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- Licochalcone A Protects Vaginal Epithelial Cells Against Candida albicans Infection Via the TLR4/NF-κB Signaling Pathway.
- Wei Li, Yujun Yin, Taoqiong Li, Yiqun Wang, Wenyin Shi
- J. Microbiol. 2024;62(7):525-533. Published online May 31, 2024
- DOI: https://doi.org/10.1007/s12275-024-00134-z
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Abstract
- Vulvovaginal candidiasis (VVC) is a prevalent condition affecting a significant portion of women worldwide. Licochalcone A (LA), a natural compound with diverse biological activities, holds promise as a protective agent against Candida albicans (C. albicans) infection. This study aims to investigate the potential of LA to safeguard vaginal epithelial cells (VECs) from C. albicans infection and elucidate the underlying molecular mechanisms. To simulate VVC in vitro, VK2-E6E7 cells were infected with C. albicans. Candida albicans biofilm formation, C. albicans adhesion to VK2-E6E7 cells, and C. albicans-induced cell damage and inflammatory responses were assessed by XTT reduction assay, fluorescence assay, LDH assay, and ELISA. CCK-8 assay was performed to evaluate the cytotoxic effects of LA on VK2-E6E7 cells. Western blotting assay was performed to detect protein expression. LA dose-dependently hindered C. albicans biofilm formation and adhesion to VK2-E6E7 cells. Furthermore, LA mitigated cell damage, inhibited the Bax/Bcl-2 ratio, and attenuated the secretion of pro-inflammatory cytokines in C. albicans-induced VK2-E6E7 cells. The investigation into LA's impact on the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway revealed that LA downregulated TLR4 expression and inhibited NF-κB activation in C. albicans-infected VK2-E6E7 cells. Furthermore, TLR4 overexpression partially abated LA-mediated protection, further highlighting the role of the TLR4/NF-κB pathway. LA holds the potential to safeguard VECs against C. albicans infection, potentially offering therapeutic avenues for VVC management.
Research Support, Non-U.S. Gov't
- Functional Characterization of the Genes tauO, tauK, and tauI in the Biosynthesis of Tautomycetin
- Fen Wang , Rixiang Kong , Bo Liu , Jing Zhao , Rongguo Qiu , Li Tang
- J. Microbiol. 2012;50(5):770-776. Published online November 4, 2012
- DOI: https://doi.org/10.1007/s12275-012-2154-x
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Abstract
- Tautomycetin is a specific protein phosphatase I inhibitor. In an effort to elucidate the biosynthetic mechanism of tautomycetin, we inactivated genes of the tautomycetin biosynthetic gene cluster, tauI, tauO, and tauK, which encode for putative P450 oxidase, citryl-CoA lyase, and esterase enzymes, respectively. The mutant STQ0606 (ΔtauO) did not produce any detectable amount of tautomycetin intermediates but could convert dialkylmaleic anhydride to tautomycetin, strongly indicating that TauO was involved in dialkylmaleic anhydride biosynthesis. STQ1211 (ΔtauK) accumulated dialkylmaleic anhydride, whereas the cofermentation of STQ1211 (ΔtauK) and STQ0606 (ΔtauO) restored the production of tautomycetin. Together, these results suggest that TauK was responsible for the conjugation of dialkylmaleic anhydride and the polyketide moiety in tautomycetin biosynthesis. The disruption of tauI resulted in the accumulation of 5-des-ketotautomycetin, revealing that TauI was responsible for the oxidation at C5 as the last step. Although the shunt pathways were involved in the biosynthesis of tautomycetin, the main post-polyketide synthase tailoring steps were dehydration, decarboxylation and oxidation, taking place consecutively. This study allowed us to predict the biosynthesis of tautomycetin more accurately and provided novel insights into the mechanism of the biosynthesis of tautomycetin.
- Solvent/Detergent Inactivation and Chromatographic Removal of Human Immunodeficiency Virus During the Manufacturing of a High Purity Antihemophilic Factor Ⅷ Concentrate
- In Seop Kim , Yong Woon Choi , Hang Sang Woo , Chong E. Chang , Soungmin Lee
- J. Microbiol. 2000;38(3):187-191.
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Abstract
- A validation study was conducted to determine the efficacy of solvent/detergent (S/D) inactivation and Q-Sepharose column chromatographic removal of the human immunodeficiency virus (HIV) during the manufacturing of a high purity antihemophilic factor VIII (GreenMono) from human plasma. S/D treatment using the organic solvent, tri (n-butyl) phosphate, and the detergent, Triton X-100, was a robust and effective step in eliminating HIV-1. The HIV-1 titer was reduced from an initial titer of 8.3 log 10 TCID 50 to undetectable levels within one minute of S/D treatment. HIV-1 was effectively partitioned from factor VIII during Q-Sepharose column chromatography with the log reduction factor of 4.1. These results strongly assure the safety of GreenMono from HIV.
- Removal and Inactivation of Hepatitis A Virus during Manufacture of a High Purity Antihemophilic Factor VIII Concentrate from Human Plasma
- In Seop Kim , Yong Woon Choi , Sung Rae Lee , Mahl Soon Lee , Ki Ho Huh , Soungmin Lee
- J. Microbiol. 2001;39(1):67-73.
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Abstract
- A validation study was conducted to evaluate the efficacy and mechanism of the cryo-precipitation, monoclonal anti-FVIIIc antibody (mAb) chromatography, Q-Sepharose chromatography, and lyophilization steps involved in the manufacture of high purity factor VIII (GreenMono) from human plasma, in the removal and/or inactivation of hepatitis A virus (HAV). Samples from the relevant stages of the production process were spiked with HAV and subjected to scale-down processes mimicking the manufacture of the high purity factor VIII concentrate. Samples were collected at each step and immediately titrated using a 50% tissue culture infectious dose (TCID50) and then the virus reduction factors were evaluated. HAV was effectively partitioned from factor VIII during cryo-precipitation with the log reduction factor of 3.2. The mAb chromatography was the most effective step for removal of HAV with the log reduction factor of ³4.3. HAV infectivity was not detected in the fraction of factor VIII, while most of HAV infectivity was recovered in the fractions of flow through and wash during mAb chromatography. Q-Sepharose chromatography showed the lowest efficacy for partitioning HAV with the log reduction factor of 0.7. Lyophilization was an effective step in inactivating HAV with the log reduction factor of 2.3. The cumulative log reduction factor, ³10.5, achieved for the entire manufacturing process was several magnitudes greater than the potential HAV load of current plasma pools.
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