Unprecedented outbreak of respiratory syncytial virus in Taiwan associated with ON1 variant emergence between 2010 and 2020.

An outbreak of respiratory syncytial virus (RSV) has been observed in Taiwan since August 2020. We reviewed a central laboratory-based surveillance network established over 20 years by Taiwan Centres for Disease Control for respiratory viral pathogens between 2010 and 2020.A retrospective study of children <5 years old hospitalized with RSV infection at Chang Gung Memorial Hospital between 2018 and 2020 was conducted, and samples positive for RSV-A were sequenced. Clinical data were obtained and stratified by genotype and year.Data from 2020 showed an approximately 4-fold surge in RSV cases compared to 2010 in Taiwan, surpassing previous years during which ON1 was prevalent. Phylogenetic analysis of G protein showed that novel ON1 variants were clustered separately from those of 2018 and 2019 seasons and ON1 reference strains. The variant G protein carried six amino acid changes that emerged gradually in 2019; high consistency was observed in 2020. A unique substitution, E257K, was observed in 2020 exclusively. The F protein of the variant carried T12I and H514N substitutions, which weren't at antigenic sites. In terms of multivariate analysis, age (OR: 0.97; 95% CI: 0.94-0.99; p = 0.02) and 2020 ON1 variant (OR:2.52; 95% CI:1.13-5.63; p = 0.025) were independently associated with oxygen saturation <94% during hospitalization.The 2020 ON1 variant didn't show higher replication or virulence compared with those in 2018 in our study. The unprecedented 2020 RSV epidemic may attribute to antigenic changes and lack of interferon-stimulated immunity induced by seasonal circulating virus under non-pharmaceutical intervention.

A potent antibody-secreting B cell response to Mycoplasma pneumoniae in children with pneumonia.

BACKGROUND: Mycoplasma pneumoniae is a major pathogen for community-acquired pneumonia and frequently causes outbreaks in children. M. pneumoniae-specific antibody response is detected upon acute infection and the serology is widely used in the clinical setting. Nevertheless, the cellular basis for antigen-specific antibody response to acute M. pneumoniae infection is largely undetermined in children. METHODS: Hospitalized children with community-acquired pneumonia were enrolled and the infection with M. pneumoniae was confirmed with positive PCR result and negative findings for other pathogens. The M. pneumoniae P1-specific antibody-secreting B cell (ASC) response was examined with the ex vivo enzyme-linked immunosorbent spot assay and the relationships between the ASC frequency and serological level and clinical parameters within M. pneumoniae patients were studied. RESULTS: A robust M. pneumoniae P1-specific ASC response was detected in the peripheral blood among M. pneumoniae-positive patients. By contrast, no M. pneumoniae-specific ASCs were detected among M. pneumoniae-negative patients. The IgM-secreting B cells are the predominant class and account for over 60% of total circulating M. pneumoniae-specific ASCs in the acute phase of illness. The M. pneumoniae P1-specific ASC frequency significantly correlated with the fever duration, and the IgG ASC frequency significantly correlated with serological titer among patients. CONCLUSION: A rapid and potent elicitation of peripheral M. pneumoniae-specific ASC response to acute infection provides the cellular basis of antigen-specific humoral response and indicates the potential of cell-based diagnostic tool for acute M. pneumoniae infection. Our findings warrant further investigations into functional and molecular aspects of antibody immunity to M. pneumoniae.

Anti-allergic Hydroxy Fatty Acids from Typhonium blumei Explored through ChemGPS-NP.

Increasing prevalence of allergic diseases with an inadequate variety of treatment drives forward search for new alternative drugs. Fatty acids, abundant in nature, are regarded as important bioactive compounds and powerful nutrients playing an important role in lipid homeostasis and inflammation. Phytochemical study on Typhonium blumei Nicolson and Sivadasan (Araceae), a folk anti-cancer and anti-inflammatory medicine, yielded four oxygenated fatty acids, 12R-hydroxyoctadec-9Z,13E-dienoic acid methyl ester (1) and 10R-hydroxyoctadec-8E,12Z-dienoic acid methyl ester (2), 9R-hydroxy-10E-octadecenoic acid methyl ester (3), and 12R*-hydroxy-10E-octadecenoic acid methyl ester (4). Isolated compounds were identified by spectroscopic methods along with GC-MS analysis. Isolated fatty acids together with a series of saturated, unsaturated and oxygenated fatty acids were evaluated for their anti-inflammatory and anti-allergic activities in vitro. Unsaturated (including docosahexaenoic and eicosapentaenoic acids) as well as hydroxylated unsaturated fatty acids exerted strong anti-inflammatory activity in superoxide anion generation (IC50 2.14-3.73 µM) and elastase release (IC50 1.26-4.57 µM) assays. On the other hand, in the anti-allergic assays, the unsaturated fatty acids were inactive, while hydroxylated fatty acids showed promising inhibitory activity in A23187- and antigen-induced degranulation assays (e.g., 9S-hydroxy-10E,12Z-octadecadienoic acid, IC50 92.4 and 49.7 µM, respectively). According to our results, the presence of a hydroxy group in the long chain did not influence the potent anti-inflammatory activity of free unsaturated acids. Nevertheless, hydroxylation of fatty acids (or their methyl esters) seems to be a key factor for the anti-allergic activity observed in the current study. Moreover, ChemGPS-NP was explored to predict the structure-activity relationship of fatty acids. The anti-allergic fatty acids formed different cluster distant from clinically used drugs. The bioactivity of T. blumei, which is historically utilized in folk medicine, might be related to the content of fatty acids and their metabolites.

