Pulmonary arterial hypertension (PAH) is a rare pulmonary vascular disease that affects people of all ethnic origins and age groups including newborns. In PAH, pulmonary arteries and arterioles undergo a series of pathological changes including remodeling of the entire pulmonary vasculatures and extracellular matrices, mis-localized growth of pulmonary arterial cells, and development of glomeruloid-like lesions called plexiform lesions. Traditionally, various animal and cellular models have been used to understand PAH pathophysiology, investigate sex-disparity in PAH and monitor therapeutic efficacy of PAH medications. However, traditional models can only partially capture various pathological features of PAH, and they are not adaptable to combinatorial study design for deciphering intricately intertwined complex cellular processes implicated in PAH pathogenesis. While many microfluidic chip-based models are currently available for major diseases, no such disease-on-a-device model is available for PAH, an under investigated disease. In the absence of any chip-based models of PAH, we recently proposed a five-channel polydimethylsiloxane (PDMS)-based microfluidic device that can emulate major pathological features of PAH. However, our proposed model can make a bigger impact on the PAH field only when the larger scientific community engaged in PAH research can fabricate the device and develop the model in their laboratory settings. With this goal in mind, in this study, we have described the detailed methodologies for fabrication and development of the PAH chip model including a thorough explanation of scientific principles for various steps for chip fabrication, a detailed list of reagents, tools and equipment along with their source and catalogue numbers, description of laboratory setup, and cautionary notes. Finally, we explained the methodologies for on-chip cell seeding and application of this model for studying PAH pathophysiology. We believe investigators with little or no training in microfluidic chip fabrication can fabricate this eminently novel PAH-on-a-chip model. As such, this study will have a far-reaching impact on understanding PAH pathophysiology, unravelling the biological mystery associated with sexual dimorphism in PAH, and developing PAH therapy based on patient sex and age.
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http://dx.doi.org/10.3390/mi13091483 | DOI Listing |
Cell Signal
January 2025
Department of Cardiovascular Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China. Electronic address:
Pulmonary artery hypertension (PAH) is characterized by a cancer-like metabolic shift towards aerobic glycolysis. Nuclear Receptor Binding SET Domain Protein 2 (NSD2), a histone methyltransferase, has been implicated in PAH, yet its precise role remains unclear. In this study, we induced PAH in C57BL/6 mice using monocrotaline (MCT) and observed increased FOLR1 expression in PAH tissues, which was suppressed by NSD2 knockdown.
View Article and Find Full Text PDFFood Chem
January 2025
Department of Food Science and Technology, School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. Electronic address:
Reductions in polycyclic aromatic hydrocarbon (PAH) concentrations have been observed during frying. However, transformation mechanisms of PAHs remain unclear. We hypothesize that PAHs may be oxidized into oxygenated polycyclic aromatic hydrocarbons (OPAHs) and other derivatives during frying.
View Article and Find Full Text PDFJ Hazard Mater
January 2025
Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Key Laboratory of Environmental Catalysis and Health Risk Control, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou 510006, China; Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control, Guangdong Basic Research Center of Excellence for Ecological Security and Green Development, School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, China. Electronic address:
Long-term occupational exposure to metals and organics have been reported to be under great health risks. However, limited data are available on the molecular mechanism between combined exposure to metals and polycyclic aromatic hydrocarbons (PAHs) and harmful health effects. In present work, non-target metabolomics study was conducted based on urine samples from nonferrous metal smelting workers (n = 207), surrounding residents (n = 180), and the control residents (n = 187) by using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS).
View Article and Find Full Text PDFEnviron Sci Pollut Res Int
January 2025
Transport Research Centre, Líšeňská 33a, 636 00, Brno, Czech Republic.
The paper deals with an analysis of the amount of 16 polycyclic aromatic hydrocarbons (PAHs (Polycyclic aromatic hydrocarbons-16 defined by US EPA.)) released from reclaimed asphalt mixtures used in base layers of road surfaces and in binder layers in road construction using cold in-place recycling. For the ten samples tested, the sum of 16 PAHs was determined directly for the crushed asphalt mixture and for its 24-h leachate.
View Article and Find Full Text PDFSTAR Protoc
January 2025
Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN, USA. Electronic address:
Tumor Treating Fields (TTFields) are electric fields clinically approved for cancer treatment, delivered via arrays attached to the patient's skin. Here, we present a protocol for applying TTFields to torso orthotopic and subcutaneous mouse tumor models using the inovivo system. We guide users on proper system component connections, study protocol design, mouse fur depilation, array application, and treatment condition adjustment and monitoring.
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