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Fluoroscopy-induced chronic radiation dermatitis (FICRD) is a complication of fluoroscopy-guided intervention. Unlike acute radiation dermatitis, FICRD is different as delayed onset and usually appears without preexisting acute dermatitis. Unfortunately, the chronic and progressive pathology of FICRD makes it difficult to treat, and some patients need to receive wide excision and reconstruction surgery. Due to lack of standard treatment, investigating underlying mechanism is needed in order to develop an effective therapy. Herein, the Hippo pathway is specifically identified using an RNA-seq analysis in mild damaged skin specimens of patients with FICRD. Furthermore, specific increase of the Yes-associated protein (YAP1), an effector of the Hippo pathway, in skin region with mild damage plays a protective role for keratinocytes via positively regulating the numerous downstream genes involved in different biological processes. Interestingly, irradiated-keratinocytes inhibit activation of fibroblasts under TGF-β1 treatment via remote control by an exosome containing YAP1. More importantly, targeting one of YAP1 downstream genes, nuclear receptor subfamily 3 group C member 1 (NR3C1), which encodes glucocorticoid receptor, has revealed its therapeutic potential to treat FICRD by inhibiting fibroblasts activation in vitro and preventing formation of radiation ulcers in a mouse model and in patients with FICRD. Taken together, this translational research demonstrates the critical role of YAP1 in FICRD and identification of a feasible, effective therapy for patients with FICRD. KEY MESSAGES: • YAP1 overexpression in skin specimens of radiation dermatitis from FICRD patient. • Radiation-induced YAP1 expression plays protective roles by promoting DNA damage repair and inhibiting fibrosis via remote control of exosomal YAP1. • YAP1 positively regulates NR3C1 which encodes glucocorticoid receptor expression. • Targeting glucocorticoid receptor by prednisolone has therapeutic potential for FICRD patient., (© 2021. The Author(s).)

Flaviviruses comprise several medically important viruses, including Japanese encephalitis virus, West Nile virus, dengue virus (DENV), yellow fever virus, and Zika virus (ZIKV). A large outbreak of DENV and ZIKV occurred recently, leading to many cases of illness and death. However, despite decades of effort, we have no clinically specific therapeutic drugs against DENV and ZIKV. Previous studies showed that inflammatory responses play a critical role in dengue and Zika virus pathogenesis. Thus, in this study, we examined a series of novel anti-inflammatory compounds and found that treatment with compound 2d could dose dependently reduce viral protein expression and viral progeny production in HEK-293 and Raw264.7 cells infected with four serotypes of DENV and ZIKV. In addition, considering medication safety, compound 2d could not suppress cyclooxygenase-1 (COX-1) enzymatic activities and thus could prevent the side effect of bleeding. Moreover, compound 2d significantly inhibited COX-2 enzymatic activities and prostaglandin E 2 levels, associated with viral replication, compared to results with a selective COX-2 inhibitor, celecoxib. Furthermore, administering 5 mg/kg compound 2d to DENV-2-infected AG129 mice prolonged survival and reduced viremia and serum cytokine levels. Overall, compound 2d showed therapeutic safety and efficacy in vitro and in vivo and could be further developed as a potential therapeutic agent for flavivirus infection., (Copyright © 2019 American Society for Microbiology.)

A new limonoid, swietemacrophin (1), was isolated from the seeds of Swietenia macrophylla, together with five known compounds 2-6. The structure of 1 was determined through extensive 1D/2D-NMR and mass-spectrometric analyses. Swietemacrophin (1), humilinolide F (2), 3,6-O,O-diacetylswietenolide (3), 3-O-tigloylswietenolide (4), and swietemahonin E (5) exhibited inhibition (IC50 values≤45.44 μM) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). Compounds 1, 4, 5, and swietenine (6) showed potent inhibition with IC50 values≤36.32 μM, against lipopolysaccharide (LPS)-induced nitric oxide (NO) generation.

