Biology subjects

Hsieh, C.-C.

Publications and source records attributed to Hsieh, C.-C..

3 recordsLinked to original sources

bioRxiv2026

Stromal state plasticity defines risk and therapeutic opportunity in recalcitrant inflammatory bowel disease

Inflammatory bowel diseases (IBD) remain a relapsing, treatment-refractory disorder marked by progressive tissue injury and inflammation despite expanding immune-targeted therapies. We established a prospective cohort integrating stromal biobanking, functional phenotyping, cross-cohort benchmarking, and outcome modeling to define disease-anchored cellular states. Colonic myofibroblasts from 34 individuals spanning health, ulcerative colitis, and Crohns disease resolved into two dominant states: inflammatory (IMFs) and quiescent (QMFs) myofibroblasts. QMF predominance forecasted remission, whereas IMF predominance increased the odds of worsening endoscopic severity despite therapy escalation during follow-up by [~]4.6-fold, linking early stromal biology to clinical outcomes. Unlike QMFs, IMFs exhibited a senescence-associated secretory phenotype that impaired epithelial stemness, barrier integrity, and innate immune fitness. State-guided prioritization identified EDNRB-antagonism as a high-confidence stromal intervention, reversing pathogenic phenotypes across orthogonal assays and species. Outcome simulation positioned stromal-state reversibility by EDNRB-antagonism as a precision axis, reducing odds of recalcitrance by [~]96.4% and reframing treatment resistance as a reversible stromal state. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=185 HEIGHT=200 SRC="FIGDIR/small/720931v2_ufig1.gif" ALT="Figure 1"> View larger version (88K): org.highwire.dtl.DTLVardef@3b2c50org.highwire.dtl.DTLVardef@da5400org.highwire.dtl.DTLVardef@1c100c1org.highwire.dtl.DTLVardef@1882e1_HPS_FORMAT_FIGEXP M_FIG C_FIG In this work, Tindle et al. identify reversible stromal states that govern remission vs. recalcitrant outcomes in IBD and nominate precision reprogramming of pathogenic myofibroblasts as a new therapeutic strategy.

physiology↗

bioRxiv2023

Characterizing Adeno-Associated Virus Capsids with both Denaturing and Intact Analysis Methods

Adeno-associated virus (AAV) capsids are among the leading gene delivery platforms used to treat a vast array of human diseases and conditions. AAVs exist in a variety of serotypes due to differences in viral protein (VP) sequences, with distinct serotypes targeting specific cells and tissues. As the utility of AAVs in gene therapy increases, ensuring their specific composition is imperative for correct targeting and gene delivery. From a quality control perspective, current analytical tools are limited in their selectivity for viral protein (VP) subunits due to their sequence similiaries, instrumental difficulties in assessing the large molecular weights of intact capsids, and the uncertainity in distinguishing empty and filled capsids. To address these challenges, we combine two distinct analytical workflows that assess the intact capsids and VP subunits separately. First, charge detection-mass spectrometry (CD-MS) was applied for characterization of the intact capsids and then liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) separations were used for capsid denaturing measurements. This multi-method combination was applied to 3 AAV serotypes (AAV2, AAV6, and AAV8) to evaluate their intact empty and filled capsid ratios and then examine the distinct VP sequences and modifications present.

biochemistry↗

bioRxiv2018

The Synergistic Effect of Antioxidant Interaction between Luteolin and Chlorogenic Acid in Lonicera japonica

Lonicera japonica Thunb. is a flower that is used in traditional Chinese medicine to prevent the common cold. The two primary active compounds of the flower bud are luteolin, a flavonoid, and chlorogenic acid, a phenolic acid. Both active compounds have demonstrated antioxidant activity. The interactions between chemicals in a plant heavily influences its total antioxidant activity. We attempted to investigate the antioxidant interactions between the two chemicals in the plant. This study aims to investigate if the antioxidants luteolin and chlorogenic acid have a synergistic effect to inhibit free radicals when combined. A 2,2-diphenyl-1-picrylhydrazyl (DPPH*) assay was performed. The half maximal inhibitory concentration (IC50) of luteolin and chlorogenic acid were first determined and then combined at a 1:1 ratio. The combined inhibition capacity was then compared with the sum of the individual inhibition capacities. The IC50 of luteolin is 26.304 g{middle dot}ml-1 {+/-} 0.120 g{middle dot}ml-1 while the IC50 of chlorogenic acid is 85.529 g{middle dot}ml-1 {+/-} 4.482 g{middle dot}ml-1. The combined solution produced a free radical percentage inhibition of 77.617% {+/-} 5.470%, more than the percentage inhibition of the separate solutions. The experiment shows that luteolin and chlorogenic acid have a synergistic effect in inhibiting DPPH free radicals.

biochemistry↗