Biology subjects

Kao, P.-L.

Publications and source records attributed to Kao, P.-L..

3 recordsLinked to original sources

bioRxiv2024

Centella asiatica Tissue Culture-Derived Extracellular Vesicles: A Multifaceted Approach to Skincare Applications

BackgroundCentella asiatica has long been used as a medicinal herb in traditional Asian medicine. Its wound healing, skin improvement, and neuroprotective properties have been widely studied. Extracellular vesicles (EVs) are secreted by cells and contain bioactive components with therapeutic properties. ObjectivesThis study aims to characterize EVs isolated from C. asiatica tissue culture and investigate their therapeutic properties using in vitro assays and a UVB-induced damage mouse model. MethodsEVs were isolated from C. asiatica tissue culture and characterized by nanoparticle tracking analysis (NTA) and scanning electron microscopy (SEM). Cytotoxicity, anti-oxidation, anti-melanin, and anti-inflammation of the EVs were evaluated by MTT assay, tyrosinase assay and RT-qPCR in chemical or in vitro assays. A UVB-induced photodamage mouse model was established to assess the anti-inflammation effect of EVs in vivo. Gels with or without EVs were applied to the damaged site and skin appearance was observed daily and skin histopathology was analyzed on day 7 by H&E and immunohistochemical staining. ResultsC. asiatica EVs were found to contain high levels of polyphenols and mitigate hydrogen peroxide-induced intracellular ROS. The EVs were further able to reduce intracellular melanin content and tyrosinase activity, and exhibited anti-inflammatory effects by downregulating the expression of pro-inflammatory genes COX2 as well as nitric oxide production. In mice with UVB-induced skin damage, daily application of C. asiatica EV gel reduced skin epidermis thickness and inflammation compared to UVB-only or blank gel at seven days after UV irradiation. ConclusionsThe beneficial effects of C. asiatica EVs on skin quality warrant further studies as promising agents in skin care applications.

pharmacology and toxicology↗

bioRxiv2024

Measuring single-cell density with high throughput enables dynamic profiling of immune cell and drug response from patient samples

Cell density, the ratio of cell mass to volume, is an indicator of molecular crowding and therefore a fundamental determinant of cell state and function. However, existing density measurements lack the precision or throughput to quantify subtle differences in cell states, particularly in primary samples. Here we present an approach for measuring the density of 30,000 single cells per hour with a precision of 0.03% (0.0003 g/mL) by integrating fluorescence exclusion microscopy with a suspended microchannel resonator. Applying this approach to human lymphocytes, we discovered that cell density and its variation decrease as cells transition from quiescence to a proliferative state, suggesting that the level of molecular crowding decreases and becomes more regulated upon entry into the cell cycle. Using a pancreatic cancer patient-derived xenograft model, we found that the ex vivo density response of primary tumor cells to drug treatment can predict in vivo tumor growth response. Our method reveals unexpected behavior in molecular crowding during cell state transitions and suggests density as a new biomarker for functional precision medicine.

bioengineering↗

bioRxiv2021

FGFR inhibitor mediated dismissal of SWI/SNF complexes from YAP-dependent enhancers induces adaptive therapeutic resistance

How cancer cells adapt to evade the therapeutic effects of drugs targeting oncogenic drivers is poorly understood. Here we report an epigenetic mechanism leading to the adaptive resistance of triple-negative breast cancer (TNBC) to fibroblast growth factor receptor (FGFR) inhibitors. Prolonged FGFR inhibition suppresses the function of BRG1-dependent chromatin remodeling leading to an epigenetic state that derepresses YAP-associated enhancers. These chromatin changes induce the expression of several amino acid transporters resulting in increased intracellular levels of specific amino acids that reactivate mTORC1. Collectively, these findings reveal a novel feedback loop involving an epigenetic state transition and metabolic reprogramming that leads to adaptive therapeutic resistance.

cancer biology↗