Search

Herein, we present a qualitative and quantitative analysis of the compositions of plasmalogens and phospholipids (PLs) in dried big head shrimp (Solenocera melantho), opossum shrimp (Neomysis awatschensis), mussel (Mytilus galloprovincialis), and sea cucumber (Apostichopus japonicus). We also analyze the fatty acid composition of the extracted lipids, phosphatidyl choline (PtdCho), and plasmalogen choline (PlsCho) from each sample. In big head shrimp, opossum shrimp, and mussel, phosphatidyl choline (PtdCho) was the most abundant PL at 1677.9, 1603, and 1661.6 mg/100 g of dried sample, respectively, whereas the most abundant PL in sea cucumber was PlsCho (206.9 mg/100 g of dried sample). In all four samples, plasmalogen ethanolamine (PlsEtn) was higher than phosphatidyl ethanolamine (PtdEtn). The content (mg/100 g of dried sample) of PlsCho was highest in mussel (379.0), and it was higher in big head shrimp (262.3) and opossum shrimp (245.6) than sea cucumber (206.9). The contents (mg/100 g of dried sample) of PlsEtn were in the order of mussel (675.4) > big head shrimp (629.5) > opossum shrimp (217.9) > sea cucumber (51.5). For analyzing the fatty acids at the sn-2 position of PlsCho, the consecutive treatment with phospholipase A1, solid phase extraction, thin-layer chromatography (TLC), and GC-FID were applied. The most abundant fatty acid was eicosapentaenoic acid (EPA, C20:5, n-3) in big head shrimp and sea cucumber, palmitoleic acid (C16:1, n-7) in opossum shrimp, and docosadienoic acid (C22:2, n-6) in mussel. [ABSTRACT FROM AUTHOR]

PIK3CA is a frequently mutated gene in cancer, including about ~15 to 20% of colorectal cancers (CRC). PIK3CA mutations lead to activation of the PI3K/AKT/mTOR signaling pathway, which plays pivotal roles in tumorigenesis. Here, we investigated the mechanism of resistance of PIK3CA‐mutant CRC cell lines to gedatolisib, a dual PI3K/mTOR inhibitor. Out of a panel of 29 CRC cell lines, we identified 7 harboring one or more PIK3CA mutations; of these, 5 and 2 were found to be sensitive and resistant to gedatolisib, respectively. Both of the gedatolisib‐resistant cell lines expressed high levels of active glycogen synthase kinase 3‐beta (GSK3β) and harbored the same frameshift mutation (c.465_466insC; H155fs*) in TCF7, which encodes a positive transcriptional regulator of the WNT/β‐catenin signaling pathway. Inhibition of GSK3β activity in gedatolisib‐resistant cells by siRNA‐mediated knockdown or treatment with a GSK3β‐specific inhibitor effectively reduced the activity of molecules downstream of mTOR and also decreased signaling through the WNT/β‐catenin pathway. Notably, GSK3β inhibition rendered the resistant cell lines sensitive to gedatolisib cytotoxicity, both in vitro and in a mouse xenograft model. Taken together, these data demonstrate that aberrant regulation of WNT/β‐catenin signaling and active GSK3β induced by the TCF7 frameshift mutation cause resistance to the dual PI3K/mTOR inhibitor gedatolisib. Cotreatment with GSK3β inhibitors may be a strategy to overcome the resistance of PIK3CA‐ and TCF7‐mutant CRC to PI3K/mTOR‐targeted therapies. What's new? Mutations in the PI3K/mTOR and WNT/β‐catenin pathways are common in colorectal cancer. Here, in colorectal cancer cells, the authors show that the frameshift mutation H155fs* in transcription factor TCF7 serves a critical role in mediating resistance to the PI3K/mTOR dual inhibitor gedatolisib. TCF7 H155fs* maintained mTOR signaling by inducing the active form of glycogen synthase kinase 3‐beta (GSK3β) and aberrant WNT/β‐catenin signaling. The latter conferred resistance to gedatolisib. Co‐treatment with a GSK3β inhibitor increased sensitivity to gedatolisib, a combination that synergistically inhibited colorectal tumor growth in mice. The findings shed light on gedatolisib resistance mechanisms and potential resistance biomarkers. [ABSTRACT FROM AUTHOR]

Introduction: 1,2-Dimyristoyl- sn -glycero-3-phosphocholine (DMPC) is a promising emulsifier for bioactive delivery systems, but its industrial applications are limited by the lack of cost-effective and scalable synthetic routes. The purpose of this study was to economically produce high-purity DMPC by replacing commonly used column chromatography methods and to evaluate the emulsifying performance., Methods: DMPC was synthesized from sn -glycero-3-phosphocholine using Steglich esterification followed by sequential recrystallization from ethyl acetate and acetone. The structure of DMPC was identified and its purity was confirmed using various spectroscopy and chromatography techniques. The emulsifying performance was evaluated by examining the effects of storage on the properties of o/w emulsions prepared using soybean oil with (i) soy PC, (ii) soy PC + DMPC (1:1, w/w), and (iii) DMPC as emulsifiers., Results: The chemical impurities formed during the synthesis of DMPC was removed, and its final purity was 96%, and the melt transition temperature was 37.6°C. No visible difference between the three emulsions (soy PC, soy PC+DMPC, and DMPC) was observed during two-week storage, and the DMPC-based emulsion was more stable than soy PC emulsion, showing smaller particle size distribution during 6 months., Discussion: The highly pure DMPC was synthesized by an economical method, and DMPC-based emulsions demonstrated physicochemical stable, highlighting its potential for food and pharmaceutical industry-related applications. Our findings suggest that DMPC holds promise as an emulsifier with broad applications in the food industry., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Park, Ji, Lee, Chang, Bang and Lee.)