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- Endale, Milkyas, et al.
(författare)
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Antiplasmodial Quinones from Pentas longiflora and Pentas lanceolata
- 2012
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Ingår i: Planta Medica. - : Georg Thieme Verlag KG. - 0032-0943 .- 1439-0221. ; 78:1, s. 31-35
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Tidskriftsartikel (refereegranskat)abstract
- The dichloromethane/methanol (1 : 1) extracts of the roots of Pentas longiflora and Pentas lanceolata showed low micromolar (IC50 = 0.9-3 µg/mL) in vitro antiplasmodial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum. Chromatographic separation of the extract of Pentas longiflora led to the isolation of the pyranonaphthoquinones pentalongin (1) and psychorubrin (2) with IC50 values below 1 µg/mL and the naphthalene derivative mollugin (3), which showed marginal activity. Similar treatment of Pentas lanceolata led to the isolation of eight anthraquinones (4-11, IC50 = 5-31 µg/mL) of which one is new (5,6-dihydroxydamnacanthol, 11), while three - nordamnacanthal (7), lucidin-ω-methyl ether (9), and damnacanthol (10) - are reported here for the first time from the genus Pentas. The compounds were identified by NMR and mass spectroscopic techniques.
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- Magnus, M. C., et al.
(författare)
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Maternal Risk of Cardiovascular Disease After Use of Assisted Reproductive Technologies
- 2023
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Ingår i: Jama Cardiology. - 2380-6583 .- 2380-6591. ; 8:9, s. 837-845
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Studies examining the associations of different combinations of intensity-specific aerobic and muscle strengthening activity (MSA) with all-cause and cause-specific mortality are scarce; the few available estimates are disparate.OBJECTIVE To examine the prospective associations of different combinations of moderate aerobic physical activity (MPA), vigorous aerobic physical activity (VPA), and MSA with all-cause, cardiovascular (CVD), and cancer mortality.DESIGN, SETTING, AND PARTICIPANTS This nationwide prospective cohort study used data from the US National Health Interview Survey. A total of 500705 eligible US adults were included in the study and followed up during a median of 10.0 years (5.6 million person-years) from 1997 to 2018. Data were analyzed from September 1 to September 30, 2022. EXPOSURES Self-reported cumulative bouts (75 weekly minutes) of MPA and VPA with recommended MSA guidelines (yes or no) to obtain 48 mutually exclusive exposure categories.MAIN OUTCOMES AND MEASURES All-cause, CVD, and cancer mortality. Participants were linked to the National Death Index through December 31, 2019.RESULTS Overall, 500 705 participants (mean [SD] age, 46.4 [17.3] years; 210 803 [58%] female; 277 504 [77%] White) were included in the study. Compared with the reference group (doing no MPA or VPA and less than recommended MSA), the category associated with the lowest hazard ratio (HR) for all-cause mortality was more than 0 to 75 minutes of MPA combined with more than 150 minutes of VPA and 2 or more MSA sessions per week (HR, 0.50; 95% CI, 0.42-0.59). The optimal combinations for CVD and cancer mortality risk reduction were more than 150 to 225 minutes of MPA, more than 0 to 75 minutes of VPA, and 2 or more MSA sessions per week (HR, 0.30; 95% CI, 0.15-0.57), and more than 300 minutes of MPA, more than 0 to 75 minutes of VPA, and 2 or more MSA sessions per week (HR, 0.44; 95% CI, 0.23-0.82), respectively. Adjusted mortality rates represented an approximately 50% lower mortality rate for all-cause and cancer mortality and an approximately 3-fold lower mortality rate for CVD mortality. CONCLUSIONS AND RELEVANCE This cohort study demonstrated that balanced levels of MPA, VPA, and MSA combined may be associated with optimal reductions of mortality risk. Higher-than-recommended levels of MPA and VPA may further lower the risk of cancer and all-cause mortality, respectively.
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- Pass, Jesper, et al.
(författare)
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Murine monoclonal antibodies against murine uPA receptor produced in gene-deficient mice: inhibitory effects on receptor-mediated uPA activity in vitro and in vivo
- 2007
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 97:6, s. 1013-1022
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Tidskriftsartikel (refereegranskat)abstract
- Binding of urokinase plasminogen activator (uPA) to its cellular receptor, uPAR, potentiates plasminogen activation and localizes it to the cell surface. Focal plasminogen activation is involved in both normal and pathological tissue remodeling processes including cancer invasion. The interaction between uPA and uPAR therefore represents a potential target for anti-invasive cancer therapy. Inhibitors of the human uPA-uPAR interaction have no effect in the murine system. To enable in-vivo studies in murine cancer models we have now generated murine monoclonal antibodies (mAbs) against murine uPAR (muPAR) by immunizing uPAR-deficient mice with recombinant muPAR and screened for antibodies, which inhibit the muPA-muPAR interaction. Two of the twelve mAbs obtained, mR1 and mR2, interfered with the interaction between muPAR and the amino-terminal fragment of muPA (mATF) when analyzed by surface plasmon resonance. The epitope for mR1 is located on domain I of muPAR, while that of mR2 is on domains (II-III). In cell binding experiments using radiolabelled mATF, the maximal inhibition obtained with mR1 was 85% while that obtained with mR2 was 50%. The IC(50) value for mR1 was 0.67 nM compared to 0.14 nM for mATF. In an assay based on modified anthrax toxins, requiring cell-bound muPA activity for its cytotoxity, an approximately 50% rescue of the cells could be obtained by addition of mR1. Importantly, in-vivo efficacy of mR1 was demonstrated by the ability of mR1 to rescue mice treated with a lethal dose of uPA-activatable anthrax toxins.
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