Biomedical subjects

Songlin Xu

Publications and source records attributed to Songlin Xu.

3 recordsLinked to original sources

PubMed2024

L3MBTL1, a polycomb protein, promotes Osimertinib acquired resistance through epigenetic regulation of DNA damage response in lung adenocarcinoma.

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI) approved for patients with EGFR T790M resistance mutations as first- or second-line treatment of EGFR-positive patients. Resistance to Osimertinib will inevitably develop, and the underlying mechanisms are largely unknown. In this study, we discovered that acquired resistance to Osimertinib is associated with abnormal DNA damage response (DDR) in lung adenocarcinoma cells. We discovered that the polycomb protein Lethal(3) Malignant Brain Tumor-Like Protein 1 (L3MBTL1) regulates chromatin structure, thereby contributing to DDR and Osimertinib resistance. EGFR oncogene inhibition reduced L3MBTL1 ubiquitination while stabilizing its expression in Osimertinib-resistant cells. L3MBTL1 reduction and treatment with Osimertinib significantly inhibited DDR and proliferation of Osimertinib-resistant lung cancer cells in vitro and in vivo. L3MBTL1 binds throughout the genome and plays an important role in EGFR-TKI resistance. It also competes with 53BP1 for H4K20Me2 and inhibits the development of drug resistance in Osimertinib-resistant lung cancer cells in vitro and in vivo. Our findings suggest that L3MBTL1 inhibition is a novel approach to overcoming EGFR-TKI-acquired resistance.

Humans↗

PubMed2006

Simulated maximum likelihood method for estimating kinetic rates in gene expression.

MOTIVATION: Kinetic rate in gene expression is a key measurement of the stability of gene products and gives important information for the reconstruction of genetic regulatory networks. Recent developments in experimental technologies have made it possible to measure the numbers of transcripts and protein molecules in single cells. Although estimation methods based on deterministic models have been proposed aimed at evaluating kinetic rates from experimental observations, these methods cannot tackle noise in gene expression that may arise from discrete processes of gene expression, small numbers of mRNA transcript, fluctuations in the activity of transcriptional factors and variability in the experimental environment. RESULTS: In this paper, we develop effective methods for estimating kinetic rates in genetic regulatory networks. The simulated maximum likelihood method is used to evaluate parameters in stochastic models described by either stochastic differential equations or discrete biochemical reactions. Different types of non-parametric density functions are used to measure the transitional probability of experimental observations. For stochastic models described by biochemical reactions, we propose to use the simulated frequency distribution to evaluate the transitional density based on the discrete nature of stochastic simulations. The genetic optimization algorithm is used as an efficient tool to search for optimal reaction rates. Numerical results indicate that the proposed methods can give robust estimations of kinetic rates with good accuracy.

Algorithms↗

PubMed2006

Characterization and quantification of eight water-soluble constituents in tubers of Pinellia ternata and in tea granules from the Chinese multiherb remedy Xiaochaihu-tang.

In traditional Chinese medicine, multiple herbs are usually used in combination to generate the joint actions of a multiherb remedy. The recent development of LC-hyphenated techniques enables efficient and rapid profiling of the chemical constituent in extracts from multiherb remedies. Xiaochaihu-tang is a seven-herb remedy that has attracted a great deal of attention for reported ability to treat liver dysfunction. Dried tubers of Pinellia ternata (banxia in Chinese) is one of the ingredients, but its chemical contribution to Xiaochaihu-tang remains poorly understood. In the study presented here, LC-UV-MS, LC-MS-MS, and LC-NMR were used in a complementary manner to determine the nature and content of eight water-soluble constituents of banxia and their presence in various tea granules from Xiaochaihu-tang. Among the eight chemicals identified in banxia, cytidine, adenosine, tryptophan, uridine, and adenine are reported for the first time, while tyrosine, guanosine, and phenylalanine were previously described. These chemicals are also present in all of the samples of Xiaochaihu-tang granules, and the amounts of the chemicals ingested due to a daily dose of the multiherb remedies range from 0.008 to 6.3mg.

Adenine↗