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- Hsu, Yu-Ming, et al.
(författare)
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Zoanthamine-Type Alkaloids from the Zoanthid Zoanthus kuroshio Collected in Taiwan and Their Effects on Inflammation
- 2016
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Ingår i: Journal of natural products (Print). - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 79:10, s. 2674-2680
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Tidskriftsartikel (refereegranskat)abstract
- Zoanthus kuroshio is a colorful zoanthid with a fluorescent pink oral disc and brown tentacles, which dominates certain parts of the Taiwanese and Japanese coasts. This sea anemone is a rich source of biologically active alkaloids. In the current investigation, two novel halogenated zoanthamines [5 alpha-iodozoanthenamine (1) and 11 beta-chloro-11-deoxykuroshine A (2)], along with four new zoanthamines [18-epi-kuroshine A (3), 7 alpha-hydroxykuroshine E (4), 5 alpha-methoxykuroshine E (5), and 18-epi-kuroshine E (6)], and six known compounds were isolated from Z. kuroshio. Compounds 1 and 2 are the first examples of halogenated zoanthamine-type alkaloids isolated from nature. Compounds 3 and 6 are the first zoanthamine stereoisomers with a cis-junction of the A/B rings. All isolated compounds were evaluated for their anti-inflammatory activities by measuring their effects on superoxide anion generation and elastase release by human neutrophils in response to fMLP.
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| 4. |
- Lai, Kuei-Hung, et al.
(författare)
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Cytotoxic Lanostanoids from Poria cocos
- 2016
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Ingår i: Journal of natural products (Print). - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 79:11, s. 2805-2813
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Tidskriftsartikel (refereegranskat)abstract
- Six new and 16 known lanostanoids were isolated from the sclerotia of Poria cocos. The structures of the new isolates were elucidated to be 16α-hydroxy-3-oxo-24-methyllanosta-5,7,9(11),24(31)-tetraen-21-oic acid (1), 3β,16α,29-trihydroxy-24-methyllanosta-7,9(11),24(31)-trien-21-oic acid (2), 3β,16α,30-trihydroxy-24-methyllanosta-7,9(11),24(31)-trien-21-oic acid (3), 3β-acetoxy-16α,24β-dihydroxylanosta-7,9(11),25-trien-21-oic acid (4), 3β,16α-dihydroxy-7-oxo-24-methyllanosta-8,24(31)-dien-21-oic acid (5), and 3α,16α-dihydroxy-7-oxo-24-methyllanosta-8,24(31)-dien-21-oic acid (6), based on extensive spectroscopic analyses. The absolute configuration of 4 was determined using Mosher's method. The antiproliferative activity of the isolated compounds (except 3 and 4) was evaluated against four leukemic cell lines (Molt 4, CCRF-CEM, HL 60, and K562). Dehydropachymic acid (9), dehydroeburicoic acid (12), pachymic acid (14), and lanosta-7,9(11),24-trien-21-oic acid (20) exhibited an antiproliferative effect on the CCRF-CEM cancer cell line with IC50 values of 2.7, 6.3, 4.9, and 13.1 μM, respectively. Both dehydropachymic acid (9) and dehydroeburicoic acid (12) showed antiproliferative effects against Molt 4 (IC50 13.8 and 14.3 μM) and HL 60 (IC50 7.3 and 6.0 μM) leukemic cell lines. Primary computational analysis using a chemical global positioning system for natural products (ChemGPS-NP) on the active lanostanoids from P. cocos suggested that targets other than topoisomerases may be involved in the antiproliferative activity.
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- Abolhassani, Hassan, et al.
