Biology subjects

Koviazina, R.

Publications and source records attributed to Koviazina, R..

3 recordsLinked to original sources

bioRxiv2025

Exposure to per- and polyfluoroalkyl substances elicits cell type-specific impacts on p53 and TGF-β signaling pathways

Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic chemicals extensively used as plastic additives. Their environmental persistence and potential for bioaccumulation have raised significant toxicological concerns. This study evaluates the cytotoxic and molecular effects of Perfluorooctanoic acid (PFOA) and its replacement compound, Perfluoro(2-methyl-3-oxohexanoic) acid (GenX), in human-derived skin (A375), liver (HepG2), kidney (SN12C), and colon (SW620) cell lines. The experimental design assessed cell viability, gene expression, and perturbations in key cellular stress pathways, with a particular focus on TGF-{beta}/SMAD-mediated inflammation and the p53-driven DNA damage response. Our results demonstrate compound- and cell-type-specific toxicity, with GenX displaying reduced cytotoxicity compared to PFOA across all cell types. Molecular analyses revealed that both PFAS compounds induced alterations in the TGF-{beta}/SMAD pathway, consistent with a pro-inflammatory cellular state. Additionally, we observed activation of the DNA damage response, as evidenced by increased expression of ATM, ATR, and p53, alongside ribosomal stress-related changes in RPL5 and RPL11. Notably, while skin and liver cells exhibited similar response profiles, kidney and colon cells showed divergent modulation of SMAD signaling, suggesting tissue-specific susceptibility and mechanistic differences. These findings contribute to a deeper understanding of the differential toxicological profiles of legacy and replacement PFAS, with implications for health risk assessment and regulatory policy. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/652004v2_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@ce20aaorg.highwire.dtl.DTLVardef@c29608org.highwire.dtl.DTLVardef@1081ae6org.highwire.dtl.DTLVardef@11e0401_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2024

Upregulation of DEK Expression in Uterine Myomas and Cervical Cancer as a Potential Prognostic Factor

The aim of this pilot study is to investigate the role of the DEK protein as a potential prognostic marker in gynecological tumors, specifically focusing on uterine myomas and cervical cancer. The study cohort comprised Chinese female patients manifesting with menorrhagia and pelvisalgia, from whom neoplastic and adjacent non-neoplastic tissue specimens were procured during surgical intervention for either leiomyomas or cervical carcinoma. DEK protein and messenger RNA (mRNA) levels were measured across normal uterine tissue, uterine myomas, and cervical cancer tissues using Western blotting, immunohistochemistry, and quantitative real time polymerase chain reaction (qRT-PCR). Results revealed a marked increase in DEK protein expression in cervical cancer tissues, moderate expression in uterine myomas, and minimal levels in normal uterine tissues. Statistical analyses confirmed significant differences in DEK protein expression between tissue types, though mRNA expression differences did not reach statistical significance. These findings suggest DEKs involvement in tumor development and suppression, making it a promising biomarker for early detection in gynecological tumors. Further research is needed to elucidate DEKs mechanisms in gynecological tumorigenesis and its potential as an early biomarker, addressing critical need in womens health.

cancer biology↗

bioRxiv2024

Detection of Nontoxic BoNT/A Levels in Post-Facial Botox Injection Breastmilk using a Multi-technique Approach

BackgroundThe use of cosmetic Botox (Botulinum Neurotoxin Type A, BoNT/A ) has become increasingly prevalent. Particularly after pregnancy, postpartum depression represents one major factor motivating women to use Botox even during the lactation and breastfeeding period. Currently, there is limited understanding of the impact of Botox on lactation and the potential of its active component passing into breastmilk and affecting the infant. MethodsBreastmilk samples were acquired from five women aged between 28 - 45 through a clinic in Suzhou, Jiangsu, P.R. China. Three sample sets ranged from 1 hour to 1 year after facial Botox treatments (64 U), whereas the remaining two sample sets were from women who never received Botox treatment. BoNT/A concentrations in samples were detected using standard Enzyme-Linked Immunosorbent Assay (ELISA), unreduced and reduced Western Blotting, confocal micro-Raman Spectroscopy, and Mass Spectrometry(LC-MS). FindingsFrom ELISA, breastmilk BoNT/A concentrations peaked at 33.4 pg/mL 4 days after Botox injection. BoNT/A concentrations were highest overall in the first week and around two months after injection. While non-reducing polyacrylamide gel electrophoresis (PAGE) showed a protein band of 150 kDa peaking at 48 hours, reduced SDS-PAGE detected a 100 kDa protein first peaking at 72 hours, then re-emerging after 7 days, respectively, and in line with previous observations by others. Interestingly, micro-Raman spectroscopy indicated additional Raman peaks at 6 hours and 48 hours that were not present in other breastmilk samples which were evaluated in this study. However, no clear indication of BoNT/A was detected in Mass Spectrometry (LC-MS). InterpretationThe amount of BoNT/A in breastmilk peaks around 48 hours, and at 2 months after facial injection. Even over a year after injection, BoNT/A can be detected. However, all quantities of BoNT/A detected in this study are highly likely to be safe for infants. Additionally, our study suggests that alternative methods, besides ELISA, may be utilized for the rapid detection of low concentrations of BoNT/A in body fluid samples. FundingDuke Kunshan University Start-Up funds, Duke Kunshan University Undergraduate Studies Signature Work Research Grant, Synear and Wang-Cai Biochemistry grants, and Kunshan Municipal Government research funding. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/595434v1_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@fcdd11org.highwire.dtl.DTLVardef@11591daorg.highwire.dtl.DTLVardef@11ab30eorg.highwire.dtl.DTLVardef@1e19311_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIBoNT/A was detected in the breastmilk of 3 women after facial Botox injections of 64 U. C_LIO_LIToxin levels peaked in the first week and at around 2 months after injection. C_LIO_LIAll detected levels (up to 33.40 pg/mL) were significantly below the lethal dose for newborns. C_LI

molecular biology↗