Three new amide derivatives from the fungus Alternaria brassicicola

Abstract Three new amide derivatives (alteralkaloids A–C, 1–3) and three known alkaloids (4–6) were afforded after phytochemical investigation of fungus Alternaria brassicicola. The structures of these compounds were confirmed by NMR spectroscopic and HRESIMS data. Furthermore, the absolute configuration of 1 was determined using the single-crystal X-ray diffraction analysis. Compounds 1–3 belong to a class of amide derivatives that have not been found in nature before, sharing the same characteristic signals of the butyl moiety and amide group. These isolated compounds mentioned above were tested for the cytotoxic activity. Graphical Abstrac

Airway reversibility in asthma and phenotypes of Th2-biomarkers, lung function and disease control

Abstract Background High bronchodilator reversibility in adult asthma is associated with distinct clinical characteristics. In this study, we aim to make a comparison with T-helper 2 (Th2)-related biomarkers, lung function and asthma control between asthmatic patients with high airway reversibility (HR) and low airway reversibility (LR). Methods Patients with asthma diagnosed by pulmonologist according to Global Initiative for Asthma guidelines were recruited from the outpatient department of our hospital from August 2014 to July 2017. Patients were divided into HR and LR subgroups based on their response to bronchodilators of lung function (HR = Δforced expiratory volume in one second (FEV1) postbronchodilator ≥ 20%). Blood eosinophil count and serum IgE level, which are biomarkers of T-helper (Th)-2 phenotypes, were detected for patients. Asthma Control Test (ACT) was used to assess asthma control after the first-month initial treatment. Results A total of 265 patients with asthma were followed 1 month after initial treatment. HR group shows a higher level of Th2-high biomarkers (blood eosinophil count (10^9/L): 0.49 ± 0.28 vs 0.36 ± 0.19, P < 0.01; IgE (ng/ml): 1306 ± 842 vs 413 ± 261, P < 0.01), lower baseline lung function (FEV1%pred: 51.91 ± 19.34% vs 60.42 ± 19.22%, P < 0.01; forced expiratory flow (FEF)25–75: 0.76 ± 0.37 vs 1.00 ± 0.67, P < 0.01; FEF25–75%pred: 21.15 ± 10.09% vs 29.06 ± 16.50%, P < 0.01), and better asthma control (ACT score: 22 ± 4 vs 20 ± 4, P = 0.01) than LR group. HR was associated with a decreased risk of uncontrolled asthma after the first-month initial treatment (adjusted OR: 0.12 [95% confidence intervals: 0.03–0.50]). Conclusions HR is a physiologic indicator of lower lung function and severe small airway obstruction, and is more related with an increased level of Th2-biomarkers than LR. Moreover, HR may indicate controlled asthma after the first-month initial treatment. This finding may contribute to identification of asthma endotype

Immunogenicity and safety evaluation of bivalent types 1 and 3 oral poliovirus vaccine by comparing different poliomyelitis vaccination schedules in China: A randomized controlled non-inferiority clinical trial

Background: The type 2 component of the oral poliovirus vaccine is targeted for global withdrawal through a switch from the trivalent oral poliovirus vaccine (tOPV) to a bivalent oral poliovirus vaccine (bOPV). The switch is intended to prevent paralytic polio caused by circulating vaccine-derived poliovirus type 2. We aimed to assess the immunogenicity and safety profile of 6 vaccination schedules with different sequential doses of inactivated poliovirus vaccine (IPV), tOPV, or bOPV. Methods: A randomized controlled trial was conducted in China in 2015. Healthy newborn babies randomly received one of the following 6 vaccination schedules: cIPV-bOPV-bOPV(I-B-B), cIPV-tOPV-tOPV(I-T-T), cIPV-cIPV-bOPV(I-I-B), cIPV-cIPV-tOPV(I-I-T), cIPV-cIPV-cIPV(I-I-I), or tOPV-tOPV-tOPV(T-T-T). Doses were administered sequentially at 4–6 week intervals after collecting baseline blood samples. Patients were proactively followed up for observation of adverse events after the first dose and 30 days after all doses. The primary study objective was to investigate the immunogenicity and safety profile of different vaccine schedules, evaluated by seroconversion, seroprotection and antibody titer against poliovirus types 1, 2, and 3 in the per-protocol population. Results: Of 600 newborn babies enrolled, 504 (84.0%) were included in the per-protocol population. For type 1 poliovirus, the differences in the seroconversion were 1.17% (95% CI = −2.74%, 5.08%) between I-B-B and I-T-T and 0.00% (95% CI: −6.99%, 6.99%) between I-I-B and I-I-T; for type 3 poliovirus, differences in the seroconversion were 3.49% (95% CI: −1.50%, 8.48%) between I-B-B and I-T-T and −2.32% (95% CI: −5.51%, 0.86%) between I-I-B and I-I-T. The non-inferiority conclusion was achieved in both poliovirus type 1 and 3 with the margin of −10%. Of 24 serious adverse events reported, no one was vaccine-related. Conclusions: The vaccination schedules with bOPV followed by one or 2 doses of IPV were recommended to substitute for vaccinations involving tOPV without compromising the immunogenicity and safety in the Chinese population. The findings will be essential for policy formulation by national and global authorities to facilitate polio elimination

Dipeniroqueforins A–B and Peniroqueforin D: Eremophilane-Type Sesquiterpenoid Derivatives with Cytotoxic Activity from <i>Penicillium roqueforti</i>

Guided by the Global Natural Products Social (GNPS) molecular networking strategy, five undescribed eremophilane-type sesquiterpenoid derivatives (1–5) were isolated and identified from fungus Penicillium roqueforti, which was separated from the root soil of plant Hypericum beanii collected in Shennongjia Forestry District, Hubei Province. Dipeniroqueforins A–B (1–2), representing a lactam-type sesquiterpenoid skeleton with a highly symmetrical and homodimeric 5/6/6–6/6/5 hexacyclic system, are reported within the eremophilane-type family for the first time. Peniroqueforin D (5) represents the first example of a 1,2-seco eremophilane-type sesquiterpenoid derivative featuring an undescribed 7/6-fused ring system. The structures of these compounds were elucidated by various spectroscopic analyses, DP4+ probability analyses, ECD calculations, and single-crystal X-ray diffraction experiments. Furthermore, these isolates were evaluated for cytotoxicity, and the result uncovered that compound 1 displayed broad-spectrum activity. Further mechanistic study revealed that compound 1 could significantly upregulate the mRNA expression of genes related to the oxidative induction, leading to the abnormal ROS levels in tumor cells and ultimately causing tumor cell apoptosis