bearing HeLa cell xenografts. Analysis revealed downregulated FOXM1 expression in HeLa cells treated with CAS. In the luciferase reporter assay, miR-342-3p was found to directly target FOXM1 in CAS-treated HeLa cells. Additionally, miR-342-3p inhibitor transfection successfully rescued CAS' suppressive impact on stemness. Furthermore, overexpression of FOXM1 did not induce changes in miR-342-3p expression. However, it effectively rescued CAS' suppressive effects on stemness. Moreover, CAS also inhibited stemness, upregulated miR-342-3p, and lowered FOXM1 expression in the SiHa cell line.

CONCLUSION:

CAS suppresses self-renewal-associated stemness by targeting FOXM1 via miR-342-3p upregulation. These findings suggest CAS is promising as a novel therapeutic candidate in CC.

2024-11-27·Journal of the Pediatric Infectious Diseases Society

Safety and Pharmacokinetics of Casirivimab and Imdevimab (CAS + IMD) in Pediatric Outpatients With COVID-19

Article

作者: Ganguly, Samit ; Hamilton, Jennifer D ; Subramaniam, Danise ; Hughes, Diana ; Mylonakis, Eleftherios ; Pan, Cynthia ; Norton, Thomas D ; Hooper, Andrea T ; Davis, John D ; Bhore, Rafia ; Thakur, Mazhar ; Roque-Guerrero, Lilia ; Hussein, Mohamed ; Turner, Kenneth C ; Waldron, Alpana ; Atmodjo, Dominique ; Xiao, Jing ; DiCioccio, A Thomas ; Braunstein, Ned ; Cox, Edward ; Herman, Gary A ; Ali, Shazia ; Kowal, Bari ; Kohli, Anita ; Irvin, Susan C ; Geba, Gregory P ; Dakin, Paula ; Chao, Jesse

Abstract:

The safety of casirivimab + imdevimab (CAS + IMD) (anti-severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] monoclonal antibodies [mAbs]) in pediatric outpatients with coronavirus disease 2019 (COVID-19) was evaluated in a randomized phase 1/2/3 trial. Consistent with adults, CAS + IMD was generally well tolerated with low drug-induced immunogenicity rates. The findings support the development of next-generation anti-SARS-CoV-2 mAbs for at-risk pediatric patients.

2024-11-01·RESEARCH IN MICROBIOLOGY

BSC2 modulates AmB resistance via the maintenance of intracellular sodium/potassium ion homeostasis in Saccharomyces cerevisiae

Article

作者: Zhang, Xiaojuan ; Shi, Ping ; Xiao, Fulong ; Huang, Zhiwei ; Wang, Qiao ; Shen, Yuhu ; Deng, Yunxia

Previous studies on BSC2 have shown that it enhances yeast cell resistance to AmB via antioxidation and induces multidrug resistance by contributing to biofilm formation. Herein, we found that BSC2 overexpression could reverse the sensitivity of pmp3Δ to AmB and help the tested strains restore the intracellular sodium/potassium balance under exposure to AmB. Meanwhile, overexpression of the chitin gene CHS2 could simulate BSC2 to reverse the sensitivity of pmp3Δ and nha1Δ to high salt or AmB. However, BSC2 overexpression in flo11Δ failed to induce AmB resistance, form biofilms, and affect cell wall biogenesis, while CHS2 overexpression compensated the resistance of flo11Δ to AmB. Additionally, BSC2 levels were positively correlated with maintaining cell membrane integrity under exposure to AmB, CAS, or a combination of both. BSC2 overexpression in nha1Δ exhibited a similar function of CHS2, which can compensate for the sensitivity of the mutant to high salt. Altogether, the results demonstrate for the first time that BSC2 may promote ion equilibrium by strengthening cell walls and inhibiting membrane damage in a FLO path-dependent manner, thus enhancing the resistance of yeast cells to AmB. This study also reveals the possible mechanism of antifungal drugs CAS and AmB combined to inhibit fungi.

100 项与 CAs inhibitors(Sookmyung Women's University) 相关的药物交易

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