(författare)
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Genetic and immunologic evaluation of children with inborn errors of immunity and severe or critical COVID-19
- 2022
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 150:5, s. 1059-1073
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals are asymptomatic or only exhibit mild disease. In about 10% of cases, the infection leads to hypoxemic pneumonia, although it is much more rare in children. Objective: We evaluated 31 young patients aged 0.5 to 19 years who had preexisting inborn errors of immunity (IEI) but lacked a molecular diagnosis and were later diagnosed with coronavirus disease 2019 (COVID-19) complications. Methods: Genetic evaluation by whole-exome sequencing was performed in all patients. SARS-CoV-2-specific antibodies, autoantibodies against type I IFN (IFN-I), and inflammatory factors in plasma were measured. We also reviewed COVID-19 disease severity/outcome in reported IEI patients. Results: A potential genetic cause of the IEI was identified in 28 patients (90.3%), including mutations that may affect IFN signaling, T- and B-cell function, the inflammasome, and the complement system. From tested patients 65.5% had detectable virus-specific antibodies, and 6.8% had autoantibodies neutralizing IFN-I. Five patients (16.1%) fulfilled the diagnostic criteria of multisystem inflammatory syndrome in children. Eleven patients (35.4%) died of COVID-19 complications. All together, at least 381 IEI children with COVID-19 have been reported in the literature to date. Although many patients with asymptomatic or mild disease may not have been reported, severe presentation of COVID-19 was observed in 23.6% of the published cases, and the mortality rate was 8.7%. Conclusions: Young patients with preexisting IEI may have higher mortality than children without IEI when infected with SARS-CoV-2. Elucidating the genetic basis of IEI patients with severe/critical COVID-19 may help to develop better strategies for prevention and treatment of severe COVID-19 disease and complications in pediatric patients.
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- Abolhassani, Hassan, et al.
(författare)
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Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome
- 2022
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Ingår i: Journal of Clinical Immunology. - : Springer Nature. - 0271-9142 .- 1573-2592. ; 42:3, s. 471-483
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Tidskriftsartikel (refereegranskat)abstract
- Background Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the causes of multisystem inflammatory syndrome in children (MIS-C) remain elusive. Objectives To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C. Methods Whole exome sequencing was performed, and the impact of candidate gene variants was investigated. Plasma levels of cytokines, specific antibodies against the virus, and autoantibodies against type I IFNs were also measured. Results We report a 3-year-old child who died on day 56 of SARS-CoV-2 infection with an unusual clinical presentation, combining both critical COVID-19 pneumonia and MIS-C. We identified a large, homozygous loss-of-function deletion in IFNAR1, underlying autosomal recessive IFNAR1 deficiency. Conclusions Our findings confirm that impaired type I IFN immunity can underlie critical COVID-19 pneumonia, while suggesting that it can also unexpectedly underlie concomitant MIS-C. Our report further raises the possibility that inherited or acquired dysregulation of type I IFN immunity might contribute to MIS-C in other patients.
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| 7. |
- Abolhassani, Hassan, et al.
(författare)
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X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia
- 2022
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Ingår i: Journal of Clinical Immunology. - : Springer Science and Business Media LLC. - 0271-9142 .- 1573-2592. ; 42:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the mechanism underlying life-threatening COVID-19 is instrumental for disease prevention and treatment in individuals with a high risk.Objectives We aimed to identify the genetic cause for critical COVID-19 pneumonia in a patient with a preexisting inborn error of immunity (IEI).Methods Serum levels of specific antibodies against the virus and autoantibodies against type I interferons (IFNs) were measured. Whole exome sequencing was performed, and the impacts of candidate gene variants were investigated. We also evaluated 247 ataxia-telangiectasia (A-T) patients in the Iranian IEI registry.Results We report a 7-year-old Iranian boy with a preexisting hyper IgM syndrome who developed critical COVID-19 pneumonia. IgM only specific COVID-19 immune response was detected but no autoantibodies against type I IFN were observed. A homozygous deleterious mutation in the ATM gene was identified, which together with his antibody deficiency, radiosensitivity, and neurological signs, established a diagnosis of A-T. Among the 247 A-T patients evaluated, 36 had SARS-CoV-2 infection, but all had mild symptoms or were asymptomatic except the index patient. A hemizygous deleterious mutation in the TLR7 gene was subsequently identified in the patient.Conclusions We report a unique IEI patient with combined ATM and TLR7 deficiencies. The two genetic defects underlie A-T and critical COVID-19 in this patient, respectively.