Flavonoids from Cyclopia genistoides and Their Xanthine Oxidase Inhibitory Activity.

The present paper reports the chemical analysis of the methanolic extracts of fermented and non-fermented Cyclopia genistoides herbs and an investigation of the xanthine oxidase inhibitory activity of the isolated constituents. Chemical analysis of the leaves and stems of C. genistoides yielded the isolation and identification of two benzophenone glucosides, iriflophenone 2-O-ß-glucopyranoside (1) and iriflophenone 3-C-ß-glucopyranoside (2), two pterocarpans, (6aR,11aR)-(-)-2-methoxymaackiain (5) and (6aR,11aR)-(-)-maackiain (6), along with the flavanones liquiritigenin (9) and hesperetin (10), the flavone diosmetin (11), the isoflavones afrormosin (7) and formononetin (8), piceol (3), and 4-hydroxybenzaldehid (4). Among the eleven compounds, nine are reported for the first time from this species, and six from the genus Cyclopia. These compounds, together with previously isolated secondary metabolites of this species, were tested for xanthine oxidase inhibitory activity. The 5,7-dihydroxyflavones luteolin and diosmetin significantly inhibited the enzyme in vitro, while hesperetin (10) and 5,7,3',5'-tetrahydroxyflavone exerted weak activity.

Estrogenic and Anti-estrogenic Constituents of Erythrina caffra.

Utilizing the pER8:GUS transgenic plant bioassay system to monitor estrogenic activity-guided fractionation, one new constituent, erycaffrain A, together with I known compounds were isolated from the ethanolic extract of Erythrina caffra. The structures of the isolated compounds were identified in combination with spectroscopic analyses. This is the first study reporting the estrogenic activity of E. caffra. The new compound exhibited as a SREM, but.also showed both estrogenic and anti-estrogenic activities in the MCF-7 cancer cell model. Several known phytoestrogens in this plant also revealed possible new functions for E. caffra stem.

Phytochemicals and Estrogen-Receptor Agonists from the Aerial Parts of Liriope platyphylla.

One new benzofuran, (2R)-(2',4'-dihydroxybenzyl)-6,7-methylenedioxy-2,3-dihydrobenzofuran (1), one new phenylisocoumarin, 3-(2'-hydroxyphenyl)-6,8-dihydroxy-7-methoxy-isocoumarin (2), and one new benzofuroisocoumarin, platyphyllarin C (3), were isolated from the ethanolic extract of Liriope platyphylla aerial parts, along with seventeen known compounds. The structures of the isolates were established by spectroscopic analysis and comparison with the literature data. The results indicated that structures 1-3 are uncommon in Nature. Benzofuroisocoumarin 4, flavonoids 9, 10, and 13-15, and homoisoflavonoids 19 and 20 exhibited significant binding activity to estrogen-receptor α and/or ß as demonstrated by the SEAP reporter assay system in an MCF-7 cell-line.

Rapid, laser-induced conversion of 20-hydroxyecdysone - a follow-up study on the products obtained.

We have recently reported the set-up of an experimental system for the laser-induced photochemical modification of bioactive substances, where two ecdysteroids, 20-hydroxyecdysone (20E) and its diacetonide derivative served as probes. As a direct continuation of our previous work, three new compounds together with five other ecdysteroid derivatives, have been identified from the novel, laser-induced photo-transformation reaction of 20E. The structures and NMR signal assignment were established by comprehensive one- and two-dimensional NMR spectroscopy supported by mass spectroscopy. Possible ways for the formation of each species is also discussed. Similar to their parental compound, the products obtained are potentially bioactive and worthy for further investigations; due to the low yields, however, a different approach for their higher scale production is suggested.

Bioactive constituents of Cirsium japonicum var. australe.

Cirsium japonicum var. australe, used as a folk medicine in Taiwan, has been employed traditionally in the treatment of diabetes and inflammatory symptoms. Bioactivity-guided fractionation of its ethanolic extract, utilizing centrifugal partition chromatography monitored by DPPH-TLC analysis, led to the isolation of three new acetylenic phenylacrylic acid esters (1-3) and two new polyacetylenes (4 and 5), together with seven known compounds (6-12). The structures of 1-5 were elucidated by spectroscopic methods including 1D and 2D NMR techniques. The absolute configurations of 4 and 7 were determined utilizing Mosher's method and ECD/CD experiments. The DPPH scavenging activity of the constituents isolated from the C. japonicum var. australe ethanolic extract was evaluated. The potential antidiabetic activity of some of the isolates was evaluated using in vitro cellular glucose uptake and oil red staining assays.