A new homoisoflavonoid, (R)-3-(2,4-dihydroxybenzyl)-5,7-dihydroxy-8-methoxychroman-4-one (1), has been isolated from the rhizomes of Polygonatum alte-lobatum, together with seven known compounds (2–8). The structure of the new compound 1 was determined through spectroscopic and MS analyses. Among the isolated compounds, compounds 1, 3, 5, and 6 showed potent inhibition with IC50 values of 18.04 ± 2.14, 19.87 ± 2.70, 16.88 ± 1.35, and 18.50 ± 1.52 μM, respectively, against LPS-induced NO generation. [ABSTRACT FROM AUTHOR]

A new coumarin, methyl (E)-4-((6-methoxy-2-oxo-2H-chromen-7-yl)oxy)-2-methylbut-2-enoate (1), has been isolated from the rhizomes of Polygonatum chingshuishanianum, together with six known compounds – scopoletin (2), rutin (3), isoquercetin (4), hyperoside (5), (3R)-5,7-dihydroxy-3-(2′,4′-dihydroxybenzyl)-chroman-4-one (6), and (3R)-5,7-dihydroxy-6-methoxy-8-methyl-3-(2′,4′-dihydroxybenzyl)-chroman-4-one (7). The structure of new compound 1 was determined through spectroscopic and MS analyses. Among the isolates compounds 3–6 showed potent inhibition with IC50 values of 10.25 ± 0.75, 17.60 ± 1.28, 18.82 ± 1.63, and 24.93 ± 2.07 μM, respectively, against LPS-induced NO generation. [ABSTRACT FROM AUTHOR]

Abstract: Zanthoxylum avicennae is commercially used as healthcare products for the improvement of chronic hepatitis and rheumatism. Its fruit is also used as a spice. Five new coumarins, 5′-methoxyauraptene (1), 6,5′-dimethoxyauraptene (2), 5′-methoxycollinin (3), 7-((2′E,5′E)-7′-methoxy-3′,7′-dimethylocta-2′,5′-dienyloxy)coumarin (4), and 6-methoxy-7-((2′E,5′E)-7′-methoxy-3′,7′-dimethylocta-2′,5′-dienyloxy)coumarin (5), have been isolated from the leaves of Z. avicennae, together with 15 known compounds (6–20). The structures of these new compounds were determined through spectroscopic and MS analyses. Compounds 6, 9–15, and 18 exhibited inhibition (IC50 ⩽8.29μg/ml) of superoxide anion generation by human neutrophils in response to formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B (fMLP/CB). Compounds 6, 10, 12, 14, and 18 inhibited fMLP/CB-induced elastase release with IC50 values ⩽6.30μg/ml. [Copyright &y& Elsevier]

The fruits of Psoralea corylifolia , known as Psoraleae Fructus ( Buguzhi in Chinese), are traditionally used for the treatment of spermatorrhea, nephritis, asthma, pollakiuria, and various inflammatory diseases. Three previously undescribed isoflavone derivatives, 7- O -methylcorylifol A, 7- O -isoprenylcorylifol A, and 7- O -isoprenylneobavaisoflavone, have been isolated from the fruits of P. corylifolia , together with 9 known compounds. The structures of these compounds were determined through spectroscopic and MS analyses. Among the isolated compounds, 7- O -methylcorylifol A and psoralen exhibited potent inhibition (IC 50 values ≤ 10.89 μM) of superoxide anion generation by human neutrophils in response to N -formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). 7- O -Isoprenylcorylifol A, 7- O -isoprenylneobavaisoflavone, and 12,13-dihydro-12,13-epoxybakuchiol inhibited fMLP/CB-induced elastase release with IC 50 values ≤ 14.30 μM. In addition, 7- O -isoprenylcorylifol A, bakuchiol, 12,13-dihydro-12,13-epoxybakuchiol, and psoralidin showed potent inhibition with IC 50 values ≤ 36.65 μM, against lipopolysaccharide (LPS)-induced nitric oxide (NO) generation. [ABSTRACT FROM AUTHOR]