Maternal and perinatal outcomes of asthma exacerbation during pregnancy in a Chinese population: a retrospective cohort study.

BACKGROUND: Asthma exacerbation (AE) is a significant clinical problem during pregnancy. This study aimed to identify maternal and perinatal outcomes associated with AE during pregnancy. METHODS: We conducted a retrospective cohort study using the Peking University Third Hospital database from January 1, 2013 to December 31, 2020. We compared the clinical characteristics and maternal, perinatal and offspring outcomes of asthma with and without exacerbations among women who delivered during this period. The primary outcome was hypertensive disorders of pregnancy (HDP). Univariable and multivariable logistic regression analyses were used to analyze the clinical characteristics of AE during pregnancy and the association between AE and adverse maternal and perinatal outcomes. RESULTS: The prevalence of asthma during pregnancy increased from 0.52% in 2013 to 0.98% in 2020. Of the 220 patients with asthma during pregnancy included in the study, 105 experienced AE during pregnancy: 62.9% (n = 66) had mild-to-moderate AE and 37.1% (n = 39) had severe AE. Pregnant women with allergic rhinitis have a higher risk of AE during pregnancy. Women who experienced AE were more at risk for hypertensive disorders of pregnancy than women who did not experience any exacerbation (12.4%vs3.5%, p < 0.05). CONCLUSIONS: The prevalence of asthma among pregnant women in China is on the rise. There is a notable correlation between pregnant women who suffer from allergic rhinitis and an elevated risk of AE during pregnancy. Studies have shown that AE during pregnancy are associated with an increased risk of hypertensive disorders of pregnancy.

Four new tirucallane-type triterpenoids from Aphanamixis polystachya.

Four new tirucallane-type triterpenoids, polystanins H-K (1-4), were obtained from the stems and leaves of Aphanamixis polystachya. Their structures were elucidated by analysis of the spectroscopic data and comparison with literature data. Compounds 1 and 2 showed week inhibitory effects against NO production in LPS-stimulated RAW264.7 cells. All the isolates were investigated for their antifungal activities against drug-resistant Candida albicans.

Two new triterpenoids from the fruits of Aphanamixis polystachya.

Two new triucallane triterpenoids, polystanin F (1) and polystanin G (2), along with eight known compounds (3-10) were isolated from the fruits of Aphanamixis polystachya. Their structures were established on the basis of extensive spectroscopic analysis. Moreover, eight compounds were evaluated for their in vitro cytotoxicity against three cancer cell lines (liver cancer RT112, colon cancer HCT-116 and breast cancer M231) using the MTT method. Compound 7 showed significant cytotoxic activity against HCT-116 with IC50 1.27 µM.

Synthesis and antitumor activity of biotinylated camptothecin derivatives as potent cytotoxic agents.

A series of biotinylated camptothecin derivatives were designed and synthesized. The key to the synthesis was achieved by employing an esterification reaction and click chemistry. All of the new derivatives were tested for cytotoxicity against five human tumor cell lines, including HL-60, SMMC-7721, A-549, MCF-7, and SW480 with IC50 values ranging from 0.13 to 21.53 µM. Most of the derivatives exhibited potent cytotoxicity, especially compound 17 (IC50 = 0.13-3.31 µM) and compound 18 (IC50 = 0.23-1.48 µM), which exhibited the highest potencies. The structure-activity relationships (SARs) of the biotinylated camptothecin derivatives were discussed for exploring novel anticancer agents.

Four new monoterpenoids from the whole plants of Valeriana stenoptera.

Four new monoterpenoids, including two new acyclic monoterpenoids (2R, 6R)-2, 6-dimethyl-8-isovaleroxyoctan-1-ol (1) and (2S, 6S)-2, 6-dimethyl-8-isovaleroxyoctan-1-ol (2), as well as two new iridoids stenopterins F-G (3 and 4), together with fifteen known compounds (5-19), were isolated from whole dried material of Valeriana stenoptera. Stenopterin F was the first reported iridoids with n-butoxyl in the Valerianaceae family. The structures of new compounds were established on the basis of extensive spectroscopic analysis.

Seco-Dendrobine-Type Alkaloids and Bioactive Phenolics from Dendrobium findlayanum.