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| 8. |
- Cai, Jing, et al.
(författare)
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Size-segregated particle number and mass concentrations from different emission sources in urban Beijing
- 2020
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 20:21, s. 12721-12740
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Tidskriftsartikel (refereegranskat)abstract
- Although secondary particulate matter is reported to be the main contributor of PM2.5 during haze in Chinese megacities, primary particle emissions also affect particle concentrations. In order to improve estimates of the contribution of primary sources to the particle number and mass concentrations, we performed source apportionment analyses using both chemical fingerprints and particle size distributions measured at the same site in urban Beijing from April to July 2018. Both methods resolved factors related to primary emissions, including vehicular emissions and cooking emissions, which together make up 76% and 24% of total particle number and organic aerosol (OA) mass, respectively. Similar source types, including particles related to vehicular emissions (1.6 +/- 1.1 mu gm(-3); 2.4 +/- 1.8 x 10(3) cm(-3) and 5.5 +/- 2.8 x 10(3) cm(-3) for two traffic-related components), cooking emissions (2.6 +/- 1.9 mu gm(-3) and 5.5 +/- 3.3 x 10(3) cm(-3)) and secondary aerosols (51 +/- 41 mu gm(-3) and 4.2 +/- 3.0 x 10(3) cm(-3)), were resolved by both methods. Converted mass concentrations from particle size distributions components were comparable with those from chemical fingerprints. Size distribution source apportionment separated vehicular emissions into a component with a mode diameter of 20 nm (traffic-ultrafine) and a component with a mode diameter of 100 nm (traffic-fine). Consistent with similar day- and nighttime diesel vehicle PM2.5 emissions estimated for the Beijing area, traffic-fine particles, hydrocarbon-like OA (HOA, traffic-related factor resulting from source apportionment using chemical fingerprints) and black carbon (BC) showed similar diurnal patterns, with higher concentrations during the night and morning than during the afternoon when the boundary layer is higher. Traffic-ultrafine particles showed the highest concentrations during the rush-hour period, suggesting a prominent role of local gasoline vehicle emissions. In the absence of new particle formation, our re-sults show that vehicular-related emissions (14% and 30% for ultrafine and fine particles, respectively) and cooking-activity-related emissions (32 %) dominate the particle number concentration, while secondary particulate matter (over 80 %) governs PM2.5 mass during the non-heating season in Beijing.
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| 9. |
- Chan, Yi-Hao, et al.
(författare)
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SARS-CoV-2 brainstem encephalitis in human inherited DBR1 deficiency.
- 2024
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Ingår i: The Journal of experimental medicine. - 1540-9538. ; 221:9
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Tidskriftsartikel (refereegranskat)abstract
- Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)-derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility of WT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron-intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2.
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| 10. |
- Chen, K., et al.
(författare)
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Ti deficiency effect on the dielectric response of CaCu3Ti4O12 ceramics
- 2007
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Ingår i: Solid State Communications. - : Elsevier. - 0038-1098 .- 1879-2766. ; 141:8, s. 440-444
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Tidskriftsartikel (refereegranskat)abstract
- Single phase ceramics CaCu3Ti4.0O12 and CaCu3Ti3.9O12 have been prepared using the traditional solid-state reaction method. Compared with the stoichiometric ceramics CaCu3Ti4.0O12, Ti-deficient ceramics CaCu3Ti3.9O12 have the larger lattice parameter, the higher force constant, and smaller dielectric constant and the lower dissipation factor, although their fundamental characters of dielectric response are similar. Their characteristic relaxation frequencies are not well fitted with the Arrhenius Law but a tentatively supposed relation. With the Cole-Cole Law, the fitted broadened factors of dissipation peaks are 0.5433 and 0.8651 for CaCu3Ti3.9O12 and CaCu3Ti4.0O12, respectively. All facts mentioned above imply that mutually correlated motion of Ti ions or defects may be expected to be responsible for the giant dielectric constant and high dissipation factor of CaCu3T4.0O12. (c) 2006 Elsevier Ltd. All rights reserved.
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