Anti-inflammatory Activity of Absinthin and Derivatives in Human Bronchoepithelial Cells.

Bitter taste receptors (hTAS2R) are expressed ectopically in various tissues, raising the possibility of a pharmacological exploitation. This seems of particular relevance in airways, since hTAS2Rs are involved in the protection of the aerial tissues from infections and in bronchodilation. The bis-guaianolide absinthin (1), one of the most bitter compounds known, targets the hTAS2R46 bitter receptor. Absinthin (1), an unstable compound, readily turns into anabsinthin (2) with substantial retention of the bitter properties, and this compound was used as a starting material to explore the chemical space around the bis-guaianolide bitter pharmacophore. Capitalizing on the chemoselective opening of the allylic lactone ring, the esters 3 and 4, and the nor-azide 6 were prepared and assayed on human bronchoepithelial (BEAS-2B) cells expressing hTAS2R46. Anti-inflammatory activity was evaluated by measuring the expression of MUC5AC, iNOS, and cytokines, as well as the production of superoxide anion, qualifying the methyl ester 3 as the best candidate for additional studies.

Integrating Genomics Into Management of Fibrotic Interstitial Lung Disease.

Fibrotic interstitial lung diseases (ILDs) have a high mortality rate with an unpredictable disease course and clinical features that frequently overlap. Recent data indicate important roles for genomics in the mechanisms underlying susceptibility and progression of pulmonary fibrosis. The impact of these genomic markers on pharmacotherapy and their contribution to outcomes is increasingly recognized. Interstitial lung abnormalities, frequently considered representative of early ILD, have been consistently associated with the MUC5B promoter polymorphism, a common gene variant. Other rare gene variant mutations, including TERT, TERC, SFTPC, and DKC1, may be present in patients with familial interstitial pneumonia and are frequently associated with a usual interstitial pneumonia pattern of fibrosis. The minor allele of the MUC5B rs35705950 genotype is prevalent in several sporadic forms of ILD, including idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis. Gene mutations that characterize familial pulmonary fibrosis may be present in patients with connective tissue disease-related ILD, such as rheumatoid arthritis-ILD. Additionally, shorter telomere lengths and mutations in telomere biology-related genes have been demonstrated in both familial and sporadic ILD, with significant implications for disease progression, lung function, and survival. An improved understanding of the impact of genetic and genomic risk factors on disease progression would better guide personalized therapeutic choices in persons with fibrotic ILD.

The effect of ethinyl estradiol and drospirenone-containing oral contraceptives upon mucoprotein content of cervical mucus.

OBJECTIVE: To report the effect of oral contraceptives (OC) on cervical mucoprotein content by evaluating quantitatively mucoprotein 1 (MUC1), mucoprotein 2 (MUC2), mucoprotein 5AC (MUC5AC) and mucoprotein 5B (MUC5B) levels. STUDY DESIGN: This prospective controlled study included 20 women of reproductive age who had requested OC. Cervical mucus samples were obtained from the women before use of the OC and after 2 months of OC use. The mucus samples were then evaluated quantitatively for MUC1, MUC2, MUC5AC and MUC5B by ELISA by using specific antibodies. RESULTS: MUC5AC mucoprotein predominated quantitatively both before and after OC use. After OC use, compared to before OC use, variable increases in the levels of all studied mucoproteins were recorded, but the increases in MUC1, MUC2 and MUC5B were statistically significant. The difference in the level of MUC2 was remarkable (+54.36 ± 31.88 ng/mL). CONCLUSION: OC use may change the mucoprotein content (especially for MUC2) of cervical mucus and thus, may cause a highly viscous pattern of cervical mucus which may enhance the contraceptive efficacy of OC pills.