Investigation of the 95% EtOH extract of stems of Dendrobium findlayanum afforded four new seco-dendrobines, findlayines A-D (1-4); two known dendrobines, dendrobine (5) and 2-hydroxydendrobine (6); and four new phenolic compounds, dendrofindlaphenols A-C (7, 9, and 10) and 6″-de-O-methyldendrofindlaphenol A (8). Compounds 1 and 2 are the first seco-dendrobines possessing a seven-membered lactam moiety, with 3 and 4 derived from the oxidative cleavage of the C-2-C-3 bond of dendrobine. The structures were established using spectroscopic methods and by comparison with literature data. The absolute configurations of 1-4 were confirmed via single-crystal X-ray diffraction data. Cytotoxic activity assays against HL-60, SMMC-7721, A-549, MCF-7, and SW480 human cancer cell lines revealed IC50 values ranging from 2.3 to 5.3 µM for compound 7, from 19.4 to 34.4 µM for 8, and from 49.4 to 96.8 µg/mL for the EtOAc extract. An assay of the inhibition of NO production with RAW 264.7 cells indicated that 8 had an IC50 value of 21.4 µM, and the EtOAc extract, 10.5 µg/mL. The EtOAc extract possessed DPPH radical scavenging activity of 69.93% at 100 µg/mL.

Synthesis and antitumor activity of novel per-butyrylated glycosides of podophyllotoxin and its derivatives.

A series of perbutyrylated glycosides of podophyllotoxin and its derivatives were synthesized and evaluated for their antitumor activity in vitro. Most of them exhibit cytotoxic activity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assays. Among the synthesized compounds, epipodophyllotoxin α-d-galactopyranoside 8b, epipodophyllotoxin α-d-arabinopyranoside 8e, and podophyllotoxin ß-d-glucopyranoside 11a show the highest potency of anticancer activity with their IC50 values ranging from 0.14 to 1.69µM. Structure activity relationship analysis indicates that the type of glycosidic linkage, the configuration at C-4 of the podophyllotoxin scaffold, and the substitution at 4'-position (OH vs OCH3) can all have significant effect on the potency of their anticancer activity. Several compounds are more active than the control drugs Etoposide and Cisplatin, suggesting their potential as anticancer agents for further development.

Cytotoxic bibenzyl dimers from the stems of Dendrobium fimbriatum Hook.

The bioassay-guided chemical investigation of the stems of Dendrobium fimbriatum Hook led to the isolation of seven first reported bibenzyl dimers with a linkage of a methylene moiety, fimbriadimerbibenzyls A-G (1-7), together with a new dihydrophenanthrene derivative (S)-2,4,5,9-tetrahydroxy-9,10-dihydrophenanthrene (8) and thirteen known compounds (9-21). The structure of the new compound was established by spectroscopic analysis. Biological evaluation of bibenzyl derivatives against five human cell lines indicated that seven of those compounds exhibited broad-spectrum and cytotoxic activities with IC50 values ranging from 2.2 to 21.2 µM. Those rare bibenzyl dimers exhibited cytotoxic activities in vitro and the cytotoxicity decreased as the number of oxygen-containing groups in the structure decreases.

Non-pharmacological interventions for asthma prevention and management across the life course: Umbrella review.

BACKGROUND: The impact of non-pharmacological interventions (NPIs) on asthma prevention and management is insufficiently examined. We aim to comprehensively evaluate and synthesize existing evidence regarding the effectiveness of various NPIs throughout the life course. METHODS: We conducted a systematic search and screening of reviews that examined the effectiveness of various NPIs on asthma prevention and control in the Cochrane Library, PubMed, Embase, and Ovid databases. Data extraction was performed by considering the type of NPIs and the life course stages of the target population. Recommendations were provided by considering the quality of review assessed using the AMSTAR2 tool and the consistency of findings across reviews. RESULTS: We identified 145 reviews and mapped the evidence on the impact of 25 subtypes of NPIs on asthma prevention and control based on five stages of life course. Reviews indicated a shift of focus and various impacts of major NPIs on asthma prevention and control across life courses, while a few types of NPIs, such as physical exercise, appeared to be beneficial in children, adolescents and adults. Consistent and high-level evidence was observed only for psychological intervention on asthma control and quality of life among adults and older adults. Potential benefit with high-level evidence was reported on certain NPIs, such as vitamin D in reducing risk of developing asthma in offsprings in the prenatal stage, digital health interventions in improving asthma control from childhood to older adulthood, and breathing exercise in improving quality of life, asthma-related symptoms and lung function in adulthood and older adulthood. CONCLUSION: This study emphasizes the significance of delivering NPIs to improve asthma prevention and management and highlights the heterogeneity regarding the impact of NPIs across life courses. High-quality research is urgently needed to further strengthen the evidence base of NPIs and tailored interventions should be considered in guideline development.

Aralianudaside A, an unusual skeleton triterpenoid saponin with anti-airway inflammatory activity from Aralia elata.

Aralianudaside A, a triterpene saponin with an unusual skeleton of pentacyclic triterpenoid, along with a new triterpene glycoside and six known compounds were obtained from the buds of Aralia elata. Their structures were determined through extensive spectral analysis, including HRESIMS, IR, 1D and 2D NMR, glycolysis and GC. All compounds were evaluated for anti-airway inflammatory activity in lipopolysaccharides (LPS)-induced airway epithelial cells (16HBE), compounds 1, 3, 5, 7 and 8 significantly decreased the expression of pro-inflammatory cytokines IL-1ß and IL-4.

