Maternal, newborn and breast milk concentrations of elexacaftor/tezacaftor/ivacaftor in a F508del heterozygous woman with cystic fibrosis following successful pregnancy.

With the introduction of elexacaftor/tezacaftor/ivacaftor (ETI), more women with cystic fibrosis (CF) are likely to grow families. Hence, an understanding long-term safety and effects of CFTR modulators on fertile women and children while monitoring their concentrations is crucial. Here, we report on the development of an improved LC-MS/MS methodology to measure ETI concentrations in maternal and child blood and breastmilk, applied in one case of successful pregnancy of a 30-year-old woman with CF (F508del/R334W).

Resolvin D1 improves airway inflammation and exercise capacity in cystic fibrosis lung disease.

Mucus plugging and non-resolving inflammation are inherent features of cystic fibrosis (CF) that may lead to progressive lung disease and exercise intolerance, which are the main causes of morbidity and mortality for people with CF. Therefore, understanding the influence of mucus on basic mechanisms underlying the inflammatory response and identifying strategies to resolve mucus-driven airway inflammation and consequent morbidity in CF are of wide interest. Here, we investigated the effects of the proresolving lipid mediator resolvin (Rv) D1 on mucus-related inflammation as a proof-of-concept to alleviate the burden of lung disease and restore exercise intolerance in CF.

Specialized pro-resolving lipid mediators and resolution of viral diseases.

The COVID-19 pandemics has made sparkly evident the importance of acute inflammation and its timely resolution to protect humans from pathogenic viruses while sparing them from collateral damages due to an uncontrolled immune response. It is clear now that resolution of inflammation is an active process regulated by endogenous specialized proresolving lipid mediators (SPM) biosynthesized from essential polyunsaturated fatty acids. Accruing evidence indicates that SPM are produced during viral infections and play key roles in controlling the magnitude and duration of the inflammatory response and in regulating adaptive immunity.

Biomarkers of Response to Low-Dose Aspirin in Familial Adenomatous Polyposis Patients.

Background: The results of Aspirin prevention of colorectal adenomas in patients with familial adenomatous polyposis (FAP) are controversial.

Methods: We conducted a biomarker-based clinical study in eight FAP patients treated with enteric-coated low-dose Aspirin (100 mg daily for three months) to explore whether the drug targets mainly platelet cyclooxygenase (COX)-1 or affects extraplatelet cellular sources expressing COX-isozymes and/or off-target effects in colorectal adenomas.

Results: In FAP patients, low-dose Aspirin-acetylated platelet COX-1 at Serine529 (>70%) was associated with an almost complete inhibition of platelet thromboxane (TX) B generation ex vivo (serum TXB).

Microvascular and Macrovascular Endothelial Cell Isolation and Purification from Lung-Derived Samples.

The availability of cells isolated from healthy and diseased tissues and organs represents a key element for personalized medicine approaches. Although biobanks can provide a wide collection of primary and immortalized cells for biomedical research, these do not cover all experimental needs, particularly those related to specific diseases or genotypes. Vascular endothelial cells (ECs) are key components of the immune inflammatory reaction and, thus, play a central role in the pathogenesis of a variety of disorders.

Characterization of the acetylation of cyclooxygenase-isozymes and targeted lipidomics of eicosanoids in serum and colon cancer cells by the new aspirin formulation IP1867B aspirin .

Aspirin(acetylsalicylic acid, ASA) is recommended for the secondary prevention of atherothrombotic events and has shown anticancer effects. The current enteric-coated drug formulation may reduce aspirin bioavailability. Liquid formulations could improve aspirin pharmacokinetics and pharmacodynamics.

The specific deletion of cyclooxygenase-1 in megakaryocytes/platelets reduces intestinal polyposis in Apc mice.

Clinical and experimental evidence sustain the role of cyclooxygenase (COX)-1 in intestinal tumorigenesis. However, the cell type expressing the enzyme involved and molecular mechanism(s) have not been clarified yet. We aimed to elucidate the role of platelet COX-1 (the target of low-dose aspirin in humans) in intestinal tumorigenesis of Apc mice, considered a clinically relevant model.

Inflammation and Cancer: From the Development of Personalized Indicators to Novel Therapeutic Strategies.

Colorectal (CRC) and hepatocellular carcinoma (HCC) are associated with chronic inflammation, which plays a role in tumor development and malignant progression. An unmet medical need in these settings is the availability of sensitive and specific noninvasive biomarkers. Their use will allow surveillance of high-risk populations, early detection, and monitoring of disease progression.

Characterization of cyclooxygenase-2 acetylation and prostanoid inhibition by aspirin in cellular systems.

The most recognized mechanism of aspirin (acetylsalicylic acid, ASA) action, at therapeutic dosing, is the inhibition of prostanoid biosynthesis through the acetylation of cyclooxygenase (COX)-isozymes (COX-1 at serine-529 and COX-2 at serine-516). Whether aspirin, also when given at the low-doses recommended for cardiovascular prevention, reduces the risk of colorectal cancer by affecting COX-2 activity in colorectal adenomatous lesions is still debated. We aimed to develop a direct biomarker of aspirin action on COX-2 by assessing the extent of acetylation of COX-2 at serine-516 using the AQUA strategy, enabling absolute protein quantitation by liquid chromatography-mass spectrometry.