Phyto-SERM constitutes from Flemingia macrophylla.

The methanolic extract of Flemingia macrophylla roots exhibited significant estrogenic activity in the transgenic plant assay system which was comparable to the activity of soybean extract. Utilizing estrogenic activity-guided fractionation, one new compound, fleminigin, together with 23 known compounds were isolated from F. macrophylla roots' methanolic extract. The structure of the new compound was identified based on intensive spectroscopic analysis and the full spectral data for one of the isolated compounds, flemichin E, was introduced for the first time in the current investigation. The estrogenic and anti-estrogenic activities of the isolated compounds were evaluated revealing that the isolated isoflavonoids may act as partial estrogen agonists, as well as antagonists. Additionally, the anti-inflammatory and the cytotoxic activities of the isolated compounds were studied. These results suggested the potential applications of F. macrophylla extract and its isolated compounds as selective estrogen receptor modulators (SERMs).

The oestrogenic and anti-platelet activities of dihydrobenzofuroisocoumarins and homoisoflavonoids from Liriope platyphylla roots.

The ethanolic extract of Liriope platyphylla (Liliaceae) roots showed potential oestrogenic and anti-platelet activities. Twenty-six compounds were isolated and classified as 10 skeletons, including two unusual new dihydrobenzofuroisocoumarins, (+)-platyphyllarin A (1) and B (2), one new butanoate, ethyltributanoate (3), and two new homoisoflavanones, (-)-liriopein A (4) and B (5), along with 21 known compounds, including six homoisoflavonoids, one chalcone, six amides, one lignan, one fatty acid derivative, one alkaloid, three benzenoids, and two steroids. The biosynthetic pathway of compounds 1 and 2 was proposed in the current investigation. The oestrogenic activity of the isolates was evaluated utilising the pER8:GUS reporter assay system in transgenic Arabidopsis plant as well as the SEAP reporter assay system in MCF-7 breast cancer cell-line; the anti-platelet activity was evaluated using the anti-platelet aggregation assay. Several components exhibited significant oestrogenic and anti-platelet activities; demonstrating for the first time the potential use of L. platyphylla as a nutritional supplement for cardiovascular and endocrine diseases.

New flavan and benzil isolated from Fissistigma latifolium.

Further investigation of the methanolic extract of Fissistigma latifolium resulted in two new compounds whose structures were assigned as 2,5,6,7-tetramethoxyflavan (1) and 2'-hydroxy-4',5',6'-trimethoxybenzil (2). These two compounds were determined on the basis of chemical and spectroscopic evidences. Compound 2 is the first report of benzil from Fissistigma species. 2,5,6,7-Tetramethoxyflavan (1) showed a potent inhibitory effect on superoxide anion production in formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)/cytochalasin B (CB)-activated human neutrophils.

Using the pER8:GUS reporter system to screen for phytoestrogens from Caesalpinia sappan.

Arabidopsis thaliana pER8:GUS, a low-cost, highly efficient, and convenient transgenic plant system, was used to assay the estrogen-like activity of 30 traditional Chinese medicines. The MeOH extract of Caesalpinia sappan exhibited significant bioactivity in this assay, and subsequent bioactivity-guided fractionation of the extract led to the isolation of one new compound, (S)-3,7-dihydroxychroman-4-one (1), and 10 known compounds. Both the plant pER8:GUS and in vitro estrogen response element reporter assays were used to evaluate the estrogenic activity of the isolated compounds, and these two systems produced comparable results. Compounds 6, 8, and 11 showed significant estrogenic activity comparable to genistein. These active compounds were determined to be nontoxic new sources of phytoestrogens. In addition, compounds 2 and 3 inhibited ERE transcription induced by 17ß-estradiol. A docking model revealed that compounds 6, 8, and 11 showed high affinity to the estrogen receptor. The pER8:GUS reporter system was demonstrated to be a useful and effective technique in phytoestrogen discovery.

Antitumor agents. 271: total synthesis and evaluation of brazilein and analogs as anti-inflammatory and cytotoxic agents.

The first total synthesis of the naturally occurring tetracyclic homoisoflavonoid brazilein (1) and 14 new analogs (1a-n) is reported. Target compounds and intermediates were assayed for anti-inflammatory effects on superoxide anion generation and elastase release by human neutrophils in response to fMLP/CB, and for cytotoxic activity against nasopharyngeal (KB), vincristine-resistant nasopharyngeal (KBvin), lung (A549) and prostate (DU-145) human cancer cell lines. The most active compound 1b showed potent effects on superoxide anion generation and elastase release with IC(50) values of 1.2 and 1.9 microM, respectively, and was 65 times more potent than phenylmethylsulfonyl fluoride (PMSF), the positive control, in the latter assay. Additionally, 1b exhibited broad spectrum in vitro anticancer activity with IC(50) values of 6-11 microM against the four tested cancer cell lines.