Inhibitory activities on nitric oxide production of stilbenoids from Pholidota yunnanensis.

Three new stilbenoids, 1-(4'-hydroxybenzyl)-imbricatin, (E)-4'-hydroxy-2',3,3',5-tetramethoxystilbene, and (E)-3,4'-dihydroxy-2,6-bis(4-hydroxybenzyl)-2',3',5-trimethoxystilbene, together with 15 known stilbene derivatives, were isolated from Pholidota yunnanensis. Their structures were elucidated by spectroscopic methods and by comparison of their NMR data with those of related compounds. Furthermore, the inhibitory activities on nitric oxide (NO) production of the isolated compounds were examined in murine macrophages (RAW 264.7) activated by lipopolysaccharide. The cytotoxicity of 18 compounds was determined by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Among the tested compounds, eight stilbenoids, including three dihydrophenanthrenes, three stilbenes, and one bibenzyl derivative showed inhibitory effects on NO production without cytotoxicity with IC50 values ranging from 4.07 to 7.77 µM, as compared to MG-132, which was used as a positive control (IC50 of 0.10 µM). One dihydrophenanthrene, phoyunnanin C, showed cytotoxic effects at the test concentrations.

Triterpenoids from the fruits of Aphanamixis polystachya and their inhibitory activities on nitric oxide production.

Nineteen triterpenoids, including five previously unknown (four triucallane-type derivatives and one highly oxidized A, B-seco limonoids), together with fourteen known triterpenoids, were isolated from the fruits of Aphanamixis polystachya. Their structures were elucidated by extensive spectroscopic analysis. All isolates were evaluated their anti-inflammatory activities. The result showed that all compounds inhibit LPS-induced nitric oxide production in RAW264.7 macrophages with their IC50 value ranging from 95 to 1332 uM, and compound 6 exhibited obvious anti-inflammatory activity comparable to that of the positive control, with IC50 values of 94.96 uM.

Serum sphingolipid profile in asthma.

Sphingolipids metabolism is an important cell process and plays critical roles in asthma. However, the involvement of sphingolipids in the pathogenesis of asthma and its subtypes is unknown. The present study aimed to determine the role of sphingolipids in asthma and its subtypes. Clinical data from 51 asthma patients and 9 healthy individuals were collected and serum samples were performed to analyze the levels of serum sphingolipids by liquid chromatography-mass spectrometry-based targeted metabolomics. Results showed that the levels of sphingomyelin (SM) including SM34:2, SM38:1, and SM40:1 were significantly decreased in asthmatic patients compared to healthy controls. Moreover, serum SM levels were obviously decreased in the blood noneosinophilic asthma (bNEA) group compared with blood eosinophilic asthma group. Similar tendencies of serum SM level changes were observed in the early-onset group compared with late-onset group. Correlation analysis revealed that SM 40:1 was negatively related to sputum IL-17A (r = -0.621, P = 0.042). The present study presented that the SM may be a protective factor of asthma and contributes to the mechanism of asthma, especially bNEA. SM may be a potential biomarker and therapeutic target in asthma.

Ten picrotoxane-type sesquiterpenoids from the stems of Dendrobium wardianum Warner.

Ten undescribed picrotoxane-type sesquiterpenoids, dendrowardins A-J, together with two known ones, were isolated from the stems of Dendrobium wardianum Warner (Orchidaceae). Dendrowardins A-D feature the unusual 5,2-δ-lactone and additionally dendrowardins C-D are the first examples containing the 11,10-γ-lactone moiety. The structures were established using spectroscopic methods and by comparison with literature data. Further, dendrowardin E, amotin, and aduncin exhibited significant effects of promoting the proliferation on human lens epithelial cells (HLECs) induced by D-galactose.

Sesquiterpenoids from the roots and rhizomes of Valeriana amurensis and their effects on NGF-induced neurite outgrowth in PC12 cells.

Two new sesquiterpenoids, including a kessane-type sesquiterpenoid (1) and one bisabolane derivative (2), together with fourteen known sesquiterpenoids (3-16), were isolated from the roots and rhizomes of Valeriana amurensis. The structures of new compounds were established on the basis of extensive spectroscopic analysis. All isolates were evaluated for their effects on nerve growth factor (NGF)-mediated neurite outgrowth in pheochromocytoma (PC12) cells. As a results, four compounds including 10-12 and 15 showed potent promoting effects at the concentration of 10 µM on NGF-induced neurite outgrowth in PC12 cells with the differentiation rate of 11.84%, 12.21%, 13.77% and 12.16%, respectively.

