ORCID Profile
0000-0003-0936-3281
Current Organisation
The University of Auckland
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Publisher: Elsevier BV
Date: 03-2021
Publisher: Springer Science and Business Media LLC
Date: 20-09-2021
DOI: 10.1038/S42255-021-00457-W
Abstract: Visceral adipose tissue (VAT) encases mesenteric lymphatic vessels and lymph nodes through which lymph is transported from the intestine and mesentery. Whether mesenteric lymphatics contribute to adipose tissue inflammation and metabolism and insulin resistance is unclear. Here we show that obesity is associated with profound and progressive dysfunction of the mesenteric lymphatic system in mice and humans. We find that lymph from mice and humans consuming a high-fat diet (HFD) stimulates lymphatic vessel growth, leading to the formation of highly branched mesenteric lymphatic vessels that 'leak' HFD-lymph into VAT and, thereby, promote insulin resistance. Mesenteric lymphatic dysfunction is regulated by cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF)-C-VEGF receptor (R)3 signalling. Lymph-targeted inhibition of COX-2 using a glyceride prodrug approach reverses mesenteric lymphatic dysfunction, visceral obesity and inflammation and restores glycaemic control in mice. Targeting obesity-associated mesenteric lymphatic dysfunction thus represents a potential therapeutic option to treat metabolic disease.
Publisher: MDPI AG
Date: 14-01-2023
DOI: 10.3390/PHARMACEUTICS15010287
Abstract: Pancreatic ductal adenocarcinoma remains a highly debilitating condition with no effective disease-modifying interventions. In our search for natural products with promising anticancer activity, we identified the aminolipopeptide trichoderin A as a potential candidate. While it was initially isolated as an antitubercular peptide, we provide evidence that it is also selectively toxic against BxPC-3 and PANC-1 human pancreatic ductal adenocarcinoma cells cultured under glucose deprivation. This has critical implications for the pancreatic ductal adenocarcinoma, which is characterized by nutrient deprivation due to its hypovascularized network. We have also successfully simplified the trichoderin A peptide backbone, allowing greater accessibility to the peptide for further biological testing. In addition, we also conducted a preliminary investigation into the role of peptide lipidation at the N-terminus. This showed that analogues with longer fatty acyl chains exhibited superior cytotoxicity than those with shorter acyl chains. Further structural optimization of trichoderin A is anticipated to improve its biological activity, whilst ongoing mechanistic studies to elucidate its intracellular mechanism of action are conducted in parallel.
Publisher: European Respiratory Society (ERS)
Date: 16-04-2021
Publisher: Elsevier BV
Date: 07-2005
Publisher: Wiley
Date: 10-02-2022
DOI: 10.1111/MICC.12748
Abstract: Conventionally, in vivo mesenteric lymphatic contractile function is measured using a high magnification transmission microscope (field of view 0.3–1.5 mm), which precludes visualization of extended lengths of vessels embedded in mesenteric fat. Existing software is not optimized for imaging at a low magnification using a contrast agent. We aimed to develop a simple and clinically transferable method for in situ visualization, image analysis, and quantitative assessment of mesenteric lymphatic contractile function over an extended area. Subserosal injection of various blue dyes was taken up by mesenteric lymphatics and visualized under a stereomicroscope (25×), allowing for video recording of 1.4 × 1.1 cm of intact mesentery. A new R package (“vmeasur”) that combines multiple high‐performance image analyses into a single workflow was developed. The edges of each vessel were determined by applying an automated threshold to each frame (with real‐time manual verification). The vessel width at every point in each frame was plotted to provide contractile parameters over time and along the lymphatic vessel length. Contractile parameters and their differences along the length of the vessel were accurately calculated in a rodent model. In a human mesenteric lymphatic, the algorithm was also able to measure changes in diameter over length. This software offers a low cost, rapid, and accessible method to measure lymphatic contractile function over a wide area, showing differences in contractility along the length of a vessel. Because the presence of mesenteric fat has less of an impact on imaging, due to the use of an exogenous contrast agent, there is potential for clinical application.
Publisher: Frontiers Media SA
Date: 21-05-2020
Publisher: American Chemical Society (ACS)
Date: 18-10-2019
DOI: 10.1021/ACS.MOLPHARMACEUT.9B00855
Abstract: Drugs are commonly administered via the intraperitoneal (IP) route to treat localized infections and cancers in patients and to test drug efficacy and toxicity in preclinical studies. Despite this, there remain large gaps in our understanding of drug absorption routes (lymph vs blood) and pharmacokinetics following IP administration. This is particularly true when drugs are administered in complex delivery systems such as liposomes which are the main marketed formulation for several drugs that are administered intraperitoneally. This study investigated the impact of liposome surface properties (charge and PEGylation) on absorption into lymph and blood, and lymphatic disposition patterns, following IP administration. To achieve this, stable
No related grants have been discovered for Jiwon Hong.