basal epithelial cells
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Author(s):  
Peng Sun ◽  
Yingying Han ◽  
Maksim Plikus ◽  
Xing Dai

AbstractStem-cell containing mammary basal epithelial cells exist in a quasi-mesenchymal transcriptional state characterized by simultaneous expression of typical epithelial genes and typical mesenchymal genes. Whether robust maintenance of such a transcriptional state is required for adult basal stem cells to fuel self-renewal and regeneration remains unclear. In this work, we utilized SMA-CreER to direct efficient basal cell-specific deletion of Ovol2, which encodes a transcription factor that inhibits epithelial-to-mesenchymal transition (EMT), in adult mammary gland. We identified a basal cell-intrinsic role of Ovol2 in promoting epithelial, and suppressing mesenchymal, molecular traits. Interestingly, Ovol2-deficient basal cells display minimal perturbations in their ability to support tissue homeostasis, colony formation, and transplant outgrowth. These findings underscore the ability of adult mammary basal cells to tolerate molecular perturbations associated with altered epithelia-mesenchymal plasticity without drastically compromising their self-renewal potential.


Author(s):  
Meenu Mehta ◽  
Vamshikrishna Malyla ◽  
Keshav R. Paudel ◽  
Dinesh Kumar Chellappan ◽  
Philip M. Hansbro ◽  
...  

Chemosensors ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 70
Author(s):  
Jamie J. Grant ◽  
Suresh C. Pillai ◽  
Tatiana S. Perova ◽  
Sarah Hehir ◽  
Steven J. Hinder ◽  
...  

Electrospun nanofibrous mats consisting of chitosan (CS) and polyvinylpyrrolidone (PVP) were constructed. Tuning of solution and process parameters was performed and resulted in an electrospun system containing a 6:4 ratio of PVP:CS. This is a significant increase in the proportion of spun CS on the previously reported highest ratio PVP:CS blend. SEM analysis showed that the nanofibrous mats with 4 wt% CS/6 wt% PVP (sample E) comprised homogenous, uniform fibres with an average diameter of 0.569 μm. XPS analysis showed that the surface of the samples consisted of PVP. Raman and FTIR analysis revealed intermolecular interactions (via H-bonding) between PVP and CS. In FTIR spectra, the contribution of chitosan to CS/PVP complexes was shown by the downshift of the C=O band and by the linear increase in intensity of C-O stretching in CS. XPS analysis showed a smaller shift at the binding energy 531 eV, which relates to the amide of the acetylated functional groups. The obtained results demonstrate a sensitivity of Raman and FTIR tests to the presence of chitosan in PVP:CS blend. The chemotherapy drug 5-Fu was incorporated into the constructs and cell viability studies were performed. WST-8 viability assay showed that exposure of A549 human alveolar basal epithelial cells to 10 mg/mL 5-Fu loaded fibres was most effective at killing cells over 24 h. On the other hand, the constructs with loading of 1 mg/mL of drug were not efficient at killing A549 human alveolar basal epithelial cells. This study showed that CS/PVP/5-Fu constructs have potential in chemotherapeutic drug delivery systems.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Monika Ruzycka-Ayoush ◽  
Patrycja Kowalik ◽  
Agata Kowalczyk ◽  
Piotr Bujak ◽  
Anna M. Nowicka ◽  
...  

Abstract Background Lung cancer is one of the most frequently diagnosed cancers all over the world and is also one of the leading causes of cancer-related mortality. The main treatment option for small cell lung cancer, conventional chemotherapy, is characterized by a lack of specificity, resulting in severe adverse effects. Therefore, this study aimed at developing a new targeted drug delivery (TDD) system based on Ag–In–Zn–S quantum dots (QDs). For this purpose, the QD nanocrystals were modified with 11-mercaptoundecanoic acid (MUA), L-cysteine, and lipoic acid decorated with folic acid (FA) and used as a novel TDD system for targeting doxorubicin (DOX) to folate receptors (FARs) on adenocarcinomic human alveolar basal epithelial cells (A549). NIH/3T3 cells were used as FAR-negative controls. Comprehensive physicochemical, cytotoxicity, and genotoxicity studies were performed to characterize the developed novel TDDs. Results Fourier transformation infrared spectroscopy, dynamic light scattering, and fluorescence quenching confirmed the successful attachment of FA to the QD nanocrystals and of DOX to the QD–FA nanocarriers. UV–Vis analysis helped in determining the amount of FA and DOX covalently anchored to the surface of the QD nanocrystals. Biological screening revealed that the QD–FA–DOX nanoconjugates had higher cytotoxicity in comparison to the other forms of synthesized QD samples, suggesting the cytotoxic effect of DOX liberated from the QD constructs. Contrary to the QD–MUA–FA–DOX nanoconjugates which occurred to be the most cytotoxic against A549 cells among others, no such effect was observed for NIH/3T3 cells, confirming FARs as molecular targets. In vitro scratch assay also revealed significant inhibition of A549 cell migration after treatment with QD–MUA–FA–DOX. The performed studies evidenced that at IC50 all the nanoconjugates induced significantly more DNA breaks than that observed in nontreated cells. Overall, the QD–MUA–FA–DOX nanoconjugates showed the greatest cytotoxicity and genotoxicity, while significantly inhibiting the migratory potential of A549 cells. Conclusion QD–MUA–FA–DOX nanoconjugates can thus be considered as a potential drug delivery system for the effective treatment of adenocarcinomic human alveolar basal epithelial cells.


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