Flower extract of Caragana sinica. ameliorates DSS-induced ulcerative colitis by affecting TLR4/NF-κB and TLR4/MAPK signaling pathway in a mouse model.

OBJECTIVES: This study aimed to find out the protective effects and preliminary mechanisms of the flower extract of Caragana sinica (FEC) on dextran sulfate sodium salt (DSS)-induced colitis. MATERIALS AND METHODS: The ulcerative colitis models of mice induced by 3% DSS were established and treated with FEC. Body weight changes, disease activity index (DAI), colon histopathological score, anti-oxidant ability, and the level of inflammatory cytokines were determined. The expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) were assessed in colonic tissue by immunohistochemical staining. Western blot was used to analyze the expression of TLR4/ nuclear factor kappa-B (NF-κB) and TLR4/ mitogen-activated protein kinase (MAPK) signaling pathway-related proteins. RESULTS: FEC significantly prevented body weight loss and colonic shortening and reduced the disease activity index and histopathological score (P<0.05). Moreover, FEC treatment remarkably down-regulated the levels of myeloperoxidase (MPO), interleukin-1beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) and up-regulated the levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and interleukin 10 (IL-10) in the colon of DSS mice (P<0.05). Furthermore, the expression of TLR4/NF-κB and TLR4/MAPK pathway-related proteins was inhibited by FEC (P<0.05). CONCLUSION: Our findings demonstrated that FEC could serve as a potential therapeutic agent for treatment of ulcerative colitis.

Symptoms, Management and Healthcare Utilization of COPD Patients During the COVID-19 Epidemic in Beijing.

Background: Social distancing and restriction measures during the COVID-19 epidemic may have impacts on medication availability and healthcare utilization for COPD patients, and thereby affect standard disease management. We aimed to investigate the change of respiratory symptoms, pharmacological treatment and healthcare utilization of COPD patients during the epidemic in Beijing, China. Methods: We conducted a single-center, cross-sectional survey performed at Peking University Third Hospital and recruited patients with COPD who were interviewed by phone call. Clinical data, including respiratory symptoms, pharmacological treatment, management and healthcare access before and during the COVID-19 epidemic from January 25 to April 25, 2020, were collected. Results: A total of 153 patients were enrolled for analysis. Before the epidemic, 81.7% (125/153) had long-term maintenance medication and ICS/LABA (60.8%) and LAMA (57.5%) were most commonly used. During the epidemic, 75.2% (115/153) maintained their pharmacological treatment and 6.5% (10/153) had to reduce or stop taking medications, with a slight decrease of patients taking ICS/LABA (53.6%) and LAMA (56.9%). Most of the patients [76.5% (117/153)] had a low symptom burden, with a CAT score <10 during the epidemic. Of 153 patients, 45 (29.4%) patients reported worsening of respiratory symptoms but only 15.6% (7/45) sought medical care in hospitals, while the remaining expressed concerns about cross-infection in the hospital (55.5%, 25/45) or had mild symptoms which were managed by themselves (28.8%, 13/45). Conclusion: During the COVID-19 epidemic in Beijing, most of our COPD patients maintained their long-term pharmacological treatment and had mild-to-moderate symptoms. Approximately, 30.0% of the patients experienced worsening of respiratory symptoms, but most of them did not seek medical care in the hospital due to concerns about cross-infection.

Two unusual dendrobine-type alkaloids from Dendrobium findlayanum.

Two unusual dendrobine-type alkaloids, findlayines E and F (1, 2), along with five known dendrobine-type alkaloids (3-7), were isolated from the stems of Dendrobium findlayanum Par. et Rchb. f. Compound 1 is the first example of dendrobine-type alkaloids with a 2-ethoxy-2-oxoethyl group attaching to the C-2, and compound 2 is a nor-dendrobine-type alkaloid, featuring a 5-decarboxylated structure. The structures of compounds 1 and 2 were elucidated by means of extensive spectroscopic analyses, and their absolute configuration were confirmed by electronic circular dichroism (ECD) calculations. All isolates were evaluated for their cytotoxicity against HL-60, SMMC-7721, A-549 and MCF-7 human cancer cells.

Synthesis and antitumor activity of camptothecin- 4ß-triazolopodophyllotoxin conjugates.

Two new compounds (9 and 10) having a camptothecin (CPT) analog conjugated to the 4ß-azido-4-deoxypodophyllotixin analog by untilizing the copper-catalyzed azide-alkyne cycloadditon (CuAAC) reaction, and were evaluated for their cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW480) using the MTT (3-(4,5-dimethyl-thiahiazo-2-yl)-2,5-diphenyltetrazolium bromide) assay. Two novel conjugates shown weak cytotoxicity, compound 10 showed highly potent against HL-60 cell line tested, with IC50 value 17.69 ± 0.19 µM. This compound suggested its potential as anticancer agents for further development. [Formula: see text].