AI Article Synopsis
- TNF-alpha plays a crucial role in the development of ARDS by inhibiting surfactant synthesis in isolated human type II pneumocytes.
- The study compared surfactant production between pneumocytes from healthy organ donors and lung cancer patients, finding that donor cells produced significantly more surfactant.
- Pentoxifylline (PTXF) was shown to block the inhibitory effects of TNF-alpha on surfactant synthesis, suggesting potential therapeutic avenues for improving lung function in ARDS patients.
Article Abstract
Tumor necrosis factor alpha (TNF-alpha) seems to play an important role in the pathogenesis of the adult respiratory distress syndrome (ARDS). This study was designed to determine the effect of TNF-alpha and pentoxifylline (PTXF) on surfactant synthesis by isolated human type II pneumocytes. In order to isolate the pneumocytes, lungs obtained from both previously healthy multiple organ donors (n = 11) and patients who underwent surgical excision for lung cancer (n = 8) were used. Surfactant synthesis was measured by the incorporation of labeled glucose into the two most important phospholipid components of surfactant: phosphatidylcholine (PC) and phosphatidylglycerol (PGL). The pneumocytes of the donor group showed a greater degree of PC synthesis than those from the cancer group (3.44 +/- 0.19 versus 2.15 +/- 01.5 pmol/micrograms protein, p < 0.001). The synthesis of PC by pneumocytes in both the donor (1.13 +/- 0.19 versus 3.44 +/- 0.19 pmol/micrograms protein, p < 0.01) and cancer (0.99 +/- 0.11 versus 2.15 +/- 0.15 pmol/micrograms protein, p < 0.01) groups was decreased by TNF-alpha (100 ng/ml). This effect was blocked by PTXF (100 micrograms/ml), a substance that also increased PC production in the control-group pneumocytes from cancer patients, the final PC levels being similar to those of the donors in the absence of TNF-alpha. These results suggest that one of the mechanisms of TNF-alpha participation in the pathophysiology of ARDS is inhibition of surfactant synthesis, and support the hypothesis of in vivo production of TNF-alpha in lung-cancer patients, with subsequent chronic exposure of the lung epithelial cells to this cytokine.(ABSTRACT TRUNCATED AT 250 WORDS)
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1164/ajrccm.149.3.8118639 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Developing Soluplus®-Based Microparticle Amorphous Solid Dispersions with High Drug Loading for Enhanced Celecoxib Dissolution via Electrospraying.
AAPS PharmSciTech
January 2025
Laboratory of Advanced Theranostic Materials and Technology, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, China.
Amorphous solid dispersion (ASD) is one of the most studied strategies for improving the dissolution performance of poorly water-soluble drugs, but ASDs often have low drug loadings, thereby necessitating larger dosage sizes. This study intended to create Soluplus® (SOL)-based microparticle ASDs with high drug loading (up to 60 w/w%) and long-term stability (at least 16 months) using electrospraying to enhance the dissolution of poorly water-soluble celecoxib (CEL). X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analyses showed that the electrosprayed SOL-CEL microparticles were amorphous, and Fourier transform infrared spectroscopy (FTIR) data indicated the presence of hydrogen bonding between SOL and CEL in the microparticles, which helped stabilize the ASDs.
View Article and Find Full Text PDFPolydopamine grafting polyether ether ketone to stabilize growth factor for efficient osteonecrosis repair.
Sci Rep
January 2025
Department of Bone Joint, Binzhou Medical University Hospital, No. 661 Huanghe 2nd Road, Binzhou, 256600, China.
This study examines the biocompatibility, osteogenic potential, and effectiveness of polyether ether ketone (PEEK) composites for treating osteonecrosis, seeking to establish a theoretical basis for clinical application. A range of PEEK composite materials, including sulfonated polyether ether ketone (SPEEK), polydopamine-sulfonated polyether ether ketone (SPEEK-PDA), bone-forming peptide-poly-dopamine-sulfonated polyether ether ketone (SPEEK-PDA-BFP), and vascular endothelial growth factor-poly-dopamine-sulfonated polyether ether ketone (SPEEK-PDA-VEGF), were constructed by concentrated sulfuric acid sulfonation, polydopamine modification and grafting of bioactive factors. The experiments involved adult male New Zealand rabbits aged 24-28 weeks and weighing 2.
View Article and Find Full Text PDFAccelerated amyloid fibril formation at the interface of liquid-liquid phase-separated droplets by depletion interactions.
Protein Sci
February 2025
Graduate School of Engineering, Osaka University, Osaka, Japan.
Amyloid fibril formation of α-synuclein (αSN) is a hallmark of synucleinopathies. Although the previous studies have provided numerous insights into the molecular basis of αSN amyloid formation, it remains unclear how αSN self-assembles into amyloid fibrils in vivo. Here, we show that αSN amyloid formation is accelerated in the presence of two macromolecular crowders, polyethylene glycol (PEG) (MW: ~10,000) and dextran (DEX) (MW: ~500,000), with a maximum at approximately 7% (w/v) PEG and 7% (w/v) DEX.
View Article and Find Full Text PDFAssembly of Genetically Engineered Ionizable Protein Nanocage-based Nanozymes for Intracellular Superoxide Scavenging.
Nat Commun
January 2025
Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, and Frontier of Science Center for Cell Response, Nankai University, Tianjin, 300071, China.
Nanozymes play a pivotal role in mitigating excessive oxidative stress, however, determining their specific enzyme-mimicking activities for intracellular free radical scavenging is challenging due to endo-lysosomal entrapment. In this study, we employ a genetic engineering strategy to generate ionizable ferritin nanocages (iFTn), enabling their escape from endo-lysosomes and entry into the cytoplasm. Specifically, ionizable repeated Histidine-Histidine-Glutamic acid (9HE) sequences are genetically incorporated into the outer surface of human heavy chain FTn, followed by the assembly of various chain-like nanostructures via a two-armed polyethylene glycol (PEG).
View Article and Find Full Text PDFTriethylamine-mediated protonation-deprotonation unlocks dual-drug self assembly to suppress breast cancer progression and metastasis.
Proc Natl Acad Sci U S A
February 2025
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China.
Carrier-free nanomedicines exhibited significant potential in elevating drug efficacy and safety for tumor management, yet their self assembly typically relied on chemical modifications of drugs or the incorporation of surfactants, thereby compromising the drug's inherent pharmacological activity. To address this challenge, we proposed a triethylamine (TEA)-mediated protonation-deprotonation strategy that enabled the adjustable-proportion self assembly of dual drugs without chemical modification, achieving nearly 100% drug loading capacity. Molecular dynamic simulations, supported by experiment evidence, elucidated the underlying self-assembly mechanism.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!